Mixed Topics

Thoracic endovascular aortic repair (TEVAR) is a “young technology with several unknowns,” say researchers from Shantou University Medical College, and Wuhan Asia Heart Hospital, both China. One of those unknowns is the risk factors for prognosis after TEVAR.

After all, thyroid hormones are critical to many areas of heart health, such as vascular remodeling; hypothyroidism can aggravate hypertension; and low levels of free thyroxine (FT4) influence arterial stiffness and C-reactive protein. In spite of the many links, however, the relationship between subclinical hypothyroidism and cardiovascular disease has not been fully elucidated, the researchers say. They conducted a study to evaluate whether thyroid hormones predicted early (30 days) and mid-term (12 months) aorta-related adverse events (AEs), such as death, progression of aortic disease, organ failure, or lower limb ischemia; and aorta-related readmissions.

In their study, 338 patients were stratified according to their levels of FT4 before undergoing TEVAR. Of the enrolled patients, 288 were followed up at 12 months for readmission; 292 were followed up on AEs.

Patients with low normal levels of FT4 had a greater risk of readmission after thoracic endovascular aortic repair. Within 30 days, the incidence of AEs and readmission were 2.7% and 4.1%; within 12 months, 8.9% and 13.5%. After the researchers adjusted for confounders, the patients with the lowest FT4 quartile were at significantly greater risk for readmission than those in the highest-quartile group, at both early and mid-term follow-up. 

The same did not hold true for AEs. The researchers say this is not uncommon in studies of predictors of AEs and readmission: Factors that are weak predictors of readmission tend to be strong predictors of AEs, and vice versa.

Thoracic endovascular aortic repair (TEVAR) is a “young technology with several unknowns,” say researchers from Shantou University Medical College, and Wuhan Asia Heart Hospital, both China. One of those unknowns is the risk factors for prognosis after TEVAR.

After all, thyroid hormones are critical to many areas of heart health, such as vascular remodeling; hypothyroidism can aggravate hypertension; and low levels of free thyroxine (FT4) influence arterial stiffness and C-reactive protein. In spite of the many links, however, the relationship between subclinical hypothyroidism and cardiovascular disease has not been fully elucidated, the researchers say. They conducted a study to evaluate whether thyroid hormones predicted early (30 days) and mid-term (12 months) aorta-related adverse events (AEs), such as death, progression of aortic disease, organ failure, or lower limb ischemia; and aorta-related readmissions.

In their study, 338 patients were stratified according to their levels of FT4 before undergoing TEVAR. Of the enrolled patients, 288 were followed up at 12 months for readmission; 292 were followed up on AEs.

Patients with low normal levels of FT4 had a greater risk of readmission after thoracic endovascular aortic repair. Within 30 days, the incidence of AEs and readmission were 2.7% and 4.1%; within 12 months, 8.9% and 13.5%. After the researchers adjusted for confounders, the patients with the lowest FT4 quartile were at significantly greater risk for readmission than those in the highest-quartile group, at both early and mid-term follow-up. 

The same did not hold true for AEs. The researchers say this is not uncommon in studies of predictors of AEs and readmission: Factors that are weak predictors of readmission tend to be strong predictors of AEs, and vice versa.

Thoracic endovascular aortic repair (TEVAR) is a “young technology with several unknowns,” say researchers from Shantou University Medical College, and Wuhan Asia Heart Hospital, both China. One of those unknowns is the risk factors for prognosis after TEVAR.

After all, thyroid hormones are critical to many areas of heart health, such as vascular remodeling; hypothyroidism can aggravate hypertension; and low levels of free thyroxine (FT4) influence arterial stiffness and C-reactive protein. In spite of the many links, however, the relationship between subclinical hypothyroidism and cardiovascular disease has not been fully elucidated, the researchers say. They conducted a study to evaluate whether thyroid hormones predicted early (30 days) and mid-term (12 months) aorta-related adverse events (AEs), such as death, progression of aortic disease, organ failure, or lower limb ischemia; and aorta-related readmissions.

In their study, 338 patients were stratified according to their levels of FT4 before undergoing TEVAR. Of the enrolled patients, 288 were followed up at 12 months for readmission; 292 were followed up on AEs.

Patients with low normal levels of FT4 had a greater risk of readmission after thoracic endovascular aortic repair. Within 30 days, the incidence of AEs and readmission were 2.7% and 4.1%; within 12 months, 8.9% and 13.5%. After the researchers adjusted for confounders, the patients with the lowest FT4 quartile were at significantly greater risk for readmission than those in the highest-quartile group, at both early and mid-term follow-up. 

The same did not hold true for AEs. The researchers say this is not uncommon in studies of predictors of AEs and readmission: Factors that are weak predictors of readmission tend to be strong predictors of AEs, and vice versa.

WASHINGTON – Injection of dehydrated alcohol through the wall of the renal artery can be added to a growing list of renal denervation strategies that have been associated with sustained blood pressure reductions, according to data presented as a latebreaker at 2019 CRT meeting.

Ted Bosworth/MDedge News

For the primary efficacy endpoint of change in systolic blood pressure at six months, the mean reduction six months after denervation was 11 mmHg as measured with 24-hour ambulatory blood pressure monitoring (ABPM), according to Horst Sievert, MD, PhD, Director of the CardioVascular Center, Frankfurt, Germany.

“Alcohol denervation was associated with efficient and safe lowering of systolic blood pressure,” reported Dr. Sievert, who said these data have prompted a new set of studies, including a phase 2 controlled trial that will evaluate the effect of renal denervation for control of blood pressure off-medication.

After consent was withdrawn from one patient, study results were available from 44 patients with treatment resistant hypertension who were enrolled in this initial study. Entry requirements included a mean systolic blood pressure greater than 150 mmHg while taking at least three antihypertensive medications from different classes.

In this study, the alcohol was delivered with a proprietary device called the Peregrine System™ infusion catheter (Ablation Solutions). This catheter is equipped with microneedles that remain retracted until the catheter is navigated into position. Once in the renal artery, the microneedles are deployed to inject alcohol into the perivascular space, which produces a neurolytic effect.

The technical success for delivery of the alcohol was achieved in 100% of the study group. There were no serious adverse events associated with treatment. Minor adverse events included those involving the access site, such as pain, as well as two dissections that resolved without treatment. One patient complained of abdominal pain on the day of the procedure, but that also resolved, according to Dr. Sievert.

Over the course of followup, patients remained on the therapies they were taking prior to the intervention. There was no change in antihypertensive therapy during the first month of followup in 84% of treated patients. Of those who did have a change in medication, all but one involved a reduction in medication prompted by improved blood pressure control. At six months, there was no change in medication for 73% of those evaluated.

Following alcohol denervation, there was a mean 7 mmHg reduction in diastolic pressure as measured with 24-hour ABBM.

Based on these data, a trials program is being launched. In addition to the phase 2 multinational off-medication trial, which is enrolling 300 patients who are being randomized to the alcohol denervation therapy or a sham control, an open-label crossover trial will be conducted to confirm the safety and tolerability of this approach.

Delivery of alcohol through the catheter device used in this study requires a renal artery diameter of at least 4 mm. This is a potential limitation for smaller individuals, but several other devices used for denervation share this requirement, according to Dr. Sievert.

The potential advantage of this approach is that “you can stay proximal,” according to Dr. Sievert, contrasting this technique with renal denervation by radiofrequency ablation. He explained that radiofrequency renal denervation requires a relatively distal approach to achieve an appropriate energy penetration for target nerve ablation. Further study is needed to determine whether more proximal delivery has any clinical advantage.

SOURCE: 2019 Cardiovascular Research Technologies (CRT) Meeting.

WASHINGTON – Injection of dehydrated alcohol through the wall of the renal artery can be added to a growing list of renal denervation strategies that have been associated with sustained blood pressure reductions, according to data presented as a latebreaker at 2019 CRT meeting.

Ted Bosworth/MDedge News

For the primary efficacy endpoint of change in systolic blood pressure at six months, the mean reduction six months after denervation was 11 mmHg as measured with 24-hour ambulatory blood pressure monitoring (ABPM), according to Horst Sievert, MD, PhD, Director of the CardioVascular Center, Frankfurt, Germany.

“Alcohol denervation was associated with efficient and safe lowering of systolic blood pressure,” reported Dr. Sievert, who said these data have prompted a new set of studies, including a phase 2 controlled trial that will evaluate the effect of renal denervation for control of blood pressure off-medication.

After consent was withdrawn from one patient, study results were available from 44 patients with treatment resistant hypertension who were enrolled in this initial study. Entry requirements included a mean systolic blood pressure greater than 150 mmHg while taking at least three antihypertensive medications from different classes.

In this study, the alcohol was delivered with a proprietary device called the Peregrine System™ infusion catheter (Ablation Solutions). This catheter is equipped with microneedles that remain retracted until the catheter is navigated into position. Once in the renal artery, the microneedles are deployed to inject alcohol into the perivascular space, which produces a neurolytic effect.

The technical success for delivery of the alcohol was achieved in 100% of the study group. There were no serious adverse events associated with treatment. Minor adverse events included those involving the access site, such as pain, as well as two dissections that resolved without treatment. One patient complained of abdominal pain on the day of the procedure, but that also resolved, according to Dr. Sievert.

Over the course of followup, patients remained on the therapies they were taking prior to the intervention. There was no change in antihypertensive therapy during the first month of followup in 84% of treated patients. Of those who did have a change in medication, all but one involved a reduction in medication prompted by improved blood pressure control. At six months, there was no change in medication for 73% of those evaluated.

Following alcohol denervation, there was a mean 7 mmHg reduction in diastolic pressure as measured with 24-hour ABBM.

Based on these data, a trials program is being launched. In addition to the phase 2 multinational off-medication trial, which is enrolling 300 patients who are being randomized to the alcohol denervation therapy or a sham control, an open-label crossover trial will be conducted to confirm the safety and tolerability of this approach.

Delivery of alcohol through the catheter device used in this study requires a renal artery diameter of at least 4 mm. This is a potential limitation for smaller individuals, but several other devices used for denervation share this requirement, according to Dr. Sievert.

The potential advantage of this approach is that “you can stay proximal,” according to Dr. Sievert, contrasting this technique with renal denervation by radiofrequency ablation. He explained that radiofrequency renal denervation requires a relatively distal approach to achieve an appropriate energy penetration for target nerve ablation. Further study is needed to determine whether more proximal delivery has any clinical advantage.

SOURCE: 2019 Cardiovascular Research Technologies (CRT) Meeting.

WASHINGTON – Injection of dehydrated alcohol through the wall of the renal artery can be added to a growing list of renal denervation strategies that have been associated with sustained blood pressure reductions, according to data presented as a latebreaker at 2019 CRT meeting.

Ted Bosworth/MDedge News

For the primary efficacy endpoint of change in systolic blood pressure at six months, the mean reduction six months after denervation was 11 mmHg as measured with 24-hour ambulatory blood pressure monitoring (ABPM), according to Horst Sievert, MD, PhD, Director of the CardioVascular Center, Frankfurt, Germany.

“Alcohol denervation was associated with efficient and safe lowering of systolic blood pressure,” reported Dr. Sievert, who said these data have prompted a new set of studies, including a phase 2 controlled trial that will evaluate the effect of renal denervation for control of blood pressure off-medication.

After consent was withdrawn from one patient, study results were available from 44 patients with treatment resistant hypertension who were enrolled in this initial study. Entry requirements included a mean systolic blood pressure greater than 150 mmHg while taking at least three antihypertensive medications from different classes.

In this study, the alcohol was delivered with a proprietary device called the Peregrine System™ infusion catheter (Ablation Solutions). This catheter is equipped with microneedles that remain retracted until the catheter is navigated into position. Once in the renal artery, the microneedles are deployed to inject alcohol into the perivascular space, which produces a neurolytic effect.

The technical success for delivery of the alcohol was achieved in 100% of the study group. There were no serious adverse events associated with treatment. Minor adverse events included those involving the access site, such as pain, as well as two dissections that resolved without treatment. One patient complained of abdominal pain on the day of the procedure, but that also resolved, according to Dr. Sievert.

Over the course of followup, patients remained on the therapies they were taking prior to the intervention. There was no change in antihypertensive therapy during the first month of followup in 84% of treated patients. Of those who did have a change in medication, all but one involved a reduction in medication prompted by improved blood pressure control. At six months, there was no change in medication for 73% of those evaluated.

Following alcohol denervation, there was a mean 7 mmHg reduction in diastolic pressure as measured with 24-hour ABBM.

Based on these data, a trials program is being launched. In addition to the phase 2 multinational off-medication trial, which is enrolling 300 patients who are being randomized to the alcohol denervation therapy or a sham control, an open-label crossover trial will be conducted to confirm the safety and tolerability of this approach.

Delivery of alcohol through the catheter device used in this study requires a renal artery diameter of at least 4 mm. This is a potential limitation for smaller individuals, but several other devices used for denervation share this requirement, according to Dr. Sievert.

The potential advantage of this approach is that “you can stay proximal,” according to Dr. Sievert, contrasting this technique with renal denervation by radiofrequency ablation. He explained that radiofrequency renal denervation requires a relatively distal approach to achieve an appropriate energy penetration for target nerve ablation. Further study is needed to determine whether more proximal delivery has any clinical advantage.

SOURCE: 2019 Cardiovascular Research Technologies (CRT) Meeting.

We received several emails from our engaged readership about one of our front-page stories from the February issue. In brief, there were concerns raised about how CHEST Physician characterized the findings of the recent study by Huo et al in JAMA Internal Medicine. On my repeat review of our story and the Huo manuscript, as well as several conversations with content experts both within and outside of CHEST, I agree that we did mischaracterize the findings in our write-up. While the study was not necessarily poorly conducted, there were some methodological concerns that deserved more careful consideration before putting the findings into our publication. CHEST Physician Editorial Board member M. Patricia Rivera, MD, FCCP, and past CHEST President Gerard Silvestri, MD, MS, FCCP, have kindly put together a brief discussion of the potential problems with this paper; while we will further address this in our next issue to go to print (and will likely host further conversations about this manuscript down the road), I wanted to make this expert opinion available to the readership as soon as possible.

For those of you who took the time to write in, thanks so very much!

David A. Schulman, MD, FCCP
Editor in Chief, CHEST Physician



The cover story of the February 2019 edition of CHEST Physician titled “In real-world setting, LDCT screen is linked to high complication risk” erroneously interpreted a study by Huo and colleagues recently published in JAMA Internal Medicine. The cover story states that “the study included 174,702 individuals who underwent an invasive diagnostic procedure as a result of abnormal findings on lung cancer screening and 169,808 control subjects,” “the rates of complications associated with diagnostic procedures following LDCT for lung cancer screening were substantially higher than the rates reported in clinical trials of LDCT” and that “the findings emphasize the importance of discussing the risk of adverse events and cost as part of the shared decision-making process before LDCT screening.”

One wonders if the data reported by Huo and colleagues was skewed by the lens it was presented through or by the lens through which it was interpreted. Let us first elucidate that the study by Huo and colleagues titled “Complication Rates and Downstream Medical Costs Associated with Invasive Diagnostic Procedures for Lung Abnormalities in the Community Setting” was NOT a study of patients who underwent LDCT for lung cancer screening but rather a retrospective, database cohort study from 2008-2013 of patients within the age eligible for screening (age 55 to 77) WITHOUT lung cancer, who underwent similar invasive diagnostic procedures as those performed in the NLST in non–protocol-driven community practices.

Huo et al. hypothesized that the rates of complications after invasive diagnostic procedures observed among screen-eligible patients in the general population would be higher than those reported in the NLST and tested their hypothesis by estimating the complication rate of common invasive diagnostic procedures using data from a database of procedure codes. The database did not however, provide the clinical condition or indication for the procedures, define the number of procedures required to achieve a diagnosis, or define what was the most invasive procedure performed. The authors followed patients for 1 year after their procedure and reported any complication that occurred during that period as related to that procedure. This is not the standard in reporting complications from diagnostic bronchoscopic or radiologic procedures (usually occur within 24-48 hours, or maybe days) or thoracic surgery (30-90 days). As a significant number of the complications reported in the NLST were cardiac, it would be atypical to consider a cardiac complication occurring 1 year after an invasive diagnostic procedure as a complication related to the procedure.

Although the results of the study by Huo and colleagues may not be representative of complications from invasive diagnostic procedures in patients undergoing lung cancer screening, they do show that diagnostic procedures performed in the inpatient and outpatient setting for any pulmonary abnormalities (nodules, masses, adenopathy, infiltrates) are associated with a high risk of complications. In an era of advanced technologies and an increasing aging and chronic critically-ill population, clinicians need to carefully appraise the risks that may be incurred following a diagnostic procedure for a pulmonary lesion and equally, the benefit and diagnostic yield of the procedure. Multidisciplinary discussions, particularly in high-risk patients, can provide guidance to clinical decision-making regarding which procedure will be the least invasive, safest, and most likely to render a diagnosis for the individual patient. Furthermore, we need to take into account that complication rates following procedures are likely higher in centers with a low volume of diagnostic procedures or the inability to provide a less-invasive procedure that can still provide a diagnosis. While it is easy to be critical of large database analyses because of the inherent limitations associated with constructing cohorts that can provide meaningful data, we should not ignore the trends outlined in this article, particularly as the size of the cohort is substantial.

One cannot argue about the importance of discussing the risk of potential complications and cost as part of the shared decision-making process before LDCT screening, but the increased rate of complications reported by Huo et al. should not be interpreted as the complication rate from lung cancer screening in real-world setting, for this is inaccurate and has potential to create additional barriers in lung cancer screening, already beset by barriers on multiple levels. Moreover, we must emphasize that discussions of potential risks and cost from diagnostic pulmonary procedures should not be isolated to lung cancer screening.

M. Patricia Rivera, MD, FCCP
Professor of Medicine
Division of Pulmonary and Critical Care Medicine
Co-Director, Multidisciplinary Thoracic Oncology Program
Director, Multidisciplinary Lung Cancer Screening Program
Medical Director Bronchoscopy and PFT Laboratory
University of North Carolina at Chapel Hill
Chapel Hill, NC

Gerard A. Silvestri, MD, MS, FCCP
Hillenbrand Professor of Thoracic Oncology
Vice-Chair of Medicine for Faculty Development
Division of Pulmonary and Critical Care Medicine
Medical University of South Carolina
Charleston, SC


 

We received several emails from our engaged readership about one of our front-page stories from the February issue. In brief, there were concerns raised about how CHEST Physician characterized the findings of the recent study by Huo et al in JAMA Internal Medicine. On my repeat review of our story and the Huo manuscript, as well as several conversations with content experts both within and outside of CHEST, I agree that we did mischaracterize the findings in our write-up. While the study was not necessarily poorly conducted, there were some methodological concerns that deserved more careful consideration before putting the findings into our publication. CHEST Physician Editorial Board member M. Patricia Rivera, MD, FCCP, and past CHEST President Gerard Silvestri, MD, MS, FCCP, have kindly put together a brief discussion of the potential problems with this paper; while we will further address this in our next issue to go to print (and will likely host further conversations about this manuscript down the road), I wanted to make this expert opinion available to the readership as soon as possible.

For those of you who took the time to write in, thanks so very much!

David A. Schulman, MD, FCCP
Editor in Chief, CHEST Physician



The cover story of the February 2019 edition of CHEST Physician titled “In real-world setting, LDCT screen is linked to high complication risk” erroneously interpreted a study by Huo and colleagues recently published in JAMA Internal Medicine. The cover story states that “the study included 174,702 individuals who underwent an invasive diagnostic procedure as a result of abnormal findings on lung cancer screening and 169,808 control subjects,” “the rates of complications associated with diagnostic procedures following LDCT for lung cancer screening were substantially higher than the rates reported in clinical trials of LDCT” and that “the findings emphasize the importance of discussing the risk of adverse events and cost as part of the shared decision-making process before LDCT screening.”

One wonders if the data reported by Huo and colleagues was skewed by the lens it was presented through or by the lens through which it was interpreted. Let us first elucidate that the study by Huo and colleagues titled “Complication Rates and Downstream Medical Costs Associated with Invasive Diagnostic Procedures for Lung Abnormalities in the Community Setting” was NOT a study of patients who underwent LDCT for lung cancer screening but rather a retrospective, database cohort study from 2008-2013 of patients within the age eligible for screening (age 55 to 77) WITHOUT lung cancer, who underwent similar invasive diagnostic procedures as those performed in the NLST in non–protocol-driven community practices.

Huo et al. hypothesized that the rates of complications after invasive diagnostic procedures observed among screen-eligible patients in the general population would be higher than those reported in the NLST and tested their hypothesis by estimating the complication rate of common invasive diagnostic procedures using data from a database of procedure codes. The database did not however, provide the clinical condition or indication for the procedures, define the number of procedures required to achieve a diagnosis, or define what was the most invasive procedure performed. The authors followed patients for 1 year after their procedure and reported any complication that occurred during that period as related to that procedure. This is not the standard in reporting complications from diagnostic bronchoscopic or radiologic procedures (usually occur within 24-48 hours, or maybe days) or thoracic surgery (30-90 days). As a significant number of the complications reported in the NLST were cardiac, it would be atypical to consider a cardiac complication occurring 1 year after an invasive diagnostic procedure as a complication related to the procedure.

Although the results of the study by Huo and colleagues may not be representative of complications from invasive diagnostic procedures in patients undergoing lung cancer screening, they do show that diagnostic procedures performed in the inpatient and outpatient setting for any pulmonary abnormalities (nodules, masses, adenopathy, infiltrates) are associated with a high risk of complications. In an era of advanced technologies and an increasing aging and chronic critically-ill population, clinicians need to carefully appraise the risks that may be incurred following a diagnostic procedure for a pulmonary lesion and equally, the benefit and diagnostic yield of the procedure. Multidisciplinary discussions, particularly in high-risk patients, can provide guidance to clinical decision-making regarding which procedure will be the least invasive, safest, and most likely to render a diagnosis for the individual patient. Furthermore, we need to take into account that complication rates following procedures are likely higher in centers with a low volume of diagnostic procedures or the inability to provide a less-invasive procedure that can still provide a diagnosis. While it is easy to be critical of large database analyses because of the inherent limitations associated with constructing cohorts that can provide meaningful data, we should not ignore the trends outlined in this article, particularly as the size of the cohort is substantial.

One cannot argue about the importance of discussing the risk of potential complications and cost as part of the shared decision-making process before LDCT screening, but the increased rate of complications reported by Huo et al. should not be interpreted as the complication rate from lung cancer screening in real-world setting, for this is inaccurate and has potential to create additional barriers in lung cancer screening, already beset by barriers on multiple levels. Moreover, we must emphasize that discussions of potential risks and cost from diagnostic pulmonary procedures should not be isolated to lung cancer screening.

M. Patricia Rivera, MD, FCCP
Professor of Medicine
Division of Pulmonary and Critical Care Medicine
Co-Director, Multidisciplinary Thoracic Oncology Program
Director, Multidisciplinary Lung Cancer Screening Program
Medical Director Bronchoscopy and PFT Laboratory
University of North Carolina at Chapel Hill
Chapel Hill, NC

Gerard A. Silvestri, MD, MS, FCCP
Hillenbrand Professor of Thoracic Oncology
Vice-Chair of Medicine for Faculty Development
Division of Pulmonary and Critical Care Medicine
Medical University of South Carolina
Charleston, SC


 

We received several emails from our engaged readership about one of our front-page stories from the February issue. In brief, there were concerns raised about how CHEST Physician characterized the findings of the recent study by Huo et al in JAMA Internal Medicine. On my repeat review of our story and the Huo manuscript, as well as several conversations with content experts both within and outside of CHEST, I agree that we did mischaracterize the findings in our write-up. While the study was not necessarily poorly conducted, there were some methodological concerns that deserved more careful consideration before putting the findings into our publication. CHEST Physician Editorial Board member M. Patricia Rivera, MD, FCCP, and past CHEST President Gerard Silvestri, MD, MS, FCCP, have kindly put together a brief discussion of the potential problems with this paper; while we will further address this in our next issue to go to print (and will likely host further conversations about this manuscript down the road), I wanted to make this expert opinion available to the readership as soon as possible.

For those of you who took the time to write in, thanks so very much!

David A. Schulman, MD, FCCP
Editor in Chief, CHEST Physician



The cover story of the February 2019 edition of CHEST Physician titled “In real-world setting, LDCT screen is linked to high complication risk” erroneously interpreted a study by Huo and colleagues recently published in JAMA Internal Medicine. The cover story states that “the study included 174,702 individuals who underwent an invasive diagnostic procedure as a result of abnormal findings on lung cancer screening and 169,808 control subjects,” “the rates of complications associated with diagnostic procedures following LDCT for lung cancer screening were substantially higher than the rates reported in clinical trials of LDCT” and that “the findings emphasize the importance of discussing the risk of adverse events and cost as part of the shared decision-making process before LDCT screening.”

One wonders if the data reported by Huo and colleagues was skewed by the lens it was presented through or by the lens through which it was interpreted. Let us first elucidate that the study by Huo and colleagues titled “Complication Rates and Downstream Medical Costs Associated with Invasive Diagnostic Procedures for Lung Abnormalities in the Community Setting” was NOT a study of patients who underwent LDCT for lung cancer screening but rather a retrospective, database cohort study from 2008-2013 of patients within the age eligible for screening (age 55 to 77) WITHOUT lung cancer, who underwent similar invasive diagnostic procedures as those performed in the NLST in non–protocol-driven community practices.

Huo et al. hypothesized that the rates of complications after invasive diagnostic procedures observed among screen-eligible patients in the general population would be higher than those reported in the NLST and tested their hypothesis by estimating the complication rate of common invasive diagnostic procedures using data from a database of procedure codes. The database did not however, provide the clinical condition or indication for the procedures, define the number of procedures required to achieve a diagnosis, or define what was the most invasive procedure performed. The authors followed patients for 1 year after their procedure and reported any complication that occurred during that period as related to that procedure. This is not the standard in reporting complications from diagnostic bronchoscopic or radiologic procedures (usually occur within 24-48 hours, or maybe days) or thoracic surgery (30-90 days). As a significant number of the complications reported in the NLST were cardiac, it would be atypical to consider a cardiac complication occurring 1 year after an invasive diagnostic procedure as a complication related to the procedure.

Although the results of the study by Huo and colleagues may not be representative of complications from invasive diagnostic procedures in patients undergoing lung cancer screening, they do show that diagnostic procedures performed in the inpatient and outpatient setting for any pulmonary abnormalities (nodules, masses, adenopathy, infiltrates) are associated with a high risk of complications. In an era of advanced technologies and an increasing aging and chronic critically-ill population, clinicians need to carefully appraise the risks that may be incurred following a diagnostic procedure for a pulmonary lesion and equally, the benefit and diagnostic yield of the procedure. Multidisciplinary discussions, particularly in high-risk patients, can provide guidance to clinical decision-making regarding which procedure will be the least invasive, safest, and most likely to render a diagnosis for the individual patient. Furthermore, we need to take into account that complication rates following procedures are likely higher in centers with a low volume of diagnostic procedures or the inability to provide a less-invasive procedure that can still provide a diagnosis. While it is easy to be critical of large database analyses because of the inherent limitations associated with constructing cohorts that can provide meaningful data, we should not ignore the trends outlined in this article, particularly as the size of the cohort is substantial.

One cannot argue about the importance of discussing the risk of potential complications and cost as part of the shared decision-making process before LDCT screening, but the increased rate of complications reported by Huo et al. should not be interpreted as the complication rate from lung cancer screening in real-world setting, for this is inaccurate and has potential to create additional barriers in lung cancer screening, already beset by barriers on multiple levels. Moreover, we must emphasize that discussions of potential risks and cost from diagnostic pulmonary procedures should not be isolated to lung cancer screening.

M. Patricia Rivera, MD, FCCP
Professor of Medicine
Division of Pulmonary and Critical Care Medicine
Co-Director, Multidisciplinary Thoracic Oncology Program
Director, Multidisciplinary Lung Cancer Screening Program
Medical Director Bronchoscopy and PFT Laboratory
University of North Carolina at Chapel Hill
Chapel Hill, NC

Gerard A. Silvestri, MD, MS, FCCP
Hillenbrand Professor of Thoracic Oncology
Vice-Chair of Medicine for Faculty Development
Division of Pulmonary and Critical Care Medicine
Medical University of South Carolina
Charleston, SC


 

Not all sedentary behavior is equal, say researchers from Universidad Autónoma de Madrid in Spain, who evaluated the sedentary habits of 5,459 women and 4,740 men.

The researchers note that several studies have found that, unlike, for example, computer use and reading, TV watching is consistently associated with adverse health outcomes, such as metabolic syndrome, obesity, and diabetes mellitus (DM). But different sedentary behaviors (SBs) have different health effects, they add. They cite research that suggests TV and other “passive” SBs (eg, listening or talking while sitting) could be more harmful than “mentally active” SBs, such as computer use and reading. In this study, “passive” sedentary time, such as TV watching, was associated with less recreational activity and higher body weight. Time at the computer and reading were linked to more recreational physical activity but less light-intensity activity at home.

Moreover, each type of SB has a distinct demographic and lifestyle profile, the researchers say. Older age, lower education, unhealthy lifestyle (smoking, worse diet, less physical activity, higher BMI) and chronic morbidity, such as DM or osteomuscular disease, were linked to more TV time. Longer time at the computer or in commuting was linked to younger age, male gender, higher education, and a sedentary job.

Watching TV had no association with total time spent on the rest of leisure-time SBs. The researchers also found that “mentally active” SBs, such as using the computer and reading, tend to cluster.

Many studies have looked at the effects of and connections between SB, lifestyle choices, and health. The researchers of this study say theirs extends knowledge in the field by considering more types of SB (using the computer, commuting, lying in the sun, listening to music, and reading). To their knowledge, they say, no previous study on a representative sample of an entire country has examined the association between TV watching time and the rest of SB, or has reported the full profile of sociodemographic, lifestyle, and health variables associated with each type of SB.

Watching TV was the predominant SB (45% of total sitting time), followed by sitting at the computer (23%), reading (15%), and commuting (12%). The participants spent a mean of 1.96 hours a day watching TV, vs > 1 hour for the other behaviors.

Not all sedentary behavior is equal, say researchers from Universidad Autónoma de Madrid in Spain, who evaluated the sedentary habits of 5,459 women and 4,740 men.

The researchers note that several studies have found that, unlike, for example, computer use and reading, TV watching is consistently associated with adverse health outcomes, such as metabolic syndrome, obesity, and diabetes mellitus (DM). But different sedentary behaviors (SBs) have different health effects, they add. They cite research that suggests TV and other “passive” SBs (eg, listening or talking while sitting) could be more harmful than “mentally active” SBs, such as computer use and reading. In this study, “passive” sedentary time, such as TV watching, was associated with less recreational activity and higher body weight. Time at the computer and reading were linked to more recreational physical activity but less light-intensity activity at home.

Moreover, each type of SB has a distinct demographic and lifestyle profile, the researchers say. Older age, lower education, unhealthy lifestyle (smoking, worse diet, less physical activity, higher BMI) and chronic morbidity, such as DM or osteomuscular disease, were linked to more TV time. Longer time at the computer or in commuting was linked to younger age, male gender, higher education, and a sedentary job.

Watching TV had no association with total time spent on the rest of leisure-time SBs. The researchers also found that “mentally active” SBs, such as using the computer and reading, tend to cluster.

Many studies have looked at the effects of and connections between SB, lifestyle choices, and health. The researchers of this study say theirs extends knowledge in the field by considering more types of SB (using the computer, commuting, lying in the sun, listening to music, and reading). To their knowledge, they say, no previous study on a representative sample of an entire country has examined the association between TV watching time and the rest of SB, or has reported the full profile of sociodemographic, lifestyle, and health variables associated with each type of SB.

Watching TV was the predominant SB (45% of total sitting time), followed by sitting at the computer (23%), reading (15%), and commuting (12%). The participants spent a mean of 1.96 hours a day watching TV, vs > 1 hour for the other behaviors.

Not all sedentary behavior is equal, say researchers from Universidad Autónoma de Madrid in Spain, who evaluated the sedentary habits of 5,459 women and 4,740 men.

The researchers note that several studies have found that, unlike, for example, computer use and reading, TV watching is consistently associated with adverse health outcomes, such as metabolic syndrome, obesity, and diabetes mellitus (DM). But different sedentary behaviors (SBs) have different health effects, they add. They cite research that suggests TV and other “passive” SBs (eg, listening or talking while sitting) could be more harmful than “mentally active” SBs, such as computer use and reading. In this study, “passive” sedentary time, such as TV watching, was associated with less recreational activity and higher body weight. Time at the computer and reading were linked to more recreational physical activity but less light-intensity activity at home.

Moreover, each type of SB has a distinct demographic and lifestyle profile, the researchers say. Older age, lower education, unhealthy lifestyle (smoking, worse diet, less physical activity, higher BMI) and chronic morbidity, such as DM or osteomuscular disease, were linked to more TV time. Longer time at the computer or in commuting was linked to younger age, male gender, higher education, and a sedentary job.

Watching TV had no association with total time spent on the rest of leisure-time SBs. The researchers also found that “mentally active” SBs, such as using the computer and reading, tend to cluster.

Many studies have looked at the effects of and connections between SB, lifestyle choices, and health. The researchers of this study say theirs extends knowledge in the field by considering more types of SB (using the computer, commuting, lying in the sun, listening to music, and reading). To their knowledge, they say, no previous study on a representative sample of an entire country has examined the association between TV watching time and the rest of SB, or has reported the full profile of sociodemographic, lifestyle, and health variables associated with each type of SB.

Watching TV was the predominant SB (45% of total sitting time), followed by sitting at the computer (23%), reading (15%), and commuting (12%). The participants spent a mean of 1.96 hours a day watching TV, vs > 1 hour for the other behaviors.

The FDA approves intranasal esketamine for refractory major depressive disorder. A behavioral intervention improves physical activity in patients with diabetes. Groups of physicians produce more accurate diagnoses than individuals. And there’s a new target for reducing sodium consumption.
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The FDA approves intranasal esketamine for refractory major depressive disorder. A behavioral intervention improves physical activity in patients with diabetes. Groups of physicians produce more accurate diagnoses than individuals. And there’s a new target for reducing sodium consumption.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify

The FDA approves intranasal esketamine for refractory major depressive disorder. A behavioral intervention improves physical activity in patients with diabetes. Groups of physicians produce more accurate diagnoses than individuals. And there’s a new target for reducing sodium consumption.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify

SNOWMASS, COLO. – Infective endocarditis in 2019 is very different from the disease most physicians encountered in training, both in terms of epidemiology and clinical presentation, Patrick T. O’Gara, MD, observed at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Bruce Jancin/MDedge News

The classic description of infective endocarditis provided by Sir William Osler, MD, was of a subacute bacterial infection characterized by a long latent phase of low-grade fever, back pain, weight loss, and night sweats. It was mainly a right-heart disease of younger individuals with an infected native valve, and the predominant pathogens were streptococci, Dr. O’Gara said.

“I think in the current era endocarditis is more often characterized by an acute illness with toxic features in the context of adults with a high burden of degenerative diseases – for example, patients with rheumatoid arthritis or psoriatic arthritis on immunosuppressive therapy, or diabetes, end-stage renal disease, and risk factors for hospital-acquired infection. Injectable drug use is through the roof, there’s a wider prevalence of cardiac implanted electronic devices, which are a wonderful place for bacteria to hide, and Staphylococcus aureus has certainly become the leading pathogen with regard to endocarditis in the United States, especially MRSA, often multidrug resistant,” said Dr. O’Gara, professor of medicine at Harvard Medical School, Boston.

“Also, no talk about endocarditis is sufficient without paying some attention to the opioid crisis in which we find ourselves. It’s one of the top three causes of death among young men in the United States, along with accidents and gun violence. No region of the country is spared. This has completely inundated our ER and hospitalist services and our inpatient cardiology services with folks who are often repeat offenders when it comes to the difficulty in being able to give up an injectable drug use habit. They have multiple infections and hospitalizations, tricuspid valve involvement, and depending upon the aggressiveness of the Staphylococcus organism, typically they have left-sided disease with multiple complications, including aortic regurgitation and heart failure,” the cardiologist continued.

This description underscored one of Dr. O’Gara’s major points about the challenges posed by infective endocarditis in contemporary practice: “Expect the unexpected,” he advised. “When you’ve seen one case of infective endocarditis, you’ve seen one case of infective endocarditis.”
 

Outcomes are ‘sobering’

In the current era, outcomes are “sobering,” the cardiologist noted. Infective endocarditis carries a 6-month mortality rate of 20%-25% despite early surgery being performed during the index hospitalization in up to 60% of patients, with a relatively high perioperative mortality rate of about 10%. However, the risk of reinfection occurring in a newly implanted cardiac valve is impressively low at about 2%.

Refer early for multimodality imaging and surgical consultation

Transesophageal echocardiography is valuable in assessment of the infected valve. However, when extravalvular extension of the infection is suspected and the echo assessment is nondiagnostic or indeterminate, it’s time to quickly move on to advanced imaging, such as PET-CT.

The ACC/American Heart Association class I recommendations for early surgery in infected native valves haven’t changed substantially in over a decade. Based largely on observational data, there is an association between early surgery and lower in-hospital mortality (Lancet. 2012 Mar 10;379[9819]:965-975).

Class IIa recommendations for native valve surgery include recurrent emboli and a persistent vegetation despite appropriate antibiotic therapy. A “very controversial” class IIb recommendation for surgery because of weak supporting data is the identification of a mobile vegetation larger than 10 mm, particularly if it’s located on an anterior mitral valve leaflet, he said.

If the decision is made to forgo early surgery, be sure to repeat transesophageal echocardiography on day 7-10 to reassess the size of the patient’s vegetation.

“There is an association between size of vegetation and 1-year mortality, with a cut point of greater than 15 mm. Some would argue this constitutes a reasonable indication for early surgery,” Dr. O’Gara noted.

The embolization rate in patients with infective endocarditis is highest during the day before presentation, the day of presentation, and through the first 2 days afterward. The rate drops precipitously within 2 weeks after initiation of appropriate antibiotic therapy. Thus, to utilize early surgery to maximum effect in order to decrease the risk of embolization, it makes sense to operate within the first several days following presentation, before antibiotics have had sufficient time to catch up with the evolving disease process.
 

Don’t use half measures when it comes to removal of cardiac implanted electronic devices

The guidelines are clear regarding infected pacemakers, implanted cardioverter-defibrillators, and cardiac resynchronization devices: “It all needs to come out,” Dr. O’Gara emphasized. That includes all leads and the generator in patients with documented infection of only one portion of the device system, as a class I, level of evidence B recommendation. Moreover, complete removal of a pacemaker or defibrillator system is deemed “reasonable” as a class IIa recommendation in all patients with valvular infection caused by S. aureus or fungi even in the absence of evidence of device infection.

“I think we as general cardiologists have become increasingly impressed about how sick and festering these kinds of patients can become, even when we’re not able to prove that the lead is infected. The lead looks okay on transesophageal echo or PET-CT, blood cultures are negative, the valvular heart disease is really not that advanced, but several days go by and the patient is just not responding. We should have a high index of suspicion that there’s an infection we cannot appreciate. But obviously, you make these difficult decisions in consultation with your electrophysiology colleagues,” he added.
 

Know when the cardiologist should say ‘no’ to early aggressive surgery

While an aggressive early surgical approach often pays off in terms of prevention of embolic sequelae and a reduction in heart failure, the timing of surgery in the 20%-40% of patients with infective endocarditis who present with stroke or other neurologic complications remains controversial. An international group of Canadian and French cardiac surgeons and neurologists developed a useful algorithm regarding the types of neurologic complications for which early cardiac surgery is a poor idea because of the high risk of neurologic exacerbation. For example, a mycotic neuroaneurysm is grounds for postponement of cardiac surgery for at least 4 weeks (Circulation. 2016 Oct 25;134[17]:1280-92).

Dr. O’Gara reported receiving funding from the National Heart, Lung and Blood Institute, the National Institute of Dental and Craniofacial Research, from Medtronic in conjunction with the ongoing pivotal APOLLO transcatheter mitral valve replacement trial, and from Edwards Lifesciences for the ongoing EARLY TAVR trial.

[email protected]

SNOWMASS, COLO. – Infective endocarditis in 2019 is very different from the disease most physicians encountered in training, both in terms of epidemiology and clinical presentation, Patrick T. O’Gara, MD, observed at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Bruce Jancin/MDedge News

The classic description of infective endocarditis provided by Sir William Osler, MD, was of a subacute bacterial infection characterized by a long latent phase of low-grade fever, back pain, weight loss, and night sweats. It was mainly a right-heart disease of younger individuals with an infected native valve, and the predominant pathogens were streptococci, Dr. O’Gara said.

“I think in the current era endocarditis is more often characterized by an acute illness with toxic features in the context of adults with a high burden of degenerative diseases – for example, patients with rheumatoid arthritis or psoriatic arthritis on immunosuppressive therapy, or diabetes, end-stage renal disease, and risk factors for hospital-acquired infection. Injectable drug use is through the roof, there’s a wider prevalence of cardiac implanted electronic devices, which are a wonderful place for bacteria to hide, and Staphylococcus aureus has certainly become the leading pathogen with regard to endocarditis in the United States, especially MRSA, often multidrug resistant,” said Dr. O’Gara, professor of medicine at Harvard Medical School, Boston.

“Also, no talk about endocarditis is sufficient without paying some attention to the opioid crisis in which we find ourselves. It’s one of the top three causes of death among young men in the United States, along with accidents and gun violence. No region of the country is spared. This has completely inundated our ER and hospitalist services and our inpatient cardiology services with folks who are often repeat offenders when it comes to the difficulty in being able to give up an injectable drug use habit. They have multiple infections and hospitalizations, tricuspid valve involvement, and depending upon the aggressiveness of the Staphylococcus organism, typically they have left-sided disease with multiple complications, including aortic regurgitation and heart failure,” the cardiologist continued.

This description underscored one of Dr. O’Gara’s major points about the challenges posed by infective endocarditis in contemporary practice: “Expect the unexpected,” he advised. “When you’ve seen one case of infective endocarditis, you’ve seen one case of infective endocarditis.”
 

Outcomes are ‘sobering’

In the current era, outcomes are “sobering,” the cardiologist noted. Infective endocarditis carries a 6-month mortality rate of 20%-25% despite early surgery being performed during the index hospitalization in up to 60% of patients, with a relatively high perioperative mortality rate of about 10%. However, the risk of reinfection occurring in a newly implanted cardiac valve is impressively low at about 2%.

Refer early for multimodality imaging and surgical consultation

Transesophageal echocardiography is valuable in assessment of the infected valve. However, when extravalvular extension of the infection is suspected and the echo assessment is nondiagnostic or indeterminate, it’s time to quickly move on to advanced imaging, such as PET-CT.

The ACC/American Heart Association class I recommendations for early surgery in infected native valves haven’t changed substantially in over a decade. Based largely on observational data, there is an association between early surgery and lower in-hospital mortality (Lancet. 2012 Mar 10;379[9819]:965-975).

Class IIa recommendations for native valve surgery include recurrent emboli and a persistent vegetation despite appropriate antibiotic therapy. A “very controversial” class IIb recommendation for surgery because of weak supporting data is the identification of a mobile vegetation larger than 10 mm, particularly if it’s located on an anterior mitral valve leaflet, he said.

If the decision is made to forgo early surgery, be sure to repeat transesophageal echocardiography on day 7-10 to reassess the size of the patient’s vegetation.

“There is an association between size of vegetation and 1-year mortality, with a cut point of greater than 15 mm. Some would argue this constitutes a reasonable indication for early surgery,” Dr. O’Gara noted.

The embolization rate in patients with infective endocarditis is highest during the day before presentation, the day of presentation, and through the first 2 days afterward. The rate drops precipitously within 2 weeks after initiation of appropriate antibiotic therapy. Thus, to utilize early surgery to maximum effect in order to decrease the risk of embolization, it makes sense to operate within the first several days following presentation, before antibiotics have had sufficient time to catch up with the evolving disease process.
 

Don’t use half measures when it comes to removal of cardiac implanted electronic devices

The guidelines are clear regarding infected pacemakers, implanted cardioverter-defibrillators, and cardiac resynchronization devices: “It all needs to come out,” Dr. O’Gara emphasized. That includes all leads and the generator in patients with documented infection of only one portion of the device system, as a class I, level of evidence B recommendation. Moreover, complete removal of a pacemaker or defibrillator system is deemed “reasonable” as a class IIa recommendation in all patients with valvular infection caused by S. aureus or fungi even in the absence of evidence of device infection.

“I think we as general cardiologists have become increasingly impressed about how sick and festering these kinds of patients can become, even when we’re not able to prove that the lead is infected. The lead looks okay on transesophageal echo or PET-CT, blood cultures are negative, the valvular heart disease is really not that advanced, but several days go by and the patient is just not responding. We should have a high index of suspicion that there’s an infection we cannot appreciate. But obviously, you make these difficult decisions in consultation with your electrophysiology colleagues,” he added.
 

Know when the cardiologist should say ‘no’ to early aggressive surgery

While an aggressive early surgical approach often pays off in terms of prevention of embolic sequelae and a reduction in heart failure, the timing of surgery in the 20%-40% of patients with infective endocarditis who present with stroke or other neurologic complications remains controversial. An international group of Canadian and French cardiac surgeons and neurologists developed a useful algorithm regarding the types of neurologic complications for which early cardiac surgery is a poor idea because of the high risk of neurologic exacerbation. For example, a mycotic neuroaneurysm is grounds for postponement of cardiac surgery for at least 4 weeks (Circulation. 2016 Oct 25;134[17]:1280-92).

Dr. O’Gara reported receiving funding from the National Heart, Lung and Blood Institute, the National Institute of Dental and Craniofacial Research, from Medtronic in conjunction with the ongoing pivotal APOLLO transcatheter mitral valve replacement trial, and from Edwards Lifesciences for the ongoing EARLY TAVR trial.

[email protected]

SNOWMASS, COLO. – Infective endocarditis in 2019 is very different from the disease most physicians encountered in training, both in terms of epidemiology and clinical presentation, Patrick T. O’Gara, MD, observed at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Bruce Jancin/MDedge News

The classic description of infective endocarditis provided by Sir William Osler, MD, was of a subacute bacterial infection characterized by a long latent phase of low-grade fever, back pain, weight loss, and night sweats. It was mainly a right-heart disease of younger individuals with an infected native valve, and the predominant pathogens were streptococci, Dr. O’Gara said.

“I think in the current era endocarditis is more often characterized by an acute illness with toxic features in the context of adults with a high burden of degenerative diseases – for example, patients with rheumatoid arthritis or psoriatic arthritis on immunosuppressive therapy, or diabetes, end-stage renal disease, and risk factors for hospital-acquired infection. Injectable drug use is through the roof, there’s a wider prevalence of cardiac implanted electronic devices, which are a wonderful place for bacteria to hide, and Staphylococcus aureus has certainly become the leading pathogen with regard to endocarditis in the United States, especially MRSA, often multidrug resistant,” said Dr. O’Gara, professor of medicine at Harvard Medical School, Boston.

“Also, no talk about endocarditis is sufficient without paying some attention to the opioid crisis in which we find ourselves. It’s one of the top three causes of death among young men in the United States, along with accidents and gun violence. No region of the country is spared. This has completely inundated our ER and hospitalist services and our inpatient cardiology services with folks who are often repeat offenders when it comes to the difficulty in being able to give up an injectable drug use habit. They have multiple infections and hospitalizations, tricuspid valve involvement, and depending upon the aggressiveness of the Staphylococcus organism, typically they have left-sided disease with multiple complications, including aortic regurgitation and heart failure,” the cardiologist continued.

This description underscored one of Dr. O’Gara’s major points about the challenges posed by infective endocarditis in contemporary practice: “Expect the unexpected,” he advised. “When you’ve seen one case of infective endocarditis, you’ve seen one case of infective endocarditis.”
 

Outcomes are ‘sobering’

In the current era, outcomes are “sobering,” the cardiologist noted. Infective endocarditis carries a 6-month mortality rate of 20%-25% despite early surgery being performed during the index hospitalization in up to 60% of patients, with a relatively high perioperative mortality rate of about 10%. However, the risk of reinfection occurring in a newly implanted cardiac valve is impressively low at about 2%.

Refer early for multimodality imaging and surgical consultation

Transesophageal echocardiography is valuable in assessment of the infected valve. However, when extravalvular extension of the infection is suspected and the echo assessment is nondiagnostic or indeterminate, it’s time to quickly move on to advanced imaging, such as PET-CT.

The ACC/American Heart Association class I recommendations for early surgery in infected native valves haven’t changed substantially in over a decade. Based largely on observational data, there is an association between early surgery and lower in-hospital mortality (Lancet. 2012 Mar 10;379[9819]:965-975).

Class IIa recommendations for native valve surgery include recurrent emboli and a persistent vegetation despite appropriate antibiotic therapy. A “very controversial” class IIb recommendation for surgery because of weak supporting data is the identification of a mobile vegetation larger than 10 mm, particularly if it’s located on an anterior mitral valve leaflet, he said.

If the decision is made to forgo early surgery, be sure to repeat transesophageal echocardiography on day 7-10 to reassess the size of the patient’s vegetation.

“There is an association between size of vegetation and 1-year mortality, with a cut point of greater than 15 mm. Some would argue this constitutes a reasonable indication for early surgery,” Dr. O’Gara noted.

The embolization rate in patients with infective endocarditis is highest during the day before presentation, the day of presentation, and through the first 2 days afterward. The rate drops precipitously within 2 weeks after initiation of appropriate antibiotic therapy. Thus, to utilize early surgery to maximum effect in order to decrease the risk of embolization, it makes sense to operate within the first several days following presentation, before antibiotics have had sufficient time to catch up with the evolving disease process.
 

Don’t use half measures when it comes to removal of cardiac implanted electronic devices

The guidelines are clear regarding infected pacemakers, implanted cardioverter-defibrillators, and cardiac resynchronization devices: “It all needs to come out,” Dr. O’Gara emphasized. That includes all leads and the generator in patients with documented infection of only one portion of the device system, as a class I, level of evidence B recommendation. Moreover, complete removal of a pacemaker or defibrillator system is deemed “reasonable” as a class IIa recommendation in all patients with valvular infection caused by S. aureus or fungi even in the absence of evidence of device infection.

“I think we as general cardiologists have become increasingly impressed about how sick and festering these kinds of patients can become, even when we’re not able to prove that the lead is infected. The lead looks okay on transesophageal echo or PET-CT, blood cultures are negative, the valvular heart disease is really not that advanced, but several days go by and the patient is just not responding. We should have a high index of suspicion that there’s an infection we cannot appreciate. But obviously, you make these difficult decisions in consultation with your electrophysiology colleagues,” he added.
 

Know when the cardiologist should say ‘no’ to early aggressive surgery

While an aggressive early surgical approach often pays off in terms of prevention of embolic sequelae and a reduction in heart failure, the timing of surgery in the 20%-40% of patients with infective endocarditis who present with stroke or other neurologic complications remains controversial. An international group of Canadian and French cardiac surgeons and neurologists developed a useful algorithm regarding the types of neurologic complications for which early cardiac surgery is a poor idea because of the high risk of neurologic exacerbation. For example, a mycotic neuroaneurysm is grounds for postponement of cardiac surgery for at least 4 weeks (Circulation. 2016 Oct 25;134[17]:1280-92).

Dr. O’Gara reported receiving funding from the National Heart, Lung and Blood Institute, the National Institute of Dental and Craniofacial Research, from Medtronic in conjunction with the ongoing pivotal APOLLO transcatheter mitral valve replacement trial, and from Edwards Lifesciences for the ongoing EARLY TAVR trial.

[email protected]

The Diagnosis: Phytophotodermatitis

Initially, there was concern for autoimmune or connective tissue disease because of the edematous plaques localized over sun-exposed regions of the hands with marked sparing of the knuckles. Lupus erythematosus (LE), mixed connective tissue disease, CREST (calcinosis, Raynaud phenomenon, esophageal motility disorders, sclerodactyly, telangiectasia) syndrome, dermatomyositis (DM), and erythromelalgia all were considered. Common disorders such as contact dermatitis and phytophotodermatitis remained in the differential diagnosis, though the patient adamantly denied any recent exposures. As part of the initial workup, laboratory studies including a complete blood cell count, comprehensive metabolic panel, serum lactate dehydrogenase, serum creatinine kinase, erythrocyte sedimentation rate, and an antinuclear antibody panel were performed. Additionally, a punch biopsy at the border of the lesion was performed.

Lupus erythematosus was considered given the patient’s age and sex and the photoexposed location of the plaques. The photosensitive rash of LE classically affects the dorsal aspects of the hands while sparing the interphalangeal joints.^1,2 However, the patient had no nail fold findings consistent with systemic LE with no evidence of erythema or dilated tortuous vessels.³ Furthermore, there were no other cutaneous symptoms, and there was a negative review of systems, including malar/discoid rash, oral ulcers, photosensitivity, history of hematologic abnormalities, and end organ damage.^4,5 A negative antinuclear antibody serologic panel combined with a negative review of systems made the diagnosis of LE less likely.

Given the presenting clinical appearance, DM also was considered. Dermatomyositis traditionally displays ragged cuticular dystrophy with nail fold telangiectasia, mechanic hands, and involvement of the dorsal aspects of the hands with violaceous accentuation of the knuckles.⁶ The patient reported pruritus, which is common among DM patients; however, the nail folds were unaffected.⁷ Finally, she demonstrated sparing rather than involvement of the knuckles, which would be an unlikely presentation for DM.⁶

CREST syndrome, systemic sclerosis, and syndromes with overlapping features such as mixed connective tissue disease also were considered. The cutaneous features of CREST syndrome are characterized by initial edema of the digits with a subsequent taut and shiny indurated phase. Flexion contractures, ulceration, tapering of the digits, and loss of cutaneous fat pads can progressively occur.^8,9 Raynaud phenomenon is a common early finding in CREST syndrome or systemic sclerosis, and patients may develop ice pick digital infarcts and calcinosis in progressed disease.⁸ Common nail fold findings include periungual telangiectasia with dropout areas.^10,11 The marked edema and white discoloration of the knuckles in this patient could be mistaken for Raynaud phenomenon; however, she lacked pain or cold sensitivity and her discoloration was static.¹² Without sclerodermoid changes, nail fold findings, matted telangiectasia, taut skin, or systemic findings, a diagnosis of CREST syndrome, scleroderma, or other mixed connective tissue disease would be unlikely.⁸

Erythromelalgia is a clinical syndrome characterized by burning pain, erythema, and increased skin temperature that intermittently affects both the arms and legs. This rare disorder can be further classified into type 1 (associated with thrombocytopenia), type 2 (primary or idiopathic), and type 3 (associated with other medical cause excluding thrombocytopenia).^1,13 The patient endorsed some discomfort from the lesions but denied any subjective feeling of burning pain or increased skin temperature. Additionally, she had no family history of inheritable skin disorders and no personal history of polycythemia. Consequently, erythromelalgia remained less likely on the differential diagnosis.

The histology of the acral skin revealed mild focal spongiosis with no increase in dermal mucin on colloidal iron or mucopolysaccharide stains (Figure). After receiving the biopsy results and additional questioning of the patient, it was discovered that 2 days prior to her initial presentation she had juiced numerous limes by hand and subsequently spent a long period of time outside with sunlight exposure. Upon discovery of this additional historical information, the diagnosis of phytophotodermatitis was made.

Phytophotodermatitis is an erythematous inflammatory reaction that occurs on the skin after exposure to a plant-derived photosensitizer followed by UVA light radiation.¹⁴ This phenomenon was first described by the ancient Egyptians as a treatment for vitiligo.¹ The most common plant families that can cause this nonimmune cutaneous reaction include Apiaceae eg, hogweed, celery, dill, fennel) and Rutaceae (eg, citrus plants, rue).¹⁴ The psoralens or furocoumarins found in these plants bind loosely to DNA at their ground state but covalently bond to pyrimidine bases during photoexcitation with UVA, resulting in DNA damage and subsequent local inflammation.¹⁴ Given the patient’s clinical examination, pathology findings, and history, phytophotodermatitis secondary to lime juice exposure was confirmed. Two weeks after applying clobetasol ointment twice daily, the patient’s hands had returned to baseline with complete resolution of the erythematous lesions.

Although lime phytophotodermatitis is a routine diagnosis, this clinical case stands as an important reminder to demonstrate how common diseases can masquerade as more exotic cutaneous disorders. There often is a clinical desire to seek out more complicated diagnoses, particularly during residency training; however, this case reinforces the invaluable importance of collecting a thorough patient history, as it can ultimately minimize excessive testing and in some cases prevent unnecessary therapy.

The Diagnosis: Phytophotodermatitis

Initially, there was concern for autoimmune or connective tissue disease because of the edematous plaques localized over sun-exposed regions of the hands with marked sparing of the knuckles. Lupus erythematosus (LE), mixed connective tissue disease, CREST (calcinosis, Raynaud phenomenon, esophageal motility disorders, sclerodactyly, telangiectasia) syndrome, dermatomyositis (DM), and erythromelalgia all were considered. Common disorders such as contact dermatitis and phytophotodermatitis remained in the differential diagnosis, though the patient adamantly denied any recent exposures. As part of the initial workup, laboratory studies including a complete blood cell count, comprehensive metabolic panel, serum lactate dehydrogenase, serum creatinine kinase, erythrocyte sedimentation rate, and an antinuclear antibody panel were performed. Additionally, a punch biopsy at the border of the lesion was performed.

Lupus erythematosus was considered given the patient’s age and sex and the photoexposed location of the plaques. The photosensitive rash of LE classically affects the dorsal aspects of the hands while sparing the interphalangeal joints.^1,2 However, the patient had no nail fold findings consistent with systemic LE with no evidence of erythema or dilated tortuous vessels.³ Furthermore, there were no other cutaneous symptoms, and there was a negative review of systems, including malar/discoid rash, oral ulcers, photosensitivity, history of hematologic abnormalities, and end organ damage.^4,5 A negative antinuclear antibody serologic panel combined with a negative review of systems made the diagnosis of LE less likely.

Given the presenting clinical appearance, DM also was considered. Dermatomyositis traditionally displays ragged cuticular dystrophy with nail fold telangiectasia, mechanic hands, and involvement of the dorsal aspects of the hands with violaceous accentuation of the knuckles.⁶ The patient reported pruritus, which is common among DM patients; however, the nail folds were unaffected.⁷ Finally, she demonstrated sparing rather than involvement of the knuckles, which would be an unlikely presentation for DM.⁶

CREST syndrome, systemic sclerosis, and syndromes with overlapping features such as mixed connective tissue disease also were considered. The cutaneous features of CREST syndrome are characterized by initial edema of the digits with a subsequent taut and shiny indurated phase. Flexion contractures, ulceration, tapering of the digits, and loss of cutaneous fat pads can progressively occur.^8,9 Raynaud phenomenon is a common early finding in CREST syndrome or systemic sclerosis, and patients may develop ice pick digital infarcts and calcinosis in progressed disease.⁸ Common nail fold findings include periungual telangiectasia with dropout areas.^10,11 The marked edema and white discoloration of the knuckles in this patient could be mistaken for Raynaud phenomenon; however, she lacked pain or cold sensitivity and her discoloration was static.¹² Without sclerodermoid changes, nail fold findings, matted telangiectasia, taut skin, or systemic findings, a diagnosis of CREST syndrome, scleroderma, or other mixed connective tissue disease would be unlikely.⁸

Erythromelalgia is a clinical syndrome characterized by burning pain, erythema, and increased skin temperature that intermittently affects both the arms and legs. This rare disorder can be further classified into type 1 (associated with thrombocytopenia), type 2 (primary or idiopathic), and type 3 (associated with other medical cause excluding thrombocytopenia).^1,13 The patient endorsed some discomfort from the lesions but denied any subjective feeling of burning pain or increased skin temperature. Additionally, she had no family history of inheritable skin disorders and no personal history of polycythemia. Consequently, erythromelalgia remained less likely on the differential diagnosis.

The histology of the acral skin revealed mild focal spongiosis with no increase in dermal mucin on colloidal iron or mucopolysaccharide stains (Figure). After receiving the biopsy results and additional questioning of the patient, it was discovered that 2 days prior to her initial presentation she had juiced numerous limes by hand and subsequently spent a long period of time outside with sunlight exposure. Upon discovery of this additional historical information, the diagnosis of phytophotodermatitis was made.

Phytophotodermatitis is an erythematous inflammatory reaction that occurs on the skin after exposure to a plant-derived photosensitizer followed by UVA light radiation.¹⁴ This phenomenon was first described by the ancient Egyptians as a treatment for vitiligo.¹ The most common plant families that can cause this nonimmune cutaneous reaction include Apiaceae eg, hogweed, celery, dill, fennel) and Rutaceae (eg, citrus plants, rue).¹⁴ The psoralens or furocoumarins found in these plants bind loosely to DNA at their ground state but covalently bond to pyrimidine bases during photoexcitation with UVA, resulting in DNA damage and subsequent local inflammation.¹⁴ Given the patient’s clinical examination, pathology findings, and history, phytophotodermatitis secondary to lime juice exposure was confirmed. Two weeks after applying clobetasol ointment twice daily, the patient’s hands had returned to baseline with complete resolution of the erythematous lesions.

Although lime phytophotodermatitis is a routine diagnosis, this clinical case stands as an important reminder to demonstrate how common diseases can masquerade as more exotic cutaneous disorders. There often is a clinical desire to seek out more complicated diagnoses, particularly during residency training; however, this case reinforces the invaluable importance of collecting a thorough patient history, as it can ultimately minimize excessive testing and in some cases prevent unnecessary therapy.

The Diagnosis: Phytophotodermatitis

Initially, there was concern for autoimmune or connective tissue disease because of the edematous plaques localized over sun-exposed regions of the hands with marked sparing of the knuckles. Lupus erythematosus (LE), mixed connective tissue disease, CREST (calcinosis, Raynaud phenomenon, esophageal motility disorders, sclerodactyly, telangiectasia) syndrome, dermatomyositis (DM), and erythromelalgia all were considered. Common disorders such as contact dermatitis and phytophotodermatitis remained in the differential diagnosis, though the patient adamantly denied any recent exposures. As part of the initial workup, laboratory studies including a complete blood cell count, comprehensive metabolic panel, serum lactate dehydrogenase, serum creatinine kinase, erythrocyte sedimentation rate, and an antinuclear antibody panel were performed. Additionally, a punch biopsy at the border of the lesion was performed.

Lupus erythematosus was considered given the patient’s age and sex and the photoexposed location of the plaques. The photosensitive rash of LE classically affects the dorsal aspects of the hands while sparing the interphalangeal joints.^1,2 However, the patient had no nail fold findings consistent with systemic LE with no evidence of erythema or dilated tortuous vessels.³ Furthermore, there were no other cutaneous symptoms, and there was a negative review of systems, including malar/discoid rash, oral ulcers, photosensitivity, history of hematologic abnormalities, and end organ damage.^4,5 A negative antinuclear antibody serologic panel combined with a negative review of systems made the diagnosis of LE less likely.

Given the presenting clinical appearance, DM also was considered. Dermatomyositis traditionally displays ragged cuticular dystrophy with nail fold telangiectasia, mechanic hands, and involvement of the dorsal aspects of the hands with violaceous accentuation of the knuckles.⁶ The patient reported pruritus, which is common among DM patients; however, the nail folds were unaffected.⁷ Finally, she demonstrated sparing rather than involvement of the knuckles, which would be an unlikely presentation for DM.⁶

CREST syndrome, systemic sclerosis, and syndromes with overlapping features such as mixed connective tissue disease also were considered. The cutaneous features of CREST syndrome are characterized by initial edema of the digits with a subsequent taut and shiny indurated phase. Flexion contractures, ulceration, tapering of the digits, and loss of cutaneous fat pads can progressively occur.^8,9 Raynaud phenomenon is a common early finding in CREST syndrome or systemic sclerosis, and patients may develop ice pick digital infarcts and calcinosis in progressed disease.⁸ Common nail fold findings include periungual telangiectasia with dropout areas.^10,11 The marked edema and white discoloration of the knuckles in this patient could be mistaken for Raynaud phenomenon; however, she lacked pain or cold sensitivity and her discoloration was static.¹² Without sclerodermoid changes, nail fold findings, matted telangiectasia, taut skin, or systemic findings, a diagnosis of CREST syndrome, scleroderma, or other mixed connective tissue disease would be unlikely.⁸

Erythromelalgia is a clinical syndrome characterized by burning pain, erythema, and increased skin temperature that intermittently affects both the arms and legs. This rare disorder can be further classified into type 1 (associated with thrombocytopenia), type 2 (primary or idiopathic), and type 3 (associated with other medical cause excluding thrombocytopenia).^1,13 The patient endorsed some discomfort from the lesions but denied any subjective feeling of burning pain or increased skin temperature. Additionally, she had no family history of inheritable skin disorders and no personal history of polycythemia. Consequently, erythromelalgia remained less likely on the differential diagnosis.

The histology of the acral skin revealed mild focal spongiosis with no increase in dermal mucin on colloidal iron or mucopolysaccharide stains (Figure). After receiving the biopsy results and additional questioning of the patient, it was discovered that 2 days prior to her initial presentation she had juiced numerous limes by hand and subsequently spent a long period of time outside with sunlight exposure. Upon discovery of this additional historical information, the diagnosis of phytophotodermatitis was made.

Phytophotodermatitis is an erythematous inflammatory reaction that occurs on the skin after exposure to a plant-derived photosensitizer followed by UVA light radiation.¹⁴ This phenomenon was first described by the ancient Egyptians as a treatment for vitiligo.¹ The most common plant families that can cause this nonimmune cutaneous reaction include Apiaceae eg, hogweed, celery, dill, fennel) and Rutaceae (eg, citrus plants, rue).¹⁴ The psoralens or furocoumarins found in these plants bind loosely to DNA at their ground state but covalently bond to pyrimidine bases during photoexcitation with UVA, resulting in DNA damage and subsequent local inflammation.¹⁴ Given the patient’s clinical examination, pathology findings, and history, phytophotodermatitis secondary to lime juice exposure was confirmed. Two weeks after applying clobetasol ointment twice daily, the patient’s hands had returned to baseline with complete resolution of the erythematous lesions.

Although lime phytophotodermatitis is a routine diagnosis, this clinical case stands as an important reminder to demonstrate how common diseases can masquerade as more exotic cutaneous disorders. There often is a clinical desire to seek out more complicated diagnoses, particularly during residency training; however, this case reinforces the invaluable importance of collecting a thorough patient history, as it can ultimately minimize excessive testing and in some cases prevent unnecessary therapy.

I was at a meeting in Orlando, sitting in the front row. The speaker was a former Disney executive who was telling us how to improve our offices. He kept walking very close to the edge of the stage – so close I was worried he might step off with the Klieg lights in his eyes. Then he got to the heart of his message, telling us that we need to make each patient encounter a marvelous experience, and how he and his staff had done so for millions of mouseketeers. “You need to make each customer feel special,” he said. He went on with saccharine examples of staff going above and beyond – for example, replacing toddlers’ dropped ice creams before they could cry.

That hit my trigger. From that point on, I was almost hoping he would fall off the stage.

Of course, there is a story behind my reaction.

One sunny day, while I was sitting at the most cluttered desk in the world, one of my staff came into my office to tell me a patient had called. The patient was very unhappy, I was told, and she planned to stink bomb me on social media. Concerned, I pulled the patient’s before-and-after photos. It looked as though she had a great result from her treatment, so I was perplexed. I phoned the patient, but she refused to tell me why she was unhappy. “I’m very unhappy, and I’m going to punish you,” she said. I urged her to come to the office and see me, at her convenience.

When we spoke face-to-face, I examined her nose and took a picture. I explained that her cancer was cured; her result was beautiful, the site was almost imperceptible. I added that I thought the appearance would continue to improve with time.

My patient refused to look at me, and refused to look at the site in the mirror. She shoved the preop defect photo away without giving it a glance. Instead, she told me how inconvenient it was for her to have had a skin cancer at all. Traffic had been terrible coming into the office on the morning of the procedure. There had been a 45-minute backup on the bridge on her way home. Her ex-husband had refused to help with her wound care. She continued in a similar vein for 15 minutes as I waited for her to accuse me of my transgressions. She concluded with a scowl and a whimper, “You just didn’t make me feel special.”

Everyone has difficult patients, and everyone has bad days, but I can’t recall ever being ambushed quite so adroitly in my 30 years of practice. I recognized my patient was being passive-aggressive and was playing a social media–augmented game of “Now I’ve got you, you S.O.B,” right out of Eric Berne’s book “Games People Play.” I’d say that this book should still be required reading for dealing with difficult patients.

There are ways to defuse such patients. One of the best is to slow things down and spread them around. The wider the array of interactions with people (the medical assistant, the nurse, the fellow, the Mohs surgeon, maybe the plastic surgeon), the more times the patient has to vent and the anger is defused across many targets. This also speaks to the value of requiring a preoperative consultation days before the procedure As I thought about this patient, I recalled that, because of the distance she was traveling, I had not done so.

I looked my patient in the eye and told her I was sorry she was unhappy. I told her I would be glad to see her again. I told her I realized how far she was driving and thought the traffic would not be a problem this early in the afternoon. I thanked her and showed her to the door. She stalked out of the office.

Technically and emotionally difficult patients are sometimes referred to you. They are patients who you might prefer not to take on but you do because, as a specialist, you may be at the end of the referral pipeline. Sometimes you can win the day, striking up a friendship or jollying them past their resentment at the world.

And there are times when, as a physician and healer, you must recognize that patient criticism cannot be taken personally. The third law of surviving internship from Samuel Shem’s book “The House of God” is germane here. Remember, “the patient is the one with the disease.” And sometimes the disease is complicated by the patient’s emotional baggage. This is one of the reasons social media ratings can be so unfair. We have to realize that we are all going to be trashed unfairly at some point, and probably sued unfairly as well. As a malpractice attorney told me once, “You doctors shouldn’t take this so personally; it’s just business.”

And my patient? Despite my admonishments to you not to take things personally, I did feel bad for a week or so after our encounter. I did mail her a copy of her pre- and postoperative photographs. I have not seen her again. I did not look to see whether she burned me online.

But, by gosh, I’d really like to lock that Disney executive in a room with her for five minutes.

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].

I was at a meeting in Orlando, sitting in the front row. The speaker was a former Disney executive who was telling us how to improve our offices. He kept walking very close to the edge of the stage – so close I was worried he might step off with the Klieg lights in his eyes. Then he got to the heart of his message, telling us that we need to make each patient encounter a marvelous experience, and how he and his staff had done so for millions of mouseketeers. “You need to make each customer feel special,” he said. He went on with saccharine examples of staff going above and beyond – for example, replacing toddlers’ dropped ice creams before they could cry.

That hit my trigger. From that point on, I was almost hoping he would fall off the stage.

Of course, there is a story behind my reaction.

One sunny day, while I was sitting at the most cluttered desk in the world, one of my staff came into my office to tell me a patient had called. The patient was very unhappy, I was told, and she planned to stink bomb me on social media. Concerned, I pulled the patient’s before-and-after photos. It looked as though she had a great result from her treatment, so I was perplexed. I phoned the patient, but she refused to tell me why she was unhappy. “I’m very unhappy, and I’m going to punish you,” she said. I urged her to come to the office and see me, at her convenience.

When we spoke face-to-face, I examined her nose and took a picture. I explained that her cancer was cured; her result was beautiful, the site was almost imperceptible. I added that I thought the appearance would continue to improve with time.

My patient refused to look at me, and refused to look at the site in the mirror. She shoved the preop defect photo away without giving it a glance. Instead, she told me how inconvenient it was for her to have had a skin cancer at all. Traffic had been terrible coming into the office on the morning of the procedure. There had been a 45-minute backup on the bridge on her way home. Her ex-husband had refused to help with her wound care. She continued in a similar vein for 15 minutes as I waited for her to accuse me of my transgressions. She concluded with a scowl and a whimper, “You just didn’t make me feel special.”

Everyone has difficult patients, and everyone has bad days, but I can’t recall ever being ambushed quite so adroitly in my 30 years of practice. I recognized my patient was being passive-aggressive and was playing a social media–augmented game of “Now I’ve got you, you S.O.B,” right out of Eric Berne’s book “Games People Play.” I’d say that this book should still be required reading for dealing with difficult patients.

There are ways to defuse such patients. One of the best is to slow things down and spread them around. The wider the array of interactions with people (the medical assistant, the nurse, the fellow, the Mohs surgeon, maybe the plastic surgeon), the more times the patient has to vent and the anger is defused across many targets. This also speaks to the value of requiring a preoperative consultation days before the procedure As I thought about this patient, I recalled that, because of the distance she was traveling, I had not done so.

I looked my patient in the eye and told her I was sorry she was unhappy. I told her I would be glad to see her again. I told her I realized how far she was driving and thought the traffic would not be a problem this early in the afternoon. I thanked her and showed her to the door. She stalked out of the office.

Technically and emotionally difficult patients are sometimes referred to you. They are patients who you might prefer not to take on but you do because, as a specialist, you may be at the end of the referral pipeline. Sometimes you can win the day, striking up a friendship or jollying them past their resentment at the world.

And there are times when, as a physician and healer, you must recognize that patient criticism cannot be taken personally. The third law of surviving internship from Samuel Shem’s book “The House of God” is germane here. Remember, “the patient is the one with the disease.” And sometimes the disease is complicated by the patient’s emotional baggage. This is one of the reasons social media ratings can be so unfair. We have to realize that we are all going to be trashed unfairly at some point, and probably sued unfairly as well. As a malpractice attorney told me once, “You doctors shouldn’t take this so personally; it’s just business.”

And my patient? Despite my admonishments to you not to take things personally, I did feel bad for a week or so after our encounter. I did mail her a copy of her pre- and postoperative photographs. I have not seen her again. I did not look to see whether she burned me online.

But, by gosh, I’d really like to lock that Disney executive in a room with her for five minutes.

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].

I was at a meeting in Orlando, sitting in the front row. The speaker was a former Disney executive who was telling us how to improve our offices. He kept walking very close to the edge of the stage – so close I was worried he might step off with the Klieg lights in his eyes. Then he got to the heart of his message, telling us that we need to make each patient encounter a marvelous experience, and how he and his staff had done so for millions of mouseketeers. “You need to make each customer feel special,” he said. He went on with saccharine examples of staff going above and beyond – for example, replacing toddlers’ dropped ice creams before they could cry.

That hit my trigger. From that point on, I was almost hoping he would fall off the stage.

Of course, there is a story behind my reaction.

One sunny day, while I was sitting at the most cluttered desk in the world, one of my staff came into my office to tell me a patient had called. The patient was very unhappy, I was told, and she planned to stink bomb me on social media. Concerned, I pulled the patient’s before-and-after photos. It looked as though she had a great result from her treatment, so I was perplexed. I phoned the patient, but she refused to tell me why she was unhappy. “I’m very unhappy, and I’m going to punish you,” she said. I urged her to come to the office and see me, at her convenience.

When we spoke face-to-face, I examined her nose and took a picture. I explained that her cancer was cured; her result was beautiful, the site was almost imperceptible. I added that I thought the appearance would continue to improve with time.

My patient refused to look at me, and refused to look at the site in the mirror. She shoved the preop defect photo away without giving it a glance. Instead, she told me how inconvenient it was for her to have had a skin cancer at all. Traffic had been terrible coming into the office on the morning of the procedure. There had been a 45-minute backup on the bridge on her way home. Her ex-husband had refused to help with her wound care. She continued in a similar vein for 15 minutes as I waited for her to accuse me of my transgressions. She concluded with a scowl and a whimper, “You just didn’t make me feel special.”

Everyone has difficult patients, and everyone has bad days, but I can’t recall ever being ambushed quite so adroitly in my 30 years of practice. I recognized my patient was being passive-aggressive and was playing a social media–augmented game of “Now I’ve got you, you S.O.B,” right out of Eric Berne’s book “Games People Play.” I’d say that this book should still be required reading for dealing with difficult patients.

There are ways to defuse such patients. One of the best is to slow things down and spread them around. The wider the array of interactions with people (the medical assistant, the nurse, the fellow, the Mohs surgeon, maybe the plastic surgeon), the more times the patient has to vent and the anger is defused across many targets. This also speaks to the value of requiring a preoperative consultation days before the procedure As I thought about this patient, I recalled that, because of the distance she was traveling, I had not done so.

I looked my patient in the eye and told her I was sorry she was unhappy. I told her I would be glad to see her again. I told her I realized how far she was driving and thought the traffic would not be a problem this early in the afternoon. I thanked her and showed her to the door. She stalked out of the office.

Technically and emotionally difficult patients are sometimes referred to you. They are patients who you might prefer not to take on but you do because, as a specialist, you may be at the end of the referral pipeline. Sometimes you can win the day, striking up a friendship or jollying them past their resentment at the world.

And there are times when, as a physician and healer, you must recognize that patient criticism cannot be taken personally. The third law of surviving internship from Samuel Shem’s book “The House of God” is germane here. Remember, “the patient is the one with the disease.” And sometimes the disease is complicated by the patient’s emotional baggage. This is one of the reasons social media ratings can be so unfair. We have to realize that we are all going to be trashed unfairly at some point, and probably sued unfairly as well. As a malpractice attorney told me once, “You doctors shouldn’t take this so personally; it’s just business.”

And my patient? Despite my admonishments to you not to take things personally, I did feel bad for a week or so after our encounter. I did mail her a copy of her pre- and postoperative photographs. I have not seen her again. I did not look to see whether she burned me online.

But, by gosh, I’d really like to lock that Disney executive in a room with her for five minutes.

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].

Psoriasis is a chronic skin condition affecting approximately 2% to 3% of the population.^1,2 Beyond cutaneous manifestations, psoriasis is a systemic inflammatory state that is associated with an increased risk for cardiovascular disease, including obesity,^3,4 type 2 diabetes mellitus,^5,6 hypertension,⁵ dyslipidemia,^3,7 metabolic syndrome,⁷ atherosclerosis,⁸ peripheral vascular disease,⁹ coronary artery calcification,¹⁰ myocardial infarction,^11-13 stroke,^9,14 and cardiac death.^15,16

Psoriasis also has been associated with inflammatory bowel disease (IBD), possibly because of similar autoimmune mechanisms in the pathogenesis of both diseases.^17,18 However, there is no literature regarding the risk for acute gastrointestinal pathologies such as appendicitis, cholecystitis, or diverticulitis in patients with psoriasis.

The primary objective of this study was to examine if patients with psoriasis are at increased risk for appendicitis, cholecystitis, or diverticulitis compared to the general population. The secondary objective was to determine if patients with severe psoriasis (ie, patients treated with phototherapy or systemic therapy) are at a higher risk for these conditions compared to patients with mild psoriasis.

Methods

Patients and Tools
A descriptive, population-based cohort study design with controls from a matched cohort was used to ascertain the effect of psoriasis status on patients’ risk for appendicitis, cholecystitis, or diverticulitis. Our cohort was selected using administrative data from Kaiser Permanente Southern California (KPSC) during the study period (January 1, 2004, through December 31, 2016).

Kaiser Permanente Southern California is a large integrated health maintenance organization that includes approximately 4 million patients as of December 31, 2016, and includes roughly 20% of the region’s population. The geographic area served extends from Bakersfield in the lower California Central Valley to San Diego on the border with Mexico. Membership demographics, socioeconomic status, and ethnicity composition are representative of California.

Patients were included if they had a diagnosis of psoriasis (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 696.1; International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] codes L40.0, L40.4, L40.8, or L40.9) for at least 3 visits between January 1, 2004, and December 31, 2016. Patients were not excluded if they also had a diagnosis of psoriatic arthritis (ICD-9-CM code 696.0; ICD-10-CM code L40.5x). Patients also must have been continuously enrolled for at least 1 year before and 1 year after the index date, which was defined as the date of the third psoriasis diagnosis.

Each patient with psoriasis was assigned to 1 of 2 cohorts: (1) severe psoriasis: patients who received UVB phototherapy, psoralen plus UVA phototherapy, methotrexate, acitretin, cyclosporine, apremilast, etanercept, adalimumab, infliximab, ustekinumab, efalizumab, alefacept, secukinumab, or ixekizumab during the study period; and (2) mild psoriasis: patients who had a diagnosis of psoriasis who did not receive one of these therapies during the study period.

Patients were excluded if they had a history of appendicitis, cholecystitis, or diverticulitis at any time before the index date. Only patients older than 18 years were included.

Patients with psoriasis were frequency matched (1:5) with healthy patients, also from the KPSC network. Individuals were matched by age, sex, and ethnicity.

Statistical Analysis
Baseline characteristics were described with means and SD for continuous variables as well as percentages for categorical variables. Chi-square tests for categorical variables and the Mann-Whitney U Test for continuous variables were used to compare the patients’ characteristics by psoriasis status. Cox proportional hazards regression models were used to examine the risk for appendicitis, cholecystitis, or diverticulitis among patients with and without psoriasis and among patients with mild and severe psoriasis. Proportionality assumption was validated using Pearson product moment correlation between the scaled Schoenfeld residuals and log transformed time for each covariate.

Results were presented as crude (unadjusted) hazard ratios (HRs) and adjusted HRs, where confounding factors (ie, age, sex, ethnicity, body mass index [BMI], alcohol use, smoking status, income, education, and membership length) were adjusted. All tests were performed with SAS EG 5.1 and R software. P<.05 was considered statistically significant. Results are reported with the 95% confidence interval (CI), when appropriate.

Results

A total of 1,690,214 KPSC patients were eligible for the study; 10,307 (0.6%) met diagnostic and inclusion criteria for the psoriasis cohort. Patients with psoriasis had a significantly higher mean BMI (29.9 vs 28.7; P<.0001) as well as higher mean rates of alcohol use (56% vs 53%; P<.0001) and smoking (47% vs 38%; P<.01) compared to controls. Psoriasis patients had a shorter average duration of membership within the Kaiser network (P=.0001) compared to controls.

A total of 7416 patients met criteria for mild psoriasis and 2891 patients met criteria for severe psoriasis (eTable). Patients with severe psoriasis were significantly younger and had significantly higher mean BMI compared to patients with mild psoriasis (P<.0001 and P=.0001, respectively). No significant difference in rates of alcohol or tobacco use was detected among patients with mild and severe psoriasis.

Diverticulitis
Patients with psoriasis had a significantly greater prevalence of diverticulitis compared to the control cohort (5.1% vs 4.2%; P<.0001). There was no difference in prevalence between the severe psoriasis group and the mild psoriasis group (P=.96), but the time to diagnosis of diverticulitis was shorter in the severe psoriasis group than in the mild psoriasis group (7.2 years vs 7.9 years; P<.0001). Psoriasis patients had an incidence rate of diverticulitis of 6.61 per 1000 patient-years compared to 5.38 per 1000 patient-years in the control group. Psoriasis conferred a higher risk for diverticulitis in both the crude and adjusted models (HR, 1.23; 95% CI, 1.11-1.35 [P<.001] and HR, 1.16; 95% CI, 1.05-1.29; [P<.01], respectively)(Table 3); however, when stratified by disease severity, only patients with severe psoriasis were found to be at higher risk (HR, 1.26; 95% CI, 1.15-1.61; P<.001 for the adjusted model).

Comment

The objective of this study was to examine the background risks for specific gastrointestinal pathologies in a large cohort of patients with psoriasis compared to the general population. After adjusting for measured confounders, patients with severe psoriasis had a significantly higher risk of diverticulitis compared to the general population. Although more patients with severe psoriasis developed appendicitis or cholecystitis, the difference was not significant.

The pathogenesis of diverticulosis and diverticulitis has been thought to be related to increased intracolonic pressure and decreased dietary fiber intake, leading to formation of diverticula in the colon.¹⁹ Our study did not correct for differences in diet between the 2 groups, making it a possible confounding variable. Studies evaluating dietary habits of psoriatic patients have found that adult males with psoriasis might consume less fiber compared to healthy patients,²⁰ and psoriasis patients also might consume less whole-grain fiber.²¹ Furthermore, fiber deficiency also might affect gut flora, causing low-grade chronic inflammation,¹⁸ which also has been supported by response to anti-inflammatory medications such as mesalazine.²² Given the autoimmune association between psoriasis and IBD, it is possible that psoriasis also might create an environment of chronic inflammation in the gut, predisposing patients with psoriasis to diverticulitis. However, further research is needed to better evaluate this possibility.

Our study also does not address any potential effects on outcomes of specific treatments for psoriasis. Brandl et al²³ found that patients on immunosuppressive therapy for autoimmune diseases had longer hospital and intensive care unit stays, higher rates of emergency operations, and higher mortality while hospitalized. Because our results suggest that patients with severe psoriasis, who are therefore more likely to require treatment with an immunomodulator, are at higher risk for diverticulitis, these patients also might be at risk for poorer outcomes.

There is no literature evaluating the relationship between psoriasis and appendicitis. Our study found a slightly lower incidence rate compared to the national trend (9.38 per 10,000 patient-years in the United States in 2008) in both healthy patients and psoriasis patients.²⁴ Of note, this statistic includes children, whereas our study did not, which might in part account for the lower rate. However, Cheluvappa et al²⁵ hypothesized a relationship between appendicitis and subsequent appendectomy at a young age and protection against IBD. They also found that the mechanism for protection involves downregulation of the helper T cell (T_H17) pathway,²⁵ which also has been found to play a role in psoriasis pathogenesis.^26,27 Although our results suggest that the risk for appendicitis is not increased for patients with psoriasis, further research might be able to determine if appendicitis and subsequent appendectomy also can offer protection against development of psoriasis.

We found that patients with severe psoriasis had a higher incidence rate of cholecystitis compared to patients with mild psoriasis. Egeberg et al²⁸ found an increased risk for cholelithiasis among patients with psoriasis, which may contribute to a higher rate of cholecystitis. Although both acute and chronic cholecystitis were incorporated in this study, a Russian study found that chronic cholecystitis may be a predictor of progression of psoriasis.²⁹ Moreover, patients with severe psoriasis had a shorter duration to diagnosis of cholecystitis than patients with mild psoriasis. It is possible that patients with severe psoriasis are in a state of greater chronic inflammation than those with mild psoriasis, and therefore, when combined with other risk factors for cholecystitis, may progress to disease more quickly. Alternatively, this finding could be treatment related, as there have been reported cases of cholecystitis related to etanercept use in patients treated for psoriasis and juvenile polyarticular rheumatoid arthritis.^30,31 The relationship is not yet well defined, however, and further research is necessary to evaluate this association.

Study Strengths
Key strengths of this study include the large sample size and diversity of the patient population. Kaiser Permanente Southern California membership generally is representative of the broader community, making our results fairly generalizable to populations with health insurance. Use of a matched control cohort allows the results to be more specific to the disease of interest, and the population-based design minimizes bias.

Study Limitations
This study has several limitations. Although the cohorts were categorized based on type of treatment received, exact therapies were not specified. As a retrospective study, it is difficult to control for potential confounding variables that are not included in the electronic medical record. The results of this study also demonstrated significantly shorter durations to diagnosis of all 3 conditions, indicating that surveillance bias may be present.

Conclusion

Patients with psoriasis may be at an increased risk for diverticulitis compared to patients without psoriasis, which could be due to the chronic inflammatory state induced by psoriasis. Therefore, it may be beneficial for clinicians to evaluate psoriasis patients for other risk factors for diverticulitis and subsequently provide counseling to these patients to minimize their risk for diverticulitis. Psoriasis patients do not appear to be at an increased risk for appendicitis or cholecystitis compared to controls; however, further research is needed for confirmation.

Psoriasis is a chronic skin condition affecting approximately 2% to 3% of the population.^1,2 Beyond cutaneous manifestations, psoriasis is a systemic inflammatory state that is associated with an increased risk for cardiovascular disease, including obesity,^3,4 type 2 diabetes mellitus,^5,6 hypertension,⁵ dyslipidemia,^3,7 metabolic syndrome,⁷ atherosclerosis,⁸ peripheral vascular disease,⁹ coronary artery calcification,¹⁰ myocardial infarction,^11-13 stroke,^9,14 and cardiac death.^15,16

Psoriasis also has been associated with inflammatory bowel disease (IBD), possibly because of similar autoimmune mechanisms in the pathogenesis of both diseases.^17,18 However, there is no literature regarding the risk for acute gastrointestinal pathologies such as appendicitis, cholecystitis, or diverticulitis in patients with psoriasis.

The primary objective of this study was to examine if patients with psoriasis are at increased risk for appendicitis, cholecystitis, or diverticulitis compared to the general population. The secondary objective was to determine if patients with severe psoriasis (ie, patients treated with phototherapy or systemic therapy) are at a higher risk for these conditions compared to patients with mild psoriasis.

Methods

Patients and Tools
A descriptive, population-based cohort study design with controls from a matched cohort was used to ascertain the effect of psoriasis status on patients’ risk for appendicitis, cholecystitis, or diverticulitis. Our cohort was selected using administrative data from Kaiser Permanente Southern California (KPSC) during the study period (January 1, 2004, through December 31, 2016).

Kaiser Permanente Southern California is a large integrated health maintenance organization that includes approximately 4 million patients as of December 31, 2016, and includes roughly 20% of the region’s population. The geographic area served extends from Bakersfield in the lower California Central Valley to San Diego on the border with Mexico. Membership demographics, socioeconomic status, and ethnicity composition are representative of California.

Patients were included if they had a diagnosis of psoriasis (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 696.1; International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] codes L40.0, L40.4, L40.8, or L40.9) for at least 3 visits between January 1, 2004, and December 31, 2016. Patients were not excluded if they also had a diagnosis of psoriatic arthritis (ICD-9-CM code 696.0; ICD-10-CM code L40.5x). Patients also must have been continuously enrolled for at least 1 year before and 1 year after the index date, which was defined as the date of the third psoriasis diagnosis.

Each patient with psoriasis was assigned to 1 of 2 cohorts: (1) severe psoriasis: patients who received UVB phototherapy, psoralen plus UVA phototherapy, methotrexate, acitretin, cyclosporine, apremilast, etanercept, adalimumab, infliximab, ustekinumab, efalizumab, alefacept, secukinumab, or ixekizumab during the study period; and (2) mild psoriasis: patients who had a diagnosis of psoriasis who did not receive one of these therapies during the study period.

Patients were excluded if they had a history of appendicitis, cholecystitis, or diverticulitis at any time before the index date. Only patients older than 18 years were included.

Patients with psoriasis were frequency matched (1:5) with healthy patients, also from the KPSC network. Individuals were matched by age, sex, and ethnicity.

Statistical Analysis
Baseline characteristics were described with means and SD for continuous variables as well as percentages for categorical variables. Chi-square tests for categorical variables and the Mann-Whitney U Test for continuous variables were used to compare the patients’ characteristics by psoriasis status. Cox proportional hazards regression models were used to examine the risk for appendicitis, cholecystitis, or diverticulitis among patients with and without psoriasis and among patients with mild and severe psoriasis. Proportionality assumption was validated using Pearson product moment correlation between the scaled Schoenfeld residuals and log transformed time for each covariate.

Results were presented as crude (unadjusted) hazard ratios (HRs) and adjusted HRs, where confounding factors (ie, age, sex, ethnicity, body mass index [BMI], alcohol use, smoking status, income, education, and membership length) were adjusted. All tests were performed with SAS EG 5.1 and R software. P<.05 was considered statistically significant. Results are reported with the 95% confidence interval (CI), when appropriate.

Results

A total of 1,690,214 KPSC patients were eligible for the study; 10,307 (0.6%) met diagnostic and inclusion criteria for the psoriasis cohort. Patients with psoriasis had a significantly higher mean BMI (29.9 vs 28.7; P<.0001) as well as higher mean rates of alcohol use (56% vs 53%; P<.0001) and smoking (47% vs 38%; P<.01) compared to controls. Psoriasis patients had a shorter average duration of membership within the Kaiser network (P=.0001) compared to controls.

A total of 7416 patients met criteria for mild psoriasis and 2891 patients met criteria for severe psoriasis (eTable). Patients with severe psoriasis were significantly younger and had significantly higher mean BMI compared to patients with mild psoriasis (P<.0001 and P=.0001, respectively). No significant difference in rates of alcohol or tobacco use was detected among patients with mild and severe psoriasis.

Diverticulitis
Patients with psoriasis had a significantly greater prevalence of diverticulitis compared to the control cohort (5.1% vs 4.2%; P<.0001). There was no difference in prevalence between the severe psoriasis group and the mild psoriasis group (P=.96), but the time to diagnosis of diverticulitis was shorter in the severe psoriasis group than in the mild psoriasis group (7.2 years vs 7.9 years; P<.0001). Psoriasis patients had an incidence rate of diverticulitis of 6.61 per 1000 patient-years compared to 5.38 per 1000 patient-years in the control group. Psoriasis conferred a higher risk for diverticulitis in both the crude and adjusted models (HR, 1.23; 95% CI, 1.11-1.35 [P<.001] and HR, 1.16; 95% CI, 1.05-1.29; [P<.01], respectively)(Table 3); however, when stratified by disease severity, only patients with severe psoriasis were found to be at higher risk (HR, 1.26; 95% CI, 1.15-1.61; P<.001 for the adjusted model).

Comment

The objective of this study was to examine the background risks for specific gastrointestinal pathologies in a large cohort of patients with psoriasis compared to the general population. After adjusting for measured confounders, patients with severe psoriasis had a significantly higher risk of diverticulitis compared to the general population. Although more patients with severe psoriasis developed appendicitis or cholecystitis, the difference was not significant.

The pathogenesis of diverticulosis and diverticulitis has been thought to be related to increased intracolonic pressure and decreased dietary fiber intake, leading to formation of diverticula in the colon.¹⁹ Our study did not correct for differences in diet between the 2 groups, making it a possible confounding variable. Studies evaluating dietary habits of psoriatic patients have found that adult males with psoriasis might consume less fiber compared to healthy patients,²⁰ and psoriasis patients also might consume less whole-grain fiber.²¹ Furthermore, fiber deficiency also might affect gut flora, causing low-grade chronic inflammation,¹⁸ which also has been supported by response to anti-inflammatory medications such as mesalazine.²² Given the autoimmune association between psoriasis and IBD, it is possible that psoriasis also might create an environment of chronic inflammation in the gut, predisposing patients with psoriasis to diverticulitis. However, further research is needed to better evaluate this possibility.

Our study also does not address any potential effects on outcomes of specific treatments for psoriasis. Brandl et al²³ found that patients on immunosuppressive therapy for autoimmune diseases had longer hospital and intensive care unit stays, higher rates of emergency operations, and higher mortality while hospitalized. Because our results suggest that patients with severe psoriasis, who are therefore more likely to require treatment with an immunomodulator, are at higher risk for diverticulitis, these patients also might be at risk for poorer outcomes.

There is no literature evaluating the relationship between psoriasis and appendicitis. Our study found a slightly lower incidence rate compared to the national trend (9.38 per 10,000 patient-years in the United States in 2008) in both healthy patients and psoriasis patients.²⁴ Of note, this statistic includes children, whereas our study did not, which might in part account for the lower rate. However, Cheluvappa et al²⁵ hypothesized a relationship between appendicitis and subsequent appendectomy at a young age and protection against IBD. They also found that the mechanism for protection involves downregulation of the helper T cell (T_H17) pathway,²⁵ which also has been found to play a role in psoriasis pathogenesis.^26,27 Although our results suggest that the risk for appendicitis is not increased for patients with psoriasis, further research might be able to determine if appendicitis and subsequent appendectomy also can offer protection against development of psoriasis.

We found that patients with severe psoriasis had a higher incidence rate of cholecystitis compared to patients with mild psoriasis. Egeberg et al²⁸ found an increased risk for cholelithiasis among patients with psoriasis, which may contribute to a higher rate of cholecystitis. Although both acute and chronic cholecystitis were incorporated in this study, a Russian study found that chronic cholecystitis may be a predictor of progression of psoriasis.²⁹ Moreover, patients with severe psoriasis had a shorter duration to diagnosis of cholecystitis than patients with mild psoriasis. It is possible that patients with severe psoriasis are in a state of greater chronic inflammation than those with mild psoriasis, and therefore, when combined with other risk factors for cholecystitis, may progress to disease more quickly. Alternatively, this finding could be treatment related, as there have been reported cases of cholecystitis related to etanercept use in patients treated for psoriasis and juvenile polyarticular rheumatoid arthritis.^30,31 The relationship is not yet well defined, however, and further research is necessary to evaluate this association.

Study Strengths
Key strengths of this study include the large sample size and diversity of the patient population. Kaiser Permanente Southern California membership generally is representative of the broader community, making our results fairly generalizable to populations with health insurance. Use of a matched control cohort allows the results to be more specific to the disease of interest, and the population-based design minimizes bias.

Study Limitations
This study has several limitations. Although the cohorts were categorized based on type of treatment received, exact therapies were not specified. As a retrospective study, it is difficult to control for potential confounding variables that are not included in the electronic medical record. The results of this study also demonstrated significantly shorter durations to diagnosis of all 3 conditions, indicating that surveillance bias may be present.

Conclusion

Patients with psoriasis may be at an increased risk for diverticulitis compared to patients without psoriasis, which could be due to the chronic inflammatory state induced by psoriasis. Therefore, it may be beneficial for clinicians to evaluate psoriasis patients for other risk factors for diverticulitis and subsequently provide counseling to these patients to minimize their risk for diverticulitis. Psoriasis patients do not appear to be at an increased risk for appendicitis or cholecystitis compared to controls; however, further research is needed for confirmation.

Psoriasis is a chronic skin condition affecting approximately 2% to 3% of the population.^1,2 Beyond cutaneous manifestations, psoriasis is a systemic inflammatory state that is associated with an increased risk for cardiovascular disease, including obesity,^3,4 type 2 diabetes mellitus,^5,6 hypertension,⁵ dyslipidemia,^3,7 metabolic syndrome,⁷ atherosclerosis,⁸ peripheral vascular disease,⁹ coronary artery calcification,¹⁰ myocardial infarction,^11-13 stroke,^9,14 and cardiac death.^15,16

Psoriasis also has been associated with inflammatory bowel disease (IBD), possibly because of similar autoimmune mechanisms in the pathogenesis of both diseases.^17,18 However, there is no literature regarding the risk for acute gastrointestinal pathologies such as appendicitis, cholecystitis, or diverticulitis in patients with psoriasis.

The primary objective of this study was to examine if patients with psoriasis are at increased risk for appendicitis, cholecystitis, or diverticulitis compared to the general population. The secondary objective was to determine if patients with severe psoriasis (ie, patients treated with phototherapy or systemic therapy) are at a higher risk for these conditions compared to patients with mild psoriasis.

Methods

Patients and Tools
A descriptive, population-based cohort study design with controls from a matched cohort was used to ascertain the effect of psoriasis status on patients’ risk for appendicitis, cholecystitis, or diverticulitis. Our cohort was selected using administrative data from Kaiser Permanente Southern California (KPSC) during the study period (January 1, 2004, through December 31, 2016).

Kaiser Permanente Southern California is a large integrated health maintenance organization that includes approximately 4 million patients as of December 31, 2016, and includes roughly 20% of the region’s population. The geographic area served extends from Bakersfield in the lower California Central Valley to San Diego on the border with Mexico. Membership demographics, socioeconomic status, and ethnicity composition are representative of California.

Patients were included if they had a diagnosis of psoriasis (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 696.1; International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] codes L40.0, L40.4, L40.8, or L40.9) for at least 3 visits between January 1, 2004, and December 31, 2016. Patients were not excluded if they also had a diagnosis of psoriatic arthritis (ICD-9-CM code 696.0; ICD-10-CM code L40.5x). Patients also must have been continuously enrolled for at least 1 year before and 1 year after the index date, which was defined as the date of the third psoriasis diagnosis.

Each patient with psoriasis was assigned to 1 of 2 cohorts: (1) severe psoriasis: patients who received UVB phototherapy, psoralen plus UVA phototherapy, methotrexate, acitretin, cyclosporine, apremilast, etanercept, adalimumab, infliximab, ustekinumab, efalizumab, alefacept, secukinumab, or ixekizumab during the study period; and (2) mild psoriasis: patients who had a diagnosis of psoriasis who did not receive one of these therapies during the study period.

Patients were excluded if they had a history of appendicitis, cholecystitis, or diverticulitis at any time before the index date. Only patients older than 18 years were included.

Patients with psoriasis were frequency matched (1:5) with healthy patients, also from the KPSC network. Individuals were matched by age, sex, and ethnicity.

Statistical Analysis
Baseline characteristics were described with means and SD for continuous variables as well as percentages for categorical variables. Chi-square tests for categorical variables and the Mann-Whitney U Test for continuous variables were used to compare the patients’ characteristics by psoriasis status. Cox proportional hazards regression models were used to examine the risk for appendicitis, cholecystitis, or diverticulitis among patients with and without psoriasis and among patients with mild and severe psoriasis. Proportionality assumption was validated using Pearson product moment correlation between the scaled Schoenfeld residuals and log transformed time for each covariate.

Results were presented as crude (unadjusted) hazard ratios (HRs) and adjusted HRs, where confounding factors (ie, age, sex, ethnicity, body mass index [BMI], alcohol use, smoking status, income, education, and membership length) were adjusted. All tests were performed with SAS EG 5.1 and R software. P<.05 was considered statistically significant. Results are reported with the 95% confidence interval (CI), when appropriate.

Results

A total of 1,690,214 KPSC patients were eligible for the study; 10,307 (0.6%) met diagnostic and inclusion criteria for the psoriasis cohort. Patients with psoriasis had a significantly higher mean BMI (29.9 vs 28.7; P<.0001) as well as higher mean rates of alcohol use (56% vs 53%; P<.0001) and smoking (47% vs 38%; P<.01) compared to controls. Psoriasis patients had a shorter average duration of membership within the Kaiser network (P=.0001) compared to controls.

A total of 7416 patients met criteria for mild psoriasis and 2891 patients met criteria for severe psoriasis (eTable). Patients with severe psoriasis were significantly younger and had significantly higher mean BMI compared to patients with mild psoriasis (P<.0001 and P=.0001, respectively). No significant difference in rates of alcohol or tobacco use was detected among patients with mild and severe psoriasis.

Diverticulitis
Patients with psoriasis had a significantly greater prevalence of diverticulitis compared to the control cohort (5.1% vs 4.2%; P<.0001). There was no difference in prevalence between the severe psoriasis group and the mild psoriasis group (P=.96), but the time to diagnosis of diverticulitis was shorter in the severe psoriasis group than in the mild psoriasis group (7.2 years vs 7.9 years; P<.0001). Psoriasis patients had an incidence rate of diverticulitis of 6.61 per 1000 patient-years compared to 5.38 per 1000 patient-years in the control group. Psoriasis conferred a higher risk for diverticulitis in both the crude and adjusted models (HR, 1.23; 95% CI, 1.11-1.35 [P<.001] and HR, 1.16; 95% CI, 1.05-1.29; [P<.01], respectively)(Table 3); however, when stratified by disease severity, only patients with severe psoriasis were found to be at higher risk (HR, 1.26; 95% CI, 1.15-1.61; P<.001 for the adjusted model).

Comment

The objective of this study was to examine the background risks for specific gastrointestinal pathologies in a large cohort of patients with psoriasis compared to the general population. After adjusting for measured confounders, patients with severe psoriasis had a significantly higher risk of diverticulitis compared to the general population. Although more patients with severe psoriasis developed appendicitis or cholecystitis, the difference was not significant.

The pathogenesis of diverticulosis and diverticulitis has been thought to be related to increased intracolonic pressure and decreased dietary fiber intake, leading to formation of diverticula in the colon.¹⁹ Our study did not correct for differences in diet between the 2 groups, making it a possible confounding variable. Studies evaluating dietary habits of psoriatic patients have found that adult males with psoriasis might consume less fiber compared to healthy patients,²⁰ and psoriasis patients also might consume less whole-grain fiber.²¹ Furthermore, fiber deficiency also might affect gut flora, causing low-grade chronic inflammation,¹⁸ which also has been supported by response to anti-inflammatory medications such as mesalazine.²² Given the autoimmune association between psoriasis and IBD, it is possible that psoriasis also might create an environment of chronic inflammation in the gut, predisposing patients with psoriasis to diverticulitis. However, further research is needed to better evaluate this possibility.

Our study also does not address any potential effects on outcomes of specific treatments for psoriasis. Brandl et al²³ found that patients on immunosuppressive therapy for autoimmune diseases had longer hospital and intensive care unit stays, higher rates of emergency operations, and higher mortality while hospitalized. Because our results suggest that patients with severe psoriasis, who are therefore more likely to require treatment with an immunomodulator, are at higher risk for diverticulitis, these patients also might be at risk for poorer outcomes.

There is no literature evaluating the relationship between psoriasis and appendicitis. Our study found a slightly lower incidence rate compared to the national trend (9.38 per 10,000 patient-years in the United States in 2008) in both healthy patients and psoriasis patients.²⁴ Of note, this statistic includes children, whereas our study did not, which might in part account for the lower rate. However, Cheluvappa et al²⁵ hypothesized a relationship between appendicitis and subsequent appendectomy at a young age and protection against IBD. They also found that the mechanism for protection involves downregulation of the helper T cell (T_H17) pathway,²⁵ which also has been found to play a role in psoriasis pathogenesis.^26,27 Although our results suggest that the risk for appendicitis is not increased for patients with psoriasis, further research might be able to determine if appendicitis and subsequent appendectomy also can offer protection against development of psoriasis.

We found that patients with severe psoriasis had a higher incidence rate of cholecystitis compared to patients with mild psoriasis. Egeberg et al²⁸ found an increased risk for cholelithiasis among patients with psoriasis, which may contribute to a higher rate of cholecystitis. Although both acute and chronic cholecystitis were incorporated in this study, a Russian study found that chronic cholecystitis may be a predictor of progression of psoriasis.²⁹ Moreover, patients with severe psoriasis had a shorter duration to diagnosis of cholecystitis than patients with mild psoriasis. It is possible that patients with severe psoriasis are in a state of greater chronic inflammation than those with mild psoriasis, and therefore, when combined with other risk factors for cholecystitis, may progress to disease more quickly. Alternatively, this finding could be treatment related, as there have been reported cases of cholecystitis related to etanercept use in patients treated for psoriasis and juvenile polyarticular rheumatoid arthritis.^30,31 The relationship is not yet well defined, however, and further research is necessary to evaluate this association.

Study Strengths
Key strengths of this study include the large sample size and diversity of the patient population. Kaiser Permanente Southern California membership generally is representative of the broader community, making our results fairly generalizable to populations with health insurance. Use of a matched control cohort allows the results to be more specific to the disease of interest, and the population-based design minimizes bias.

Study Limitations
This study has several limitations. Although the cohorts were categorized based on type of treatment received, exact therapies were not specified. As a retrospective study, it is difficult to control for potential confounding variables that are not included in the electronic medical record. The results of this study also demonstrated significantly shorter durations to diagnosis of all 3 conditions, indicating that surveillance bias may be present.

Conclusion

Patients with psoriasis may be at an increased risk for diverticulitis compared to patients without psoriasis, which could be due to the chronic inflammatory state induced by psoriasis. Therefore, it may be beneficial for clinicians to evaluate psoriasis patients for other risk factors for diverticulitis and subsequently provide counseling to these patients to minimize their risk for diverticulitis. Psoriasis patients do not appear to be at an increased risk for appendicitis or cholecystitis compared to controls; however, further research is needed for confirmation.

To the Editor:

In 1995, one of the authors (A.G.L.) reported the case of a 14-year-old boy who was diagnosed with pseudotumor cerebri following treatment with isotretinoin and tetracycline, both of which were implicated in the development of elevated intracranial pressure (ICP). The patient subsequently underwent optic nerve sheath fenestration for decompression due to progressive deterioration of the visual field despite discontinuation of both drugs.¹

This patient recently returned to our office 28 years after his initial presentation with a recurrence of similar symptoms. He was subsequently diagnosed with elevated ICP after a single dose of doxycycline. His vision was 20/20 with correction for distance. Pupil size and extraocular motility were within normal limits. Physical examination was normal, and a dilated fundus examination showed a Frisen stage 1 disc edema in the right eye and a Frisen stage 3 disc edema in the left eye at presentation. The visual field showed enlarged blind spots in both eyes consistent with papilledema. Optical coherence tomography for optic nerve was 93 µm in the right eye and 124 µm in the left eye compared to earlier measures of 66 and 68 µm in the right and left eyes, respectively, indicating pseudonormalization of the parameters (disc edema in the setting of prior optic atrophy). In the setting of optic atrophy, when the nerve develops any swelling the thickness measured on optical coherence tomography may reach normal values, which are in fact abnormal and elevated in this case. Magnetic resonance imaging and magnetic resonance venography were within normal limits. Cerebrospinal fluid opening pressure was 26 cm of water, and analysis revealed high levels of West Nile virus antibodies (IgM and IgG), suggesting a recent viral infection. In addition to an established predisposition to develop elevated ICP on tetracycline antibiotics, this patient also had the precipitating factor of recent viral infection contributing to his raised ICP. Prior to his most recent presentation, his condition was stable with evidence of mild optic atrophy in both eyes and stable visual fields.

Various case reports have linked the use of tetracycline antibiotics to increased ICP. Gardner et al² reported a case of fraternal twins who developed elevated ICP while on tetracycline for acne, suggesting a possible genetic susceptibility. In one nested case-control study, it was found that the relative risk (RR) of developing elevated ICP with tetracycline antibiotics was increased (RR=2.68 [95% CI, 0.89-8.11] for 15 days of current use; RR=3.64 [95% CI, 1.67-7.91] for 30 days of current use).³ Retrospective studies have demonstrated that 9% of the population (N=207) had prior treatment with tetracylines in a cohort of patients diagnosed with elevated ICP.⁴

In this group of drugs, minocycline has been closely associated with development of elevated ICP. One retrospective study showed that 75% of patients (9/12) with minocycline-associated ICP developed symptoms of elevated ICP within 8 weeks of starting therapy; however, half of the patients included in the study were obese. The inclusion of obese patients in this study is a confounding variable because idiopathic intracranial hypertension (IIH) is a disease that predominantly affects obese young females. The diagnosis of IIH, however, should be considered a diagnosis of exclusion, and it is uncommon in thin elderly or male patients.⁵

Tetracyclines have a half-life of 6 to 11 hours, and usually the elevated ICP decreases once the offending agent is discontinued, though papilledema could take months to resolve.

We describe an inadvertent rechallenge with a tetracycline antibiotic 28 years after presumed minocycline-induced IIH of childhood. Clinicians should be aware that any agent in the tetracycline family of antibiotics may cause increased ICP and that the predisposition to medication-induced IIH may be a lifelong risk.

To the Editor:

In 1995, one of the authors (A.G.L.) reported the case of a 14-year-old boy who was diagnosed with pseudotumor cerebri following treatment with isotretinoin and tetracycline, both of which were implicated in the development of elevated intracranial pressure (ICP). The patient subsequently underwent optic nerve sheath fenestration for decompression due to progressive deterioration of the visual field despite discontinuation of both drugs.¹

This patient recently returned to our office 28 years after his initial presentation with a recurrence of similar symptoms. He was subsequently diagnosed with elevated ICP after a single dose of doxycycline. His vision was 20/20 with correction for distance. Pupil size and extraocular motility were within normal limits. Physical examination was normal, and a dilated fundus examination showed a Frisen stage 1 disc edema in the right eye and a Frisen stage 3 disc edema in the left eye at presentation. The visual field showed enlarged blind spots in both eyes consistent with papilledema. Optical coherence tomography for optic nerve was 93 µm in the right eye and 124 µm in the left eye compared to earlier measures of 66 and 68 µm in the right and left eyes, respectively, indicating pseudonormalization of the parameters (disc edema in the setting of prior optic atrophy). In the setting of optic atrophy, when the nerve develops any swelling the thickness measured on optical coherence tomography may reach normal values, which are in fact abnormal and elevated in this case. Magnetic resonance imaging and magnetic resonance venography were within normal limits. Cerebrospinal fluid opening pressure was 26 cm of water, and analysis revealed high levels of West Nile virus antibodies (IgM and IgG), suggesting a recent viral infection. In addition to an established predisposition to develop elevated ICP on tetracycline antibiotics, this patient also had the precipitating factor of recent viral infection contributing to his raised ICP. Prior to his most recent presentation, his condition was stable with evidence of mild optic atrophy in both eyes and stable visual fields.

Various case reports have linked the use of tetracycline antibiotics to increased ICP. Gardner et al² reported a case of fraternal twins who developed elevated ICP while on tetracycline for acne, suggesting a possible genetic susceptibility. In one nested case-control study, it was found that the relative risk (RR) of developing elevated ICP with tetracycline antibiotics was increased (RR=2.68 [95% CI, 0.89-8.11] for 15 days of current use; RR=3.64 [95% CI, 1.67-7.91] for 30 days of current use).³ Retrospective studies have demonstrated that 9% of the population (N=207) had prior treatment with tetracylines in a cohort of patients diagnosed with elevated ICP.⁴

In this group of drugs, minocycline has been closely associated with development of elevated ICP. One retrospective study showed that 75% of patients (9/12) with minocycline-associated ICP developed symptoms of elevated ICP within 8 weeks of starting therapy; however, half of the patients included in the study were obese. The inclusion of obese patients in this study is a confounding variable because idiopathic intracranial hypertension (IIH) is a disease that predominantly affects obese young females. The diagnosis of IIH, however, should be considered a diagnosis of exclusion, and it is uncommon in thin elderly or male patients.⁵

Tetracyclines have a half-life of 6 to 11 hours, and usually the elevated ICP decreases once the offending agent is discontinued, though papilledema could take months to resolve.

We describe an inadvertent rechallenge with a tetracycline antibiotic 28 years after presumed minocycline-induced IIH of childhood. Clinicians should be aware that any agent in the tetracycline family of antibiotics may cause increased ICP and that the predisposition to medication-induced IIH may be a lifelong risk.

To the Editor:

In 1995, one of the authors (A.G.L.) reported the case of a 14-year-old boy who was diagnosed with pseudotumor cerebri following treatment with isotretinoin and tetracycline, both of which were implicated in the development of elevated intracranial pressure (ICP). The patient subsequently underwent optic nerve sheath fenestration for decompression due to progressive deterioration of the visual field despite discontinuation of both drugs.¹

This patient recently returned to our office 28 years after his initial presentation with a recurrence of similar symptoms. He was subsequently diagnosed with elevated ICP after a single dose of doxycycline. His vision was 20/20 with correction for distance. Pupil size and extraocular motility were within normal limits. Physical examination was normal, and a dilated fundus examination showed a Frisen stage 1 disc edema in the right eye and a Frisen stage 3 disc edema in the left eye at presentation. The visual field showed enlarged blind spots in both eyes consistent with papilledema. Optical coherence tomography for optic nerve was 93 µm in the right eye and 124 µm in the left eye compared to earlier measures of 66 and 68 µm in the right and left eyes, respectively, indicating pseudonormalization of the parameters (disc edema in the setting of prior optic atrophy). In the setting of optic atrophy, when the nerve develops any swelling the thickness measured on optical coherence tomography may reach normal values, which are in fact abnormal and elevated in this case. Magnetic resonance imaging and magnetic resonance venography were within normal limits. Cerebrospinal fluid opening pressure was 26 cm of water, and analysis revealed high levels of West Nile virus antibodies (IgM and IgG), suggesting a recent viral infection. In addition to an established predisposition to develop elevated ICP on tetracycline antibiotics, this patient also had the precipitating factor of recent viral infection contributing to his raised ICP. Prior to his most recent presentation, his condition was stable with evidence of mild optic atrophy in both eyes and stable visual fields.

Various case reports have linked the use of tetracycline antibiotics to increased ICP. Gardner et al² reported a case of fraternal twins who developed elevated ICP while on tetracycline for acne, suggesting a possible genetic susceptibility. In one nested case-control study, it was found that the relative risk (RR) of developing elevated ICP with tetracycline antibiotics was increased (RR=2.68 [95% CI, 0.89-8.11] for 15 days of current use; RR=3.64 [95% CI, 1.67-7.91] for 30 days of current use).³ Retrospective studies have demonstrated that 9% of the population (N=207) had prior treatment with tetracylines in a cohort of patients diagnosed with elevated ICP.⁴

In this group of drugs, minocycline has been closely associated with development of elevated ICP. One retrospective study showed that 75% of patients (9/12) with minocycline-associated ICP developed symptoms of elevated ICP within 8 weeks of starting therapy; however, half of the patients included in the study were obese. The inclusion of obese patients in this study is a confounding variable because idiopathic intracranial hypertension (IIH) is a disease that predominantly affects obese young females. The diagnosis of IIH, however, should be considered a diagnosis of exclusion, and it is uncommon in thin elderly or male patients.⁵

Tetracyclines have a half-life of 6 to 11 hours, and usually the elevated ICP decreases once the offending agent is discontinued, though papilledema could take months to resolve.

We describe an inadvertent rechallenge with a tetracycline antibiotic 28 years after presumed minocycline-induced IIH of childhood. Clinicians should be aware that any agent in the tetracycline family of antibiotics may cause increased ICP and that the predisposition to medication-induced IIH may be a lifelong risk.