Wound complications after pre- or post-operative radiation for soft tissue sarcomas are well established.¹ The ability to predict who will have a wound complication remains difficult. Some studies have looked at risk factors such as smoking, and the preoperative nutritional status of patients has been identified as a risk factor for wound complication in patients with elective orthopedic surgical procedures.² One validated method of measuring preoperative nutritional status in patients with gastrointestinal malignant tumors has been with Onodera’s Prognostic Nutritional Index (OPNI). It uses the patient’s preoperative albumin (g/dL) and absolute lymphocyte values (per mm³). The prognostic value of the OPNI has been demonstrated in patients with colorectal, esophageal, and gastric cancers, and has been shown to be prognostic for postoperative wound healing and overall prognosis.^3-5 In this study, we investigate the significance of preoperative nutritional status, measured by OPNI, as a predictor of wound complications in patients treated with pre- or postoperative radiation for soft tissue sarcoma.

Methods

After receiving Institutional Review Board approval for the study, we conducted a retrospective review of consecutive patients treated during July 2012-April 2016 for a soft tissue sarcoma by the orthopedic oncology division at Cooper University Hospital in Camden, New Jersey. Inclusion criteria were patients with biopsy-proven soft tissue sarcoma, who were older than 18 years, had received pre- or postoperative radiation, and who had a recorded preoperative albumin and total lymphocyte count. A minimum follow-up of 3 months was required to assess for postoperative wound complications. Exclusion criteria included patients who had a bone sarcoma, had not received radiation therapy, or had a missing preoperative albumin or total lymphocyte count.

All of the surgeries were performed by 2 fellowshiptrained orthopedic oncologists. Patients received either pre- or postoperative radiation therapy by multiple radiation oncologists.

The OPNI was calculated based on the published formula OPNI = (10*albumin level [g/dL]) + (0.005*total lymphocyte count [per mm³]). The albumin level and total lymphocyte counts closest to the index operation were chosen.

Demographic information including gender, age at diagnosis, height, and weight were recorded. Data related to the patients’ pathologic diagnosis, stage at presentation, radiation therapy, and surgical resection were collected. A minor wound complication was defined as a wound problem that did not require operative intervention. Major wound complication was defined as a complication requiring operative intervention with or without flap reconstruction. Wound complications occurring within the 3-month postoperative period were considered.

Univariate and multiple variable analysis was performed. A P value <.05 was considered significant. A receiver operating curve as well as recursive partitioning was performed for OPNI and age to determine the best cut-off point to use in the analysis. The Sobel test was used to evaluate mediation. All statistical analysis was performed using SAS v9.4 and JMP10. (SAS Institute, Cary, NC).

Results

In all, 44 patients (28 men, 16 women) were included in the study. Their mean age was 61.2 years (range, 19-94). The average size of the tumors was 8.5 cm in greatest dimension (range, 1.2-27.4 cm), and all of the patients had nonmetastatic disease at the time of surgical resection; 37 patients had R0 resections, and 7 patients had a positive margin from an outside hospital, but obtained R0 resections on a subsequent resection (Table 1 and Table 2).

In all, 30 patients received preoperative radiation, 14 patients received postoperative radiation, 32 patients received external beam radiation, 8 received Cyberknife treatment, and information for 4 patients was not unavailable. Mean preoperative external beam radiation and Cyberknife dose was 4,931 Gy and 3,750 Gy, respectively. Mean postoperative external beam and Cyberknife radiation dose was 6,077 Gy and 4,000 Gy, respectively. When evaluating radiation dose delivered between those who had wound complications and those who did not, there was no significant difference (Table 3).

Discussion

Wound complications after pre- and postoperative radiation for soft tissue sarcomas are well known. The best study to date to demonstrate that relationship was a randomized controlled trial performed in Canada, which showed that preoperative radiation resulted in 37% wound complications, compared with 17% for postoperative radiation.⁶ In that study, of the wound complications in both radiation types, more than 50%-60% required a secondary surgical procedure, designating it as a major wound complication. Other variables that have been shown to contribute to wound complications include being older than 40 years and/or having large tumors, diabetes, peripheral vascular disease, and begin a smoker.^7-10

In our study, we applied OPNI to orthopedic oncology and showed that the patient’s age and preoperative nutritional status were significant predictors of developing a wound complication. An OPNI of <45.4 increased the chance of a wound complication by 7.5 times. Being older than 73 years increased the risk of a wound complication by 6.8 times. Most of these wound complications were major and required surgical intervention.

In general surgical oncology, the evaluation of nutritional status has had a significant impact on the care of patients, especially for those patients undergoing gastrointestinal surgery. The OPNI was initially designed to assess the nutritional and immunological statuses of patients undergoing gastrointestinal surgery.¹¹ Preoperative OPNI has been shown to be a good predictor of postoperative complications and survival in patients with colorectal cancer, malignant mesothelioma, hepatocellular carcinoma and in patients who undergo total gastrectomy.^12-15 Chen and colleagues evaluated the significance of OPNI in patients with colorectal cancer. They found an optimal cut-off value of 45. An OPNI value <45 has a sensitivity and specificity of 85% and 69%, respectively, in predicting 5-year overall survival.¹⁶ Hong and colleagues noted that an OPNI cut-off value of 52.6 as a predictor of overall survival.¹⁷

Poor preoperative nutritional status has been shown to have a negative impact on wound healing. In patients who underwent emergency laparotomy, a low OPNI had significantly higher rates of wound dehiscence and infection.¹⁸ This happens because protein deficiency leads to decreased wound tensile strength, decreased T-cell function, decreased phagocytic activity, which ultimately diminish the patient’s ability to heal and defend against wound infections.^19-21

In soft tissue sarcoma patients, poor preoperative nutritional status is further compromised by radiation therapy to the wound. Gu and colleagues showed that radiation to wounds in mice showed early inhibition of the inflammatory phase, injury and inhibition of fibroblasts, and collagen formation, and then prolonged re-epithelialization.²² This “double hit” with radiation onto host tissue that is already nutritionally compromised could be an important cause of why wound complications occur at such high rates in our soft tissue sarcoma patients.

There are several limitations to this study. First, the study has a small sample size, which was a direct result of the number of patients who were excluded because an OPNI value could not be calculated for them. Second, we could not determine if the OPNI was more valuable in patients who underwent pre- or postoperative radiation. This study did not look at other nutritional indices such as prealbumin and vitamin levels. Third, the radiation was provided by different providers, so technique was variable, but the patients received nearly equivalent doses and variability in technique is likely limited. Fourth, we were not able to meaningfully analyze the role of chemotherapy in this patient population because there was a significant heterogeneity of patients receiving pre- and postoperative chemotherapy.

Our findings strongly suggest that a preoperative OPNI of <45.4 and being older than 73 years are strong predictors of patients who will experience a wound complication after radiation therapy for soft tissue sarcomas. This study has led us to start measuring preoperative albumin levels and assess complete metabolic panels. Our goal is to identify patients who are at high risk of wound complication and perform interventions to improve nutrition, then to study whether the interventions help lower the rates of wound complications.

Wound complications after pre- or post-operative radiation for soft tissue sarcomas are well established.¹ The ability to predict who will have a wound complication remains difficult. Some studies have looked at risk factors such as smoking, and the preoperative nutritional status of patients has been identified as a risk factor for wound complication in patients with elective orthopedic surgical procedures.² One validated method of measuring preoperative nutritional status in patients with gastrointestinal malignant tumors has been with Onodera’s Prognostic Nutritional Index (OPNI). It uses the patient’s preoperative albumin (g/dL) and absolute lymphocyte values (per mm³). The prognostic value of the OPNI has been demonstrated in patients with colorectal, esophageal, and gastric cancers, and has been shown to be prognostic for postoperative wound healing and overall prognosis.^3-5 In this study, we investigate the significance of preoperative nutritional status, measured by OPNI, as a predictor of wound complications in patients treated with pre- or postoperative radiation for soft tissue sarcoma.

Methods

After receiving Institutional Review Board approval for the study, we conducted a retrospective review of consecutive patients treated during July 2012-April 2016 for a soft tissue sarcoma by the orthopedic oncology division at Cooper University Hospital in Camden, New Jersey. Inclusion criteria were patients with biopsy-proven soft tissue sarcoma, who were older than 18 years, had received pre- or postoperative radiation, and who had a recorded preoperative albumin and total lymphocyte count. A minimum follow-up of 3 months was required to assess for postoperative wound complications. Exclusion criteria included patients who had a bone sarcoma, had not received radiation therapy, or had a missing preoperative albumin or total lymphocyte count.

All of the surgeries were performed by 2 fellowshiptrained orthopedic oncologists. Patients received either pre- or postoperative radiation therapy by multiple radiation oncologists.

The OPNI was calculated based on the published formula OPNI = (10*albumin level [g/dL]) + (0.005*total lymphocyte count [per mm³]). The albumin level and total lymphocyte counts closest to the index operation were chosen.

Demographic information including gender, age at diagnosis, height, and weight were recorded. Data related to the patients’ pathologic diagnosis, stage at presentation, radiation therapy, and surgical resection were collected. A minor wound complication was defined as a wound problem that did not require operative intervention. Major wound complication was defined as a complication requiring operative intervention with or without flap reconstruction. Wound complications occurring within the 3-month postoperative period were considered.

Univariate and multiple variable analysis was performed. A P value <.05 was considered significant. A receiver operating curve as well as recursive partitioning was performed for OPNI and age to determine the best cut-off point to use in the analysis. The Sobel test was used to evaluate mediation. All statistical analysis was performed using SAS v9.4 and JMP10. (SAS Institute, Cary, NC).

Results

In all, 44 patients (28 men, 16 women) were included in the study. Their mean age was 61.2 years (range, 19-94). The average size of the tumors was 8.5 cm in greatest dimension (range, 1.2-27.4 cm), and all of the patients had nonmetastatic disease at the time of surgical resection; 37 patients had R0 resections, and 7 patients had a positive margin from an outside hospital, but obtained R0 resections on a subsequent resection (Table 1 and Table 2).

In all, 30 patients received preoperative radiation, 14 patients received postoperative radiation, 32 patients received external beam radiation, 8 received Cyberknife treatment, and information for 4 patients was not unavailable. Mean preoperative external beam radiation and Cyberknife dose was 4,931 Gy and 3,750 Gy, respectively. Mean postoperative external beam and Cyberknife radiation dose was 6,077 Gy and 4,000 Gy, respectively. When evaluating radiation dose delivered between those who had wound complications and those who did not, there was no significant difference (Table 3).

Discussion

Wound complications after pre- and postoperative radiation for soft tissue sarcomas are well known. The best study to date to demonstrate that relationship was a randomized controlled trial performed in Canada, which showed that preoperative radiation resulted in 37% wound complications, compared with 17% for postoperative radiation.⁶ In that study, of the wound complications in both radiation types, more than 50%-60% required a secondary surgical procedure, designating it as a major wound complication. Other variables that have been shown to contribute to wound complications include being older than 40 years and/or having large tumors, diabetes, peripheral vascular disease, and begin a smoker.^7-10

In our study, we applied OPNI to orthopedic oncology and showed that the patient’s age and preoperative nutritional status were significant predictors of developing a wound complication. An OPNI of <45.4 increased the chance of a wound complication by 7.5 times. Being older than 73 years increased the risk of a wound complication by 6.8 times. Most of these wound complications were major and required surgical intervention.

In general surgical oncology, the evaluation of nutritional status has had a significant impact on the care of patients, especially for those patients undergoing gastrointestinal surgery. The OPNI was initially designed to assess the nutritional and immunological statuses of patients undergoing gastrointestinal surgery.¹¹ Preoperative OPNI has been shown to be a good predictor of postoperative complications and survival in patients with colorectal cancer, malignant mesothelioma, hepatocellular carcinoma and in patients who undergo total gastrectomy.^12-15 Chen and colleagues evaluated the significance of OPNI in patients with colorectal cancer. They found an optimal cut-off value of 45. An OPNI value <45 has a sensitivity and specificity of 85% and 69%, respectively, in predicting 5-year overall survival.¹⁶ Hong and colleagues noted that an OPNI cut-off value of 52.6 as a predictor of overall survival.¹⁷

Poor preoperative nutritional status has been shown to have a negative impact on wound healing. In patients who underwent emergency laparotomy, a low OPNI had significantly higher rates of wound dehiscence and infection.¹⁸ This happens because protein deficiency leads to decreased wound tensile strength, decreased T-cell function, decreased phagocytic activity, which ultimately diminish the patient’s ability to heal and defend against wound infections.^19-21

In soft tissue sarcoma patients, poor preoperative nutritional status is further compromised by radiation therapy to the wound. Gu and colleagues showed that radiation to wounds in mice showed early inhibition of the inflammatory phase, injury and inhibition of fibroblasts, and collagen formation, and then prolonged re-epithelialization.²² This “double hit” with radiation onto host tissue that is already nutritionally compromised could be an important cause of why wound complications occur at such high rates in our soft tissue sarcoma patients.

There are several limitations to this study. First, the study has a small sample size, which was a direct result of the number of patients who were excluded because an OPNI value could not be calculated for them. Second, we could not determine if the OPNI was more valuable in patients who underwent pre- or postoperative radiation. This study did not look at other nutritional indices such as prealbumin and vitamin levels. Third, the radiation was provided by different providers, so technique was variable, but the patients received nearly equivalent doses and variability in technique is likely limited. Fourth, we were not able to meaningfully analyze the role of chemotherapy in this patient population because there was a significant heterogeneity of patients receiving pre- and postoperative chemotherapy.

Our findings strongly suggest that a preoperative OPNI of <45.4 and being older than 73 years are strong predictors of patients who will experience a wound complication after radiation therapy for soft tissue sarcomas. This study has led us to start measuring preoperative albumin levels and assess complete metabolic panels. Our goal is to identify patients who are at high risk of wound complication and perform interventions to improve nutrition, then to study whether the interventions help lower the rates of wound complications.

Wound complications after pre- or post-operative radiation for soft tissue sarcomas are well established.¹ The ability to predict who will have a wound complication remains difficult. Some studies have looked at risk factors such as smoking, and the preoperative nutritional status of patients has been identified as a risk factor for wound complication in patients with elective orthopedic surgical procedures.² One validated method of measuring preoperative nutritional status in patients with gastrointestinal malignant tumors has been with Onodera’s Prognostic Nutritional Index (OPNI). It uses the patient’s preoperative albumin (g/dL) and absolute lymphocyte values (per mm³). The prognostic value of the OPNI has been demonstrated in patients with colorectal, esophageal, and gastric cancers, and has been shown to be prognostic for postoperative wound healing and overall prognosis.^3-5 In this study, we investigate the significance of preoperative nutritional status, measured by OPNI, as a predictor of wound complications in patients treated with pre- or postoperative radiation for soft tissue sarcoma.

Methods

After receiving Institutional Review Board approval for the study, we conducted a retrospective review of consecutive patients treated during July 2012-April 2016 for a soft tissue sarcoma by the orthopedic oncology division at Cooper University Hospital in Camden, New Jersey. Inclusion criteria were patients with biopsy-proven soft tissue sarcoma, who were older than 18 years, had received pre- or postoperative radiation, and who had a recorded preoperative albumin and total lymphocyte count. A minimum follow-up of 3 months was required to assess for postoperative wound complications. Exclusion criteria included patients who had a bone sarcoma, had not received radiation therapy, or had a missing preoperative albumin or total lymphocyte count.

All of the surgeries were performed by 2 fellowshiptrained orthopedic oncologists. Patients received either pre- or postoperative radiation therapy by multiple radiation oncologists.

The OPNI was calculated based on the published formula OPNI = (10*albumin level [g/dL]) + (0.005*total lymphocyte count [per mm³]). The albumin level and total lymphocyte counts closest to the index operation were chosen.

Demographic information including gender, age at diagnosis, height, and weight were recorded. Data related to the patients’ pathologic diagnosis, stage at presentation, radiation therapy, and surgical resection were collected. A minor wound complication was defined as a wound problem that did not require operative intervention. Major wound complication was defined as a complication requiring operative intervention with or without flap reconstruction. Wound complications occurring within the 3-month postoperative period were considered.

Univariate and multiple variable analysis was performed. A P value <.05 was considered significant. A receiver operating curve as well as recursive partitioning was performed for OPNI and age to determine the best cut-off point to use in the analysis. The Sobel test was used to evaluate mediation. All statistical analysis was performed using SAS v9.4 and JMP10. (SAS Institute, Cary, NC).

Results

In all, 44 patients (28 men, 16 women) were included in the study. Their mean age was 61.2 years (range, 19-94). The average size of the tumors was 8.5 cm in greatest dimension (range, 1.2-27.4 cm), and all of the patients had nonmetastatic disease at the time of surgical resection; 37 patients had R0 resections, and 7 patients had a positive margin from an outside hospital, but obtained R0 resections on a subsequent resection (Table 1 and Table 2).

In all, 30 patients received preoperative radiation, 14 patients received postoperative radiation, 32 patients received external beam radiation, 8 received Cyberknife treatment, and information for 4 patients was not unavailable. Mean preoperative external beam radiation and Cyberknife dose was 4,931 Gy and 3,750 Gy, respectively. Mean postoperative external beam and Cyberknife radiation dose was 6,077 Gy and 4,000 Gy, respectively. When evaluating radiation dose delivered between those who had wound complications and those who did not, there was no significant difference (Table 3).

Discussion

Wound complications after pre- and postoperative radiation for soft tissue sarcomas are well known. The best study to date to demonstrate that relationship was a randomized controlled trial performed in Canada, which showed that preoperative radiation resulted in 37% wound complications, compared with 17% for postoperative radiation.⁶ In that study, of the wound complications in both radiation types, more than 50%-60% required a secondary surgical procedure, designating it as a major wound complication. Other variables that have been shown to contribute to wound complications include being older than 40 years and/or having large tumors, diabetes, peripheral vascular disease, and begin a smoker.^7-10

In our study, we applied OPNI to orthopedic oncology and showed that the patient’s age and preoperative nutritional status were significant predictors of developing a wound complication. An OPNI of <45.4 increased the chance of a wound complication by 7.5 times. Being older than 73 years increased the risk of a wound complication by 6.8 times. Most of these wound complications were major and required surgical intervention.

In general surgical oncology, the evaluation of nutritional status has had a significant impact on the care of patients, especially for those patients undergoing gastrointestinal surgery. The OPNI was initially designed to assess the nutritional and immunological statuses of patients undergoing gastrointestinal surgery.¹¹ Preoperative OPNI has been shown to be a good predictor of postoperative complications and survival in patients with colorectal cancer, malignant mesothelioma, hepatocellular carcinoma and in patients who undergo total gastrectomy.^12-15 Chen and colleagues evaluated the significance of OPNI in patients with colorectal cancer. They found an optimal cut-off value of 45. An OPNI value <45 has a sensitivity and specificity of 85% and 69%, respectively, in predicting 5-year overall survival.¹⁶ Hong and colleagues noted that an OPNI cut-off value of 52.6 as a predictor of overall survival.¹⁷

Poor preoperative nutritional status has been shown to have a negative impact on wound healing. In patients who underwent emergency laparotomy, a low OPNI had significantly higher rates of wound dehiscence and infection.¹⁸ This happens because protein deficiency leads to decreased wound tensile strength, decreased T-cell function, decreased phagocytic activity, which ultimately diminish the patient’s ability to heal and defend against wound infections.^19-21

In soft tissue sarcoma patients, poor preoperative nutritional status is further compromised by radiation therapy to the wound. Gu and colleagues showed that radiation to wounds in mice showed early inhibition of the inflammatory phase, injury and inhibition of fibroblasts, and collagen formation, and then prolonged re-epithelialization.²² This “double hit” with radiation onto host tissue that is already nutritionally compromised could be an important cause of why wound complications occur at such high rates in our soft tissue sarcoma patients.

There are several limitations to this study. First, the study has a small sample size, which was a direct result of the number of patients who were excluded because an OPNI value could not be calculated for them. Second, we could not determine if the OPNI was more valuable in patients who underwent pre- or postoperative radiation. This study did not look at other nutritional indices such as prealbumin and vitamin levels. Third, the radiation was provided by different providers, so technique was variable, but the patients received nearly equivalent doses and variability in technique is likely limited. Fourth, we were not able to meaningfully analyze the role of chemotherapy in this patient population because there was a significant heterogeneity of patients receiving pre- and postoperative chemotherapy.

Our findings strongly suggest that a preoperative OPNI of <45.4 and being older than 73 years are strong predictors of patients who will experience a wound complication after radiation therapy for soft tissue sarcomas. This study has led us to start measuring preoperative albumin levels and assess complete metabolic panels. Our goal is to identify patients who are at high risk of wound complication and perform interventions to improve nutrition, then to study whether the interventions help lower the rates of wound complications.

Image by Tom Ellenberger

Preclinical research suggests the TOX protein is an oncogenic driver of T-cell acute lymphoblastic leukemia (T-ALL).

Results indicate that TOX may be expressed in as many as 95% of human T-ALL cases, and the protein is required for the cancer’s growth and persistence.

“A major role for TOX in T-ALL is to elicit defects in DNA repair, leading to genetic changes that drive normal cells into cancer,” said study author David Langenau, PhD, of Massachusetts General Hospital in Boston.

“TOX then continues to be expressed within leukemic cells and is required for continued tumor growth. That means that, if we can successfully target TOX with small molecules in the future, the 95% of T-ALL patients whose tumors express TOX would have new treatment options for this aggressive leukemia.”

Dr Langenau and his colleagues described this new role for TOX in Cancer Discovery.

The team noted that T-ALL has several molecular subtypes, many of which are driven by common oncogenes such as MYC and NOTCH. However, evidence has suggested the cancer’s initiation is likely driven by aberrations in DNA repair.

To identify genes that might help drive T-ALL, the researchers performed a transgenic screen in zebrafish.

The team found that TOX collaborates with known oncogene pathways to transform T-cell precursors into leukemia cells by altering DNA repair and then expanding the population of transformed cells.

In human T-ALL cells, TOX was shown to suppress non-homologous end joining (NHEJ) repair, a pathway required for repairing double-strand DNA breaks that, when disrupted, is known to cause errant DNA repair and genomic instability.

Nearly all of the human T-ALL samples the researchers tested were found to express TOX. And TOX proved essential for the proliferation and survival of T-ALL.

Dr Langenau explained that TOX is known to have important roles in the development and maturation of several types of immune cells, yet its roles in leukemia initiation and genomic instability were not described until this work.

TOX belongs to a group of proteins known to regulate the configuration or expression of genes by binding to DNA molecules, yet its mechanism in T-ALL—blocking NHEJ repair by binding to DNA repair proteins rather than directly to DNA—was totally unexpected.

The researchers believe that, in addition to better understanding how TOX regulates the continued growth of T-ALL, it will be important to determine whether related proteins have similar molecular functions in other cancers.

Image by Tom Ellenberger

Preclinical research suggests the TOX protein is an oncogenic driver of T-cell acute lymphoblastic leukemia (T-ALL).

Results indicate that TOX may be expressed in as many as 95% of human T-ALL cases, and the protein is required for the cancer’s growth and persistence.

“A major role for TOX in T-ALL is to elicit defects in DNA repair, leading to genetic changes that drive normal cells into cancer,” said study author David Langenau, PhD, of Massachusetts General Hospital in Boston.

“TOX then continues to be expressed within leukemic cells and is required for continued tumor growth. That means that, if we can successfully target TOX with small molecules in the future, the 95% of T-ALL patients whose tumors express TOX would have new treatment options for this aggressive leukemia.”

Dr Langenau and his colleagues described this new role for TOX in Cancer Discovery.

The team noted that T-ALL has several molecular subtypes, many of which are driven by common oncogenes such as MYC and NOTCH. However, evidence has suggested the cancer’s initiation is likely driven by aberrations in DNA repair.

To identify genes that might help drive T-ALL, the researchers performed a transgenic screen in zebrafish.

The team found that TOX collaborates with known oncogene pathways to transform T-cell precursors into leukemia cells by altering DNA repair and then expanding the population of transformed cells.

In human T-ALL cells, TOX was shown to suppress non-homologous end joining (NHEJ) repair, a pathway required for repairing double-strand DNA breaks that, when disrupted, is known to cause errant DNA repair and genomic instability.

Nearly all of the human T-ALL samples the researchers tested were found to express TOX. And TOX proved essential for the proliferation and survival of T-ALL.

Dr Langenau explained that TOX is known to have important roles in the development and maturation of several types of immune cells, yet its roles in leukemia initiation and genomic instability were not described until this work.

TOX belongs to a group of proteins known to regulate the configuration or expression of genes by binding to DNA molecules, yet its mechanism in T-ALL—blocking NHEJ repair by binding to DNA repair proteins rather than directly to DNA—was totally unexpected.

The researchers believe that, in addition to better understanding how TOX regulates the continued growth of T-ALL, it will be important to determine whether related proteins have similar molecular functions in other cancers.

Image by Tom Ellenberger

Preclinical research suggests the TOX protein is an oncogenic driver of T-cell acute lymphoblastic leukemia (T-ALL).

Results indicate that TOX may be expressed in as many as 95% of human T-ALL cases, and the protein is required for the cancer’s growth and persistence.

“A major role for TOX in T-ALL is to elicit defects in DNA repair, leading to genetic changes that drive normal cells into cancer,” said study author David Langenau, PhD, of Massachusetts General Hospital in Boston.

“TOX then continues to be expressed within leukemic cells and is required for continued tumor growth. That means that, if we can successfully target TOX with small molecules in the future, the 95% of T-ALL patients whose tumors express TOX would have new treatment options for this aggressive leukemia.”

Dr Langenau and his colleagues described this new role for TOX in Cancer Discovery.

The team noted that T-ALL has several molecular subtypes, many of which are driven by common oncogenes such as MYC and NOTCH. However, evidence has suggested the cancer’s initiation is likely driven by aberrations in DNA repair.

To identify genes that might help drive T-ALL, the researchers performed a transgenic screen in zebrafish.

The team found that TOX collaborates with known oncogene pathways to transform T-cell precursors into leukemia cells by altering DNA repair and then expanding the population of transformed cells.

In human T-ALL cells, TOX was shown to suppress non-homologous end joining (NHEJ) repair, a pathway required for repairing double-strand DNA breaks that, when disrupted, is known to cause errant DNA repair and genomic instability.

Nearly all of the human T-ALL samples the researchers tested were found to express TOX. And TOX proved essential for the proliferation and survival of T-ALL.

Dr Langenau explained that TOX is known to have important roles in the development and maturation of several types of immune cells, yet its roles in leukemia initiation and genomic instability were not described until this work.

TOX belongs to a group of proteins known to regulate the configuration or expression of genes by binding to DNA molecules, yet its mechanism in T-ALL—blocking NHEJ repair by binding to DNA repair proteins rather than directly to DNA—was totally unexpected.

The researchers believe that, in addition to better understanding how TOX regulates the continued growth of T-ALL, it will be important to determine whether related proteins have similar molecular functions in other cancers.

Woman on a scale

Cancers associated with being overweight or obese accounted for about 40% of all cancers diagnosed in the US in 2014, according to the latest Vital Signs report by the US Centers for Disease Control and Prevention.

The International Agency for Research on Cancer has identified 13 cancers associated with overweight and obesity—multiple myeloma (MM), meningioma, adenocarcinoma of the esophagus, and thyroid, postmenopausal breast, gallbladder, stomach, liver, pancreatic, kidney, ovarian, uterine, and colorectal cancers.

For the Vital Signs report, researchers reviewed US data from 2005 to 2014 to determine trends for cancers associated with being overweight (having a body mass index [BMI] of 25 to 29.9 kg/m²) or obese (having a BMI of 30 kg/m² and higher).

In 2014, roughly 631,000 people were diagnosed with cancers associated with overweight and obesity, which represents 40% of all cancers diagnosed.

Fifty-five percent of all cancers diagnosed in women and 24% of those diagnosed in men were associated with overweight and obesity.

Incidence rates of the 13 cancers combined were highest in non-Hispanic blacks, followed by non-Hispanic whites, American Indians/Alaska Natives, Hispanics, and Asians/Pacific Islanders.

Incidence over time

Overall, the incidence of cancers associated with overweight and obesity decreased 2% from 2005 to 2014.

However, when colorectal cancer was excluded, the incidence of the other 12 cancers combined increased 7% from 2005 to 2014. The incidence of colorectal cancer decreased 23% during that time. Researchers said this was due, in large part, to screening.

The incidence of cancers not associated with overweight and obesity decreased 13% from 2005 to 2014.

The incidence of MM increased over the period studied, but it was not a significant increase. The incidence rate of MM was 5.6 per 100,000 persons (age-adjusted to the 2000 US standard population) in 2005 and 6.0 per 100,000 persons in 2014.

So overall, there was an 8% increase in MM incidence rate from 2005 to 2014, or a 1.1% average annual increase. There was a 2% increase in the risk of MM per 1 kg/m² increase in BMI.

Like MM, 3 other cancers had fairly stable incidence rates over the study period—adenocarcinoma of the esophagus, gallbladder cancer, and postmenopausal breast cancer.

However, incidence rates increased significantly each year for thyroid cancer (4.0% per year), liver cancer (2.9%), gastric cardia cancer (1.2%), endometrial cancer (1.1%), pancreatic cancer (0.8%), and kidney cancer (0.7%).

And incidence rates decreased signifi­cantly each year for meningioma (-3.8%), colorectal cancer (-2.9%), and ovarian cancer (-2.0%).

Woman on a scale

Cancers associated with being overweight or obese accounted for about 40% of all cancers diagnosed in the US in 2014, according to the latest Vital Signs report by the US Centers for Disease Control and Prevention.

The International Agency for Research on Cancer has identified 13 cancers associated with overweight and obesity—multiple myeloma (MM), meningioma, adenocarcinoma of the esophagus, and thyroid, postmenopausal breast, gallbladder, stomach, liver, pancreatic, kidney, ovarian, uterine, and colorectal cancers.

For the Vital Signs report, researchers reviewed US data from 2005 to 2014 to determine trends for cancers associated with being overweight (having a body mass index [BMI] of 25 to 29.9 kg/m²) or obese (having a BMI of 30 kg/m² and higher).

In 2014, roughly 631,000 people were diagnosed with cancers associated with overweight and obesity, which represents 40% of all cancers diagnosed.

Fifty-five percent of all cancers diagnosed in women and 24% of those diagnosed in men were associated with overweight and obesity.

Incidence rates of the 13 cancers combined were highest in non-Hispanic blacks, followed by non-Hispanic whites, American Indians/Alaska Natives, Hispanics, and Asians/Pacific Islanders.

Incidence over time

Overall, the incidence of cancers associated with overweight and obesity decreased 2% from 2005 to 2014.

However, when colorectal cancer was excluded, the incidence of the other 12 cancers combined increased 7% from 2005 to 2014. The incidence of colorectal cancer decreased 23% during that time. Researchers said this was due, in large part, to screening.

The incidence of cancers not associated with overweight and obesity decreased 13% from 2005 to 2014.

The incidence of MM increased over the period studied, but it was not a significant increase. The incidence rate of MM was 5.6 per 100,000 persons (age-adjusted to the 2000 US standard population) in 2005 and 6.0 per 100,000 persons in 2014.

So overall, there was an 8% increase in MM incidence rate from 2005 to 2014, or a 1.1% average annual increase. There was a 2% increase in the risk of MM per 1 kg/m² increase in BMI.

Like MM, 3 other cancers had fairly stable incidence rates over the study period—adenocarcinoma of the esophagus, gallbladder cancer, and postmenopausal breast cancer.

However, incidence rates increased significantly each year for thyroid cancer (4.0% per year), liver cancer (2.9%), gastric cardia cancer (1.2%), endometrial cancer (1.1%), pancreatic cancer (0.8%), and kidney cancer (0.7%).

And incidence rates decreased signifi­cantly each year for meningioma (-3.8%), colorectal cancer (-2.9%), and ovarian cancer (-2.0%).

Woman on a scale

Cancers associated with being overweight or obese accounted for about 40% of all cancers diagnosed in the US in 2014, according to the latest Vital Signs report by the US Centers for Disease Control and Prevention.

The International Agency for Research on Cancer has identified 13 cancers associated with overweight and obesity—multiple myeloma (MM), meningioma, adenocarcinoma of the esophagus, and thyroid, postmenopausal breast, gallbladder, stomach, liver, pancreatic, kidney, ovarian, uterine, and colorectal cancers.

For the Vital Signs report, researchers reviewed US data from 2005 to 2014 to determine trends for cancers associated with being overweight (having a body mass index [BMI] of 25 to 29.9 kg/m²) or obese (having a BMI of 30 kg/m² and higher).

In 2014, roughly 631,000 people were diagnosed with cancers associated with overweight and obesity, which represents 40% of all cancers diagnosed.

Fifty-five percent of all cancers diagnosed in women and 24% of those diagnosed in men were associated with overweight and obesity.

Incidence rates of the 13 cancers combined were highest in non-Hispanic blacks, followed by non-Hispanic whites, American Indians/Alaska Natives, Hispanics, and Asians/Pacific Islanders.

Incidence over time

Overall, the incidence of cancers associated with overweight and obesity decreased 2% from 2005 to 2014.

However, when colorectal cancer was excluded, the incidence of the other 12 cancers combined increased 7% from 2005 to 2014. The incidence of colorectal cancer decreased 23% during that time. Researchers said this was due, in large part, to screening.

The incidence of cancers not associated with overweight and obesity decreased 13% from 2005 to 2014.

The incidence of MM increased over the period studied, but it was not a significant increase. The incidence rate of MM was 5.6 per 100,000 persons (age-adjusted to the 2000 US standard population) in 2005 and 6.0 per 100,000 persons in 2014.

So overall, there was an 8% increase in MM incidence rate from 2005 to 2014, or a 1.1% average annual increase. There was a 2% increase in the risk of MM per 1 kg/m² increase in BMI.

Like MM, 3 other cancers had fairly stable incidence rates over the study period—adenocarcinoma of the esophagus, gallbladder cancer, and postmenopausal breast cancer.

However, incidence rates increased significantly each year for thyroid cancer (4.0% per year), liver cancer (2.9%), gastric cardia cancer (1.2%), endometrial cancer (1.1%), pancreatic cancer (0.8%), and kidney cancer (0.7%).

And incidence rates decreased signifi­cantly each year for meningioma (-3.8%), colorectal cancer (-2.9%), and ovarian cancer (-2.0%).

University of Washington

A new microfluidic device could improve testing for anemia, according to researchers.

The team said the device can detect the level of hemoglobin in a whole blood sample using optical absorbance.

The device is portable, requires only a few drops of blood for analysis, and eliminates the need for chemical preparations.

In addition, researchers believe the device could be integrated with other microfluidic approaches to blood analysis.

The researchers described their device in AIP Advances.

The team noted that blood analyzers currently on the market measure hemoglobin via hemolysis. This requires hands-on expertise to prepare and run a sample, limiting the ability to monitor anemia in many parts of the world.

“The most exciting aspect to this analyzer is that it uses whole blood and does not require the additional steps and reagents to prepare a sample,” said study author Nathan Sniadecki, PhD, of the University of Washington in Seattle.

“You just run blood into the channel, and that’s it,” added Nikita Taparia, a doctoral candidate in Sniadecki’s lab. “It can be used anywhere.”

The analyzer takes advantage of the optical properties of blood, such as absorption and scattering, to measure hemoglobin concentration. Anemic blood transmits more light than normal blood, so the severity of anemia can be measured as a ratio of transmitted to original light intensity.

To simulate anemia, the researchers diluted blood samples with a buffer solution. The blood analyzer was effective at predicting cases of moderate to severe anemia, defined as less than 10 g/dL of hemoglobin in a sample. The analyzer did not produce any false-negative results.

The optical density of samples did not increase linearly, so a higher concentration of hemoglobin defines the upper limit of detection for the device.

The researchers said the device could be integrated with other microfluidic devices to analyze whole blood samples in parallel to diagnose anemia and other underlying factors that could contribute to the condition.

The team said such an integrated diagnostic tool would “aid the global health community in their continued surveillance of anemia and its etiology in high-risk subpopulations.”

University of Washington

A new microfluidic device could improve testing for anemia, according to researchers.

The team said the device can detect the level of hemoglobin in a whole blood sample using optical absorbance.

The device is portable, requires only a few drops of blood for analysis, and eliminates the need for chemical preparations.

In addition, researchers believe the device could be integrated with other microfluidic approaches to blood analysis.

The researchers described their device in AIP Advances.

The team noted that blood analyzers currently on the market measure hemoglobin via hemolysis. This requires hands-on expertise to prepare and run a sample, limiting the ability to monitor anemia in many parts of the world.

“The most exciting aspect to this analyzer is that it uses whole blood and does not require the additional steps and reagents to prepare a sample,” said study author Nathan Sniadecki, PhD, of the University of Washington in Seattle.

“You just run blood into the channel, and that’s it,” added Nikita Taparia, a doctoral candidate in Sniadecki’s lab. “It can be used anywhere.”

The analyzer takes advantage of the optical properties of blood, such as absorption and scattering, to measure hemoglobin concentration. Anemic blood transmits more light than normal blood, so the severity of anemia can be measured as a ratio of transmitted to original light intensity.

To simulate anemia, the researchers diluted blood samples with a buffer solution. The blood analyzer was effective at predicting cases of moderate to severe anemia, defined as less than 10 g/dL of hemoglobin in a sample. The analyzer did not produce any false-negative results.

The optical density of samples did not increase linearly, so a higher concentration of hemoglobin defines the upper limit of detection for the device.

The researchers said the device could be integrated with other microfluidic devices to analyze whole blood samples in parallel to diagnose anemia and other underlying factors that could contribute to the condition.

The team said such an integrated diagnostic tool would “aid the global health community in their continued surveillance of anemia and its etiology in high-risk subpopulations.”

University of Washington

A new microfluidic device could improve testing for anemia, according to researchers.

The team said the device can detect the level of hemoglobin in a whole blood sample using optical absorbance.

The device is portable, requires only a few drops of blood for analysis, and eliminates the need for chemical preparations.

In addition, researchers believe the device could be integrated with other microfluidic approaches to blood analysis.

The researchers described their device in AIP Advances.

The team noted that blood analyzers currently on the market measure hemoglobin via hemolysis. This requires hands-on expertise to prepare and run a sample, limiting the ability to monitor anemia in many parts of the world.

“The most exciting aspect to this analyzer is that it uses whole blood and does not require the additional steps and reagents to prepare a sample,” said study author Nathan Sniadecki, PhD, of the University of Washington in Seattle.

“You just run blood into the channel, and that’s it,” added Nikita Taparia, a doctoral candidate in Sniadecki’s lab. “It can be used anywhere.”

The analyzer takes advantage of the optical properties of blood, such as absorption and scattering, to measure hemoglobin concentration. Anemic blood transmits more light than normal blood, so the severity of anemia can be measured as a ratio of transmitted to original light intensity.

To simulate anemia, the researchers diluted blood samples with a buffer solution. The blood analyzer was effective at predicting cases of moderate to severe anemia, defined as less than 10 g/dL of hemoglobin in a sample. The analyzer did not produce any false-negative results.

The optical density of samples did not increase linearly, so a higher concentration of hemoglobin defines the upper limit of detection for the device.

The researchers said the device could be integrated with other microfluidic devices to analyze whole blood samples in parallel to diagnose anemia and other underlying factors that could contribute to the condition.

The team said such an integrated diagnostic tool would “aid the global health community in their continued surveillance of anemia and its etiology in high-risk subpopulations.”

Photo from MRC Laboratory of Molecular Biology

Three researchers have received the Nobel Prize in Chemistry 2017 for the development of cryo-electron microscopy (EM), which has simplified and improved the imaging of biomolecules.

Cryo-EM is a method used to image frozen biological molecules without the use of structure-altering dyes or fixatives or the need to coax the molecules into crystalline form.

This provides a simpler way to generate images of molecules in their normal states and greater understanding of biological function. It also aids the development of pharmaceuticals.

For developing cryo-EM, this year’s Nobel Prize in Chemistry* was awarded to:

• Jacques Dubochet, PhD, of University of Lausanne in Switzerland
• Joachim Frank, PhD, of Columbia University in New York, New York
• Richard Henderson, PhD, of MRC Laboratory of Molecular Biology in Cambridge, UK.

About the work

Electron microscopes were long believed to be suitable only for imaging dead matter because the electron beam destroys biological material.

However, in 1990, Dr Henderson succeeded in using an electron microscope to generate a 3-dimensional image of a protein at atomic resolution. This breakthrough proved the technology’s potential.

Dr Frank made the technology generally applicable. Between 1975 and 1986, he developed an image processing method in which the electron microscope’s fuzzy, 2-dimensional images are analyzed and merged to reveal a sharp, 3-dimensional structure.

Dr Dubochet added water to the mix. Liquid water evaporates in the electron microscope’s vacuum, which makes the biomolecules collapse.

In the early 1980s, Dr Dubochet succeeded in vitrifying water. He cooled water so rapidly that it solidified in its liquid form around a biological sample, allowing the biomolecules to retain their natural shape even in a vacuum.

Following these discoveries, the electron microscope’s every nut and bolt have been optimized. The desired atomic resolution was reached in 2013, and researchers can now routinely produce 3-dimensional structures of biomolecules.

In the past few years, the scientific literature has been filled with images of everything from proteins that cause antibiotic resistance to the surface of the Zika virus.

*The prize amount is 9 million Swedish krona to be shared equally among the Laureates.

Photo from MRC Laboratory of Molecular Biology

Three researchers have received the Nobel Prize in Chemistry 2017 for the development of cryo-electron microscopy (EM), which has simplified and improved the imaging of biomolecules.

Cryo-EM is a method used to image frozen biological molecules without the use of structure-altering dyes or fixatives or the need to coax the molecules into crystalline form.

This provides a simpler way to generate images of molecules in their normal states and greater understanding of biological function. It also aids the development of pharmaceuticals.

For developing cryo-EM, this year’s Nobel Prize in Chemistry* was awarded to:

• Jacques Dubochet, PhD, of University of Lausanne in Switzerland
• Joachim Frank, PhD, of Columbia University in New York, New York
• Richard Henderson, PhD, of MRC Laboratory of Molecular Biology in Cambridge, UK.

About the work

Electron microscopes were long believed to be suitable only for imaging dead matter because the electron beam destroys biological material.

However, in 1990, Dr Henderson succeeded in using an electron microscope to generate a 3-dimensional image of a protein at atomic resolution. This breakthrough proved the technology’s potential.

Dr Frank made the technology generally applicable. Between 1975 and 1986, he developed an image processing method in which the electron microscope’s fuzzy, 2-dimensional images are analyzed and merged to reveal a sharp, 3-dimensional structure.

Dr Dubochet added water to the mix. Liquid water evaporates in the electron microscope’s vacuum, which makes the biomolecules collapse.

In the early 1980s, Dr Dubochet succeeded in vitrifying water. He cooled water so rapidly that it solidified in its liquid form around a biological sample, allowing the biomolecules to retain their natural shape even in a vacuum.

Following these discoveries, the electron microscope’s every nut and bolt have been optimized. The desired atomic resolution was reached in 2013, and researchers can now routinely produce 3-dimensional structures of biomolecules.

In the past few years, the scientific literature has been filled with images of everything from proteins that cause antibiotic resistance to the surface of the Zika virus.

*The prize amount is 9 million Swedish krona to be shared equally among the Laureates.

Photo from MRC Laboratory of Molecular Biology

Three researchers have received the Nobel Prize in Chemistry 2017 for the development of cryo-electron microscopy (EM), which has simplified and improved the imaging of biomolecules.

Cryo-EM is a method used to image frozen biological molecules without the use of structure-altering dyes or fixatives or the need to coax the molecules into crystalline form.

This provides a simpler way to generate images of molecules in their normal states and greater understanding of biological function. It also aids the development of pharmaceuticals.

For developing cryo-EM, this year’s Nobel Prize in Chemistry* was awarded to:

• Jacques Dubochet, PhD, of University of Lausanne in Switzerland
• Joachim Frank, PhD, of Columbia University in New York, New York
• Richard Henderson, PhD, of MRC Laboratory of Molecular Biology in Cambridge, UK.

About the work

Electron microscopes were long believed to be suitable only for imaging dead matter because the electron beam destroys biological material.

However, in 1990, Dr Henderson succeeded in using an electron microscope to generate a 3-dimensional image of a protein at atomic resolution. This breakthrough proved the technology’s potential.

Dr Frank made the technology generally applicable. Between 1975 and 1986, he developed an image processing method in which the electron microscope’s fuzzy, 2-dimensional images are analyzed and merged to reveal a sharp, 3-dimensional structure.

Dr Dubochet added water to the mix. Liquid water evaporates in the electron microscope’s vacuum, which makes the biomolecules collapse.

In the early 1980s, Dr Dubochet succeeded in vitrifying water. He cooled water so rapidly that it solidified in its liquid form around a biological sample, allowing the biomolecules to retain their natural shape even in a vacuum.

Following these discoveries, the electron microscope’s every nut and bolt have been optimized. The desired atomic resolution was reached in 2013, and researchers can now routinely produce 3-dimensional structures of biomolecules.

In the past few years, the scientific literature has been filled with images of everything from proteins that cause antibiotic resistance to the surface of the Zika virus.

*The prize amount is 9 million Swedish krona to be shared equally among the Laureates.

The FP was aware that HCTZ might precipitate lichen planus or create a lichenoid drug reaction, so he performed a 4-mm punch biopsy and asked the patient to stop taking her HCTZ while the biopsy results were pending. (The patient also had several of the 5 Ps of lichen planus: planar, polygonal, pruritic, papular, and purple lesions. She didn’t have any papular lesions and the lesions she did have were more brown than purple because of her dark skin color.)

The FP prescribed topical fluocinonide 0.05% ointment to be applied twice daily to the affected areas until the biopsy results were available. The FP also increased her lisinopril dose, hoping to keep her BP under control.

Biopsy results came back as probable lichen planus and possible lichenoid drug reaction. As treatment for each condition would be the same, it didn’t matter that the pathologist couldn’t be more specific.

On the patient’s second visit for suture removal and discussion of the biopsy results, she said she was feeling better. Her BP was still under control, so the FP decided to continue the treatment plan. At follow-up one month later, the pruritus had resolved completely and the skin lesions were no longer palpable. There was postinflammatory hyperpigmentation at the sites of the lesions, but the patient was not concerned about this because most of it was on her back.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Kraft RL, Usatine R. Lichen planus. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 901-909.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The FP was aware that HCTZ might precipitate lichen planus or create a lichenoid drug reaction, so he performed a 4-mm punch biopsy and asked the patient to stop taking her HCTZ while the biopsy results were pending. (The patient also had several of the 5 Ps of lichen planus: planar, polygonal, pruritic, papular, and purple lesions. She didn’t have any papular lesions and the lesions she did have were more brown than purple because of her dark skin color.)

The FP prescribed topical fluocinonide 0.05% ointment to be applied twice daily to the affected areas until the biopsy results were available. The FP also increased her lisinopril dose, hoping to keep her BP under control.

Biopsy results came back as probable lichen planus and possible lichenoid drug reaction. As treatment for each condition would be the same, it didn’t matter that the pathologist couldn’t be more specific.

On the patient’s second visit for suture removal and discussion of the biopsy results, she said she was feeling better. Her BP was still under control, so the FP decided to continue the treatment plan. At follow-up one month later, the pruritus had resolved completely and the skin lesions were no longer palpable. There was postinflammatory hyperpigmentation at the sites of the lesions, but the patient was not concerned about this because most of it was on her back.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Kraft RL, Usatine R. Lichen planus. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 901-909.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The FP was aware that HCTZ might precipitate lichen planus or create a lichenoid drug reaction, so he performed a 4-mm punch biopsy and asked the patient to stop taking her HCTZ while the biopsy results were pending. (The patient also had several of the 5 Ps of lichen planus: planar, polygonal, pruritic, papular, and purple lesions. She didn’t have any papular lesions and the lesions she did have were more brown than purple because of her dark skin color.)

The FP prescribed topical fluocinonide 0.05% ointment to be applied twice daily to the affected areas until the biopsy results were available. The FP also increased her lisinopril dose, hoping to keep her BP under control.

Biopsy results came back as probable lichen planus and possible lichenoid drug reaction. As treatment for each condition would be the same, it didn’t matter that the pathologist couldn’t be more specific.

On the patient’s second visit for suture removal and discussion of the biopsy results, she said she was feeling better. Her BP was still under control, so the FP decided to continue the treatment plan. At follow-up one month later, the pruritus had resolved completely and the skin lesions were no longer palpable. There was postinflammatory hyperpigmentation at the sites of the lesions, but the patient was not concerned about this because most of it was on her back.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Kraft RL, Usatine R. Lichen planus. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 901-909.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

To improve patient care and outcomes, leading dermatologists offered their recommendations on postprocedural makeup. Consideration must be given to:

• Dual Action Redness Relief
  PCA Skin
  “This product is great immediately after laser treatment or filler/botulinum toxin injections to reduce postprocedural redness.”— Gary Goldenberg, MD, New York, New York
   
• Isdinceutics Skin Drops
  ISDIN
  “This product is great to reduce or camouflage postprocedural bruising or redness.”—Gary Goldenberg, MD, New York, New York
   
• Oxygenating Foundation
  Oxygenetix
  “This is my favorite postprocedural makeup. Originally designed for burn victims, this makeup has botanicals, SPF, and is water resistant and soothing.”—Jeannette Graf, MD, Great Neck, New York
   
• Quick-Fix Concealer Stick
  Dermablend
  “This product is customized to match your patient’s skin type. It’s great at covering up purpura postprocedure.”—Shari Lipner, MD, PhD, New York, New York
  
  “I love Dermablend because it can essentially camouflage anything postprocedure, getting patients back to work or their social activities.”— Jerome Potozkin, MD, Danville, California

Cutis invites readers to send us their recommendations. Pigment corrector, lip plumper, moisturizers for men, and wet skin moisturizers will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

To improve patient care and outcomes, leading dermatologists offered their recommendations on postprocedural makeup. Consideration must be given to:

• Dual Action Redness Relief
  PCA Skin
  “This product is great immediately after laser treatment or filler/botulinum toxin injections to reduce postprocedural redness.”— Gary Goldenberg, MD, New York, New York
   
• Isdinceutics Skin Drops
  ISDIN
  “This product is great to reduce or camouflage postprocedural bruising or redness.”—Gary Goldenberg, MD, New York, New York
   
• Oxygenating Foundation
  Oxygenetix
  “This is my favorite postprocedural makeup. Originally designed for burn victims, this makeup has botanicals, SPF, and is water resistant and soothing.”—Jeannette Graf, MD, Great Neck, New York
   
• Quick-Fix Concealer Stick
  Dermablend
  “This product is customized to match your patient’s skin type. It’s great at covering up purpura postprocedure.”—Shari Lipner, MD, PhD, New York, New York
  
  “I love Dermablend because it can essentially camouflage anything postprocedure, getting patients back to work or their social activities.”— Jerome Potozkin, MD, Danville, California

Cutis invites readers to send us their recommendations. Pigment corrector, lip plumper, moisturizers for men, and wet skin moisturizers will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

To improve patient care and outcomes, leading dermatologists offered their recommendations on postprocedural makeup. Consideration must be given to:

• Dual Action Redness Relief
  PCA Skin
  “This product is great immediately after laser treatment or filler/botulinum toxin injections to reduce postprocedural redness.”— Gary Goldenberg, MD, New York, New York
   
• Isdinceutics Skin Drops
  ISDIN
  “This product is great to reduce or camouflage postprocedural bruising or redness.”—Gary Goldenberg, MD, New York, New York
   
• Oxygenating Foundation
  Oxygenetix
  “This is my favorite postprocedural makeup. Originally designed for burn victims, this makeup has botanicals, SPF, and is water resistant and soothing.”—Jeannette Graf, MD, Great Neck, New York
   
• Quick-Fix Concealer Stick
  Dermablend
  “This product is customized to match your patient’s skin type. It’s great at covering up purpura postprocedure.”—Shari Lipner, MD, PhD, New York, New York
  
  “I love Dermablend because it can essentially camouflage anything postprocedure, getting patients back to work or their social activities.”— Jerome Potozkin, MD, Danville, California

Cutis invites readers to send us their recommendations. Pigment corrector, lip plumper, moisturizers for men, and wet skin moisturizers will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

Click here to learn about what happens when epilepsy does not respond to treatment.

Click here to learn about what happens when epilepsy does not respond to treatment.

Click here to learn about what happens when epilepsy does not respond to treatment.

SAN FRANCISCO – The benefit of lowering blood pressure exceeded the potential for harm, even among the most frail elderly, in SPRINT, but it’s important to remember who was excluded from the trial when using the findings in the clinic, according to Mark Supiano, MD.

SPRINT (Systolic Blood Pressure Intervention Trial) excluded people with histories of stroke, diabetes, heart failure, and chronic kidney disease with a markedly reduced glomerular filtration rate. People living in nursing homes, assisted living centers, and those with prevalent dementia were also excluded, as were individuals with a standing systolic pressure below 110 mm Hg (N Engl J Med. 2015 Nov 26;373:2103-16).

Even with those exclusions, however, the 2,636 patients in SPRINT who were 75 years and older “were not a super healthy group of older people,” Dr. Supiano said at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

They were at high risk for cardiovascular disease (CVD), with a median 10-year Framingham risk score of almost 25%. More than a quarter had gait speeds below 0.8 m/sec, and almost a third were classified as frail. Many had mild cognitive impairment at baseline.

In the United States, Dr. Supiano and his colleagues estimate that there are almost 6 million similar people 75 years or older with hypertension who would likely achieve the same benefits from hypertension control as elderly subjects in the trial. “As a geriatrician, there are very few things that I can offer patients 75 years and older that will have a profound improvement in their overall mortality.” Blood pressure control is one of them, said Dr. Supiano, chief of geriatrics at the University of Utah, Salt Lake City, and a SPRINT investigator.

In SPRINT, intensive treatment to systolic pressure below 120 mm Hg showed greater benefit for patients 75 years and older than it did for younger patients, even among the frail, with a 34% reduction in fatal and nonfatal CVD events versus patients treated to below 140 mm Hg, and a 33% lower rate of death from any cause.

It should be no surprise that older patients had greater benefit from tighter control, because elderly patients have “a greater CVD risk. There’s more bang for the buck” with blood pressure lowering in an older population. “Overall, benefits exceed the potential for harm, even among the frailest older patients,” Dr. Supiano said.

“A systemic target of less than 140 mm Hg is, I believe, appropriate for most healthy people age 60 and older. A benefit-based systemic target of less than 120 mm Hg may be appropriate for those at higher CVD risk.” Among patients 60-75 years old, that would include those with a Framingham score above 15%. Among patients older than age 75 with an elevated CVD risk, treatment to below 120 mm Hg makes sense if it aligns with patient’s goals of care, Dr. Supiano said.

The 120–mm Hg target in SPRINT was associated with a greater incidence of some transient side effects in the elderly, including hypotension, syncope, acute kidney injury, and electrolyte imbalance, but not a higher risk of serious adverse events or injurious falls.

There were concerns raised at the joint sessions about the effect of blood pressure lowering on the cognitive function of older people. Dr. Supiano noted that the cognitive outcomes in SPRINT, as well as outcomes in patients with chronic kidney disease, have not yet been released, but are expected soon.

Dr. Supiano had no relevant disclosures.

[email protected]

SAN FRANCISCO – The benefit of lowering blood pressure exceeded the potential for harm, even among the most frail elderly, in SPRINT, but it’s important to remember who was excluded from the trial when using the findings in the clinic, according to Mark Supiano, MD.

SPRINT (Systolic Blood Pressure Intervention Trial) excluded people with histories of stroke, diabetes, heart failure, and chronic kidney disease with a markedly reduced glomerular filtration rate. People living in nursing homes, assisted living centers, and those with prevalent dementia were also excluded, as were individuals with a standing systolic pressure below 110 mm Hg (N Engl J Med. 2015 Nov 26;373:2103-16).

Even with those exclusions, however, the 2,636 patients in SPRINT who were 75 years and older “were not a super healthy group of older people,” Dr. Supiano said at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

They were at high risk for cardiovascular disease (CVD), with a median 10-year Framingham risk score of almost 25%. More than a quarter had gait speeds below 0.8 m/sec, and almost a third were classified as frail. Many had mild cognitive impairment at baseline.

In the United States, Dr. Supiano and his colleagues estimate that there are almost 6 million similar people 75 years or older with hypertension who would likely achieve the same benefits from hypertension control as elderly subjects in the trial. “As a geriatrician, there are very few things that I can offer patients 75 years and older that will have a profound improvement in their overall mortality.” Blood pressure control is one of them, said Dr. Supiano, chief of geriatrics at the University of Utah, Salt Lake City, and a SPRINT investigator.

In SPRINT, intensive treatment to systolic pressure below 120 mm Hg showed greater benefit for patients 75 years and older than it did for younger patients, even among the frail, with a 34% reduction in fatal and nonfatal CVD events versus patients treated to below 140 mm Hg, and a 33% lower rate of death from any cause.

It should be no surprise that older patients had greater benefit from tighter control, because elderly patients have “a greater CVD risk. There’s more bang for the buck” with blood pressure lowering in an older population. “Overall, benefits exceed the potential for harm, even among the frailest older patients,” Dr. Supiano said.

“A systemic target of less than 140 mm Hg is, I believe, appropriate for most healthy people age 60 and older. A benefit-based systemic target of less than 120 mm Hg may be appropriate for those at higher CVD risk.” Among patients 60-75 years old, that would include those with a Framingham score above 15%. Among patients older than age 75 with an elevated CVD risk, treatment to below 120 mm Hg makes sense if it aligns with patient’s goals of care, Dr. Supiano said.

The 120–mm Hg target in SPRINT was associated with a greater incidence of some transient side effects in the elderly, including hypotension, syncope, acute kidney injury, and electrolyte imbalance, but not a higher risk of serious adverse events or injurious falls.

There were concerns raised at the joint sessions about the effect of blood pressure lowering on the cognitive function of older people. Dr. Supiano noted that the cognitive outcomes in SPRINT, as well as outcomes in patients with chronic kidney disease, have not yet been released, but are expected soon.

Dr. Supiano had no relevant disclosures.

[email protected]

SAN FRANCISCO – The benefit of lowering blood pressure exceeded the potential for harm, even among the most frail elderly, in SPRINT, but it’s important to remember who was excluded from the trial when using the findings in the clinic, according to Mark Supiano, MD.

SPRINT (Systolic Blood Pressure Intervention Trial) excluded people with histories of stroke, diabetes, heart failure, and chronic kidney disease with a markedly reduced glomerular filtration rate. People living in nursing homes, assisted living centers, and those with prevalent dementia were also excluded, as were individuals with a standing systolic pressure below 110 mm Hg (N Engl J Med. 2015 Nov 26;373:2103-16).

Even with those exclusions, however, the 2,636 patients in SPRINT who were 75 years and older “were not a super healthy group of older people,” Dr. Supiano said at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

They were at high risk for cardiovascular disease (CVD), with a median 10-year Framingham risk score of almost 25%. More than a quarter had gait speeds below 0.8 m/sec, and almost a third were classified as frail. Many had mild cognitive impairment at baseline.

In the United States, Dr. Supiano and his colleagues estimate that there are almost 6 million similar people 75 years or older with hypertension who would likely achieve the same benefits from hypertension control as elderly subjects in the trial. “As a geriatrician, there are very few things that I can offer patients 75 years and older that will have a profound improvement in their overall mortality.” Blood pressure control is one of them, said Dr. Supiano, chief of geriatrics at the University of Utah, Salt Lake City, and a SPRINT investigator.

In SPRINT, intensive treatment to systolic pressure below 120 mm Hg showed greater benefit for patients 75 years and older than it did for younger patients, even among the frail, with a 34% reduction in fatal and nonfatal CVD events versus patients treated to below 140 mm Hg, and a 33% lower rate of death from any cause.

It should be no surprise that older patients had greater benefit from tighter control, because elderly patients have “a greater CVD risk. There’s more bang for the buck” with blood pressure lowering in an older population. “Overall, benefits exceed the potential for harm, even among the frailest older patients,” Dr. Supiano said.

“A systemic target of less than 140 mm Hg is, I believe, appropriate for most healthy people age 60 and older. A benefit-based systemic target of less than 120 mm Hg may be appropriate for those at higher CVD risk.” Among patients 60-75 years old, that would include those with a Framingham score above 15%. Among patients older than age 75 with an elevated CVD risk, treatment to below 120 mm Hg makes sense if it aligns with patient’s goals of care, Dr. Supiano said.

The 120–mm Hg target in SPRINT was associated with a greater incidence of some transient side effects in the elderly, including hypotension, syncope, acute kidney injury, and electrolyte imbalance, but not a higher risk of serious adverse events or injurious falls.

There were concerns raised at the joint sessions about the effect of blood pressure lowering on the cognitive function of older people. Dr. Supiano noted that the cognitive outcomes in SPRINT, as well as outcomes in patients with chronic kidney disease, have not yet been released, but are expected soon.

Dr. Supiano had no relevant disclosures.

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BALTIMORE – Prehospital tourniquet use on injured civilians in trauma situations was associated with a nearly sixfold decrease in mortality, according to a study presented at the annual meeting of the American Association for Surgery of Trauma.

While tourniquets have been an effective tool in military settings, data on successful applications in civilian settings have been scarce.

Wikimedia Creative Commons License/INDNAM

[email protected]

On Twitter @eaztweets

BALTIMORE – Prehospital tourniquet use on injured civilians in trauma situations was associated with a nearly sixfold decrease in mortality, according to a study presented at the annual meeting of the American Association for Surgery of Trauma.

While tourniquets have been an effective tool in military settings, data on successful applications in civilian settings have been scarce.

Wikimedia Creative Commons License/INDNAM

[email protected]

On Twitter @eaztweets

BALTIMORE – Prehospital tourniquet use on injured civilians in trauma situations was associated with a nearly sixfold decrease in mortality, according to a study presented at the annual meeting of the American Association for Surgery of Trauma.

While tourniquets have been an effective tool in military settings, data on successful applications in civilian settings have been scarce.

Wikimedia Creative Commons License/INDNAM

[email protected]

On Twitter @eaztweets