Clinical Edge Journal Scan Commentary

In the study, 60 patients were classified as having EPI based on the gold standard test of PABA excretion, then the FBHC of the two groups were compared. According to the study findings FBHC levels were higher in the EPI group 15.70 (1.4 to 77.0) ppm than in the non-PEI group 2.80 (0.7 to 28.2) ppm (P < 0.0001).  The cutoff value for FBHC of 10.7 ppm (95% CI: 0.678–0.913; P < 0.001) showed a sensitivity of 73.3% and a specificity of 83.3% for PEI diagnosis. Interestingly, to prove biologic plausibility, the researchers also looked at microbiome analysis and found that there was a significant increase of relative abundance of phylum Firmicutes (P < 0.05) and the genus Clostridium (P < 0.05) in the EPI group. The researchers suggested that the flow of undigested food in EPI may select for Clorstridia species, which are the main hydrogen producing bacteria in the intestine. 

In AZN Journal of Surgery, Chan-Min Choi, et al looked at management of palliative stage pancreatic ductal adenocarcinomas (PDAC)  in 67 patients with locally advanced or metastatic pancreatic cancer at Western Health in Melbourne.² Weight loss and steatorrhea were present in 83.6% and 13.4% of patients, respectively, and median body mass index decreased by 13.3% from pre-illness to cancer diagnosis. Yet, despite high rates of referral to dieticians (79.1%), only 24 patients were prescribed pancreatic enzyme replacement therapy. The researchers concluded that the "study shows a lack of clear guideline for diagnosis and management of EPI for palliative PDAC.”

Finally a study by Johnston et al. in Gastroenterology looked at predictors of exocrine pancreatic insufficiency in 68 patients who underwent pancreatectomy (distal, n=23; pancreaticoduodenectomy, n=45).³ EPI, requiring pancreatic enzyme replacement therapy, developed in 50% of patients at 1-year postpancreatectomy. The researchers looked at predictors of EPI including variables such as preoperative A1c, smoking status, neoadjuvant chemo and radio therapy, and age, among others. In the final multivariate analysis, the only factor associated with EPI development was postoperative remnant pancreas volume (odds ratio, 0.93; 95% CI, 0.88-0.98; P < 0.01). While these studies may not immediately change practice, they offer further steps in the direction towards better diagnostics and more appropriate management of EPI.  

References 

1. Uetsuki K, Kawashima H, Ohno E, et al. Measurement of fasting breath hydrogen concentration as a simple diagnostic method for pancreatic exocrine insufficiency. BMC Gastroenterol 2021;21(1):211.

2. Choi CC-M, Choi J, Houli N, et al. Evaluation of palliative treatments in unresectable pancreatic cancer. ANZ J Surg 2021;

3. Johnston ME, Wahab SA, Turner K, et al. 298 post-pancreatectomy volumetric analysis: a missing variable in the development of post-operative endocrine and exocrine dysfunction. Gastroenterology 2021;160(6):S-878.

In the study, 60 patients were classified as having EPI based on the gold standard test of PABA excretion, then the FBHC of the two groups were compared. According to the study findings FBHC levels were higher in the EPI group 15.70 (1.4 to 77.0) ppm than in the non-PEI group 2.80 (0.7 to 28.2) ppm (P < 0.0001).  The cutoff value for FBHC of 10.7 ppm (95% CI: 0.678–0.913; P < 0.001) showed a sensitivity of 73.3% and a specificity of 83.3% for PEI diagnosis. Interestingly, to prove biologic plausibility, the researchers also looked at microbiome analysis and found that there was a significant increase of relative abundance of phylum Firmicutes (P < 0.05) and the genus Clostridium (P < 0.05) in the EPI group. The researchers suggested that the flow of undigested food in EPI may select for Clorstridia species, which are the main hydrogen producing bacteria in the intestine. 

In AZN Journal of Surgery, Chan-Min Choi, et al looked at management of palliative stage pancreatic ductal adenocarcinomas (PDAC)  in 67 patients with locally advanced or metastatic pancreatic cancer at Western Health in Melbourne.² Weight loss and steatorrhea were present in 83.6% and 13.4% of patients, respectively, and median body mass index decreased by 13.3% from pre-illness to cancer diagnosis. Yet, despite high rates of referral to dieticians (79.1%), only 24 patients were prescribed pancreatic enzyme replacement therapy. The researchers concluded that the "study shows a lack of clear guideline for diagnosis and management of EPI for palliative PDAC.”

Finally a study by Johnston et al. in Gastroenterology looked at predictors of exocrine pancreatic insufficiency in 68 patients who underwent pancreatectomy (distal, n=23; pancreaticoduodenectomy, n=45).³ EPI, requiring pancreatic enzyme replacement therapy, developed in 50% of patients at 1-year postpancreatectomy. The researchers looked at predictors of EPI including variables such as preoperative A1c, smoking status, neoadjuvant chemo and radio therapy, and age, among others. In the final multivariate analysis, the only factor associated with EPI development was postoperative remnant pancreas volume (odds ratio, 0.93; 95% CI, 0.88-0.98; P < 0.01). While these studies may not immediately change practice, they offer further steps in the direction towards better diagnostics and more appropriate management of EPI.  

References 

1. Uetsuki K, Kawashima H, Ohno E, et al. Measurement of fasting breath hydrogen concentration as a simple diagnostic method for pancreatic exocrine insufficiency. BMC Gastroenterol 2021;21(1):211.

2. Choi CC-M, Choi J, Houli N, et al. Evaluation of palliative treatments in unresectable pancreatic cancer. ANZ J Surg 2021;

3. Johnston ME, Wahab SA, Turner K, et al. 298 post-pancreatectomy volumetric analysis: a missing variable in the development of post-operative endocrine and exocrine dysfunction. Gastroenterology 2021;160(6):S-878.

In the study, 60 patients were classified as having EPI based on the gold standard test of PABA excretion, then the FBHC of the two groups were compared. According to the study findings FBHC levels were higher in the EPI group 15.70 (1.4 to 77.0) ppm than in the non-PEI group 2.80 (0.7 to 28.2) ppm (P < 0.0001).  The cutoff value for FBHC of 10.7 ppm (95% CI: 0.678–0.913; P < 0.001) showed a sensitivity of 73.3% and a specificity of 83.3% for PEI diagnosis. Interestingly, to prove biologic plausibility, the researchers also looked at microbiome analysis and found that there was a significant increase of relative abundance of phylum Firmicutes (P < 0.05) and the genus Clostridium (P < 0.05) in the EPI group. The researchers suggested that the flow of undigested food in EPI may select for Clorstridia species, which are the main hydrogen producing bacteria in the intestine. 

In AZN Journal of Surgery, Chan-Min Choi, et al looked at management of palliative stage pancreatic ductal adenocarcinomas (PDAC)  in 67 patients with locally advanced or metastatic pancreatic cancer at Western Health in Melbourne.² Weight loss and steatorrhea were present in 83.6% and 13.4% of patients, respectively, and median body mass index decreased by 13.3% from pre-illness to cancer diagnosis. Yet, despite high rates of referral to dieticians (79.1%), only 24 patients were prescribed pancreatic enzyme replacement therapy. The researchers concluded that the "study shows a lack of clear guideline for diagnosis and management of EPI for palliative PDAC.”

Finally a study by Johnston et al. in Gastroenterology looked at predictors of exocrine pancreatic insufficiency in 68 patients who underwent pancreatectomy (distal, n=23; pancreaticoduodenectomy, n=45).³ EPI, requiring pancreatic enzyme replacement therapy, developed in 50% of patients at 1-year postpancreatectomy. The researchers looked at predictors of EPI including variables such as preoperative A1c, smoking status, neoadjuvant chemo and radio therapy, and age, among others. In the final multivariate analysis, the only factor associated with EPI development was postoperative remnant pancreas volume (odds ratio, 0.93; 95% CI, 0.88-0.98; P < 0.01). While these studies may not immediately change practice, they offer further steps in the direction towards better diagnostics and more appropriate management of EPI.  

References 

1. Uetsuki K, Kawashima H, Ohno E, et al. Measurement of fasting breath hydrogen concentration as a simple diagnostic method for pancreatic exocrine insufficiency. BMC Gastroenterol 2021;21(1):211.

2. Choi CC-M, Choi J, Houli N, et al. Evaluation of palliative treatments in unresectable pancreatic cancer. ANZ J Surg 2021;

3. Johnston ME, Wahab SA, Turner K, et al. 298 post-pancreatectomy volumetric analysis: a missing variable in the development of post-operative endocrine and exocrine dysfunction. Gastroenterology 2021;160(6):S-878.

Due to the heterogeneity of outcomes and study designs, consensus on definitive prostate cancer risk assessment has been somewhat elusive. Differences in outcomes based on ethnicity and race have been observed, but much data on risk has originally been obtained in populations with lower ethnic and racial diversity, complicating extrapolation to larger populations. Huynh-Le et al developed an updated polygenic hazard score (PHS₂) based on a single nucleotide polymorphism (SNP) panel (46 total SNPs) for prostate cancer patients with multiple ethnicities (African, Asian, and European ancestries). This updated PHS₂ score stratified men into higher and lower risks for any, aggressive, and fatal prostate cancers in a statistically significant way. Camargo et al took a different approach and evaluated whether 2 SNPs were prognostic in prostate cancer: rs1834306 corresponding to microRNA 100 (miR 100) and rs2910164 from miR 146a. There were no differences in miR 100 or miR 156a between patients with local prostate cancer or a control group of men without prostate cancer. In addition, there were no differences in the chance of particular genotypes between the 2 groups. There was an association between lower presence of rs1834306 (miR 100) and patients with PSA > 10 mg/mL and between a higher amount of the polymorphic allele for rs2910164 (miR 146A).

The 3 studies summarized here demonstrate the ongoing challenges in how to identify nuances that will affect clinical decision-making in PSA screening and to identify prognostic features that associate with particular outcomes. The study by Bergengren confirmed the current state of PSA screening in that balancing diagnosis and potential overtreatment with modest survival outcomes is challenging. While the studies by Huynh-Le  et al and Camargo et al have interesting findings, the use of SNPs and miR in prostate cancer prognosis is still not ready for routine clinical use in prostate cancer management.

Due to the heterogeneity of outcomes and study designs, consensus on definitive prostate cancer risk assessment has been somewhat elusive. Differences in outcomes based on ethnicity and race have been observed, but much data on risk has originally been obtained in populations with lower ethnic and racial diversity, complicating extrapolation to larger populations. Huynh-Le et al developed an updated polygenic hazard score (PHS₂) based on a single nucleotide polymorphism (SNP) panel (46 total SNPs) for prostate cancer patients with multiple ethnicities (African, Asian, and European ancestries). This updated PHS₂ score stratified men into higher and lower risks for any, aggressive, and fatal prostate cancers in a statistically significant way. Camargo et al took a different approach and evaluated whether 2 SNPs were prognostic in prostate cancer: rs1834306 corresponding to microRNA 100 (miR 100) and rs2910164 from miR 146a. There were no differences in miR 100 or miR 156a between patients with local prostate cancer or a control group of men without prostate cancer. In addition, there were no differences in the chance of particular genotypes between the 2 groups. There was an association between lower presence of rs1834306 (miR 100) and patients with PSA > 10 mg/mL and between a higher amount of the polymorphic allele for rs2910164 (miR 146A).

The 3 studies summarized here demonstrate the ongoing challenges in how to identify nuances that will affect clinical decision-making in PSA screening and to identify prognostic features that associate with particular outcomes. The study by Bergengren confirmed the current state of PSA screening in that balancing diagnosis and potential overtreatment with modest survival outcomes is challenging. While the studies by Huynh-Le  et al and Camargo et al have interesting findings, the use of SNPs and miR in prostate cancer prognosis is still not ready for routine clinical use in prostate cancer management.

Due to the heterogeneity of outcomes and study designs, consensus on definitive prostate cancer risk assessment has been somewhat elusive. Differences in outcomes based on ethnicity and race have been observed, but much data on risk has originally been obtained in populations with lower ethnic and racial diversity, complicating extrapolation to larger populations. Huynh-Le et al developed an updated polygenic hazard score (PHS₂) based on a single nucleotide polymorphism (SNP) panel (46 total SNPs) for prostate cancer patients with multiple ethnicities (African, Asian, and European ancestries). This updated PHS₂ score stratified men into higher and lower risks for any, aggressive, and fatal prostate cancers in a statistically significant way. Camargo et al took a different approach and evaluated whether 2 SNPs were prognostic in prostate cancer: rs1834306 corresponding to microRNA 100 (miR 100) and rs2910164 from miR 146a. There were no differences in miR 100 or miR 156a between patients with local prostate cancer or a control group of men without prostate cancer. In addition, there were no differences in the chance of particular genotypes between the 2 groups. There was an association between lower presence of rs1834306 (miR 100) and patients with PSA > 10 mg/mL and between a higher amount of the polymorphic allele for rs2910164 (miR 146A).

The 3 studies summarized here demonstrate the ongoing challenges in how to identify nuances that will affect clinical decision-making in PSA screening and to identify prognostic features that associate with particular outcomes. The study by Bergengren confirmed the current state of PSA screening in that balancing diagnosis and potential overtreatment with modest survival outcomes is challenging. While the studies by Huynh-Le  et al and Camargo et al have interesting findings, the use of SNPs and miR in prostate cancer prognosis is still not ready for routine clinical use in prostate cancer management.

The next study explored ways to identify patients who have HCC using PIVKA-II (prothrombin induced by vitamin K deficiency/antagonist – II), a promising marker that may be more sensitive/specific than AFP in identifying patients with liver cancer. Feng et al. used enzyme-linked immunosorbent assay (ELISA) to measure serum PIVKA-II levels in 168 patients with HCC, 150 patients with benign liver disease, and 153 healthy controls. Patients with HCC had significantly higher median PIVKA-II levels (181.50 mAu/mL), compared with atients with noncancerous liver disease (28.6 mAU/mL) or healthy controls 21.82 mAU/mL), with p<0.0001. In addition, PIVKA-II was more sensitive (83.9% vs 64.3%) and more specific (91.5% vs 84.7%) than AFP in identifying patients with HCC. When PIVKA-II and AFP were combined, sensitivity (81.95%) and specificity (89.3%) were increased more, suggesting that this combination of markers may be most useful in clinical practice to identify patients who have HCC.

Finally, in patients whose HCC was treated with orthotopic liver transplantation, acute organ rejection was found to be linked to HCC recurrence. Gul-Klein et al. identified 252 patients who underwent liver transplantation for HCC between 2001 and 2015, 91 of whom had confirmed acute rejection, and 47 of whom had recurrent HCC (the median time to HCC recurrence was 20 months). HCC recurrence was identified in 28.6% of patients with acute rejection, and in 13% of patients without acute rejection (p=0.002). Acute rejection within 20 months of liver transplantation was identified as a significant risk factor for HCC recurrence in multivariate analysis (hazard ratio of 2.91). The authors suggested that more intensive monitoring for HCC recurrence may be appropriate for patients who have evidence of acute rejection.

The next study explored ways to identify patients who have HCC using PIVKA-II (prothrombin induced by vitamin K deficiency/antagonist – II), a promising marker that may be more sensitive/specific than AFP in identifying patients with liver cancer. Feng et al. used enzyme-linked immunosorbent assay (ELISA) to measure serum PIVKA-II levels in 168 patients with HCC, 150 patients with benign liver disease, and 153 healthy controls. Patients with HCC had significantly higher median PIVKA-II levels (181.50 mAu/mL), compared with atients with noncancerous liver disease (28.6 mAU/mL) or healthy controls 21.82 mAU/mL), with p<0.0001. In addition, PIVKA-II was more sensitive (83.9% vs 64.3%) and more specific (91.5% vs 84.7%) than AFP in identifying patients with HCC. When PIVKA-II and AFP were combined, sensitivity (81.95%) and specificity (89.3%) were increased more, suggesting that this combination of markers may be most useful in clinical practice to identify patients who have HCC.

Finally, in patients whose HCC was treated with orthotopic liver transplantation, acute organ rejection was found to be linked to HCC recurrence. Gul-Klein et al. identified 252 patients who underwent liver transplantation for HCC between 2001 and 2015, 91 of whom had confirmed acute rejection, and 47 of whom had recurrent HCC (the median time to HCC recurrence was 20 months). HCC recurrence was identified in 28.6% of patients with acute rejection, and in 13% of patients without acute rejection (p=0.002). Acute rejection within 20 months of liver transplantation was identified as a significant risk factor for HCC recurrence in multivariate analysis (hazard ratio of 2.91). The authors suggested that more intensive monitoring for HCC recurrence may be appropriate for patients who have evidence of acute rejection.

The next study explored ways to identify patients who have HCC using PIVKA-II (prothrombin induced by vitamin K deficiency/antagonist – II), a promising marker that may be more sensitive/specific than AFP in identifying patients with liver cancer. Feng et al. used enzyme-linked immunosorbent assay (ELISA) to measure serum PIVKA-II levels in 168 patients with HCC, 150 patients with benign liver disease, and 153 healthy controls. Patients with HCC had significantly higher median PIVKA-II levels (181.50 mAu/mL), compared with atients with noncancerous liver disease (28.6 mAU/mL) or healthy controls 21.82 mAU/mL), with p<0.0001. In addition, PIVKA-II was more sensitive (83.9% vs 64.3%) and more specific (91.5% vs 84.7%) than AFP in identifying patients with HCC. When PIVKA-II and AFP were combined, sensitivity (81.95%) and specificity (89.3%) were increased more, suggesting that this combination of markers may be most useful in clinical practice to identify patients who have HCC.

Finally, in patients whose HCC was treated with orthotopic liver transplantation, acute organ rejection was found to be linked to HCC recurrence. Gul-Klein et al. identified 252 patients who underwent liver transplantation for HCC between 2001 and 2015, 91 of whom had confirmed acute rejection, and 47 of whom had recurrent HCC (the median time to HCC recurrence was 20 months). HCC recurrence was identified in 28.6% of patients with acute rejection, and in 13% of patients without acute rejection (p=0.002). Acute rejection within 20 months of liver transplantation was identified as a significant risk factor for HCC recurrence in multivariate analysis (hazard ratio of 2.91). The authors suggested that more intensive monitoring for HCC recurrence may be appropriate for patients who have evidence of acute rejection.

Immediate postpartum long-acting reversible contraception (LARC) represents a safe and effective contraceptive strategy. Despite national guidelines recommending universal patient access, hospitals face significant barriers to offering inpatient LARCs. It is unclear why some hospitals successfully implement immediate postpartum LARCs, while others do not.

Moniz et al conducted a comparative, multiple case study of immediate postpartum LARC implementation at eleven “early adopter” U.S. hospitals and analyzed each hospital’s implementation strategy to produce generalizable knowledge about how and under what circumstances implementation of immediate postpartum LARCs unfold successfully. Between 2017-2018, the authors conducted single-day site visits and 78 semi-structured interviews with a variety of stakeholders (clinician champions, nurses, pharmacists, revenue cycle staff, and hospital administration). On average, sites used 18 (range 11-22) implementation strategies, including assessing institutional readiness for, and barriers to, implementation of immediate postpartum LARC, engaging reproductive justice experts and community resources to address social determinants of health, involving patients in implementation planning, and developing quality monitoring processes to evaluate clinical processes and outcomes. The researchers found that successful implementation of immediate postpartum LARC required three essential conditions: effective implementation champions who are supported by a multidisciplinary implementation team; creating an enabling financial environment; and engaging hospital administration. Additional findings from this study call for more support for individuals leading change in complex care settings, intentionally designing implementation interventions that take into account local contextual influences, and meaningfully engaging patients in the implementation process.

Of postpartum women, 61% in low- and middle-income countries (LMIC) have an unmet contraceptive need and many face high rates of short interpregnancy intervals (Moore). Additionally, 51%-96% of postpartum women in LMIC use short-acting methods of contraception (Moore), further highlighting the need for increased access to immediate postpartum LARC in LMIC. Data on the use and continuation of immediate postpartum LARC in LMIC is limited. Marchin et al conducted a systematic review and meta-analysis to determine 6-month continuation rates of immediate postpartum LARCs among women in 69 low-income countries that were enrolled in the Family Planning 2020 initiative. The meta-analysis ultimately focused on the copper IUD due to the absence of relevant studies on other LARC methods. The meta-analysis of 12 studies resulted in a pooled 6-month continuation rate for immediate postpartum copper IUDs of 87%, a rate comparable to continuation rates found in higher-income countries. This estimate had significant heterogeneity between studies. Secondary outcomes of expulsion, removal, and infection rates were low at 6%, 5%, and 0.2% respectively. High 6-month continuation rates and a low rate of adverse outcomes suggest immediate postpartum copper IUD insertion represents a feasible and acceptable postpartum contraceptive option for women living in LMIC.

In cases where contraception methods fail, are used incorrectly, or are not used at all, emergency contraception (EC) can be used after intercourse to prevent pregnancy. Timely access to, and accurate knowledge of, EC are especially important for rural women who are more likely to experience an unintended pregnancy resulting in a live birth compared to urban women. Milkowski et al analyzed publicly available data from the National Survey of Family Growth to estimate differences in oral EC use, access, and counseling by rural-urban county of residence among U.S. women aged 15-44 years. 10% of rural and 19% of urban women who had ever been sexually active reported ever using EC pills. Over the course of the study period (2006-2017), the percentage of women reporting ever-use of EC increased linearly in both rural and urban populations, with the prevalence of EC ever-use more than doubling in each group. This observation likely reflects an overall increase in EC use during a time period in which the federal government enacted several policies to improve access to EC. The study findings also highlight the need for improved patient counseling on EC. While the overall prevalence of EC counseling was low among all women, rural women were less likely to have received counseling on EC when compared to urban women.

Although many studies report weight gain in users of progestin-only hormonal contraception (POC), a recent Cochrane systematic review found that there was insufficient evidence to determine the effect of POCs on weight (Lopez). Beksinska et al conducted a secondary analysis of prospective weight change among women enrolled in the Evidence for Contraceptive options and HIV Outcomes (ECHO) trial, which was an open label, prospective, randomized multicenter trial that compared the risk of HIV acquisition among women randomized to injectable contraception (DMPA), the copper IUD, or a second generation two rod levonorgestrel (LNG) implant Jadelle^Ò. This trial was conducted at 12 sites across four African countries between 2015 and 2018. Eligible study participants were nonpregnant, HIV negative, sexually active women aged 16-35 years who desired contraception. The final sample size included 7,014 women randomly assigned to receive DMPA (2,293), the LNG implant (2,372), or the copper IUD (2,349). Using a standardized protocol and calibrated equipment across all study sites, weight and height were measured at baseline and at study exit at 12, 15, or 18 months. The mean weight increased amongst all three contraceptive groups and was significantly different in magnitude, with the largest gain in the DMPA group (3.5 kg), 2.4 kg in the LNG implant group, and 1.5 kg in the copper IUD group. Unlike copper IUD users, women in the DMPA and LNG implant group continued to gain weight after 1 year of contraceptive use. It is noteworthy that, regardless of contraceptive method allocation, not all women gained weight and a small proportion of women lost weight. When choosing a contraceptive method, women using POCs should be counselled about the potential side effect of weight gain.

References:
Moniz MH, Bonawitz K, Wetmore MK, et al. Implementing immediate postpartum contraception: a comparative case study at 11 hospitals. Implement Sci Commun. 2021;2(1):42. Published 2021 Apr 12.

Moore Z, Pfitzer A, Gubin R, et al. Missed opportunities for family planning: an analysis of pregnancy risk and contraceptive method use among postpartum women in 21 low- and middle-income countries. Contraception 92 (2015): 31–39.
 

Marchin A, Moss A, Harrison M. A Meta-Analysis of Postpartum Copper IUD Continuation Rates in Low- and Middle-Income Countries. J Womens Health Dev. 2021;4(1):36-46.

Milkowski CM, Ziller EC, Ahrens KA. Rural-urban residence and emergency contraception use, access, and counseling in the United States, 2006-2017. Contracept X. 2021;3:100061.

Lopez L.M., Ramesh S., Chen M. Progestin-only contraceptives: effects on weight. Cochrane Database Syst Rev. 2016 doi: 10.1002/14651858.CD008815.pub2.

Beksinska et al. “Weight change among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: Findings from a randomised, multicentre, open-label trial. EClinicalMedicine. 2021;34:100800.

Immediate postpartum long-acting reversible contraception (LARC) represents a safe and effective contraceptive strategy. Despite national guidelines recommending universal patient access, hospitals face significant barriers to offering inpatient LARCs. It is unclear why some hospitals successfully implement immediate postpartum LARCs, while others do not.

Moniz et al conducted a comparative, multiple case study of immediate postpartum LARC implementation at eleven “early adopter” U.S. hospitals and analyzed each hospital’s implementation strategy to produce generalizable knowledge about how and under what circumstances implementation of immediate postpartum LARCs unfold successfully. Between 2017-2018, the authors conducted single-day site visits and 78 semi-structured interviews with a variety of stakeholders (clinician champions, nurses, pharmacists, revenue cycle staff, and hospital administration). On average, sites used 18 (range 11-22) implementation strategies, including assessing institutional readiness for, and barriers to, implementation of immediate postpartum LARC, engaging reproductive justice experts and community resources to address social determinants of health, involving patients in implementation planning, and developing quality monitoring processes to evaluate clinical processes and outcomes. The researchers found that successful implementation of immediate postpartum LARC required three essential conditions: effective implementation champions who are supported by a multidisciplinary implementation team; creating an enabling financial environment; and engaging hospital administration. Additional findings from this study call for more support for individuals leading change in complex care settings, intentionally designing implementation interventions that take into account local contextual influences, and meaningfully engaging patients in the implementation process.

Of postpartum women, 61% in low- and middle-income countries (LMIC) have an unmet contraceptive need and many face high rates of short interpregnancy intervals (Moore). Additionally, 51%-96% of postpartum women in LMIC use short-acting methods of contraception (Moore), further highlighting the need for increased access to immediate postpartum LARC in LMIC. Data on the use and continuation of immediate postpartum LARC in LMIC is limited. Marchin et al conducted a systematic review and meta-analysis to determine 6-month continuation rates of immediate postpartum LARCs among women in 69 low-income countries that were enrolled in the Family Planning 2020 initiative. The meta-analysis ultimately focused on the copper IUD due to the absence of relevant studies on other LARC methods. The meta-analysis of 12 studies resulted in a pooled 6-month continuation rate for immediate postpartum copper IUDs of 87%, a rate comparable to continuation rates found in higher-income countries. This estimate had significant heterogeneity between studies. Secondary outcomes of expulsion, removal, and infection rates were low at 6%, 5%, and 0.2% respectively. High 6-month continuation rates and a low rate of adverse outcomes suggest immediate postpartum copper IUD insertion represents a feasible and acceptable postpartum contraceptive option for women living in LMIC.

In cases where contraception methods fail, are used incorrectly, or are not used at all, emergency contraception (EC) can be used after intercourse to prevent pregnancy. Timely access to, and accurate knowledge of, EC are especially important for rural women who are more likely to experience an unintended pregnancy resulting in a live birth compared to urban women. Milkowski et al analyzed publicly available data from the National Survey of Family Growth to estimate differences in oral EC use, access, and counseling by rural-urban county of residence among U.S. women aged 15-44 years. 10% of rural and 19% of urban women who had ever been sexually active reported ever using EC pills. Over the course of the study period (2006-2017), the percentage of women reporting ever-use of EC increased linearly in both rural and urban populations, with the prevalence of EC ever-use more than doubling in each group. This observation likely reflects an overall increase in EC use during a time period in which the federal government enacted several policies to improve access to EC. The study findings also highlight the need for improved patient counseling on EC. While the overall prevalence of EC counseling was low among all women, rural women were less likely to have received counseling on EC when compared to urban women.

Although many studies report weight gain in users of progestin-only hormonal contraception (POC), a recent Cochrane systematic review found that there was insufficient evidence to determine the effect of POCs on weight (Lopez). Beksinska et al conducted a secondary analysis of prospective weight change among women enrolled in the Evidence for Contraceptive options and HIV Outcomes (ECHO) trial, which was an open label, prospective, randomized multicenter trial that compared the risk of HIV acquisition among women randomized to injectable contraception (DMPA), the copper IUD, or a second generation two rod levonorgestrel (LNG) implant Jadelle^Ò. This trial was conducted at 12 sites across four African countries between 2015 and 2018. Eligible study participants were nonpregnant, HIV negative, sexually active women aged 16-35 years who desired contraception. The final sample size included 7,014 women randomly assigned to receive DMPA (2,293), the LNG implant (2,372), or the copper IUD (2,349). Using a standardized protocol and calibrated equipment across all study sites, weight and height were measured at baseline and at study exit at 12, 15, or 18 months. The mean weight increased amongst all three contraceptive groups and was significantly different in magnitude, with the largest gain in the DMPA group (3.5 kg), 2.4 kg in the LNG implant group, and 1.5 kg in the copper IUD group. Unlike copper IUD users, women in the DMPA and LNG implant group continued to gain weight after 1 year of contraceptive use. It is noteworthy that, regardless of contraceptive method allocation, not all women gained weight and a small proportion of women lost weight. When choosing a contraceptive method, women using POCs should be counselled about the potential side effect of weight gain.

References:
Moniz MH, Bonawitz K, Wetmore MK, et al. Implementing immediate postpartum contraception: a comparative case study at 11 hospitals. Implement Sci Commun. 2021;2(1):42. Published 2021 Apr 12.

Moore Z, Pfitzer A, Gubin R, et al. Missed opportunities for family planning: an analysis of pregnancy risk and contraceptive method use among postpartum women in 21 low- and middle-income countries. Contraception 92 (2015): 31–39.
 

Marchin A, Moss A, Harrison M. A Meta-Analysis of Postpartum Copper IUD Continuation Rates in Low- and Middle-Income Countries. J Womens Health Dev. 2021;4(1):36-46.

Milkowski CM, Ziller EC, Ahrens KA. Rural-urban residence and emergency contraception use, access, and counseling in the United States, 2006-2017. Contracept X. 2021;3:100061.

Lopez L.M., Ramesh S., Chen M. Progestin-only contraceptives: effects on weight. Cochrane Database Syst Rev. 2016 doi: 10.1002/14651858.CD008815.pub2.

Beksinska et al. “Weight change among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: Findings from a randomised, multicentre, open-label trial. EClinicalMedicine. 2021;34:100800.

Immediate postpartum long-acting reversible contraception (LARC) represents a safe and effective contraceptive strategy. Despite national guidelines recommending universal patient access, hospitals face significant barriers to offering inpatient LARCs. It is unclear why some hospitals successfully implement immediate postpartum LARCs, while others do not.

Moniz et al conducted a comparative, multiple case study of immediate postpartum LARC implementation at eleven “early adopter” U.S. hospitals and analyzed each hospital’s implementation strategy to produce generalizable knowledge about how and under what circumstances implementation of immediate postpartum LARCs unfold successfully. Between 2017-2018, the authors conducted single-day site visits and 78 semi-structured interviews with a variety of stakeholders (clinician champions, nurses, pharmacists, revenue cycle staff, and hospital administration). On average, sites used 18 (range 11-22) implementation strategies, including assessing institutional readiness for, and barriers to, implementation of immediate postpartum LARC, engaging reproductive justice experts and community resources to address social determinants of health, involving patients in implementation planning, and developing quality monitoring processes to evaluate clinical processes and outcomes. The researchers found that successful implementation of immediate postpartum LARC required three essential conditions: effective implementation champions who are supported by a multidisciplinary implementation team; creating an enabling financial environment; and engaging hospital administration. Additional findings from this study call for more support for individuals leading change in complex care settings, intentionally designing implementation interventions that take into account local contextual influences, and meaningfully engaging patients in the implementation process.

Of postpartum women, 61% in low- and middle-income countries (LMIC) have an unmet contraceptive need and many face high rates of short interpregnancy intervals (Moore). Additionally, 51%-96% of postpartum women in LMIC use short-acting methods of contraception (Moore), further highlighting the need for increased access to immediate postpartum LARC in LMIC. Data on the use and continuation of immediate postpartum LARC in LMIC is limited. Marchin et al conducted a systematic review and meta-analysis to determine 6-month continuation rates of immediate postpartum LARCs among women in 69 low-income countries that were enrolled in the Family Planning 2020 initiative. The meta-analysis ultimately focused on the copper IUD due to the absence of relevant studies on other LARC methods. The meta-analysis of 12 studies resulted in a pooled 6-month continuation rate for immediate postpartum copper IUDs of 87%, a rate comparable to continuation rates found in higher-income countries. This estimate had significant heterogeneity between studies. Secondary outcomes of expulsion, removal, and infection rates were low at 6%, 5%, and 0.2% respectively. High 6-month continuation rates and a low rate of adverse outcomes suggest immediate postpartum copper IUD insertion represents a feasible and acceptable postpartum contraceptive option for women living in LMIC.

In cases where contraception methods fail, are used incorrectly, or are not used at all, emergency contraception (EC) can be used after intercourse to prevent pregnancy. Timely access to, and accurate knowledge of, EC are especially important for rural women who are more likely to experience an unintended pregnancy resulting in a live birth compared to urban women. Milkowski et al analyzed publicly available data from the National Survey of Family Growth to estimate differences in oral EC use, access, and counseling by rural-urban county of residence among U.S. women aged 15-44 years. 10% of rural and 19% of urban women who had ever been sexually active reported ever using EC pills. Over the course of the study period (2006-2017), the percentage of women reporting ever-use of EC increased linearly in both rural and urban populations, with the prevalence of EC ever-use more than doubling in each group. This observation likely reflects an overall increase in EC use during a time period in which the federal government enacted several policies to improve access to EC. The study findings also highlight the need for improved patient counseling on EC. While the overall prevalence of EC counseling was low among all women, rural women were less likely to have received counseling on EC when compared to urban women.

Although many studies report weight gain in users of progestin-only hormonal contraception (POC), a recent Cochrane systematic review found that there was insufficient evidence to determine the effect of POCs on weight (Lopez). Beksinska et al conducted a secondary analysis of prospective weight change among women enrolled in the Evidence for Contraceptive options and HIV Outcomes (ECHO) trial, which was an open label, prospective, randomized multicenter trial that compared the risk of HIV acquisition among women randomized to injectable contraception (DMPA), the copper IUD, or a second generation two rod levonorgestrel (LNG) implant Jadelle^Ò. This trial was conducted at 12 sites across four African countries between 2015 and 2018. Eligible study participants were nonpregnant, HIV negative, sexually active women aged 16-35 years who desired contraception. The final sample size included 7,014 women randomly assigned to receive DMPA (2,293), the LNG implant (2,372), or the copper IUD (2,349). Using a standardized protocol and calibrated equipment across all study sites, weight and height were measured at baseline and at study exit at 12, 15, or 18 months. The mean weight increased amongst all three contraceptive groups and was significantly different in magnitude, with the largest gain in the DMPA group (3.5 kg), 2.4 kg in the LNG implant group, and 1.5 kg in the copper IUD group. Unlike copper IUD users, women in the DMPA and LNG implant group continued to gain weight after 1 year of contraceptive use. It is noteworthy that, regardless of contraceptive method allocation, not all women gained weight and a small proportion of women lost weight. When choosing a contraceptive method, women using POCs should be counselled about the potential side effect of weight gain.

References:
Moniz MH, Bonawitz K, Wetmore MK, et al. Implementing immediate postpartum contraception: a comparative case study at 11 hospitals. Implement Sci Commun. 2021;2(1):42. Published 2021 Apr 12.

Moore Z, Pfitzer A, Gubin R, et al. Missed opportunities for family planning: an analysis of pregnancy risk and contraceptive method use among postpartum women in 21 low- and middle-income countries. Contraception 92 (2015): 31–39.
 

Marchin A, Moss A, Harrison M. A Meta-Analysis of Postpartum Copper IUD Continuation Rates in Low- and Middle-Income Countries. J Womens Health Dev. 2021;4(1):36-46.

Milkowski CM, Ziller EC, Ahrens KA. Rural-urban residence and emergency contraception use, access, and counseling in the United States, 2006-2017. Contracept X. 2021;3:100061.

Lopez L.M., Ramesh S., Chen M. Progestin-only contraceptives: effects on weight. Cochrane Database Syst Rev. 2016 doi: 10.1002/14651858.CD008815.pub2.

Beksinska et al. “Weight change among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: Findings from a randomised, multicentre, open-label trial. EClinicalMedicine. 2021;34:100800.

The association of RA and cardiovascular disease has been extensively described. Beta adrenergic receptors are not known to be involved in RA, though Abuhelwa et al. suggest a potential role in “immunologic balance” in their study of beta blocker use and RA remission. In a pooled analysis of five tocilizumab trials, use of beta blockers was associated with lower proportions of CDAI remission. However, without information on beta blocker dose or duration of therapy as well as potential confounding by indication, the significance of this finding is uncertain.

Another known association of RA and its treatment is malignancy, perhaps due to decrease in immunosurveillance; it remains a concern in choice of therapy and long-term effects. Solipuram et al. performed a systematic review of combination JAK inhibitor and methotrexate therapy in RA to evaluate the evidence regarding malignancy risk. Among the 13 trials included for analysis, 40 cases of malignancy were reported for over 3,600 patient-years in patients receiving combination therapy, compared to 7 cases among nearly 1,000 patient-years in patients receiving methotrexate alone; no change in relative risk was seen in non-melanomatous skin cancer or other cancers. While this information is reassuring, it does not eliminate the possibility of increased malignancy given variations in duration of followup in different studies.  There is also a need for longer follow-up because of a potential latency period before the development of cancer. Ideally, long-term extension studies could help better define this risk, though those studies tend to be single-armed and without a control.

Though different JAK inhibitors generally are thought to have similar efficacy and class-associated side effects, few studies have compared immunomodulatory effects of the medications. Reddig et al compared the effects of baricitinib, upadicitinib, filgotinib, tofacitinib, and methotrexate on cell proliferation, cell activation, and apoptosis, as well as induction of DNA damage and repair in an in vitro study. The study authors used human peripheral blood monocytes treated with phytohemagglutinin to activate T cells and induce proliferation. Tofacitinib, baricitinib, and upadicitinib were associated with comparable dose-dependent inhibition of lymphocyte activation and proliferation. Higher doses of filgotinib were required to obtain the same effect. Filgotinib at high concentrations also were associated with higher levels of DNA damage markers. These findings are interesting as to the shared mechanism of action of JAK inhibitors, regardless of JAK specificity. However, given the lack of “universal” patterns in vitro, their clinical importance or relevance in distinguishing between the medications is unclear.

Kim et al. investigates the pathogenesis of RA in their in vitro study of mast cells. Though previously identified in RA synovial fluid and tissue and not in OA synovium, their role is not entirely clear. Though normally associated with allergic responses, mast cells have been postulated to have pro- and anti-inflammatory effects, and release inflammatory cytokines and mediators, such as histamine. Synovial fluid and serum samples from RA and OA patients, as well as healthy volunteers, were analyzed for tryptase, chymase, and histamine; serum levels of all three were higher in RA than in OA patients and healthy volunteers. Synovial fluid levels of histamine were higher in RA. Cell culture studies were performed using IL-33 to activate human mast cells, causing an increase in tryptase –positive cells, as well as an increased expression of RANKL and MMP-9. This suggests a role for mast cells in osteoclastogenesis and tissue degradation. In addition to providing more information about the involvement of mast cells in RA pathogenesis, these findings suggest mast cells as a potential therapeutic target.

The association of RA and cardiovascular disease has been extensively described. Beta adrenergic receptors are not known to be involved in RA, though Abuhelwa et al. suggest a potential role in “immunologic balance” in their study of beta blocker use and RA remission. In a pooled analysis of five tocilizumab trials, use of beta blockers was associated with lower proportions of CDAI remission. However, without information on beta blocker dose or duration of therapy as well as potential confounding by indication, the significance of this finding is uncertain.

Another known association of RA and its treatment is malignancy, perhaps due to decrease in immunosurveillance; it remains a concern in choice of therapy and long-term effects. Solipuram et al. performed a systematic review of combination JAK inhibitor and methotrexate therapy in RA to evaluate the evidence regarding malignancy risk. Among the 13 trials included for analysis, 40 cases of malignancy were reported for over 3,600 patient-years in patients receiving combination therapy, compared to 7 cases among nearly 1,000 patient-years in patients receiving methotrexate alone; no change in relative risk was seen in non-melanomatous skin cancer or other cancers. While this information is reassuring, it does not eliminate the possibility of increased malignancy given variations in duration of followup in different studies.  There is also a need for longer follow-up because of a potential latency period before the development of cancer. Ideally, long-term extension studies could help better define this risk, though those studies tend to be single-armed and without a control.

Though different JAK inhibitors generally are thought to have similar efficacy and class-associated side effects, few studies have compared immunomodulatory effects of the medications. Reddig et al compared the effects of baricitinib, upadicitinib, filgotinib, tofacitinib, and methotrexate on cell proliferation, cell activation, and apoptosis, as well as induction of DNA damage and repair in an in vitro study. The study authors used human peripheral blood monocytes treated with phytohemagglutinin to activate T cells and induce proliferation. Tofacitinib, baricitinib, and upadicitinib were associated with comparable dose-dependent inhibition of lymphocyte activation and proliferation. Higher doses of filgotinib were required to obtain the same effect. Filgotinib at high concentrations also were associated with higher levels of DNA damage markers. These findings are interesting as to the shared mechanism of action of JAK inhibitors, regardless of JAK specificity. However, given the lack of “universal” patterns in vitro, their clinical importance or relevance in distinguishing between the medications is unclear.

Kim et al. investigates the pathogenesis of RA in their in vitro study of mast cells. Though previously identified in RA synovial fluid and tissue and not in OA synovium, their role is not entirely clear. Though normally associated with allergic responses, mast cells have been postulated to have pro- and anti-inflammatory effects, and release inflammatory cytokines and mediators, such as histamine. Synovial fluid and serum samples from RA and OA patients, as well as healthy volunteers, were analyzed for tryptase, chymase, and histamine; serum levels of all three were higher in RA than in OA patients and healthy volunteers. Synovial fluid levels of histamine were higher in RA. Cell culture studies were performed using IL-33 to activate human mast cells, causing an increase in tryptase –positive cells, as well as an increased expression of RANKL and MMP-9. This suggests a role for mast cells in osteoclastogenesis and tissue degradation. In addition to providing more information about the involvement of mast cells in RA pathogenesis, these findings suggest mast cells as a potential therapeutic target.

The association of RA and cardiovascular disease has been extensively described. Beta adrenergic receptors are not known to be involved in RA, though Abuhelwa et al. suggest a potential role in “immunologic balance” in their study of beta blocker use and RA remission. In a pooled analysis of five tocilizumab trials, use of beta blockers was associated with lower proportions of CDAI remission. However, without information on beta blocker dose or duration of therapy as well as potential confounding by indication, the significance of this finding is uncertain.

Another known association of RA and its treatment is malignancy, perhaps due to decrease in immunosurveillance; it remains a concern in choice of therapy and long-term effects. Solipuram et al. performed a systematic review of combination JAK inhibitor and methotrexate therapy in RA to evaluate the evidence regarding malignancy risk. Among the 13 trials included for analysis, 40 cases of malignancy were reported for over 3,600 patient-years in patients receiving combination therapy, compared to 7 cases among nearly 1,000 patient-years in patients receiving methotrexate alone; no change in relative risk was seen in non-melanomatous skin cancer or other cancers. While this information is reassuring, it does not eliminate the possibility of increased malignancy given variations in duration of followup in different studies.  There is also a need for longer follow-up because of a potential latency period before the development of cancer. Ideally, long-term extension studies could help better define this risk, though those studies tend to be single-armed and without a control.

Though different JAK inhibitors generally are thought to have similar efficacy and class-associated side effects, few studies have compared immunomodulatory effects of the medications. Reddig et al compared the effects of baricitinib, upadicitinib, filgotinib, tofacitinib, and methotrexate on cell proliferation, cell activation, and apoptosis, as well as induction of DNA damage and repair in an in vitro study. The study authors used human peripheral blood monocytes treated with phytohemagglutinin to activate T cells and induce proliferation. Tofacitinib, baricitinib, and upadicitinib were associated with comparable dose-dependent inhibition of lymphocyte activation and proliferation. Higher doses of filgotinib were required to obtain the same effect. Filgotinib at high concentrations also were associated with higher levels of DNA damage markers. These findings are interesting as to the shared mechanism of action of JAK inhibitors, regardless of JAK specificity. However, given the lack of “universal” patterns in vitro, their clinical importance or relevance in distinguishing between the medications is unclear.

Kim et al. investigates the pathogenesis of RA in their in vitro study of mast cells. Though previously identified in RA synovial fluid and tissue and not in OA synovium, their role is not entirely clear. Though normally associated with allergic responses, mast cells have been postulated to have pro- and anti-inflammatory effects, and release inflammatory cytokines and mediators, such as histamine. Synovial fluid and serum samples from RA and OA patients, as well as healthy volunteers, were analyzed for tryptase, chymase, and histamine; serum levels of all three were higher in RA than in OA patients and healthy volunteers. Synovial fluid levels of histamine were higher in RA. Cell culture studies were performed using IL-33 to activate human mast cells, causing an increase in tryptase –positive cells, as well as an increased expression of RANKL and MMP-9. This suggests a role for mast cells in osteoclastogenesis and tissue degradation. In addition to providing more information about the involvement of mast cells in RA pathogenesis, these findings suggest mast cells as a potential therapeutic target.

Two recently published studies added to our knowledge on the clinical benefit of gemtuzumab in patients with AML. The first study by Bouvier A et al demonstrated no survival benefit with the addition of gemtuzumab in patients with intermediate risk AML. The second study by Duncan et al was a retrospective study by the CIBMTR. That study demonstrated increased risk of VOD in pediatric patients who received gemtuzmab. However, overall survival and event free survival was similar in both groups. These results highlight the need for increased awareness post-transplant for the possibility of VOD, and also reduces concern regarding overall survival for patients receiving gemtuzumab.

Another study by the EBMT (Debaja et al) evaluated factors affecting the outcome of patients with AML receiving a second allogeneic HCT. Outcome was worse for patients not in CR and those with a short time from allo-HCT.  Overall survival was similar for patients receiving a MUD or haploidentical donor. Two year overall survival was 31% vs. 29% for patients receiving MUD vs. haploidentical allo-HCT. This study clearly expands options for patients receiving a second allo-HCT. In addition, a prior study by EBMT demonstrated no difference in overall survival between patients receiving same vs. different vs. haplo donor.

Finally, a large study by the CIBMTR (Percival et al) demonstrated that in AML patients, achieving CRi and having persistent MRD prior to transplantation were associated with worse outcome compared to CR with no evidence of MRD. The adjusted 5 year survival for patient with CR/MRD-ve, CR/MRD+ve, CRi/MRD-ve and CRi/MRD+ve was 52%, 37%, 44% and 34% respectively.

Two recently published studies added to our knowledge on the clinical benefit of gemtuzumab in patients with AML. The first study by Bouvier A et al demonstrated no survival benefit with the addition of gemtuzumab in patients with intermediate risk AML. The second study by Duncan et al was a retrospective study by the CIBMTR. That study demonstrated increased risk of VOD in pediatric patients who received gemtuzmab. However, overall survival and event free survival was similar in both groups. These results highlight the need for increased awareness post-transplant for the possibility of VOD, and also reduces concern regarding overall survival for patients receiving gemtuzumab.

Another study by the EBMT (Debaja et al) evaluated factors affecting the outcome of patients with AML receiving a second allogeneic HCT. Outcome was worse for patients not in CR and those with a short time from allo-HCT.  Overall survival was similar for patients receiving a MUD or haploidentical donor. Two year overall survival was 31% vs. 29% for patients receiving MUD vs. haploidentical allo-HCT. This study clearly expands options for patients receiving a second allo-HCT. In addition, a prior study by EBMT demonstrated no difference in overall survival between patients receiving same vs. different vs. haplo donor.

Finally, a large study by the CIBMTR (Percival et al) demonstrated that in AML patients, achieving CRi and having persistent MRD prior to transplantation were associated with worse outcome compared to CR with no evidence of MRD. The adjusted 5 year survival for patient with CR/MRD-ve, CR/MRD+ve, CRi/MRD-ve and CRi/MRD+ve was 52%, 37%, 44% and 34% respectively.

Two recently published studies added to our knowledge on the clinical benefit of gemtuzumab in patients with AML. The first study by Bouvier A et al demonstrated no survival benefit with the addition of gemtuzumab in patients with intermediate risk AML. The second study by Duncan et al was a retrospective study by the CIBMTR. That study demonstrated increased risk of VOD in pediatric patients who received gemtuzmab. However, overall survival and event free survival was similar in both groups. These results highlight the need for increased awareness post-transplant for the possibility of VOD, and also reduces concern regarding overall survival for patients receiving gemtuzumab.

Another study by the EBMT (Debaja et al) evaluated factors affecting the outcome of patients with AML receiving a second allogeneic HCT. Outcome was worse for patients not in CR and those with a short time from allo-HCT.  Overall survival was similar for patients receiving a MUD or haploidentical donor. Two year overall survival was 31% vs. 29% for patients receiving MUD vs. haploidentical allo-HCT. This study clearly expands options for patients receiving a second allo-HCT. In addition, a prior study by EBMT demonstrated no difference in overall survival between patients receiving same vs. different vs. haplo donor.

Finally, a large study by the CIBMTR (Percival et al) demonstrated that in AML patients, achieving CRi and having persistent MRD prior to transplantation were associated with worse outcome compared to CR with no evidence of MRD. The adjusted 5 year survival for patient with CR/MRD-ve, CR/MRD+ve, CRi/MRD-ve and CRi/MRD+ve was 52%, 37%, 44% and 34% respectively.

One of the most important goals in the treatment of patients with CP-CML is to avoid the progression to advanced phases, such as accelerated and blast phase, where the treatments are limited and the outcomes inferior. The long term outcomes of patients with lymphoid blast crisis treated with HyperCVAD plus dasatinib was recently reported by Morita et al. The authors reviewed 85 patients (23 with CML- LBP and 62 with newly diagnosed Ph- positive ALL) who received hyper- CVAD plus dasatinib. In the CML- LBP cohort, 19 had prior chronic myeloid leukemia as chronic phase (n = 17; 74%), accelerated phase (n = 1; 4%), or myeloid blastic phase (n = 1; 4%); 4 (17%) presented with de novo CML- LBP. Patients with CML- LBP were less likely to achieve deep molecular remission than patients with Ph- positive ALL. The major molecular response (MMR) rates were 70% and 95%, respectively (P = .007), and the complete molecular response (CMR) rates were 55% and 74%, respectively (P = .16). However, the survival outcomes were similar for CML- LBP and Ph- positive ALL: The 5- year overall survival (OS) rates were 59% and 48%, respectively (P = .97). Allogeneic stem cell transplantation was associated with a better outcome in CML- LBP (5- year OS rate, 88% vs 57%; P = .04), while in Ph- positive ALL, the outcome was driven by deeper molecular remission: the 5- year OS rates were 63% and 25% with CMR and MMR, respectively (P = .002). Although the outcome of CML- LBP has improved with hyper- CVAD plus dasatinib therapy with survival comparable to that of Ph- positive ALL, data with third generation TKI may even improve these outcomes in the near future.

Allogeneic BMT is the ultimate therapy for resistant or intolerant to TKI patients with CP-CML as well as for advances phases of this disease. Since the introduction of TKI the rates of allo BMT had overall decreased, so Yassine and colleagues performed a systematic review/meta-analysis of the available literature to assess the evidence regarding allo-HCT efficacy in CP-CML patients. Data from eligible studies were extracted in relation to benefits (overall survival [OS], progression-free survival, disease-free survival [DFS], complete remission [CR], and molecular response [MR]) and harms (nonrelapse mortality [NRM], relapse, and acute and chronic graft-versus-host disease) and stratified by age into adult and pediatric groups. Overall for adult allo-HCT recipients, the pooled OS, DFS, CR and, MR were 84%, 66%, 56%, and 88%, respectively. Pooled NRM and relapse were 20% and 19%, respectively. As a conclusion, these results suggest that allo-HCT still is an effective treatment for TKI-resistant or TKI-intolerant CP-CML and the risk-befit ratio is favorable based on the lack of other alternatives.

One of the most important goals in the treatment of patients with CP-CML is to avoid the progression to advanced phases, such as accelerated and blast phase, where the treatments are limited and the outcomes inferior. The long term outcomes of patients with lymphoid blast crisis treated with HyperCVAD plus dasatinib was recently reported by Morita et al. The authors reviewed 85 patients (23 with CML- LBP and 62 with newly diagnosed Ph- positive ALL) who received hyper- CVAD plus dasatinib. In the CML- LBP cohort, 19 had prior chronic myeloid leukemia as chronic phase (n = 17; 74%), accelerated phase (n = 1; 4%), or myeloid blastic phase (n = 1; 4%); 4 (17%) presented with de novo CML- LBP. Patients with CML- LBP were less likely to achieve deep molecular remission than patients with Ph- positive ALL. The major molecular response (MMR) rates were 70% and 95%, respectively (P = .007), and the complete molecular response (CMR) rates were 55% and 74%, respectively (P = .16). However, the survival outcomes were similar for CML- LBP and Ph- positive ALL: The 5- year overall survival (OS) rates were 59% and 48%, respectively (P = .97). Allogeneic stem cell transplantation was associated with a better outcome in CML- LBP (5- year OS rate, 88% vs 57%; P = .04), while in Ph- positive ALL, the outcome was driven by deeper molecular remission: the 5- year OS rates were 63% and 25% with CMR and MMR, respectively (P = .002). Although the outcome of CML- LBP has improved with hyper- CVAD plus dasatinib therapy with survival comparable to that of Ph- positive ALL, data with third generation TKI may even improve these outcomes in the near future.

Allogeneic BMT is the ultimate therapy for resistant or intolerant to TKI patients with CP-CML as well as for advances phases of this disease. Since the introduction of TKI the rates of allo BMT had overall decreased, so Yassine and colleagues performed a systematic review/meta-analysis of the available literature to assess the evidence regarding allo-HCT efficacy in CP-CML patients. Data from eligible studies were extracted in relation to benefits (overall survival [OS], progression-free survival, disease-free survival [DFS], complete remission [CR], and molecular response [MR]) and harms (nonrelapse mortality [NRM], relapse, and acute and chronic graft-versus-host disease) and stratified by age into adult and pediatric groups. Overall for adult allo-HCT recipients, the pooled OS, DFS, CR and, MR were 84%, 66%, 56%, and 88%, respectively. Pooled NRM and relapse were 20% and 19%, respectively. As a conclusion, these results suggest that allo-HCT still is an effective treatment for TKI-resistant or TKI-intolerant CP-CML and the risk-befit ratio is favorable based on the lack of other alternatives.

One of the most important goals in the treatment of patients with CP-CML is to avoid the progression to advanced phases, such as accelerated and blast phase, where the treatments are limited and the outcomes inferior. The long term outcomes of patients with lymphoid blast crisis treated with HyperCVAD plus dasatinib was recently reported by Morita et al. The authors reviewed 85 patients (23 with CML- LBP and 62 with newly diagnosed Ph- positive ALL) who received hyper- CVAD plus dasatinib. In the CML- LBP cohort, 19 had prior chronic myeloid leukemia as chronic phase (n = 17; 74%), accelerated phase (n = 1; 4%), or myeloid blastic phase (n = 1; 4%); 4 (17%) presented with de novo CML- LBP. Patients with CML- LBP were less likely to achieve deep molecular remission than patients with Ph- positive ALL. The major molecular response (MMR) rates were 70% and 95%, respectively (P = .007), and the complete molecular response (CMR) rates were 55% and 74%, respectively (P = .16). However, the survival outcomes were similar for CML- LBP and Ph- positive ALL: The 5- year overall survival (OS) rates were 59% and 48%, respectively (P = .97). Allogeneic stem cell transplantation was associated with a better outcome in CML- LBP (5- year OS rate, 88% vs 57%; P = .04), while in Ph- positive ALL, the outcome was driven by deeper molecular remission: the 5- year OS rates were 63% and 25% with CMR and MMR, respectively (P = .002). Although the outcome of CML- LBP has improved with hyper- CVAD plus dasatinib therapy with survival comparable to that of Ph- positive ALL, data with third generation TKI may even improve these outcomes in the near future.

Allogeneic BMT is the ultimate therapy for resistant or intolerant to TKI patients with CP-CML as well as for advances phases of this disease. Since the introduction of TKI the rates of allo BMT had overall decreased, so Yassine and colleagues performed a systematic review/meta-analysis of the available literature to assess the evidence regarding allo-HCT efficacy in CP-CML patients. Data from eligible studies were extracted in relation to benefits (overall survival [OS], progression-free survival, disease-free survival [DFS], complete remission [CR], and molecular response [MR]) and harms (nonrelapse mortality [NRM], relapse, and acute and chronic graft-versus-host disease) and stratified by age into adult and pediatric groups. Overall for adult allo-HCT recipients, the pooled OS, DFS, CR and, MR were 84%, 66%, 56%, and 88%, respectively. Pooled NRM and relapse were 20% and 19%, respectively. As a conclusion, these results suggest that allo-HCT still is an effective treatment for TKI-resistant or TKI-intolerant CP-CML and the risk-befit ratio is favorable based on the lack of other alternatives.

Potential advantages of a neoadjuvant systemic therapy approach including downstaging of the primary breast tumor and axilla, as well the ability to assess tumor response which can have prognostic and adjuvant therapy implications. Samiei and colleagues performed a systematic review and meta-analysis of 33 studies (57,531 patients) in the neoadjuvant setting to assess axillary pathologic complete response (pCR) rates among clinically node-positive breast cancer of various subtypes. HR-negative/HER2-positive subtype was associated with the highest pCR rate (60%) followed by 59% for HER2-positive, 48% for triple-negative, 45% for HR+/HER2-positive, 35% for luminal B, 18% for HR+/HER2-negative, and 13% for luminal A. Achievement of axillary pCR after pre-operative chemotherapy has been associated with improvement in relapse-free survival and overall survival. Furthermore, this data stimulates consideration of less invasive axillary staging in certain patients pending chemotherapy response, and the contribution of breast cancer subtype and impact on outcomes deserves further investigation.

Chemotherapy-induced alopecia (CIA) during breast cancer treatment can affect an individual’s perception of their own appearance, body image, overall health and therefore may impact quality of life. Wang et al performed a meta-analysis including 27 studies with 2,202 participants and demonstrated a 61% effectiveness rate of scalp cooling to protect hair loss. The effectiveness rates of scalp cooling when taxanes and anthracyclines were used alone were higher compared to combination therapy (74% for taxanes, 66% for anthracyclines, and 54% for combination). A prospective study including 139 patients treated with anthracycline chemotherapy for breast cancer receiving scalp cooling found a 43% success rate (hair loss £50%). It is important to consider chemotherapy regimen, side effects (headache, dizziness, pain, nausea), resources and cost when counseling patients regarding scalp cooling. Future studies exploring ways to address these potential challenges will be beneficial to improve patient access and tolerance to scalp cooling.

Obesity is associated with increased risk of various types of cancers, and can have a detrimental effect on cancer prognosis as well as treatment response and tolerance. Potential mechanisms to explain the relationship between obesity, physical activity and breast cancer prognosis include increased levels of sex and metabolic hormones, alteration in adipokine levels, and increased inflammation, oxidative stress and angiogenesis. A retrospective cohort study including 6,481 patients with an initial non-metastatic breast cancer diagnosis, majority of whom were overweight (33.4%) or obese (33.8%), observed increasing BMI (for every 5 kg/m² BMI increase) was associated with an increased risk of second cancer development (7%, RR=1.07; p=0.01), obesity-related cancer (13%, RR=1.13; p<0.001), second breast cancer (11%, RR=1.11; p0.01) and second ER-positive breast cancer (15%, RR1.15; p0.008). There are several ongoing clinical trials that are examining the impact of diet and weight loss interventions on breast cancer outcomes (DIANA-5, B-AHEAD3, Breast Cancer Weight Loss Study). These studies will be key to counseling and empowering patients to address potentially modifiable variables that can positively impact their health.

References:

Kalinsky K, Diamond JR, Vahdat LT, Tolaney SM, Juric D, O’Shaughnessy J, Moroose RL, Mayer IA, Abramson VG, Goldengerg DM, Sharkey RM, Maliakel P, Hong Q, Goswami T, Wegener WA, Bardia A. Sacituzumab govitecan in previously treated hormone receptor-positive/ HER2-negative metastatic breast cancer: final results from a phase I/II, single-arm, basket trial. Ann Oncol. 2020;31:1709-1718.

Mougalian SS, Hernandez M, Lei X, Lynch S, Kuerer HM, Symmans WF, Theriault RL, Fornage BD, Hsu L, Buchholz TA, Sahin AA, Hunt KK, Yang WT, Hortobagyi GN, Valero V. Ten-year outcomes of patients with breast cancer with cytologically confirmed axillary lymph node metastases and pathologic complete response after primary systemic chemotherapy. JAMA Oncol. 2016;2:508-516.

Munzone M, Bagnardi V, Campennì G, Mazzocco K, Pagan E, Tramacere A, Masiero M, Iorfida M, Mazza M, Montagna E, Cancello G, Bianco N, Palazzo A, Cardillo A, Dellapasqua S, Sangalli C, Pettini G, Pravettoni G, Colleoni M, Veronesi P. Preventing chemotherapy-induced alopecia: a prospective clinical trial on the efficacy and safety of a scalp-cooling system in early breast cancer patients treated with anthracyclines. Br J Cancer. 2019;121:325–331.

McTiernan A. Weight, physical activity and breast cancer survival. Proc Nutr Soc. 2018;77:403–411.

Potential advantages of a neoadjuvant systemic therapy approach including downstaging of the primary breast tumor and axilla, as well the ability to assess tumor response which can have prognostic and adjuvant therapy implications. Samiei and colleagues performed a systematic review and meta-analysis of 33 studies (57,531 patients) in the neoadjuvant setting to assess axillary pathologic complete response (pCR) rates among clinically node-positive breast cancer of various subtypes. HR-negative/HER2-positive subtype was associated with the highest pCR rate (60%) followed by 59% for HER2-positive, 48% for triple-negative, 45% for HR+/HER2-positive, 35% for luminal B, 18% for HR+/HER2-negative, and 13% for luminal A. Achievement of axillary pCR after pre-operative chemotherapy has been associated with improvement in relapse-free survival and overall survival. Furthermore, this data stimulates consideration of less invasive axillary staging in certain patients pending chemotherapy response, and the contribution of breast cancer subtype and impact on outcomes deserves further investigation.

Chemotherapy-induced alopecia (CIA) during breast cancer treatment can affect an individual’s perception of their own appearance, body image, overall health and therefore may impact quality of life. Wang et al performed a meta-analysis including 27 studies with 2,202 participants and demonstrated a 61% effectiveness rate of scalp cooling to protect hair loss. The effectiveness rates of scalp cooling when taxanes and anthracyclines were used alone were higher compared to combination therapy (74% for taxanes, 66% for anthracyclines, and 54% for combination). A prospective study including 139 patients treated with anthracycline chemotherapy for breast cancer receiving scalp cooling found a 43% success rate (hair loss £50%). It is important to consider chemotherapy regimen, side effects (headache, dizziness, pain, nausea), resources and cost when counseling patients regarding scalp cooling. Future studies exploring ways to address these potential challenges will be beneficial to improve patient access and tolerance to scalp cooling.

Obesity is associated with increased risk of various types of cancers, and can have a detrimental effect on cancer prognosis as well as treatment response and tolerance. Potential mechanisms to explain the relationship between obesity, physical activity and breast cancer prognosis include increased levels of sex and metabolic hormones, alteration in adipokine levels, and increased inflammation, oxidative stress and angiogenesis. A retrospective cohort study including 6,481 patients with an initial non-metastatic breast cancer diagnosis, majority of whom were overweight (33.4%) or obese (33.8%), observed increasing BMI (for every 5 kg/m² BMI increase) was associated with an increased risk of second cancer development (7%, RR=1.07; p=0.01), obesity-related cancer (13%, RR=1.13; p<0.001), second breast cancer (11%, RR=1.11; p0.01) and second ER-positive breast cancer (15%, RR1.15; p0.008). There are several ongoing clinical trials that are examining the impact of diet and weight loss interventions on breast cancer outcomes (DIANA-5, B-AHEAD3, Breast Cancer Weight Loss Study). These studies will be key to counseling and empowering patients to address potentially modifiable variables that can positively impact their health.

References:

Kalinsky K, Diamond JR, Vahdat LT, Tolaney SM, Juric D, O’Shaughnessy J, Moroose RL, Mayer IA, Abramson VG, Goldengerg DM, Sharkey RM, Maliakel P, Hong Q, Goswami T, Wegener WA, Bardia A. Sacituzumab govitecan in previously treated hormone receptor-positive/ HER2-negative metastatic breast cancer: final results from a phase I/II, single-arm, basket trial. Ann Oncol. 2020;31:1709-1718.

Mougalian SS, Hernandez M, Lei X, Lynch S, Kuerer HM, Symmans WF, Theriault RL, Fornage BD, Hsu L, Buchholz TA, Sahin AA, Hunt KK, Yang WT, Hortobagyi GN, Valero V. Ten-year outcomes of patients with breast cancer with cytologically confirmed axillary lymph node metastases and pathologic complete response after primary systemic chemotherapy. JAMA Oncol. 2016;2:508-516.

Munzone M, Bagnardi V, Campennì G, Mazzocco K, Pagan E, Tramacere A, Masiero M, Iorfida M, Mazza M, Montagna E, Cancello G, Bianco N, Palazzo A, Cardillo A, Dellapasqua S, Sangalli C, Pettini G, Pravettoni G, Colleoni M, Veronesi P. Preventing chemotherapy-induced alopecia: a prospective clinical trial on the efficacy and safety of a scalp-cooling system in early breast cancer patients treated with anthracyclines. Br J Cancer. 2019;121:325–331.

McTiernan A. Weight, physical activity and breast cancer survival. Proc Nutr Soc. 2018;77:403–411.

Potential advantages of a neoadjuvant systemic therapy approach including downstaging of the primary breast tumor and axilla, as well the ability to assess tumor response which can have prognostic and adjuvant therapy implications. Samiei and colleagues performed a systematic review and meta-analysis of 33 studies (57,531 patients) in the neoadjuvant setting to assess axillary pathologic complete response (pCR) rates among clinically node-positive breast cancer of various subtypes. HR-negative/HER2-positive subtype was associated with the highest pCR rate (60%) followed by 59% for HER2-positive, 48% for triple-negative, 45% for HR+/HER2-positive, 35% for luminal B, 18% for HR+/HER2-negative, and 13% for luminal A. Achievement of axillary pCR after pre-operative chemotherapy has been associated with improvement in relapse-free survival and overall survival. Furthermore, this data stimulates consideration of less invasive axillary staging in certain patients pending chemotherapy response, and the contribution of breast cancer subtype and impact on outcomes deserves further investigation.

Chemotherapy-induced alopecia (CIA) during breast cancer treatment can affect an individual’s perception of their own appearance, body image, overall health and therefore may impact quality of life. Wang et al performed a meta-analysis including 27 studies with 2,202 participants and demonstrated a 61% effectiveness rate of scalp cooling to protect hair loss. The effectiveness rates of scalp cooling when taxanes and anthracyclines were used alone were higher compared to combination therapy (74% for taxanes, 66% for anthracyclines, and 54% for combination). A prospective study including 139 patients treated with anthracycline chemotherapy for breast cancer receiving scalp cooling found a 43% success rate (hair loss £50%). It is important to consider chemotherapy regimen, side effects (headache, dizziness, pain, nausea), resources and cost when counseling patients regarding scalp cooling. Future studies exploring ways to address these potential challenges will be beneficial to improve patient access and tolerance to scalp cooling.

Obesity is associated with increased risk of various types of cancers, and can have a detrimental effect on cancer prognosis as well as treatment response and tolerance. Potential mechanisms to explain the relationship between obesity, physical activity and breast cancer prognosis include increased levels of sex and metabolic hormones, alteration in adipokine levels, and increased inflammation, oxidative stress and angiogenesis. A retrospective cohort study including 6,481 patients with an initial non-metastatic breast cancer diagnosis, majority of whom were overweight (33.4%) or obese (33.8%), observed increasing BMI (for every 5 kg/m² BMI increase) was associated with an increased risk of second cancer development (7%, RR=1.07; p=0.01), obesity-related cancer (13%, RR=1.13; p<0.001), second breast cancer (11%, RR=1.11; p0.01) and second ER-positive breast cancer (15%, RR1.15; p0.008). There are several ongoing clinical trials that are examining the impact of diet and weight loss interventions on breast cancer outcomes (DIANA-5, B-AHEAD3, Breast Cancer Weight Loss Study). These studies will be key to counseling and empowering patients to address potentially modifiable variables that can positively impact their health.

References:

Kalinsky K, Diamond JR, Vahdat LT, Tolaney SM, Juric D, O’Shaughnessy J, Moroose RL, Mayer IA, Abramson VG, Goldengerg DM, Sharkey RM, Maliakel P, Hong Q, Goswami T, Wegener WA, Bardia A. Sacituzumab govitecan in previously treated hormone receptor-positive/ HER2-negative metastatic breast cancer: final results from a phase I/II, single-arm, basket trial. Ann Oncol. 2020;31:1709-1718.

Mougalian SS, Hernandez M, Lei X, Lynch S, Kuerer HM, Symmans WF, Theriault RL, Fornage BD, Hsu L, Buchholz TA, Sahin AA, Hunt KK, Yang WT, Hortobagyi GN, Valero V. Ten-year outcomes of patients with breast cancer with cytologically confirmed axillary lymph node metastases and pathologic complete response after primary systemic chemotherapy. JAMA Oncol. 2016;2:508-516.

Munzone M, Bagnardi V, Campennì G, Mazzocco K, Pagan E, Tramacere A, Masiero M, Iorfida M, Mazza M, Montagna E, Cancello G, Bianco N, Palazzo A, Cardillo A, Dellapasqua S, Sangalli C, Pettini G, Pravettoni G, Colleoni M, Veronesi P. Preventing chemotherapy-induced alopecia: a prospective clinical trial on the efficacy and safety of a scalp-cooling system in early breast cancer patients treated with anthracyclines. Br J Cancer. 2019;121:325–331.

McTiernan A. Weight, physical activity and breast cancer survival. Proc Nutr Soc. 2018;77:403–411.

Human leukocyte antigen (HLA)-mismatched hematopoetic stem cell microtransplantation (MST) has previously been evaluated in AML in combination with chemotherapy and suggests potential improvement in outcomes. Li et al evaluated MST combined with decitabine in patients with intermediate or high risk MDS compared to decitabine alone.  Out of 22 patients in the study, the cohort that received MST with decitabine had higher median OS (24 vs 14.2 months, p=0.04), although there was no statistical significant difference in overall response rate. There was no reported graft vs host disease, and adverse events were similar between the two groups. The main limitation of the study was the very small sample size; further prospective studies utilizing MST in MDS are needed to demonstrate benefit.

MDS patients often present with neutropenia and develop worsening neutropenia due to myelosuppression from HMA therapy, resulting in increased risk of infections including invasive fungal infection (IFI). Tey et al reported a retrospective analysis of the rate of IFI in patients with MDS or low blast count AML receiving azacitidine. Out of 117 patients, 61% received antifungal prophylaxis, either with posaconazole (n=70) or voriconazole (n=1). The IFI rate was 7.7% in the cohort with median time of onset of 74 days from start of azacitidine treatment (range 1-226); the IFI rate did not differ statistically between those receiving prophylaxis vs not (5.6% vs 10.9%, p=0.30). However, presence of neutropenia at three months of treatment was associated with increased IFI risk (HR 8.29, p=0.01), and IFI was associated with increased mortality in a multivariate analysis (HR 8.37, p<0.0001). Anti-fungal prophylaxis is currently standard practice for MDS patients who present or develop neutropenia; however, HMA treatment is associated with prolonged neutropenia due to myelosuppression and time to response. A more effective therapy with less myelosuppression is needed for treatment of MDS.

Human leukocyte antigen (HLA)-mismatched hematopoetic stem cell microtransplantation (MST) has previously been evaluated in AML in combination with chemotherapy and suggests potential improvement in outcomes. Li et al evaluated MST combined with decitabine in patients with intermediate or high risk MDS compared to decitabine alone.  Out of 22 patients in the study, the cohort that received MST with decitabine had higher median OS (24 vs 14.2 months, p=0.04), although there was no statistical significant difference in overall response rate. There was no reported graft vs host disease, and adverse events were similar between the two groups. The main limitation of the study was the very small sample size; further prospective studies utilizing MST in MDS are needed to demonstrate benefit.

MDS patients often present with neutropenia and develop worsening neutropenia due to myelosuppression from HMA therapy, resulting in increased risk of infections including invasive fungal infection (IFI). Tey et al reported a retrospective analysis of the rate of IFI in patients with MDS or low blast count AML receiving azacitidine. Out of 117 patients, 61% received antifungal prophylaxis, either with posaconazole (n=70) or voriconazole (n=1). The IFI rate was 7.7% in the cohort with median time of onset of 74 days from start of azacitidine treatment (range 1-226); the IFI rate did not differ statistically between those receiving prophylaxis vs not (5.6% vs 10.9%, p=0.30). However, presence of neutropenia at three months of treatment was associated with increased IFI risk (HR 8.29, p=0.01), and IFI was associated with increased mortality in a multivariate analysis (HR 8.37, p<0.0001). Anti-fungal prophylaxis is currently standard practice for MDS patients who present or develop neutropenia; however, HMA treatment is associated with prolonged neutropenia due to myelosuppression and time to response. A more effective therapy with less myelosuppression is needed for treatment of MDS.

Human leukocyte antigen (HLA)-mismatched hematopoetic stem cell microtransplantation (MST) has previously been evaluated in AML in combination with chemotherapy and suggests potential improvement in outcomes. Li et al evaluated MST combined with decitabine in patients with intermediate or high risk MDS compared to decitabine alone.  Out of 22 patients in the study, the cohort that received MST with decitabine had higher median OS (24 vs 14.2 months, p=0.04), although there was no statistical significant difference in overall response rate. There was no reported graft vs host disease, and adverse events were similar between the two groups. The main limitation of the study was the very small sample size; further prospective studies utilizing MST in MDS are needed to demonstrate benefit.

MDS patients often present with neutropenia and develop worsening neutropenia due to myelosuppression from HMA therapy, resulting in increased risk of infections including invasive fungal infection (IFI). Tey et al reported a retrospective analysis of the rate of IFI in patients with MDS or low blast count AML receiving azacitidine. Out of 117 patients, 61% received antifungal prophylaxis, either with posaconazole (n=70) or voriconazole (n=1). The IFI rate was 7.7% in the cohort with median time of onset of 74 days from start of azacitidine treatment (range 1-226); the IFI rate did not differ statistically between those receiving prophylaxis vs not (5.6% vs 10.9%, p=0.30). However, presence of neutropenia at three months of treatment was associated with increased IFI risk (HR 8.29, p=0.01), and IFI was associated with increased mortality in a multivariate analysis (HR 8.37, p<0.0001). Anti-fungal prophylaxis is currently standard practice for MDS patients who present or develop neutropenia; however, HMA treatment is associated with prolonged neutropenia due to myelosuppression and time to response. A more effective therapy with less myelosuppression is needed for treatment of MDS.

Interestingly the authors propose possible causative mechanisms. They note that normal pancreatic secretion is regulated by neural and endocrine control mechanisms that require intact gastro-pancreatico-duodenal anatomy. Disruptions to this include “extensive pancreatic denervation because of lymph node dissection and truncal vagotomy, the asynchronous release of pancreatic enzymes for food particles (pancreaticocibal-asynchrony) because of newly made reconstructions, and gastric reservoir and neural gastric stimulation losses.” They also include the possibility of effects of adjuvant therapies as well. 

While 64% of this patient population had some form of EPI, another study from this month’s selection by Sridhar et al out of Vellore, India tells a different story. In this cross-sectional study, they looked at symptomatic and biochemical evidence of EPI on pre and post questionnaires following gastric resection for adenocarcinoma. Of 27 patients that completed pre and post questionnaires, none of the patients on short-term follow-up (mean follow up of 3 months) had clinical symptoms of EPI following gastric resection. However, more than a third of the patients developed asymptomatic EPI after gastric resection, based on FE testing. The authors conclude that pancreatic supplementation might not be necessary following gastric resection, but perhaps their follow up window was much too short to draw such a conclusion. 

Interestingly the authors propose possible causative mechanisms. They note that normal pancreatic secretion is regulated by neural and endocrine control mechanisms that require intact gastro-pancreatico-duodenal anatomy. Disruptions to this include “extensive pancreatic denervation because of lymph node dissection and truncal vagotomy, the asynchronous release of pancreatic enzymes for food particles (pancreaticocibal-asynchrony) because of newly made reconstructions, and gastric reservoir and neural gastric stimulation losses.” They also include the possibility of effects of adjuvant therapies as well. 

While 64% of this patient population had some form of EPI, another study from this month’s selection by Sridhar et al out of Vellore, India tells a different story. In this cross-sectional study, they looked at symptomatic and biochemical evidence of EPI on pre and post questionnaires following gastric resection for adenocarcinoma. Of 27 patients that completed pre and post questionnaires, none of the patients on short-term follow-up (mean follow up of 3 months) had clinical symptoms of EPI following gastric resection. However, more than a third of the patients developed asymptomatic EPI after gastric resection, based on FE testing. The authors conclude that pancreatic supplementation might not be necessary following gastric resection, but perhaps their follow up window was much too short to draw such a conclusion. 

Interestingly the authors propose possible causative mechanisms. They note that normal pancreatic secretion is regulated by neural and endocrine control mechanisms that require intact gastro-pancreatico-duodenal anatomy. Disruptions to this include “extensive pancreatic denervation because of lymph node dissection and truncal vagotomy, the asynchronous release of pancreatic enzymes for food particles (pancreaticocibal-asynchrony) because of newly made reconstructions, and gastric reservoir and neural gastric stimulation losses.” They also include the possibility of effects of adjuvant therapies as well. 

While 64% of this patient population had some form of EPI, another study from this month’s selection by Sridhar et al out of Vellore, India tells a different story. In this cross-sectional study, they looked at symptomatic and biochemical evidence of EPI on pre and post questionnaires following gastric resection for adenocarcinoma. Of 27 patients that completed pre and post questionnaires, none of the patients on short-term follow-up (mean follow up of 3 months) had clinical symptoms of EPI following gastric resection. However, more than a third of the patients developed asymptomatic EPI after gastric resection, based on FE testing. The authors conclude that pancreatic supplementation might not be necessary following gastric resection, but perhaps their follow up window was much too short to draw such a conclusion.