Publications

BACKGROUND: Surgery is the only curative option for patients with neuroendocrine tumors (NET) and is also indicated for debulking of liver metastasis. Intraoperative carcinoid crisis (CC) is thought to be a potentially lethal complication. Though perioperative octreotide is often recommended for prevention, recent NET society guidelines raised concerns regarding limited data supporting its use. We sought to evaluate existing evidence characterizing CC and evaluating the efficacy of prophylactic octreotide.

METHODS: A systematic review was performed on studies including patients having surgery for well-differentiated NET and/or NET liver metastasis (2000-2021), and reporting data on the incidence, risk factors, or prognosis of CC, and/or use of prophylactic octreotide. Meta-analysis was performed using random-effects models.

RESULTS: Eight studies met inclusion criteria (n = 943 operations). The pooled incidence of CC was 19% (95% CI [0.06-0.36]). Liver metastasis (odds ratio 2.85 [1.49-5.47]) and gender (male 0.58 [0.34-0.99]) were the only significant risk factors. The occurrence of CC was associated with increased risk of major postoperative complications (2.12 [1.03-4.35]). The use of prophylactic octreotide was not associated with decreased risk of CC (0.73 [0.32-1.66]). Notably, there was no standard prophylactic octreotide strategy used.

CONCLUSIONS: Intraoperative carcinoid crisis is a common complication occurring in up to 20% of patients with midgut NET and/or liver metastasis undergoing surgery. Prophylactic octreotide may not provide an efficient way to prevent this complication. Future studies should focus on prospective evaluation of well-defined prophylactic protocols using a standardized definition for CC.

Over the past decade, therapeutic options in multiple myeloma (MM) have changed dramatically. Given the unprecedented efficacy of novel agents, the role of hematopoietic cell transplantation (HCT) in MM remains under scrutiny. Rapid advances in myeloma immunotherapy including the recent approval of chimeric antigen receptor (CAR) T-cell therapy will impact the MM therapeutic landscape. The American Society for Transplantation and Cellular Therapy convened an expert panel to formulate clinical practice recommendations for role, timing, and sequencing of autologous (auto-HCT), allogeneic (allo-HCT) and CAR T-cell therapy for patients with newly diagnosed (NDMM) and relapsed/refractory MM (RRMM). The RAND-modified Delphi method was used to generate consensus statements. Twenty consensus statements were generated. The panel endorsed continued use of auto-HCT consolidation for patients with NDMM as a standard-of-care option, whereas in the front line allo-HCT and CAR-T were not recommended outside the setting of clinical trial. For patients not undergoing auto-HCT upfront, the panel recommended its use in first relapse. Lenalidomide as a single agent was recommended for maintenance especially for standard risk patients. In the RRMM setting, the panel recommended the use of CAR-T in patients with 4 or more prior lines of therapy. The panel encouraged allo-HCT in RRMM setting only in the context of clinical trial. The panel found RAND-modified Delphi methodology effective in providing a formal framework for developing consensus recommendations for the timing and sequence of cellular therapies for MM.

OBJECTIVE: To describe the self-reported needs of family caregivers of service members and veterans (SMVs) who sustained a traumatic brain injury (TBI) and to identify predictors of the unmet family caregiver needs.

SETTING: Five Department of Veterans Affairs (VA) Polytrauma Rehabilitation Centers (PRCs).

PARTICIPANTS: Family caregivers of SMVs enrolled in the VA PRC TBI Model Systems (TBIMS) national database who were within their first 5 years post-TBI ( n = 427).

DESIGN: Observational study.

MAIN OUTCOME MEASURE: The Family Needs Questionnaire-Revised (FNQ-R) was completed by each SMV's designated caregiver.

ANALYSES: Descriptive analyses were conducted on the FNQ-R responses at the item, domain, and total score levels. Unadjusted univariable and adjusted multivariable regression models were fitted to identify predictors of total unmet needs and unmet family need domains.

RESULTS: FNQ-R item-level and domain-level descriptive results indicated that health information was the most frequently met need domain. In contrast, emotional and instrumental support domains were the least often met. On average, family caregivers reported that 59.2% of the 37 FNQ-R needs were met at the time of the follow-up assessment. Regression models indicated that both the number of SMV-perceived environmental barriers and whether the SMV received mental health treatment within the past year predicted the number of unmet FNQ-R needs. SMV-reported environmental barriers predicted increased unmet needs in all 6 family caregiver domains, and SMV mental health treatment in the past year predicted more unmet family caregiver emotional support, community support, and professional support needs.

CONCLUSIONS: The current findings can be used to inform policy and programming for VA and Department of Defense to proactively address the specific needs of families and caregivers experienced in the first 5 years post-TBI.

This article provides a systematic assessment of the efficacy, risks, and methodological quality of evidence from five major publicly available vaccine trials. Results from Pfizer-BioNTech mRNA, Moderna-US NIH mRN-1273, AstraZeneca-Oxford ChAdOx1 nCov-19, Gamaleya GamCovidVac (Sputnik V), and Ad26.COV2.S Johnson & Johnson vaccines were included. Extracted benefits and risks data from each trial were summarized using the GRADE approach denoting the overall certainty of evidence along with relative and absolute effects. Relative risk reduction across all five vaccine trials ranged from 45% to 96%. Absolute risk reduction in symptomatic COVID-19 ranged from 6 to 17 per 1000 across trials. None of the vaccines were associated with a significant increase in serious adverse events compared to placebo. The overall certainty of evidence varied from low to moderate. All five vaccines are effective and safe, but suggest room for improvement in the conduct of large-scale vaccine trials. Certainty of evidence was downrated due to risk of bias, which can be mitigated by improving transparency and thoroughness in conduct and reporting of outcomes.

PURPOSE: Medical student mistreatment is pervasive, yet whether all physicians have a shared understanding of the problem is unclear. The authors presented professionally designed trigger videos to physicians from 6 different specialties to determine if they perceive mistreatment and its severity similarly.

METHOD: From October 2016 to August 2018, resident and attending physicians from 10 U.S. medical schools viewed 5 trigger videos showing behaviors that could be perceived as mistreatment. They completed a survey exploring their perceptions. The authors compared perceptions of mistreatment across specialties and, for each scenario, evaluated the relationship between specialty and perception of mistreatment.

RESULTS: Six-hundred fifty resident and attending physicians participated. There were statistically significant differences in perception of mistreatment across specialties for 3 of the 5 scenarios: aggressive questioning (range, 74.1%-91.2%), negative feedback (range, 25.4%-63.7%), and assignment of inappropriate tasks (range, 5.5%-25.5%) (P ≤ .001, for all). After adjusting for gender, race, professional role, and prior mistreatment, physicians in surgery viewed 3 scenarios (aggressive questioning, negative feedback, and inappropriate tasks) as less likely to represent mistreatment compared with internal medicine physicians. Physicians from obstetrics-gynecology and "other" specialties perceived less mistreatment in 2 scenarios (aggressive questioning and negative feedback), while family physicians perceived more mistreatment in 1 scenario (negative feedback) compared with internal medicine physicians. The mean severity of perceived mistreatment on a 1 to 7 scale (7 most serious) also varied statistically significantly across the specialties for 3 scenarios: aggressive questioning (range, 4.4-5.4; P < .001), ethnic insensitivity (range, 5.1-6.1; P = .001), and sexual harassment (range, 5.5-6.3; P = .004).

CONCLUSIONS: Specialty was associated with differences in the perception of mistreatment and rating of its severity. Further investigation is needed to understand why these perceptions of mistreatment vary among specialties and how to address these differences.

Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only known treatment modality that can offer the possibility of cure for acute myeloid leukemia (AML). Unfortunately, relapse and disease progression still occur in more than one third of cases even when patients are allografted in complete hematologic remission (CR). Treatment of AML relapsing after a first allo-HCT is particularly challenging. A second allo-HCT is offered to patients considered fit for the procedure, but reported outcomes have been conflicting. To perform a systematic review and meta-analysis to assess the totality of evidence on the role of a second allo-HCT in patients with AML, we performed a comprehensive literature search using PUBMED/MEDLINE and EMBASE on August 25, 2021, and extracted clinical outcome data relating to benefits (CR, overall survival [OS], and progression-free/disease-free survival [PFS/DFS]) and harms (acute and chronic graft-versus-host disease, non-relapse mortality [NRM], and relapse). The search identified 821 studies. Only 20 studies (n = 2772 patients) met our inclusion criteria. A second allo-HCT resulted in pooled CR, OS, PFS/DFS, NRM and relapse rates of 67%, 34%, 30%, 27%, and 51%, respectively. OS was 2-fold higher when the second allo-HCT was performed in CR (38% versus 17%) and 3-fold higher in patients who had a later relapse from the first allo-HCT (34% versus 10%). There was no apparent difference in pooled OS (hazard ratio = 1.01; 95% confidence interval, 0.78-1.31; P = .94) whether the same original donor or a different one was used. Notwithstanding several limitations apart from the high heterogeneity among included studies, this analysis shows that a second allo-HCT is a reasonable treatment option for relapsed AML. The procedure appears to be more effective when performed in CR and in patients who had a later relapse from the first allo-HCT. The high pooled relapse rates exceeding 50%, even when receiving the second allo-HCT in CR is worrisome and emphasizes the need to incorporate new therapies whether as post-transplantation maintenance or consolidation to mitigate relapse risk. This analysis was limited to patients receiving a second allo-HCT for the sole purpose of treating AML relapse. Accordingly, we caution against extrapolating these findings to other indications such as treatment of graft failure, poor graft function, or mixed donor chimerism.

Approximately 15-20% of chronic myeloid leukemia (CML) patients fail tyrosine kinase inhibitor (TKI) therapy secondary to resistance or intolerance. In the pre-TKI era, front-line allogeneic hematopoietic cell transplantation (allo- HCT) represented the standard approach for patients with chronic phase-CML (CP-CML) who were deemed fit to tolerate the procedure and had a human leukocyte antigen compatible donor available. Currently, CP-CML patients are eligible for allo-HCT only if they fail more than one TKI and/or are intolerant to the drug. We 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. For adult allo-HCT recipients, the pooled OS, DFS, CR and, MR were 84% [95% confidence interval (CI) 59-99%], 66% (95% CI 59-73%), 56% (95% CI 30-80%), and 88% (95% CI 62-98%), respectively. Pooled NRM and relapse were 20% (95% CI 15-26%) and 19% (95% CI 10-28%), respectively. For the pediatric group, the OS rate was reported in one study and was 91% (95% CI 72-99%). Our results suggest that allo-HCT is an effective treatment for TKI-resistant or TKI-intolerant CP-CML. Post-transplant strategies are still needed to further mitigate the risk of relapse.

Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for patients with malignant and benign hematologic conditions. Graft-versus-host disease (GVHD) is a known complication of allo-HCT that results in significant morbidity and mortality. A common GVHD prophylaxis strategy combines a calcineurin inhibitor with methotrexate. When mucositis and organ toxicity develop, the day +11 dose is frequently omitted to limit further organ damage. The potential impact of this practice on allo-HCT outcomes is unclear as published data show conflicting results. Thus, we performed a systematic review/meta-analysis of the available literature to assess the impact of omitting day +11 methotrexate on allo-HCT recipients. Data were extracted in relation to benefits (overall survival [OS], progression-free survival [PFS]) and harms (acute and chronic GVHD, non-relapse mortality [NRM], and relapse). Pooled OS rate favored those who received day +11 methotrexate vs. those who did not (HR = 1.21; 95% CI = 1.02-1.43; p = 0.03). There was no significant difference in pooled rates of PFS (HR = 0.96; 95% CI = 0.60-1.52; p = 0.85), acute GVHD (HR = 1.03; 95% CI = 0.35-2.98; p = 0.96), chronic GVHD (HR = 0.83; 95% CI = 0.44-1.57; p = 0.57), NRM (HR = 0.86; 95% CI = 0.67-1.11; p = 0.25), and relapse (HR = 0.97; 95% CI = 0.75-1.26; p = 0.83) between the two groups. Large prospective multicenter studies are needed to better define the significance of day +11 methotrexate omission.

BACKGROUND: The presence of an inguinal hernia has been associated with an increased risk of identifying colon cancer, and therefore colonoscopy is recommended prior to inguinal hernia repair. However, the evidence on the association between the presence of an inguinal hernia and colon cancer is conflicting and uncertain. We performed a systematic review and meta-analysis to synthesize all available evidence on this topic.

METHODS: A comprehensive search of PubMed and EMBASE was performed. Any comparative study (case-control or cohort study) comparing the rate of colon cancer detection in patients with and without inguinal hernias who underwent screening colonoscopy or flexible sigmoidoscopy was eligible for inclusion. Data were extracted and pooled under a random effects model.

RESULTS: The initial search identified 692 references, of which 4 comparative studies (1462 patients) met the inclusion criteria. The overall risk of bias in the included studies was low. Pooled results showed a statistically non-significant difference in the incidence of detection of colon cancer, with patients with inguinal hernia having a 1.26 times increased likelihood of colon cancer diagnosis compared with patients without inguinal hernia (odds ratio (OR) 1.26; 95% confidence interval (CI) 0.63-2.51; P = 0.51). Although patients with inguinal hernia were also 1.23 times more likely to be diagnosed with colon polyps compared to patients without inguinal hernia, this difference was statistically non-significant (OR 1.23; 95% CI 0.94-1.60; P = 0.12).

CONCLUSION: The findings from this first systematic review and meta-analysis show that there is no difference in the incidence of either colon cancer or colon polyps in patients presenting with inguinal hernias compared to those without. Nevertheless, larger prospective studies are needed to further investigate the relationship between the risk of colon cancer or polyps and the presence of inguinal hernia.

INTRODUCTION: Special Operations Forces (SOF) personnel are at increased risk for traumatic brain injury (TBI), when compared with conventional forces (CF). Prior studies of TBI in military samples have not typically investigated SOF vs. CF as specific subgroups, despite documented differences in premorbid resilience and post-injury comorbidity burden. The aim of the current study was to compare SOF vs. CF on the presence of neurobehavioral symptoms after TBI, as well as factors influencing perception of symptom intensity.

MATERIALS AND METHODS: This study conducted an analysis of the prospective veterans affairs (VA) TBI Model Systems Cohort, which includes service members and veterans (SM/V) who received inpatient rehabilitation for TBI at one of the five VA Polytrauma Rehabilitation Centers. Of those with known SOF status (N = 342), 129 participants identified as SOF (average age = 43 years, 98% male) and 213 identified as CF (average age = 38.7 years, 91% male). SOF vs. CF were compared on demographics, injury characteristics, and psychological and behavioral health symptoms. These variables were then used to predict neurobehavioral symptom severity in univariable and multivariable analyses.

RESULTS: SOF personnel reported significantly greater posttraumatic stress disorder (PTSD) symptoms but less alcohol and drug use than the CF. SOF also reported greater neurobehavioral symptoms. When examining those with TBIs of all severities, SOF status was not associated with neurobehavioral symptom severity, while race, mechanism of TBI, and PTSD symptoms were. When examining only those with mTBI, SOF status was associated with lower neurobehavioral symptoms, while PTSD severity, white race, and certain mechanisms of injury were associated with greater neurobehavioral symptoms.

CONCLUSIONS: Among those receiving inpatient treatment for TBI, SOF SM/V reported higher neurobehavioral and symptom severity. PTSD was the strongest predictor of neurobehavioral symptoms and should be considered an important treatment target in both SOF and CF with co-morbid PTSD/TBI. A proactive human performance approach towards identification and treatment of psychological and neurobehavioral symptoms is recommended for SOF.