Association Between Immunoparesis and Treatment Outcomes of Patients With Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis.

BACKGROUND: Immunoparesis, defined as suppression of uninvolved polyclonal immunoglobulins, occurs in up to 80% of patients with newly diagnosed multiple myeloma (NDMM). Infections are the second most common cause of mortality in this population, yet evidence regarding prognostic impact of immunoparesis in NDMM remains unclear. MATERIALS AND METHODS: Using a prepublished protocol (CRD42022308687), we searched seven bibliographic databases from inception to February 2023 for studies reporting the impact of immunoparesis on clinical outcomes among adults with NDMM. The primary outcome of interest was overall survival (OS) and secondary outcomes were progression free survival (PFS) and infection risk. Effect sizes were quantified in terms of hazards ratio (HR) and pooled across studies using a random effects restricted maximum likelihood method. Heterogeneity was assessed using Cochran Q and the I2 statistic. Publication bias was assessed using contour enhanced funnel plots. RESULTS: Of 5175 studies screened, 7 studies involving 6091 patients met our search criteria. Immunoparesis was not associated with worse OS (pooled hazard ratio 1.30; 95% CI, 0.91-1.84; P-value .11), with significant heterogeneity among the studies (I2 = 72.9%; Cochran's Q P-value .003). However, immunoparesis was associated with a significantly worse PFS (pooled hazard ratio 1.42; 95% CI 1.11-1.82; p value 0.013), with moderate heterogeneity (I2 statistic = 51%; Cochran's Q P-value .056). Infection rates were not uniformly reported precluding meta-analysis. Visual examination of funnel plot revealed the possibility of publication bias. CONCLUSION: Overall, our findings suggest that immunoparesis did not have a detrimental impact on OS, but was associated with a significantly shorter PFS. Further studies are needed to understand the complexity of immune system perturbations in NDMM.

"Peace of Mind" After Mastectomy: A Scoping Review.

BACKGROUND: Many women eligible for breast conservation therapy (BCT) elect unilateral mastectomy (UM) with or without contralateral prophylactic mastectomy (CPM) and cite a desire for "peace of mind." This study aimed to characterize how peace of mind is defined and measured and how it relates to surgical choice. METHODS: Nine databases were searched for relevant articles through 8 October 2023, and data were extracted from articles meeting the inclusion criteria. RESULTS: The inclusion criteria were met by 20 studies. Most were prospective cohort studies (65%, 13/20). In the majority of the studies (72%, 13/18), Non-Hispanic white/Caucasian women comprised 80 % or more of the study's sample. Almost half of the studies used the phrase "peace of mind" in their publication (45%, 9/20), and few directly defined the construct (15%, 3/20). Instead, words representing an absence of peace of mind were common, specifically, "anxiety" (85%, 17/20), "fear" (75%, 15/20), and "concern" (75%, 15/20). Most of the studies (90%, 18/20) measured peace of mind indirectly using questionnaires validated for anxiety, fear, worry, distress, or concern, which were administered at multiple postoperative time points (55%, 11/20). Most of the studies (95%, 18/19) reported at least one statistically significant result showing no difference in peace of mind between BCT, UM, and/or CPM at their latest time of assessment. CONCLUSION: Peace of mind is largely framed around concepts that suggest its absence, namely, anxiety, fear, and concern. Existing literature suggests that peace of mind does not differ among average-risk women undergoing BCT, UM, or CPM. Shared surgical decisions should emphasize at least comparable emotional and/or psychosocial well-being between CPM and breast conservation.

Low skeletal muscle mass and treatment outcomes among adults with haematologic malignancies: A systematic review and meta-analysis.

BACKGROUND: Low skeletal muscle mass (LSMM) and/or, function associated with an increased risk of treatment-related toxicities and inferior overall survival (OS) among adults with solid malignancies. However, the association between LSMM and treatment-related toxicities among adults with haematologic malignancies remains unclear. METHODS: Using a pre-published protocol (CRD42020197814), we searched seven bibliographic databases from inception to 08/2021 for studies reporting the impact of LSMM among adults ≥18 years with a known haematologic malignancy. The primary outcome of interest was OS, and secondary outcomes included progression free survival (PFS) and non-relapse mortality (NRM). These effect sizes were quantified in terms of hazards ratio (HR) along with 95% confidence interval (CI) and pooled across studies using a DerSimonian-Laird random-effects model. Heterogeneity was assessed using the Cochran's Q and the I2 statistic. All hypothesis testing was two-sided with an alpha of 0.05. RESULTS: Of 3791 studies screened, we identified 20 studies involving 3468 patients with a mean age of 60 years; 44% were female and the most common malignancy was diffuse large B-cell lymphoma (42%). Most studies measured muscle mass using single slice computed tomography imaging at the L3 level. The presence of LSMM was associated with worse OS (pooled HR = 1.81, 95% CI = 1.48-2.22, P < 0.001) with moderate heterogeneity (Cochran's Q, I2 = 60.4%), PFS (pooled HR = 1.61, 95% CI = 1.28-2.02, P < 0.001) with moderate heterogeneity (Cochran's Q, I2 = 66.0%). Similarly, LSMM was associated with worse NRM (HR = 1.72, 95% CI = 1.34-2.22, P < 0.001) with little evidence of heterogeneity (Cochran's Q, I2 = 0.0%). CONCLUSIONS: LSMM is associated with worse survival outcomes among adults with haematologic malignancies. Further research into understanding the underlying mechanism of this association and mitigating the negative effects of LSMM among adults with haematologic malignancies is needed.

Disparities in race, ethnicity, sex, and age inclusion in pancreatic cancer screening studies: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Substantial differences exist in pancreatic cancer outcomes across ethnoracial stratifications. We sought to assess racial, ethnic, sex, and age reporting and inclusion of participants in pancreatic cancer screening studies. METHODS: A systematic search of Cochrane Library, Ovid Embase, Google Scholar, Ovid MEDLINE, PubMed, Scopus, and Web of Science Core Collection from inception to 2022 was conducted. Original studies on pancreatic cancer screening were identified and assessed for reporting and inclusion on race, ethnicity, sex, and age. The pooled proportions of study participants for these characteristics were calculated and compared with population-based benchmarks. RESULTS: Among 27 eligible pancreatic cancer screening studies, 26 reported data on either sex, race, or ethnicity, with a total of 5273 participants. Information on participant sex was reported by 26, race by 12, and ethnicity by 8 studies. Participants in these studies were almost all white (pooled proportion, 93.1%; 95% confidence interval [CI], 89.7-96.4) and non-Latino (pooled proportion, 97.4%; 95% CI, 94.0-100), and these groups were over-represented when compared with the general population. Female participants were well represented, with a pooled proportion of 63.2% (95% CI, 59.9-66.6). When reported, mean or median participant age was <60 years. Meta-regression revealed higher proportions of female participants in studies from the United States (P = .002). No association between increasing participation of racial or ethnic under-represented populations and study quality, ascending year of publication, or source of study funding was noted. CONCLUSIONS: Substantial disparities in race, ethnicity, sex, and age reporting and inclusion in pancreatic cancer studies were noted, even among high-quality and publicly funded studies.

Gender Disparity in Full Professor Rank Among Academic Physicians: A Systematic Review and Meta-Analysis.

PURPOSE: The gender gap in promotion in academic medicine is well established. However, few studies have reported gender differences in promotion adjusted for scholarly production and national or international reputation, namely, career duration, publications, grant funding, and leadership positions. The authors performed a systematic review and meta-analysis of the differences between men and women in achieving benchmarks for promotion and analyze where such differences lie geographically and within specialties. METHOD: A systematic search of Academic Search Premier, Business Source Complete, Cochrane Library, ERIC, GenderWatch, Google Scholar, Embase, MEDLINE, PubMed, Scopus, and Web of Science was conducted from inception to August 17, 2022. All studies that reported the number of male and female full professors on medical school faculty were included. The primary outcome was the adjusted odds ratio (AOR) for promotion to full professor for women compared with men. RESULTS: Two hundred forty-four studies met the inclusion criteria. The unadjusted OR for promotion to full professor for women was 0.38 (95% confidence interval [CI], 0.36-0.41). Sixteen studies reported an AOR. The pooled AOR of promotion for women to full professor was 0.60 (95% CI, 0.46-0.77). The AOR for promotion to full professor was 0.55 (95% CI, 0.34-0.88) in surgery and 0.80 (95% CI, 0.57-1.11) in internal medicine. Statistical heterogeneity was high ( Q = 66.6, I2 = 79.4%, P < .001). On meta-regression, 77% of the heterogeneity was from studies outside the United States, where more disparity was reported (AOR, 0.29; 95% CI, 0.22-0.38). CONCLUSIONS: Most studies continued to find decreased promotion of women. Gender disparity was particularly notable in surgery and in studies from outside the United States. The results suggest that differences in promotion were due to differences in productivity and leadership and to gender bias.

Systematic Review of Interventions Addressing Racial and Ethnic Disparities in Cancer Care and Health Outcomes.

PURPOSE: Cancer health disparities result from complex interactions among socioeconomic, behavioral, and biological factors, disproportionately affecting marginalized racial and ethnic groups. The objective of this review is to synthesize existing evidence on interventions addressing racial or ethnic disparities in cancer-related health care access and clinical outcomes. METHODS: A comprehensive search of Cochrane Library, Google Scholar, Ovid MEDLINE, Ovid Embase, PubMed, Scopus, and Web of Science Core Collection was conducted from database inception to February 23, 2023. Controlled vocabulary and keywords helped to identify studies on cancer-related disparities and interventions in adults age 18 years or older. Two reviewers followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis reporting guidelines. Study quality was assessed using the Joanna Briggs Institute Critical Appraisal Tool. RESULTS: Of 7,526 screened studies, 34 met the inclusion criteria involving 24,134 participants. Most studies focused on breast cancer (n = 17) and Hispanic/Latino populations (n = 10) and enrolled participants primarily from community-based sites (n = 19). Twenty-one studies examined patient-centered outcomes, such as health-related quality of life and psychological well-being, while 15 studies assessed process-of-care outcomes, such as timeliness of care. Most studies followed a community-based participatory research framework. Five patient-centered outcome studies reported a positive intervention effect, often combining cancer education with psychological well-being interventions. Among the 15 process-of-care outcome studies, nine reported positive effects, with the majority (n = 8) being navigation-based interventions. CONCLUSION: This systematic review emphasizes the vital role of community partnerships in addressing racial and ethnic disparities in oncology care and highlights the need for standardized approaches in intervention research because of the heterogeneity of studied interventions. Furthermore, the prevailing emphasis on breast cancer and Hispanic populations indicates the need for future investigations into other priority demographic groups.

A state-of-the-art review of quality-of-life assessment in venous disease.

OBJECTIVE: Chronic venous disease is a common condition and has a significant impact on patients' health status. Validated patient-reported outcome measures (PROMs) used to assess health status are needed to measure health status. This state-of-the-art review summarizes the current validation evidence for disease-specific PROMs for chronic venous disease and provides a framework for their use in the clinical setting. METHODS: A literature search in OVID Embase and Medline was conducted to identify relevant English-language studies of chronic venous disease that used disease-specific PROMs between January 1, 1993, and June 30, 2022. Abstracts and titles from identified studies were screened by four investigators, and full-text articles were subsequently screened for eligibility. Data on validation of disease-specific PROMs was abstracted from each included article. Classical test theory was used as a framework to examine a priori defined validation criteria for content validity, reliability (construct validity, internal reliability, and test-retest reliability), responsiveness, and expansion of the validation evidence base (use in randomized controlled trials and comparative effectiveness research, cultural or linguistic translations, predictive validity, or establishing the minimal clinically important difference threshold, defined as smallest amount an outcome or measure is perceived as a meaningful change to patients). The PROMs were categorized into three groups based on the manifestations of disease of the population for which they were developed. The overall validity of each PROM was assessed across three stages of validation including content validity (phase 1); construct validity, reliability, and responsiveness (phase 2); and expansion of the validation evidence base (phase 3). RESULTS: Of 2338 unique studies screened, 112 studies (4.8%) met inclusion criteria. The eight disease-specific PROMs identified were categorized into three groups: (1) overall chronic venous disease (C1 to C6); (2) C1 to C4 disease; and (3) C5 to C6 disease. Assessed by group, the Chronic Venous Insufficiency Questionnaire met criteria for validation at all three phases for patients with C1 to C4 disease, and the Charing Cross Venous Ulcer Questionnaire met criteria for validation at all three phases for patients with C5 to C6 disease. There were no PROMs that met all criteria for validation for use in overall chronic venous disease (C1 to C6). CONCLUSIONS: Of the eight PROMs assessed in this review, only two met prespecified criteria at each phase for validation. The Chronic Venous Insufficiency Questionnaire and Charing Cross Venous Ulcer Questionnaire should be considered for use in patients with chronic venous disease without venous ulcers and with venous ulcers, respectively.

Do Polygenic Risk Scores Add to Clinical Data in Predicting Pancreatic Cancer? A Scoping Review.

BACKGROUND: Polygenic risk scores (PRS) summarize an individual's germline genetic risk, but it is unclear whether PRS offer independent information for pancreatic cancer risk prediction beyond routine clinical data. METHODS: We searched 8 databases from database inception to March 10, 2023 to identify studies evaluating the independent performance of pancreatic cancer-specific PRS for pancreatic cancer beyond clinical risk factors. RESULTS: Twenty-one studies examined associations between a pancreatic cancer-specific PRS and pancreatic cancer. Seven studies evaluated risk factors beyond age and sex. Three studies evaluated the change in discrimination associated with the addition of PRS to routine risk factors and reported improvements (AUCs: 0.715 to 0.745; AUC 0.791 to 0.830; AUC from 0.694 to 0.711). Limitations to clinical applicability included using source populations younger/healthier than those at risk for pancreatic cancer (n = 10), exclusively of European ancestry (n = 13), or controls without relevant exposures (n = 1). CONCLUSIONS: While most studies of pancreatic cancer-specific PRS did not evaluate the independent discrimination of PRS for pancreatic cancer beyond routine risk factors, three that did showed improvements in discrimination. IMPACT: For pancreatic cancer PRS to be clinically useful, they must demonstrate substantial improvements in discrimination beyond established risk factors, apply to diverse ancestral populations representative of those at risk for pancreatic cancer, and use appropriate controls.

Offspring neurodevelopmental outcomes born to parents with chronic inflammatory arthritis using antirheumatic therapies: A scoping review.

INTRODUCTION: Most women with rheumatic diseases discontinue antirheumatic therapies in anticipation of, or during pregnancy due to concerns around medication safety and fetal wellbeing. OBJECTIVE: We performed a scoping review of available evidence investigating the risks of adverse offspring neurodevelopmental outcomes amongst parents with chronic inflammatory arthritis, taking antirheumatic therapies during conception or pregnancy. METHODS: We designed a scoping review protocol and search strategy a priori in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We performed an exhaustive search in Cochrane Library, Embase, Google Scholar, Medline, and Web of Science for relevant literature in January 2023. Articles needed to include offspring neurodevelopmental outcomes born to parents with CIA who took antirheumatic therapies during conception or pregnancy. Independent reviewers extracted data from eligible articles using a standard abstraction tool and performed critical appraisal of study quality. RESULTS: Six studies were included for full data abstraction. Use of Nonsteroidal Anti-inflammatory Drugs, Tumor Necrosis Factor Alpha inhibitors, and exposure to methotrexate during early first trimester of pregnancy did not seem to increase risk for adverse offspring neurodevelopmental outcomes. Corticosteroid use during pregnancy seemed to pose an increased risk for attention deficit hyperactive disorders in offspring. CONCLUSION: Use of some antirheumatic therapies during pregnancy may not be associated with adverse offspring neurodevelopmental outcomes. Further investigations are needed to elucidate if other confounding factors affect long term offspring health outcomes born to parents with chronic inflammatory arthritis.

Endometrial responses to bacterial and viral infection: a scoping review.

BACKGROUND: The endometrium is a highly dynamic tissue that undergoes dramatic proliferation and differentiation monthly in order to prepare the uterus for implantation and pregnancy. Intrauterine infection and inflammation are being increasingly recognized as potential causes of implantation failure and miscarriage, as well as obstetric complications later in gestation. However, the mechanisms by which the cells of the endometrium respond to infection remain understudied and recent progress is slowed in part owing to similar overlapping studies being performed in different species. OBJECTIVE AND RATIONALE: The aim of this scoping review is to systematically summarize all published studies in humans and laboratory animals that have investigated the innate immune sensing and response of the endometrium to bacteria and viruses, and the signaling mechanisms involved. This will enable gaps in our knowledge to be identified to inform future studies. SEARCH METHODS: The Cochrane Library, Ovid Embase/Medline, PubMed, Scopus, Google Scholar, and Web of Science databases were searched using a combination of controlled and free text terms for uterus/endometrium, infections, and fertility to March 2022. All primary research papers that have reported on endometrial responses to bacterial and viral infections in the context of reproduction were included. To focus the scope of the current review, studies in domesticated animals, included bovine, porcine, caprine, feline, and canine species were excluded. OUTCOMES: This search identified 42 728 studies for screening and 766 full-text studies were assessed for eligibility. Data was extracted from 76 studies. The majority of studies focused on endometrial responses to Escherichia coli and Chlamydia trachomatis, with some studies of Neisseria gonorrhea, Staphylococcus aureus, and the Streptococcus family. Endometrial responses have only been studied in response to three groups of viruses thus far: HIV, Zika virus, and the herpesvirus family. For most infections, both cellular and animal models have been utilized in vitro and in vivo, focusing on endometrial production of cytokines, chemokines, and antiviral/antimicrobial factors, and the expression of innate immune signaling pathway mediators after infection. This review has identified gaps for future research in the field as well as highlighted some recent developments in organoid systems and immune cell co-cultures that offer new avenues for studying endometrial responses to infection in more physiologically relevant models that could accelerate future findings in this area. WIDER IMPLICATIONS: This scoping review provides an overarching summary and benchmark of the current state of research on endometrial innate immune responses to bacterial and viral infection. This review also highlights some exciting recent developments that enable future studies to be designed to deepen our understanding of the mechanisms utilized by the endometrium to respond to infection and their downstream effects on uterine function.

Idiopathic myointimal hyperplasia of the mesenteric veins: A systematic review and individual patient data regression analysis.

BACKGROUND AND AIM: Idiopathic myointimal hyperplasia of the mesenteric veins (IMHMV) is an uncommon cause of colonic ischemia for which surgical treatment is typically curative. We describe clinical, radiologic, and endoscopic findings in IMHMV patients to provide clinicians with a framework for pre-surgical identification of this rare disease. METHODS: We performed a systematic review of seven databases for IMHMV cases and identified additional cases from Yale New Haven Hospital records. To identify features specifically associated with colonic ischemia due to IMHMV, we performed multivariate logistic regression analysis incorporating data from a large cohort of patients with biopsy-proven ischemic colitis. RESULTS: A total of 124 patients with IMHMV were identified (80% male, mean age 53 years, 56% Caucasian). Presenting symptoms were most commonly abdominal pain (86%) and diarrhea (68%). The most affected areas were the sigmoid colon (91%) and rectum (61%). Complications associated with diagnostic delay occurred in 29% of patients. Radiologic vascular abnormalities including non-opacification of the inferior mesenteric vein were observed in 35% of patients. Of the patients, 97% underwent curative surgical resection. Compared with non-IMHMV colonic ischemia, IMHMV was significantly associated with younger age, male sex, absence of rectal bleeding on presentation, rectal involvement, and mucosal ulcerations on endoscopy. CONCLUSION: IMHMV is a rare, underreported cause of colonic ischemia that predominantly involves the rectosigmoid. Our findings suggest younger age, rectal involvement, and absence of rectal bleeding as clinical features to help identify select patients presenting with colonic ischemia as having higher likelihood of IMHMV and therefore consideration of upfront surgical management.

Burden of bone disease in chronic pancreatitis: A systematic review and meta-analysis.

BACKGROUND: Bone disease is an under-recognized cause of morbidity in chronic pancreatitis (CP). Over the past decade, publications of original studies on bone disease in CP has warranted synthesis of the evidence to ascertain the true burden of the problem. AIM: To quantify the prevalence of osteopenia, osteoporosis, and fragility fractures in CP patients and investigate the associated clinical features and outcomes. METHODS: A systematic search identified studies investigating bone disease in CP patients from Cochrane Library, Embase, Google Scholar, Ovid Medline, PubMed, Scopus, and Web of Science, from inception until October 2022. The outcomes included prevalence of osteopenia, osteoporosis, and fragility fractures, which were meta-analyzed using a random-effects model and underwent metaregression to delineate association with baseline clinical features. RESULTS: Twenty-one studies were included for systematic review and 18 studies were included for meta-analysis. The pooled prevalence of osteopenia and osteoporosis in CP patients was 41.2% (95%CI: 35.2%-47.3%) and 20.9% (95%CI: 14.9%-27.6%), respectively. The pooled prevalence of fragility fractures described among CP was 5.9% (95%CI: 3.9%-8.4%). Meta-regression revealed significant association of pancreatic enzyme replacement therapy (PERT) use with prevalence of osteoporosis [coefficient: 1.7 (95%CI: 0.6-2.8); P < 0.0001]. We observed no associations with mean age, sex distribution, body mass index, alcohol or smoking exposure, diabetes with prevalence of osteopenia, osteoporosis or fragility fractures. Paucity of data on systemic inflammation, CP severity, and bone mineralization parameters precluded a formal meta-analysis. CONCLUSION: This meta-analysis confirms significant bone disease in patients with CP. Other than PERT use, we observed no patient or study-specific factor to be significantly associated with CP-related bone disease. Further studies are needed to identify confounders, at-risk population, and to understand the mechanisms of CP-related bone disease and the implications of treatment response.

Benefit of Extended Surveillance of Low-Risk Pancreatic Cysts After 5-Year Stability: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Low-risk branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) lacking worrisome features (WF) and high-risk stigmata (HRS) warrant surveillance. However, their optimal duration, especially among cysts with initial 5 years of size stability, warrants further investigation. We systematically reviewed the surveillance of low-risk BD-IPMNs and investigated the incidence of WF/HRS and advanced neoplasia, high-grade dysplasia, and pancreatic cancer during the initial (<5 years) and extended surveillance period (>5-years). METHODS: A systematic search (CRD42020117120) identified studies investigating long-term IPMN surveillance outcomes of low-risk IPMN among the Cochrane Library, Embase, Google Scholar, Ovid Medline, PubMed, Scopus, and Web of Science, from inception until July 9, 2021. The outcomes included the incidence of WF/HRS and advanced neoplasia, disease-specific mortality, and surveillance-related harm (expressed as percentage per patient-years). The meta-analysis relied on time-to-event plots and used a random-effects model. RESULTS: Forty-one eligible studies underwent systematic review, and 18 studies were meta-analyzed. The pooled incidence of WF/HRS among low-risk BD-IPMNs during initial and extended surveillance was 2.2% (95% CI, 1.0%-3.7%) and 2.9% (95% CI, 1.0%-5.7%) patient-years, respectively, whereas the incidence of advanced neoplasia was 0.6% (95% CI, 0.2%-1.00%) and 1.0% (95% CI, 0.6%-1.5%) patient-years, respectively. The pooled incidence of disease-specific mortality during initial and extended surveillance was 0.3% (95% CI, 0.1%-0.6%) and 0.6% (95% CI, 0.0%-1.6%) patient-years, respectively. Among BD-IPMNs with initial size stability, extended surveillance had a WF/HRS and advanced neoplasia incidence of 1.9% (95% CI, 1.2%-2.8%) and 0.2% (95% CI, 0.1%-0.5%) patient-years, respectively. CONCLUSIONS: A lower incidence of advanced neoplasia during extended surveillance among low-risk, stable-sized BD-IPMNs was a key finding of this study. However, the survival benefit of surveillance among this population warrants further exploration through high-quality studies before recommending surveillance cessation with certainty.

Non-communicable diseases and maternal health: a scoping review.

BACKGROUND: Non-communicable diseases [NCDs] are leading causes of ill health among women of reproductive age and an increasingly important cause of maternal morbidity and mortality worldwide. Reliable data on NCDs is necessary for accurate measurement and response. However, inconsistent definitions of NCDs make reliable data collection challenging. We aimed to map the current global literature to understand how NCDs are defined, operationalized and discussed during pregnancy, childbirth and the postnatal period.  METHODS: For this scoping review, we conducted a comprehensive global literature search for NCDs and maternal health covering the years 2000 to 2020 in eleven electronic databases, five regional WHO databases and an exhaustive grey literature search without language restrictions. We used a charting approach to synthesize and interpret the data.  RESULTS: Only seven of the 172 included sources defined NCDs. NCDs are often defined as chronic but with varying temporality. There is a broad spectrum of conditions that is included under NCDs including pregnancy-specific conditions and infectious diseases. The most commonly included conditions are hypertension, diabetes, epilepsy, asthma, mental health conditions and malignancy. Most publications are from academic institutions in high-income countries [HICs] and focus on the pre-conception period and pregnancy. Publications from HICs discuss NCDs in the context of pre-conception care, medications, contraception, health disparities and quality of care. In contrast, publications focused on low- and middle-income countries discuss NCDs in the context of NCD prevention. They take a life cycle approach and advocate for integration of NCD and maternal health services. CONCLUSION: Standardising the definition and improving the articulation of care for NCDs in the maternal health setting would help to improve data collection and facilitate monitoring. It would inform the development of improved care for NCDs at the intersection with maternal health as well as through a woman's life course. Such an approach could lead to significant policy and programmatic changes with the potential corresponding impact on resource allocation.

Microangiopathic Hemolytic Anemia Is a Late and Fatal Complication of Gastric Signet Ring Cell Carcinoma: A Systematic Review and Case-Control Study.

BACKGROUND: Microangiopathic hemolytic anemia (MAHA) is a rare paraneoplastic syndrome that has been reported in patients with gastric signet ring cell carcinoma (SRCC). Clinical and prognostic features of MAHA in this setting have been poorly described. MATERIALS AND METHODS: We conducted a systematic review in 8 databases of gastric SRCC complicated by MAHA and performed a case-control study assessing factors associated with survival in patients with gastric SRCC and MAHA in our pooled cohort compared with age-, sex-, and stage-matched cases of gastric SRCC from the Surveillance, Epidemiology, and End Results (SEER) database. Descriptive analyses were performed and multivariable Cox-proportional hazards regression modeling was used to determine factors associated with overall survival. RESULTS: All identified patients (n = 47) were symptomatic at index presentation, commonly with back/bone pain, and dyspnea. Microangiopathic hemolytic anemia was the first manifestation of gastric SRCC in 94% of patients. Laboratory studies were notable for anemia (median 7.7 g/dL), thrombocytopenia (median 45.5 × 103/µL), and hyperbilirubinemia (median 2.3 mg/dL). All patients with MAHA had metastatic disease at presentation, most often to the bone, bone marrow, and lymph nodes. Median survival in patients with gastric SRCC and MAHA was significantly shorter than a matched SEER-derived cohort with metastatic gastric SRCC (7 weeks vs 28 weeks, P < .01). In multivariate analysis, patients with MAHA were at significantly increased risk of mortality (HR 3.28, 95% CI 2.11-5.12). CONCLUSION: Microangiopathic hemolytic anemia is a rare, late-stage complication of metastatic gastric SRCC and is associated with significantly decreased survival compared with metastatic gastric SRCC alone.

Clinical Presentation, Risk Factors, and Outcomes of Immune Effector Cell-Associated Neurotoxicity Syndrome Following Chimeric Antigen Receptor T Cell Therapy: A Systematic Review.

Chimeric antigen receptor (CAR) T cell therapy is a novel therapy for patients with relapsed or refractory hematologic malignancies. Most CAR T cell therapy recipients will experience clinical features of the immune effector cell-associated neurotoxicity syndrome (ICANS), a potentially life-threatening condition. Here we describe the clinical, biological, and radiological findings associated with ICANS in adults with hematologic malignancies treated with CAR T cell therapy, as well as the acute and long-term outcomes of ICANS. A literature search of Ovid Medline, Embase, PubMed, Scopus, Web of Science Core Collection, Cochrane Library, and Google Scholar was conducted from each database's inception through February 1, 2022, using search terms reflecting CAR T cell therapy and ICANS. We included studies that enrolled adults (age ≥18 years) who received CAR T cell therapy as management for hematologic malignancies and reported the clinical presentation, predictors, and/or acute or long-term outcomes of ICANS. Two reviewers independently extracted data following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) reporting guidelines. Quality was assessed using the Joanna Briggs Institute critical appraisal tool for cohort studies. Of the 2928 studies screened, 23 observational studies (10 prospective, 11 retrospective, 1 mixed design, and 1 cross-sectional) with a total of 1666 participants met our eligibility criteria and were included in our review. The most common hematologic malignancies were diffuse large B cell lymphoma, acute lymphocytic leukemia, non-Hodgkin lymphoma, and chronic lymphocytic leukemia. ICANS onset was most often associated with the presence and severity of cytokine release syndrome, as well as with C-reactive protein and ferritin levels. Aphasia was the most common ICANS-related symptom reported, although the neurologic manifestations of ICANS were highly variable. Neuroimaging studies (magnetic resonance imaging or computed tomography) were often normal in cases of ICANS; however, electroencephalography often showed generalized background slowing, abnormal rhythmic, and periodic discharge patterns. The pooled mean (± SD) onset of ICANS was 6.4 ± 3.2 days, with a pooled mean duration of 8.3 ± 10.5 days. Two of the 23 studies (9%) reported 5 ICANS-related deaths among 233 participants. A subset of patients experienced persistent neurocognitive complaints at ≥1-year after CAR T cell therapy. The clinical presentation, onset, severity, long-term sequelae, and grading system of ICANS are variable. Future studies should consider using a consensus grading/reporting scale that would permit cross-trial comparisons of the safety profile of various CAR T cell products and enable the development of interventions to mitigate or manage these neurotoxicities. © 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. This systematic review was conducted according to a published protocol (PROSPERO CRD42020207864) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and Synthesis without Meta-Analysis (SWiM) in systematic review reporting guidelines (Supplementary Table S1) [15,16].

Late-Stage Pancreatic Cancer Detected During High-Risk Individual Surveillance: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Identification and resection of successful targets, that is, T1 N0M0 pancreatic ductal adenocarcinoma (PDAC) and high-grade precursors during surveillance of high-risk individuals (HRIs) confers improved survival. Late-stage PDACs refer to T2-4 N0M0 and nodal or distant metastatic PDAC stages diagnosed during the follow-up phase of HRI surveillance. This study aimed to quantify late-stage PDACs during HRI surveillance and identify associated clinicoradiologic factors. METHODS: A systematic search (PROSPERO:CRD42018117189) from Cochrane Library, Embase, Google Scholar, Medline, PubMed, Scopus, and Web of Science was last performed on April 18, 2021. Only original HRI surveillance manuscripts that specified follow-up strategies were included, and studies with only baseline information were excluded. Cumulative incidences of advanced neoplasia: high-grade precursors and all PDACs, and surveillance-detected/interval late-stage PDACs were calculated through random-effects model. Incidence of late-stage PDACs underwent metaregression to identify association with HRI clinicoradiologic features. Publication bias was assessed through the funnel plot and Egger's regression line. RESULTS: Thirteen original surveillance studies included 2169 HRIs followed over 7302.72 patient-years. Cumulative incidence of advanced neoplasia and late-stage PDACs was 3.3 (95% confidence interval [CI]: 0.6-7.4) and 1.7 (95% CI: 0.2-4.0) per 1000 patient-years, respectively. Late-stage PDACs lacked significant association with surveillance imaging, baseline pancreatic morphology, study location, genetic background, gender, or age. Limited information on diagnostic error, symptoms, timing of presentation, lesion site, and surveillance adherence precluded formal meta-analysis. CONCLUSION: A sizeable proportion of late-stage PDACs were detected during follow-up. Their incidence lacked association with baseline clinicoradiologic features. Further causal investigation of stage-based outcomes is warranted for overall improvement in HRI surveillance.

Pregnancy in physicians: A scoping review.

BACKGROUND: The personal health and professional impact of physician pregnancy requires further study. We performed a comprehensive scoping review of physician pregnancy to synthesize and assess the evidence to aid decision-making for relevant stakeholders. METHODS: A search of 7 databases resulted in 3733 citations. 407 manuscripts were included and scored for evidence level. Data were extracted into themes using template analysis. RESULTS: Physician pregnancy impacted colleagues through perceived increased workload and resulted in persistent stigmatization and discrimination despite work productivity and academic metrics being independent of pregnancy events. Maternity leave policies were inconsistent and largely unsatisfactory. Women physicians incurred occupational hazard risk and had high rates of childbearing delay, abortion, and fertility treatment; obstetric and fetal complication rates compared to controls are conflicting. CONCLUSIONS: Comprehensive literature review found that physician pregnancy impacts colleagues, elicits negative perceptions of productivity, and is inadequately addressed by current parental leave policies. Data are poor and insufficient to definitively determine the impact of physician pregnancy on maternal and fetal health. Prospective risk-matched observational studies of physician pregnancy should be pursued.