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The Risk Analysis Index (RAI) frailty scoring system has recently undergone revision and external validation using the National Surgical Quality Improvement Program (NSQIP) database. We set forth to evaluate the association of RAI-rev ranges with outcomes following lower extremity surgical revascularization and verify equivalent applicability across genders.All elective NSQIP Targeted Lower Extremity Open cases from 2015-2019 were divided by EMR-recorded gender. Aggregate demographics, perioperative factors, and 30-day outcomes were compared using unpaired t-test and Fisher's exact test. Adjusted odds-ratios (aOR) for each outcome were generated by applying a multivariate binary logistic regression model (IBM SPSS8,155 cases included 2,498 (31%) performed in women who demonstrated slightly lower RAI-rev scores than men (22.1 ± 5.8 vs. 24.2 ± 5.1; P = 0.0001). Univariate trends demonstrated dose-dependent increases in frequency of most outcomes with rising frailty score ranges, most substantially regarding mortality (0.4% non-frail to 14.7% most-frail), disposition to skilled nursing facility (8% non-frail to 27% most-frail), and extended length of stay (16% non-frail to 44% most-frail). After adjusting for co-variates, patients with RAI-rev scores of 26-30 had aOR of 1.4 (95% CI: 1.2-1.6; P0.001), 1.9 (95% CI: 1.6-2.2; P0.001), and 2.4 (95% CI:1.3-4.4; P0.001) for extended stay, disposition to skilled nursing, and mortality respectively. Trends were similar across genders in both univariate and multivariate analyses.Mortality, extended stay, and increased rehabilitation needs after surgical revascularization were associated with higher RAI-rev score ranges in a dose dependent manner similarly across genders.

The purpose of this study was to identify and characterize casualties hospitalized with assault (non-terror) related gunshot wounds (GSW) in Israel as a basis for determining the incidence, trends and at-risk population groups.This retrospective cohort study is based on data from the Israel National Trauma Registry. The data includes GSW casualties hospitalized between January 1, 2011 and December 31, 2020. Attempted suicide, unintentional injury, legal intervention, children (ages 0-9) and terror (Israeli-Arab conflict) related GSW were excluded. The remaining population was classified with an ICD-9-CM diagnosis code of 965.0-965.4.The study population included 2,763 GSW admissions. A noticeable increase in GSW casualties was reported, from 206 hospitalization in 2011 to 456 in 2020. The proportion of Arab casualties increased from 73.3% of all GSW casualties in 2011 to 90.8% in 2020, far more than their proportion in the population (∼20%). The majority of the GSW casualties were males (95.8%) and between the ages of 20 and 29 (42.2%). Among severe/critical casualties, 19% of Arabs and 9.9% of Jews arrived by private car. Severe thoracic and abdominal injuries were the prominent injuries among fatal casualties (47.6 and 40.8, respectively). While the all-severity mortality rate was 5.6% (n = 147), 24.4% (n = 135) of severe/critical (ISS16+) casualties died, with no significant differences between Jews and Arabs. Forty percent of deaths occurred in the emergency department.This study establishes that during the past decade in Israel, not only has there been a continuous increase in hospitalizations due to GSW, but also Arabs are at great risk of such related hospitalizations. Preventive strategies targeting at-risk groups are crucial for minimizing morbidity and mortality related to GSW in Israel.

BNT162b2 messenger RNA (mRNA) COVID-19 vaccine administered during pregnancy was found to produce a strong maternal immunoglobulin (IgG) response which crosses the placenta to the newborn. Our aim was to evaluate maternal and neonatal SARS-CoV-2 IgG antibody levels at birth, following a COVID-19 booster vaccine during the third trimester.A prospective cohort study including women admitted to delivery ward at least 7 days after their BNT162b2 (Pfizer/BioNTech) booster vaccination without a prior clinical COVID-19 infection. SARS-CoV-2 IgG antibodies levels were measured in maternal blood upon admission to delivery and in the umbilical blood within 30 min following delivery. The correlation between antibody titers, feto-maternal characteristics, maternal side effects following vaccination, and time interval from vaccination to delivery were analyzed.Between September to November 2021, high antibody levels were measured in all 102 women and 93 neonatal blood samples, at a mean ± standard deviation duration of 7.0 ± 2.9 weeks after the third vaccine. We found positive correlation between maternal and neonatal antibodies (r = 0.73, 95% confidence interval [CI] 0.61 to 0.81, p 0.001), with neonatal titers approximately 1.4 times higher compared to maternal titers. In the multivariable analysis maternal antibody levels dropped by -7.2% (95% CI -12.0 to -2.3%, p = 0.005) for each week that passed since the receipt of the third vaccine dose. In contrary, systemic side effects after the third vaccine were associated with higher maternal antibody levels of 52.0% (95% CI 4.7 to 120.8%, p = 0.028). Also, for each 1 unit increase in maternal body mass index, maternal antibody levels increased by 3.6% (95% CI 0.4 to 6.9%, p = 0.025).BNT162b2 mRNA COVID-19 booster dose during the third trimester of pregnancy was associated with strong maternal and neonatal responses as reflected by maternal and neonatal SARS-CoV-2 IgG antibody levels measured at birth. These findings support the administration of the COVID-19 booster to pregnant women to restore maternal and neonatal protection during the ongoing pandemic.

The effect of severe maternal infectious morbidity on fetal growth during the second half of pregnancy is under debate. Preliminary evidence suggests that such association may be plausible. The objectives of this study were to determine: 1) The association between severe maternal infectious morbidity and adverse pregnancy outcome; and 2) The effect of maternal infection during pregnancy on fetal growth.This retrospective population - based cohort study included 4771 women who gave birth at our medical center during the study period. Parturients were allocated into two groups: 1) patients with severe maternal infection during the second half of pregnancy (n = 368); and 2) control group comprised of normal pregnant women who were matched to the study group by maternal age, gravidity and parity (n = 4403).The severe maternal infection group included women with pneumonia (n = 198), pyelonephritis (n = 131), and viral pneumonitis (n = 39). In comparison to the normal patients group: 1) having had pneumonia during the second half of pregnancy was associated with increased rates of fetal growth restriction, placental abruption, fetal demise (P 0.001, for all comparisons) and preeclampsia (P = 0.041); 2) Pyelonephritis during the second half of gestation was associated with higher rates of fetal growth restriction (P 0.001), placental abruption (P = 0.006) and labor induction (P = 0.039). As a group, women with severe maternal infection had higher rates of small for gestational age neonates compared to normal parturients (P 0.001). Among women with infections, only those who had pyelonephritis (P = 0.032) or pneumonia (P = 0.008), had a higher rate of small for gestational age neonates than those in the control group. After adjustment to confounding factors, maternal infection (OR = 1.42, 95% CI 1.085-1.85) and previous delivery of a small for gestational age neonate (OR = 2.54, 95% CI 2.02-3.19), were independent risk factors for the delivery of a small for gestational age neonate.Severe maternal infectious morbidity during the second half of pregnancy is an independent risk factor for the delivery of a small for gestational age neonate and is associated with adverse pregnancy outcomes. Both, pneumonia and pyelonephritis, during the second half of gestation affect fetal growth and are related to higher rates of small for gestational age neonates.

To evaluate maternal and neonatal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) antibody levels at birth after a third (booster) dose of the Pfizer-BioNTech messenger RNA (Pfizer) coronavirus disease 2019 (COVID-19) vaccine during the second trimester of pregnancy, and compare them with those in women who received two vaccine doses during the second trimester.We conducted a prospective cohort study of women admitted to the delivery ward at a single center who received the third Pfizer COVID-19 vaccine dose (booster group) at 17-30 weeks of pregnancy and who did not have previous SARS-CoV-2 infection. Maternal and neonatal antibody levels were measured on admission for delivery and in the umbilical cord blood after birth. Antibody levels for the booster group were compared with those in a historical control group of pregnant women who received their second vaccine dose (two-dose group) within the same gestational age window.Between October 2021 and February 2022, antibody levels were measured in 121 women and 109 neonates at a mean±SD of 15.3±3.9 weeks after booster vaccination. Neonatal titers measured two times higher than maternal titers, with inverse correlation between maternal and neonatal titers at birth and time interval from third vaccination. The two-dose group included 121 women and 107 neonates, with antibody levels measured at a mean±SD of 14.6±2.6 weeks after the second dose. Median [interquartile range] maternal antibody titers were higher in the booster group (4,485 [2,569-9,702] AU/mL) compared with the two-dose group (1,122 [735-1,872] AU/mL) (P.001). Furthermore, neonatal antibody titers were higher in the booster group (8,773 [5,143-18,830] AU/mL) compared with the two-dose group (3,280 [2,087-5,754] AU/mL) (P.001).Maternal and neonatal SARS-CoV-2 IgG antibody titers after second-trimester maternal Pfizer COVID-19 vaccination were significantly higher after the booster dose compared with the two-dose vaccination series. Although there is uncertainty as to whether antibody levels correlate with protection, these data support the importance of booster vaccination during pregnancy to restore maternal and neonatal protection against COVID-19.

Background Endometrial serous carcinoma (ESC) is an aggressive neoplasm wherein the recent studies have shown that it arises from its putative precursor namely the serous endometrial intraepithelial carcinoma (SEIC). SEIC usually arises in inactive/ atrophic endometrium but surprisingly is frequently associated endometrial polyps (EPs). The aim of this study was to assess the incidence of SEIC with or without invasion, its clinical behaviour and association with endometrial polyp. Materials and Methods After Institutional review board approval, a total of 205 samples (belonging to 120 patients); diagnosed as ESC from January 2009 to December 2015 were retrieved and reviewed for presence of in situ carcinoma and also for associated endometrial polyp. Results The mean age at diagnosis was 62.40 years with postmenopausal bleeding being the most common presenting symptom. The incidence of SEIC with or without invasive tumor was 40% (48/120). Of these 48 cases; 25 cases were associated with in-situ carcinoma arising in the EPs which amounted to 52% of the total cases. The overall three year survival and disease free survival in SEIC with or without invasion were 1.9% and 0.25%, indicating the aggressive nature of the disease. Conclusion SEIC is a difficult histopathological diagnosis and one should carefully look for these lesion, especially in the EPs which are frequently associated with them. Extensive sampling of the EP will be helpful to pick up in-situ carcinoma arising in EP. SEIC is an aggressive disease on its own with a propensity to develop distant metastasis even in the absence of myometrial invasion and hence should be treated with optimum surgical staging and if indicated aggressive adjuvant treatment protocols.

Objective Surgical frailty and its assessment have become essential considerations in perioperative management for the modern aging surgical population. The risk analysis index is a validated frailty score that has been proven to predict short-term outcomes and long-term mortality in several surgical subspecialties and high-risk procedures. We examined the association of risk analysis index scores with postoperative outcomes in a retrospective nationwide database of patients who underwent lower extremity amputation in the Veterans Health Administration Health Care System. Methods The Veteran Affairs Surgical Quality Improvement Program data was queried across the Veteran Affairs Health Care System with institutional review board approval for lower extremity amputations. Records of above and below knee amputation, Current Procedural Terminology codes 27590, 27591, 27592, 27594, 27596 and 27880, 27881, 27882, 27884, and 27886, respectively, from 1999 to 2018 were obtained. Incomplete and traumatic entries were removed. Risk Analysis Index score was calculated from preoperative variables and patients were separated into five score cohorts (≤15, 16-25, 26-35, 36-45, ≥46). The χ2 test and analysis of variance were used to compare the cohorts. Forward binary logistic regression modeling was used to determine covariate-adjusted odds ratios for outcomes in each cohort (SPSS software; version 25, IBM Corp). Results A total of 47,197 patients (98.9% male) with an average age of 66.4 ± 10.6 years underwent nontraumatic lower extremity amputation, including 27,098 below knee and 20,099 above knee amputations, during the study period. Frailty was associated with increased rates of deep vein thrombosis, sepsis, cardiac arrest, myocardial infarction, pneumonia, intubation for more than 48 hours, pulmonary embolism, reintubation, acute kidney injury, renal failure, increased length of stay, overall complications, and death. Increases in the frailty score were associated with up to three times the likelihood for the occurrence of a postoperative complication and up to 32 times likelihood to perish within 30 days than those with low frailty scores. Conclusions Risk analysis index assessment of frailty was found to be associated with several postoperative outcomes in a dose-dependent manner in patients undergoing lower extremity amputation in the Veterans Health Care System, with higher scores associated with higher rates of death and major cardiac (myocardial infarction, cardiac arrest), pulmonary (pneumonia, failure to wean vent, reintubation), and renal (renal insufficiency, renal failure) complications. We recommend the use of risk analysis index score as a frailty screening tool for patients undergoing lower extremity amputation to enable providers to adequately inform and counsel patients regarding potential significant risks.

Poor obstetric consequences of unexpected events in the delivery room, such as a shoulder dystocia and umbilical cord prolapse at birth or severe maternal infection cause harm to the mother, the newborn, the extended family and the staff. A vigorous attempt has been made to anticipate or prevent those events and try to deal with them skillfully and quickly in order to reduce the rate of complications. One of the methods to bring about successful treatment of these events is by integrated staff training in the delivery room, that is, joint training of obstetricians, midwives in the field of nursing, and anesthesiologists. The PROMPT (Practical Obstetrics Multi Professional Training) method has proven effective in improving medical outcomes in cases of shoulder dystocia at birth, significantly improving the response rate in birth management with changes in fetal monitoring and reducing the rate of neonates with a low Apgar score at birth. The training method was brought from England and was recently taught by joint teams from two Clalit hospitals. The system trained local "coaches" from the medical staff, whose task would be to bring the training at all stages into the hospitals selected for the task. The training stages, which take place inside the delivery rooms and not in training centers as is customary today, include practicing selected cases with players, using practice dolls, dedicated flow charts and customized action boxes, as well as creating a sharing atmosphere and improving communication among staff members. In the advanced stage, training programs will be prepared for additional delivery rooms and we will be able to monitor and document a change for the better in managing such events in the future.

Background The incidence of the highly morbid and potentially lethal gangrenous cholecystitis was reportedly increased during the COVID-19 pandemic. The aim of the ChoCO-W study was to compare the clinical findings and outcomes of acute cholecystitis in patients who had COVID-19 disease with those who did not. Methods Data were prospectively collected over 6 months (October 1, 2020, to April 30, 2021) with 1-month follow-up. In October 2020, Delta variant of SARS CoV-2 was isolated for the first time. Demographic and clinical data were analyzed and reported according to the STROBE guidelines. Baseline characteristics and clinical outcomes of patients who had COVID-19 were compared with those who did not. Results A total of 2893 patients, from 42 countries, 218 centers, involved, with a median age of 61.3 (SD: 17.39) years were prospectively enrolled in this study; 1481 (51%) patients were males. One hundred and eighty (6.9%) patients were COVID-19 positive, while 2412 (93.1%) were negative. Concomitant preexisting diseases including cardiovascular diseases (p p p = 0.005) were significantly more frequent in the COVID-19 group. Markers of sepsis severity including ARDS (p p p p p p p p p Conclusions The incidence of gangrenous cholecystitis is higher in COVID patients compared with non-COVID patients admitted to the emergency department with acute cholecystitis. Gangrenous cholecystitis in COVID patients is associated with high-grade Clavien-Dindo postoperative complications, longer hospital stay and higher mortality rate. The open cholecystectomy rate is higher in COVID compared with non -COVID patients. It is recommended to delay the surgical treatment in COVID patients, when it is possible, to decrease morbidity and mortality rates. COVID-19 infection and gangrenous cholecystistis are not absolute contraindications to perform laparoscopic cholecystectomy, in a case by case evaluation, in expert hands. Graphical abstract

Introduction The standard diagnosis for adrenocortical carcinoma (ACC) is clinical diagnosis (CD) based on radiographic and biochemical studies. Biopsy diagnosis (BD) is seldom required for the suspicion of secondary malignancy. We aim to study the impact of BD in the context of underlying T1/T2 ACC on overall survival (OS) compared with CD. Methods National Cancer Database (NCDB) for endocrine malignancies was utilized. Only patients with non-metastatic ACC, whose method of diagnosis and local disease extension were reported, and received a surgical adrenalectomy with curative intent were included. Patients were divided by disease stage into T1/T2, T3, and T4 groups. A propensity score match was applied to those with T1/T2 disease who received CD versus BD and the Kaplan-Meier method was used to compare OS. Results In total, 4000 patients with ACC were reported in the database, 1410 met selection criteria. Eight hundred and thirty patients had T1/T2, 365 had T3, and 162 had T4 ACC. Of patients with T1/T2 ACC, 742 (89.4%) received CD versus 88 (11.6%) with BD. A propensity score was calculated per a multivariable regression model with 79 patients matched from each group. Exact matching was applied for margin status and adjuvant therapies. Kaplan-Meier analysis showed a significant difference in median OS between CD versus BD patients in the matched data set (103.89 ± 15.65 vs. 54.93 ± 8.22 months; p = 0.001). In all comers, patients with T1/T2 ACC and BD had comparable median OS to that of patients with T3 ACC (52.21 ± 9.69 vs. 36.01 ± 3.33 months; p = 0.446). Conclusion BD in T1/T2 ACC could be associated with disease upstaging and worse OS outcomes.

A retrospective cohort study was conducted to assess clinical characteristics and outcomes of coronavirus disease-19 (COVID-19) among people living with HIV (PLHIV) in western India. Out of 86 PLHIV with COVID-19 illness, 19.7% had severe/critical illness and 6 (6.9%) individuals died. Median (interquartile range) age was 51 (47-56) years and 77.6% were male. Eighty-five PLHIV were on antiretroviral treatment with 98% having a viral load

ObjectiveTo compare clinical and imaging features of multiple sclerosis (MS) severity between Black Americans (BAs) and White Americans (WAs) and to evaluate the role of socioeconomic status.MethodsWe compared BA and WA participants in the Multiple Sclerosis Partners Advancing Technology Health Solutions (MS PATHS) cohort with respect to MS characteristics, including self-reported disability, objective neurologic function assessments, and quantitative brain MRI measurements, after covariate adjustment (including education level, employment, or insurance as socioeconomic indicators). In a subgroup, we evaluated within-race, neighborhood-level indicators of socioeconomic status (SES) using 9-digit zip codes.ResultsOf 1,214 BAs and 7,530 WAs with MS, BAs were younger, had lower education level, and were more likely to have Medicaid insurance or to be disabled or unemployed than WAs. BAs had worse self-reported disability (1.47-fold greater odds of severe vs mild disability, 95% confidence interval [CI] 1.18, 1.86) and worse performances on tests of cognitive processing speed (−5.06 fewer correct, 95% CI −5.72, −4.41), walking (0.66 seconds slower, 95% CI 0.36, 0.96), and manual dexterity (2.11 seconds slower, 95% CI 1.69, 2.54). BAs had more brain MRI lesions and lower overall and gray matter brain volumes, including reduced thalamic (−0.77 mL, 95% CI −0.91, −0.64), cortical (−30.63 mL, 95% CI −35.93, −25.33), and deep (−1.58 mL, 95% CI −1.92, −1.23) gray matter volumes. While lower SES correlated with worse neuroperformance scores in WAs, this association was less clear in BAs.ConclusionWe observed a greater burden of disease in BAs with MS relative to WAs with MS, despite adjustment for SES indicators. Beyond SES, future longitudinal studies should also consider roles of other societal constructs (e.g., systemic racism). Such studies will be important for identifying prognostic factors; developing optimal treatment strategies among BAs with MS is warranted.

Background Long‐COVID is emerging as a significant problem among individuals who recovered from COVID‐19. Scant information is available on the prevalence, characteristics, and risk factors for long‐COVID among people living with HIV (PLHIV). Setting A tertiary level, private, HIV clinic in western India. Methods A prospective, observational study was conducted to assess the prevalence of long‐COVID among PLHIV. Long‐COVID was defined as the presence of at least one symptom after 30 days of illness onset. A questionnaire for assessing general, cardiorespiratory, neuro‐psychiatric, and gastro‐intestinal symptoms was used to screen individuals with history of confirmed COVID‐19. Data on demographics, HIV‐related variables, comorbidities, and severity of COVID‐19 were abstracted from electronic medical records. Univariate and multivariate logistic regression were used to identify risk factors for long‐COVID. Results Ninety‐four PLHIV were screened for long‐COVID. Median (interquartile range [IQR]) age was 51 (47–56) years and 73.4% were males. The majority (76.6%) had a history of asymptomatic–mild COVID‐19 illness. The prevalence of long‐COVID was 43.6% (95% confidence interval [CI], 33.4–54.2). Moderate–severe COVID‐19 illness was significantly associated with long‐COVID (adjusted odds ratio, 4.7; 95% CI, 1.4–17.9; p = .016). Among individuals with long‐COVID, cough (22.3%) and fatigue (19.1%) were the commonest symptoms. The median (IQR) duration for resolution of symptoms was 15 (7–30) days. Ten individuals (10.6%) had persistent symptoms at a median of 109 days since the onset of COVID‐19. Conclusion Long‐COVID is common among PLHIV with moderate–severe acute COVID‐19 illness. There is a need for integration of long‐COVID diagnosis and care services within antiretroviral therapy clinics for PLHIV with COVID‐19., Long‐COVID‐19 was documented among 43.6% of people living with HIV in western India. Moderate/severe COVID‐19 illness was independently associated with long COVID‐19 in this cohort.

Background Naturally occurring aflatoxins may contribute to poor growth and nutritional statuses in children. Objectives We analyzed the relationship between contemporary and lagged aflatoxin exposure and 1) length-for-age z-score (LAZ); and 2) length, knee-heel length, stunting, weight-for-age z-score (WAZ), and weight-for-length z-score (WLZ). Methods We conducted a longitudinal birth cohort study involving 1675 mother-infant dyads in rural Nepal. Participants were repeatedly visited from pregnancy to 2 years of age (2015–2019). One blood sample was collected during pregnancy and 4 samples were collected from the children at 3, 6, 12, and 18–22 months of age to measure concentrations of aflatoxin B1 (AFB1)-lysine adduct. Multivariate linear fixed-effects and logistic models with generalized estimating equations were used to identify associations between child growth and aflatoxin exposure. Results AFB1-lysine adducts were detected in the majority of children (at 3 months, 80.5%; at 6 months, 75.3%; at 12 months, 81.1%; and at 18–22 months, 85.1%) and in 94.3% of pregnant women. Changes in contemporary ln child AFB1‐lysine adduct concentrations were significantly associated with changes in LAZ (β, −0.05; 95% CI, −0.09 to −0.02; P = 0.003), length (β, −0.19; 95% CI, −0.29 to −0.10; P

Objective It is common knowledge among clinicians who treat PFAPA (Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis) patients that emotional stress can trigger PFAPA attacks similarly to other autoinflammatory diseases. However, it has never been proved scientifically. Our aim was to examine whether emotional stress serves as a trigger for PFAPA attacks. Methods Patients aged 3-12 years, with active PFAPA, from two Israeli medical centers were enrolled to this study. Patient's parents were reached via phone calls in two occasions: a stressful period related to the COVID-19 pandemic restrictions and a less stressful period. In both times they were asked to report occurrence of PFAPA attacks in the preceding 2 weeks. The relative stress levels of the two periods were validated by an emotional distress scale questionnaire. The significance level was set at 0.05. Results Mean age was 7.28 ± 2.7 for the 99 paediatric patients enrolled in the study. Scores for the mean emotional distress questionnaire were statistically significant higher in the stressful period compared to the less stressful period (35.6 ± 8.1 vs. 32.1 ±7.7, respectively, P = 0.047). In the stressful period, 41 (38.7%) reported at least one attack during the preceding 2 weeks, compared to 24 (22.6%) in the less stressful period (p = 0.017). Conclusion PFAPA flares during COVID-19 outbreak are described. This study is the first to suggest that emotional stress is associated with PFAPA attacks.

Despite declining physical function, individuals with ALS report relative preservation of overall health perception, or health-related quality of life (HRQoL). This paradoxical finding is attributed to psychological adaptation to deficits.The aim of this cross-sectional study was to examine reprioritization of factors that determine HRQoL with disease progression.As standard care, patients with ALS self-reported ALSFRS-R (measure of bulbar, motor, and respiratory function), PHQ-9 (measure of depression), and EQ-5D-3L (utility index that includes a visual analog scale asking about health perception [EQ-VAS]). ALS was staged by the FT9 method and classified into early (stages 0-2) and late (stages 3-4) disease. Multigroup structural equation modeling was used to evaluate weights of physical (PHY) and psychological well-being (PSY) for early and late disease, on EQ-VAS (as a measure of overall HRQoL).There were 578 patients (mean age 61.5 ± 11.9, 59% male) with ALS: 423 (73%) early and 155 (27%) late disease. A measurement model was established with good model fit (RMSEA = 0.076, CFI = 0.943, SRMR = 0.045). In adjusted models, standardized weights of PHY and PSY on HRQoL in early disease were 0.34 (standard error = 0.06) and 0.24 (0.06) respectively, whereas for late disease they were 0.39 (0.07) and 0.42 (0.07). Importantly, PHY and PSY were significantly correlated in early but not in late disease.Our study found health perception is more representative of psychological well-being and less representative of physical function across the disease progression. Greater allocation for psychological health would be the most effective strategy to maximize subjective health status as ALS advances.

Despite having a high risk of soil-transmitted helminths (STHs) infection, no national level study has been conducted to assess incidence and correlates of STHs in Nepal. Thus, we hypothesized that micronutrients and social status are linked with incidence of STHs infection among 6–59 months children and 15–49 years non-pregnant women in Nepal and Kato-Katz technique was adopted to measure the type and intensity of STHs infections using fresh stool specimens and venous blood was used to examine micronutrients biomarkers. Anthropometric measurements such as height and weight, sociodemographic and health status were determined using structured questionnaire. Logistic regression was used to assess unadjusted and adjusted odds ratio (AOR) and the 95% CIs of ORs. The bivariate association of STHs was assessed with the covariates variables. Overall, 12% children and 19% non-pregnant women had STHs infection; A. lumbricoides was the predominant helminth in both study participants. In multivariate model; age, ethnicity, anaemia and zinc deficiency were associated with STHs infections in children. Similarly, higher odds of STHs occurrence was observed among non-pregnant women with vitamin A deficiency. Findings from this study suggest that high-risk population, with a focus on those of lower socioeconomic status should be on priority of deworming program, nutrition intervention, and mass administration of preventive chemotherapy and sanitation champions supplement to reduce the STHs infections in Nepal.

Background Using mobile application for postural assessments has been drawing a rising interest due to widespread use of smartphones. Although there are some mobile applications in use, validated mobile tools for accurate postural assessment are still warranted. Aims This study aimed to develop Fizyoprint mobile application tool to assess standing posture and investigate the validity and reliability of the application in young adults. Methods A convenience sample of 20 young adults (12 men and 8 women with a mean age of 21.3 +/- 2.2 years) and 2 physiotherapists as raters participated in the study. The participant's digital images were obtained from the anterior, posterior, and right lateral sides. The raters selected the anatomic reference points by using digital markers in the app screen, and the Fizyoprint application, with Turkish language option, calculated a total of 26 posture variables, including 11 distance and 15 angle variables. Each participant was assessed twice (1-week interval) by 2 raters with Fizyoprint. Inter- and intra-rater reliabilities were estimated using the intraclass correlation coefficient. The BioTonix (TM) posture analysis system was used for validation. Results A total of 80.7% (21 variables) indicated acceptable to excellent intra-rater reliability results. A total of 57.7% (15 variables) were found to be acceptable to excellent for inter-rater measurements. The results confirmed the validity of the Fizyoprint application for testing the standing posture. Conclusions Fizyoprint application is a new, valid, free mobile tool with acceptable concordance with BioTonix (TM) postural analysis system for assessing standing posture. Further studies are warranted to test the current application in different populations and musculoskeletal conditions.

The Pelvic Floor Disorders Consortium (PFDC) is a multidisciplinary organization of colorectal surgeons, urogynecologists, urologists, gynecologists, gastroenterologists, radiologists, physiotherapists, and other advanced care practitioners. Specialists from these fields are all dedicated to the diagnosis and management of patients with pelvic floor conditions, but they approach, evaluate, and treat such patients with their own unique perspectives given the differences in their respective training. The PFDC was formed to bridge gaps and enable collaboration between these specialties. The goal of the PFDC is to develop and evaluate educational programs, create clinical guidelines and algorithms, and promote high quality of care in this unique patient population. The recommendations included in this article represent the work of the PFDC Working Group on Magnetic Resonance Imaging of Pelvic Floor Disorders (members listed alphabetically in Table 1). The objective was to generate inclusive, rather than prescriptive, guidance for all practitioners, irrespective of discipline, involved in the evaluation and treatment of patients with pelvic floor disorders.

Background In Nepal, traditional treatment using medicinal plants is popular. Whereas medication-overuse headache is, by definition, caused by excessive use of acute headache medication, we hypothesized that medicinal plants, being pharmacologically active, were as likely a cause. Methods We used data from a cross-sectional, nationwide population-based study, which enquired into headache and use of medicinal plants and allopathic medications. We searched the literature for pharmacodynamic actions of the medicinal plants. Results Of 2100 participants, 1794 (85.4%) reported headache in the preceding year; 161 (7.7%) reported headache on ≥15 days/month, of whom 28 (17.4%) had used medicinal plants and 117 (72.7%) allopathic medication(s). Of 46 with probable medication-overuse headache, 87.0% (40/46) were using allopathic medication(s) and 13.0% (6/46) medicinal plants, a ratio of 6.7:1, higher than the overall ratio among those with headache of 4.9:1 (912/185). Of 60 plant species identified, 49 were pharmacodynamically active on the central nervous system, with various effects of likely relevance in medication-overuse headache causation. Conclusions MPs are potentially a cause of medication-overuse headache, and not to be seen as innocent in this regard. Numbers presumptively affected in Nepal are low but not negligible. This pioneering project provides a starting point for further research to provide needed guidance on use of medicinal plants for headache.

Purpose In 2018, the International Federation of Gynecology and Obstetrics (FIGO) proposed a new staging for cervical cancer. The present study was designed to reclassify patients with locally advanced cervix cancer and perform a comparative evaluation with FIGO 2009. Methods and Materials Patients with locally advanced cervical cancer (stage IB2-IVA) who had baseline cross-sectional imaging and received (chemo-) radiation and brachytherapy were included. Survival outcomes were analyzed according to FIGO 2009. Patients were then reclassified according to FIGO 2018, and TNM classification outcomes were analyzed. FIGO stage and known prognostic factors were included in univariate analysis, and multivariate analysis was performed to investigate the prognostic value of clinical stage. Results Six hundred thirty-two patients were included. Overall, 185 (29.3%) patients had pelvic adenopathy, and 51 (8.2%) had positive paraortic nodes. At a median follow-up of 33 months, 116 (18.3%) patients had recurrence. Three-year disease-free survival (DFS) according to FIGO 2009 for stage IB, IIA, IIB, IIIA, IIIB, and IVA was 86%, 91%, 76%, 57%, 65%, and 61%, respectively. The 3-year DFS after restaging according to FIGO 2018 for stage IB, IIA, IIB, IIIA, IIIB, IIIC1, IIIC2, and IVA was 100%, 93%, 84%, 53%, 77%, 74%, 61%, and 61%, respectively. Patients with clinically significant lymphadenopathy had inferior outcomes compared with node-negative patients (62.9% vs 77.8%; P = .002). Patients with ≥3 paraortic nodes had poorer DFS than patients with 30 cm3 had worse 3-year DFS than those with primary tumor volume ≤30 cm3 (67.4% vs 78.5%; P = .002). Conclusions FIGO 2018 modification is associated with heterogenous outcomes in node-positive patients that are affected by primary tumor and nodal volume. We propose a modification to the existing TNM staging system to allow more robust classification of outcomes.

BackgroundHigh rates of Adverse Events (AEs) during treatment is one of the leading causes of unsuccessful treatment outcomes among patients with drug resistant tuberculosis (DR-TB). However, information related to AEs is not systematically collected and managed under programmatic setting. The present study assessed the a) incidence and pattern of adverse events in first three months of DR-TB treatment initiation; b) treatment seeking behaviour for AE management; and c) explore the challenges in seeking treatment and reporting AEs.MethodsThis mixed methods study included all patients diagnosed and initiated on treatment under RNTCP during July–September 2018 at Ahmedabad DR-TB centre. The patients were interviewed telephonically and assessed for all AEs experienced by them. In-depth interviews and key-informant interviews were conducted among patients, DOTS supervisors and programme staff (treatment supervisors, medical officer and district program managers).ResultsTotal 207 AEs were reported by the 74 DR-TB patients. All patients experienced at least one AE during initial treatment period. Incidence rate of AEs (experienced) was 3.11 (1st month-4.6, 2nd month-2.7, 3rd month-2.02) per 100 person days. Of the 207 AEs, gastro-intestinal (59, 28.3%), ophthalmic (32, 15.4%) and otolaryngology (25, 11.9%) system related AEs were commonly experienced. Treatment was not sought in two-fifths of the AEs. Themes and sub-themes related to challenges in treatment seeking or reporting of AEs were 1) Patient related-Misconceptions, accessibility and affordability of management, lack of counselling support, stigma and discrimination, and past treatment experience; 2) Health system related- lack of guidelines and training for AE management, 3) Poor coordination between hospital and tuberculosis centre.ConclusionThe incidence of AEs was high among patients with DR-TB in the first three months of treatment and treatment seeking/reporting was low. Adequate health education and counselling of the patient and orientation of the health systems is the need of the hour. An efficient real-time reporting and management of AE should be developed and tested for effective DR-TB control.

PURPOSE Women with recurrent, multiply-treated epithelial ovarian cancer (EOC) have unfavorable prognosis with limited treatment options after failure of platinum-based regimens. We report here a retrospective analysis of women with recurrent, platinum-resistant EOC treated with an oral regimen of pazopanib and cyclophosphamide. PATIENTS AND METHODS Women with recurrent platinum-resistant or -refractory EOC were treated with pazopanib (600 mg orally daily in 2 divided doses, 400 and 200 mg) and cyclophosphamide (50 mg orally daily for 21 days every 28 days) until disease progression or unacceptable toxicity. RESULTS Twenty patients (17 with platinum-resistant and 3 with platinum-refractory disease) were treated between April 2014 and April 2018. Patients had a median age of 52 years (range, 40-60 years) and median of 4 previous lines of chemotherapy (range, 2-8 previous lines), including 3 patients with progressive disease on bevacizumab. Patients received a median of 6 cycles (range, 2-48 cycles) of pazopanib and cyclophosphamide, with best responses of partial response in 9 patients (45%, including 1 of 3 patients treated previously with bevacizumab), stable disease in 6 patients (30%), and disease progression in 5 patients (25%). The median progression-free survival time was 5.5 months, and median overall survival was 9.5 months. Common adverse events (grade 3 or 4) were fatigue (25%), diarrhea (15%), hand-foot syndrome (10%), mucositis (10%), transaminitis (5%), and hypertension (5%). Dose reduction as a result of toxicity was required in 14 patients (70%), and no patient stopped treatment as a result of toxicity. CONCLUSION Pazopanib plus oral cyclophosphamide is a well-tolerated regimen with clinically relevant benefit in patients with platinum-resistant or -refractory EOC.

Background and Aims: Hepatic sinusoidal cells are known actors in the fibrogenic response to injury. Activated hepatic stellate cells (HSCs), liver sinusoidal endothelial cells, and Kupffer cells are responsible for sinusoidal capillarization and perisinusoidal matrix deposition, impairing vascular exchange and heightening the risk of advanced fibrosis. While the overall pathogenesis is well understood, functional relations between cellular transitions during fibrogenesis are only beginning to be resolved. At single-cell resolution, we here explored the heterogeneity of individual cell types and dissected their transitions and crosstalk during fibrogenesis. Approach and Results: We applied single-cell transcriptomics to map the heterogeneity of sinusoid-associated cells in healthy and injured livers and reconstructed the single-lineage HSC trajectory from pericyte to myofibroblast. Stratifying each sinusoidal cell population by activation state, we projected shifts in sinusoidal communication upon injury. Weighted gene correlation network analysis of the HSC trajectory led to the identification of core genes whose expression proved highly predictive of advanced fibrosis in patients with nonalcoholic steatohepatitis (NASH). Among the core members of the injury-repressed gene module, we identified plasmalemma vesicle–associated protein (PLVAP) as a protein amply expressed by mouse and human HSCs. PLVAP expression was suppressed in activated HSCs upon injury and may hence define hitherto unknown roles for HSCs in the regulation of microcirculatory exchange and its breakdown in chronic liver disease. Conclusions: Our study offers a single-cell resolved account of drug-induced injury of the mammalian liver and identifies key genes that may serve important roles in sinusoidal integrity and as markers of advanced fibrosis in human NASH.

ABBV-321 (serclutamab talirine), a next-generation EGFR-targeted antibody–drug conjugate (ADC) incorporates a potent pyrrolobenzodiazepine (PBD) dimer toxin conjugated to the EGFR-targeting ABT-806 affinity-matured AM1 antibody. ABBV-321 follows the development of related EGFR-targeted ADCs including depatuxizumab mafodotin (depatux-m, ABT-414), ABT-806 conjugated to monomethyl auristatin F (MMAF), and ABBV-221 (losatuxizumab vedotin), AM1 antibody conjugated to monomethyl auristatin E (MMAE). The distinct tumor selectivity of ABBV-321 differentiates it from many previous highly active antibody PBD conjugates that lack a therapeutic window. Potency of the PBD dimer, combined with increased binding of AM1 to EGFR-positive tumor cells, opens the possibility to target a wide array of tumors beyond those with high levels of EGFR overexpression or amplification, including those insensitive to auristatin-based ADCs. ABBV-321 exhibits potent antitumor activity in cellular and in vivo studies including xenograft cell line and patient-derived xenograft glioblastoma, colorectal, lung, head and neck, and malignant mesothelioma tumor models that are less sensitive to depatux-m or ABBV-221. Combination studies with ABBV-321 and depatux-m suggest a promising treatment option permitting suboptimal, and potentially better tolerated, doses of both ADCs while providing improved potency. Collectively, these data suggest that ABBV-321 may offer an extended breadth of efficacy relative to other EGFR ADCs while extending utility to multiple EGFR-expressing tumor indications. Despite its highly potent PBD dimer payload, the tumor selectivity of ABBV-321, coupled with its pharmacology, toxicology, and pharmacokinetic profiles, support continuation of ongoing phase I clinical trials in patients with advanced EGFR-expressing malignancies.

Introduction The yield of mycobacteria is shown to be very low in pleural effusions as it is a pauci-bacillary disease. The present study looked at the yield of mycobacterium tuberculosis (MTB) in terms of GeneXpert for acid fast bacilli (AFB) and culture using a medical thoracoscopy guided biopsy and analysed whether the yield increases in more complicated effusions. Materials and methods This is a retrospective analysis of patients who underwent medical thoracoscopy for tubercular pleural effusions at our institute over the last 5-years. Patients who had no or minimal thin septations were considered as simple effusions and were subjected to semi-rigid thoracoscopy (n = 61). While patients who had multiple loculations and thick septations were considered as complicated effusions and were subjected to rigid thoracoscopy (n = 64). We considered granuloma on a biopsy as the standard for diagnosis of Tuberculosis (TB). Xpert MTB/RIF and The BACTEC MGIT was used for culture. Results Out 125 patients with granulomatous inflammation on biopsy, 56 (44.8%) were positive for either GeneXpert or culture for MTB. Only GeneXpert was positive in 43 and only culture was positive in 13. Amongst 61 patients with simple effusion, 14 had either GeneXpert for AFB or AFB culture being positive and 9 out of these patients had GeneXpert for MTB detected on biopsy sample. Only culture was positive in 5 patients. In complicated pleural effusion group either GeneXpert or culture for mycobacterium was positive in 42 (65.6%) out of 64 patients. Only GeneXpert was positive in 34 and culture alone was positive in 8 patients. Conclusion The yield of MTB increases as the pleural effusion becomes more complicated. GeneXpert in a biopsy sample is a useful marker for MTB yield especially in a complicated effusion.

The rigidity and relatively primitive modes of operation of catheters equipped with sensing or actuation elements impede their conformal contact with soft-tissue surfaces, limit the scope of their uses, lengthen surgical times and increase the need for advanced surgical skills. Here, we report materials, device designs and fabrication approaches for integrating advanced electronic functionality with catheters for minimally invasive forms of cardiac surgery. By using multiphysics modelling, plastic heart models and Langendorff animal and human hearts, we show that soft electronic arrays in multilayer configurations on endocardial balloon catheters can establish conformal contact with curved tissue surfaces, support high-density spatiotemporal mapping of temperature, pressure and electrophysiological parameters and allow for programmable electrical stimulation, radiofrequency ablation and irreversible electroporation. Integrating multimodal and multiplexing capabilities into minimally invasive surgical instruments may improve surgical performance and patient outcomes.

Objective: To estimate, among people with multiple sclerosis, the extent to which a personally tailored exercise programme (MSTEP©) resulted in greater improvements in exercise capacity and related outcomes over 12 months in comparison with general exercise guidelines. Design: Two-group randomized trial. Subjects: Ambulatory and sedentary. Interventions: MSTEP©, a personally adapted exercise regimen done on most days including two days of high intensity exercise; guidelines recommending 30 minutes of moderate intensity aerobic and strength training two times per week. Main measures: Primary outcome was peak oxygen consumption (VO2peak) at 12 months; secondary outcomes were composite measures of physical function, fatigue, and health-related quality of life. Results: In total, 137 people were randomized, 66 were lost over 12 months leaving 71 with outcome data, 34 in MSTEP© group, and 37 in the Guideline group. Exercise enjoyment and confidence and exercise-induced fatigue predicted retention. There were no differences between groups on the proportion making a 10% increase in VO2peak (27.1% MSTEP© vs 29.6% Guidelines; OR: 0.83; 95% CI: 0.23–3.08) by the 12 month assessment. The effect on fatigue was larger in the MSTEP© group than the Guideline groups (OR: 1.59; 95% CI: 0.93–2.74), the effect on physical function was more modest (OR: 1.35; 95% CI: 0.80–2.25), and null for health-related quality of life outcomes. Conclusions: The disappointing exercise retention suggests that people with multiple sclerosis may not consider exercise important to their brain health. Either type of exercise resulted in stable exercise capacity over 1 year in those sticking with the programme.

Qiu et al. present a novel deep learning strategy to generate high-resolution visualizations of Alzheimer’s disease risk in humans that are highly interpretable and can accurately predict Alzheimer’s disease status. They then test the model by comparing its performance to that of neurologists and neuropathological data., Alzheimer’s disease is the primary cause of dementia worldwide, with an increasing morbidity burden that may outstrip diagnosis and management capacity as the population ages. Current methods integrate patient history, neuropsychological testing and MRI to identify likely cases, yet effective practices remain variably applied and lacking in sensitivity and specificity. Here we report an interpretable deep learning strategy that delineates unique Alzheimer’s disease signatures from multimodal inputs of MRI, age, gender, and Mini-Mental State Examination score. Our framework linked a fully convolutional network, which constructs high resolution maps of disease probability from local brain structure to a multilayer perceptron and generates precise, intuitive visualization of individual Alzheimer’s disease risk en route to accurate diagnosis. The model was trained using clinically diagnosed Alzheimer’s disease and cognitively normal subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset (n = 417) and validated on three independent cohorts: the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL) (n = 382), the Framingham Heart Study (n = 102), and the National Alzheimer’s Coordinating Center (NACC) (n = 582). Performance of the model that used the multimodal inputs was consistent across datasets, with mean area under curve values of 0.996, 0.974, 0.876 and 0.954 for the ADNI study, AIBL, Framingham Heart Study and NACC datasets, respectively. Moreover, our approach exceeded the diagnostic performance of a multi-institutional team of practicing neurologists (n = 11), and high-risk cerebral regions predicted by the model closely tracked post-mortem histopathological findings. This framework provides a clinically adaptable strategy for using routinely available imaging techniques such as MRI to generate nuanced neuroimaging signatures for Alzheimer’s disease diagnosis, as well as a generalizable approach for linking deep learning to pathophysiological processes in human disease.

Factors underlying gastroparesis are not well defined. We hypothesized that multiple systems may be involved in patients with gastroparesis symptoms and performed a comparative physiologic study. We studied 43 consecutive eligible patients with gastroparetic symptoms categorized by GI symptoms, metabolic status, illness quantification, and gastric physiology. Patients were evaluated by two methods in each of five core areas: inflammatory, autonomic, enteric, electrophysiologic, and hormonal with abnormalities examined by correlations. Patients had similar GI symptoms regardless of baseline gastric emptying or diabetic/idiopathic status, and all patients demonstrated abnormalities in each of the 5 areas studied. Nearly all patients presented with elevated markers of serum TNFα (88%) and serum IL-6 (91%); elevated cutaneous electrogastrogram frequency (95%); and interstitial cells of Cajal count abnormalities (inner: 97%, outer: 100%). Measures of inflammation correlated with a number of autonomic, enteric anatomy, electrophysiologic and hormonal abnormalities. We conclude that patients with the symptoms of gastroparesis have multiple abnormalities, when studied by traditional, as well as newer, diagnostic assessments. Inflammation appears to be a fundamental abnormality that affects other organ systems in symptomatic patients. Future work on gastroparetic syndromes and their treatment may benefit from a focus on the diffuse nature of their illness, diverse pathophysiologic mechanisms involved, especially the possible causes of underlying inflammation and disordered hormonal status. This study is registered with Clinicaltrials.gov under study # NCT03178370 https://clinicaltrials.gov/ct2/show/NCT03178370 .

BACKGROUND: Anemia is a major concern for children in Nepal; however, little is known about context-specific causes of anemia. OBJECTIVE: We used cross-sectional data from the 2016 Nepal National Micronutrient Status Survey to evaluate factors associated with anemia in a nationally representative, population-based sample of children 6–59 mo (n = 1367). METHODS: Hemoglobin, biomarkers of iron status and other micronutrients, infection, inflammation, and blood disorders were assessed from venous blood samples. Soil-transmitted helminth (STH) and Helicobacter pylori infections were assessed from stool. Anthropometry was measured with standard procedures. Sociodemographic and household characteristics, diet, micronutrient powder (MNP) intake, pica, and morbidity recall were ascertained by caregiver interview. Multivariable logistic regression that accounted for complex sampling design, determined predictors of anemia (hemoglobin

This study aimed to describe considerations for developing supportive care interventions targeted to head and neck cancer (HNC) survivors.One-time semi-structured interviews (N = 33) were conducted with HNC survivors who had recently finished treatment (n = 20) and HNC providers (e.g., physicians, nurses; n = 13). Interviews were transcribed verbatim and coded using inductive applied thematic analysis techniques to identify themes.HNC survivors (75% male; M = 61 years old) and providers (54% physicians; 62% female) were unanimously supportive of developing HNC-specific supportive care interventions. Participants described potential benefits of offering interventions at various points throughout the HNC treatment and survivorship trajectory rather than at a single critical time. Many participants preferred group-based interventions because of the high value of peer-support. Others described how group interventions may not be appropriate for all HNC survivors due to risks for negative social comparisons and exacerbated anxiety. Participants suggested topics that should be addressed in HNC-specific interventions including education about acute and long-term side effects, symptom management, nutritional support, relationship/social role changes, grief/loss, and fear of recurrence.HNC-specific supportive care interventions are critically needed, as survivors experience persistent symptoms and distinct psychosocial concerns that impact quality of life. Findings from this study can inform the development of supportive care interventions targeted to the unique psychosocial concerns of HNC survivors.

PURPOSE There are limited data on management of cervical cancer in women living with HIV in the modern antiretroviral therapy era. The study aimed to evaluate outcomes and toxicities of these patients treated with radiotherapy. MATERIALS AND METHODS A retrospective analysis of HIV-positive cervical cancer patients treated with radiotherapy between 2011 and 2018 was conducted at a tertiary care center in India. RESULTS Eighty-two HIV-positive cervical cancer patients treated with radiotherapy were identified. Their median age was 45 years. Seventy-four (90%) patients received radiotherapy with curative-intent and eight patients received palliative radiotherapy. Median CD4 count at the start of treatment was 342 cells/mm3 (interquartile range: 241-531). Among patients planned for definitive radiotherapy, concurrent cisplatin was planned in 52 (70%) patients with a median of four chemotherapy cycles, and 81% (n = 60) patients received brachytherapy. Among patients who received brachytherapy, the median prescription dose was 80 Gy. Seventy-seven patients completed their prescribed treatment. At a median follow-up of 37 months, 3-year disease-free survival of patients planned with curative-intent was 54%. On multivariate analysis, treatment completion was associated with favorable disease-free survival. Grade III/IV acute gastrointestinal toxicity was seen in five (6.8%) patients, whereas 30% patients had grade III/IV acute hematologic toxicity. All these patients completed their planned radiotherapy with good supportive care. CONCLUSION Standard treatment of chemoradiation should be planned in women living with HIV with well-managed HIV presenting with locally advanced cervical cancer. Our study highlights the need for optimal management of these patients by a multidisciplinary team with intensive supportive care to ensure completion of planned treatment to achieve better outcomes.

Loop electrosurgical procedure of the transformation zone of the cervix (LEEP) is the preferred method for many investigators for early detection and treatment of high grade intraepithelial neoplasia(HGCIN). Histopathology reports of LEEP should contain information about the diagnosis, presence or absence of neoplasia ( with its grade) and comment on excison margins.Our aim was to study LEEP reports for its contents and to see their correlation with preprocudure histology and/or cytology report.Between 2011 and 2017, 44 LEEP reports were archived and studied for their contents from our records. Slides were not reviewed. Mean age was 47.66 years (median 47 years). Forty two (( 95.45%) reports mentioned that all the tissue was examined. Deep cut examination was mentioned in 17/44 cases (38.64%). The concordance rate between LEEP and preprocudure histology and /or cytology for CIN II plus diagnosis is 65.9%. A strict definition is used. If, however, diagnoses between inflammation and CIN I, ASC-H and inflammation, and ASC-H and CIN I are considered non discordant, then the concordance rate rises to 72.7 %. The breakup of discordant cases is given.Literature shows wide range of concordance due to variable definitions and variety of reasons; possible reasons are discussed.

LPS-responsive beige-like anchor protein (LRBA) deficiency abolishes LRBA protein expression due to biallelic mutations in the LRBA gene that lead to autoimmune manifestations, inflammatory bowel disease, hypogammaglobulinemia in early stages, and variable clinical manifestations.Mutational analysis of theWe report an unusual case of a female patient born of a consanguineous marriage, presented with severe anaemia and jaundice with a history of multiple blood transfusions of unknown cause up to the age of 5 yrs. She had hepatosplenomegaly with recurrent viral and bacterial infections. Tests for hemoglobinopathies, enzymopathies, and hereditary spherocytosis were within the normal limits. The t-NGS revealed a novel homozygous missense variation in exon 53 of theThis study concludes the importance of a timely decision of targeted exome sequencing for the molecular diagnostic tool of unexplained haemolytic anaemia with heterogeneous clinical phenotypes.

IntroductionIn locally advanced cervical cancer, nodal, local and distant relapse continue to be significant patterns of relapse. Therefore, strategies to improve the efficacy of chemoradiation are desirable such as biological pathway modifiers and immunomodulating agents. This trial will investigate the impact of nelfinavir, a protease inhibitor that targets the protein kinase B (AKT) pathway on disease-free survival (DFS).Methods and analysisRadiosensitising effect of nelfinavir in locally advanced carcinoma of cervix is a single-centre, open-label, parallel-group, 1:1 randomised phase-III study. Patients aged over 18 years with a diagnosis of carcinoma cervix stage III are eligible for the study. After consenting, patients will undergo randomisation to chemoradiation and brachytherapy arm or nelfinavir with chemoradiation and brachytherapy arm. The primary aim of the study is to compare the difference in 3-year DFS between the two arms. Secondary aims are locoregional control, overall survival, toxicity and quality of life between the two arms. Pharmacokinetics of nelfinavir and its impact on tumour AKT, programmed cell death ligand 1, cluster of differentiation 4, cluster of differentiation 8 and natural killer 1.1 expression will be investigated. The overall sample size of 348 with 1 planned interim analysis achieves 80% power at a 0.05 significance level to detect a HR of 0.66 when the proportion surviving in the control arm is 0.65. The planned study duration is 8 years.Ethics and disseminationThe trial is approved by the Institutional Ethics Committee-I of Tata Memorial Hospital, Mumbai (reference number: IEC/0317/1543/001) and will be monitored by the data safety monitoring committee. The study results will be disseminated via peer-reviewed scientific journals, and conference presentations. Study participants will be accrued after obtaining written informed consent from them. The confidentiality and privacy of study participants will be maintained.Trial registration numberThe trial is registered with Clinical Trials Registry-India (CTRI/2017/08/009265) and ClinicalTrials.gov (NCT03256916).

Breast cancer (BC) is the most extensively accounted malignancy among the women across the globe and is treatable in 70-80% of patients with early-stage, non-metastatic cancer. The current available therapies have been found to be less effective to treat distant organ metastases and advanced breast cancers. The clinical efficacy hugely suffers from chemoresistance, non-specific toxicity, relapse and other associated adverse effects. Furthermore, lack of controlled delivery and effective temporospatial presence of chemotherapeutics has resulted in suboptimal therapeutic response. Nanotechnology based approaches have been widely used over the period as they are nanometric, offer controlled and site-specific drug release along with reduced toxicity, improved half-life, and stability. Lipid-based nanoplatforms have grabbed a tremendous attention for delivering cancer therapeutics as they are cost-effective, scalable and provide better entrapment efficiency. In this review, all the promising applications of lipid-engineered nanotechnological tools for breast cancer will be summarized and discussed. Subsequently, BC therapy achieved with the aid of chemotherapeutics, phytomedicine, genes, peptides, photosensitizers, diagnostic and immunogenic agents etc. will be reviewed and discussed. This review gives tabular information on all the results obtained pertaining to the physicochemical properties of the lipidic nanocarrier, in vitro studies conferring to mechanistic drug release profile, cell viability, cellular apoptosis and in vivo studies referring to cellular internalisation, reduction of tumor volume, PK-PD profile, bioavailability achieved and anti-tumor activity in detail. It also gives complete information on the most relevant clinical trials done on lipidic nanoplatforms over two decades in tabular form. The review highlights the current status and future prospects of lipidic nanoplatforms with streamlined focus on cancer nanotherapeutics.

The aim of the study was to investigate the clinical utility of estimated levator ani subtended volume (eLASV) as a prospective preoperative biomarker for prediction of surgical outcomes.This is a prospective case-control pilot study. Patients were recruited and gave consent between January 2018 and December 2020. Surgical failure was defined by composite score. The eLASV was calculated for each patient based on a previously published algorithm. Descriptive statistics, Fisher exact test, log-binomial regression, area under a receiver operating characteristics, Bland-Altman plot, Lin coefficient, and κ coefficient were all performed for analysis.Fifty-one patients gave consent, 31 completed preoperative magnetic resonance imaging, 27 underwent surgery (uterosacral ligament suspension), and 19 followed up for 1-year examination. Five patients (26.3%) were defined as surgical failure with median eLASV volume of 57.0 (interquartile range, 50.1-66.2). Fourteen patients (73.7%) were defined as surgical success with median eLASV of 28.2 (interquartile range, 17.2-24.3). Eighty percent of the surgical failure group (4/5) had elevated volume of eLASV, where only 14.3% of the success group (2/14) had an elevated volume (P = 0.0173). No confounders were found and unadjusted log-binomial regression suggested that patients with a high eLASV were 8.7 (95% confidence interval, 1.2-61.9) times more likely to experience surgical failure compared with those with low eLASV. The c-statistic (area under a receiver operating characteristics) was high at 0.829 along with Lin concordance coefficient of 0.949 (95% confidence interval, 0.891-0.977) for continuous data between the 2 interrater observer teams.In this small prospective pilot study, patients with elevated eLASV on a preoperative pelvic magnetic resonance imaging were associated with an increased risk for surgical failure at 1 year regardless of age, body mass index, stage, or parity.CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov, NCT03534830.

Background: Right ventricular outflow tract (RVOT) is a common source of ventricular tachycardia, which often requires ablation. However, the mechanisms underlying the RVOT’s unique arrhythmia susceptibility remain poorly understood due to lack of detailed electrophysiological and molecular studies of the human RVOT. Methods: We conducted optical mapping studies in 16 nondiseased donor human RVOT preparations subjected to pharmacologically induced adrenergic and cholinergic stimulation to evaluate susceptibility to arrhythmias and characterize arrhythmia dynamics. Results: We found that under control conditions, RVOT has shorter action potential duration at 80% repolarization relative to the right ventricular apical region. Treatment with isoproterenol (100 nM) shortened action potential duration at 80% repolarization and increased incidence of premature ventricular contractions ( P =0.003), whereas acetylcholine (100 μM) stimulation alone had no effect on action potential duration at 80% repolarization or premature ventricular contractions. However, acetylcholine treatment after isoproterenol stimulation reduced the incidence of premature ventricular contractions ( P =0.034) and partially reversed action potential duration at 80% repolarization shortening ( P =0.029). Immunolabeling of RVOT (n=4) confirmed the presence of cholinergic marker VAChT (vesicular acetylcholine transporter) in the region. Rapid pacing revealed RVOT susceptibility to both concordant and discordant alternans. Investigation into transmural arrhythmia dynamics showed that arrhythmia wave fronts and phase singularities (rotors) were relatively more organized in the endocardium than in the epicardium ( P =0.006). Moreover, there was a weak but positive spatiotemporal autocorrelation between epicardial and endocardial arrhythmic wave fronts and rotors. Transcriptome analysis (n=10 hearts) suggests a trend that MAPK (mitogen-activated protein kinase) signaling, calcium signaling, and cGMP-PKG (protein kinase G) signaling are among the pathways that may be enriched in the male RVOT, whereas pathways of neurodegeneration may be enriched in the female RVOT. Conclusions: Human RVOT electrophysiology is characterized by shorter action potential duration relative to the right ventricular apical region. Cholinergic right ventricular stimulation attenuates the arrhythmogenic effects of adrenergic stimulation, including increase in frequency of premature ventricular contractions and shortening of wavelength. Right ventricular arrhythmia is characterized by positive spatial-temporal autocorrelation between epicardial-endocardial arrhythmic wave fronts and rotors that are relatively more organized in the endocardium.

Lymphedema is a pathological condition in which intercellular protein-rich fluid accumulates and leads over time to inflammation, adipose tissue hypertrophy and fibrosis. Secondary lymphedema is caused by injury or blockage of the lymphatic system and the main cause in the Western world is the treatment of a variety of cancers, the main one being breast cancer. Chronic arm edema after breast cancer surgery is a common problem with an estimated incidence of 1 in 5 patients after breast cancer treatment. In this article we review the main risk factors, approaches to reducing the risk of developing lymphedema after treatment for breast cancer and existing treatment protocols for lymphedema including the surgical innovations in this field and our experience in these innovative surgical approaches. To date, 26 physiological surgeries have been performed at the Tel Aviv Medical Center using the microsurgical approach for treating lymphedema. These surgeries had no significant complications and the improvement was observed to be greater in the group of patients with secondary lymphedema. Lymphovenous anastomosis and vascularized lymph node transfer offer promising solutions for the treatment of breast cancer related lymphedema. The introduction of additional techniques and the refinement of these procedures will probably continue to improve the results in the future.

Primary hepatic epithelioid hemangioendothelioma (HEHE) is a rare tumor with an incidence of0.1 per 100,000. The clinical course is variable with variable outcomes. Due to its rarity, treatment protocols, prognostic and predictive factors are not well established underscoring the need for such a study. Pathologists' awareness of this entity, a meticulous morphologic examination coupled with immunohistochemistry can aid in accurate diagnosis.

BRCA1/2 founder pathogenic variants (PVs) occur in various populations, but data on the mutational spectrum in Africans are limited. We examined BRCA1/2 PVs in breast cancer patients of Ethiopian Jewish (EJ) origin.We retrospectively analyzed BRCA1/2 test results and clinical features of EJ breast cancer patients from seven medical institutions. We obtained heterozygote carrier rates in affected individuals from the laboratories of the largest Israeli HMO (Clalit). Population carrier frequency was determined in EJ controls.We identified three recurrent BRCA2 PVs in 11 EJ breast cancer patients (9 females, 2 males): c.7579delG, c.5159C A, and c.9693delA. Only c.5159C A was previously reported in Africans. In women, mean age at diagnosis was 35.7y; 8/9 were diagnosed with advanced disease. All tumors were invasive, 4/9 were triple negative. Only 3/11 carriers had relevant family history. Carrier rate in high-risk breast cancer patients was 11% (3/28; 95%CI [2.3%, 28.2%]). Combined carrier rate among controls was 1.8% (5/280; 95%CI [0.6%, 4.1%]).EJs harbor 3 recurrent BRCA2 PVs presenting with relatively severe breast cancer morbidity. Combined with the high BRCA2 carrier rate in the EJ population, these findings merit increasing awareness in this community and suggest that a culturally adapted population screening approach may be warranted.

BACKGROUND: The low cost and small specimen volume of the VitMin Lab ELISA assays for serum ferritin (Fer), soluble transferrin receptor (sTfR), C-reactive protein (CRP), and α−1-acid glycoprotein (AGP) have allowed their application to micronutrient surveys conducted in low-resource countries for ~2 decades. OBJECTIVES: We conducted a comparison between the ELISA and reference-type assays used in the US NHANES. METHODS: Using the Roche clinical analyzer as a reference, we measured random subsets of the 2016 Nepal National Micronutrient Status Survey (200 serum samples from children aged 6–59 mo; 100 serum samples from nonpregnant women) for Fer, sTfR, CRP, and AGP. We compared the combined data sets with the ELISA survey results using descriptive analyses. RESULTS: The Lin’s concordance coefficients between the 2 assays were ≥0.89 except for sTfR (Lin’s ρ = 0.58). The median relative difference to the reference was as follows: Fer, −8.5%; sTfR, 71.2%; CRP, −19.5%; and AGP, −8.2%. The percentage of VitMin samples agreeing within ±30% of the reference was as follows: Fer, 88.5%; sTfR, 1.70%; CRP, 74.9%; and AGP, 92.9%. The prevalence of abnormal results was comparable between the 2 assays for Fer, CRP, and AGP, and for sTfR after adjusting to the Roche assay. Continued biannual performance (2007–2019) of the VitMin assays in CDC’s external quality assessment program (6 samples/y) demonstrated generally acceptable performance. CONCLUSIONS: Using samples from the Nepal survey, the VitMin ELISA assays produced mostly comparable results to the Roche reference-type assays for Fer, CRP, and AGP. The lack of sTfR assay standardization to a common reference material explains the large systematic difference observed for sTfR, which could be corrected by an adjustment equation pending further validation. This snapshot comparison together with the long-term external quality assessment links the survey data generated by the VitMin Lab to the Roche assays used in NHANES.

Background & objectives Aetiology of cervical cancer (CaCx) is multifactorial. Besides human papillomavirus (HPV) infection, many immunogenetic factors are involved in this complex process. The present study was carried out to investigate one such factor, interleukin-6 (IL-6), a central pro-inflammatory cytokine and a polymorphism at its promoter region -174 G/C (rs1800795) with CaCx. Methods HPV-infected women with or without CaCx were enrolled in group I and II, respectively. Another group of uninfected healthy women was also included as group III for comparison. Polymorphism in IL-6-174 G/C and IL-6 levels were analyzed by sequence-specific primer PCR (PCR-SSP) and ELISA, respectively. Results Groups I (n=111) and II (n=87) had significantly higher frequency of IL-6-174 GG genotype [odds ratios (OR)=3.9; P

We used data from the 2016 Nepal National Micronutrient Status Survey to evaluate factors associated with anaemia (World Health Organization cut‐points using altitude‐ and smoking‐adjusted haemoglobin [Hb]) among nationally representative samples of adolescents 10–19 years. Hb, biomarkers of micronutrients, infection and inflammation were assessed from venous blood. Sociodemographic and household characteristics, dietary diversity, pica and recent morbidity were ascertained by interview. We explored bivariate relationships between candidate predictors and anaemia among boys (N = 967) and girls (N = 1,680). Candidate predictors with P < 0.05 in bivariate analyses were included in sex‐specific multivariable logistic regression models. Anaemia prevalence was 20.6% (95% confidence interval [CI] [17.1, 24.1]) among girls and 10.9% (95% CI [8.2, 13.6]) among boys. Among girls, living in the Mountain and Hill ecological zones relative to the Terai (adjusted odds ratio [AOR] 0.28, 95% CI [0.15, 0.52] and AOR 0.42, 95% CI [0.25, 0.73], respectively), ln ferritin (μg/L) (AOR 0.53, 95% CI [0.42, 0.68]) and ln retinol binding protein (RBP) (μmol/L) (AOR 0.08, 95% CI [0.04, 0.16]) were associated with reduced anaemia odds. Older age (age in years AOR 1.19, 95% CI [1.12, 1.27]) and Janajati ethnicity relative to the Muslim ethnicity (AOR 3.04, 95% CI [1.10, 8.36]) were associated with higher anaemia odds. Among boys, ln RBP [μmol/L] (AOR 0.25, 95% CI [0.10, 0.65]) and having consumed flesh foods (AOR 0.57, 95% CI [0.33, 0.99]) were associated with lower anaemia odds. Open defecation (AOR 2.36, 95% CI [1.15, 4.84]) and ln transferrin receptor [mg/L] (AOR 3.21, 95% CI [1.25, 8.23]) were associated with increased anaemia odds. Anaemia among adolescents might be addressed through effective public health policy and programs targeting micronutrient status, diet and sanitation.

Childhood linear growth faltering remains a major public health concern in Nepal. Nevertheless, over the past 20 years, Nepal sustained one of the most rapid reductions in the prevalence of stunting worldwide. First, our study analysed the trends in height‐for‐age z‐score (HAZ), stunting prevalence, and available nutrition‐sensitive and nutrition‐specific determinants of linear growth faltering in under‐three children across Nepal's Family Health Survey 1996 and Nepal's Demographic and Health Surveys 2001, 2006, 2011, and 2016. Second, we constructed pooled multivariable linear regression models and decomposed the contributions of our time‐variant determinants on the predicted changes in HAZ and stunting over the past two decades. Our findings indicate substantial improvements in HAZ (38.5%) and reductions in stunting (−42.6%) and severe stunting prevalence (−63.9%) in Nepalese children aged 0–35 months. We also report that the increment in HAZ, across the 1996–2016 period, was significantly associated (confounder‐adjusted p < .05) with household asset index, maternal and paternal years of education, maternal body mass index and height, basic child vaccinations, preceding birth interval, childbirth in a medical facility, and prenatal doctor visits. Furthermore, our quantitative decomposition of HAZ identified advances in utilisation of health care and related services (31.7% of predicted change), household wealth accumulation (25%), parental education (21.7%), and maternal nutrition (8.3%) as key drivers of the long‐term and sustained progress against child linear growth deficits. Our research reiterates the multifactorial nature of chronic child undernutrition and the need for coherent multisectoral nutrition‐sensitive and nutrition‐specific strategies at national scale to further improve linear growth in Nepal. [Correction added on 6 November 2020, after first online publication: in abstract, the citation year in the fourth sentence has been changed from ‘2001’ to ‘2011’.]

Radiation therapy, a common treatment for head, neck, and brain cancers, can result in iatrogenic damage to neural tissue, including cranial nerves.1-4 Postradiation neurologic injuries present during acute (days to weeks after radiation), early-delayed (weeks to months), or late-delayed (beyond 6 months) phases.5 Cranial neuropathy is uncommon and occurs during the late-delayed phase, usually months to a few years after radiation treatment,1,3-5 but can also occur decades later.6 Here, we describe a presentation of bilateral, sequential, radiation-induced oculomotor nerve palsy that developed after 2 decades.