Microbiological Characteristics and Resistance Patterns in a Neonatal Intensive Care Unit: A Retrospective Surveillance Study.

BACKGROUND AND OBJECTIVE: This study aims to assess the prevalence and antimicrobial susceptibility patterns of bacterial infections associated with both early-onset sepsis (EOS) and late-onset sepsis (LOS). METHODOLOGY: This descriptive retrospective surveillance research was conducted on all neonates admitted to the neonatal ICU with bacterial sepsis, where positive cultures were isolated from sterile sites (either cerebrospinal fluid or blood) at Tawam Hospital, Al Ain, Emirate of Abu Dhabi, UAE, from January 2012 and December 2021. Antimicrobial susceptibility analysis was performed. RESULTS: The incidence of LOS (94.43%) was higher compared to EOS (5.56%). The most prevalent isolates (59.2%) were gram-positive bacteria, with gram-negative bacteria accounting for 40.8%. The leading isolates included coagulase-negative Staphylococci (CONS, 40.98%), Klebsiella (16.04%), Staphylococcus aureus (8.46%), Escherichia coli (8.24%), Pseudomonas (7.57%), and Group B Streptococcus (GBS, 5.12%). CONS were predominant in LOS cases (42.9%), while GBS was the main pathogen in EOS cases (44%). CONCLUSIONS: We observed reduced resistance levels of CONS against ampicillin, benzylpenicillin, clindamycin, erythromycin, fusidic acid, gentamicin, oxacillin, rifampicin, and trimethoprim/sulfa. S. aureus exhibited increased resistance to erythromycin, fusidic acid, gentamicin, and levofloxacin, while E. coli demonstrated decreased resistance against cephalothin, gentamicin, and trimethoprim/sulfa. The antibiotics currently employed empirically appear to provide adequate coverage against the most prevalent bacteria causing early- and late-onset neonatal infections.

Patient Selection for Living Donor Liver Transplantation in Acute-on-chronic Liver Failure.

Background and objectives: Acute-on-chronic liver failure (ACLF) is associated with high short-term mortality without liver transplantation (LT). The selection criteria for LT in these patients are not well defined. The objective of this study was to determine factors associated with post-transplant survival in ACLF. Methods: This was a single-center retrospective study of patients who underwent living donor liver transplantation (LDLT) for ACLF between 2012 and 2022. Out of 1093 transplants, 110 patients had underlying ACLF, based on the European Association for the Study of the Liver-Chronic Liver Failure Consortium (EASL-CLIF) criteria. We looked at factors associated with 1-year posttransplant survival. Results: The median model for end-stage liver disease (MELD) score was 33.5 (31-38), and the 1-year posttransplant survival was 72%. Six risk factors were associated with posttransplant survival, namely, body mass index > 30 kg/m2 [HR, 4.4; 95% CI, 1.8-10.7], platelet count < 66,000/µl [HR, 2.91; CI,1.2-6.6], poor response to medical treatment [HR, 2.6; CI, 1.1-5.7], drug-resistant bacterial or fungal cultures [HR, 4.2; CI, 1.4-12.4], serum creatinine > 2.5 mg/dl [HR, 3.4; CI, 1.5-7.7], and graft-to-recipient weight ratio < 0.7 [HR, 4.8; CI, 1.4-16.3]. The 1-year post-transplant survival was 84% in patients with 0-2 risk factors (n = 89) and was 6% with 3 risk factors (n = 15) (P < 0.001). For 1-year posttransplant survival, the area under curve (AUC) for the current model was 0.8 (0.69-0.9). The AUC for CLIF-ACLF, Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA), and EASL-CLIF ACLF grades was < 0.5. Conclusion: In LT for ACLF, acceptable survival can be achieved when less than three high-risk factors are present.

Design of experiment approach to identify the dominant geometrical feature of left coronary artery influencing atherosclerosis.

Background and Objective. Coronary artery geometry heavily influences local hemodynamics, potentially leading to atherosclerosis. Consequently, the unique geometrical configuration of an individual by birth can be associated with future risk of atherosclerosis. Although current researches focus on exploring the relationship between local hemodynamics and coronary artery geometry, this study aims to identify the order of influence of the geometrical features through systematic experiments, which can reveal the dominant geometrical feature for future risk assessment.Methods. According to Taguchi's method of design of experiment (DoE), the left main stem (LMS) length (lLMS), curvature (kLMS), diameter (dLMS) and the bifurcation angle between left anterior descending (LAD) and left circumflex (LCx) artery (αLAD-LCx) of two reconstructed patient-specific left coronary arteries (LCA) were varied in three levels to create L9 orthogonal array. Computational fluid dynamic (CFD) simulations with physiological boundary conditions were performed on the resulting eighteen LCA models. Average helicity intensity (h2) and relative atheroprone area (RAA) of near-wall hemodynamic descriptors were analyzed.Results. The proximal LAD (LADproximal) was identified to be the most atheroprone region of the left coronary artery due to higherh2,large RAA of time averaged wall shear stress (TAWSS < 0.4 Pa), oscillatory shear index (OSI ∼ 0.5) and relative residence time (RRT > 4.17 Pa-1). In both patient-specific cases, based onh2and TAWSS,dlmsis the dominant geometric parameter while based on OSI and RRT,αLAD-LCxis the dominant one influencing hemodynamic condition in proximal LAD (p< 0.05). Based on RRT, the rank of the geometrical factors is:αLAD-LCx>dLMS>lLMS>kLMS, indicating thatαLAD-LCxis the most dominant geometrical factor affecting hemodynamics at proximal LAD which may influence atherosclerosis.Conclusion. The proposed identification of the rank of geometrical features of LCA and the dominant feature may assist clinicians in predicting the possibility of atherosclerosis, of an individual, long before it will occur. This study can further be translated to be used to rank the influence of several arterial geometrical features at different arterial locations to explore detailed relationships between the arterial geometrical features and local hemodynamics.

Factors associated with multimorbidity in England: an analysis of the English Longitudinal Study of Ageing.

BACKGROUND: Multimorbidity, defined as the presence of two or more long-term conditions, is a growing public health challenge, especially in terms of prevention and accumulation of long-term conditions among particular population cohorts. To date, efforts to understand multimorbidity has focused mainly on specific disease combinations, with little known about the sociodemographic factors associated with it. The study aimed to assess the factors associated with multimorbidity in England. METHODS: A cross-sectional study was conducted using the English Longitudinal Study of Ageing (ELSA), a dataset of people aged 50 years and older. The study identified ten long-term conditions from waves 2 to 9. Wave 2 to 9 were conducted between June 2004 to July 2005, May 2006 to August 2007, May 2008 to July 2009, June 2010 to July 2011, May 2012 to June 2013, June 2014 to May 2015, May 2016 to June 2017 and June 2018 to July 2019, respectively. The study included people with two or more long-term conditions. We identified the number of long-term conditions and multimorbidity, and we examined their association with age, gender, ethnicity, marital status, employment status, education, weekly contact with relative, and feeling lonely, sad or depressed using multinomial logistic regression. FINDINGS: Of 16 731 people recruited from wave 2 to wave 9, we identified 10 026 people with multimorbidity aged 50 years and older. The majority had two conditions (39%) and were female (55%), aged 50-69 years (32%), of white ethnicity (96%), married (69%) and unemployed (65·3%). The adjusted odds ratio (aOR) of having more than two long-term conditions increased with age, after adjusting for sex and ethnicity (≥5 conditions: aOR 12·89, 95% CI 2·23-3·76). Being female was associated with an increased risk of having more than two long-term conditions (≥5 conditions: aOR 1·21, 1·04-1·42). Similarly, being separated, divorced, or widowed were associated with having more than two long-term conditions (≥5 conditions: aOR 1·45, 1·21-1·74). Not owning a home was independently associated with more than two long-term conditions (≥5 conditions: aOR 1·59, 1·35-1·88). INTERPRETATION: The current analysis used only ten long-term conditions that were available in the ELSA data, so a different association might have arisen if other conditions had been considered. Our findings provide insights into which particular groups of the multimorbid population could be the target of preventive public health strategies and wider clinical and social care interventions in England to reduce the burden of multimorbidity. FUNDING: National Institute for Health and Care Research (NIHR).

Liver transplantation with interposition saphenous vein conduits for arterial reconstruction: Impact of morbidity and arterial ischemia time.

BACKGROUND: The outcomes of liver transplantation with hepatic arterial reconstruction using interposition saphenous vein conduits are not widely reported. Here, we share our experience using great saphenous vein conduits for hepatic arterial reconstruction in living donor liver transplantation. METHODS: This was a single-center retrospective review of patients who underwent living donor liver transplantation (n = 950). The saphenous vein conduits were used in 39 patients. We compared hepatic artery thrombosis, graft dysfunction, and 30-day and 1-year survival in the early (2012-2017) and late (2017-2020) transplant periods. RESULTS: Among 39 patients (of whom 30 [76.9%] were males, median Model for End-Stage Liver Disease was 24 [interquartile range, 17-27], median age was 50 [interquartile range, 43-54]), saphenous vein conduits were placed on supra celiac aorta in 7 (17.9%), infrarenal aorta in 25 (64.1%), and other arteries in 7 (17.9%) patients. The number of biliary and hepatic vein anastomoses, total arterial ischemia time, portal vein-hepatic artery reperfusion time, and duration of surgery was different in the 2 groups (P < .05). The 30-day mortality was 5/21 (23.8%) and 0 in the early and late periods (P = .05). The 30-day survival was >90% in patients with portal vein-hepatic artery reperfusion time <240 minutes, ≤2 grade 3 complications, no graft dysfunction, and later period of transplantation (P < .05). The 1-year survival with standard transplantation, transplantation with saphenous vein conduits in the early and late period was 87%, 62%, and 89% (P = .022). CONCLUSION: Liver transplantation with saphenous vein conduits is associated with acceptable outcomes. Major complications and arterial ischemia times are major determinants of outcomes.

Wheat Water-Soluble Carbohydrate Remobilisation under Water Deficit by 1-FEH w3.

Fructan 1-exohydrolase (1-FEH) is one of the major enzymes in water-soluble carbohydrate (WSC) remobilisation for grains in wheat. We investigated the functional role of 1-FEH w1, w2, and w3 isoforms in WSC remobilisation under post-anthesis water deficit using mutation lines derived from the Australian wheat variety Chara. F1 seeds, developed by backcrossing the 1-FEH w1, w2, and w3 mutation lines with Chara, were genotyped using the Infinium 90K SNP iSelect platform to characterise the mutated region. Putative deletions were identified in FEH mutation lines encompassing the FEH genomic regions. Mapping analysis demonstrated that mutations affected significantly longer regions than the target FEH gene regions. Functional roles of the non-target genes were carried out utilising bioinformatics and confirmed that the non-target genes were unlikely to confound the effects considered to be due to the influence of 1-FEH gene functions. Glasshouse experiments revealed that the 1-FEH w3 mutation line had a slower degradation and remobilisation of fructans than the 1-FEH w2 and w1 mutation lines and Chara, which reduced grain filling and grain yield. Thus, 1-FEH w3 plays a vital role in reducing yield loss under drought. This insight into the distinct role of the 1-FEH isoforms provides new gene targets for water-deficit-tolerant wheat breeding.

Clustering by multiple long-term conditions and social care needs: a cross-sectional study among 10 026 older adults in England.

BACKGROUND   : People with multiple long-term conditions (MLTC) face health and social care challenges. This study aimed to classify people by MLTC and social care needs (SCN) into distinct clusters and quantify the association between derived clusters and care outcomes. METHODS : A cross-sectional study was conducted using the English Longitudinal Study of Ageing, including people with up to 10 MLTC. Self-reported SCN was assessed through 13 measures of difficulty with activities of daily living, 10 measures of mobility difficulties and whether health status was limiting earning capability. Latent class analysis was performed to identify clusters. Multivariable logistic regression quantified associations between derived MLTC/SCN clusters, all-cause mortality and nursing home admission. RESULTS: Our study included 9171 people at baseline with a mean age of 66.3 years; 44.5% were men. Nearly 70.8% had two or more MLTC, the most frequent being hypertension, arthritis and cardiovascular disease. We identified five distinct clusters classified as high SCN/MLTC through to low SCN/MLTC clusters. The high SCN/MLTC included mainly women aged 70-79 years who were white and educated to the upper secondary level. This cluster was significantly associated with higher nursing home admission (OR=8.71; 95% CI: 4.22 to 18). We found no association between clusters and all-cause mortality. CONCLUSIONS: We have highlighted those at risk of worse care outcomes, including nursing home admission. Distinct clusters of individuals with shared sociodemographic characteristics can help identify at-risk individuals with MLTC and SCN at primary care level.

Clinical learning environments across two different healthcare settings using the undergraduate clinical education environment measure.

BACKGROUND: The clinical placements of our medical students are almost equally distributed across private and public sectors. This study aims to assess medical students' perceptions of their Clinical learning Environment (CLE) across these two different healthcare settings, using the Undergraduate Clinical Education Environment Measure (UCEEM). METHODS: 76 undergraduate medical students (Year 5 and 6), were invited to participate. Data were collected using an online UCEEM with additional questions related to demographics and case load exposure. The UCEEM consists of two overarching domains of experiential learning and social participation, with four subdomains of learning opportunities, preparedness, workplace interaction, and inclusion. RESULTS: 38 questionnaires were received. Of 225 responses to the individual UCEEM items, 51 (22.6%) scored a mean of ≥ 4 (range 4-4.5, representing strong areas), 31 (13.7%) scored a mean of ≤ 3 (range 2.1-3, needing attention) and 143 (63.6%) scored a mean of 3.1-3.9 (areas that could be improved). The majority (63%) of the case load exposure responses scored a mean of ≥ 4 (range 4-4.5). Compared to the private sittings, there is a significant reduction in total UCEEM (p = 0.008), preparedness for student entry (p = 0.003), and overarching dimension of social participation (p = 0.000) scores for the public sector. Similarly, both workplace interaction patterns and student inclusion and equal treatment scored significantly lower for the public sector (p = 0.000 and p = 0.011 respectively). Two out of three case load exposure items scored significantly higher for the public sector (p = 0.000). DISCUSSION: The students' CLE perceptions were generally positive. The lower UCEEM ratings in the public sector items were related to student entry preparedness, workplace interactions, student inclusiveness and workforce equity of treatment. In contrast the students were exposed to more variety and larger number of patients in the public sector. These differences indicated some significantly different learning environments between the two sectors.

Trajectories of multiple long-term conditions and mortality in older adults: A retrospective cohort study using English Longitudinal Study of Ageing (ELSA).

Objectives: To classify older adults with MLTC into clusters based on accumulating conditions as trajectories over time, characterise clusters and quantify associations between derived clusters and all-cause mortality. Design: We conducted a retrospective cohort study using the English Longitudinal Study of Ageing (ELSA) over nine years (n=15,091 aged 50 years and older). Group-based trajectory modelling was used to classify people into MLTC clusters based on accumulating conditions over time. Derived clusters were used to quantify the associations between MLTC trajectory memberships, sociodemographic characteristics, and all-cause mortality. Results: Five distinct clusters of MLTC trajectories were identified and characterised as: "no-LTC" (18.57%), "single-LTC" (31.21%), "evolving MLTC" (25.82%), "moderate MLTC" (17.12%), and "high MLTC" (7.27%). Increasing age was consistently associated with an increased number of MLTC. Female sex (aOR = 1.13; 95%CI 1.01 to 1.27) and ethnic minority (aOR = 2.04; 95%CI 1.40 to 3.00) were associated with the "moderate MLTC" and "high MLTC" clusters, respectively. Higher education and paid employment were associated with a lower likelihood of progression over time towards an increased number of MLTC. All the clusters had higher all-cause mortality than the "no-LTC" cluster. Conclusions: The development of MLTC and the increase in the number of conditions over time follow distinct trajectories. These are determined by non-modifiable (age, sex, ethnicity) and modifiable factors (education and employment). Stratifying risk through clustering will enable practitioners to identify older adults with a higher likelihood of worsening MLTC over time to tailor effective interventions.

Comparison of various models for the estimation of heritability and breeding values.

The exploration of additive genetic variance for the selection of animals is the central paradigm in quantitative genetics and it is important to use appropriate animal models considering important factors. This study compares various factor effects for heritability and breeding values estimations on data collected on the Corriedale. Overall, the heritability estimates were the highest for birthweight (BW). Both the additive genetic variance and the heritability values were reduced upon adding more random effects. Year-effect as random reduced the heritability except for BW. The highest average accuracy for breeding values for birth, weaning, 6, 9, and 12-month-weights for were 0.656, 0.567, 0.519, 0.486, and 0.515. These were observed for models having sex or sex and parity as fixed effects. It is concluded that fixed and random factors have a significant impact on genetic-factors and breeding-value accuracies and should be considered during selection programs and make the selection program more effective.

Outcomes of hepaticojejunostomy for post-cholecystectomy bile duct injury.

OBJECTIVES: Long-term results of hepaticojejunostomy (HJ) for complex bile duct injury (BDI) remain under-reported. The objective of this study was to assess short-term and long-term outcomes of HJ for post-cholecystectomy BDI. METHODS: This was a retrospective cohort study and included patients who underwent Roux-en-Y HJ for BDI (n = 87). Short-term (90-day) and long-term morbidity and mortality were assessed. RESULTS: At presentation, 42 (48.2%) patients had E3 or E4 BDI, 27 (31%) patients had vascular injury, and liver resection was performed in 12 (13.7%) patients. The 90-day morbidity was 51.7% (n = 45), and the 90-day mortality was 2.3% (n = 2). The long-term mortality was 3.4% (n = 3). The 10-year estimated stricture-free survival was 95%. The 10-year estimated overall survival rate was 100% in patients who underwent major hepatectomy and 91% in patients who did not. The 10-year estimated overall survival rate was 100% in patients with vasculobiliary injury and was not reached in patients without vascular injury. CONCLUSIONS: Vascular injury with proximal BDI is not uncommon. Excellent long-term outcomes might be achieved with Roux-en-Y HJ for BDI with vascular injury and in patients requiring liver resection.

Morphometric indices of native sheep breeds of the Himalayan region of India using multivariate principal component analysis.

This study was performed to analyze the morphometric traits and indices in 3000 animals of five registered sheep breeds in the Himalayan region under a multivariate approach. Data were recorded under field conditions with equal coverage of the five breeds, viz., Karnah, Gurez, Poonchi, Bakerwal and Changthangi on body length (BL), height at withers (HW), chest girth (CG), ear length (EL), and tail length (TL). Furthermore, four derived traits (indices) were studied, which included an index of body frame (IBF), an index of thorax development (ITD), a Baron-Crevat index (BCI), and an index of body weight (IBW). Multivariate principal component analysis (PCA) was undertaken on nine morphometric traits. Kaiser's criterion was used to reduce the number of principal components for further analysis and interpretation. The adequacy of sampling was evaluated using Kaiser-Meyer-Olkin (KMO) test and Bartlett's test of sphericity. The mean BL ranged from 52.15 (Changthangi) to 71.13 (Gurez). The estimates of HW, CG, EL and TL were highest in Gurez (63.49), Bakerwal (84.82), Bakerwal (7.26), and Karnah (8.18) breeds, respectively. Among the derived traits, the highest IBF was observed in the Gurez breed with an estimate of 112.22. Upon multivariate PCA on the dataset, the first four principal components were able to explain 92.117% of the total variance. The KMO test, Bartlett's test of sphericity and estimated communalities showed the appropriateness of PCA on the evaluated traits. Four eigenvalues were greater than one and were extracted for further analysis. Morphometric traits were highly correlated, except for EL and TL that showed lower correlation estimates with other traits. The Changthangi population showed the lowest estimates of BL, HW, CG and rectangular body frame. The present study ascertained important morphometric traits/indices that can help in developing selection criteria and formulating sustainable breeding and conservation plans vis-à-vis the unique sheep breeds of the temperate Himalayas.

HRAS Mutations Define a Distinct Subgroup in Head and Neck Squamous Cell Carcinoma.

PURPOSE: In head and neck squamous cell carcinoma (HNSCC), HRAS mutation is a new actionable oncogene driver. We aimed to evaluate HRAS mutational variants, comutation profile, and survival outcomes of this molecularly defined population. METHODS: We leveraged four deidentified patient data sets with HRAS-mutant HNSCC, MD Anderson Cancer Center, Kura Oncology, Inc trial, Foundation Medicine, and American Association for Cancer Research GENIE v.12. Patient demographic information and clinical courses were extracted, when available, in addition to HRAS mutation type and co-occurring mutations. Survival outcomes were analyzed (Kaplan-Meier method). RESULTS: Two hundred forty-nine patients with HRAS-mutant HNSCC were identified from the four data sets. Median age ranged from 55 to 65 years, with a higher frequency in male patients (64%); the majority of HRAS-mutant HNSCC occurred in human papillomavirus-negative HNSCC. HRAS mutation patterns were similar across data sets; G12S was the most common (29%). Treatment responses to tipifarnib were not codon-specific. Compared with wild-type, significantly co-occurring mutations with HRAS were Casp8 (Fisher's exact test, P < .00013), TERT (P < .0085), and NOTCH1 (P < .00013). Analysis of clinical courses from the MD Anderson Cancer Center and Kura Oncology, Inc data sets demonstrated poor clinical outcomes with a high rate of recurrence following primary definitive treatment (50%-67% relapse < 6 months) and short disease-free survival (4.0 months; 95% CI, 1.0 to 36.0) and overall survival (OS; 15.0 months; 95% CI, 6.0 to 52.0). Use of tipifarnib in this data set demonstrated improved OS (25.5 months; 95% CI, 18.0 to 48.0). CONCLUSION: Oncogenic mutations in HRAS occur in 3%-4% of HNSCC, with G12S being the most frequent. Without targeted therapy, patients with HRAS-mutant HNSCC had poor clinic outcomes; observable trend toward improvement in OS has been noted in cohorts receiving treatments such as tipifarnib. The comutation pattern of HRAS-mutant in HNSCC is distinct, which may provide insight to future therapeutic combination strategies.

Survival after extended resections for gallbladder cancer.

Backgrounds/Aims: Locally advanced gallbladder cancer (GBC) is associated with survival limited to a few months. Extended resections (ER) are occasionally performed in this group and outcomes remain inconclusive. This study assessed outcomes after ER for locally advanced GBC. Methods: Patients who underwent ER for GBC between 2011 and 2020 were reviewed. ER was defined as a major hepatectomy alone (n = 9), a pancreaticoduodenectomy (PD) with or without minor hepatectomy (n = 3), a major hepatectomy with PD (HPD) (n = 3) or vascular resection and reconstruction (n = 4). We assessed 30-day morbidity, mortality, and 2-year overall survival (OS). Results: Among 19 patients, negative margins were achieved in 14 (73.6%). The 30-day mortality was 1/9 (11.1%) for a major hepatectomy, 0/3 (0%) for a minor HPD, 2/3 (66.7%) for a major HPD, and 1/4 (25.0%) for vascular resection. All short term survivors (< 6 months) (n=8) had preoperative jaundice and 6/8 (75.0%) underwent a major HPD or vascular resection. There were five (26.3%) long term survivors. The median OS in patients with and without preoperative jaundice was 4.1 months (0.7-11.1 months) and 13.7 months (12-30.4 months), respectively (p = 0.009) (2-year OS = 7% vs. 75%; p = 0.008). The median OS in patients who underwent a major hepatectomy alone or a minor HPD was 11.3 months (6.8-17.3 months) versus 1.4 months (0.3-4.1 months) (p = 0.02) in patients who underwent major HPD or vascular resection (2 year OS = 33% vs. not reached) (p = 0.010) respectively. Conclusions: In selected patients with GBC, when ER is limited to a major hepatectomy alone, or a minor HPD, acceptable survival can be achieved.

Textbook outcome among voluntary donors undergoing major living donor hepatectomy.

PURPOSE: Textbook outcome (TO) is a composite measure of outcome and provides superior assessment of quality of care after surgery. TO after major living donor hepatectomy (MLDH) has not been assessed. The objective of this study was to determine the rate of TO and its associated factors, after MLDH. METHODS: This was a single center retrospective review of living liver donors who underwent MLDH between 2012 and 2021 (n = 1022). The rate of TO and its associated factors was determined. RESULTS: Among 1022 living donors (of whom 693 [67.8%] were males, median age 26 [range, 18-54] years), TO was achieved in 714 (69.9%) with no donor mortality. Majority of donors met the cutoffs for individual outcome measures: 908 (88.8%) for no major complications, 904 (88.5%) for ICU stay ≤ 2 days, 900 (88.1%) for hospital stay ≤ 10 days, 990 (96.9%) for no perioperative blood transfusion, 1004 (98.2%) for no 30-day re-admission, and 1014 (99.2%) for no post-hepatectomy liver failure. Early donation era (before streamlining of donor operative pathways) was associated with failure to achieve TO [OR 1.4, CI 1.1-1.9, P = 0.006]. TO was achieved in 506/755 (67%) donors in the early donation era versus 208/267 (77.9%) in the later period (P = 0.001). CONCLUSION: Despite zero mortality and low complication rate, TO was achieved in approximately 70% donors. TO was modifiable and improved with changes in donor operative pathway.

Women's health status before and during the COVID-19 pandemic in rural Bangladesh: A prospective longitudinal study.

The coronavirus disease (COVID-19) pandemic has widely spread worldwide since 2020. Several countries have imposed lockdown or stay-at-home policies to prevent the infection. Bangladesh experienced a lockdown from March 2020 to May 2020, and internal travel was restricted. Such long and strict confinement may impact women's health. Herein, we aimed to assess the impact of the COVID-19 pandemic on women's health by comparing their health status before and during the pandemic. We conducted a prospective longitudinal study in two zones in the Chhaygaon union, rural district Shariatpur, Bangladesh. The study population comprised non-pregnant women aged 15-49 years. We visited the household of all eligible women and invited them for health checkups. The survey staff examined their health status at the checkup camps and conducted questionnaire interviews. In total, 121 non-pregnant women received health checkups both from June 2019 to July 2019 and in October 2020, before and during the COVID-19 pandemic, respectively. Compared with those during the 2019 health checkup, the medians of body mass index, systolic blood pressure, and diastolic blood pressure were significantly higher (22.7 kg/m2 to 23.6 kg/m2; 110.0 mmHg to 111.0 mmHg; and 73.0 mmHg to 75.0 mmHg, respectively, p<0.05) during the 2020 health checkup. In contrast, urine glucose levels were significantly lower (10.1% to 3.4%, p = 0.021). The lack of physical activity and other inconvenience accumulation caused by the prolonged confinement might have affected their health status. This necessitates local health workers to promote physical activity to prevent health deterioration during the pandemic.

Assessment of initial vancomycin trough levels and risk factors of vancomycin-induced nephrotoxicity in neonates.

OBJECTIVES: Vancomycin is a glycopeptide antibiotic commonly used in neonatal intensive care units (NICUs) to treat late onset sepsis. It is recommended that vancomycin trough levels at steady state following intermittent dosing regimen be maintained at 10-20 mg/L, which is largely dependent on the type of infection. Our objective is to assess the ability of initial vancomycin dosing regimens to obtain target trough levels and to assess the percentage and risk factors associated with the development of acute kidney injury (AKI) while on vancomycin. METHODS: This is a retrospective review of all NICU patients admitted between January 2016 and December 2017 who received vancomycin according to the NeoFax at either 10 mg/kg/dose (low-dose group, LDG) or 15 mg/kg/dose (high-dose group, HDG), with a frequency based on the postmenstrual age (PMA) and postnatal age (PNA). Both regimens were compared by their ability to attain target trough levels and the episodes of vancomycin-induced AKI. Other outcomes included identification of risk factors associated with the development of vancomycin-induced nephrotoxicity. RESULTS: Of 182 patients evaluated, 44 (24%) were in the LDG and 138 patients (76%) were in the HDG. Ninety-one patients (50%) attained target trough levels of 10-20 mg/L. Among these and according to patients' PMA, 48% in the HDG versus 7% in the LDG in PMA ≤29 weeks and 69% in the HDG versus 18% in the LDG in PMA 30-36 weeks attained target trough levels (p=0.006 and p<0.001, respectively). According to PNA, 47% in the HDG versus none in the LDG in patients <7 days old and 61% in the HDG versus 10% in the LDG in patients aged 8-14 days attained target trough levels (p=0.025 and p=0.016, respectively). A total of 14% developed AKI in the LDG vs 7% in the HDG (p=0.225). Only PMA ≤29 weeks (OR, 4.5, 95% CI 1.5 to 13), vancomycin trough levels >20 mg/L (OR 5.1, 95% CI 1.5 to 17), hypotension (OR 11.02, 95% CI 3.5 to 34) and furosemide (OR 4.4, 95% CI 1.4 to 13.5) were significantly associated with vancomycin-induced AKI in our NICU. CONCLUSION: Vancomycin dosing in neonates according to the NeoFax did not provide sufficient attainment of target trough levels (10-20 mg/L). However, using the higher dosing range at 15 mg/kg/dose was more likely to reach target levels, with no measured increased risk of nephrotoxicity. Extreme premature neonates, supratherapeutic vancomycin trough levels, hypotension and furosemide use are associated with an increased incidence of vancomycin-induced nephrotoxicity.

Vector engineering, strategies and targets in cancer gene therapy.

Understanding the molecular basis of disease and the design of rationally designed molecular therapies has been the holy grail in the management of human cancers. Gene-based therapies are an important avenue for achieving a possible cure. Focused research in the last three decades has provided significant clues to optimize the potential of cancer gene therapy. The development of gene therapies with a high potential to kill the target cells at the lowest effective dose possible, the development of vectors with significant ability to target cancer-associated antigen, the application of adjunct therapies to target dysregulated microRNA, and embracing a hybrid strategy with a combination of gene therapy and low-dose chemotherapy in a disease-specific manner will be pivotal. This article outlines the advances and challenges in the field with emphasis on the biology and scope of vectors used for gene transfer, newer targets identified, and their outcome in preclinical and clinical studies.

Risk Score Model for Liver Transplant Outcomes after Preoperative Locoregional Therapy for Hepatocellular Carcinoma.

PURPOSE: The role of preoperative locoregional therapy (LRT) for hepatocellular carcinoma (HCC) before liver transplantation (LT) remains unclear. Moreover, LRT in the setting of living donor liver transplantation (LDLT) merits further exploration. The objective of the current study was to determine risk factors for poor outcomes after LDLT in patients who received locoregional therapy (LRT). METHODS: We reviewed patients (n = 46) who underwent LDLT after LRT. Multivariate analysis was performed to determine independent predictors of recurrence-free survival (RFS). Risk scores were developed to define prognostic groups. RESULTS: Median tumor size was 3.7 (1.2-12) cm and tumor number was 1 (1-6). Macrovascular invasion was seen in 10/46 (21.7%) patients. There was a significant difference in 5-year RFS with > 3 tumor nodules (P = 0.005), tumors outside University of California San Francisco criteria (P = 0.03), bilobar disease (P = 0.002), AFP > 600 ng/ml (P = 0.006), and poor response to LRT (P = 0.007). On multivariate analysis, bilobar disease (HR = 2.9, P = 0.01), AFP > 600 ng/ml (HR = 2.3 P = 0.008), and poor response to LRT (HR = 2, P = 0.02) were predictors of 5-year RFS. The 5-year RFS in low risk (score = 0), intermediate risk (score = 1-3), and high risk (score = 4-7) groups was 86%, 76%, and 9% (P < 0.0001). There was no recurrence seen in 4/4 (100%) patients with macrovascular invasion in the low-intermediate risk group. The 5-year RFS in the low-intermediate risk group within and outside Milan criteria was 100% and 74% (P = 0.1). CONCLUSIONS: LDLT can provide excellent long-term RFS in patients after preoperative LRT in the low and intermediate risk groups.

Living donor liver transplantation for advanced hepatocellular carcinoma including macrovascular invasion.

BACKGROUND: The indications for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) continue to evolve. The aim of this study was to report outcomes in patients who underwent living donor liver transplantation (LDLT) for HCC outside traditional criteria including macrovascular invasion (MVI). METHODS: We reviewed outcomes in patients who met the University of California San Francisco (UCSF) criteria (n = 159) and our center-specific criteria (UCSF+) (largest tumor diameter ≤ 10 cm, any tumor number, AFP ≤ 1000 ng/ml) (n = 58). We also assessed outcomes in patients with MVI (n = 27). RESULTS: The median follow was 28 (10.6-42.7) months. The 5 year overall survival and risk of recurrence (RR) in the UCSF and UCSF + group was 71% vs 69% (P = 0.7) and 13% vs 36% (P = 0.1) respectively. When patients with AFP > 600 ng/ml were excluded from the UCSF + group, RR was 27% (P = 0.3). Among patients with MVI who had downstaging (DS), 4/5(80%) in low-risk group (good response and AFP ≤ 100 ng/ml) and 2/10 (20%) in the high-risk group (poor response or AFP > 100 ng/ml) were alive at the last follow-up. When DS was not feasible, 3/3 (100%) in the low-risk group (AFP ≤ 100 ng/ml + Vp1-2 MVI) and 1/9 (9.1%) in the high-risk group (AFP > 100 or Vp3 MVI) were alive. The 5 year OS in the low-risk MVI group was 85% (P = 0.003). CONCLUSION: With inclusion of AFP, response to downstaging and degree of MVI, acceptable survival can be achieved with LDLT for HCC outside traditional criteria.