An Implementation Science Study of a Heat-Producing Wrap to Complement KMC in Rwanda.

Background: Neonatal hypothermia is a major cause of preventable morbidity and mortality, especially among the world's poorest newborns. A heat-producing wrap is necessary when kangaroo mother care (KMC) is insufficient or unavailable, yet there is little published research on such wraps. The Dream Warmer is a wrap designed to complement KMC and has been extensively studied in formal research settings but not in real-world conditions. Objectives: We used implementation science methodology to understand the safety, effectiveness, and functionality of the Dream Warmer (hereafter, "Warmer"); its effect on clinical workflows; its interaction with other aspects of care such as KMC; and the Warmer's reception by healthcare providers (HCPs) and parents. Methods: We conducted a prospective, interventional, one-arm, open-label, mixed-methods study in 6 district hospitals and 84 associated health centers in rural Rwanda. Our intervention was the provision of the Warmer and an educational curriculum on thermoregulation. We compared pre and post intervention data using medical records, audits, and surveys. Findings: The Warmer raised no safety concerns. It was used correctly in the vast majority of cases. The mean admission temperature rose from slightly hypothermic (36.41 °C) pre, to euthermic (36.53 °C) post intervention (p = 0.002). Patients achieved a temperature ≥36.5 °C in 86% of uses. In 1% of audits, patients were hyperthermic (37.6-37.9 °C). Both HCPs and parents reported a generally positive experience with the Warmer. HCPs were challenged to prepare it in advance of need. Conclusions: The Warmer functions similarly well in research and real-world conditions. Ongoing education directed toward both HCPs and parents is critical to ensuring the provision of a continuous heat chain. Engaging families in thermoregulation could ease the burden of overtaxed HCPs and improve the skill set of parents. Hypothermia is a preventable condition that must be addressed to optimize neonatal survival and outcome.

Effect of nusinersen on respiratory and bulbar function in children with spinal muscular atrophy: Real world experience from a single center.

AIM: Due to the limited data from clinical trials and real-world settings in the realm of nusinersen, there is a need for further evidence. This study seeks to assess the impact of nusinersen, when combined with standard care, on bulbar function, respiratory function, and the necessity for respiratory support among pediatric patients with spinal muscular atrophy (SMA). METHODS: Prospective observational study, involving pediatric SMA patients (types 1-3) undergoing nusinersen treatment at the Hospital Universitario Virgen del Rocío in Spain over at least a 24-month period. The cohort included 11 SMA type 1 patients, comprising 6 type 1b and 5 type 1c, 12 SMA type 2 patients, and 5 SMA type 3 patients. RESULTS: 28 pediatric patients were enrolled, with a majority being male (n=20). Patients with type 1 were diagnosed and received treatment significantly earlier than those with types 2 and 3 (P<0.001). Additionally, there was a longer period between diagnosis and the start of treatment in types 2/3 (P=0.002). Follow-up revealed statistically improved functional and respiratory outcomes associated with earlier initiation of nusinersen treatment at 6, 12, and 24 months in all phenotypes. The ability to swallow and feed correctly remained unchanged throughout the study, with SMA type 1c patients maintaining oral feeding in contrast to patients with SMA type 1b. Notably, no deaths were recorded. CONCLUSIONS: This study provides important insights into the real-world clinical progress of pediatric SMA patients and their response to nusinersen treatment, highlighting the significance of early intervention for better functional and respiratory outcomes.

Surgical Outcome After Distal Pancreatectomy With and Without Portomesenteric Venous Resection in Patients with Pancreatic Adenocarcinoma: A Transatlantic Evaluation of Patients in North America, Germany, Sweden, and The Netherlands (GAPASURG).

BACKGROUND: Pancreatic adenocarcinoma located in the pancreatic body might require a portomesenteric venous resection (PVR), but data regarding surgical risks after distal pancreatectomy (DP) with PVR are sparse. Insight into additional surgical risks of DP-PVR could support preoperative counseling and intraoperative decision making. This study aimed to provide insight into the surgical outcome of DP-PVR, including its potential risk elevation over standard DP. METHODS: We conducted a retrospective, multicenter study including all patients with pancreatic adenocarcinoma who underwent DP ± PVR (2018-2020), registered in four audits for pancreatic surgery from North America, Germany, Sweden, and The Netherlands. Patients who underwent concomitant arterial and/or multivisceral resection(s) were excluded. Predictors for in-hospital/30-day major morbidity and mortality were investigated by logistic regression, correcting for each audit. RESULTS: Overall, 2924 patients after DP were included, of whom 241 patients (8.2%) underwent DP-PVR. Rates of major morbidity (24% vs. 18%; p = 0.024) and post-pancreatectomy hemorrhage grade B/C (10% vs. 3%; p = 0.041) were higher after DP-PVR compared with standard DP. Mortality after DP-PVR and standard DP did not differ significantly (2% vs. 1%; p = 0.542). Predictors for major morbidity were PVR (odds ratio [OR] 1.500, 95% confidence interval [CI] 1.086-2.071) and conversion from minimally invasive to open surgery (OR 1.420, 95% CI 1.032-1.970). Predictors for mortality were higher age (OR 1.087, 95% CI 1.045-1.132), chronic obstructive pulmonary disease (OR 4.167, 95% CI 1.852-9.374), and conversion from minimally invasive to open surgery (OR 2.919, 95% CI 1.197-7.118), whereas concomitant PVR was not associated with mortality. CONCLUSIONS: PVR during DP for pancreatic adenocarcinoma in the pancreatic body is associated with increased morbidity, but can be performed safely in terms of mortality.

National Surgical Quality Improvement Program audit of contemporary perioperative care for radical cystectomy.

OBJECTIVE: To examine the impact of increased compliance to contemporary perioperative care measures, as outlined by enhanced recover after surgery (ERAS) guidelines, among patients undergoing radical cystectomy (RC). PATIENTS AND METHODS: From the National Surgical Quality Improvement Program database we captured patients undergoing RC between 2019 and 2021. We identified five perioperative care measures: regional anaesthesia block, thromboembolism prophylaxis, ≤24 h perioperative antibiotic administration, absence of bowel preparation, and early oral diet. We stratified patients by the number of measures utilised (one to five). Statistical endpoints included 30-day complications, hospital length of stay (LOS), readmissions, and optimal RC outcome. Optimal RC outcome was defined as absence of any postoperative complication, re-operation, prolonged LOS (75th percentile, 8 days) with no readmission. Multivariable regressions with Bonferroni correction were performed to assess the association between use of contemporary perioperative care measures and outcomes. RESULTS: Of the 3702 patients who underwent RC, 73 (2%), 417 (11%), 1010 (27%), 1454 (39%), and 748 (20%) received one, two, three, four, and five interventions, respectively. On multivariable analysis, increased perioperative care measures were associated with lower odds of any complication (odds ratio [OR] 0.66, 99% confidence interval [CI] 0.6-0.73), and shorter LOS (ß -0.82, 99% CI -0.99 to -0.65). Furthermore, patients with increased compliance to contemporary care measures had increased odds of an optimal outcome (OR 1.38, 99% CI 1.26-1.51). CONCLUSIONS: Among the measures we assessed, greater adherence yielded improved postoperative outcomes among patients undergoing RC. Our work supports the efficacy of ERAS protocols in reducing the morbidity associated with RC.

Low neighborhood socioeconomic status is associated with poor outcomes in young adults with colorectal cancer.

BACKGROUND: The incidence of early-onset colorectal cancer has increased markedly over the past decade. Although established for older adults, there are limited data on socioeconomic and racial disparities in screening, treatment, and outcomes in this distinct group. METHODS: Adults with primary colorectal cancer diagnosed at age <50 were identified from the Surveillance, Epidemiology, and End Results database. The exposure of interest was neighborhood socioeconomic status based on the Yost Index, a census-tract level composite score of neighborhood economic health. Univariate analysis was performed with χ2 analyses. Logistic regression models were created to evaluate the association of neighborhood socioeconomic status (Yost Index quintile) with metastasis at presentation and surgical intervention. Kaplan-Meier and Cox proportional hazards models were created. RESULTS: In total, 45,660 early-onset colorectal cancer patients were identified; 16.8% (7,679) were in the lowest quintile of neighborhood socioeconomic status. Patients with the lowest neighborhood socioeconomic status were 1.13 times (95% confidence interval 1.06-1.21) more likely to present with metastases and had lower survival (hazard ratio 1.45, 95% confidence interval 1.37-1.53) compared to those with the highest neighborhood socioeconomic status. Non-Hispanic Black patients were more likely to present with metastatic disease (odds ratio 1.11, 95% confidence interval 1.05-1.19), less likely to undergo surgery for localized or regional disease (odds ratio 0.48, 95% confidence interval 0.43-0.53), and had lower survival (hazard ratio 1.21, 95% confidence interval 1.15-1.27) than non-Hispanic White patients. CONCLUSION: Socioeconomic and racial disparities in early-onset colorectal cancer span diagnosis, treatment, and survival. As the disease burden of early-age onset colorectal cancer increases, interventions to boost early diagnosis and access to surgery are necessary to improve survival among minorities and patients with low neighborhood socioeconomic status.

Outcome evaluation of technical strategies on reduction of patient waiting time in the outpatient department at Kilimanjaro Christian Medical Centre-Northern Tanzania.

BACKGROUND: The Tanzania healthcare system is beset by prolonged waiting time in its hospitals particularly in the outpatient departments (OPD). Previous studies conducted at Kilimanjaro Christian Medical Centre (KCMC) revealed that patients typically waited an average of six hours before receiving the services at the OPD making KCMC have the longest waiting time of all the Zonal and National Referral Hospitals. KCMC implemented various interventions from 2016 to 2021 to reduce the waiting time. This study evaluates the outcome of the interventions on waiting time at the OPD. METHODS: This is an analytical cross-sectional mixed method using an explanatory sequential design. The study enrolled 412 patients who completed a structured questionnaire and in-depth interviews (IDI) were conducted among 24 participants (i.e., 12 healthcare providers and 12 patients) from 3rd to 14th July, 2023. Also, a documentary review was conducted to review benchmarks with regards to waiting time. Quantitative data analysis included descriptive statistics, bivariable and multivariable. All statistical tests were conducted at 5% significance level. Thematic analysis was used to analyse qualitative data. RESULTS: The findings suggest that post-intervention of technical strategies, the overall median OPD waiting time significantly decreased to 3 h 30 min IQR (2.51-4.08), marking a 45% reduction from the previous six-hour wait. Substantial improvements were observed in the waiting time for registration (9 min), payment (10 min), triage (14 min for insured patients), and pharmacy (4 min). Among the implemented strategies, electronic medical records emerged as a significant predictor to reduced waiting time (AOR = 2.08, 95% CI, 1.10-3.94, p-value = 0.025). IDI findings suggested a positive shift in patients' perceptions of OPD waiting time. Problems identified that still need addressing include, ineffective implementation of block appointment and extension of clinic days was linked to issues of ownership, organizational culture, insufficient training, and ineffective follow-up. The shared use of central modern diagnostic equipment between inpatient and outpatient services at the radiology department resulted in delays. CONCLUSION: The established technical strategies have been effective in reducing waiting time, although further action is needed to attain the global standard of 30 min to 2 h OPD waiting time.

Multidimensional and Longitudinal Impact of a Genetic Diagnosis for Critically Ill Infants.

Background and Objectives: Many genetic conditions present in the neonatal intensive care unit (NICU), where a diagnostic evaluation is pursued. However, understanding of the impact of a genetic diagnosis on clinical outcomes and health-related quality of life for these infants remains incomplete. We therefore evaluated parent-reported outcomes complemented by clinical outcomes measures over one year for a cohort of infants in the NICU undergoing genetic evaluation. Methods: Prospective cohort study evaluating outcomes after genetics consultation in a level IV NICU via parent-report and electronic medical records (EMR) review. Eligible infants were genetically undiagnosed at enrollment. Parent surveys were administered at baseline and three, six-, and 12-months following enrollment and assessed genetic testing utility as well as parent-reported infant health-related quality of life using the Infant Toddler Quality of Life Questionnaire. Results: 110 infant-parent pairs were enrolled. Infants had a median age at enrollment of 15 days (interquartile range 8-37.75). At baseline, 74% (81/110) of parents endorsed high importance of finding a genetic diagnosis, but perceived importance significantly decreased over time. Over the study period, 38 infants received a molecular diagnosis per parent report, though this was discordant with EMR review. Identification of a diagnosis did not significantly impact health-related quality of life across most domains, which was lower overall than population norms. Conclusions: A genetic diagnosis is highly desired by parents in the NICU, though waning interest over time for undiagnosed families may reflect parental emotional adaptation and acceptance. Additional supports are needed to improve perceived quality of life.

International differences in the selection and outcome of minimally invasive and open distal pancreatectomy: A transatlantic analysis.

BACKGROUND: The efficacy and safety of minimally invasive distal pancreatectomy have been confirmed by randomized trials, but current patient selection and outcome of minimally invasive distal pancreatectomy in large international cohorts is unknown. This study aimed to compare the use and outcome of minimally invasive distal pancreatectomy in North America, the Netherlands, Germany, and Sweden. METHODS: All patients in the 4 Global Audits on Pancreatic Surgery Group (GAPASURG) registries who underwent minimally invasive distal pancreatectomy or open distal pancreatectomy during 2014-2020 were included. RESULTS: Overall, 20,158 distal pancreatectomies were included, of which 7,316 (36%) were minimally invasive distal pancreatectomies. Use of minimally invasive distal pancreatectomy varied from 29% to 54% among registries, of which 13% to 35% were performed robotically. Both the use of minimally invasive distal pancreatectomy and robotic surgery were the highest in the Netherlands. Patients undergoing minimally invasive distal pancreatectomy tended to have a younger age (Germany and Sweden), female sex (North America, Germany), higher body mass index (North America, the Netherlands, Germany), lower comorbidity classification (North America, Germany, Sweden), lower performance status (Germany), and lower rate of pancreatic adenocarcinoma (all). The minimally invasive distal pancreatectomy group had fewer vascular resections (all) and lower rates of severe complications and mortality (North America, Germany). In the multivariable regression analysis, country was associated with severe complications but not with 30-day mortality. Minimally invasive distal pancreatectomy was associated with a lower risk of 30-day mortality compared with open distal pancreatectomy (odds ratio 1.633, 95% CI 1.159-2.300, P = .005). CONCLUSIONS: Considerable disparities were seen in the use of minimally invasive distal pancreatectomy among 4 transatlantic registries of pancreatic surgery. Overall, minimally invasive distal pancreatectomy was associated with decreased mortality as compared with open distal pancreatectomy. Differences in patient selection among countries could imply that countries are in different stages of the learning curve.

Increased basal fibronectin is sufficient to promote excess endothelial cell matrix assembly causing localized barrier dysfunction.

Endothelial cell behavior is regulated by subendothelial extracellular matrix (ECM). The ECM protein fibronectin (FN) is rare in healthy blood vessels but accumulates in disease accompanied by endothelial dysfunctions. Here, we report that excess assembly of FN disrupts key endothelial functions. We mimicked increased FN expression as in diseased stroma by providing exogenous FN basally in a Transwell insert and found dose-dependent upregulation of subendothelial FN matrix assembly. Taking advantage of discontinuous matrix assembly by endothelial cells, we show correlations between regional increases in FN matrix and disruptions in endothelial cell morphology, VE-cadherin junctions, and the cell cycle, all of which were not changed in FN-deficient regions of the monolayer. These changes affected endothelial barrier function with increased monolayer permeability exposing basal regions of high FN matrix and permitting FN-dependent adhesion of MDA-MB-231 tumor cells from the apical side of the monolayer. FN matrix accumulation was quick and increases in FN matrix preceded all other changes in the endothelium. Therefore, subendothelial accumulation of FN matrix is a cause, not an effect, of endothelial monolayer disorganization and leakiness. Regulating FN accumulation in the subendothelial space could be an important target for controlling progression of fibrosis and related diseases.

Adverse cardiac events of hypercholesterolemia are enhanced by sitagliptin in sprague dawley rats.

BACKGROUND: Cardiovascular disease (CVD) affects millions worldwide and is the leading cause of death among non-communicable diseases. Western diets typically comprise of meat and dairy products, both of which are rich in cholesterol (Cho) and methionine (Met), two well-known compounds with atherogenic capabilities. Despite their individual effects, literature on a dietary combination of the two in the context of CVD are limited. Therefore, studies on the combined effects of Cho and Met were carried out using male Sprague Dawley rats. An additional interest was to investigate the cardioprotective potential of sitagliptin, an anti-type 2 diabetic drug. We hypothesized that feeding a dietary combination of Cho and Met would result in adverse cardiac effects and would be attenuated upon administration of sitagliptin. METHODS: Adult male Sprague-Dawley rats were fed either a control (Con), high Met (1.5%), high Cho (2.0%), or high Met (1.5%) + high Cho (2.0%) diet for 35 days. They were orally gavaged with an aqueous preparation of sitagliptin (100 mg/kg/d) or vehicle (water) from day 10 through 35. On day 36, rats were euthanized, and tissues were collected for analysis. RESULTS: Histopathological evaluation revealed a reduction in myocardial striations and increased collagen deposition in hypercholesterolemia (HChol), responses that became exacerbated upon sitagliptin administration. Cardiac pro-inflammatory and pro-fibrotic responses were adversely impacted in similar fashion. The addition of Met to Cho (MC) attenuated all adverse structural and biochemical responses, with or without sitagliptin. CONCLUSIONS: Adverse cardiac outcomes in HChol were enhanced by the administration of sitagliptin, and such effects were alleviated by Met. Our findings could be significant for understanding or revisiting the risk-benefit evaluation of sitagliptin in type 2 diabetics, and especially those who are known to consume atherogenic diets.

Sex differences in the association of pretransfusion haemoglobin and cognition in preterm infants.

OBJECTIVES: To assess sex-specific differences in the association between pre-transfusion haemoglobin values and early neurodevelopmental function. DESIGN: Observational follow-up of infants with birth weights <1000 g and gestational ages 22-28 weeks who were enrolled in the NICHD Neonatal Research Network Transfusion of Prematures (TOP) Trial at 19 U.S. sites, 2012-2017. MAIN OUTCOME MEASURES: Pretransfusion haemoglobin values were obtained longitudinally through 36 weeks' postmenstrual age. The infant's mean pretransfusion haemoglobin was used as a marker of degree of anaemia (n=1655 measures). Measures of brain function were obtained at 22-26 months' corrected age using the Bayley Scales of Infant & Toddler Development, third edition (BSID-III) (n=1290 BSID-III scores). Sex-specific estimates for the linear relation between pretransfusion haemoglobin and BSID-III scores were obtained from repeated-measures regression analysis, adjusted for gestational age, birth weight, study site, clinical characteristics, and demographic covariates. RESULTS: The relation of pretransfusion haemoglobin with 24-month BSID-III scores showed significant, independent interactions with both (1) sex (p=0.046) and (2) retinopathy of prematurity (ROP; p=0.004). In 614 males, BSID-III scores were higher by 1.07 points per g/dL (95% CI 1.58 to 4.33; p=0.008), not differing significantly among the three subscales (cognitive, language and motor; p=0.94). In 247 infants with ROP, BSID-III scores were higher by 2.95 points per g/dL (95% CI 0.28 to 1.87; p<0.0001), uniformly across subscales (p=0.73). These associations were non-significant in 676 females (p=0.96) and 1043 infants without ROP (p=0.81). CONCLUSIONS: This study demonstrates sex-specific associations between mean pretransfusion haemoglobin (a marker of the severity of anaemia throughout the neonatal intensive care unit [NICU] hospitalisation) and early neurodevelopmental function at 22-26 months' corrected age.

Evaluation of Ilex guayusa and Piper marginatum Extract Cytotoxicity on Human Dental Pulp Mesenchymal Stem Cells.

BACKGROUND: Amelogenesis imperfecta is a hereditary disorder affecting dental enamel. Among its phenotypes, hypocalcified AI is characterized by mineral deficiency, leading to tissue wear and, consequently, dental sensitivity. Excessive fluoride intake (through drinking water, fluoride supplements, toothpaste, or by ingesting products such as pesticides or insecticides) can lead to a condition known as dental fluorosis, which manifests as stains and teeth discoloration affecting their structure. Our recent studies have shown that extracts from Colombian native plants, Ilex guayusa and Piper marginatum, deposit mineral ions such as phosphate and orthophosphate into the dental enamel structure; however, it is unknown whether these extracts produce toxic effects on the dental pulp. OBJECTIVE: To assess cytotoxicity effects on human dental pulp stem cells (hDPSCs) exposed to extracts isolated from I. guayusa and P. marginatum and, hence, their safety for clinical use. METHODS: Raman spectroscopy, fluorescence microscopy, and flow cytometry techniques were employed. For Raman spectroscopy, hDPSCs were seeded onto nanobiochips designed to provide surface-enhanced Raman spectroscopy (SERS effect), which enhances their Raman signal by several orders of magnitude. After eight days in culture, I. guayusa and P. marginatum extracts at different concentrations (10, 50, and 100 ppm) were added. Raman measurements were performed at 0, 12, and 24 h following extract application. Fluorescence microscopy was conducted using an OLIMPUS fv1000 microscope, a live-dead assay was performed using a kit employing a BD FACS Canto TM II flow cytometer, and data analysis was determined using a FlowJo program. RESULTS: The Raman spectroscopy results showed spectra consistent with viable cells. These findings were corroborated using fluorescence microscopy and flow cytometry techniques, confirming high cellular viability. CONCLUSIONS: The analyzed extracts exhibited low cytotoxicity, suggesting that they could be safely applied on enamel for remineralization purposes. The use of nanobiochips for SERS effect improved the cell viability assessment.

Respiratory Severity Score and Oxygen Saturation Index during the First 2 Hours of Life as Predictors for Noninvasive Respiratory Support Failure in Respiratory Distress Syndrome.

OBJECTIVE: Noninvasive respiratory support (NRS) failure is common in preterm infants with respiratory distress syndrome (RDS). We evaluated the utility of respiratory severity score (RSS) and oxygen saturation index (OSI) during the first 2 hours of life (HOL) as predictors for NRS failure in moderate preterm infants. STUDY DESIGN: We conducted a retrospective cohort study of infants born between 280/7 and 336/7 weeks with RDS. Univariate and multivariable logistic regression analyses were used to assess whether the RSS and OSI summary measures were associated with NRS failure. RESULTS: A total of 282 infants were included in the study. Median gestational age and birth weights were 32 weeks and 1.7 kg, respectively. Fifty-eight infants (21%) developed NRS failure at the median age of 10.5 hours. RSS and OSI summary measures in the first 2 HOL were associated with NRS failure within 72 HOL. CONCLUSION: RSS and OSI during the first 2 HOL can predict NRS failure. Optimal RSS and OSI cutoffs for the prediction of NRS failure need to be determined in large cohort studies. KEY POINTS: · Nearly one in five moderate preterm infants on NRS at 2 hours of life developed NRS failure.. · RSS and OSI during the first 2 HOL can predict NRS failure.. · Optimal RSS and OSI cutoffs for the prediction of NRS failure need to be determined..

Blood Pressure Pattern and Prevalence of Hypertension amongst Apparently Healthy Primary School Pupils in Abuja, Nigeria.

OBJECTIVES: The objective of this study was to determine the blood pressure (BP) pattern and prevalence of hypertension amongst apparently healthy primary school pupils in Abuja. METHODOLOGY: This was a descriptive, cross-sectional study carried out on apparently healthy primary school children aged 6-12 years. BP was measured using a standard mercury sphygmomanometer according to standard guidelines. Data were analysed using SPSS version 17.0. Pearson's correlation coefficient (r) and analysis of variance were used to determine the relationship between BP and various variables where applicable. P = 0.05 was considered statistically significant. RESULTS: Out of 1011 pupils recruited for the study, 457 (42.2%) were male. The mean systolic and diastolic BP (SBP and DBP) increased significantly with age from 94.5 mmHg to 101.0 mmHg and from 61.5 mmHg to 65.3 mmHg from 6 to 12 years for SBP and DBP, respectively (P < 0.05). The prevalence of high BP was 9.1%. Age was the only predictor of SBP (ß = -0.629, 95% confidence interval [CI] -1.115, -0.142), while age, height and body mass index (BMI) were the predictors of DBP (ß = -0.686, 95% CI of -1.152, -0.221; ß = 0.490, 95% CI of 0.172, 0.809; ß = 1.753, 95% CI of 0.374, 3.160) for age, height and BMI, respectively, at P < 0.05. CONCLUSION: The predictors of SBP and DBP as shown in this study support the recommendations by various reports for taking body size into consideration in developing reference values for various populations. Age and body size are important determinants of BP in children. Its measurement should be encouraged in schools.

Non-invasive prenatal testing of beta-hemoglobinopathies using next generation sequencing, in-silico sequence size selection, and haplotyping.

AIM: To develop a non-invasive prenatal test for beta-hemoglobinopathies based on analyzing maternal plasma by using next generation sequencing. METHODS: We applied next generation sequencing (NGS) of maternal plasma to the non-invasive prenatal testing (NIPT) of autosomal recessive diseases, sickle cell disease and beta-thalassemia. Using the Illumina MiSeq, we sequenced plasma libraries obtained via a Twist Bioscience probe capture panel covering 4 Kb of chromosome 11, including the beta-globin (HBB) gene and >450 genomic single-nucleotide polymorphisms (SNPs) used to estimate the fetal fraction (FF). The FF is estimated by counting paternally transmitted allelic sequence reads present in the plasma but absent in the mother. We inferred fetal beta-globin genotypes by comparing the observed mutation (Mut) and reference (Ref) read ratios to those expected for the three possible fetal genotypes (Mut/Mut; Mut/Ref; Ref/Ref), based on the FF. RESULTS: We bioinformatically enriched the FF by excluding reads over a specified length via in-silico size selection (ISS), favoring the shorter fetal reads, which increased fetal genotype prediction accuracy. Finally, we determined the parental HBB haplotypes, which allowed us to use the read ratios observed at linked SNPs to help predict the fetal genotype at the mutation site(s). We determined HBB haplotypes via Oxford Nanopore MinION sequencing of a 2.2 kb amplicon and aligned these sequences using Soft Genetics' NextGENe LR software. CONCLUSION: The combined use of ISS and HBB haplotypes enabled us to correctly predict fetal genotypes in cases where the prediction based on variant read ratios alone was incorrect.

Effects of Surgeon-Preferred Staff and Staff Turnover on Operating Time and Complication Rates in Reverse and Anatomic Total Shoulder Arthroplasty.

BACKGROUND: This study focuses on investigating the risk factors of increased operating room time and patient complication rates after total shoulder arthroplasty cases (both reverse and anatomic). We hypothesize that the use of surgeon-preferred staff will improve operating room efficiency and reduce complication rates while increased staff turnover will decrease efficiency and increase complications. METHODS: This is a single-center, retrospective study focused on determining the effects of staffing on operating room time and efficiency in total shoulder arthroplasty. The study included patients who underwent total shoulder arthroplasty by a single fellowship-trained orthopaedic surgeon from 2018 to 2023. RESULTS: Four hundred twenty-three patients were included in the study from August 2018 to April 2023, 264 of which were reverse total shoulder arthroplasty (rTSA) and 159 were anatomic total shoulder arthroplasty (aTSA). In both rTSA and aTSA, the presence of surgeon-preferred staff markedly decreased operating room time. In rTSA, staff turnover increased risk of 90-day complications. CONCLUSION: Because the presence of surgeon-preferred staff affects operating room time and efficiency, orthopaedic surgeons should train multiple surgical teams so that efficiency is not affected by the loss of personnel during a case. To reduce 90-day complication rates in rTSA, staff breaks and turnover should be minimized as much as possible because this has a direct effect on patient outcomes. Effort from hospital administration and management should be put toward reducing turnover to improve patient outcomes.

A study protocol to characterise pathophysiological and molecular markers of rheumatic heart disease and degenerative aortic stenosis using multiparametric cardiovascular imaging and multiomics techniques.

INTRODUCTION: Rheumatic heart disease (RHD), degenerative aortic stenosis (AS), and congenital valve diseases are prevalent in sub-Saharan Africa. Many knowledge gaps remain in understanding disease mechanisms, stratifying phenotypes, and prognostication. Therefore, we aimed to characterise patients through clinical profiling, imaging, histology, and molecular biomarkers to improve our understanding of the pathophysiology, diagnosis, and prognosis of RHD and AS. METHODS: In this cross-sectional, case-controlled study, we plan to recruit RHD and AS patients and compare them to matched controls. Living participants will undergo clinical assessment, echocardiography, CMR and blood sampling for circulatory biomarker analyses. Tissue samples will be obtained from patients undergoing valve replacement, while healthy tissues will be obtained from cadavers. Immunohistology, proteomics, metabolomics, and transcriptome analyses will be used to analyse circulatory- and tissue-specific biomarkers. Univariate and multivariate statistical analyses will be used for hypothesis testing and identification of important biomarkers. In summary, this study aims to delineate the pathophysiology of RHD and degenerative AS using multiparametric CMR imaging. In addition to discover novel biomarkers and explore the pathomechanisms associated with RHD and AS through high-throughput profiling of the tissue and blood proteome and metabolome and provide a proof of concept of the suitability of using cadaveric tissues as controls for cardiovascular disease studies.