Impact of Physician Characteristics on Late-Onset Sepsis (LOS) Evaluation in the NICU.

The threshold for a late-onset sepsis (LOS) evaluation varies considerably across NICUs. This unexplained variability is probably related in part to physician bias regarding when sepsis should be "ruled out". The aim of this study is to determine if physician characteristics (race, gender, immigration status, years of experience and academic rank) effect LOS evaluation in the NICU. This study includes a retrospective chart review of all Level III NICU infants who had a LOS evaluation over 54 months. Physician characteristics were compared between positive and negative blood culture groups and whether CBC and CRP were obtained at LOS evaluations. There were 341 LOS evaluations performed during the study period. Two patients were excluded due to a contaminant. Patients in this study had a birth weight of [median (Q1, Q3)]+ 992 (720, 1820) grams and birth gestation of [median (Q1, Q3)] 276/7 (252/7, 330/7) weeks. There are 10 neonatologists in the group, 5/10 being female and 6/10 being immigrant physicians. Experienced physicians were more likely to obtain a CBC at the time of LOS evaluation. Physician characteristics of race, gender and immigration status impacted whether to include a CRP as part of a LOS evaluation but otherwise did not influence LOS evaluation, including the likelihood of bacteremia.

Errors in diabetic insulin therapy and the vitality of proper precautions in Bangladesh: Real-life insights from the developing world.

Background: Insulin therapy errors can have life-threatening consequences in patients with diabetes. Given the increasing prevalence of diabetes and insulin therapy in Bangladesh, it is crucial to identify and prevent these errors. This study uses case-based clinical experiences to thematically analyze insulin therapy errors and propose preventive measures. The study aims to provide valuable insights into the challenges faced in managing insulin therapy in a developing country setting and the importance of involving various stakeholders. Materials and Methods: This is a qualitative research that used a case study approach to identify and analyze errors in insulin therapy in diabetic patients who had experienced adverse clinical consequences. The cases were thematically analyzed to generate insights into current global health problems resulting from erroneous insulin therapy. Results: The two case studies highlight potential risks of errors in insulin therapy, including poor glycemic control, complications, and death. The analysis also highlights the importance of careful monitoring, checks, and communication among health-care providers, patients, and pharmacists to prevent such errors. In addition, it emphasizes the need for education and awareness among patients and health-care providers to ensure safe and effective insulin therapy. Conclusion: Accurate insulin therapy is crucial for diabetes management and preventing adverse outcomes. Identified themes emphasize improved communication, education, and monitoring to minimize therapy errors. Insights from this study can inform policies and practices for better patient outcomes. Further research can identify the root causes and develop interventions to prevent errors, leading to improved quality of life for diabetics.

Trends and Immediate Outcomes of Syncope During Pregnancy: A Narrative Review.

Pregnancy-related syncope presents special difficulties due to the rapid physiological changes that occur throughout gestation. This narrative review provides a thorough summary of the patterns and pregnancy outcomes secondary to syncope during pregnancy. There is an increase in syncope burden during pregnancy, and hence it is critical that medical professionals understand the significance of syncope during pregnancy. Syncope can have a negative impact on the health of the mother as well as the fetus. Therefore, this review summarizes data from studies on syncope in pregnancy. It includes observational studies, case reports, and review articles. Early detection and proper management are very important because pregnant women who experience cardiac syncope are at risk of unfavorable neonatal and maternal outcomes. The review reveals diverse trends in syncope incidence during pregnancy, emphasizing the need for a nuanced understanding of temporal variations. Risks of injury, uteroplacental insufficiency, psychological effects, interruptions in prenatal treatment, possible aggravation of pre-existing diseases, and lifestyle changes are examples of immediate maternal repercussions. Pregnancy-related syncope is a complex condition that affects the health of the mother and the fetus. The study stresses the need for careful clinical treatment due to the rapid results and the diversity in incidence patterns. The unique component of a possible relationship to the brain health of offspring justifies further investigation in this area.

Improved polarimetric analysis of human skin through stitching: advantages, limitations, and applications in dermatology.

Polarimetry is a powerful tool for the analysis of the optical properties of materials and systems, such as human skin. However, in many polarimetric setups, the field of view is limited to a few square centimeters. In these cases, it is possible to resort to stitching techniques, which involve combining multiple Mueller matrix measurements obtained from different overlapping regions of the sample. In this paper, we propose a stitching technique for polarimetric data and discuss its advantages and limitations. We also describe the potential of image stitching for improving the accuracy and robustness ofin vivopolarimetry in the presence of random patient movement. We conducted our research using a diverse set of samples which included porcine skin, human skin from arms and fingers, cold cuts of chicken and gelatine, alongside synthetically created sample data. Our results demonstrate the effectiveness of this technique for the application in dermatology. Each additionalin vivomeasurement enhances the field of view by approximately one third, thereby considerably augmenting the total observation area. We show that stitching enables for the polarimetric assessment of large skin patches which is useful for the diagnosis of inflammatory skin diseases.

Shifting Trends in Prostate Treatment: A Systematic Review Comparing Transurethral Resection of the Prostate and Holmium Laser Enucleation of the Prostate.

Our systematic review aimed to assess the effectiveness and suitability of holmium laser enucleation of the prostate (HoLEP) as a treatment for benign prostatic hyperplasia (BPH) in comparison to transurethral resection of the prostate (TURP). We analyzed 12 studies involving male participants aged 45-85 years, all of whom had BPH. In our analysis, we compared HoLEP and TURP, with a focus on several primary outcomes, including postoperative International Prostate Symptom Score (IPSS), postvoid residual (PVR) volume, maximum flow rate (Qmax), and changes in sexual function post-treatment. HoLEP demonstrated advantages in certain aspects when compared to TURP. HoLEP generally resulted in an improved postoperative IPSS in some studies, but not all studies showed a significant difference when compared to TURP. HoLEP was associated with improved Qmax in most studies, but one study found no significant difference between HoLEP and TURP. Patients who underwent HoLEP showed improvement in the PVR volume in some studies, while others found no significant change in the PVR volume with either HoLEP or TURP. Some studies reported a reduction in orgasm and ejaculatory scores following TURP, while no significant changes were observed in erectile function, intercourse satisfaction, and overall satisfaction scores. It is worth noting that previous reviews and meta-analyses had limited data on the effects of HoLEP and TURP on sexual dysfunction. TURP is associated with a higher risk of morbidity and mortality, which has led to its replacement with HoLEP as the gold standard for treating BPH, particularly due to its size-independent applicability. HoLEP also demonstrated greater efficacy in the postoperative period.

Choices and Challenges With Treatment of Myasthenia Gravis in Pregnancy: A Systematic Review.

Myasthenia gravis (MG) is an autoimmune disease affecting young women in their second and third decades, coinciding with their reproductive years. We aim to explore the choices and challenges in the treatment of MG in pregnancy. Cochrane, PubMed, Google Scholar, and Embase were the four databases systematically searched for studies with patients reporting pregnancy outcomes for women with MG during pregnancy using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) technique. Quality assessment was done using the Joanna Briggs Institute critical tool (JBI, Adelaide, Australia) for methodological quality. From 2000 to 2023, 40 studies from database search results were considered. There is a substantial risk of complications with MG, especially if it appears during pregnancy. In particular, widespread weakness is a cause of severe, life-threatening disorders, but several treatment options are available.

Unlocking the Potential of Immunotherapy in Cardiovascular Disease: A Comprehensive Review of Applications and Future Directions.

Immunotherapy has emerged as a pioneering therapeutic approach that harnesses the immune system's abilities to combat diseases, particularly in the field of oncology where it has led to significant advancements. However, despite its significant impact in the field of oncology, the potential of immunotherapy in the context of cardiovascular disease (CVD) has not been thoroughly investigated. The purpose of this narrative review is to address the existing knowledge and potential uses of immunotherapy in the field of cardiovascular disease (CVD), with the intention of filling the existing gap in understanding. Furthermore, the review thoroughly examines the future prospects of this swiftly advancing field, providing insights into the aspects that necessitate further investigation and addressing the forthcoming challenges. The review is organized into four distinct sections to enhance comprehension. The first section introduces immunotherapy, presenting the fundamental concepts and principles. The second section explores the immunomodulatory mechanisms in cardiovascular disease (CVD), with a specific focus on the intricate interplay between the immune system and the development of cardiovascular pathogenesis. The utilization of immunotherapy in specific cardiovascular conditions will be examined, investigating the application of immunotherapy in the context of different cardiovascular diseases. The future prospects and challenges in immunotherapy for cardiovascular diseases will be discussed, highlighting the potential areas for future research and addressing the barriers that must be overcome to effectively implement immunotherapeutic interventions in the management of cardiovascular diseases.

Comparative yield of molecular diagnostic algorithms for autism spectrum disorder diagnosis in India: evidence supporting whole exome sequencing as first tier test.

BACKGROUND: Autism spectrum disorder (ASD) affects 1 in 100 children globally with a rapidly increasing prevalence. To the best of our knowledge, no data exists on the genetic architecture of ASD in India. This study aimed to identify the genetic architecture of ASD in India and to assess the use of whole exome sequencing (WES) as a first-tier test instead of chromosomal microarray (CMA) for genetic diagnosis. METHODS: Between 2020 and 2022, 101 patient-parent trios of Indian origin diagnosed with ASD according to the Diagnostic and Statistical Manual, 5th edition, were recruited. All probands underwent a sequential genetic testing pathway consisting of karyotyping, Fragile-X testing (in male probands only), CMA and WES. Candidate variant validation and parental segregation analysis was performed using orthogonal methods. RESULTS: Of 101 trios, no probands were identified with a gross chromosomal anomaly or Fragile-X. Three (2.9%) and 30 (29.7%) trios received a confirmed genetic diagnosis from CMA and WES, respectively. Amongst diagnosis from WES, SNVs were detected in 27 cases (90%) and CNVs in 3 cases (10%), including the 3 CNVs detected from CMA. Segregation analysis showed 66.6% (n = 3 for CNVs and n = 17 for SNVs) and 16.6% (n = 5) of the cases had de novo and recessive variants respectively, which is in concordance with the distribution of variant types and mode of inheritance observed in ASD patients of non-Hispanic white/ European ethnicity. MECP2 gene was the most recurrently mutated gene (n = 6; 20%) in the present cohort. Majority of the affected genes identified in the study cohort are involved in synaptic formation, transcription and its regulation, ubiquitination and chromatin remodeling. CONCLUSIONS: Our study suggests de novo variants as a major cause of ASD in the Indian population, with Rett syndrome as the most commonly detected disorder. Furthermore, we provide evidence of a significant difference in the diagnostic yield between CMA (3%) and WES (30%) which supports the implementation of WES as a first-tier test for genetic diagnosis of ASD in India.

Post-Severe-COVID-19 Cardiopulmonary Rehabilitation: A Comprehensive Study on Patient Features and Recovery Dynamics in Correlation with Workout Intensity.

The aftermath of severe COVID-19 frequently involves considerable cardiopulmonary damage, necessitating rehabilitation. This study aimed to evaluate the impact of COVID-19 on cardiopulmonary health and assess the effectiveness of various rehabilitative interventions. Conducted between September 2021 and September 2022, this prospective study included patients who had been diagnosed with severe COVID-19 and admitted at the "Victor Babes" Infectious Diseases and Pulmonology Hospital, Timisoara, Romania. The patients were stratified into low- and high-intensity rehabilitation groups. The rehabilitation protocols were individually tailored, and the patient recovery was closely monitored over a 3-month period. Our cohort comprised 84 patients, with a mean age of 56.3 years for the low-intensity group (n = 42) and 53.1 years for the high-intensity group (n = 42). Both groups showed significant improvements in the lung injury area, need for oxygen supplementation, ejection fraction, systolic pulmonary artery pressure, and forced vital capacity. Additionally, considerable enhancements were observed in maximal voluntary ventilation, FEV1, FEV1/FVC ratio, peak expiratory flow, and forced expiratory flow at 25-75%. The work intensity also demonstrated substantial improvements from the initial testing to the 3-month mark in both groups. This study provides evidence that personalized, targeted rehabilitation strategies can improve long-term cardiopulmonary health in patients recovering from severe COVID-19, proving both low-intensity and high-intensity training as sufficient to improve heart and lung function if performed correctly and over a relatively short duration of 3 months. The study findings underscore the importance of implementing comprehensive cardiopulmonary rehabilitation protocols in the care of post-COVID-19 patients and highlight the value of stratified rehabilitation intensity based on individual patient dynamics and recovery features.

Registration of polarimetric images for in vivo skin diagnostics.

SIGNIFICANCE: Mueller matrix (MM) polarimetry is a promising tool for the detection of skin cancer. Polarimetric in vivo measurements often suffer from misalignment of the polarimetric images due to motion, which can lead to false results. AIM: We aim to provide an easy-to-implement polarimetric image data registration method to ensure proper image alignment. APPROACH: A feature-based image registration is implemented for an MM polarimeter for phantom and in vivo human skin measurements. RESULTS: We show that the keypoint-based registration of polarimetric images is necessary for in vivo skin polarimetry to ensure reliable results. Further, we deliver an efficient semiautomated method for the registration of polarimetric images. CONCLUSIONS: Image registration for in vivo polarimetry of human skin is required for improved diagnostics and can be efficiently enhanced with a keypoint-based approach.

Predictors of colorectal carcinoma and inflammatory bowel disease in patients with colonic wall thickening.

Background and Aim: Colonic wall thickening (CWT) is commonly associated with clinically significant pathologies, but predictive factors of such pathologies are not well known. This study aims to identify the predictors of clinically significant pathologies, such as colorectal carcinoma (CRC) and inflammatory bowel disease (IBD), in patients with CWT. Methods: Subjects with an abnormal abdominal computed tomography (CT) and a follow-up colonoscopy between 2010 and 2020 were retrospectively reviewed. Patients with CWT in the CT were included and examined in this study. A multivariable logistic regression analysis was performed to assess for factors independently associated with CRC or IBD in these subjects. Receiver operating characteristic (ROC) curve analysis was used to further examine significant parameters in multivariable logistic regression analysis. Results: Among 403 patients with CWT on CT scans who underwent a colonoscopy, 269 subjects who met the inclusion criteria were identified and studied. On multivariable logistic regression models, elevated platelet count, low hematocrit, and localized CWT were found to be independently associated with CRC, while elevated platelet count and younger age were independently associated with IBD. On ROC curve analysis for CRC, area under the curve (AUC) for hematocrit, platelets, and localized CWT was 0.76, 0.75, and 0.61, respectively. On ROC curve analysis for IBD, AUC for age and platelets was 0.90 and 0.69, respectively. Conclusion: Elevated platelet count, low hematocrit, and localized CWT can be potentially used as predictors of CRC in patients with CWT. Elevated platelet count and young age can be used to predict IBD in these patients.

Clinical and molecular spectrum associated with Polymerase-γ related disorders.

BACKGROUND: POLG pathogenic variants are the commonest single-gene cause of inherited mitochondrial disease. However, the data on clinicogenetic associations in POLG-related disorders are sparse. This study maps the clinicogenetic spectrum of POLG-related disorders in the pediatric population. METHODS: Individuals were recruited across 6 centers in India. Children diagnosed between January 2015 and August 2020 with pathogenic or likely pathogenic POLG variants and age of onset <15 years were eligible. Phenotypically, patients were categorized into Alpers-Huttenlocher syndrome; myocerebrohepatopathy syndrome; myoclonic epilepsy, myopathy, and sensory ataxia; ataxia-neuropathy spectrum; Leigh disease; and autosomal dominant / recessive progressive external ophthalmoplegia. RESULTS: A total of 3729 genetic reports and 4256 hospital records were screened. Twenty-two patients with pathogenic variants were included. Phenotypically, patients were classifiable into Alpers-Huttenlocher syndrome (8/22; 36.4%), progressive external ophthalmoplegia (8/22; 36.4%), Leigh disease (2/22; 9.1%), ataxia-neuropathy spectrum (2/22; 9.1%), and unclassified (2/22; 9.1%). The prominent clinical manifestations included developmental delay (n = 14; 63.7%), neuroregression (n = 14; 63.7%), encephalopathy (n = 11; 50%), epilepsy (n = 11; 50%), ophthalmoplegia (n = 8; 36.4%), and liver dysfunction (n = 8; 36.4%). Forty-four pathogenic variants were identified at 13 loci, and these were clustered at exonuclease (18/44; 40.9%), linker (13/44; 29.5%), polymerase (10/44; 22.7%), and N-terminal domains (3/44; 6.8%). Genotype-phenotype analysis suggested that serious outcomes including neuroregression (odds ratio [OR] 11, 95% CI 2.5, 41), epilepsy (OR 9, 95% CI 2.4, 39), encephalopathy (OR 5.7, 95% CI 1.4, 19), and hepatic dysfunction (OR 4.6, 95% CI 21.3, 15) were associated with at least 1 variant involving linker or polymerase domain. CONCLUSIONS: We describe the clinical subgroups and their associations with different POLG domains. These can aid in the development of follow-up and management strategies of presymptomatic individuals.

Derivatization and determination of residual N,N-Carbonyldiimidazole by LC for an in-process control test.

For the robust analysis of N,N-Carbonyldiimidazole (CDI), its derivatization into a more stable compound may be needed. Herein, the reaction of CDI with N-benzylmethylamine followed by LC-UV quantitative analysis was explored. Reaction conditions as well as LC method feasibility were demonstrated by qualification of selectivity from other impurities and reagents, linearity across a range of 0.05-0.15%w/w, spike and recovery across a range of 0.05-0.15%w/w, reaction reproducibility with various samples, reagents and analytical chemists, and sample stability of over 24 h. Rapid and quantitative derivatization of residual CDI was achieved at 0.1% w/w relative to the synthetic product under consideration. A fit-for-purpose limit test using a RPLC-UV method as an in-process control for the reaction completion of product, at scale, was successfully implemented and executed.

Candida-Induced Emphysematous Gastritis in a Multiple Myeloma Patient: Conservative Management With Favorable Outcome.

Emphysematous gastritis is a rare, and often fatal, infection with unclear recommendations on management. We report the first documented case of emphysematous gastritis caused by Candida species in a patient on chemotherapy for multiple myeloma. Our patient, who presented with gastrointestinal symptoms was found to have gas in the stomach wall, peri-gastric, and portal veins on CT scan. Nasogastric tube cultures grew Candida albicans and Candida glabrata and the patient was treated with antibiotics and antifungals. Prompt recognition and conservative management led to a favorable outcome.

Causative agents of urinary tract infections and their antimicrobial susceptibility patterns at a referral center in Western India: An audit to help clinicians prevent antibiotic misuse.

BACKGROUND: Urinary tract infections (UTIs) remain one of the most common infections in community and susceptibility of uropathogens to commonly used antimicrobials has declined over years. It is important to periodically study susceptibility patterns of uropathogens, so that empiric treatment can be determined using recent data, helping improve patient outcomes. METHODS: Urine samples received by the laboratory for culture and susceptibility testing over a period of 3 months were analyzed and included in this study. Antimicrobial susceptibility testing was done on cultured isolates. RESULTS: Of total 3,151 urine samples received, 3,066 were processed, and organisms were isolated from 1,401 (45.69%) samples. Isolation rate from male and female urine samples was 45.29% and 46.32%, respectively. The most commonly isolated organism was Escherichia coli (36.11%), followed by Candida spp. (18.56%), and Klebsiella spp. (18.06%). E. coli was most susceptible to meropenem (91.89%) and imipenem (91.69%). Klebsiella spp. was most susceptible to imipenem(75.89%) and meropenem(75.49%). Susceptibility of E. coli and Klebsiella spp. to nitrofurantoin, cotrimoxazole, and ciprofloxacin was 72.33%, 32.02%, and 18.97%, and 51.77%, 27.27%, and 22.13%, respectively. Candida spp. was most susceptible to amphotericin B (97.30%). CONCLUSION: Treatment for UTIs should be determined based on current local antimicrobial susceptibility patterns of uropathogens to minimise therapeutic failures and prevent antibiotic misuse.

Formation of Chiral Allylic Ethers via an Enantioselective Palladium-Catalyzed Alkenylation of Acyclic Enol Ethers.

This report details a palladium-catalyzed process to access highly functionalized, optically active allylic aryl ethers. A number of electron-deficient alkenyl triflates underwent enantioselective and site-selective coupling with acyclic aryl enol ethers in the presence of a chiral palladium catalyst. This transform provides chiral allylic ether products in high yields and excellent enantiomeric ratios, furnishing a unique disconnection to incorporate heteroatoms at a stereocenter. Finally, the applicability of the products to target synthesis was demonstrated through the formation of a chiral allylic alcohol and the generation of a flavone-inspired product.

Enantioselective Palladium-Catalyzed Alkenylation of Trisubstituted Alkenols To Form Allylic Quaternary Centers.

In this report, we describe the generation of remote allylic quaternary stereocenters ß, γ, and δ relative to a carbonyl in high enantioselectivity. We utilize a redox-relay Heck reaction between alkenyl triflates and acyclic trisubstituted alkenols of varying chain-lengths. A wide array of terminal (E)-alkenyl triflates are suitable for this process. The utility of this functionalization is validated further by conversion of the products, via simple organic processes to access remotely functionalized chiral tertiary acid, amine, and alcohol products.

Palladium-catalyzed enantioselective Heck alkenylation of acyclic alkenols using a redox-relay strategy.

We report a highly enantioselective intermolecular Heck reaction of alkenyl triflates and acyclic primary or racemic secondary alkenols. The mild reaction conditions permit installation of a wide range of alkenyl groups at positions ß, γ, or δ to a carbonyl group in high enantioselectivity. The success of this reaction is attributed to the use of electron-withdrawing alkenyl triflates, which offer selective ß-hydride elimination followed by migration of the catalyst through the alkyl chain to give the alkenylated carbonyl products. The synthetic utility of the process is demonstrated by a two-step modification of a reaction product to yield a tricyclic core structure, present in various natural products.

Enantioselective construction of remote quaternary stereocentres.

Small molecules that contain all-carbon quaternary stereocentres-carbon atoms bonded to four distinct carbon substituents-are found in many secondary metabolites and some pharmaceutical agents. The construction of such compounds in an enantioselective fashion remains a long-standing challenge to synthetic organic chemists. In particular, methods for synthesizing quaternary stereocentres that are remote from other functional groups are underdeveloped. Here we report a catalytic and enantioselective intermolecular Heck-type reaction of trisubstituted-alkenyl alcohols with aryl boronic acids. This method provides direct access to quaternary all-carbon-substituted ß-, γ-, δ-, ε- or ζ-aryl carbonyl compounds, because the unsaturation of the alkene is relayed to the alcohol, resulting in the formation of a carbonyl group. The scope of the process also includes incorporation of pre-existing stereocentres along the alkyl chain, which links the alkene and the alcohol, in which the stereocentre is preserved. The method described allows access to diverse molecular building blocks containing an enantiomerically enriched quaternary centre.