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Background: Currently, 21−30% supplemental oxygen is recommended during resuscitation of preterm neonates. Recent studies have shown that 58% of infants < 32 week gestation age are born with a heart rate (HR) < 100 bpm. Prolonged bradycardia with the inability to achieve a preductal saturation (SpO2) of 80% by 5 min is associated with mortality and morbidity in preterm infants. The optimal oxygen concentration that enables the achievement of a HR ≥ 100 bpm and SpO2 of ≥80% by 5 min in preterm lambs is not known. Methods: Preterm ovine model (125−127 d, gestation equivalent to human neonates < 28 weeks) was instrumented, and asphyxia was induced by umbilical cord occlusion until bradycardia. Ventilation was initiated with 30% (OX30), 60% (OX60), and 100% (OX100) for the first 2 min and titrated proportionately to the difference from the recommended preductal SpO2. Our primary outcome was the incidence of the composite of HR ≥ 100 bpm and SpO2 ≥ 80%, by 5 min. Secondary outcomes were to evaluate the time taken to achieve the primary outcome, gas exchange, pulmonary/systemic hemodynamics, and the oxidative injury. Results: Eighteen lambs (OX30-6, OX60-5. OX100-7) had an average HR < 91 bpm with a pH of

This study aimed to document the safety and efficacy of a single infusion of autologous umbilical cord blood (UCB) in 20 autistic children aged 24–72 months. A pre‐post treatment within‐subjects open label design was used. At T = 0, 6, 12, and 18 months, participants underwent detailed and structured safety evaluations (via caregiver report), Vineland Adaptive Behavior Scale (Vineland‐3), Stanford Binet Intelligence Scale (SB‐5), Expressive One‐Word Picture Vocabulary Test, Brief Observation of Social Communication Change (BOSCC), Pervasive Developmental Disorder‐Behavior Inventory, Repetitive Behavior Scale‐Revised, Sensory Experience Questionnaire (SEQ‐2.1), Child Behavior Checklist, Clinical Global Impression‐Severity and Improvement (CGI‐I) Scales, and eye‐gaze tracking. UCB infusion was conducted at T = 6 months, hence, 0–6 months was the control period, and 6–18 months the follow‐up period. Of 20 children recruited, 19 completed the study and 1 was withdrawn due to UCB not meeting quality control criteria for infusion. There were 15 males and 4 females with an overall mean (SD) age of 4.15 (0.62) years. Mean (SD) cell dose administered was 38.16 (9.82) million cells/kg. None suffered serious adverse events although there were mild behavioral side effects and one unit grew coagulase negative staphylococcus from a post‐thaw sample. There were no significant differences in Vineland‐3, SB‐5, BOSCC, and SEQ‐2.1 scores at T = 12 and T = 18 months. Twelve participants had T = 18 CGI‐I scores of 2–3 (minimally to much improved), seven participants had scores of 4 (no change). Autologous UCB infusion in autistic children is generally safe but not without risks, including that of infection. In this within‐subjects study, some children showed global symptom improvements while others showed no change. Stem cell therapies for autism should only be conducted under strict clinical trial conditions with clear risk discussions. Lay Summary: This open label clinical trial investigated changes in language, social communication, autism symptoms, behavior, and eye‐gaze tracking in 20 autistic children, comparing a period when they were on regular behavioral interventions to a period after they had received an infusion of their own cord blood. Nineteen children completed the study, as one had to be withdrawn due to the cord blood unit not meeting quality control criteria to be safe enough for infusion. Although cord blood infusion was found to be generally safe, some children had mild temporary side effects affecting their behavior (increased repetitive behaviors, aggression/irritability, hyperactivity, mood swings, sleep problems). One child's cord blood unit sample also showed bacterial growth, although that child remained well after the infusion. Some children showed global symptom improvements while others showed no change. Stem cell therapies for autism should therefore only be conducted within clinical trials with clear risk discussions, including that of infection. [ABSTRACT FROM AUTHOR]

Background: Weaning protocols from Non-invasive ventilation (NIV) are scant. We set out to study a protocol that was different from the British Thoracic Society protocol and lay down a weaning protocol from NIV in patients with Acute acidotic hypercapnic respiratory failure (AAHRF). Materials and Methods: Patients admitted with AAHRF and treated with NIV (baseline pH<7.35, PaCO2 >45 mmHg, and not requiring intubation) at a tertiary care teaching hospital, after taking into consideration the inclusion and the exclusion criteria were randomised in to one of the two group of weaning form NIV and serial ABGs were monitored. Results: The primary outcome of the study shows that there was no significant differences in the success rates of weaning from NIV in both the arms. The secondary outcome shows a few factors such as age, gender, SAPS2 score having an effect on the determination of weaning failure. Conclusion: Our study showed that both weaning by duration reduction and pressure reduction had equal success rates but a point on noting the SAPS II score on admission and the age of a particular patient will help decide on weaning initiation. CTRI/2019/12/022560 [Registered on: 30/12/2019]. [ABSTRACT FROM AUTHOR]

Background: A major proportion of preterm neonates require positive pressure ventilation (PPV) immediately after delivery. PPV may be administered through a face mask (FM) or nasal prongs. Current literature indicates that either of these are associated with similar outcomes. Summary: Nonetheless, FM remains the most utilized and the best choice. However, most available FM sizes are too large for extremely preterm infants, which leads to mask leak and ineffective PPV. Challenges to providing effective PPV include poor respiratory drive, complaint chest wall, weak thoracic muscle, delayed liquid clearance, and surfactant deficiency in preterm infants. Mask leak, airway obstruction, poor technique, and inappropriate size are correctable causes of ineffective PPV. Visual assessment of chest rise is often used to assess the efficacy of PPV. However, its accuracy is debatable. Though end tidal CO2 may adjudge the effectiveness of PPV, clinical studies are limited. The compliance of a preterm lung is highly dynamic. The inflating pressure set on T-piece is constant throughout the resuscitation, but the lung volume and dynamics changes with every breath. This leads to huge fluctuations of tidal volume delivery and can trigger inflammatory cascade in preterm infants leading to brain and lung injury. Respiratory function monitoring in the delivery room has potential for guiding and optimizing delivery room resuscitation. This is, however, limited by high costs, complex information that is difficult to interpret during resuscitation, and absence of clinical trials. Key Messages: This review summarizes the existing literature on PPV in preterm infants, the various aspects related to it such as the pathophysiology, interfaces, devices utilized to deliver it, appropriate technique, emerging technologies, and future directions. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of Type 2 Diabetes Mellitus (T2DM) is increasing worldwide. Microangiopathic and macroangiopathic complications are the main causes of morbidity and mortality in diabetes. Endothelial dysfunction is important in the early pathophysiology of vascular complications. Screening is very important in order to prevent these complications. Aim: To investigate endothelial dysfunction, as measured by Flow Mediated Vasodilation (FMD) of the brachial artery, in diabetic individuals. It also aims to explore the correlation between FMD and Glycated Haemoglobin (HbA1c), as well as the association between FMD and microvascular complications such as diabetic neuropathy, diabetic retinopathy, and albuminuria. Materials and Methods: This cross-sectional study was conducted at Mahatma Gandhi Medical College and Research Institute, Puducherry, India, between 2020 and 2021 on 160 patients. All patients diagnosed with T2DM, attending the Outpatient Department (OPD) or admitted to the ward, were enrolled in the study using consecutive sampling. FMD was measured for each patient, and Urine Albumin Creatinine Ratio (UACR) was also assessed. Diabetic retinopathy was evaluated through fundus examination, and diabetic neuropathy was screened using the monofilament test. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) version 27.0 to determine the correlation between FMD and these variables. Results: A total of 160 patients were enrolled in this study, including 104 (65%) males and 56 (35%) females. The median age was 52 years, and the participants had a median Body Mass Index (BMI) of 29.5 kg/m2. The median HbA1c was 8.7%. The median Fasting Blood Sugar (FBS) and Postprandial Blood Sugar (PPBS) levels were 145 mg/dL and 242 mg/dL, respectively. The median FMD among all patients was 5.6%, with an Interquartile Range (IQR) of 4.9% to 6.6%. There was an inverse correlation between HbA1C and FMD values, with a correlation coefficient of -0.718 (p-value <0.01), indicating a strong and significant inverse correlation. Patients with significant macroalbuminuria had a lower median FMD compared to non albuminuric patients, and this difference was statistically significant. The median FMD was also lower in patients with diabetic neuropathy and retinopathy. Conclusion: The study findings suggest that endothelial dysfunction, as measured by FMD, is significantly impaired in patients with elevated HbA1c and microvascular complications of diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background: Dry eye disease is a significant disease in Singapore. While there have been studies using allogenic cord serum for the treatment of dry eye disease, treatment of dry eyes with allogenic umbilical cord plasma drops has yet to be started in Singapore. Purpose: To evaluate the effectiveness of umbilical cord plasma eyedrops for the treatment of recalcitrant dry eyes in a local Singaporean context. Methods: This is an observational, longitudinal, interventional study for dry eye patients who did not show clear improvement after standard therapy. Patients were recruited from 2020 to 2023 from the dry eye clinic of the Singapore National Eye Center. Umbilical cord plasma was delivered frozen to patients and stored in home freezers. All participants underwent a standardized clinical evaluation for dry eye, and data were collected. Results: There were 40 participants (7 males and 33 females). The duration of follow-up was 5.52 ± 1.57 months. Kerato-epitheliopathy staining score, TBUT (tear breakup time), and SPEED (Standard Patient Evaluation of Eye Dryness Questionnaire) scores significantly improved after treatment. No statistically significant improvement was found in terms of visual acuity, according to Schirmer's score. Conclusion: Cord plasma eye drops significantly improved kerato-epitheliopathy staining scores in recalcitrant dry eye patients. Allogeneic plasma is a promising form of treatment for recalcitrant dry eye. [ABSTRACT FROM AUTHOR]

Neonatal alloimmune neutropenia, variably referred to in the literature as NAIN, FNAIN or NIN, is a disorder of neutrophil destruction in newborns similar to better-known conditions such as hemolytic disease of the newborn and neonatal alloimmune thrombocytopenia (FNAIT). Infants affected by this self-limiting condition can present asymptomatically or have a wide range of symptoms, from skin manifestations and mucositis to severe infections such as sepsis and pneumonia. In our case, we report an otherwise asymptomatic term infant born with severe neutropenia to a mother affected by COVID-19 in the 3rd trimester. However, it is unclear if COVID-19 contributed to our patients' neutropenia. Diagnostic testing eventually revealed the presence of anti-neutrophil antibodies, confirming the diagnosis of alloimmune neutropenia. The infant was conservatively managed with early discharge prior to resolution of neutropenia and close post-discharge follow up. [ABSTRACT FROM AUTHOR]

Background: The IL‐3‐pSTAT5 assay, a new, rapid, and standardized flow‐cytometry‐based assay may compensate for several limitations of the colony‐forming unit (CFU) assay typically used for stem cell potency assessments of cord blood units (CBU). We performed an inter‐laboratory evaluation of the performance of this new assay. Study design and methods: This Biomedical Excellence for Safer Transfusion (BEST) Collaborative multicenter, international study included 15 participants from public cord blood banks (CBBs), CBB‐supporting research laboratories, and stem cell laboratories. To perform the IL‐3‐pSTAT5 assay, participating centers received reagents, instructions, and 10 blind CBU samples, including eight normal samples and two samples exposed to a transient warming event. We measured inter‐laboratory agreement qualitatively (proportion of correctly classified samples) and quantitatively (coefficient of variation [CV], correlation coefficients, receiver operating characteristics (ROC) curve, and intraclass correlation coefficient [ICC]). Results: The qualitative agreement was 97.3% (i.e., 107/110; Fleiss' kappa = 0.835). The average CV on a per‐sample basis was 11.57% among all samples, 8.99% among normal samples, and on a per‐center basis was 9.42% among normal samples. In a correlation matrix that compared results across centers, the mean Pearson's correlation coefficient was 0.88 (standard deviation = 0.04). The ICC was 0.83 (95% confidence interval = 0.68–0.95). The area under the curve (AUC) from the ROC curve was 0.9974. Discussion: Excellent qualitative and quantitative agreement was exhibited across laboratories. The IL‐3‐pSTAT5 assay may therefore be implemented in flow cytometry laboratories to rapidly and reliably provide standardized measures of stem cell potency in CBUs. [ABSTRACT FROM AUTHOR]

Fibrillary glomerulonephritis (FGN) is a rare form of glomerulonephritis, usually occurring in concurrence with other conditions such as hepatitis C, dysproteinemia, autoimmune conditions, diabetes mellitus, and malignancy. The diagnosis is made by the presence of randomly oriented fibrillar deposits with a mean diameter of 20 nm, which stain positive for IgG and C3 and are negative for congo red and thioflavin T stains. Staining for DNAJB9 (DnaJ homolog subfamily B member 9) is a recently discovered mode of diagnosis of FGN without electron microscopy. The prognosis is poor and optimal treatment is yet not clearly defined, though rituximab may be useful in FGN patients with relatively preserved renal functions. In this case report, we discuss a case of post-renal transplant patient with de novo occurrence of fibrillary glomerulonephritis. [ABSTRACT FROM AUTHOR]

Introduction: Solid Organ Transplants (SOT) is at increased risk of Coronavirus Disease 2019 (COVID-19) infection, which may result in acute graft dysfunction and even death. While the disease has been well studied in the general population, it is not the case in renal transplant recipients. The poor immunological response of the vaccine in post renal transplant patients, the emergence of newer strains, and the possibility of a third wave in India, makes it even more important to know more about the course and outcome of the disease in post renal transplant patients. Aim: To evaluate the demographics, clinical presentation, biochemical profile, course of hospitalisation in post kidney transplant patients with COVID-19. Materials and Methods: This retrospective observational study study with 18 patients was conducted in Madurai Medical College, Tamil Nadu, India for duration of four months, from May 2021 to August 2021 and data collection from May 2021 to July 2021 and data analysis in August 2021. All post kidney transplant patients having evidence of COVID-19 were included. Detailed clinical history, biochemical profile, radiological findings, treatment, and final outcomes were collected and compared. Non parametric statistical tests were used, in addition to Chi-square test and odds ratio. Kaplan-Meier plot was used for survival analysis. Results: The most common presentation was fever 15 (83.3%), followed by cough 10 (55.6%). C-reactive Protein (CRP) {65 mg/L (11.48-94.48)}, D-dimer {0.72 mcg/mL (0.59-1.1)}, serum creatinine {3.5 mg/dL (2.12-5.93)}, and platelet count {200,000 cells/cu.mm (1.75-2.22)} and showed statistically significant (p<0.05) association with the outcome. About 15 (83.3%) patients developed Acute Kidney Injury (AKI). Seven patients (38.9%) had stage three AKI necessitating haemodialysis, of which six did not survive. The median survival time was 22 days, with 95% confidence interval (19.792-24.208), with case fatality rate of 33.3%. Conclusion: Post kidney transplant patients are at high risk of contracting COVID-19. CRP, D-dimer, serum creatinine, platelet counts, and arterial oxygen saturation may serve as prognostic markers. Dialysis may be required in view of high incidence of AKI and acute graft dysfunction, though the outcome seems dismal in such patients. Hence, the need for early hospitalisation and more effective treatment protocol is essential to improve outcome. [ABSTRACT FROM AUTHOR]

Introduction: Sleep disturbances are common in patients with end-stage kidney disease on hemodialysis (hemodialysis population: HDP). Higher rates of primary sleep disorders, demographic characteristics, metabolic abnormalities, and the efficacy of treatment place HDP at higher risk. The pattern observed is delayed onset of sleep, frequent awakening episodes, insomnia, sleep apnoea, excessive daytime sleepiness, restless leg syndrome, abnormal limb movements, pain in limbs, confusion, and nightmares. Two commonly used subjective assessment scores are the Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality and the Epworth Sleepiness Scale (ESS) to assess excessive daytime sleepiness. Objective: Subjective assessment of sleep using PSQI and ESS scores in HDP and correlation with clinical and demographic characteristics. Patients and Methods: A cross-sectional descriptive study of 148 patients with ESKD undergoing in-center hemodialysis. From June 2021 to October 2021 in Madurai medical college, Madurai, India. Subjective assessment with PSQI and ESS scores was done to identify sleep quality and daytime sleepiness, respectively. Results: The median PSQI score was 6 (IQ:4– 10), and as much as 68.24% scored > 5 on the PSQI (poor sleepers). The median ESS score of the study participants was 4 (Iq range 3– 7), and 19.59% had a total ESS score of more than 10 (excessive daytime sleepiness). The mean age of the participants was 44± 14.5. Age more than 60, lower body mass index, unemployment, higher dialysis vintage of more than 2 years, lower hemoglobin, high calcium-phosphorus product are statistically significant for both PSQI and ESS scores. Conclusion: The prevalence of poor sleep quality and excessive daytime sleepiness is high in HDP. Subjective assessment scores (PSQI and ESS) on the bedside are valuable tools in identifying sleep quality and EDS where objective assessment methods are not feasible and will help in the short time identification and management of sleep disturbances. [ABSTRACT FROM AUTHOR]

Uremic optic neuropathy (UON) is one of the rare causes of vision loss in chronic kidney disease patients. It is infrequently seen nowadays as most of the patients are dialyzed early owing to better availability of medical services. It is a clinical diagnosis, correlating loss of vision with optic disc edema in a patient with kidney failure which improves noticeably with hemodialysis and steroids. We describe a patient with UON with excellent improvement on timely institution of hemodialysis and steroid therapy. [ABSTRACT FROM AUTHOR]

Objective: Novel coronavirus disease-19 is spreading rapidly, and therefore, optimal management of the disease in end-stage kidney disease patients requiring hemodialysis is not fully explained. We report the clinical characteristics and the short-term outcomes in patients with end-stage renal disease who require hospitalization for coronavirus disease-19 and who underwent hemodialysis. Methods: In this retrospective, observational, single-center study, we analyzed the clinical course and outcomes of 116 consecutive end-stage kidney disease patients hospitalized with laboratory-confirmed coronavirus disease-19 who underwent at least 1 hemodialysis session in our hospital between June 26 and August 10, 2020. Baseline clinical features, laboratory data, and treatment given were compared between survivors and non-survivors to identify risk factors associated with mortality. Results: Among the 116 patients who were enrolled in our study, males constituted 81% (n = 94). Many had underlying comorbidities, of which hypertension (90.4%) was the most common. The most common symptoms were fever (76.1%), dyspnoea (61.2%), cough (58.6%), and diarrhea (18.1%). In total, 66.4% of patients had arteriovenous fistula or grafts. Inflammatory markers like C-reactive protein and serum ferritin were significantly higher in non-survivors group. Multivariate logistic regression analysis revealed that dialysis vintage less than 6 months was the most important predictor for mortality. Mortality was 27.5% in our cohort. Conclusion: Mortality among hospitalized end-stage kidney disease patients who underwent hemodialysis was higher when compared to the general population. The presence of comorbid conditions like hypertension, diabetes mellitus, and pre-existing pulmonary disease had a poor prognosis. Patients having central venous catheters as their dialysis access had a poor prognosis. Dialysis vintage less than 6 months was the most important predictor of mortality. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19), a condition associated with SARS-CoV-2, typically results in mild infection in infants and children. However, children with risk factors such as chronic lung disease and immunosuppression have higher risk of severe illness from COVID-19. We report a case of a 27-week-gestation extremely premature infant born to a mother with COVID-19 infection. The infant, initially treated for surfactant deficiency, developed worsening hypoxic respiratory failure on the fifth day of life requiring escalating ventilatory support, an elevated level of C-reactive protein, thrombocytopenia, and an elevated level of d-dimer. The infant was positive for SARS-CoV-2 by RTPCR from Day 1 to Day 42 of his life. The infant responded to a seven-day course of dexamethasone with a gradually decreasing oxygen requirement and could be extubated to non-invasive ventilation by the end of the fifth week after birth. The infant is currently on home oxygen by nasal cannula. Prolonged shedding of the virus may be a unique feature of the disease in premature infants. Extreme prematurity, immature lungs, and an immunocompromised status may predispose these infants to severe respiratory failure and a prolonged clinical course. Instituting appropriate COVID-19 protocols to prevent the spread of the disease in the neonatal intensive care unit (NICU) is of utmost importance. Infection with SARS-CoV-2 may have implications in the management of extremely premature infants in the NICU. [ABSTRACT FROM AUTHOR]

The article discusses various therapeutic options for the treatment of Dry Eye Disease (DED). It emphasizes the importance of understanding the different subtypes of DED and targeting the underlying mechanisms for effective treatment. The article highlights the efficacy of Diquafosol sodium 3% (Diquas) in improving tear production and reducing conjunctival epithelial damage. It also mentions the effectiveness of blood-derived products such as autologous serum eye drops (ASED), platelet-rich plasma (PRP), and umbilical cord blood serum (UCBS) in alleviating DED symptoms. The article further mentions other therapeutic options available in different centers, including topical rebamipide, systemic pilocarpine, and amniotic membrane-related treatments. It concludes by emphasizing the importance of practitioners having a global view of available therapeutics to facilitate discussions with patients and support their ongoing evaluation and management. [Extracted from the article]

The ever-growing use of inorganic nanoparticles (NPs) in biomedicine provides an exciting approach to develop novel imaging and drug delivery systems, owing to the ease with which these NPs can be functionalized to cater to various applications. In cancer therapeutics, nanomedicine generally relies on the enhanced permeability and retention (EPR) effect observed in tumour vasculature to deliver anti-cancer drugs across the endothelium. However, such a phenomenon is dependent on the tumour microenvironment and is not consistently observed in all tumour types, thereby limiting drug transport to the tumour site. On the other hand, there is a rise in utilizing inorganic NPs to intentionally induce endothelial leakiness, creating a window of opportunity to control drug delivery across the endothelium. While this active targeting approach creates a similar phenomenon compared to the EPR effect arising from tumour tissues, its drug delivery applications extend beyond cancer therapeutics and into other vascular-related diseases. In this review, we summarize the current findings of the EPR effect and assess its limitations in the context of anti-cancer drug delivery systems. While the EPR effect offers a possible route for drug passage, we further explore alternative uses of NPs to create controllable endothelial leakiness within short exposures, a phenomenon we coined as nanomaterial-induced endothelial leakiness (NanoEL). Furthermore, we discuss the main mechanistic features of the NanoEL effect that make it unique from conventionally established endothelial leakiness in homeostatic and pathologic conditions, as well as examine its potential applicability in vascular-related diseases, particularly cancer. Therefore, this new paradigm changes the way inorganic NPs are currently being used for biomedical applications. [ABSTRACT FROM AUTHOR]

Introduction: Acute pancreatitis (AP) is one of the common conditions encountered in the emergency room. The course of the disease ranges from mild form to severe acute form. Most of these episodes are mild and spontaneously subsiding within 3 to 5 days. In contrast, Severe Acute Pancreatitis (SAP) occurring in around 15-20% of all cases, mortality can range between 10 to 85% across various centres and countries. In such a situation we need an indicator which can predict the outcome of an attack, as severe or mild, as early as possible and such an indicator should be sensitive and specific enough to trust upon. PANC-3 scoring is such a scoring system in predicting the outcome of an attack of AP. Aim: To assess the accuracy and predictability of PANC-3 scoring system over APACHE II in predicting severity in an attack of AP. Materials and Methods: This prospective study was conducted on 82 patients admitted with the diagnosis of pancreatitis. Investigations to evaluate PANC-3 and APACHE II were done on all the patients and the PANC-3 and APACHE II score was calculated. Results : PANC-3 score has a sensitivity of 82.6% and specificity of 77.9%, the test had a Positive Predictive Value (PPV) of 0.59 and Negative Predictive Value (NPV) of 0.92. Sensitivity of APACHE II in predicting SAP was 91.3% and specificity was 96.6% with PPV of 0.91, NPV was 0.96. Conclusion : Our study shows that PANC-3 can be used to predict the severity of pancreatitis as efficiently as APACHE II. The interpretation of PANC-3 does not need expertise and can be applied at the time of admission which is an advantage when compared to classical scoring systems. [ABSTRACT FROM AUTHOR]

Sir, Bilateral pleural effusions are usually caused by a single factor, such as congestive cardiac failure or malignant diseases.[[1]] However, Contarini's syndrome is an exceptional case characterized by bilateral pleural effusion of different etiologies with different fluid characteristics of the lungs.[[2]] In this case, bilateral diagnostic thoracentesis is performed because the patient is devoid of any underlying causes.[[3]] A 68-year-old female patient was admitted to the hospital with C/O breathlessness for 2 weeks (mMRC Grade 2), weight loss, and loss of appetite over the previous 3 months. The most common cause of Contarini's syndrome is the development of transudative effusions due to congestive cardiac failure (opportunistic infections) with preexisting pneumonia/parapneumonic effusion. Due to a greater number of risk factors, immunocompromised people may be more susceptible to develop pleural effusions of various etiologies.[[8]] Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. [Extracted from the article]

Atypical hemolytic-uremic syndrome (aHUS) in neonates is a rare entity. We report a neonate with aHUS presenting at 16 days of life. She was diagnosed to have a heterozygous pathogenic variant in the gene encoding factor H and was treated with repeated plasma infusions. [ABSTRACT FROM AUTHOR]

Magnetic Resonance Imaging (MRI) images of the brain are used for detection of various brain diseases including tumor. In such cases, classification of MRI images captured with respect to ventricular and eye ball regions helps in automated location and classification of such diseases. The methods employed in the paper can segregate the given MRI images of brain into images of brain captured with respect to ventricular region and images of brain captured with respect to eye ball region. First, the given MRI image of brain is segmented using Particle Swarm Optimization (PSO) algorithm, which is an optimized algorithm for MRI image segmentation. The algorithm proposed in the paper is then applied on the segmented image. The algorithm detects whether the image consist of a ventricular region or an eye ball region and classifies it accordingly. [ABSTRACT FROM AUTHOR]

Nucleotide replacements in codons 145 and 149 of HLA‐A*02:03:01 result in a new allele, HLA‐A*02:402. [ABSTRACT FROM AUTHOR]

Predicting clinical response to anticancer drugs remains a major challenge in cancer treatment. Emerging reports indicate that the tumour microenvironment and heterogeneity can limit the predictive power of current biomarker-guided strategies for chemotherapy. Here we report the engineering of personalized tumour ecosystems that contextually conserve the tumour heterogeneity, and phenocopy the tumour microenvironment using tumour explants maintained in defined tumour grade-matched matrix support and autologous patient serum. The functional response of tumour ecosystems, engineered from 109 patients, to anticancer drugs, together with the corresponding clinical outcomes, is used to train a machine learning algorithm; the learned model is then applied to predict the clinical response in an independent validation group of 55 patients, where we achieve 100% sensitivity in predictions while keeping specificity in a desired high range. The tumour ecosystem and algorithm, together termed the CANScript technology, can emerge as a powerful platform for enabling personalized medicine.

Anal canal malignancy is one of the dreadful conditions. Most of the anal canal malignancies are squamous cell carcinomas for which the treatment is well established and the prognosis is usually favourable. Small cell carcinoma of anal canal is a very rare condition and poorly understood, which can present as haemorrhoids in its early stages and has an aggressive course. We present a case of small cell carcinoma of anal canal who underwent Abdomino Perineal Resection (APR) and chemotherapy. He developed liver metastasis during the course of chemotherapy and succumbed to the condition 4 months later. [ABSTRACT FROM AUTHOR]

The PI3K/AKT/mTOR pathway is an important signaling axis that is perturbed in majority of cancers. Biomarkers such as pS6RP, GLUT1, and tumor FDG uptake are being evaluated in patient stratification for mTOR pathway inhibitors. In the absence of a clear understanding of the underlying mechanisms in tumor signaling, the biomarker strategy for patient stratification is of limited use. Here, we show that no discernible correlation exists between FDG uptake and the corresponding Ki67, GLUT1, pS6RP expression in tumor biopsies from patients with head and neck cancer. Correlation between GLUT1 and pS6RP levels in tumors was observed but elevated pS6RP was noticed even in the absence of concomitant AKT activation, suggesting that other downstream molecules of PI3K/AKT and/or other pathways upstream of mTOR are active in these tumors. Using an platform, we ex vivo identified putative responders to rapamycin, an mTOR inhibitor in these tumors. However, rapamycin did not induce antitumor effect in the majority of tumors with activated mTOR, potentially attributable to the observation that rapamycin induces feedback activation of AKT. Accordingly, treatment of these tumors with an AKT inhibitor and rapamycin uniformly resulted in abrogation ofmTOR inhibition-induced AKT activation in all tumors but failed to induce antitumor response in a subset. Phosphoproteomic profiling of tumors resistant to dual AKT/mTOR inhibitors revealed differential activation of multiple pathways involved in proliferation and survival. Collectively, our results suggest that, in addition to biomarker-based segregation, functional assessment of a patient's tumor before treatment with mTOR/AKT inhibitors may be useful for patient stratification. [ABSTRACT FROM AUTHOR]

Abstract: Both WHO and IAP encourage using combination vaccines, wherever feasible. The phase III trial reported here was conducted to assess and compare the immunogenicity, tolerability and safety of two quadravalent vaccines, Quadrovax® (new vaccine), and TETRAct-Hib® (available in the market) in a multicentre study, in India. In all, 361 infants aged 6–8 weeks were enrolled, out of which 339 completed the study. The vaccination was done at 6–10–14 weeks following EPI/WHO recommended immunization schedule. Blood samples were collected prior to the administration of first dose and one month after the third dose. Postvaccination, geometric mean titres for each component did not differ significantly between the single dose vial and multi dose vial subgroups and among the two study groups. Adverse events observed were within the range quoted in literature. Quadrovax® vaccine manufactured by SIIL was found to be safe, immunogenic and non-inferior to the comparator vaccine. The quadravalent vaccine is best recommended in the second year of life when children receive their booster dose at 15–18 months. It can be given to infants during primary immunization series at 6, 10 and 14 weeks of age when Hepatitis B vaccine is given in a separate arm or to infants at 10 weeks who receive the Hepatitis B vaccine separately following the 0, 6 and 14 weeks or 0, 1 and 6 months schedule. [Copyright &y& Elsevier]

Objective: The traditional intravenous (IV) route of administration for hematopoietic stem cell transplantation (HSCT) may result in inefficient placement of donor cells, possibly contributing to suboptimal engraftment and higher risk of graft-vs-host reactions. In order to perform detailed studies of engraftment and donor cell distribution in an animal model with anatomical similarity to man, we performed the first direct homing/engraftment efficiency comparison between intraosseus (IO) and IV HSCT in allogeneic nonhuman primate animal model to assess the utility and mechanism of donor cell homing after IO delivery. Materials and Methods: Donor bone marrow (BM) cells labeled with PKH26 membrane dye were transplanted to nonmyeloablative-conditioned nonhuman primate animals. Chimerism was confirmed by polymerase chain reaction amplification of donor-specific short tandem repeat locus. Results: Compared to the IO route, IV infusion trapped 2.4- to 4.8-fold more donor cells in peripheral organs, including the lung, heart, spleen, kidney, and liver. IO injection resulting in a 6.2-fold increase in donor cells retained in the BM at the site of injection and a 2.7-fold increase in donor cells retained in distant BM sites. A profile of selected cell adhesion molecules (CAMs) demonstrated that after IO HSCT, more donor cells express CAMs that could facilitate BM homing and redistribution to non–injection-side BM cavities. This change in homing efficiency may be clinically significant because IO transplantation in haploidentical recipients enhanced donor cell engraftment when compared to IV delivery. Conclusion: Our results suggest that IO injection enhances both homing and engraftment in nonhuman primate HSCT. [Copyright &y& Elsevier]

Background The most common sleep-disordered breathing (SBD) is obstructive sleep apnea (OSA), which affects nearly a billion adults worldwide. OSA is characterized by frequent episodes of a complete (apnea) or partial (hypopnea) collapse of the upper airway, mainly the oropharyngeal tract during sleep, with a consequent cessation or reduction of the airflow. Undiagnosed and untreated OSA can lead to cognitive and neurobehavioral dysfunction, cardiovascular comorbidities, inability to concentrate, memory impairment, and mood changes like irritability and depression, with a remarkable effect on quality of life. Polysomnography (PSG) remains the gold standard for diagnosis; however, it is expensive, less accessible, and has a long waiting period to get it done. Home nocturnal oximetry, measuring the oxygen desaturation index (ODI), is a promising alternative for diagnosis.  Materials and methods A prospective observational study was conducted over two years, involving patients with a high pre-test probability of OSA. Patients underwent both home nocturnal oximetry and in-lab PSG. Statistical analysis was performed using the Spearman correlation, the Wilcoxon signed-rank test, and the receiver operating characteristic (ROC) curves to compare ODI and apnea-hypopnea index (AHI) values. Results Out of 67 participants, 43 (64%) had abnormal home oximetry results (ODI>5) and 62 (92.5%) had abnormal PSG (AHI>5). There was a significant correlation between ODI and AHI (r=0.734, p=0.001). No significant difference was found between ODI values from home oximetry and in-lab PSG. The sensitivity, specificity, and diagnostic accuracy of home oximetry in detecting OSA (ODI>5) were 69%, 100%, and 71%, respectively. The ROC analysis demonstrated an area under the curve (AUC) of 0.98 for predicting AHI>5. Conclusion Home nocturnal oximetry correlates well with level 1 PSG and provides a reliable diagnostic tool for OSA, especially in resource-limited settings. However, further validation is required to improve its sensitivity when ruling out OSA., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Pondicherry Institute of Medical Sciences (PIMS) Institute Ethics Committee (IEC) issued approval IEC: RC/18/90. Approved on 17/10/2018 for a period of three years until 16/10/2021. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Undrajavarapu et al.)

This study aimed to document the safety and efficacy of a single infusion of autologous umbilical cord blood (UCB) in 20 autistic children aged 24-72 months. A pre-post treatment within-subjects open label design was used. At T = 0, 6, 12, and 18 months, participants underwent detailed and structured safety evaluations (via caregiver report), Vineland Adaptive Behavior Scale (Vineland-3), Stanford Binet Intelligence Scale (SB-5), Expressive One-Word Picture Vocabulary Test, Brief Observation of Social Communication Change (BOSCC), Pervasive Developmental Disorder-Behavior Inventory, Repetitive Behavior Scale-Revised, Sensory Experience Questionnaire (SEQ-2.1), Child Behavior Checklist, Clinical Global Impression-Severity and Improvement (CGI-I) Scales, and eye-gaze tracking. UCB infusion was conducted at T = 6 months, hence, 0-6 months was the control period, and 6-18 months the follow-up period. Of 20 children recruited, 19 completed the study and 1 was withdrawn due to UCB not meeting quality control criteria for infusion. There were 15 males and 4 females with an overall mean (SD) age of 4.15 (0.62) years. Mean (SD) cell dose administered was 38.16 (9.82) million cells/kg. None suffered serious adverse events although there were mild behavioral side effects and one unit grew coagulase negative staphylococcus from a post-thaw sample. There were no significant differences in Vineland-3, SB-5, BOSCC, and SEQ-2.1 scores at T = 12 and T = 18 months. Twelve participants had T = 18 CGI-I scores of 2-3 (minimally to much improved), seven participants had scores of 4 (no change). Autologous UCB infusion in autistic children is generally safe but not without risks, including that of infection. In this within-subjects study, some children showed global symptom improvements while others showed no change. Stem cell therapies for autism should only be conducted under strict clinical trial conditions with clear risk discussions., (© 2024 International Society for Autism Research and Wiley Periodicals LLC.)

We describe the allele and haplotype frequencies seen in a volunteer unrelated bone marrow donor registry, a public cord blood bank, and donor/recipient samples processed by the Health Sciences Authority (HSA) in Singapore. Historical human leukocyte antigen (HLA) typing reports were anonymized and combined. They were checked for HLA typing nomenclature discrepancies or ambiguities using the HLA-net UNIFORMATE tool, and for analysis, the validated data were subsequently separated into Chinese, Malay, Indian, and "Others," according to the race classification system used in Singapore. Individual ethnic allele and haplotype frequencies were calculated with the HLA-net GENE[RATE] pipeline using basic statistics. The Basic Statistics Tool of HLA-net was used to estimate haplotype frequency using an expectation maximization algorithm, given a set of multi-allelic data pairs for a given HLA locus. The outputs downloaded from the site comprised plain text files with haplotype frequency estimates, results of a global linkage disequilibrium test, and standardized residuals (stdres) corresponding to deviations from expected frequencies. HLA typing results from 59,186 individuals met the inclusion criteria, yielding 118,372 analyzable alleles. In our study population, the haplotype A*33:03-B*58:01-C*03:02-DRB1*03:01～DQB1*02:01:01G with a frequency of 4.91% was the most common. This haplotype was also the most common among Singaporean Chinese donors. Consistent with the predominant Chinese population, haplotypes with a frequency greater than 1% were also the most frequently observed haplotypes in the Singaporean population. In the Malay donor population, the most common haplotype was A*33:03～B*44:03～C*07:01:01G～ DRB1*07:01-DQB1*02:01:01G, with a frequency of 3.41%, whereas within the Indian donor population, the most common haplotype was A*01:01-B*57:01-C*06:02～DRB1*07:01-DQB1*03:03, with a frequency of 3.42%. Haplotype diversity and composition statistics within donor pools provide HLA background data required for the targeted recruitment of donors to support the hematopoietic stem cell donor requirements of the country. These data may be used in the future to devise donor recruitment strategies for optimizing the donor pool through targeted publicity and accruals., Competing Interests: The authors declare no conflict of interest. Disclosure forms provided by the authors are available on the website., (Copyright Ⓒ2022 Asia-Pacific Blood and Marrow Transplantation Group (APBMT).)

Background: The coronavirus disease 2019 (COVID-19) vaccine is not readily available in many countries where dosing interval is spaced more than ideal. Patients with chronic kidney disease, especially those on maintenance hemodialysis, have a tendency for a reduced immune response. This study was undertaken to demonstrate the distinct humoral immune response to the viral vector COVID-19 vaccine in patients with kidney failure receiving maintenance hemodialysis., Methods: The study was carried out with two cohorts: 1) patients receiving maintenance hemodialysis and 2) healthcare workers from the same dialysis center as controls, each group with 72 subjects. Participants received a dose of Covishield ChAdOx1 nCoV-19 coronavirus vaccine. The humoral immunological response was determined using electrochemiluminescence immunoassay which quantitatively measures antibodies to the severe acute respiratory syndrome coronavirus 2 spike protein receptor-binding domain., Results: All study subjects in the control group developed a humoral response (antibody titer of ≥0.8 U/mL), while only 64 of 72 in the dialysis group (88.9%) were responders. Age (ρ = -0.234, p = 0.04) and sodium level (ρ = 0.237, p = 0.04) correlated with low antibody titer in bivariate analysis. In multivariate analysis, only age (odds ratio, 1.10; 95% confidence interval, 1.01-1.22; p = 0.045) was associated with nonresponders., Conclusion: Our study demonstrated a weak antibody response of hemodialysis patients to the viral vector COVID-19 vaccine. Older age was associated with nonresponders. Evaluation of both humoral and cellular immunity after the second vaccine dose and serial antibody titers can help determine the need for booster shots.

Schwartz Jampel syndrome is a very rare genetically heterogenous disorder characterized by myotonia, typical facies, growth retardation and osteoarticular changes. Prevelance of this syndrome is <1 in 100000. 150 cases have been reported in medical literature so far. We hereby report this rare syndrome in neurology., (© Journal of the Association of Physicians of India 2011.)

Introduction: Acute Pancreatitis (AP) is one of the common conditions encountered in the emergency room. The course of the disease ranges from mild form to severe acute form. Most of these episodes are mild and spontaneously subsiding within 3 to 5 days. In contrast, Severe Acute Pancreatitis (SAP) occurring in around 15-20% of all cases, mortality can range between 10 to 85% across various centres and countries. In such a situation we need an indicator which can predict the outcome of an attack, as severe or mild, as early as possible and such an indicator should be sensitive and specific enough to trust upon. PANC-3 scoring is such a scoring system in predicting the outcome of an attack of AP., Aim: To assess the accuracy and predictability of PANC-3 scoring system over APACHE II in predicting severity in an attack of AP., Materials and Methods: This prospective study was conducted on 82 patients admitted with the diagnosis of pancreatitis. Investigations to evaluate PANC-3 and APACHE II were done on all the patients and the PANC-3 and APACHE II score was calculated., Results: PANC-3 score has a sensitivity of 82.6% and specificity of 77.9%, the test had a Positive Predictive Value (PPV) of 0.59 and Negative Predictive Value (NPV) of 0.92. Sensitivity of APACHE II in predicting SAP was 91.3% and specificity was 96.6% with PPV of 0.91, NPV was 0.96., Conclusion: Our study shows that PANC-3 can be used to predict the severity of pancreatitis as efficiently as APACHE II. The interpretation of PANC-3 does not need expertise and can be applied at the time of admission which is an advantage when compared to classical scoring systems.

Background: Little is known about survival on peritoneal dialysis (PD) in Indian patients since the initiation of continuous ambulatory PD (CAPD) in India in 1991. Survival data from single centers with small numbers have been published., Objective: A retrospective 4-center analysis for predictors of survival >3 years in south Indian chronic PD patients., Methods: A total of 309 patients were trained during the observation period (from 1999 to 2004) and were analyzed in a multicenter study (4 centers), including 150 patients (male:female 109:41) that survived > or = 3 years and 59 patients that did not survive > or = 3 years (nonsurvivors; male: female 43:16) that were taken as controls. The patients were on chronic PD, predominantly CAPD, using double-bag disconnect systems. They were supervised by 4 nephrologists. Mean age in the nonsurvival group was 56.6 +/- 10.6 years. In the survival group, mean age was 50.9 +/- 14.9 years; there were 92 (62%) nondiabetics and 58 (38%) diabetics; the majority were nonvegetarians; 148 patients were doing 6 - 8 L exchanges and 2 were doing >8 L exchanges daily; 93 of 102 patients were average transporters based on peritoneal equilibration testing. At the beginning, mean combined Kt/V was 2.31 and weekly creatinine clearance was 73 L. Patients making one lifetime payment were 46% and 21% belonged to the full reimbursement group., Results: Body mass index (BMI) was normal in 114 patients (76%). Ultrafiltration volume was 1377 +/- 452 at the start and 1400 +/- 461 mL/day after 3 years. Anuric patients at the start were 12% and after 3 years 44%; urine output decreased from 527 +/- 26 to 253 +/- 14 mL/day from the start to after 3 years. Peritonitis rate was 1 episode/75 patient-months at the beginning and after 3 years it was 1 episode/30 patient-months. Exit-site care was done daily by 88% and 3 times weekly by 12%. Nonsmokers were 92% and smokers were 8%. Those that lived in the city were 62% and rural areas were 38%. Mean blood pressure was 143 +/- 16/88 +/- 10 and 136 +/- 18/85 +/- 9 mmHg, calcium x phosphorus product 44.6 +/- 15.6 and 45.9 +/- 15.7 mg(2)/dL(2), albumin 3.33 +/- 0.5 and 3.25 +/- 0.4 g/dL, hemoglobin 9.18 +/- 2 and 9.48 +/- 1.8 g/dL at the beginning and after 3 years, respectively. Statistical analysis showed a significant fall in both systolic (p < or = 0.001) and diastolic blood pressure (p < or = 0.05), an increase in BMI (p < or = 0.01), and a decrease in blood urea (p < or = 0.001) in the survival group. Those with Hb > or = 11 g/dL survived longer (p < or= 0.001), those with serum albumin > or = 3 g/dL had better survival (p = 0.001), and anuric patients survived longer (p = 0.001)., Conclusion: This multicenter cohort study of prevalent continuous PD patients in south India showed nondiabetics, average transporters, nonsmokers with reasonable nutritional status, with Hb 11 g/dL, with low peritonitis rate, with over 1 L ultrafiltration volume per day, the great majority that joined the once per lifetime payment scheme, and the reimbursement group survived for 3 years or longer.