Search

Background: Critically ill patients on Non- invasive Ventilation (NIV) or Continuous Positive Airway Pressure (CPAP) tend to desaturate off ventilatory support. Hence, they are unable to meet their nutritional needs, leading to increase in hospital stay. It was evident during the COVID 19 pandemic. The failure rates of NIV were unusually high, from 30-45%. Despite the overall success of the treatment modality, NIV failure rates still range between 18% and 40% in the acute setting. It was seen that the patients on NIV get only 650 Kcal/ day which is far lower than the required energy requirement. There is a need to have an affordable and sustainable solution to deliver adequate nutrition to critically ill patients on NIV and CPAP, which is able to maintain a NG/ OG tube without frequent disconnections from the ventilator. With this fact in mind a NIV mask with inbuilt feeding port (NIV-IFP) was designed. Aims and Objectives: The aim of this case series was to compare the modified NIV-IFP mask with the conventional mask in terms of both effectiveness of ventilation as well as caloric replacement in critically ill patients. For the purpose of this study, we enlisted three patients who were critically ill and required NIV. Results: With the use of NIV-IFP mask we were able to substitute adequate amount of nutrition (2000Kcal to 2500 Kcal) without any discontinuation of NIV application and with minimal leak in the mask. Conclusion: When compared to other available technologies in this field, the NIV mask with the inbuilt feeding port is very economical and can be a boon in third world countries. The placement of this unique mechanism in the mask was instrumental in weaning off patients from NIV and avoided Invasive ventilation. It was proved beyond doubt that addition of this gland nut assembly was extremely effective in delivering adequate nutrition to our patients without compromising on the ventilation.

Uterocutaneous fistula is a rare pathology that commonly occurs following uterine surgeries, endometriosis, chronic infection, malignancy, and foreign bodies. Many diagnostic and management strategies have been practiced. In this case series, we describe three cases of uterocutaneous fistula following cesarean and myomectomy, which was diagnosed clinically, confirmed by magnetic resonance imaging, and managed successfully by surgery with fertility preservation.

Abstract Cervical cancer is still the leading cause of cancer mortality worldwide even after introduction of vaccine against Human papillomavirus (HPV), due to low vaccine coverage, especially in the developing world. Cervical cancer is primarily treated by Chemo/Radiotherapy, depending on the disease stage, with Carboplatin/Cisplatin-based drug regime. These drugs being non-specific, target rapidly dividing cells, including normal cells, so safer options are needed for lower off-target toxicity. Natural products offer an attractive option compared to synthetic drugs due to their well-established safety profile and capacity to target multiple oncogenic hallmarks of cancer like inflammation, angiogenesis, etc. In the current study, we investigated the effect of Bergenin (C-glycoside of 4-O-methylgallic acid), a natural polyphenol compound that is isolated from medicinal plants such as Bergenia crassifolia, Caesalpinia digyna, and Flueggea leucopyrus. Bergenin has been shown to have anti-inflammatory, anti-ulcerogenic, and wound healing properties but its anticancer potential has been realized only recently. We performed a proteomic analysis of cervical carcinoma cells treated with bergenin and found it to influence multiple hallmarks of cancers, including apoptosis, angiogenesis, and tumor suppressor proteins. It was also involved in many different cellular processes unrelated to cancer, as shown by our proteomic analysis. Further analysis showed bergenin to be a potent-angiogenic agent by reducing key angiogenic proteins like Galectin 3 and MMP-9 (Matrix Metalloprotease 9) in cervical carcinoma cells. Further understanding of this interaction was carried out using molecular docking analysis, which indicated MMP-9 has more affinity for bergenin as compared to Galectin-3. Cumulatively, our data provide novel insight into the anti-angiogenic mechanism of bergenin in cervical carcinoma cells by modulation of multiple angiogenic proteins like Galectin-3 and MMP-9 which warrant its further development as an anticancer agent in cervical cancer.

Background and Aims: Awake intubation is the preferred method for securing difficult airways. We compared intravenous (IV) propofol and dexmedetomidine for C-MAC® D-blade-guided anticipated difficult nasotracheal intubation under conscious sedation. Methods: This randomised study included 60 patients with difficult airway (El-Ganzouri Score 4–9). After adequate airway preparation with IV midazolam 0.03 mg/kg and IV fentanyl 1 µg/kg, in Group P, propofol was infused at 250 µg/kg/min and in Group D, dexmedetomidine was infused at 1 μg/kg over 10 min, then at 0.5 μg/kg/h till a bispectral index (BIS) value 65–70 was achieved. Patients underwent C-MAC® D-blade video laryngoscope-guided nasotracheal intubation. The intubation score was the primary outcome measure. Secondary outcome measures included haemodynamic parameters, intubation time, number of attempts, the incidence of failed awake intubation, glottic view, time to achieve desired BIS, complications, study drug consumption and patient-reported satisfaction with the awake intubation technique. Quantitative variables were compared between groups using unpaired t-test/Welsch test/Mann–Whitney Test. Qualitative variables were correlated using the Chi-square test/Fisher's exact test. A P value of 0.05). The time to target BIS was four times longer, and the time to intubate was 6 seconds longer in Group D. Conclusion: Successful awake C-MAC® D-blade video laryngoscopic intubation can be performed under dexmedetomidine/propofol conscious sedation, with propofol giving a better intubation score.

Background and Purpose: Congenital deformities occur due to abnormal development of limbs in the intrauterine life. The exact cause of this type of defect is not known but can be associated with environmental factors (drug history or exposure of chemical effluents from factory) or genetic predisposition. Cases involving the occurrence of single digits in all four limbs were witnessed, and the aim was to study and trace the cause of such deformities. Knowledge of thalidomide induced phocomelia which has already being published in the literature also contributed to our knowledge and understanding. Objectives: (1) Primary objective was to identify the causative agent or genetic factor for the occurrence of single digits in hands and feet in multiple families. (2) Secondary objective was to create awareness among patients and the general public as well as local government authorities regarding such families of “Divyang” patients. We present a case series of multiple families with complete absence of all fingers and toes except one across villages in Haryana. Materials and Methods: Clinical setting: (1) Study was based on a detailed questionnaire which was taken from multiple villagers (Tarawari Village, Nilokheri Village, etc.) and (2) phenotypic examination. Five affected patients from multiple families for 1 year were taken for study from March 2022 to March 2023. Their habitus, lifestyle, and environmental status were all studied and compared with other studies. Efforts were taken to study the license and toxic effluent treatment plan of a chemical factory present in the near vicinity. Results: A strong genetic association was suggested for the occurrence of single digits in the hands and feet of multiple patients across multiple villages close to a chemical factory. They have well adjusted with writing, eating, riding bikes, and four-wheelers with single fingers and toes. Conclusion: There is a need to establish genetic analysis so that the cause of such deformities could be known and prevented. There is also a need for general and government awareness toward pollutants released from chemical factories and their effects.

Abstract Background Subtotal petrosectomy (STP) has attracted massive interest over last two decades. The aim is to present our experience of this uncommon surgery. The indications, outcomes, and our variation in surgical technique would be presented and literature reviewed. Methods A retrospective observational study of all patients who underwent STP at a tertiary care center in India was analyzed. Results A total of 9 ears (in 8 patients) underwent STP over last 5 years at our center. The pathological conditions for which STP was done included chronic otitis media squamous (four ears), middle ear tumors (three ears), petrous apicitis (one ear), and traumatic cerebrospinal fluid (CSF) otorhinorrhea (one ear). The indication of STP included disease clearance (eight ears), unserviceable hearing (seven ears), hearing rehabilitation with otological implants (six ears), and intraoperative CSF gusher (one ear). Intraoperative indications included CSF gusher, large tegmen defect with erosion of apical turn of cochlea, and erosion of anterior bony wall of external auditory canal. The mean follow-up period was 36 months (range of 6 months to 60 months). None of the patients had any dehiscence of blind sac closure or secondary acquired cholesteatoma on imaging. Conclusions STP facilitates disease clearance by providing unmatchable exposure in difficult otological scenarios and additionally isolates middle ear cleft from external environment, thereby eliminating problems of mastoid cavity. Furthermore, it also prepares ear for second stage otological implants. It is a safe surgery with minimal complications.

Introduction: Dental trauma sustained while participating in sports is the main element that connects dentistry and sports. Sports involving frequent physical contact with other athletes increase the risk of dentofacial injuries. This association underscores the importance of preventive measures, with well-fitted athletic mouthguards identified as a key intervention to mitigate the risk of dentofacial injuries. Aim: To assess awareness about sports-related dental injuries and mouthguard use among young trainees in three contact sports-khokho, kabaddi, and football. Materials and Methods: A cross-sectional study was conducted from May 2023 to July 2023, which included 226 young trainees from the Government College of Physical Education, Bhubaneswar, engaged in football, kabaddi, and khokho. Data was collected using a self-structured questionnaire and were subjected to analysis employing the Chi-square test. Sports-related dental injury was assessed using the Traumatic Dental Injury codes of the World Health Organisation (WHO) Oral Health Assessment Form for Adults, 2013. Results: Eight (8.3%) football players had the highest incidence of upper left central incisor enamel fracture, as determined by the dental injury codes. The majority of the trainees, 206 (91.2%), were aware of what a mouthguard is. However, 135 (59.7%) agreed that mouthguard use should be mandatory during sports practice. A p-value

Objective: Bullous pemphigoid is a rare autoimmune skin disorder characterized by blistering, urticarial lesions, which are sometimes associated with adverse drug reactions. Vildagliptin is an oral anti-diabetic agent that selectively inhibits the dipeptidyl peptidase-4 (DPP-4) enzyme. Materials and Methods: A 75-year-old female with a known case of type 2 Diabetes Mellitus, hypertension, and hypothyroidism for the last 10 years presented with pruriginous tense bullous skin lesions over her both palms and soles. There was no mucosal involvement. Further interrogation revealed that she started taking Vildagliptin 5 days ago which was prescribed due to high levels of post-prandial blood sugar level despite already intake of Glimepiride-4 mg and Metformin-3 gm. Results: Vildagliptin was immediately advised to be stopped. She was treated with antihistamines, steroids, and conservative management which led to remission of the blisters. Conclusion: Vildagliptin is the probable causative drug for developing bullous pemphigoid skin lesion which shows temporal association in this case as other concomitant drugs has no direct correlation. Therefore physicians must be aware of this rare life-threatening side effect of this medicine and advice patients to visit the hospital even the slightest cutaneous manifestation. Bullous pemphigoid can result in fatal life-threatening conditions if not treated early.

Abstract The purpose of this study is to understand the impact of community mobilization initiatives on citizens’ health-seeking behavior through the lens of COVID-19 vaccination in the state of Madhya Pradesh, India. This study follows a case study approach to understand community mobilization initiatives that led to increased COVID-19 vaccination uptake. The study delineates the process to increase community mobilization to improve the uptake of COVID-19 vaccination. It highlights the key components of community mobilization that were adopted: the involvement of local leadership (at district, block, and village level), support of vaccination/mobilizer team, the role of in-person communication, involvement of influential community heads and social workers, localized strategies and IEC materials, and support from the state administration. Additionally, the key communication themes that played a crucial role in increasing COVID-19 vaccination coverage are identified. The findings of this study will help the policymakers and practitioners in the domains of Health and Medical Humanities, Health Policy and Services, and Social Sciences to clarify the roles of community mobilization activities and initiatives in increasing vaccination coverage. Furthermore, the study provides evidence for the adaptation, integration, and enhancement of these activities based on the four case studies discussed.

This paper provides a comprehensive review of academic research pertaining to the interaction of emotions and false memory, elucidating the malleable nature of human memories. False memories can have serious effects in forensic and clinical settings, like misremembering events or making up events. In these contexts, the influence of emotions and misinformation can frequently lead to distortions in memory. The presence of intense emotional experiences within these environments, combined with the presence of multiple sources of deceptive information, increases the likelihood of the formation of false memories induced by suggestion. Clinically, understanding these dynamics is crucial for developing therapeutic interventions to mitigate the impact of false memories on individuals' mental health. This review paper delves into the intricate relationship between emotions and false memory, examining two primary paradigms: the Deese-Roediger-McDermott (DRM) and misinformation paradigms. The paper comprehensively synthesizes existing research, revealing that emotions significantly influence the generation and retrieval of false memories. Findings indicate that mood states and emotional content play pivotal roles in shaping memory distortions. In the DRM paradigm, negative mood tends to reduce false memory formation, while positive mood can amplify it. Emotional valence also impacts false recollections, with negative content often associated with increased false memories. In the misinformation paradigm, mood is impacting the confidence attributed to false recollections rather than affecting susceptibility to misinformation. When comparing emotional content, negative events are leading to induce more false memories due to their ease of recalling negative gist and semantic connections. Both the DRM and misinformation paradigms offer valuable insights into the underlying mechanisms of emotional false memory. The paper discusses the implications of these findings for various fields, such as forensic psychology and clinical settings, and highlights the need for further research to elucidate the complex interplay between emotions and memory.

Chimeric Antigen Receptor (CAR) T cells targeting CD19 induce durable remissions in patients with relapsed or refractory non-Hodgkin lymphoma (NHL), but many patients experience treatmentrelated toxicity. Cytokine release syndrome and immune effector cell-associated neurologic syndrome are extensively characterized. However, limited data exist on the burden, predictors, and implications of acute kidney injury (AKI) after CAR T cell therapy. On initial screening of the FDA adverse event reporting system, we identified a disproportionately high rate of renal adverse events among nearly 6,000 CAR T adverse event reports, suggesting it is clinically important in this patient population. In a subsequent single-center analysis of 399 NHL patients treated with CD19 CAR T cells, we found a substantial burden of AKI after CAR T infusion (10% and 5% of any grade and grade ≥2 AKI) with pre-renal causes being predominant (72%). Evolution to chronic kidney disease was rare, however, 3 patients required hemodialysis. Importantly, patients experiencing cytokine release syndrome and/or neurotoxicity as well as those with low serum albumin and high inflammatory cytokines, including IL-6 and TNF-alpha, were more likely to develop AKI. While pre-CAR T renal dysfunction was not associated with adverse outcomes, patients developing post-CAR T AKI had lower overall survival compared to their counterparts. Our findings indicate that renal dysfunction is a common toxicity of CAR T cell therapy with meaningful prognostic impact. Notably, the link between systemic inflammation and renal dysfunction, suggests that readily available biomarkers may inform on renal injury risk after CAR T cell therapy.

Tobacco quitline services offer telephone-based counseling to assist tobacco users in quitting through behavioral modification. It is a sponsored scheme by the Ministry of Health and Family Welfare, Government of India. The present study has two objectives: primarily, to study the correlation between socio-demographic variables and tobacco abuse, and secondly, to study the impact of National Tobacco Quit-Line Services (NTQLS) in India. The data for the study was collected from the registered callers who have completed at least one year of follow-ups at NTQLS, Vallabhbhai Patel Chest Institute, University of Delhi, between May 2016 and May 2021. The questionnaire was directly administered to the people who had called NTQLS for the first time to quit tobacco use. Callers were provided one year of continuous follow-up to ensure they remain long-term abstinent from tobacco and permanently quit. All the data were managed through an electronic database. A total of 85,807 individuals’ data was taken for the study. The maximum number of callers were from Uttar Pradesh (28.03%), followed by Rajasthan (24.67%) and Madhya Pradesh (7.59%). The female population represented only 1.43%; the male population was significantly higher (98.57%). Youth (44.83%) and adults (53.78%) were more than seniors (0.9%) and adolescents (0.4%). Smokeless tobacco users (67.32%) were more common than smoking tobacco users (20.11%). Duration of tobacco use among the 71.74% of callers was found to be between 1 and 10 years; the remaining 24.03% had been using tobacco for over 10 years, while 4.23% were novice users. The abstinence rate achieved by NTQLS was 33.42% after one month of quitting and 21.91% after one year of quitting. We found a significant association between tobacco users’ socioeconomic and demographic status. The number of male tobacco users was significantly higher than the number of female tobacco users. Among all the tobacco users, youth was persistently using tobacco the most. Individuals from low socio-economic status were more likely to use tobacco as compared to those from high socioeconomic status. These associations indicate the need for strengthening the enforcement of tobacco control policies and developing and monitoring comprehensive smoke-free legislation.

ObjectiveOral cancer is a widespread global health problem characterised by high mortality rates, wherein early detection is critical for better survival outcomes and quality of life. While visual examination is the primary method for detecting oral cancer, it may not be practical in remote areas. AI algorithms have shown some promise in detecting cancer from medical images, but their effectiveness in oral cancer detection remains Naïve. This systematic review aims to provide an extensive assessment of the existing evidence about the diagnostic accuracy of AI-driven approaches for detecting oral potentially malignant disorders (OPMDs) and oral cancer using medical diagnostic imaging.MethodsAdhering to PRISMA guidelines, the review scrutinised literature from PubMed, Scopus, and IEEE databases, with a specific focus on evaluating the performance of AI architectures across diverse imaging modalities for the detection of these conditions.ResultsThe performance of AI models, measured by sensitivity and specificity, was assessed using a hierarchical summary receiver operating characteristic (SROC) curve, with heterogeneity quantified through I2 statistic. To account for inter-study variability, a random effects model was utilized. We screened 296 articles, included 55 studies for qualitative synthesis, and selected 18 studies for meta-analysis. Studies evaluating the diagnostic efficacy of AI-based methods reveal a high sensitivity of 0.87 and specificity of 0.81. The diagnostic odds ratio (DOR) of 131.63 indicates a high likelihood of accurate diagnosis of oral cancer and OPMDs. The SROC curve (AUC) of 0.9758 indicates the exceptional diagnostic performance of such models. The research showed that deep learning (DL) architectures, especially CNNs (convolutional neural networks), were the best at finding OPMDs and oral cancer. Histopathological images exhibited the greatest sensitivity and specificity in these detections.ConclusionThese findings suggest that AI algorithms have the potential to function as reliable tools for the early diagnosis of OPMDs and oral cancer, offering significant advantages, particularly in resource-constrained settings.Systematic Review Registrationhttps://www.crd.york.ac.uk/, PROSPERO (CRD42023476706).

Desalination brine can negatively impact the marine environment in several ways, although there are ongoing discussions regarding the severity and magnitude of environmental effects. A fascinating strategy to lessen any adverse effects is to undertake resource recovery from the brine, which also has the potential for additional revenue generation. More recently, the increasing demand for secure and less geographically restricted sources of precious or rare earth minerals, integrated with growing awareness of waste management and environmental sustainability, is driving the development of economically viable technologies to recover valuable materials from waste streams. This article provides an overview of different methods and technologies, including reverse osmosis (RO), electrodialysis (ED), and distillation, that can be used to recover precious materials, including Li, Mg, Na, and Rb and valuable blends from various waste sources and thus create a more sustainable and circular economy. The mechanisms are discussed in detail, including electrochemical processes (electrolysis, ED, and capacitive deionization), thermal desalination (multistage flash distillation and membrane distillation), pressure‐driven desalination (RO and nanofiltration), and microbial desalination cells. Challenges associated with recovering precious materials from waste streams, such as fouling, scaling, and environmental impact, along with further research directions and potential applications of desalination technologies, are also addressed.

Background: Exosome (EXOs) are rapidly being identified as key mediators of cell-to-cell communication. They convey biologically active molecules to target cells, serve important roles in a range of physiological and pathological processes, and have enormous potential as novel therapeutic strategies. Methods: Preclinical research published between 2019 and 2023 provided the study's data searched on different medline search engine, and clinicaltrials.gov was searched for clinical data. These papers were chosen because they are relevant to the research of mesenchymal stem cell-derived exosomes (MSC-EXOs). Thematic synthesis and meta-analysis were used to perform the meta-analysis of diabetic wound healing. Results: For data extraction, a total of 18 preclinical and 4 clinical trials were selected. Preclinical investigations involving EXOs across various animal wound healing models showed promising potential for treatment. Specifically, following EXO treatment, there was a notable correlation with wound closure rates, with a pooled proportion of 46 % (95 % CI: 0.34; 0.59) and τ2 of 0.0593 after 3 ± 2 days, 54 % (95 % CI: 0.43; 0.65) and τ2 of 0.0465 after 7 ± 2 days, and 69 % (95 % CI: 0.62; 0.76) and τ2 of 0.0221 after 14 ± 2 days, with an egger's test p-value of

Not available.

Mutations in UBQLN2 cause ALS and frontotemporal dementia (FTD). The pathological signature in UBQLN2 cases is deposition of highly unusual types of inclusions in the brain and spinal cord that stain positive for UBQLN2. However, what role these inclusions play in pathogenesis remains unclear. Here we show cellular prion protein (PrPC) is found in UBQLN2 inclusions in both mouse and human neuronal induced pluripotent (IPSC) models of UBQLN2 mutations, evidenced by the presence of aggregated forms of PrPC with UBQLN2 inclusions. Turnover studies indicated that the P497H UBQLN2 mutation slows PrPC protein degradation and leads to mislocalization of PrPC in the cytoplasm. Immunoprecipitation studies indicated UBQLN2 and PrPC bind together in a complex. The abnormalities in PrPC caused by UBQLN2 mutations may be relevant in disease pathogenesis.

Vitex negundo is an Indian medicinal plant containing steroids, flavonoids, lignans and terpenoids that can be used as a precursor for commercial production. An efficient marker system such as Random Amplified Polymorphic DNA (RAPD) was used to assess the genetic integrity of V. negundo. The straightforward method RAPD can be used to evaluate genomic integrity because it uses a small amount of DNA for PCR amplification. Six out of thirteen RAPD primers generated 150 distinct bands, of which 31 were polymorphic, with an average of 5.16 polymorphic bands per primer. A maximum of up to 32 fragments were amplified, and an average of 25 per primer, and the amplicons varied in size between 100 and 2000bp. The percentage of polymorphism ranges from 12.9 to 22.5, with an average of 16.6. The PIC values ranged from 0.11 to 0.63 for RAPD primers. The study pointed out that RAPD markers evaluate the genetic fidelity in Vitex negundo. The UPGMA cluster analysis grouped all in vitro raised plantlets treated with different growth regulators such as BAP, DPU, TDZ, and mT. The principal component analysis also substantiates this clustering pattern. Thus, the phylogenetic relationship and a high genetic variation revealed in the present study could provide baseline data for the conservation and improvement of this plant in future. Also, the molecular marker identified in this study will be helpful in the authentication of this species to prevent adulteration in herbal medicine.

OBJECTIVES:. Extracorporeal membrane oxygenation (ECMO) is often withheld in patients with significant neurologic injury or recent neurosurgical intervention due to perceived futility. Studies of neurosurgical interventions before or during ECMO are limited to case reports or single-center series, limiting generalizability, and outcomes in this population are unknown. We therefore sought to report the outcomes of ECMO patients with acute neurosurgical interventions at four high-volume ECMO and comprehensive stroke centers. DESIGN:. Retrospective case series. SETTING:. Four academic tertiary referral hospitals in the United States. PATIENTS:. Adults (n = 24) having undergone neurosurgical procedures before or during ECMO. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. We retrospectively reviewed adults at four institutions who had undergone neurosurgical procedures immediately before or during ECMO from 2015 to 2023. The primary outcome was survival to hospital discharge. Secondary outcomes included favorable neurologic outcome (Cerebral Performance Category 1 or 2) and neurosurgical complications. Twenty-four of 2957 ECMO patients (0.8%) were included. Primary indications for neurosurgical intervention included traumatic brain (n = 8) or spinal (n = 3) injury, spontaneous intracranial hemorrhage (n = 6), and acute ischemic stroke (n = 5). Procedures included extraventricular drain (EVD) and/or intracranial pressure monitor placement (n = 10), craniectomy/craniotomy (n = 5), endovascular thrombectomy (n = 4), and spinal surgery (n = 3). Fifteen patients (63%) survived to hospital discharge, of whom 12 (80%) were discharged with favorable neurologic outcomes. Survival to discharge was similar for venoarterial and venovenous ECMO patients (8/12 vs. 7/12; p = 0.67) and those who had neurosurgery before vs. during ECMO (8/13 vs. 7/11; p = 0.92). One patient (4%) experienced a neurosurgical complication, a nonlethal tract hemorrhage from EVD placement. Survival to discharge was similar for neurosurgical and nonneurosurgical ECMO patients at participating institutions (63% vs. 57%; p = 0.58). CONCLUSIONS:. Patients with acute neurologic injury can feasibly undergo neurosurgery during ECMO or can undergo ECMO after recent neurosurgery. Larger studies are needed to fully understand risks for bleeding and other procedure-related complications.

Introduction: This case report presents a rare instance of hypervirulent Klebsiella pneumoniae invasive syndrome (KPIS) without hepatic involvement. It highlights an atypical presentation as this syndrome is characterized by liver abscesses. Case Presentation: A 54-year-old female of South Asian descent presented to the emergency department with abdominal pain, fever, chills, nausea, and vomiting. Lab investigations showed hyperglycaemia, leukocytosis, and elevated procalcitonin. Imaging revealed bilateral acute pyelonephritis with early abscess formation in the left kidney, bilateral pleural effusions, diffuse multi-lobar consolidations, minimal ascites, and left renal vein thrombosis. The patient was treated as a case of septic shock secondary to hypervirulent K. pneumoniae with complications evolving into acute pyelonephritis and endogenous endophthalmitis. K. pneumoniae, known for its polysaccharide capsule, can lead to severe complications in immunocompromised patients, such as endogenous endophthalmitis, liver abscess, and pyelonephritis. Endophthalmitis, a critical ocular emergency, can result in permanent vision loss. The patient’s ocular outcomes remain uncertain due to a lack of follow-up, but prompt interdisciplinary intervention led to the resolution of other comorbidities. Conclusion: This case highlights the importance of considering hypervirulent K. pneumoniae as a cause of severe infection without liver abscess. It also underscores the importance of immediate multidisciplinary management to address the systemic complications associated with this infection and the importance of connecting different symptoms to one aetiology.

Globally increasing antibiotic resistance has been linked to the extensive use of antibiotics in medical, veterinary, and agricultural Practices. This study aims to investigate the correlations of antimicrobial-resistant of various pathogens in three compartments: humans, animals and the environment in India and Germany. A systematic search was carried out in Medline via PubMed, Google Scholar, and science direct, including studies published in 2022. Out of 532 papers, 24 were considered for meta-analysis. Our findings reveals that in India, β-lactam is highly resistant in animals. Quinolone, on the other hand, was highly resistant in humans. In the environmental sectors, aminoglycosides and β-lactams is resistant. While in Germany, β-lactam resistance is high across all three sectors. However, E. coli was the most frequent and resistant pathogen in both countries, with significant resistance to β-lactams and cephalosporins across all compartments. These results underscore the critical need for monitoring antibiotic resistance patterns and developing targeted antibiotic regimens. A One Health-based intervention strategy is essential to mitigate the spread of AMR and improve health outcomes globally.

Abstract Orphan diseases, exemplified by T-cell prolymphocytic leukemia, present inherent challenges due to limited data availability and complexities in effective care. This study delves into harnessing the potential of machine learning to enhance care strategies for orphan diseases, specifically focusing on allogeneic hematopoietic cell transplantation (allo-HCT) in T-cell prolymphocytic leukemia. The investigation evaluates how varying numbers of variables impact model performance, considering the rarity of the disease. Utilizing data from the Center for International Blood and Marrow Transplant Research, the study scrutinizes outcomes following allo-HCT for T-cell prolymphocytic leukemia. Diverse machine learning models were developed to forecast acute graft-versus-host disease (aGvHD) occurrence and its distinct grades post-allo-HCT. Assessment of model performance relied on balanced accuracy, F1 score, and ROC AUC metrics. The findings highlight the Linear Discriminant Analysis (LDA) classifier achieving the highest testing balanced accuracy of 0.58 in predicting aGvHD. However, challenges arose in its performance during multi-class classification tasks. While affirming the potential of machine learning in enhancing care for orphan diseases, the study underscores the impact of limited data and disease rarity on model performance.

Abstract Despite being the mainstay of management for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), there is limited data regarding the impact of tocilizumab (TCZ) and corticosteroids (CCS) on chimeric antigen receptor (CAR) T-cell efficacy in multiple myeloma (MM). The present study aims to evaluate the prognostic impact of these immunosuppressants in recipients of BCMA- or GPRC5D-directed CAR T cells for relapsed/refractory MM. Our retrospective cohort involved patients treated with commercial or investigational autologous CAR T-cell products at a single institution from March 2017–March 2023. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rate (ORR), complete response rate (CRR), and overall survival (OS). In total, 101 patients (91% treated with anti-BCMA CAR T cells and 9% treated with anti-GPRC5D CAR T cells) were analyzed. Within 30 days post-infusion, 34% received CCS and 49% received TCZ for CRS/ICANS management. At a median follow-up of 27.4 months, no significant difference in PFS was observed between CCS and non-CCS groups (log-rank p = 0.35) or between TCZ and non-TCZ groups (log-rank p = 0.69). ORR, CRR, and OS were also comparable between evaluated groups. In our multivariable model, administering CCS with/without TCZ for CRS/ICANS management did not independently influence PFS (HR, 0.74; 95% CI, 0.36–1.51). These findings suggest that, among patients with relapsed/refractory MM, the timely and appropriate use of CCS or TCZ for mitigating immune-mediated toxicities does not appear to impact the antitumor activity and long-term outcomes of CAR T-cell therapy.

Lung cancer, a major global cause of cancer-related deaths, demands continual advancements in diagnostic methodologies. This review delves into the transformative role of Robotic-Assisted Bronchoscopy (RAB) in redefining lung cancer diagnostics. As lung cancer screenings intensify, leading to a surge in pulmonary nodule diagnoses, navigational bronchoscopy, notably electromagnetic navigational bronchoscopy (ENB), faces persistent limitations. Examining key RAB platforms—Monarch™, Ion™ and the Galaxy System™—reveals their distinctive features, with RAB demonstrating superior diagnostic yields over traditional biopsy methods. However, challenges include CT-to-body divergence (CBCT) and divergent findings in diagnostic yield studies and a lack of head-to-head comparisons with non-RAB modalities. Future directions should explore RAB’s potential therapeutic applications, shaping the landscape of both diagnostics and therapeutics in lung cancer management.

Abstract B-cell-maturation-antigen (BCMA)-directed therapies are highly active for multiple myeloma, but infections are emerging as a major challenge. In this retrospective, single-center analysis we evaluated infectious complications after BCMA-targeted chimeric-antigen-receptor T-cell therapy (CAR-T), bispecific-antibodies (BsAb) and antibody-drug-conjugates (ADC). The primary endpoint was severe (grade ≥3) infection incidence. Amongst 256 patients, 92 received CAR-T, 55 BsAb and 109 ADC. The incidence of severe infections was higher with BsAb (40%) than CAR-T (26%) or ADC (8%), including grade 5 infections (7% vs 0% vs 0%, respectively). Comparing T-cell redirecting therapies, the incidence rate of severe infections was significantly lower with CAR-T compared to BsAb at 1-year (incidence-rate-ratio [IRR] = 0.43, 95%CI 0.25−0.76, P = 0.004). During periods of treatment-emergent hypogammaglobulinemia, BsAb recipients had higher infection rates (IRR:2.27, 1.31−3.98, P = 0.004) and time to severe infection (HR 2.04, 1.05–3.96, P = 0.036) than their CAR-T counterparts. During periods of non-neutropenia, CAR-T recipients had a lower risk (HR 0.44, 95%CI 0.21−0.93, P = 0.032) and incidence rate (IRR:0.32, 95% 0.17–0.59, P

In response to the growing complexities in supply chain management, there is an imperative need for a data-driven methodology aimed at optimizing inventory allocation strategies. The purpose of this research is to enhance the efficiency of allocation and operational scheduling, particularly concerning the stock keeping units (SKUs). To achieve this, one year's operational data from a specific organization's SKUs is taken and machine learning tools are employed on the data collected. These tools are instrumental in identifying clusters of SKUs that exhibit similar behaviour. Consequently, this research offers recommendations for rational inventory allocation strategies that are finely attuned to the unique characteristics of each SKU cluster. Results obtained reveals substantial disparities between the recommended strategies for the organization's SKUs and those typically found in the literature such as same strategy cannot be used for all different types for products. This underscores the critical importance of adopting a tailored approach to supply chain management. Furthermore, the research demonstrates the remarkable efficiency of unsupervised machine learning algorithms in determining the optimal number of segments within the SKUs. The current research differentiates from others in a way that in most of the research, the holistic data-driven approach is underutilized, right from the selection of the clustering algorithm to the validation of segments.

We performed a clinical-radiographic association study investigating the hypothesis that paroxysmal sympathetic hyperactivity (PSH) occurs in traumatic brain injury (TBI) patients with structural damage to the central autonomic network (CAN). To this end, we identified critically ill acute TBI patients who underwent magnetic resonance imaging (MRI) of the brain between January 2016 and July 2018. All patients were scored retrospectively according to the PSH-Assessment Measure (PSH-AM), which provides a clinical feature score, a diagnosis likelihood score, and a total score. All MRIs were reviewed for lesions within a priori CAN regions of interest, including the brainstem, ventral diencephalon, thalamus, medial temporal lobes, insula, anterior cingulate/medial prefrontal cortex, corpus callosum, and bilateral hemispheric white matter, on diffusion-weighted imaging (DWI), fluid attenuated inversion recovery (FLAIR), and susceptibility-weighted imaging (SWI) sequences. PSH-AM scores were compared using non-parametric tests according to lesion presence in each region and sequence. Imaging features independently associated with PSH-AM scores were ascertained from multivariable linear regression models using backwards elimination feature selection. The strongest predictive models were adjusted for known PSH risk factors including age, sex, and Glasgow Coma Scale (GCS), to determine the independent contribution of imaging features to PSH-AM scores. We found that of 128 patients meeting inclusion criteria, 60 (47%) were clinically diagnosed with PSH. PSH-AM diagnosis likelihood and total scores and clinical diagnosis were strongly associated with CAN lesions. The strongest multivariable model, adjusted for age, sex, and GCS, identified SWI lesions in the corpus callosum and medial temporal lobes as independent imaging predictors of PSH diagnosis likelihood. This exploratory study supports the hypothesis that structural damage to CAN regions is associated with the clinical syndrome of PSH after TBI, and provides foundational evidence for future data-driven studies.

Abstract Relapse and toxicity limit the effectiveness of chimeric antigen receptor T-cell (CAR-T) therapy for large B-cell lymphoma (LBCL), yet biomarkers that predict outcomes and toxicity are lacking. We examined radiomic features extracted from pre-CAR-T 18F-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) scans (n = 341) of 180 patients (121 male; median age, 66 years). Three conventional (maximum standardized uptake value [SUVmax], metabolic tumor volume [MTV], total lesion glycolysis [TLG]) and 116 novel radiomic features were assessed, along with inflammatory markers, toxicities, and outcomes. At both pre-apheresis and pre-infusion time points, conventional PET features of disease correlated with elevated inflammatory markers. At pre-infusion, MTV was associated with grade ≥ 2 cytokine release syndrome (odds ratio [OR] for 100 mL increase: 1.08 [95% confidence interval (CI), 1.01–1.20], P = 0.031), and SUVmax was associated with failure to achieve complete response (CR) (OR 1.72 [95% CI, 1.24–2.43], P

Aim: Implant therapy in partially edentulous patients has become the most adapted and predictable treatment modality. The success rate of implants has been measured in terms of esthetic, biological, and technical factors such as radiographic bone loss, prosthetic complications, and stability. Despite the existence of several indices for the esthetic assessment of implant crowns, a need for functional evaluation of the implant crown with an objective and reproducible score has arisen. The study aims to validate the reproducibility of the functional implant prosthodontic score (FIPS) and the influence exerted by different dental specialties while evaluating posterior single-unit implant crowns. Study Setting and Design: This was a prospective clinical study. Materials and Methods: Fifteen patients with cement-retained single-implant crowns in the posterior region of the jaws were included. Eight examiners, two prosthodontists, two periodontists, two oral surgeons, and two orthodontists evaluated 15 photographs of single-unit implant crowns during the 1-year follow-up examination. The examiners assessed the photographs for FIPS, which includes five parameters for objectively evaluating the single-unit implant crowns. Assessments were performed twice at a gap of 4 weeks. Statistical Analysis Used: Pearson's correlation with a 95% confidence interval was calculated for the intra-examiner and the Kruskal–Wallis test for inter-examiner reproducibility. Results: The mean total FIPS scores for all included examiners were 7.133 for time T1 and 7.074 for time T2, showing a strong Pearson correlation coefficient for intra-examiner reproducibility. No significant difference was analyzed among different specialties with statistically significant values of the Kruskal–Wallis test. Conclusion: Intra- and inter-examiner analysis showed very consistent results during the reproducibility assessment of FIPS. The results validated the use of FIPS as a long-term predictive functional evaluation tool for the single-implant crowns in posterior sites irrespective of the effect of different dental specialties. It could be used for risk estimation and prognosis for long-term survival and performance of implant crowns.

Abstract Accurate indel calling plays an important role in precision medicine. A benchmarking indel set is essential for thoroughly evaluating the indel calling performance of bioinformatics pipelines. A reference sample with a set of known-positive variants was developed in the FDA-led Sequencing Quality Control Phase 2 (SEQC2) project, but the known indels in the known-positive set were limited. This project sought to provide an enriched set of known indels that would be more translationally relevant by focusing on additional cancer related regions. A thorough manual review process completed by 42 reviewers, two advisors, and a judging panel of three researchers significantly enriched the known indel set by an additional 516 indels. The extended benchmarking indel set has a large range of variant allele frequencies (VAFs), with 87% of them having a VAF below 20% in reference Sample A. The reference Sample A and the indel set can be used for comprehensive benchmarking of indel calling across a wider range of VAF values in the lower range. Indel length was also variable, but the majority were under 10 base pairs (bps). Most of the indels were within coding regions, with the remainder in the gene regulatory regions. Although high confidence can be derived from the robust study design and meticulous human review, this extensive indel set has not undergone orthogonal validation. The extended benchmarking indel set, along with the indels in the previously published known-positive set, was the truth set used to benchmark indel calling pipelines in a community challenge hosted on the precisionFDA platform. This benchmarking indel set and reference samples can be utilized for a comprehensive evaluation of indel calling pipelines. Additionally, the insights and solutions obtained during the manual review process can aid in improving the performance of these pipelines.

Abstract Determination of prognosis in the triage process after traumatic brain injury (TBI) is difficult to achieve. Current severity measures like the Trauma and injury severity score (TRISS) and revised trauma score (RTS) rely on additional information from the Glasgow Coma Scale (GCS) and the Injury Severity Score (ISS) which may be inaccurate or delayed, limiting their usefulness in the rapid triage setting. We hypothesized that machine learning based estimations of GCS and ISS obtained through modeling of continuous vital sign features could be used to rapidly derive an automated RTS and TRISS. We derived variables from electrocardiograms (ECG), photoplethysmography (PPG), and blood pressure using continuous data obtained in the first 15 min of admission to build machine learning models of GCS and ISS (ML-GCS and ML-ISS). We compared the TRISS and RTS using ML-ISS and ML-GCS and its value using the actual ISS and GCS in predicting in-hospital mortality. Models were tested in TBI with systemic injury (head abbreviated injury scale (AIS) ≥ 1), and isolated TBI (head AIS ≥ 1 and other AIS ≤ 1). The area under the receiver operating characteristic curve (AUROC) was used to evaluate model performance. A total of 21,077 cases (2009–2015) were in the training set. 6057 cases from 2016 to 2017 were used for testing, with 472 (7.8%) severe TBI (GCS 3–8), 223 (3.7%) moderate TBI (GCS 9–12), and 5913 (88.5%) mild TBI (GCS 13–15). In the TBI with systemic injury group, ML-TRISS had similar AUROC (0.963) to TRISS (0.965) in predicting mortality. ML-RTS had AUROC (0.823) and RTS had AUROC 0.928. In the isolated TBI group, ML-TRISS had AUROC 0.977, and TRISS had AUROC 0.983. ML-RTS had AUROC 0.790 and RTS had AUROC 0.957. Estimation of ISS and GCS from machine learning based modeling of vital sign features can be utilized to provide accurate assessments of the RTS and TRISS in a population of TBI patients. Automation of these scores could be utilized to enhance triage and resource allocation during the ultra-early phase of resuscitation.

The oral cavity serves as a primary site where the adverse effects of tobacco usage manifest. Smokers and users of smokeless tobacco are at a higher risk for several health issues. Tobacco use remains one of the foremost public health challenges in India, where it is deeply woven into the social and cultural fabric. The impact of tobacco is not merely limited to systemic health issues; it profoundly affects oral health, leading to a myriad of dental problems, including gum disease, tooth decay, and oral cancer.

IntroductionTraumatic brain injury (TBI) even in the mild form may result in long-lasting post-concussion symptoms. TBI is also a known risk to late-life neurodegeneration. Recent studies suggest that dysfunction in the glymphatic system, responsible for clearing protein waste from the brain, may play a pivotal role in the development of dementia following TBI. Given the diverse nature of TBI, longitudinal investigations are essential to comprehending the dynamic changes in the glymphatic system and its implications for recovery.MethodsIn this prospective study, we evaluated two promising glymphatic imaging markers, namely the enlarged perivascular space (ePVS) burden and Diffusion Tensor Imaging-based ALPS index, in 44 patients with mTBI at two early post-injury time points: approximately 14 days (14Day) and 6–12 months (6–12Mon) post-injury, while also examining their associations with post-concussion symptoms. Additionally, 37 controls, comprising both orthopedic patients and healthy individuals, were included for comparative analysis.ResultsOur key findings include: (1) White matter ePVS burden (WM-ePVS) and ALPS index exhibit significant correlations with age. (2) Elevated WM-ePVS burden in acute mTBI (14Day) is significantly linked to a higher number of post-concussion symptoms, particularly memory problems. (3) The increase in the ALPS index from acute (14Day) to the chronic (6–12Mon) phases in mTBI patients correlates with improvement in sleep measures. Furthermore, incorporating WM-ePVS burden and the ALPS index from acute phase enhances the prediction of chronic memory problems beyond socio-demographic and basic clinical information.ConclusionePVS burden and ALPS index offers distinct values in assessing glymphatic structure and activity. Early evaluation of glymphatic function could be crucial for understanding TBI recovery and developing targeted interventions to improve patient outcomes.

Aim: To assess the oral health status of the Sevayats of Sakhigopal temple, Puri, Odisha. Methodology: An assessment of the oral health status of 111 Sevayats at the Sakhigopal temple in Puri was carried out using a cross-sectional survey. The World Health Organization oral health assessment form for adults (2013) was used to collect data. Chi-square test and one-way analysis of variance were the statistical tests used for the investigation using Statistical Package for the Social Sciences 27 version. When the P value was less than 0.05, it was deemed statistically significant. Results: The mean DMFT of all the participants was 3.70 ± 1.71. The prevalence of caries was 91%. Bleeding and periodontal pocket were present in 82.9% and 83.8% of Sevayats, respectively. Conclusion: There was a higher prevalence of dental caries and periodontal disease among the subjects.

Summary: Background: Mucositis is a common and highly impactful side effect of conventional and emerging cancer therapy and thus the subject of intense investigation. Although common practice, mucositis assessment is heterogeneously adopted and poorly guided, impacting evidence synthesis and translation. The Multinational Association of Supportive Care in Cancer (MASCC) Mucositis Study Group (MSG) therefore aimed to establish expert recommendations for how existing mucositis assessment tools should be used, in clinical care and trials contexts, to improve the consistency of mucositis assessment. Methods: This study was conducted over two stages (January 2022–July 2023). The first phase involved a survey to MASCC-MSG members (January 2022–May 2022), capturing current practices, challenges and preferences. These then informed the second phase, in which a set of initial recommendations were prepared and refined using the Delphi method (February 2023–May 2023). Consensus was defined as agreement on a parameter by >80% of respondents. Findings: Seventy-two MASCC-MSG members completed the first phase of the study (37 females, 34 males, mainly oral care specialists). High variability was noted in the use of mucositis assessment tools, with a high reliance on clinician assessment compared to patient reported outcome measures (PROMs, 47% vs 3%, 37% used a combination). The World Health Organization (WHO) and Common Terminology Criteria for Adverse Events (CTCAE) scales were most commonly used to assess mucositis across multiple settings. Initial recommendations were reviewed by experienced MSG members and following two rounds of Delphi survey consensus was achieved in 91 of 100 recommendations. For example, in patients receiving chemotherapy, the recommended tool for clinician assessment in clinical practice is WHO for oral mucositis (89.5% consensus), and WHO or CTCAE for gastrointestinal mucositis (85.7% consensus). The recommended PROM in clinical trials is OMD/WQ for oral mucositis (93.3% consensus), and PRO-CTCAE for gastrointestinal mucositis (83.3% consensus). Interpretation: These new recommendations provide much needed guidance on mucositis assessment and may be applied in both clinical practice and research to streamline comparison and synthesis of global data sets, thus accelerating translation of new knowledge into clinical practice. Funding: No funding was received.

OBJECTIVES:. Accurate classification of disorders of consciousness (DoC) is key in developing rehabilitation plans after brain injury. The Coma Recovery Scale—Revised (CRS-R) is a sensitive measure of consciousness validated in the rehabilitation phase of care. We tested the feasibility, safety, and impact of CRS-R-guided rehabilitation in the ICU for patients with DoC after acute hemorrhagic stroke. DESIGN:. Retrospective cohort study. SETTING:. This single-center study was conducted in the neurocritical care unit at the University of Maryland Medical Center. PATIENTS:. We analyzed records from consecutive patients with subarachnoid hemorrhage (SAH) or intracerebral hemorrhage (ICH), who underwent serial CRS-R assessments during ICU admission from April 1, 2018, to December 31, 2021, where CRS-R less than 8 is vegetative state/unresponsive wakefulness syndrome (VS/UWS); CRS-R greater than or equal to 8 is a minimally conscious state (MCS). INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Outcomes included adverse events during CRS-R evaluations and associations between CRS-R and discharge disposition, therapy-based function, and mobility. We examined the utility of CRS-R compared with other therapist clinical assessment tools in predicting discharge disposition. Seventy-six patients (22 SAH, 54 ICH, median age = 59, 50% female) underwent 276 CRS-R sessions without adverse events. Discharge to acute rehabilitation occurred in 4.4% versus 41.9% of patients with a final CRS-R less than 8 and CRS-R greater than or equal to 8, respectively (odds ratio [OR] 13.4; 95% CI, 2.7–66.1; p < 0.001). Patients with MCS on final CRS-R completed more therapy sessions during hospitalization and had improved mobility and functional performance. Compared with other therapy assessment tools, the CRS-R had the best performance in predicting discharge disposition (area under the curve: 0.83; 95% CI, 0.72–0.94; p < 0.0001). CONCLUSIONS:. Early neurorehabilitation guided by CRS-R appears to be feasible and safe in the ICU following hemorrhagic stroke complicated by DoC and may enhance access to inpatient rehabilitation, with the potential for lasting benefit on recovery. Further research is needed to assess generalizability and understand the impact on long-term outcomes.

Radiotherapy (RT) and immunotherapy (IT) are the powerful tools for cancer treatment which act through the stimulation of immune response, and evidence suggest that combinatorial actions of these therapies may augment each other’s beneficial effect through complex synergistic mechanisms. These molecular strategies are designed to target rapidly dividing cancer cells by either directly or indirectly inducing DNA damage. However, when cells detect DNA damage, they activate a range of signalling pathways known as the DNA damage response (DDR) to repair. Strategies are being developed to interfere with the DDR pathways in cancer cells to ensure their damage-induced degeneration. The stability of a cell’s genetic material is largely dependent on the efficacy of DNA repair and therefore, an in-depth understanding of DNA damages and repair mechanism(s) in cancer cells is important to develop a promising therapeutic strategies for ensuring the efficacy of damage-induced tumor cell death. In recent years, a wide range of small molecule drugs have been developed which are currently being employed to combat the DNA repair deficiencies associated with tumor cells. Sequential or concurrent use of these two modalities significantly enhances the anti-tumor response, however with a concurrent probability of increased incidence of symptomatic adverse effects. With advent of newer IT agents, and administration of higher doses of radiation per fraction, such effects are more difficult to predict owing to the paucity of randomized trial data. It is well established that anti cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4), anti- Programmed cell death protein 1(PD-1), anti-Programmed cell death one ligand 1 (PD-L1) can be safely administered with RT and many studies have demonstrated survival benefit with such combination for patients with metastatic malignancy. However, the biology of radioimmunotherapy (RT/IT) is still an open area where research need to be focused to determine optimum dosage specially the interaction of the RT/IT pathways to determine optimum dosing schedule. In the current article we have summarised the possible intracellular immunological events that might be triggered when RT and IT modalities are combined with the DDR antagonists and highlighted present clinical practices, outcome, and toxicity profile of this novel treatment strategy.

IntroductionDespite the advances in vaccination, there are still several challenges in reaching millions of children in low- and middle-income countries (LMICs). In this review, we present an extensive summary of the various strategies used for improving routine immunization in LMICs to aid program implementers in designing vaccination interventions.MethodsExperimental and quasi-experimental impact evaluations conducted in LMICs evaluating the effectiveness of interventions in improving routine immunization of children aged 0–5 years or the intermediate outcomes were included from 3ie’s review of systematic reviews. Some additional impact evaluation studies published in recent years in select LMICs with large number of unvaccinated children were also included. Studies were coded to identify interventions and the barriers in the study context using the intervention framework developed in 3ie’s Evidence Gap Map and the WHO’s Behavioral and Social Drivers (BeSD) of vaccination framework, respectively. Qualitative analysis of the content was conducted to analyze the intervention strategies and the vaccination barriers that they addressed.Results and conclusionOne hundred and forty-two impact evaluations were included to summarize the interventions. To address attitudinal and knowledge related barriers to vaccination and to motivate caregivers, sensitization and educational programs, media campaigns, and monetary or non-monetary incentives to caregivers, that may or may not be conditional upon certain health behaviors, have been used across contexts. To improve knowledge of vaccination, its place, time, and schedule, automated voice messages and written or pictorial messages have been used as standalone or multicomponent strategies. Interventions used to improve service quality included training and education of health workers and providing monetary or non-monetary perks to them or sending reminders to them on different aspects of provision of vaccination services. Interventions like effective planning or outreach activities, follow-up of children, tracking of children that have missed vaccinations, pay-for-performance schemes and health system strengthening have also been used to improve service access and quality. Interventions aimed at mobilizing and collaborating with the community to impact social norms, attitudes, and empower communities to make health decisions have also been widely implemented.

The activity of anti-CD19 CAR T cell therapy in chronic lymphocytic leukemia (CLL) with Richter's transformation (RT) to aggressive large B cell lymphoma (LBCL) is largely unknown. In a multicenter retrospective study, we report the safety and efficacy of CAR T cell therapy in patients with RT (n=30) compared to patients with aggressive B cell lymphoma (n=283) and patients with transformed indolent Non-Hodgkins Lymphoma (iNHL) (n=141) between April 2016 and January 2023. Two-thirds of patients received prior therapy for CLL before RT and 89% of them received B-cell receptor and B-cell lymphoma 2 (BCL-2) inhibitors. Toxicities of CAR T cell therapy in RT were similar to other lymphomas, with no fatalities related to cytokine release syndrome or immune effector-cell associated neurotoxicity synderome. The 100-day overall response rate and complete response rates in patients with RT were 57% and 47%, respectively. With a median follow up of 19 months, the median overall survival (OS) was 9.9 months in patients with RT compared to 18 months in de-novo LBCL and not reached in patients with transformed iNHL. The OS at 12 months was 45% in patients with RT compared with 62% and 75% in patients with de novo LBCL and transformed iNHL, respectively. In a multivariate analysis, worse OS was associated with RT histology, elevated LDH, and more prior lines of therapy. CAR T cell therapy can salvage a proportion of patients with CLL and RT exposed to prior targeted agents; however, efficacy in RT is inferior compared to de novo LBCL and transformed iNHL

Abstract Objectives The aim of the present study was to follow the daily course of patients with olfactory dysfunction and healthy controls and to assess (i) how many times a day, (ii) at which time, and (iii) in which aspect of daily life participants are conscious about their sense of smell. Methods In this longitudinal study, 49 patients with smell loss and 30 healthy participants were enrolled. Olfactory function was assessed using the Sniffin’ Sticks. All participants received paper diaries designed for a 14‐day period, featuring 12 rows representing 12 daily hours and six columns for various daily life aspects. They were instructed to mark their awareness of smell by indicating the relevant row and column in the diary. Following the return of the diaries, a second olfactory test was conducted within the patient group. Results On average, patients were consciously aware of their sense of smell around 8 times daily, while healthy participants noted it about 6.5 times a day. Both groups primarily focused on their sense of smell during activities related to “eating,” followed by considerations in “social life” and “personal hygiene.” Interestingly, distinct patterns emerged: patients peaked in awareness at 8 a.m. and 7 p.m., whereas healthy individuals showed peaks at 6 a.m., 12 p.m., and 7 p.m. Despite regular diary use, we observed no improvement in patients' olfactory function or related quality of life. Conclusion The olfactory diary is a valuable tool unveiling individual smell awareness patterns in patients with smell loss, aiding in counseling and patient management. Level of Evidence 4

Background Paediatric lower urinary tract symptoms (LUTS) are common experiences among school-aged children, with prevalence rates reaching as high as 20%. Paediatricians are often first-line stakeholders in providing treatment for these bothersome symptoms, yet there is no formal resource to support them with the treatment of LUTS. Evaluating paediatricians’ experiences is an important step in informing health promotion efforts to improve health outcomes in children. This study aims to explore paediatricians’ knowledge, beliefs, practice patterns, and perceived barriers and facilitators in providing LUTS care.Methods In this qualitative study, we conducted semistructured focus groups of paediatricians within California. Focus groups were conducted via Zoom, and participants were enrolled until thematic saturation was reached. Participants were asked about their current practices, knowledge and beliefs, barriers and facilitators to care, training and education, and responsibility for behaviour and action. Thematic analysis was performed using deductive and inductive approaches; themes were mapped through an iterative, team-based process.Results 15 paediatricians, aged 30–69 years, with 13 (86.7%) women, were interviewed. Most (11, 73.3%) practised in general outpatient settings. Interviewed paediatricians recognised paediatric LUTS as a common problem that can significantly impact children’s well-being. In practice, paediatricians did not actively screen for LUTS beyond the potty-training milestone due to short visit duration and competing healthcare demands. Lack of guidelines, parental mistrust and inadequate clinical education were barriers identified by paediatricians.Conclusions Paediatricians expressed a willingness to help patients but indicated several limitations to providing adequate LUTS care. Future professional development work can emphasise guideline development, early screening strategies to support timely intervention and better education for clinicians.

Objectives: To evaluate the current evidence of digital workflow feasibility based on the data acquisition methods and the software tools used to fabricate intraoral prostheses for patients with partial or total maxillary and mandibular defects. Materials and methods: An electronic search was performed in PubMed, SCOPUS, and Web of Science using a combination of relevant keywords: digital workflow, digital designing, computer-assisted design-computer aided manufacturing, 3D printing, maxillectomy, and mandibulectomy. The Joanna Briggs Institute Critical Appraisal Tool was used to assess the quality of evidence in the studies reviewed. Results: From a total of 542 references, 33 articles were selected, including 25 on maxillary prostheses and 8 on mandibular prostheses. The use of digital workflows was limited to one or two steps of the fabrication of the prostheses, and only four studies described a complete digital workflow. The most preferred method for data acquisition was intraoral scanning with or without a cone beam computed tomography combination. Conclusion: Currently, the fabrication process of maxillofacial prostheses requires combining digital and conventional methods. Simplifying the data acquisition methods and providing user-friendly and affordable software may encourage clinicians to use the digital workflow more frequently for patients requiring maxillofacial prostheses.

Bowler's thumb is an uncommon traumatic neuropathy of the thumb ulnar digital nerve. We present a case of bowler's thumb in an individual who is an avid bowler, however, only manifesting following an unrelated injury. We describe the clinical and imaging findings, differential diagnostic considerations, and the treatment options. Knowledge of this entity and its sonographic features is important in order to identify this uncommon entity.

Abstract Prostate cancer (PCa) progression leads to bone modulation in approximately 70% of affected men. A nutraceutical, namely, α-lipoic acid (α-LA), is known for its potent anti-cancer properties towards various cancers and has been implicated in treating and promoting bone health. Our study aimed to explore the molecular mechanism behind the role of α-LA as therapeutics in preventing PCa and its associated bone modulation. Notably, α-LA treatment significantly reduced the cell viability, migration, and invasion of PCa cell lines in a dose-dependent manner. In addition, α-LA supplementation dramatically increased reactive oxygen species (ROS) levels and HIF-1α expression, which started the downstream molecular cascade and activated JNK/caspase-3 signaling pathway. Flow cytometry data revealed the arrest of the cell cycle in the S-phase, which has led to apoptosis of PCa cells. Furthermore, the results of ALP (Alkaline phosphatase) and TRAP (tartrate-resistant acid phosphatase) staining signifies that α-LA supplementation diminished the PCa-mediated differentiation of osteoblasts and osteoclasts, respectively, in the MC3T3-E1 and bone marrow macrophages (BMMs) cells. In summary, α-LA supplementation enhanced cellular apoptosis via increased ROS levels, HIF-1α expression, and JNK/caspase-3 signaling pathway in advanced human PCa cell lines. Also, the treatment of α-LA improved bone health by reducing PCa-mediated bone cell modulation.