Covid Antibody Titers in Cancer Patients Following Vaccination with ChAdOx1 nCOV-19 Vaccine.

Dr. Vikram GotaCovid-19 has led to significant mortality worldwide, with an increased risk in cancer patients. Vaccination provides significant protection against the infection. The study focuses on the immunogenicity and effectiveness of ChAdOx1 nCoV-19 vaccine in cancer patients within a real-world setting. Blood samples for measuring Covid antibody titers against the receptor binding domain were collected according to a convenient sparse sampling strategy in a real-world setting, with the days of the collection coinciding with their hospital appointment. The antibody titers between different groups were analyzed descriptively. A total of 56 patients were enrolled in the study. There was no apparent effect in antibody titers between patients with solid tumors and hematological malignancies (mean ± standard deviation [SD]: 36.80 ± 41.18 vs. 52.02 ± 26.27), among patients who were undergoing chemotherapy, immunotherapy, or local therapy (mean ± SD: 42.50 ± 44.46 vs. 50.06 ± 51.39 vs. 28.70 ± 25.03), and in patients with up to 90 days and more than 90 days' interval between their last treatment and date of vaccination (mean ± SD: 38.96 ± 42.66 vs. 40.51 ± 38.65). Additionally, there were only 2/56 patients with breakthrough infection, which points out the effectiveness of this vaccine in cancer patients. The ChAdOx1 nCoV-19 vaccine has activity in cancer regardless of the tumor type, type of treatment, or time from the last treatment.

A Bayesian meta-analysis of double kissing (DK) crush or provisional stenting for coronary artery bifurcation lesions.

OBJECTIVE: Despite the development of dedicated, two-stent strategies, including the double kissing (DK) crush technique, the ideal technique for coronary artery bifurcation stenting has not been identified. We aimed to compare and determine the absolute risk difference (ARD) of the DK crush technique alone versus provisional stenting approaches for coronary bifurcation lesions, using the Bayesian technique. METHOD: We queried PubMed/MEDLINE to identify randomized controlled trials (RCTs) that compared DK crush technique with provisional stenting for bifurcation lesions, published till January 2023. We used Bayesian methods to calculate the ARD and 95% credible interval (CrI). RESULTS: We included three RCTs, with 916 patients, in the final analysis. The ARD of cardiac death was centered at -0.01 (95% CrI: -0.04 to 0.02; Tau: 0.02, 85% probability of ARD of DK crush vs. provisional stenting <0). ARD for myocardial infarction was centered at -0.03 (95%CrI: -0.9 to 0.03; Tau: 0.05, 87% probability of ARD of DK crush vs. provisional stenting <0). ARD for stent thrombosis was centered at 0.00 (95% CrI: -0.04 to 0.03, Tau: 0.03, 51% probability of ARD for DK crush vs. provisional stenting <0). Finally, ARD for target lesion revascularization was centered at -0.05 (95% CrI: -0.08 to -0.03, Tau: 0.02, 99.97% probability of ARD for DK crush vs. provisional stenting <0). CONCLUSIONS: Bayesian analysis demonstrated a lower probability of cardiac death, myocardial infarction and target lesion revascularization, with DK crush compared with provisional stenting techniques, and a minimal probability of difference in stent thrombosis.

Financial barriers and inequity in medical education in India: challenges to training a diverse and representative healthcare workforce.

India has been historically challenged by an insufficient and heterogeneously clustered distribution of healthcare infrastructure. While resource-limited healthcare settings, such as major parts of India, require multidisciplinary approaches for improvement, one key approach is the recruitment and training of a healthcare workforce representative of its population. This requires overcoming barriers to equity and representation in Indian medical education that are multi-faceted, historical, and rooted in inequality. However, literature is lacking regarding the financial or economic barriers, and their implications on equity and representation in the Indian allopathic physician workforce, which this review sought to describe. Keyword-based searches were carried out in PubMed, Google Scholar, and Scopus in order to identify relevant literature published till November 2023. This state-of-the-art narrative review describes the existing multi-pronged economic barriers, recent and forthcoming changes deepening these barriers, and how these may limit opportunities for having a diverse workforce. Three sets of major economic barriers exist to becoming a specialized medical practitioner in India - resources required to get selected into an Indian medical school, resources required to pursue medical school, and resources required to get a residency position. The resources in this endeavor have historically included substantial efforts, finances, and privilege, but rising barriers in the medical education system have worsened the state of inequity. Preparation costs for medical school and residency entrance tests have risen steadily, which may be further exacerbated by recent major policy changes regarding licensing and residency selection. Additionally, considerable increases in direct and indirect costs of medical education have recently occurred. Urgent action in these areas may help the Indian population get access to a diverse and representative healthcare workforce and also help alleviate the shortage of primary care physicians in the country. Discussed are the reasons for rural healthcare disparities in India and potential solutions related to medical education.

Masqueraders of pneumonia in children: A case series.

Pneumonia remains the top most killer of under-five Indian children. Pneumonia in children is usually caused by viral or bacterial infections. However, there are some unusual causes of pneumonia that merit consideration when pneumonia is recurrent or persistent.

Rapid scan white light two-dimensional electronic spectroscopy with 100 kHz shot-to-shot detection.

We demonstrate an approach to two-dimensional electronic spectroscopy (2DES) that combines the benefits of shot-to-shot detection at high-repetition rates with the simplicity of a broadband white light continuum input and conventional optical elements to generate phase-locked pump pulse pairs. We demonstrate this through mutual synchronization between the laser repetition rate, the acousto-optical deflector, the pump delay stage, and the CCD line camera, which allows for rapid scanning of pump optical delay synchronously with the laser repetition rate, while the delay stage is moved at a constant velocity. The resulting shot-to-shot detection scheme is repetition rate scalable and only limited by the CCD line rate and the maximum stage velocity. Using this approach, we demonstrate the measurement of an averaged 2DES absorptive spectrum in as much as 1.2 s of continuous sample exposure per 2D spectrum. We achieve a signal-to-noise ratio of 6.8 for optical densities down to 0.05 with 11.6 s of averaging at 100 kHz laser repetition rate. Combining rapid scanning of mechanical delay lines with shot-to-shot detection as demonstrated here provides a viable alternative to acousto-optic pulse shaping approaches that is repetition-rate scalable, has comparable throughput and sensitivity, and minimizes sample exposure per 2D spectrum with promising micro-spectroscopy applications.

Gitelman Syndrome Manifesting With Acute Hypokalemic Paralysis: A Case Report.

Gitelman syndrome (GS) is a rare renal tubulopathy, classically characterized by renal salt wasting and metabolic alkalosis. It is usually an incidental diagnosis, being asymptomatic or with mild symptoms. GS manifesting with acute flaccid paralysis is extremely uncommon. We report a case of GS that mimicked Guillain-Barré syndrome (GBS), manifesting with acute hypokalemic paralysis. A middle-aged male with no known comorbidities presented to our center with paresthesias of all four limbs for one month and progressive, asymmetric limb weakness over the past eight days. Neurological examination revealed hypotonia, global areflexia, and power ranging from 3/5 to 4/5 in all four limbs, leading to our initial clinical diagnosis of GBS. Our patient's laboratory panel revealed hypokalemia, hypomagnesemia, metabolic alkalosis, and hypocalcemia, characteristic of GS. Additionally, he had significantly elevated creatine phosphokinase, suggestive of rhabdomyolysis. Further urine studies revealed renal potassium wasting, confirming the diagnosis of GS. Whole exome genome sequencing for common causative genes and workup for autoimmune disease were both negative. With gradual electrolyte correction, the patient rapidly improved symptomatically. Our case highlights an uncommon initial presentation of GS and emphasizes the need for more literature on its manifestations from the Indian subcontinent.

Delftia acidovorans: An Unusual Pathogen from an Adenocarcinoma Lung Patient with Pleural Effusion.

Delftia acidovorans (D. acidovorans) is an aerobic, nonfermentative Gram-negative bacillus infrequently isolated from clinical specimens. The pathogenicity and clinical significance of the organism has not been ascertained due to uncommon clinical isolation and suspected low virulence. The organism has been reported to be inherently resistant to aminoglycoside group of drugs which remain as a widely used first-line drug of choice for febrile neutropenic patients. Hereby, we report a case of D. acidovorans-associated pleural effusion in a patient of metastatic adenocarcinoma diagnosed and treated timely and successfully with appropriate antibiotics.

Tracheal Duplication Cyst Presenting as Chest Pain.

Tracheal duplication cysts (TDCs) are congenital malformations that are rarely diagnosed in adulthood. The authors present a case of a 43-year-old female with no known comorbidities with a two-year history of chest and upper abdominal pain. Her previous imaging on an outpatient basis was suggestive of an esophageal duplication cyst, and she was lost to follow-up until the current admission. She gave a past surgical history of video-assisted thoracoscopic surgery for a "cyst" excision, with the relevant details unavailable. On examination, the findings were unremarkable. Repeat imaging was suggestive of an esophageal duplication cyst with no change in dimensions. She underwent a right-sided elective thoracotomy and cyst excision. Intraoperatively, a smooth globular mass was visualized next to the esophagus below the level of the carina. The biopsy revealed a TDC. The patient had an uneventful postoperative period and was asymptomatic on follow-up after three months. TDCs pose a diagnostic challenge as they can only be diagnosed by imaging and histopathology. However, when the imaging is atypical, histopathology clinches the diagnosis. Complete surgical excision is recommended for symptomatic patients after ruling out malignancy. Recurrence of the lesion must be considered in patients such as ours. Our case emphasizes the consideration of TDCs in the differential diagnosis and advocates the importance of complete surgical resection to prevent a recurrence.

Dropped Head Syndrome Secondary to Danon Disease: A Case Report.

Dropped head syndrome (DHS) is characterized by neck extensor muscle weakness, which may be isolated or secondary to another neurologic diagnosis. DHS, due to lysosomal storage disorders, has not been reported in the literature. We present a 21-year-old male who had complaints of slowly worsening difficulty swallowing for the past eight years, along with difficulty keeping his head erect. His past medical history was significant for apical hypertrophic cardiomyopathy (HCM), and he had a history of sudden cardiac death in his immediate family. Clinical examination was significant only for neck extensor muscle weakness. His laboratory investigations were unremarkable, save for a significantly elevated creatine kinase (CK). Finally, whole exome sequencing identified a hemizygous stop gain variant in the lysosome-associated membrane protein 2 (LAMP-2) gene, pointing to a diagnosis of Danon disease (DD). DD is a rare, X-linked, inherited disease, due to a defect in the LAMP-2 gene that disrupts lysosomal autophagy. It is characterized by a triad of HCM, skeletal myopathy, and intellectual disability. Males typically suffer a more severe phenotype, and the cardiac disease drives its prognosis. Management involves regular cardiac monitoring, with appropriate physical therapy for myopathy and multidisciplinary treatment for intellectual disability. We suggest that DD be considered in the differential diagnosis for patients with HCM and elevated CK.

SARS-CoV-2-induced autoimmune hemolytic anemia in pediatric age-group.

SARS coronavirus (SARS-CoV-2) since the year 2020 has been affecting people of all age groups involving all systems possible. The effect of COVID-19 on hematological system has been commonly seen in the form of cytopenia, prothrombotic states, or disorders of coagulation, but it has been rarely implicated as a causal factor for hemolytic anemia in children. We present a 12-year-old male child who presented in congestive cardiac failure due to severe hemolytic anemia caused by SARS-CoV-2, with hemoglobin falling to a nadir of 1.8 g/dL. Child was diagnosed as a case of autoimmune hemolytic anemia and managed with supportive management and long-term steroids. This case highlights one of the lesser known effects of the virus, causing severe hemolysis and the role of steroids in its treatment.

Salivary IgA as a Surrogate Biomarker for Microbial Infections in Postoperative Patients Receiving Chemo-Radio-Therapy for Head and Neck Cancer.

Objective Radiotherapy (RT) and chemotherapy (CT) are important treatment options in patients with head and neck cancers. A common complication of this is microbial colonization or infection of mucosal surfaces. These infections may commonly be due to bacteria or yeasts. Salivary proteins with their buffering activity and immunoglobulin, especially immunoglobulin A (IgA), protect oral tissue, mucosal surfaces, and teeth from various microorganisms. This study characterizes the common microorganisms encountered and evaluates the role of salivary IgA in predicting microbial infections in this group of patients with mucositis. Methods A total of 150 adult head and neck cancer patients on CTRT were evaluated at baseline and at the end of 3 and 6 weeks, respectively. Oral swabs collected from buccal mucosa were processed in the microbiology laboratory for the presence of microorganisms. Saliva was processed for IgA level estimation on Siemens Dimension Automated biochemistry analyzer. Results Pseudomonas aeruginosa and Klebsiella pneumonia e were the most common organisms found in our patients, followed by Escherichia coli and group A beta-hemolytic Streptococci . A significant increase ( p = 0.0203) in the incidence of bacterial infection was observed in post-CTRT patients (61%) compared to pre-CTRT patients (49.33%). There was significant increase in levels of salivary IgA ( p = 0.003) in patients with bacterial and fungal infection ( n = 135/267) when compared to those in samples showing no growth ( n = 66/183). Conclusion A significant increase in the incidence of bacterial infection in post-CTRT patients was observed in this study. This study also indicated that postoperative head and neck cancer patients with oral mucositis that developed an infection were associated with high salivary IgA levels, and it may serve as a surrogate biomarker of infection in these patients.

Ipsilateral Hemiparesis in a Patient With Existing Contralateral Hemiparesis: A Case Report of a Rare Presentation of Ischemic Stroke.

Supratentorial strokes causing ipsilateral hemiparesis (ILH) are rare. We report a middle-aged male with multiple atherosclerotic risk factors, who had previously suffered a right-hemispheric stroke that caused left hemiplegia. Subsequently, he presented with worsening left-sided hemiplegia, with imaging revealing a left-hemispheric stroke. Diffusion tensor tract imaging showed crossed motor tracts, with disruption of the left-sided pyramidal tract. During his stay, he developed right hemiplegia due to the expansion of the same left-hemispheric infarct. Potential mechanisms for ILH in a stroke include injury to reorganized tracts following an initial insult and congenitally uncrossed motor tracts. In our patient, after his first stroke, the left hemisphere likely assumed greater ipsilateral motor control, causing ILH after the recent stroke. Our case adds to the literature on this interesting phenomenon and provides further insight into post-stroke recovery.

Impact of a simple educational intervention on awareness regarding cardiovascular disease among school-going adolescents in a rural area of Bengaluru district, India.

BACKGROUND: Cardiovascular disease (CVD) is the number one cause of death in India. Atherosclerosis begins in the second decade of life; thus, preventive efforts beginning in adolescence are crucial. Yet, there are no national or regional school-based educational programs in India for the prevention of CVD. We aimed to assess the impact of a simple educational intervention on the awareness regarding CVD among school-going adolescents in a rural area of Bengaluru. MATERIALS AND METHODS: This study was conducted using a convenience sample of school-going adolescents of classes 8, 9, and 10 in three schools in a rural area of Anekal subdistrict, Bengaluru, with a sample size of 170. A standardized, validated questionnaire testing CVD awareness was administered, followed by a simple lecture with audio-visual aids on key aspects of CVD. Three weeks later, the same questionnaire was administered to the same students. The results were then analyzed using appropriate descriptive (mean, percentage) and inferential analyses (Chi-square, paired t-test). RESULTS: The mean (SD) age was 14.5 (1.0) years, and 54% (n = 100) were boys. 75% (139) belonged to privately funded schools. 23% (43) belonged to class 8, 37% (69) to class 9, and 40% (74) to class 10. The mean (SD) total score on baseline assessment was 27.4 (9.3) out of 100, with girls and students of private schools scoring higher. The mean (SD) post-test total score was 48.5 (15.7), with significant increases in all domains of awareness, and in all categories of students. DISCUSSION: Awareness regarding CVD among adolescents from rural Bengaluru was poor, highlighting the need for educational interventions to aid preventive efforts. A simple educational intervention resulted in significant improvements in CVD awareness, even after 3 weeks.

Safety, immunogenecity and effectiveness of ChAdOx1 nCoV-19 vaccine during the second wave of pandemic in India: a real-world study.

OBJECTIVES: This real-world study was conducted to assess the adverse effects following immunization (AEFI) and immunogenicity of ChAdO×1 nCoV-19 vaccine in terms of neutralising antibody titers and to study the effects of covariates such as age, sex, comorbidities and prior COVID status on these outcomes. Also, the effectiveness of the vaccine based on interval between the two doses was also investigated. METHODS: A total of 512 participants (M/F=274/238) aged 35(18-87) years comprising a mixed population of healthcare workers, other frontline workers and general public were enrolled between March and May 2021. Records for adverse events if any were collected telephonically by following up with participants up to 6 months post first dose and graded as per Common Terminology Criteria for Adverse Events (CTCAE) version 5. Blood samples for measuring antibody titers against the receptor binding domain (RBD) were collected serially using a convenient sampling strategy up to 6 months after the first dose. Data on breakthrough COVID infection was collected telephonically till December 2021. RESULTS: Incidence of local reactions was higher after first dose at 33.4 % (171/512) compared to those after second dose at 12.9 % (66/512). Commonest side effect observed was injection site pain after the first (87.1 %; 149/171) and second (87.9 %; 56/66) dose respectively. Among systemic reactions, fever was the most common manifestation followed by myalgia and headache. Female sex (p<0⸱001) and age less than 60 years (p<0⸱001) had significantly higher predilection for systemic toxicities. Age ≤60 years (p=0.024) and prior-COVID (p<0.001) were found to be significantly associated with higher antibody titers, however, no association was found between these variables and breakthrough COVID infection. Longer spacing between the doses (≥6 weeks) was found to offer better protection against breakthrough infection compared to a spacing of 4 weeks. All breakthroughs were mild-moderate in severity, not requiring hospitalization. CONCLUSIONS: The ChAdOx1 nCov-19 vaccine is apparently safe and effective against SARS-CoV-2 virus infection. Prior COVID infection and younger age group achieve higher antibody titers, but no additional protection. Delaying the second dose up to at least 6 weeks is more effective compared to shorter spacing between doses.

Combined saposin deficiency: A rare occurrence.

Combined saposin deficiency (OMIM #611721), an exceedingly rare lysosomal storage disorder, is caused by a mutation in the gene PSAP. This gene encodes a protein, prosaposin, that cleaves into four constituent proteins, each of which has a role as a cofactor for the enzymes whose deficiency results in Krabbe disease, metachromatic leukodystrophy, Gaucher disease, and Farber disease, respectively. Intact prosaposin itself is essential for neuronal survival. The typical manifestation of combined saposin deficiency is of severe neurological features in the neonatal period, hepatosplenomegaly, thrombocytopenia, and early death. We report, to the best of our knowledge, the first Indian case with these clinical manifestations and confirmation by genetic and enzymatic testing.

DNA Methylation and Histone Modification in Low-Grade Gliomas: Current Understanding and Potential Clinical Targets.

Gliomas, the most common type of malignant primary brain tumor, were conventionally classified through WHO Grades I-IV (now 1-4), with low-grade gliomas being entities belonging to Grades 1 or 2. While the focus of the WHO Classification for Central Nervous System (CNS) tumors had historically been on histopathological attributes, the recently released fifth edition of the classification (WHO CNS5) characterizes brain tumors, including gliomas, using an integration of histological and molecular features, including their epigenetic changes such as histone methylation, DNA methylation, and histone acetylation, which are increasingly being used for the classification of low-grade gliomas. This review describes the current understanding of the role of DNA methylation, demethylation, and histone modification in pathogenesis, clinical behavior, and outcomes of brain tumors, in particular of low-grade gliomas. The review also highlights potential diagnostic and/or therapeutic targets in associated cellular biomolecules, structures, and processes. Targeting of MGMT promoter methylation, TET-hTDG-BER pathway, association of G-CIMP with key gene mutations, PARP inhibition, IDH and 2-HG-associated processes, TERT mutation and ARL9-associated pathways, DNA Methyltransferase (DNMT) inhibition, Histone Deacetylase (HDAC) inhibition, BET inhibition, CpG site DNA methylation signatures, along with others, present exciting avenues for translational research. This review also summarizes the current clinical trial landscape associated with the therapeutic utility of epigenetics in low-grade gliomas. Much of the evidence currently remains restricted to preclinical studies, warranting further investigation to demonstrate true clinical utility.

The US Residency Selection Process After the United States Medical Licensing Examination Step 1 Pass/Fail Change: Overview for Applicants and Educators.

The United States Medical Licensing Examination (USMLE) Step 1, arguably the most significant assessment in the USMLE examination series, changed from a 3-digit score to a pass/fail outcome in January 2022. Given the rapidly evolving body of literature on this subject, this paper aims to provide a comprehensive review of the historical context and impact of this change on various stakeholders involved in residency selection. For this, relevant keyword-based searches were performed in PubMed, Google Scholar, and Scopus to identify relevant literature. Given the unique history of USMLE Step 1 in the US residency selection process and the score's correlation with future performance in board-certifying examinations in different specialties, this scoring change is predicted to significantly impact US Doctor of Medicine students, US Doctor of Osteopathic Medicine students, international medical graduates, and residency program directors, among others. The significance and the rationale of the pass/fail change along with the implications for both residency applicants and educators are also summarized in this paper. Although medical programs, academic institutions, and residency organizing bodies across the United States have swiftly stepped up to ensure a seamless transition and have attempted to ensure equity for all, the conversion process carries considerable uncertainty for residency applicants. For educators, the increasing number of applications conflicts with holistic application screening, leading to the expected greater use of objective measures, with USMLE Step 2 Clinical Knowledge likely becoming the preferred screening tool in lieu of Step 1.

High-sensitivity fluorescence-detected multidimensional electronic spectroscopy through continuous pump-probe delay scan.

Fluorescence-detected multidimensional electronic spectroscopy (fMES) promises high sensitivity compared to conventional approaches and is an emerging spectroscopic approach toward combining the advantages of MES with the spatial resolution of a microscope. Here, we present a visible white light continuum-based fMES spectrometer and systematically explore the sensitivity enhancement expected from fluorescence detection. As a demonstration of sensitivity, we report room temperature two-dimensional coherence maps of vibrational quantum coherences in a laser dye at optical densities of ∼2-3 orders of magnitude lower than conventional approaches. This high sensitivity is enabled by a combination of biased sampling along the optical coherence time axes and a rapid scan of the pump-probe waiting time T at each sample. A combination of this approach with acousto-optic phase modulation and phase-sensitive lock-in detection enables measurements of room temperature vibrational wavepackets even at the lowest ODs. Alternative faster data collection schemes, which are enabled by the flexibility of choosing a non-uniform undersampled grid in the continuous T scanning approach, are also demonstrated.