Demographic and clinical characteristics of primary lung cancer patients in Kerala: Analysis of data from six teaching centers.

Background: Lung cancer continues to be the leading cause of cancer-related deaths in men and women. A breakdown by level of economic development shows no differences in cancer deaths in men but a higher rate of lung cancer deaths in women in industrialized countries as compared with developing nations. The risk factors for lung cancer most commonly include lifestyle, environmental, and occupational exposures. The role these factors play varies depending on geographic location, sex and race characteristics, genetic predisposition, as well as their synergistic interactions. Materials and Methods: It was a hospital-based registry, wherein hospitals were selected from three zones-north, central, and south zones of Kerala. The study was registered with clinical trial registry of India with Registration No. CTRI/2021/02/031299. Registry of lung cancer patients was prepared at all sites and institutional ethical clearance was received from all sites. All patients with primary lung cancer, histologically proven of all age groups were included in the study. Results: A total of 761 patients were registered from six teaching hospitals in Kerala who were diagnosed with primary lung cancer during the period 2017-2019. The mean age of the study population was 65.1 ± 10.2 years. Of all, 81.1% of them were males and 18.9% were females. Histologically, 56.4% had adenocarcinoma and 25.6% had squamous cell carcinoma. Conclusion: It was observed that the proportion of females diagnosed with primary lung cancer is increasing. Patients get diagnosed at a later stage of the disease, which calls for screening and early detection of lung cancer. As it accounts for the highest mortality among all other cancers, there is high scope for prevention and screening strategies.

Improving surgical wound classification accuracy through education and audit processes.

Precise wound classification is essential for surgical site infection risk stratification and appropriate hospital reimbursement. We instituted a multifaceted approach to improve institutional wound class identification including an education and awareness bundle, as well as a formal audit process. Overall, we saw significant improvements in wound class accuracy, interprofessional collaboration and provider compliance.

Evidence-based suggestions to improve the methodological issues in reporting of prevalence studies on gingival recession.

Gingival recession (GR) is considered a public health problem which is highly prevalent across different populations. Accuracy of psychometric properties of prevalence estimates of GR reported in epidemiological studies is important to facilitate setting public health goals, planning of public health programs, implementation of best practices and thereby developing public health policy. However, the reported prevalence estimates are influenced by the methodological variations among different studies, as observed in our recently published systematic review and meta-analysis on the global prevalence of GR. It substantially limits the comparability between studies and inferences about the true global variation in the prevalence of GR are difficult to establish. To address these issues, this commentary suggests to follow the standardized principles related to study design, clinical examination protocol, and characteristics of study subjects in future epidemiological studies on prevalence estimates of GR. Furthermore, the inclusion of additional domains in the reporting data is suggested for a deeper insight into the patterns of GR in different populations. Our suggestions are derived from a pragmatic approach and their consistent implementation would improve the reporting quality and achieve uniformity in future studies, thus benefitting the research in this area.

Bacterial infection-related glomerulonephritis in patients with diabetes.

AIM: Diabetic patients are prone to infections, thus making them a unique cohort at risk of developing bacterial infection-related glomerulonephritis (IRGN). METHODS: In total, 1693 adult diabetic patients underwent kidney biopsy between 2005 and 2021 at our tertiary care hospital in South India. Of these, 121 consecutive cases which met criteria of bacterial IRGN were included in this study. RESULTS: The mean age of the cohort was 53.1 ± 10.1 years and 83/121 (68.5%) were males. Majority (98.3%) had type 2 diabetes for a median duration of 6 (IQR, 2-12) years. The most common sites of infection were skin (47/121, 38.8%) and urinary tract (15/121, 12.4%). Fifty percent (58/121) of patients had underlying advanced diabetic kidney disease (DKD). Isolated C3 deposits (without immunoglobulin) occurred in 66/121 (54.5%) patients predominantly in advanced DKD patients. IgA-dominant glomerulonephritis occurred in only 9/121 (7.4%) patients. Short-course oral steroid was given to 86/121 (71.1%) patients. Steroid related dysglycemia and immunosuppression related infections occurred in 9/61 (14.8%) and 16/61 (26.2%) patients respectively. Of the 90 patients with follow up details >3 months, 46 (51.1%) progressed to kidney failure over a median period of 0.5 (IQR, 0-7.2) months. Patients diagnosed in the latter half of our study period (2013-2021) were older, less commonly presented with fever, had more pronounced hypocomplementemia and severe renal histology predominantly with a 'starry sky' immunofluorescence pattern. CONCLUSION: Superimposed bacterial IRGN on underlying DKD is associated with poor renal outcomes. Use of short course steroid was associated with significant toxicity.

Patterns of Renal Dysfunction and Profile of Kidney Biopsies in Hematopoietic Stem Cell Transplant Recipients.

Introduction: Post hematopoietic stem cell transplant (HSCT), kidney can be subjected to injury by various causes. Of these, graft versus host disease (GvHD) affecting the kidney is an under-recognized entity with no clear guidelines on its diagnosis, clinicopathological manifestations, and outcomes. Material and Methods: Out of 2,930 patients who underwent HSCT at our center between 2005 and 2020, kidney biopsy was performed in 19 allogenic and 5 autologous recipients. Results: The mean age of the cohort at transplant was 33.2 ± 7 years, and 15 (62%) were males. Median time to kidney biopsy from HSCT was 14 (IQR, 9-30) months. Aplastic anemia was the most common underlying hematological disease (54.2%). All 19 allogenic recipients were classified based on clinicopathological manifestations into either thrombotic microangiopathy (TMA, 12/19 [63%]) or nephrotic syndrome (NS, 7/19 [37%]) pattern. Glomerular tuft "mesangiolysis" was the dominant pattern of injury noted in 9/12 cases of TMA pattern. There was a predominance of acute microangiopathic changes restricted primarily to the glomerular compartment. Of the 7 patients with NS pattern, membranous nephropathy was seen in 4 (57%) and minimal change disease in 3 (43%) patients. Thirty-nine percent (7/18) stained positive for C4d which was predominantly glomerular. Allogenic recipients who did not receive immunosuppression (IS) for renal disease had a lower eGFR at biopsy, a longer latency between withdrawal of GvHD prophylaxis and biopsy, and were significantly at a higher risk of kidney failure (IS: 2/11, 18.1% vs. no IS: 2/6, 33.3%, p = 0.04). "Associated extra-renal GvHD" occurred in 11/19 (57.9%) allogenic recipients. Patients with "associated extra-renal GvHD" had significantly more deaths (6/11, 60% vs. 0, p = 0.02) but comparable renal outcomes. Conclusion: Renal GvHD can present with or without "associated extra-renal GvHD" after a prolonged period of withdrawal of GvHD prophylaxis, requiring careful diagnostic vigilance and consideration of IS.

Diffuse Alveolar Hemorrhage (DAH) in the Immediate Post-Transplant Setting: An Unusual Case and a Review of Literature.

Diffuse alveolar hemorrhage is known to be a devastating clinical condition with myriad etiologies. The immediate post-transplant period is plagued by immunosuppression, surgical complications, and nosocomial sources of infection. Diffuse alveolar hemorrhage in this setting is usually attributed to infection. In this case report, an unusual cause of diffuse alveolar hemorrhage due to anti-thymocyte globulin used as an induction agent is described, and an approach to DAH in the immediate post-transplant setting is discussed.

Formative acceptance of ingestible biosensors to measure adherence to TB medications.

BACKGROUND: Tuberculosis (TB) represents a significant public health threat in India. Adherence to antitubercular therapy (ATT) is the key to reducing the burden of this infectious disease. Suboptimal adherence to ATT and lack of demonstrated feasibility of current strategies for monitoring ATT adherence highlights the need for alternative adherence monitoring systems. METHODS: A quantitative survey was conducted to assess the acceptance of and willingness to use a digital pill system (DPS) as a tool for monitoring ATT adherence among stakeholders directly involved in the management of patients with TB in India. Participants reviewed a video explaining the DPS and completed a survey, which covered sociodemographics, degree of involvement with TB patients, initial impressions of the DPS, and perceived challenges for deploying the technology in India. Participants were also asked to interpret mock DPS adherence data. RESULTS: The mean age was 34.3 (SD = 7.3), and participants (N = 50) were predominantly male (70%). The sample comprised internists (52%) and pulmonologists (30%), with a median of 4 years' experience (IQR 3, 6) in the management of TB patients. No participants had previously used a DPS, but some reported prior awareness of the technology (22%). Most reported that they would recommend use of a DPS to patients on ATT (76%), and that they would use a DPS in both the intensive and continuation phases of TB management (64%). The majority viewed the DPS (82%) as a useful alternative to directly observed therapy-short course (DOTS), particularly given the ongoing COVID-19 pandemic. Participants reported that a DPS would be most effective in patients at risk of nonadherence (64%), as well as those with past nonadherence (64%). Perceived barriers to DPS implementation included lack of patient willingness (92%), cost (86%), and infrastructure constraints (66%). The majority of participants were able to accurately interpret patterns of adherence (80%), suboptimal adherence (90%), and frank nonadherence (82%) when provided with mock DPS data. CONCLUSIONS: DPS are viewed as an acceptable, feasible, and useful technology for monitoring ATT adherence by stakeholders directly involved in TB management. Future investigations should explore patient acceptance of DPS and pilot demonstration of the system in the TB context.

Barriers and facilitators of noncommunicable disease (NCD) prevention in Kerala: A qualitative study.

Context: The burden of noncommunicable diseases (NCD) is increasing at an alarming rate, contributing to about 23% of the mortality in the rural and 30% of the total mortality in the urban population in India. Even with high health literacy in Kerala, the state has higher rates of NCD risk factors and lower diabetes and hypertension control rates. Aims: The objectives were to qualitatively assess the facilitators and barriers of NCD prevention from the patients' and health care providers' perspectives and assess the perceptions of healthy lifestyle behaviors among NCD risk persons and patients. Settings and Design: This was a qualitative study conducted in Thrissur district, Kerala, India. Methods and Material: Qualitative study was conducted using the grounded theory approach. A total of nine in-depth interviews and ten focus group discussions were conducted among health care providers and NCD risk persons and patients. The audio-recorded data were transcribed, coded, and thematically analyzed. Statistical Analysis: The data were transcribed and analyzed using the Framework approach to qualitative data analysis. Results: The main themes identified were healthy lifestyle behaviors, facilitators, and barriers to NCD prevention. The main facilitators for NCD prevention were NCD screening, the national program for NCD, health education sessions, and yoga classes in school. Lack of time, laziness, unavailability of space for exercise, and safety issues were identified as barriers to physical activity. Conclusions: People are aware of the facilitators and barriers of NCD prevention. Availability of a favorable environment and behavior change is needed to combat the silent epidemic of NCDs.

The Acceptability of Adherence Support via Mobile Phones for Antituberculosis Treatment in South India: Exploratory Study.

BACKGROUND: India has the greatest burden of tuberculosis (TB). However, over 15% of the people on antitubercular therapy (ATT) in India are nonadherent. Several adherence monitoring techniques deployed in India to enhance ATT adherence have had modest effects. Increased adoption of mobile phones and other technologies pose potential solutions to measuring and intervening in ATT adherence. Several technology-based interventions around ATT adherence have been demonstrated in other countries. OBJECTIVE: The objective of our study was to understand the acceptance of mobile phone adherence supports for ATT using self-administered quantitative measures among patients with TB in South India. METHODS: This exploratory study was conducted at a TB treatment center (TTC) at a tertiary care center in Thrissur District, Kerala, India. We recruited 100 patients with TB on ATT using convenience sampling after obtaining written informed consent. Trained study staff administered the questionnaire in Malayalam, commonly spoken in Kerala, India. We used frequency, mean, median, and SD or IQR to describe the data. RESULTS: Of the 100 participants diagnosed with TB on ATT, 90% used mobile phones routinely, and 84% owned a mobile phone. Ninety-five percent of participants knew how to use the calling function, while 65% of them did not know how to use the SMS function on their mobile phone. Overall, 89% of the participants did not consider mobile phone-based ATT adherence interventions an intrusion in their privacy, and 93% did not fear stigma if the adherence reminder was received by someone else. Most (95%) of the study participants preferred mobile phone reminders instead of directly observed treatment, short-course. Voice calls (n=80, 80%) were the more preferred reminder modality than SMS reminders (n=5, 5%). CONCLUSIONS: Mobile phones are likely an acceptable platform to deliver ATT adherence interventions among individuals with TB in South India. Preference of voice call reminders may inform the architecture of future adherence interventions surrounding ATT in South India.

An Unusual Neurological Syndrome in a Haemodialysis Patient.

Advanced age and immunosuppressed states allow for complications of herpes zoster such as encephalitis. In this case report, we describe a patient with encephalopathy two days after initiation of antiviral therapy. After the necessary imaging and cerebrospinal fluid (CSF) analysis, it became evident that the neurological syndrome was due to acyclovir. Despite currently practised renal dose modification, the patient developed acyclovir-induced neurotoxicity and required intensification of his dialysis schedule to eliminate the drug. Acyclovir-induced neurotoxicity is a rare clinical presentation and presents a clinical dilemma to the physician who has to distinguish this entity from herpes zoster encephalitis and posterior circulation stroke.

Immune predictors of oral poliovirus vaccine immunogenicity among infants in South India.

Identification of the causes of poor oral vaccine immunogenicity in low-income countries might lead to more effective vaccines. We measured mucosal and systemic immune parameters at the time of vaccination with oral poliovirus vaccine (OPV) in 292 Indian infants aged 6-11 months, including plasma cytokines, leukocyte counts, fecal biomarkers of environmental enteropathy and peripheral blood T-cell phenotype, focused on gut-homing regulatory CD4+ populations. We did not find a distinct immune phenotype associated with OPV immunogenicity, although viral pathogens were more prevalent in stool at the time of immunization among infants who failed to seroconvert (63.9% vs. 45.6%, p = 0.002). Using a machine-learning approach, we could predict seroconversion a priori using immune parameters and infection status with a median 58% accuracy (cross-validation IQR: 50-69%) compared with 50% expected by chance. Better identification of immune predictors of OPV immunogenicity is likely to require sampling of mucosal tissue and improved oral poliovirus infection models.

In vitro Characterization of Gut Microbiota-Derived Bacterial Strains With Neuroprotective Properties.

Neurodegenerative diseases are disabling, incurable, and progressive conditions characterized by neuronal loss and decreased cognitive function. Changes in gut microbiome composition have been linked to a number of neurodegenerative diseases, indicating a role for the gut-brain axis. Here, we show how specific gut-derived bacterial strains can modulate neuroinflammatory and neurodegenerative processes in vitro through the production of specific metabolites and discuss the potential therapeutic implications for neurodegenerative disorders. A panel of fifty gut bacterial strains was screened for their ability to reduce pro-inflammatory IL-6 secretion in U373 glioblastoma astrocytoma cells. Parabacteroides distasonis MRx0005 and Megasphaera massiliensis MRx0029 had the strongest capacity to reduce IL-6 secretion in vitro. Oxidative stress plays a crucial role in neuroinflammation and neurodegeneration, and both bacterial strains displayed intrinsic antioxidant capacity. While MRx0005 showed a general antioxidant activity on different brain cell lines, MRx0029 only protected differentiated SH-SY5Y neuroblastoma cells from chemically induced oxidative stress. MRx0029 also induced a mature phenotype in undifferentiated neuroblastoma cells through upregulation of microtubule-associated protein 2. Interestingly, short-chain fatty acid analysis revealed that MRx0005 mainly produced C1-C3 fatty acids, while MRx0029 produced C4-C6 fatty acids, specifically butyric, valeric and hexanoic acid. None of the short-chain fatty acids tested protected neuroblastoma cells from chemically induced oxidative stress. However, butyrate was able to reduce neuroinflammation in vitro, and the combination of butyrate and valerate induced neuronal maturation, albeit not to the same degree as the complex cell-free supernatant of MRx0029. This observation was confirmed by solvent extraction of cell-free supernatants, where only MRx0029 methanolic fractions containing butyrate and valerate showed an anti-inflammatory activity in U373 cells and retained the ability to differentiate neuroblastoma cells. In summary, our results suggest that the pleiotropic nature of live biotherapeutics, as opposed to isolated metabolites, could be a promising novel drug class in drug discovery for neurodegenerative disorders.

B cell activation in the cecal patches during the development of an experimental colitis model.

Although previous studies have suggested that appendix seems to be involved in the colitis, the role of this in the pathogenesis remains unclear. In this study, we assessed the importance of appendiceal lymphoid follicles, specifically the cecal patches (CP) in mice, using an experimental colitis model. Treatment with oxazolone resulted in ulcerations particularly at CP with follicular expansion as well as colitis. The colitis was attenuated by either appendectomy or the absence of mature B cells. We therefore established an intravital imaging system accompanied by the fluorescence resonance energy transfer technology to analyze the dynamic immune response of CP B cells. Our observation revealed frequent Ca2+ signaling in CP B cells during the early phase of colitis development. These findings suggested that the CP B cells may be involved in the pathogenesis of colitis including inflammatory bowel diseases in humans.

Leptomeningeal carcinomatosis in a patient with gallbladder carcinoma.

Carcinomatous meningitis is a rare manifestation of malignancy. It is increasingly being recognized in lung carcinoma, breast carcinoma, melanomas, gastrointestinal malignancies, lymphomas, and leukemia and it is almost never seen in gallbladder malignancies. We present a case whose primary presentation was as a carcinomatous meningitis that was subsequently found to be secondary to a gallbladder primary.

Schimidt Syndrome: An Unusual Cause of Hypercalcaemia.

Autoimmune polyglandular syndrome type 2 also known as Schmidt syndrome. It is a rare disorder involving a combination of Addison's disease with autoimmune thyroid disease with or without type 1 diabetes mellitus. In this case report one such patient with this rare syndrome is described who presented with hyperpigmentation of knuckles, palms and soles with significant weight loss for 2 months. At presentation she also had severe hypercalcaemia. Severe hypercalcaemia is rare and hypercalcaemia at the initial presentation of Addison's disease is also unusual. The mechanism of hypercalcaemia in addisons and management of this patient is discussed.

Epithelial Nuclear Factor-x03BA;B Activation in Inflammatory Bowel Diseases and Colitis-Associated Carcinogenesis.

Prolonged inflammatory bowel diseases (IBD) may lead to colitis-associated carcinogenesis (CAC). Previous studies had shown that nuclear factor-x03BA;B (NF-x03BA;B) activation in both macrophages and epithelia in inflamed colonic tissue is associated with CAC development. However, the mechanism by which epithelial NF-x03BA;B activation leading to CAC development had not previously been rigorously studied. We and others had observed the increased expression of the type 2 receptor for tumor necrosis factor (TNFR2/TNFRSF1b/p75) in IBD models. Myosin light chain kinase (MLCK) is suggested to be associated with epithelial permeability via TNF signaling. Therefore, the relationship between epithelial MLCK expression and NF-x03BA;B activation via TNFR2 signaling on CAC development was investigated. Pro-tumorigenic cytokines such as interleukin (IL)-1ß, IL-6 and macrophage inflammatory protein-2 at the lamina propria were increased in the setting of colitis and further increased in tumor tissues with upregulated epithelial TNFR2 and MLCK expressions in an animal model of CAC. The upregulated MLCK expression was also observed in TNF-stimulated colonic epithelial cells in vitro in association with the upregulation of TNFR2 but not TNFR1/TNFRSF1a/p55. Gene silencing of tnfrsf1b, but not tnfrsf1a, resulted in restoration of epithelial tight junction (TJ) associated with decreased MLCK expression. The presence of anti-TNF antibody also resulted in restoration of TJ in association with suppressed MLCK expression, and interestingly, similar results including the suppressed TNFR2 and MLCK expressions were observed by inhibiting MLCK in the epithelial cells. MLCK silencing also led to suppressed TNFR2 expression, suggesting that the restored TJ leads to reduced TNFR2 signaling. Such suppression of MLCK as well as blockade of TNFR2 signaling resulted in reduced CAC development, restored TJ, and decreased pro-tumorigenic cytokines. These imply that TNF-induced NF-x03BA;B activation and MLCK expression may be a potential target for the prevention of IBD-associated carcinogenesis.

Chlorantraniliprole: An unusual insecticide poisoning in humans.

A 26-year-old female presented with deliberate self-harm using chlorantraniliprole, an unknown substance in human toxicology. She developed symptomatic Mobitz Type I atrioventricular block during observation, for which a temporary pacemaker was inserted. She reverted to sinus rhythm after 48 h and was discharged. Although claimed to be nontoxic to humans, chlorantraniliprole, an insecticide, could cause conduction defects by activating ryanodine receptors. To the best of our knowledge, this is the first case of chlorantraniliprole poisoning reported in the medical literature.