A rare case of isoniazid mono-resistant tuberculosis presenting as cardiac tamponade along with an anterior mediastinal mass in a 15-year-old immunocompetent patient.

ABSTRACT: A 15-year-old boy presented with a sudden onset of breathlessness for 7 days, gradual loss of weight of 17.6 lbs over the last month and progressive hoarseness of voice for 7 months. The contrast-enhanced computed tomography (CECT) scan revealed a heterogeneously enhancing lesion in the anterior mediastinum with multiple discrete lymph nodes in the cervical and mediastinal locations. The GeneXpert MTB/RIF assay performed on the CT-guided biopsy of the mass was negative, but the culture for Mycobacterium tuberculosis was positive at 7 weeks of incubation. There was a suboptimal radiological response after 6 months of treatment. First-line drug susceptibility testing (DST) performed by line probe assay (LPA) on the positive culture detected high-level resistance to isoniazid. The treatment was modified as per DST results to which the patient responded well.

Influences of amyloid-ß and tau on white matter neurite alterations in dementia with Lewy bodies.

Dementia with Lewy bodies (DLB) is a neurodegenerative condition often co-occurring with Alzheimer's disease (AD) pathology. Characterizing white matter tissue microstructure using Neurite Orientation Dispersion and Density Imaging (NODDI) may help elucidate the biological underpinnings of white matter injury in individuals with DLB. In this study, diffusion tensor imaging (DTI) and NODDI metrics were compared in 45 patients within the dementia with Lewy bodies spectrum (mild cognitive impairment with Lewy bodies (n = 13) and probable dementia with Lewy bodies (n = 32)) against 45 matched controls using conditional logistic models. We evaluated the associations of tau and amyloid-ß with DTI and NODDI parameters and examined the correlations of AD-related white matter injury with Clinical Dementia Rating (CDR). Structural equation models (SEM) explored relationships among age, APOE ε4, amyloid-ß, tau, and white matter injury. The DLB spectrum group exhibited widespread white matter abnormalities, including reduced fractional anisotropy, increased mean diffusivity, and decreased neurite density index. Tau was significantly associated with limbic and temporal white matter injury, which was, in turn, associated with worse CDR. SEM revealed that amyloid-ß exerted indirect effects on white matter injury through tau. We observed widespread disruptions in white matter tracts in DLB that were not attributed to AD pathologies, likely due to α-synuclein-related injury. However, a fraction of the white matter injury could be attributed to AD pathology. Our findings underscore the impact of AD pathology on white matter integrity in DLB and highlight the utility of NODDI in elucidating the biological basis of white matter injury in DLB.

Plasma biomarkers of Alzheimer's disease in the continuum of dementia with Lewy bodies.

INTRODUCTION: Patients with dementia with Lewy bodies (DLB) may have Alzheimers disease (AD) pathology that can be detected by plasma biomarkers. Our objective was to evaluate plasma biomarkers of AD and their association with positron emission tomography (PET) biomarkers of amyloid and tau deposition in the continuum of DLB, starting from prodromal stages of the disease. METHODS: The cohort included patients with isolated rapid eye movement (REM) sleep behavior disorder (iRBD), mild cognitive impairment with Lewy bodies (MCI-LB), or DLB, with a concurrent blood draw and PET scans. RESULTS: Abnormal levels of plasma glial fibrillary acidic protein (GFAP) were found at the prodromal stage of MCI-LB in association with increased amyloid PET. Abnormal levels of plasma phosphorylated tau (p-tau)-181 and neurofilament light (NfL) were found at the DLB stage. Plasma p-tau-181 showed the highest accuracy in detecting abnormal amyloid and tau PET in patients with DLB. DISCUSSION: The range of AD co-pathology can be detected with plasma biomarkers in the DLB continuum, particularly with plasma p-tau-181 and GFAP.

Assessment of Oral Health Status and Treatment Needs of School Teachers in Indore City, Madhya Pradesh, India: A Cross-Sectional Study.

INTRODUCTION: Teachers are central to the well-being of a community. Being an influential part of society, their role can be broadened to promote oral health and healthy oral hygiene habits. This study was aimed at the assessment of the oral health status and treatment needs of school teachers in Indore City. METHOD: A descriptive cross-sectional study was carried out over a period of five months on 470 school teachers working in various government schools of Indore city selected through random sampling technique. The modified WHO Oral Health Assessment Form for Adults 2013 was used to record oral health status and treatment needs, while the WHO Questionnaire for Adults 2013 was used to document oral hygiene practices, dietary habits, and deleterious habits. Data was analyzed using IBM SPSS Version 25 (IBM Corp., Armonk, NY). Chi-square test, independent t-test, and one-way ANOVA were used. RESULTS: The gender distribution of the representative sample showed female predominance. The prevalence of smokeless tobacco consumption was 5.1% among the study subjects. The mean number of Decayed, Missing, and Filled Teeth (DMFT) was 3.45 ± 3.10, and the mean number of 1.52 ± 2.40 teeth showed the presence of bleeding. Around 37.2% had shallow pockets of 4-5 mm. A mean number of 4.26 ± 1.97 sextants showed 0-3 mm attachment loss. There was a significant association between the frequency and technique of toothbrushing with a decayed number of teeth (p<0.001). CONCLUSION: High proportion of dental caries and periodontal disease was seen which could be related to their oral health care-seeking behavior and the impairment related to age changes.

Functional Foods: A Promising Strategy for Restoring Gut Microbiota Diversity Impacted by SARS-CoV-2 Variants.

Natural herbs and functional foods contain bioactive molecules capable of augmenting the immune system and mediating anti-viral functions. Functional foods, such as prebiotics, probiotics, and dietary fibers, have been shown to have positive effects on gut microbiota diversity and immune function. The use of functional foods has been linked to enhanced immunity, regeneration, improved cognitive function, maintenance of gut microbiota, and significant improvement in overall health. The gut microbiota plays a critical role in maintaining overall health and immune function, and disruptions to its balance have been linked to various health problems. SARS-CoV-2 infection has been shown to affect gut microbiota diversity, and the emergence of variants poses new challenges to combat the virus. SARS-CoV-2 recognizes and infects human cells through ACE2 receptors prevalent in lung and gut epithelial cells. Humans are prone to SARS-CoV-2 infection because their respiratory and gastrointestinal tracts are rich in microbial diversity and contain high levels of ACE2 and TMPRSS2. This review article explores the potential use of functional foods in mitigating the impact of SARS-CoV-2 variants on gut microbiota diversity, and the potential use of functional foods as a strategy to combat these effects.

Lower Circulating Cytotoxic T-Cell Frequency and Higher Intragraft Granzyme-B Expression Are Associated with Inflammatory Interstitial Fibrosis and Tubular Atrophy in Renal Allograft Recipients.

Background and Objectives: Inflammatory interstitial fibrosis and tubular atrophy (i-IFTA) is an inflammation in the area of tubular atrophy and fibrosis. i-IFTA is poorly associated with graft outcome and associated with infiltration of inflammatory mononuclear cells. A cytotoxic T cell is a granzyme B+CD8+CD3+ T cell, mainly secret granzyme B. Granzyme B is a serine protease that may mediate allograft injury and inflammatory interstitial fibrosis and tubular atrophy (i-IFTA). However, there is no report identifying the association of granzyme B with i-IFTA after a long post-transplant interval. Material and Methods: In this study, we have measured the cytotoxic T-cell frequency with flow cytometry, serum and PBMCs culture supernatants granzyme-B levels with ELISA and intragraft granzyme-B mRNA transcript expression with the RT-PCR in RTRs in 30 patients with biopsy-proven i-IFTA and 10 patients with stable graft function. Result: The frequency of cytotoxic T cells (CD3+CD8+ granzyme B+) in SGF vs. i-IFTA was (27.96 ± 4.86 vs. 23.19 ± 3.85%, p = 0.011), the serum granzyme-B level was (100.82 ± 22.41 vs. 130.32 ± 46.60, p = 0.038 pg/mL) and the intragraft granzyme-B mRNA transcript expression was (1.01 ± 0.048 vs. 2.10 ± 1.02, p < 0.001 fold). The frequency of CD3+ T cells in SGF vs. i-IFTA was (66.08 ± 6.8 vs. 65.18 ± 9.35%; p = 0.68) and that of CD3+CD8+ T cells was (37.29 ± 4.11 vs. 34.68 ± 5.43%; p = 0.28), which were similar between the 2 groups. CTLc frequency was negatively correlated with urine proteinuria (r = -0.51, p < 0.001), serum creatinine (r = -0.28, p = 0.007) and eGFR (r = -0.28, p = 0.037). Similarly, the PBMC culture supernatants granzyme-B level was negatively correlated with urine proteinuria (r = -0.37, p < 0.001) and serum creatinine (r = -0.31, p = 0.002), while the serum granzyme-B level (r = 0.343, p = 0.001) and intragraft granzyme-B mRNA transcript expression (r = 0.38, p < 0.001) were positively correlated with proteinuria. Conclusions: A decrease in the CTLc frequency in circulation and an increased serum granzyme-B level and intragraft granzyme-B mRNA expression shows that cytotoxic T cells may mediate the allograft injury in RTRs with i-IFTA by releasing granzyme B in serum and intragraft tissue.

Pediatric Glomerular Diseases in North India-Epidemiology and Clinicopathologic Correlation.

Background: Glomerular diseases vary with age, and it is important to investigate the spectrum of glomerular diseases in pediatric patients to help in a more precise clinical diagnosis and optimize the management of patients. We aimed to study the clinicopathologic pattern of pediatric glomerular diseases in North India. Methods: This is a 5-year retrospective, single-center cohort study. The database was searched to identify all pediatric patients with glomerular diseases in their native kidney biopsies. Results: About 2890 native renal biopsies were studied, of which 409 were pediatric glomerular diseases. The median age was 15 years with a male preponderance. Nephrotic syndrome was the most common presentation (60.8%), followed by non-nephrotic proteinuria with hematuria (18.5%), rapidly proliferative glomerulonephritis (7%), isolated hematuria (5.3%), acute nephritic syndrome (3.4%), non-nephrotic proteinuria (1.9%), and advanced renal failure (0.7%). Minimal change disease (MCD) was the most common histological diagnosis, followed by focal segmental glomerulosclerosis (17.4%), IgA nephropathy (IgAN; 10%), membranous nephropathy (6.6%), lupus nephritis (5.9%), crescentic glomerulonephritis (2.9%), and C3 glomerulopathy (2.9%). Diffuse proliferative glomerulonephritis (DPGN) was the most common histological diagnosis in patients with hematuria and non-nephrotic as well as nephrotic range proteinuria. The most common histological diagnoses for isolated hematuria and acute nephritic syndrome were IgAN and postinfectious glomerulonephritis (PIGN), respectively. Conclusions: MCD and lupus nephritis are the most common pediatric primary and secondary histopathologic diagnoses, respectively. The adolescent-onset glomerular diseases have a higher frequency of IgAN, membranous nephropathy, and DPGN. PIGN is still an important differential in our pediatric patients presenting with acute nephritic syndrome.

Clinicopathologic Manifestations of Immunoglobulin A Nephropathy in a Northern Indian Cohort: A Mute Assassin with Delayed Diagnosis.

Introduction: Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide, but there is a marked geographic difference in its prevalence and prognosis. IgAN is known to have an aggressive course in Asians. However, its exact prevalence and clinicopathologic spectrum in North India are not well documented. Materials and Methods: The study included all patients aged above 12 years with primary IgAN on kidney biopsy from January 2007 to December 2018. Clinical and pathological parameters were noted. Two histopathologists independently reviewed all kidney biopsies, and MEST-C score was assigned as per the Oxford classification. Results: IgAN was diagnosed in 681 (11.85%) out of 5751 native kidney biopsies. The mean age was 32 ± 12.3 years, and the male to female ratio was 2.5:1. At presentation, 69.8% had hypertension, 68% had an estimated glomerular filtration rate (eGFR) of less than 60 ml/min, 63.2% had microscopic hematuria, and 4.6% had gross hematuria. The mean proteinuria was 3.61 ± 2.26 g/day, with 46.8% showing nephrotic range proteinuria and 15.2% showing nephrotic syndrome manifestation. Histopathologically, 34.4% of patients had diffuse global glomerulosclerosis. Oxford MEST-C scoring revealed M1 in 67%, E1 in 23.9%, S1 in 46.9%, T1/T2 in 33%, and crescents in 19.6% of biopsies. The mean serum creatinine was significantly higher in cases with E1, T1/2, and C1/2 scores (P < 0.05). Hematuria and proteinuria were significantly higher (P < 0.05) with E1 and C1/2 scores. Coexisting C3 was associated with higher serum creatinine at presentation (P < 0.05). Conclusion: IgAN patients with late presentation and advanced disease became less amenable to immunomodulation in our cohort. The implementation of point-of-care screening strategies, early diagnosis, and retarding disease progression should be prioritized in the Indian strategy.

ß-Amyloid Load on PET Along the Continuum of Dementia With Lewy Bodies.

BACKGROUND AND OBJECTIVES: ß-Amyloid (Aß) plaques can co-occur with Lewy-related pathology in patients with dementia with Lewy bodies (DLB), but Aß load at prodromal stages of DLB still needs to be elucidated. We investigated Aß load on PET throughout the DLB continuum, from an early prodromal stage of isolated REM sleep behavior disorder (iRBD) to a stage of mild cognitive impairment with Lewy bodies (MCI-LB), and finally DLB. METHODS: We performed a cross-sectional study in patients with a diagnosis of iRBD, MCI-LB, or DLB from the Mayo Clinic Alzheimer Disease Research Center. Aß levels were measured by Pittsburgh compound B (PiB) PET, and global cortical standardized uptake value ratio (SUVR) was calculated. Global cortical PiB SUVR values from each clinical group were compared with each other and with those of cognitively unimpaired (CU) individuals (n = 100) balanced on age and sex using analysis of covariance. We used multiple linear regression testing for interaction to study the influences of sex and APOE ε4 status on PiB SUVR along the DLB continuum. RESULTS: Of the 162 patients, 16 had iRBD, 64 had MCI-LB, and 82 had DLB. Compared with CU individuals, global cortical PiB SUVR was higher in those with DLB (p < 0.001) and MCI-LB (p = 0.012). The DLB group included the highest proportion of Aß-positive patients (60%), followed by MCI-LB (41%), iRBD (25%), and finally CU (19%). Global cortical PiB SUVR was higher in APOE ε4 carriers compared with that in APOE ε4 noncarriers in MCI-LB (p < 0.001) and DLB groups (p = 0.049). Women had higher PiB SUVR with older age compared with men across the DLB continuum (ß estimate = 0.014, p = 0.02). DISCUSSION: In this cross-sectional study, levels of Aß load was higher further along the DLB continuum. Whereas Aß levels were comparable with those in CU individuals in iRBD, a significant elevation in Aß levels was observed in the predementia stage of MCI-LB and in DLB. Specifically, APOE ε4 carriers had higher Aß levels than APOE ε4 noncarriers, and women tended to have higher Aß levels than men as they got older. These findings have important implications in targeting patients within the DLB continuum for clinical trials of disease-modifying therapies.

Isolated Cardiac Paraganglioma Encasing Right Coronary Artery With Evidence of Succinyl Dehydrogenase Gene Mutation: Successful Management Using Multimodality Imaging.

This report involves a young woman with isolated cardiac paraganglioma that was diagnosed using 68Gallium-labeled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI3-octreotide positron emission tomographic scintigraphy. For the preoperative evaluation, multimodality imaging accurately described the anatomic location of the tumor and its relationship with the surrounding tissues. The patient underwent successful surgical resection of the tumor along with right coronary artery bypass grafting. The 2-month follow-up scintigraphy was normal. Next-generation sequencing evaluation revealed a novel germline mutation for the succinate dehydrogenase subunit B gene.

Divergent manifestations and outcomes of diffuse crescentic immunoglobulin A nephropathy and pauci-immune crescentic glomerulonephritis on long-term.

BACKGROUND: Diffuse crescentic IgAN (CIgAN) is an uncommon phenotype of IgAN, which presents as rapidly progressive renal failure, similar to patients with pauci-immune crescentic glomerulonephritis(PCGN). There are limited data on outcomes comparisons between the two. METHODS: In this single-center, retrospective cohort study, we compared the clinical features, pathological presentation, and renal outcomes of 52 patients with CIgAN and 42 patients with renal-limited PCGN from January 2007 to December 2019. RESULTS: The CIgAN patients were younger (30.5 ± 13.8 years) than PCGN patients (46.1 ± 11.8 years) (P = 0.001). The CIgAN patients had a higher prevalence of hypertension (86.5% Vs. 41.3%, P = 0.001); and degree of proteinuria (4.2 ± 2.7 g/24 h Vs. 2.3 ± 1.16 g/24 h; P = 0.001) than PCGN patients. The chronicity in terms of global glomerulosclerosis, interstitial fibrosis, and tubular atrophy was higher in the CIgAN group than in the PCGN group. The remission rate with immunosuppression was significantly higher in the PCGN group than in the CIgAN group (P = 0.016). The end-stage renal disease (ESRD) or death within 1 year of diagnosis was significantly more in the CIgAN group (62.3% Vs. 39.1%) than PCGNgroup. For patients who were dialysis-dependent at presentation, the primary outcome of ESRD or death within one year was seen in 90.9% of patients of CIgAN and 44.1% in the PCGN group (P = 0.001). The long-term death non-censored renal survival is poor in the CIgAN group than in PCGN patients. However, patient survival is poor in PCGN patients. CONCLUSION: CIgAN is a different form of RPGN compared to PCGN and carries a poor prognosis despite similar immunosuppressive therapy in the long term.

Non-Diabetic Kidney Disease in Type 2 Diabetes Mellitus: A Changing Spectrum with Therapeutic Ascendancy.

BACKGROUND AND OBJECTIVES: Owing to changing epidemiology and therapeutic practices, a change in the spectrum of renal involvement in Type-2 diabetes mellitus (T2DM) has also been noted. The treatment of non-diabetic kidney disease (NDKD) differs from diabetic kidney disease (DKD) and the reversibility of NDKD in many cases to normal, prompts biopsy for rapid and accurate diagnosis. Data are scarce on kidney biopsy findings in T2DM. STUDY DESIGN & SETTING: In this observational study, we prospectively collected the data of kidney biopsies of patients aged ≥ 18 years with T2DM admitted between 1 August 2005 and 31 July 2022. The clinical, demographic and histopathological data were evaluated. The spectrum of kidney involvement in the form of DKD and/or NDKD was studied. The impact of these findings with the use of drugs retarding disease progression was also analyzed. RESULTS: A total of 5485 biopsies were performed during the study period and of these 538 patients had T2DM. The mean age of the study population was 56.9 ± 11.5 years and 81% were males. The mean duration of DM was 6.4 ± 6.1 years. Diabetic retinopathy (DR) was noted in 29.7%. The most common indication for biopsy was an acute rise in creatinine (147, 27.3%). Amongst the 538 diabetic patients who underwent biopsy, histological features only of DKD were noted in 166 patients (33%), NDKD alone in 262 (49%) and NDKD with DKD lesions in 110 (20%). On multivariate analysis, duration of DM less than 5 years, absence of CAD, absence of DR, oliguria at presentation, an acute rise in creatinine and low C3 were associated with NDKD. CONCLUSIONS: The prevalence of NDKD among diabetics and ATIN in particular might be on an increasing trend in the current era of changing T2DM epidemiological patterns. The use of anti-pro-teinuric agents was associated with lesser degrees of histopathological chronicity in T2DM.

Technologist-Based Implementation of Total Metabolic Tumor Volume into Clinical Practice.

Metabolic tumor volume (MTV) is defined as the total metabolically active tumor volume seen on 18F-FDG PET/CT examinations. Calculating MTV is often time-consuming, requiring a high degree of manual input. In this study, the MTV calculations of a board-certified nuclear radiologist were compared with those of 2 nuclear medicine technologists. As part of the technologists' educational program, after their classroom time they were trained by the radiologist for 30 min. The technologists calculated MTV within 7.5% of the radiologist's calculations in a set of patients who had diffuse large B-cell lymphoma and were undergoing initial staging 18F-FDG PET/CT. These findings suggest that nuclear medicine technologists may help accelerate implementation of MTV into clinical practice with favorable accuracy, possibly as an initial step followed by validation by the interpreting physician. The aim of this study was to explore whether efficiency is improved by integrating nuclear medicine technologists into a semiautomated workflow to calculate total MTV.

Intracranial neuroendocrine tumour simulating meningioma for several years: an overview of diagnosis and treatment.

Metastatic neuroendocrine tumour (NET) to brain has been reported in 1.5-5% of patients with NETs. Differentiation between intracranial NET metastasis and meningiomas can cause a diagnostic dilemma. We present a symptomatic case of a 66-year-old male with a history of left-sided skull base mass. The diagnosis of a meningioma was made based on the MRI findings and clinical presentation. The patient received radiation and the mass remained stable on serial MRI images at follow-up visits. Five years after his initial presentation, the patient's mass showed further growth. He also complained of worsening of his recent diagnosis of irritable bowel syndrome and fluctuations in his blood pressure. Surgical resection was performed, and histopathological features were consistent with moderately differentiated neuroendocrine tumour. Further evaluation with 68 Gallium-DOTATATE positron emission-computed tomography (Ga-68 PET/CT) showed metastatic disease involving the bones, lymph nodes, and liver without convincing evidence of the location of primary malignancy within the bowel loops or the pancreas. The patient was started on combination of capecitabine and temozolomide with partial response and significant improvement of his symptoms. This case highlights the clinical and radiological behaviour of intracranial NET that can mimic the diagnosis of meningioma.

Two Decades Outcomes of Posttransplant Immunoglobulin A Nephropathy in Live Donor Renal Transplantation.

Background: The data on long-term outcomes of posttransplant immunoglobulin A nephropathy (IgAN) are confounding and vary with geography and ethnicity worldwide. We aimed to study the long-term graft outcomes of patients with posttransplant IgAN in the northern Indian cohort. Methods: The long-term graft outcomes of 51 live donor renal transplant recipients with biopsy-proven posttransplant IgAN (recurrence/de novo) were analyzed. The risk factors for graft failure in the posttransplant IgA groups were analyzed using the Cox regression analysis. Results: Out of the total of 51 patients who had posttransplant IgAN, 40 patients had a biopsy-proven native kidney IgAN. The mean duration of the clinical presentation of posttransplant IgAN was 62.4 months (5.2 years) posttransplant. Proteinuria at the time of biopsy was 3.03 ± 2.2 g/day, and 41.2% had proteinuria of more than 3 g/day at the time of biopsy. The estimated 1, 5, 10, and 20 years patient survival was 98%, 95.4%, 75.9%, and 25.2%, respectively, and the estimated 1, 5, 10, and 20 years graft survival was 98%, 88.5%, 44.6%, and 11.9%, respectively, in patients who had posttransplant IgA. Many of the traditional risk factors associated with progression in native kidney IgAN, such as the degree of proteinuria, Oxford MEST (mesangial and endocapillary hypercellularity, segmental sclerosis, and interstitial fibrosis/tubular atrophy) scoring, recipient's age, and sex were not predictive of early graft failure among patients with posttransplant IgAN. In our cohort, the only significant graft failure predictor was serum creatinine at 5 years. Chronic antibody-mediated rejection (ABMR) was seen in 21.6% of patients with posttransplant IgAN. Whether this coexistence of chronic ABMR is an incidental finding or posttransplant IgAN predisposes to chronic ABMR requires further investigation. Conclusion: Posttransplant IgAN is associated with poor long-term graft outcomes in live donor renal transplants. Proteinuria and MEST scoring were not predictive of graft failure in living donor posttransplant IgAN.