Introduction: The term monoclonal gammopathy of renal significance (MGRS) has been described to i... more Introduction: The term monoclonal gammopathy of renal significance (MGRS) has been described to include patients with renal manifestations associated with circulating monoclonal proteins with or without a clonal lymphoproliferation (B-cell or plasma cell) and not meeting diagnostic criteria for an overt hematological malignancy. A host of MGRS-associated lesions have been described that involve various renal compartments. Our study describes the histomorphological spectrum of MGRS cases at our center in the last 5 years and description as per the classification system of the International Kidney and Monoclonal Gammopathy Research Group (IKMG). Material and Methods: Retrospective analysis was carried out of all the renal biopsies with characteristic monoclonal immunoglobulin lesions for histopathological diagnosis between years 2015 and 2020 and reviewed by two independent pathologists. Results: Most patients in the study belonged to the fifth decade, with a median age of 50 years (m...
ABSTRACT Objectives To study the histopathology of patients dying of COVID-19 using post-mortem m... more ABSTRACT Objectives To study the histopathology of patients dying of COVID-19 using post-mortem minimally invasive sampling techniques. Methods This was a single-center observational study conducted at JPNATC, AIIMS. Thirty-seven patients who died of COVID-19 were enrolled. Post-mortem percutaneous biopsies were taken from lung, heart, liver, kidney and stained with hematoxylin and eosin. Immunohistochemistry was performed using CD61 and CD163. SARS-CoV-2 virus was detected using IHC with primary antibodies. Results The mean age was 48.7 years and 59.5% were males. Lung histopathology showed diffuse alveolar damage in 78% patients. Associated bronchopneumonia was seen in 37.5% and scattered microthrombi in 21% patients. Immunopositivity for SARS-CoV-2 was observed in Type II pneumocytes. Acute tubular injury with epithelial vacuolization was seen in 46% of renal biopsies. Seventy-one percent of liver biopsies showed Kupffer cell hyperplasia and 27.5% showed submassive hepatic necrosis. Conclusions Predominant finding was diffuse alveolar damage with demonstration of SARS-CoV-2 protein in the acute phase. Microvascular thrombi were rarely identified in any organ. Substantial hepatocyte necrosis, Kupffer cell hypertrophy, microvesicular, and macrovesicular steatosis unrelated to microvascular thrombi suggested that liver might be a primary target of COVID-19.
Indian Journal of Medical and Paediatric Oncology, 2018
Background: The incidence of renal cell cancer (RCC) is increasing worldwide. However, scant info... more Background: The incidence of renal cell cancer (RCC) is increasing worldwide. However, scant information is available from the Indian subcontinent regarding its clinicopathological characteristics and survival outcomes. We retrospectively analyzed data of patients suffering from RCC at our center over the last one decade (2004–2013) to generate information on these aspects. Materials and Methods: Case records of 423 patients treated between 2004 and 2013 were retrospectively analyzed. Baseline characteristics, histopathological information, and survival outcomes were assessed. Overall survival was calculated from the time of diagnosis to death due to any cause. Results: The median age was 52 years (range: 18–87 years). Male: female ratio was 3.5:1. The median duration of symptoms was 3 months (range: 0–24 months). Thirty-five patients (8.3%) were detected in asymptomatic state. The most common symptom was hematuria (53.2%) followed by flank pain (46.3%). The most common histology was clear cell subtype (71.4%). Two hundred and ninety-three (69.3%) patients presented with nonmetastatic disease whereas 130 (30.7%) had upfront metastatic disease. Five-year survival in Stages 1, 2, 3, and 4 was 92.7%, 72.9%, 54.6%, and 11.5%, respectively. Conclusion: Younger age, higher male–female ratio, lower proportion of asymptomatic patients, higher proportion of advanced stage at diagnosis, and lower stage-wise survival were some of the key findings.
AJR. American journal of roentgenology, Jan 24, 2018
The primary objective of this study was to compare triple-bolus dual-energy CT (DECT) against sta... more The primary objective of this study was to compare triple-bolus dual-energy CT (DECT) against standard triple-phase MDCT in terms of appropriateness of patient treatment. One hundred twenty-four patients with suspected renal masses seen at ultrasound were randomized into triple-bolus DECT and triple-phase MDCT groups. Patients in the triple-bolus DECT group underwent synchronous corticomedullary nephrographic delayed-phase triple-bolus DECT. In the triple-phase MDCT group, single-energy triple-phase scans were acquired after an unenhanced scan. The primary outcome was appropriateness of treatment received at 1 year. The predefined noninferiority limit was 10%. Histopathologic analysis or follow-up confirmed the benign or malignant nature of the masses. Diagnostic accuracy to differentiate benign from malignant masses was calculated. Size-specific dose estimates were compared. After excluding six patients, 118 patients were analyzed (62 triple-bolus DECT; 56 triple-phase MDCT). Treat...
Institutional review board statement: This study was not required to provide institutional review... more Institutional review board statement: This study was not required to provide institutional review board statement because the material used were fresh frozen tissue. Informed consent statement: This study was not required to provide informed consent statement because the material used were fresh frozen tissue.
Infections by dematiaceous fungi are an emerging group of infectious diseases worldwide with a va... more Infections by dematiaceous fungi are an emerging group of infectious diseases worldwide with a variety of clinical presentations. Though generally localized, they can disseminate in immunocompromised settings, therefore, early diagnosis and prompt therapy can prevent significant morbidity and mortality in these patients. Fungi of genus Exophiala are common causative organisms; however, Exophiala jeanselmei (E. jeanselmei) has not yet been reported from environmental sources in India. We present here the case of a renal transplant recipient who presented with an innocuous lesion on the foot, diagnosed on fine needle aspiration cytology (FNAC) as phaeohyphomycosis, and promptly treated with excision and antifungal therapy. To the best of our knowledge, this is the first case report from India of E. jeanselmei causing phaeohyphomycosis in a transplant recipient and highlights the role a cytopathologist can play in the timely management of such cases.
Dear Editor, We read with great interest the case report by Roy et al in the October 2012 issue o... more Dear Editor, We read with great interest the case report by Roy et al in the October 2012 issue of the International Journal of Surgical Pathology. We recently encountered an interesting renal tumor in a 40-year-old woman who underwent a radical nephrectomy. Grossly, the tumor was located in the upper pole, measured 12 × 9 × 7cm and had a fleshy graywhite cut surface (Figure 1A). Thorough sectioning revealed an encapsulated tumor composed of tall columnar cells arranged in tubules separated by fibrovascular septae (Figure 1B). The cells had basally located monomorphic nuclei with smooth nuclear contours, bland chromatin, and conspicuous nucleoli. Cytoplasm was pale to clear (Figure 1C and D). No mitotic activity or necrosis was identified. The overlying capsule, perinephric fat, renal sinus, hilar vessels, and ureter were free of the tumor. Our initial impression was of a renal carcinoid. On immunohistochemistry, the tumor cells were immunopositive for epithelial membrane antigen and cytokeratin 7 (Figure 2A and B) and were negative for chromogranin, synaptophysin, CD 56, vimentin, CD 10, CD 99, and CD 117. The MIB-1 labeling index was 2%. At this point, further sectioning revealed focal areas with a trabecular arrangement of cells with clear cytoplasm, few perinuclear halos and prominent cell borders, features more classically seen in chromophobe renal cell carcinoma (RCC; Figure 1E]. Performing Hale’s colloidal iron demonstrated the intracytoplasmic acid mucopolysaccharides (Figure 1F) and electron microscopy confirmed the presence of cytoplasmic vesicles consistent with the ultrastructure of chromophobe RCC (Figure 2C and D). No abnormal mitochondria or dense core neurosecretory granules were identified. We were therefore dealing with a chromophobe RCC with a nearly complete tubular architecture. Chromophobe RCC is recognized as a distinct subtype of RCC, with a less aggressive clinical behavior compared with conventional RCCs. The classical appearance is that of solid sheets of tumor cells separated by incomplete vascular septae. Predominantly tubular architecture is rare and has been described as a “nonclassical” architectural pattern by Przybycin et al in their study on 203 chromophobe RCCs, which also included nested, acinar, solid-acinar, papillary, trabecular, and sarcomatoid patterns, representing 29% of all the cases. Though these patterns are not of prognostic importance, they can lead to diagnostic confusion as seen in our case where the tumor resembled a neuroendocrine tumor. Unlike classical chromophobe RCCs, such tumors will require ancillary diagnostic techniques, including immunohistochemistry and electron microscopy to reach the correct diagnosis.
Introduction: Anti-GBM nephritis in the pediatric age group is exceedingly rare with concurrent a... more Introduction: Anti-GBM nephritis in the pediatric age group is exceedingly rare with concurrent additional pathologies being even rarer. Tissue diagnosis requires a combination of crescentic histomorphology, immunofluorescence showing “paint brush stroke” pattern of linear IgG or rarely IgA, and serum anti-GBM antibodies subject to the disease course and treatment. The authors describe one such case with a dual pathology involving IgA nephropathy and atypical anti-GBM disease. Case Presentation: A 13-year-old girl presenting with features of rapidly progressive glomerulonephritis underwent a renal biopsy showing a mesangioproliferative histology with crescents and an immunofluorescence pattern indicating a dual pathology of IgA nephropathy and anti-GBM nephritis. Additional ancillary testing including staining for IgG subclasses and galactose-deficient IgA (KM55) helped to confirm the diagnosis. She responded to steroid pulses and plasma exchange therapy, was off dialysis after 8 we...
Background: This pilot study examines whether a novel diabetes screening approach using gingival ... more Background: This pilot study examines whether a novel diabetes screening approach using gingival crevicular blood (GCB) could be used to test for hemoglobin A1c (HbA1c) during periodontal visits. Methods: Finger-stick blood (FSB) samples from 120 patients and GCB samples from those patients with adequate bleeding on probing (BOP) were collected on special blood collection cards and analyzed for HbA1c levels in a laboratory. The Pearson correlation coefficient was used to measure correlation between FSB and GCB HbA1c values for 75 paired FSB and GCB samples. A receiver-operator characteristic curve (ROC) analysis was performed to determine an optimal GCB HbA1c criterion value for a positive diabetes screen. Results: For the 75 paired samples, the Pearson correlation coefficient was 0.842. The ROC analysis identified a criterion value of 6.3% for the GCB HbA1c test with high sensitivity (0.933) and high specificity (0.900), corresponding to FSB HbA1c values ‡6.5% (in the diabetes range). Using this GCB HbA1c criterion value for 27 additional paired samples, in which there was an unidentified component observed to coelute within the elution window of GCB HbA1c in the laboratory, there was agreement between FSB and GCB values for 24 of the pairs according to whether both were within or outside of the diabetes range. Conclusion: Using a criterion value of 6.3%, GCB samples are acceptable for HbA1c testing to screen for diabetes in most persons with BOP at the GCB collection site.
The purpose of this study was to establish the feasibility and utility of screening for elder mis... more The purpose of this study was to establish the feasibility and utility of screening for elder mistreatment in a dental clinic population. We approached older adults in a busy dental clinic, and enrolled 139 persons over the age of 65 who completed an Audio Computer Assisted Self Interview (ACASI), which included the Hwalek-Sengstock Elder Abuse Screening Test (HS-EAST). Overall, 48.4% of the participants scored 3 or greater on the HS-EAST, and 28.3% scored 4 or greater. Our study suggests that there is an opportunity to screen in busy dental clinics and to facilitate early detection for those patients who screen positive for elder mistreatment.
BackgroundThe Covid-19 pandemic began in China in December 2019. India is the second most affecte... more BackgroundThe Covid-19 pandemic began in China in December 2019. India is the second most affected country, as of November 2020 with more than 8.5million cases. Covid-19 infection primarily involves the lung with severity of illness varying from influenza-like illness to acute respiratory distress syndrome. Other organs have also found to be variably affected. Studies evaluating the histopathological changes of Covid-19 are critical in providing a better understanding of the disease pathophysiology and guiding treatment. Minimally invasive biopsy techniques (MITS/B) provide an easy and suitable alternative to complete autopsies. In this prospective single center study we present the histopathological examination of 37 patients who died with complications of Covid-19.MethodsThis was an observational study conducted in the Intensive Care Unit of JPN Trauma Centre AIIMS. A total of 37 patients who died of Covid-19 were enrolled in the study. Post-mortem percutaneous biopsies were taken...
Angiotensin-converting enzyme 2 (ACE2) is a key host protein by which severe acute respiratory sy... more Angiotensin-converting enzyme 2 (ACE2) is a key host protein by which severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters and multiplies within cells. The level of ACE2 expression in the lung is hypothesised to correlate with an increased risk of severe infection and complications in COVID-19 (COrona VIrus Disease 2019). To test this hypothesis, we compared the protein expression status of ACE2 by immunohistochemistry (IHC) in post-mortem lung samples of patients who died of severe COVID-19 and lung samples obtained from non-COVID-9 patients for other indications. IHC for CD61 and CD163 were performed for assessment of platelet-rich microthrombi and macrophages, respectively. IHC for SARS-CoV-2 viral antigen was also performed. Quantification of immunostaining, random sampling, and correlation analysis was used to substantiate the morphologic findings. Our results show that among a total of 44 COVID-19 post-mortem lung tissues and 15 lung biopsies in non-COVID-19 pat...
Introduction: The majority of primary membranous nephropathy (MN) cases are no longer considered ... more Introduction: The majority of primary membranous nephropathy (MN) cases are no longer considered idiopathic with the discovery of the podocytic autoantigens: phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain-containing 7A (THSD7A). Limited data on PLA2R-related MN in Indians exist in literature, and THSD7A-related MN remains undocumented in this population. We aimed to characterize the baseline PLA2R and THSD7A profile of adult and pediatric membranous nephropathy (MN) in a large Indian single-institution cohort. Methods: A retrospective analysis of all cases of MN (primary and secondary) between 2014 and 2017 was performed with PLA2R direct immunofluorescence and THSD7A immunohistochemistry on the biopsies and anti-PLA2R enzyme-linked immunosorbent assay (ELISA) on baseline sera. Results: MN constituted 10% of kidney biopsies received in the study period. A total of 216 cases with adequate tissue underwent PLA2R direct immunofluorescence, and 110 of them had available sera for PLA2R ELISA. Combining both testing methods, the prevalence of PLA2R-related primary MN was 72.8%, with moderate concordance between the 2 methods (kappa 0.61). PLA2R was also detected in 16.7% cases of secondary MN, most commonly lupus MN. THSD7A immunohistochemistry performed on 176 cases showed a prevalence of 3.4% in primary MN. One case of lupus MN was also positive for THSD7A. Dual positivity (PLA2R and THSD7A) was noted in 2 cases. The large pediatric cohort tested showed a prevalence of 44% of PLA2R based on tissue testing, whereas 1 case demonstrated THSD7A positivity. Conclusion: This study in a large cohort of Indian patients demonstrates prevalence rates of PLA2R-and THSD7A-related MN similar to world literature, including the substantial cohort of pediatric MN. It also confirms variation in MN in the form of outliers within PLA2R (related to tissue and serum testing), dual positivity for PLA2R and THSD7A, and PLA2R/THSD7A-positive secondary MN.
International Journal Of Community Medicine And Public Health, 2020
Background: Anemia in pregnancy remains a public health problem and is an important indirect caus... more Background: Anemia in pregnancy remains a public health problem and is an important indirect cause of maternal mortality accounting for 20% of total maternal deaths in India. However, it is largely preventable and easily treatable. Since, decades, the Government of India has recommended iron folic acid (IFA) supplementation as prophylaxis but adherence to IFA tablets is invariably poor. Health education of antenatal women can be an effective tool for improvement in IFA consumption and compliance. Thus, this study was conducted to assess the problem of anemia and its epidemiological determinants among pregnant women in rural field practice area of Punjab as well as to evaluate the compliance and utilization of IFA tablets before and after the health education intervention.Methods: Author filled in the predesigned and pretested proforma and imparted health education to all the pregnant women who were then followed. Hb was estimated on two different occasions, before and after the inte...
Background IgA nephropathy(IgAN) is a common glomerular disease with a higher risk of progression... more Background IgA nephropathy(IgAN) is a common glomerular disease with a higher risk of progression to end stage renal disease (ESRD) in certain ethnic populations. Since galactose deficient IgA1(Gd-IgA1) is a critical molecule in its pathogenesis, it has generated interest as a biomarker for this disease. Methods We measured serum Gd-IgA1 levels using a non-lectin based enzyme linked immunoassay (ELISA) in 136 immunosuppression naïve patients with primary IgAN and 110 controls(60non IgA glomerular diseases, 50-healthy volunteers). Results Median serum Gd-IgA1 levels were significantly higher in IgAN patients [13135.6(2723.3, 59603.8)ng/ml] compared to those with non IgA glomerular disease [4954.8(892.9,18256.2) ng/ml] and healthy controls [6299.5(1993.2,19256) ng/ml] and this was observed even after log transformation and adjustment for age and gender(p<0.0001). Considering a cutoff value of serum Gd-IGA1�7982.1ng/ml, the sensitivity for diagnosing IgAN compared to healthy controls was 74.3% and specificity was 72.0% with a positive predictive value of 87.8% and negative predictive value of 50.7%. The serum Gd-IgA1 level did not co-relate with baseline estimated glomerular filtration rate, urine protein creatinine ratio and the M, E, S, T and C scores on renal biopsy. The renal survival (absence of >30% decrease in eGFR, ESRD or death) was lower in patients with higher serum Gd-IgA1 levels(�7982ng/ml) than those who had lower levels but it was not statistically significant(p = 0.486).
Introduction: C4d, an early product in the classical/lectin complement pathway has shown potentia... more Introduction: C4d, an early product in the classical/lectin complement pathway has shown potential in the evaluation of C3 glomerulopathy where its absence would support an alternative pathway abnormality. As autoimmune/genetic complement testing is not readily available to most parts of the world, glomerular C4d staining may serve as a useful additional step toward the diagnosis. Methods: To test this hypothesis, C4d staining was performed on a large cohort of C3 glomerulopathy. Archival cases from 2011 to 2017 were reviewed and immunohistochemistry for C4d was performed, scored (scale of 0 to 3þ), and correlated with the immunofluorescence and ultrastructural findings. Paraffin immunofluorescence was performed in cases of "discordant C4d" to unmask Igs. Results: Twenty-seven cases of dense deposit disease (DDD) and 14 cases of C3 glomerulonephritis (C3GN) were retrieved. C4d demonstrated a range of staining intensities with negative/traces in only 22% of DDD and 64% of C3GN. Lower-intensity C4d staining (1 to 2þ) was mostly concordant with similar amounts of Igs/C1q. Discordant 3þ staining was noted in approximately 50% of cases of DDD and 20% of cases of C3GN. Among them, paraffin immunofluorescence unmasked polyclonal Igs in 2 of 5 cases of DDD and 1 of 3 cases of C3GN. Conclusion: This observational study suggests that the presence of glomerular C4d should not exclude a C3 glomerulopathy. In lower intensities, it appears to represent overlying classical/lectin pathway activation with concordant Ig/C1q deposits. A subset of cases, however, displays intense and discordant C4d staining, which raises the possibility of an associated lectin pathway abnormality, a potential future area of study.
Background: Persistent significant proteinuria has been associated with increased risk of progres... more Background: Persistent significant proteinuria has been associated with increased risk of progression to end-stage kidney disease in patients with idiopathic membranous nephropathy (IMN). Rituximab (RTX) therapy has given encouraging results in IMN, but most of the studies have used a higher dose, which is limited by the high cost as well as a potential increased risk of infections. Our study aimed to assess the efficacy and safety of low-dose RTX in patients with immunosuppression-resistant IMN. Methods: A total of 21 patients with treatment-resistant IMN treated with RTX from 2015 to 2016 at our center were included in the study. They received two doses of RTX (500 mg each) infusion 7 days apart. CD19 count was performed after 4 weeks. A single dose of RTX was repeated after 4-6 weeks if CD19 count was not depleted. Results: The mean standard deviation age of patients was 33.3 6 12.3 years and 33.3% were females. Mean proteinuria before RTX therapy was 6.2 6 2.2 g/day, serum creatinine was 0.9 6 0.3 mg/dL and estimated glomerular filtration rate (eGFR) was 95.8 6 26.9 mL/min/1.73 m 2. All the patients were non-responders to prior immunosuppressive treatment. Twenty (95.2%) patients achieved targeted CD19 depletion with two doses of RTX. One patient required one additional RTX dose due to inadequate B-cell suppression. A total of 13 (61.9%) patients achieved remission with RTX therapy: 4 (19.0%) complete and 9 (42.9%) partial remission. Patients who did not respond to RTX had a significantly lower baseline eGFR compared with those who achieved remission (P ¼ 0.022). One patient developed respiratory tract infection following RTX during the follow-up, which responded to a course of oral antibiotics. During median follow-up of 13.1 (10-23.9) months, four (19%) patients had deterioration in renal function and one patient relapsed after achieving partial remission. Renal survival was significantly better in patients who responded to RTX therapy as compared with those who did not achieve remission (P ¼ 0.0037). Conclusion: Low-dose RTX therapy is effective and safe in immunosuppression-resistant IMN.
Journal of the American Society of Nephrology : JASN, Jan 11, 2015
Dense deposit disease is caused by fluid-phase dysregulation of the alternative complement pathwa... more Dense deposit disease is caused by fluid-phase dysregulation of the alternative complement pathway and frequently deviates from the classic membranoproliferative pattern of injury on light microscopy. Other patterns of injury described for dense deposit disease include mesangioproliferative, acute proliferative/exudative, and crescentic GN. Regardless of the histologic pattern, C3 glomerulopathy, which includes dense deposit disease and C3 GN, is defined by immunofluorescence intensity of C3c two or more orders of magnitude greater than any other immune reactant (on a 0-3 scale). Ultrastructural appearances distinguish dense deposit disease and C3 GN. Focal and segmental necrotizing glomerular lesions with crescents, mimicking a small vessel vasculitis such as ANCA-associated GN, are a very rare manifestation of dense deposit disease. We describe our experience with this unusual histologic presentation and distinct clinical course of dense deposit disease, discuss the pitfalls in di...
Journal of dental hygiene : JDH / American Dental Hygienists' Association, 2013
Although there is a bidirectional relationship between periodontal disease and diabetes, little i... more Although there is a bidirectional relationship between periodontal disease and diabetes, little is known about the diabetes-related knowledge of periodontal patients. This study examines what patients with periodontal disease know about diabetes and its association with periodontitis. It also examines their sources of diabetes-related information. Patients (n=111) with or at risk for diabetes who were receiving care at a university-based periodontics and implant clinic completed a written survey assessing their socio-demographic characteristics, health-related activities, diabetes knowledge and sources of diabetes-related information. Survey results were summarized using descriptive statistics. Fisher's exact tests were used to compare patients who had and had not been diagnosed with diabetes according to responses on diabetes-related knowledge items and sources of diabetes information. Although respondents endorsed various diabetes-related information sources, including family ...
Introduction: The term monoclonal gammopathy of renal significance (MGRS) has been described to i... more Introduction: The term monoclonal gammopathy of renal significance (MGRS) has been described to include patients with renal manifestations associated with circulating monoclonal proteins with or without a clonal lymphoproliferation (B-cell or plasma cell) and not meeting diagnostic criteria for an overt hematological malignancy. A host of MGRS-associated lesions have been described that involve various renal compartments. Our study describes the histomorphological spectrum of MGRS cases at our center in the last 5 years and description as per the classification system of the International Kidney and Monoclonal Gammopathy Research Group (IKMG). Material and Methods: Retrospective analysis was carried out of all the renal biopsies with characteristic monoclonal immunoglobulin lesions for histopathological diagnosis between years 2015 and 2020 and reviewed by two independent pathologists. Results: Most patients in the study belonged to the fifth decade, with a median age of 50 years (m...
ABSTRACT Objectives To study the histopathology of patients dying of COVID-19 using post-mortem m... more ABSTRACT Objectives To study the histopathology of patients dying of COVID-19 using post-mortem minimally invasive sampling techniques. Methods This was a single-center observational study conducted at JPNATC, AIIMS. Thirty-seven patients who died of COVID-19 were enrolled. Post-mortem percutaneous biopsies were taken from lung, heart, liver, kidney and stained with hematoxylin and eosin. Immunohistochemistry was performed using CD61 and CD163. SARS-CoV-2 virus was detected using IHC with primary antibodies. Results The mean age was 48.7 years and 59.5% were males. Lung histopathology showed diffuse alveolar damage in 78% patients. Associated bronchopneumonia was seen in 37.5% and scattered microthrombi in 21% patients. Immunopositivity for SARS-CoV-2 was observed in Type II pneumocytes. Acute tubular injury with epithelial vacuolization was seen in 46% of renal biopsies. Seventy-one percent of liver biopsies showed Kupffer cell hyperplasia and 27.5% showed submassive hepatic necrosis. Conclusions Predominant finding was diffuse alveolar damage with demonstration of SARS-CoV-2 protein in the acute phase. Microvascular thrombi were rarely identified in any organ. Substantial hepatocyte necrosis, Kupffer cell hypertrophy, microvesicular, and macrovesicular steatosis unrelated to microvascular thrombi suggested that liver might be a primary target of COVID-19.
Indian Journal of Medical and Paediatric Oncology, 2018
Background: The incidence of renal cell cancer (RCC) is increasing worldwide. However, scant info... more Background: The incidence of renal cell cancer (RCC) is increasing worldwide. However, scant information is available from the Indian subcontinent regarding its clinicopathological characteristics and survival outcomes. We retrospectively analyzed data of patients suffering from RCC at our center over the last one decade (2004–2013) to generate information on these aspects. Materials and Methods: Case records of 423 patients treated between 2004 and 2013 were retrospectively analyzed. Baseline characteristics, histopathological information, and survival outcomes were assessed. Overall survival was calculated from the time of diagnosis to death due to any cause. Results: The median age was 52 years (range: 18–87 years). Male: female ratio was 3.5:1. The median duration of symptoms was 3 months (range: 0–24 months). Thirty-five patients (8.3%) were detected in asymptomatic state. The most common symptom was hematuria (53.2%) followed by flank pain (46.3%). The most common histology was clear cell subtype (71.4%). Two hundred and ninety-three (69.3%) patients presented with nonmetastatic disease whereas 130 (30.7%) had upfront metastatic disease. Five-year survival in Stages 1, 2, 3, and 4 was 92.7%, 72.9%, 54.6%, and 11.5%, respectively. Conclusion: Younger age, higher male–female ratio, lower proportion of asymptomatic patients, higher proportion of advanced stage at diagnosis, and lower stage-wise survival were some of the key findings.
AJR. American journal of roentgenology, Jan 24, 2018
The primary objective of this study was to compare triple-bolus dual-energy CT (DECT) against sta... more The primary objective of this study was to compare triple-bolus dual-energy CT (DECT) against standard triple-phase MDCT in terms of appropriateness of patient treatment. One hundred twenty-four patients with suspected renal masses seen at ultrasound were randomized into triple-bolus DECT and triple-phase MDCT groups. Patients in the triple-bolus DECT group underwent synchronous corticomedullary nephrographic delayed-phase triple-bolus DECT. In the triple-phase MDCT group, single-energy triple-phase scans were acquired after an unenhanced scan. The primary outcome was appropriateness of treatment received at 1 year. The predefined noninferiority limit was 10%. Histopathologic analysis or follow-up confirmed the benign or malignant nature of the masses. Diagnostic accuracy to differentiate benign from malignant masses was calculated. Size-specific dose estimates were compared. After excluding six patients, 118 patients were analyzed (62 triple-bolus DECT; 56 triple-phase MDCT). Treat...
Institutional review board statement: This study was not required to provide institutional review... more Institutional review board statement: This study was not required to provide institutional review board statement because the material used were fresh frozen tissue. Informed consent statement: This study was not required to provide informed consent statement because the material used were fresh frozen tissue.
Infections by dematiaceous fungi are an emerging group of infectious diseases worldwide with a va... more Infections by dematiaceous fungi are an emerging group of infectious diseases worldwide with a variety of clinical presentations. Though generally localized, they can disseminate in immunocompromised settings, therefore, early diagnosis and prompt therapy can prevent significant morbidity and mortality in these patients. Fungi of genus Exophiala are common causative organisms; however, Exophiala jeanselmei (E. jeanselmei) has not yet been reported from environmental sources in India. We present here the case of a renal transplant recipient who presented with an innocuous lesion on the foot, diagnosed on fine needle aspiration cytology (FNAC) as phaeohyphomycosis, and promptly treated with excision and antifungal therapy. To the best of our knowledge, this is the first case report from India of E. jeanselmei causing phaeohyphomycosis in a transplant recipient and highlights the role a cytopathologist can play in the timely management of such cases.
Dear Editor, We read with great interest the case report by Roy et al in the October 2012 issue o... more Dear Editor, We read with great interest the case report by Roy et al in the October 2012 issue of the International Journal of Surgical Pathology. We recently encountered an interesting renal tumor in a 40-year-old woman who underwent a radical nephrectomy. Grossly, the tumor was located in the upper pole, measured 12 × 9 × 7cm and had a fleshy graywhite cut surface (Figure 1A). Thorough sectioning revealed an encapsulated tumor composed of tall columnar cells arranged in tubules separated by fibrovascular septae (Figure 1B). The cells had basally located monomorphic nuclei with smooth nuclear contours, bland chromatin, and conspicuous nucleoli. Cytoplasm was pale to clear (Figure 1C and D). No mitotic activity or necrosis was identified. The overlying capsule, perinephric fat, renal sinus, hilar vessels, and ureter were free of the tumor. Our initial impression was of a renal carcinoid. On immunohistochemistry, the tumor cells were immunopositive for epithelial membrane antigen and cytokeratin 7 (Figure 2A and B) and were negative for chromogranin, synaptophysin, CD 56, vimentin, CD 10, CD 99, and CD 117. The MIB-1 labeling index was 2%. At this point, further sectioning revealed focal areas with a trabecular arrangement of cells with clear cytoplasm, few perinuclear halos and prominent cell borders, features more classically seen in chromophobe renal cell carcinoma (RCC; Figure 1E]. Performing Hale’s colloidal iron demonstrated the intracytoplasmic acid mucopolysaccharides (Figure 1F) and electron microscopy confirmed the presence of cytoplasmic vesicles consistent with the ultrastructure of chromophobe RCC (Figure 2C and D). No abnormal mitochondria or dense core neurosecretory granules were identified. We were therefore dealing with a chromophobe RCC with a nearly complete tubular architecture. Chromophobe RCC is recognized as a distinct subtype of RCC, with a less aggressive clinical behavior compared with conventional RCCs. The classical appearance is that of solid sheets of tumor cells separated by incomplete vascular septae. Predominantly tubular architecture is rare and has been described as a “nonclassical” architectural pattern by Przybycin et al in their study on 203 chromophobe RCCs, which also included nested, acinar, solid-acinar, papillary, trabecular, and sarcomatoid patterns, representing 29% of all the cases. Though these patterns are not of prognostic importance, they can lead to diagnostic confusion as seen in our case where the tumor resembled a neuroendocrine tumor. Unlike classical chromophobe RCCs, such tumors will require ancillary diagnostic techniques, including immunohistochemistry and electron microscopy to reach the correct diagnosis.
Introduction: Anti-GBM nephritis in the pediatric age group is exceedingly rare with concurrent a... more Introduction: Anti-GBM nephritis in the pediatric age group is exceedingly rare with concurrent additional pathologies being even rarer. Tissue diagnosis requires a combination of crescentic histomorphology, immunofluorescence showing “paint brush stroke” pattern of linear IgG or rarely IgA, and serum anti-GBM antibodies subject to the disease course and treatment. The authors describe one such case with a dual pathology involving IgA nephropathy and atypical anti-GBM disease. Case Presentation: A 13-year-old girl presenting with features of rapidly progressive glomerulonephritis underwent a renal biopsy showing a mesangioproliferative histology with crescents and an immunofluorescence pattern indicating a dual pathology of IgA nephropathy and anti-GBM nephritis. Additional ancillary testing including staining for IgG subclasses and galactose-deficient IgA (KM55) helped to confirm the diagnosis. She responded to steroid pulses and plasma exchange therapy, was off dialysis after 8 we...
Background: This pilot study examines whether a novel diabetes screening approach using gingival ... more Background: This pilot study examines whether a novel diabetes screening approach using gingival crevicular blood (GCB) could be used to test for hemoglobin A1c (HbA1c) during periodontal visits. Methods: Finger-stick blood (FSB) samples from 120 patients and GCB samples from those patients with adequate bleeding on probing (BOP) were collected on special blood collection cards and analyzed for HbA1c levels in a laboratory. The Pearson correlation coefficient was used to measure correlation between FSB and GCB HbA1c values for 75 paired FSB and GCB samples. A receiver-operator characteristic curve (ROC) analysis was performed to determine an optimal GCB HbA1c criterion value for a positive diabetes screen. Results: For the 75 paired samples, the Pearson correlation coefficient was 0.842. The ROC analysis identified a criterion value of 6.3% for the GCB HbA1c test with high sensitivity (0.933) and high specificity (0.900), corresponding to FSB HbA1c values ‡6.5% (in the diabetes range). Using this GCB HbA1c criterion value for 27 additional paired samples, in which there was an unidentified component observed to coelute within the elution window of GCB HbA1c in the laboratory, there was agreement between FSB and GCB values for 24 of the pairs according to whether both were within or outside of the diabetes range. Conclusion: Using a criterion value of 6.3%, GCB samples are acceptable for HbA1c testing to screen for diabetes in most persons with BOP at the GCB collection site.
The purpose of this study was to establish the feasibility and utility of screening for elder mis... more The purpose of this study was to establish the feasibility and utility of screening for elder mistreatment in a dental clinic population. We approached older adults in a busy dental clinic, and enrolled 139 persons over the age of 65 who completed an Audio Computer Assisted Self Interview (ACASI), which included the Hwalek-Sengstock Elder Abuse Screening Test (HS-EAST). Overall, 48.4% of the participants scored 3 or greater on the HS-EAST, and 28.3% scored 4 or greater. Our study suggests that there is an opportunity to screen in busy dental clinics and to facilitate early detection for those patients who screen positive for elder mistreatment.
BackgroundThe Covid-19 pandemic began in China in December 2019. India is the second most affecte... more BackgroundThe Covid-19 pandemic began in China in December 2019. India is the second most affected country, as of November 2020 with more than 8.5million cases. Covid-19 infection primarily involves the lung with severity of illness varying from influenza-like illness to acute respiratory distress syndrome. Other organs have also found to be variably affected. Studies evaluating the histopathological changes of Covid-19 are critical in providing a better understanding of the disease pathophysiology and guiding treatment. Minimally invasive biopsy techniques (MITS/B) provide an easy and suitable alternative to complete autopsies. In this prospective single center study we present the histopathological examination of 37 patients who died with complications of Covid-19.MethodsThis was an observational study conducted in the Intensive Care Unit of JPN Trauma Centre AIIMS. A total of 37 patients who died of Covid-19 were enrolled in the study. Post-mortem percutaneous biopsies were taken...
Angiotensin-converting enzyme 2 (ACE2) is a key host protein by which severe acute respiratory sy... more Angiotensin-converting enzyme 2 (ACE2) is a key host protein by which severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters and multiplies within cells. The level of ACE2 expression in the lung is hypothesised to correlate with an increased risk of severe infection and complications in COVID-19 (COrona VIrus Disease 2019). To test this hypothesis, we compared the protein expression status of ACE2 by immunohistochemistry (IHC) in post-mortem lung samples of patients who died of severe COVID-19 and lung samples obtained from non-COVID-9 patients for other indications. IHC for CD61 and CD163 were performed for assessment of platelet-rich microthrombi and macrophages, respectively. IHC for SARS-CoV-2 viral antigen was also performed. Quantification of immunostaining, random sampling, and correlation analysis was used to substantiate the morphologic findings. Our results show that among a total of 44 COVID-19 post-mortem lung tissues and 15 lung biopsies in non-COVID-19 pat...
Introduction: The majority of primary membranous nephropathy (MN) cases are no longer considered ... more Introduction: The majority of primary membranous nephropathy (MN) cases are no longer considered idiopathic with the discovery of the podocytic autoantigens: phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain-containing 7A (THSD7A). Limited data on PLA2R-related MN in Indians exist in literature, and THSD7A-related MN remains undocumented in this population. We aimed to characterize the baseline PLA2R and THSD7A profile of adult and pediatric membranous nephropathy (MN) in a large Indian single-institution cohort. Methods: A retrospective analysis of all cases of MN (primary and secondary) between 2014 and 2017 was performed with PLA2R direct immunofluorescence and THSD7A immunohistochemistry on the biopsies and anti-PLA2R enzyme-linked immunosorbent assay (ELISA) on baseline sera. Results: MN constituted 10% of kidney biopsies received in the study period. A total of 216 cases with adequate tissue underwent PLA2R direct immunofluorescence, and 110 of them had available sera for PLA2R ELISA. Combining both testing methods, the prevalence of PLA2R-related primary MN was 72.8%, with moderate concordance between the 2 methods (kappa 0.61). PLA2R was also detected in 16.7% cases of secondary MN, most commonly lupus MN. THSD7A immunohistochemistry performed on 176 cases showed a prevalence of 3.4% in primary MN. One case of lupus MN was also positive for THSD7A. Dual positivity (PLA2R and THSD7A) was noted in 2 cases. The large pediatric cohort tested showed a prevalence of 44% of PLA2R based on tissue testing, whereas 1 case demonstrated THSD7A positivity. Conclusion: This study in a large cohort of Indian patients demonstrates prevalence rates of PLA2R-and THSD7A-related MN similar to world literature, including the substantial cohort of pediatric MN. It also confirms variation in MN in the form of outliers within PLA2R (related to tissue and serum testing), dual positivity for PLA2R and THSD7A, and PLA2R/THSD7A-positive secondary MN.
International Journal Of Community Medicine And Public Health, 2020
Background: Anemia in pregnancy remains a public health problem and is an important indirect caus... more Background: Anemia in pregnancy remains a public health problem and is an important indirect cause of maternal mortality accounting for 20% of total maternal deaths in India. However, it is largely preventable and easily treatable. Since, decades, the Government of India has recommended iron folic acid (IFA) supplementation as prophylaxis but adherence to IFA tablets is invariably poor. Health education of antenatal women can be an effective tool for improvement in IFA consumption and compliance. Thus, this study was conducted to assess the problem of anemia and its epidemiological determinants among pregnant women in rural field practice area of Punjab as well as to evaluate the compliance and utilization of IFA tablets before and after the health education intervention.Methods: Author filled in the predesigned and pretested proforma and imparted health education to all the pregnant women who were then followed. Hb was estimated on two different occasions, before and after the inte...
Background IgA nephropathy(IgAN) is a common glomerular disease with a higher risk of progression... more Background IgA nephropathy(IgAN) is a common glomerular disease with a higher risk of progression to end stage renal disease (ESRD) in certain ethnic populations. Since galactose deficient IgA1(Gd-IgA1) is a critical molecule in its pathogenesis, it has generated interest as a biomarker for this disease. Methods We measured serum Gd-IgA1 levels using a non-lectin based enzyme linked immunoassay (ELISA) in 136 immunosuppression naïve patients with primary IgAN and 110 controls(60non IgA glomerular diseases, 50-healthy volunteers). Results Median serum Gd-IgA1 levels were significantly higher in IgAN patients [13135.6(2723.3, 59603.8)ng/ml] compared to those with non IgA glomerular disease [4954.8(892.9,18256.2) ng/ml] and healthy controls [6299.5(1993.2,19256) ng/ml] and this was observed even after log transformation and adjustment for age and gender(p<0.0001). Considering a cutoff value of serum Gd-IGA1�7982.1ng/ml, the sensitivity for diagnosing IgAN compared to healthy controls was 74.3% and specificity was 72.0% with a positive predictive value of 87.8% and negative predictive value of 50.7%. The serum Gd-IgA1 level did not co-relate with baseline estimated glomerular filtration rate, urine protein creatinine ratio and the M, E, S, T and C scores on renal biopsy. The renal survival (absence of >30% decrease in eGFR, ESRD or death) was lower in patients with higher serum Gd-IgA1 levels(�7982ng/ml) than those who had lower levels but it was not statistically significant(p = 0.486).
Introduction: C4d, an early product in the classical/lectin complement pathway has shown potentia... more Introduction: C4d, an early product in the classical/lectin complement pathway has shown potential in the evaluation of C3 glomerulopathy where its absence would support an alternative pathway abnormality. As autoimmune/genetic complement testing is not readily available to most parts of the world, glomerular C4d staining may serve as a useful additional step toward the diagnosis. Methods: To test this hypothesis, C4d staining was performed on a large cohort of C3 glomerulopathy. Archival cases from 2011 to 2017 were reviewed and immunohistochemistry for C4d was performed, scored (scale of 0 to 3þ), and correlated with the immunofluorescence and ultrastructural findings. Paraffin immunofluorescence was performed in cases of "discordant C4d" to unmask Igs. Results: Twenty-seven cases of dense deposit disease (DDD) and 14 cases of C3 glomerulonephritis (C3GN) were retrieved. C4d demonstrated a range of staining intensities with negative/traces in only 22% of DDD and 64% of C3GN. Lower-intensity C4d staining (1 to 2þ) was mostly concordant with similar amounts of Igs/C1q. Discordant 3þ staining was noted in approximately 50% of cases of DDD and 20% of cases of C3GN. Among them, paraffin immunofluorescence unmasked polyclonal Igs in 2 of 5 cases of DDD and 1 of 3 cases of C3GN. Conclusion: This observational study suggests that the presence of glomerular C4d should not exclude a C3 glomerulopathy. In lower intensities, it appears to represent overlying classical/lectin pathway activation with concordant Ig/C1q deposits. A subset of cases, however, displays intense and discordant C4d staining, which raises the possibility of an associated lectin pathway abnormality, a potential future area of study.
Background: Persistent significant proteinuria has been associated with increased risk of progres... more Background: Persistent significant proteinuria has been associated with increased risk of progression to end-stage kidney disease in patients with idiopathic membranous nephropathy (IMN). Rituximab (RTX) therapy has given encouraging results in IMN, but most of the studies have used a higher dose, which is limited by the high cost as well as a potential increased risk of infections. Our study aimed to assess the efficacy and safety of low-dose RTX in patients with immunosuppression-resistant IMN. Methods: A total of 21 patients with treatment-resistant IMN treated with RTX from 2015 to 2016 at our center were included in the study. They received two doses of RTX (500 mg each) infusion 7 days apart. CD19 count was performed after 4 weeks. A single dose of RTX was repeated after 4-6 weeks if CD19 count was not depleted. Results: The mean standard deviation age of patients was 33.3 6 12.3 years and 33.3% were females. Mean proteinuria before RTX therapy was 6.2 6 2.2 g/day, serum creatinine was 0.9 6 0.3 mg/dL and estimated glomerular filtration rate (eGFR) was 95.8 6 26.9 mL/min/1.73 m 2. All the patients were non-responders to prior immunosuppressive treatment. Twenty (95.2%) patients achieved targeted CD19 depletion with two doses of RTX. One patient required one additional RTX dose due to inadequate B-cell suppression. A total of 13 (61.9%) patients achieved remission with RTX therapy: 4 (19.0%) complete and 9 (42.9%) partial remission. Patients who did not respond to RTX had a significantly lower baseline eGFR compared with those who achieved remission (P ¼ 0.022). One patient developed respiratory tract infection following RTX during the follow-up, which responded to a course of oral antibiotics. During median follow-up of 13.1 (10-23.9) months, four (19%) patients had deterioration in renal function and one patient relapsed after achieving partial remission. Renal survival was significantly better in patients who responded to RTX therapy as compared with those who did not achieve remission (P ¼ 0.0037). Conclusion: Low-dose RTX therapy is effective and safe in immunosuppression-resistant IMN.
Journal of the American Society of Nephrology : JASN, Jan 11, 2015
Dense deposit disease is caused by fluid-phase dysregulation of the alternative complement pathwa... more Dense deposit disease is caused by fluid-phase dysregulation of the alternative complement pathway and frequently deviates from the classic membranoproliferative pattern of injury on light microscopy. Other patterns of injury described for dense deposit disease include mesangioproliferative, acute proliferative/exudative, and crescentic GN. Regardless of the histologic pattern, C3 glomerulopathy, which includes dense deposit disease and C3 GN, is defined by immunofluorescence intensity of C3c two or more orders of magnitude greater than any other immune reactant (on a 0-3 scale). Ultrastructural appearances distinguish dense deposit disease and C3 GN. Focal and segmental necrotizing glomerular lesions with crescents, mimicking a small vessel vasculitis such as ANCA-associated GN, are a very rare manifestation of dense deposit disease. We describe our experience with this unusual histologic presentation and distinct clinical course of dense deposit disease, discuss the pitfalls in di...
Journal of dental hygiene : JDH / American Dental Hygienists' Association, 2013
Although there is a bidirectional relationship between periodontal disease and diabetes, little i... more Although there is a bidirectional relationship between periodontal disease and diabetes, little is known about the diabetes-related knowledge of periodontal patients. This study examines what patients with periodontal disease know about diabetes and its association with periodontitis. It also examines their sources of diabetes-related information. Patients (n=111) with or at risk for diabetes who were receiving care at a university-based periodontics and implant clinic completed a written survey assessing their socio-demographic characteristics, health-related activities, diabetes knowledge and sources of diabetes-related information. Survey results were summarized using descriptive statistics. Fisher's exact tests were used to compare patients who had and had not been diagnosed with diabetes according to responses on diabetes-related knowledge items and sources of diabetes information. Although respondents endorsed various diabetes-related information sources, including family ...
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