Kidney histopathology in predicting flares following drug withdrawal in proliferative lupus nephritis in clinical remission.

Residual renal histopathological activity at clinical remission in Proliferative Lupus Nephritis (PLN) can predict renal flare upon immunosuppression withdrawal. Data on the role of histological renal remission in predicting extra-renal flares is lacking. We assessed renal histopathology prior to drug withdrawal and the occurrence of renal and extra-renal flares over 52 weeks after drug withdrawal in PLN patients in long-term clinical remission. This is a subgroup analysis of a non-inferiority, open-label randomized (1:1) controlled trial. Patients with biopsy-proven Class III/IV LN in the past (biopsy 1), on immunosuppressants (IS) ≥ 3 years, in clinical remission for ≥ 1 year, on stable prednisolone dose (≤ 7.5 mg/day) plus a maintenance IS and hydroxychloroquine (HCQ) were subjected to a repeat renal biopsy (biopsy 2). Individuals with biopsy 2 having activity index (AI) < 4/24 were randomised to either prednisolone or IS withdrawal. Primary end-point was the proportion experiencing a flare [SELENA-SLEDAI flare index (SFI)] at week 52. Twenty-eight eligible patients underwent biopsy 2 and randomized to prednisolone (n = 15) and IS (n = 13) withdrawal. At biopsy 1, 12 (43%) had class III, 15 (53.5%) had class IV, and 1 (3.5%) had class III + V. At biopsy 2, PLN persisted in 4 (14.2%) while 18 (64.2%) were in histological remission (AI = 0) with 6 (21.4%) in class II. Following drug withdrawal, 9/28 (32%) had flares especially musculoskeletal (55.5%), mucocutaneous (44.4%), and renal (33.3%). Among the four persistent PLN patients, one of the two (50%) with AI = 1 had extra-renal flare while both the two with AI = 2 (100%) had renal and extra-renal flares. In those with histological remission (biopsy 2), 6/18 (66.6%) experienced extra-renal flare of whom one also had renal flare. Upon drug withdrawal, renal histopathology findings with any activity index can predict renal flare while histological remission is not enough to predict extra-renal flare, thus making it an unsuitable marker for deep SLE remission.

Nimbolide attenuates gut dysbiosis and prevents bacterial translocation by improving intestinal barrier integrity and ameliorating inflammation in hepatocellular carcinoma.

Gut microbiota imbalance plays a key pathological role in hepatocellular carcinoma (HCC) progression; however, the mechanism is poorly understood. We previously showed nimbolide impede tumor development by improving hepatic tight junction (TJ) proteins expression and attenuating inflammation in HCC mice. Here, we aimed to study the role of nimbolide in regulating gut microbiota imbalance and bacterial translocation (BT) through modulating intestinal TJ proteins in an experimental hepatocarcinogenesis. Nimbolide (6 mg/kg) was administered orally for 4 weeks following induction of HCC in mice at the 28th week. Nimbolide treatment attenuated the gut microbiota imbalance by decreasing 16 s rRNA levels of Escherichia coli, Enterococcus, Bacteroides and increasing Bifidobacterium, and Lactobacillus in the intestinal tissue, which was otherwise altered in HCC mice. Furthermore, nimbolide improved intestinal barrier integrity in HCC mice by upregulating TJ proteins such as occludin and ZO-1 expression and subsequently prevented hepatic BT and decreased BT markers such as LBP, sCD14, and procalcitonin in the plasma of HCC mice. Moreover, nimbolide ameliorated intestinal and hepatic inflammation by downregulating TLR4, MyD88, and NF-κB protein expression in HCC mice. Thus, nimbolide represents a novel therapeutic drug for HCC treatment by targeting the gut-liver axis, which plays an imperative role in HCC pathogenesis.

Neuroectodermal tumours of the sino-nasal tract: a clinicopathological study of 18 cases with a newly proposed revised classification and a brief review of literature.

AIM: Sino-nasal tract tumours constitute 3% of the head and neck malignancies. Among these tumours, neuroectodermal tumours are rare with histo-morphological and immunohistochemical overlap making them a challenge for the pathologist. We included Ewing's/PNET, olfactory neuroblastoma (OFN), mucosal malignant melanomas (MMM), Melanotic neuroectodermal tumour of infancy (MNTI), small-cell neuroendocrine carcinoma (SNEC), and the newest entity Adamantinoma like Ewing's sarcoma (ALES) as part of the neuroectodermally derived tumours of the sino-nasal tract. The last three entities were added to the existing ones, which also has been emphasized in this paper. METHODS AND RESULTS: A comprehensive analysis was done on all neuroectodermally derived tumours from 2016 to 2020. A total of 18 cases were collected, which included OFN (10 cases), SNEC (2 cases), MMM (2 cases), Ewing's/PNET (2 cases), MNTI (1 case), and ALES (1 case). The most common presentation in NE tumours was nasal obstruction (80-100%). Except for OFN, all other tumours were confined to the nasal and paranasal sinuses. 4/10 cases of OFN showed orbital extension. Cervical lymph-node metastasis was seen in 50% of cases of SNEC and MMM groups. An array of relevant immune-histochemical markers were performed. The marker expression was very subtle among the groups. On follow-up, recurrence was seen in the OFN and MMM groups in 30 and 50%, respectively. Metastasis was seen in SNEC group (100%) and OFN group (10%). CONCLUSION: As sino-nasal neuroectodermal tumours pose a diagnostic challenge and have different therapies and are prognostically different, the pathologist must be aware of the subtle morphological, immunohistochemical clues which have been dealt with in-depth in this study.

The utility of fine needle aspiration cytology in orbital haematolymphoid neoplasms.

BACKGROUND: Orbital hematolymphoid lesions are rare and usually encountered in elderly patients. Orbital lesions are not easy to biopsy: hence fine needle aspiration cytology (FNAC) can be a very good diagnostic modality for these lesions. MATERIALS AND METHODS: Cases of orbital masses subjected to FNAC dating from 2013 to 2020 were retrieved from our archives. A total of 16 cases with biopsy confirmation were included. All clinical details, the type of procedure, details of the immunocytochemistry (ICC) performed on smear, follow-up biopsy, and their haematological work-up were analysed in detail. RESULTS: Sixteen biopsy-confirmed cases had been diagnosed as orbital haematolymphoid lesions on cytomorphology and further categorised with ancillary studies including ICC. In twelve instances, the cytology impression was congruent with the histopathological diagnosis and eight of the sixteen cases (50%) proved to be primary orbital lymphoma. Four were secondary orbital lymphomas and the remaining four included one case each of plasmacytoma, myeloid sarcoma, Rosai-Dorfman disease and angiolymphoid hyperplasia with eosinophilia. CONCLUSION: FNAC is a minimally invasive procedure for diagnosing most of the haematolymphoid orbital lesions and it has a rapid turnaround time. The accuracy of cytomorphology combined with ICC on smears/cell blocks can be as good as a biopsy for exact categorisation. Additionally, aspirate smears are preferred samples for cytogenetics compared to formalin-fixed tissue blocks, as molecular cytogenetics techniques are frequently employed for diagnostic, prognostic, and therapeutic purposes.

Thoracic mucormycosis in immunocompetent patients.

BACKGROUND: Mucormycosis is an invasive fungal infection. It is rare and commonly associated with fatal outcomes. METHODS: We report two cases of thoracic mucormycosis in immunocompetent patients. First, is an immunocompetent child with mediastinal mass and extension into the pericardium and left atrium. The second is a young woman with a left pulmonary artery pseudoaneurysm. RESULTS: The first patient could not be salvaged while the second patient was successfully managed with surgical intervention and systemic antifungal treatment. CONCLUSION: Mucormycosis should be considered as a differential diagnosis in the management of immunocompetent patients in patients with pyrexia of unknown origin and a mediastinal mass. Early and aggressive surgical management along with systemic antifungal treatment improves the survival in this subset of patients.

Acenocoumarol as an alternative anticoagulant in a patient with warfarin-related nephropathy.

ADVERSE EVENT: Warfarin-related nephropathy. DRUG IMPLICATED: Warfarin. THE PATIENT: A 31-year-old female, managed with warfarin for rheumatic heart disease with atrial fibrillation. EVIDENCE THAT LINKS THE DRUG TO THE EVENT: There were no alternative causes of nephropathy that could have caused the adverse event in this patient. MANAGEMENT: Shifting the drug from warfarin to acenocoumarol. MECHANISM: Difference in renal elimination between warfarin and acenocoumarol. IMPLICATION FOR THERAPY: Clinicians should be aware of this rare adverse effect of warfarin, and acenocoumarol can be considered as an alternative therapy for this condition. HYPOTHESES TO BE TESTED: Further prospectively designed studies are needed to consider acenocoumarol as an alternative therapy in warfarin-related nephropathy.

Renal involvement in primary Sjogren's syndrome: a prospective cohort study.

The objective of the study is to prospectively evaluate the spectrum of clinical and subclinical renal involvement in patients with primary Sjogren's syndrome (pSS). Of the 174 patients screened, seventy patients with pSS underwent renal function tests, urine examination, renal ultrasound, arterial blood gases, urine pH followed by urine acidification test and renal biopsy (if indicated). Renal tubular acidosis (RTA) was treated with alkali replacement and moderate-severe tubulointerstitial nephritis (TIN) was treated with oral prednisolone. Sixty-two patients completed 1-year follow-up. A comparison was made between patients with and without renal involvement. Thirty-five (50%) patients had renal involvement. They had a lower baseline eGFR (71.85 ± 18.04 vs. 83.8 ± 17, p = 0.005). Twenty-nine patients had RTA (25 complete and 4 incomplete). Eleven patients had urinary abnormalities. Patients with RTA (n = 29) were younger (34.9 ± 9 vs. 42 ± 11.3, p = 0.006), had fewer articular (34% vs. 78%, p = 0.001) and ocular sicca (62% vs. 88%, P = 0.01) than those without RTA (n = 41) and commonly presented with hypokalemic paralysis. On biopsy, TIN (9/17) and IgA nephropathy (3/17) were most common. On follow-up, there was no clinically significant change in eGFR; however, one patient with renal calculi and incomplete distal renal tubular acidosis (dRTA) progressed to complete dRTA. Two patients treated with steroids had marginal improvement in eGFR. Renal involvement in pSS is under-recognized with the most common manifestation being RTA presenting with hypokalemic paralysis. These patients are younger with less articular and sicca symptoms. Subclinical RTA may progress to complete RTA. Renal biopsy should be considered in all patients with renal involvement.

Utility of C4d Immunohistochemistry as an Adjunct Stain in Diagnostic Renal Pathology of Glomerular Diseases.

C4d is a byproduct of the activation of the classic and lectin complement pathways. Being routinely used as a marker for antibody-mediated rejection, the significance of C4d in native kidney disease is currently being widely studied. We evaluated glomerular and extraglomerular C4d staining in 82 biopsies of proliferative and nonproliferative glomerulonephritis diagnosed in our institution. The staining pattern of C4d was tabulated in various glomerular diseases. All biopsies of membranous nephropathy including membranous lupus nephritis (Class V) and immune complex-mediated membranoproliferative glomerulonephritis (MPGN) consistently showed C4d deposits along glomerular basement membrane mirroring the location of immunoglobulin and complement in these conditions. Conversely, other glomerular diseases like IgA nephropathy, postinfectious glomerulonephritis, focal segmental glomerulosclerosis, minimal change disease, and diabetic nephropathy showed variable mesangial and capillary wall C4d deposits. To summarize, the consistent pattern of C4d staining in membranous nephropathy (primary and secondary)and immune complex-mediated MPGN can be used as a valuable adjunct tool in establishing the diagnosis, especially when immunofluorescence findings are limited by inadequate sampling.C4d reactivity in other glomerular diseases are variable and may not aid as a diagnostic tool in renal biopsy evaluation.