Hemopoietic stem cell transplantation in rheumatic diseases--an update

Hematopoietic stem cell transplant (HSCT) for autoimmune diseases has been recognized as a potential treatment for patients who have failed conventional therapy. Autologous (self) donor cells have been preferred over allogeneic (HLA-matched) cells for rescue after high dose immunotherapy, given the previous higher rates of mortality, graft versus host disease (GVHD), and the need for more intense myeloablation associated with the latter. The European Group for bone Marrow Transplantation in Basel Switzerland (EBMT) and various groups within the US funded by the NIH (including the Autologous Blood and Marrow Transplant Registry (ABMTR)) have been pivotal in maintaining registries on patients transplanted as well as promoting homogeneity for future studies including Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE) and Systemic Sclerosis (SSc). Although, patients transplanted for RA show initial success, relapse of the disease is common. In many, however, a second positive result can be obtained with the addition of DMARD therapy to which they were previously unresponsive, suggesting a "debulking" of disease by HSCT. SLE patients also have a high rate of success after HSCT, although current mortality rates appear high. Transplant in SSc patients has offered durable responses with improving transplant-related mortality related to careful patient selection.     

Course of bipolar disorder in eastern India.

The life course of affective episodes was determined for 95 consecutively admitted patients from eastern India fulfilling RDC criteria for definite mania during the current episode, using SADS-L interviews. There was a significantly greater frequency of manic compared to depressive relapses. Presentation as recurrent mania was very common. The total numbers of affective and manic episodes were significantly higher among those with recurrent mania and in cases where the first illness episode was manic.     

Cytokine induction of heat shock protein in human granulosa-luteal cells

The infiltration of leukocytes is a characteristic feature ofluteolysis in humans. Leukocytes are known to generate physiologicalinducers of cell stress such as cytokines which have been implicatedas mediators of functional luteal regression. In cells exposedto stress, a response characterized by an increase in heat shockprotein (HSP) synthesis occurs. Recently, the induction of HSP-70in rat luteal cells has been shown to inhibit luteinizing hormone(LH) and cAMP-sensitive progesterone production, possibly byinterfering with the translocation of cholesterol to the mitochondrialcytochrome P450_SCC. We therefore investigated whether HSP-70is induced in human granulosa-luteal cells and its relationshipto steroidogenesis. [³⁵S]Methionine labelling showed an increasein a 70 kDa protein after heat treatment which was demonstratedto be HSP-70 by Western analysis using monoclonal antibodiesagainst the constitutive and inducible forms of HSP-70. Inductionof HSP-70 in human granulosa-luteal cells was also seen withinterferon (IFN) (10 ng/ml), tumour necrosis factor (TNF)-     

Ectopia lentis in Loeys‐Dietz syndrome type 4

Loeys‐Dietz syndrome is a heritable disorder of the connective tissue leading to multisystem involvement including craniofacial features, skeletal abnormalities, cutaneous findings and early‐onset and aggressive disease of the aorta and its branches. There are multiple types of Loeys‐Dietz syndrome related to pathogenic variants in TGFBR1, TGFBR2, SMAD3, TGFB2, and TGFB3. Individuals with Loeys‐Dietz syndrome may be misdiagnosed as having Marfan syndrome due to shared phenotypic features and aortic root dilation. However, ectopia lentis has been an important discriminating feature, being unique to Marfan syndrome and not reported to be associated with Loeys‐Dietz syndrome. We report the case of a 46‐year‐old woman with Loeys‐Dietz syndrome type 4 due to a pathogenic variant in TGFB2 who was diagnosed with ectopia lentis at age 44. The patient underwent whole exome sequencing and no other pathogenic variants were found to explain the ectopia lentis. Our findings indicate that ectopia lentis may be an uncommon finding in Loeys‐Dietz syndrome type 4 and emphasize the importance of genetic testing in familial thoracic aortic aneurysm disease.     

Clinico-Radio-Histopathological Correlation by C-Arm Image-Guided Biopsy in Spinal Tuberculosis

Background/Purpose of the StudyC-arm-guided biopsy is a safe and effective technique for evaluating TB spine and is useful in planning therapy. The purpose of this study was to find a correlation between clinically and radiologically suspected TB spine and C-arm image-guided biopsy-proven cases and to study the complications encountered.MethodsAfter evaluating the clinical, laboratory, X-ray and MRI findings, 92 patients with provisionally diagnosed tubercular spine were subjected to C-arm image-guided biopsy.ResultsAmong our 92 cases, histopathology was positive in 55 cases (59.78%). Out of these 55 histologically positive cases, CBNAAT was positive in 42 cases and negative in the rest 13 cases. Overall, among the 92 cases, CBNAAT was positive in 51(55.43%) of cases, and out of these, histopathology turned out to be positive in 42 of cases. Out of 41 cases with negative CBNAAT, histopathology was suggestive of tuberculosis in 13. The strength of agreement between CBNAAT and histopathology was statistically significant (p < 0.0001; kappa = 0.511). No complication such as bleeding, nerve/cord injury, infection, injury to aorta or pneumothorax was encountered during and after the C-arm biopsy in any case.ConclusionC-arm image-guided biopsy is reasonably accurate and should be used as a tool for diagnosis of TB spine. We recommend histopathological examination as a key component for the diagnosis of TB spine, as it is precise and consumes relatively shorter time. CBNAAT is more rapid but is not a substitute for histopathology for spine TB diagnosis.     

Comparison of renal function after open radical cystectomy,extracorporeal robot assisted radical cystectomy,and intracorporeal robot assisted radical cystectomy

PurposeRenal function outcomes following robot-assisted radical cystectomy (RARC) have not been well established. We sought to compare long-term renal function outcomes between open radical cystectomy, RARC with extracorporeal urinary diversion and intracorporeal urinary diversion at a high volume institution.Materials and MethodsWe retrospectively reviewed our institutional bladder cancer database for patients who underwent RC from 2010 to 2019 with pre-operative estimated glomerular filtration rate (eGFR) > 45 ml/min/1.73m². Changes in renal function were assessed through locally weighted scatter plot smoothing and comparison of median eGFR between surgical groups. Chronic Kidney Disease Stage 3B was defined as eGFR < 45 ml/min/1.73m². Renal function decline was defined as a ≥10 ml/min/1.73m² drop in eGFR. Kaplan Meier method with log-rank was used to compare CKD 3B-free survival and renal function decline. Cox Proportional Hazards model was used to identify predictors of CKD 3B.ResultsSix hundred and forty four patients were included with median follow-up of 32 months (IQR 12–56). Preoperative characteristics were similar among the groups with no differences in median pre-operative eGFR (ORC: 74.6, extracorporeal urinary diversion: 74.3, intracorporeal urinary diversion: 71.6 ml/min/1.73m², P = 0.15). Median postoperative eGFR on follow up was not different between groups (P = 0.56). 33% of patients developed CKD 3B. There were no differences in CKD 3B-free survival by surgical approach (P = 0.23) or urinary diversion (P = 0.09). 64% of patients experienced renal function decline with a median time of 2.4 years (P 0.23). Predictors of CKD were pathologic T3 disease or greater (HR: 1.77, P = 0.01), ureteroenteric anastomotic stricture (HR: 2.80, P < 0.001), preoperative CKD Stage 2 (HR: 1.81, P =0.02), and preoperative CKD Stage 3A (HR: 5.56, P < 0.001).ConclusionRenal function decline is common after RC. Tumor stage, pre-operative eGFR, and ureteral stricture development, not surgical approach, influence renal function decline.