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Treatment resistant M-type phospholipase A2 receptor associated membranous nephropathy responds to obinutuzumab: a report of two cases
Background
Membranous Nephropathy (MN) is a common cause of nephrotic syndrome (NS) in adults. Recognition of MN as an antibody mediated autoimmune disease has enabled the introduction of anti-B-cell therapy. Rituximab, a type I anti-CD20 antibody has been used in the management of MN, but has a 35-45% failure rate. Obinutuzumab, a fully humanised type II anti-CD20 monoclonal antibody produces greater CD20 depletion and is superior to rituximab in the treatment of certain B-cell malignancies. In the two reports published to date involving nine patients with M-type phospholipase A2 receptor (PLA2R) associated MN (six of whom were rituximab resistant), treatment with obinutuzumab lead to immunological remission (IR) in 75% of patients, with improvement of proteinuria, normalisation of serum albumin and stable renal function in all patients.
Case presentation
We report on two cases of PLA2R-associated MN, two males aged 33 and 36-years, who presented with NS and bilateral sub massive pulmonary emboli requiring anticoagulation. Both were diagnosed serologically as PLA2R-associated MN where a renal biopsy was initially deferred due to bleeding risk on anticoagulation, but later confirmed. Both patients were refractory to multiple lines of therapy including rituximab, but achieved IR, normalistation of serum albumin, improved proteinuria and stable renal function with obinutuzumab.
Conclusions
Our cases add to the current limited literature on the successful use of obinutuzumab in PLA2R associated MN refractory to standard therapy including rituximab.
Journal Article
Zygomycosis in Solid Organ Transplant Recipients: A Prospective, Matched Case-Control Study to Assess Risks for Disease and Outcome
BackgroundClinical characteristics, risks, and outcomes in solid organ transplant (SOT) recipients with zygomycosis in the era of modern immunosuppressive and newer antifungal agent use have not been defined MethodsIn a matched case-controlled study, SOT recipients with zygomycosis were prospectively studied. The primary outcome measure was success (complete or partial response) at 90 days ResultsRenal failure (odds ratio [OR], 3.17; P=.010), diabetes mellitus (OR, 8.11; P<.001), and prior voriconazole and/or caspofungin use (OR, 4.41; P=.033) were associated with a higher risk of zygomycosis, whereas tacrolimus (OR, 0.23; P=.002) was associated with a lower risk of zygomycosis. Liver transplant recipients were more likely to have disseminated disease (OR, 5.48; P=.021) and developed zygomycosis earlier after transplantation than did other SOT recipients (median, 0.8 vs 5.7 months; P<.001). Overall the treatment success rate was 60%. Renal failure (OR, 11.3; P=.023) and disseminated disease (OR, 14.6; P=.027) were independently predictive of treatment failure, whereas surgical resection was associated with treatment success (OR, 33.3; P=.003). The success rate with liposomal amphotericin B was 4-fold higher even when controlling for the aforementioned variables ConclusionsThe risks identified for zygomycosis and for disseminated disease, including those that were previously unrecognized, have implications for further elucidating the biologic basis and for optimizing outcomes in SOT recipients with zygomycosis
Journal Article
What do we know about chronic kidney disease in India: first report of the Indian CKD registry
Background
There are no national data on the magnitude and pattern of chronic kidney disease (CKD) in India. The Indian CKD Registry documents the demographics, etiological spectrum, practice patterns, variations and special characteristics.
Methods
Data was collected for this cross-sectional study in a standardized format according to predetermined criteria. Of the 52,273 adult patients, 35.5%, 27.9%, 25.6% and 11% patients came from South, North, West and East zones respectively.
Results
The mean age was 50.1 ± 14.6 years, with M:F ratio of 70:30. Patients from North Zone were younger and those from the East Zone older. Diabetic nephropathy was the commonest cause (31%), followed by CKD of undetermined etiology (16%), chronic glomerulonephritis (14%) and hypertensive nephrosclerosis (13%). About 48% cases presented in Stage V; they were younger than those in Stages III-IV. Diabetic nephropathy patients were older, more likely to present in earlier stages of CKD and had a higher frequency of males; whereas those with CKD of unexplained etiology were younger, had more females and more frequently presented in Stage V. Patients in lower income groups had more advanced CKD at presentation. Patients presenting to public sector hospitals were poorer, younger, and more frequently had CKD of unknown etiology.
Conclusions
This report confirms the emergence of diabetic nephropathy as the pre-eminent cause in India. Patients with CKD of unknown etiology are younger, poorer and more likely to present with advanced CKD. There were some geographic variations.
Journal Article
Flashpoint. The world of Flashpoint, featuring Batman
\"Flashpoint has changed the DC Universe, and nothing is as it was before. Now Batman is Thomas Wayne, driven by the death of his son Bruce to punish criminals, and in pursuit of a Joker whose twisted crimes will bring him to the brink of madness himself ... Now, Dick Grayson travels with his parents and the death-defying Deadman across war-torn Europe, performing in their circus until an Amazon attack leads them to their true fate ... In this world, Deathstroke is a pirate on the world's most dangerous waters, questing for the only treasure that really matters ... Shade the Changing Man leads a secret team of bizarre heroes, but will he lead them to their deaths?\"--P. [4] of cover.
Book
Cryptococcus neoformans in Organ Transplant Recipients: Impact of Calcineurin-Inhibitor Agents on Mortality
Variables influencing the risk of dissemination and outcome of Cryptococcus neoformans infection were assessed in 111 organ transplant recipients with cryptococcosis in a prospective, multicenter, international study. Sixtyone percent (68/111) of the patients had disseminated infection. The risk of disseminated cryptococcosis was significantly higher for liver transplant recipients (adjusted hazard ratio [HR], 6.65; P=.048). The overall mortality rate at 90 days was 14% (16/111). The mortality rate was higher in patients with abnormal mental status (P=.023), renal failure at baseline (P=.028), fungemia (P=.006), and disseminated infection (P=.035) and was lower in those receiving a calcineurin-inhibitor agent (P=.003). In amultivariable analysis, the receipt of a calcineurin-inhibitor agent was independently associated with a lower mortality (adjusted HR, 0.21; P=.008), and renal failure at baseline with a higher mortality rate (adjusted HR, 3.14; P=.037). Thus, outcome in transplant recipients with cryptococcosis appears to be influenced by the type of immunosuppressive agent employed. Additionally, discerning the basis for transplant type-specific differences in disease severity has implications relevant for yielding further insights into the pathogenesis of C. neoformans infection in transplant recipients.
Journal Article
Autologous Epstein–Barr virus‐specific adoptive T‐cell therapy in a patient with lupus nephritis
Objectives Dysregulation of Epstein–Barr virus (EBV)‐specific cellular immunity has been hypothesised as one of the contributing factors in the pathogenesis of systemic lupus erythematosus (SLE). Lupus nephritis is a major risk factor for overall morbidity in SLE. Immune‐based strategies directed to EBV have been proposed as potential therapeutic strategy for SLE and lupus nephritis. Methods Autologous EBV latent antigen‐specific CD4+ and CD8+ T cells were expanded in vitro and adoptively transferred to a lupus nephritis patient. Results This adoptive immunotherapy had no immediate adverse effects, and the patient was subsequently treated with the anti‐CD20 antibody, obinutuzumab. The patient showed a reduction in anti‐dsDNA antibodies and improved glomerular filtration rate but remained nephrotic. These observations were coincident with a reduction in anti‐viral and global T‐cell activation. Conclusion To our knowledge, this is the first report of the use of EBV‐specific adoptive immunotherapy to treat a patient with lupus nephritis. In this Case Report, we show that adoptive T‐cell therapy specific for Epstein–Barr virus for a lupus patient is safe and may offer clinical benefit. Further clinical studies will be required to validate these findings.
Journal Article
An Immune Reconstitution Syndrome-Like Illness Associated with Cryptococcus neoformans Infection in Organ Transplant Recipients
Background. We describe an immune reconstitution syndrome (IRS)-like entity in the course of evolution of Cryptococcus neoformans infection in organ transplant recipients. Methods. The study population comprised a cohort of 83 consecutive organ transplant recipients with cryptococcosis who were observed for a median of 2 years in an international, multicenter study. Results. In 4 (4.8%) of the 83 patients, an IRS-like entity was observed a median of 5.5 weeks after the initiation of appropriate antifungal therapy. Worsening of clinical manifestations was documented, despite cultures being negative for C. neoformans. These patients were significantly more likely to have received tacrolimus, mycophenolate mofetil, and prednisone as the regimen of immunosuppressive therapy than were all other patients (P = .007). The proposed basis of this phenomenon is reversal of a predominantly Th2 response at the onset of infection to a Th1 proinflammatory response as a result of receipt of effective antifungal therapy and a reduction in or cessation of immunosuppressive therapy. Conclusions. This study demonstrated that an IRS-like entity occurs in organ transplant recipients with C. neoformans infection. Furthermore, this entity may be misconstrued as a failure of therapy. Immunomodulatory agents may have a role as adjunctive therapy in such cases.
Journal Article