Role of Pirfenidone in Idiopathic Pulmonary Fibrosis - A Longitudinal Cohort Study.

BACKGROUND: But so far there is no proven pharmacological treatment for Idiopathic pulmonary fibrosis (IPF). As trials investigating different agents with different mechanisms of actions are going on, encouraging results have led to the licensing of the first IPF-specific drug, Pirfenidone. OBJECTIVE: To assess the proportion of IPF among interstitial lung disease patients and to assess their treatment response to Pirfenidone. MATERIAL AND METHODS: All consecutive patients attending the outpatient department from 1st January 2012 to 30th June 2012 with a proven diagnosis of Interstitial lung Disease (ILD) were included in this longitudinal cohort study. Out of the total ILDs, patients with IPF were identified. The disease, its natural course, available treatment options and the risks and benefits of drugs were discussed with each IPF patient along with their family members. After obtaining their consent, we started 23 patients on a combination of Pirfenidone, N-acetyl cysteine (NAC) and proton pump inhibitors (PPI). Patients were followed up for 52 weeks. Pirfenidone was discontinued in one patient due to an adverse effect 1 month after onset of treatment. Anova test using SPSS software and independent T test was used to analyse the data. RESULTS: During the study period 69 patients with ILD attended our OPD which included 24 IPF patients representing 34.8% and 23 of these patients received treatment with Pirfenidone, NAC and PPI. One patient discontinued Pirfenidone due to adverse effects. After 12 months, 8 patients had worsening of FVC ≥10%, the FVC of 7 patients remained stable, 8 patients could not repeat the tests and none of them had improvement. There was less than 15% decline in DLCO for 9 patients, 7 patients could not repeat the test and none improved. 8 patients had stable dyspnoea on exertion and 11 had worsening. Three patients died. Combining all the above parameters, only 4 patients had stable disease with the rest having no improvement. CONCLUSIONS: The present study does not show any significant beneficial effect for Pirfenidone. Only four patients remained stable which cannot be attributed to the effect of any particular management strategy.

Improvement in Gemcitabine-Induced Thrombotic Microangiopathy with Rituximab in a Patient with Ovarian Cancer: Mechanistic Considerations.

Gemcitabine is a potent and widely used anticancer drug. We report a case of gemcitabine-induced thrombotic microangiopathy (GCI-TMA), a known but not widely recognized complication of gemcitabine use, and our experience of treating GCI-TMA with rituximab. A 74-year-old woman was referred to our clinic for an evaluation of worsening renal function. She has recently been treated for ovarian cancer (diagnosed in 2011) with surgery (tumor debulking and bilateral salpingo-oophorectomy) along with cisplatin chemotherapy in 2012, followed by carboplatin/doxorubicin in 2013 and recent therapy for resistant disease with gemcitabine. Laboratory tests showed anemia, normal platelets and elevated lactate dehydrogenase. A peripheral smear revealed numerous schistocytes, and a kidney biopsy showed acute as well as chronic TMA. The patient continued on gemcitabine therapy, and treatment with plasma exchange was started. Since there was no response to treatment even after 5 sessions of plasma exchange, one dose of rituximab was given, which was associated with a drop in the creatinine level to 2 mg/dl. The pathogenesis of renal injury could be the effect of direct injury to the endothelium mediated by cytokines. Usual treatment includes withdrawing the drug and initiation of treatment with plasmapheresis with or without steroids. In cases resistant to plasmapheresis, treatment with rituximab can be tried. The mechanism of action of rituximab might be due to the reduced production of B-cell-dependent cytokines that drive endothelial dysfunction by depleting B cells. Patients receiving gemcitabine chemotherapy should be monitored for the development of TMA, and early treatment with plasma exchange along with rituximab might benefit these patients who already have a bad prognosis.

Bone marrow transplantation helps restore the intestinal mucosal barrier after total body irradiation in mice.

Bone marrow transplantation (BMT) substantially improves 10-day survival after total body irradiation (TBI), consistent with an effect on intestinal radiation death. Total body irradiation, in addition to injuring the intestinal epithelium, also perturbs the mucosal immune system, the largest immune system in the body. This study focused on how transplanted bone marrow cells (BMCs) help restore mucosal immune cell populations after sublethal TBI (8.0 Gy). We further evaluated whether transplanted BMCs: (a) home to sites of radiation injury using green fluorescent protein labeled bone marrow; and (b) contribute to restoring the mucosal barrier in vivo. As expected, BMT accelerated recovery of peripheral blood (PB) cells. In the intestine, BMT was associated with significant early recovery of mucosal granulocytes (P = 0.005). Bone marrow transplantation did not affect mucosal macrophages or lymphocyte populations at early time points, but enhanced the recovery of these cells from day 14 onward (P = 0.03). Bone marrow transplantation also attenuated radiation-induced increase of intestinal CXCL1 and restored IL-10 levels (P = 0.001). Most importantly, BMT inhibited the post-radiation increase in intestinal permeability after 10 Gy TBI (P = 0.02) and modulated the expression of tight junction proteins (P = 0.01-0.05). Green fluorescent protein-positive leukocytes were observed both in intestinal tissue and in PB. These findings strongly suggest that BMT, in addition to enhancing general hematopoietic and immune system recovery, helps restore the intestinal immune system and enhances intestinal mucosal barrier function. These findings may be important in the development and understanding of strategies to alleviate or treat intestinal radiation toxicity.

Dopaminergic function and progression of Parkinson's disease: PET findings.

Recent PET studies in Parkinson's disease (PD) have shown that the progression of neurodegeneration follows an exponential decay pattern. Most of the damage to the nigrostriatal dopamine system occurs during the presymptomatic phase of the disease and the first few years following symptom onset. The progressive loss of dopaminergic neurons is accompanied by several functional adaptive changes in surviving nerve terminals, which lead to increased dopamine turnover and raise the risk of treatment-related motor complications. Younger PD patients seem to have more efficient compensatory mechanisms and a slower rate of progression of neurodegeneration.