Environmental pollution has the potential to have a significant impact on animal’s health especially on birds due to daily exposure and habitat. This experimental study was carried out for a 60 days period in which, a total of 24 pigeon birds with suitable weight (80-100 g) were kept in Animal house with suitable environmental conditions viz, controlled temperature, humidity & light source to minimize any other stress. Out of twenty-four, eighteen birds were divided into three treatment groups (6 birds in each group). Whole experiment was run in triplicate manner in breeding season. One served as Control (Group 1) and remaining three were experimental groups including Road traffic noise (Group 2), Military noise (Group 3) & Human activities noise (Group 4). Noise was applied as recorded high intensity music (1125 Hz/ 90 dB) through speakers for 5-6 hrs. daily. Blood sampling was done after 20, 40 and 60 days by sacrificing treatment birds. Noise stress significantly (p<0.05) increase the serum levels of corticosterone and thyroid stimulating hormone (TSH) in Group 2 while significantly (p<0.05) decrease the serum levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) of Group 3 birds. Moreover, major fault bars formation was seen both in Group 2 and Group 3. It was concluded as that Noise stress caused rise in serum levels of Corticosterone and TSH but fall in LH and FSH. Along with fault bars formation was also prominent in all treatment groups due to stress hormone.
Introduction: Multiple myeloma (MM) is a plasma cell dyscrasia characterized by neoplastic proliferation of plasma cells. Despite advances in treatment, therapeutic uncertainties persist. The addition of a fourth drug with the standard regimen gives a favorable prognosis and efficacy profile in MM. This systematic review highlights four-drug regimens' efficacy and safety for the treatment of newly diagnosed (ND) and relapsed refractory (RR) MM. Methodology: We performed a comprehensive literature search using four major databases (Pubmed, Cochrane Library, Embase, and ClinicalTrials.gov). Our search strategy included MeSH terms and keywords for multiple myeloma and antineoplastic agents from the date of inception to June 2020. The initial search revealed 6104 articles. After excluding review articles, duplicates, and non-relevant articles, we included 10 phase II/III clinical trials reporting the efficacy of four-drug regimens for treatment of MM. Results: Out of 2464 enrolled patients, 2321 patients had NDMM, and 143 patients had RRMM, 1791 patients were in phase III trials, and 673 patients were in phase II trials. Phase III trials: Moreau et al. (2019) studied the efficacy of daratumumab (D), bortezomib (V), thalidomide (T) and dexamethasone (d) vs VTd in NDMM patients (pts) (n=1085) in CASSIOPEIA trial. DVTd group showed better progression free survival (PFS) 93% vs 85% at 18 months (mo) (hazard ratio (HR) 0.42 [0.34-0.51]; p<0.0001), and an overall response rate (ORR) of 92.6% vs 89.9% compared to VTd group. Minimal residual disease (MRD) negative status in bone marrow was 64% in DVTd vs 44% in VTd group (P <0.0001). Mateos et al. (2018) reported the role of DV + melphalan (M) + prednisone (P) vs VMP in NDMM pts (n=706) (ALCYONE trial). DVMP group showed better PFS: 63% vs 36% at 24 mo (HR: 0.47, 95% CI 0.33-0.67, p<0.0001), ORR: 90.9% vs 73.9%, and MRD negative status of 28% vs 7% (p<0.0001) in DVMP vs VMP group. Vorhees et al. reported DVd + lenolidamide (R) vs RVd in GRIFFIN study in transplant eligible NDMM patients (n= 207). It showed better PFS: 95.8% (95% CI, 89.2- 98.4) vs 89.8% (95% CI, 77.1-95.7) at 24 mo, an ORR of 99% [Odd's ratio (OR) in DVRd group vs VRd group (91.8%) (p=0.0160) and MRD negative status of (51% vs 20.4%) (p<0.0001) in DVRd vs VRd group. Phase II trials: Yimer et al. (2017) studied the role of DVd + cyclophosphamide (C) in pts with NDMM (n=86) and RRMM (n=14) with ORR of 81.4% (95% CI, 71.6-89.0%) and 71.4% (95% CI, 41.9-91.6%) respectively for NDMM and RRMM. The 12-month PFS rate was 87.0% (95% CI, 57.1-96.6%), and 12-month OS rate was 98.8% (95% CI, 92.0-99.8%) for NDMM pts. Median PFS was 13.3 (95% CI, 6.8-13.3) mo and 12-month PFS rate was 66.2% (95% CI, 32.4-86.0%) and OS of 54.5% (95% CI, 8.6-86.1%) in RRMM. respectively. San et al. (2014) studied siltuximab (S) +VMP vs. VMP in NDMM pts (n=98) with ORR of 88% (95% CI 75%, 95%) in SVMP and 80% (95% CI 66%, 90%) in VMP and PFS of 88% in both arms; though median survival and overall survival were not reached in either arm despite a median follow-up of 23.3 months & 21.9 mo respectively. Laubach et al. (2017) studied the role of elotuzumab (E) + Lenalidomide (R) + VP in NDMM pts (n=41 with ORR of 100%). Mikhael et al. (2015) studied the role of Carfilzomib (K) + CTd in NDMM pts (n=64) with ORR of 91% and median PFS of 85% [95% CI (71-93%)] and 76% [95% CI (59-87%)] at 12 mo and 24 mo and OS of 96% [95% CI (86-99%)] in NDMM pts. Bahlis et al. (2019) studied the role of venetoclax (VEN) + DVd vs. VEN-Dd (n=48) with RRMM pts with ORR of 92% and 88% in Ven-Dd and Ven-DVd group. Popat et al. (2016) studied the role of Panobinostat + VTd in RRMM pts (n=56) with of ORR of 91% (80% CI 83.4-96.2) and PFS of 75.4% after a median follow-up of 15 mo. Waldschmidt et al. (2018) studied the role of vorinostat + doxorubicin + Vd in RRMM pts (n=38) with PFS of 9.6 mo, and an ORR of 67%. With a median follow-up of 30.8 mo, OS was 33.8 mo with no safety concerns. Toxicities were hematological (cytopenias) and non-hematological (fatigue, infections) and generally mild (Table). Conclusion:Four drug combinations, primarily daratumumab based regimens, are very effective and well-tolerated. The achievement of higher MRD negative status implies a more profound response. Long term follow-up is needed to see the effect on long-term survival. Table Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.
Background: Acute lymphoblastic leukemia (ALL) is rare but aggressive. For refractory and relapsed ALL (R/R ALL), various treatment strategies are adopted, of which the use of blinatumomab has shown promising results in recent decades. Blinatumomab is a CD-19 directed CD3 bispecific T-cell engager antibody that has been approved by the FDA for the treatment of both adults and pediatric ALL. We report the efficacy and toxicity of blinatumomab in relapsed and refractory ALL adult patients. Materials/Methods: Following the PRISMA guideline, we performed a comprehensive literature search PubMed, Embase, Cochrane Library, Web of Science, and Clinicaltrials.gov. We used the following keywords, "acute lymphocytic leukemia" and "Blinatumomab" from the inception of data till 06/17/2020. We screened 1199 articles and included 7 trials and 6 retrospective studies. We excluded all case reports, case series, preclinical trials, review articles, and meta-analysis. We extracted the data for efficacy (complete response, relapse, overall survival, etc.) and safety (≥Grade 3 adverse events). Results: A total of 1393 patients with relapsed/refractory ALL were included. Monotherapy: In phase 3 TOWER trial, a total of 405 patients with heavily pretreated B-cell precursor ALL were randomized in a 2:1 ratio to either receive blinatumomab (n=271) or standard of care (SOC) (N=134). The mean age of both groups was 40.8 years and 41.1, respectively. The dose of blinatumomab (9-28 ug/d) was instituted to the intervention group, whereas the control group received investigator-chosen chemotherapy regimens. The CR/CRi rate for both groups was 95/267 (35.5 %) and 27/134 (31.34%), respectively (p<0.01). The median overall survival was 7.7 (5.6 to 9.6 months) vs. 4.0 (2.9 to 5.3 months); the hazard rate for death: 0.71 (95% CI 0.55-0.93) p=0.01 and MRD negativity was 76 % and 48 %, respectively. The most common grade 3 and 4 adverse events (AEs) were neutropenia 45.7%) vs. 61.94% and cytopenia 67.80% vs. 81.34% respectively. In 6 phase 1b/2 studies (N=469), the starting dose of blinatumomab was 5 µg /m2/d and subsequently increased to 30 µg/m2/d. The pooled CR/CRi for these studies was 180/469 (38.37%). The most common hematological grade ≥3 adverse events were neutropenia 89/448 (19.87%), anemia 45/422 (10.70%), and thrombocytopenia 41/422 (9.7%). A total of 509 patients were included in 5 observational studies. The overall CR/CRi reported was 129/509 (25.34%). Grade ≥3 neutropenia and thrombocytopenia were reported as 14/52(26.92%) in one study.CRS was reported in another study as 5/14 (35 %). Combination regimens: In a phase II trial of Blinatumomab when given with a TKI (Dastanib), CR/CRi achieved was 27/47 (56.3%). Blinatumomab related neurotoxicity was observed in 2/12 (16.67%) patients. A total of 38 patients were included in 3 observational studies involving Blinatumomab and TKIs. The overall CR/CRi reported was 25/30(83.33%). In a multicenter phase I/II trial blinatumomab when given with PD-1 inhibitor pembrolizumab (pembro) achieved a CR/CRi of 2/4 (50%). In a phase II study, Blinatumomab and PD-1 and CTLA-4 inhibitors were used in combination in 8 patients. The CR/CRi achieved was 4/5 (80%). Grade ≥3 non-hematological adverse events (AEs) were observed in 1/5 (20%) patients. Blinatumomab has been used in combination with Hyper-CVAD in a phase II study. The ORR and CR achieved have been 14/14 (100%) and 13/14 (93%) respectively. In a recent study, blinatumomab has been used along with miniHCVD + INO in 17 patients. The CR/CRi achieved was 13/17 (76.47%). Conclusion: Blinatumomab alone and in combination with TKIs, PD-1 inhibitors, CTLA-4 inhibitors,hyper-CVAD and miniHCVD + INO were well tolerated by adult patients with acute lymphocytic leukemia. Blinatumomab in combination therapy has shown superior efficacy in adult ALL patients as compared to blinatumomab monotherapy. Additional multicenter randomized, double-blind clinical trials are needed to confirm these results. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.:Honoraria, Research Funding, Speakers Bureau.
The risk of stroke is increased during pregnancy and the postpartum period. It can lead to significant maternal morbidity and mortality. The physiologically mediated hemodynamic changes in circulation and vascular tissue, and the increased coagulability account for this increased risk of stroke. Pregnancy-related strokes can be hemorrhagic or ischemic. We present a rare case of postpartum ischemic stroke. A 25-year-old female with no known comorbidities and a history of cesarean section 10 days back presented with a right-sided weakness and sensory loss for one day. An MRI of the head revealed a large area of restricted diffusion on diffusion-weighted 1 (DW1) image in the left parietal region with comparable low signals on apparent diffusion coefficient (ADC) map and a small area of blooming suggesting hemorrhage on susceptibility-weighted 1 (SW1) image. This area appeared hypointense on T1 and hyperintense on fluid-attenuated inversion recovery (FLAIR) and T2 images. These findings suggested acute ischemic infarction. She was started on antiplatelet therapy, and subsequently, her weakness improved. She was discharged upon improvement in her symptoms and was asked to follow up in the outpatient department. Numerous studies have shown an increased risk of ischemic stroke in the immediate postpartum period in women who undergo a cesarean section. Thus, we conclude that clinicians should be aware of this complication and high-risk patients should be identified and monitored more aggressively in their immediate postpartum period.
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