SUPPLEMENTATION OF Α-LIPOIC ACID IN DIABETIC PERIPHERAL NEUROPATHY: A PROSPECTIVE OPEN LABEL RANDOMIZED CONTROLLED TRIAL

Abstract Objective: Diabetic peripheral neuropathy is the most common long term complications associated with reduced nerve conduction and blood flow. The present study was designed to investigate the effect of oral supplementation of α-lipoic acid (600 mg/day) on peripheral, sensory and motor nerve conduction and glycaemic control in type 2 diabetes mellitus with peripheral neuropathy. Methods: A total of 20 patients were enrolled in this study, then randomly allocated to two groups control (n=10) and intervention group (n=10). Patients in control group received only oral hypoglycaemic treatment and in intervention group received α-lipoic acid (600 mg/day) oral supplementation along with their oral hypoglycaemic treatment for a period of 3 months. Nerve conduction and glycaemic control were measured at the base line and at the end of 3 months by using specific methods. Results: In intervention group α-lipoic acid supplementation significantly improves 6 of 15 electrophysiological parameters of nerve conduction. Distal latency of peroneal (mean ± SD 5.13 ± 0.52 vs 4.92±0.55; p<0.02), median (mean ± SD 3.66 ± 0.76 vs 3.53±0.63; p<0.03) & ulnar motor nerves (mean ± SD 2.91 ± 0.32 vs 2.82±0.36; p<0.01), and Nerve Conduction Velocity of peroneal (mean ± SD 42.0 ± 3.07 vs 43.4±2.13; p<0.03), median (mean ± SD 51.4 ± 3.31 vs 52.2±3.59; p<0.01) & ulnar motor nerves (mean ± SD 51.0 ± 5.84 vs 52.1±5.46; p<0.03) shows significant improvement. Conclusion: Oral supplementation of α-lipoic acid was found to be effective in improving motor nerve conduction of upper and lower extremities in patients with diabetic peripheral neuropathy

Perforation in a patient with stercoral colitis and diverticulosis: who did it?

Stercoral colitis with perforation of the colon is an uncommon, yet life-threatening cause of the acute abdomen. No one defining symptom exists for stercoral colitis; it may present asymptomatically or with vague symptoms. Diagnostic delay may result in perforation of the colon resulting in complications, even death. Moreover, stercoral perforation of the colon can also present with localized left lower quadrant abdominal pain masquerading as diverticulitis. Diverticular diseases and stercoral colitis share similar pathophysiology; furthermore, they may coexist, further complicating the diagnostic dilemma. The ability to decide the cause of perforation in a patient with both stercoral colitis and diverticulosis has not been discussed. We, therefore, report this case of stercoral perforation in a patient with diverticulosis and include a discussion of the epidemiology, clinical presentation, and a review of helpful diagnostic clues for a rapid differentiation to allow for accurate diagnosis and treatment

Redox-responsive nanoplatform for codelivery of miR-519c and gemcitabine for pancreatic cancer therapy

Copyright © 2020 The Authors, some rights reserved. Desmoplastic and hypoxic pancreatic cancer microenvironment induces aberrant expression of miRNAs and hypoxia-inducible factor-1α (HIF-1α) responsible for gemcitabine (GEM) resistance. We demonstrated that miR-519c was down-regulated in pancreatic cancer and transfection of miR-519c in GEM-resistant pancreatic cancer cells inhibited HIF-1α level under hypoxia. We synthesized redox-sensitive mPEG-co-P(Asp)-g-DC-g-S-S-GEM polymer, with GEM payload of 14% (w/w) and 90% GEM release upon incubation with l-glutathione. We synthesized mPEGco- P(Asp)-g-TEPA-g-DC for complex formation with miRNA. Chemical modification of miR-519c with 2\u27-O-methyl phosphorothioate (OMe-PS) at 3\u27 end enhanced its stability and activity without being immunogenic. Epidermal growth factor receptor targeting peptide GE11 decoration increased tumor accumulation of micelles after systemic administration and significantly inhibited orthotopic desmoplastic pancreatic cancer growth in NSG mice by down-regulating HIF-1α and genes responsible for glucose uptake and cancer cell metabolism. Our multifunctional nanomedicine of GEM and OMe-PS-miR-519c offers a novel therapeutic strategy to treat desmoplasia and hypoxia-induced chemoresistance in pancreatic cancer

Cerebral Venous Sinus Thrombosis (CVST): Long-Term Single-Center Experience

CVST is a rare location of thrombosis involving Dural/ cerebral venous sinuses. It affects around 5-10 people per million population annually. It is an uncommon but life-threatening form of stroke affecting younger individuals. Therefore, identifying and treating in a timely manner is critical. Rarer thrombotic disorders like paroxysmal nocturnal hemoglobinuria (PNH) or Janus Kinase 2 (JAK2) mutation positive myeloproliferative neoplasms (MPN) can rarely present with CVST. It can also present during pregnancy for the first time. Diagnosis is often established by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI). Infections, certain medication use (asparaginase or birth control pills) could lead to CVST. Patients often present with headaches, seizures or neurological deficits. Management is often with systemic anticoagulation despite intraparenchymal hemorrhage. Reducing intracranial pressure by invasive approaches is sometimes needed.https://digitalcommons.unmc.edu/surp2022/1024/thumbnail.jp

GRFS and CRFS in alternative donor hematopoietic cell transplantation for pediatric patients with acute leukemia.

We report graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) (a composite end point of survival without grade III-IV acute GVHD [aGVHD], systemic therapy-requiring chronic GVHD [cGVHD], or relapse) and cGVHD-free relapse-free survival (CRFS) among pediatric patients with acute leukemia (n = 1613) who underwent transplantation with 1 antigen-mismatched (7/8) bone marrow (BM; n = 172) or umbilical cord blood (UCB; n = 1441). Multivariate analysis was performed using Cox proportional hazards models. To account for multiple testing, P \u3c .01 for the donor/graft variable was considered statistically significant. Clinical characteristics were similar between UCB and 7/8 BM recipients, because most had acute lymphoblastic leukemia (62%), 64% received total body irradiation-based conditioning, and 60% received anti-thymocyte globulin or alemtuzumab. Methotrexate-based GVHD prophylaxis was more common with 7/8 BM (79%) than with UCB (15%), in which mycophenolate mofetil was commonly used. The univariate estimates of GRFS and CRFS were 22% (95% confidence interval [CI], 16-29) and 27% (95% CI, 20-34), respectively, with 7/8 BM and 33% (95% CI, 31-36) and 38% (95% CI, 35-40), respectively, with UCB (P \u3c .001). In multivariate analysis, 7/8 BM vs UCB had similar GRFS (hazard ratio [HR], 1.12; 95% CI, 0.87-1.45; P = .39), CRFS (HR, 1.06; 95% CI, 0.82-1.38; P = .66), overall survival (HR, 1.07; 95% CI, 0.80-1.44; P = .66), and relapse (HR, 1.44; 95% CI, 1.03-2.02; P = .03). However, the 7/8 BM group had a significantly higher risk for grade III-IV aGVHD (HR, 1.70; 95% CI, 1.16-2.48; P = .006) compared with the UCB group. UCB and 7/8 BM groups had similar outcomes, as measured by GRFS and CRFS. However, given the higher risk for grade III-IV aGVHD, UCB might be preferred for patients lacking matched donors. © 2019 American Society of Hematology. All rights reserved

Allogeneic Hematopoietic Stem Cell Transplantation Following the Use of Hypomethylating Agents among Patients with Relapsed or Refractory AML: Findings from an International Retrospective Study

Abstract Patients with primary refractory or relapsed acute myeloid leukemia (RR-AML) have very poor prognosis. Due to limited treatment options, some patients are treated with hypomethylating agents (HMAs) due to their tolerability. Little is known about the role of allogeneic hematopoietic stem cell transplantation (HSCT) following HMA therapy in this setting. We retrospectively analyzed an international cohort of 655 RR-AML patients who received HMA therapy to study patterns and outcomes with HSCT. Only 37 patients (5.6%) patients underwent HSCT after HMA therapy. The conditioning regimen was myeloablative in 57% and nonmyeloablative in 43%. Patients received matched unrelated donor, matched sibling, haploidentical and mismatched unrelated HSCT in 56%, 24%, 16% and 4% of cases, respectively. Acute GvHD and chronic GvHD were observed in 40% and 17% of patients. While the median OS for the entire cohort of patients was 15.3 months (95% CI 9.5 – 21.7 months), OS reached 29.7 months (95% CI 7.01 – not-reached) for patients who achieved a complete remission (CR) to HMA and no intervening therapies between HMA therapy and HSCT. Our study suggests that HMA therapy can effectively bridge some patients with RR-AML to HSCT

Special considerations in the management of adult patients with acute leukaemias and myeloid neoplasms in the COVID-19 era: recommendations from a panel of international experts

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 is a global public health crisis. Multiple observations indicate poorer post-infection outcomes for patients with cancer than for the general population. Herein, we highlight the challenges in caring for patients with acute leukaemias and myeloid neoplasms amid the COVID-19 pandemic. We summarise key changes related to service allocation, clinical and supportive care, clinical trial participation, and ethical considerations regarding the use of lifesaving measures for these patients. We recognise that these recommendations might be more applicable to high-income countries and might not be generalisable because of regional differences in health-care infrastructure, individual circumstances, and a complex and highly fluid health-care environment. Despite these limitations, we aim to provide a general framework for the care of patients with acute leukaemias and myeloid neoplasms during the COVID-19 pandemic on the basis of recommendations from international experts

Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and KMT2A-rearranged AML.

Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes for acute myeloid leukemia (AML) patients. We evaluated 8709 AML patients from the CIBMTR database and, after selection and manual curation of cytogenetics data, 3779 patients in CR1 were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis compared to intermediate-risk patients detected an increased risk of relapse for KMT2A-rearranged and adverse-risk patients (HR 1.27, p = 0.01 and HR 1.71, p < 0.001, respectively). Leukemia-free survival (LFS) was similar for KMT2A and adverse-risk patients (HR 1.26, p = 0.002 and HR 1.47, p < 0.001), as was overall survival (OS) (HR 1.32, p < 0.001 and HR 1.45, p < 0.001). No differences in outcome could be detected when patients were stratified by KMT2A fusion partner. This is the largest study conducted to date on post-HCT outcomes in AML using manually curated cytogenetics for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A rearrangements and adverse-risk disease

The use of immunosuppressive therapy in MDS: clinical outcomes and their predictors in a large international patient cohort

Most studies of immunosuppressive therapy (IST) in myelodysplastic syndromes (MDS) are limited by small numbers and their single-center nature, and report conflicting data regarding predictors for response to IST. We examined outcomes associated with IST and predictors of benefit in a large international cohort of patients with MDS. Data were collected from 15 centers in the United States and Europe. Responses, including red blood cell (RBC) transfusion independence (TI), were assessed based on the 2006 MDS International Working Group criteria, and overall survival (OS) was estimated by Kaplan-Meier methods. Logistic regression models estimated odds for response and TI, and Cox Proportional Hazard models estimated hazards ratios for OS. We identified 207 patients with MDS receiving IST, excluding steroid monotherapy. The most common IST regimen was anti-thymocyte globulin (ATG) plus prednisone (43%). Overall response rate (ORR) was 48.8%, including 11.2% (95% confidence interval [CI], 6.5%-18.4%) who achieved a complete remission and 30% (95% CI, 22.3%-39.5%) who achieved RBC TI. Median OS was 47.4 months (95% CI, 37-72.3 months) and was longer for patients who achieved a response or TI. Achievement of RBC TI was associated with a hypocellular bone marrow (cellularity < 20%); horse ATG plus cyclosporine was more effective than rabbit ATG or ATG without cyclosporine. Age, transfusion dependence, presence of paroxysmal nocturnal hemoglobinuria or large granular lymphocyte clones, and HLA DR15 positivity did not predict response to IST. IST leads to objective responses in nearly half the selected patients with the highest rate of RBC TI achieved in patients with hypocellular bone marrows

Haploidentical vs. sibling, unrelated, or cord blood hematopoietic cell transplantation for acute lymphoblastic leukemia

The role of haploidentical hematopoietic cell transplantation (HCT) using posttransplant cyclophosphamide (PTCy) for acute lymphoblastic leukemia (ALL) is being defined. We performed a retrospective, multivariable analysis comparing outcomes of HCT approaches by donor for adults with ALL in remission. The primary objective was to compare overall survival (OS) among haploidentical HCTs using PTCy and HLA-matched sibling donor (MSD), 8/8 HLAmatched unrelated donor (MUD), 7 /8 HLA-MUD, or umbilical cord blood (UCB) HCT. Comparing haploidentical HCT to MSD HCT, we found that OS, leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and acute graft-versus-host disease (aGVHD) were not different but chronic GVHD (cGVHD) was higher in MSD HCT. Compared with MUD HCT, OS, LFS, and relapse were not different, but MUD HCT had increased NRM (hazard ratio [HR], 1.42; P = .02), grade 3 to 4 aGVHD (HR, 1.59; P = .005), and cGVHD. Compared with 7/8 UD HCT, LFS and relapse were not different, but 7/8 UD HCT had worse OS (HR, 1.38; P = .01) and increased NRM (HR, 2.13; P <_ .001), grade 3 to 4 aGVHD (HR, 1.86; P = .003), and cGVHD (HR, 1.72; P <_ .001). Compared with UCB HCT, late OS, late LFS, relapse, and cGVHD were not different but UCB HCT had worse early OS (<_18 months; HR, 1.93; P < .001), worse early LFS (HR, 1.40; P = .007) and increased incidences of NRM (HR, 2.08; P < .001) and grade 3 to 4 aGVHD (HR, 1.97; P < .001). Haploidentical HCT using PTCy showed no difference in survival but less GVHD compared with traditional MSD and MUD HCT and is the preferred alternative donor HCT option for adults with ALL in complete remission