Eatonquinlan7384

BACKGROUND The 90-day BCR-ABL1 (breakpoint cluster region-Abelson 1) level has been one of the accepted milestones for predicting the molecular response in patients with chronic myeloid leukemia (CML). The rate of decline in BCR-ABL1 has been considered a better predictor of the response but has not been uniformly accepted. A paucity of evidence is available to predict the accuracy of the rate of decline in the Indian context. Therefore, we tested the accuracy of the rate of decline of BCR-ABL1 in predicting the molecular response compared with the single 90-day values in a retrospective cohort study of selected cancer centers in south India. METHODS AND MATERIALS Patients with chronic-phase CML diagnosed from January 2013 to December 2018, the serial BCR-ABL1 levels were estimated at 0, 45, and 90 days, 6 months, and 1 year. Data on patient demographics, risk stratification assessed using the Sokal and EUTOS (European Treatment and Outcome Study) scores were extracted using a mobile-based data capture tool from the medical records of the enrolled patients. The halving time, determined by log reduction, was compared with the 90-day BCR-ABL1 values using the receiver operating characteristic curve for the major and complete molecular response at 6 months and 1 year as standards. Accuracy was determined from the area under the curve. The cutoff for the halving time was chosen to balance the sensitivity and specificity. RESULTS The rate of decline had more predictive accuracy compared with the 90-day BCR-ABL1 values (area under the curve for rate of decline, 0.83; 90-day, 0.80). A halving time of  less then 20 days identified 95% of the patients who had achieved major molecular response at 12 months compared with 80% using the single 90-day BCR-ABL1 response. CONCLUSIONS The halving time of BCR-ABL1 appears promising as a predictor of the outcomes for patients with CML. BACKGROUND CyBorD (cyclophosphamide, bortezomib, and dexamethasone) is an effective regimen for the treatment of patients with newly diagnosed immunoglobulin light chain (AL) amyloidosis. CyBorD can induce rapid hematologic responses (HRs). However, it remains inadequate to enhance outcomes in high-risk groups. In addition, minimal information is available on the impact of minimal residual disease (MRD) in overall survival. PATIENTS AND METHODS All consecutive patients with newly diagnosed AL amyloidosis treated with CyBorD from January 2012 to August 2018 were evaluated. HR and organ response was assessed as per standard guidelines. Further, MRD was evaluated by multiparameter flow cytometry in patients with confirmed complete response (CR). RESULTS After a median of 4 cycles, HR was seen in 31 (91.2%) cases, including CR in 9 (26.5%), very good partial response in 9 (26.5%), and partial response in 13 patients (38.2%). Organ response at 6 months was documented in 11 (32.4%) cases. With respect to cardiac response, a > 30% decrease of NT-proBNP was observed in 4 (19%) of 21 evaluable cases (NTproBNP > 650 ng/L) at a median of 6 months. The median progression-free survival was 26.7 months. Patients who achieved CR exhibited a better overall survival compared with those without CR (P = .001). No difference on overall or progression-free survival among cases achieving CR irrespective of their MRD status was observed (P > .05). CONCLUSIONS In summary, CyBorD showed a ≥ very good partial response rate of 53% with 26.5% achieving CR, which is similar to that seen in previous studies. In addition, MRD negativity assessed by multiparameter flow cytometry in patients with CR resulted in no difference on survival outcomes. We aimed to characterize withdrawal syndrome (WS) and evaluate factors associated with its development in the prospective clinical study RU-SKI in patients with chronic myeloid leukemia with deep molecular response who discontinued tyrosine kinase inhibitor (TKI) therapy. In total, 98 adult patients with chronic myeloid leukemia chronic phase, TKI therapy ≥ 3 years, and deep molecular response (BCR-ABL ≤ 0.01%) ≥ 2 years were enrolled and observed without treatment. WS was defined as newly observed or worsening musculoskeletal pain after TKI cessation. WS symptoms were found in 41 (42%) of 98 patients with a median time of observation of 25 months (range, 12-42 months). WS grades 1 to 2 and grade 3 were observed in 39 (95%) and in 2 (5%) patients, respectively. The median duration of WS was 5 months (range, 1-25 months). WS was resolved in 37 (90%) patients. Anti-inflammatory therapy was used in 21 (51%) patients. Older age (P = .039) and longer TKI therapy (P = .001) were associated with WS. The 2-month landmark analysis found no association of WS development and the rate of molecular relapses. In total, 42% of the patients experienced WS after TKI therapy discontinuation in the RU-SKI study. Physicians should be warned about the possibility of WS development, and patients of older age and with longer TKI treatment need special attention. Collection of HPC by apheresis requires adequate venous access for inflow and for outflow. The use of midline has never been reported in this setting. We prospectively analyzed the use of midline for performing apheresis on 3 healthy donors and 3 adults patients requiring autologous transplantation. A total of 8 polyurethane midlines, with an external diameter of 5 French, was inserted (2 midlines in both arms in 2 healthy donors) by our PICC team the day before apheresis and removed at the end of target collection. Mean flow rate was 35 ml/min. Target cellular dose was reached in all patients / donors with a maximum of 2 procedures without any complications. Midline is effective and safe for HPC collection either in donors or patients avoiding the placement of a central venous catheter. OBJECTIVE Voice tremor represents a common but frequently overlooked clinical feature of neurological disease. Therefore, we aimed to quantitatively and objectively assess the characteristics of voice tremor in a large sample of patients with various progressive neurological diseases. METHODS Voice samples were acquired from 240 patients with neurological disease and 40 healthy controls. The robust automated method was designed, allowing precise tracking of multiple tremor frequencies and distinguish pathological from the physiological tremor. RESULTS Abnormal tremor was revealed in Huntington's disease (65%), essential tremor (50%), multiple system atrophy (40%), cerebellar ataxia (40%), amyotrophic lateral sclerosis (40%), progressive supranuclear palsy (25%), Parkinson's disease (20%), cervical dystonia (10%), and multiple sclerosis (8%) but not in controls. Low-frequency voice tremor ( less then 4 Hz) was common in all investigated diseases, whereas medium tremor frequencies (4-7 Hz) were specific for movement disorders of Parkinson's disease, multiple system atrophy, essential tremor, and cervical dystonia. CONCLUSIONS Careful estimation of vocal tremor may help with accurate diagnosis and tailored treatment. SIGNIFICANCE This study provides (i) more insights into the pathophysiology of vocal tremor in a wide range of neurological diseases and (ii) an accurate method for estimation of vocal tremor suitable for clinical practice. Ductal cancer in situ (DCIS) is mainly a screen-detected disease and although the risk for breast cancer is age-dependent, most screening programs do not include women over the age of 75 years. Older women are usually excluded from clinical trials and treatment practices are largely based on observational studies or extrapolation of trial results from younger patients, leading to either over- or under-treatment of this population. We systematically reviewed available electronic databases for DCIS treatment patterns and outcomes in older patients 15 years. Inclusion criteria allowed for randomised controlled trials, cohort studies, case-control and cross-sectional studies, as well as meta-analyses, systematic reviews and position papers. Results showed that, although elderly are not necessarily frail, they are generally treated as such by physicians, aiming to de-escalate therapeutic interventions. After adjusting for frailty, age seems to be a significant factor for less surgery; however, older women with DCIS are more probable to receive surgery than their counterparts with early invasive cancer. DCIS biology and subtypes are independent risk factors for local recurrence or progression to invasive carcinoma, if DCIS is under-treated. The end-benefit of surgery, radio- and endocrine-therapy depend on additional parameters, such as life expectancy, co-morbidities and competing risks of death. Screen-detected DCIS in older women is a challenging clinical problem, mainly due to the lack of high-level data. Therapeutic strategies should be tailored to life expectancy and performance status, DCIS features and patient preference, aiming at combining optimal oncological outcomes with maintenance of quality of life. OBJECTIVES The survival impact of the preoperative prognostic nutritional index (PNI) has been investigated in older patients with gastric carcinoma (GC), while that of the postoperative PNI has yet to be addressed. We evaluated the significance of PNI before and after surgery in older GC patients (≥75 years). MATERIALS AND METHODS In total, 309 older GC patients undergoing radical gastrectomy between 2006 and 2016 were retrospectively reviewed. The PNI was evaluated before and at six months after gastrectomy. Patients were divided into low ( less then 45) and high (≥45) PNI groups. The impact of low PNI on overall survival (OS), cancer-specific survival (CSS), and non-GC-related death were investigated. RESULTS Low PNI was present in 134 patients (43.4%) preoperatively and 121 (39.2%) postoperatively. Low pre-PNI was independently associated with poor overall survival (P  less then  .001). Similarly, OS was significantly stratified by post-PNI (P  less then  .001). The significant survival difference according to post-PNI was present only in pStage I disease (P  less then  .001). Low post-PNI independently increased the risk of non-GC-related death in a multivariable analysis (P = .002). In contrast, CSS was not stratified by post-PNI (P = .45). In the high pre-PNI group, total gastrectomy and super-older age (≥80 years) independently increased the risk of low post-PNI, which was significantly associated with poor survival outcomes. CONCLUSIONS Pre- and post-operative PNI are useful for predicting long-term outcomes in older patients with GC. Low postoperative PNI is a powerful determinant of mortality due to other diseases. Optimal perioperative management is required for those at high risk of malnutrition postoperatively. Ulipristal has recently been suspected to be hepatotoxic by the European Medicines Agency but the evidence base for hepatotoxicity is sparse. This is a brief formal report of a patient administered ulipristal for 6-8 weeks and who developed acute liver failure leading to liver transplantation. Epalrestat The explanted liver showed extensive hepatocyte necrosis and inflammation compatible with drug-induced liver injury and cirrhosis. The usual causes of acute hepatitis and cirrhosis were eliminated. There were no other potential causative drugs. This case suggests that ulipristal may cause acute hepatitis, with pre-existing cirrhosis probably contributing to the severity of liver injury observed in this case. Ulipristal prescribers must remain vigilant and monitor liver function in their patients.