Challenges in overcoming advanced-stage or relapsed refractory extranodal NK/T-cell lymphoma: meta-analysis of individual patient data

IntroductionExtranodal NK/T-cell lymphoma (ENKTCL), a non-Hodgkin lymphoma, is known for its destructive local impact on nasal structures and systemic induction of inflammatory cytokines. Concurrent treatment with radiation and nonanthracycline- based chemotherapy has improved survival rates in patients with localized disease stages. However, survival outcomes vary significantly in advanced-stage and relapsed or refractory (R/R) cases.MethodsTherefore, we conducted a meta-analysis using random effects models to assess prognostic factors in advanced or R/R ENKTCL, employing a digital extractor on Kaplan–Meier graphs owing to the scarcity of published prospective trials for these patients.ResultsWe observed that patients with advanced ENKTCL treated with Lasparaginase had a median progression-free survival (PFS) of 14.3 months and an overall survival (OS) of 19 months. In R/R ENKTCL, PFS and OS were 11.7 and 15.6 months, respectively. Additionally, OS outcomes in advanced-stage ENKTCL were better in the asparaginase group than that in the non-asparaginase group, with PEG-asparaginase showing superior results compared with that using Lasparaginase. Epstein–Barr Virus (EBV)-DNA positivity in the bloodstream prior to treatment was associated with poor outcomes in advanced-stage ENKTCL, and similar trends were observed in patients with R/R ENKTCL and post-treatment EBV viremia.DiscussionCollectively, these findings suggest that chemotherapy with Lasparaginase or PEG-asparaginase can enhance survival in advanced or R/R ENKTCL. However, future strategies must be developed to effectively suppress EBV viremia and achieve a deep response toward tumor eradication

Relative Contribution among Physical Fitness Factors Contributing to the Performance of Modern Pentathlon

This study reveals the relationship between physical fitness factors and performance in modern pentathlon and identifies the contribution of each physical factor to overall performance. The physical fitness assessment data and the competition records collected by the Korean national team pentathletes for the years 2005 to 2019 were tracked. The correlation between the competition records and fitness factors was confirmed by correlation analysis. In addition, the physical factors affecting performance were identified through multiple regression analysis, and the average difference between national and international competitions was verified by t-test. The first result was that fencing, swimming, and horseback riding rankings were more relevant to the overall pentathlon performance score than the combined rankings in national competitions. In the international competitions, performance in the combined running and shooting event was more relevant than fencing, swimming, and horseback riding. Second, the basic fitness factors of grip strength and sergeant jump and the specific fitness factors of leg strength—left and right average flexor were correlated with overall pentathlon performance national competitions. However, in international competitions, sergeant jump, 20 m shuttle run, reaction time, lung capacity, and back strength were correlated (presented in high to low order). In terms of the specific fitness factors, relative (%BW) and absolute (Nm) leg strength—left and right average flexor, lower body anaerobic fatigue rate, half squat, relative (W/kg) and absolute (Watts) maximal lower body anaerobic power were correlated accordingly with overall pentathlon performance. Third, we analyzed the differences between average performance in national and international competitions. Only the combined running and shooting event out of the five modern pentathlon events showed a difference. Grip strength and relative leg strength—average extensor AP (%BW) appeared to be different among the physical fitness factors. Fourth, we examined the level of contribution of each of the fitness factors on overall performance. The model’s goodness of fit was confirmed, and grip strength was found to have a significant contribution on overall performance. Furthermore, the level of contribution was higher in the following order: relative leg strength—left and right average flexor (%BW), bench press, half squat, relative leg strength— average extensor AP(%BW), GXT—time to exhaustion, relative lower body anaerobic average power (W/kg), and maximal lactic acid concentration. With the 2020 Tokyo Olympics just around the corner, combined running and shooting performance appeared to be a decisive factor in the final ranking in modern pentathlon according to the analysis of the basic and specific fitness factors of pentathletes. The basic fitness factors are critical in order of sergeant jump, grip strength, reaction time, lung capacity, side-step, back strength, 20 m shuttle run, sit-and-reach, sit-ups, and single leg standing. With respect to the specific fitness factors, relative leg strength—left and right average flexor (%BW), bench press, half squat, relative leg strength—average extensor AP (%BW), GXT—time to exhaustion, relative lower body anaerobic average power (W/kg), and maximal lactic acid concentration showed their relevance accordingly. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.1

Impact of glycemic control on the progression of aortic stenosis: a single-center cohort study using a common data model

Background Diabetes mellitus (DM) is a well-established risk factor for the progression of degenerative aortic stenosis (AS). However, no study has investigated the impact of glycemic control on the rate of AS progression. We aimed to assess the association between the degree of glycemic control and the AS progression, using an electronic health record-based common data model (CDM). Methods We identified patients with mild AS (aortic valve [AV] maximal velocity [Vpeak] 2.0–3.0 m/sec) or moderate AS (Vpeak 3.0–4.0 m/sec) at baseline, and follow-up echocardiography performed at an interval of ≥ 6 months, using the CDM of a tertiary hospital database. Patients were divided into 3 groups: no DM (n = 1,027), well-controlled DM (mean glycated hemoglobin [HbA1c] < 7.0% during the study period; n = 193), and poorly controlled DM (mean HbA1c ≥ 7.0% during the study period; n = 144). The primary outcome was the AS progression rate, calculated as the annualized change in the Vpeak (△Vpeak/year). Results Among the total study population (n = 1,364), the median age was 74 (IQR 65–80) years, 47% were male, the median HbA1c was 6.1% (IQR 5.6–6.9), and the median Vpeak was 2.5 m/sec (IQR 2.2–2.9). During follow-up (median 18.4 months), 16.1% of the 1,031 patients with mild AS at baseline progressed to moderate AS, and 1.8% progressed to severe AS. Among the 333 patients with moderate AS, 36.3% progressed to severe AS. The mean HbA1c level during follow-up showed a positive relationship with the AS progression rate (β = 2.620; 95% confidence interval [CI] 0.732–4.507; p = 0.007); a 1%-unit increase in HbA1c was associated with a 27% higher risk of accelerated AS progression defined as △Vpeak/year values > 0.2 m/sec/year (adjusted OR = 1.267 per 1%-unit increase in HbA1c; 95% CI 1.106–1.453; p < 0.001), and HbA1c ≥ 7.0% was significantly associated with an accelerated AS progression (adjusted odds ratio = 1.524; 95% CI 1.010–2.285; p = 0.043). This association between the degree of glycemic control and AS progression rate was observed regardless of the baseline AS severity. Conclusion In patients with mild to moderate AS, the presence of DM, as well as the degree of glycemic control, is significantly associated with accelerated AS progression

Serial Measurement of WT1 Expression and Decrement Ratio Until Hematopoietic Cell Transplantation as a Marker of Residual Disease in Patients with Cytogenetically Normal Acute Myelogenous Leukemia

AbstractUsing real-time quantitative PCR, we monitored Wilms tumor gene 1 (WT1) expression from diagnosis to hematopoietic stem cell transplantation (HSCT) in adult patients with cytogenetically normal acute myelogenous leukemia (CN-AML) and FLT3-ITD and NPM1 mutations. The values at diagnosis were evaluated in 104 patients. Data collected after induction chemotherapy were available for all patients, but only 68 patients were treated with HSCT. Significant WT1 expression cut-offs were determined by receiver operation characteristic curve analysis, and rates of overall survival (OS) and disease-free survival (DFS) were estimated. WT1 decrement ratios (DR) at postinduction chemotherapy and at pre- and post-HSCT compared with the diagnostic level were calculated. Higher WT1 expression at diagnosis, postinduction chemotherapy, and pre-HSCT showed inferior OS (P = .015, <.001, and .002) and DFS (P = .006, <.001, and .003). The cut-offs were determined at the median for diagnostic WT1 expression and at the 25% level from the top for other time points excluding post-HSCT. The WT1 DR ≥ 1-log after induction chemotherapy showed superior OS and DFS (P = .009 and .002) and WT1 DR ≥ 1-log preceding HSCT also showed superior OS and DFS (P = .009 and .003). Results of WT1 DR were consistently applicable in each subgroup with higher (≥1.0) and lower (<1.0) WT1 expression at diagnosis and also in NPM1-wild-type/FLT3-ITD–negative CN-AML. The WT1 DR therefore predicted survival outcomes after HSCT more accurately than did the diagnostic WT1 expression. WT1 expression may serve as a reliable marker for residual disease and WT1 DR as a prognostic indicator, particularly in NPM1-wild-type/FLT3-ITD–negative CN-AML. These measures may be applied throughout the course of treatment and even after HSCT

Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase study

Background: Mantle-cell lymphoma is an aggressive B-cell lymphoma with a poor prognosis. Both ibrutinib and temsirolimus have shown single-agent activity in patients with relapsed or refractory mantle-cell lymphoma. We undertook a phase 3 study to assess the efficacy and safety of ibrutinib versus temsirolimus in relapsed or refractory mantle-cell lymphoma. Methods: This randomised, open-label, multicentre, phase 3 clinical trial enrolled patients with relapsed or refractory mantle-cell lymphoma confirmed by central pathology in 21 countries who had received one or more rituximab-containing treatments. Patients were stratified by previous therapy and simplified mantle-cell lymphoma international prognostic index score, and were randomly assigned with a computer-generated randomisation schedule to receive daily oral ibrutinib 560 mg or intravenous temsirolimus (175 mg on days 1, 8, and 15 of cycle 1; 75 mg on days 1, 8, and 15 of subsequent 21-day cycles). Randomisation was balanced by using randomly permuted blocks. The primary efficacy endpoint was progression-free survival assessed by a masked independent review committee with the primary hypothesis that ibrutinib compared with temsirolimus significantly improves progression-free survival. The analysis followed the intention-to-treat principle. The trial is ongoing and is registered with ClinicalTrials.gov (number NCT01646021) and with the EU Clinical Trials Register, EudraCT (number 2012-000601-74). Findings: Between Dec 10, 2012, and Nov 26, 2013, 280 patients were randomised to ibrutinib (n=139) or temsirolimus (n=141). Primary efficacy analysis showed significant improvement in progression-free survival (p<0.0001) for patients treated with ibrutinib versus temsirolimus (hazard ratio 0.43 [95% CI 0.32-0.58]; median progression-free survival 14.6 months [95% CI 10.4-not estimable] vs 6.2 months [4.2-7.9], respectively). Ibrutinib was better tolerated than temsirolimus, with grade 3 or higher treatment-emergent adverse events reported for 94 (68%) versus 121 (87%) patients, and fewer discontinuations of study medication due to adverse events for ibrutinib versus temsirolimus (9 [6%] vs 36 [26%]). Interpretation: Ibrutinib treatment resulted in significant improvement in progression-free survival and better tolerability versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma. These data lend further support to the positive benefit-risk ratio for ibrutinib in relapsed or refractory mantle-cell lymphoma

Primary Malignant Melanoma of the Female Urethra

We report here on a rare case of primary malignant melanoma of the female urethra. A 69-year-old female presented at our hospital with a several month history of dysuria, poor stream, gross hematuria, intermittent blood spots, and a painful mass at the external urethral meatus. The physical examination revealed a soft, small, chestnut-sized lesion through the urethral orifice. The mass was tan colored, ulcerated, covered with necrotic tissue, and protruded from the external urethral meatus. The mass was removed by wide local excision under spinal anesthesia. The pathological diagnosis was malignant melanoma of the urethra. Computed tomography of the abdomen as well as a whole-body bone scan showed no evidence of metastasis. The patient has been free of disease for 6 months postoperatively. We discuss the clinicopathologic features and treatment of this tumor

Seq-Scope protocol in MiSeq system for profiling hepatic and colonic spatial transcriptome.

http://deepblue.lib.umich.edu/bitstream/2027.42/168395/5/Seq-Scope Protocol M1.0.0 version.pdfSEL