Move-PCD-a multi-center longitudinal randomized controlled superiority trial on the effect of a 6-month individualized supported physical activity (PA) program on quality of life (QoL) in children, adolescents, and adults with primary ciliary dyskinesia.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare genetical disease with malfunction of the motile cilia leading to impaired muco-ciliary clearance in the respiratory tract. There is no cure for PCD, only supportive therapy aimed at minimizing the progression of the disease and improving the patient's quality of life (QoL). Physical activity (PA) is one of these recommended supportive therapies for people with PCD (pwPCD). However, there is no scientific evidence to support this recommendation. In addition, regular medical advice to increase PA remains largely ineffective in pwPCD. METHODS: To test the main hypothesis, that an individualized and supported PA program leads to a better QoL 6 months after randomization (QoL-PCD questionnaire) compared to usual recommendation in pwPCD, 158 pwPCD aged 7 to 55 years are to be included in this multi-center randomized controlled trial (RCT). After the screening visit, a 1:1 randomization stratified by age group and FEV1 will be performed. A QoL-PCD questionnaire, motor test, and lung function will be carried out at regular intervals in both groups. PA is recorded in both groups using activity trackers during the study period. The main aim of the trial is to estimate the difference in the change of QoL between the groups after 6 months. Therefore, our full analysis set consists of all randomized patients and analysis is performed using the intention-to-treat principle. Statistical software R ( http://www.r-project.org ) is used. Ethical approvement without any reservations: RUB Bochum Ethics Committee (No. 23-7938; December 4, 2023). Recruitment start: March 2024. DISCUSSION: Limitations result from the rarity of PCD with its broad disease spectrum and the large age range. These are reduced by stratified randomization and the measurement of the individual change in QoL as primary endpoint. In our view, only a PA program tailored to individual needs with close contact to trainers offers the chance to meet personal needs of pwPCD and to establish PA as a pillar of therapy in the long term. The study protocol explains all procedures and methods of recruitment, implementation of the study visits and intervention, measures for patient and data safety, and for minimizing risks and bias. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) 00033030. Registered on December 7, 2023. Update 10 July 2024. STUDY PROTOCOL VERSION 10: Version 1.2; 12 June 2024.

Protocolized Foot Exercises Help in Improvement of Diabetic Foot Ulcers and Quality of Life When Added to Standard Therapy-A Randomized Clinical Trial.

CONTEXT: Diabetic foot disease is the major cause of nontraumatic limb amputations worldwide causing a high socioeconomic and psychological toll and a huge burden to the healthcare system. Currently, standard treatment of diabetic foot ulcer is through multidisciplinary therapy. Foot exercises have been shown to improve healing in diabetic ulcers although evidence is limited and applicability is non-uniform. Our study aimed to generate more evidence regarding the benefit of addition of protocolized foot exercises so that it can be instituted as a standard of care. METHODS AND MATERIAL: It was an open label Randomized controlled trial with seventy-two patients and study duration of one and half years Patients with diabetic foot ulcers were randomized into two groups. Both groups received standard therapy for diabetic foot ulcer. The intervention group in addition received three months of protocolized foot exercises. At the end of three months ulcer healing and quality of life were m compared among both the groups. RESULTS: Regular exercises for three months caused significant reduction in ulcer area compared to the non-intervention group [100% versus 45.22%, 95% CI =36.30(16.04-56.56), P-value = 0.001]. Quality of life analyzed by SF-36 score showed significant improvement in components like physical function [69.4 ± 8.9 versus 63.7 ± 11.0, 95% CI = 5.73 (0.97-10.48), P-value = 0.01], emotional well-being [65.2 ± 7.6 versus 60.8 ± 7.9, 95% CI = 4.44 (0.79-8.10), P-value = 0.01], and pain components [55.4 ± 18.5 versus 47.5 ± 14.5, 95% CI = 7.99 (0.16-15.81), P-value = 0.04) at 3 months although change in social functioning, physical health limitation, health change, energy and general health improvement were not significant. CONCLUSIONS: Addition of protocolized foot exercises are beneficial for patients of diabetic foot ulcers in terms of ulcer healing as well as improvement of quality of life provided compliance to exercises can be ensured.

Glycaemic control and macrovascular and microvascular outcomes: A systematic review and meta-analysis of trials investigating intensive glucose-lowering strategies in people with type 2 diabetes.

AIM: We aimed to determine the macrovascular and microvascular outcomes of intensive versus standard glucose-lowering strategies in type 2 diabetes (T2D) and investigate the relationships between these outcomes and trial arm glycated haemoglobin (HbA1c) reduction. MATERIALS AND METHODS: In this systematic review and meta-analysis, we identified relevant trials from MEDLINE, Embase, the Cochrane Library, and bibliographies up to August 2023. Macrovascular and microvascular outcomes, along with safety outcomes, were evaluated. Pooled study-specific hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated, and meta-regression was employed to analyse the relationships between outcomes and HbA1c reduction. RESULTS: We included 11 unique RCTs involving 51 469 patients with T2D (intensive therapy, N = 26 691; standard therapy, N = 24 778). Intensive versus standard therapy reduced the risk of non-fatal myocardial infarction (MI) (HR 0.84; 95% CI 0.75-0.94) with no difference in the risk of major adverse cardiovascular events (HR 0.97; 95% CI 0.92-1.03) and other adverse cardiovascular outcomes. Intensive versus standard therapy reduced the risk of retinopathy (HR 0.85; 0.78-0.93), nephropathy (HR 0.71; 0.58-0.87) and composite microvascular outcomes (HR 0.88; 0.77-1.00). Meta-regression analyses showed modest evidence of inverse linear relationships between HbA1c reduction and the outcomes of major adverse cardiovascular events, non-fatal MI, stroke and retinopathy, but these were not statistically significant. CONCLUSIONS: In people with T2D, intensive glucose control was associated with a reduced risk of non-fatal MI and several microvascular outcomes, particularly retinopathy and nephropathy. The lack of an effect of intensive glucose-lowering on most macrovascular outcomes calls for a more comprehensive approach to managing cardiovascular risk factors alongside glycaemic control.

Clinical applications of neurofeedback based on sensorimotor rhythm: a systematic review and meta-analysis.

Background: Among the brain-machine interfaces, neurofeedback is a non-invasive technique that uses sensorimotor rhythm (SMR) as a clinical intervention protocol. This study aimed to investigate the clinical applications of SMR neurofeedback to understand its clinical effectiveness in different pathologies or symptoms. Methods: A systematic review study with meta-analysis of the clinical applications of EEG-based SMR neurofeedback performed using pre-selected publication databases. A qualitative analysis of these studies was performed using the Consensus tool on the Reporting and Experimental Design of Neurofeedback studies (CRED-nf). The Meta-analysis of clinical efficacy was carried out using Review Manager software, version 5.4.1 (RevMan 5; Cochrane Collaboration, Oxford, UK). Results: The qualitative analysis includes 44 studies, of which only 27 studies had some kind of control condition, five studies were double-blinded, and only three reported a blind follow-up throughout the intervention. The meta-analysis included a total sample of 203 individuals between stroke and fibromyalgia. Studies on multiple sclerosis, insomnia, quadriplegia, paraplegia, and mild cognitive impairment were excluded due to the absence of a control group or results based only on post-intervention scales. Statistical analysis indicated that stroke patients did not benefit from neurofeedback interventions when compared to other therapies (Std. mean. dif. 0.31, 95% CI 0.03-0.60, p = 0.03), and there was no significant heterogeneity among stroke studies, classified as moderate I2 = 46% p-value = 0.06. Patients diagnosed with fibromyalgia showed, by means of quantitative analysis, a better benefit for the group that used neurofeedback (Std. mean. dif. -0.73, 95% CI -1.22 to -0.24, p = 0.001). Thus, on performing the pooled analysis between conditions, no significant differences were observed between the neurofeedback intervention and standard therapy (0.05, CI 95%, -0.20 to -0.30, p = 0.69), with the presence of substantial heterogeneity I2 = 92.2%, p-value < 0.001. Conclusion: We conclude that although neurofeedback based on electrophysiological patterns of SMR contemplates the interest of numerous researchers and the existence of research that presents promising results, it is currently not possible to point out the clinical benefits of the technique as a form of clinical intervention. Therefore, it is necessary to develop more robust studies with a greater sample of a more rigorous methodology to understand the benefits that the technique can provide to the population.

Effect of Educational Handouts With Standard Therapy Versus Standard Therapy Alone on Compliance With Oral Iron Supplementation in Antenatal Women With Iron Deficiency Anemia: A Randomized Controlled Trial.

Background Iron requirements rise dramatically throughout the second and third trimesters of pregnancy. Pregnant women are more susceptible to anemia because their need for iron increases during pregnancy, which is difficult to achieve through diet alone. Methodology A randomized controlled trial (non-blinded and parallel group) was undertaken with the recruitment of 174 women. However, 35 women were lost to follow-up, and the study was ultimately completed with 139 participants distributing 68 women in Group A (intervention group) and 71 women in Group B (non-interventional group). Educational handouts were explained to the participants with iron supplements in Group A and only supplements were given to Group B, and the participants were followed up till three months before the recruitment period. Compliance with iron supplementation and a rise in hemoglobin were noted. Results In this study, maximum women were in the 22-30 years age group and were almost evenly distributed with respect to parity with no statistically significant difference in the groups. All the participants were started with oral iron therapy. No additional parenteral iron therapy was given. Women in Group A showed good compliance for iron supplementation than those in Group B. It was determined that this difference was statistically insignificant (>0.05). In the majority of women, the reason for poor compliance was frustration to follow oral iron therapy daily (52.3% in Group A and 21.7% in Group B). There were other reasons like forgetfulness, heartburn, vomiting, constipation, and nausea as the reason for poor compliance. The hemoglobin levels were compared at the recruitment and a mean rise in hemoglobin levels was noted in groups A and B at the follow-up period after three months. There was a greater mean rise in hemoglobin concentration in Group A (1.28) than in Group B (0.63), which was statistically insignificant (>0.05). Conclusion The current study found that among pregnant women with iron-deficient anemia, instructional handouts did not promote compliance with oral iron treatment. The main reasons for low compliance were frustration with taking the oral drug, followed by forgetfulness, heartburn, vomiting, constipation, and nausea. In pregnant females with anemia brought on by iron deficiency, educational handouts did not enhance hemoglobin status.

Unique natural history of an EGFR mutated adenocarcinoma.

BACKGROUND: Supportive care alone cannot be indicated for cancers for which established standard therapy exists unless there is a specific reason. Due to the refusal of standard therapy by the patient after proper explanation of the therapy, we experienced a long-term follow-up of >10 years with supportive care alone in an epidermal growth factor receptor (EGFR) mutated lung cancer patient. CASE: A 70-year-old woman was referred due to the right lung with some ground glass opacities (GGOs). One of the GGOs which was resected in another hospital had been confirmed to be EGFR mutation-positive lung adenocarcinoma. Although EGFR-tyrosine kinase inhibitor (TKI) was explained to be the standard therapy, the patient refused receiving the therapy and wished to follow up imaging of the remaining GGOs. During the follow-up period of 13 years, the each GGO showed a gradual increase. The doubling time of the largest GGO and that of serum carcinoembryonic antigen was > 2,000 days, respectively. CONCLUSION: Although very rare, some of EGFR mutated lung adenocarcinoma might have a very slow progression. Clinical course of this patient provides useful information to the clinical practice of future patients who may have similar clinical courses.

Comparative Effectiveness of First-Line Selpercatinib versus Standard Therapies in Patients with RET-Activated Cancers: An Exploratory Interpatient Analysis of LIBRETTO-001.

Selpercatinib is indicated for locally advanced/metastatic RET-activated solid tumors after progression or following prior systemic therapies. Until the recently published data from LIBRETTO-431 and LIBRETTO-531, there were limited effectiveness data comparing selpercatinib with other first-line treatments in RET-activated non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC), and thyroid cancer (TC). This study analyzed patient data from LIBRETTO-001 and compared the outcomes (time to treatment discontinuation {TTD}, time to next treatment or death {TTNT-D}, time to progression {TTP}, and the objective response rate {ORR}) of first-line selpercatinib (selpercatinib arm) use with the outcomes of first-line standard therapies in patients who then received selpercatinib in later lines of treatment (comparator arm). Overall, the first-line selpercatinib arm had a longer TTD, TTNT-D, and TTP versus the first-line comparator arm. The hazard ratios (HRs) for TTD were 0.29 (NSCLC), 0.15 (MTC), 0.08 (TC); for TTNT-D, the HRs were 0.48 (NSCLC), 0.11 (MTC), 0.09 (TC); and for TTP, the HRs were 0.54 (NSCLC), 0.15 (MTC), and 0.12 (TC). The ORR was higher for first-line selpercatinib versus the first-line comparator (NSCLC: 85.3% vs. 39.7%; MTC: 82.6% vs. 15.2%; and TC: 81.8% vs. 31.8%). First-line selpercatinib use is associated with improved outcomes compared to first-line comparator therapies for patients with advanced/metastatic RET-activated cancers.

[Current status and future prospects of diffuse large B-cell lymphoma treatment].

R-CHOP therapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) has been used as the standard treatment regimen for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), since the introduction of rituximab in the early 2000s. Recently, polatuzumab vedotin and anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy have been introduced as potential treatment options for relapsed or refractory DLBCL. The effectiveness of polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone for newly diagnosed CD20-positive DLBCL, except for the low-risk group of the international prognostic index, was reported in 2022. Bispecific antibodies such as epcoritamab, mosunetuzumab, and glofitamab, anti-CD19 antibody drug tafasitamab combined with lenalidomide, CD19 antibody drug conjugate loncastuximab tesirine, oral selective inhibitor of nuclear export selinexor, and several new agents have been investigated for DLBCL. For non-germinal center B-cell type DLBCL, R-CHOP combined with acalabrutinib is being evaluated. This review summarizes the current standard of care for DLBCL and outlines the recently introduced therapeutic agents or those that are under development in Japan.

Prognostic impact of surgical treatment for high-grade neuroendocrine carcinoma of the lung: a multi-institutional retrospective study.

Background: High-grade neuroendocrine carcinoma (HGNEC) of the lung, which includes small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC), is an aggressive form of lung cancer. Although lobectomy followed by adjuvant chemotherapy is regarded as the standard therapy for this disease, it would be an uphill struggle for HGNEC patients to receive that multidisciplinary therapy perfectly. This study aimed to examine recurrence and survival outcomes in surgically treated patients with HGNEC of the lung. Methods: The medical records of 104 HGNEC patients who underwent surgical treatment in five institutions were retrospectively analyzed. Standard treatment (ST) was defined as lobectomy, bilobectomy, or pneumonectomy with mediastinal lymph node dissection followed by adjuvant platinum-doublet chemotherapy with more than two cycles. Results: Patients in the ST group (n=31; 30%) were younger and had fewer respiratory complications than those in the non-standard treatment (NST) group (n=73; 70%). A significantly higher proportion of patients in the NST group developed ipsilateral lymph node recurrence (21% vs. 3%; P=0.035) and ipsilateral or contralateral lung recurrence (15% vs. 0%; P=0.031). Five-year overall survival (OS) was 64.2% in the ST group and 38.3% in the NST group (P=0.038). NST was independently associated with worse OS in multivariate analysis (hazard ratio, 2.044; 95% confidence interval, 1.016-4.113; P=0.045). Conclusions: Surgically treated HGNEC patients who received ST had a more favorable outcome than those who received NST. Patients who receive NST may require additional treatment.

Synergistic anti-tumor efficacy of mutant isocitrate dehydrogenase 1 inhibitor SYC-435 with standard therapy in patient-derived xenograft mouse models of glioma.

Clinical outcomes in patients with WHO grade II/III astrocytoma, oligodendroglioma or secondary glioblastoma remain poor. Isocitrate dehydrogenase 1 (IDH1) is mutated in > 70% of these tumors, making it an attractive therapeutic target. To determine the efficacy of our newly developed mutant IDH1 inhibitor, SYC-435 (1-hydroxypyridin-2-one), we treated orthotopic glioma xenograft model (IC-BT142AOA) carrying R132H mutation and our newly established orthotopic patient-derived xenograft (PDX) model of recurrent anaplastic oligoastrocytoma (IC-V0914AOA) bearing R132C mutation. In addition to suppressing IDH1 mutant cell proliferation in vitro, SYC-435 (15 mg/kg, daily x 28 days) synergistically prolonged animal survival times with standard therapies (Temozolomide + fractionated radiation) mediated by reduction of H3K4/H3K9 methylation and expression of mitochondrial DNA (mtDNA)-encoded molecules. Furthermore, RNA-seq of the remnant tumors identified genes (MYO1F, CTC1 and BCL9) and pathways (base excision repair, TCA cycle II, sirtuin signaling, protein kinase A, eukaryotic initiation factor 2 and α-adrenergic signaling) as mediators of therapy resistance. Our data demonstrated the efficacy SYC-435 in targeting IDH1 mutant gliomas when combined with standard therapy and identified a novel set of genes that should be prioritized for future studies to overcome SYC-435 resistance.

Effect of Tocilizumab in Reducing the Mortality Rate in COVID-19 Patients: A Systematic Review with Meta-Analysis.

Data supporting the use of Tocilizumab (TCZ) in COVID-19 are contrasting and inconclusive. This meta-analysis aimed to assess TCZ effectiveness in reducing the mortality rate in COVID-19 patients. PubMed, Scopus, Embase, Cochrane, WILEY, and ClinicalTrials.gov were searched to evaluate observational studies and RCTs. The outcome was the mortality rate. Forty observational studies and seven RCTs, involving 9640 and 5556 subjects treated with Standard Therapy (ST) + TCZ or ST alone, respectively, were included. In patients treated with ST+TCZ, a higher survival (Log odds ratio = -0.41; 95% CI: -0.68 -0.14; p < 0.001) was found. Subgroups analyses were performed to better identify the possible interference of some parameters in modifying the efficacy of TCZ therapy on COVID-19 mortality. Separating observational from RCTs, no statistically significant (p = 0.70) TCZ-related reduction of mortality regarding RCTs was found, while a significant reduction (Log odds ratio = -0.52; 95% CI: -0.82 -0.22, p < 0.001) was achieved regarding the observational studies. Stratifying for the use of Invasive Mechanic Ventilation (IMV), a higher survival was found in patients treated with TCZ in the No-IMV and IMV groups (both p < 0.001), but not in the No-IMV/IMV group. Meta-regression analyses were also performed. The meta-analysis of observational studies reveals that TCZ is associated with reducing the mortality rate in both severe and critically ill patients. Although the largest RCT, RECOVERY, is in line with this result, the meta-analysis of RCTs failed to found any difference between ST + TCZ and ST. It is crucial to personalize the therapy considering the patients' characteristics.

Favipiravir versus standard of care in patients with severe COVID-19 infections: A retrospective comparative study.

OBJECTIVE: To assess the efficacy of Favipiravir compared to the standard therapy in treating patients with severe COVID-19 infection. METHODS: This is a retrospective cohort of patients with COVID-19 pneumonia who were treated with favipiravir, versus comparison group that received the standard of care. RESULTS: A total of 226 patients were included; 110 patients received favipiravir and 116 patients received standard of care. Patients who received favipiravir had longer time to recovery (14.2 ± 8.8 versus 12.8 ± 5.2, p = 0.17). Favipiravir was associated with an improved early day 14 mortality (4 [3.6%] versus 11 [9.5%]), p = 0.008), but was associated with a higher day 28 mortality (26 [23.6%] versus 11 [9.5%], p = 0.02). The overall mortality was higher in the favipiravir versus the standard of care group but difference was not statistically significant (33 [30.0%] versus 24 [20.7%], p = 0.10). CONCLUSION: The addition of favipiravir to standard of care was not associated with any improvement in clinical outcomes or mortality. Larger randomized controlled clinical trials are needed to further assess the efficacy of favipiravir.

Results and Prospects of Using Activator of Hematopoietic Stem Cell Differentiation in Complex Therapy for Patients with COVID-19.

The paper presents the results of a standard and complex treatment method using the peptide drug thymus thymalin in patients with COVID-19. One of the mechanisms of the immunomodulatory effect of thymalin is considered to be the ability of this peptide drug to influence the differentiation of human hematopoietic stem cells (HSCs). It was found that, as a result of standard treatment, patients in the control group showed a decrease in the concentration of the pro-inflammatory cytokine IL-6, C-reactive protein, D-dimer. The addition of thymalin to standard therapy accelerated the decline in both these indicators and the indicators of the T cell system. This has helped reduce the risk of blood clots in COVID-19 patients. The revealed properties of the thymus peptide preparation are the rationale for its inclusion in the complex treatment of coronavirus infection. Peptideswith potential biological activity against SARS-CoV-2 virus [29]. Note: Nitrogen atoms are shown in blue, oxygen atoms - in red, carbon atoms - in gray, hydrogen atoms - in white, and phosphorus atoms - in yellow.

Nonoperative treatment of chronic, massive irreparable rotator cuff tears: a systematic review with synthesis of a standardized rehabilitation protocol.

PURPOSE: A massive, irreparable rotator cuff tear may cause significant pain and dysfunction. However, the efficacy of nonoperative treatment modalities in this subset of patients is not currently well known. Also, there is currently no gold standard nonoperative protocol to guide treatment. The goal of the present systematic review is to determine if there is any evidence to support the use of various nonoperative treatment modalities and synthesize a standardized nonoperative treatment protocol for the patient with a massive irreparable rotator cuff tear. METHODS: A comprehensive review of the literature utilizing PRISMA guidelines was performed. Studies involving clinical outcomes of nonoperative treatment of massive, irreparable rotator cuff tears were included. Articles were reviewed by 2 reviewers to determine inclusion or exclusion based on established criteria. Selected articles were reviewed for results of clinical and functional outcomes. The studies were also reviewed to determine their level of evidence and potential sources of bias. A standardized nonoperative treatment protocol was developed by taking described elements of the protocols used in studies that demonstrated clinical improvement beyond the MCID for the outcome scores used by the authors. RESULTS: A total of 10 studies met inclusion criteria for our studies. Of the included studies, 1 was Level III evidence and the remaining 9 were Level IV evidence. Multiple studies showed significant improvement exceeding the MCID for functional outcome scores following treatment. Also, several studies demonstrated significant improvements in strength and range of motion. The overall success of nonoperative treatment ranged from 32%-96%. The synthesized nonoperative treatment protocol is characterized by requiring some supervised physical therapy, often requiring 12 weeks or more, focusing on supine exercises with gradual progression to upright. Corticosteroid injections and nonsteroidal anti-inflammatory drugs may also be of benefit. CONCLUSION: Despite low-quality evidence, nonoperative treatment has been shown to be efficacious for patients with chronic, massive, irreparable rotator cuff tears. Using these results, a synthesized rehabilitation program was developed to guide clinicians when treating patients with massive irreparable rotator cuff tears.

Tumor treating fields for high-grade gliomas.

High-grade gliomas (HGG) are the most common malignant intracranial tumors with poor prognosis. Current treatments have not yielded optimal remission rates; there are no standard treatments for recurrent and drug-resistant gliomas. Tumor treating fields, which was recently approved by the Food and Drug Administration (FDA), could significantly improve progression free survival and the overall survival of glioma patients. In this review, we elaborate on the mechanism of tumor treating fields in tumor cells and detail various preclinical and clinical studies on gliomas. Tumor treating fields could be a promising option for patients with malignant tumors for which there are no standard treatment plans. Moreover, we identify several potential problems for the practical application of tumor treating fields and predict future directions for further studies. Tumor treating fields may be a potential therapy with high efficacy, fewer adverse effects, and high cost-effectiveness.

Compliance With Standard Therapies and Remission Rates After Implementation of an Infantile Spasms Management Guideline.

BACKGROUND: We implemented an infantile spasms management guideline recommending standard therapies and, early start of next treatment. After six years, we determined (1) our compliance with standard therapies, (2) time to next treatment, and (3) rate of initial and three-month electroclinical remission with first, second, and third treatments. METHODS: This is a retrospective record review of newly diagnosed spasms from September 2012 to September 2018, with the onset age of two months to two years. RESULTS: Standard therapies (hormone or vigabatrin) were the first treatments in 114 of 115 consecutive patients. The second and third treatments were started within 14 days of failed treatment in only 21% and 24%, respectively. Remission with the first and second treatments was similar (41% and 40%). Remission was lower for the third treatment (15%), although higher if standard therapy was used (36%). Initial and three-month remission by the first treatment was significantly higher for adrenocorticotropic hormone (ACTH, 66% and 79%, respectively) and prednisolone (53% and 83%, respectively) than for vigabatrin (19% and 40%, respectively). There were no significant differences in patient characteristics or rates of remission between ACTH and prednisolone. CONCLUSIONS: Although we achieved excellent compliance with standard therapies as initial treatment, a next treatment often started after two weeks. Given the superiority of hormone therapies over vigabatrin and standard therapies over nonstandard therapies, as well as the potentially negative impact of delays in effective treatment, future interventions need to focus on increasing the use of hormone over vigabatrin (for patients without tuberous sclerosis complex), use of standard therapies as second and third treatments, and reducing delays to next treatment.

The rapidly changing landscape in mature T-cell lymphoma (MTCL) biology and management.

Historical advances in the care of patients with non-Hodgkin lymphoma (NHL) have been restricted largely to patients with B-cell lymphoma. The peripheral T-cell lymphomas (PTCLs), which are rare and heterogeneous in nature, have yet to experience the same degree of improvement in outcome over the past 20 to 30 years. It is estimated that there are approximately 80,000 and 14,000 cases, respectively, of NHL and Hodgkin lymphoma per year in the United States. As a subgroup of NHL, the PTCLs account for 6% to 10% of all cases of NHL, making them exceedingly rare. In addition, the World Health Organization 2017 classification describes 29 distinct subtypes of PTCL. This intrinsic diversity, coupled with its rarity, has stymied progress in the disease. In addition, most subtypes carry an inferior prognosis compared with their B-cell counterparts, an outcome largely attributed to the fact that most treatment paradigms for patients with PTCL have been derived from B-cell neoplasms, a radically different disease. In fact, the first drug ever approved for patients with PTCL was approved only a decade ago. The plethora of recent drug approvals in PTCL, coupled with a deeper understanding of the molecular pathogenesis of the disease, has stimulated the field to pursue new avenues of research that are now largely predicated on the development of novel, targeted small molecules, which include a host of epigenetic modifiers and biologics. There is an expectation these advances may begin to favorably challenge the chemotherapy paradigms that have been used in the T-cell malignancies.

Real-world data on initial treatment strategies for older adult patients with endometrial cancer in Japan.

OBJECTIVE: Current strategies for the treatment of endometrial cancer in older adult patients require re-evaluation given the global trend in population aging, especially in Japan. We sought to evaluate initial treatment offered to older adult patients with endometrial cancer in Japan. METHODS: We retrospectively analyzed data on the standard treatment by age group in patients with endometrial cancer who underwent surgery between January 2005 and December 2013 at the National Cancer Center Hospital (Tokyo, Japan). Patients were stratified into four groups according to age: a younger group, aged 64 years or younger; older adult group 1, aged 65-69 years; older adult group 2, aged 70-74 years; and older adult group 3, aged ≥75 years. RESULTS: Among 551 patients with endometrial cancer diagnosed and treated at our hospital, data from 531 eligible patients were analyzed. The proportion of patients in the older adult groups 1 or 2 who received standard treatment was the same as in the younger group. However, significantly fewer patients in older adult group 3 received standard treatment compared with the younger group (26% vs. 71%, p = 0.0001). Furthermore, the proportion of patients in older adult group 3 who underwent standard surgery was significantly lower than that in the younger group (26% vs. 72%, p = 0.0001). CONCLUSIONS: The results indicate that age 75 years and older might represent a cutoff for the development of age-based treatment strategies for endometrial cancer. This information could be used to determine the upper age limit for participation in clinical trials in Japan.