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Abnormal CTLA-4 trafficking is also observed in patients with LRBA deficiency, a syndrome caused by biallelic mutations in LRBA that abolishes the LRBA protein expression. Both immune checkpoint deficiencies are biologically characterized by low levels of CTLA-4 protein on the cell surface of Tregs, accounting for the autoimmune manifestations observed in CTLA4-insufficient and LRBA-deficient patients. In addition, both immune checkpoint deficiencies present with an overlapping but heterogeneous clinical picture despite the difference in inheritance and penetrance. In this review, we describe the most prominent clinical features of ALPS, CTLA-4 insufficiency and LRBA deficiency, emphasizing their corresponding biological mechanisms. We also provide some clinical and laboratory approaches to diagnose these three rare immune disorders, together with therapeutic strategies that have worked best at improving prognosis and quality life of patients.
Tracheobronchoplasty (TBP) is the gold-standard treatment for severe symptomatic excessive central airway collapse (ECAC), however outcomes among obese patients are unknown.
A retrospective, single-center analysis was conducted on consecutive patients undergoing TBP for severe symptomatic ECAC from 2003 to 2020. GSK3326595 Demographics, comorbidities, functional status, and peri-operative complications were collected. Functional status was assessed with a six-minute walk test (6MWT). Health-related quality of life (HRQOL) was assessed with the St. George's Respiratory Questionnaire (SGRQ), Cough-Specific Quality of Life Questionnaire (CSQL), and modified Medical Research Council dyspnea scale (mMRC) at baseline and post-operatively. Wilcoxon rank-sum and chi-squared tests were used to compare outcomes between groups. A mixed-effects regression model compared 6MWT and HRQOL over time.
One-hundred and three patients underwent TBP with complete follow-up data. Thirty-four patients (33%) were obese (BMI ≥ 35 kg/m
). Baseline demographics were similar between obese and non-obese groups, however obese patients had worse pre-operative SGRQ and mMRC. Overall complication rates were similar (52.9% vs. 43.5%, p=0.36). At 3-months, there was no significant difference in SGRQ, CSQL, or 6MWT, however, mMRC was higher in obese patients (p=0.04). At 12 months, there was no significant difference in SGRQ, CSQL, mMRC, or 6MWT. Correcting for age, sex, and Charlson Comorbidity Index, a mixed-effects regression model demonstrated obesity was not an independent predictor for lower 6MWT or HRQOL.
Obese patients achieve similar improvement in HRQOL and functional capacity with comparable morbidity following TBP as non-obese patients. Obesity should not preclude patients with severe symptomatic ECAC from TBP.
Obese patients achieve similar improvement in HRQOL and functional capacity with comparable morbidity following TBP as non-obese patients. Obesity should not preclude patients with severe symptomatic ECAC from TBP.
Non-coronary vascular disease (NCVD) is associated with adverse cardiovascular events. Little is known about physician risk assessment, prevalence of CAD, cardiac catheterization, and the performance of the ASCVD risk score in patients with NCVD.
Retrospective analysis of outpatients with angina and no known CAD from the PROMISE trial. NCVD included carotid artery stenosis ≥ 50%, or history of stroke or peripheral artery disease. Multivariable models of physician estimates of the probability of obstructive CAD, prevalence of non-obstructive and obstructive CAD, referral to cardiac catheterization, and all-cause death/myocardial infarction/unstable angina were performed.
Among 10,001 patients in the PROMISE trial, 379 (3.8%) patients had NCVD. Only 8.5% of participants with NCVD were categorized as high-risk for obstructive CAD by physicians, though 15.5% (25/161) had obstructive CAD in those randomized to coronary CTA. NCVD was independently associated with non-obstructive (aOR = 1.58; 95% CI 1.18 - 2.6ciated CV risk and optimize diagnostic testing and therapies.
Obesity in the child population and its effect in the development of metabolic diseases are a public health issue. One of the aims of the European Project in a health system, is the evaluation of the effectiveness of a multidisciplinary health promotion program directed at adolescents with risk factors associated with the development of type 2 Diabetes Mellitus (T2DM).
Randomised clinical trial with two groups of 12-14 year-old overweight adolescents. The intervention group took part in a multidisciplinary program for 24 months. This program was based on 11 group sessions (8 main sessions and 3 additional support ones) for adolescents and their guardians. The control group received usual care at primary care level. Longitudinal regression models were adjusted to assess the evolution of anthropometric measures and living habits at baseline, 3, 6, 12, and 24 months in both groups.
There were 92 participants, equally distributed by group. Statistically significant differences were observed between intervention and control groups in several results evolution of the body mass index; increase in the consumption of fruits and vegetables; decrease in the consumption of snacks and sweetened drinks; and increase in the number of days per week with more than one hour of physical activity.
The results confirm the effectiveness of this multidisciplinary program, both in the evolution of the body mass index, and in the improvement of the eating and physical activity habits, all of them risk factors for the future development of metabolic diseases, such as T2DM.
The results confirm the effectiveness of this multidisciplinary program, both in the evolution of the body mass index, and in the improvement of the eating and physical activity habits, all of them risk factors for the future development of metabolic diseases, such as T2DM.Multiple myeloma is a progressive and incurable hematologic malignancy. It is predominantly a disease of older individuals, with a third of these patients considered to be elderly. In recent years, there has been a focus and emphasis on identifying and stratifying patients based on their functional status and frailty. There are several hallmark complications of the disease-hypercalcemia, renal insufficiency, anemia, bone pain-along with thromboembolism and compromised immunity that are common in patients with multiple myeloma. Due to the wide range of patient ages and functional status, there are, accordingly, different considerations for management of the above complications based on numerous factors, including frailty status. This review focuses on considerations and management of common complications of multiple myeloma in elderly patients. These include renal failure, skeletal complications, anemia, thromboembolism, and infectious complications.
Immunoglobulin heavy chain variable region (IGHV) repertoire narrowing could be an evidence for the involvement of a limited set of antigens in the development of lymphomas. For chronic lymphocytic leukemia (CLL) the existence of more than 200 subgroups of tumor IGHV antigen-binding sites, so called "stereotypical" antigen receptors (SAR) has been shown. For others lymphomas the possibility of SARs is also suggested. The aim of this study is to compare the tumor IGHVs and possible SARs in various B-cell malignancies in Russia and other countries.
The study included samples of 1800 CLL patients, 52 patients with mantle cell lymphoma, 48 patients with hairy cell lymphoma and 37 patients with splenic marginal cell lymphoma. The nucleotide sequences of the IGHV genes were determined according to ERIC protocol.
In CLL most common IGHV genes were IGHV1-69, IGHV1-2, IGHV3-30 and IGHV4-34. The most common SARs were CLL#1, CLL#6, CLL#2, CLL#3. In MCL the most common genes were IGHV4-34, IGHV3-21, IGHV3-23. In 5 the development of new diagnostic and prognostic markers.
Light chain (AL) amyloidosis and B-cell lymphoma represent 5% to 7% of all AL, Systemic amyloidosis, deposits in sites remote from the underlying lymphoma, and peritumoral amyloidosis deposition is within the immediate vicinity.
We conducted a retrospectively study to identify and describe AL with B cell lymphoma at Princess Margaret Cancer Center from 01 January 1997 to 31 July 2019.
Thirty-five patients with AL and lymphoma, an incidence of 6, 2%, median age of diagnosis of 66 (range 47 to 86), majority male, most had underlying Waldestrom's Macroglobulinemia. 21 patients with peritumoral AL (PAL), and 15 with systemic AL. 42.8% of the patients had major organ involvement. 35% got treatment with Rituximab with alkylator, 20% received proteasome inhibitors, 17% patients were on a watch and wait approach, amyloid response showed very good partial response > 45.8%, and lymphoma ORR was 42.8%, with a median follow up of 31.5 months. A 36 month overall survival (OS) and progression-free survival (PFS) showed worse outcomes for heart involvement OS (P = .002), PFS (0.057) and IgM subtype OS (P = .02), PFS (0.01).
We have shown adverse outcome with IgM AL and to document a differences in OS and PFS not previously reported for PAL.
We have shown adverse outcome with IgM AL and to document a differences in OS and PFS not previously reported for PAL.
Premature ejaculation (PE) is one of the most common ejaculatory disorders. Recent studies have suggested a close relationship between the serotonin (5-hydroxytryptamine [5-HT]) system and brain-derived neurotrophic factor (BDNF), raising the question of whether BDNF plays a role in ejaculation regulation. To our knowledge, no previous studies have explored BDNF level of the central nervous system in ejaculatory disorders. At the same time, the interaction of central BDNF and 5-HT systems has not been undertaken in ejaculation regulation field.
The aim of this study was to investigate the interaction between BDNF and 5-HT levels in raphe nuclei which contains the serotonergic neurons in a rat animal model with different ejaculatory behavior.
Eighteen male rats were selected and classified as "sluggish," "normal," and "rapid" ejaculators on the basis of ejaculation frequency during copulatory behavioral testing. BDNF and 5-HT levels were determined by enzyme-linked immunosorbent assay (ELISA). Real-Time aculator Rats. J Sex Med 2021;181491-1499.
Nephro- and hematotoxicity after peptide receptor radionuclide therapy (PRRT) have been described in multiple studies with heterogeneous cumulative activities, number of cycles or radiolabelled peptides. Though highly differentiated metastasized neuroendocrine tumours (NET) have long progression free survival, they may progress. We analysed long-term side effects in a homogenous treatment schedule in PRRT-patients and their impact on future oncologic treatment in case of progression.
From our database 89/384 patients receiving the same PRRT (Lu-177-DOTATATE or Y-90-DOTATOC) 4 times every 10 to 12 weeks and a follow-up at 12 months were analysed. One patient had three and 11 patients had two times four PRRT-cycles resulting in 102 cases. eGFR, Hb, WBC and platelets before the first and one year after the fourth therapy cycle were compared. eGFR-Grading was done according to chronic kidney disease classification (CKD) and grading of hematotoxicity according to Common Terminology Criteria for Adverse Events (CTCAE).
