Medical sciences (Basel, Switzerland)最新文献

Background: There has been growing interest in exploring combined interventions to achieve a more effective heparin-free treatment approach.

Aim: to evaluate combination of interventions compared to standard practice (intermittent flushes) to prevent clotting and consequently reduce premature interruptions of hemodialysis.

Methods: This open-label randomized controlled trial recruited chronic hemodialysis patients with contra-indication to systemic heparinization. Participants were randomized into one of five groups to receive different strategies of heparin-free hemodialysis treatment for up to three sessions.

Primary endpoint: the successful completion of hemodialysis without clotting.

Secondary outcomes: the clotting of the air traps assessed by a semi-quantitative scale, online KT/V, and safety of the interventions.

Results: Forty participants were recruited and randomized between May and December 2020. Participants showed similar baseline biochemistry results and coagulation profiles. The highest success rates were observed in group 3 (heparin-coated dialyzers combined with intermittent flushes) (100%) and group 5 (hemodiafiltration with online predilution combined with heparin-coated dialyzers), with 91% vs. the control (intermittent flushes) (64%). Group 2 (heparin-coated dialyzers alone) had the poorest success rate, with 38% of the sessions being prematurely terminated due to clotting. KT/V and clotting scores were similar between groups. No adverse events related to the trial interventions were observed.

Conclusions: The proposed combination of interventions may have had additive effects, leading to less frequent clotting and the premature termination of an HD/HDF session. Our study supports the feasibility of conducting a larger randomized controlled trial focusing on the efficacy of combined interventions for heparin-free HD in patients with a high risk of bleeding.

The accurate diagnosis of gout frequently constitutes a challenge in clinical practice, as it bears a close resemblance to other rheumatologic conditions. An undelayed diagnosis and an early therapeutic intervention using uric acid lowering therapy (ULT) is of the utmost importance for preventing bone destruction, the main point of managing gout patients. Advanced and less invasive imaging techniques are employed to diagnose the pathology and ultrasonography (US) stands out as a non-invasive, widely accessible and easily reproducible method with high patient acceptability, enabling the evaluation of the full clinical spectrum in gout. The 2023 EULAR recommendations for imaging in diagnosis and management of crystal-induced arthropathies in clinical practice state that US is a fundamental imagistic modality. The guidelines underline its effectiveness in detecting crystal deposition, particularly for identifying tophi and the double contour sign (DCS). Its utility also arises in the early stages, consequent to synovitis detection. US measures of monosodium urate (MSU) deposits are valuable indicators, sensitive to change consequent to even short-term administration of ULT treatment, and can be feasibly used both in current daily practice and clinical trials. This paper aimed to provide an overview of the main US features observed in gout patients with reference to standardized imaging guidelines, as well as the clinical applicability both for diagnosis accuracy and treatment follow-up. Our research focused on summarizing the current knowledge on the topic, highlighting key data that emphasize gout as one of the few rheumatological conditions where US is recognized as a fundamental diagnostic and monitoring tool, as reflected in the most recent classification criteria.

Background: The prognostic role of imaging with [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) in oropharynx cancer (OPC) has been demonstrated in the past. The aim of this study was to assess the prognostic impact of both baseline and post-treatment PET/CT in patients with OPC and treated with chemo- and/or radiotherapy.

Methods: The PET/CT parameters of scans performed before and after therapy were collected and analyzed to find significant prognosticators for progression-free survival (PFS) and overall survival (OS). Human papillomavirus (HPV) infection's influence on the prognosis was also taken into account.

Results: A total of 66 patients were included in the study. The staging volumetric parameters of PET/CT were significant prognosticators for OS, while the same parameters were affordable predictors for PFS at the restaging evaluation. No significant correlations between HPV infection and PET/CT parameters were reported.

Conclusion: The prognostic role of volumetric [18F]FDG PET/CT parameters in patients with OPC was reported.

Introduction: Lumbar foraminal stenosis (LFS) occurs primarily due to degenerative changes in older adults, affecting the spinal foramina and leading to nerve compression. Characterized by pain, numbness, and muscle weakness, LFS arises from structural changes in discs, joints, and ligaments, further complicated by factors like inflammation and spondylolisthesis. Diagnosis combines patient history, physical examination, and imaging, while management ranges from conservative treatment to surgical intervention, underscoring the need for a tailored approach.

Materials and methods: This multicenter study, conducted over six years at a tertiary hospital, analyzed the volumetric dimensions of lumbar foramina and their correlation with nerve structures in 500 patients without lumbar pathology. Utilizing high-resolution MRI with a standardized imaging protocol, eight experienced researchers independently reviewed the images for accurate measurements. The study emphasized quality control through the calibration of measurement tools, double data entry, validation checks, and comprehensive training for researchers. To ensure reliability, interobserver and intraobserver agreements were analyzed, with statistical significance determined by kappa statistics and the Student's t-test. Efforts to minimize bias included blinding observers to patient information and employing broad inclusion criteria to mitigate referral and selection biases. The methodology and findings aim to enhance the understanding of normal lumbar foramina anatomy and its implications for diagnosing and treating lumbar conditions.

Results: The study's volumetric analysis of lumbar foramina in 500 patients showed a progressive increase in foraminal volume from the L1/L2 to the L5/S1 levels, with significant enlargement at L5/S1 indicating anatomical and biomechanical complexity in the lumbar spine. Lateral asymmetry suggested further exploration. High interobserver and intraobserver agreement levels (ICC values of 0.91 and 0.95, respectively) demonstrated the reliability and reproducibility of measurements. The patient cohort comprised 58% males and 42% females, highlighting a balanced gender distribution. These findings underscore the importance of understanding foraminal volume variations for lumbar spinal health and pathology.

Conclusion: Our study significantly advances spinal research by quantifying lumbar foraminal volumes, revealing a clear increase from the L1/L2 to the L5/S1 levels, indicative of the spine's adaptation to biomechanical stresses. This provides clinicians with a precise tool to differentiate between pathological narrowing and normal variations, enhancing the detection and treatment of lumbar foraminal stenosis. Despite limitations like its cross-sectional design, the strong agreement in measurements underscores the method's reliability, encouraging future research to further

Human Immunodeficiency Virus (HIV) remains a significant global health challenge with approximately 38 million people currently having the virus worldwide. Despite advances in treatment development, the virus persists in the human population and still leads to new infections. The virus has a powerful ability to mutate and hide from the human immune system in reservoirs of the body. Current standard treatment with antiretroviral therapy effectively controls viral replication but requires lifelong adherence and does not eradicate the virus. This review explores the potential of Advanced Therapy Medicinal Products as novel therapeutic approaches to HIV, including cell therapy, immunisation strategies and gene therapy. Cell therapy, particularly chimeric antigen receptor T cell therapy, shows promise in preclinical studies for targeting and eliminating HIV-infected cells. Immunisation therapies, such as broadly neutralising antibodies are being investigated to control viral replication and reduce reservoirs. Despite setbacks in recent trials, vaccines remain a promising avenue for HIV therapy development. Gene therapy using technologies like CRISPR/Cas9 aims to modify cells to resist HIV infection or eliminate infected cells. Challenges such as off-target effects, delivery efficiency and ethical considerations persist in gene therapy for HIV. Future directions require further research to assess the safety and efficacy of emerging therapies in clinical trials. Combined approaches may be necessary to achieve complete elimination of the HIV reservoir. Overall, advanced therapies offer new hope for advancing HIV treatment and moving closer to a cure.

Hemodialyzed patients have innate immunity activation and adaptive immunity senescence. Diabetes mellitus is a frequent cause for chronic kidney disease and systemic inflammation. We studied the immunological pattern (innate and acquired immunity) and the tissular regeneration capacity in two groups of hemodialyzed patients: one comprised of diabetics and the other of non-diabetics. For inflammation, the following serum markers were determined: interleukin 6 (IL-6), interleukin 1β (IL-1β), tumoral necrosis factor α (TNF-α), IL-6 soluble receptor (sIL-6R), NGAL (human neutrophil gelatinase-associated lipocalin), and interleukin 10 (IL-10). Serum tumoral necrosis factor β (TNF-β) was determined as a cellular immune response marker. Tissue regeneration capacity was studied using neurotrophin-3 (NT-3) and vascular endothelial growth factor β (VEGF-β) serum levels. The results showed important IL-6 and sIL-6R increases in both groups, especially in the diabetic patient group. IL-6 generates trans-signaling at the cellular level through sIL-6R, with proinflammatory and anti-regenerative effects, confirmed through a significant reduction in NT-3 and VEGF-β. Our results suggest that the high serum level of IL-6 significantly influences IL-1β, TNF-β, NT-3, VEGF-β, and IL-10 behavior. Our study is the first that we know of that investigates NT-3 in this patient category. Moreover, we investigated VEGF-β and TNF-β serum behavior, whereas most of the existing data cover only VEGF-α and TNF-α in hemodialyzed patients.

Background: Electroconvulsive therapy (ECT) is a procedure commonly used to treat a number of severe psychiatric disorders, including pharmacologic refractory depression, mania, and catatonia by purposefully inducing a generalized seizure that results in significant hemodynamic changes as a result of an initial transient parasympathetic response that is followed by a marked sympathetic response from a surge in catecholamine release. While the physiologic response of ECT on classic hemodynamic parameters such as heart rate and blood pressure has been described in the literature, real-time visualization of cardiac function using point-of-care ultrasound (POCUS) during ECT has never been reported. This study utilizes POCUS to examine cardiac function in two patients with different ages and cardiovascular risk profiles undergoing ECT.

Methods: Two patients, a 74-year-old male with significant cardiovascular risks and a 23-year-old female with no significant cardiovascular risks presenting for ECT treatment, were included in this study. A portable ultrasound device was used to obtain apical four-chamber images of the heart before ECT stimulation, after seizure induction, and 2 min after seizure resolution to assess qualitative cardiac function. Two physicians with expertise in echocardiography reviewed the studies. Hemodynamic parameters, ECT settings, and seizure duration were recorded.

Results: Cardiac standstill was observed in both patients during ECT stimulation. The 74-year-old patient with a significant cardiovascular risk profile exhibited a transient decline in cardiac function during ECT, while the 23-year-old patient showed no substantial worsening of cardiac function. These findings suggest that age and pre-existing cardiovascular conditions may influence the cardiac response to ECT. Other potential contributing factors to the cardiac effects of ECT include the parasympathetic and sympathetic responses, medication regimen, and seizure duration with ECT. This study also demonstrates the feasibility of using portable POCUS for real-time cardiac monitoring during ECT.

Conclusion: This study reports for the first time cardiac standstill during ECT stimulation visualized using POCUS imaging. In addition, it reports on the potential differential impact of ECT on cardiac function based on patient-specific factors such as age and cardiovascular risks that may have implications for ECT and perioperative anesthetic management and optimization.

Background and objectives: The implications of the genetic component in the initiation and development of chronic lymphoproliferative disorders have been the subject of intense research efforts. Some of the most important genes involved in the occurrence and evolution of these pathologies are the HLA genes. The aim of this study is to analyze, for the first time, possible associations between chronic lymphoproliferative diseases and certain HLA alleles in the Romanian population.

Materials and methods: This study included 38 patients with chronic lymphoproliferative disorders, diagnosed between 2021 and 2022 at Fundeni Clinical Institute, Bucharest, Romania, and 50 healthy controls. HLA class I and class II genes (HLA-A/B/C, HLA-DQB1/DPB1/DRB1) were investigated by doing high resolution genotyping using sequence specific primers (SSP).

Results: Several HLA alleles were strongly associated with chronic lymphoproliferative disorders. The most important finding was that the HLA-C*02:02 (p = 0.002, OR = 1.101), and HLA-C*12:02 (p = 0.002, OR = 1.101) have a predisposing role in the development of chronic lymphoproliferative disorders. Moreover, we identified that HLA-A*11:01 (p = 0.01, OR = 0.16), HLA-B*35:02 (p = 0.037, OR = 0.94), HLA-B*81:01 (p = 0.037, OR = 0.94), HLA-C*07:02 (p = 0.036, OR = 0.34), HLA-DRB1*11:01 (p = 0.021, OR = 0.19), and HLA-DRB1*13:02 (p = 0.037, OR = 0.94), alleles have protective roles.

Conclusions: Our study indicates that HLA-C*02:02 and HLA-C*12:02 are positively associated with chronic lymphoproliferative disorders for our Romanian patients while HLA-DRB1*11:01, HLA-DRB1*13:02, and HLA-B*35:02 alleles have a protective role against these diseases.

Background: Tobacco use disorder (TUD) adversely impacts older patients with established cardiovascular disease (CVD) risk. However, CVD risk in chronic habitual cannabis users without the confounding impact of TUD hasn't been explored. We aimed to determine the risk of major adverse cardiac and cerebrovascular events (MACCE) in older non-tobacco smokers with established CVD risk with vs. without cannabis use disorder (CUD).

Methods: We queried the 2019 National Inpatient Sample for hospitalized non-tobacco smokers with established traditional CVD risk factors aged ≥65 years. Relevant ICD-10 codes were used to identify patients with vs. without CUD. Using multivariable logistic regression, we evaluated the odds of MACCE in CUD cohorts compared to non-CUD cohorts.

Results: Prevalence of CUD in the sample was 0.3% (28,535/10,708,815, median age 69), predominantly male, black, and non-electively admitted from urban teaching hospitals. Of the older patients with CVD risk with CUD, 13.9% reported MACCE. The CUD cohort reported higher odds of MACCE (OR 1.20, 95% CI 1.11-1.29, p < 0.001) compared to the non-CUD cohort. Comorbidities such as hypertension (OR 1.9) and hyperlipidemia (OR 1.3) predicted a higher risk of MACCE in the CUD cohort. The CUD cohort also had higher unadjusted rates of acute myocardial infarction (7.6% vs. 6%) and stroke (5.2% vs. 4.8%).

Conclusions: Among older non tobacco smokers with known CVD risk, chronic cannabis use had a 20% higher likelihood of MACCE compared to those who did not use cannabis.

Familial kidney tumors represent a rare variety of hereditary cancer syndromes, although systematic gene sequencing studies revealed that as many as 5% of renal cell carcinomas (RCCs) are associated with germline pathogenic variants (PVs). Most instances of RCC predisposition are attributed to the loss-of-function mutations in tumor suppressor genes, which drive the malignant progression via somatic inactivation of the remaining allele. These syndromes almost always have extrarenal manifestations, for example, von Hippel-Lindau (VHL) disease, fumarate hydratase tumor predisposition syndrome (FHTPS), Birt-Hogg-Dubé (BHD) syndrome, tuberous sclerosis (TS), etc. In contrast to the above conditions, hereditary papillary renal cell carcinoma syndrome (HPRCC) is caused by activating mutations in the MET oncogene and affects only the kidneys. Recent years have been characterized by remarkable progress in the development of targeted therapies for hereditary RCCs. The HIF2aplha inhibitor belzutifan demonstrated high clinical efficacy towards VHL-associated RCCs. mTOR downregulation provides significant benefits to patients with tuberous sclerosis. MET inhibitors hold promise for the treatment of HPRCC. Systematic gene sequencing studies have the potential to identify novel RCC-predisposing genes, especially when applied to yet unstudied populations.