Journal of clinical medicine research最新文献

The aim of the present study was to report the remodeling of the basement membrane through physiological stimulus during the treatment of fibrosis in a lower limb with lymphedema. A clinical trial was conducted involving the evaluation of the basement membrane in skin biopsies before and after treatment for clinical stage II lower limb lymphedema using the Godoy method for the reversal of lymphedema and skin fibrosis. The samples were stained with Gomori's reticulin stain and evaluated using Weibel's multipoint morphometric method at the Godoy Clinic. Prior to treatment for lymphedema, rupture and important discontinuity of the basement membrane was found. After treatment, structural continuity and thickness had returned to the regions of previous rupture. The difference was statistically significant (P < 0.05, paired t-test). The present study reports that physiological stimuli targeting the lymphatic system led to the clinical reversal of fibrosis, as well as stimulate the synthesis of extracellular matrix proteins and the reconstruction of the basal lamina of the skin.

Granulomatosis with polyangiitis (GPA) has three clinicopathological features, namely, necrotizing granulomatosis of the upper respiratory tract and lungs, focal segmental necrotizing glomerulonephritis of the kidney, and necrotizing vasculitis of small vessels throughout the body. A 92-year-old man with clinically diagnosed probable Alzheimer's disease (AD) exhibited subacute deterioration in cognitive function. On admission, he was diagnosed with acute renal failure with an elevated creatinine level (5.48 mg/dL) as well as severe disturbance of consciousness. Antineutrophil cytoplasmic antibodies (ANCAs) directed against proteinase 3 (PR3-ANCA) were highly positive with ≥ 350 U/mL. The patient was diagnosed with GPA and was managed with steroid pulse therapy. However, he died without any improvement in renal function. As a result of the autopsy, the patient was diagnosed with definite AD, and his impaired consciousness was found not to be caused by central nervous system involvement due to GPA. As necrotizing crescentic glomerulonephritis was observed, the cause of the acute progressive renal failure was found to be PR3-ANCA-positive GPA. The autopsy revealed no GPA-related lesions in other parts of the body aside from the kidneys. It is rare to encounter cases of PR3-ANCA-positive GPA with renal-limited vasculitis and acute renal failure as the initial manifestation, as in the present case. Making an accurate clinical diagnosis of older patients suffering from various diseases in multiple organs is challenging. Although autopsy has the limitation of a terminal image, it is extremely useful in elucidating the pathophysiology of the older patient in this case.

Thalassemia encompasses a group of inherited hemoglobin disorders characterized by reduced or absent production of the α- or β-globin chains, leading to anemia and other complications. Current management relies on lifelong blood transfusions and iron chelation, which is burdensome for patients. This review summarizes the emerging therapeutic potential of modulating microRNAs (miRNAs) to treat thalassemia. MiRNAs are small non-coding RNAs that regulate gene expression through sequence-specific binding to messenger RNAs (mRNAs). While they commonly repress gene expression by binding to the 3' untranslated regions (UTRs) of target mRNAs, miRNAs can also interact with 5'UTRs and gene promoters to activate gene expression. Many miRNAs are now recognized as critical regulators of erythropoiesis and are abnormally expressed in β-thalassemia. Therapeutically restoring levels of deficient miRNAs or inhibiting overexpression through miRNA mimics or inhibitors (antagomir), respectively, has shown preclinical efficacy in ameliorating thalassemic phenotypes. The miR-144/451 cluster is especially compelling for targeted upregulation to reactivate fetal hemoglobin synthesis. Advances in delivery systems are addressing previous challenges in stability and targeting of miRNA-based drugs. While still early, gene therapy studies suggest combinatorial approaches with miRNA modulation may provide synergistic benefits. Several key considerations remain including enhancing delivery, minimizing off-target effects, and demonstrating long-term safety and efficacy. While no miRNA therapies have yet progressed to clinical testing for thalassemia specifically, important lessons are being learned through clinical trials for other diseases and conditions, such as cancer, cardiovascular diseases, and viral. If limitations can be overcome through multi-disciplinary collaboration, miRNAs hold great promise to expand and transform treatment options for thalassemia in the future by precisely targeting pathogenic molecular networks. Ongoing innovations, such as advancements in miRNA delivery systems, improved targeting mechanisms, and enhanced understanding of miRNA biology, continue to drive progress in this emerging field towards realizing the clinical potential of miRNA-based medicines for thalassemia patients.

The management of heart failure (HF) in patients with type 2 diabetes has significantly evolved with the introduction of sodium-glucose cotransporter 2 (SGLT2) inhibitors. This article aims to consolidate existing knowledge on the efficacy of these inhibitors in managing HF in this patient population. Major medical databases, including PubMed, Scopus, and Web of Science, were reviewed, prioritizing research from the last decade. The results of this review highlight the mechanisms of action of SGLT2 inhibitors, their clinical benefits, challenges in patient management, and outcomes associated with their use. These medications were found to not only improve glycemic control but also offer significant cardiovascular and renal benefits, reducing cardiovascular mortality and major adverse cardiovascular events. However, challenges and knowledge gaps persist, particularly regarding long-term effects and safety in diverse populations. The conclusions of this review underscore the importance of updating clinical guidelines to incorporate these findings and propose the need for future research to address existing gaps and optimize the use of SGLT2 inhibitors in clinical practice.

Background: Cesarean sections (C-section) often require blood transfusions in cases of severe bleeding, particularly challenging in Rh-negative pregnancies due to the scarcity of Rh-negative donors, with only approximately 0.3% of the population in Thailand. Autologous blood donation, where individuals donate their own blood before surgery, offers a promising solution. Our study focused on preparing preoperative autologous blood donations (PAD) for Rh-negative pregnancies.

Methods: We conducted blood screening on 7,182 pregnancies at Takuapa Hospital from October 2013 to September 2018, identifying 21 Rh-negative pregnant women. We established criteria based on hemoglobin (Hb) levels, which are crucial for autologous blood preparation (Hb at 11.0 g/dL, and hematocrit (Hct) above 33%). Blood samples were collected twice during pregnancy, at 36 and 37 weeks, with the second collection 1 week before the C-section. Pregnancies testing positive for infectious markers were excluded following standard blood donation guidelines. Twelve pregnant women testing negative for infectious markers were enrolled.

Results: The demographic data showed 12 subjects aged 17 to 41 years, with an average of 27.83. Initial blood tests indicated Hb and Hct levels of 12.5 g/dL, and 36.4%, slightly decreasing to 12.2 g/dL and 35.8% in the second collection. On the day of the cesarean, levels further declined to 11.6 g/dL and 34.4%, respectively, within normal ranges. At discharge, the Hct measured 34.8%. Maternal and infant health post-C-section were good, with baby weights ranging from 2,640 to 4,080 g. None of the 12 cases required autologous blood transfusion, validating the safety of standard autologous blood preparation practices.

Conclusions: This study highlights the safety of autologous blood donation for pregnant women with rare blood types, which was achieved through effective planning and collaboration among hospital departments. These findings can serve as a model for other hospitals and significantly reduce the burden of searching for Rh-negative donors.

Background: Surgical site infection (SSI) is a significant concern in patients undergoing emergency surgery, particularly in those with underlying comorbidities. This meta-analysis aimed to evaluate the effect of comorbidities, including diabetes mellitus, hypertension, obesity, pulmonary disease, cardiac disease, liver disease, and renal disease, on the incidence of SSI in patients undergoing emergency surgery.

Methods: We performed a systematic literature search across electronic databases including PubMed, ScienceDirect, Cochrane Library, ProQuest, and Google Scholar to identify studies examining the effect of comorbidities on the incidence of SSI in patients undergoing emergency surgery. To determine the effect size, pooled odds ratios (ORs) were calculated. Statistical analysis was performed using Review Manager 5.3 software.

Results: Thirteen studies involving 8,952 patients undergoing emergency surgery were included in this meta-analysis. The pooled analysis showed that the following comorbidities significantly increased the risk of SSI following emergency surgery: diabetes mellitus (OR = 2.22; 95% confidence interval (CI) = 1.52 - 3.25; P < 0.0001), obesity (OR = 1.43; 95% CI = 1.19 - 1.72; P = 0.0001), and liver disease (OR = 1.66; 95% CI = 1.37 - 2.00; P < 0.00001). However, hypertension, pulmonary disease, cardiac disease, and renal disease showed no significant association with SSI.

Conclusions: In patients undergoing emergency surgery, the presence of comorbidities including diabetes mellitus, obesity, and liver disease increases the incidence of developing SSI.

Background: Different variants of single nucleotide polymorphisms (SNPs) of angiotensinogen (AGT), angiotensin-converting enzyme type 1 (ACE1), and angiotensin II receptors type 1 (AGTR1) and 2 (AGTR2) genes determine different susceptibility to cardiovascular disease (CVD) and hypertension, which can be considered as risk factors for fatal outcomes among coronavirus disease 2019 (COVID-19) patients. The objective of our study was to assess the relation between the frequency of SNPs of the renin-angiotensin system (RAS) components, and the severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Methods: The cross-sectional study included 100 patients with a laboratory-confirmed diagnosis of COVID-19 admitted to the hospital. Criteria for severe COVID-19 included respiratory rate (RR) > 30/min, blood oxygen saturation (SpO₂) ≤ 93%, signs of unstable hemodynamics with systolic blood pressure (SBP) < 90 and/or diastolic blood pressure (DBP) < 60 mm Hg. All patients were identified with alleles and genotypes of the polymorphic markers rs4762 of the AGT gene, rs1799752 of the ACE1 gene, rs5186 of the AGTR1 gene and rs1403543 of the AGTR2 gene using the polymerase chain reaction method in human DNA preparations on real-time CFX96C1000 Touch, Bio-Rad equipment (Syntol, Russia). Statistical analysis was performed in R v.4.2.

Results: Patients were divided into groups with severe (n = 44) and moderate COVID-19 (n = 56). For ACE1 rs1799752, a significant deviation from the population distribution was detected in both studied subgroups. A higher frequency of the C allele SNP rs5186 AGTR1 gene was detected in the group with severe disease. More frequent A/A genotype of SNP rs1403543 AGTR2 was detected among females with severe COVID-19. Haplotype analysis revealed more common DCG haplotype among patients with severe COVID-19. The odds ratio for severe COVID-19 in the presence of the DCG haplotype was 3.996 (95% confidential interval: 1.080 -14.791, P < 0.05).

Conclusions: Our data suggest that the SNP genes of the RAS components, may allow to identify groups of patients predisposed to a more severe course of COVID-19.

Background: Acute kidney injury (AKI) following cardiac surgery is a well-described phenomenon, usually associated with hemodynamic changes ultimately leading to ischemic injury to the kidneys. In this study, we assessed the occurrence of AKI in a cohort of patients undergoing elective cardiac surgery at a single center.

Methods: Patients undergoing elective cardiac surgery (coronary artery bypass grafting (CABG) and/or valve repair) between the years 2016 and 2022 were retrospectively included in the study.

Results: During the study, 167 patients underwent CABG, valve replacement, or both procedures. The majority were male (85.0%). Post-operative AKI was observed in 27.5% of patients, with 2.4% requiring continuous renal replacement therapy (CRRT)/dialysis. The majority of AKI cases were staged as Kidney Disease: Improving Global Outcomes (KDIGO) stage 1. Among patients needing CRRT/dialysis, 1.8% recovered renal function within 3 months, with 0.6% experiencing 30-day mortality. In univariate analysis, factors associated with AKI included older age (P = 0.003), severe anemia (P < 0.0001), pre-operative creatinine elevation (P < 0.0001), complex surgeries (P < 0.0001), blood product transfusion (P < 0.0001), longer cross-clamp (XC) and cardiopulmonary bypass (CPB) times (P < 0.0001), and inotropes usage (P < 0.0001). Classical risk factors like diabetes mellitus (DM) and hypertension did not show significant differences. The majority of these factors (severe anemia, age, pre-operative creatinine, post-operative inotrope usage, and cross-clamp times) were consistently significant (P < 0.05) in logistic regression analysis.

Conclusion: Post-operative AKI following cardiac surgery is frequent, with significant associations seen especially with pre-operative anemia. Future investigations focusing on the specific causes of anemia linked to AKI development are essential, considering the high prevalence of hemoglobinopathy traits in our population.

Background: The current study was conducted to explore the impact of macrophages and programmed cell death protein 1 (PD-1) expression on tumor-infiltrating lymphocytes (TILs) on treatment outcomes and to define the interaction between these factors and the clinicopathologic features of advanced cholangiocarcinoma (CCA) patients.

Methods: Twenty-five patients with metastatic CCA were recruited for the current study from El-Rajhi Hospital and the Clinical Oncology Department of Assiut University. Additionally, 19 healthy controls were included. Before the flow cytometric detection of immune cells, the diagnosis and staging of CCA were performed based on surgical intervention, imaging, carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA) determinations. This was followed by flow cytometric detection of CD4⁺, CD8⁺, CD4⁺PD-1⁺, CD8⁺PD-1⁺, and CD11b⁺CD68⁺ macrophages in the peripheral blood of both patients and controls.

Results: The current results revealed higher levels of CD4⁺, CD8⁺, and CD11b⁺CD68⁺ macrophages in controls compared to patients. At the same time, PD-1 expression was significantly higher in patients compared to controls. CD4⁺ was correlated with improved progression-free survival (PFS), while CD8⁺PD-1 was associated with shorter PFS. In general, CD4⁺ and CD8⁺ levels progressively increased with improved response to treatments, differentiation, single organ site metastasis, and surgical interventions. On the contrary, PD-1 expression and macrophages progressively increased with worsening response, dedifferentiation, multiple organ sites, and surgical interventions. The median PFS was 12 months, and the mean ± standard error (SE) was 13.1 ± 1.3.

Conclusions: CCA has a desmoplastic microenvironment with complex immunologic topography and tumor-reactive stroma. The immune landscape of the peripheral blood mononuclear cells (PBMCs) in CCA patients before treatment could reflect the state of systemic immune function and response to treatments. Our results revealed that T-lymphocytes correlated with better prognosis while macrophages and PD-1⁺ expression were associated with poor outcomes.