Advances in medical sciences最新文献

Purpose

We explored the efficacy and influencing factors of chemoradiotherapy and radiotherapy alone in patients with locally advanced oesophageal squamous cell carcinoma.

Methods

We retrospectively analysed 226 locally advanced oesophageal squamous cell carcinoma patients who underwent chemoradiotherapy and radiotherapy alone. Univariate and multivariate Cox regression analyses were used to analyse the impact of relevant factors. The endpoint was overall survival and progression-free survival.

Results

Compared with the radiotherapy group, the chemoradiotherapy group had a significant difference in the overall survival rate and the progression-free survival rate between 3 and 5 years (both p ​< ​0.05). The incidences of radiation pneumonitis and radiation oesophagitis were analysed, and the differences were not significant (all p ​> ​0.05). The incidence of haematological toxicity in the chemoradiotherapy group was significantly higher than that in the radiotherapy group (p ​= ​0.001). There was a significant difference in the incidence of haematological toxicity between the ≤65 and the >65 age groups (p ​< ​0.05). Tumour location, T stage, tumour length, tumour target volume, and short-term curative effect were the main factors affecting the prognosis (all p ​< ​0.05). T stage, gross tumour volume, and short-term curative effect were all independent factors affecting the prognosis (all p ​< ​0.05).

Conclusions

Patients with locally advanced oesophageal cancer who received intensity-modulated radiotherapy (IMRT) combined with chemotherapy had significant survival benefits compared with radiotherapy alone. Haematological toxicity was the main adverse reaction. T-stage, gross tumour volume and short-term curative effect were independent factors influencing the prognosis.

Purpose

Starting in 2019, coronavirus disease 2019 (COVID-19) caused an epidemic that was growing rapidly and has harmed millions of people globally. It has been demonstrated that survivin regulates lymphocyte survival, a main route involved in COVID-19 pathogenesis. Survivin belongs to the inhibitor of apoptosis protein (IAP) family, and its primary functions comprise regulating mitosis and inhibiting apoptosis. Since lower survivin expression has been shown to increase the sensitivity of lymphocytes to apoptotic induction, we looked into the function of survivin and its corresponding pathways in COVID-19 pathogenesis.

Materials and methods

The expression of survivin, X-linked inhibitor of apoptosis protein (XIAP), caspases 3, 7, 9, and poly (ADP-ribose) polymerase (PARP) was evaluated at both mRNA and protein levels in peripheral blood mononuclear cells (PBMCs) derived from healthy donors and patients with severe and moderate COVID-19 by qRT-PCR and Western blotting, respectively. Then, we enforced apoptosis to COVID-19 patient-derived lymphocytes, and the percent was assessed by flow cytometry.

Results

Survivin and XIAP were less expressed in PBMCs derived from COVID-19 patients as apoptosis inhibitors than PARP, cleaved-PARP, caspase 9, and cleaved caspases 3 and 7, according to the results of real-time PCR and Western blot analysis. Additionally, according to the flow cytometry results, the down-regulation of survivin served as a potential factor in the lymphocyte depletion observed in patients with COVID-19.

Conclusion

The role of survivin and its related pathway was first discovered in the development of COVID-19 and may serve as a potential prognostic and therapeutic target.

Purpose

Heart failure (HF) with improved ejection fraction (HFimpEF) is a new category of HF introduced in the newest European Society of Cardiology guidelines. However, clinical characteristics and long-term outcomes of HFimpEF patients remain insufficiently elucidated. We sought to characterize Polish HFimpEF patients and determine their long-term mortality.

Material and methods

Of 1186 patients enrolled in the single-center Lesser Poland Cracovian Heart Failure (LECRA-HF) registry between 2009 and 2019 and hospitalized due to HF decompensation, 340 (28.7%) were those with HF with reduced ejection fraction (HFrEF). Based on follow-up echocardiography, 61 (17.9%) of them were classified as HFimpEF and the remaining as HFnon-impEF.

Results

HFimpEF patients were more frequently females (P ​< ​0.001), had higher baseline left ventricular ejection fraction (LVEF, P ​< ​0.001), had less often a history of diabetes (P ​= ​0.024), severe chronic kidney disease (P ​= ​0.026) or prior myocardial infarction (P ​= ​0.008) than HFnon-impEF patients. By multivariable analysis the HFimpEF diagnosis was independently predicted by baseline NYHA I/II (odds ratio [OR] 2.347, 95% confidence interval [95%CI] 1.020–5.405), non-ischemic etiology (OR 3.096, 95%CI 1.587–6.024), lack of diabetes mellitus (OR 2.016, 95%CI 1.059–3.846) and higher baseline LVEF (OR 1.084, 95%CI 1.042–1.126, per 1%). Within the median 49 (25–77) months all-cause mortality was lower in HFimpEF than in HFnon-impEF (10.8 vs 16.4%/year, P ​= ​0.004).

Conclusions

Our findings indicate that every sixth Polish patient with HFrEF has a chance to improve LVEF during follow-up and to become a HFimpEF patient. Baseline characteristics of HFimpEF patients are different from HFnon-impEF. Simultaneously, the HFimpEF diagnosis is associated with higher long-term survival.

Purpose

New-onset diabetes after transplantation (NODAT) is a frequent metabolic complication associated with podocyte damage and renal allograft dysfunction. Thus, Wilm's tumor-1 (WT-1) protein, as a podocyte marker, holds promise as an option to evaluate renal allograft dysfunction in NODAT. Therefore, the study aimed to investigate urinary WT-1 levels in NODAT patients during the first year after kidney transplantation (KTx).

Materials and methods

KTx patients were categorized into non-NODAT and NODAT groups. Fasting blood glucose, glycated hemoglobin (HbA1c), urinary albumin/creatinine ratio (ACR), serum creatinine, estimated glomerular filtration rate (eGFR), and urinary WT-1 were measured at 3, 6, 9, and 12-months post-KTx.

Results

The NODAT group manifested elevated levels of blood glucose and HbA1c during the first year post-KTx. Also, exhibited elevations in ACR and serum creatinine levels at 6, 9, and 12-months post-KTx when compared to non-NODAT group. Conversely, eGFR values in the NODAT group demonstrated significant declines at 3, 6, and 9-months post-KTx relative to non-NODAT. Furthermore, NODAT group exhibited a median annual eGFR of 47 ​mL/min/1.73 ​m². Urinary WT-1 levels at 3, 6, 9, and 12-months post-KTx were significantly higher in the NODAT group compared to non-NODAT. Additionally, noteworthy positive correlations were identified between urinary WT-1 and HbA1c levels, along with significant negative correlations between urinary WT-1 and eGFR at the 3, 6, 9, and 12-months post-KTx.

Conclusion

The increased urinary WT-1 levels from 3-months post-KTx in NODAT patients may indicate the first sign of podocyte injury, predicting a renal allograft dysfunction in these patients.

We present the results of an association study involving hospitalized coronavirus disease 2019 (COVID-19) patients with a clinical background during the 3rd pandemic wave of COVID-19 in Slovakia. Seventeen single nucleotide variants (SNVs) in the eleven most relevant genes, according to the COVID-19 Host Genetics Initiative, were investigated. Our study confirms the validity of the influence of LZTFL1 and 2′-5′-oligoadenylate synthetase (OAS)1/OAS3 genetic variants on the severity of COVID-19. For two LZTFL1 SNVs in complete linkage disequilibrium, rs17713054 and rs73064425, the odds ratios of baseline allelic associations and logistic regressions (LR) adjusted for age and sex ranged in the four tested designs from 2.04 to 2.41 and from 2.05 to 3.98, respectively. The OAS1/OAS3 haplotype ‘gttg’ carrying a functional allele G of splice-acceptor variant rs10774671 manifested its protective function in the Delta pandemic wave. Significant baseline allelic associations of two DPP9 variants in all tested designs and two IFNAR2 variants in the Omicron pandemic wave were not confirmed by adjusted LR. Nevertheless, adjusted LR showed significant associations of NOTCH4 rs3131294 and TYK2 rs2304256 variants with severity of COVID-19. Hospitalized patients' reported comorbidities were not correlated with genetic variants, except for obesity, smoking (IFNAR2), and hypertension (NOTCH4). The results of our study suggest that host genetic variations have an impact on the severity and duration of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Considering the differences in allelic associations between pandemic waves, they support the hypothesis that every new SARS-CoV-2 variant may modify the host immune response by reconfiguring involved pathways.

Purpose

Metabolic syndrome (MetS) is a common disorder associated with disturbed neurotransmitter homeostasis. Memantine, an N-methyl-d-aspartate receptor (NMDAR) antagonist, was first used in Alzheimer's disease. Allopregnanolone (Allo), a potent positive allosteric modulator of the Gamma-Amino-Butyric Acid (GABA)-A receptors, decreases in neurodegenerative diseases. The study investigated the impact of Memantine versus Allo administration on the animal model of MetS to clarify whether the mechanism of abnormalities is related more to excitatory or inhibitory neurotransmitter dysfunction.

Materials and methods

Fifty-six male rats were allocated into 7 groups: 4 control groups, 1 MetS group, and 2 treated MetS groups. They underwent assessment of cognition-related behavior by open field and forced swimming tests, electroencephalogram (EEG) recording, serum markers confirming the establishment of MetS model and hippocampal Glial Fibrillary Acidic Protein (GFAP) and Brain-Derived Neurotrophic Factor (BDNF).

Results

Allo improved anxiety-like behavior and decreased grooming frequency compared to Memantine. Both drugs increased GFAP and BDNF expression, improving synaptic plasticity and cognition-related behaviors. The therapeutic effect of Allo was more beneficial regarding lipid profile and anxiety. We reported progressive slowing of EEG waves in the MetS group with Memantine and Allo treatment with increased relative theta and decreased relative delta rhythms.

Conclusions

Both Allo and Memantine boosted the outcome parameters in the animal model of MetS. Allo markedly improved the anxiety-like behavior in the form of significantly decreased grooming frequency compared to the Memantine-treated groups. Both drugs were associated with increased hippocampal GFAP and BDNF expression, indicating an improvement in synaptic plasticity and so, cognition-related behaviors.

Purpose

Acute exacerbations (AE) are severe complications of chronic obstructive pulmonary disease (COPD); however, the need for biomarkers which predict them is still unmet. High platelet count (PLC) and platelet-to-lymphocyte ratio (PLR) are associated with higher mortality in patients with COPD. We investigated if PLC and PLR at the onset of a severe AE could predict the time of the next relapse.

Methods

In a prospective observational cohort study, data of 152 patients hospitalized with AECOPD were collected, and patients were divided into PLC-low (<239 ​× ​10⁹/L, n ​= ​51), PLC-medium (239-297 ​× ​10⁹/L, n ​= ​51) and PLC-high (>297 ​× ​10⁹/L, n ​= ​50) or PLR-low (<147, N ​= ​51), PLR-medium (147–295, n ​= ​51) and PLR high (>295, n ​= ​50) groups based on PLC and PLR tertiles using admission laboratory results. Clinical characteristics and the time to the next severe or moderate AE within 52 weeks were compared among subgroups using log-rank test.

Results

PLC and PLR tertiles did not differ in clinical characteristics or the time till the next AE (p ​> ​0.05). PLC and PLR showed a direct weak correlation to neutrophil count (Pearson r ​= ​0.26, p ​< ​0.01 and r ​= ​0.20, p ​= ​0.01) and PLC also demonstrated a weak relationship to white blood cell counts (Pearson r ​= ​0.29, p ​< ​0.001). However, PLR presented an inverse relationship to monocyte and eosinophil counts (r ​= ​−0.32, p ​< ​0.001 and r ​= ​−0.17, p ​= ​0.03).

Conclusion

PLC and PLR do not predict the time till the next relapse; however, they may reflect on neutrophilic inflammatory response during an exacerbation of COPD.

Purpose

Mitral valve surgery in children involves correcting congenital and acquired pathologies, with a reported mortality rate of 0.9%. Low cardiac output syndrome (LCOS) is a serious complication with the incidence of 20–25%. The aim of the study was to estimate possible prognostic factors of LCOS in children undergoing mitral valve procedure.

Material and method

This single-center retrospective analysis enrolled children aged <18 years who underwent mitral valve surgery during 24 year period. Preoperative clinical and laboratory parameters, and operative factors were analyzed.

Results

Thirty consecutive pediatric patients (11 (37%) males and 19 (63%) females) in median (Q₁ – Q₃) age of 57 (25–115) months, who underwent mitral valve replacement, were included. The 30-day mortality was 7% (2 patients) and was related to postoperative multiorgan failure. LCOS occurred in 8 (27%) children. The receiver operator curve (ROC) analysis established parameters that have predictive value for LCOS occurrence: cardiopulmonary bypass (CPB) time, with 89 ​min as optimal cut-off point (AUC ​= ​0.744, p ​= ​0.011) yielding sensitivity of 100% and specificity of 42.9%; left ventricular ejection fraction (LVEF) ​< ​60 % (AUC ​= ​0.824, okp ​= ​0.001) with sensitivity of 62.5% and specificity of 93.75%; and red blood cell distribution width (RDW) above 14.5 % (AUC ​= ​0.840, p ​< ​0.001; sensitivity of 87.5% and specificity of 75%).

Conclusions

In mitral valve replacement in pediatric patients, CPBtime above 89 ​min, preoperative LVEF below 60% and preoperative RDW above 14.5% can be regarded as the potential predictors of LCOS.

Obesity continues to be a significant global health concern, giving rise to various complications. This review article explores the current standards and emerging innovations in diagnosing and treating obesity, including recent disease name change, staging system or therapeutic goals. This narrative review has been based on recent scientific articles from PubMed database, limiting the scope of topics to current standards and upcoming developments and breakthroughs in the diagnosis and treatment of obesity. The educational and informative nature of the review has been maintained in order to make the information presented accessible to both researchers and clinical practitioners. The recognition of diverse obesity phenotypes has prompted a paradigm shift towards a complex and patient-centered approach to diagnosis and therapy. Pharmacotherapy for obesity is evolving rapidly, with ongoing research focusing on novel molecular targets and metabolic pathways. Promising developments include dual or triple incretin analogs, oral incretin drugs, neurotransmitter-based therapies, muscle mass-increasing treatments, and therapies targeting visceral adipose tissue browning. Despite current evidence-based international standards, the field of obesity diagnosis and treatment continues to expand, with new diagnostic tools and pharmacotherapies potentially replacing current practices. Therapeutic management should be tailored to individual patients, considering obesity phenotype, health status, lifestyle, and preferences. Looking ahead, the future holds promising opportunities for obesity management, but further research is required to assess the efficacy and safety of emerging therapies. A multifactorial and personalized approach will be pivotal in addressing the diverse challenges posed by obesity.

Purpose

The aim of this study was to compare High Carbohydrates Low Fat (HCLF) and Low Carbohydrate High Fat (LCHF) diets in terms of changes in body composition and maximal strength.

Patients/methods

The study involved 48 men aged 25 ​± ​2.5, divided into two groups, one of which (n ​= ​23) was following the LCHF diet and the other (n ​= ​25) the HCLF diet. Both groups performed the same resistance training protocol for 15 weeks. Maximal strength in squat, bench press and deadlift was assessed pre- and post-intervention. Measurements of selected body circumferences and tissue parameters were made using the multifunctional, multi-frequency, direct bioelectric impedance InBody 770 analyzer from InBody Co., Ltd (Cerritos, California, USA). The team with the necessary qualifications and experience in research performed all the measurements and maintained participants’ oversight throughout the entire length of the study.

Results

Both nutritional approaches were effective in terms of reducing body fat mass. The HCLF group achieved greater skeletal muscle hypertrophy. Significant decreases in body circumferences, especially in the abdominal area, were observed for both dietary approaches. Maximal strength significantly increased in the HCLF group and decreased in the LCHF group.

Conclusion

Holistic analysis of the results led to the conclusion that both dietary approaches may elicit positive adaptations in body composition. The two approaches constitute useful alternatives for both recreational exercisers and physique athletes with body composition goals.