There is a changing trend in mortality causes in kidney transplant recipients (KTR), with a decline in deaths due to cardiovascular causes along with a relative increase in cancer mortality rates. Vitamin C, a well-known antioxidant with anti-inflammatory and immune system enhancement properties, could offer protection against cancer. We aimed to investigate the association of plasma vitamin C with long-term cancer mortality in a cohort of stable outpatient KTR without history of malignancies other than cured skin cancer. Primary and secondary endpoints were cancer and cardiovascular mortality, respectively. We included 598 KTR (mean age 51 ± 12 years old, 55% male). Mean (SD) plasma vitamin C was 44 ± 20 μmol/L. At a median follow-up of 7.0 (IQR, 6.2-7.5) years, 131 patients died, of which 24% deaths were due to cancer. In Cox proportional hazards regression analyses, vitamin C was inversely associated with cancer mortality (HR 0.50; 95%CI 0.34-0.74; P < 0.001), independent of potential confounders, including age, smoking status and immunosuppressive therapy. In secondary analyses, vitamin C was not associated with cardiovascular mortality (HR 1.16; 95%CI 0.83-1.62; P = 0.40). In conclusion, plasma vitamin C is inversely associated with cancer mortality risk in KTR. These findings underscore that relatively low circulating plasma vitamin C may be a meaningful as yet overlooked modifiable risk factor of cancer mortality in KTR.

Descriptive and retrospective studies without control groups have suggested a possible association between primary Sjögren's syndrome (pSS) and vitamin B12 (B12) deficiency. This is of importance because several mucosal and neurological features are common to these two conditions and could be prevented or reversed in case of B12 deficiency. We aimed to evaluate the association between pSS and B12 deficiency. We prospectively assessed the B12 status of 490 patients hospitalized in an internal medicine department over a 15-week period. Patients with pernicious anemia were excluded. We extracted patients with pSS and paired them with controls according to age and sex, with a 1:5 ratio. Twenty-one pSS patients were paired with 105 control patients. The median age was 70 years old (51-75) and 95.2% of patients were women. The plasma B12 level was lower in pSS patients (329 (293-521) ng/L vs. 456 (341-587) ng/L, p < 0.0001). B12 deficiency was associated with pSS (42.9% among pSS patients vs. 11.4% among controls), even after adjustment for other causes of B12 deficiency (OR 6.45 (95%CI: 2.08-20.0)). In conclusion, pSS appeared to be associated with B12 deficiency, even after the exclusion of pernicious anemia. This justifies screening and treating B12 deficiency in pSS patients.

Vitamin D deficiency is an important issue in the worldwide population, especially in older people. According to the World Health Organization data, in 2030, 1 in 6 people in the world will be 60 years old or older. The main storage site for vitamin D is adipose tissue. Further, 25(OH)D regulates the expression of adipogenic genes and apoptosis of adipocytes and directly influences the secretion of the appetite-regulating hormone-leptin. Thus, we investigated the impact of the serum concentrations of leptin, adiponectin, omentin, ghrelin, visfatin, and biochemical parameters on vitamin D and estimated glomerular filtration rate (eGFR) in geriatric females. Our studies indicate that the leptin, visfatin and ghrelin are linked with vitamin D concentration and the eGFR rate in the geriatric females. (1) Background: Vitamin D deficiency is common in older people, and researchers are looking for a link between vitamin D deficiency and the occurrence of diseases in advanced age. The study aimed to evaluate the association between serum 25(OH)D levels and clinical variables in older females. (2) Methods: We investigated the impact of the serum concentrations of leptin, adiponectin, omentin, ghrelin, visfatin, and biochemical parameters on vitamin D and estimated the glomerular filtration rate (eGFR) in 74 geriatric females. (3) Results: We observed a significantly higher concentration of creatinine and visfatin in the G2 stage (eGFR = 60-89 mL/min./1.73 m2). We performed an additional analysis to exclude the effect of vitamin D supplementation and obtained a significantly higher vitamin D concentration in the G2 stage. We found significantly lower vitamin D concentrations in older people. In addition, in a person with low levels of vitamin D, we observed significantly lower levels of albumin and ghrelin. Older patients (80 to 89 years old) had significantly lower levels of vitamin D, albumin, insulin, HOMA-IR, and ghrelin than younger patients (60 to 69 years old). Spearman's correlations performed to examine the relationship between clinical variables seemed to confirm previous results. According to ROC curve analysis, leptin concentration was the strongest predictor of vitamin D fluctuations (the area under the curve, AUC = 0.685; with 79.5% sensitivity and 51.4% specificity; p = 0.0291). However, visfatin reached the most accurate AUCROC = 0.651 with 84.2% sensitivity and 49.1% specificity for predicting effects on eGFR. (4) Conclusions: The results suggest that serum levels of leptin, visfatin, and ghrelin are linked with vitamin D concentration and the eGFR rate in the population of geriatric females.

The 25-Hydroxyvitamin D (25[OH)D) serum concentration depends on vitamin D intake, endogenous vitamin D production and genetic factors. The latter have been demonstrated in large genome-wide association studies indicating that single nucleotide polymorphisms (SNPs) in genes related to the vitamin D metabolism are as important for serum 25(OH)D levels as the influence of season. The mechanism on how these SNPs influence serum 25(OH)D levels are still unclear. The aim of the present study was to investigate the genetic effects of ten selected SNPs related to vitamin D metabolism on 25-hydroxyvitamin D increase (∆25(OH)D) after vitamin D supplementation in three randomized controlled trials. Genotypes of SNPs related to vitamin D metabolism were determined in 411 participants with 25(OH)D concentrations < 75 nmol/l receiving 20,000 IU cholecalciferol per week for 8 or 12 weeks after study inclusion. For the vitamin D receptor (VDR) rs10783219 polymorphism, the minor A-allele was associated with lower ∆25(OH)D values in the entire study population (p = 0.022), which was not consistent in all three cohorts when analysed separately. VDR rs10783219 might therefore be a genetic modulator of increasing 25-hydroxyvitamin D concentrations. Considering the wide-spread use of vitamin D supplementation, future large and well-designed randomized controlled trials (RCTs) should investigate the clinical impact of this polymorphism.

The incidences of colorectal cancer and inflammatory bowel diseases are increasing in the developed countries of Western Europe and North America, and consequently, the prevalence rate of temporary or permanent stomas has increased in recent years. Nevertheless, the amount of research in the nutrition field in the case of patients with stoma is rather limited. This review article aims to assess the impact of nutrition on an intestinal stoma and possible sequelae resolved with nutritional therapy. The research analyses conducted thus far indicate a significantly increased risk of developing malnutrition, vitamin deficiency (especially group B), and an increased number of discharges from the stoma and its relevance with abnormalities found in electrolyte concentrations.

Hand eczema is a common disease with economic and social ramifications. This study undertakes a review of certain existing literature to provide insight into contributory factors which may result in the varying prevalence and severity of hand eczema among different ethnic groups, particularly to identify modifiable risk factors, as well as to ascertain knowledge gaps for future research direction. The existing literature suggests that factors including (a) genes, (b) differing skin physiology, (c) cultural practices, (d) dietary habits and associated food preparation, (e) climate, (f) predominant occupations, (g) socioeconomic factors, and (h) dissimilar laws and regulations may account for the disparity in the risk of hand eczema among different ethnicities. Given that endogenous factors cannot be avoided, but certain exogenous aspects can be modified, especially as the environment plays an important role in hand eczema flares, it is helpful from a practical perspective to focus on addressing the modifiable risk factors. These factors pertain to unique cultural practices, customs, and food preparation methods. Healthcare professionals should be well-acquainted with such factors to tailor the treatment approach for patients of different ethnicities accordingly because, with globalization, physicians face increasingly diverse patient populations such that cultural customs no longer remain limited to particular geographic regions.

Influenza viruses can cause several complications during pregnancy. Therefore, we aimed to investigate the effects of influenza on the development of congenital abnormalities (CAs) by analyzing the database of the Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA). In our multicenter, case-control, population-based study, we processed clinician-reported outcomes and diagnoses collected in the HCCSCA. The case group included newborns with different non-chromosomal birth defects, while the controls were newborns without CAs. Maternal influenza, as a risk factor for CAs, was analyzed by using a logistic regression model and odds ratios with 95% confidence intervals (CIs). Our results showed that maternal influenza in the first trimester was associated with increased odds of developing non-chromosomal CAs (OR: 1.41, CI: 1.28-1.55). There were increased odds of neural tube defects (OR: 2.22, CI: 1.78-2.76), orofacial clefts (OR: 2.28, CI: 1.87-2.78), and congenital heart defects (OR: 1.28, CI: 1.10-1.49) after influenza infection. In all cases, we found a protective effect of folic acid supplementation in the first trimester. In summary, the odds of non-chromosomal birth defects are higher after maternal influenza in the first trimester, and folic acid or pregnancy vitamin supplementation and antipyretic therapy may reduce the effect of maternal influenza during the first trimester.

Periodontal ligament-derived mesenchymal stem cells (hPDLSCs) possess immunomodulatory abilities which are strongly enhanced by various inflammatory cytokines. Vitamin D3 has anti-inflammatory effects on hPDLSCs and immune cells. However, no study to date has directly compared the influence of 1,25(OH)2D3 on the immunomodulatory activities of hPDLSCs in the presence of different cytokines. In the present study, the effects of hPDLSCs treated with tumor necrosis factor (TNF)-α, interleukin (IL)-1β, or interferon (IFN)-γ in the presence of 1,25(OH)2D3 on the proliferation of allogenic CD4+ T lymphocyte or on the functional status of primary CD68+ macrophages were analyzed in coculture models. Additionally, the effects of 1,25(OH)2D3 on TNF-α-, IL-1β-, and IFN-γ-induced gene expression of some immunomodulatory factors in hPDLSCs were compared. Under coculture conditions, 1,25(OH)2D3 increased or decreased CD4+ T lymphocyte proliferation via hPDLSCs, depending on the cytokine. hPDLSCs primed with 1,25(OH)2D3 and different cytokines affected pro- and anti-inflammatory cytokine expression in macrophages variably, depending on the priming cytokine. With one exception, 1,25(OH)2D3 significantly reduced TNF-α-, IL-1β-, and IFN-γ-induced expression of all the investigated immunomediators in hPDLSCs, albeit to different extents. These results suggest that 1,25(OH)2D3 influences the immunomodulatory activities of hPDLSCs depending qualitatively and quantitatively on the presence of certain inflammatory cytokines.

PNPT1 (PNPase-polynucleotide phosphorylase) is involved in multiple RNA processing functions in the mitochondria. Bi-allelic pathogenic PNPT1 variants cause heterogeneous clinical phenotypes affecting multiple organs without any established genotype-phenotype correlations. Defects in PNPase can cause variable combined respiratory chain complex defects. Recently, it has been suggested that PNPase can lead to activation of an innate immune response. To better understand the clinical and molecular spectrum of patients with bi-allelic PNPT1 variants, we captured detailed clinical and molecular phenotypes of all 17 patients reported in the literature, plus seven new patients, including a 78-year-old male with the longest reported survival. A functional follow-up of genomic sequencing by cDNA studies confirmed a splicing defect in a novel, apparently synonymous, variant. Patient fibroblasts showed an accumulation of mitochondrial unprocessed PNPT1 transcripts, while blood showed an increased interferon response. Our findings suggest that functional analyses of the RNA processing function of PNPase are more sensitive than testing downstream defects in oxidative phosphorylation (OXPHPOS) enzyme activities. This research extends our knowledge of the clinical and functional consequences of bi-allelic pathogenic PNPT1 variants that may guide management and further efforts into understanding the pathophysiological mechanisms for therapeutic development.

Chronic tinnitus, the perception of sound without an external source, can significantly affect individuals' well-being. As an often medically unexplained symptom, chronic tinnitus can present as a "somatoform" or "functional" difficulty. Some evidence has pointed to alexithymia as a transdiagnostically relevant risk factor for both symptom clusters. Using a two-part rapid review-searching within EBSCO, Embase by Ovid, PubMed, Web of Science-we summarize psychological studies regarding alexithymia, i.e., difficulties in recognizing and expressing emotions and (1) somatoform conditions and (2) chronic tinnitus. For the former (inclusion criteria: (1) adult human beings with different kinds of somatization, (2) longitudinal study designs, (3) publication between 2001 and 2021, (4) full-text in English or German) we identified eight studies that revealed significant links between alexithymia and somatoform conditions. Psychotherapy improved alexithymia in most studies. Additionally, alexithymia was associated with broader treatment outcomes such as improvements in pain intensity, gastrointestinal symptoms, and patient-therapist alliance. The 'Risk Of Bias In Non-randomized Studies-of Interventions' tool (ROBINS-I) and 'Revised Cochrane risk-of-bias tool for randomized trials' (RoB 2) were used for risk of bias assessment. Summarizing all available studies on alexithymia and chronic tinnitus, we identified three studies. Inclusion criteria were: (1) adult human beings with chronic tinnitus, (2) publication between 2001 and 2021, (3) full-text in English or German. Risk of bias was assessed by the 'JBI Critical Appraisal Checklist for Analytical Cross Sectional Studies'. The available studies suggested a high rate of alexithymia (65.7%) in patients with chronic tinnitus. Tinnitus-related distress was significantly associated with alexithymia in two studies, one of which, however, found no differences in alexithymia between patients with bothersome versus non-bothersome tinnitus. Conversely, one study reported high levels of alexithymia in patients with low levels of tinnitus-related distress. Overall, alexithymia may be a transdiagnostic psychological indicator of somatization phenomena, which might include some chronic tinnitus presentations. Psychotherapy likely improves alexithymia as well as somatoform symptom presentations.

Intraoperative adverse events (iAEs) impact the outcomes of surgery, and yet are not routinely collected, graded, and reported. Advancements in artificial intelligence (AI) have the potential to power real-time, automatic detection of these events and disrupt the landscape of surgical safety through the prediction and mitigation of iAEs. We sought to understand the current implementation of AI in this space. A literature review was performed to PRISMA-DTA standards. Included articles were from all surgical specialties and reported the automatic identification of iAEs in real-time. Details on surgical specialty, adverse events, technology used for detecting iAEs, AI algorithm/validation, and reference standards/conventional parameters were extracted. A meta-analysis of algorithms with available data was conducted using a hierarchical summary receiver operating characteristic curve (ROC). The QUADAS-2 tool was used to assess the article risk of bias and clinical applicability. A total of 2982 studies were identified by searching PubMed, Scopus, Web of Science, and IEEE Xplore, with 13 articles included for data extraction. The AI algorithms detected bleeding (n = 7), vessel injury (n = 1), perfusion deficiencies (n = 1), thermal damage (n = 1), and EMG abnormalities (n = 1), among other iAEs. Nine of the thirteen articles described at least one validation method for the detection system; five explained using cross-validation and seven divided the dataset into training and validation cohorts. Meta-analysis showed the algorithms were both sensitive and specific across included iAEs (detection OR 14.74, CI 4.7-46.2). There was heterogeneity in reported outcome statistics and article bias risk. There is a need for standardization of iAE definitions, detection, and reporting to enhance surgical care for all patients. The heterogeneous applications of AI in the literature highlights the pluripotent nature of this technology. Applications of these algorithms across a breadth of urologic procedures should be investigated to assess the generalizability of these data.

The objective was to evaluate the association of the immunoexpression of cancer stem cell (CSC) markers with clinicopathological and survival outcomes in tongue squamous cell carcinoma (TSCC) patients. This systematic review and meta-analysis [PROSPERO (CRD42021226791)] included observational studies that compared the association of clinicopathological and survival outcomes with CSC immunoexpression in TSCC patients. Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CI) were used as outcome measures. Six studies identified the association with three surface markers (c-MET, STAT3, CD44) and four transcription markers (NANOG, OCT4, BMI, SOX2). The odds of early-stage presentation were 41% (OR = 0.59, 95% CI 0.42-0.83) and 75% (OR = 0.25; 95% CI 0.14-0.45) lower in CSC and SOX2 immuno-positive cases than immuno-negative cases, respectively. The odds of well-differentiated tumors in transcription marker immuno-positive cases were 45% lower compared to immuno-negative cases (OR = 0.55, 95% CI 0.32-0.96). The odds of positive lymph nodes were 2.01 times higher in CSC immuno-positive cases compared to immuno-negative cases (OR = 2.01, 95% CI 1.11-3.65). Mortality in immuno-positive cases was 121% higher than that in immuno-negative cases (HR = 2.21; 95% CI 1.16-4.21). Advanced tumor staging and grading, lymph node metastasis, and mortality were significantly associated with positive immunoexpression of CSC markers.

The objective of this study is to present the current outcomes of fenestrated/branched endovascular repair (F/BEVAR) for post-dissection thoracoabdominal aortic aneurysms (PDTAAAs). A systematic review of the literature according to PRISMA guidelines up to October 2023 was conducted (protocol CRD42023473403). Studies were included if ≥10 patients were reported and at least one of the major outcomes was stated. A total of 10 studies with 585 patients overall were included. The pooled estimate for technical success was 94.3% (95% CI 91.4% to 96.2%). Permanent paraplegia developed with a pooled rate of 2.5% (95% CI 1.5% to 4.3%), whereas a cerebrovascular event developed with a pooled rate of 1.6% (95% CI 0.8% to 3.0%). An acute renal function impairment requiring new-onset dialysis occurred with a pooled rate of 2.0% (95% CI 1.0% to 3.8%). Postoperative respiratory failure was observed with a pooled estimate of 5.5% (95% CI 3.8% to 8.1%). The pooled estimate for 12-month overall survival was 90% (95% CI 85% to 93.5%), and the pooled estimates for 24-month and 36-month survival were 87.8% (95% CI 80.9% to 92.5%) and 85.5% (95% CI 76.5% to 91.5%), respectively. Freedom from reintervention was estimated at 83.9% (95% CI 75.9% to 89.6%) for 12 months, 82.8% (95% CI 68.7% to 91.4%) for 24 months and 76.1% (95% CI 60.6% to 86.8%) for 36 months. According to the present findings, F/BEVAR can be performed in PD-TAAAs with high rates of technical success and good mid-term results.

Asthma is caused by complex interactions between environmental and genetic factors. Various genes have been implicated as potential risk factors in the development of asthma; among them is cystic fibrosis transmembrane conductance regulator (CFTR) gene. The aim of this systematic review was to investigate the association of CFTR mutation heterozygosity with the development of asthma, by updating the existing data with recent studies' findings. Therefore, a systematic review of the literature was conducted on Pubmed, ESBCO (Cinahl) and Scopus Databases up to December 2022. After the eligibility assessment, 17 studies were included in this review. Nine of them supported a lack of relationship between CFTR mutation heterozygosity and asthma susceptibility, and eight reported a positive association. Consequently, more extensive research is needed through high-quality studies to provide valid evidence and highlight the clinical benefits of identifying CFTR mutations in asthma patients, their impact on asthma severity, or treatment perspectives.

Immaturity in digestive-tract motor function and altered intestinal microbiome may play roles in pathogenesis of infantile colic. We assessed the impact of probiotic therapy on crying duration day, in newborns experiencing colic attacks. The PubMed, Embase, Cinnahl, Web of Science databases, and a clinical trials registry (ClinicalTrials.gov) were searched from inception until 12/02/2020. Random-effects meta-analyses were used to derive standardized mean differences/differences in means and risk ratios. We included 16 studies, which involved 1319 newborns aged up to 6 months. Lactobacillus reuteri strain DSM17938 was administered predominantly (n = 10). Probiotic intervention reduced the duration of crying (standardized mean difference = -2.012, 95% confidence interval: -2.763 to -1.261, z = -5.25, p < 0.0001). The probability of at least a 50% reduction in crying duration was at least 1.98 times higher in the intervention group than in controls (Z = 4.80, p < 0.0001). The effects of the intervention were not significantly affected by the risk of bias assessment, percentage of breastfed infants, and duration of the study. In 11 studies, data concerning gut microbiota composition and function and/or immunological markers were given. Probiotics significantly shortened the crying duration, but a causal relationship between the modulatory effect of probiotics on microbiota and the immune system has not been confirmed.

Approximately 11% to 14% of subjects with neuroendocrine neoplasms (NENs) have metastatic lesions with unknown primary origin (UPO), with the majority of UPO-NENs found in the small bowel. Herein, we assessed the available literature on UPO-NENs, focusing on clinical presentation and diagnostic techniques to identify the primary site. The identification of the primary tumor is important as it affects the prognosis; however, the clinical presentation can be non-specific in non-functioning forms. In the presence of metastatic disease, the histological sample is fundamental to obtain immunohistochemical markers that might orientate the clinician in the search for the primary tumor through radiology, functional imaging and endoscopic techniques. In summary, multidisciplinary management plays a key role in UPO-NENs, even more than in other NENs. Molecular biology and gene-expression profiling represent areas of great interest which might be developed in the near future for both the diagnosis and the treatment of these neoplasms.

Exercise therapy as part of the clinical management of patients with neuromuscular diseases (NMDs) is complicated by the limited insights into its efficacy. There is an urgent need for sensitive and non-invasive quantitative muscle biomarkers to monitor the effects of exercise training. Therefore, the objective of this systematic review was to critically appraise and summarize the current evidence for the sensitivity of quantitative, non-invasive biomarkers, based on imaging and electrophysiological techniques, for measuring the effects of physical exercise training. We identified a wide variety of biomarkers, including imaging techniques, i.e., magnetic resonance imaging (MRI) and ultrasound, surface electromyography (sEMG), magnetic resonance spectroscopy (MRS), and near-infrared spectroscopy (NIRS). Imaging biomarkers, such as muscle maximum area and muscle thickness, and EMG biomarkers, such as compound muscle action potential (CMAP) amplitude, detected significant changes in muscle morphology and neural adaptations following resistance training. MRS and NIRS biomarkers, such as initial phosphocreatine recovery rate (V), mitochondrial capacity (Qmax), adenosine phosphate recovery half-time (ADP t1/2), and micromolar changes in deoxygenated hemoglobin and myoglobin concentrations (Δ[deoxy(Hb + Mb)]), detected significant adaptations in oxidative metabolism after endurance training. We also identified biomarkers whose clinical relevance has not yet been assessed due to lack of sufficient study.

: The aim of this systematic review and meta-analysis is to determine the role of physical activity as a conservative treatment for older people with knee or hip osteoarthritis. The effect on pain, physical function, stiffness, quality of life, and dynamic balance of Aquatic Exercise, Land-based Exercise, and Sports were compared in a specific population composed of osteoarthritic patients aged 65 or over. A systematic search using Pubmed-Medline, Google Scholar, and the Cochrane Library was carried out to select randomized clinical trials, observational studies, or case series that evaluated outcome measures after physical activity. Twenty randomized controlled trials (RCTs) and two case series were included in this review. Four trials were at low risk of bias (A), 12 at unclear risk of bias (B), and four at high risk of bias (C). Compared to controls, Aquatic Exercise, Land-based Exercise, Tai Chi, and Yoga showed a small to high effect for improving pain, physical function, quality of life, and stiffness. Active exercise and sport are effective to improve pain and physical function in elderly people with osteoarthritis. Nevertheless, further studies are required to validate the use of land-based exercise, aquatic exercise, or sport to treat the symptoms of older adults that suffer from knee and hip osteoarthritis.

Atrial fibrillation (AF) is the most common cardiac arrhythmia associated with high morbidity and mortality. AF treatment is guided by a patient-provider risk-benefit discussion regarding drug versus ablation or combination. Thermal ablation has a high rate of adverse events compared to pulsed field ablation (PFA). In this systematic review, we aimed to determine the safety and efficacy of PFA.

Acute appendicitis is a frequently encountered surgical emergency. Despite several scoring systems, the possibility of delayed diagnosis persists. In addition, a delayed diagnosis leads to an increased risk of complicated appendicitis. Hence, there is a need to identify biological markers to help clinicians rapidly and accurately diagnose and prognosticate acute appendicitis with a high sensitivity and specificity. Although several markers have been evaluated, the pressing concern is still the low specificity of these markers. One such marker is serum ischemia-modified albumin (IMA), which can be a novel biomarker for accurately diagnosing and prognosticating acute appendicitis.