Ahmet Yalcinkaya

BackgroundPilonidal sinus disease (PSD) is common in young adults, yet real-world data integrating quality of life (QoL) with surgical outcomes are limited. We aimed to describe national surgical practice for PSD in Turkey and to compare complications, recurrence, and QoL between excision-based and non-excisional (minimally invasive) procedures.MethodsThis was a retrospective analysis of a prospectively maintained nationwide database including adults undergoing first surgery for PSD in 41 centers between January 2019 and January 2020. Sociodemographic and clinical data, perioperative variables, complications, and recurrence were recorded. QoL was assessed using the EQ-5D-5L (including EQ-VAS) and pain using a 10-point visual analog scale (VAS) at baseline and at postoperative day 1, day 7, 6 months, and 12 months. Patients were grouped according to surgical approach: simple excision, excision + flap and non-excisional procedures.ResultsData from 1369 patients were analyzed (simple excision, n = 194; excision + flap, n = 983; non-excisional, n = 192). Overall, postoperative bleeding occurred in 12.3%, wound infection in 9.2%, and wound separation in 10.2% of patients, with wound separation being more frequent after excision + flap than non-excisional procedures. Recurrence at 12 months was observed in 51 patients (3.7% overall), with rates of 3.1% in the simple excision group, 4.1% in the excision + flap group, and 2.6% in the non-excisional group (p = 0.545). Median pain VAS decreased from 4 (IQR 2–6) at baseline to 0 (0–0) at 12 months in all groups (p < 0.001 within groups). EQ-VAS improved by a median of 18 (IQR 8–40) points in the simple excision group, 15 (6–30) in the excision + flap group, and 29 (15–40) in the non-excisional group (p < 0.001 between groups).ConclusionsIn this nationwide real-world cohort, non-excisional procedures were associated with shorter operative time, shorter hospital stay, fewer wound-related complications, and greater early improvements in QoL and patient satisfaction compared with excision-based procedures, without an apparent increase in 12-month recurrence. Given the retrospective design, baseline imbalances between groups, and limited follow-up, these findings should be confirmed in prospective comparative studies with longer follow-up.

Background: Interferons play a central role in antiviral defense, but their dysregulation contributes to inflammation and immune dysfunction in respiratory viral infections, including COVID-19. While interferon-stimulated genes (ISGs) are essential effectors of this response, their expression patterns in patients are heterogeneous and not always predictive of disease severity. The immunometabolic consequences of this heterogeneity remain poorly understood.Methods: We analyzed hospitalized COVID-19 patients (n = 37) and uninfected controls (n = 31) using whole-blood transcriptomics, immune cell deconvolution, plasma proteomics, and standardized plasma metabolomics from a previously generated dataset within this cohort. Patients were stratified into low (LIS), moderate (MIS), and high (HIS) ISG score clusters. Plasma innate immune activation markers were measured by ELISA. Interferon-directed antibody reactivity was analyzed by multiplex bead-based assays measuring antigen reactivity. Functional immune responses were assessed via ex vivo stimulation of healthy donor immune cells with patient plasma, and correlations were performed between metabolites and immune activation markers.Results: HIS patients exhibited increased inflammatory mediators and innate immune cell expansion compared with LIS and MIS groups. However, within the HIS group, severe cases displayed distinct metabolic and immune dysregulation. Specifically, severe HIS cases showed reductions in phospholipids, sphingolipids, and tricarboxylic acid cycle intermediates, suggestive of disrupted mitochondrial and lipid metabolism. Plasma from severe HIS patients tended to impair neutrophil and monocyte activation, indicating functional attenuation of innate immune activation within a shared high-ISG background. Correlation analysis revealed that branched-chain lipids, tryptophan-derived metabolites, and a branched-chain dicarboxylic acid were positively associated with immune activation markers. Although type-I interferon neutralization was detected in a subset of patients with IFN antigen reactivity, these samples did not fully account for the observed ISG heterogeneity or disease severity.Conclusions: High ISG expression in COVID-19 defines a transcriptional endotype associated with systemic inflammation and innate immune activation. However, severe cases within this group exhibit metabolic constraints and reduced innate immune responsiveness, supporting an immune-metabolic axis in which inflammatory mediators and altered lipid/energy metabolism intersect with innate immune function. These findings motivate future studies to determine whether interferon-associated immune-metabolic states during acute infection relate to persistent inflammation or post-acute sequelae in selected patient subsets.

Fulminant viral hepatitis (FVH) is a devastating condition caused by hepatotropic viruses such as hepatitis A virus (HAV), hepatitis B virus (HBV), and HSV-1/2. We studied 149 FVH patients (73 males and 76 females, aged 1-76) for blood autoantibodies (auto-Abs) neutralizing type I interferons (IFNs; IFN-alpha 2, -beta, -omega). Six of 16 (37.5%) HSV-triggered FVH patients carried such auto-Abs on admission, including three with a previously known autoimmune disease. These patients contrasted with 133 HAV- (n = 46) or HBV-triggered (n = 87) patients, none of whom had such detectable auto-Abs. Odds ratios for HSV-triggered FVH in individuals with auto-Abs ranged from 35.3 (95% CI: 13.0-96.2; P < 10-7) for those neutralizing only 100 pg/ml IFN-alpha/omega to 1,895 (CI: 448.5-8,002; P < 10-12) for those neutralizing both IFN-alpha and IFN-omega at 10 ng/ml. Over one third of HSV-triggered FVH cases in this international cohort were due to preexisting auto-Abs. This finding highlights auto-Abs against type I IFNs as a major determinant of HSV-FVH and paves the way for targeted preventive or therapeutic interventions.

This genome-wide association study (GWAS) explores the genetic components of severe adverse events following COVID-19 vaccination, with focus on myocarditis and pericarditis. Three SNPs (rs536572545, rs146289966 and rs142297026) near the SCAF11 gene were linked to pericarditis, while rs570375365 in the LRRC4C gene was associated with myocarditis. These findings suggest that genetic variants may influence inflammation pathways, providing a basis for further investigation into the immunological responses triggered by vaccines.

Biological sex is closely associated with the properties and extent of the immune response, with males and females showing different susceptibilities to diseases and variations in immunity. Androgens, predominantly in males, generally suppress immune responses, while estrogens, more abundant in females, tend to enhance immunity. It is also established that sex hormones at least partially explain sex biases in different diseases, particularly autoimmune diseases in females. These differences are influenced by hormonal, genetic, and environmental factors, and vary throughout life stages. The advent of gender-affirming hormone therapy offers a novel opportunity to study the immunological effects of sex hormones. Despite the limited studies on this topic, available research has revealed that testosterone therapy in transgender men may suppress certain immune functions, such as type I interferon responses, while increasing inflammation markers like TNF-alpha. Transgender women on estrogen therapy also experience alterations in coagulation-related and inflammatory characteristics. Furthermore, other possible alterations in immune regulation can be inferred from the assessment of inflammatory and autoimmune markers in transgender individuals receiving hormone therapy. Understanding the complex interactions between sex hormones and the immune system, particularly through the unique perspective offered by gender-affirming hormone therapies, may facilitate the development of targeted therapies for infections and autoimmune diseases while also improving healthcare outcomes for transgender individuals. Here we review immune dynamics throughout life in both sexes and provide a summary of novel findings drawn from studies exploring gender-affirming hormone therapy.

Purpose: The purpose of this study is to investigate the recurrence rates for the treatment of pilonidal sinus disease (PSD) in Turkey and the factors associated with recurrence of PSD after surgery on a nationwide scale.Methods: This national, multicenter, database review was conducted in Turkey by the PISI TURKEY Research Group, and included recipients of PSD surgery in 41 select hospitals in Turkey, between January 2019 and January 2020. Data were collected by completion of standardized data forms. Sociodemographic and anthropometric data, comorbidities, PSD type, previous PSD interventions, index PSD intervention, recurrence, and complications were collected from baseline to postoperative 12 months.Results: The data of 1662 patients from 41 centers were analyzed. The median age was 25 (21-32) years, and 80.26% of the cases were male. The recurrence rate following index operations was 6.26% in the 12-month period. Age (p = 0.594) and sex distribution (p = 0.441) were similar in patients with and without recurrence. The recurrent group had significantly higher frequencies of type V PSD (p < 0.001), wound site infection (p < 0.001), and wound separation (p < 0.001), whereas the non-recurrent group had a significantly higher frequency of type III PSD (p < 0.001). Multivariable logistic regression revealed that prior recurrence, postoperative wound site infection, and postoperative wound separation were independently associated with recurrence.Conclusions: The recurrence rate after PSD surgery in Turkey was close to the lower ranges reported in prior literature. Turkish patients with a history of prior recurrence, postoperative wound site infection, or postoperative wound separation should be considered to have higher risks for recurrence.

While Coronavirus disease 2019 (COVID-19) vaccines have proven to be both effective and generally safe, rare but severe adverse events following immunization (AEFIs) are described. Autoantibodies to platelet factor-4 are associated with catastrophic thrombotic AEFIs, but comprehensive investigations of other autoantibodies are lacking. We aimed to detect and describe autoantibodies targeting coagulation-related proteins in a population-wide cohort (SWEDEGENE) including AEFIs attributed to COVID-19 vaccines in Sweden. Subjects were recruited from December 2020 to October 2022 and were stratified based on diagnosis and COVID-19 exposure. Screening was carried out in two phases, with a multiplex bead-based assay in the first subset (until September 2021) and with targeted assays for the second (until October 2022). Positivity was defined based on absolute, relative, and biological/technical thresholds. Patients with coagulation-related AEFIs were older and the Vaxzevria vaccine was overrepresented in this group. Two cases had antiphospholipid antibodies but none had PF4 antibodies. We identified six positives for protein S autoantibodies. Protein S concentrations were negatively correlated with autoantibody response in patients with immunoreactivity and functional analysis revealed low protein S activity in three subjects. Our population-wide analysis reveals cases with autoantibodies against protein S which possibly underlie coagulopathic AEFIs.

BackgroundAppendicitis is the most prevalent surgical emergency. The negative appendicectomy rate and diagnostic uncertainty are important concerns. This study aimed to assess the effectiveness of current appendicitis risk prediction models in patients with acute right iliac fossa pain.MethodsA nationwide prospective observational study was conducted, including all consecutive adult patients who presented with right iliac fossa pain. Diagnostic, clinical and negative appendicectomy rate data were recorded. The Alvarado score, Appendicitis Inflammatory Response (AIR), Raja Isteri Pengiran Anak Saleha Appendicitis (RIPASA) and Adult Appendicitis Score systems were calculated with collected data to classify patients into risk categories. Diagnostic value and categorization performance were evaluated, with use of risk category-based metrics including ‘true positive rate’ (percentage of appendicitis patients in the highest risk category), ‘failure rate’ (percentage of patients with appendicitis in the lowest risk category) and ‘categorization resolution’ (true positive rate/failure rate).ResultsA total of 3358 patients from 84 centres were included. Female patients were less likely to undergo surgery than men (71.5% versus 82.5% respectively; relative risk 0.866, 95% c.i. 0.834 to 0.901, P < 0.001); with a three-fold higher negative appendicectomy rate (11.3% versus 4.1% respectively; relative risk 2.744, 95% c.i. 2.047 to 3.677, P < 0.001). Ultrasonography was utilized in 56.8% and computed tomography in 75.2% of all patients. The Adult Appendicitis Score had the best diagnostic performance for the whole population; however, only RIPASA was significant in men. All scoring systems were successful in females patients, but Adult Appendicitis Score had the highest area under the receiver operating characteristic curve value. The RIPASA and the Adult Appendicitis Score had the best categorization resolution values, complemented by their exceedingly low failure rates in both male and female patients. Alvarado and AIR had extremely high failure rates in men.ConclusionThe negative appendicectomy rate was low overall, but women had an almost three-fold higher negative appendicectomy rate despite lower likelihood to undergo surgery. The overuse of imaging tests, best exemplified by the 75.2% frequency of patients undergoing computed tomography, may lead to increased costs. Risk-scoring systems such as RIPASA and Adult Appendicitis Score appear to be superior to Alvarado and AIR.

Type I interferons act as gatekeepers against viral infection, and autoantibodies that neutralize these signaling molecules have been associated with COVID-19 severity and adverse reactions to the live-attenuated yellow fever vaccine. On this background, we sought to examine whether autoantibodies against type I interferons were associated with adverse events following COVID-19 vaccination. Our nationwide analysis suggests that type I interferon autoantibodies were not associated with adverse events after mRNA or viral-vector COVID-19 vaccines.

The characteristic steroid skeleton, with its 4-ringed 17-carbon structure, is one of the most recognizable organic compounds in biochemistry. In the presence of a hydroxyl ion bound to the third carbon, this structure is defined as a “sterol” (chemical formula: C17H28O). The hydroxyl group provides a hydrophilic site for the otherwise hydrophobic molecule, yielding an amphipathic lipid, which is a vital property for cellular function. It is crucial to remark that the term “steroid” describes a larger group of compounds that often retain the hydroxyl group but are primarily characterized by methyl groups, double bonds in the rings, and an aliphatic side-chain extending from the 17th carbon. In addition to serving various structural roles in the cellular membrane, sterols and steroids contribute to cellular and systemic functions as messengers, hormones, and regulators of several critical metabolic pathways.Sterol nomenclature is often confusing, partly due to structural complexity and partly due to the sheer number of different compounds that fall under the definition. Fortunately, the foremost sterols of interest in biochemistry are much fewer, and therefore, these lipids have been defined and studied vigorously. With the renaissance of lipid research during the 1990s and 2000s, many different metabolites of sterols, and more specifically phytosterols, were found to be associated with various diseases and conditions, including cardiovascular disease, hypercholesterolemia, cancer, obesity, inflammation, diabetes, and inborn errors of metabolism; thus, it is evident that the ever-evolving research in this field has been, and will continue to be, exceedingly productive.With respect to inflammation and inflammatory diseases, plant-based sterols (i.e., phytosterols) have gained considerable fame due to their anti-inflammatory and cholesterol-lowering effects demonstrated by experimental and clinical research. Besides, the exceptional pharmacological benefits of these sterols, which operate as antioxidant, antidiabetic, and anti-atherosclerotic agents, have been the subject of various investigations. While the underlying mechanisms necessitate further research, the possible function of phytosterols in improving health outcomes is an important topic to explore.In this regard, the current review aims to offer comprehensive information on the therapeutic potential of plant-based sterols in the context of human health, with a focus on preclinical effects, bioavailability, and clinical use.

Background: Available guidelines describing the procedural treatment of thrombosed external hemorrhoids (TEH) rely solely on expert opinion. We aimed to compare local excision (LE) and thrombectomy (incision) in terms of treatment success, factors affecting success, and outcomes.Methods: This was a multicenter, prospective, observational study conducted in eight centers from September 2020 to September 2021. A total of 96 patients (58 LE, 38 thrombectomy) were included. Risk factors, demographics and clinical characteristics were recorded. Follow-up studies were scheduled for the 1(st) week, 1(st), 3(rd) and 6(th) months. Surgical success was assessed at 1 month. Hemorrhoidal Disease Symptom Score (HDSS) and Short Health Scale (SHS) were applied at baseline and the 6(th) month. Wexner fecal incontinence score was applied at all follow-up studies.Results: Overall mean age was 41.5 & PLUSMN; 12.7 years. At baseline, groups were similar with regard to demographics and disease severity (HDSS) (p > 0.05 for all). Success was relatively higher in the thrombectomy group (86.8%) compared to the LE group (67.2%) (p = 0.054). Constipation and travel history were significantly associated with lower likelihood of LE success. Symptoms during follow-up were similarly distributed in the groups. Both methods yielded significant improvements in HDSS, SHS and Wexner scores; however, SHS scores (6 months) and Wexner scores (all time points) were significantly better in the thrombectomy group.Conclusion: The in-office thrombectomy procedure may have better short-term outcomes compared to LE in terms of relative success, recurrence and quality of life-despite the fact that success rates were statistically similar with the two interventions. LE may yield particularly worse results in patients with constipation and travel history; thus, thrombectomy appears to be especially advantageous in these patient subsets.