A study on obese patients' participation in cancer screening programs: an example from Turkey.

OBJECTIVE: Obesity is associated with many types of cancers. Despite this, the participation of obese individuals in cancer screenings is limited. The aim of this study was to evaluate the cancer screening-related attitudes of obese patients. METHODS: The study included 185 obese patients who presented to the obesity center (OC) and 191 obese patients who presented to the family medicine outpatient clinic from October to December 2019. The participants in both groups were first asked whether or not they had ever undergone any cancer screening tests and then provided with relevant training. After 3 months, the participants were contacted again and their attitudes toward cancer screening tests were re-evaluated. RESULTS: Patients who followed in the OC were found to have higher awareness of and compliance with cancer screening tests than the obese patients admitted to the outpatient clinic. The factors of being female, being followed in the OC, and residing in an urban area were positively associated with participation in cancer screening tests. CONCLUSION: Monitoring obese patients in target-oriented facilities such as an OC increases the chance of success in the fight against obesity and related health problems.

Rare case of mantle cell lymphoma of the lacrimal sac.

Mantle cell lymphoma of the ocular and periorbital regions is extremely rare but should be considered in the differential diagnosis of lesions affecting the periorbital tissues. In this study, we present a rare case of mantle cell lymphoma of the lacrimal sac in a 65-year-old male presenting with a mass in the lacrimal sac region and epiphora. After clinical examinations and imaging studies, the mucocele was misdiagnosed. Considering the unexpected findings during external dacryocystorhinostomy, a frozen biopsy was performed, which confirmed the diagnosis of lymphoma.

Bilateral Synchronous Testicular Cancer with Discordant Histopathology: A Case Report.

Bilateral testicular tumors account for 1 to 5% of all testicular tumors. Most bilateral tumors are observed metachronously. Synchronous tumors usually present with the similar histological pattern. Bilateral synchronous testicular tumors with discordant pathology are extremely rare. Only 56 cases have been documented since Bidard first described synchronous testicular tumors with discordant pathology in 1853. To our best knowledge, this study will be the 57th case in the literature.

Determining the Risk Factors for Anastomotic Stricture Development after Esophageal Atresia Repair: Results from the Turkish Esophageal Atresia Registry.

INTRODUCTION: Anastomotic stricture (AS) is the second most common complication after esophageal atresia (EA) repair. We aimed to evaluate the data in the Turkish Esophageal Atresia Registry to determine the risk factors for AS development after EA repair in a large national cohort of patients. METHODS: The data between 2015 and 2021 were evaluated. Patients were enrolled into two groups according to the occurrence of AS. Patients with AS (AS group) and without AS (non-AS group) were compared according to demographic and operative features, postoperative intubation status, and postoperative complications, such as anastomotic leaks, fistula recanalization, and the presence of gastroesophageal reflux (GER). A multivariable logistic regression analysis was performed to define the risk factors for the development of AS after EA repair. RESULTS: Among the 713 cases, 144 patients (20.19%) were enrolled into the AS group and 569 (79.81%) in the non-AS group. The multivariable logistic regression showed that, being a term baby (odds ratio [OR]: 1.706; p = 0.006), having a birth weight over 2,500 g (OR: 1.72; p = 0.006), presence of GER (OR: 5.267; p < 0.001), or having a recurrent tracheoesophageal fistula (TEF, OR: 4.363; p = 0.006) were the risk factors for the development of AS. CONCLUSIONS: The results of our national registry demonstrate that 20% of EA patients developed AS within their first year of life. In patients with early primary anastomosis, birth weight greater than 2,500 g and presence of GER were risk factors for developing AS. When patients with delayed anastomosis were included, in addition to the previous risk factors, being a term baby, and having recurrent TEF also became risk factors. LEVEL OF EVIDENCE: III.

Surgical Outcomes in Congenital Nasolacrimal Duct Obstruction After Probing Failure: A One-Stage Approach.

Objectives: This study evaluates the outcomes of a one-stage obstruction-based strategy for congenital nasolacrimal duct obstruction (CNLDO) in children who have prior probing failure. The objective is to assess the success rates of probing, balloon dacrioplasty (BDP), monocanalicular intubation (MCI), and external dacryocystorhinostomy (external DCR) performed in the same anesthesia session. Methods: A retrospective analysis included 55 eyes (45 patients, aged 12-120 months) with initial probing at another center. Procedures involved probing, probing plus BDP, MCI, and external DCR. For membranous obstruction (MO), the procedure concludes after probing; for incomplete complex obstruction (ICO) it includes BDP or MCI; and for complete complex obstruction (CCO), external DCR is performed. Success rates were assessed based on obstruction types and age groups, with improvement in symptoms and signs as the measure of success. Statistical analysis utilized Kruskal-Wallis, Fisher's exact test, and logistic regression. Results: The overall success rate for all procedures was 72.7%. Success rates were 77.8% for MO, 66.7% for ICO, and 100% for CCO, introducing a promising perspective for the management of different CNLDO types. External DCR exhibited a 100% success rate, highlighting its effectiveness in cases of CCO. Success rates for interventions were 77.8% for probing, 61.5% for probing plus BDP, and 73.1% for MCI, emphasizing the feasibility and success of one-stage obstruction-based treatments. Age did not significantly correlate with success rates. Conclusion: The one-stage obstruction-based approach, which demonstrated favorable success rates in treating CNLDO and introduced a paradigm shift in the treatment strategy after probing failure, underscores the importance of tailoring interventions to the specific obstruction type. The study also highlights the feasibility and cost-effectiveness of performing multiple BDP, MCI, or external DCR procedures concurrently during the same anesthesia session, further emphasizing the crucial role of customizing treatments based on the nature of the obstruction.

The effect of systemic sclerosis and its subtypes on ocular anterior and posterior segment parameters.

PURPOSE: To evaluate anterior and posterior segment parameters in the eyes of patients with systemic sclerosis (SSc) and examine the effect of disease and disease subtypes on these parameters. METHODS: This cross-sectional study included 54 eyes of 27 SSc patients and 54 eyes of 27 age- and sex-matched healthy controls. In addition to a complete ophthalmologic examination, all patients were examined using a Scheimpflug camera, specular microscopy, and spectral domain optical coherence tomography. RESULTS: The mean age of the patients was 52.5 ± 11.4 years and 19 patients were female. Anterior chamber volume, central corneal thickness, and central macular thickness (CMT) were significantly lower in the eyes of SSc patients compared to healthy controls (p = 0.01, p = 0.03, and p = 0.006, respectively). When evaluated according to SSc subtype, CMT was lower in diffuse SSc patients (p = 0.001), while mean retinal nerve fiber layer (RNFL) and inferior quadrant RNFL values were lower in limited SSc (p = 0.003 and p = 0.005, respectively). CONCLUSION: In the eyes of patients with SSc, some ocular parameters may show decreases compared to healthy individuals, presumably secondary to disease-related vasculopathy and fibrosis. CMT and RNFL parameters may be affected differently according to disease subtype.

Systematic Analysis of Tissue-Derived and Biofluid Extracellular Vesicle miRNAs Associated with Prostate Cancer.

Extracellular vesicles (EVs) are emerging as biomarker candidates for early detection of prostate cancer. Studies compare EV-microRNA (miRNA) expression in individuals with prostate cancer (PCa) with cancer-free samples for diagnostic purposes. The aim of this study is to review miRNA signatures to investigate the overlap between miRNAs enriched in PCa tissue and miRNAs enriched in EVs isolated from subjects with PCa biofluids (i.e., urine, serum, and plasma). Signatures dysregulated in EVs from PCa biofluids and tissue are potentially associated with the primary tumor site and might be more indicative of PCa at an early stage. A systematic review of EV-derived miRNAs and a reanalysis of PCa tissue miRNA sequencing data for comparison is presented. Articles in the literature are screened for validated miRNA dysregulation in PCa and compared with TCGA primary PCa tumor data using DESeq2. This resulted in 190 dysregulated miRNAs being identified. Thirty-one eligible studies are identified, indicating 39 dysregulated EV-derived miRNAs. The top ten markers identified as significantly dysregulated in the PCa tissue dataset TCGA (e.g., miR-30b-3p, miR-210-3p, miR-126-3p, and miR-196a-5p) have a significant expression change in EVs with the same directionality in one or several statistically significant results. This analysis highlights several less frequently studied miRNAs in PCa literature.

Evaluation of corneal endothelium and correlation with disease severity in patients with Graves' ophthalmopathy: A specular microscopy-based study.

PURPOSE: To investigate the possible corneal endothelial damage in Graves' ophthalmopathy (GO) and its relationship with GO activity. METHODS: This cross-sectional study included 101 eyes of 55 patients with GO. Each eye was assigned a specific clinical activity score (CAS). Accordingly, they were classified as active (CAS ≥ 3) or inactive (CAS< 3). The corneal endothelium was measured using a non-contact specular microscope (Tomey EM-4000; Tomey Corp.). Endothelial cell density (ECD), average cell area (ACA), standard deviation of cell area (SD), coefficient of variation in cell area (CV), hexagonal cell ratio (HEX), and central corneal thickness (CCT) were recorded. RESULTS: Among the eyes included in the study, 71 had inactive GO and 30 had active GO. ACA and HEX levels were lower (p<0,001) and CV values were higher (p<0.001) in patients with GO than in healthy subjects. Corneal endothelial cell morphology was altered in active GO compared to inactive GO. The SD (p = 0,009) and CV (p<0,001) were significantly higher in active GO than in inactive GO. When the parameters examined were correlated with CAS, a statistically significant positive correlation was observed between proptosis (p = 0,036, r = 0,385) and CV (p = 0,001, r = 0,595). CONCLUSION: Our study confirmed that morphological changes occur in the corneal endothelium of patients with GO. CV and SD values, in conjunction with CAS, can be used as non-invasive and quantitative indices to examine the activity status of GO. The demonstration of endothelial changes even in GO eyes with low CAS may be considered an incentive to include non-contact specular microscopy in the routine clinical evaluation of all patients with GO.

Label-Free Identification of Exosomes using Raman Spectroscopy and Machine Learning.

Exosomes, nano-sized extracellular vesicles (EVs) secreted from cells, carry various cargo molecules reflecting their cells of origin. As EV content, structure, and size are highly heterogeneous, their classification via cargo molecules by determining their origin is challenging. Here, a method is presented combining surface-enhanced Raman spectroscopy (SERS) with machine learning algorithms to employ the classification of EVs derived from five different cell lines to reveal their cellular origins. Using an artificial neural network algorithm, it is shown that the label-free Raman spectroscopy method's prediction ratio correlates with the ratio of HT-1080 exosomes in the mixture. This machine learning-assisted SERS method enables a new direction through label-free investigation of EV preparations by differentiating cancer cell-derived exosomes from those of healthy. This approach will potentially open up new avenues of research for early detection and monitoring of various diseases, including cancer.

Werner helicase is required for proliferation and DNA damage repair in multiple myeloma.

BACKGROUND: Multiple myeloma (MM), characterized by extensive genomic instability and aberrant DNA damage repair, is a plasma cell malignancy due to the excessive proliferation of monoclonal antibody-producing plasma cells in the bone marrow. Despite the significant improvement in the survival of patients with the development of novel therapeutic agents, MM remains an incurable disease. Werner (WRN) helicase, a member of the RecQ helicase family that contributes to DNA replication, recombination, and repair, has been highlighted in cancer cell survival, yet the role and mechanism of WRN in MM remain unclear. METHODS AND RESULTS: Increased mRNA expression of WRN in newly diagnosed and relapsed CD138+ myeloma plasma cells than normal CD138+ plasma cells and their matched CD138- non-tumorigenic cells were detected by qPCR. Using NSC19630, a specific WRN helicase inhibitor, we further showed decreased cell viability, proliferation, and DNA repair and increased DNA damage and apoptosis in MM cells by MTT assay, cell cycle assay, apoptosis assay, and Western blotting. CONCLUSIONS: The results of the present study demonstrate that WRN is essential in MM cell viability, proliferation, and genomic stability, indicating its inhibition may enhance the efficacy of chemotherapy in MM.

The effect of postoperative ventilation strategies on postoperative complications and outcomes in patients with esophageal atresia: Results from the Turkish Esophageal Atresia Registry.

OBJECTIVES: Postoperative ventilatory strategies in patients with esophageal atresia (EA) and tracheoesophageal fistula (TEF) may have an impact on early postoperative complications. Our national Esophageal Atresia Registry was evaluated to define a possible relationship between the type and duration of respiratory support on postoperative complications and outcome. STUDY DESIGN: Among the data registered by 31 centers between 2015 and 2021, patients with esophago-esophageal anastomosis (EEA)/tracheoesophageal fistula (TEF) were divided into two groups; invasive ventilatory support (IV) and noninvasive ventilatory support and/or oxygen support (NIV-OS). The demographic findings, gestational age, type of atresia, associated anomalies, and genetic malformations were evaluated. We compared the type of repair, gap length, chest tube insertion, follow-up times, tensioned anastomosis, postoperative complications, esophageal dilatations, respiratory problems requiring treatment after the operation, and mortality rates. RESULTS: Among 650 registered patients, 502 patients with EEA/TEF repair included the study. Four hundred and seventy of patients require IV and 32 of them had NIV-OS treatment. The IV group had lower mean birth weights and higher incidence of respiratory problems when compared to NIV-OS group. Also, NIV-OS group had significantly higher incidence of associated anomalies than IV groups. The rates of postoperative complications and mortality were not different between the IV and NIV-OS groups. CONCLUSION: We demonstrated that patients who required invasive ventilation had a higher incidence of low birth weight and respiratory morbidity. We found no relation between mode of postoperative ventilation and surgical complications. Randomized controlled trials and clinical guidelines are needed to define the best type of ventilation strategy in children with EA/TEF.

Multi-Center Experience of Coronary Artery Perforation During Percutaneous Coronary Intervention: Clinical and Angiographic Characteristics, Management, and Outcomes Between 2010 and 2020.

BACKGROUND: Coronary artery perforations are one of the most feared, rare, and catastrophic complication of percutaneous coronary intervention. Despite the remarkable increase in coronary angiography and percutaneous coronary intervention, there is no large database that collects coronary artery perforation for the Turkish population. Our study aimed to report our experience over a 10-year period for clinical and angiographic characteristics, management strategies, and outcomes of coronary artery perforation during the percutaneous coronary intervention at different cardiology departments in Turkey. METHODS: The study data came from a retrospective analysis of 48 360 percutaneous coronary intervention procedures between January 2010 and June 2020. A total of 110 cases who had coronary artery perforation during the percutaneous coronary intervention were found by angiographic review. Analysis has been performed for the basic clinical, angiographic, procedural characteristics, the management of coronary artery perforation, and outcome of all patients. RESULTS: The coronary artery perforation rate was 0.22%. Out of 110 patients with coronary artery perforation, 66 patients showed indications for percutaneous coronary intervention with acute coronary syndrome and 44 patients with stable angina pectoris. The most common lesion type and perforated artery were type C (34.5%) and left anterior descending (41.8%), respectively. The most observed coronary artery perforation according to Ellis classification was type III (37.2%). Almost 52.7% of patients have a covered stent implanted in the perforated artery. The all-cause mortality rate of coronary artery perforation patients in the hospital was 18.1%. CONCLUSION: The observed rate of coronary artery perforation in our study is consistent with the studies in this literature. However, the mortality rates related to coronary artery perforation are higher than in other studies in this literature. Especially, the in-hospital mortality rate was higher in type II and type III groups due to perforation and its complications. Nevertheless, percutaneous coronary intervention should be done in selected patients despite catastrophic complications.

Validation of the Clinical Frailty Scale version 2.0 in Turkish older patients.

AIM: Frailty is a syndrome that affects certain older adults more than others, and it has physical, cognitive, psychological, social and environmental aspects. The aim of our study was to determine the validity and reliability of the Clinical Frailty Scale (CFS) version 2.0 in Turkish. In total, 204 older adults aged ≥65 years took part in this study. METHODS: The necessary permissions were obtained from Rockwood et al. The Turkish version of CFS version 2.0 had been appropriately translated through translation to the back-translation process. A questionnaire was used to investigate certain descriptive features, as well as the newly edited Turkish translation of CFS version 2.0, the Turkish version of the FRAIL Scale and the Turkish version of the Edmonton Frail Scale. RESULTS: The age range was 65-95 years. In a Pearson correlation analysis, a positive link was discovered between FRAIL and CFS (r = 0.761 and P = 0.000) as well as CFS and Edmonton (r = 0.895 and P = 0.000). CONCLUSION: The Turkish translation of CFS version 2.0 has been determined to be suitable, valid and reliable for use in frailty screening in outpatient clinics. Geriatr Gerontol Int 2022; 22: 730-735.

Mutant KRAS regulates transposable element RNA and innate immunity via KRAB zinc-finger genes.

RAS genes are the most frequently mutated oncogenes in cancer, yet the effects of oncogenic RAS signaling on the noncoding transcriptome remain unclear. We analyzed the transcriptomes of human airway and bronchial epithelial cells transformed with mutant KRAS to define the landscape of KRAS-regulated noncoding RNAs. We find that oncogenic KRAS signaling upregulates noncoding transcripts throughout the genome, many of which arise from transposable elements (TEs). These TE RNAs exhibit differential expression, are preferentially released in extracellular vesicles, and are regulated by KRAB zinc-finger (KZNF) genes, which are broadly downregulated in mutant KRAS cells and lung adenocarcinomas in vivo. Moreover, mutant KRAS induces an intrinsic IFN-stimulated gene (ISG) signature that is often seen across many different cancers. Our results indicate that mutant KRAS remodels the repetitive noncoding transcriptome, demonstrating the broad scope of intracellular and extracellular RNAs regulated by this oncogenic signaling pathway.

Endogenous Retroviral Elements Generate Pathologic Neutrophils in Pulmonary Arterial Hypertension.

Rationale: The role of neutrophils and their extracellular vesicles (EVs) in the pathogenesis of pulmonary arterial hypertension is unclear. Objectives: To relate functional abnormalities in pulmonary arterial hypertension neutrophils and their EVs to mechanisms uncovered by proteomic and transcriptomic profiling. Methods: Production of elastase, release of extracellular traps, adhesion, and migration were assessed in neutrophils from patients with pulmonary arterial hypertension and control subjects. Proteomic analyses were applied to explain functional perturbations, and transcriptomic data were used to find underlying mechanisms. CD66b-specific neutrophil EVs were isolated from plasma of patients with pulmonary arterial hypertension, and we determined whether they produce pulmonary hypertension in mice. Measurements and Main Results: Neutrophils from patients with pulmonary arterial hypertension produce and release increased neutrophil elastase, associated with enhanced extracellular traps. They exhibit reduced migration and increased adhesion attributed to elevated ß1-integrin and vinculin identified by proteomic analysis and previously linked to an antiviral response. This was substantiated by a transcriptomic IFN signature that we related to an increase in human endogenous retrovirus K envelope protein. Transfection of human endogenous retrovirus K envelope in a neutrophil cell line (HL-60) increases neutrophil elastase and IFN genes, whereas vinculin is increased by human endogenous retrovirus K deoxyuridine triphosphate diphosphatase that is elevated in patient plasma. Neutrophil EVs from patient plasma contain increased neutrophil elastase and human endogenous retrovirus K envelope and induce pulmonary hypertension in mice, mitigated by elafin, an elastase inhibitor. Conclusions: Elevated human endogenous retroviral elements and elastase link a neutrophil innate immune response to pulmonary arterial hypertension.

Frontal QRS/T angle can predict mortality in COVID-19 patients.

AIMS: The frontal QRS-T (fQRS) angle has been investigated in the general population, including healthy people and patients with heart failure. The fQRS angle can predict mortality due to myocarditis, ischaemic and non-ischaemic cardiomyopathies, idiopathic dilated cardiomyopathy, and chronic heart failure in the general population. Moreover, no studies to date have investigated fQRS angle in coronavirus disease 2019 (COVID-19) patients. Thus, the purpose of this retrospective multicentre study was to evaluate the fQRS angle of COVID-19 patients to predict in-hospital mortality and the need for mechanical ventilation. METHODS AND RESULTS: An electrocardiogram was performed for 327 COVID-19 patients during admission, and the fQRS angle was calculated. Mechanical ventilation was needed in 119 patients; of them, 110 died in the hospital. The patients were divided into two groups according to an fQRs angle >90° versus an fQRS angle ≤90°. The percentages of mortality and the need for mechanical ventilation according to fQRS angle were 67.8% and 66.1%, respectively, in the fQRs >90° group and 26.1% and 29.9% in the fQRS ≤90°group. Heart rate, oxygen saturation, fQRS angle, estimated glomerular filtration rate, and C-reactive protein level were predictors of mortality on the multivariable analysis. The mortality risk increased 2.9-fold on the univariate analysis and 1.6-fold on the multivariate analysis for the fQRS >90° patient group versus the fQRS ≤90° group. CONCLUSION: In conclusion, a wide fQRS angle >90° was a predictor of in-hospital mortality and associated with the need for mechanical ventilation among COVID-19 patients.

Is serum fibroblast growth factor 21 associated with the severity or presence of coronary artery disease?

Background: Recent studies have shown that increased circulating concentrations of fibroblast growth factor 21 (FGF21) are associated with obesity, metabolic disorder, and atherosclerosis. However the relationship between FGF21 and coronary artery disease (CAD) is controversial This study was planned to investigate the role of FGF21 in CAD development and CAD severity. Methods: Seventy-eight patients with stable angina pectoris (SAP) (lesion positive) and 40 control patients (lesion negative) with similar cardiovascular risk factors were included in the study. Serum FGF21 levels were measured by ELISA method. CAD severity was evaluated by using SYNTAX and GENSINI risk scores. Results: FGF21 concentrations were found significantly higher in the SAP group than in the control group. [101.18 ± 141.62 vs. 47.93 ± 58.74 pg/mL; p = 0.03], no correlation was found between the SYNTAX (r = 0.146 and p = 0.134) and GENSINI (r = 0.211 and p = 0.084) scores with serum FGF21 levels. There was a negative relationship between serum FGF21 and serum HDL-C levels in correlation analysis (r = - 0.272; p = 0.026). Conclusions: The serum FGF21 levels are different between SAP and control patients. FGF21 is a marker for CAD diagnosis, but not for the evaluation of CAD severity.

Antioxidant and inflammatory biomarkers in herpes zoster.

The risk of herpes zoster (HZ) increases as cell-mediated immunity declines with age. Even though oxidative stress plays a crucial role in the development of HZ, there are few serum biomarkers of the disease's antioxidant activity. The purpose of this study is to investigate the blood levels of major antioxidants in HZ patients. To the best of our knowledge, this is the first study on this issue in the literature. The serum levels of antioxidants including uric acid (UA), total bilirubin (TBIL), albumin (ALB), vitamin D levels, and inflammatory markers such as homocysteine (Hcy) and C-reactive protein (CRP) was retrospectively analyzed in 53 patients with HZ and 53 age-and sex-matched healthy controls (HCs). The relationships between these markers and postherpetic neuralgia (PHN) and the clinical severity of HZ were also evaluated. Serum levels of UA, TBIL, and ALB in patients with HZ were significantly lower than those in the HCs (p < 0.001), while no statistical differences were found in vitamin D levels between the groups. Hcy and CRP levels were significantly increased in HZ patients compared to HCs. Significant differences were observed in the serum levels of UA, Hcy, CRP, and vitamin D in the PHN group versus the non-PHN group (p < 0.001). The presence of inflammatory markers was found to be positively related to disease activity. Furthermore, when compared to the mild or moderate clinical types of HZ, these biomarkers were statistically significant in the severe clinical type. These results suggest that uncontrolled varicella-zoster virus reactivation, acute nerve damage, and PHN may all be associated with low antioxidant levels. These biomarkers may be a protective factor for HZ, but more research is needed to clarify the underlying mechanism.