Genetic and Epigenetic Association of FOXP3 with Papillary Thyroid Cancer Predisposition.

Papillary thyroid cancer (PTC) is the most common type of thyroid malignancy with an increased female incidence ratio. The specific traits of X chromosome inheritance may be implicated in gender differences of PTC predisposition. The aim of this study was to investigate the association of two X-linked genes, Forkhead Box P3 (FOXP3) and Protein Phosphatase 1 Regulatory Subunit 3F (PPP1R3F), with PTC predisposition and gender disparity. One hundred thirty-six patients with PTC and an equal number of matched healthy volunteers were enrolled in the study. Genotyping for rs3761548 (FOXP3) and rs5953283 (PPP1R3F) was performed using polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). The methylation status of FOXP3 was assessed using the combined bisulfite restriction analysis (COBRA) method. The SPSS software was used for statistical analyses. Gender stratification analysis revealed that the CA and AA genotypes and the A allele of FOXP3 rs3761548 variant are associated with PTC predisposition only in females. Moreover, different methylation status was observed up to the promoter locus of FOXP3 between PTC female patients, carrying the CA and CC genotype, and controls. Both revealed associations may explain the higher PTC incidence in females through reducing FOXP3 expression as reported in immune related blood cells.

Thyroidectomy in children and adolescents: a systematic review.

Background: Thyroid surgery in pediatric population is not as common as that in adults, although they share the same indications, techniques and complications. This review aims to evaluate the surgical management of thyroid disease in patients under 18 years old. Methods: We conducted a bibliographic search in the international literature. Data from the identified studies such as demographics, indication for surgery, type of procedure, complications and length of hospital stay were recorded. A retrospective review study of all patients under 18 years old who underwent thyroidectomy was performed. Results: We included 37 retrospective studies and a total of 12,728 patients. Thyroidectomy was more common in female patients and the mean age was approximately 14 years old. The leading indication for surgery was benign thyroid pathology. Due to the surgical treatments' safety and effectiveness in young patients, total and subtotal thyroidectomy, whether for malignancies or benign diseases, is becoming more popular today. The most often occurring complication of pediatric thyroid surgery is hypoparathyroidism. Despite the high likelihood of recurrence of pediatric malignancies, overall survival rates of pediatric thyroid cancer are excellent. Conclusions: Thyroidectomy performed by high-volume thyroid surgeons in children and adolescents is considered an efficient and safe method of treatment of thyroid disease.

Exploring the Link between BMI and Aggressive Histopathological Subtypes in Differentiated Thyroid Carcinoma-Insights from a Multicentre Retrospective Study.

Obesity's role in thyroid cancer development is still debated, as well as its association with aggressive histopathological subtypes (AHSs). To clarify the link between Body Mass Index (BMI) and AHS of differentiated thyroid carcinoma (DTC), we evaluated patients who underwent thyroidectomy for DTC from 2020 to 2022 at four European referral centres for endocrine surgery. Based on BMI, patients were classified as normal-underweight, overweight, or obese. AHSs were defined according to 2022 WHO guidelines. Among 3868 patients included, 34.5% were overweight and 19.6% obese. Histological diagnoses were: 93.6% papillary (PTC), 4.8% follicular (FTC), and 1.6% Hürthle cell (HCC) thyroid carcinoma. Obese and overweight patients with PTC had a higher rate of AHSs (p = 0.03), bilateral, multifocal tumours (p = 0.014, 0.049), and larger nodal metastases (p = 0.017). In a multivariate analysis, BMI was an independent predictor of AHS of PTC, irrespective of gender (p = 0.028). In younger patients (<55 years old) with PTC > 1 cm, BMI predicted a higher ATA risk class (p = 0.036). Overweight and obese patients with FTC had larger tumours (p = 0.036). No difference was found in terms of AHS of FTC and HCC based on BMI category. Overweight and obese patients with PTC appear to be at an increased risk for AHS and aggressive clinico-pathological characteristics.

The Impact of Change Management in the Greek National Health System: A Quantitative Study.

INTRODUCTION:  Serious changes took place in Greece due to the economic crisis of 2008, which led to significant changes in Greece's health sector. The reforms and changes that were made to the National Health System (NHS) aimed to improve it, provide quality services to its users, and adapt it to Greece's new external environment. The aim of this study was to assess the management of these changes by the leadership of the NHS and to examine their effectiveness. MATERIAL AND METHODS: The survey was based on quantitative research methods, using a questionnaire as a research tool. The sample population comprised employees of a tertiary-care public hospital in northern Greece. RESULTS:  We recruited a sample size of 100 participants for the survey. The questionnaire's Cronbach's alpha was equal to 0.724. The overall change management was moderate, and Greece's NHS did not follow a specific change-management model that provided principles facilitating the success of the effort. The most serious problems identified by using the questionnaire were the following: the changes were not structured and clear, the management set unrealistic goals and objectives, the changes to the NHS were made without the appropriate financial support, and there is uncertainty about the future of health care in Greece. CONCLUSION: The present study showed that changes cannot be made randomly; rather, they require careful planning and organization. Further changes, continuous feedback, and development are required to improve the status of Greece's healthcare system.

Gastrointestinal Stromal Tumors: Our Ten-Year Experience of a Single-Center Tertiary Hospital.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal neoplasms of the gastrointestinal tract. They have variable clinical presentation, prognosis, and molecular characteristics. Here, we present the results of our retrospective study including patients operated on for GIST during the last decade. METHODS: All the patients who underwent GIST resection during the decade 2008-2018 were included in the study. The diagnosis was based on the pathology report. All the data were collected and analyzed statistically using the Statistical Package for Social Science v25.0. Finally, after having applied the proper search terms, a comprehensive review of articles published in the Medline database was held. RESULTS: Thirty-two patients (sixteen women) were included in the study with a mean age of 69.6 years old (SD = 13.9). Twenty-one patients had a GIST in the stomach, eight in the small intestine, and three had an extra GIST. Of the 29 patients contacted, 21 were alive with a mean survival time of 74.3 months (SD = 49.6 months, min: 3.0 months, max: 161.0 months), whereas eight patients passed away. Finally, 13 patients were treated with tyrosine kinase inhibitors (TKIs) of whom only one died, while 9 patients passed away from those treated with surgery alone (p = 0.031). CONCLUSIONS: Our results were in concordance with the existing data in the literature. GISTs require patient-based therapeutical management depending on the histology of the tumors. Gastric tumors present a better prognosis than those localized in the intestine, while the use of TKIs has led to an improvement in patient survival rate.

Visualization of the recurrent laryngeal nerve alone versus intraoperative nerve monitoring in primary thyroidectomy: a framework approach to a missing typology.

Introduction: Surgical studies evaluating a device or technology in comparison to an established surgical technique should accurately report all the important components of the surgical technique in order to reduce the risk of intervention bias. In the debate of visualization of the recurrent laryngeal nerve alone (VONA) versus intraoperative nerve monitoring (IONM) during thyroidectomy, surgical technique plays a key role in both strategies. Our aim was to investigate whether the surgical technique was considered as a risk of intervention bias by relevant meta-analyses and reviews and if steps of surgical intervention were described in their included studies. Methods: We searched PUBMED, CENTRAL-Cochrane library, PROSPERO and GOOGLE for reviews and meta-analyses focusing on the comparison of IONM to VONA in primary open thyroidectomy. Τhen, primary studies were extracted from their reference lists. We developed a typology for surgical technique applied in primary studies and a framework approach for the evaluation of this typology by the meta-analyses and reviews. Results: Twelve meta-analyses, one review (388,252 nerves at risk), and 84 primary studies (128,720 patients) were included. Five meta-analyses considered the absence of typology regarding the surgical technique as a source of intervention bias; 48 primary studies (57.14%) provided information about at least one item of the typology components and only 1 for all of them. Discussion: Surgical technique of thyroidectomy in terms of a typology is underreported in studies and undervalued by meta-analyses comparing VONA to IONM. This missing typology should be reconsidered in the comparative evaluation of these two strategies.

A Pilot Study of the Association VDR Polymorphisms With Primary Hyperparathyroidism.

BACKGROUND/AIM: Primary hyperparathyroidism (PHPT) is the third most common endocrine disorder characterized by autonomous parathyroid hormone (PTH) production from one or more parathyroid glands and hypocalcemia. Vitamin D through its receptor is a principal regulator of parathyroid glands function. VDR gene polymorphisms, which affect the expression or structure of VDR protein, may be involved in the genetic pathogenesis of PHPT. The aim of this study was to investigate the role of FokI, ApaI, TaqI, and BsmI VDR gene polymorphisms as genetic predisposing factors for PHPT. PATIENTS AND METHODS: Fifty unrelated patients with sporadic PHPT and an equal number of corresponding ethnicity, sex and age range healthy volunteers were enrolled in the study. Genotyping was performed with polymerase chain reaction and restriction fragment length polymorphism assay. RESULTS: Statistically significant difference was observed in TaqI genotype distribution between PHPT patients and controls, while no association was detected for the other studied polymorphisms. CONCLUSION: TaqI TT and TC genotypes may be associated with PHPT risk in Greek population. Further independent studies are needed to replicate and validate the role of VDR TaqI polymorphism in PHPT predisposition.

Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Predictive Factors for Mortality and Length of Hospital Stay after Cardiac Surgery.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are widely accepted indices positively correlated with disease severity, progression, and mortality. In this study, we tested whether NLR and PLR could predict mortality and length of hospital stay (LOS) after cardiac surgery. METHODS: NLR and PLR were calculated on days 0, 3, 5, and 7 postoperatively. A ROC curve was generated to assess their prognostic value; multivariate logistic analysis identified independent risk factors for 90-day mortality. RESULTS: Analysis was performed on 179 patients' data, 11 of whom (6.15%) died within 90 days. The discriminatory performance for predicting 90-day mortality was better for NLR7 (AUC = 0.925, 95% CI:0.865-0.984) with the optimal cut-off point being 7.10. NLR5 and PLR3 also exhibited a significant strong discriminative performance. Similarly, a significant discriminative performance was prominent for PLR3, NLR5, and NLR7 with respect to LOS. Moreover, NLR7 (OR: 2.143, 95% CI: 1.076-4.267, p = 0.030) and ICU LOS (OR:1.361, 95% CI: 1.045-1.774, p = 0.022) were significant independent risk factors for 90-day mortality. CONCLUSIONS: NLR and PLR are efficient predictive factors for 90-day mortality and LOS in cardiac surgery patients. Owing to the simplicity of determining NLR and PLR, their postoperative monitoring may offer a reliable predictor of patients' outcomes in terms of LOS and mortality.

Buried bumper syndrome: A critical analysis of endoscopic release techniques.

Buried bumper syndrome (BBS) is the situation in which the internal bumper of the gastrostomy tube, due to prolonged compression of the tissues between the external and the internal bumper, migrates from the gastric lumen into the gastric wall or further, into the tract outside the gastric lumen, ending up anywhere between the stomach mucosa and the surface of the skin. This restricts liquid food from entering the stomach, since the internal opening is obstructed by gastric mucosal overgrowth. We performed a comprehensive search of the PubMed literature to retrieve all the case-reports and case-series referring to BBS and its management, after which we focused on the endoscopic techniques for releasing the internal bumper to re-establish the functionality of the tube. From the "push" and the "push and pull T" techniques to the most sophisticated-using high tech instruments, all 10 published techniques have been critically analysed and the pros and cons presented, in an effort to optimize the criteria of choice based on maximum efficacy and safety.

Effect of Parathyroidectomy on Left Ventricular Mass Index in Patients With Primary Hyperparathyroidism.

Aim Primary hyperthyroidism (PHPT) is known to affect left ventricular structure and function and may contribute to increased cardiovascular morbidity and mortality. Whether parathyroidectomy (PTX) reverses left ventricular hypertrophy/remodeling among PHPT patients remains controversial. Method In this prospective, single-center study, we enrolled patients with the diagnosis of PHPT who were scheduled for PTX. Patients underwent a complete biochemical workup and an echocardiographic examination at baseline and a six-month follow-up. The primary objective was to compare the left ventricular mass index (LVMI) at baseline and six-month follow-up. Result Eighteen patients (15 female, three male, mean age 58.7 years) were enrolled. PTH and serum calcium returned to normal immediately post-PTX and remained normal at six months. LVMI at baseline was within normal limits and reduced further at the six-month follow-up. The left ventricular ejection fraction was in the normal range before the PTX and remained unchanged during follow-up. Conclusion Curative PTX reduced LVMI further within the normal range at six months in patients with asymptomatic hyperparathyroidism, providing evidence for benefit in an important non-traditional disease manifestation.

Effect of common OPRM1, COMT, SLC6A4, ABCB1, and CYP2B6 polymorphisms on perioperative analgesic and propofol demands on patients subjected to thyroidectomy surgery.

BACKGROUND: Perioperative anesthetic and/or analgesic demand present considerable variation, and part of that variation appears to be genetic in origin. Here we investigate the impact of common polymorphisms in OPRM1, COMT, SLC6A4, ABCB1, and CYP2B6 genes, on the intra-operative consumption of remifentanil and propofol, as well as the postoperative analgesic needs, in patients subjected to thyroidectomy surgery. METHODS: We conducted a prospective cohort study with 90 patients scheduled to undergo elective thyroidectomy, under total intravenous anesthesia achieved by target control infusion (TCI) of propofol and remifentanil. Postoperative analgesics were administered by protocol and on-demand by the individual patient. Genotyping was established by PCR-RFLP methods. Genotyping data, intra-operative hemodynamics, and total consumption of remifentanil and propofol, as well as postoperative analgesic needs and pain perception, were recorded for each individual. RESULTS: Patients with the ABCB1 3435TT genotype appeared to experience significantly less pain within one hour post-operatively, compared to C carriers [mean VAS (SD) = 0.86 (1.22) vs. 2.42 (1.75); p = 0.017], a finding limited to those seeking rescue analgesic treatment. Intra-operatively, homozygotes patients for the minor allele of OPRM1 A118G and CYP2B6 G516T appeared to consume less remifentanil [mean (SD) = 9.12 (1.01) vs. 13.53 (5.15), for OPRM1 118GG and A carriers] and propofol [median (range) = 14.95 (11.53, 1359.5) vs. 121.4 (1.43, 2349.4), for CYP2B6 516TT and G carriers, respectively] but the difference was not statistically significant in our sample. CONCLUSIONS: The ABCB1 C3435T polymorphism appears to affect the postoperative perception of surgical pain among patients with low pain threshold. The small number of minor allele homozygotes for the OPRM1 A118G and CYP2B6 G516T polymorphisms precludes a definitive conclusion regarding the inclusion of the latter in a TCI-programming algorithm, based on the results of this study. CLINICAL TRIAL REGISTRATION NUMBER: ACTRN12616001598471.

The Role of Vitamin D in Kidney Transplantation Outcomes: A Systematic Review.

The aim of this systematic review is to assess the impact of vitamin D on the outcomes of kidney transplantation and investigate whether its deficiency is associated with a negative impact. Methods: We conducted a systematic literature search in PubMed, Scopus and Cochrane databases, as well as gray literature. Ultimately, 16 articles with an average of 255.75 patients were included in this review. These articles compared the long-term outcomes of vitamin D deficiency and/or vitamin D supplementation therapy on kidney transplant recipients by assessing various parameters. Results: Most of the included studies showed a negative effect of vitamin D deficiency on kidney transplantation by being associated with a worse graft function, higher incidence of acute rejection episodes, higher incidence of proteinuria and lower overall graft and patient survival rate. Conclusions: We suggest that patients awaiting kidney transplantation have a careful evaluation in order to assess their vitamin D status and the optimal supplementation therapy. Regular follow-up of vitamin D levels post-transplant is also suggested. Prospective studies will be needed to establish the positive effects of vitamin D supplementation therapy on kidney transplant outcomes.

The Role of Carbon Nanoparticles in Lymph Node Dissection and Parathyroid Gland Preservation during Surgery for Thyroid Cancer: A Systematic Review and Meta-Analysis.

Thyroid cancer is the most common endocrine malignancy with an increasing incidence over the past few years. Surgery is considered the primary therapeutic option, which often involves lymph node dissection. The aim of this study was to assess the role of carbon nanoparticles, a novel agent, in thyroid cancer surgery. For that purpose, we conducted a systematic review of the literature on MEDLINE, EMBASE, Scopus, Cochrane and Google Scholar databases from 1 January 2002 to 31 January 2022. Ultimately, 20 articles with a total number of 2920 patients were included in the analysis. The outcome of the analysis showed that the use of carbon nanoparticles is associated with a higher number of harvested lymph nodes (WMD, 1.47, 95% CI, 1.13 to 1.82, p < 0.001) and a lower rate of accidental parathyroid gland removal (OR 0.34, CI 95% 0.24 to 0.50, p < 0.001). Based on these results, we suggest that carbon nanoparticles are applied in thyroid cancer surgery on a wider scale, so that these findings can be confirmed by future research on the subject.

A Four-Probiotic Regime to Reduce Surgical Site Infections in Multi-Trauma Patients.

Investigations that focused on the protective role of probiotics against Surgical Site Infections (SSI) in multiple-trauma (MT) patients are generally few, probably due to the complexity of the concept of trauma. We aimed to assess the efficacy of a four-probiotic regime to reduce the incidence of SSI in MT patients, with a brain injury included. MT patients, being intubated and expected to require mechanical ventilation for >10 days, were randomly allocated into placebo (n = 50) or probiotic treatment (n = 53) comprising Lactobacillus acidophilus LA-5 (1.75 × 109 cfu), Lactiplantibacillus plantarum UBLP-40 (0.5 × 109 cfu), Bifidobacterium animalis subsp. lactis BB-12 (1.75 × 109 cfu), and Saccharomycesboulardii Unique-28 (1.5 × 109 cfu) in sachets. All patients received two sachets of placebo or probiotics twice/day for 15 days and were followed-up for 30 days. The operations were classified as neurosurgical, thoracostomies, laparotomies, orthopedics, and others; then, the SSI and the isolated pathogen were registered. A total of 23 (46.0%) and 13 (24.5%) infectious insults in 89 (50 placebo patients) and 88 (53 probiotics-treated) operations (p = 0.022) were recorded, the majority of them relating to osteosynthesis­17 and 8, respectively. The most commonly identified pathogens were Staphylococcus aureus and Acinetobacter baumannii. Our results support published evidence that the prophylactic administration of probiotics in MT patients exerts a positive effect on the incidence of SSI.

The Implication of X-Linked Genetic Polymorphisms in Susceptibility and Sexual Dimorphism of Cancer.

The X-chromosome is implicated in cancer development through various mechanisms, including X-inactivation defects, loss of heterozygosity, and germline and somatic alterations of X-linked genes. Sex is a key factor which influences cancer susceptibility as many cancer types show sexual dimorphism in their incidence. The aim of this review was to summarize the germline genetic polymorphisms lying on the X-chromosome that have been associated with cancer susceptibility and to evaluate their possible implication in cancer-related sexual dimorphism. PubMed and Web of Science were searched using the terms "X-chromosome", "polymorphism" and "cancer". The literature review revealed 39 articles reporting 33 genetic variants in 22 X-linked genes as being associated with cancer risk. Most of these genes interact with each other in a direct or indirect way, as GeneMANIA software revealed, demonstrating the complication of the mechanisms through which they are involved in tumorigenesis. Polymorphisms in eight genes [androgen receptor (AR), fibroblast growth factor 13 (FGF13), forkhead box P3 (FOXP3), L1 cell adhesion molecule (L1CAM), nudix hydrolase 11 (NUDT11), Shroom family member 2 (SHROOM2), transcription elongation factor A-like 7 (TCEAL7) and TIMP metallopeptidase inhibitor 1 (TIMP1)] are reported to have a sex-specific association with cancer susceptibility, which might explain the sexual dimorphism of certain cancer types. All of the above eight mentioned genes, with the exception of L1CAM, exhibit differences in their expression pattern between breast tumor (sex-specific)/thyroid tumor (sex-influenced) vs. normal tissues according to our analysis using GENT2 software. Additionally, differences in breast or thyroid tumor compared with normal tissues were also observed in five genes analyzed with GENT2 software that were previously related to sex-influenced cancer according to literature. Finally, the present review points out the need for the development of appropriate free and user-friendly statistical software in order to reduce bias/errors in statistical analyses and overcome researchers' reluctance to include X-chromosome variants in their genetic-association studies.

Retrosternal goiter masquerading as type II respiratory failure. A case report.

INTRODUCTION AND IMPORTANCE: Retrosternal Goiter (RG) represents a challenging clinical entity for surgeons. Although the vast majority of cases are successfully operated via a cervical access, there still remains a small minority that require an extra-cervical approach, even in experienced hands. Factors that shift the odds towards an extra-cervical approach are mainly related to the anatomic characteristics of the retrosternal mass. CASE PRESENTATION: We herein report a case of RG presenting as type 2 respiratory failure without a palpable neck mass, in an 81-year-old female. Despite her history of subtotal thyroidectomy for Graves' disease, the patient's chest x-ray showed a central mediastinal mass shifting the trachea to the left. The retrosternal mass extended below the aortic arch, and carina on computed tomography. It also extended into the posterior mediastinum. All these anatomical features of the RG along with the patient's previous neck surgery were in favor of an extra-cervical approach. Nevertheless, a cervical approach was attempted, and was concluded successfully. CONCLUSION: CT plays a key role in determining the likelihood of requiring an extra-cervical approach in RG. Even if the odds seem to be in favor of an extra-cervical approach, an attempt to remove the goiter through a cervical incision should always be made by an experienced surgeon, using all available techniques, and taking all required precautions, on account of less risk of surgical and aesthetic damage obtained with this approach.

Composite Paraganglioma of the Celiac Trunk: A Case Report and a Comprehensive Review of the Literature.

Introduction: Composite paragangliomas consist of two components, paraganglioma and ganglioneuroma, representing a rare subgroup of paragangliomas. The purpose of the study is to describe a case of composite paraganglioma of the celiac trunk and a brief review of the existing literature. Case Presentation: A 64-year-old female patient with a history of epigastric abdominal pain and a 51 mm-diameter tumor found in a Computerized Tomography of the abdomen was admitted to our surgical department for further evaluation and treatment. After a brief preoperative surgical assessment, the patient underwent a mini-laparotomy for the excision of this tumor. After having the results of the pathology report, a comprehensive review of the international literature was carried out by applying the appropriate search terms. Results: As it was found intraoperatively, the tumor was located at the cephalad aspect of the common hepatic artery, over the portal vein and the inferior vena cava. A negative-margin resection was achieved and the tumor was sent for pathology analysis. The final pathology report revealed a composite paraganglioma, with α paraganglioma and a ganglioneuroma component. Seventeen cases of extra-adrenal composite paraganglioma have been reported in the international literature so far. This case was the first one found in the area of the celiac trunk. Conclusions: Composite paragangliomas comprise rare and potentially malignant tumors with variable prognosis. Establishing their diagnosis promptly is of vital significance. Due to the first-described location of the composite paraganglioma in our case, the differential diagnosis of tumors in this area should also include composite paragangliomas.

Translation of the Pasieka's Parathyroid Assessment of Symptoms Questionnaire (PAS-Q) for Use in the Greek Population.

Introduction: In Europe, primary hyperparathyroidism is mainly considered an asymptomatic disorder, although there is evidence that patients' health-related quality of life is impaired. This aspect is mostly evaluated using Pasieka's Questionnaire: a disease-specific diagnostic tool. The purpose of this study was to translate the Pasieka's Questionnaire into the Greek language and adapt it to the Greek population. Materials and Methods: Pasieka's Questionnaire consists of 13 questions. Two bilingual, native Greek experts were selected for step one, each of whom offered a blinded Greek version of the questionnaire. In the second step, these two versions were merged into one which was retranslated back into the English language (step three) by two bilingual translators (English native speakers). In the fourth step, a committee was formed to draft the pre-final version of the questionnaire which was then submitted to the co-authors for final approval. Finally, after the approval of the final version, 50 patients with primary hyperparathyroidism were recruited for the pilot study of the questionnaire. Results: All 13 questions of the Pasieka's Questionnaire were translated without any major discrepancy. A high level of internal consistency was achieved (Cronbach's alpha was 0.904) and agreement between test-retest was excellent for every question. Conclusion: The Greek version of Pasieka's Questionnaire was validated and can be applied to evaluate the health-related quality of life of patients with primary hyperparathyroidism in Greek-speaking populations.