Latent Tuberculosis Infection Management in Solid Organ Transplantation Recipients: A National Snapshot.

OBJECTIVE:  Latent tuberculosis infection (LTBI) screening is strongly recommended in the pre-transplant evaluation of solid organ transplant (SOT) recipients, although it remains inadequate in many transplant centers. We decided to investigate pre-transplant TB risk assessment, LTBI treatment, and registry rates in Turkey. MATERIAL AND METHODS:  Adult SOT recipients who underwent tuberculin skin test (TST) and/or interferon-gamma release test (IGRA) from 14 centers between 2015 and 2019 were included in the study. An induration of ≥5 mm on TST and/or probable/positive IGRA (QuantiFERON-TB) was considered positive for LTBI. Demographic features, LTBI screening and treatment, and pre-/post-transplant TB history were recorded from the electronic database of transplantation units across the country and pooled at a single center for a unified database. RESULTS:  TST and/or IGRA were performed in 766 (33.8%) of 2266 screened patients most of whom were kidney transplant recipients (n = 485, 63.4%). LTBI screening test was positive in 359 (46.9%) patients, and isoniazid was given to 203 (56.5%) patients. Of the patients treated for LTBI, 112 (55.2%) were registered in the national registry, and 82 (73.2%) completed the treatment. Tuberculosis developed in 6 (1.06%) of 563 patients who were not offered LTBI treatment. CONCLUSION:  We determined that overall, only one-third of SOT recipients in our country were evaluated in terms of TB risk, only 1 of the 2 SOT recipients with LTBI received treatment, and half were registered. Therefore, we want to emphasize the critical importance of pretransplant TB risk stratification and registration, guided by revised national guidelines.

Voltage-gated sodium channel epilepsies in a tertiary care center: Phenotypic spectrum with correlation to predicted functional effects.

BACKGROUND: Variants in sodium channel genes (SCN) are strongly associated with epilepsy phenotypes. Our aim in this study to evaluate the genotype and phenotype correlation of patients with SCN variants in our tertiary care center. METHODS: In this retrospective study, patients with SCN variants and epilepsy who were followed up at our clinic between 2018 and 2022 were evaluated. Our study discussed the demographics of the patients, the seizure types, the age of seizure onset, the SCN variants, the domains and the functions of the variants, the magnetic resonance imaging findings, the motor, cognitive, and psychiatric comorbidities, and the response to anti-seizure medication. Genetic testing was conducted using a next-generation sequencing gene panel (epilepsy panel) or a whole-exome sequencing. For evaluating variant function, we used a prediction tool (https://funnc.shinyapps.io/shinyappweb/ site). To assess protein domains, we used the PER viewer (http://per.broadinstitute.org/). RESULTS: Twenty-three patients with SCN variants and epilepsy have been identified. Sixteen patients had variants in the SCN1A, six patients had variants in the SCN2A, and one patient had a variant in the SCN3A. Two novel SCN1A variants and two novel SCN2A variants were identified. The analysis revealed 14/23 missense, 6/23 nonsense, 2/23 frameshift, and 1/23 splice site variants in the SCN. There are seven variants predicted to be gain-of-function and 13 predicted to be loss-of-function. Among 23 patients; 11 had Dravet Syndrome, 6 had early infantile developmental and epileptic encephalopathy, three had genetic epilepsy with febrile seizures plus spectrum disorder, one had self-limited familial neonatal-infantile epilepsy, one had self-limited infantile epilepsy and one had infantile childhood development epileptic encephalopathy. CONCLUSION: Our cohort consists of mainly SCN1 variants, most of them were predicted to be loss of function. Dravet syndrome was the most common phenotype. The prediction tool used in our study demonstrated overall compatibility with clinical findings. Due to the diverse clinical manifestations of variant functions, it may assist in guiding medication selection and predicting outcomes. We believe that such a tool will help the clinician in both prognosis prediction and solving therapeutic challenges in this group where refractory seizures are common.

Genetic Evaluation of the Patients with Clinically Diagnosed Inborn Errors of Immunity by Whole Exome Sequencing: Results from a Specialized Research Center for Immunodeficiency in Türkiye.

Molecular diagnosis of inborn errors of immunity (IEI) plays a critical role in determining patients' long-term prognosis, treatment options, and genetic counseling. Over the past decade, the broader utilization of next-generation sequencing (NGS) techniques in both research and clinical settings has facilitated the evaluation of a significant proportion of patients for gene variants associated with IEI. In addition to its role in diagnosing known gene defects, the application of high-throughput techniques such as targeted, exome, and genome sequencing has led to the identification of novel disease-causing genes. However, the results obtained from these different methods can vary depending on disease phenotypes or patient characteristics. In this study, we conducted whole-exome sequencing (WES) in a sizable cohort of IEI patients, consisting of 303 individuals from 21 different clinical immunology centers in Türkiye. Our analysis resulted in likely genetic diagnoses for 41.1% of the patients (122 out of 297), revealing 52 novel variants and uncovering potential new IEI genes in six patients. The significance of understanding outcomes across various IEI cohorts cannot be overstated, and we believe that our findings will make a valuable contribution to the existing literature and foster collaborative research between clinicians and basic science researchers.

Factors associated with pulmonary function decline of patients in the cystic fibrosis registry of Turkey: A retrospective cohort study.

BACKGROUND: The decline in pulmonary function is a predictor of disease progression in patients with cystic fibrosis (CF). This study aimed to determine the decline rate of percent predicted forced expiratory volume in 1 s (ppFEV1) based on the data of the CF Registry of Turkey. The secondary aim was to investigate the risk factors related to the decline in ppFEV1. METHODS: A retrospective cohort study of CF patients over 6 years old, with pulmonary function data over at least 2 years of follow-up was extracted from the national CF registry for years 2017-2019. Patients were classified according to disease severity and age groups. Multivariate analysis was used to predict the decline in ppFEV1 and to investigate the associated risk factors. RESULTS: A total of 1722 pulmonary function test results were available from 574 patients over the study period. Mean diagnostic age was older and weight for age, height for age, and body mass index z scores were significantly lower in the group of ppFEV1 < 40, while chronic Pseudomonas aeruginosa (p < .001) and mucoid P. aeruginosa colonization (p < .001) were significantly higher in this group (p < .001). Overall mean annual ppFEV1 decline was -0.97% (95% confidence interval [CI] = -0.02 to -1.92%). The mean change of ppFEV1 was significantly higher in the group with ppFEV1 ≥ 70 compared with the other (ppFEV1 < 40 and ppFEV1: 40-69) two groups (p = .004). Chronic P. aeruginosa colonization (odds ratio [OR] = 1.79 95% CI = 1.26-2.54; p = .01) and initial ppFEV1 ≥ 70 (OR = 2.98 95% CI = 1.06-8.36), p = .038) were associated with significant ppFEV1 decline in the whole cohort. CONCLUSIONS: This data analysis recommends close follow-up of patients with normal initial ppFEV1 levels at baseline; advocates for early interventions for P. aeruginosa; and underlines the importance of nutritional interventions to slow down lung disease progression.

Thiol/Disulfide Ratios, HOMA Score, and Quality of Sleep in Renal Transplant Recipients Without Diabetes.

OBJECTIVES: Thiols play an important role in defense against reactive oxygen species. We aimed to evaluate the relation between oxidative stress, glucose tolerance, and sleep quality in kidney transplant recipients without diabetes. MATERIALS AND METHODS: We enrolled 95 kidney transplant recipients without diabetes from living and deceased donors with stable allograft function and 60 healthy controls. We included recipients who received a kidney from a living donor with a first-degree relation. Insulin resistance was determined using the Homeostasis Model Assessment score. Native thiol, total thiol, and disulfide levels were measured, and disulfide versus native thiol/total thiol ratios were calculated from all patients. We used the Pittsburg Sleep Quality Index to assess sleeping patterns. According to standard cutoff value of the index (≤5 indicates good quality sleep; >5 indicates poor sleep quality), we stratified kidney transplant recipients as group 1 (Pittsburg Sleep Quality Index ≤5; n = 41) and group 2 (Pittsburg Sleep Quality Index >5; n = 54). RESULTS: In correlation analysis, Pittsburg Sleep Quality Index was positively correlated with age, the Homeostasis Model Assessment score, body mass index, serum disulfide levels, disulfide/total thiol ratio, and native/total thiol ratio. The Pittsburgh Sleep Quality Index was negatively correlated with total thiol levels. In subgroup analysis, the Homeostasis Model Assessment score, disulfide levels, and disulfide/total thiol and native/total thiol ratios were significantly lower in group 1; however, total thiol level was significantly higher in this group. In multivariate regression analysis, age, the Homeostasis Model Assessment score, disulfide/total thiol ratio, and renal resistivity index were detected as predictors of sleep quality score. CONCLUSIONS: Sleep quality moderates oxidative stress identified by thiol-disulfide homeostasis and insulin resistance in renal transplant recipients without diabetes.

Catalytic Potential of Supported Superatoms.

The importance of catalysts in industrial products is a driving factor in the search of efficient and cost-effective catalysts, creating considerable interest in the past decade in single-atom catalysis. One of the first requirements of a good catalyst is that it should bind to the molecules with energies intermediate between physisorption and chemisorption while simultaneously activating them. Herein, it is shown that superatoms, which are atomic clusters with fixed size and composition, can meet this challenge even better than the atoms whose chemistry they mimic. The reactions of molecules such as H2, O2, N2, CO, NO, and CO2 with an atom (Li) and its corresponding superatom (Li3O) are confirmed through study. As these clusters need to be supported on a substrate for practical applications, the study focuses on the reaction of CO2 with Li and Li3O supported on graphene, Au(111), and Cu(111) substrates. Using density functional theory, it is shown that the Li3O superatom can activate CO2 far greater than the Li atom - stretching the CO bond from 1.16 Å to as large as 1.30 Å and bending the O─C─O bond angle from 180° to as low as 120°. Equally interesting, the results are not very sensitive to the substrate.

Does vanillic acid affect fracture healing? An experimental study in a rat model of femur fracture.

BACKGROUND AND OBJECTIVES: We aimed to determine the effects of vanillic acid (VA) on fracture healing radiologically, histologically, immunohistochemically, and biomechanically using a rat femur open fracture injury model. METHODS: 32 male Wistar-Albino rats were used and divided into two groups: the study group (VA) and the control group. From the time they were operated on until they were sacrificed, the rats in the study group were given 100 mg/kg/day VA by oral gavage. After sacrification, the femurs were analyzed. RESULTS: It was observed that the Huo histological scoring was significantly higher in the VA group (p = 0.001), and the ratio of the amount of callus tissue compared to intact bone tissue was significantly higher. While no significant difference was observed in immunohistochemical H-scores in ColI antibody staining (p = 1.000), a borderline significant difference in favor of VA was observed in ColIII antibody staining (p = 0.078). In biomechanical analysis, failure load (N), total energy (J), maximum stress (MPa), and stiffness (N/mm) measurements were significantly higher in the VA group (p = 0.040, p = 0.021, p = 0.015, and p = 0.035, respectively). CONCLUSION: It has been observed that VA, with its antioxidative properties, increases fracture healing in rats, in which an open fracture model was created. We are hopeful that such an antioxidant, which is common in nature, will increase fracture healing. Since this study is the first to examine the effect of VA on fracture healing, further studies are needed.

Membrane Receptor-Mediated Disruption of Cellular Homeostasis: Changes in Intracellular Signaling Pathways Increase the Toxicity of Ochratoxin A.

Organisms maintain their cellular homeostatic balance by interacting with their environment through the use of their cell surface receptors. Membrane based receptors such as the transforming growth factor ß receptor (TGFR), the prolactin receptor (PRLR), and hepatocyte growth factor receptor (HGFR), along with their associated signaling cascade, play significant roles in retaining cellular homeostasis. While these receptors and related signaling pathways are essential for health of cell and organism, their dysregulation can lead to imbalance in cell function with severe pathological conditions such as cell death or cancer. Ochratoxin A (OTA) can disrupt cellular homeostasis by altering expression levels of these receptors and/or receptor-associated intracellular downstream signaling modulators and/or pattern and levels of their phosphorylation/dephosphorylation. Recent studies have shown that the activity of the TGFR, the PRLR, and HGFR and their associated signaling cascades change upon OTA exposure. A critical evaluation of these findings suggests that while increased activity of the HGFR and TGFR signaling pathways leads to an increase in cell survival and fibrosis, decreased activity of the PRLR signaling pathway leads to tissue damage. This review explores the roles of these receptors in OTA-related pathologies and effects on cellular homeostasis.

Comparison of clinical features of cystic fibrosis patients eligible but not on CFTR modulators to ineligible for CFTR modulators.

INTRODUCTION: Cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs target the underlying defect and improve CFTR function. They are a part of standard care in many countries, but not all patients are eligible for these drugs due to age and genotype. Here, we aimed to determine the characteristics of non-eligible patients for CFTR modulators in the CF registry of Turkey (CFRT) to highlight their clinical needs. METHODS: This retrospective cohort study included CF patient data from the CFRT in 2021. The decision of eligibility for the CFTR modulator was determined according to the 'Vertex treatment-Finder' on the Vertex® website. Demographic and clinical characteristics of patients were compared between eligible (group 1) and ineligible (group 2) groups for CFTR modulators. RESULTS: Among the study population (N = 1527), 873 (57.2%) were in group 1 and 654 (42.8%) were in group 2. There was no statistical difference between groups regarding sex, meconium ileus history, diagnoses via newborn screening, FEV1 z-score, CF-associated complications, organ transplant history, and death. Patients in group 2 had a higher incidence of pancreatic insufficiency (87.7% vs. 83.2%, p = .010), lower median height z-scores (-0.87 vs. -0.55, p < .001), lower median body mass index z-scores (-0.65 vs. -0.50, p < .001), longer days receiving antibiotics due to pulmonary exacerbation (0 [interquartile range, IQR: 0-2] vs. 0 [IQR: 0-7], p = 0.001), and more non-invasive ventilation support (2.6% vs. 0.9%, p = 0.008) than patients in group 1. CONCLUSION: The ineligible group had worse clinical outcomes than the eligible group. This highlights their need for life-changing drugs to improve clinical outcomes.

A case of lung adenocarcinoma developing chylothorax after transthoracic Tru-cut biopsy.

Chylothoraces are mostly secondary to trauma and tumors, and rarely idiopathic. Chylothoraces secondary to lung tumors are mostly seen postoperatively. In this article, we, for the first time, present massive chylothorax developing after diagnostic transthoracic Tru-cut biopsy in a lung adenocarcinoma case. The patient was successfully treated with drainage and octreotide. In conclusion, it should be kept in mind that chylothorax can be also seen as a complication after interventional biopsy procedures; therefore, the patients should be followed carefully.

Activation of Small Molecules by Modified Dodecaborate Anions.

Two of the basic requirements of a good catalyst are that molecules be bound to it with energies intermediate between physisorption and chemisorption and be simultaneously activated in the process. Using density functional theory, we have studied the interaction of small molecules such as H2, O2, N2, CO2, CO, and NH3 with modified dodecaborate anion [B12H12]2-, namely, [B12X11]- and [B12X11]2- (X = H, F, CN). Calculations of the structure, stability, and electronic properties of these species interacting with the above molecules show that they meet the above requirements. In addition, [B12X11]2- (X = F, CN) species are not only more stable than [B12X11]- species but also bind to O2 more strongly than their monoanion counterparts.

A Retrospective Review of 18 Patients With Childhood-Onset Hereditary Spastic Paraplegia, Nine With Novel Variants.

BACKGROUND: Hereditary spastic paraplegias (HSPs) are a group of genetically heterogeneous neurodegenerative disorders. Our objective was to determine the clinical and molecular characteristics of patients with genetically confirmed childhood-onset HSPs and to expand the genetic spectrum for some rare subtypes of HSP. METHODS: We reviewed the charts of subjects with genetically confirmed childhood-onset HSP. The age at the disease onset was defined as the point at which the delayed motor milestones were observed. Delayed motor milestones were defined as being unable to hold the head up by four months, sitting unassisted by nine months, and walking independently by 17 months. If there were no delayed motor milestones, age at disease onset was determined by leg stiffness, frequent falls, or unsteady gait. Genetic testing was performed based on delayed motor milestones, progressive leg spasticity, and gait difficulty. The variant classification was determined based on the American College of Medical Genetics standard guidelines for variant interpretation. Variants of uncertain significance (VUS) were considered disease-associated when clinical findings were consistent with the previously described disease phenotypes for pathogenic variants. In addition, in the absence of another pathogenic, likely pathogenic, or VUS variant that could explain the phenotype of our cases, we concluded that the disease is associated with VUS in the HSP-causing gene. Segregation analysis was also performed on the parents of some patients to demonstrate the inheritance model. RESULTS: There were a total of 18 patients from 17 families. The median age of symptom onset was 18 months (2 to 84 months). The mean delay between symptom onset and genetic diagnosis was 5.8 years (5 months to 17 years). All patients had gait difficulty caused by progressive leg spasticity and weakness. Independent walking was not achieved at 17 months for 67% of patients (n = 12). In our cohort, there were two subjects each with SPG11, SPG46, and SPG 50 followed by single subject each with SPG3A, SPG4, SPG7, SPG8, SPG30, SPG35, SPG43, SPG44, SPG57, SPG62, infantile-onset ascending spastic paralysis (IAHSP), and spastic paraplegia and psychomotor retardation with or without seizures (SPPRS). Eight novel variants in nine patients were described. Two affected siblings had a novel variant in the GBA2 gene (SPG46), and one subject each had a novel variant in WASHC5 (SPG8), SPG11 (SPG11), KIF1A (SPG30), GJC2 (SPG44), ERLIN1 (SPG62), ALS2 (IAHSP), and HACE1 (SPPRS). Among the novel variants, the variant in the SPG11 was pathogenic and the variants in the KIF1A, GJC2, and HACE1 were likely pathogenic. The variants in the GBA2, ALS2, ERLIN1, and WASHC5 were classified as VUS. CONCLUSIONS: There was a significant delay between symptom onset and genetic diagnosis of HSP. An early diagnosis may be possible by examining patients with delayed motor milestones, progressive spasticity, gait difficulties, and neuromuscular weakness in the context of HSP. Eight novel variants in nine patients were described, clinically similar to the previously described disease phenotype associated with pathogenic variants. This study contributes to expanding the genetic spectrum of some rare subtypes of HSP.

Formulation of a fast-disintegrating drug delivery system from cyclodextrin/naproxen inclusion complex nanofibrous films.

Naproxen is a well-known non-steroidal anti-inflammatory drug (NSAID) that suffers from limited water solubility. The inclusion complexation with cyclodextrin (CD) can eliminate this drawback and the free-standing nanofibrous film (NF) generated from these inclusion complexes (ICs) can be a promising alternative formula as an orally disintegrating drug delivery system. For this, naproxen/CD IC NFs were generated using the highly water soluble hydroxypropylated derivative of ßCD (HPßCD) with two different molar ratios of 1/1 and 1/2 (drug/CD). The complexation energy calculated by the modeling study demonstrated a more favorable interaction between HPßCD and naproxen for the 1/2 molar ratio than 1/1. HPßCD/naproxen IC NFs were generated with loading concentrations of ∼7-11% and without using toxic chemicals. HPßCD/naproxen IC NFs indicated a faster and enhanced release profile in aqueous medium compared to pure naproxen owing to inclusion complexation. Moreover, rapid disintegration in less than a second was achieved in an artificial saliva environment.

Single-plate versus double-plate comparison in the surgical treatment of comminuted clavicle fractures: Is the secondary plate reliable?

The objective of this study is to retrospectively assess the use of single-plate (SP) and double-plate (DP) fixation in the open reduction and internal fixation of comminuted clavicle fractures, focusing on fracture union and complications. We retrospectively evaluated comminuted diaphyseal clavicle fractures (Arbeitsgemeinschaft für Osteosynthesefragen type 15.B1-3) treated with open reduction and internal fixation and having a minimum 1-year follow-up. Two patient cohorts were identified: DP (utilizing a superiorly located clavicle-specific plate and an anteriorly located tubular plate) and SP (utilizing a superiorly located clavicle-specific plate). These groups were compared in terms of union time, peri-incisional numbness, implant irritation, return to work time, union rates, re-operation rates, Disabilities of Arm, Shoulder and Hand (DASH), and American Shoulder and Elbow Surgeons (ASES) scores. The study included 27 SP and 23 DP patients meeting the inclusion criteria. There was no significant difference between the 2 cohorts in terms of union time, peri-incisional numbness, implant irritation, return to work time, union rates, re-operation rates, DASH, and ASES scores at the end of the first year (P = .889, P = 1.00, P = .122, P = 1.00, P = 1.00, P = .493, P = .736, P = .762, P = .937 respectively). However, it was observed that the DP group showed a significantly earlier return to work time and better DASH scores at 3rd and 6th months, whereas the SP group exhibited significantly better ASES scores at 3rd and 6th months (P = .034, P = .016, P = .032, P = .036, P = .021, respectively). No significant difference was observed in terms of union and complications in acute clavicle fractures treated with SP and DP fixation. The DP group demonstrated an earlier return to work and superior early functional scores compared to the SP group. Our findings suggest that a secondary plate can be reliably used, particularly in situations where clavicle fracture fixation is insufficient or in cases of comminuted clavicle fractures.

Effect of learning curve on the perioperative course of robotic-assisted laparoscopic donor nephrectomy compared with laparoscopic donor nephrectomy

Summary OBJECTIVE: This study was designed to compare the standard and robotic-assisted laparoscopic donor nephrectomy in terms of perioperative course, short-term postoperative outcome, and to evaluate the effect of surgeon's learning curve on these parameters. METHODS: This was a prospective randomized study including 60 patients (mean age, 47 years; age, 21-72 years; 26 males, 34 females) who had been planned laparoscopic donor nephrectomies in our clinic. For comparison of standard and robot-assisted techniques and to evaluate the impact of learning curve, patients were randomized into three groups by a computer, each group containing 20 patients. Group 1: standard laparoscopic donor nephrectomies; Group 2: the first 20 patients who underwent robot-assisted laparoscopic donor nephrectomy; and Group 3: the next 20 patients who underwent robot-assisted laparoscopic donor nephrectomy. RESULTS: Operative time was significantly higher in Group 2 (221.0±45.1 min) than both Group 1 (183.5±16.9 min, p=0.001) and Group 3 (186.5±20.6 min, p=0.002). Similarly, time for laparoscopic system setup was significantly higher in Group 2 (39.5±8.6 min), which contained the first cases of robot-assisted laparoscopic donor nephrectomy where surgeon had least experience than Group 1 (19.3±3.7 min, p<0.001) and Group 3 (24.0±9.4 min, p<0.001). On the other hand, duration of operation and time for laparoscopic system setup was similar between Groups 1 and 3. CONCLUSIONS: Learning curve extends the operative time and laparoscopic system setup time in robotic-assisted laparoscopic donor nephrectomy, however, after the learning process was completed, these parameters were similar between robotic-assisted and standard laparoscopic nephrectomy.

Evaluation of some predictive parameters for baked-milk tolerance in children with cow’s milk allergy

Background Inclusion of baked-milk products to the diet appears to markedly accelerate tolerance to unheated milk compared to a strict avoidance diet. Objective : The present study aims to investigate the predictors of baked-milk tolerance in children with Immunoglobulin E (IgE)-mediated cow’s milk (CM) allergy. Methods The study included 80 patients diagnosed with IgE-mediated CM allergy upon oral food challenge (OFC) testing at our clinic. Patients who developed and did not develop reactions during OFC with baked milk were compared considering clinical and laboratory parameters. Results Eighty patients with CM allergy comprised 48 male and 32 female infants with an average age of 7.25 ± 2.45 (3–13) months. We found that 62.5% of them showed tolerance to baked milk in the OFC test performed with cakes containing 2.6-g milk protein. When the patients who tolerated and could not tolerate baked-milk products were compared for test results, we detected a statistically significant intergroup difference regarding diameter of wheal in skin prick test (SPT) performed with muffin slurry, levels of specific Immunoglobulin E (sIgE) in CM, sheep’s milk (SM), goat’s milk (GM), casein, and the amount of unheated milk consumed until a reaction developed in the OFC test performed with unheated milk (P < 0.05). Conclusion We defined novel decision points based on CM, SM, GM, casein sIgE levels, wheal diameter in SPT with muffin slurry, and the amount of milk ingested during OFC performed with unheated milk that may be useful in predicting outcomes of baked-milk ingestion (AU)

Is thyroid nodule volume predictive for malignancy?

ABSTRACT Objective: We aimed to determine the roles of preoperative thyroid nodule diameter and volume in the prediction of malignancy. Subjects and methods: The medical records of patients who underwent thyroidectomy between January 2007 and December 2014 were reviewed. The nodule diameters were grouped as < 1 cm, 1-1.9 cm, 2-3.9 cm and ≥ 4 cm, and volume was grouped as > 5 cm3, 5-9.9 cm3 and > 10 cm3. ROC (Receiver Operating Characteristic) curve analysis was performed to find the optimal cutoff value of diameter and volume that can predict malignancy. Results: There were 5561 thyroid nodules in 2463 patients. Five hundred and forty (9.7%) nodules were < 1 cm, 2,413 (43.4%) were 1-1.9 cm, 1,600 (28.8%) were 2-3.9 cm and 1,008 (18.1%) were ≥ 4 cm. Malignancy rates were 25.6%,10.6%, 9.7% and 8.5% in nodules < 1 cm, 1-1.9 cm, 2-3.9 cm and ≥ 4 cm, respectively. When classified according to volume, 3,664 (65.9%) nodules were < 5 cm3, 594 (10.7%) were 5-9.9 cm3 and 1,303 (23.4%) were ≥ 10 cm3. The malignancy rates were 12.7%, 11.4% and 7.8% for the nodules < 5 cm3, 5-9.9 cm3 and ≥ 10 cm3, respectively (p < 0.001). In ROC curve analysis, an optimal cutoff value for diameter or volume that can predict malignancy in all thyroid nodules or nodules ≥ 4 cm could not be determined. Conclusion: In this surgical series, malignancy risk did not increase with increasing nodule diameter or volume. Although the volume of malignant nodules ≥ 4 cm was higher than that of benign nodules ≥ 4 cm, there was no optimal cutoff value. The diameter or volume of the nodule cannot be used to predict malignancy or decide on surgical resection.

Effects of diurnal and nocturnal strenuous exercise on serum melatonin levels / Efeitos do exercício extenuante diurno e noturno sobre os níveis séricos de melatonina / Efectos del ejercicio extenuante diurno y nocturno en los niveles séricos de la melatonina

ABSTRACT Introduction: There are reports of a possible relationship between melatonin, a hormone secreted by the pineal gland, and exercise. Objective: The present study aims to investigate how diurnal and nocturnal strenuous exercise affects melatonin levels. Methods: The study enrolled 10 healthy sedentary males who did not actively exercise. The subjects had a mean age of 22.20±0.24 years, a mean height of 174.60±2.33 cm, and a mean weight of 69.70±2.42 kg. Two blood samples were collected from the subjects, one at rest, at 10:00 am, and the other immediately after strenuous exercise. Likewise, blood samples were taken from the same group of subjects after 48 hours: at 24:00 hours at rest and immediately after strenuous exercise. Samples were analyzed using the ELISA method to determine the serum melatonin levels (pg/ml). Results: By comparing the values at rest and after exercise, it was found that serum melatonin values remained unchanged with exercise. Serum melatonin values at rest or post-exercise measured at night were higher when compared with those measured during the day (p<0.05). Conclusions: Higher levels of melatonin found in the study appear to result from the increased release of melatonin at night, and not from exercise. The results of this study indicate that strenuous exercise carried out day or night, did not significantly influence serum melatonin levels.

RESUMO Introdução: Há relatos de uma possível relação entre a melatonina, hormônio secretado pela glândula pineal, e exercício. Objetivo: O presente estudo tem como objetivo investigar como o exercício extenuante diurno e noturno afeta os níveis de melatonina. Métodos: O estudo inscreveu 10 homens sedentários saudáveis que não se exercitavam ativamente. Os sujeitos tinham média de idade de 22,20 ± 0,24 anos, estatura média de 174,60 ± 2,33 cm e peso médio de 69,70 ± 2,42 kg. Duas amostras de sangue foram coletadas dos sujeitos, uma em repouso, às 10h00 da manhã e a outra imediatamente após exercício extenuante. Da mesma forma, foram coletadas amostras de sangue do mesmo grupo de sujeitos depois de 48 horas: às 24h00 em repouso e imediatamente após exercício extenuante. As amostras foram analisadas pelo método ELISA para determinar os níveis séricos de melatonina (pg/ml). Resultados: Ao serem comparados os valores de repouso e depois do exercício, verificou-se que os valores séricos de melatonina permaneceram inalterados após exercício. Os valores séricos de melatonina em repouso e pós-exercício, medidos à noite foram mais elevados em comparação com os valores medidos durante o dia (p < 0,05). Conclusões: Os níveis elevados de melatonina encontrados no estudo parecem resultar do aumento da liberação de melatonina à noite, e não do exercício. Os resultados deste estudo indicam que o exercício extenuante realizado durante o dia ou à noite, não influenciou significativamente os níveis séricos de melatonina.

RESUMEN Introducción: Hay reportes de una posible relación entre la melatonina, una hormona secretada por la glándula pineal, y el ejercicio. Objetivo: Este estudio tiene como objetivo investigar cómo el ejercicio extenuante diurno y nocturno afecta a los niveles de melatonina. Métodos: En el estudio participaron 10 hombres sanos sedentarios que no hacían ejercicio de forma activa. Los sujetos tenían una edad promedio de 22,20 ± 0,24 años, altura promedio de 174,60 ± 2,33 cm, y peso promedio de 69,70 ± 2,42 kg. Dos muestras de sangre se obtuvieron de los sujetos, una en reposo, a las 10:00 horas de la mañana y la otra inmediatamente después del ejercicio vigoroso. Igualmente, las muestras de sangre se recogieron del mismo grupo de sujetos después de 48 horas: a las 24:00 horas en reposo e inmediatamente después del ejercicio extenuante. Las muestras se analizaron usando el método ELISA para determinar los niveles de melatonina en suero (pg/ml). Resultados: Mediante la comparación de los valores en reposo y después del ejercicio, se encontró que los valores séricos de melatonina se mantuvieron sin cambios después del ejercicio. Ambos valores de melatonina en reposo y después del ejercicio, medidos por la noche fueron más altos en comparación con los medidos durante el día (p < 0,05). Conclusiones: Los altos niveles de melatonina encontrados en el estudio parecen ser el resultado del aumento de la liberación de melatonina en la noche, y no del ejercicio. Los resultados de este estudio indican que el ejercicio extenuante realizado durante el día o por la noche, no afectó significativamente los niveles de melatonina en suero.

Evaluation of preoperative ultrasonographic and biochemical features of patients with aggressive parathyroid disease: is there a reliable predictive marker?

ABSTRACT Objective Parathyroid cancer (PC) represents < 1% of cases of PHPT. Tumors demonstrating atypical histopathologic features and don’t fulfill criteria for carcinoma are classified as atypical adenomas (APA). The purpose of this study was to determine a biochemical or ultrasonographic feature that can predict aggressive disease requiring more extensive surgery and closer follow-up. Subjects and methods Twenty eight patients operated for PHPT and diagnosed with atypical adenoma (23 patients) or carcinoma (5 patients) were enrolled in this study. The control group consisted of 102 patients operated between the same dates and diagnosed with classical PA. Classical adenomas, atypical adenomas, and carcinomas were compared according to their biochemical and ultrasonographic parameters. Results Serum Ca levels were significantly higher in the PC group compared with the APA and classical PA groups. Serum median PTH, Serum ALP and UCa was significantly higher in the APA and carcinoma groups compared to the classical PA group. ROC analysis was made to determine the best cut off values for predicting aggressive disease were 12.45 mg/dL, 265.05 pg/mL, 154.5 IU/l, 348.5 mg/day and 21.5 mm for Ca, PTH, ALP, UCa and the adenoma diameter, respectively. Multivariate analysis showed that serum Ca, ALP and isoechoic/cystic appearance were independent predictors for aggressive disease. Conclusion Preoperatively high PTH, ALP, and UCa levels and large lesions with isoechoic or cystic appearances may be predictive of atypical adenoma or carcinoma in patients being evaluated for PHPT. In such cases, surgeons may prefer en bloc parathyroidectomy to minimally invasive surgery.

Correlation between the serum and tissue levels of oxidative stress markers and the extent of inflammation in acute appendicitis

OBJECTIVES: To determine the serum and tissue levels of markers of impaired oxidative metabolism and correlate these levels with the histopathology and Alvarado score of acute appendicitis patients. METHOD: Sixty-five acute appendicitis patients (mean age, 31.4±12.06 years; male/female, 30/35) and 30 healthy control subjects were studied. The Alvarado score was recorded. Serum samples were obtained before surgery and 12 hours postoperatively to examine the total antioxidant status, total oxidant status, paraoxonase, stimulated paraoxonase, arylesterase, catalase, myeloperoxidase, ceruloplasmin, oxidative stress markers (advanced oxidized protein products and total thiol level) and ischemia-modified albumin. Surgical specimens were also evaluated. RESULTS: The diagnoses were acute appendicitis (n = 37), perforated appendicitis (n = 8), phlegmonous appendicitis (n = 12), perforated+phlegmonous appendicitis (n = 4), or no appendicitis (n = 4). The Alvarado score of the acute appendicitis group was significantly lower than that of the perforated+phlegmonous appendicitis group (p = 0.004). The serum total antioxidant status, total thiol level, advanced oxidized protein products, total oxidant status, catalase, arylesterase, and ischemia-modified albumin levels were significantly different between the acute appendicitis and control groups. There was no correlation between the pathological extent of acute appendicitis and the tissue levels of the markers; additionally, there was no correlation between the tissue and serum levels of any of the parameters. CONCLUSIONS: The imbalance of oxidant/antioxidant systems plays a role in the pathogenesis acute appendicitis. The Alvarado score can successfully predict the presence and extent of acute appendicitis. .