Disease-free survival and the prognostic factors affecting disease-free survival in patients with medullary thyroid carcinoma: a multicenter cohort study.

PURPOSE: Despite several factors that may have been associated with poor disease-free survival (DFS) in patients with medullary thyroid carcinoma (MTC), only a few studies have evaluated the prognostic factors affecting DFS in MTC patients. Therefore, this study evaluated the prognostic factors affecting DFS, in a large number of patients with MTC. METHODS: Patients treated for MTC were retrospectively analyzed. Patients were stratified as having persistent/recurrent disease and no evidence of disease (NOD) at the last follow-up. The factors affecting DFS after the initial therapy and during the follow-up period were investigated. RESULTS: This study comprised 257 patients [females 160 (62.3%), hereditary disease 48 (18.7%), with a mean follow-up time of 66.8 ± 48.5 months]. Persistent/recurrent disease and NOD were observed in 131 (51%) and 126 (49%) patients, respectively. In multivariate analysis, age > 55 (HR: 1.65, p = 0.033), distant metastasis (HR: 2.41, p = 0.035), CTN doubling time (HR: 2.7, p = 0.031), and stage III vs. stage II disease (HR 3.02, p = 0.048) were independent predictors of persistent/recurrent disease. Although 9 (8%) patients with an excellent response after the initial therapy experienced a structural recurrence, the absence of an excellent response was the strongest predictor of persistent/recurrent disease (HR: 5.74, p < 0.001). CONCLUSIONS: The absence of an excellent response after initial therapy is the strongest predictor of a worse DFS. However, a significant proportion of patients who achieve an excellent response could experience a structural recurrence. Therefore, careful follow-up of patients, including those achieving an excellent response is essential.

Is There A Connection Between Primary Hypophysitis and Celiac Disease?

AIM: To investigate the autoimmune and genetic relationship between primary hypophysitis (PH) and celiac disease (CD). METHODS: The study was retrospective and patients with PH followed in our clinic between 2007 and 2022 were evaluated. Clinical, endocrinologic, pathologic, and radiologic findings and treatment modalities were assessed. Patients diagnosed with CD in the Gastroenterology outpatient clinic in 2020-2022 were included in the study as a control group. Information such as sociodemographic data, year of diagnosis, human leukocyte antigen (HLA) DQ2/8 information, CD-specific antibody levels, pathologic results of duodenal biopsy, treatment received, follow-up status, additional diseases, hormone use, and surgical history was obtained from patient records at PH.In patients diagnosed with PH, a duodenal biopsy was obtained, and the tissue was examined for CD by experienced pathologists. Anti-pituitary antibody (APA) and anti-arginine-vasopressin (AAVP) antibody levels of individuals with PH and CD were measured. RESULTS: The study included 19 patients with lymphocytic hypophysitis, 30 celiac patients, and 30 healthy controls. When patients diagnosed with lymphocytic hypophysitis were examined by duodenal biopsy, no evidence of CD was found in the pathologic findings. The detection rate of HLA-DQ2/8 was 80% in celiac patients and 42% in PH (p=0.044). (APA and AAVP antibodies associated with PH were tested in two separate groups of patients and in the control group. APA and anti-arginine vasopressin (AAVP) levels in PH, CD and healthy controls, respectively M [IQR]: 542 [178-607];164 [125-243]; 82 [74-107] ng/dL (p=0.001), 174 [52-218]; 60 [47-82]; 59 [48-76] ng/dL (p=0.008) were detected. The presence of an HLA-DQ2/8 haplotype correlates with posterior hypophysitis and panhypophysitis (r=0.598, p=0.04 and r=0.657, p=0.02, respectively). CONCLUSION: Although patients with PH were found to have significant levels of HLA-DQ2/8, no CD was found in the tissue. Higher levels of pituitary antibodies were detected in celiac patients compared with healthy controls, but no hypophysitis clinic was observed at follow-up. Although these findings suggest that the two diseases may share a common genetic and autoimmune basis, the development of the disease may be partially explained by exposure to environmental factors.

The impact of microscopic extrathyroidal extension on the clinical outcome of classic subtype papillary thyroid microcarcinoma: a multicenter study.

OBJECTIVES: Despite the presumed overdiagnosis of papillary thyroid microcarcinoma (PTMC) which has resulted in a new trend toward less-extensive surgery and a preference for active surveillance, the impact of microscopic extrathyroidal extension (mETE) on the clinical outcomes of PTMC is still controversial. This study assessed the impact of mETE on the clinical outcomes of patients with classic subtype PTMC. METHODS: The data of consecutive patients who underwent thyroidectomy and were histopathologically diagnosed as classic subtype PTMC were analyzed. Cox's proportional hazards model was used to assess the impact of contributing variables on persistent/recurrent disease. Disease-free survival was estimated using the Kaplan-Meier method. RESULTS: This study included 1013 patients (84% females), with a mean follow-up period of 62.5 ± 35.3 months. Patients with mETE had a significantly higher rate of locoregional persistent/recurrent disease than patients without mETE (9.8% vs 2.1%, p < 0.001). The disease-free survival rate was significantly lower in patients with mETE than in those without (90.2% vs 97%, Log-Rank p < 0.001). Furthermore, mETE and neck lymph node involvement were independent predictors of persistent/recurrent disease in multivariate analysis (HR: 2.43, 95% CI:1.02-5.81, p = 0.043; HR: 4.38, 95% CI: 1.7-11.2, p = 0.002, respectively). CONCLUSIONS: In patients with the classic subtype of PTMC, mETE is an independent predictor of persistent/recurrent disease and is associated with a lower DFS rate. However, neck lymph node involvement is the strongest predictor of persistent/recurrent disease. Therefore, PTMCs with mETE and neck lymph node involvement are at a higher risk of persistent/recurrent disease than individuals lacking both characteristics.

The effect of radioiodine therapy on blood cell count in patients with differentiated thyroid cancer.

PURPOSE: This study aimed to investigate the long-term effects of radioiodine treatment (RAI) on blood cell counts in patients with differentiated thyroid cancer (DTC) and to describe the characteristics of patients at high risk for blood cell count abnormalities. METHODS: The study included patients with DTC who underwent RAI treatment between 2007 and 2017. Patients with regular complete blood counts for at least 5 years were included, while those with diseases or treatments that could influence blood count parameters were excluded. Blood cell count abnormalities were defined according to the Common Terminology Criteria for Adverse Events version 5.0, and factors influencing these abnormalities were examined. RESULTS: A total of 225 patients were analyzed. The mean age at diagnosis was 45.8 ± 13.9 years, and 76.5% of patients were female. In the first year after RAI, leukocyte, neutrophil, and lymphocyte counts were significantly reduced compared with baseline values. The leukocyte and neutrophil counts returned to baseline values by the third year, while the decrease in lymphocytes continued until the fifth year. Blood cell count abnormalities developed in 16 patients (7.1%) within the first year after RAI. Risk factors for blood cell count abnormalities within the first year after RAI included male sex, older age, T4, N1, and M1 disease, as well as higher RAI doses. In logistic regression analysis, only RAI dose remained independently associated with blood cell count abnormalities. CONCLUSION: These results suggest an association between RAI dose and blood cell count abnormalities, characterized by mild lymphopenia, and indicate that the risk of mild lymphopenia persists over time. Careful consideration should be given when planning high-dose RAI for patients at a high risk of blood cell count abnormalities, such as males with metastatic disease and of advanced age.

Does the Association of Hashimoto's Thyroiditis with Differentiated Thyroid Cancer Really Have a Protective Role?

The study is an investigation of aggressive tumor features, prognosis, and disease-specific mortality rates of differentiated thyroid cancer (DTC) in the presence of concomitant Hashimoto's Thyroiditis (HT). The data of patients with DTC followed in our tertiary care center between 2000-2022 were analyzed. Variables such as patient age, gender, preoperative serum autoantibody levels, tumor characteristics, and treatment modalities were obtained from medical records. The diagnosis of HT was based either on the presence of a positive result in the pathological examination and/or on antibody positivity. A total of 637 patients [mean±SD age, 44.9±13.5 years; 485 women [76.1%)] were included in the analysis. The overall prevalence of coexistent HT was 22.9% (n=146). The disease-specific mortality associated with DTC was 2.9%. DTC patients with HT compared to those without; have more positive lymphovascular invasion (p<0.001), and lymph node metastases (p<0.001). According to the Kaplan-Meier curves, disease-specific survival rates among DTC patients without HT were significantly higher than patients with HT (log-rank p=0.002). The disease-specific mortality rate was 4.79% in DTC patients with HT, it was 1.43% in those without HT. Hashimoto thyroiditis was not associated with a 10-year recurrence-free survival (p=0.059). Differentiated thyroid cancers with concomitant HT are associated with some aggressive tumor features (such as lymphovascular invasion and nodal metastasis) and lower survival. In staging systems based on tumor risk factors, it may be useful to evaluate the presence of concomitant HT as a prognostic factor.

Do Histologically Aggressive Subtypes of Papillary Thyroid Microcarcinoma have Worse Clinical Outcome than Non-Aggressive Papillary Thyroid Microcarcinoma Subtypes? A Multicenter Cohort Study.

Histologically aggressive micropapillary thyroid carcinomas (PTMC) subtypes are thought to be associated with an aggressive clinical course. However, evidence for unfavorable clinical outcomes in patients with aggressive PTMC subtypes is not clear. In this study, we intended to determine the difference in clinical outcomes between patients with aggressive and non-aggressive PTMC subtypes. In this multicenter cohort study, the computer-recorded clinical and histopathological data of patients who underwent thyroid surgery between January 2000 - January 2021 in 9 referral centers and were diagnosed as PTMC were analyzed. A total of 1585 patients [female 1340 (84.5%), male 245 (15.5%), mean age 47.9±11.63 years), with a mean follow-up time of 66.55±37.16 months], were included in the study. Ninety-eight cases were diagnosed as aggressive and 1487 as non-aggressive subtypes. Persistent/recurrent disease was observed in 33 (33.7% )and 41 (2.8%) patients with aggressive and non-aggressive subtypes (p<0.001). Diseases-free survival rates were markedly lower in patients with aggressive than in those with non-aggressive PTMC subtypes (66.3 vs. 94.8%, log-rank p<0.001). Moreover, in multivariate analysis, aggressive histology was an independent predictor of persistent/recurrent disease, after controlling for other contributing factors (HR 5.78, 95% CI 3.32-10, p<0.001). Patients with aggressive PTMC subtypes had higher rates of incomplete biochemical and structural response than patients with non-aggressive subtypes as well (p<0.001). Aggressive PTMC subtypes share many characteristics with histologically identical tumors>1 cm in size. Therefore, the histopathological subtype of PTMC should be taken into consideration to tailor a personalized management plan.

Visceral Adiposity Index as an Indicator of Cardiometabolic Risk in Patients with Congenital Adrenal Hyperplasia.

Aim: To evaluate the cardiometabolic risk in patients with CAH (21 (OH) enzyme deficiency) on the basis of the visceral adiposity index (VAI), which indicates dysfunction of the visceral adipose tissue (VAT). Materials and Methods: A total of 41 patients and 38 body mass index (BMI), age, and gender-matched healthy controls (HC) were included. The patients' and HCs' age, gender, waist circumference (WC), BMI information and total cholesterol (TC), high-density lipoprotein (HDL), triglyceride (TG) values, smoking, and medication history were obtained from medical charts. Weight, height, WC, and blood pressure levels were measured. Patients' and HCs' BMI, Framingham risk scores (FRS), VAI and Ferriman-Gallwey scores were calculated. The patients' and HCs' age, gender TC, HDL, and TG, androstenedione, dehydroepiandrosterone sulfate (DHEASO4), 17 hydroxyprogesterone (17(OH)P) values, smoking, and medication history were obtained from medical charts. Body fat and muscle mass levels were measured with Tanita T 6360. Results: Gender distribution, mean age, and BMI of patients with CAH were 34/7, 30 ± 8, 27 ± 5.4; HC subjects 30/8, 30 ± 6, 27 ± 3.8 (P = 0.9, 0.6, 0.9, respectively). The VAI values of patients with a diagnosis of CAH 3.7 (2.3-6.9) were found to be significantly higher than those of HC patients 2.5 (1.8-3.9; P = 0.02). The mean glucocorticoid doses of the patients were 17 ± 9 mg/day. The glucocorticoid dose level was determined as independent risk factor on the FRS (P = 0.03, ß = 0.04) and VAI (P = 0.018, ß = 0.17). Conclusion: Glucocorticoid dose optimization should be done more carefully to improve metabolic and cardiovascular outcomes in CAH patients.

Role of large unstained cells in predicting successful stem cell collection in autologous stem cell transplantation.

INTRODUCTION: Sufficient stem cell collection is mandatory for Autologous stem cell transplantation (ASCT). Peripheral CD34+ stem CD34 + stem cell counting by flow cytometry is the gold standard method in both the predicting and timing of successful stem cell collection. Large unstained cells (LUC) are large peroxidase-negative cells that are displayed on certain automatic cell counters and present large lymphocytes, virocytes, blasts, abnormal cells and hematopoietic stem cells. In this study, we evaluated the role of LUC parameters in the timing and prediction of successful stem cell collection. METHODS: Patients with a diagnosis of multiple myeloma, lymphoma and testis tumor who proceed to ASCT were included in this study. Preapheresis LUC parameters were analyzed with Siemens ADVIA® 2120i system., Kruskal Wallis, Mann-Whitney U, Spearman Rho and receiver-operator curve (ROC) tests were used for analyses. RESULTS: Ninety patients were evaluated. Peripheral CD34 + cell count was positively correlated with both LUC count (p = 0014) and LUC percentage (p = 0,01). LUC percentage in peripheral blood was positively correlated with mobilized stem cell count in the yield (p = 0.003). We found a LUC count of > 0.485 × 109/L as a cut-off value for detecting > 20 × 106/L CD34 +cells in the peripheral blood with a sensitivity of 64.6% and specificity of 75%. We defined > 2.15% as a cut-off value for LUC percentage to collect > 5 × 106/kg of stem cells with a sensitivity of 64% and specificity of 63%. Additionally, total nucleated cell (TNC) count was negatively correlated with LUC percentage (p = 0.014) and positively correlated with LUC count (p = 0.001). CONCLUSION: LUC parameters are readily available, simple and cheap tools that can be useful in both timing of CD34 count by flow cytometry in peripheral blood and in the prediction of successful mobilization. LUCs can also be an indicator of graft composition.

Treatment of ventilator-associated pneumonia (VAP) caused by Acinetobacter: results of prospective and multicenter ID-IRI study.

Ventilator-associated pneumonia (VAP) due to Acinetobacter spp. is one of the most common infections in the intensive care unit. Hence, we performed this prospective-observational multicenter study, and described the course and outcome of the disease. This study was performed in 24 centers between January 06, 2014, and December 02, 2016. The patients were evaluated at time of pneumonia diagnosis, when culture results were available, and at 72 h, at the 7th day, and finally at the 28th day of follow-up. Patients with coexistent infections were excluded and only those with a first VAP episode were enrolled. Logistic regression analysis was performed. A total of 177 patients were included; empiric antimicrobial therapy was appropriate (when the patient received at least one antibiotic that the infecting strain was ultimately shown to be susceptible) in only 69 (39%) patients. During the 28-day period, antibiotics were modified for side effects in 27 (15.2%) patients and renal dose adjustment was made in 38 (21.5%). Ultimately, 89 (50.3%) patients died. Predictors of mortality were creatinine level (OR, 1.84 (95% CI 1.279-2.657); p = 0.001), fever (OR, 0.663 (95% CI 0.454-0.967); p = 0.033), malignancy (OR, 7.095 (95% CI 2.142-23.500); p = 0.001), congestive heart failure (OR, 2.341 (95% CI 1.046-5.239); p = 0.038), appropriate empiric antimicrobial treatment (OR, 0.445 (95% CI 0.216-0.914); p = 0.027), and surgery in the last month (OR, 0.137 (95% CI 0.037-0.499); p = 0.003). Appropriate empiric antimicrobial treatment in VAP due to Acinetobacter spp. was associated with survival while renal injury and comorbid conditions increased mortality. Hence, early diagnosis and appropriate antibiotic therapy remain crucial to improve outcomes.

A neglected causative agent in diabetic foot infection: a retrospective evaluation of 13 patients with fungal etiology

Background/aim: Clinicians often neglect fungal infections and do not routinely investigate deep tissue from the wound for fungal culture and sensitivity due to insufficient information in the literature. In this study, we aimed to evaluate fungal etiology of invasive fungal diabetic foot which is rarely reported in the literature. Materials and methods: The patients who were unresponsive to antibiotic therapy and those with positive fungal in bone or deep tissue culture were enrolled in the study. Detailed hospital records were retrieved for demographics and clinical features. Results: A total of 13 patients who were diagnosed with invasive fungal diabetic foot (ten females, three males, mean age 59.8 ± 9 years) were included. All of the patients had type-2 diabetes mellitus. Eleven (84.6%) patients had mixed infection. The most common cause of fungal infections of diabetic foot ulcers was the Candida species. Ten (76.9%) patients underwent amputation, two (15.4%) patients refused amputation, and one patient died before surgery. Conclusion: Invasive fungal infections may also be a causative pathogen in deep tissue infections. Therefore, fungal pathogens should be considered in patients unresponsive to long-term antibiotic therapy. Early detection of fungal infections in high-risk individuals is critical for the prevention of severe consequences such as foot amputation.

Human myiasis in patients with diabetic foot: 18 cases.

BACKGROUND: Myiasis complication of diabetic foot ulcer has only been presented in a few case reports. Therefore, there is a need for additional data on this infestation. OBJECTIVE: Evaluate clinical characteristics of human myiasis in patients with diabetic foot. DESIGN: Case series. SETTINGS: A tertiary referral healthcare institution and a diabetic foot center. PATIENTS AND METHODS: Patients with diabetic foot infection com.plicated by myiasis who were admitted between June 2012 and July 2017. MAIN OUTCOME MEASURES: Bacterial infection rate, accompanying bacterial agents, amputation (morbidity) and mortality rate. SAMPLE SIZE: 18. RESULTS: Eight (44.4%) of the patients were female. Sixteen (88.9%) had moderate-to-severe infections; 15 (83.3%) had necrotic tissue. Larval debridement therapy was performed on all patients at the bed.side in consecutive sessions. A third-stage larva of Calliphora was detected in one case (5.6%). Second- and third-stage larvae of Lucilia sericata were detected in 5 (27.8%) and 7 (38.9%) patients, respectively. All the patients had a bacterial infection with myiasis. Twelve (66.7%) patients underwent amputation. Three (16.7%) patients died. Myiasis was more frequent in the months of May, June and July. CONCLUSION: To our knowledge, this is the largest reported series of cases of diabetic foot with myiasis. The most common parasitic agent was Lucilia sericata. Bacterial soft tissue infections were observed in all cases. Poor hygienic conditions were noteworthy and all patients were in need of radical surgery. Myiasis complication of diabetic foot is more frequently seen in the spring and summer. LIMITATIONS: Insufficient follow-up time for analysis of possible confounding factors. CONFLICT OF INTEREST: None.

Intralesional epidermal growth factor therapy fordiabetic foot ulcers: an evaluation of 15 cases

Background/aim: Intralesional recombinant epidermal growth factor (EGF) is a new treatment approach for diabetic foot ulcer, approved in 2006. EGF therapy is given as an adjunct to the standard treatment regimen of antibiotics, surgery, and hyperbaric oxygen. EGF accelerates the healing of diabetic foot ulcers and reduces healing time. This single-center study was conducted to evaluate the outcomes of intralesional EGF therapy in patients with diabetic foot ulcers.Materials and methods: We present the data of the follow-up patients treated in our clinics. Fifteen patients with diabetic foot ulcers or infections, who had been followed up and treated in our clinics, were included in this retrospective study. All patients were administered intralesional injections of 75 µg of EGF after treatment for infection on their diabetic foot ulcers, three times a week on alternate days. The patients were monitored with respect to treatment response and side effects of EGF.Results: Thirteen patients (86.7%) developed new granulation tissue, 10 patients (66.7%) had complete wound closure, and three patients (20%) showed partial wound closure. No serious side effects requiring discontinuation of EGF therapy were observed. A total of twenty-one bacterial agents were isolated in thirteen patients, and no bacterial growth was observed in the tissue cultures of two patients. Pseudomonas aeruginosa was the most common isolated infectious agent in the tissue cultures (n: 6, 28%). Conclusion: Intralesional injection of EGF on top of the standard treatment regimen appears to be a useful adjuvant therapy option in selected patients.

[Dyslipidemia and cardiovascular risk assessment in HIV-positive patients]. / HIV pozitif hastalarda dislipidemi ve kardiyovasküler risk degerlendirilmesi.

OBJECTIVE: Dyslipidemia is a major complication of antiretroviral treatment. Aim of the present study was to screen baseline lipid levels and cardiovascular disease risk in HIV-positive patients and analyze change in those parameters after initiation of antiretroviral treatment (ART). METHODS: HIV-positive patients who presented at our clinic between April 2011 and August 2012 were included. Study included 19 female (22.1%) and 67 male (77.9%) patients (mean age 39.5±10.3 years). Blood pressure, smoking habit, alcohol consumption, serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), glucose level, and antiretroviral treatment status data were reviewed retrospectively. Changes in lipid profile and lifetime risk for atherosclerotic cardiovascular disease (ASCVD) according to the American College of Cardiology guidelines were compared with baseline data and analyzed. RESULTS: At baseline, 13 (15.1%) patients were already receiving ART and 73 (84.9%) patients were treatment-naive or had stopped therapy ≥3 months prior to enrollment. At last visit, 73 (84.9%) patients were taking ART. Results of baseline and final visit TC levels were 175.5 mg/dL (range: 90-346 mg/dL) and 196.5 mg/dL (range: 104-317 mg/dL), respectively (p=0.001). HDL levels were 40 mg/dL (range: 21-81 mg/dL) and 35 mg/dL (range: 10-75 mg/dL; p=0.001), and LDL levels were 101.5 mg/dL (range: 32-191 mg/dL) and 120.5 mg/dL (range: 32-250 mg/dL; p<0.001). TG levels were 145.5 mg/dL (range: 43-2580 mg/dL and 152.5 mg/dL (range: 67-884 mg/dL; p=0.102). Baseline ASCVD risk score was 46% (range: 5-69%) while last visit ASCVD risk score was 50% (range: 5-69%; p<0.001). CONCLUSION: HIV infection has adverse effects on lipid profiles and cardiovascular risk of HIV-positive patients. Therefore, patients should be closely monitored for lifestyle interventions and lipid-lowering agents.