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    Disease-free survival and the prognostic factors affecting disease-free survival in patients with medullary thyroid carcinoma: a multicenter cohort study
    (Springer, 2024) Zuhur, Sayid Shafi; Ozturk, Beyza Olcay; Keskin, Umran; Uysal, Serhat; Hacioglu, Aysa; Avci, Ugur; Karsli, Seda
    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.
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    Do Histologically Aggressive Subtypes of Papillary Thyroid Microcarcinoma have Worse Clinical Outcome than Non-Aggressive Papillary Thyroid Microcarcinoma Subtypes? A Multicenter Cohort Study
    (Georg Thieme Verlag Kg, 2023) Zuhur, Sayid Shafi; Aggul, Hunkar; Avci, Ugur; Erol, Selvinaz; Tuna, Mazhar Muslum; Uysal, Serhat; Akbaba, Gulhan
    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.
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    Evaluation and follow-up of patients diagnosed with hypophysitis: a cohort study
    (Oxford Univ Press, 2024) Hacioglu, Aysa; Karaca, Zuleyha; Uysal, Serhat; Ozkaya, Hande Mefkure; Kadioglu, Pinar; Selcukbiricik, Ozlem Soyluk; Gul, Nurdan
    Objective Primary hypophysitis might be challenging to diagnose, and there is a lack of evidence regarding optimal treatment strategies due to rarity of the disease. We aim to investigate the clinical features and compare the outcomes of different management strategies of primary hypophysitis in a large group of patients recruited on a nationwide basis.Design A retrospective observational study.Methods The demographic, clinical, and radiologic features and follow-up data were collected in study protocol templates and analyzed.Results One hundred and thirteen patients (78.8% female, median age: 36 years) were included. Lymphocytic (46.7%) and granulomatous hypophysitis (35.6%) were the prevailing subtypes out of 45 patients diagnosed after pathologic investigations. Headache (75.8%) was the most common symptom, and central hypogonadism (49.5%) was the most common hormone insufficiency. Of the patients, 52.2% were clinically observed without interventions, 18.6% were started on glucocorticoid therapy, and 29.2% underwent surgery at presentation. Headache, suprasellar extension, and chiasmal compression were more common among glucocorticoid-treated patients than who were observed. Cox regression analysis revealed higher hormonal and radiologic improvement rates in the glucocorticoid-treated group than observation group (hazard ratio, 4.60; 95% CI, 1.62-12.84 and HR, 3.1; 95% CI, 1.40-6.68, respectively). The main indication for surgery was the inability to exclude a pituitary adenoma in the presence of compression symptoms, with a recurrence rate of 9%.Conclusion The rate of spontaneous improvement might justify observation in mild cases. Glucocorticoids proved superior to observation in terms of hormonal and radiologic improvements. Surgery may not be curative and might be considered in indeterminate, treatment-resistant, or severe cases.
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    Profiles of multidrug-resistant organisms among patients with bacteremia in intensive care units: an international ID-IRI survey
    (Springer, 2021) El-Sokkary, Rehab; Uysal, Serhat; Erdem, Hakan; Kullar, Ravina; Pekok, Abdullah Umut; Amer, Fatma; Rello, Jordi; Doğan, Mustafa
    Evaluating trends in antibiotic resistance is a requisite. The study aimed to analyze the profile of multidrug-resistant organisms (MDROs) among hospitalized patients with bacteremia in intensive care units (ICUs) in a large geographical area. This is a 1-month cross-sectional survey for blood-borne pathogens in 57 ICUs from 24 countries with different income levels: lower-middle-income (LMI), upper-middle-income (UMI), and high-income (HI) countries. Multidrug-resistant (MDR), extensively drug-resistant (XDR), or pan-drug-resistant isolates were searched. Logistic regression analysis determined resistance predictors among MDROs. Community-acquired infections were comparable to hospital-acquired infections particularly in LMI (94/202; 46.5% vs 108/202; 53.5%). Although MDR (65.1%; 502/771) and XDR (4.9%; 38/771) were common, no pan-drug-resistant isolate was recovered. In total, 32.1% of MDR were Klebsiella pneumoniae, and 55.3% of XDR were Acinetobacter baumannii. The highest MDR and XDR rates were in UMI and LMI, respectively, with no XDR revealed from HI. Predictors of MDR acquisition were male gender (OR, 12.11; 95% CI, 3.025-15.585) and the hospital-acquired origin of bacteremia (OR, 2.643; 95%CI, 1.462-3.894), and XDR acquisition was due to bacteremia in UMI (OR, 3.344; 95%CI, 1.189-5.626) and admission to medical-surgical ICUs (OR, 1.481; 95% CI, 1.076-2.037). We confirm the urgent need to expand stewardship activities to community settings especially in LMI, with more paid attention to the drugs with a higher potential for resistance. Empowering microbiology laboratories and reports to direct prescribing decisions should be prioritized. Supporting stewardship in ICUs, the mixed medical-surgical ones in particular, is warranted.
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    The impact of microscopic extrathyroidal extension on the clinical outcome of classic subtype papillary thyroid microcarcinoma: a multicenter study
    (Springer, 2024) Zuhur, Sayid Shafi; Aggul, Hunkar; Avci, Ugur; Erol, Selvinaz; Tuna, Mazhar Muslum; Uysal, Serhat; Akbaba, Gulhan
    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.
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    Treatment of ventilator-associated pneumonia (VAP) caused by Acinetobacter: results of prospective and multicenter ID-IRI study
    (Springer, 2020) Erdem, Hakan; Çağ, Yasemin; Gencer, Serap; Uysal, Serhat; Karakurt, Zuhal; Harman, Rezan; Rello, Jordi; Doğan, Mustafa
    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.