Milan Gajic

Nondiabetic patients with either subclinical Cushing's or nonfunctional adrenal incidentalomas have lower insulin sensitivity than healthy controls: clinical implications.

OBJECTIVE The aim of this study was to estimate insulin sensitivity (IS) in nondiabetic patients with adrenal incidentalomas (AI): nonfunctional adrenal incidentalomas (NAI) and patients with AI and subclinical Cushings syndrome (SCS). METHODS Based on the inclusion criteria (normal fasting glucose levels, no previous history of impaired fasting glucose and/or diabetes, and no medications or concomitant relevant diseases) and the exclusion criteria (pheochromocytoma, overt hypercortisolism, hyperaldosteronism, adrenal carcinoma, metastasis of extra-adrenal tumors, extra-adrenal malignancies), 142 subjects were drawn from a series of patients with AI. The subjects were age-, sex- and body mass index (BMI)-matched: 70 with NAI (50 women and 20 men), 37 with AI and SCS (31 women and 6 men) and 35 healthy control (HC) subjects (30 women and 5 men). The oral glucose tolerance test (OGTT) and several indices of insulin sensitivity (IS) were used: homeostasis model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI), triglycerides and glucose index (TyG), index of whole-body insulin sensitivity (ISI-composite) and glucose to insulin ratio (G/I). RESULTS There was a significant difference in IS between subjects with NAI and HC (HOMA, p=0.049; QUICKI, p=0.036; TyG, p=0.002; ISI-composite, p=0.024) and subjects with SCS and HC (AUC insulin, p=0.01; HOMA, p=0.003; QUICKI, p=0.042; TyG, p=0.008; ISI-composite, p=0.002). There was no difference in the tested indices of IS between subjects with NAI and SCS (p>0.05). However, subjects with SCS had a significantly higher prevalence of impaired glucose tolerance and higher area under the curve for glucose than subjects with NAI (p=0.0174). The linear regression analysis showed that 1 mg-DST cannot be used as a predictor of HOMA (R(2)=0.004, F=0.407, p=0.525). Significant relationship was found between 1 mg-DST and ISI-composite (R(2)=0.042, F=4.981, p=0.028) but this relationship was weak and standard error of estimate was high. The linear regression model also showed that ACTH cannot be used as a predictor of HOMA (R(2)=0.001, F=0.005, p=0.943) or ISI-composite (R(2)=0.015, F=1.819, p=0.187). CONCLUSIONS Insulin resistance is a major cardiovascular risk factor; therefore, the assessment of IS in patients with AI, even nonfunctional, has a valuable place in the endocrine workup of these patients.

Relapse in resected lung cancer revisited: does intensified follow up really matter? A prospective study

Backgroundbeside the well known predominance of distant vs. loco-regional relapse, several aspects of the relapse pattern still have not been fully elucidated.Methodsprospective, controlled study on 88 patients operated for non-small cell lung cancer (NSCLC) in a 15 months period. Stage IIIA existed in 35(39.8%) patients, whilst stages IB, IIA and IIB existed in 10.2%, 4.5% and 45.5% patients respectively. Inclusion criteria: stage I-IIIA, complete resection, systematic lymphadenectomy with at least 6 lymph node groups examined, no neoadjuvant therapy, exact data of all aspects of relapse, exact data about the outcome of the treatment.Resultspostoperative lung cancer relapse occurred in 50(56.8%) patients. Locoregional, distant and both types of relapse occurred in 26%, 70% and 4% patients respectively. Postoperative cancer relapse occurred in 27/35(77.1%) pts. in the stage IIIA and in 21/40(52.55) pts in the stage IIB. In none of four pts. in the stage IIA cancer relapse occurred, unlike 22.22% pts. with relapse in the stage IB. The mean disease free interval in the analysed group was 34.38 ± 3.26 months.The mean local relapse free and distant relapse free intervals were 55 ± 3.32 and 41.62 ± 3.47 months respectively Among 30 pts. with the relapse onset inside the first 12 month after the lung resection, in 20(66.6%) pts. either T3 tumours or N2 lesions existed. In patients with N0, N1 and N2 lesions, cancer relapse occurred in 30%, 55.6% and 70.8% patients respectivelyRadiographic aspect T stage, N stage and extent of resection were found as significant in terms of survival. Related to the relapse occurrence, although radiographic aspect and extent of resection followed the same trend as in the survival analysis, only T stage and N stage were found as significant in the same sense as for survival. On multivariate, only T and N stage were found as significant in terms of survival.Specific oncological treatment of relapse was possible in 27/50(54%) patients.Conclusionthe intensified follow up did not increase either the proportion of patients detected with asymptomatic relapse or the number of patients with specific oncological treatment of relapse.

Home mechanical ventilation in children is feasible in developing countries

Background:  The results of many national surveys on pediatric home mechanical ventilation (HMV) in developed countries have been presented elsewhere, but data from developing countries with low national incomes are scarce.

Static Hyperinflation Is Associated With Decreased Peak Exercise Performance in Children With Cystic Fibrosis

BACKGROUND: We evaluated the exercise capacity of children with cystic fibrosis to determine whether ventilatory limitation associated with static hyperinflation is related with decreased exercise capacity, thus predisposing these children to arterial hypoxemia during progressive exercise. METHODS: Thirty-seven children, ages 8–17 years, underwent spirometry, body plethysmography, and cardiopulmonary exercise testing after arterial catheter placement. According to the ratio of residual volume to total lung capacity (RV/TLC), the subjects were categorized as either with (RV/TLC > 30%) or without static hyperinflation (RV/TLC < 30%). RESULTS: Children with static hyperinflation showed lower values of maximum load per kilogram (% predicted) (P = .01), which was aggravated by ventilatory limitation (FEV1 < 80% of predicted, peak oxygen consumption [% predicted] < 85%, and breathing reserve index > 0.7). Subjects with ventilatory limitation had significantly lower oxygen saturation (P = .04) and hypoxemia (P = .03) than did subjects without ventilatory limitation. CONCLUSIONS: In children with cystic fibrosis, static hyperinflation and ventilatory limitation are associated with decrease in exercise performance, oxygen saturation, and PaO2 during maximum cardiopulmonary exercise testing. All children with cystic fibrosis who exhibit static hyperinflation and ventilatory limitation may require SaO2 monitoring during progressive exercise.

siMS Score: Simple Method for Quantifying Metabolic Syndrome

Objective To evaluate siMS score and siMS risk score, novel continuous metabolic syndrome scores as methods for quantification of metabolic status and risk. Materials and Methods Developed siMS score was calculated using formula: siMS score = 2*Waist/Height + Gly/5.6 + Tg/1.7 + TAsystolic/130—HDL/1.02 or 1.28 (for male or female subjects, respectively). siMS risk score was calculated using formula: siMS risk score = siMS score * age/45 or 50 (for male or female subjects, respectively) * family history of cardio/cerebro-vascular events (event = 1.2, no event = 1). A sample of 528 obese and non-obese participants was used to validate siMS score and siMS risk score. Scores calculated as sum of z-scores (each component of metabolic syndrome regressed with age and gender) and sum of scores derived from principal component analysis (PCA) were used for evaluation of siMS score. Variants were made by replacing glucose with HOMA in calculations. Framingham score was used for evaluation of siMS risk score. Results Correlation between siMS score with sum of z-scores and weighted sum of factors of PCA was high (r = 0.866 and r = 0.822, respectively). Correlation between siMS risk score and log transformed Framingham score was medium to high for age groups 18+,30+ and 35+ (0.835, 0.707 and 0.667, respectively). Conclusions siMS score and siMS risk score showed high correlation with more complex scores. Demonstrated accuracy together with superior simplicity and the ability to evaluate and follow-up individual patients makes siMS and siMS risk scores very convenient for use in clinical practice and research as well.

Matrix metalloproteinase-9 and the Cu/Zn ratio as ancillary diagnostic tools in distinguishing between the classical and follicular variants of papillary thyroid carcinoma.

The most common histological variants of papillary thyroid carcinoma (PTC), classical (CPTC) and follicular (FPTC), have different diagnostic features, molecular biology, and prognosis. Matrix metalloproteinase-9 (MMP-9) endopeptidase which degrades the components of the extracellular matrix is essential in the invasive growth and metastasizing of malignant tumors. The serum copper (Cu)/zinc (Zn) ratios are sensitive diagnostic and prognostic indicators in oncology since Cu- and Zn-dependent enzymes play important roles in the genesis and the progression of tumors. The aim of this study was to examine the expressions of MMP-9 in tissues of CPTC and FPTC, as well as to determine the Cu/Zn ratios in the same samples. MMP-9 was determined immunohistochemically, and the concentrations of copper and zinc in thyroid tissue were determined by means of flame atomic absorption spectrometry. The results obtained revealed significantly higher expressions of MMP-9 in CPTC in comparison with FPTC, as well as higher Cu/Zn ratios in CPTC than in FPTC. Thus, determining MMP-9 activities and the Cu/Zn ratios could improve the accuracy of the standard histopathological diagnosis of these two types of PTC.

Lung resection for lung cancer after pleural empyema.

BACKGROUND The association of pleural empyema and lung cancer has traditionally been considered as a contraindication for lung resection. However, several aspects of this problem still remain controversial. MATERIALS AND METHODS A retrospective study was conducted including 15 patients (12 pneumonectomies and 3 lobectomies) who underwent a lung resection for primary lung cancer after previous pleural empyema. RESULTS In all but one patient, empyema was treated by chest tube for 15 to 40 days. In only two patients, the diagnosis of empyema preceded the diagnosis of lung cancer. Among patients with pneumonectomy, a good intrapleural cleavage plane existed in only one patient with no signs of infection. In each patient with a lobectomy, preoperative chest tube aspiration took 20 to 30 days and in none of them intraoperative signs of infection existed. In patients with pneumonectomy, empyema without bronchopleural fistula occurred in two patients, while in one patient, empyema was associated with fistula. The operative morbidity after pneumonectomy was 33.3%. CONCLUSION Association of pleural empyema and lung cancer is not an absolute contraindication for surgery. Potentially curative operation is possible, provided a full control of infection is achieved.

Standard versus extended pneumonectomy for lung cancer: what really matters?

BackgroundIt is still not clear whether an intrapericardial pneumonectomy indicates a more advanced stage of the disease compared to a standard pneumonectomy.MethodsThis was a retrospective study of 164 patients who underwent a pneumonectomy for lung cancer. The first group consisted of 82 patients who had a standard pneumonectomy and the second group was 38 patients who had a intrapericardial pneumonectomy, for both groups in the latest 5-year period. The third group was 44 patients with had a sleeve pneumonectomy in the latest 10-year period. The groups were compared in relation to the overall and stage-related survival, influence of T and N factors, operative morbidity and mortality. The statistics used were Kaplan–Meier, U-test, t-test, χ2 test.ResultsThere was no statistically significant difference in stage distribution between standard and intrapericardial pneumonectomies; stages I, II, IIIA and IIIB occurred for 10.9% vs 2.6%, 30.5% vs 26.3%, 46.4% vs 65.8% and 12.2% vs 5.3% of patients, respectively. For patients who had a sleeve pneumonectomy, stage IIIA was significantly more frequent. Although the overall survival (63.5% vs 57.6%) and stage-related 5-year survival were better in the first compared to the second group, especially for stage IIIA (58.6% vs 42.6%), these differences were not statistically significant. There were no significant differences in operative morbidity and mortality between groups 1 and 2, but both were significantly higher in the third group (35.7% and 15.9%).ConclusionsAn intrapericardial pneumonectomy does not always indicate a more advanced stage of the disease. The need for an intrapericardial pneumonectomy, either established preoperatively or during the operation, as a single factor, even for marginal surgical candidates, is not strong enough to reject these patients for surgery.

Higher concentration of interleukin 6 - A possible link between major depressive disorder and childhood abuse

Little is known about the correlation between IL-6 and childhood abuse and neglect which may be risk factors for the development of affective disorders in adulthood. The aim of this study was to analyze differences in serum concentrations of IL-6 between patients with major depressive disorder and healthy controls, and to investigate possible correlations with adverse childhood experiences. Peripheral venous blood samples were obtained from 64 patients who fulfilled DSM-IV-R criteria for a current major depressive episode without psychotic symptoms (MDD) and 53 healthy controls, matched for age and gender. Participants were assessed by the Beck Depression Inventory (BDI), Childhood Trauma Questionnaire (CTQ), Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS). The concentration of IL-6 was significantly higher in patients with major depressive disorder compared to healthy controls. The total score of childhood trauma questionnaire highly statistically significantly correlated with IL-6 levels in patient group. Persons who were physically abused, physically neglected and emotionally abused had higher levels of IL-6. Interleukin 6 as a pro-inflammatory immune marker could be an important developmental mediator linking physical and emotional abuse in early life with the development of depressive disorder in adulthood.

Lung function changes and complications after lobectomy for lung cancer in septuagenarians

BACKGROUND: In septuagenarians, lobectomy is the preferable operation, with lower morbidity than for pneumonectomy. However, the 1-year impact of lobectomy on lung function has not been well studied in elderly patients. MATERIALS AND METHODS: Retrospective study including 30 patients 70 years or older (study group), 25 patients with chronic obstructive pulmonary disease (COPD) under 70 years (control group 1), and 22 patients under 70 years with normal lung function (control group 2) operated for lung cancer in a 2-year period. The study and control groups were compared related to lung function changes after lobectomy, operative morbidity, and mortality. RESULTS: Postoperative lung function changes in the elderly followed the similar trend as in patients with COPD. There were no significant differences between these two groups related to changes in forced expiratory volume in the first second (FEV1) and vital capacity (VC). Unlike that, the pattern of the lung function changes in the elderly was significantly different compared with patients with normal lung function. The mean postoperative decrease in FEV1 was 14.16% in the elderly, compared with a 29.23% decrease in patients with normal lung function (P < 0.05). In the study and control groups, no patients died within the first 30 postoperative days. The operative morbidity in the elderly group was significantly lower than in patients with COPD (23.3% vs. 60%). CONCLUSIONS: The lung function changes after lobectomy in the elderly are similar to those in patients with COPD. The explanation for such a finding needs further investigation. Despite a high proportion of concomitant diseases, the age itself does not carry a prohibitively high risk of operative mortality and morbidity.