Milan Milošević

Hippocampal Hypertrophy and Sleep Apnea: A Role for the Ischemic Preconditioning?

The full impact of multisystem disease such as obstructive sleep apnoea (OSA) on regions of the central nervous system is debated, as the subsequent neurocognitive sequelae are unclear. Several preclinical studies suggest that its purported major culprits, intermittent hypoxia and sleep fragmentation, can differentially affect adult hippocampal neurogenesis. Although the prospective biphasic nature of chronic intermittent hypoxia in animal models of OSA has been acknowledged, so far the evidence for increased ‘compensatory’ neurogenesis in humans is uncertain. In a cross-sectional study of 32 patients with mixed severity OSA and 32 non-apnoeic matched controls inferential analysis showed bilateral enlargement of hippocampi in the OSA group. Conversely, a trend for smaller thalami in the OSA group was noted. Furthermore, aberrant connectivity between the hippocampus and the cerebellum in the OSA group was also suggested by the correlation analysis. The role for the ischemia/hypoxia preconditioning in the neuropathology of OSA is herein indicated, with possible further reaching clinical implications.

Changes in Neurocognitive Architecture in Patients with Obstructive Sleep Apnea Treated with Continuous Positive Airway Pressure

Background Obstructive sleep apnea (OSA) is a chronic, multisystem disorder that has a bidirectional relationship with several major neurological disorders, including Alzheimers dementia. Treatment with Continuous Positive Airway Pressure (CPAP) offers some protection from the effects of OSA, although it is still unclear which populations should be targeted, for how long, and what the effects of treatment are on different organ systems. We investigated whether cognitive improvements can be achieved as early as one month into CPAP treatment in patients with OSA. Methods 55 patients (mean (SD) age: 47.6 (11.1) years) with newly diagnosed moderate–severe OSA (Oxygen Desaturation Index: 36.6 (25.2) events/hour; Epworth sleepiness score (ESS): 12.8 (4.9)) and 35 matched healthy volunteers were studied. All participants underwent neurocognitive testing, neuroimaging and polysomnography. Patients were randomized into parallel groups: CPAP with best supportive care (BSC), or BSC alone for one month, after which they were re-tested. Findings One month of CPAP with BSC resulted in a hypertrophic trend in the right thalamus [mean difference (%): 4.04, 95% CI: 1.47 to 6.61], which was absent in the BSC group [− 2.29, 95% CI: − 4.34 to − 0.24]. Significant improvement was also recorded in ESS, in the CPAP plus BSC group, following treatment [mean difference (%): − 27.97, 95% CI: − 36.75 to − 19.19 vs 2.46, 95% CI: − 5.23 to 10.15; P = 0.012], correlated to neuroplastic changes in brainstem (r = − 0.37; P = 0.05), and improvements in delayed logical memory scores [57.20, 95% CI: 42.94 to 71.46 vs 23.41, 95% CI: 17.17 to 29.65; P = 0.037]. Interpretation One month of CPAP treatment can lead to adaptive alterations in the neurocognitive architecture that underlies the reduced sleepiness, and improved verbal episodic memory in patients with OSA. We propose that partial neural recovery occurs during short periods of treatment with CPAP.

Prognostic value of galectin-3 in primary cutaneous melanoma

Background  Galectin‐3, one of the β‐galactoside‐binding lectins, has been suggested as a marker of disease progression in melanoma patients because of its overexpression observed in recent studies. However, prognostic value of galectin‐3 in primary cutaneous melanoma (PCM) has not been clearly defined.

The IMPACT-III (HR) Questionnaire: A valid measure of health-related quality of life in Croatian children with inflammatory bowel disease

BACKGROUND AND AIMS To assess the reliability and validity of IMPACT-III (HR), a disease-specific, health-related quality of life instrument in Croatian children with inflammatory bowel disease. METHODS In a multicenter study, 104 children participated in a validation study of IMPACT-III (HR) cross-culturally adapted for Croatia. Factor analysis was used to determine optimal domain structure for this cohort, analysis of Cronbachs alpha coefficients to test internal reliability, ANOVA to assess discriminant validity, and correlation with Pediatric Quality of Life Inventory, Version 4.0 (PedsQL) using Pearson correlation coefficients to assess concurrent validity. RESULTS Cronbachs alpha for the IMPACT-III (HR) total score was 0.92. The most robust factor solution was a 5-domain structure: Symptoms, Concerns, Socializing, Body Image, and Worry about Stool, all of which demonstrated good internal reliability (α=0.60-0.89), but two items were dropped to achieve this. Discriminant validity was demonstrated by significant differences (P<0.001) in mean IMPACT-III (HR) scores between quiescent and mild or moderate-severe disease activity groups for total (148 vs. 139 or 125) and following factor scores: Symptoms (84 vs. 71 or 61), Socializing (91 vs. 83 or 76), and Worry about Stool (significant only between quiescent and moderate-severe groups, 90 vs. 62, respectively). Concurrent validity of IMPACT-III (HR) with PedsQL showed significant correlation, which was strongest when similar domains were compared. CONCLUSION IMPACT-III (HR) appears to be useful tool to measure health-related quality of life in Croatian children with Crohns disease and ulcerative colitis.

Lower incidence of hepatic metastases of colorectal cancer in patients with chronic liver diseases: meta-analysis.

BACKGROUND/AIMS The rarity of metastatic malignancy in injured liver has been noticed. This meta-analysis evaluates the difference in occurrence of metastatic colorectal cancer in healthy and chronically injured liver. METHODOLOGY Literature search of occurrence of metastatic colorectal cancer in chronically injured liver opposed to healthy liver was conducted. Chronically injured/damaged liver included cirrhosis, steatosis or fatty liver and infection with Hepatitis virus B or C. RESULTS A total of 7 retrospective studies between 1992 and 2010 matched the selection criteria with total of 4049 patients. Results suggest significantly lower incidence of colorectal metastasis in chronically injured liver (Pooled odds ratio = 0.260 (95% CI = 0.18 to 0.38); χ² (test odds ratio differs from 1) = 45.90 (df = 1); p <0.0001). CONCLUSIONS Patients with chronic liver injury have significantly lower occurrence of hepatic metastasis of primary colorectal cancer than the patients with healthy liver.

Intensity of stromal changes predicts biochemical recurrence-free survival in prostatic carcinoma

Abstract Objective. The reactive stroma of prostate cancer contains a mixture of myofibroblasts and fibroblasts, while fully differentiated smooth-muscle cells are very rare or absent. In experimental prostate cancer models, prostatic stromal cells promote angiogenesis and stimulate prostate tumorigenesis. The aim of this study is to analyse whether the intensity of stromal changes can predict survival in patients with prostatic carcinoma. Material and methods. Stromal reaction was quantified histochemically and imunohistochemically in 50 patients treated with radical prostatectomy for clinically localized prostate carcinoma and its relationship with established prognostic factors was assessed. Results. Kaplan–Meier analysis showed a significant association between the pattern of vimentin and desmin expression and the length of disease-free period; patients with a higher vimentin or lower desmin expression had a shorter disease-free period. On multivariate analysis only vimentin expression (odds ratio 4.06, 95% confidence interval 1.01–16.26, p = 0.049) was a significant predictor of biochemical recurrence. In patients with identical Gleason pattern and Gleason score the level of vimentin expression could identify patients with a higher risk of disease recurrence. Conclusions. Intensity of stromal changes could serve as an independent prognostic factor in the assessment of biochemical recurrence-free survival. Among prostate cancer patients with an identical Gleason score, it could identify patients with a higher risk of biochemical recurrence. Thus, stromal changes and their intensity could serve as a novel marker for the recognition of patients with an increased risk of disease recurrence.

Immunohistochemical expression of tumor antigens MAGE-A3/4 and NY-ESO-1 in renal oncocytoma and chromophobe renal cell carcinoma

The distinction between renal oncocytoma (RO) and chromophobe renal cell carcinoma (ChRCC), especially the eosinophilic variant, can often be difficult. Our study has documented for the first time the expression of MAGE-A3/4 and NY-ESO-1 cancer testis antigens (CTAs) in these tumors. A total of 35 patients (17 ROs and 18 ChRCCs) were included in the study. Two antibodies were used for immunohistochemical staining: 57B recognizing multiple MAGE-A and D8.38 recognizing NY-ESO-1 CTAs. Fifteen (88.2%) samples of RO stained positively for both MAGE-A3/4 and NY-ESO-1 antigens. Regarding ChRCC, seven (38.9%) stained positively for MAGE-A3/4 and six (33.3%) for NY-ESO-1 antigens. Median MAGE-A3/4 expression was moderately positive in RO and negative in ChRCC. The difference in MAGE-A3/4 expression between two tumor groups was significant (P=0.0013). Median NY-ESO-1 expression was strongly positive in RO and negative in ChRCC. The difference in NY-ESO-1 expression between two tumor groups was also significant (P=0.0008). Our study has shown that RO had a significantly higher expression of both CTAs. However, additional research is needed to clarify their potential diagnostic implications.

Association between total serum cholesterol and depression, aggression, and suicidal ideations in war veterans with posttraumatic stress disorder: a cross-sectional study

Aim To investigate the relationship between total serum cholesterol and levels of depression, aggression, and suicidal ideations in war veterans with posttraumatic stress disorder (PTSD) without psychiatric comorbidity. Methods A total of 203 male PTSD outpatients were assessed for the presence of depression, aggression, and suicidality using the 17-item Hamilton Depression Rating Scale (HAM-D17), Corrigan Agitated Behavior Scale (CABS), and Scale for Suicide Ideation (SSI), respectively, followed by plasma lipid parameters determination (total cholesterol, high density lipoprotein [HDL]-cholesterol, low density lipoprotein [LDL]-cholesterol, and triglycerides). PTSD severity was assessed using the Clinician-Administered PTSD Scale for DSM-IV, Current and Lifetime Diagnostic Version (CAPS-DX) and the Clinical Global Impressions of Severity Scale (CGI-S), before which Mini-International Neuropsychiatric Interview (MINI) was administered to exclude psychiatric comorbidity and premorbidity. Results After adjustments for PTSD severity, age, body mass index, marital status, educational level, employment status, use of particular antidepressants, and other lipid parameters (LDL- and HDL- cholesterol and triglycerides), higher total cholesterol was significantly associated with lower odds for having higher suicidal ideation (SSI≥20) (odds ratio [OR] 0.09; 95% confidence interval [CI] 0.03-0.23], clinically significant aggression (CABS≥22) (OR 0.28; 95% CI 0.14-0.59), and at least moderate depressive symptoms (HAM-D17≥17) (OR 0.20; 95% CI 0.08-0.48). Association of total cholesterol and HAM-D17 scores was significantly moderated by the severity of PTSD symptoms (P < 0.001). Conclusion Our results indicate that higher total serum cholesterol is associated with lower scores on HAM-D17, CABS, and SSI in patients with chronic PTSD.

Extensive retraction artefact predicts biochemical recurrence‐free survival in prostatic carcinoma

Tomas D, Spajić B, Milošević M, Demirović A, Marušić Z & Krušlin B
(2011) Histopathology58, 447–454
Extensive retraction artefact predicts biochemical recurrence‐free survival in prostatic carcinoma

Burnout and health behaviors in health professionals from seven European countries

ObjectivesWithin an underlying health-impairing process, work stressors exhaust employees’ mental and physical resources and lead to exhaustion/burnout and to health problems, with health-impairing behaviors being one of the potential mechanisms, linking burnout to ill health. The study aims to explore the associations between burnout and fast food consumption, exercise, alcohol consumption and painkiller use in a multinational sample of 2623 doctors, nurses and residents from Greece, Portugal, Bulgaria, Romania, Turkey, Croatia and Macedonia, adopting a cross-national approach.MethodsData are part of the international cross-sectional quantitative ORCAB survey. The measures included the Maslach Burnout Inventory and the Health Behaviors Questionnaire.ResultsBurnout was significantly positively associated with higher fast food consumption, infrequent exercise, higher alcohol consumption and more frequent painkiller use in the full sample, and these associations remained significant after the inclusion of individual differences factors and country of residence. Cross-national comparisons showed significant differences in burnout and health behaviors, and some differences in the statistical significance and magnitude (but not the direction) of the associations between them. Health professionals from Turkey, Greece and Bulgaria reported the most unfavorable experiences.ConclusionsBurnout and risk health behaviors among health professionals are important both in the context of health professionals’ health and well-being and as factors contributing to medical errors and inadequate patient safety. Organizational interventions should incorporate early identification of such behaviors together with programs promoting health and aimed at the reduction of burnout and work-related stress.