The vicious interplay between disrupted sleep and malignant brain tumors: a narrative review.

Malignant brain tumors are among the most aggressive human neoplasms. One of the most common and severe symptoms that patients with these malignancies experience is sleep disruption. Disrupted sleep is known to have significant systemic pro-tumor effects, both in patients with other types of cancer and those with malignant brain lesions. We therefore provide a review of the current knowledge on disrupted sleep in malignant diseases, with an emphasis on malignant brain tumors. More specifically, we review the known ways in which disrupted sleep enables further malignant progression. In the second part of the article, we also provide a theoretical framework of the reverse process. Namely, we argue that due to the several possible pathophysiological mechanisms, patients with malignant brain tumors are especially susceptible to their sleep being disrupted and compromised. Thus, we further argue that addressing the issue of disrupted sleep in patients with malignant brain tumors can, not just improve their quality of life, but also have at least some potential of actively suppressing the devastating disease, especially when other treatment modalities have been exhausted. Future research is therefore desperately needed.

Validation of a clinical score in predicting pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) is one of the most severe complications after cephalic pancreaticoduodenectomy, with mortality as high as 30%. Risk scores may help predict the risk of POPF. Multiple external validations substantially improve generalized clinical acceptability of a scoring system. AIM: The aim of this study was to externally validate previously described fistula risk score in the prediction of clinically relevant POPF. METHODS: All patients who underwent pancreaticoduodenectomy for any indication during a 5-year period were prospectively analyzed. A total of 132 patients were analyzed. RESULTS: Of the 132 patients, 44 (33.3%) developed pancreatic fistula, including 12.9% biochemical leaks, 7.6% grade B fistula, and 12.9% grade C fistula. Cut-off point of 4.5 was determined to best separate patients who developed clinically relevant POPF with area under curve of 78% (p = .00003). Sensitivity and specificity for the prediction of clinically relevant POPF with the cut-off value of 4.5 was 70.4 and 74.3%, respectively. Positive predictive value with cut-off value 4.5 was 57.8%, and negative predictive value was 83.4%. CONCLUSION: Fistula risk score identified low risk patients with false negative rate of 16.6%. Further external validation studies on large cohorts of patients and with wide case-mix may enable additional refinements of the score model.

Utilization of somatic healthcare in Croatian patients with schizophrenia spectrum disorder, major depression, PTSD and the general population.

BACKGROUND: Utilization of somatic healthcare services is highly predictive of the development of chronic physical illnesses and increased mortality risks. The objective of this study was to assess the differences in healthcare utilization among patients with schizophrenia spectrum disorders (SSD), major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) and the general population in Croatia. METHODS: We enrolled 566 Croatian participants from the general population, 282 with SSD, 178 with MDD, and 86 with PTSD. The primary outcome was a self-reported specialist consultation for non-psychiatric (e.g., somatic) causes within the previous 12 months. RESULTS: Although SSD patients with chronic physical illnesses were significantly more often hospitalized for physical illness than the general population, the proportion of patients who had a specialist consultation were equal in SSD and the general population. MDD and PTSD patients had significantly higher adjusted odds for specialist consultation than the general population and SSD patients (MDD compared to SSD: OR = 2.14; 95% CI 1.27-3.59; PTSD compared to SSD: OR = 2.03; 95% CI 1.00-4.10). CONCLUSIONS: SSD patients' utilization of somatic healthcare is equal to the general population, despite their increased healthcare needs. However, their utilization is lower than in MDD and PTSD patients and, therefore, probably not adequate. TRIAL REGISTRATION: The study protocol was registered at ClinicalTrials.gov ( NCT02773108 ) on May 16, 2016.

Comparison of Different Surgical Procedures with Local Infiltration Analgesia in Day Surgery.

Purpose of this study was assessing of local infiltration analgesia (LIA) with levobupivacaine on the trend of acute postoperative pain and outcome in individuals who underwent rhinoplasty procedure and abdominoplasty performed in general anaesthesia. The research was conducted on 60 patients, of which 30 patients underwent rhinoplasty procedure and the other 30 patients underwent abdominoplasty procedure in general anaesthesia with LIA in "Bagatin" Polyclinic in the time period between 01.01.2014. and 01.01.2017. Postoperative analgesics doses on the same day of surgery were noted in 85% of participants who underwent an abdominoplasty procedure and in 45% of participants underwent rhinoplasty procedure. Patients who underwent abdominoplasty were discharged from the facility within 48 hours, while all patients who underwent rhinoplasty procedure were discharged on the same day of the surgery. During the first postoperative day patients who underwent a rhinoplasty procedure did not require analgesics, while only 3% of patients who underwent an abdominal liposuction procedure required an additional dose of analgesics. The research results had shown, when LIA was performed, the manifestation of acute postoperative pain and vomiting did not lead to prolonged stay in day surgery.

RANKL/RANK/OPG Axis Is Deregulated in the Cerebrospinal Fluid of Multiple Sclerosis Patients at Clinical Onset.

OBJECTIVES: Our study focused on the RANKL (receptor activator of nuclear factor-κB ligand)/RANK/OPG (osteoprotegerin) axis and selected proinflammatory/immunoregulatory upstream mediators in the peripheral blood (PBL) and cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. METHODS: PBL and CSF were collected from healthy controls (n = 35) and MS patients at the clinical onset of the disease (n = 33). In addition, PBL samples were obtained from relapse-remitting (RR)-MS patients (n = 30). Patients were assessed by means of the expanded disability status scale (EDSS) and routine laboratory parameters. Soluble (s)RANKL and OPG were measured in the CSF and plasma; gene expression was detected for RANKL, RANK, OPG, and selected cytokines/chemokines (interleukin [IL]-4, IL-10, IL-17, CCL2, and CXCL12) in PBL mononuclear cells. RESULTS: The OPG level in the CSF was lower in MS patients at clinical onset than in controls. Moreover, the sRANKL/OPG ratio was higher in the CSF of MS patients at clinical onset and in the plasma of RR-MS patients than in controls. Gene expression of RANKL/RANK/OPG in PBL mononuclear cells was higher only in RR-MS patients. IL-4, CCL2, and CXCL12 were positively correlated and IL-10 was negatively correlated with RANKL/RANK expression. OPG was negatively correlated with EDSS and alkaline phosphatase level. CONCLUSION: Our study revealed that changes of RANKL/RANK/OPG axis are associated with MS, particularly the decreased OPG level in the CSF at disease onset. Therefore, these factors may serve as disease biomarkers and molecular targets of novel therapeutic approaches.

Efficacy and safety of repetitive transcranial magnetic stimulation using an H1-coil or figure-8-coil in the treatment of unipolar major depressive disorder: A study protocol for a randomized controlled trial.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique with few side effects that has been reported to be effective in the treatment of major depressive disorder (MDD). At present, no randomized controlled trials (RCT) have compared the efficacy and safety of rTMS delivered by the figure-8-coil and the H1-coil. We describe an industry-independent, randomized, controlled, single-blinded, single-center study protocol assessing the differences in efficacy and safety of rTMS for patients diagnosed with MDD with the H1-coil and figure-8-coil as an add-on to stable pharmacotherapy or pharmacotherapy alone. Stimulation protocols follow those that led to the FDA clearance of these treatments for MDD. The sample of 76 patents in each of the three groups will be enrolled and assessed with clinical and neuropsychological tests. The primary outcome is remission rate defined as Hamilton depression rating scale (HAM-D17) score ≤7 at the end of week-4. This clinical trial will address the efficacy and safety of rTMS modalities for MDD. The evaluation of biological markers will also help to elucidate the pathophysiology of MDD and the mechanisms of action of rTMS.

Early Intervention Services for Early-Phase Psychosis - Centre for integrative psychiatry in Psychiatric Hospital "Sveti Ivan", Croatia.

BACKGROUND: There is a growing body of evidence suggesting that early and effective management in the critical early years of schizophrenia can improve long-term outcomes. The objective of this study was to evaluate time to relapse of the patients with early-phase psychosis treated in the Centre for integrative psychiatry (CIP). SUBJECT AND METHODS: We performed a retrospective cohort study on the sample of 373 early-phase psychosis patients admitted to Psychiatric Hospital "Sveti Ivan", Zagreb Croatia: from January 1, 2015 to December 31, 2017. The primary outcome was time to relapse. RESULTS: Patients who were admitted to group psychotherapeutic program after the end of acute treatment had 70% lower hazard for relapse (HR=0.30; 95% CI 0.16-0.58). Patients who were included first in the psychotherapeutic program and then treated and controlled in the daily hospital had 74% lower hazard for relapse (HR=0.26; 95% CI 0.10-0.67). CONCLUSIONS: In early-phase psychosis, integrative early intervention service has relevant beneficial effects compare to treatment as usual. These results justified the implementation of multimodal early intervention services in treatment of patients with early-phase psychosis.

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio help identify patients with lung cancer, but do not differentiate between lung cancer subtypes.

AIM: To assess the diagnostic value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in lung cancer (LC). We compared the ratios between healthy participants and all LC patients, as well patients with different pathohistological LC subtypes. METHODS: We retrieved the data on neutrophil, lymphocyte, and platelet levels in 449 patients with different pathohistological LC subtypes (non-small cell LC, small-cell LC, atypical or metastatic LC, neuroendocrine, and sarcomatoid carcinoma) and 47 healthy controls. NLR and PLR were calculated by dividing the absolute number of neutrophils or platelets with the absolute number of lymphocytes. RESULTS: There were significant differences in both NLR and PLR (P<0.001) between all LC patients and the control group, but there were no differences between patients with different LC subtypes. Reciever operating characteristics analysis for NLR showed the optimal cut-off value of 2.71, with a sensitivity of 77.05% and specificity of 87.23%. The optimal cut-off value for PLR was 182.31, with a sensitivity of 51.09% and specificity of 91.49%. CONCLUSION: The results showed that the NLR and PLR may have added value in the early diagnosis of LC, but further research is needed to confirm these results.

Giant Spinal Schwannoma in a 76-year-old Woman--A Case Report.

A schwannoma is a benign nerve sheath tumor composed of Schwann cells. Spinal schwannoma originates from dorsal roots of the spinal cord, causing symptoms due to the compression of neighboring structures. We present a patient with a low back pain and left L2 and L3 radiculopathy. Neuroimaging techniques (CT, MRI) showed a large expansive mass in the left lumbar paraspinal area. The tumor was removed totally by the posterior approach and was verified to originate from the left L2 spinal nerve root. The histopathological examination revealed typical findings of a schwannoma. The pain was resolved promptly after the surgery, however the patient's neurological condition wasn't improved. Surgical treatment was a final treatment, and no additonal therapy was necessary.

Effect of unilateral ureteral obstruction and anti-angiotensin II treatment on renal tubule cell apoptosis and interstitial fibrosis in rats.

Unilateral ureteral obstruction (UUO) results in a number of pathophysiological and morphological changes in the renal parenchyma, including interstitial inflammation and fibrosis, apoptotic changes of tubular and interstitial cells. Recent studies have indicated an association between renin-angiotensin system and apoptotic alterations in the kidney after unilateral obstructive nephropathy. In this study, the effect of ACE inhibitors and AT1 receptor antagonists on tubular cell apoptosis and interstitial fibrosis in obstructive nephropathy after UUO in rats was investigated. The study was conducted on Wistar rats with unilaterally ligated ureter and sham operated animals (control group). The rats with UUO were treated with ACE inhibitor (cilazapril) or AT1 receptor antagonists (losartan) and control group was treated with H2O. Sham-operated animals were treated in the same way. Tubular and interstitial cell apoptosis was detected morphologically by hematoxylin and eosin (HE) staining and terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL). The area of intersitial fibrosis was determined using computer-assisted image processing after Gomory silver impregnation of paraffin sections. All experimental animal groups with unilateral ureter ligation showed a significantly increased number of apoptotic tubular and interstitial cells in the obstructed kidney compared with the contralateral, unobstructed kidney. Histomorphometric analysis of renal interstitial fibrotic changes in the groups of rats treated with losartan or water showed a statistically significant difference (p < 0.05) between the operated and sham--operated animals. In conclusion, following UUO there is a significantly increased number of apoptotic tubular cells and interstitial fibrosis in the ipsilateral kidney compared with the contralateral kidney. ACE inhibitors and AT1 receptor antagonists could not decrease the extent of renal cells apoptosis and interstitial fibrosis after UUO.

Retrorenal fat predicts grade C pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND: Pancreatic fistula after pancreaticoduodenectomy is one of the most severe complications with mortality rates as high as 45%, and the prediction of most severe form of fistula (grade C) is crucial for successful management of patients who are to undergo cephalic pancreatoduodenectomy. It has been found that the amount of abdominal fat may predict grade C postoperative pancreatic fistula. In this study, we analysed the value of retrorenal fat thickness in the prediction of grade C pancreatic fistula. METHODS: A total of 140 patients who underwent pancreaticoduodenectomy were retrospectively analysed. Retrorenal fat thickness and intra-abdominal fat, expressed as total fat area, visceral fat area and subcutaneous fat area, were determined from computed tomography slices using the known range of attenuation values (-190 to -30). Blood loss, operating time, pancreatic texture and main pancreatic duct diameter as well as body mass index were also analysed. RESULTS: Retrorenal fat thickness (P = 0.0004), duct diameter (P = 0.0008), subcutaneous fat area (P = 0.023) and total fat area (P = 0.014) were found to be significant predictors of grade C pancreatic fistula. CONCLUSION: Although retrorenal fat tissue thickness may seem robust, it is a simple measure that can be used to predict the most severe grade of pancreatic fistula after pancreaticoduodenectomy.

Intraspinal calcinosis mimicking intervertebral disc extrusion: A clinical and surgical case report.

BACKGROUND: Subcutaneous calcinosis is a well-recognized manifestation of systemic sclerosis that usually involves multiple pressure points and may also be found in the paraspinal or intraspinal regions. In this case, intraspinal calcinosis uniquely led to a severe neurological deficit. CASE DESCRIPTION: A patient with severe systemic sclerosis/calcinosis exhibited left greater than right lower extremity radiculopathy attributed to intraspinal left-sided L4-L5 calcinosis. On examination, the patient exhibited bilateral positive Lasegue signs, distal lower extremity weakness (left greater than right), and bilaterally decreased Achilles responses. When the magnetic resonance imaging (MRI) revealed a significant intracanalicular mass on the left side at the L4-L5 level, the patient underwent a left-sided L4-L5 decompressive laminectomy. The MRI scan 5 years later revealed no recurrence of the calcinosis, and the patient had no residual neurological deficit. CONCLUSIONS: Spinal calcinosis rarely involves the lumbar spinal canal. Here, a patient with a large left-sided L4-L5 focus of intraspinal calcinosis, mimicking a disc herniation, required a laminectomy to resect the lesion. Lumbar calcinosis should be radiologically evaluated utilizing using X-ray, MRI, and computed tomography studies to adequately document the pathology. Patients, when symptomatic, may require surgical decompression and excision of these lesions.

Gastrostomy Under Paravertebral Block in High-Risk Patients with Esophageal Cancer - Two Case Reports.

Here we present two cases of gastrostomy insertion via laparotomy in patients with malignant esophageal disease. Patients were ASA (American Society of Anesthesiologists) physical status III and IV. The patients presented as very high risk for general anesthesia, so we decided to use unilateral left sided paravertebral block (PVB) on four thoracic levels along with contralateral local infiltration at the gastrostomy insertion site. We present two cases, one of them a 57-year-old male ASA III patient scheduled for a gastrostomy procedure due to esophageal cancer with infiltration of the trachea. We also present a case of a 59-year-old male patient, ASA IV status, scheduled for the same procedure due to advanced esophageal cancer with a fistula between the left main bronchus and the esophagus and metastases in the left lung. The paravertebral space was identified with the use of an 8 Hertz (Hz) linear ultrasound probe and a nerve stimulator. Paravertebral block was successfully used for insertion of a gastrostomy, thereby enabling adequate anesthesia and perioperative analgesia without hemodynamic or respiratory complications.

FACET ORIENTATION AND TROPISM: ASSOCIATION WITH ACCELERATED DEGENERATION OF STABILIZING STRUCTURES IN LOWER LUMBAR SPINE.

The influence of facet orientation and tropism on the process of spinal degeneration has been extensively studied during the last few decades, but there are still many controversies and conflicting results in this field of research. The biomechanical cause of accelerated degeneration of stabilizing structures in lower lumbar spine lies within the combination of several factors, but two most important ones are compressive load and more coronal facet orientation that offers less resistance against torsional loading. Axial rotation of lower lumbar spine is undoubtedly associated with higher strain in disc annulus, and enhanced range of secondary rotational movements may be even more significant for the progression of annular degeneration. Accordingly, more pronounced facet tropism could be having part in faster progression of disc degeneration in lower lumbar spine, as indicated by a number of recent studies. More sagittal facet orientation in patients with a higher facet osteoarthritis score at lower lumbar segments is very likely related to arthritic remodeling commonly seen in other synovial joints. There is also a possibility that it could be associated with the adaptation to partial loss of lumbar lordosis, as both coincide with advanced age.

AGE AND GENDER DIFFERENCES IN ACUTE STROKE HOSPITAL PATIENTS.

Stroke is the second leading cause of death and the most important cause of adult disability worldwide and in Croatia. In the past, stroke was almost exclusively considered to be a disease of the elderly; however, today the age limit has considerably lowered towards younger age. The aim of this study was to determine age and gender impact on stroke patients in a Croatian urban area during one-year survey. The study included all acute stroke patients admitted to our Department in 2004. A compiled stroke questionnaire was fulfilled during hospitalization by medical personnel on the following items: stroke risk factors including lifestyle habits (smoking and alcohol), pre-stroke physical ability evaluation, stroke evolution data, laboratory and computed tomography findings, outcome data and post-stroke disability assessment. Appropriate statistical analysis of numerical and categorical data was performed at the level of p < 0.05. Analysis was performed on 396 patients, 24 of them from the younger adult stroke group. Older stroke patients had worse disability at hospital discharge and women had worse disabilities at both stroke onset and hospital discharge, probably due to older age at stroke onset. Younger patients recovered better, while older patients had to seek secondary medical facilities more often, as expected. The most important in-hospital laboratory findings in young stroke patients were elevated lipid levels, while older patients had elevated serum glucose and C-reactive protein. Stroke onset in younger patients most often presented with sudden onset headache; additionally, onset seizure was observed more frequently than expected. Stroke risk factor analysis showed that women were more prone to hypertension, chronic heart failure and atrial fibrillation, whereas men had carotid disease more frequently, were more often smokers and had higher alcohol intake. Additionally, age analysis showed that heart conditions and smoking were more prevalent among older stroke patients. In conclusion, considerable differences were established between age and gender stroke patient groups, confirming the need of permanent national stroke registry and subsequent targeted action in secondary care, and prevention with education on risk factors, preferably personally tailored.

Unrecognized hemangiopericytoma of posterior cervical region with intracranial extension.

Hemangiopericytoma of the posterior cervical space and occipital bone is an uncommon lesion which should be considered in the differential diagnosis of a lumpy and highly vascular lesion of the posterior cervical space. We report the case of a 47-year-old woman who experienced sudden and painful occipital and posterior cervical swelling. She underwent a blind biopsy which was complicated by profuse bleeding. The palpable lesion was not properly diagnosed preoperatively, and the endocranial extension of the lesion was overlooked by her surgeon who performed a blind biopsy without adequate diagnostic imaging who inadvertently invaded the posterior cranial fossa during biopsy. We would like to emphasize the need for appropriate non-invasive diagnostic investigations before any biopsy of head and neck lesions that may extend deeply.

Factors influencing medical informatics examination grade--can biorhythm, astrological sign, seasonal aspect, or bad statistics predict outcome?

AIM: To investigate whether and to what extent various parameters, such as individual characteristics, computer habits, situational factors, and pseudoscientific variables, influence Medical Informatics examination grade, and how inadequate statistical analysis can lead to wrong conclusions. METHODS: The study included a total of 382 second-year undergraduate students at the Rijeka University School of Medicine in the period from 1996/97 to 2000/01 academic year. After passing the Medical Informatics exam, students filled out an anonymous questionnaire about their attitude toward learning medical informatics. They were asked to grade the course organization and curriculum content, and provide their date of birth; sex; study year; high school grades; Medical Informatics examination grade, type, and term; and describe their computer habits. From these data, we determined their zodiac signs and biorhythm. Data were compared by the use of t-test, one-way ANOVA with Tukey's honest significance difference test, and randomized complete block design ANOVA. RESULTS: Out of 21 variables analyzed, only 10 correlated with the average grade. Students taking Medical Informatics examination in the 1998/99 academic year earned lower average grade than any other generation. Significantly higher Medical Informatics exam grade was earned by students who finished a grammar high school; owned and regularly used a computer, Internet, and e-mail (p< or =0.002 for all items); passed an oral exam without taking a written test (p=0.004), or did not repeat the exam (p<0.001). Better high-school students and students with better grades from high-school informatics course also scored significantly better (p=0.032 and p<0.001, respectively). Grade in high-school mathematics, student's sex, and time of year when the examination was taken were not related to the grade, and neither were pseudoscientific parameters, such as student zodiac sign, zodiac sign quality, or biorhythm cycles, except when intentionally inadequate statistics was used for data analysis. CONCLUSION: Medical Informatics examination grades correlated with general learning capacity and computer habits of students, but showed no relation to other investigated parameters, such as examination term or pseudoscientific parameters. Inadequate statistical analysis can always confirm false conclusions.