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Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is characterized by recurring episodes of thrombotic microangiopathy, causing ischemic organ impairment. Black patients are overrepresented in iTTP cohorts in the United States, but racial disparities in iTTP outcome and response to therapy have not been studied. Using the United States Thrombotic Microangiopathies Consortium iTTP Registry, we evaluated the impact of race on mortality and relapse-free survival (RFS) in confirmed iTTP in the United States from 1995 to 2020. We separately examined the impact of rituximab therapy and presentation with newly diagnosed (de novo) or relapsed iTTP on RFS by race. A total of 645 participants with 1308 iTTP episodes were available for analysis. Acute iTTP mortality did not differ by race. When all episodes of iTTP were included, Black race was associated with shorter RFS (hazard ratio [HR], 1.60; 95% CI, 1.16-2.21); the addition of rituximab to corticosteroids improved RFS in White (HR, 0.37; 95% CI, 0.18-0.73) but not Black patients (HR, 0.96; 95% CI, 0.71-1.31). In de novo iTTP, rituximab delayed relapse, but Black patients had shorter RFS than White patients, regardless of treatment. In relapsed iTTP, rituximab significantly improved RFS in White but not Black patients. Race affects overall relapse risk and response to rituximab in iTTP. Black patients may require closer monitoring, earlier retreatment, and alternative immunosuppression after rituximab treatment. How race, racism, and social determinants of health contribute to the disparity in relapse risk in iTTP deserves further study.

Immune-mediated thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy characterized by an acquired ADAMTS13 deficiency as a result of the presence of an antibody inhibitor of ADAMTS13 leading to the formation of ultralarge von Willebrand multimers. Treatment of iTTP includes plasma exchange, high-dose glucocorticoids, rituximab, and, more recently, caplacizumab, to prevent the development of exacerbations. There is the risk of both relapse and long-term complications that include neurocognitive deficits and cardiovascular events that occur in patients in remission after recovery from an acute iTTP episode. Data on the risk factors for the development of these complications, the appropriate screening, and treatment are limited due to the paucity of research. This article is a review of the current understanding on the risk factors for exacerbation, relapse, and long-term complications of iTTP and discusses an approach to observing patients with iTTP after hospital discharge and during the long-term follow-up in the outpatient setting.

To gather information about prescription of triptans and to evaluate whether vascular comorbidity differs in users and nonusers of triptans over the age of 50 years.Beyond the age of 50 years, migraine is still common-yet the incidence of vascular disorders increases. Triptans, medications for treating migraine attacks, are vasoconstrictive drugs and contraindicated in persons with vascular disorders.Based on a nationwide insurance database from 2011, we compared the prescription of vascular drugs (identified by Anatomical Therapeutic Chemical codes), vascular diagnoses and hospitalizations, between triptan users greater than 50 years and a matched control group.Of the 3,116,000 persons over 50 years, 13,833 (0.44%) had at least one triptan prescription; 11,202 (81%) were women. Thirty percent of the triptan users (13,833/47,336 persons) were over 50 years. Of those over 50 years, 6832 (49.4%) had at least one vascular drug and 870 (6.3%) had at least one inpatient vascular diagnosis; 15.7% (2166 of 13,833 users) overused triptans. We compared triptan-users to 41,400 nonusers, using a 1:3 match. In triptan-users, prescriptions of cardiac therapies and beta blockers were significantly more common (odds ratio [OR] = 1.35, 95% confidence interval [CI] = 1.24-1.47 and OR = 1.19, 95% CI = 1.14-1.25, respectively); whereas prescriptions of calcium channel blockers and renin/angiotensin inhibitors were significantly less common (OR = 0.82, 95% CI = 0.76-0.88 and OR = 0.75, 95% CI = 0.72-0.79, respectively). The prescriptions of antihypertensive, diuretic, and antilipidemic drugs as well as platelet inhibitors and direct thrombin inhibitors did not differ in users and nonusers. Triptan users had significantly more hospital stays (OR = 1.39, 95% CI = 1.33-1.45); however, the number of days spent in the hospital and more importantly the frequency of inpatient vascular diagnoses did not differ statistically significantly between the two groups.In persons over 50 years of age, a prescription of triptans is common. Vascular comorbidity is comparable in users and nonusers of triptans showing that triptans are prescribed despite vascular comorbidity and suggesting that triptan use does not increase vascular risk in patients with migraine over the age of 50 years. Nevertheless, regular evaluation for contraindications against triptans and for vascular risk factors is recommended in this age group.

BackgroundAlpha-1 antitrypsin deficiency (AATD) is a genetic condition that causes early onset pulmonary emphysema and airways obstruction. The complete mechanisms via which AATD causes lung disease are not fully understood. To improve our understanding of the pathogenesis of AATD, we investigated gene expression profiles of bronchoalveolar lavage (BAL) and peripheral blood mononuclear cells (PBMCs) in AATD individuals.MethodsWe performed RNA-Seq on RNA extracted from matched BAL and PBMC samples isolated from 89 subjects enrolled in the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study. Subjects were stratified by genotype and augmentation therapy. Supervised and unsupervised differential gene expression analyses were performed using Weighted Gene Co-expression Network Analysis (WGCNA) to identify gene profiles associated with subjects’ clinical variables. The genes in the most significant WGCNA module were used to cluster AATD individuals. Gene validation was performed by NanoString nCounter Gene Expression Assay.ResultWe observed modest effects of AATD genotype and augmentation therapy on gene expression. When WGCNA was applied to BAL transcriptome, one gene module, ME31 (2312 genes), correlated with the highest number of clinical variables and was functionally enriched with numerous immune T-lymphocyte related pathways. This gene module identified two distinct clusters of AATD individuals with different disease severity and distinct PBMC gene expression patterns.ConclusionsWe successfully identified novel clusters of AATD individuals where severity correlated with increased immune response independent of individuals’ genotype and augmentation therapy. These findings may suggest the presence of previously unrecognised disease endotypes in AATD that associate with T-lymphocyte immunity and disease severity.

Background The bryophytes are a plant group that is smaller than and not as well known as the vascular plants. They are less used and are almost completely neglected in ethnobotanical studies. Traditional nativity scenes depicting the birth of Christ are commonly decorated with both vascular plants and bryophytes. The aim of this study was to document the diversity of decorative bryophytes sold during the Advent season at farmers’ markets in Croatia (Southeastern Europe, Balkan Peninsula). Methods Twenty-eight farmers’ markets in the two largest Croatian cities (Zagreb in the continental part and Split in the Mediterranean part) were studied in the search for local vendors selling bryophytes during the pre-Christmas season. The bryophytes collected were identified and analysed with respect to families, growth type, life forms and threat status. Results Among 275 collected specimens, 43 moss and four liverwort species were identified. The mean number of species per vendor was 3.5. The most frequent species were Hypnum cupressiforme, Homalothecium sericeum and Ctenidium molluscum. Mats, wefts and tufts were the most common life-forms, while pleurocarpous prevailed over acrocarpous mosses, as they are usually pinnately branched and form large carpets, suitable for decorations. The overall selection of bryophytes and the decorations made of them were more diverse and abundant in inland Croatia, where 49 vendors at 15 farmers’ markets sold goods containing 43 species. In Mediterranean Croatia, at six farmers’ markets only 29 vendors sold goods, which contained 18 species. A considerable number of species that are less attractive to harvesters were collected non-intentionally, entangled in carpets of other, more frequent species. Among them, Rhodobryum ontariense and Loeskeobryum brevirostre are rare and insufficiently recorded in Croatia so far. Conclusions The present study provided a first perspective on the use of bryophytes in traditional nativity scenes in Croatia and Southeastern Europe, contributing to scarce ethnobotanical documentation of the decorative use of bryophytes in Christmas festivities in Europe and globally.

Key Points How TPEx impacts rituximab effectiveness in iTTP patients is not fully understood. In iTTP patients on therapeutic plasma exchange, rituximab eliminates circulating CD20+ B and T cells in 24 hours for at least 1 week.

Alcoholics Anonymous is, according to the Program's basic documents, a spiritual program - especially regarding Steps 2-3, 5-7, and 11-12. This paper reviews the history of the Program with emphasis on its spiritual background, as well as on the roots of the spiritual side of the program, and showing the spiritual accents in the Big Book of Alcoholics Anonymous. The paper also considers the Christian background of the movement and, more broadly, explores the connection of AA founders William (Bill) Wilson and Dr. Robert (Bob) Smith with several Catholic people, such as Edward (Ed) Dowling, SJ, and John C. Ford, SJ, and indicates some points of contact between the Program and Ignatian spirituality. The paper illustrates the pioneering role of the Alcoholics Anonymous program in integrating spirituality into the process of recovery from and treatment of addictions, an integration that just recently has been embraced by modern psychotherapy and psychiatry. The paper shows the theoretical and spiritual underpinnings of the Program in the religious context. The paper illustrates the orientation of the Program in assisting addicts to integrate into their recovery their own spirituality, a clearer image of God, and personal spiritual and religious progress.

The World Health Organisation predicts a lack of 15 million health professionals by 2030. The lack of licenced professionals is a problem that keeps emerging and is carefully studied on a global level. Strategic objectives aimed at stimulating employment, improving working conditions, and keeping the nurses on board greatly depends on identifying factors that contribute to their turnover. The aim of this study was to present a conceptual model based on predictors of nurses’ turnover intention. Methods: A quantitative, non-experimental research design was used. A total of 308 registered nurses (RNs) took part in the study. The Multidimensional Work Motivation Scale (MWMS) and Practice Environment Scale of the Nursing Work Index (PES-NWI) were used. Results: The conceptual model, based on the binary regression models, relies on two direct significant predictors and four indirect significant predictors of turnover intention. The direct predictors are job satisfaction (OR = 0.23) and absenteeism (OR = 2.5). Indirect predictors that affect turnover intention via job satisfaction are: amotivation (OR = 0.59), identified regulation (OR = 0.54), intrinsic motivation (OR = 1.67), and nurse manager ability, leadership and support of nurses (OR = 1.51). Conclusions: The results of the study indicate strategic issues that need to be addressed to retain the nursing workforce. There is a need to ensure positive perceptions and support from managers, maintain intrinsic motivation, and promote even higher levels of motivation to achieve satisfactory levels of job satisfaction.

Objectives Computerized tomography (CT) is the most accurate method for evaluating pelvic calcifications, which are of utmost importance for planning kidney transplantation (KT). The aim of our study was to evaluate the incidence and distribution of iliac artery calcifications and correlate the novel pelvic calcification score (PCS) with cardiovascular risk factors and graft and overall survival in KT patients. Methods We retrospectively included 118 KT patients operated at our institution with pretransplant pelvic CT. Calcification morphology, circumference and length of both common and external iliac arteries were independently scored by two uroradiologists. PCS was calculated as the total score sum of all three calcification features in all vessels. PCS correlation with graft and patient survival was performed. Results Calcification in at least one vascular segment was found in 79% of patients. PCS was significantly higher in male patients (p = 0.006), patients over 55 years (p < 0.001), and patients on haemodialysis (p = 0.016). Patients with a PCS >3 had significantly shorter graft and overall survival rates (p = 0.041 and p = 0.039, respectively). Conclusions The extent of iliac artery calcification in KT recipients quantified by PCS on pretransplant CT correlates with graft and overall patient survival. A PCS over three was associated with worse clinical outcomes and could become a possible prognostic factor. Advances in knowledge Our novel PCS is a robust method for quantifying iliac artery calcification burden. Since higher a PCS correlates with worse patient and graft survival, PCS has the potential to become a prognostic factor in kidney transplant patients.

Kidney transplantation is the most efficient method of renal replacement therapy. When this method is performed, native urinary bladder is the preferred urinary reservoir. However, in some patients with an anatomically and functionally abnormal lower urinary tract, the urinary bladder cannot be used for transplantation. In these patients, urinary diversion should be performed before kidney transplantation. We present a case of a 32- year-old male patient with orthotopic kidney transplantation performed using a colon pouch (Mainz-pouch III). He was born with severe anomalies including sacral agenesis, anorectal atresia, and hypospadias, which were corrected during childhood. Neurogenic bladder with severe vesicoureteral reflux led to end-stage renal disease. This dysfunctional bladder was unsuitable for kidney transplantation, and a staged approach for future transplantation was chosen. The first step was the creation of urinary diversion. Due to a short appendix, we created a continent, colon pouch (Mainz pouch III). Two years later, orthotopic kidney transplantation was performed using a right cadaveric kidney. The renal vessels were anastomosed to the aorta and inferior vena cava and the pyelon to the native ureter. Four years after transplantation, the patient has stable renal function without any complications. This is the first documented case of using Mainz- pouch III as a reliable option for kidney transplantation in selected patients.

Sarcoidosis is a multisystem granulomatous disease of unknown origin with a variable and often unpredictable course and pattern of organ involvement. In this study we sought to identify specific bronchoalveolar lavage (BAL) cell gene expression patterns indicative of distinct disease phenotypic traits.RNA sequencing by Ion Torrent Proton was performed on BAL cells obtained from 215 well characterized patients with pulmonary sarcoidosis enrolled in the multicenter Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study. Weighted Gene Co-expression Network Analysis (WGCNA) and non-parametric statistics were used to analyze genome wide BAL transcriptome. Validation of results was performed using a microarray expression data set of an independent sarcoidosis cohort (Freiburg, Germany (n=50)).Our supervised analysis found associations between distinct transcriptional programs and major pulmonary phenotypic manifestations of sarcoidosis including; TH1 and TH17 pathways associated with hilar lymphadenopathy; TGFB1 and MTOR signaling with parenchymal involvement, and IL7 and IL2 with airway involvement. Our unsupervised analysis revealed gene modules that uncovered four potential sarcoidosis endotypes including hilar lymphadenopathy with increased acute T cell immune response; extraocular organ involvement with PI3K activation pathways; chronic and multiorgan disease with increased immune response pathways; and multiorgan with increased IL-1 and IL-18 immune and inflammatory responses. We validated the occurrence of these endotypes using gene expression, pulmonary function tests and cell differentials from Freiburg. Taken together our results identify BAL gene expression programs that characterize major pulmonary sarcoidosis phenotypes and suggest the presence of distinct disease molecular endotypes.Take home messageGenome wide BAL transcriptomics identified novel gene expression profiles associated with distinct phenotypic traits in sarcoidosis and is suggestive of the presence of novel molecular and clinical sarcoidosis endotypes that could help with further understanding of this heterogenous disease.

Purpose During arthroscopy training process, determination of anteromedial portal is more difficult in contrast with anterolateral portal and frequently results in suboptimal position, and longer operating times. The aim of our study was to identify an anatomical landmark which could facilitate anteromedial portal placement. Methods The relationship of the cutaneous veins at the anteromedial side of the knee was analysed regarding the optimally placed anteromedial portal and anatomical landmarks of the anteromedial part of the knee in 70 patients undergoing knee arthroscopy. The study was designed as case series. Results In 70% of the patients, the joining of the cutaneous veins was seen after transillumination resembling Y letter. In the remaining 30% of patients, a solitary vein with a curve which corresponds to the joining point was observed. The curve and the joining was located adjacent to optimally placed anteromedial portal measured 2 cm +/- 0.3 from the medial patellar tendon border, and 1.1 cm +/- 0.1 from the palpable edge of the medial tibial plateau. Conclusions The "Y sign" can assist knee arthroscopy trainees in anteromedial portal placement, with the resulting avoidance of multiple puncturing of the skin with the needle, shorter operating room times to find the optimal portal placement, and potential reduction of damage to intraarticular structures.

Metabolic syndrome, characterized by obesity, low-grade inflammation, insulin resistance, hyperglycemia, dyslipidemia and hypertension, is a major risk factor for cardiovascular mortality. Preclinical studies on recently discovered classes of lipids – fatty acid esters of hydroxy fatty acids (FAHFA) have revealed their anti-inflammatory and insulin- sensitizing potential. The FAHFA levels are significantly decreased in insulin-resistant individuals, their application exhibited anti- inflammatory effects and restoring the glucose- insulin homeostasis. The aim of our research was to analyze the overall FAHFA composition in a common diet, as only a partial FAHFA composition has been revealed so far (only the PAHSA subclass was analyzed in a few foods). A new approach to the FAHFAs analysis includes nano-LC and post-column modifier followed by negative ion mass spectrometry, in order to obtain maximum sensitivity. Analysis of different foods – oat (whole grain, coarse flakes and fine flakes), apple, clementine, lemon, strawberry, blueberry, mango, kiwi, avocado, pineapple, banana, onion, garlic, cherry tomato, carrot, parsley root, pepper and radish – exhibited wide inter-food variation in the FAHFA profiles. Sixteen analyzed FAHFAs (palmitic, oleic, palmitoleic and stearic hydroxy-esters) showed microgram to low nanogram levels (0.165 ng/g – 32 μg/g FW), with the highest abundancy in oat, clementine, garlic and pineapple. Stearic acid hydroxy stearic acid (SAHSA) was the most abundant FAHFA, especially in the food with antioxidative, anti-inflammatory and beneficial metabolic effects. In contrary, the PAHSA - previously proven to have the strongest antihyperglycemic and insulin-sensitizing effects, was not present in some foods (radish, avocado, mango, lemon, cherry tomato, kiwi). Our study proves the importance of overall FAHFA analysis in food (especially in a functional food), because of their potential metabolic benefits and possible future incorporation in special diets.

Aim: To assess the immunomodulatory effect of tonsil-derived mesenchymal stem cells (MSCs) on T-lymphocyte proliferation and cytokine production. Methods: Tonsils were obtained from children aged 3 to 12 years (n = 15) who underwent tonsillectomy for obstructive sleep apnea from April 2012-October 2014 at the Merkur University Hospital, Zagreb. Tonsil-derived MSCs were co-cultured with peripheral blood mononuclear cells (PBMCs) and phytohemagglutinin as a mitogen. PBMCs were induced to differentiate into T helper 1 or T helper 2 cells in the presence or absence of tonsil-derived MSCs, after which the production of interferon-gamma in T helper 1 and interleukin-4 in T helper 2 cells was assessed. Results: Tonsil-derived MSC suppressed phytohemagglutinin-induced proliferation of PBMCs. Compared with controls, tonsil-derived MSC co-culture significantly decreased interferon-gamma production (P

Contains fulltext : 238746.pdf (Publisher’s version ) (Closed access) Recent biomarker innovations hold potential for transforming diagnosis, prognostic modeling, and precision therapeutic targeting of traumatic brain injury (TBI). However, many biomarkers, including brain imaging, genomics, and proteomics, involve vast quantities of high-throughput and high-content data. Management, curation, analysis, and evidence synthesis of these data are not trivial tasks. In this review, we discuss data management concepts and statistical and data sharing strategies when dealing with biomarker data in the context of TBI research. We propose that application of biomarkers involves three distinct steps-discovery, evaluation, and evidence synthesis. First, complex/big data has to be reduced to useful data elements at the stage of biomarker discovery. Second, inferential statistical approaches must be applied to these biomarker data elements for assessment of biomarker clinical utility and validity. Last, synthesis of relevant research is required to support practice guidelines and enable health decisions informed by the highest quality, up-to-date evidence available. We focus our discussion around recent experiences from the International Traumatic Brain Injury Research (InTBIR) initiative, with a specific focus on four major clinical projects (Transforming Research and Clinical Knowledge in TBI, Collaborative European NeuroTrauma Effectiveness Research in TBI, Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe, and Approaches and Decisions in Acute Pediatric TBI Trial), which are currently enrolling subjects in North America and Europe. We discuss common data elements, data collection efforts, data-sharing opportunities, and challenges, as well as examine the statistical techniques required to realize successful adoption and use of biomarkers in the clinic as a foundation for precision medicine in TBI.

Lately, we became witnesses a rapid increase in the use of silver coatings, based on nanocrystalline technology, for various indications, including burns. Although the manufacturers of such coatings still state with caution that the indication of the use of such coatings for the first and second degree of burns, more and more often such coatings are also used for third-degree burns of large areas.

Patients with urolithiasis, particularly hypercalciuria, may have reduced bone mineral density (BMD). There are numerous risk factors contributing to reduction of BMD such as advanced age, sedentary life-style, smoking, low calcium intake, etc. The aim of our study was to investigate the association of lifestyle risk factors and daily intake of milk and dairy products with determinants of BMD in a group of recurrent calcium stone formers (RSF) compared with healthy subjects (HS). The study was carried out at the De-partment of Mineral Research, Faculty of Medicine in Osijek, Croatia. The study included 144 subjects, i.e. 56 RSF and 78 HS. BMD was assessed by dual-energy x-ray absorptiometry. A standard self-reported questionnaire was used to collect data on lifestyle risk factors. Current dietary intake was assessed by personal interview that included questions about milk and dairy product intake. Low BMD was observed in 44.64% of RSF and 35.90% of HS. RSF consumed significantly less milk and dairy products than HS. Calcium restriction in dietary recommendations might be unnecessary due to the impact on bone mineral loss in RSF and dual-energy x-ray absorptiometry should be included in the routine evaluation of RSF., Bolesnici s urolitijazom, osobito oni s hiperkalciurijom, imaju smanjenu koštanu mineralnu gustoću (bone mineral density, BMD). Rizični čimbenici gubitka koštane mase su uznapredovala dob, sjedilački način života, pušenje i smanjen unos kalcija. Cilj našeg istraživanja bio je ustanoviti povezanost rizičnih čimbenika i dnevnog unosa mlije-ka i mliječnih prerađevina s odrednicama BMD u bolesnika s recidivirajućom kalcijskom urolitijazom te ih usporedi-ti sa zdravim ispitanicima. Istraživanje je provedeno na Zavodu za mineralni metabolizam Medicinskog fakulteta u Osijeku. U istraživanju su sudjelovala 144 ispitanika, od čega 56 bolesnika s recidivirajućom kalcijskom urolitija-zom i 78 zdravih ispitanika. BMD je određen metodom dvoenergetske apsorpciometrije X zraka (DXA). Podatci o čimbenicima rizika dobiveni su anketnim upitnikom, a unos hrane je ocijenjen osobnim intervjuom koji je uključi-vao pitanja o unosu mlijeka i mliječnih proizvoda. Snižen BMD zabilježen je u 44,64% bolesnika s recidivirajućom urolitijazom i u 35,90% zdravih ispitanika. Bolesnici s recidivirajućom urolitijazom konzumirali su znatno manje mlijeka i mliječnih proizvoda u odnosu na zdrave ispitanike. Nepotrebna je preporuka smanjenog unosa kalcija bolesnicima s recidivirajućom urolitijazom zbog utjecaja na gubitak koštane mase, a DXA treba biti dio rutinske procjene bolesnika s recidivirajućom urolitijazom.

Left ventricular hypertrophy is a common adaptive response to increased cardiac workload. Cardiomyocytes growth and increase in contractile force are conditioned by sufficient energy production, which implies appropriate mitochondrial function. The 60kDa heat shock protein (HSP60) is a chaperone essential for mitochondrial proteostasis, but when translocates from mitochondria, it can also act as a potent inflammatory mediator binding to toll-like receptors (TLRs). In this study, we aimed to compare the expression pattern of HSP60, TLR2, and TLR4 in hypertrophic vs non-hypertrophic, normal human myocardium. We further examined whether HSP60 in situ binds to TLRs in hypertrophic myocardial tissue. In addition, expression of activated downstream targets of TLR 2/4 pathways was also evaluated. For this purpose, immunohistochemical expression analyses were performed on myocardial tissue samples obtained during the autopsy of human subjects in which left ventricular hypertrophy was the only cardiopathological finding and had died from sudden cardiac death, as well as from the subjects without any cardiac pathology, that died by unnatural death (accident or suicide). Double immunofluorescence was used to examine HSP60 translocation, while proximity ligation assay (PLA) was performed to assess HSP60 and TLRs interactions. Hypertrophic myocardium showed significantly higher expression of HSP60, TLR2, and TLR4 compared to normal myocardium. Furthermore, in hypertrophic cardiomyocytes, we found membrane translocation of HSP60 and signs of HSP60/TLR interactions. Conclusion: The obtained data point to an important supportive role of HSP60 in adaptive cardiomyocytes growth, while concomitant induction of TLR2 and TLR4 candidates HSP60-TLRs interactions as an early events duriing pathogenesis of secondary complications consequently to the left ventricular hypertrophy.

Source at https://doi.org/10.1186/s13054-018-2241-4. Licensed CC BY-NC-ND 4.0. Background: We aimed to investigate the extent of the agreement on practices around brain death and postmortem organ donation. Methods: Investigators from 67 Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study centers completed several questionnaires (response rate: 99%). Results: Regarding practices around brain death, we found agreement on the clinical evaluation (prerequisites and neurological assessment) for brain death determination (BDD) in 100% of the centers. However, ancillary tests were required for BDD in 64% of the centers. BDD for nondonor patients was deemed mandatory in 18% of the centers before withdrawing life-sustaining measures (LSM). Also, practices around postmortem organ donation varied. Organ donation after circulatory arrest was forbidden in 45% of the centers. When withdrawal of LSM was contemplated, in 67% of centers the patients with a ventricular drain in situ had this removed, either sometimes or all of the time. Conclusions: This study showed both agreement and some regional differences regarding practices around brain death and postmortem organ donation. We hope our results help quantify and understand potential differences, and provide impetus for current dialogs toward further harmonization of practices around brain death and postmortem organ donation.

Distress effects are widely examined in cross-sectional studies with less known about effects on future health. This review summarizes distress impacts on health among adults in prospective studies and describes available distress measurement tools. Four inter-disciplinary databases were searched. Effects of distress on mortality and other outcomes were reviewed and estimated in a meta-analysis. A total of 19 studies were assessed which incorporated 10 distress tools. Distress had a detrimental effect on health regardless of the population studied, distress tool used, and health outcome examined. There was an increased mortality risk among those reporting high versus low distress (pooled hazard ratio (95% confidence interval) = 1.29 (1.15–1.46)).

Objectives To investigate differences in hemodynamic profile between hyperadrenergic and non-hyperadrenergic postural orthostatic tachycardia syndrome (POTS) in response to head-up tilt test (HUTT). Methods Ten patients with hyperadrenergic and 33 patients with non-hyperadrenergic POTS underwent HUTT consisting of a 10-min supine phase and 30-min 70° tilted phase. Heart rate (HR), systolic and diastolic blood pressure (dBP), and heart rate variability (HRV) parameters of the two groups were compared. Results Hyperadrenergic patients had higher supine HR (82.6 ± 16.3 bpm vs. 73.8 ± 10.4 bpm, p=0.048). Supine HRV analysis showed significantly lower cardiac vagal activity and possible predominance of cardiac sympathetic activity in the hyperadrenergic group. Non-hyperadrenergic patients had lower dBP during the first four minutes of tilt. Furthermore, 60% of non-hyperadrenergic patients had lower average dBP in the 1st minute of tilted phase when compared to supine values, whereas only 2 of 10 hyperadrenergic patients exhibited the same response. Syncope or intolerable symptoms, causing early ending of HUTT, developed earlier in the non-hyperadrenergic group (8.9 ± 6.8 min vs. 21.2 ± 3.5 min, p=0.001). Conclusion Hyperadrenergic and non-hyperadrenergic type of POTS seem to have distinctly different response to HUTT. Significance This study has shown significant differences in hemodynamic response to HUTT between hyperadrenergic and non-hyperadrenergic type of POTS indicating possible differences in their pathophysiology.

With the increasing incidence of obesity and metabolic syndrome the incidence of nonalcoholic fatty liver ­disease (NAFLD) is increasing as well. These patients have a significant risk of progression to the end-stage liver disease, but also these patients are at increased risk of developing hepatocellular carcinoma. In recent years there is a growing ­number of publications that support the idea that NAFLD is not just a disease that is limited to the liver, but is associated with a number of extrahepatic manifestations. For example, NAFLD increases the risk of type 2 diabetes mellitus, cardiovascular diseases and chronic kidney disease. Consequently NAFLD has become a growing public health problem. A number of sub-specialists as well as primary care physicians should be aware of these potential extrahepatic associations, given the availability of numerous methods for screening in clinical practice. The above approach is important in order to recognize potentially modifiable events in the early stages, and thus manage them and at least prevent the progression of certain diseases.

This chapter will discuss the recent literature of macrocycles and drug-like property space moving beyond the rule of five (bRo5). Trends in chemical classes that fall within this definition are discussed and the impact of the latest technologies in the field assessed. The physicochemical properties, which have provided both successes and challenges, especially in scale-up, are discussed. A recent patent literature is reviewed and the chapter concludes with a perspective on the future of macrocyclic drug discovery.

Although drowning in rainwater tanks is a generally rare phenomenon, this method for suicide has been observed in parts of Croatia. Review of autopsy records at the University of Rijeka, Croatia, was undertaken from 1987 to 2016 to examine this phenomenon. Of 469 drowning deaths, there were 35 suicides in rainwater tanks (7.5%). Overall drowning deaths showed no temporal trends. In contrast, suicidal drownings in rain water tanks showed a marked decline over the years, with 15 cases in 1987-1991, seven in 1992-1996, six in 1997-2001, six in 2002-2006, one in 2007-2011, and none in 2012-2016. Thus, suicidal drowning cases as a percentage of overall drownings dropped from 18% to zero (p

BACKGROUND Immune tolerance induction (ITI) in patients with congenital hemophilia A is successful in up to 70%. Although there is growing understanding of predictors of response to ITI, the probability and predictors of inhibitor recurrence after successful ITI are not well understood. OBJECTIVES To determine the association of clinical characteristics, particularly adherence to factor VIII (FVIII) prophylaxis after ITI, with inhibitor recurrence in patients with hemophilia A who were considered tolerant after ITI. METHODS In this multicenter retrospective cohort study, 64 subjects with FVIII level

Background: Peritoneal dialysis (PD) catheter placement is usually performed using general or local anesthesia. We present our PD catheter placement experience using an ultrasound-guided transversus abdominis plane (TAP) block, which is a regional anesthesia technique. Methods: In this study, we analyzed 33 patients from our center with ESRD who underwent PD catheter placement using a TAP block between June 2011 and April 2014. Results: The TAP block was successful for 29/33 (87.9%) patients. Four patients (12.1%) had pain at the incision site and required general anesthesia. There were no anesthesia-, surgery- or catheter-related complications. Conclusion: ESRD patients have a substantial number of comorbidities that can be negatively influenced by general anesthesia. Because regional anesthesia has no systemic effect, this procedure could be recommended for this group of patients. A TAP block is an effective, safe method and can be used as the principal anesthesia technique for PD catheter placement.

More than 90% of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients receive red blood cell (RBC) or platelet transfusions in the peritransplantation period. We tested the hypothesis that transfusions are associated with the development of severe (grade III-IV) acute graft-versus-host disease (aGVHD) or mortality after allo-HSCT in a retrospective study of 322 consecutive patients receiving an allogeneic bone marrow or granulocyte colony-stimulating factor-mobilized blood stem cell graft for a hematologic malignancy. Counting transfused RBC and platelet units between day −7 pretransplantation and day +27 post-transplantation, but excluding transfusions administered after a diagnosis of aGVHD, yielded medians of 5 RBC units and 2 platelet units transfused. Sixty-three patients (20%) developed a maximal grade III-IV aGVHD with onset up to day +150 post-transplantation (median aGVHD onset of 28 days). HLA mismatch (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.2 to 4.7; P = .01), and transfusion of more than the median number of RBC units (HR, 2.1; 95% CI, 1.1 to 3.7; P = .02) were independently associated with greater risk of grade III-IV aGVHD in a multivariable analysis model. Disease risk strata (HR, 1.7; 95% CI, 1.2 to 2.4 for high risk versus low risk; P = .005) and transfusion of more than the median number of RBC units (HR, 1.4; 95% CI, 1.0 to 2.0; P = .054) were independently associated with inferior overall survival. These data support our hypothesis that peritransplantation RBC transfusions are associated with the risk of developing severe aGVHD and worse overall survival following allo-HSCT, and suggest that strategies to reduce routine RBC transfusion may favorably reduce the incidence and severity of GVHD.

During routine diagnostic laboratory work, the clinical microbiologist observed an increase of Acinetobacter baumannii isolates with three different carbapenem susceptibility patterns: susceptible, intermediate and resistant. Isolates belonging to the same carbapenem susceptibility phenotype exhibited identical susceptibility/resistance patterns to non-β-lactam antibiotics. This prompted us to analyse the mechanisms of carbapenem-resistance and the molecular epidemiology of the isolates. A total of 59 A. baumannii isolates were analysed and grouped according to their susceptibility to imipenem: group 1 were susceptible (N=24), group 2 were intermediate (N=8) and group 3 were resistant (N=27) to imipenem. PCR and sequencing was used to detect resistance genes. Genotyping of the isolates was performed by PFGE and MLST. Out of 27 resistant isolates, 20 harboured blaOXA-40-like and 7 blaOXA-23-like genes. ISAba1 was found upstream of blaOXA-51 and blaOXA-23 genes. PFGE genotyping demonstrated the existence of three major A. baumannii clones in GH Pula and determination of sequence groups showed that the isolates belonged to international clones commonly associated with multidrug-resistance. MLST (performed on six isolates) showed diverse population structure of isolates belonging to the same cluster, including ST 195, ST 231, ST 775 and ST 1095. A previous study conducted in 2009-2010 showed that reduced susceptibility to carbapenems in GH Pula was only associated with upregulation of the intrinsic OXA-51 β-lactamase. In this study a shift to isolates with acquired oxacillinases, belonging to two major clones was reported. Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

PURPOSE: Postprandial hypotension (PPH) has been associated with increased risk of syncope, falls, stroke, angina and mortality. As the majority of patients with PPH are asymptomatic, the diagnosis is often overlooked. The aim of this study was to perform a systematic review and meta-analysis of available scientific evidence on the likelihood of PPH in neurological diseases. ----- METHODS: A systematic review of the literature (PubMed library, Cochrane Database for Systematic Reviews and Cochrane Central Register of Controlled Trials for results up to January 2017) identified 327studies, of which 11 reported the frequency of PPH in patients with neurological diseases compared to healthy controls. These 11 studies were on patients with Parkinson’s disease (PD; n = 6 studies), multiple system atrophy (MSA; n = 1), Alzheimer’s disease (AD; n = 1)and diabetic neuropathy (DN; n = 2). ----- RESULTS: The meta-analysis revealed that patients with neurological diseases had a significantly higher frequency of PPH than healthy controls [147/289 patients vs. 41/217 controls; odd ratio (OR) 5.23, 95% confidence interval (CI) 2.90–9.45, p

Renal cell carcinoma (RCC) is the most common malignant tumor of the kidney. The major goal of imaging techniques is to correctly differentiate between benign and malignant renal lesions. We present the cases of six patients with renal masses that were interpreted completely differently based on ultrasound (US) and computerized tomography (CT) findings. From January 1st, 2008 to March 1st, 2014, 307 patients from our center underwent nephrectomy for RCC. In all patients US and CT were performed before the operation. In six patients, the US indicated a focal, solid renal lesion that was interpreted by CT as a cystic lesion (Bosniak II-III). Because discrepancies were evident, renal biopsies were performed. The biopsies revealed RCC in the six patients, all of whom underwent subsequent nephrectomy. All of the patients were confirmed to have macroscopically solid RCC without any cystic components. In most cases, CT is the most accurate diagnostic technique for the clinical diagnostic classification of renal masses. In cases where US characterizes a renal lesion as solid, despite CT findings of a cystic lesion, kidney biopsies are recommended. The 6 cases reported here support our belief that, in diagnostic processes of RCC, these techniques should be complementary used.

Objective To investigate the optimal timing for blood sample collection of catecholamines and the possible correlations between neurohumoral and hemodynamic responses to prolonged head-up tilt (HUT) in postural orthostatic tachycardia syndrome (POTS). Methods Nineteen patients underwent a 30-minute, 70° HUT test. Blood samples (norepinephrine (NE), epinephrine and dopamine) were taken in the 10th minute of supine, and 10th, 20th and 30th minutes of HUT. Results There were no significant differences in the proportion of high and normal standing NE patients in the different time points. Mean NE (nmol/L) values in 10th, 20th and 30th minute of HUT were 4.37, 4.87, and 4.35 in the high standing NE, and 2.49, 2.59 and 2.88 in the normal standing NE group. High standing NE patients had higher blood pressure (BP) during the first 6 min of HUT (2nd minute after the HUT systolic BP (sBP): 118.29 ± 15.65 vs. 95.70 ± 13.43, p = 0.004; diastolic BP (dBP): 78.71 ± 6.68 vs. 65.10 ± 9.04, p = 0.003), while normal standing NE patients exhibited a drop in BP compared to resting values during the same time period. The normal standing NE group exhibited a progressive increase in norepinephrine values during the HUT. Conclusion One blood sample taken at the 10th minute of HUT correctly identifies high and normal standing NE POTS patients, but a small number of patients (1 out of 19, 5.2%) can be misidentified. High and normal standing NE POTS patients display distinctly different neurohumoral and hemodynamic responses to HUT.

Animal-inflicted injuries to humans are a major public health problem around the world resulting in great morbidity, money loss, and mortality. They are related to wild and domestic animals alike. Animals can cause injuries by various mechanisms--biting, stinging, crushing, goring, stomping, butting, kicking, pecking, etc. We present a case of a ram's attack with fatal consequences. A 4-year-old, 120 kg jezersko-solčava breed ram with prior history of aggressive behavior inflicted multiple injuries to his 83-year-old owner, who died in the hospital a few hours later due to severe blunt force injuries sustained in the attack. The autopsy revealed the cause of death to be multiple injuries of the thorax and the head. Sheep, even though they are not considered aggressive or large farm animals such as cattle and horses, can inflict serious injuries with devastating results.

Summary The aim of this study was to evaluate the effect of haemophilia disease severity and potential intermediaries on body mass index (BMI) in patients with haemophilia. A secondary analysis of a cross-sectional study of 88 adults with haemophilia was undertaken. On bivariate analysis, persons with severe haemophilia had 9.8% lower BMI (95% CI −17.1, −3.0) than persons with non-severe haemophilia. The effect of haemophilia severity on BMI varied significantly by human immunodeficiency virus (HIV) status. Among HIV-positive subjects, haemophilia severity was not associated with BMI (+5.0%, 95% CI −22.4, 41.9). Among HIV-negative subjects, severe haemophilia was associated with 15.1% lower BMI (95% CI, −23.6, −5.7). Older (>41 years) HIV-negative subjects with severe haemophilia had a BMI that was 24.8% lower (95% CI −39.1, −7.0) than those with non-severe haemophilia. No statistically significant association was detected between BMI and severe vs. non-severe haemophilia for younger HIV-negative subjects. Although joint disease, as measured by the World Federation of Hemophilia (WFH) joint score, did not influence the association between haemophilia disease severity and BMI, adjustment for the atrophy component of the WFH score reduced the association between haemophilia severity and BMI by 39.1–69.9%. This suggested that muscle atrophy mediated at least part of the relationship between haemophilia severity and BMI. Haemophilia disease severity is associated with BMI and appears to be mediated by muscle atrophy of surrounding joints. This association appears to be modified by HIV status and possibly age.

Haemophilia has been associated with low bone mineral density (BMD). However, prior clinical studies of this population have neither clearly elucidated risk factors for development of low BMD nor identified who may warrant screening for osteoporosis. The aim of the study was to evaluate the relationship between BMD and haemophilic arthropathy and other demographic and clinical variables. We undertook a cross-sectional study of BMD in adult men with haemophilia. Measures of predictor variables were collected by radiographic studies, physical examination, patient questionnaires and review of medical records. Among 88 enrolled subjects, the median age was 41 years (IQR: 20); median femoral neck BMD (n = 87) was 0.90 g cm(-2) (IQR: 0.24); and median radiographic joint score was 7.5 (IQR: 18). Among subjects

Patients with cancer are at high risk for developing venous thromboembolism (VTE), and the presence of a central venous catheter (CVC) further increases this risk. CVC-related VTE has serious implications related to the loss of vascular access, development of pulmonary embolism, recurrent VTE, infections and post-thrombotic syndrome. The pathogenesis of CVC-related VTE is complex and multifactorial, with risk factors associated with the catheter, the vessel selected for insertion and the underlying cancer as well as the anti-cancer therapy. Clinical presentation of CVC-related VTEs is often non-specific, and ultrasonography is the most commonly used radiological diagnostic test. Management of CVC-related VTE in patients with cancer requires a balance between the need for venous access, the risk of VTE recurrence and the risk of bleeding from treatment-induced thrombocytopenia. Effective VTE prophylaxis methods have yet to be defined. Ongoing studies are evaluating the role of newer oral antithrombotic agents and alternative interventional strategies for the prevention and treatment of CVC-related VTE in patients with cancer.

Physical activity and functional ability are important determinants of quality of life and these metrics are affected by both haemophilia and ageing. Outside haemophilic arthropathy, risk factors leading to reduced physical activity and function in people with haemophilia (PWH) are under-explored. The purpose of this analysis was to determine risk factors for reduced physical activity and functional limitations in PWH. A secondary analysis was conducted on data indexing physical activity and functioning of 88 PWH using data originally collected as part of a cross-sectional study at a single large haemophilia treatment centre. The Framingham Physical Activities Index (PAI), the Hemophilia Activities List (HAL) and the Timed Up-and-Go Test (TUG) were the outcome measures. The World Federation of Haemophilia (WFH) orthopaedic joint score was used as a measure of arthropathy. Multiple linear regression analysis was used to assess the relationship between the outcome measures and covariates. Worsening WFH joint score was independently associated with all three outcome measures (P < 0.05). Increasing age was associated with reduced PAI and increased TUG time (P < 0.05). The HAL summary score was decreased in patients with chronic liver disease (P = 0.006). The adjusted R(2) for each model was ≤ 0.35. This study provides evidence for the relationship between arthropathy and reduced physical functioning/activity, but also highlights that much of the variation in physical functioning/activity is not explained by haemophilia-related characteristics.

BackgroundPeritoneal dialysis (PD) catheter surgery can be performed using regional anesthesia. We present our PD catheter placement and extraction experience using ultrasound-guided transversus abdominis plane (TAP) block.MethodsIn the present study, we analyzed 74 patients from our center with end-stage renal disease (ESRD) who underwent PD catheter placement (60 patients) and removal (14 patients) using a TAP block between June 2011 and December 2015.ResultsThe TAP block was successful for 55/60 (91.7%) patients (insertion) and 13/14 (92.9%) patients (extraction). Other patients had pain at the incision site and required general anesthesia. There were no anesthesia-, surgery- or PD catheter-related complications.ConclusionThe TAP block is a safe and effective technique not only for high-risk ESRD patients but for all patients undergoing PD catheter placement or extraction.

Introduction Poor adherence to factor replacement therapy among patients with haemophilia can lead to joint bleeding and eventual disability. Aim The aim of this study was to determine patient-related characteristics associated with adherence to factor replacement in adults with haemophilia. Methods Adults with haemophilia were recruited to participate in this cross-sectional study. Adherence was measured using either the Validated Hemophilia Regimen Treatment Adherence Scale (VERITAS)-Pro or the VERITAS-PRN questionnaire. Simple and multiple regression analyses that controlled for confounding were performed to determine the association between patient-related characteristics and adherence to factor replacement therapy. Results Of the 99 subjects enrolled, all were men; 91% had haemophilia A and 78% had severe disease. Age ranged from 18 to 62 years. Most (95%) had functional health literacy; but only 23% were numerate. Mean adherence scores were 45.6 (SD 18) and 51.0 (SD 15) for those on a prophylactic and those on an episodic regimen, respectively, with a lower score indicating better adherence. On multivariable analysis, being on any chronic medication, longer duration followed at our haemophilia treatment centre, higher physician trust and better quality of life were associated with higher adherence. A history of depression was associated with lower adherence. Conclusion Two potentially modifiable characteristics, physician trust and depression, were identified as motivator and barrier to adherence to factor replacement therapy. Promoting a high level of trust between the patient and the healthcare team as well as identifying and treating depression may impact adherence to factor replacement therapy and accordingly reduce joint destruction.

The purpose of this study was to create a fibrin-based human skin substitute in vitro with epidermal and dermal component and to assess its healing potential in deep partial and full thickness burns. Fibrin scaffolds were prepared from commercial fibrin glue kits. Human fibroblasts were cultured in fibrin gel. Human keratinocytes were seeded on the top of the gel. Viability of cells was determined fluorimetrically. Scanning electron microscope and immunocytochemistry analysis of cultured cells were performed. After hydrosurgical preparation of deep burn necrotic tissue, wound bed was prepared for skin substitutes. Progress of healing was documented using visual estimation and photos. Scanning electron microscope images showed good cell attachment and colony spreading of keratinocytes and fibroblasts on fibrin scaff old. Immunofluorescent staining of cell cultures on fibrin scaffold showed expression of vimentin, a marker of fibroblast cells, cytokeratin 19, a marker of epithelial stem cells, as well as involucrin, a marker of differentiated keratinocytes. Clinical results clearly showed that appearance of the skin did not differ significantly from the areas of transplanted skin using split-thickness skin graft techniques. In conclusion, using these fibrin-cultured autografts on massive full-thickness burn resulted in good healing.

Background Encephalocraniocutaneous lipomatosis is a rare congenital neurocutaneous syndrome resulting from ectomesodermal dysgenesis and characterized by unique hairless scalp lesions in the form of nevus psiloliparus, ipsilateral ocular malformations, and central nervous system anomalies. According to the 2009 diagnostic criteria proposed by Moog et al., ocular abnormalities are supposed to be the most consistent feature of encephalocraniocutaneous lipomatosis. Patient Description We describe an 18-year-old girl with most of the central nervous system manifestations of encephalocraniocutaneous lipomatosis, major skin alterations including nevus psiloliparus, but no ocular involvement. Conclusion Our patient suggests more variability in clinical features and a more complex genetic/embryonic etiology of encephalocraniocutaneous lipomatosis.

The study evaluated secular trends in dental development during a period of 30 years, correlation between dental and chronological age in Istria and the littoral region of Croatia. The sample consisted of 1000 panoramic radiographs of children, aged 6-16 years (mean 10.0±1.8), taken in the period 1977-1979 (N=500 ; 243 females) and 2007 -2009 (N=500 ; 299 females). Dental age was assessed according to Demirjian's method. Correlation between chronological and dental age was linear, positive, high and statistically significant in both periods and genders, ranging from 0.73 to 0.86. Dental age was underestimated when compared to chronological age by one year on average, more 30 years ago (-1.35±1.17) than today (-0.63±1.09), less for girls (-0.80±1.22) than boys (-1.21±1.10). A statistically significant positive secular trend in acceleration of dental development was present of 0.72 year during the 30 year period, and was more significant in girls than boys (0.83 and 0.51 year acceleration).

A 52-year-old woman was admitted with a painful right breast tumor measuring more than 20 cm in largest diameter, which ulcerated the overlying skin. The lesion had appeared 4 years previously but the patient hesitated to seek medical care due to 'fear of cancer'. Microscopically, the tumor was composed of spindle cells that formed cuffs around multiple open tubules and ducts set in an abundant, myxoid stroma. The spindle cells had significant atypia with nuclear pleomorphism, occasional cytoplasmic vacuolation and moderate mitotic activity. The ducts and lobules surrounded by the proliferating tumor cells had minimal distortion, with a pericanalicular growth pattern devoid of the phyllodes pattern. The tumor had a multinodular growth pattern with coalesced and individual tumor nodules, the latter being found mostly at the periphery of the lesion. On immunohistochemistry the tumor cells were positive for smooth muscle actin, CD34, and vimentin, and focally positive for CD10. A diagnosis of low-grade periductal stromal sarcoma (PDSS) with myxoid features was established. PDSS is a distinct low-grade breast sarcoma, the appropriate diagnosis of which requires extensive tumor sampling and additional broad immunohistochemistry. PDSS should not be confused with other spindle cell breast tumors because they require different treatment.

Background The aim of this study was to identify risk factors associated with survival after pneumonectomy for non-small cell lung cancer. Methods This was a retrospective study of 155 patients who underwent a pneumonectomy for non-small cell lung cancer at Roswell Park Cancer Institute between 1986 and 2002. Medical record review ascertained information on preoperative assessment including pulmonary function tests and clinical characteristics, postoperative complications, and overall survival. Multivariate Cox proportional hazards models to calculate the hazard ratios and 95% confidence intervals were used. Kaplan-Meier cumulative survival curves (with log-rank p values) were generated for selected variables. Results The median age was 58 years at the time of surgery; 65% of patients were males. Squamous cell carcinoma (54%) and adenocarcinoma (33%) were the predominant histologic types. The median time to relapse was 11 months, and the overall median survival was 15.6 months. An American Society of Anesthesiology score of less than 3, squamous histology, and lower pathologic stage were significant independent predictors of improved survival. Current smoking status (hazard ratio=1.87, 95% confidence interval: 1.30 to 2.70) and left tumor location (hazard ratio=1.40, 95% confidence interval: 0.97 to 2.03) were associated with a trend toward poorer survival. Sixty-four patients (41%) had postoperative complications. The operative mortality from pneumonectomy was 9 of 155 (5.8%). Conclusions American Society of Anesthesiology score, histology, pathologic stage, smoking status, and location of the tumor were important predictors of survival in this patient sample. Pneumonectomy for non-small cell lung cancer carries an acceptable operative mortality and provides an important survival benefit.

Introduction Distress may affect a patient's ability to cope with and manage disease. Aim To report distress prevalence in adult patients with bleeding disorders and determine whether specific clinical and health characteristics, including disease severity and employment status, are associated with distress. Methods Patients who visited a Haemophilia Treatment Centre (HTC) between January 1st, 2012 through February 28th, 2014 and who completed a distress screen, pain screen and questionnaire were evaluated cross sectionally. Distress was measured by the National Comprehensive Cancer Network Distress Management Tool, which allowed patients to rate recent distress on a 0–10 point scale. A rating of five or more was categorized as high distress. Pain was measured by the Brief Pain Inventory Short Form, which asked patients to rate pain types on 0–10 point scales. Patients reported employment and other demographic and behavioural information on the questionnaire. Primary diagnosis, age, HIV and HCV status were abstracted from medical records. Adjusted logistic regression was used to identify distress associations. Results High distress prevalence among 152 patients with bleeding disorders was 31.6%. Unemployment, disability, greater depressive symptoms and higher pain were associated with high distress in multivariable models. Bleeding disorder diagnosis, race/ethnicity, HIV/HCV status and on-demand treatment regimen were not associated with high distress. Conclusion Distress among patients with congenital bleeding disorders followed at a comprehensive HTC was high and similar to that reported among patients with cancer. Future research should determine whether distress impacts clinical outcomes in patients with bleeding disorders as demonstrated in other chronic disorders.

In daily practice, neuroimaging studies are frequently performed for the management of childhood headache. The aim of this study was to determine whether there is significant discrepancy between clinical practice and clinical practice guidelines on the indications for neuroimaging studies. Medical records of children with chronic headache, aged 2 to 18 years and treated at Rijeka University Hospital Center, Kantrida Department of Pediatrics, were retrospectively reviewed. Indications for brain magnetic resonance imaging and computed tomography (MRI/CT) scanning were reviewed and compared with clinical practice guidelines. Brain imaging was performed in 164 (76.3%) of 215 children, MRI in 93 (56.7%) and CT in 71 (43.3%) children. Indications for brain MRI/CT were as follows: anxiety and/or insistence by the child's family (71.3%), presence of associated features suggesting neurologic dysfunction (13.4%), age under 5 years (12.8%) and abnormal neurologic examination (2.4%). The majority of children (71.4%) had normal neuroimaging findings. In the rest of imaging studies (28.1%), MRI/CT revealed different intracerebral/extracerebral findings not influencing changes in headache management. Only one (0.60%) patient required change in headache management after MRI/CT. Study results proved that, despite available evidence-based clinical guidelines, brain imaging in children with chronic headaches is overused, mostly in order to decrease anxiety of the family/patient.

Summary Aim The topic of pretransplantation body mass index (BMI) is still a matter of controversy. The aim of this study was to investigate the influence of pretransplant BMI on short- and long-term outcomes in patients receiving kidney transplant. Methods We have analysed 521 renal transplant recipients (RTRs). BMI was categorised as follows: less than or equal to 20, more than 20 to less than or equal to 25, more than 25 to less than or equal to 30 and more than 30 Results The distribution of the RTRs per category of BMI at baseline was: ≤ 20 (14.4%), > 20 to ≤ 25 (50.9%), > 25 ≤ 30 (26.9%) and > 30 (7.9%). In further analysis, the patients were stratified into four groups according to their pretransplant BMI values. There was no difference in the rates of delayed graft function between the four analysed groups of patients. Recipients with normal pre-transplant BMI were less likely to develop wound complications in comparison to the recipients with high BMI (p = 0.04) and obese recipients (p = 0.0001). RTRs with normal BMI were less likely to develop lymphoceles in comparison to the recipients with high BMI (p = 0.0003). Obese patients were more likely to develop lymphocele in comparison to the recipients with high BMI (p = 0.01). Obese recipients had a longer mean length of hospital stay in comparison to the recipients with normal BMI (p = 0.04). There was no significant difference regarding 1-year graft and patient survival, as well as because of acute rejection crisis between the investigated groups of recipients. We did not find any significant difference in 5-year patients and graft survival between those RTRs with BMI > 20 to ≤ 25 and to those recipients with BMI > 25. Conclusion Overweight and obese transplant candidates should not be excluded from kidney transplantation.

We report a first case of ureterolithiasis in patient with en bloc kidney transplantation, treated with extracorporeal shockwave lithotripsy (ESWL). Patient presented with asymptomatic macrohaematuria. A computed tomography revealed an ureteral calculus just below the pyeloureteral junction, with consecutive hydronephrosis of the medially positioned kidney. It took two sessions of ESWL for complete disintegration of the stone. After three years of successful treatment the patient has an excellent functioning and stone free graft.