Knowledge on heparin-induced thrombocytopenia keeps increasing. Recent progress on diagnosis and management as well as several discoveries concerning its pathogenesis have been made. However, many aspects of heparin-induced thrombocytopenia remain partly unknown, and exact application of these new insights still need to be addressed. This article reviews the main new concepts in pathogenesis, diagnosis, and management of heparin-induced thrombocytopenia. Full article

In vivo body exposure therapy is considered an effective and suitable intervention to help patients with anorexia nervosa (AN) reduce their body image disturbances (BIDs). However, these interventions have notable limitations and cannot effectively reproduce certain fears usually found in AN, such as the fear of gaining weight (FGW). The latest developments in virtual reality (VR) technology and embodiment-based procedures could overcome these limitations and allow AN patients to confront their FGW and BIDs. This study aimed to provide further evidence of the efficacy of an enhanced (by means of embodiment) VR-based body exposure therapy for the treatment of AN. Thirty-five AN patients (16 in the experimental group, 19 in the control group) participated in the study. FGW, BIDs, and other body-related and ED measures were assessed before and after the intervention and three months later. The experimental group received treatment as usual (TAU) and five additional sessions of VR-based body exposure therapy, while the control group received only TAU. After the intervention, ED symptoms were clearly reduced in both groups, with most of the changes being more noticeable in the experimental group. Specifically, after the intervention and at follow-up, significant group differences were found in the FGW and BIDs, with the experimental group showing significantly lower values than the control group. The current study provides new insights and encouraging findings in the field of exposure-based therapies in AN. VR technology might improve research and clinical practice in AN by providing new tools to help patients confront their core fears (i.e., food- or weight-related cues) and improve their emotional, cognitive, and behavioral responses to their body image. Full article

Anterior skull base meningiomas represent a wide cohort of tumors with different locations, extensions, configurations, and anatomical relationships. Diagnosis of these tumors and review of their therapies are inseparably connected with cranial imaging. We analyzed the influence of three-dimensional-virtual reality (3D-VR) reconstructions versus conventional computed tomography (CT) and magnetic resonance imaging (MRI) images (two-dimensional (2D) and screen 3D) on the identification of anatomical structures and on the surgical planning in patients with anterior skull base meningiomas. Medical files were retrospectively analyzed regarding patient- and disease-related data. Preoperative 2D-CT and 2D-MRI scans were retrospectively reconstructed to 3D-VR images and visualized via VR software to detect the characteristics of tumors. A questionnaire of experienced neurosurgeons evaluated the influence of the VR visualization technique on identification of tumor morphology and relevant anatomy and on surgical strategy. Thirty patients were included and 600 answer sheets were evaluated. The 3D-VR modality significantly influenced the detection of tumor-related anatomical structures (p = 0.002), recommended head positioning (p = 0.005), and surgical approach (p = 0.03). Therefore, the reconstruction of conventional preoperative 2D scans into 3D images and the spatial and anatomical presentation in VR models enabled greater understanding of anatomy and pathology, and thus influenced operation planning and strategy. Full article

Chronic kidney disease (CKD) is an inflammatory disease leading to kidney insufficiency and uremia. Renalase is a novel flavoprotein with enzymatic activities. Previous studies have shown that chronic kidney disease may influence renalase serum levels. Renalase metabolises catecholamines and therefore may be involved in the pathogenesis of hypertension and other diseases of the circulatory system. In this study, we examined renalase levels in serum, erythrocytes and urine from haemodialysis CKD patients. The study enrolled 77 haemodialysis CKD patients and 30 healthy subjects with normal kidney function as the control group. Renalase serum and urine concentrations in CKD patients were significantly increased when compared with control subjects (185.5 ± 64.3 vs. 19.6 ± 5.0 ng/mL; p < 0.00001 and 207.1 ± 60.5 vs. 141.6 ± 41.3 ng/mL; p = 0.00040, respectively). In contrast, renalase levels in erythrocytes were significantly lower in CKD patients when compared with control subjects (176.5 ± 60.9 vs. 233.2 ± 83.1 ng/mL; p = 0.00096). Plasma levels of dopamine, adrenaline and noradrenaline were also significantly lower in CKD patients when compared with controls. Conclusions: Increased serum and urine concentrations of renalase in haemodialysis CKD patients are likely related to compensatory production in extrarenal organs as a result of changes in the cardiovascular system and hypertension. The decreased plasma concentrations of catecholamines may be due to their increased degradation by plasma renalase. Decreased renalase levels in erythrocytes may be probably due to lower renalase synthesis by the kidneys in CKD. The results indicate the presence of renalase in erythrocytes. Full article

In cochlear implants (CI), spread of neural excitation may produce channel interaction. Channel interaction disturbs the spectral resolution and, among other factors, seems to impair speech recognition, especially in noise. In this study, two tests were performed with 20 adult normal-hearing (NH) subjects under different vocoded simulations. First, there was a measurement of word recognition in noise while varying the number of selected channels (4, 8, 12 or 16 maxima out of 20) and the degree of simulated channel interaction (“Low”, “Medium” and “High”). Then, there was an evaluation of spectral resolution function of the degree of simulated channel interaction, reflected by the sharpness (Q10dB) of psychophysical tuning curves (PTCs). The results showed a significant effect of the simulated channel interaction on word recognition but did not find an effect of the number of selected channels. The intelligibility decreased significantly for the highest degree of channel interaction. Similarly, the highest simulated channel interaction impaired significantly the Q10dB. Additionally, a strong intra-individual correlation between frequency selectivity and word recognition in noise was observed. Lastly, the individual changes in frequency selectivity were positively correlated with the changes in word recognition when the degree of interaction went from “Low” to “High”. To conclude, the degradation seen for the highest degree of channel interaction suggests a threshold effect on frequency selectivity and word recognition. The correlation between frequency selectivity and intelligibility in noise supports the hypothesis that PTCs Q10dB can account for word recognition in certain conditions. Moreover, the individual variations of performances observed among subjects suggest that channel interaction does not have the same effect on each individual. Finally, these results highlight the importance of taking into account subjects’ individuality and to evaluate channel interaction through the speech processor. Full article

The key to the successful management of pancreatic cystic neoplasm (PCN), among which intraductal papillary mucinous neoplasm (IPMN) is the one with the highest risk of advanced neoplasia in resected patients, is a careful combination of clinical, radiological, and histopathological findings. This study aims to perform the comparison of a preoperative evaluation with pathological reports in IPMN and further, to evaluate and compare the diagnostic performance of European evidence-based guidelines on pancreatic cystic neoplasms (EEBGPCN) and Fukuoka Consensus guidelines (FCG). We analyzed 106 consecutive patients diagnosed with different types of PCN, among whom 68 had IPMN diagnosis, at the Clinical Center of Serbia. All the patients diagnosed with IPMNs were stratified concerning the presence of the absolute and relative indications according to EEBGPCN and high-risk stigmata and worrisome features according to FCG. Final histopathology revealed that IPMNs patients were further divided into malignant (50 patients) and benign (18 patients) groups, according to the pathological findings. The preoperative prediction of malignancy according to EEBGPCN criteria was higher than 70% with high sensitivity of at least one absolute or relative indication for resection. The diagnostic performance of FCG was shown as comparable to EEBGPCN. Nevertheless, the value of false-positive rate for surgical resection showed that in some cases, overtreating patients or treating them too early cannot be prevented. A multidisciplinary approach is essential to adequately select patients for the resection considering at the same time both the risks of surgery and malignancy. Full article

Coagulation factor XIII (FXIII) is a protransglutaminase which plays an important role in clot stabilization and composition by cross-linking the α- and γ-chains of fibrin and increasing the resistance of the clot to mechanical and proteolytic challenges. In this study, we selected six DNA aptamers specific for activated FXIII (FXIIIa) and investigated the functional characterization of FXIIIa after aptamer binding. One of these aptamers, named FA12, efficiently captures FXIIIa even in the presence of zymogenic FXIII subunits. Furthermore, this aptamer inhibits the incorporation of FXIII and α2-antiplasmin (α2AP) into fibrin(ogen) with IC₅₀-values of 38 nM and 17 nM, respectively. In addition to FA12, also another aptamer, FA2, demonstrated significant effects in plasma-based thromboelastometry (rotational thromboelastometry analysis, ROTEM)-analysis where spiking of the aptamers into plasma decreased clot stiffness and elasticity (p < 0.0001). The structure–function correlations determined by combining modeling/docking strategies with quantitative in vitro assays revealed spatial overlap of the FA12 binding site with the binding sites of two FXIII substrates, fibrinogen and α2AP, while FA2 binding sites only overlap those of fibrinogen. Taken together, these features especially render the aptamer FA12 as an interesting candidate molecule for the development of FXIIIa-targeting therapeutic strategies and diagnostic assays. Full article

Due to current depression prevalence, it is crucial to make the correct diagnosis as soon as possible. The study aimed to identify commonly available, easy to apply, and quick to interpret tools allowing for a differential diagnosis between unipolar and bipolar disorder. The study group includes women with long duration of unipolar (UP, N = 34) and bipolar (BP, N = 43) affective disorder. The diagnosis was established according to the DSM criteria using SCID questionnaire. Additional questionnaires were used to differentiate between UP and BP. BP patients had an earlier age of onset, were hospitalized more times, and more often had a family history of psychiatric disorders than UP (p-value < 0.05). Moreover, BP achieved a higher impulsiveness score and more frequently had experienced severe problems with close individuals. To our knowledge, this is the first publication presenting results of numerous questionnaires applied simultaneously in patients on clinical group. Several of them suggest the direction of clinical assessment, such as: the age of onset, family psychiatric burdens, history of stressful life events, learning problems, social and job relations. Further studies are necessary to confirm the utility of this approach. Full article

(1) Background: Caesarean sections in obese patients are associated with an increased risk of surgical wound complications, including hematomas, seromas, abscesses, dehiscence, and surgical site infections. The aim of the present study is to perform a meta-analysis and systematic review of the current literature focusing on the strategies available to decrease wound complications in this population. (2) Methods: We reviewed the data available from the PubMed and the Science Direct databases concerning wound complications after caesarean sections in obese women. The following key words were used: “caesarean section”, “cesarean section”, “wound complication”, “wound morbidity”, and “wound infection”. A total of 540 papers were retrieved, 40 of which were selected for the final systematic review and whereas 21 articles provided data for meta-analysis. (3) Results: The conducted meta-analyses revealed that the use of prophylactic drainage does not increase the risk of wound complications in obese women after a caesarean sections (pooled OR = 1.32; 95% CI 0.64–2.70, p = 0.45) and that vertical skin incisions increase wound complications (pooled OR = 2.48; 95% CI 1.85–3.32, p < 0.01) in obese women, including extremely obese women. (4) Conclusions: Subcutaneous drainage does not reduce the risk of a wound complications, wound infections, and fever in obese women after caesarean sections. Negative prophylactic pressure wound therapy (NPWT) may reduce the risk of surgical site infections. The evidence of using a prophylactic dose of an antibiotic before the caesarean section is still lacking. Full article

The number of obese individuals worldwide continues to increase every year, thus, the number of bariatric/metabolic operations performed is on a constant rise as well. Beside exclusively restrictive procedures, most of the bariatric operations have a more or less malabsorptive component. Several different bypass procedures exist alongside each other today and each type of bypass is performed using a distinct technique. Furthermore, the length of the bypassed intestine may differ as well. One might add that the operations are performed differently in different parts of the world and have been changing and evolving over time. This review evaluates the most frequently performed bariatric bypass procedures (and their variations) worldwide: Roux-en-Y Gastric Bypass, One-Anastomosis Gastric Bypass, Single-Anastomosis Duodeno-Ileal Bypass + Sleeve Gastrectomy, Biliopancreatic Diversion + Duodenal Switch and operations due to weight regain. The evaluation of the procedures and different limb lengths focusses on weight loss, remission of comorbidities and the risk of malnutrition and deficiencies. This narrative review does not aim at synthesizing quantitative data. Rather, it provides a summary of carefully selected, high-quality studies to serve as examples and to draw tentative conclusions on the effects of the bypass procedures mentioned above. In conclusion, it is important to carefully choose the procedure and small bowel length excluded from the food passage suited best to each individual patient. A balance has to be achieved between sufficient weight loss and remission of comorbidities, as well as a low risk of deficiencies and malnutrition. In any case, at least 300 cm of small bowel should always remain in the food stream to prevent the development of deficiencies and malnutrition. Full article

Non-alcoholic fatty liver disease (NAFLD) has emerged as the hepatic component of the metabolic syndrome and now seemingly affects one-fourth of the world population. Features associated with NAFLD and the metabolic syndrome have frequently been linked to cognitive dysfunction, i.e. systemic inflammation, vascular dysfunction, and sleep apnoea. However, emerging evidence suggests that NAFLD may be a cause of cognitive dysfunction independent of these factors. NAFLD in addition exhibits dysbiosis of the gut microbiota and impaired urea cycle function, favouring systemic ammonia accumulation and further promotes systemic inflammation. Such disruption of the gut–liver–brain axis is essential in the pathogenesis of hepatic encephalopathy, the neuropsychiatric syndrome associated with progressive liver disease. Considering the growing burden of NAFLD, the morbidity from cognitive impairment is expected to have huge societal and economic impact. The present paper provides a review of the available evidence for cognitive dysfunction in NAFLD and outlines its possible mechanisms. Moreover, the clinical challenges of characterizing and diagnosing cognitive dysfunction in NAFLD are discussed. Full article

Liver injury—expressed as elevated liver enzymes—is common in patients with COVID-19. Little is known about the potential mechanisms of liver damage by SARS-CoV-2. A direct cytopathic effect on hepatocytes as well as injury related to hypoxia or hepatotoxicity are being considered. The aim of the study was to compare the clinical characteristic of COVID-19 disease in patients with normal and abnormal liver enzymes activity. A group of 150 patients with COVID-19, hospitalized in our center, was analyzed. Patients with the known liver comorbidities were excluded (n = 15). Clinical features and laboratory parameters were compared between patients with normal and abnormal aminotransferase values. Liver injury expressed as any alanine aminotransferase (ALT) elevation was noted in 45.6% of patients hospitalized due to COVID-19. The frequencies of aspartate aminotransferase (AST) elevation were lower. It was noted that elevated ALT/AST unfavorably affected other parameters related to liver function such as albumin level; gamma-glutamyl transpeptidase (GGTP); and partly, ALP activity and influenced inflammation-related parameters. The most probable cause of mild hepatitis during COVID-19 was anoxia and immune-mediated damage due to the inflammatory response following SARS-CoV-2 infection. A direct cytopathic effect of SARS-CoV-2 on hepatocytes, albeit less probable, can be considered as well. The use of potentially hepatotoxic drugs may contribute to liver damage. Full article

Background: Coronavirus disease-2019 (COVID-19) triggers systemic infection with involvement of the respiratory tract. There are some patients developing haemostatic abnormalities during their infection with a considerably increased risk of death. Materials and Methods: Patients (n = 85) with SARS-CoV-2 infection attending the University Medical Center, Mainz, from 3 March to 15 May 2020 were retrospectively included in this study. Data regarding demography, clinical features, treatment and laboratory parameters were analyzed. Twenty patients were excluded for assessment of disseminated intravascular coagulation (DIC) and thrombotic microangiopathy (TMA) due to lack of laboratory data. Results: COVID-19 patients (n = 65) were investigated, 19 with uncomplicated, 29 with complicated, and 17 with critical course; nine (13.8%) died. Seven patients showed overt DIC according to the ISTH criteria. The fibrinogen levels dropped significantly in these patients, although not below 100 mg/dl. Hallmarks of TMA, such as thrombocytopenia and microangiopathic haemolytic anaemia, were not detected in any of our COVID-19 patients. ADAMTS13 activity was mildly to moderately reduced in 4/22 patients, all having strongly elevated procalcitonin levels. Conclusion: DIC occurred in 7/65 COVID-19 patients but fibrinogen and platelet consumption were compensated in almost all. ADAMTS13 assays excluded TTP and hallmarks of classic TMA were absent in all investigated patients. We hypothesize that the lacking erythrocyte fragmentation and only mild platelet consumption in severe COVID-19 are due to a microangiopathy predominantly localized to the alveolar microcirculation with a low blood pressure gradient. Full article

Lupus nephritis (LN) is a frequent and severe manifestation of systemic lupus erythematosus. The main goal of the management of LN is to avoid chronic kidney disease (CKD). Current treatment strategies remain unsatisfactory in terms of complete renal response, prevention of relapses, CKD, and progression to end-stage kidney disease. To improve the prognosis of LN, recent data suggest that we should (i) modify our treat-to-target approach by including, in addition to a clinical target, a pathological target and (ii) switch from conventional sequential therapy to combination therapy. Here, we also review the results of recent controlled randomized trials. Full article

Non-alcoholic fatty liver disease (NAFLD) is frequent in patients with features of the metabolic syndrome (MetS), obesity, or type 2 diabetes. Lipoprotein lipase (LPL) is the main driver of triglyceride (TG) hydrolysis in chylomicrons and very-low density lipoproteins (VLDL). In some patients with MetS, dysfunction of this pathway can lead to plasma TG values > 10 mmol/L (multifactorial chylomicronemia or MCS). Chylomicronemia also characterizes LPL deficiency (LPLD), a rare autosomal recessive disease called familial chylomicronemia syndrome (FCS), which is associated with an increased risk of recurrent pancreatitis. This study aims to investigate the expression of NAFLD, as assessed by transient elastography, in MCS and FCS subjects. Data were obtained from 38 subjects with chylomicronemia; 19 genetically confirmed FCS and 19 sex- and age-matched MCS. All participants underwent liver ultrasonography and stiffness measurement after a 4-h fast using transient elastography (FibroScan^®, Echosens, Waltham, MA, USA). NAFLD (controlled attenuation parameter (CAP) > 280 dB/m) was observed in 42.1% of FCS and 73.7% of MCS subjects (p = 0.05). FCS subjects had lower body mass index (BMI) than MCS. Only 25% of FCS subjects with NAFLD had a BMI ≥ 30 compared to 64.3% in MCS (p = 0.004). In FCS, NAFLD occurred even in the presence of very low (≤18 kg/m²) BMI. In both FCS and MCS, CAP was negatively associated with acute pancreatitis risk. In this study, NAFLD was commonly observed in both FCS and MCS subjects and occurred independently of the BMI and fasting glucose values in FCS; NAFLD was associated with a lower occurrence of acute pancreatitis episodes. Full article