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Background/objective Complete resection is the most effective treatment of hilar cholangiocarcinoma (HC) but may result in high morbidity and mortality. Most HC patients have jaundice, and preoperative biliary drainage may reduce their risk of obstructive jaundice. ERCP and PTBD have been advocated for this purpose. This retrospective study investigated the influence of ERCP versus PTBD versus their combination on the short-term outcomes of curative HC resection. Methods Patients having curative HC resection with preoperative biliary drainage in a span of 26 years were reviewed and divided into groups according to drainage modality. Drainage-related and surgical complications and hospital mortality were compared between groups. Intention-to-treat analysis using a separate set of initial drainage data was performed. Results Eighty-six patients were divided into: Group A, ERCP only, n = 32 (32/86 = 37.2%); Group B, PTBD only, n = 10 (10/86 = 11.6%); Group C, ERCP + PTBD, n = 44 (44/86 = 51.2%). International normalized ratio was significantly higher in Group B (p = 0.008). The three groups were comparable in operative details, hospital stay, and mortality. Fifty-two patients had postoperative complications. Significantly more patients in Groups A and C had subphrenic abscess (A: 25%, B: 0%, C: 9.1%; p = 0.035) and subsequent radiological drainage. Group A had insignificantly more patients with wound infection (31.3% vs 10% vs 22.7%, p = 0.334), chest infection (28.1% vs 20% vs 11.4%, p = 0.178), and urinary tract infection (6.3% vs 0% vs 0%, p = 0.133). The three groups had similar rates of major complications (p = 0.501). They also had comparable survival outcomes (overall, p = 0.370; disease-free, p = 0.569). Fifteen and 71 patients received PTBD and ERCP respectively as first drainage mode. These two groups were comparable in liver function, preoperative comorbidity, intraoperative details, and postoperative outcomes. Conclusion In the preoperative management of HC, the use of ERCP, PTBD or their combination is acceptable and can optimize patients' condition for curative HC resection.

High-intensity focused ultrasound (HIFU) has been shown to be a valuable tool in the management of small liver tumors such as hepatocellular carcinoma (HCC). It has been shown to be a safe and effective means to ablate small HCC even in the presence of advanced cirrhosis. This review examines the challenges faced during HIFU ablation when the target tumors are located in difficult locations such as the liver dome, close to the rib cage, near large blood vessels or the heart, or adjacent to hollow viscera; and the special maneuvers employed to tackle such lesions.

This retrospective, single-center study aimed to investigate the importance of chemotherapy and to come up with the optimal liver resection margin length for patients with resectable colorectal liver metastasis (CRLM). Patients who had undergone any form of liver resection for CRLM were reviewed and analyzed. The analyses were broken down into three parts: (1) overall effect of chemotherapy, (2) effect of chemotherapy with positive/negative resection margin, and (3) result of discriminative analysis with optimal margin length analysis. In total, 381 patients were studied. Among them, 279 received chemotherapy whereas 102 did not. Survival was significantly better in patients with chemotherapy (5-year, 43.6% vs. 25.8%) (p < 0.001). Patients who received chemotherapy (n = 93) with negative margins had better survival than patients (n = 8) with positive margins (5-year, 28.1% vs. 0%) (p = 0.019). On multivariate analysis, margin involvement was the poor prognostic factor for survival. Patients who had chemotherapy (n = 238) with negative margin showed a trend of better survival than patients (n = 41) with positive margins (5-year, 45.7% vs. 29.3%) (p = 0.085). Patients (n = 93) with negative margin and no chemotherapy and patients (n = 41) with positive margin and chemotherapy had comparable survival at 5 years (p = 0.422). On multivariate analysis, tumor number was the prognostic factor for survival. By the discriminant method, 1.09 cm (sensitivity 0.242, specificity 0.718) was determined as the cut-off for optimal margin length. Patients who had margin ≥ 1.09 cm (n = 81) enjoyed significantly better survival (5-year, 54.3% vs. 33.5%) (p = 0.041). On multivariate analysis, margin length ≥ 1.09 cm was the prognostic factor for favorable survival. The results demonstrated the important effect of perioperative chemotherapy and negative margin liver resection in management of patients suffered from CRLM.

OverviewMachine learning (ML) is rapidly being adopted by archaeologists interested in analyzing a range of geospatial, material cultural, textual, natural, and artistic data. The algorithms are particularly suited toward rapid identification and classification of archaeological features and objects. The results of these new studies include identification of many new sites around the world and improved classification of large archaeological datasets. ML fits well with more traditional methods used in archaeological analysis, and it remains subject to both the benefits and difficulties of those approaches. Small datasets associated with archaeological work make ML vulnerable to hidden complexity, systemic bias, and high validation costs if not managed appropriately. ML's scalability, flexibility, and rapid development, however, make it an essential part of twenty-first-century archaeological practice. This review briefly describes what ML is, how it is being used in archaeology today, and where it might be used in the future for archaeological purposes.

Acute toxicity caused by New Psychoactive Substances (NPS) has created a significant burden for Emergency Departments (EDs). Here we report characteristics of people presenting with toxicity after ...

Left ventricular end-diastolic volume (EDV) is an important parameter for monitoring patients with left ventricular assist devices (LVADs) and might be useful for automatic LVAD work adaptation. However, continuous information on the EDV is unavailable to date. The depolarization amplitude (DA) of the noncontact intracardiac electromyogram (iEMG) is physically related to the EDV. Here, we show how a left ventricular (LV) volume sensor based on the iEMG might provide beat-wise EDV estimates. The study was performed in six pigs while undergoing a series of controlled changes in hemodynamic states. The LV volume sensor consisted of four conventional pacemaker electrodes measuring the far-field iEMG inside the LV blood pool, using a novel unipolar amplifier. Simultaneously, noninvasive measurements of EDV and hematocrit were recorded. The proposed EDV predictor was tested for statistical significance using a mixed-effect model and associated confidence intervals. A statistically significant (p = 3e–07) negative correlation was confirmed between the DA of the iEMG and the EDV as measured by electric impedance at a slope of –0.069 (–0.089, –0.049) mV/mL. The DA was slightly decreased by increased hematocrit (p = 0.039) and moderately decreased with the opening of the thorax (p = 0.003). The DA of the iEMG proved to be a significant, independent predictor of EDV. The proposed LV volume sensor is simple to integrate into the inflow cannula of an LVAD and thus has the potential to inform the clinician about the state of LV volume in real time and to automatically control the LVAD., ASAIO Journal, 67 (12), ISSN:1058-2916, ISSN:1538-943X

Introduction: During the past five years the approach to procedural planning, operative techniques and perfusion strategies for minimally invasive mitral valve surgery (MIMVS) has evolved. With the goal to provide a maximum of patient safety the procedure has been modified according to individual patient characteristics and is largely based on preoperative imaging.Areas covered: In this review article we describe the important factors in image based therapy planning and simulation, different access strategies, the operative key-steps, a rationale use of devices, and highlight a few future developments in the field of MIMVS. Published studies were identified through pearl growing, citation chasing, a search of PubMed using the systematic review methods filter, and the authors' topic knowledge.Expert opinion: With the help of expert teams including surgeons specialized in mitral repair, anesthesiologists and perfusionists a broad spectrum of mitral valve pathologies and related pathologies can be treated with excellent functional outcomes. Avoiding procedure related complications is the key for success for any MIMVS program.

Background Cleft lip and palate is one of the commonest congenital anomalies, which have an impact on feeding, speech, and dental development away from the significant psychosocial sequel. Early surgical repair aims to restore appearance and function, and the modern techniques can leave many defects undetectable. Therefore, the anesthetic challenge facing the pediatric airway with such abnormalities is still of a great impact. The aim of our study among 189 patients enrolled is to correlate alveolar gap and maximum cleft width measurements as predictors of difficult laryngoscopy and intubation in infants with unilateral complete cleft lip/palate aging from 1 to 6 months. As a secondary outcome, their weight is to be correlated too as another parameter. Results The alveolar gap and maximum cleft width are both of equal high predictive power (p value ≤ 0.001) with 100% sensitivity for both and specificity of 76.10% and 82.39% respectively, with a cut off value of ≤ 10 mm and 11 mm for these dimensions respectively, and odds ratio of incidence of difficult intubation is 4.18 and 5.68 respectively, while body weight ≤ 5.75 kg has an odds ratio of 2.32. Conclusion Alveolar cleft and maximum cleft width can be used as predictors for anticipation of difficult laryngoscopy and intubation infant patients with unilateral complete cleft lip and palate, while body weight ≤ 5.75 kg increases the risk more than twice.

Objective While vitamin D regulates immune cells, little is known about it in autoimmune Addison’s disease (AAD). We investigated the vitamin D status in AAD patients from five European populations to assess its deficiency. In addition, we studied two case-control cohorts for vitamin D metabolism and pathway genes. Design Cross-sectional study. Methods A total of 1028 patients with AAD from Germany (n = 239), Italy (n = 328), Norway (n = 378), UK (n = 44) and Poland (n = 39) and 679 controls from Germany (n = 301) and Norway (n = 378) were studied for 25(OH)D3 (primary objective). Secondary objectives (1,25(OH)2D3 and pathway genes) were examined in case-controls from Germany and Norway correlating 25(OH)D3 and single nucleotide polymorphisms within genes encoding the vitamin D receptor (VDR), 1-α-hydroxylase (CYP27B1), 25-hydroxylase (CYP2R1), 24-hydroxylase (CYP24A1) and vitamin D binding protein (GC/DBP). Results Vitamin D deficiency (25(OH)D3 10–20 ng/mL) was highly prevalent in AAD patients (34–57%), 5–22% were severely deficient (30 ng/mL). Lower 25(OH)D3 and 1,25(OH)2D3 levels were observed both in Norwegian and German AAD (P = 0.03/0.003 and P = 1 × 10-5/< 1 × 10-7, respectively) the former was associated with CYP2R1 (rs1553006) genotype G. Whereas controls achieved sufficient median 25(OH)D3 in summers (21.4 to 21.9 ng/mL), AAD patients remained largely deficient (18.0 to 21.2 ng/mL) and synthesize less 1,25(OH)2D3. Conclusion Vitamin D deficiency and insufficiency are highly prevalent in AAD patients. The vitamin D status of AAD may be influenced by genetic factors and suggests individual vitamin D requirements throughout the year.

This paper finds that banking firms’ unexpected loan loss provisions had a significant effect of increasing bank opacity, both before and during the 2007–2009 financial crisis. Furthermore, during the financial crisis, the extent to which banks delayed loan loss recognition is found to have had a significant effect on bank opacity, confirming an important concern raised by the Financial Crisis Advisory Group. Overall, banks’ practices in managing reserves seem to have a material impact on their opacity.

Over the last 10 years, evidence has accumulated that autoimmune Addison’s disease (AAD) is a heterogeneous disease. Residual adrenal function, characterised by persistent secretion of cortisol, other glucocorticoids and mineralocorticoids is present in around 30% of patients with established AAD, and appears commoner in men. This persistent steroidogenesis is present in some patients with AAD for more than 20 years, but it is commoner in people with shorter disease duration. The clinical significance of residual adrenal function is not fully clear at the moment, but as it signifies an intact adrenocortical stem cell population, it opens up the possibility of regeneration of adrenal steroidogenesis and improvement in adrenal failure for some patients.

Background & Aims Nonalcoholic fatty liver disease (NAFLD) is considered a health epidemic with potential devastating effects on the patients and the healthcare systems. Current preclinical models of NAFLD are invariably imperfect and generally take a long time to develop. A mouse model of survival motor neuron (SMN) depletion (Smn2B/- mice) was recently shown to develop significant hepatic steatosis in less than 2 weeks from birth. The rapid onset of fatty liver in Smn2B/- mice provides an opportunity to identify molecular markers of NAFLD. Here, we investigated whether Smn2B/- mice display typical features of NAFLD/nonalcoholic steatohepatitis (NASH). Methods Biochemical, histologic, electron microscopy, proteomic, and high-resolution respirometry were used. Results The Smn2B/- mice develop microvesicular steatohepatitis within 2 weeks, a feature prevented by AAV9-SMN gene therapy. Although fibrosis is not overtly apparent in histologic sections of the liver, there is molecular evidence of fibrogenesis and presence of stellate cell activation. The consequent liver damage arises from mitochondrial reactive oxygen species production and results in hepatic dysfunction in protein output, complement, coagulation, iron homeostasis, and insulin-like growth factor-1 metabolism. The NAFLD phenotype is likely due to non-esterified fatty acid overload from peripheral lipolysis subsequent to hyperglucagonemia compounded by reduced muscle use and insulin resistance. Despite the low hepatic mitochondrial content, isolated mitochondria show enhanced β-oxidation, likely as a compensatory response, resulting in the production of reactive oxygen species. In contrast to typical NAFLD/NASH, the Smn2B/- mice lose weight because of their associated neurological condition (spinal muscular atrophy) and develop hypoglycemia. Conclusions The Smn2B/- mice represent a good model of microvesicular steatohepatitis. Like other models, it is not representative of the complete NAFLD/NASH spectrum. Nevertheless, it offers a reliable, low-cost, early-onset model that is not dependent on diet to identify molecular players in NAFLD pathogenesis and can serve as one of the very few models of microvesicular steatohepatitis for both adult and pediatric populations., Graphical abstract

Background /Aim: Laparoscopic hepatectomy has been gaining popularity but its evidence in major hepatectomy for cirrhotic liver is lacking. We studied the long-term outcomes of the pure laparoscopic approach versus the open approach in major hepatectomy without Pringle maneuver in patients with hepatocellular carcinoma (HCC) and cirrhosis using the propensity score analysis. Methods We reviewed patients diagnosed with HCC and cirrhosis who underwent major hepatectomy as primary treatment. The outcomes of patients who received the laparoscopic approach were compared with those of propensity-case-matched patients (ratio, 4:1) who received the open approach. The matching was made on the following factors: tumor size, tumor number, age, sex, hepatitis serology, HCC staging, comorbidity, and liver function. Results Twenty-four patients underwent pure laparoscopic major hepatectomy for HCC with cirrhosis. Ninety-six patients who underwent open major hepatectomy were matched by propensity scores. The laparoscopic group had less median blood loss (300 ml vs 645 ml, p = 0.001), shorter median hospital stay (6 days vs 10 days, p = 0.002), and lower rates of overall complication (12.5% vs 39.6%, p = 0.012), pulmonary complication (4.2% vs 25%, p = 0.049) and pleural effusion (p = 0.026). The 1-year, 3-year and 5-year overall survival rates in the laparoscopic group vs the open group were 95.2%, 89.6% and 89.6% vs 87.5%, 72.0% and 62.8% (p = 0.211). Correspondingly, the disease-free survival rates were 77.1%, 71.2% and 71.2% vs 75.8%, 52.7% and 45.5% (p = 0.422). Conclusions The two groups had similar long-term survival. The laparoscopic group had favorable short-term outcomes. Laparoscopic major hepatectomy without routine Pringle maneuver for HCC with cirrhosis is a safe treatment option at specialized centers.

Background and Aims Historical and emerging data implicate fungi in Crohn’s disease [CD] pathogenesis. However, a causal link between mycobiota, dysregulated immunity, and any impact of NOD2 variants remains elusive. This study aims to evaluate associations between NOD2 variants and faecal mycobiota in CD patients and non-CD subjects. Methods Faecal samples were obtained from 34 CD patients [18 NOD2 mutant, 16 NOD2 wild-type] identified from the UK IBD Genetics Consortium. To avoid confounding influence of mucosal inflammation, CD patients were in clinical remission and had a faecal calprotectin Results CD was associated with higher numbers of fungal observed taxonomic units [OTUs] [p = 0.033]. Principal coordinates analysis using Jaccard index [p = 0.018] and weighted Bray-Curtis dissimilarities [p = 0.01] showed Candida spp. clustered closer to CD patients whereas Cryptococcus spp. clustered closer to non-CD. In CD, we found higher relative abundance of Ascomycota [p = 0.001] and lower relative abundance Basidiomycota [p = 0.019] phyla. An inverse relationship was found between bacterial and fungal Shannon diversity in NOD2 wild-type which was independent of CD [r = -0.349; p = 0.029]. Conclusions This study confirms compositional changes in the gut mycobiota in CD and provides evidence that fungi may play a role in CD pathogenesis. No NOD2 genotype-specific differences were observed in the faecal mycobiota.

Purpose Decision support systems for mitral valve disease are an important step toward personalized surgery planning. A simulation of the mitral valve apparatus is required for decision support. Building a model of the chordae tendineae is an essential component of a mitral valve simulation. Due to image quality and artifacts, the chordae tendineae cannot be reliably detected in medical imaging. Methods Using the position-based dynamics framework, we are able to realistically simulate the opening and closing of the mitral valve. Here, we present a heuristic method for building an initial chordae model needed for a successful simulation. In addition to the heuristic, we present an interactive editor to refine the chordae model and to further improve pathology reproduction as well as geometric approximation of the closed valve. Results For evaluation, five mitral valves were reconstructed based on image sequences of patients scheduled for mitral valve surgery. We evaluated the approximation of the closed valves using either just the heuristic chordae model or a manually refined model. Using the manually refined models, prolapse was correctly reproduced in four of the five cases compared to two of the five cases when using the heuristic. In addition, using the editor improved the approximation in four cases. Conclusions Our approach is suitable to create realistically parameterized mitral valve apparatus reconstructions for the simulation of normally and abnormally closing valves in a decision support system., International Journal of Computer Assisted Radiology and Surgery, 16 (1), ISSN:1861-6410, ISSN:1861-6429

Background In the management of operable hilar cholangiocarcinoma (HC) patients with hyperbilirubinemia, preoperative biliary drainage is a measure to bring down the bilirubin to a certain level so as to avoid adverse postoperative outcomes that would otherwise result from hyperbilirubinemia. A cutoff value of bilirubin level in this context is needed but has not been agreed upon without controversy. This retrospective study aimed to identify a cutoff of preoperative bilirubin level that would minimize postoperative morbidity and mortality. Methods Data of patients having hepatectomy with curative intent for HC were analyzed. Discriminative analysis was performed to identify the preoperative bilirubin level that would make a survival difference. The identified level was used as the cutoff to divide patients into two groups. The groups were compared. Results Ninety patients received hepatectomy with curative intent for HC. Their median preoperative bilirubin level was 23 μmol/L. A cutoff preoperative bilirubin level of 75 μmol/L was derived from Youden’s index (sensitivity 0.333; specificity 0.949) and confirmed to be optimal by logistic regression (relative risk 9.250; 95% confidence interval 1.932–44.291; p = 0.005), with mortality shown to be statistically different at 90 days (p = 0.008). Patients were divided into Group A (≤75 μmol/L; n = 82) and Group B (> 75 μmol/L; n = 8). Group B had a higher preoperative bilirubin level (p p = 0.008), transfusion (100% vs 42.0%; p = 0.011) and replacement (2.45 vs 0.0 L; p p = 0.036), more in-hospital deaths (50% vs 8.5%; p = 0.004), and more 90-day deaths (50% vs 9.8%; p = 0.008). Group A had a longer follow-up period (p = 0.008). The groups were otherwise comparable. Disease-free survival was similar between groups (p = 0.142) but overall survival was better in Group A (5-year, 25.2% vs 0%; p Conclusion A cutoff value of preoperative bilirubin level of 75 μmol/L is suggested, as the study showed that a preoperative bilirubin level ≤ 75 μmol/L resulted in significantly less blood replacement necessitated by blood loss during operation and significantly better patient survival after surgery.

Introduction Evaluation of aesthetics after breast reconstruction is challenging. In the absence of an objective measurement, panel assessment is widely adopted. Heterogeneity of scales and poor internal consistency make comparison difficult. Development and validation of an expert panel scale using a Delphi consensus process is described. It was designed specifically for use as the gold standard for development of an objective evaluation tool using 3-Dimensional Surface Imaging (3D-SI). Materials and methods 20 items relating to aesthetic assessment were identified for consideration in the Delphi consensus process. Items were selected for inclusion in the definitive panel scale by iterative rounds of voting according to importance, consensus discussion, and a final vote. The Delphi-derived scale was tested on a clinical research series for intra- and inter-panellist, and intra-panel reliability, and correlation with Patient Reported Outcome Measures (PROMs). Results 61 surgeons participated in the Delphi process. Oncoplastic and plastic surgeons were represented. The Delphi-derived scale included symmetry, volume, shape, position of breast mound, nipple position, and a global score. Intra-panellist reliability ranged from poor to almost perfect (wκ, Highlights • Aesthetic outcome has well described influence on long term quality of life • Many scoring systems exist, each with methodological flaws. • A Delphi consensus process was used to derive a contemporary panel scoring system for expert aesthetic evaluation • The scoring system was tested and performed well on a series of images of women who have undergone breast reconstruction

Background: International societies have recommended that levothyroxine should not routinely be prescribed in older individuals for the management of mild subclinical hypothyroidism (SCH). However, it is unknown whether clinicians managing people with SCH are either aware of or adhere to these guidelines. Methods: A web-based survey of members of several international thyroid associations and general practitioners in North-East England was conducted. Respondents were presented with a vignette of an 80-year-old gentleman with mild persistent SCH experiencing tiredness. Multivariable logistic regression analyses were performed to evaluate predictors of awareness of guidelines and responses to treatment. Results: The survey response rate was 21.9% (565/2,583). Only 7.6% of clinicians were unaware of guidelines regarding management of SCH in older people. Twenty percent of clinicians stated that they would treat the older patient with mild SCH, whereas 13% were unsure. Clinicians from North America were more likely to treat the older person with mild SCH than clinicians from elsewhere (OR 2.24 [1.25–3.98]). Likewise, non-endocrinologists were also more likely than endocrinologists to treat the older person with mild SCH (OR 3.26 [1.45–6.47]). Conclusion: The majority of clinicians are aware of guidelines regarding management of SCH in older individuals. However, a considerable proportion of clinicians would still treat an older person with non-specific symptoms and mild SCH. These guidelines need to be disseminated more widely and more research is required to understand barriers to adherence to international recommendations.

Expanded carrier screening (ECS) for recessive monogenic diseases requires prior knowledge of genomic variation, including DNA variants that cause disease. The composition of pathogenic variants differs greatly among human populations, but historically, research about monogenic diseases has focused mainly on people with European ancestry. By comparison, less is known about pathogenic DNA variants in people from other parts of the world. Consequently, inclusion of currently underrepresented Indigenous and other minority population groups in genomic research is essential to enable equitable outcomes in ECS and other areas of genomic medicine. Here, we discuss this issue in relation to the implementation of ECS in Australia, which is currently being evaluated as part of the national Government’s Genomics Health Futures Mission. We argue that significant effort is required to build an evidence base and genomic reference data so that ECS can bring significant clinical benefit for many Aboriginal and/or Torres Strait Islander Australians. These efforts are essential steps to achieving the Australian Government’s objectives and its commitment “to leveraging the benefits of genomics in the health system for all Australians.” They require culturally safe, community-led research and community involvement embedded within national health and medical genomics programs to ensure that new knowledge is integrated into medicine and health services in ways that address the specific and articulated cultural and health needs of Indigenous people. Until this occurs, people who do not have European ancestry are at risk of being, in relative terms, further disadvantaged.

OBJECTIVE To study the impact of LT experience on the outcome of CLR for locally advanced hepatobiliary malignancy SUMMARY OF BACKGROUND DATA:: Despite evolution in LT knowledge and surgical techniques in the past decades, there is yet data to evaluate the significance of LT experience in performing CLR. METHODS Postoperative outcome after CLR between 1995 and 2019 were reviewed and correlated with LT experience in a single center with both LT and CLR service. CLR was defined as hepatectomy with vasculobiliary reconstruction, or multivisceral resection, central bisectionectomy (S4/5/8), or associating liver partition and portal vein ligation for staged hepatectomy. Spearman rank correlation and receiver operating characteristic analysis were used to define the association between CLR-related outcomes and LT experience. RESULTS With cumulative single-center experience of 1452 LT, 222 CLR were performed during the study period [hepatectomy with biliary (27.0%), or vascular (21.2%) reconstruction, with multivisceral resections (9.9%), with associating liver partition and portal vein ligation for staged hepatectomy (18.5%)] mainly for hepatocellular carcinoma (53.2%), and hilar cholangiocarcinoma (14%). Median tumor size was 7.0 cm. Other features include macrovascular invasion (23.4%), and juxta-visceral invasion (14%). Major postoperative complication rate was 25.2% and mortality rate was 6.3%. CLR-complication rate was inversely associated with LT experience (R = -0.88, P < 0.005). Receiver operator characteristic analysis revealed the cutoff for LT experience to have the greatest influence on CLR was 95 with a sensitivity of 100% and Youden index of 1. Multivariable analysis showed that blood transfusion, prolonged operating time, LT experience

Background. Endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) are commonly used for assessing pancreatic lesions. This study aimed to evaluate the diagnostic yield and accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in a single tertiary institution. Methods. Consecutive patients who underwent EUS-FNA of the pancreas at Queen Mary Hospital, Hong Kong, from January 2015 to March 2016 were retrospectively reviewed. Endoscopic findings and FNA results were analysed. For patients who subsequently underwent surgical resection of pancreatic lesion, EUS-FNA diagnoses were compared to histopathological findings of surgical specimens to determine its diagnostic accuracy. Results. One hundred twelve EUS-FNA were performed in 99 patients within the study time period and were included for analysis. Sixty-six (66.7%) pancreatic lesions were solid in nature and 33 (33.3%) were cystic. The overall diagnostic yield of EUS-FNA was 70.5% (n = 79). On multivariate analysis, more passes of needle were associated with a higher diagnostic yield (odds ratio = 2.000, P = .049). 57.1% (n = 64) of EUS-FNA results had an impact on management. Sixteen patients with diagnostic EUS-FNA subsequently underwent surgery for resection of the pancreatic lesion. Upon correlation to the histopathological findings of surgical specimens, there were 12 true-positive, 2 true-negative, 0 false-positive, and 2 false-negative cases. Sensitivity was 85.7%, specificity was 100%, positive predictive value was 100%, and negative predictive value was 50%. The diagnostic accuracy of EUS-FNA was 87.5%. Conclusion. EUS-FNA is accurate and reliable for diagnosing pancreatic lesions.

The coronavirus disease 2019 (COVID-19) pandemic is caused by a novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), similar to SARS-CoV and Middle East respiratory syndrome (MERS-CoV), which cause acute respiratory distress syndrome and case fatalities. COVID-19 disease severity is worse in older obese patients with comorbidities such as diabetes, hypertension, cardiovascular disease, and chronic lung disease. Cell binding and entry of betacoronaviruses is via their surface spike glycoprotein; SARS-CoV binds to the metalloprotease angiotensin-converting enzyme 2 (ACE2), MERS-CoV utilizes dipeptidyl peptidase 4 (DPP4), and recent modeling of the structure of SARS-CoV-2 spike glycoprotein predicts that it can interact with human DPP4 in addition to ACE2. DPP4 is a ubiquitous membrane-bound aminopeptidase that circulates in plasma; it is multifunctional with roles in nutrition, metabolism, and immune and endocrine systems. DPP4 activity differentially regulates glucose homeostasis and inflammation via its enzymatic activity and nonenzymatic immunomodulatory effects. The importance of DPP4 for the medical community has been highlighted by the approval of DPP4 inhibitors, or gliptins, for the treatment of type 2 diabetes mellitus. This review discusses the dysregulation of DPP4 in COVID-19 comorbid conditions; DPP4 activity is higher in older individuals and increased plasma DPP4 is a predictor of the onset of metabolic syndrome. DPP4 upregulation may be a determinant of COVID-19 disease severity, which creates interest regarding the use of gliptins in management of COVID-19. Also, knowledge of the chemistry and biology of DPP4 could be utilized to develop novel therapies to block viral entry of some betacoronaviruses, potentially including SARS-CoV-2.摘要: 2019年新冠肺炎冠状病毒大流行是由一种新型β新冠状病毒-严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)引起的, 类似于SARS-CoV和中东呼吸综合征(MERS-CoV), 可引起急性呼吸窘迫综合征和死亡。新冠肺炎病的严重程度在患有糖尿病, 高血压, 心血管疾病和慢性肺部疾病的老年肥胖患者中更严重。β冠状病毒结合并进入细胞是通过它们的表面刺状糖蛋白；SARS-CoV是与金属蛋白酶血管紧张素转换酶2(ACE2)结合, 而MERS-CoV利用二肽肽酶4(DPP4)进入细胞。最近对SARS-CoV-2刺激性糖蛋白结构的模拟, 预测除了ACE2之外, 它还可以与人DPP4相互作用。DPP4是一种无处不在的膜结合型氨基肽酶, 在血浆中循环, 具有多种功能, 在营养, 代谢, 免疫和内分泌系统中发挥作用。DPP4通过其酶活性和非酶免疫调节作用, 调节葡萄糖稳态和炎症。DPP4抑制剂或格列普汀被批准用于治疗2型糖尿病, 这突显了DPP4对医学界的重要性。本文就新冠肺炎合并疾病时DPP4的异常调节进行综述。老年人DPP4活性较高, 血浆DPP4升高是代谢综合征发病的预测因子。DPP4上调可能是新冠肺炎疾病严重程度的决定因素, 这引起了人们对格列普汀在新冠肺炎治疗中使用的兴趣。此外, DPP4的化学和生物学知识可以用来开发新的疗法, 阻止一些β冠状病毒如SARS-CoV-2等入侵体内。.

BACKGROUND The aggressive approach of vascular resection plus reconstruction in curative resection of hilar cholangiocarcinoma (HC) remains controversial. This retrospective study investigated its short- and long-term outcomes. METHODS Data of HC patients from 1989 to 2016 were reviewed. Operated patients were divided into two groups (with and without vascular resection) and compared in terms of perioperative results. Patients who had unresectable HC were also compared with patients who had been operated. RESULTS Ninety patients underwent curative HC resection. They were divided into group A (without aggressive approach, n = 68) and group B (with aggressive approach, n = 22). The groups were comparable in all parameters including rates of overall and major complication and in-hospital, 30-day and 90-day mortality except that group B had more patients with more advanced disease (P = 0.008), more patients with tumour invasion of the vasculature (40.9% versus 7.4%, P = 0.001), and fewer patients with blood transfusion (27.3% versus 52.9%, P = 0.036). The groups had similar disease-free survival (group A: median, 17.9 months, 5 years, 27.4%; group B: median, 11.7 months, 5 years, 14.3%; P = 0.427) and overall survival (group A: median, 22.0 months, 5 years, 26.5%; group B: median, 26.5 months, 5 years, 14.7%; P = 0.90). Two hundred patients with unresectable HC were compared with patients who had received operation and found to have worse survival outcomes (P

Objective(s): To study the relation between the systolic and diastolic right ventricular (RV) function in relation to the time of extubation after total repair of tetralogy of Fallot (TOF) in a pediatric population. Design: Prospective, descriptive, non-randomized study. Setting: Pediatric cardiac surgery unit at Ain Shams University Hospitals, Cairo, Egypt. The study was conducted from January 2016 to February 2018. Participants: A total of 60 patients having elective primary total repairs of TOF made up the study sample. The patients were divided into two groups based on the time of extubation: Group I included patients who were extubated 6 hours or more after the procedure, while Group II included patients who were extubated within the first 6 hours. Interventions: Total corrective surgery involving open-heart surgery with cardiopulmonary bypass. Measurements and Main Results: Early outcomes of mortality and morbidity were evaluated. RV systolic and diastolic functions were evaluated in the routine echocardiography performed on the first and fifth postoperative days. Additionally, patients’ inotropic drug requirements during their intensive care unit (ICU) stays were calculated to produce the inotropic index for evaluation of postoperative low cardiac output. Group I contained 32 patients, while Group II contained 28. The mean ages in Group I and II, respectively, were 1.2 0.8 years and 1.5 0.9 years (p = 0.180). The mean weight in Group I and II, respectively, was 10.5 2.5 kg and 9.86 3.2 kg (p = 0.396). There were 20 (62.5%) males in Group I and 18 (64.29%) males in Group II (p = 0.886). Mortality was 2 cases (6.3%) in Group I and 1 case (3.6%) in Group II, with no statistical difference. Postoperative echocardiographic examination revealed significantly better RV functional parameters in Group II than in Group I. Keywords: Early extubation, Right ventricular function, Tetralogy of Fallot.

We provide guidance on prevention of adrenal crisis during the global COVID-19 crisis, a time with frequently restricted access to the usual level of healthcare. Patients with adrenal insufficiency are at an increased risk of infection, which may be complicated by developing an adrenal crisis; however, there is currently no evidence that adrenal insufficiency patients are more likely to develop a severe course of disease. We highlight the need for education (sick day rules, stringent social distancing rules), equipment (sufficient glucocorticoid supplies, steroid emergency self-injection kit) and empowerment (steroid emergency card, COVID-19 guidelines) to prevent adrenal crises. In patients with adrenal insufficiency developing an acute COVID-19 infection, which frequently presents with continuous high fever, we suggest oral stress dose cover with 20 mg hydrocortisone every 6 h. We also comment on suggested dosing for patients who usually take modified release hydrocortisone or prednisolone. In patients with adrenal insufficiency showing clinical deterioration during an acute COVID-19 infection, we advise immediate (self-)injection of 100 mg hydrocortisone intramuscularly, followed by continuous i.v. infusion of 200 mg hydrocortisone per 24 h, or until this can be established, and administration of 50 mg hydrocortisone every 6 h. We also advise on doses for infants and children.

Many poisons affect the heart or blood vessels or their autonomic control; these direct or indirect effects result in cardiovascular complications that contribute substantially to morbidity and mortality in poisoned patients. Direct cardiotoxic effects can alter heart rate, conduction or rhythm, resulting in sinus bradycardia (e.g. β-adrenoceptor blockers, calcium channel blockers) or tachycardia (e.g. sympathomimetic agents such as cocaine) or dysrhythmias such as torsade de pointes, ventricular tachycardia or ventricular fibrillation. Hypertension can be caused by cardiac stimulation or vasoconstriction, and hypotension by hypovolaemia, vasoplegia or poor cardiac output. The cardiovascular impact of poisoning can be exacerbated by pre-existing co-morbidities such as heart, respiratory or liver disease. Here we describe a pragmatic approach to the identification, monitoring and treatment of common cardiovascular complications of poisoning.

Objective Patients with thyrotoxicosis are treated with anti-thyroid drug (ATD) using block and replace (BR) or a smaller, titrated dose of ATD (dose titration, DT). Design A multi-centre, phase III, open-label trial of newly diagnosed paediatric thyrotoxicosis patients randomised to BR/DT. We compared the biochemical response to BR/DT in the first 6 months of therapy. Methods Patients commenced 0.75 mg/kg carbimazole (CBZ) daily with randomisation to BR/DT. We examined baseline patient characteristics, CBZ dose, time to serum thyroid-stimulating hormone (TSH)/free thyroxine (FT4) normalisation and BMI Z-score change. Results There were 80 patients (baseline) and 78 patients (61 female) at 6 months. Mean CBZ dose was 0.9 mg/kg/day (BR) and 0.5 mg/kg/day (DT). There was no difference in time to non-suppressed TSH concentration; 16 of 39 patients (BR) and 11 of 39 (DT) had suppressed TSH at 6 months. Patients with suppressed TSH had higher mean baseline FT4 levels (72.7 vs 51.7 pmol/L; 95% CI for difference 1.73, 31.7; P = 0.029). Time to normalise FT4 levels was reduced in DT (log-rank test, P = 0.049) with 50% attaining normal FT4 at 28 days (95% CI 25, 32) vs 35 days in BR (95% CI 28, 58). Mean BMI Z-score increased from 0.10 to 0.81 at 6 months (95% CI for difference 0.57, 0.86; P < 0.001) and was greatest in patients with higher baseline FT4 concentrations. Conclusions DT-treated patients normalised FT4 concentrations more quickly than BR. Overall, 94% of patients have normal FT4 levels after 6 months, but 33% still have TSH suppression. Excessive weight gain occurs with both BR and DT therapy.

Hyperthyroidism caused by Graves’ disease (GD) is a relatively rare disease in children. Treatment options are the same as in adults – antithyroid drugs (ATD), radioactive iodine (RAI) or thyroid surgery, but the risks and benefits of each modality are different. The European Thyroid Association guideline provides new recommendations for the management of pediatric GD with and without orbitopathy. Clinicians should be alert that GD may present with behavioral changes or declining academic performance in children. Measurement of serum TSH receptor antibodies is recommended for all pediatric patients with hyperthyroidism. Management recommendations include the first-line use of a prolonged course of methimazole/carbimazole ATD treatment (3 years or more), a preference for dose titration instead of block and replace ATD, and to avoid propylthiouracil use. Where definitive treatment is required either total thyroidectomy or RAI is recommended, aiming for complete thyroid ablation with a personalized RAI activity. We recommend avoiding RAI in children under 10 years of age but favor surgery in patients with large goiter. Pediatric endocrinologists should be involved in all cases.

25X-NBOMe compounds are halogenated, phenethylamine-related novel psychoactive drugs, with hallucinogenic and stimulant effects. NBOMes are potent and highly efficacious agonists at the 5HT2a receptor with binding affinities in the low nanomolar range, accounting for their psychoactive and toxic effects. 25I-, 25B-, and 25C-NBOMes are the most frequently encountered compounds; they are typically sold as blotter papers, or in powder, liquid, or tablet forms, and administered by several routes including sublingual or buccal ingestion, nasal insufflation, through smoking or more rarely through intravenous injection. 25X-NBOMes have been identified worldwide and are associated with clinical presentations consistent with sympathomimetic, hallucinogenic, and possibly serotonergic toxidromes. 25X-NBOMEs have been associated with cases of severe toxicity and death, and therefore physicians should remain vigilant for features that may be consistent with toxicity, particularly in those who report ingesting using blotters or LSD. In this chapter, the current understanding of 25X-NBOMe pharmacology and toxicology is reviewed

Background Despite excellent outcomes and reduced invasiveness, the right anterolateral thoracotomy approach for aortic valve replacement (RALT-AVR) has not been broadly adopted. This study provides results regarding the initial experience and learning curve of a single surgeon performing this procedure. Methods Periprocedural details and postoperative outcomes of the first 100 consecutive patients who underwent RALT-AVR at our institution were retrospectively analysed. We conducted a cumulative sum analysis of surgical failure, defined as occurrence of 30-day-mortality, surgical revision for bleeding, conversion to sternotomy, 3rd degree heart block, paravalvular leakage, postoperative stroke or mean transvalvular gradient >20 mmHg. Results The cohort was of low surgical risk (mean EuroSCORE II 1.31% ± 0.85, mean STS PROM 1.45% ± 0.97), 58% were males. Median cross-clamp time was 67.5 [57.8-76] min, median CPB time 105 [91.8-119] min, and median operation time 164.5 [144.5-183.2] min. There were no conversions to full sternotomy, 4 cases of revision for bleeding and 2 pacemaker implantations for 3rd degree heart block. Prosthesis function was good (median ∆Pmean 10.9 [7.4-13.6] mmHg). Thirty-day-mortality was 0%. The log-likelihood graph never crossed the upper boundary, and after a steady decrease, crossed the lower boundary at 93 patients. Conclusions RALT-AVR can be performed with acceptable procedural times and satisfactory outcomes. For a well-trained surgeon, adapting to this new procedure does not expose patients to an increased risk, when patient selection and procedural planning are applied appropriately. Cumulative sum failure analysis is an appropriate tool to monitor the transition from standard AVR to the technically more demanding RALT-AVR.

Context Remission rates in young people with Graves hyperthyroidism are less than 25% after 2 years of thionamide antithyroid drug (ATD). Objective We explored whether rituximab (RTX), a B-lymphocyte–depleting agent, would increase remission rates when administered with a short course of ATD. Methods This was an open-label, multicenter, single-arm, phase 2 trial in young people (ages, 12-20 years) with Graves hyperthyroidism. An A’Hern design was used to distinguish an encouraging remission rate (40%) from an unacceptable rate (20%). Participants presenting with Graves hyperthyroidism received 500 mg RTX and 12 months of ATD titrated according to thyroid function. ATDs were stopped after 12 months and primary outcome assessed at 24 months. Participants had relapsed at 24 months if thyrotropin was suppressed and free 3,5,3′-triiodothyronine was raised; they had received ATD between months 12 and 24; or they had thyroid surgery/radioiodine. Results A total of 27 participants were recruited and completed the trial with no serious side effects linked to treatment. Daily carbimazole dose at 12 months was less than 5 mg in 21 of 27 participants. Thirteen of 27 participants were in remission at 24 months (48%, 90% one-sided CI, 35%-100%); this exceeded the critical value (9) for the A’Hern design and provided evidence of a promising remission rate. B-lymphocyte count at 28 weeks, expressed as a percentage of baseline, was related to likelihood of remission. Conclusion Adjuvant RTX, administered with a 12-month course of ATD, may increase the likelihood of remission in young people with Graves hyperthyroidism. A randomized trial of adjuvant RTX in young people with Graves hyperthyroidism is warranted.

IntroductionRecent discoveries have identified shortened telomeres and related mutations in people with pulmonary fibrosis (PF). There is evidence to suggest that androgens, including danazol, may be effective in lengthening telomeres in peripheral blood cells. This study aims to assess the safety and efficacy of danazol in adults and children with PF associated with telomere shortening.Methods and analysisA multi-centre, double-blind, placebo-controlled, randomised trial of danazol will be conducted in subjects aged >5 years with PF associated with age-adjusted telomere length ≤10th centile measured by flow fluorescence in situ hybridisation; or in children, a diagnosis of dyskeratosis congenita. Adult participants will receive danazol 800 mg daily in two divided doses or identical placebo capsules orally for 12 months, in addition to standard of care (including pirfenidone or nintedanib). Paediatric participants will receive danazol 2 mg/kg/day orally in two divided doses or identical placebo for 6 months. If no side effects are encountered, the dose will be escalated to 4 mg/kg/day (maximum 800 mg daily) orally in two divided doses for a further 6 months. The primary outcome is change in absolute telomere length in base pairs, measured using the telomere shortest length assay (TeSLA), at 12 months in the intention to treat population.Ethics and disseminationEthics approval has been granted in Australia by the Metro South Human Research Ethics Committee (HREC/2020/QMS/66385). The study will be conducted and reported according to Standard Protocol Items: Recommendations for Interventional Trials guidelines. Results will be published in peer-reviewed journals and presented at international and national conferences.Trial registration numbersNCT04638517; Australian New Zealand Clinical Trials Registry (ACTRN12620001363976p).

Background The transversus abdominis plane (TAP) block is a known approach for blocking the abdominal wall neural afferents via the bilateral lumbar triangles of Petit. Different adjuvants have been used to intensify the quality and the duration of local anesthetics. Aim of the Work The aim of this study is to detect the efficacy and safety of magnesium sulphate as an adjuvant to the analgesia offered by local anesthetic in ultrasound guided TAP block in patients undergoing surgical repair of moderate sized umilical hernia under general anathesia. As regard postoperative pain and opioid consumption using Visual Analogue scale VAS. Patients and Methods the study was carried out on 40 patients who was undergo surgical hernial repair, after ethical approval of Ain Shams University Hospital and informed consent from patients ,patients assigned in two group ,each group include 20 patients, Group 1: receive TAP block with Bupivacaine 0.25% 20 ml per side. Group 2: receive TAP block with Bupivacaine 0.25% 18 mL+2 ml magnesium sulphate. Results By the end of our study we found that VAS pain score was less in group II than in group I at 0,1,2 and 24 hours postoperatively and most significant at 4,6 and 12 hours the VAS score less in group II than group I (p value Conclusion MgSO4 as an adjuvant to Bupivacaine in Ultra-sounded guided TAP block reduces postoperative pain scores, prolong the duration of analgesia and decreases demand for rescue analgesics.

Background Patients undergoing Open Appendectomy experience pain postoperatively, requiring a multimodal approach to analgesia. The transversus abdominis plane (TAP) block seems to be an ideal approach. This block may be achieved using bupivacaine with adjuvants such as magnesium sulfate, which we were used in this study. Aim of the Work to detect the efficacy and safety of magnesium sulphate as an adjuvant to the analgesia offered by local anesthetic in ultrasound guided TAP block in patients undergoing open appendectomy. Patients and Methods A prospective double blinded randomized controlled trial was conducted on 60 patients undergoing open appendectomy at Ain Shams University Hospital, Cairo, Egypt. Results Our study concluded that co administration of 500mg MgSo4 to 0.5 % bupivacaine in US guided TAP block lead to: Significant decrease in VAS pain score especially at 4hrs, 6hrs and 12hrs,1st rescue dose of nalbuphine was delayed. And number of patients require rescue doses of nalbuphine in 1st 4 hrs, while only 2 patients require rescue doses of nalbuphine between 4&6 hrs.4 patients require rescue doses of nalbuphine between 6&12 hrs, while 26 patients require rescue doses of nalubuphine between 12&24hrs. we also cocluded that there were a significant decrease in HR and MABP especially at 4hrs and 6 hrs postoperative,. Conclusion MgSO4 as an adjuvant to bupivacaine in Ultra-sounded guided TAP block reduces post-operative pain scores, prolong the duration of analgesia and decreases demand for rescue analgesics.

Most patients with rare diseases do not receive a molecular diagnosis and the aetiological variants and causative genes for more than half such disorders remain to be discovered1. Here we used whole-genome sequencing (WGS) in a national health system to streamline diagnosis and to discover unknown aetiological variants in the coding and non-coding regions of the genome. We generated WGS data for 13,037 participants, of whom 9,802 had a rare disease, and provided a genetic diagnosis to 1,138 of the 7,065 extensively phenotyped participants. We identified 95 Mendelian associations between genes and rare diseases, of which 11 have been discovered since 2015 and at least 79 are confirmed to be aetiological. By generating WGS data of UK Biobank participants2, we found that rare alleles can explain the presence of some individuals in the tails of a quantitative trait for red blood cells. Finally, we identified four novel non-coding variants that cause disease through the disruption of transcription of ARPC1B, GATA1, LRBA and MPL. Our study demonstrates a synergy by using WGS for diagnosis and aetiological discovery in routine healthcare.

An 87-year-old patient donated his body to the Institute of Anatomy and Cell Biology in gratefulness for the longevity of a Bjork-Shiley convexo-concave (BSCC) prosthetic aortic valve, implanted 34 years ago. The dissection of the enlarged heart showed no major signs of thrombosis, malignant fibrosis, or any other relevant issue that could potentially lead to valve failure as in other patients. Despite the reported high mortality rate of the earlier designs, especially of the BSCC valves, some patients survived for longer than expected. In more than 34 years after the BSCC valve implantation, the patient was a very active and lively man, working both as full-time and volunteer firefighter. The lifespan of this BSCC valve is among the longest reported.

Transcatheter repair systems are becoming increasingly popular as a potential solution for high-risk and inoperable patients with mitral regurgitation. The cardioband (Edwards Lifesciences, Irvine, California) is a transcatheter direct annuloplasty device, based on the concept of an undersized ring annuloplasty. We report a case of minimally invasive surgical explantation of a failed cardioband device 21 months after its implantation. Intraoperatively, it was found that three anchors of the cardioband device were detached from the posterior annulus at P2. In this report, a "cut and unscrew" technique with some tips and tricks is presented for the removal of the device.

Currently, there are over 1.9 million confirmed cases of coronavirus disease 2019 (COVID-19) globally with over 590,000 cases in the United States.1 The number of COVID-19–positive children in the United States is unknown. A report summarizing 72,314 COVID-19 cases from the Chinese Center for Disease Control and Prevention noted 416 COVID-19–positive children younger than 10.2 An observational study at Wuhan Children's Hospital noted 31 COVID-19–positive children younger than 1 year with the youngest confirmed case in a 1-day-old.3 Cases were largely characterized by upper respiratory tract infection or pneumonia, fever, cough, and pharyngeal erythema.3 Concomitant neurologic problems have been reported among COVID-19–positive adult patients.4

We have developed polymer composite inks that may be three-dimensionally (3D) printed to produce new reactor designs for CO2 capture. These inks are composed of solid sodium carbonate particles dispersed within an uncured silicone and are printed using direct ink writing (DIW). After printing, the silicone is cured, and the structures are hydrated to form aqueous sodium carbonate domains dispersed throughout the silicone. These domains enable high CO2 absorption rates by creating domains with high surface area of solvent per unit volume in the printed structures. These results demonstrate an order-of-magnitude improvement in CO2 absorption rates relative to a liquid pool of sodium carbonate. The results from this class of composite inks demonstrate the potential for the use of 3D printing to shape new and advanced CO2 capture reactors.

The vascular system of the spinal cord is particularly complex and vulnerable. Damage to the main vessels or alterations to the regulation of blood flow will result in a reduction or temporary cessation of blood supply. The resulting tissue hypoxia may be brief: acute, or long lasting: chronic. Damage to the vascular system of the spinal cord will develop after a traumatic event or as a result of pathology. Traumatic events such as road traffic accidents, serious falls and surgical procedures, including aortic cross-clamping, will lead to an immediate cessation of perfusion, the result of which may not be evident for several days, but may have long-term consequences including neurodegeneration. Pathological events such as arterial sclerosis, venous occlusion and spinal cord compression will result in a progressive reduction of blood flow, leading to chronic hypoxia. While in some situations the initial pathology is exclusively vascular, recent research in neurodegenerative disease has drawn attention to concomitant vascular anomalies in disorders, including amyotrophic lateral sclerosis, spinal muscular atrophy and muscular sclerosis. Understanding the role of, and tissue response to, chronic hypoxia is particularly important in these cases, where inherent neural damage exacerbates the vulnerability of the nervous system to stressors including hypoxia.

Purpose: For planning and guidance of minimally invasive mitral valve repair procedures, 3D+t transesophageal echocardiography (TEE) sequences are acquired before and after the intervention. The valve is then visually and quantitatively assessed in selected phases. To enable a quantitative assessment of valve geometry and pathological properties in all heart phases, as well as the changes achieved through surgery, we aim to provide a new 4D segmentation method. Methods: We propose a tracking-based approach combining gradient vector flow (GVF) and position-based dynamics (PBD). An open-state surface model of the valve is propagated through time to the closed state, attracted by the GVF field of the leaflet area. The PBD method ensures topological consistency during deformation. For evaluation, one expert in cardiac surgery annotated the closed-state leaflets in 10 TEE sequences of patients with normal and abnormal mitral valves, and defined the corresponding open-state models. Results: The average point-to-surface distance between the manual annotations and the final tracked model was 1.00mm±1.08mm. Qualitatively, four cases were satisfactory, five passable and one unsatisfactory. Each sequence could be segmented in 2-6 min. Conclusion: Our approach enables to segment the mitral valve in 4D TEE image data with normal and pathological valve closing behavior. With this method, in addition to the quantification of the remaining orifice area, shape and dimensions of the coaptation zone can be analyzed and considered for planning and surgical result assessment.

This paper studies the relation between the complexity of global banking organizations and their foreign banking operations (FBOs) in Hong Kong. Our empirical evidence indicates that the complexity of the parent company has significant effects on their Hong Kong branch’s business model, liquidity management, risk-taking, and profitability. The more complex the global banking organizations, their Hong Kong FBOs are more likely to derive a larger share of revenues from fee-based activities, and incur a higher cost of production despite enjoying a funding cost advantage. Notwithstanding the FBOs in Hong Kong may serve as a funding hub for its parent company, FBOs of more complex global banks tend to hold more liquid assets. While our empirical evidence suggests that the complexity of global banks has significant effects on FBOs risk-taking and profitability, the relation depends on how complexity is measured. For example, both the BCBS complexity score and the measure of geographic complexity are significant in explaining FBO profitability, but they have different signs. Likewise, geographic complexity and scope complexity are often found to have significantly different effects on FBOs performance. Taken together, the concept of global bank complexity has multiple dimensions, where different facets could have qualitatively different effects on FBOs in Hong Kong.

Summary Background The incidence of head and neck cancer (H&N) continues to increase together with the need for reconstructive surgery. Head and Neck microsurgeons are likely to encounter challenging secondary free flap surgery on the background of failed primary flaps, radiotherapy treatment or recurrence. The aim of this study was to review our experience of treating such cases in a tertiary referral centre in the United Kingdom. Methods We performed a retrospective analysis of all patients undergoing sequential free flap surgery for head and neck defects in our unit during 2010–2017. Parameters recorded included indication for surgery, type and sequence of reconstruction, recipient vessel use and post-operative complications. Results We identified 17 patients who underwent 39 free tissue transfers for the reconstruction of head and neck defects (five transfers were performed at other units). The radial forearm and anterolateral thigh flaps were most commonly used. Almost a quarter of patients underwent three or more free flap reconstructive procedures. In over a third, the same vein and artery were used for subsequent anastomoses, and we used five vein grafts over 68 anastomoses. There were no flap failures recorded. Conclusions Secondary free flaps in the head and neck are required for a variety of aetiologies and can have success rates similar to those for primary free tissue transfers with minimal morbidity and mortality. Free tissue transfer is the best reconstructive option in H&N patients and should still be considered the first choice option in salvage cases until the patient's donor sites have been depleted.

Background: Graves' disease is one of the most common autoimmune conditions, but treatment remains imperfect. This study explores the first-in-human use of antigen-specific immunotherapy with a combination of two thyrotropin receptor (TSHR) peptides (termed ATX-GD-59) in Graves' hyperthyroidism. Methods: Twelve participants (11 female) with previously untreated mild to moderate Graves' hyperthyroidism were enrolled in a Phase I open label trial to receive 10 doses of ATX-GD-59 administered intradermally over an 18-week period. Adverse events, tolerability, changes in serum free thyroid hormones, and TSHR autoantibodies were measured. Results: Ten subjects received all 10 doses of ATX-GD-59, five (50%) of whom had free triiodothyronine within the reference interval by the 18-week visit. Two further subjects had improved free thyroid hormones by the end of the study (7/10 responders), whereas three subjects showed worsening thyrotoxicosis during the study. Serum TSHR autoantibody concentrations reduced during the study and correlated with changes in free thyroid hormones (r = 0.85, p = 0.002 for TSHR autoantibody vs. free triiodothyronine). Mild injection-site swelling and pain were the most common adverse events. Conclusions: These preliminary data suggest that ATX-GD-59 is a safe and well-tolerated treatment. The improvement in free thyroid hormones in 70% of subjects receiving the medication suggests potential efficacy as a novel treatment for Graves' hyperthyroidism.

Obesity is associated with altered responses to food stimuli in prefrontal brain networks that mediate inhibitory control of ingestive behavior. In particular, activity of the dorsolateral prefrontal cortex (dlPFC) is reduced in obese compared to normal-weight subjects and has been linked to the success of weight-loss dietary interventions. In a randomized controlled trial in overweight/obese subjects, we investigated the effect on eating behavior of volitional up-regulation of dlPFC activity via real-time functional magnetic resonance imaging (fMRI) neurofeedback training. Thirty-eight overweight or obese subjects (BMI 25–40 kg/m2) took part in fMRI neurofeedback training with the aim of increasing activity of the left dlPFC (dlPFC group; n = 17) or of the visual cortex (VC/control group; n = 21). Participants were blinded to group assignment. The training session took place on a single day and included three training runs of six trials of up-regulation and passive viewing. Food appraisal and snack intake were assessed at screening, after training, and in a follow-up session four weeks later. Participants of both groups succeeded in up-regulating activity of the targeted brain area. However, participants of the control group also showed increased left dlPFC activity during up-regulation. Functional connectivity between dlPFC and ventromedial PFC, an area that processes food value, was generally increased during up-regulation compared to passive viewing. At follow-up compared to baseline, both groups rated pictures of high-, but not low-calorie foods as less palatable and chose them less frequently. Actual snack intake remained unchanged but palatability and choice ratings for chocolate cookies decreased after training. We demonstrate that one session of fMRI neurofeedback training enables individuals with increased body weight to up-regulate activity of the left dlPFC. Behavioral effects were observed in both groups, which might have been due to dlPFC co-activation in the control group and, in addition, unspecific training effects. Improved dlPFC-vmPFC functional connectivity furthermore suggested enhanced food intake-related control mechanisms. Neurofeedback training might support therapeutic strategies aiming at improved self-control in obesity, although the respective contributions of area-specific mechanisms and general regulation effects are in need of further investigation.