Primary biliary cholangitis has the highest waitlist mortality in patients with cirrhosis and acute on chronic liver failure awaiting liver transplant

Background: Data are sparse on etiology specific outcomes on waitlist (WL) and post-transplant outcomes among patients with acute on chronic liver failure (ACLF). / Methods and results: In a retrospective cohort of 14,774 adults from United network for organ sharing (UNOS) database listed for Liver transplantation (LT) with cirrhosis and ACLF (January 2013–June 2019), 40% were due to alcohol-associated liver disease (ALD), followed by hepatitis C virus (HCV) at 20%, non-alcoholic steatohepatitis (19%), cryptogenic cirrhosis (7%), autoimmune hepatitis (5%), primary sclerosing cholangitis (PSC) at 3%, and 2% each for hepatitis B, primary biliary cholangitis (PBC), and metabolic etiology. Using competing risk analysis, cumulative risk of WL mortality was highest for PBC at 20.5% and lowest for PSC at 13.3%, P < .001. Compared with ALD as reference, WL mortality was higher for PBC (1.45 [1.16–1.82]), and similar for other etiologies, P < .001. Of this cohort, 9650 (65.3%) patients received LT, with 1-year. patient survival of 91.6% for PBC, worst for cryptogenic cirrhosis (89.5%) and best for PSC and ALD (93.4%), P < .001. / Conclusion: Among listed candidates with ACLF, those with PBC have highest WL mortality 1-year. post-transplant survival was excellent among recipients for PBC. If these findings are validated in prospective studies, liver disease etiology should be considered for LT selection among patients in ACLF

Validating a novel score based on interaction between ACLF grade and MELD score to predict waitlist mortality

Background and Aim: Among candidates listed for liver transplant (LT), MELD score may not capture acute on chronic liver failure (ACLF) severity. Data on interaction between ACLF and MELD score in predicting waitlist (WL) mortality are scanty. / Methods: UNOS database (01/2002 to 06/2018) on LT listings for adults with cirrhosis and ACLF (without HCC) was analyzed. ACLF grades 1, 2, 3a, and 3b- were defined using modified EASL-CLIF criteria. / Results: Of 18,416 candidates with ACLF at listing (mean age 54 years, 69% males, 63% Caucasians), 90-d WL mortality (patient death or being too sick for LT) was 21.6% (18%, 20%, 25%, and 39% for ACLF grades 1, 2, 3a, and 3b respectively). Fine and Gray regression model identified interaction between MELD and ACLF grade, with higher impact of ACLF at lower MELD score. Other variables included candidate’s age, gender, liver disease etiology, listing MELD, ACLF grade, obesity, and performance status. A score developed using parameter estimates from the interaction model on the derivation cohort (N=9181) stratified the validation cohort (N=9235) to four quartiles Q1 (score 15.50). WL mortality increased with each quartile from 13%, 18%, 23%, and 36% respectively. Observed versus expected deciles on WL mortality in validation cohort showed good calibration (goodness of fit P=0.98) and correlation (R=0.99). / Conclusion: Among selected candidates who are in ACLF at listing, MELD score and ACLF interact in predicting cumulative risk of 90-d WL mortality, with higher impact of ACLF grade at lower listing MELD score. Validating these findings in large prospective studies will support to factor in both MELD and ACLF in prioritizing transplant candidates and allocation of liver grafts

A note on clinical presentations of amebic liver abscess: an overview from 62 Thai patients

BACKGROUND: Amebic liver abscess is a tropical disease with a wide spectrum of clinical presentations. Given the often nonspecific nature of the complaints related to amebic abscess, a retrospective review of patients with confirmed disease to recognize the most common patterns of presentation is useful. Here, we study the clinical presentations of 62 Thai patients with amebic liver abscess. We also compare the clinical presentations of Anti HIV seronegative and Anti HIV seropositive patients. METHODS: A retrospective case review was carried out for 62 Thai patients who had been diagnosed with amebic liver abscess. Clinical information was collected, including symptoms and signs, location and number of abscesses. The Anti HIV serology laboratory investigation was also reviewed. RESULTS: According to our study, the common clinical symptoms and signs are abdominal pain (85.5 %), fever and chills (74.2 %), and abdominal tenderness (69.4 %). The location of the abscess was predominantly in the right lobe (74.2 %), and most of patients had a single abscess (77.4 %). Similar trends in clinical presentations were observed in both Anti HIV seropositive and Anti HIV seronegative subjects. CONCLUSIONS: In conclusion, the clinical presentations of our amebic liver abscess patients were similar to those in previous reports. A similarity to those in the pyogenic liver abscess patients can be observed. Nevertheless, we could not detect important significant differences in the clinical presentations between Anti HIV seropositive and Anti HIV seronegative groups of patients

Measuring attitudes, behaviours, and influences in inner city victims of interpersonal violence (VIVs) - a Swiss emergency room pilot study

Background Switzerland is confronted with the problem of interpersonal violence. Violence is in the increase and the potential for aggression seems to be rising. Observations by hospitals discern an appalling increase of the severity of the injuries. The aim of this study is to collect accurate information about the social environment, the motivation and possible reasons for violence. We also intend to investigate whether sociocultural, or ethnic differences among male victims exist. Materials and methods For the first time in Switzerland, this survey employed a validated questionnaire from the division of violence prevention, Atlanta, Georgia. The first part of the questionnaire addressed social and demographic factors which could influence the risk of violence: age, gender, duration of stay in Switzerland, nationality and educational level. Beside these social structural factors, the questionnaire included questions on experience of violent offences in the past, information about the most recent violent offence and intra and interpersonal facts. The questionnaire itself consists of 27 questions, translated into German and French. In a pilot study, the questionnaire was checked with adolescents for feasibility and comprehensibility. Results 69 male VIVs were interviewed at two hospitals in the Canton of Bern. Most of the adolescents emphasised that weapons were not used during their confrontations. It is astonishing that all of the young men considered themselves to be victims. Most of the brawls were incited after an exchange of verbal abuse and provocations with unfamiliar individuals. The rivals could neither be classified with the help of ethnic categories nor identifiable groups of the youth scenes. The incidents took place in scenes, where violence was more likely to happen. Interestingly and contrary to a general perception the offenders are well integrated into sport and leisure clubs. A further surprising result of our research is that the attitude towards religion differs between young men with experience of violence and non-violent men. Discussion Youth violence is a health issue, which concerns us globally. The human and economic toll of violence on victims and offenders, their families, and on society in general is high. The economic costs associated with violence-related illness and disability is estimated to be millions of Swiss francs each year. Physicians and psychologists are compelled to identify the factors, which cause young people to be violent, to find out which interventions prove to be successful, and to design effective prevention programs. The identification of effective programs depends on the availability of reliable and valid measures to assess changes in violence-related attitudes. In our efforts to create healthier communities, we need to investigate; document and do research on the causes and circumstances of youth violence

Triphasic Computed Tomography Enterography with Polyethylene Glycol to Detect Renal Cell Carcinoma Metastases to the Small Bowel

Enteroclysis was first used to diagnose small bowel obstruction in 1996. However, nasojejunal intubation required during enteroclysis causes discomfort to the patient. Triphasic computed tomography (CT) enterography, a noninvasive procedure that does not require intubation, was found to be an efficient method to diagnose small bowel lesions. We describe our experience of using triphasic CT enterography with polyethylene glycol (PEG) for diagnosing renal cell carcinoma (RCC) metastases to the small intestine. RCC can metastasize to many organs and can cause variable clinical presentations. We report the case of a 56-year-old man with RCC who had psoas muscle involvement and lung metastasis. The patient presented with melena and intermittent abdominal pain. Two conventional CT and small bowel series examinations had shown no obstructive lesion in the small intestine. However, triphasic CT enterography with PEG detected two enhanced masses suggestive of small bowel metastasis. The patient underwent laparotomy and segmental resection of the jejunum with primary anastomosis. Histologic examination was compatible with RCC. This is the first report where RCC metastasis to the small bowel was diagnosed using triphasic CT enterography. Our study emphasizes the importance of triphasic CT enterography in cases of obscure gastrointestinal bleeding, especially in patients suspected of having small bowel metastasis

Seatbelt use and risk of major injuries sustained by vehicle occupants during motor-vehicle crashes: A systematic review and meta-analysis of cohort studies

BackgroundIn 2004, a World Health Report on road safety called for enforcement of measures such as seatbelt use, effective at minimizing morbidity and mortality caused by road traffic accidents. However, injuries caused by seatbelt use have also been described. Over a decade after publication of the World Health Report on road safety, this study sought to investigate the relationship between seatbelt use and major injuries in belted compared to unbelted passengers.MethodsCohort studies published in English language from 2005 to 2018 were retrieved from seven databases. Critical appraisal of studies was carried out using the Scottish Intercollegiate Guidelines Network (SIGN) checklist. Pooled risk of major injuries was assessed using the random effects meta-analytic model. Heterogeneity was quantified using I-squared and Tau-squared statistics. Funnel plots and Egger's test were used to investigate publication bias. This review is registered in PROSPERO (CRD42015020309).ResultsEleven studies, all carried out in developed countries were included. Overall, the risk of any major injury was significantly lower in belted passengers compared to unbelted passengers (RR 0.47; 95%CI, 0.29 to 0.80; I-2=99.7; P=0.000). When analysed by crash types, belt use significantly reduced the risk of any injury (RR 0.35; 95%CI, 0.24 to 0.52). Seatbelt use reduces the risk of facial injuries (RR=0.56, 95% CI=0.37 to 0.84), abdominal injuries (RR=0.87; 95% CI=0.78 to 0.98) and, spinal injuries (RR=0.56, 95% CI=0.37 to 0.84). However, we found no statistically significant difference in risk of head injuries (RR=0.49; 95% CI=0.22 to 1.08), neck injuries (RR=0.69: 95%CI 0.07 to 6.44), thoracic injuries (RR 0.96, 95%CI, 0.74 to 1.24), upper limb injuries (RR=1.05, 95%CI 0.83 to 1.34) and lower limb injuries (RR=0.77, 95%CI 0.58 to 1.04) between belted and non-belted passengers.ConclusionIn sum, the risk of most major road traffic injuries is lower in seatbelt users. Findings were inconclusive regarding seatbelt use and susceptibility to thoracic, head and neck injuries during road traffic accidents. Awareness should be raised about the dangers of inadequate seatbelt use. Future research should aim to assess the effects of seatbelt use on major injuries by crash type

A model building exercise of mortality risk for Taiwanese women with breast cancer

Abstract Background The accurate estimation of outcome in patients with malignant disease is an essential component of the optimal treatment, decision-making and patient counseling processes. The prognosis and disease outcome of breast cancer patients can differ according to geographic and ethnic factors. To our knowledge, to date these factors have never been validated in a homogenous loco-regional patient population, with the aim of achieving accurate predictions of outcome for individual patients. To clarify this topic, we created a new comprehensive prognostic and predictive model for Taiwanese breast cancer patients based on a range of patient-related and various clinical and pathological-related variables. Methods Demographic, clinical, and pathological data were analyzed from 1 137 patients with breast cancer who underwent surgical intervention. A survival prediction model was used to allow analysis of the optimal combination of variables. Results The area under the receiver operating characteristic (ROC) curve, as applied to an independent validation data set, was used as the measure of accuracy. Results were compared by comparing the area under the ROC curve. Conclusions our model building exercise of mortality risk was able to predict disease outcome for individual patients with breast cancer. This model could represent a highly accurate prognostic tool for Taiwanese breast cancer patients.</p

Comprehensive Study in the Inhibitory Effect of Berberine on Gene Transcription, Including TATA Box

Berberine (BBR) is an established natural DNA intercalator with numerous pharmacological functions. However, currently there are neither detailed reports concerning the distribution of this alkaloid in living cells nor reports concerning the relationship between BBR's association with DNA and the function of DNA. Here we report that the distribution of BBR within the nucleus can be observed 30 minutes after drug administration, and that the content of berberine in the nucleus peaks at around 4 µmol, which is twelve hours after drug administration. The spatial conformation of DNA and chromatin was altered immediately after their association with BBR. Moreover, this association can effectively suppress the transcription of DNA in living cell systems and cell-free systems. Electrophoretic mobility shift assays (EMSA) demonstrated further that BBR can inhibit the association between the TATA binding protein (TBP) and the TATA box in the promoter, and this finding was also attained in living cells by chromatin immunoprecipitation (ChIP). Based on results from this study, we hypothesize that berberine can suppress the transcription of DNA in living cell systems, especially suppressing the association between TBP and the TATA box by binding with DNA and, thus, inhibiting TATA box-dependent gene expression in a non-specific way. This novel study has significantly expanded the sphere of knowledge concerning berberine's pharmacological effects, beginning at its paramount initial interaction with the TATA box

Tryptophan Scanning Analysis of the Membrane Domain of CTR-Copper Transporters

Membrane proteins of the CTR family mediate cellular copper uptake in all eukaryotic cells and have been shown to participate in uptake of platinum-based anticancer drugs. Despite their importance for life and the clinical treatment of malignancies, directed biochemical studies of CTR proteins have been difficult because high-resolution structural information is missing. Building on our recent 7Å structure of the human copper transporter hCTR1, we present the results of an extensive tryptophan-scanning analysis of hCTR1 and its distant relative, yeast CTR3. The comparative analysis supports our previous assignment of the transmembrane helices and shows that most functionally and structurally important residues are clustered around the threefold axis of CTR trimers or engage in helix packing interactions. The scan also identified residues that may play roles in interactions between CTR trimers and suggested that the first transmembrane helix serves as an adaptor that allows evolutionarily diverse CTRs to adopt the same overall structure. Together with previous biochemical and biophysical data, the results of the tryptophan scan are consistent with a mechanistic model in which copper transport occurs along the center of the trimer