Mechanical valve replacement for patients with rheumatic heart disease: the reality of INR control in Africa and beyond.

The majority of patients requiring heart valve replacement in low- to middle-income countries (LMICs) need it for rheumatic heart disease (RHD). While the young age of such patients largely prescribes replacement with mechanical prostheses, reliable anticoagulation management is often unattainable under the prevailing socioeconomic circumstances. Cases of patients with clotted valves presenting for emergency surgery as a consequence of poor adherence to anticoagulation control are frequent. The operative mortality rates of reoperations for thrombosed mechanical valves are several times higher than those for tissue valves, and long-term results are also disappointing. Under-anticoagulation prevails in these regions that has clearly been linked to poor international normalised ratio (INR) monitoring. In industrialised countries, safe anticoagulation is defined as >60%-70% of the time in the therapeutic range (TTR). In LMICs, the TTR has been found to be in the range of twenty to forty percent. In this study, we analysed >20,000 INR test results of 552 consecutive patients receiving a mechanical valve for RHD. Only 27% of these test results were in the therapeutic range, with the vast majority (61%) being sub-therapeutic. Interestingly, the post-operative frequency of INR tests of one every 3-4 weeks in year 1 had dropped to less than 1 per year by year 7. LMICs need to use clinical judgement and assess the probability of insufficient INR monitoring prior to uncritically applying Western guidelines predominantly based on chronological age. The process of identification of high-risk subgroups in terms of non-adherence to anticoagulation control should take into account both the adherence history of >50% of patients with RHD who were in chronic atrial fibrillation prior to surgery as well as geographic and socioeconomic circumstances.

Association of Broad-Spectrum Antibiotic Therapy and Vitamin E Supplementation with Vitamin K Deficiency-Induced Coagulopathy: A Case Report and Narrative Review of the Literature.

Vitamin K is a lipid-soluble vitamin that is normally maintained within appropriate levels by means of dietary intake and bacterial production in the intestinal microflora. It holds a central role in coagulation homeostasis, and thus its depletion leads to hypocoagulation and haemorrhagic diathesis. The association of antibiotic therapy and vitamin E supplementation with vitamin K deficiency was previously described in animal experiments, clinical studies, and case reports. Broad-spectrum antibiotic therapy potentially leads to intestinal microflora dysbiosis and restriction of vitamin K-producing bacterial populations, resulting in decreased vitamin K levels, whereas antibiotics of the cephalosporin class with 1-N-methyl-5-thiotetrazole (NMTT) or 2-methyl-1,3,4-thiadiazole (MTD) side groups inhibit vitamin K function. Vitamin E supplementation interferes with both the bioavailability and function of vitamin K, yet its mechanisms are not fully understood. We present the case of a 45-year-old male patient, with a history of epilepsy and schizophrenia, catatonically incapacitated and immobilised, who was hospitalised in our centre for the investigation and management of aspiration pneumonia. He demonstrated a progressively worsening prolongation of international normalised ratio (INR), which was attributed to both broad-spectrum antibiotic therapy and vitamin E supplementation and was reversed upon administration of vitamin K. We highlight the need for close monitoring of coagulation parameters in patients receiving broad-spectrum antibiotic therapy, especially those with underlying malnutritive or malabsorptive conditions, and we further recommend the avoidance of NMTT- or MTD-containing antibiotics or vitamin E supplementation, unless absolutely necessary, in those patients.

Implications of anaemia and response to anaemia treatment on outcomes in patients with cirrhosis.

Background & Aims: Anaemia is frequently observed in patients with cirrhosis and was identified as a predictor of adverse outcomes, such as increased mortality and occurrence of acute-on-chronic liver failure. To date, the possible effects of iron supplementation on these adverse outcomes are not well described. We therefore aimed to assess the role of iron supplementation in patients with cirrhosis and its capability to improve prognosis. Methods: Laboratory diagnostics were performed in consecutive outpatients with cirrhosis admitted between July 2018 and December 2019 to the University Hospital Essen. Associations with transplant-free survival were assessed in regression models. Results: A total of 317 outpatients with cirrhosis were included, of whom 61 received a liver transplant (n = 19) or died (n = 42). In multivariate Cox regression analysis, male sex (hazard ratio [HR] = 3.33, 95% CI [1.59, 6.99], p = 0.001), model for end-stage liver disease score (HR = 1.19, 95% CI [1.11, 1.27], p <0.001) and the increase of haemoglobin levels within 6 months (ΔHb6) (HR = 0.72, 95% CI [0.63, 0.83], p <0.001) were associated with transplant-free survival. Regarding the prediction of haemoglobin increase, intake of rifaximin (beta = 0.50, SD beta = 0.19, p = 0.007) and iron supplementation (beta = 0.79, SD beta = 0.26, p = 0.003) were significant predictors in multivariate analysis. Conclusions: An increase of haemoglobin levels is associated with improvement of transplant-free survival in patients with cirrhosis. Because the prediction of haemoglobin increase significantly depends on rifaximin and iron supplementation, application of these two medications can have an important impact on the outcome of these patients. Impact and implications: Anaemia is very common in patients with cirrhosis and is known to be a predictor of negative outcomes, but little is known about the effect of iron substitution in these individuals. In our cohort, increase of haemoglobin levels improved transplant-free survival of patients with cirrhosis. The increase of haemoglobin levels was mainly induced by iron supplementation and was even stronger in the case of concomitant use of iron and rifaximin. Clinical trial registration: UME-ID-10042.

Determining a preoperative international normalised ratio threshold safe for hip fracture surgery.

INTRODUCTION: The purpose of this study was first, to assess the relationship between preoperative INR (international normalised ratio) and postoperative complication rates in patients with a hip fracture, and second, to establish a threshold for INR below which the risk of complications is comparable to those in patients with a normal INR. METHODS: We retrospectively reviewed the American College of Surgeons National Surgical Quality Improvement Program and found 35,910 cases who had undergone surgery for a hip fracture between 2012 and 2018. Cases were stratified into 4 groups based on their preoperative INR levels: <1.4; ⩾1.4 and <1.6; ⩾1.6 and <1.8 and ⩾1.8. These cohorts were assessed for differences in preoperative factors, intraoperative factors, and postoperative course. Multivariate logistic regression was used to assess the risk of transfusion, 30-day mortality, cardiac complications, and wound complications adjusting for all preoperative and intraoperative factors. RESULTS: Of the 35,910 cases, 33,484 (93.2%) had a preoperative INR < 1.4; 867 (2.4%) an INR ⩾1.4 and <1.6; 865 (2.4%) an INR ⩾ 1.6 and <1.8 and 692 (1.9%) an INR ⩾ 1.8. A preoperative INR ⩾ 1.8 was independently associated with an increased risk of bleeding requiring transfusion. A preoperative INR ⩾ 1.6 was associated with an increased risk of mortality. CONCLUSIONS: We found that an INR of <1.6 is a safe value for patients who are to undergo surgery for a hip fracture. Below this value, patients avoid an increased risk of both transfusion and 30-day mortality seen with higher INR values. These findings may allow adjustment of preoperative protocols and improve the outcome of hip fracture surgery in this group of patients.

Correct dosing of Prothrombinex-VF in normalising elevated international normalised ratio in critically ill patients: a prospective cohort pilot study.

BACKGROUND: Prothrombinex-VF is being increasingly used as an off-label therapy to correct non-warfarin-related elevations in international normalised ratio (INR) in the critically ill. Currently there are no dosing guidelines for such use. AIMS: To validate a prediction equation, embedded in a smartphone application (app), to guide dosing of Prothrombinex-VF in critically ill patients. METHODS: A prospective pilot cohort study of critically ill adult patients with elevated INRs who were treated with Prothrombinex-VF. The main outcome measured was INR following Prothrombinex-VF administration. RESULTS: Of the 31 patients included, five (16%) were taking warfarin prior to admission and 14 (45%) had chronic liver disease. There was a significant decrease in INR after Prothrombinex-VF treatment (P < 0.001) and a significant correlation between the app's predicted INRs and the measured INRs (r = 0.63 and P < 0.001). The app's predicted INRs were less accurate for patients with chronic liver disease than for those without. Overall, the app's recommendations achieved an INR either similar to (29.6%) or better than (55.6%) what would have been achieved had the warfarin reversal guidelines been applied to dose the Prothrombinex-VF. CONCLUSION: The app appeared to be reasonably accurate at predicting normalisation of elevated INRs after administration of Prothrombinex-VF, especially among patients without liver disease. Its dosing recommendations were similar to or possibly better than preexisting warfarin reversal guidelines in over 85% of the situations analysed, if we assume a higher dose of Prothrombinex-VF would achieve a greater reduction in INR than a lower dose.

Evaluation of perioperative routine coagulation testing versus thromboelastography for major liver resection - A single-arm, prospective, interventional trial (PORTAL trial).

Background and Aims: The International Normalised Ratio (INR), which assesses the loss of procoagulant factors in the extrinsic pathway, fails to evaluate the coagulation abnormalities comprehensively after a major liver resection, which often leads to reduced synthesis of procoagulant and anticoagulant-factors. This study was conducted with an aim to study the trend and compare the results of routine coagulation tests and thromboelastography (TEG) during the perioperative period in patients undergoing major liver resections (≥3 segments). Methods: Twenty-five patients who underwent a major liver resection were enrolled. This prospective, single-arm, interventional study was performed with the primary objective of determining the serial changes in conventional coagulation tests and TEG during the perioperative period in patients undergoing major liver resections, at the preincision period, intraoperative period, postoperatively, at 48 h and on the fifth postoperative day. Transfusion requirements of blood components were also assessed with a TEG-guided replacement strategy. Spearman rank-order correlation was used to study the relationships of coagulation tests (both TEG and conventional tests) at each time point. Results: The prothrombin time (PT)-INR was elevated in 14 patients (56%) at the intraoperative, immediate postoperative and 48-h time points in contrast to the TEG parameters, which remained normal in all patients. Blood component transfusion was avoided in 4, 11 and 10 patients at the intraoperative, immediate postoperative and 48-h time points, respectively. Conclusion: International Normalised Ratio overestimates the coagulopathy in patients undergoing major liver resection, and a thromboelastography-guided transfusion strategy reduces overall transfusion requirements.

Estudio del desempeño analítico del dispositivo portátil microINR en pacientes anticoagulados con acenocumarol / Analytical performance of the microINR portable device in acenocoumarol anticoagulated patients

Resumen La razón internacional normalizada (RIN) se utiliza para controlar a los pacientes anticoagulados con antagonistas de la vitamina K. El objetivo de este estudio fue evaluar el desempeño del nuevo dispositivo portátil microINR, que utiliza tromboplastina recombinante, en pacientes anticoagulados con acenocumarol. Grupo 1: los pacientes proporcionaron muestras de sangre venosa y capilar para realizar pruebas paralelas que permitieron comparar microINR con cinco combinaciones diferentes de reactivo/sistema de detección: tromboplastina de cerebro de conejo con detección nefelométrica, foto-óptica y por viscosidad y tromboplastina humana recombinante con detección nefelométrica y fotoóptica. Todas las tromboplastinas tenían un índice de sensibilidad internacional (ISI) específico de equipo informado por el fabricante menor de 1,10. Grupo 2: los resultados de microINR se compararon con CoaguChek como dispositivo preestablecido. La precisión se evaluó utilizando materiales de control líquidos. El coeficiente de variación del material de control en microINR fue de 6,2%. El análisis de regresión de Passing-Bablok y Bland-Altman mostró un coeficiente de correlación superior a 0,92 y un pequeño sesgo cercano a cero para todas las comparaciones de microINR con cada método tradicional realizado con sangre venosa. Ambos dispositivos portátiles tuvieron un muy buen coeficiente de correlación (r=0,98) y un pequeño sesgo de 0,02. Los resultados muestran un acuerdo clínico del 100% con un grado de concordancia Kappa mayor de 0,63 para todos los métodos tradicionales y de 0,82 para la comparación con Coagu- Chek. De acuerdo a los resultados obtenidos, el microINR es adecuado para el control de pacientes anticoagulados con acenocumarol.

Abstract The international normalised ratio (INR) is used to monitor vitamin K antagonist anticoagulated patients. The aim of this study was to evaluate the performance of the microINR portable device in acenocoumarol anticoagulated patients. Group 1: patients provided capillary and venous blood samples for parallel testing comparing microINR with five different pairs of reagent/clot detection systems: brain rabbit thromboplastin with nephelometric, photooptic and viscocity clot detection and recombinant human thromboplastin with nephelometric and photooptical detection. All thromboplastins have an instrument-specific International Sensitivity Index (ISI) lower than 1.10 reported by the manufacturer. Group 2: microINR results were compared with CoaguChek as an established device. Precision was assessed using liquid control materials. The control material coefficient of variation obtained in microINR device was 6.2%. The Passing-Bablok and Bland-Altman regression analysis showed a correlation coefficient greater than 0.92 and a small bias close to zero for all comparisons of microINR with each traditional coagulation method performed on venous blood samples. Both portable devices had a good correlation (r=0.98) and a very low bias of 0.02. The results show clinical agreement of 100% with a Kappa greater than 0.63 for different traditional INR and greater than 0.83 for CoaguChek. The performance microINR is suitable for the anticoagulation control of patients taking acenocumarol.

Resumo A razão normalizada internacional (INR) é utilizada para monitorar pacientes anticoagulados com antagonistas da vitamina K. O objetivo deste estudo foi avaliar o desempenho do dispositivo portátil microINR, um novo dispositivo que utiliza tromboplastina recombinante, em pacientes anticoagulados com acenocumarol. Grupo 1: os pacientes forneceram amostras de sangue venoso e capilar para testes paralelos que permitiram a comparação do microINR com cinco combinações diferentes de reagente/ sistema de detecção: tromboplastina de cérebro de coelho com detecção nefelométrica, foto-óptica e de viscosidade. Tromboplastina humana recombinante com detecção nefelométrica e foto-óptica. Todas as tromboplastinas tinham o Índice de Sensibilida de Internacional (ISI) específico do kit relatado pelo fabricante inferior a 1,10. Grupo 2: os resultados do microINR foram comparados com o CoaguChek como dispositivo padrão. A precisão foi avaliada usando materiais de controle líquidos. O coeficiente de variação do material de controle em microINR foi de 6,2%. A análise de regressão de Passing-Bablok e Bland-Altman mostrou um coeficiente de correlação maior que 0,92 e um pequeno viés próximo a zero para todas as variáveis. sangue. Ambos os wearables tiveram um coeficiente de correlação muito bom (r=0,98) e um pequeno viés de 0,02. Os resultados mostram 100% de concordância clínica com grau de concordância Kappa maior que 0,63 para todos os métodos tradicionais e 0,82 para a comparação com CoaguChek. De acordo com os resultados obtidos, o microINR é adequado para o controle de pacientes anticoagulados com acenocumarol.

CLIF-C AD score predicts survival benefit from pre-emptive TIPS in individuals with Child-Pugh B cirrhosis and acute variceal bleeding.

Background & Aims: Among individuals with Child-Pugh B cirrhosis and acute variceal bleeding (AVB), the Baveno VII workshop recommended pre-emptive TIPS in those with a Child-Pugh score of 8-9 and active bleeding at initial endoscopy (Child B8-9 + AB criteria). Nevertheless, whether this criterion is superior to the CLIF-Consortium acute decompensation score (CLIF-C ADs) remains unclear. Methods: Data on 1,021 consecutive individuals with Child-Pugh B cirrhosis and AVB from 13 university hospitals in China who were treated with pre-emptive TIPS (n = 297) or drug plus endoscopic treatment (n = 724) between 2010 to 2019 were retrospectively analysed. A competing risk regression model was used to compare the outcomes between the two groups after adjusting for confounders. The concordance-statistic for benefit (c-for-benefit) was used to evaluate a models' ability to predict treatment benefit (risk difference between treatment groups). Results: Pre-emptive TIPS was associated with reduced mortality compared to drug plus endoscopic treatment (adjusted hazard ratio 0.62, 95% CI 0.44 to 0.88). A higher baseline CLIF-C AD score was associated with greater survival benefit (i.e., larger absolute mortality risk reduction). After adjusting for confounders, a survival benefit was observed in individuals with CLIF-C ADs ≥48 or Child-Pugh B8-9 with active bleeding, but not in those with CILF-C ADs <48, no active bleeding or Child-Pugh B7 with active bleeding. The c-for-benefit of CILF-C ADs for predicting survival benefit was higher than that of Child B8-9+AB criteria. Conclusions: In individuals with Child-Pugh B cirrhosis and AVB, CLIF-C ADs predicts survival benefit from pre-emptive TIPS and outperforms the Child B8-9+AB criteria. Prospective validation should be performed to confirm this result, especially for other aetiologies of cirrhosis. Impact and implications: In this study, among individuals with Child-Pugh B cirrhosis and acute variceal bleeding, the CLIF-Consortium acute decompensation (CLIF-C AD) score could predict the survival benefit from pre-emptive TIPS, with patients with higher CLIF-C AD scores benefiting more from pre-emptive TIPS. Furthermore, the CLIF-C AD score outperformed the Child B8-9 plus active bleeding criteria in terms of discriminating between those who obtained more benefit vs. less benefit from pre-emptive TIPS. Depending on prospective validation, the CLIF-C AD score could be used as the model of choice to determine who should undergo pre-emptive TIPS.

Development and validation of a mobile application based on a machine learning model to aid in predicting dosage of vitamin K antagonists among Indian patients post mechanical heart valve replacement.

Patients who undergo heart valve replacements with mechanical valves need to take Vitamin K Antagonists (VKA) drugs (Warfarin, Nicoumalone) which has got a very narrow therapeutic range and needs very close monitoring using PT-INR. Accessibility to physicians to titrate drugs doses is a major problem in low-middle income countries (LMIC) like India. Our work was aimed at predicting the maintenance dosage of these drugs, using the de-identified medical data collected from patients attending an INR Clinic in South India. We used artificial intelligence (AI) - machine learning to develop the algorithm. A Support Vector Machine (SVM) regression model was built to predict the maintenance dosage of warfarin, who have stable INR values between 2.0 and 4.0. We developed a simple user friendly android mobile application for patients to use the algorithm to predict the doses. The algorithm generated drug doses in 1100 patients were compared to cardiologist prescribed doses and found to have an excellent correlation.

Point of care testing to monitor INR control in patients with antiphospholipid syndrome.

Patients with antiphospholipid syndrome (APS) typically require lifelong warfarin anticoagulation following a thrombotic event due to a significant risk of recurrent thrombosis. Point of care testing (POCT) to monitor INR is discouraged in patients with APS as interactions between antiphospholipid antibodies and thromboplastin used for INR testing may influence results. Review of INR testing in 36 APS patients showed 87.2% of paired POCT and venous INRs (n = 94) having acceptable variation (≤0.5 difference), and high correlation (r = 0.9) excluding INRs ≥4.8. Six-month TTR was comparable for APS patients using POCT (57.1% ± 24.8%) to those using venous INR monitoring (59.2% ± 23.2%) (p = 0.66). These results support POCT management of APS but requires further study.

Alcohol and Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is a clinical syndrome that occurs in patients with cirrhosis and is characterised by acute deterioration, organ failure and high short-term mortality. Alcohol is one of the leading causes of ACLF and the most frequently reported aetiology of underlying chronic liver disease. Among patients with alcoholic hepatitis (AH), ACLF is a frequent and severe complication. It is characterised by both immune dysfunction associated to an increased risk of infection and high-grade systemic inflammation that ultimately induce organ failure. Diagnosis and severity of ACLF determine AH prognosis, and therefore, ACLF prognostic scores should be used in severe AH with organ failure. Corticosteroids remain the first-line treatment for severe AH but they seem insufficient when ACLF is associated. Novel therapeutic targets to contain the excessive inflammatory response and reduce infection have been identified and are under investigation. With liver transplantation remaining one of the most effective therapies for severe AH and ACLF, adequate organ allocation represents a growing challenge. Hence, a clear understanding of the pathophysiology, clinical implications and management strategies of ACLF in AH is essential for hepatologists, which is narrated briefly in this review.

Medical Treatment for Rheumatic Heart Disease: A Narrative Review.

BACKGROUND: Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are rare in high-income countries; however, in Aotearoa New Zealand ARF and RHD disproportionately affect Indigenous Maori and Pacific Peoples. This narrative review explores the evidence regarding non-surgical management of patients with clinically significant valve disease or heart failure due to RHD. METHODS: Medline, EMBASE and Scopus databases were searched, and additional publications were identified through cross-referencing. Included were 28 publications from 1980 onwards. RESULTS: Of the available interventions, improved anticoagulation management and a national RHD register could improve RHD outcomes in New Zealand. Where community pharmacy anticoagulant management services (CPAMS) are available good anticoagulation control can be achieved with a time in the therapeutic range (TTR) of more than 70%, which is above the internationally recommended level of 60%. The use of pharmacists in anticoagulation control is cost-effective, acceptable to patients, pharmacists, and primary care practitioners. There is a lack of local data available to fully assess other interventions; including optimal therapy for heart failure, equitable access to specialist RHD care, prevention, and management of endocarditis. CONCLUSION: As RHD continues to disproportionately affect Indigenous and minority groups, pro-equity tertiary prevention interventions should be fully evaluated to ensure they are reducing disease burden and improving outcomes in patients with RHD.

Risk of further decompensation/mortality in patients with cirrhosis and ascites as the first single decompensation event.

Background & Aims: Although ascites is the most frequent first decompensating event in cirrhosis, the clinical course after ascites as the single index decompensation is not well defined. The aim of this multicentre study was thus to systematically investigate the incidence and type of further decompensation after ascites as the first decompensating event and to assess risk factors for mortality. Methods: A total of 622 patients with cirrhosis presenting with grade 2/3 ascites as the single index decompensating event at 2 university hospitals (Padova and Vienna) between 2003 and 2021 were included. Events of further decompensation, liver transplantation, and death were recorded. Results: The mean age was 57 ± 11 years, and most patients were male (n = 423, 68%) with alcohol-related (n = 366, 59%) and viral (n = 200,32%) liver disease as the main aetiologies. In total, 323 (52%) patients presented with grade 2 and 299 (48%) with grade 3 ascites. The median Child-Pugh score at presentation was 8 (IQR 7-9), and the mean model for end-stage liver disease (MELD) was 15 ± 6. During a median follow-up period of 49 months, 350 (56%) patients experienced further decompensation: refractory ascites (n = 130, 21%), hepatic encephalopathy (n = 112, 18%), spontaneous bacterial peritonitis (n = 32, 5%), hepatorenal syndrome-acute kidney injury (n = 29, 5%). Variceal bleeding as an isolated further decompensation event was rare (n = 18, 3%), whereas non-bleeding further decompensation (n = 161, 26%) and ≥2 concomitant further decompensation events (n = 171, 27%) were frequent. Transjugular intrahepatic portosystemic shunt was used in only 81 (13%) patients. In patients presenting with grade 2 ascites, MELD ≥15 indicated a considerable risk for further decompensation (subdistribution hazard ratio [SHR] 2.18; p <0.001; 1-year incidences: <10: 10% vs. 10-14: 13% vs. ≥15: 28%) and of mortality (SHR 1.89; p = 0.004; 1-year incidences: <10: 3% vs. 10-14: 6% vs. ≥15: 14%). Importantly, mortality was similarly high throughout MELD strata in grade 3 ascites (p = n.s. for different MELD strata; 1-year incidences: <10: 14% vs. 10-14: 15% vs. ≥15: 20%). Conclusions: Further decompensation is frequent in patients with ascites as a single index decompensation event and only rarely owing to bleeding. Although patients with grade 2 ascites and MELD <15 seem to have a favourable prognosis, those with grade 3 ascites are at a high risk of mortality across all MELD strata. Lay summary: Decompensation (the development of symptoms as a result of worsening liver function) marks a turning point in the disease course for patients with cirrhosis. Ascites (i.e. , the accumulation of fluid in the abdomen) is the most common first decompensating event, yet little is known about the clinical course of patients who develop ascites as a single first decompensating event. Herein, we show that the severity of ascites is associated with mortality and that in patients with moderate ascites, the widely used prognostic MELD score can predict patient outcomes.

Value of Liver Function Tests in Cirrhosis.

The liver comprises both parenchymal and non-parenchymal cells with varying functions. Cirrhosis is often complicated by the development of portal hypertension and its associated complications. Hence, assessment of liver in cirrhosis should include assessment of its structural, function of both hepatic and non-hepatic tissue and haemodynamic assessment of portal hypertension. There is no single test that can evaluate all functions of liver and assess prevalence and severity of portal hypertension. Commonly available tests like serum bilirubin, liver enzymes (alanine [ALT] and aspartate aminotransferase [AST], serum alkaline phosphatase [ALP], gamma glutamyl transpeptidase [GGT]), serum albumin and prothrombin time for assessment of liver functions partly assess liver functions. quantitative liver functions like indocyanine clearance tests [ICG-K], methacetin breath test [MBT] were developed to assess dynamic status of liver but has its own limitation and availability. Imaging based assessment of liver by transient elastography, MRI based 99 mTc-coupled asialoglycoprotein mebrofenin scan help the clinician to assess liver function, functional volume of liver left after surgery and portal hypertension [PH]. Hepatic venous pressure gradient still remains the gold standard for the assessment of portal hypertension but is invasive and not available in all centres. Combinations of blood parameters in form of various indices like fibrosis score of 4 [FIB-4], Lok index, scores like model for end stage liver disease (MELD) and Child-Turcotte Pugh score are commonly used for assessing liver function in clinical practice.

Presence of Ascites at Presentation is Associated With Absence of Long-Term Response Amongst Patients With Budd-Chiari Syndrome When Treated With Medical Therapy Alone: A Single Centre Real-Life Experience.

Background: There is lack of data on long-term outcomes of patients with Budd-Chairi Syndrome (BCS) treated with medical therapy including anticoagulation alone. Methods: Consecutive patients (N = 138, mean [standard deviation, SD] age 29.3 [12.9] years; 66 men) with BCS, treated with medical therapy alone including anticoagulation, with minimum follow-up of 12 months were included. Initial response was classified as complete (CR), partial (PR) or nonresponse (NR) and on follow-up as loss of response (LoR) or maintenance of response (MoR). The association of baseline, clinical and biochemical parameters with different responses was evaluated. Results: Seventy-six patients (55.1%) had CR, 26 (18.8%) had PR and 36 (26.1%) had NR. None with PR or NR had CR later. At a median follow-up of 40 (range 12-174) months, LoR was more common in PR group than in CR group (12 [46.2%] vs 18 [23.7%], P = 0.03). LoR was associated with presence of ascites (odds ratio [OR] 1.5; 95% confidence interval [CI] 0.06-0.71), gastrointestinal bleed (OR 1.33; 95% CI 0.09-0.82) or jaundice (OR 1.01; 95% CI 0.11-0.97) at baseline and duration of follow-up (OR 0.018; 95% CI 1.006-1.030). Mortality was higher in NR (28 [77.8%]) compared with CR (15 [19.7%], P = 0.001) and PR (8 [30.8%], P = 0.001). On binary logistic regression analysis, presence of ascites at baseline was associated with LoR (OR 0.303 [0.098-0.931]). Conclusion: Patients with initial CR have better survival than nonresponders. One-third had LoR on follow-up. The presence of ascites at baseline is associated with LoR.

Molecular epidemiology and clinical characteristics of hepatitis D virus infection in Canada.

Background & Aims: HDV affects 4.5-13% of chronic hepatitis B (CHB) patients globally, yet the prevalence of HDV infection in Canada is unknown. To investigate the prevalence, genotype, demographics, and clinical characteristics of HDV in Canada, we conducted a retrospective analysis of (1) HDV antibody and RNA positivity among referred specimens, and (2) a cross-sectional subset study of 135 HDV seropositive +/-RNA (HDV+) patients compared with 5,132 HBV mono-infected patients in the Canadian HBV Network. Methods: Anti-HDV IgG-positive specimens collected between 2012 and 2019 were RNA tested and the genotype determined. Patients enrolled in the Canadian HBV Network were >18 years of age and HBsAg-positive. Clinical data collected included risk factors, demographics, comorbidities, treatment, fibrosis assessment, and hepatic complications. Results: Of the referred patients, 338/7,080 (4.8%, 95% CI 4.3-5.3) were HDV seropositive, with 219/338 RNA-positive (64.8%, 95% CI 59.6-69.7). The HDV+ cohort were more likely to be born in Canada, to be White or Black/African/Caribbean than Asian, and reporting high-risk behaviours, compared with HBV mono-infected patients. Cirrhosis, complications of end-stage liver disease, and liver transplantation were significantly more frequent in the HDV+ cohort. HDV viraemia was significantly associated with elevated liver transaminases and cirrhosis. Five HDV genotypes were observed among referred patients but no association between genotype and clinical outcome was detected within the HDV+ cohort. Conclusions: Nearly 5% of the Canadian HBV referral population is HDV seropositive. HDV infection is highly associated with risk behaviours and both domestic and foreign-born patients with CHB. HDV was significantly associated with progressive liver disease highlighting the need for increased screening and surveillance of HDV in Canada. Lay summary: Evidence of HDV infection was observed in approximately 5% of Canadians who were infected with HBV referred to medical specialists. HDV-positive patients were more likely to be male, born in Canada, or White or Black/African/Caribbean compared to Asian, and to have reported high-risk activities such as injection or intranasal drug use or high-risk sexual contact compared with patients infected with only HBV. Patients infected with HDV were also more likely to suffer severe liver disease, including liver cancer, compared with HBV mono-infected patients.

The international normalised ratio predicts perioperative complications in revision total hip arthroplasty.

BACKGROUND: Standard preoperative protocols in total joint arthroplasty utilise the international normalised ratio (INR) to determine patient coagulation profiles. However, the relevance of preoperative INR values in joint arthroplasty remains controversial. Therefore, we examined (1) the relationship between preoperative INR values and various outcome measures, including, but not limited to: surgical site complications, medical complications, bleeding, number of readmissions, and mortality. Additionally, we sought to determine (2) specific INR values associated with these complications and (3) cutoff INR levels which correlated with specific outcomes. We additionally applied these analyses to (4) examine the relationship between INR and length-of-stay (LOS). METHODS: The American College of Surgeons National Surgical Quality Improvement Program database (ACS-NSQIP) was queried for rTHA procedures performed between 2006 and 2017. INR ranges were used to stratify cohorts: ⩽1.0, 1.0-⩽1.25, 1.25-⩽1.5, >1.5. INR values were determined using receiver operating characteristics (ROC) curves for each outcome of interest. Optimal cutoff INR values for each outcome were then obtained using univariate/multivariate models. 2012 patients who underwent rTHA met inclusion criteria. RESULTS: Patients with progressively higher INR values had a significantly different risk of mortality within 30 days (p = 0.005), bleeding requiring transfusion (p < 0.001), sepsis (p = 0.002), stroke (p < 0.001), failure to wean from ventilator within 48 hours (p = 0.001), readmission (p = 0.01), and hospital length of stay (p < 0.001). Similar results were obtained when utilising optimal INR cutoff values. When correcting for other factors, the following poor outcomes were significantly associated with the respective INR cutoff values (Estimate, 95% CI, p-value): LOS >4 days (1.67, 1.34-2.08, p < 0.001), bleeding requiring transfusion (1.65, 1.30-2.09, p < 0.001), sepsis (2.15, 1.11-4.17, p = 0.022), and any infection (1.82, 1.01-3.29, p = 0.044). CONCLUSIONS: Our analysis illustrates a direct relationship between specific preoperative INR levels and poor outcomes following rTHA, including increased LOS, transfusion requirements and infection. Therefore, current INR guideline targets may need to be re-examined when optimising patients for revision arthroplasty.

Immunomodulatory receptor VSIG4 is released during spontaneous bacterial peritonitis and predicts short-term mortality.

BACKGROUND & AIMS: V-set Ig-domain-containing 4 (VSIG4) is an immunomodulatory macrophage complement receptor modulating innate and adaptive immunity and affecting the resolution of bacterial infections. Given its expression on peritoneal macrophages (PMs), we hypothesised a prognostic role of peritoneal VSIG4 concentrations in patients with spontaneous bacterial peritonitis (SBP). METHODS: We isolated PMs from patients with cirrhosis and analysed VSIG4 expression and release by flow cytometry, quantitative real-time PCR, ELISA, and confocal microscopy. We measured soluble VSIG4 concentrations in ascites from 120 patients with SBP and 40 patients without SBP and investigated the association of soluble VSIG4 in ascites with 90-day survival after SBP using Kaplan-Meier statistics, Cox regression, and competing-risks regression analysis. RESULTS: VSIG4 expression was high on resting, large PMs, which co-expressed CD206, CD163, and tyrosine-protein kinase Mer (MERTK). VSIG4 gene expression in PMs decreased in patients with SBP and normalised after resolution. During SBP, VSIG4hi PMs were depleted (25% vs. 57%; p <0.001) and soluble VSIG4 in ascites were higher in patients with SBP than in patients without (0.73 vs. 0.35 µg/ml; p <0.0001). PM activation by Toll-like receptor (TLR) agonists or infection with live bacteria in vitro resulted in a loss of surface VSIG4 and the release of soluble VSIG4. Mechanistically, shedding of VSIG4 from PMs was protease-dependent and susceptible to microtubule transport inhibition. Soluble VSIG4 in ascites exceeded serum concentrations and correlated with serum creatinine, model for end-stage liver disease score and C-reactive protein during SBP. Concentrations of 1.0206 µg/ml or higher indicated increased 90-day mortality (hazard ratio 1.70; 95% CI 1.01-2.86; p = 0.046). CONCLUSIONS: VSIG4 is released from activated PMs into ascites during SBP. Higher peritoneal VSIG4 levels indicate patients with organ failure and poor prognosis. LAY SUMMARY: Patients with liver cirrhosis who develop ascites have an increased risk of infection and mortality. Our study shows that in patients with infected ascites, the complement receptor VSIG4 is released by resident macrophages into the abdominal fluid where it can be measured. Patients with elevated levels of this protein in ascites are at high risk of dying within 90 days.

A Study of Prevalence of Occult Hepatitis B Virus Infection, Knowledge and Preventive Practices Against Hepatitis B Virus in Barbers Serving the Armed Forces.

OBJECTIVE: Hepatitis B virus (HBV) infection is a major health problem in the world. Barbers deal with frequent abrasions/lacerations due to sharp equipment, making them a high-risk group. Determination of HBsAg positive status excludes most reservoirs of transmission in the population. However, Occult Hepatitis B continues to be a source of transmission. The aim of this study was to study the prevalence of occult HBV infection in barbers serving the armed forces clientele and evaluate their knowledge and preventive practices against HBV transmission. METHODS: Seventy-nine HBsAg negative barbers were included in this study and interviewed for the status of immunisation and preventive practices. Anti-HBc total and HBV DNA levels were measured along with a complete haemogram, LFT, PT INR, ultrasound abdomen and Fibroscan of the liver. RESULTS: The prevalence of occult Hepatitis B status was 3.79%. Among barbers who were anti-HBc total positive, 100% were found to have replicative HBV DNA status. All barbers (100%) were unaware of the existence and modes of HBV transmission and were never screened for HBV; 98.73% of barbers followed improper disinfection practices and were never immunised. CONCLUSION: The prevalence of occult HBV infection in barbers, absence of immunisation, unawareness and improper disinfection practices are significantly at risk for transmission to the unaware clients. It is important to educate barbers, establish a universal disinfection procedure and implement a system of compulsory Hepatitis B vaccination before the commencement of their trade work.