Satellite liver transplant centres significantly improve transplant assessment outcomes for patients with chronic liver disease but not hepatocellular carcinoma: a retrospective cohort study.

Introduction: Liver transplantation (LT) remains integral to the management of end-stage chronic liver disease (CLD). However, referral thresholds and assessment pathways remain poorly defined. Distance from LT centre has been demonstrated to impact negatively on patient outcomes resulting in the development of satellite LT centres (SLTCs). We aimed to evaluate the impact of SLTCs on LT assessment in patients with CLD and hepatocellular carcinoma (HCC). Methods: A retrospective cohort study was undertaken including all patients with CLD or HCC assessed for LT at King's College Hospital (KCH) between October 2014 and October 2019. Referral location, social, demographic, clinical and laboratory data were collected. Univariable and multivariable analyses (MVA) were performed to assess the impact of SLTCs on patients being accepted as LT candidates and contraindications being identified. Results: 1102 and 240 LT assessments were included for patients with CLD and HCC, respectively. MVA demonstrated significant associations with; patients living greater than 60 min from KCH/SLTCs and LT candidacy acceptance in CLD, and less deprived patients and LT candidacy acceptance in HCC. However, neither variable was associated with identification of LT contraindications. MVA demonstrated that referrals from SLTCs were more likely to result in acceptance of LT candidacy and less likely to result in a contraindication being identified in CLD. However, such associations were not demonstrated in HCC. Conclusion: SLTCs improve LT assessment outcomes in CLD but not HCC reflecting the standardised HCC referral pathway. Developing a formal regional LT assessment pathway across the UK would improve equity of access to transplantation.

Readiness of health facilities to provide services related to non-communicable diseases in Nepal: evidence from nationally representative Nepal Health Facility Survey 2021.

OBJECTIVE: To assess the readiness of public and private health facilities (HFs) in delivering services related to non-communicable diseases (NCDs) in Nepal. METHODS: We analysed data from nationally representative Nepal Health Facility Survey 2021 to determine the readiness of HFs for cardiovascular diseases (CVDs), diabetes mellitus (DM), chronic respiratory diseases (CRDs) and mental health (MH)-related services using Service Availability and Readiness Assessment Manual of the WHO. Readiness score was measured as the average availability of tracer items in per cent, and HFs were considered 'ready' for NCDs management if they scored ≥70 (out of 100). We performed weighted univariate and multivariable logistic regression to determine the association of HFs readiness with province, type of HFs, ecological region, quality assurance activities, external supervision, client's opinion review and frequency of meetings in HFs. RESULTS: The overall mean readiness score of HFs offering CRDs, CVDs, DM and MH-related services was 32.6, 38.0, 38.4 and 24.0, respectively. Guidelines and staff training domain had the lowest readiness score, whereas essential equipment and supplies domain had the highest readiness score for each of the NCD-related services. A total of 2.3%, 3.8%, 3.6% and 3.3% HFs were ready to deliver CRDs, CVDs, DM and MH-related services, respectively. HFs managed by local level were less likely to be ready to provide all NCD-related services compared with federal/provincial hospitals. HFs with external supervision were more likely to be ready to provide CRDs and DM-related services and HFs reviewing client's opinions were more likely to be ready to provide CRDs, CVDs and DM-related services. CONCLUSION: Readiness of the HFs managed by local level to provide CVDs, DM, CRDs and MH-related services was relatively poor compared with federal/provincial hospitals. Prioritisation of policies to reduce the gaps in readiness and capacity strengthening of the local HFs is essential for improving their overall readiness to provide NCD-related services.

A-GAS: A Probabilistic Approach for Generating Automated Gait Assessment Score for Cerebral Palsy Children.

Gait disorders in children with cerebral palsy (CP) affect their mental, physical, economic, and social lives. Gait assessment is one of the essential steps of gait management. It has been widely used for clinical decision making and evaluation of different treatment outcomes. However, most of the present methods of gait assessment are subjective, less sensitive to small pathological changes, time-taking and need a great effort of an expert. This work proposes an automated, comprehensive gait assessment score (A-GAS) for gait disorders in CP. Kinematic data of 356 CP and 41 typically developing subjects is used to validate the performance of A-GAS. For the computation of A-GAS, instance abnormality index (AII) and abnormality index (AI) are calculated. AII quantifies gait abnormality of a gait cycle instance, while AI quantifies gait abnormality of a joint angle profile during walking. AII is calculated for all gait cycle instances by performing probabilistic and statistical analyses. Abnormality index (AI) is a weighted sum of AII, computed for each joint angle profile. A-GAS is a weighted sum of AI, calculated for a lower limb. Moreover, a graphical representation of the gait assessment report, including AII, AI, and A-GAS is generated for providing a better depiction of the assessment score. Furthermore, the work compares A-GAS with a present rating-based gait assessment scores to understand fundamental differences. Finally, A-GAS's performance is verified for a high-cost multi-camera set-up using nine joint angle profiles and a low-cost single camera set-up using three joint angle profiles. Results show no significant differences in performance of A-GAS for both the set-ups. Therefore, A-GAS for both the set-ups can be used interchangeably.

Mental Health, Cognitive, and Neuropsychiatric Needs in Children and Young People With Wilson Disease.

Wilson disease (WD) is associated with neurological, psychiatric, cognitive, and psychosocial difficulties, but there is little data regarding the nature and prevalence of these problems in children and young people (CYP). Methods: A single-center case-note review to establish the incidence and nature of these issues in CYP with WD, managed before and after multidisciplinary team (MDT) clinics, was established. Results: Out of 69 (43 males) CYP with WD, 37.8% presented with acute liver failure, 48.6% with chronic liver disease and 13.5% after family screening. Medical treatment was with penicillamine (40), trientene (18), zinc and penicillamine/trientene (11), and zinc monotherapy (2). Twenty-one underwent liver transplantation. After a median follow-up of 9.8 (IQR 6.4-16.9) years, 86% are alive. Six died posttransplantation and 7 grafts were lost. Mental health difficulties were recorded in 49.3%, particularly prevalent in the acute liver failure group (70.8%). Nonadherence was common (50.7%) and associated with greater mental health prevalence. Neurological issues were reported in 36.2% and poor cognition/attainment in 14.5%, consistent across modes of presentation. Four patients had diagnoses of autism spectrum conditions, all diagnosed pre WD. CYP seen within an MDT-clinic had more frequent documentation of all issues examined, but lower levels of late graft loss (94% versus 80%, P = 0.07). Conclusion: Our data highlight the need to offer management in WD patients especially as these aspects are underrecognized in CYP presenting with liver involvement. We aim to highlight the importance of multidisciplinary input when looking after this population beyond transition through to adult services.

Incidence, management and outcome assessment of post operative infection following single bundle and double bundle acl reconstruction.

INTRODUCTION: Post-operative infection is a dreadful complication of ACL reconstruction with gray zone over management guidelines. We aimed to establish commonest etiology, assess incidence of infection and effect on outcome, individually for single and double bundle ACL reconstruction techniques, so as to formulate appropriate management guidelines. METHODS: Our prospective study involved 1152 patients operated for ACL reconstruction (437- DBACL, 715- SBACL) from 2010-2013. Post-operative infection was diagnosed clinically supported by positive gram stain/ culture and increased cell count in knee aspirate. All patients were started on empirical antibiotics and arthroscopic lavage and debridement was done. Graft was retained if it was stable and intact. Data recorded at follow up was analysed statistically. RESULTS: In SBACL infection rate was 0.84% while in DBACL it was 2.52%. All patients with infection presented with pain, effusion, fever and increased WBC, ESR & CRP. Average time of presentation after the surgery was 2.27 weeks for DBACL and 2.16 weeks for SBACL. In both groups, S.aureus followed by S. epidermidis were commonest isolates. Patients were given IV antibiotics for 2 weeks and oral for further 4 weeks. DISCUSSION: Incidence of infection is higher with the double bundle technique, however, the functional outcome is not affected (p value 0.231). Joint aspirate is the gold standard diagnostic test for infection. CRP and ESR are the next dependable tests with high sensitivity but their specificity is low. A thorough debridement is necessary apart from recommended antibiotic cover of 2 weeks IV followed by 4 weeks oral antibiotics.

The advantages of live/real time three-dimensional transesophageal echocardiography in the assessment of tricuspid valve infective endocarditis.

Currently, tricuspid valve infective endocarditis (TVIE) is encountered in daily clinical practice more frequently due to the increasing prevalence of illicit intravenous drug use and the implantation of intracardiac devices. In this study, we compared findings from intra-operative live/real time three-dimensional transesophageal echocardiograms (3DTEE) and two-dimensional transesophageal echocardiograms (2DTEE) of 10 patients who underwent surgery for native tricuspid valve (TV) endocarditis. Unlike 2DTEE, 3DTEE allowed en face visualization of the 3 TV leaflets from both, atrial and ventricular aspects, in 9 of the 10 cases. In the remaining patient, in whom 3DTEE could not identify all 3 leaflets en face, the TV was found essentially destroyed at surgery. Using 3DTEE, the number of vegetations was accurately reported when compared with the surgical record. Furthermore, the orientation of each vegetation was the same as noted in the surgical findings. 2DTEE missed the identification of vegetations in 5 patients. The attachment site of vegetations to the TV were also not characterized by 2DTEE in 5 patients. In all 10 cases, 3DTEE characterized the vegetations more accurately with larger dimensions, including those in the azimuthal axis, and volumes. In addition, a perivalvular abscess that lead to surgical intervention was identified by 3DTEE, however, missed by 2DTEE. In conclusion, 3DTEE allows en face visualization of the TV apparatus permitting accurate description of the number and dimensions of vegetations identified by our surgical standard, which ultimately informs patients' prognosis and dictates the timing and planning for surgical intervention. Its use should be in conjunction with 2DTEE when evaluating TVIE.

Wolbachia strain wAlbB confers both fitness costs and benefit on Anopheles stephensi.

BACKGROUND: Wolbachia is a maternally transmitted intracellular bacterium that is estimated to infect up to 65% of insect species, but it is not naturally present in Anopheles malaria vectors. Wolbachia-based strategies for malaria vector control can be developed either through population replacement to reduce vectorial capacity or through population suppression to reduce the mosquito population. We have previously generated An. stephensi mosquitoes carrying a stable wAlbB Wolbachia infection and have demonstrated their ability to invade wild-type laboratory populations and confer resistance to Plasmodium on these populations. METHODS: We assessed wAlbB-associated fitness by comparing the female fecundity, immature development and survivorship, body size, male mating competiveness, and adult longevity of the infected An. stephensi to that of wild-type mosquitoes. RESULTS: We found that wAlbB reduced female fecundity and caused a minor decrease in male mating competiveness. We also observed that wAlbB increased the life span of both male and female mosquitoes when they were maintained solely on sugar meals; however, there was no impact on the life span of blood-fed females. In addition, wAlbB did not influence either immature development and survivorship or adult body sizes. CONCLUSIONS: These results provide significant support for developing Wolbachia-based strategies for malaria vector control.

Recurrent HCV after liver transplantation-mechanisms, assessment and therapy.

Chronic HCV infection is the leading indication for liver transplantation. However, as a result of HCV recurrence, patient and graft survival after liver transplantation are inferior compared with other indications for transplantation. HCV recurrence after liver transplantation is associated with considerable mortality and morbidity. The development of HCV-related fibrosis is accelerated after liver transplantation, which is influenced by a combination of factors related to the virus, donor, recipient, surgery and immunosuppression. Successful antiviral therapy is the only treatment that can attenuate fibrosis. The advent of direct-acting antiviral agents (DAAs) has changed the therapeutic landscape for the treatment of patients with HCV. DAAs have improved tolerability, and can potentially be used without PEG-IFN for a shorter time than previous therapies, which should result in better outcomes. In this Review, we describe the important risk factors that influence HCV recurrence after liver transplantation, highlighting the mechanisms of fibrosis and the integral role of hepatic stellate cells. Indirect and direct assessment of fibrosis, in addition to new antiviral therapies, are also discussed.

Two- and three-dimensional transthoracic echocardiography in the assessment of aortic arch vasum vasi to pulmonary artery fistula.

We report an elderly patient presenting with a stroke and also hemolytic anemia secondary to mitral and tricuspid valve repair 3 years earlier, in whom two-dimensional transesophageal echocardiography (2DTEE) suspected a fistula into the pulmonary artery (APAF) from the posterior wall of the aortic arch. For further assessment, two-dimensional transthoracic echocardiography (2DTTE) and live/real time three-dimensional transthoracic echocardiography (3DTTE) were performed. 2DTTE showed findings similar to 2DTEE. Color Doppler guided continuous-wave Doppler showed continuous flow throughout the cardiac cycle with systolic preponderance across the fistula with a small peak pressure gradient of 22 mmHg. Sequential systematic cropping of the 3D datasets obtained from 3DTTE confirmed that the flow signals originated from the posterior wall of the aortic arch and not the lumen. Thus, 3DTTE served to increase the confidence level that the fistula most likely originated from a vasum vasi in the wall of the aortic arch. To our knowledge, this type of fistula has not been reported previously. Fistulas from the aortic lumen to the pulmonary artery are also rare and so far only 24 cases have been reported in the literature. These are also reviewed by us.

Live/Real time three-dimensional transthoracic echocardiographic assessment of the involvement of cardiac valves and chambers in carcinoid disease.

We present an adult with metastatic carcinoid disease affecting the heart, in whom live/real time three-dimensional transthoracic echocardiography (3DTTE) provided incremental value over two-dimensional transthoracic echocardiography (2DTTE). Initial 2DTTE was able to demonstrate severe pulmonic and tricuspid regurgitation, but was unable to visualize the posterior leaflet of the tricuspid valve or the right (right anterior) leaflet of the pulmonic valve. Further analysis with 3DTTE demonstrated thickening, restricted mobility, and noncoaptation of all three leaflets of both the tricuspid and the pulmonary valves. En face viewing of tricuspid and pulmonary regurgitation vena contractas permitted more reliable quantification of regurgitation severity. In addition, localized, linear, echogenic areas consistent with carcinoid deposits were noted along the inner walls of the right atrium, atrial septum, and inferior vena cava. To the best of our knowledge, endocardial carcinoid deposits have never been reported by 2D or 3D echocardiography. En face viewing of these deposits by 3DTTE enabled measurement of their dimensions and areas. Subcostal examination also identified large circumscribed hepatic lesions consistent with metastatic disease. Neither the carcinoid deposits nor the metastatic lesions were detected by 2DTTE. This case demonstrates the usefulness of 3DTTE as a supplement to 2DTTE in more comprehensively assessing carcinoid involvement of the heart.

Incremental value of live/real time three-dimensional transesophageal echocardiography over the two-dimensional technique in the assessment of aortic aneurysm and dissection.

We compared findings from intraoperative live/real time three-dimensional transesophageal echocardiography (3DTEE) and two-dimensional transesophageal echocardiography (2DTEE) with surgery in 67 patients having aortic aneurysm and/or aortic dissection. Of these, 20 patients had aortic aneurysm without dissection, 21 aortic aneurysm and dissection, and 26 aortic dissection without aneurysm. 3DTEE diagnosed the type and location of aneurysm correctly in all patients unlike 2DTEE, which missed an aneurysm in one case. There were four cases of aortic aneurysm rupture. Three of them were diagnosed by 3DTEE but only one by 2DTEE, and one missed by both techniques. The mouth of saccular aneurysm, site of aortic aneurysm rupture, and communication sites between perfusing and nonperfusing lumens of aortic dissection could be viewed en face only with 3DTEE, enabling comprehensive measurements of their area and dimensions as well as increasing the confidence level of their diagnosis. In all patients with aortic dissection, 3DTEE enabled a more confident diagnosis of dissection because the dissection flap when viewed en face presented as a sheet of tissue rather than a linear echo seen on 2DTEE which can be confused with an artifact. 2DTEE missed dissection in one patient. In six cases the dissection flap involved the right coronary artery orifice by 3DTEE and surgery. These were missed by 2DTEE. Aortic regurgitation severity was more comprehensively assessed by 3DTEE than 2DTEE. Aneurysm size by 3DTEE correlated well with 2DTEE and surgery/computed tomography scan. In conclusion, 3DTEE provides incremental information over 2DTEE in patients with aortic aneurysm and dissection.

Incremental role of three-dimensional transesophageal echocardiography in the assessment of mitral-aortic intervalvular fibrosa abscess.

We report a case of an elderly patient in whom live/real time three-dimensional transesophageal echocardiography (3DTEE) provided definitive diagnosis of mitral-aortic intervalvular fibrosa abscess. This could not be done by two-dimensional transthoracic echocardiography (2DTTE) and two-dimensional transesophageal echocardiography (2DTEE). 3DTEE was also helpful in ruling out associated mitral valve endocarditis, which was initially suspected by 2DTEE leading to a mitral valve sparing surgery. Thus, 3DTEE provided incremental information over 2DTTE and 2DTEE in this patient.

Live/real time three-dimensional transthoracic echocardiographic assessment of the involvement of cardiac valves and chambers in carcinoid disease.

We present an adult with metastatic carcinoid disease affecting the heart, in whom live/real time three-dimensional transthoracic echocardiography (3DTTE) provided incremental value over two-dimensional transthoracic echocardiography (2DTTE). Initial 2DTTE was able to demonstrate severe pulmonic and tricuspid regurgitation, but was unable to visualize the posterior leaflet of the tricuspid valve or the right (right anterior) leaflet of the pulmonic valve. Further analysis with 3DTTE demonstrated thickening, restricted mobility, and noncoaptation of all three leaflets of both the tricuspid and the pulmonary valves. En face viewing of tricuspid and pulmonary regurgitation vena contractas permitted more reliable quantification of regurgitation severity. In addition, localized, linear, echogenic areas consistent with carcinoid deposits were noted along the inner walls of the right atrium, atrial septum, and inferior vena cava. To the best of our knowledge, endocardial carcinoid deposits have never been reported by 2D or 3D echocardiography. En face viewing of these deposits by 3DTTE enabled measurement of their dimensions and areas. Subcostal examination also identified large circumscribed hepatic lesions consistent with metastatic disease. Neither the carcinoid deposits nor the metastatic lesions were detected by 2DTTE. This case demonstrates the usefulness of 3DTTE as a supplement to 2DTTE in more comprehensively assessing carcinoid involvement of the heart.

Increasing burden of liver disease in patients with HIV infection.

Introduction of effective combined antiretroviral therapy has made HIV infection a chronic illness. Substantial reductions in the number of AIDS-related deaths have been accompanied by an increase in liver-related morbidity and mortality due to co-infection with chronic hepatitis B and C viruses. Increases in non-alcoholic fatty liver disease and drug-induced hepatotoxicity, together with development of hepatocellular carcinoma, also potentiate the burden of liver disease in individuals with HIV infection. We provide an overview of the key causes, disease mechanisms of pathogenesis, and recommendations for treatment options including the evolving role of liver transplantation.