Myosteatosis, the More Significant Predictor of Outcome: An Analysis of the Impact of Myosteatosis, Sarcopenia, and Sarcopenic Obesity on Liver Transplant Outcomes in Johannesburg, South Africa.

OBJECTIVES: In high-income countries, myosteatosis, sarcopenia, and obesity with sarcopenia (sarcopenic obesity) are associated with adverse outcomes after liver transplantation. In South Africa, an upper-middleincome country, we investigated the prevalence and impact of these muscle abnormalities on posttransplant outcomes in adult liver transplant recipients. MATERIALS AND METHODS: We reviewed 106 liver transplant recipients and measured muscle abnormalities on computed tomography using segmentation software. The parameters evaluated were myosteatosis by mean muscle attenuation, sarcopenia by skeletal muscle index at the third lumbar vertebra using validated cutoffs, and sarcopenic obesity as sarcopenia and a body mass index of ≥25 kg/m². The effects of these abnormalities on 1-year patient and graft survival (primary endpoint) and length of hospital and intensive care unit stay, costs, and 90-day and overall postoperative complications (secondary endpoints) were assessed. RESULTS: Most liver transplant recipients were male (n = 64, 60%). Alcoholic and/or nonalcoholic steatohepatitis were the most frequent indications for transplant (n = 38, 36%). Myosteatosis occurred in 76 patients (72%), 69 patients (65%) had sarcopenia, and 36 patients (34%) had sarcopenic obesity. One year after transplant, myosteatosis was associated with higher mortality (hazard ratio of 3.3; 95% confidence interval, 1.00-11.13; P = .049), greater risk of allograft failure (hazard ratio of 4.1; 95% confidence interval, 1.2-13.5; P = .021), and longer hospital and intensive care unit stays compared with those without myosteatosis. All patients with no body composition abnormalities were alive at 1 year compared with 69% with coexisting myosteatosis and sarcopenia. CONCLUSIONS: In our setting, liver transplant recipients with myosteatosis had a higher risk of death and allograft failure at 1 year compared with patients without body composition abnormalities.

Age significantly influences the sensitivity of SARS-CoV-2 rapid antibody assays.

BACKGROUND: Point-of-care serological assays are a promising tool in COVID-19 diagnostics but do have limitations. Our study evaluated the sensitivity of five rapid antibody assays and explored factors influencing their sensitivity in detecting SARS-CoV-2-specific IgG and IgM antibodies. METHODS: Finger-prick blood samples from 102 participants, within 2-6 weeks of PCR-confirmed COVID-19 diagnosis, were tested for IgG and IgM using five rapid serological assays. The assay sensitivities were compared, and patient factors evaluated in order to investigate potential associations with assay sensitivity. RESULTS: Sensitivity ranged from 36% to 69% for IgG and 13% to 67% for IgM. Age was the only factor significantly influencing the likelihood of a detectable IgG or IgM response. Individuals aged 40 years and older had an increased likelihood of a detectable IgG or IgM antibody response by rapid antibody assay. CONCLUSION: Rapid serological assays demonstrate significant variability when used in a real-world clinical context. There may be limitations in their use for COVID-19 diagnosis among the young.

Comparison of outcomes in HIV-positive and HIV-negative patients with COVID-19.

BACKGROUND: South Africa has the highest prevalence of HIV in the world and to date has recorded the highest number of cases of COVID-19 in Africa. There is uncertainty as to what the significance of this dual infection is, and whether people living with HIV (PLWH) have worse outcomes compared to HIV-negative patients with COVID-19. This study compared the outcomes of COVID-19 in a group of HIV-positive and HIV-negative patients admitted to a tertiary referral centre in Johannesburg, South Africa. METHODS: Data was collected on all adult patients with known HIV status and COVID-19, confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR), admitted to the medical wards and intensive care unit (ICU) between 6 March and 11 September 2020. The data included demographics, co-morbidities, laboratory results, severity of illness scores, complications and mortality, and comparisons were made between the HIV-positive and HIV negative groups. RESULTS: Three-hundred and eighty-four patients, 108 HIV-positive and 276 HIV-negative, were included in the study. Median 4C score was significantly higher in the HIV-positive patients compared to the HIV-negative patients, but there was no significant difference in mortality between the HIV-positive and HIV-negative groups (15% vs 20%, p = 0.31). In addition, HIV-positive patients who died were younger than their HIV-negative counterparts, but this was not statistically significant (47.5 vs 57 years, p = 0.06). CONCLUSION: Our findings suggest that HIV is not a risk factor for moderate or severe COVID-19 disease neither is it a risk factor for mortality. However, HIV-positive patients with COVID-19 requiring admission to hospital are more likely to be younger than their HIV-negative counterparts. These findings need to be confirmed in future, prospective, studies.

Metronidazole-induced encephalopathy.

Metronidazole is a widely used antibacterial and antiprotozoal agent for a number of conditions. Whilst its more common gastrointestinal side effects are well known, neurotoxicity remains under-recognised. Both central and peripheral neurological side effects have been described. This report describes a case of radiologically confirmed metronidazole-induced cerebellar ataxia in a cirrhotic patient with a review of the literature. Awareness of this side effect is essential for prompt recognition as early drug withdrawal leads to resolution in the majority of cases.

Colchicine overdose: A South African experience, a case report.

INTRODUCTION: Colchicine overdose is uncommon but is associated with a high mortality rate. It has a narrow therapeutic index and has been described to have a 100% mortality with ingestion of >0.8 mg/kg (Finkelstein et al., 2010; Herran-Monge et al., 2013; Aghabiklooei et al., 2014; Erden et al., 2013). CASE REPORT: This is a case report of a 19-year-old male who ingested 0.4 mg/kg of colchicine in a suicide attempt. He developed multiorgan dysfunction. He was managed supportively, and the dysfunction resolved. DISCUSSION: The clinical presentation and management should be familiar to all those who work in acute care in order to be able to identify and treat it timeously thus preventing morbidity and mortality. Treatment is largely supportive. To the best of our knowledge this is the first case of colchicine overdose described in Sub-Saharan Africa.

Efficacy and safety of glecaprevir/pibrentasvir in patients with chronic hepatitis C virus genotype 5 or 6 infection (ENDURANCE-5,6): an open-label, multicentre, phase 3b trial.

BACKGROUND: The pangenotypic direct-acting antiviral regimen of glecaprevir coformulated with pibrentasvir is approved to treat chronic hepatitis C virus (HCV) genotype 1-6 infection in adults. In registrational studies, 84 (99%) of 85 patients with HCV genotype 5 or 6 infection achieved a sustained virological response (SVR) with glecaprevir/pibrentasvir, with no virological failures. To increase the body of data for these less prevalent genotypes, ENDURANCE-5,6 evaluated the efficacy and safety of glecaprevir/pibrentasvir exclusively in patients infected with HCV genotype 5 or 6. METHODS: ENDURANCE-5,6 was a phase 3b, single-arm, open-label, multicentre trial done in 24 hospitals or clinics in Europe, Oceania, North America, South Africa, and southeast Asia. Adults with chronic HCV genotype 5 or 6 infection who were previously untreated or treatment-experienced were eligible to be enrolled. Glecaprevir/pibrentasvir (300 mg/120 mg) was given orally once daily for 8 weeks (for patients without cirrhosis) or 12 weeks (for patients with compensated cirrhosis). The primary efficacy endpoint was SVR12 (ie, HCV RNA <15 IU/mL at 12 weeks post-treatment), assessed within each HCV genotype, and analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02966795. FINDINGS: Between Feb 9, 2017, and Aug 28, 2018, 84 patients were enrolled: 23 with genotype 5 infection and 61 with genotype 6 infection. Overall, 82 (97·6%, 95% CI 94·4-100·0) of the 84 patients achieved SVR12. 22 (95·7%, 95% CI 87·3-100·0) of 23 patients with genotype 5 infection achieved SVR12, as did 60 (98·4%, CI 95·2-100·0) of 61 with genotype 6 infection. One patient with an HCV genotype 6f infection and cirrhosis had on-treatment virological failure at treatment week 12, and one patient with HCV genotype 5a without cirrhosis who had achieved SVR at post-treatment week 4 relapsed at post-treatment week 12. Five (6%) patients had serious adverse events, none of which were deemed related to glecaprevir/pibrentsavir or led to discontinuation. Fatigue (11 [13%] patients) and headache (11 [13%]) were the only adverse events that occurred in 10% or more of patients. No post-baseline grade 3 or higher increases in aminotransferase concentrations were reported. INTERPRETATION: Glecaprevir/pibrentasvir achieved high SVR12 rates, comparable with data reported in registrational studies, and was well tolerated in patients with HCV genotype 5 or 6 infection with compensated liver disease. FUNDING: AbbVie.

Living donor liver transplant from an HIV-positive mother to her HIV-negative child: opening up new therapeutic options.

OBJECTIVE: Transplant a liver from an HIV-positive mother to her HIV-negative child to save the child's life. DESIGN: A unique case of living donor liver transplantation from an HIV-positive mother to her HIV-negative child in South Africa. Two aspects of this case are ground-breaking. First, it involves living donation by someone who is HIV-positive and second it involves controlled transplant of an organ from an HIV-positive donor into an HIV-negative recipient, with the potential to prevent infection in the recipient. METHODS: Standard surgical procedure for living donor liver transplantation at our centre was followed. HIV-prophylaxis was administered preoperatively. Extensive, ultrasensitive HIV testing, over and above standard diagnostic assays, was undertaken to investigate recipient serostatus and is ongoing. RESULTS: Both mother and child are well, over 1 year posttransplantation. HIV seroconversion in our recipient was detected with serological testing at day 43 posttransplant. However, a decline in HIV antibody titres approaching undetectable levels is now being observed. No plasma, or cell-associated HIV-1 DNA has been detected in the recipient at any time-point since transplant. CONCLUSION: This case potentially opens up a new living liver donor pool which might have clinical relevance in countries where there is a high burden of HIV and a limited number of deceased donor organs or limited access to transplantation. However, our recipient's HIV status is equivocal at present and additional investigation regarding seroconversion events in this unique profile is ongoing.

Takotsubo cardiomyopathy post liver transplantation.

A patient with end-stage liver disease developed stress-induced Takotsubo cardiomyopathy post liver transplantation, with haemodynamic instability requiring a left ventricular assist device. We discuss the diagnosis and management of this condition.

Overdose with HAART: are we managing these patients adequately?

Increasing numbers of HIV/AIDS-infected individuals have presented to medical casualty at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) after attempting suicide by overdosing on their antiretroviral therapy. Since 2009, medical gastro-enterology at CMJAH has been the primary specialty unit for cases of accidental or intentional overdose. Psychiatry and other medical sub-specialties are consulted as needed. Our unit sees approximately 1 case a month of accidental/intentional overdose with antiretrovirals. Between January and September 2010, 6% of all overdoses seen at CMJAH were of antiretroviral origin. Supportive care is provided and patients undergo psychiatric evaluation. The information available on overdoses with antiretrovirals is from studies in developed countries, where intravenous drug users and men who have sex with men make up the bulk of the HIV-positive population. This differs significantly from South Africa, which now has the largest antiretroviral programme in the world. With little evidence related to this type of overdose, are we approaching the management, monitoring and follow-up of these patients correctly?

Does endogenous testosterone mediate the lower preconditioning threshold in males?

BACKGROUND: Preconditioning is injury-induced protection from subsequent insult. Recent data indicates that males have lower preconditioning thresholds compared to females. Therefore, we hypothesized that testosterone may mediate the lower preconditioning threshold observed in males. MATERIALS AND METHODS: Adult normal and castrated male Sprague-Dawley rats (n = 4-5) were given intraperitoneal (i.p.) injections of 125 or 500 microg/kg Salmonella typhimurium lipopolysaccharide (ETX) or 0.4 ml normal saline (NS). Another i.p. injection of 500 microg/kg ETX (injury dose) was given 24 h later. After 6 h, myocardial function was evaluated via the Langendorff perfusion model. Shams received only NS, while non-preconditioned rats (PC-) received NS followed by the 500 microg/kg ETX injury dose. Preconditioned rats received injections of 125 mug/kg ETX (PC +125) or 500 microg/kg ETX (PC +500), followed by the 500 microg/kg ETX injury dose. RESULTS: Normal PC +125 and PC +500 males were preconditioned and maintained cardiac function similar to shams (P > 0.05). Castrated PC +125 and PC +500 males were also preconditioned and maintained cardiac function similar to castrated shams (P > 0.05). Conversely, both normal and castrated PC-males showed significantly decreased cardiac function compared to shams (P < 0.05). CONCLUSIONS: Endogenous testosterone does not mediate the lower preconditioning threshold in males.