Comparison of early fungicidal activity and mortality between daily liposomal amphotericin B and daily amphotericin B deoxycholate among patients with HIV-associated cryptococcal meningitis.

BACKGROUND: Limited data exist on the antifungal activity of daily liposomal amphotericin B with flucytosine induction regimens for cryptococcal meningitis, which are recommended in high-income countries. Liposomal amphotericin B monotherapy at 3 mg/kg previously failed to meet non-inferiority criteria compared to amphotericin B deoxycholate in its registrational clinical trial. We aimed to compare the quantitative antifungal activity and mortality between daily amphotericin B deoxycholate and daily liposomal amphotericin among persons with HIV-related cryptococcal meningitis receiving adjunctive flucytosine 100 mg/kg/day. METHODS: We analyzed data from three clinical studies involving participants with HIV-associated cryptococcal meningitis receiving either daily liposomal amphotericin B at 3 mg/kg/day with flucytosine (N = 94) or amphotericin B deoxycholate at 0.7-1.0 mg/kg/day with flucytosine (N = 404) as induction therapy. We compared participant baseline characteristics, CSF early fungicidal activity (EFA), and 10-week mortality. RESULTS: We included 498 participants in this analysis, of whom 201 had available EFA data (N = 46 liposomal amphotericin; N = 155 amphotericin deoxycholate). Overall, there is no statistical evidence that the antifungal activity of liposomal amphotericin B (mean EFA = 0.495 log10 CFU/mL/day; 95%CI, 0.355-0.634) differ from amphotericin B deoxycholate (mean EFA = 0.402 log10 CFU/mL; 95%CI, 0.360-0.445) (P = 0.13). Mortality at 10 weeks trended lower for liposomal amphotericin (28.2%) vs amphotericin B deoxycholate (34.6%) but was not statistically different when adjusting for baseline characteristics (adjusted Hazard Ratio = 0.74; 95%CI, 0.44-1.25; P = 0.26). CONCLUSIONS: Daily liposomal amphotericin B induction demonstrated a similar rate of CSF fungal clearance and 10-week mortality as amphotericin B deoxycholate when combined with flucytosine for the treatment of HIV-associated cryptococcal meningitis.

Oral Lipid Nanocrystal Amphotericin B for Cryptococcal Meningitis: A Randomized Clinical Trial.

BACKGROUND: Amphotericin B is the gold standard treatment for severe mycoses. A new orally delivered, less-toxic formulation of amphotericin has been developed. METHODS: In our randomized clinical trial, we tested oral lipid nanocrystal (LNC) amphotericin B (MAT2203, Matinas Biopharma) vs intravenous (IV) amphotericin for human immunodeficiency virus-associated cryptococcal meningitis in 4 sequential cohorts. Two pilot cohorts assessed safety and tolerability (n = 10 each), and 2 cohorts assessed efficacy with/without 2 IV loading doses (n = 40 each). The experimental arm received 1.8 g/d oral LNC amphotericin through 2 weeks with 100 mg/kg/d flucytosine, then 1.2 g/d LNC amphotericin through 6 weeks. The randomized control arm (n = 41) received 7 days of IV amphotericin with flucytosine, then 7 days of fluconazole 1200 mg/d. The primary end point was cerebrospinal fluid (CSF) early fungicidal activity (EFA). RESULTS: We randomized 80 participants to oral LNC amphotericin + flucytosine with (n = 40) and without (n = 40) 2 IV loading doses and 41 control participants to IV amphotericin + flucytosine. Mean EFA was 0.40 log10 colony-forming units (CFU)/mL/d for all-oral LNC amphotericin, 0.42 log10  Cryptococcus CFU/mL/d for oral LNC amphotericin with IV loading doses, and 0.46 log10 CFU/mL/d for IV amphotericin controls. LNC amphotericin groups achieved 2-week CSF sterility in 63% (44 of 70) vs 68% (23 of 34) of controls. The 18-week survival was 85% (34 of 40) with all-oral LNC amphotericin, 90% (36 of 40) with oral LNC amphotericin given IV loading doses, and 85% (35 of 41) with IV amphotericin.Grade 3-4 laboratory adverse events occurred less frequently in LNC amphotericin groups (41%) than the IV amphotericin group (61%, P = .05), particularly for anemia (21% vs 44%; P = .01) and potassium (5% vs 17%; P = .04). CONCLUSIONS: This new oral amphotericin B LNC formulation appears promising for cryptococcal meningitis with antifungal activity, similar survival, and less toxicity than IV amphotericin. CLINICAL TRIALS REGISTRATION: NCT04031833.

Advancing Diagnosis and Treatment in People Living with HIV and Tuberculosis Meningitis.

PURPOSE OF REVIEW: Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Inadequate diagnostic testing and treatment regimens adapted from pulmonary tuberculosis without consideration of the unique nature of TBM are among the potential drivers. This review focuses on the progress being made in relation to both diagnosis and treatment of TBM, emphasizing promising future directions. RECENT FINDINGS: The molecular assay GeneXpert MTB/Rif Ultra has improved sensitivity but has inadequate negative predictive value to "rule-out" TBM. Evaluations of tests focused on the host response and bacterial components are ongoing. Clinical trials are in progress to explore the roles of rifampin, fluoroquinolones, linezolid, and adjunctive aspirin. Though diagnosis has improved, novel modalities are being explored to improve the rapid diagnosis of TBM. Multiple ongoing clinical trials may change current therapies for TBM in the near future.

Transverse colon volvulus presenting as bowel obstruction, atelectasis, and displacement of the right lobe of the liver into the left upper abdominal quadrant: a case report.

BACKGROUND: Transverse colon volvulus is an uncommon cause of intestinal obstruction. It is a surgical emergency that can lead to bowel infarction, peritonitis, and death. CASE PRESENTATION: We report a case of transverse colon volvulus in a 35-year-old Congolese immigrant man who had a rare presentation with features of intestinal obstruction associated with right lung collapse and left mediastinal shift. CONCLUSION: This case is unusual because it presented with respiratory features that mimicked a pneumothorax in addition to features of intestinal obstruction. The use of point-of-care lung ultrasound was helpful in ruling out a pneumothorax, and this could help avoid situations such as unintentional chest drain insertions by other professionals who may encounter a similar case. Because transverse colon volvulus is rare, a high level of suspicion and awareness is required to make an accurate diagnosis.

Protocol for scoping review to identify and characterise surgery, obstetric, trauma and anaesthesia care in Ugandan health policy databases.

INTRODUCTION: Diseases addressed by surgical, obstetric, trauma and anaesthesia (SOTA) care are rising globally due to an anticipated rise in the burden of non-communicable diseases and road traffic accidents. Low- and middle-income countries (LMICs) disproportionately bear the brunt. Evidence-based policies and political commitment are required to reverse this trend. The Lancet Commission of Global Surgery proposed National Surgical and Obstetric and Anaesthesia Plans (NSOAPs) to alleviate the respective SOTA burdens in LMICs. NSOAPs success leverages comprehensive stakeholder engagement and appropriate health policy analyses and recommendations. As Uganda embarks on its NSOAP development, policy prioritisation in Uganda remains unexplored. We, therefore, seek to determine the priority given to SOTA care in Uganda's healthcare policy and systems-relevant documents. METHODS AND ANALYSIS: We will conduct a scoping review of SOTA health policy and system-relevant documents produced between 2000 and 2022 using the Arksey and O'Malley methodological framework and additional guidance from the Joanna Briggs Institute Reviewer's manual. These documents will be sought from the websites of SOTA stakeholders by hand searching. We shall also search from Google Scholar and PubMed using well-defined search strategies. The Knowledge Management Portal for the Ugandan Ministry of Health, which was created to provide evidence-based decision-making data, is the primary source. The rest of the sources will include the following: other repositories like websites of relevant government institutions, international and national non-governmental organisations, professional associations and councils, and religious and medical bureaus. Data retrieved from the eligible policy and decision-making documents will include the year of publication, the global surgery specialty mentioned, the NSOAP surgical system domain, the national priority area involved and funding. The data will be collected in a preformed extraction sheet. Two independent reviewers will screen the collected data, and results will be presented as counts and their respective proportions. The findings will be reported narratively using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for scoping reviews. ETHICS AND DISSEMINATION: This study will generate evidence-based information on the state of SOTA care in Uganda's health policy, which will inform NSOAP development in this nation. The review's findings will be presented to the Ministry of Health planning task force. The study will also be disseminated through a peer-reviewed publication; oral and poster presentations at local, regional, national and international conferences and over social media.

Cutaneous larva migrans in early infancy: A Ugandan case report.

Helminths are an important cause of worm infestation in low-income countries. The majority spread with soil to skin contact. In unusual patients presenting below 1 year, treatment can be challenging. The disease can be self-limiting; however, treatment is believed to reduce progression to more serious disease. Here, we present a case of a 3-month-old with cutaneous larva migrans.