Haemoptysis is concerning for both patient and healthcare provider and points to the presence of severe underlying lung disease warranting investigation. Approximately 8% of patients with pulmonary tuberculosis (PTB) infection will experience haemoptysis at some point during their life [1;2]. The aetiology of haemoptysis in the setting of PTB is diverse and may occur during active or following prior PTB infection due to pulmonary complications. We describe the case of a 33-year-old female who presented with massive haemoptysis on two separate occasions within a five-month period. Her background history included PTB 6 years prior and subsequent post-TB bronchiectasis with a destroyed left lung, and the development of apical mycetoma's. Despite numerous pre-existing aetiologies that could account for haemoptysis in this patient, on this admission, a newly identified ruptured Rasmussen's aneurysm was identified by angiography and successfully treated with arterial embolization. This report serves to highlight the multitude of reasons for haemoptysis in a patient with post PTB lung destruction and the associated diagnostic challenges that may be present. In particular, we highlight the Rasmussen's aneurysm, a rare entity, as a hidden cause of haemoptysis, where despite extensive parenchymal lung disease identified on chest radiography, specialised imaging is needed to confirm the diagnosis.

There are limited data describing acute kidney injury (AKI) in HIV-infected adult patients in resource-limited settings where tenofovir disoproxil fumarate (TDF), which is potentially nephrotoxic, is increasingly prescribed. We describe risk factors for and prognosis of AKI in HIV-infected individuals, stratified by those receiving and those naive to TDF. A prospective case cohort study of hospitalized HIV-infected adults with AKI stratified by TDF exposure. Adults (≥18 years) were recruited: clinical and biochemical data were collected at admission; their renal recovery, discharge, or mortality was ascertained as an in-patient and, subsequently, to a scheduled 3-month follow-up. Among this predominantly female (61%), almost exclusively black African cohort of 175 patients with AKI, 93 (53%) were TDF exposed; median age was 41 years (interquartile range 35–50). Median CD4 count and viral load and creatinine at baseline were 116 cells/mm ³ and 110,159 copies/ml, respectively. A greater proportion of the TDF group had severe AKI on admission (61% vs. 43%, p = .014); however, both groups had similar rates of newly diagnosed tuberculosis (TB; 52%) and nonsteroidal anti-inflammatory drug (NSAID; 32%) use. Intravenous fluid was the therapeutic mainstay; only seven were dialyzed. Discharge median serum creatinine (SCr) was higher in the TDF group ( p = .032) and fewer in the TDF group recovered renal function after 3 months ( p = .043). Three-month mortality was 27% in both groups, but 55% of deaths occurred in hospital. Those that died had a higher SCr and more severe AKI than survivors; TB was diagnosed in 33 (70%) of those who died. AKI was more severe and renal recovery slower in the TDF group; comorbidities, risk factors, and prognosis were similar regardless of TDF exposure. Because TB is linked to higher mortality, TB coinfection in HIV-infected patients with AKI warrants more intensive monitoring. In all those with poor renal recovery, our data suggest that a lower threshold for dialysis is needed.

To determine the association of human leukocyte antigen (HLA) alleles as correlates of risk for and protection against tuberculin skin test (TST) positivity and active TB disease amongst HIV-infected adults. Genomic DNA was extracted from 754 HIV-infected adults whole-blood. HLA-A, -B, -C and -DRB1 loci were genotyped by next generation sequencing methods. HLA alleles were analysed by the presence/absence of TST immune conversion and active TB disease and further stratified by exposure to a household TB contact, CD4+ T-cell count and, for active TB disease, TST-positivity. HLA-A*29:11 and - B*45:01/07 were associated with TST-positivity, while HLA-A*24:02, -A*29:02 and -B*15:16 with TST-negativity. In participants with a household TB contact, HLA-A*66:01, -A*68:02 and -B*49:01 were associated with TST-negativity. For TB disease, HLA-B*41:01, -C*06:02, -DRB1*04:01 and -DRB1*15:01 were associated with susceptibility, while HLA-B*07:02 and -DRB1*11:01 were protective, even for CD4+ T-cell count <350 cells/mm3. For initial TST-positivity and subsequent TB disease, HLA-A*01:01 and -DRB1*11:01 conveyed protection including for those with CD4+ T-cell count <350 cells/mm3. Several HLA alleles are noted as correlates of TB infection, risk and natural protection in HIV-infected individuals. HLA associations may enable risk stratification of those with HIV infection. Protective alleles may assist in future TB vaccine development.

Physiological changes during pregnancy support foetal growth, including adaptations in pancreatic islets to maintain glucose homeostasis. We investigate these adaptations using rare, high-quality pancreatic tissue from pregnant human donors and matched controls. We profile islets from pregnant donors using proteomics and assess α- and β-cell characteristics, as well as prolactin receptor and serotonin 2B receptor expression. Proteomic profiling of microdissected human islets identifies 7546 proteins but shows minimal differences in protein expression. In pregnancy, we show that islet area increases 1.9-fold, α- and β-cell areas increase 4.3- and 1.9-fold, driven by an increase in cell number rather than hypertrophy. Prolactin receptor expression is higher in α but not β cells, and serotonin 2B receptor is undetectable in β cells. Glucagon-like peptide-1 abundance increases 2.9-fold in α cells. These findings indicate that the molecular mechanisms driving pregnancy-induced islet adaptations in humans differ from those in mice, highlighting the need for human-based studies.

Tshepong Hospital multidrug resistant (MDR) unit between April 2011 and February 2014. Rifampicin resistant (RR) tuberculosis (TB) on X-pert MTB/Rif is assumed a surrogate for MDR TB. Following a RR result, a second specimen is taken for confirmatory culture and drug susceptibility testing (DST). We compare the initial diagnostic X-pert MTB/RIF result to the confirmatory DST in a high HIV seroprevalence setting. We retrospectively reviewed records analyzing demographics, HIV serostatus, prior TB treatments and DST results. Of 604 patients with X-pert MTB/RIF RR, 374(61.9%) had a DST and were included. The mean age was 36.9 years and 82% were HIV-infected. Following DST, MDR was confirmed in 49% and Rif mono-resistant (RMR) TB in 36%. Amongst RMR TB, 84% were HIV-infected and amongst those with CD4 < 50 versus those 50-350 cells/mm3 RMR TB was noted in 51% versus 33% (p = 0.012). Primary DR was diagnosed in 43% (61% MDR and 33% RMR). RR detected on a diagnostic X-pert MTB/Rif assay did not always predict MDR. RMR is emerging amongst those with HIV co - infection and low CD4 count (<50cells/mm3) and research is needed to reduce the number of drugs and treatment durations for RMR TB.

Unilateral absent pulmonary artery (UAPA) is a congenital abnormality rarely diagnosed in adults. UAPA has a myriad of clinical presentations and pulmonary hypertension is present in a quarter of all cases. Isolated UAPA commonly affects the right pulmonary artery and occurs as a result of abnormal development of the sixth aortic arch segment. Due to its rarity, it remains a diagnostic and therapeutic challenge. We describe a case of UAPA in an adult presenting with severe pulmonary hypertension. We describe the appropriate diagnostic approach to a patient with pulmonary hypertension and illustrate the importance of a detailed evaluation to determine the underlying aetiology, particularly in rare causes. Furthermore, we review the clinical presentation, diagnosis and management challenges of UAPA in adults.