Adaptation of a respiratory service to provide CPAP for patients with COVID-19 pneumonia, outside of a critical care setting, in a district general hospital.

INTRODUCTION: One-hundred and forty patients at Croydon University Hospital received continuous positive airway pressure (CPAP) on a specialist respiratory ward, as a bridge to invasive mechanical ventilation (IMV) or as a ceiling of care for COVID-19. This retrospective study aimed to outline service expansion, patient characteristics and explore risk factors in outcomes. RESULTS: Mean age of patients on CPAP was 64 years (standard deviation 12). The median number of days from admission to CPAP initiation was 1 day (interquartile range (IQR) 0-3), and time before successful wean off CPAP was 4 days (IQR 2-6). Twenty-eight-day mortality was 64%. Thirty-four per cent of patients went onto require IMV, 24% improved off CPAP and 41% were palliated. The 28-day non-survivor group were of older age, had statistically significant higher admission creatinine and higher peak oxygen requirement. Age above 65 years was associated with higher mortality (odds ratio 5.9; 95% confidence interval 2.63-13.3). CONCLUSION: CPAP is a viable ceiling-of-treatment option in those unsuitable for ventilation, and may even avoid the need for ventilation in others. Duration on CPAP may be useful for service provision to predict resource allocation. The rapidity from admission to CPAP initiation highlights the need for early ceilings of care to be established.

Implementation of a routine HIV testing policy in an acute medical setting in a UK general hospital: a cross-sectional study.

OBJECTIVES: To report the implementation and outcomes of a routine opt-out HIV testing policy in an acute medical unit (AMU) of a district general hospital in an area of high diagnosed HIV prevalence. METHODS: Since July 2011, all patients aged 16-79 years attending AMU were offered an HIV test as a hospital policy. Consenting and arranging the test was carried out by general medical staff, with training and motivational support by local HIV specialists. A retrospective cross-sectional review was conducted: testing rate and outcomes of those testing HIV seropositive were determined by review of hospital data systems and case notes. RESULTS: Over a 21-month period, there were 12 682 admissions; 4122 (32.5%) had HIV tests. 20 patients (0.48%) were diagnosed with HIV; 17 (85%) of them were new diagnoses. Compared with those patients targeted as a result of clinical suspicion of HIV (n=6), patients who were diagnosed solely due to the scheme (n=14) had higher baseline CD4 counts (median 111 vs 313 cells/mm(3); p=0.01). Two patients had renal disease which improved on antiretroviral therapy. Two long-term defaulters to HIV care with very advanced disease have re-engaged resulting in excellent clinical outcomes. 11 patients are now on treatment with undetectable HIV viral loads. One contact tested HIV positive. CONCLUSIONS: Our experience shows that routine opt-out testing can be delivered and sustained by general medical staff in an AMU with no money spent other than laboratory processing of the test. We believe that success and sustainability of this policy is due to the high level of commitment from and ownership by the AMU staff, particularly nurses. Ongoing support and motivation from the HIV team has facilitated the delivery of this policy.

Differential regulation of E-cadherin and alpha-smooth muscle actin by BMP 7 in human renal proximal tubule epithelial cells and its implication in renal fibrosis.

Chronic kidney diseases are characterized by progressive tubulointerstitial fibrosis, and TGFbeta1 plays a crucial role in its development. Bone morphogenic protein 7 (BMP 7), another member of the TGF superfamily, antagonized the profibrotic effects of TGFbeta1, including epithelial mesenchymal transition and E-cadherin loss, in the previous studies from animal models. We investigated the effect of BMP 7 on TGFbeta1-mediated E-cadherin loss in two different transformed human adult proximal tubule epithelia. We found that BMP 7 not only failed to prevent TGFbeta1-mediated E-cadherin loss but itself downregulated E-cadherin levels and that it had an additive effect with TGFbeta1 in inducing E-cadherin loss. The downregulation of E-cadherin by BMP 7 was mediated through the Smad1/5 pathway. BMP 7-mediated E-cadherin loss was not followed by de novo alpha-smooth muscle actin (alpha-SMA) expression (a marker of myofibroblastic phenotype), which was due to the concurrent induction of Inhibitor of DNA binding 1 (Id1, a basic helix loop helix class transcriptional regulator) through a non-Smad pathway. Concurrent treatment of BMP 7 and TGFbeta1 prevented TGFbeta1-mediated alpha-SMA induction. In summary, our results suggest that E-cadherin loss, the key feature of epithelial mesenchymal transition, will not necessarily be followed by total phenotype change; rather, cells may undergo some loss of phenotypic marker in a ligand-dependent manner and participate in reparative processes. The inhibition of de novo expression of alpha-SMA could explain the antifibrotic effect of BMP 7. Id1 might play a crucial role in maintaining proximal tubule epithelial cell phenotype and its signaling regulation could be a potential therapeutic target.

BMP-7 and proximal tubule epithelial cells: activation of multiple signaling pathways reveals a novel anti-fibrotic mechanism.

PURPOSE: Bone morphogenic protein-7 (BMP-7) is a member of the transforming growth factor beta (TGFbeta) superfamily involved in organogenesis. Recent work suggests that BMP-7 can reverse the fibrotic effects of TGFbeta but the underlying mechanism is unknown. We sought to determine BMP-7 signaling and its modulation of TGFbeta induced fibrotic outcomes in adult human proximal tubule epithelial cells (PTECs). METHODS: The effect of BMP-7 on phospho-p38 was assessed by Western blotting, p38 ELISA and Bio-plex phospho-protein assay. Secreted fibronectin (Fn) was measured by ELISA. RESULTS: BMP-7 had a concentration-dependent effect on intracellular signaling activating Smad 1/5/8 at higher concentrations and p38 mitogen activated protein (MAP) kinase at lower concentrations in both primary and transformed PTECs; BMP-7 caused phosphorylation of p38 at 2.5 ng/ml and Smads at 200 ng/ml. Similarly, nuclear accumulation of phospho-p38 and Smad were observed at these respective concentrations. These results suggested an inverse relationship between activation of Smads and p38 MAP kinase in this context. Consistent, with this BMP7 at 200 ng/ml reduced TGFbeta-induced p38 MAP activation and the p38-dependent TGFbeta-induced Fn secretion by PTECs. CONCLUSION: We have shown novel p38/Smad signaling along a BMP-7 gradient and demonstrated BMP-7 regulation of TGFbeta MAP kinase signaling and fibrotic outcomes.