Right ventricular dysfunction in patients with COVID-19 pneumonitis whose lungs are mechanically ventilated: a multicentre prospective cohort study.

Cardiovascular complications due to COVID-19, such as right ventricular dysfunction, are common. The combination of acute respiratory distress syndrome, invasive mechanical ventilation, thromboembolic disease and direct myocardial injury creates conditions where right ventricular dysfunction is likely to occur. We undertook a prospective, multicentre cohort study in 10 Scottish intensive care units of patients with COVID-19 pneumonitis whose lungs were mechanically ventilated. Right ventricular dysfunction was defined as the presence of severe right ventricular dilation and interventricular septal flattening. To explore the role of myocardial injury, high-sensitivity troponin and N-terminal pro B-type natriuretic peptide plasma levels were measured in all patients. We recruited 121 patients and 118 (98%) underwent imaging. It was possible to determine the primary outcome in 112 (91%). Severe right ventricular dilation was present in 31 (28%), with interventricular septal flattening present in nine (8%). Right ventricular dysfunction (the combination of these two parameters) was present in seven (6%, 95%CI 3-13%). Thirty-day mortality was 86% in those with right ventricular dysfunction as compared with 45% in those without (p = 0.051). Patients with right ventricular dysfunction were more likely to have: pulmonary thromboembolism (p < 0.001); higher plateau airway pressure (p = 0.048); lower dynamic compliance (p = 0.031); higher plasma N-terminal pro B-type natriuretic peptide levels (p = 0.006); and raised plasma troponin levels (p = 0.048). Our results demonstrate a prevalence of right ventricular dysfunction of 6%, which was associated with increased mortality (86%). Associations were also observed between right ventricular dysfunction and aetiological domains of: acute respiratory distress syndrome; ventilation; thromboembolic disease; and direct myocardial injury, implying a complex multifactorial pathophysiology.

Same day discharge, surgical training and early complications after open and laparoscopic repair of primary paraumbilical hernia.

AIMS: The aims of this study were to compare same day discharges and early complications after open and laparoscopic primary paraumbilical hernia (PUH) repair, including the procedures performed by surgical trainees (STs). METHODS: All patients who had open (suture or mesh) and laparoscopic repair of primary PUH in the Day Surgery Unit (DSU) between January 2007 and June 2009 were identified from the hospital database. The database was questioned regarding the grade of operating surgeon, type of surgical repair, day of admission and discharge from the DSU, and a patient's return to surgical services. Data were stored in Microsoft Excel(®) (TM 2007). Statistical significance was determined using Fisher's exact test. RESULTS: PUH was repaired in 337 patients: 252/337 (74.8 %) had open and 85/337 (25.2 %) had laparoscopic repair. Significantly, more patients were discharged home on the day of surgery after an open repair compared to the laparoscopic repair: open repair 187/252 (74.2 %), laparoscopic repair 35/85 (41.17 %), P = 0.0001. Overall early complications such as wound complications and hospital re-visits were similar in both groups: open repair 6.3 % (16/252), laparoscopic repair 11.7 % (10/85), P = 0.1554. STs performed 142/337 (42.1 %) of the PUH repairs with similar same day discharges from the DSU: STs 64.7 % (92/142), consultant surgeons 66.7 % (130/195), P = 0.7285. The difference in hernia recurrence between open repair 7/252 (2.78 %) and laparoscopic group 0/85 was not significant (P = 0.1985). CONCLUSION: Patients with PUH repair were more likely to go home on the day of surgery after open than after laparoscopic repair. This was not affected by the grade of the operating surgeon. Early complications were similar following open and laparoscopic repair of primary PUH.

Androgen receptor phosphorylation at serine 515 by Cdk1 predicts biochemical relapse in prostate cancer patients.

BACKGROUND: Prostate cancer cell growth is dependent upon androgen receptor (AR) activation, which is regulated by specific kinases. The aim of the current study is to establish if AR phosphorylation by Cdk1 or ERK1/2 is of prognostic significance. METHODS: Scansite 2.0 was utilised to predict which AR sites are phosphorylated by Cdk1 and ERK1/2. Immunohistochemistry for these sites was then performed on 90 hormone-naive prostate cancer specimens. The interaction between Cdk1/ERK1/2 and AR phosphorylation was investigated in vitro using LNCaP cells. RESULTS: Phosphorylation of AR at serine 515 (pAR(S515)) and PSA at diagnosis were independently associated with decreased time to biochemical relapse. Cdk1 and pCdk1(161), but not ERK1/2, correlated with pAR(S515). High expression of pAR(S515) in patients with a PSA at diagnosis of ≤20 ng ml(-1) was associated with shorter time to biochemical relapse (P=0.019). This translated into a reduction in disease-specific survival (10-year survival, 38.1% vs 100%, P<0.001). In vitro studies demonstrated that treatment with Roscovitine (a Cdk inhibitor) caused a reduction in pCdk1(161) expression, pAR(S515)expression and cellular proliferation. CONCLUSION: In prostate cancer patients with PSA at diagnosis of ≤20 ng ml(-1), phosphorylation of AR at serine 515 by Cdk1 may be an independent prognostic marker.

The accuracy of magnetic resonance imaging in radical prostatectomy.

AIMS: The aim of this study was to examine the accuracy of standard magnetic resonance imaging (MRI) in the localised staging of prostate cancer in those who had undergone radical prostatectomy. PATIENTS AND METHODS: The cohort consisted of 110 patients who had undergone MRI for staging of prostate cancer and subsequently underwent radical prostatectomy. T stage was analysed both on MRI and from the specimen following radical surgery. RESULTS: Of the patients 57% of patients had their disease up-staged following radical surgery from preoperative MRI findings. Of those patients who had their disease up-staged following surgery, nearly 50% of patients had gone from organ confined disease at time of MRI to extra-prostatic involvement from the surgical specimen. CONCLUSION: We have reported that MRI has a wide range of accuracy. Given developments in MRI technologies further work should be pursued to help in the staging of this disease for which decision to treat is difficult.