The Use of miRNAs in Predicting Response to Neoadjuvant Therapy in Oesophageal Cancer.

Oesophageal cancer (OC) is the ninth most common cancer worldwide. Patients receive neoadjuvant therapy (NAT) as standard of care, but less than 20% of patients with oesophageal adenocarcinoma (OAC) or a third of oesophageal squamous cell carcinoma (OSCC) patients, obtain a clinically meaningful response. Developing a method of determining a patient's response to NAT before treatment will allow rational treatment decisions to be made, thus improving patient outcome and quality of life. (1) Background: To determine the use and accuracy of microRNAs as biomarkers of response to NAT in patients with OAC or OSCC. (2) Methods: MEDLINE, EMBASE, Web of Science and the Cochrane library were searched to identify studies investigating microRNAs in treatment naïve biopsies to predict response to NAT in OC patients. (3) Results: A panel of 20 microRNAs were identified as predictors of good or poor response to NAT, from 15 studies. Specifically, miR-99b, miR-451 and miR-505 showed the strongest ability to predict response in OAC patients along with miR-193b in OSCC patients. (4) Conclusions: MicroRNAs are valuable biomarkers of response to NAT in OC. Research is needed to understand the effects different types of chemotherapy and chemoradiotherapy have on the predictive value of microRNAs; studies also require greater standardization in how response is defined.

Clinical audit as a quality improvement tool in the Gaza Strip: an audit of audits.

BACKGROUND: Clinical audit plays a fundamental role in improving the quality of patient care and hence, is considered a cornerstone of clinical governance. This quality improvement tool is newly introduced in the health-care system of the Gaza Strip. Although the number of audits completed in Gaza has been increasing over the past few years, little evidence is available of subsequent quality improvements in practice. METHODS: An online survey was used to collect information on the audit team, location, applied methods, outcomes, presentation of data, and reaudit. Medical students and health-care professionals who had conducted audits between 2015 and 2018 were invited to complete the survey from Oct 12 to Nov 2, 2018. FINDINGS: Data on 62 audits were collected. Training in clinical governance was received by 55 auditors (89%) and a senior supervisor was available in 56 audits (90%). Audits were performed across different hospitals and specialties: 18 (29%) in obstetrics, 16 (26%) in medicine, and 11 (18%) in each of surgery and paediatrics, with six (10%) in other specialties. A clear trend of increasing numbers of audits was observed, with four (6%) having been done in 2015, 12 (19%) in 2016, 22 (35%) in 2017, and 24 audits (39%) in 2018. Students were involved in 46 audits (74%) whereas practising doctors were involved in only 29 audits (47%). 17 (27.4%) audits were done at more than one health-care facility and the remaining audits were done at one of 13 other main hospitals or community centres across the Gaza Strip. Clear standards were identified in 54 audits (90%) while eight audits (13%) reported not setting standards at all. Improvement of documentation was recommended in 44 audits (71%), development of national guidelines in 37 (60%), and staff training in 32 (52%). Only 32 audits (51.6%) were presented to the local staff. The audit cycle was completed in 13 projects (20.9%) with only seven of them reporting subsequent improvements in practice. INTERPRETATION: A rise in the numbers of audits reflects a growing awareness of their key role in health care and patients' safety. However, completion of audit cycles and the actual implementation of recommendations are lagging. Therefore, more focused efforts supported by both clinical and administrative leaderships are needed to implement changes and ensure continuous evaluation of their effectiveness. FUNDING: None.

Impacts of combining anti-PD-L1 immunotherapy and radiotherapy on the tumour immune microenvironment in a murine prostate cancer model.

BACKGROUND: Radiotherapy enhances innate and adaptive anti-tumour immunity. It is unclear whether this effect may be harnessed by combining immunotherapy with radiotherapy fractions used to treat prostate cancer. We investigated tumour immune microenvironment responses of pre-clinical prostate cancer models to radiotherapy. Having defined this landscape, we tested whether radiotherapy-induced tumour growth delay could be enhanced with anti-PD-L1. METHODS: Hypofractionated radiotherapy was delivered to TRAMP-C1 and MyC-CaP flank allografts. Tumour growth delay, tumour immune microenvironment flow-cytometry, and immune gene expression were analysed. TRAMP-C1 allografts were then treated with 3 × 5 Gy ± anti-PD-L1. RESULTS: 3 × 5 Gy caused tumour growth delay in TRAMP-C1 and MyC-CaP. Tumour immune microenvironment changes in TRAMP-C1 at 7 days post-radiotherapy included increased tumour-associated macrophages and dendritic cells and upregulation of PD-1/PD-L1, CD8+ T-cell, dendritic cell, and regulatory T-cell genes. At tumour regrowth post-3 × 5 Gy the tumour immune microenvironment flow-cytometry was similar to control tumours, however CD8+, natural killer and dendritic cell gene transcripts were reduced. PD-L1 inhibition plus 3 × 5 Gy in TRAMP-C1 did not enhance tumour growth delay versus monotherapy. CONCLUSION: 3 × 5 Gy hypofractionated radiotherapy can result in tumour growth delay and immune cell changes in allograft prostate cancer models. Adjuncts beyond immunomodulation may be necessary to improve the radiotherapy-induced anti-tumour response.

Inpatient management of community-acquired pneumonia at the European Gaza Hospital: a clinical audit.

BACKGROUND: Disease severity scores such as CURB-65 are often used to guide the management of patients with community-acquired pneumonia. Early and adequate empirical antibiotic treatment reduces mortality. The aim of this study was to examine the severity assessment and management of patients presenting with community-acquired pneumonia at the European Gaza Hospital in the Gaza Strip and to compare this to the best available evidence. METHODS: Medical records of all patients admitted to the European Gaza Hospital with a diagnosis of community-acquired pneumonia between Dec 1, 2015, and March 31, 2016, were reviewed retrospectively. Clinical practice was compared with recommendations for severity assessment and the management of community-acquired pneumonia, as reported in guidelines by the National Institute for Health and Care Excellence and the American Thoracic Society. Ethical approval was obtained from the General Directorate of Human Resources. FINDINGS: 141 patients were admitted to the European Gaza Hospital with community-acquired pneumonia during the study period. Records of 41 patients were missing or could not be retrieved. The mean age of patients was 55·9 years (SD 20·2). Blood urea and nitrogen concentrations were not documented for 48 (48%) patients, and respiratory rate was not documented for 73 (73%) patients. The CURB-65 score was determined only for 12 (12%) patients. Microbiological testing was done only for two (2%) patients. Although 18 different antibiotic regimens were used, 81 (81%) patients received a ß-lactam plus macrolide combination therapy, either given alone (49 [49%] patients) or with another antibiotic (32 [32%] patients), which is in line with the recommendations for patients admitted to hospital with community-acquired pneumonia. 43 (43%) patients received anti-viral drugs, and 41 (41%) patients received corticosteroids. INTERPRETATION: Clinicians were poorly adherent to current standards of care in severity assessment and management of community-acquired pneumonia. Moreover, the broad range of antibiotic regimes used, without microbiological guidance, was inappropriate and will have increased the risk of antibiotic resistance. A local evidence-based clinical practice guideline should be developed and implemented. Furthermore, the documentation system should be improved to enhance the continuity of care and clinical auditing. FUNDING: None.