COVID-19 vaccination and breakthrough infections in patients with cancer.

BACKGROUND: Vaccination is an important preventive health measure to protect against symptomatic and severe COVID-19. Impaired immunity secondary to an underlying malignancy or recent receipt of antineoplastic systemic therapies can result in less robust antibody titers following vaccination and possible risk of breakthrough infection. As clinical trials evaluating COVID-19 vaccines largely excluded patients with a history of cancer and those on active immunosuppression (including chemotherapy), limited evidence is available to inform the clinical efficacy of COVID-19 vaccination across the spectrum of patients with cancer. PATIENTS AND METHODS: We describe the clinical features of patients with cancer who developed symptomatic COVID-19 following vaccination and compare weighted outcomes with those of contemporary unvaccinated patients, after adjustment for confounders, using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19). RESULTS: Patients with cancer who develop COVID-19 following vaccination have substantial comorbidities and can present with severe and even lethal infection. Patients harboring hematologic malignancies are over-represented among vaccinated patients with cancer who develop symptomatic COVID-19. CONCLUSIONS: Vaccination against COVID-19 remains an essential strategy in protecting vulnerable populations, including patients with cancer. Patients with cancer who develop breakthrough infection despite full vaccination, however, remain at risk of severe outcomes. A multilayered public health mitigation approach that includes vaccination of close contacts, boosters, social distancing, and mask-wearing should be continued for the foreseeable future.

Core outcome set for surgical trials in gastric cancer (GASTROS study): international patient and healthcare professional consensus.

BACKGROUND: Surgery is the primary treatment that can offer potential cure for gastric cancer, but is associated with significant risks. Identifying optimal surgical approaches should be based on comparing outcomes from well designed trials. Currently, trials report different outcomes, making synthesis of evidence difficult. To address this, the aim of this study was to develop a core outcome set (COS)-a standardized group of outcomes important to key international stakeholders-that should be reported by future trials in this field. METHODS: Stage 1 of the study involved identifying potentially important outcomes from previous trials and a series of patient interviews. Stage 2 involved patients and healthcare professionals prioritizing outcomes using a multilanguage international Delphi survey that informed an international consensus meeting at which the COS was finalized. RESULTS: Some 498 outcomes were identified from previously reported trials and patient interviews, and rationalized into 56 items presented in the Delphi survey. A total of 952 patients, surgeons, and nurses enrolled in round 1 of the survey, and 662 (70 per cent) completed round 2. Following the consensus meeting, eight outcomes were included in the COS: disease-free survival, disease-specific survival, surgery-related death, recurrence, completeness of tumour removal, overall quality of life, nutritional effects, and 'serious' adverse events. CONCLUSION: A COS for surgical trials in gastric cancer has been developed with international patients and healthcare professionals. This is a minimum set of outcomes that is recommended to be used in all future trials in this field to improve trial design and synthesis of evidence.

Machine learning to predict early recurrence after oesophageal cancer surgery.

BACKGROUND: Early cancer recurrence after oesophagectomy is a common problem, with an incidence of 20-30 per cent despite the widespread use of neoadjuvant treatment. Quantification of this risk is difficult and existing models perform poorly. This study aimed to develop a predictive model for early recurrence after surgery for oesophageal adenocarcinoma using a large multinational cohort and machine learning approaches. METHODS: Consecutive patients who underwent oesophagectomy for adenocarcinoma and had neoadjuvant treatment in one Dutch and six UK oesophagogastric units were analysed. Using clinical characteristics and postoperative histopathology, models were generated using elastic net regression (ELR) and the machine learning methods random forest (RF) and extreme gradient boosting (XGB). Finally, a combined (ensemble) model of these was generated. The relative importance of factors to outcome was calculated as a percentage contribution to the model. RESULTS: A total of 812 patients were included. The recurrence rate at less than 1 year was 29·1 per cent. All of the models demonstrated good discrimination. Internally validated areas under the receiver operating characteristic (ROC) curve (AUCs) were similar, with the ensemble model performing best (AUC 0·791 for ELR, 0·801 for RF, 0·804 for XGB, 0·805 for ensemble). Performance was similar when internal-external validation was used (validation across sites, AUC 0·804 for ensemble). In the final model, the most important variables were number of positive lymph nodes (25·7 per cent) and lymphovascular invasion (16·9 per cent). CONCLUSION: The model derived using machine learning approaches and an international data set provided excellent performance in quantifying the risk of early recurrence after surgery, and will be useful in prognostication for clinicians and patients.

ANTECEDENTES: la recidiva precoz del cáncer tras esofaguectomía es un problema frecuente con una incidencia del 20-30% a pesar del uso generalizado del tratamiento neoadyuvante. La cuantificación de este riesgo es difícil y los modelos actuales funcionan mal. Este estudio se propuso desarrollar un modelo predictivo para la recidiva precoz después de la cirugía para el adenocarcinoma de esófago utilizando una gran cohorte multinacional y enfoques con aprendizaje automático. MÉTODOS: Se analizaron pacientes consecutivos sometidos a esofaguectomía por adenocarcinoma y que recibieron tratamiento neoadyuvante en 6 unidades de cirugía esofagogástrica del Reino Unido y 1 de los Países Bajos. Con la utilización de características clínicas y la histopatología postoperatoria se generaron modelos mediante regresión de red elástica (elastic net regression, ELR) y métodos de aprendizaje automático Random Forest (RF) y XG boost (XGB). Finalmente, se generó un modelo combinado (Ensemble) de dichos métodos. La importancia relativa de los factores respecto al resultado se calculó como porcentaje de contribución al modelo. RESULTADOS: En total se incluyeron 812 pacientes. La tasa de recidiva a menos de 1 año fue del 29,1%. Todos los modelos demostraron una buena discriminación. Las áreas bajo la curva ROC (AUC) validadas internamente fueron similares, con el modelo Ensemble funcionando mejor (ELR = 0,791, RF = 0,801, XGB = 0,804, Ensemble = 0,805). El rendimiento fue similar cuando se utilizaba validación interna-externa (validación entre centros, Ensemble AUC = 0,804). En el modelo final, las variables más importantes fueron el número de ganglios linfáticos positivos (25,7%) y la invasión linfovascular (16,9%). CONCLUSIÓN: El modelo derivado con la utilización de aproximaciones con aprendizaje automático y un conjunto de datos internacional proporcionó un rendimiento excelente para cuantificar el riesgo de recidiva precoz tras la cirugía y será útil para clínicos y pacientes a la hora de establecer un pronóstico.

A Modified AUGIS Delphi Process to Establish Future Research Priorities in Benign Upper Gastrointestinal Surgery.

BACKGROUND: The aim of our study was to use a modified Delphi process to determine the research priorities amongst benign upper gastrointestinal (UGI) surgeons in the United Kingdom. METHODS: Delphi methodology may be utilised to develop consensus opinion amongst a group of experts. Members of the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland were invited to submit individual research questions via an online survey (phase I). Two rounds of prioritisation by multidisciplinary expert healthcare professionals (phase II and III) were completed to determine a final list of high-priority research questions. RESULTS: Four hundred and twenty-seven questions were submitted in phase I, and 51 with a benign UGI focus were taken forward for prioritisation in phase II. Twenty-eight questions were ranked in phase III. A final list of 11 high-priority questions had an emphasis on acute pancreatitis, Barrett's oesophagus and benign biliary disease. CONCLUSION: A modified Delphi process has produced a list of 11 high-priority research questions in benign UGI surgery. Future studies and awards from funding bodies should reflect this consensus list of prioritised questions in the interest of improving patient care and encouraging collaborative research.

Study protocol for a multicenter prospective cohort study on esophagogastric anastomoses and anastomotic leak (the Oesophago-Gastric Anastomosis Audit/OGAA).

Esophagectomy is a mainstay in curative treatment for esophageal cancer; however, the reported techniques and outcomes can vary greatly. Thirty-day mortality of patients with an intact anastomosis is 2-3% as compared to 17-35% in patients who have an anastomotic leak. The subsequent management of leaks postesophagectomy has great global variability with little consensus on a gold standard of practice. The aim of this multicentre prospective audit is to analyze current techniques of esophagogastric anastomosis to determine the effect on the anastomotic leak rate. Leak rates and leak management will be assessed to determine their impact on patient outcomes. A 12-month international multicentre prospective audit started in April 2018 and is coordinated by a team from the West Midlands Research Collaborative. This will include patients undergoing esophagectomy over 9 months and encompassing a 90-day follow-up period. A pilot data collection period occurred at four UK centers in 2017 to trial the data collection form. The audit standards will include anastomotic leak and the conduit necrosis rate should be less than 13% and major postoperative morbidity (Clavien-Dindo Grade III or more) should be less than 35%. The 30-day mortality rate should be less than 5% and the 90-day mortality rate should be less than 8%. This will be a trainee-led international audit of esophagectomy practice. Key support will be given by consultant colleagues and anesthetists. Individualized unit data will be distributed to the respective contributing sites. An overall anonymized report will be made available to contributing units. Results of the audit will be published in peer-reviewed journals with all collaborators fully acknowledged. The key information and results from the audit will be disseminated at relevant scientific meetings.

Does the Pittsburgh Severity Score predict outcome in esophageal perforation?

Esophageal perforation is an uncommon and challenging surgical emergency associated with high rates of morbidity and mortality. At present, no consensus exists on optimal management of the condition. The Pittsburgh Severity Score (PSS) is a tool intended to stratify perforation severity and guide treatment. However, there is a paucity of literature examining the validity of the score or its application in a UK population. This study aims to validate the PSS and explore its use in stratifying patients with esophageal perforation into distinct subgroups with differential outcomes in an independent UK study population.All patients treated for esophageal perforation at Queen Elizabeth Hospital, Birmingham between September 2003 and October 2017 were included in this study. Cases were identified using a combination of ICD-10 and OPCS informatics search codes and prospective case collection. Data relating to the clinical presentation, diagnosis, management, and outcome of cases were recorded using a preformed data collection form. PSS predictive performance was assessed against five outcomes: rates of post-perforation and post-operative complications, in-hospital mortality, length of intensive care (ICU/HDU) stay, and total length of hospital stay.A total of 87 cases were identified, consisting of 48 (55%) iatrogenic perforations, 24 (28%) cases of spontaneous (Boerhaave's) perforation, and 15 perforations due to other etiologies (17%). Operative management was favored in this series, with 47% of all perforations being treated surgically. Overall in-hospital mortality was 13%, coupled with a median length of hospital stay of 24 days (interquartile range [IQR]: 12-49), of which a median of 2 days was spent in intensive care facilities (IQR: 0-14). A total of 46% of patients developed post-perforation complications, with 59% of the operatively managed cohort developing complications post-operatively.The PSS was not found to be significantly predictive of post-perforation complications (area under the ROC curve [AUROC]: 0.62, p = 0.053) or in-hospital mortality (AUROC: 0.69, p = 0.057) for the cohort as a whole. However, a subgroup analysis found the accuracy of the PSS to vary considerably by etiology, being significantly predictive of post-perforation complications within the subgroup of Boerhaave's perforations (AUROC: 0.86, p = 0.004).In conclusion, we found that the PSS has some utility in stratifying esophageal perforation severity and predicting specific patient outcomes. However, it appears to be of more value when applied to the subgroup of patients with Boerhaave's perforations.

The learning curve to achieve satisfactory completion rates in upper GI endoscopy: an analysis of a national training database.

OBJECTIVE: The aim of this study was to determine the number of OGDs (oesophago-gastro-duodenoscopies) trainees need to perform to acquire competency in terms of successful unassisted completion to the second part of the duodenum 95% of the time. DESIGN: OGD data were retrieved from the trainee e-portfolio developed by the Joint Advisory Group on GI Endoscopy (JAG) in the UK. All trainees were included unless they were known to have a baseline experience of >20 procedures or had submitted data for <20 procedures. The primary outcome measure was OGD completion, defined as passage of the endoscope to the second part of the duodenum without physical assistance. The number of OGDs required to achieve a 95% completion rate was calculated by the moving average method and learning curve cumulative summation (LC-Cusum) analysis. To determine which factors were independently associated with OGD completion, a mixed effects logistic regression model was constructed with OGD completion as the outcome variable. RESULTS: Data were analysed for 1255 trainees over 288 centres, representing 243 555 OGDs. By moving average method, trainees attained a 95% completion rate at 187 procedures. By LC-Cusum analysis, after 200 procedures, >90% trainees had attained a 95% completion rate. Total number of OGDs performed, trainee age and experience in lower GI endoscopy were factors independently associated with OGD completion. CONCLUSIONS: There are limited published data on the OGD learning curve. This is the largest study to date analysing the learning curve for competency acquisition. The JAG competency requirement for 200 procedures appears appropriate.

Multicentre cohort study to define and validate pathological assessment of response to neoadjuvant therapy in oesophagogastric adenocarcinoma.

BACKGROUND: This multicentre cohort study sought to define a robust pathological indicator of clinically meaningful response to neoadjuvant chemotherapy in oesophageal adenocarcinoma. METHODS: A questionnaire was distributed to 11 UK upper gastrointestinal cancer centres to determine the use of assessment of response to neoadjuvant chemotherapy. Records of consecutive patients undergoing oesophagogastric resection at seven centres between January 2000 and December 2013 were reviewed. Pathological response to neoadjuvant chemotherapy was assessed using the Mandard Tumour Regression Grade (TRG) and lymph node downstaging. RESULTS: TRG (8 of 11 centres) was the most widely used system to assess response to neoadjuvant chemotherapy, but there was discordance on how it was used in practice. Of 1392 patients, 1293 had TRG assessment; data were available for clinical and pathological nodal status (cN and pN) in 981 patients, and TRG, cN and pN in 885. There was a significant difference in survival between responders (TRG 1-2; median overall survival (OS) not reached) and non-responders (TRG 3-5; median OS 2·22 (95 per cent c.i. 1·94 to 2·51) years; P < 0·001); the hazard ratio was 2·46 (95 per cent c.i. 1·22 to 4·95; P = 0·012). Among local non-responders, the presence of lymph node downstaging was associated with significantly improved OS compared with that of patients without lymph node downstaging (median OS not reached versus 1·92 (1·68 to 2·16) years; P < 0·001). CONCLUSION: A clinically meaningful local response to neoadjuvant chemotherapy was restricted to the small minority of patients (14·8 per cent) with TRG 1-2. Among local non-responders, a subset of patients (21·3 per cent) derived benefit from neoadjuvant chemotherapy by lymph node downstaging and their survival mirrored that of local responders.

Cost-effectiveness of emergency versus delayed laparoscopic cholecystectomy for acute gallbladder pathology.

BACKGROUND: The optimal timing of cholecystectomy for patients admitted with acute gallbladder pathology is unclear. Some studies have shown that emergency cholecystectomy during the index admission can reduce length of hospital stay with similar rates of conversion to open surgery, complications and mortality compared with a 'delayed' operation following discharge. Others have reported that cholecystectomy during the index acute admission results in higher morbidity, extended length of stay and increased costs. This study examined the cost-effectiveness of emergency versus delayed cholecystectomy for acute benign gallbladder disease. METHODS: Using data from a prospective population-based cohort study examining the outcomes of cholecystectomy in the UK and Ireland, a model-based cost-utility analysis was conducted from the perspective of the UK National Health Service, with a 1-year time horizon for costs and outcomes. Probabilistic sensitivity analysis was used to investigate the impact of parameter uncertainty on the results obtained from the model. RESULTS: Emergency cholecystectomy was found to be less costly (£4570 versus £4720; €5484 versus €5664) and more effective (0·8868 versus 0·8662 QALYs) than delayed cholecystectomy. Probabilistic sensitivity analysis showed that the emergency strategy is more than 60 per cent likely to be cost-effective across willingness-to-pay values for the QALY from £0 to £100 000 (€0-120 000). CONCLUSION: Emergency cholecystectomy is less costly and more effective than delayed cholecystectomy. This approach is likely to be beneficial to patients in terms of improved health outcomes and to the healthcare provider owing to the reduced costs.

A national audit of colonic interposition for esophageal replacement.

Esophageal replacement by colonic interposition is an uncommon procedure. This study sought to identify the frequency of this operation in England, identify techniques and associated problems, and also assess health-related quality of life (HR QOL) from the two largest centers performing this procedure. Hospital Episode Statistics were used to identify patients and centers undertaking colon interposition between March 2001 and March 2015. An online survey of UK consultants discussed methods and experience. HR QOL was assessed using the Short Form 36(SF-36v2) with additional gastrointestinal questions. Hospital Episode Statistics identified 328 interpositions (22 in pediatric hospitals). The two highest volume units did 42 and 45 operations, respectively. Thirty-four surgeons (79% response rate) replied to the survey. Fifty-two percent preferred to use the left colon with 81% preferring a substernal placement. The HR QOL survey was performed on 24 patients with a median of 3 years after surgery (ranging from 9 months to 10 years) from the two largest centers and a 56% response rate. Five patients had physical QOL scores above population average and 10 had mental scores above population average. All patients had early satiety, 20 described dysphagia, and 18 regularly took antireflux medication. There was an estimated mean loss of 13.1% body weight (10.6 kg) postoperatively and three patients still relied on a feeding tube for nutrition after an average of 3 years. Colon interposition results in an acceptable long-term QOL. Few centers regularly perform this operation, and centralizing to high-volume centers may lead to better outcomes.

Meta-analysis of perioperative antibiotics in patients undergoing laparoscopic cholecystectomy.

BACKGROUND: The effectiveness of perioperative antibiotics in reducing surgical-site infection (SSI) and overall nosocomial infections in patients undergoing laparoscopic cholecystectomy for biliary colic and low- and moderate-risk cholecystitis (Tokyo classification) is unclear. A systematic review and meta-analysis was performed to assess this. METHODS: Searches were conducted of the MEDLINE, Embase and Cochrane databases. Only randomized clinical trials (RCTs) were included. The analysis was performed using the random-effects method, and the risk ratio (RR) with 95 per cent c.i. was employed. RESULTS: Nineteen RCTs, published between 1997 and 2015, with a total of 5259 participants, of whom 2709 (51·5 per cent) were treated with antibiotics, were included. SSI and overall nosocomial infections were detected in 2·4 and 4·2 per cent respectively of patients given perioperative antibiotics, and in 3·2 and 7·2 per cent of those who received no antibiotics. Antibiotics did not significantly reduce the risk of SSI (RR 0·81, 95 per cent c.i. 0·58 to 1·13; P = 0·21) or overall nosocomial infections (RR 0·64, 0·36 to 1·14; P = 0·13). There was no significant between-study heterogeneity for SSI, but significant between-study heterogeneity in the eight studies that reported nosocomial infections. Analysis of studies considered to be high quality, grouped according to the timing of antibiotics (preoperative only or perioperative) and reporting intention-to-treat analyses, again failed to show a significant reduction in SSI. CONCLUSION: Antibiotics should not be administered before laparoscopic cholecystectomy in patients with biliary colic and/or low- and moderate-risk cholecystitis.

Pattern Formation by Staphylococcus epidermidis via Droplet Evaporation on Micropillars Arrays at a Surface.

We evaluate the effect of epoxy surface structuring on the evaporation of water droplets containing Staphylococcus epidermidis (S. epidermidis). During evaporation, droplets with S. epidermidis cells yield to complex wetting patterns such as the zipping-wetting1-3 and the coffee-stain effects. Depending on the height of the microstructure, the wetting fronts propagate circularly or in a stepwise manner, leading to the formation of octagonal or square-shaped deposition patterns.4,5 We observed that the shape of the dried droplets has considerable influence on the local spatial distribution of S. epidermidis deposited between micropillars. These changes are attributed to an unexplored interplay between the zipping-wetting1 and the coffee-stain6 effects in polygonally shaped droplets containing S. epidermidis. Induced capillary flows during evaporation of S. epidermidis are modeled with polystyrene particles. Bacterial viability measurements for S. epidermidis show high viability of planktonic cells, but low biomass deposition on the microstructured surfaces. Our findings provide insights into design criteria for the development of microstructured surfaces on which bacterial propagation could be controlled, limiting the use of biocides.

Reported co-infection deaths are more common in early adulthood and among similar infections.

BACKGROUND: Many people have multiple infections at the same time, but the combined contribution of those infections to disease-related mortality is unknown. Registered causes of death offer a unique opportunity to study associations between multiple infections. METHODS: We analysed over 900,000 death certificates that reported infectious causes of death. We tested whether reports of multiple infections (i.e., co-infections) differed across individuals' age or sex. We also tested whether each pair of infections were reported together more or less often than expected by chance, and whether this co-reporting was associated with the number of biological characteristics they had in common. RESULTS: In England and Wales, and the USA, 10 and 6 % respectively of infection-related deaths involved co-infection. Co-infection was reported reported most often in young adults; 30 % of infection-related deaths among those aged 25-44 from the USA, and 20 % of infection-related deaths among those aged 30-39 from England and Wales, reported multiple infections. The proportion of infection-related deaths involving co-infection declined with age more slowly in males than females, to less than 10 % among those aged >65. Most associated pairs of infections co-occurred more often than expected from their frequency of being reported alone (488/683 [71 %] in the USA, 129/233 [55 %] in England and Wales), and tended to share biological characteristics (taxonomy, transmission mode, tropism or timescale). CONCLUSIONS: Age, sex, and biologically similar infections are associated with death from co-infection, and may help indicate patients at risk of severe co-infection.

Oesophagopleural fistula after pneumonectomy: A systematic review and case series.

INTRODUCTION: There is a paucity of data on the optimal management of oesophagopleural fistula (OPF) following pneumonectomy. The current published literature is limited to case reports and small case series. Although rare, OPF can have a significant impact on both the morbidity and mortality of patients. METHODS: Two cases of OPF managed at our institution were reported. A systematic review was then conducted in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance concerning OPF following pneumonectomy. Demographic, operative and management data were analysed. FINDINGS: Systematic review-identified data pertaining to 59 patients from 31 papers was collated. Median patient age was 59.5 years with pneumonectomy performed typically for malignancy (68%) or tuberculosis (19%). Median time from pneumonectomy to a diagnosis of OPF was 12.5 months. Twenty-five per cent of the patients had a synchronous bronchopleural fistula. Management of OPF in this setting is heterogenous. Conservative management was often reserved for asymptomatic or unfit patients. The remainder underwent endoscopic or surgical correction of the fistulae or a combination of the two with varying outcomes. Median follow-up was 18 months. All-cause mortality was 31% (18/59) with a median duration from pneumonectomy to death of 35 days (range 1-1,095). CONCLUSIONS: Major heterogeneity of management for this rare complication hinders the introduction of standardised guidance of post-pneumonectomy OPF. Surgical and endoscopic intervention is feasible and can be successful in specialist centres. Adopting an multidisciplinary team approach involving both oesophagogastric and thoracic surgery teams and the introduction of a registry database of postoperative complications are likely to yield optimal outcomes.

A preoperative predictive tool to assess the need for staging laparoscopy in oesophagogastric cancer patients.

INTRODUCTION: Staging laparoscopy (SL) has become commonplace in the preoperative staging pathway for oesophagogastric (OG) cancer. SL is often performed before curative treatment to examine for macroscopic peritoneal metastases (PM) or positive peritoneal cytology (PPC). The aim of this study was to develop an objective risk scoring system to predict both PM and PPC at SL. METHODS: A prospectively collected and maintained database of all OG cancer patients treated between 2006 and 2020 was reviewed. Univariate and multivariate analyses were performed to identify risk factors for both PM and PPC at SL. A risk score was produced for both PM and PPC, and then validated internally. RESULTS: Among 968 patients who underwent SL, 96 (9.9%) had PM and 81 (8.4%) had PPC at SL. Tumour site (p < 0.001), computed tomography (CT) T stage (p < 0.001) and N stage (p = 0.029) were significantly associated with PM at SL (p < 0.001). Tumour site (p < 0.001), biopsy histology (p = 0.041), CT T stage (p < 0.001) and N stage (p < 0.001) were significantly associated with PPC. The risk scoring model for PM included cancer site and CT T stage. This was successfully tested on the validation set (area under the receiver operating characteristic [AUROC] = 0.730). The risk scoring model for PPC included cancer site, CT T and N stage. This was successfully tested on the validation set (AUROC = 0.773). CONCLUSIONS: The current risk scores are valid tools with which to predict the risk PM and PPC in patients undergoing SL for OG cancer and may help to avoid subjecting patients to unnecessary SL.

The underwater soundscape of the North Sea.

As awareness on the impact of anthropogenic underwater noise on marine life grows, underwater noise measurement programs are needed to determine the current status of marine areas and monitor long-term trends. The Joint Monitoring Programme for Ambient Noise in the North Sea (JOMOPANS) collaborative project was funded by the EU Interreg to collect a unique dataset of underwater noise levels at 19 sites across the North Sea, spanning many different countries and covering the period from 2019 to 2020. The ambient noise from this dataset has been characterised and compared - setting a benchmark for future measurements in the North Sea area. By identifying clusters with similar sound characteristics in three broadband frequency bands (25-160 Hz, 0.2-1.6 kHz, and 2-10 kHz), geographical areas that are similarly affected by sound have been identified. The measured underwater sound levels show a persistent and spatially uniform correlation with wind speed at high frequencies (above 1 kHz) and a correlation with the distance from ships at mid and high frequencies (between 40 Hz and 4 kHz). Correlation with ocean current velocity at low frequencies (up to 200 Hz), which are susceptible to nonacoustic contamination by flow noise, was also evaluated. These correlations were evaluated and simplified linear scaling laws for wind and current speeds were derived. The presented dataset provides a baseline for underwater noise measurements in the North Sea and shows that spatial variability of the dominant sound sources must be considered to predict the impact of noise reduction measures.

Psychiatric consequences of needlestick injury.

BACKGROUND: Needlestick injuries (NSIs) are a common occupational hazard with potential physical health effects, including viral infections such as hepatitis and HIV. Less appreciated are the psychiatric consequences of NSIs, potentially including post-traumatic stress disorder (PTSD) and adjustment disorder (AD). AIMS: To study psychiatric consequences of NSIs by diagnosis, duration and severity of depressive symptoms. METHODS: Case control study from patients referred to a psychiatric trauma clinic diagnosed according to ICD-10 diagnostic research criteria guidelines. The Beck Depression Inventory (BDI) was administered to measure depressive symptomatology and assess differences in depression severity between psychiatric trauma patients who had or had not experienced an NSI, and for relationships between the severity of depression and time since NSI using linear models. RESULTS: There were 17 NSI cases and 125 controls. NSI patients had moderately severe depressive symptoms (mean BDI score 22.7 15), which was similar to 125 non-NSI trauma patients. 13 of these 17 cases had AD and four had PTSD. None contracted infections from their NSI, but most described secondary effects of psychiatric illness on occupational, family and sexual functioning. Severity of depressive symptoms declined with time after NSI, but psychiatric illness lasted 1.78 months longer for every month a NSI patient waited for seronegative test results (P < 0.05). CONCLUSIONS: Enduring psychiatric illness can result from NSIs with a severity similar to other psychiatric trauma. Swift delivery of test results may reduce the duration of depression associated with NSI. Occupational health professionals need to be aware of the psychiatric and physical effects of NSIs.

SGI-110: DNA Methyltransferase Inhibitor Oncolytic.

SGI-110 is a second-generation hypomethylating prodrug whose active metabolite is the well-characterized drug decitabine. This novel compound is an oligonucleotide consisting of decitabine linked through a phosphodiester bond to the endogenous nucleoside deoxyguanosine. The dinucleotide configuration provides protection from drug clearance by deamination, while maintaining at least equivalent effects on gene-specific and global hypomethylation both in vitro and in animal model systems. This agent is currently being tested in phase I and II clinical trials in humans and has been demonstrated to be safe and well tolerated as a single agent, with evidence of promising activity in heavily pretreated (including currently FDA approved hypomethylating drugs) myelodysplastic syndrome and acute myeloid leukemia patients. Ongoing trials are also open in platinum-resistant ovarian cancer and hepatocellular carcinoma.

Urgent surgical repair of symptomatic Bochdalek hernia containing an intrathoracic kidney.

Bochdalek hernias rarely contain an intrathoracic kidney, and there are few reports of their operative repair. A woman presented with progressive dyspnoea limiting her quality of life. Imaging showed a Bochdalek hernia containing omentum, large bowel and the left kidney. The woman was unexpectedly admitted to the intensive care unit with respiratory failure secondary to gallstone pancreatitis whilst awaiting elective repair of her hernia. Surgical repair of the hernia was performed via laparotomy with cholecystectomy to treat both problems. The woman recovered well and is independently mobile without any exertional dyspnoea.