A national propensity score-matched analysis of emergency laparoscopic versus open abdominal surgery.

BACKGROUND: Laparoscopy has been widely adopted in elective abdominal surgery but is still sparsely used in emergency settings. The study investigated the effect of laparoscopic emergency surgery using a population database. METHODS: Data for all patients from December 2013 to November 2018 were retrieved from the NELA national database of emergency laparotomy for England and Wales. Laparoscopically attempted cases were matched 2 : 1 with open cases for propensity score derived from a logistic regression model for surgical approach; included co-variates were age, gender, predicted mortality risk, and diagnostic, procedural and surgeon variables. Groups were compared for mortality. Secondary endpoints were blood loss and duration of hospital stay. RESULTS: Of 116 920 patients considered, 17 040 underwent laparoscopic surgery. The most common procedures were colectomy, adhesiolysis, washout and perforated ulcer repair. Of these, 11 753 were matched exactly to 23 506 patients who had open surgery. Laparoscopically attempted surgery was associated with lower mortality (6.0 versus 9.1 per cent, P < 0.001), blood loss (less than 100 ml, 64.4 versus 52.0 per cent, P < 0.001), and duration of hospital stay (median 8 (i.q.r. 5-14) versus 10 (7-18) days, P < 0.001). Similar trends were seen when comparing only successful laparoscopic cases with open surgery, and also when comparing cases converted to open surgery with open surgery. CONCLUSION: In appropriately selected patients, laparoscopy is associated with superior outcomes compared with open emergency surgery.

Minimally invasive (laparoscopic) surgery has been widely adopted in elective surgery but is sparsely used in emergencies. The study used national data to look at outcomes for patients having laparoscopic or open surgery, and used statistical methods to match patients in each group for critical variables such as type of operation, age and how unwell they were at time of surgery. Laparoscopy was found significantly to improve outcomes with reduced duration of stay in hospital, and lower rates of death after surgery. This suggests laparoscopy should be considered for much wider use than is currently employed.

A Public Health Framework for Preventing Mental Disorders in the Context of Pandemics.

The COVID-19 pandemic has universally threatened the building blocks of mental health, well-being, and quality of life, namely, expectations of safety, connectedness, hope, and individual and societal efficacy. Consequently, unprecedently large numbers of individuals are significantly stressed and many are at risk for relapse of mental health problems, exacerbations of existing mental and behavioral health problems, and new onset clinical problems. Because of the scope of the problem, a population-based public health perspective is needed, which in the context of disasters has well-established theories and prevention approaches. Public health approaches to disasters and pandemics focus on preventing subclinical problems from becoming clinical disorders, in comparison to clinical care approaches that focus on treating established disorders. Fortunately, specialty care clinicians who typically think about assessing and treating established disorders have the training and clinical competencies to deliver prevention-focused interventions. This paper is designed to help specialty care clinicians who use cognitive-behavioral strategies to understand the biopsychosocial impacts and resource deficits associated with COVID-19-related stressors and the public health perspective to address them. We also provide ways clinicians can help people who are suffering from significant stress and resource deficits bounce back and regain functioning. We describe psychological first aid, stress management, repeated ecological assessment, writing about stressors, problem-solving, and behavioral activation approaches to assist individuals at risk for enduring stress-linked problems.

The effectiveness of ω-3 polyunsaturated fatty acid interventions during pregnancy on obesity measures in the offspring: an up-to-date systematic review and meta-analysis.

BACKGROUND: The potential role of ω-3 long chain polyunsaturated fatty acid (LCPUFA) supplementation during pregnancy on subsequent risk of obesity outcomes in the offspring is not clear and there is a need to synthesise this evidence. OBJECTIVE: A systematic review and meta-analysis of randomised controlled trials (RCTs), including the most recent studies, was conducted to assess the effectiveness of ω-3 LCPUFA interventions during pregnancy on obesity measures, e.g. BMI, body weight, fat mass in offspring. METHODS: Included RCTs had a minimum of 1-month follow-up post-partum. The search included CENTRAL, MEDLINE, SCOPUS, WHO's International Clinical Trials Reg., E-theses and Web of Science databases. Study quality was evaluated using the Cochrane Collaboration's risk of bias tool. RESULTS: Eleven RCTs, from ten unique trials, (3644 children) examined the effectiveness of ω-3 LCPUFA maternal supplementation during pregnancy on the development of obesity outcomes in offspring. There were heterogeneities between the trials in terms of their sample, type and duration of intervention and follow-up. Pooled estimates did not show an association between prenatal intake of fatty acids and obesity measures in offspring. CONCLUSION: These results indicate that maternal supplementation with ω-3 LCPUFA during pregnancy does not have a beneficial effect on obesity risk. Due to the high heterogeneity between studies along with small sample sizes and high rates of attrition, the effects of ω-3 LCPUFA supplementation during pregnancy for prevention of childhood obesity in the long-term remains unclear. Large high-quality RCTs are needed that are designed specifically to examine the effect of prenatal intake of fatty acids for prevention of childhood obesity. There is also a need to determine specific sub-groups in the population that might get a greater benefit and whether different ω-3 LCPUFA, i.e. eicosapentaenoic (EPA) vs. docosahexanoic (DHA) acids might potentially have different effects.

Incidence and risk factors for esophageal cancer following achalasia treatment: national population-based case-control study.

The objective of this study is to identify the incidence of and risk factors associated with the development of esophageal cancer in treated achalasia patients in a national cohort. Patients with esophageal achalasia diagnosed and receiving a treatment between 2002 and 2012 were identified in England. Patient and treatment factors were compared between individuals who developed esophageal cancer and those that did not using univariate and multivariate analyses. A total of 7487 patients receiving an interventional treatment for esophageal achalasia were included and 101 patients (1.3%) developed esophageal cancer. The incidence of esophageal cancer was 205 cases per 100,000 patient years at risk. Patients who developed esophageal cancer were older and more commonly primarily treated with pneumatic dilation (82.2% vs. 60.3%; P < 0.001). In the esophageal cancer group, there was an increase in the number of patients requiring reinterventions (47.5% vs. 38.0%; P = 0.041) and the average total number of reinterventions per patient (1.2 vs. 0.8; P = 0.026). Multivariate analysis suggested associations between increased reintervention following both surgical myotomy (HR = 5.1; 95%CI 1.12-23.16) and pneumatic dilation (HR = 1.48; 95%CI 0.95-2.29), and esophageal cancer risk. Increasing patient age and reintervention following primary achalasia treatment are important potential risk factors for the development of esophageal cancer. Treated achalasia patients with symptom recurrence should be carefully evaluated for potential development of esophageal cancer prior to considering reintervention, and increased vigilance may help diagnose esophageal cancer in these individuals at an early stage.

Obesity surgery and risk of cancer.

BACKGROUND: Obesity increases the risk of several types of cancer. Whether bariatric surgery influences the risk of obesity-related cancer is not clear. This study aimed to uncover the risk of hormone-related (breast, endometrial and prostate), colorectal and oesophageal cancers following obesity surgery. METHODS: This national population-based cohort study used data from the Hospital Episode Statistics database in England collected between 1997 and 2012. Propensity matching on sex, age, co-morbidity and duration of follow-up was used to compare cancer risk among obese individuals undergoing bariatric surgery (gastric bypass, gastric banding or sleeve gastrectomy) and obese individuals not undergoing such surgery. Conditional logistic regression provided odds ratios (ORs) with 95 per cent confidence intervals. RESULTS: In the study period, from a cohort of 716 960 patients diagnosed with obesity, 8794 patients who underwent bariatric surgery were matched exactly with 8794 obese patients who did not have surgery. Compared with the no-surgery group, patients who had bariatric surgery exhibited a decreased risk of hormone-related cancers (OR 0·23, 95 per cent c.i. 0·18 to 0·30). This decrease was consistent for breast (OR 0·25, 0·19 to 0·33), endometrium (OR 0·21, 0·13 to 0·35) and prostate (OR 0·37, 0·17 to 0·76) cancer. Gastric bypass resulted in the largest risk reduction for hormone-related cancers (OR 0·16, 0·11 to 0·24). Gastric bypass, but not gastric banding or sleeve gastrectomy, was associated with an increased risk of colorectal cancer (OR 2·63, 1·17 to 5·95). Longer follow-up after bariatric surgery strengthened these diverging associations. CONCLUSION: Bariatric surgery is associated with decreased risk of hormone-related cancers, whereas gastric bypass might increase the risk of colorectal cancer.

Population-based cohort study of surgical myotomy and pneumatic dilatation as primary interventions for oesophageal achalasia.

BACKGROUND: The aim of this national population-based cohort study was to compare rates of reintervention after surgical myotomy versus sequential pneumatic dilatation for the primary management of oesophageal achalasia. METHODS: Patients with oesophageal achalasia diagnosed between 2002 and 2012, and without an intervention in the preceding 5 years were identified from the Hospital Episode Statistics database. Patients were divided into two groups based on the primary treatment, and propensity score matching was used to compensate for differences in baseline characteristics. RESULTS: Some 14 705 patients were diagnosed with oesophageal achalasia, of whom 7487 (50·9 per cent) received interventional treatment: 1742 (23·3 per cent) surgical myotomy, 4534 (60·6 per cent) pneumatic dilatation and 1211 (16·2 per cent) endoscopic botulinum toxin injection. As age increased, the proportion of patients receiving myotomy decreased and the proportion undergoing dilatation increased. Patients who underwent surgical myotomy were younger (mean age 44·8 years versus 58·5 years among those who had pneumatic dilatation; P < 0·001), a greater proportion had a Charlson co-morbidity index score of 0 (90·1 versus 87·7 per cent; P = 0·003) and they were more commonly men (55·6 versus 51·8 per cent; P = 0·020). Following propensity score matching, the safety of the two initial treatment approaches was equivalent, with no difference in incidence of oesophageal perforation (1·3 and 1·4 per cent after myotomy and dilatation respectively; P = 0·750). However, dilatation was associated with increased need for reintervention (59·6 versus 13·8 per cent; P < 0·001) and frequency of reinterventions (mean 0·34 versus 0·06 per year; P < 0·001). CONCLUSION: Surgical myotomy was associated with a lower rate of reintervention and could be offered as primary treatment in patients with oesophageal achalasia who are fit for surgery. For those unfit for surgery, pneumatic dilatation may provide symptomatic relief with approximately 60 per cent of patients requiring reintervention.

Influence of national centralization of oesophagogastric cancer on management and clinical outcome from emergency upper gastrointestinal conditions.

BACKGROUND: In England in 2001 oesophagogastric cancer surgery was centralized. The aim of this study was to evaluate whether centralization of oesophagogastric cancer to high-volume centres has had an effect on mortality from different emergency upper gastrointestinal conditions. METHODS: The Hospital Episode Statistics database was used to identify patients admitted to hospitals in England (1997-2012). The influence of oesophagogastric high-volume cancer centre status (20 or more resections per year) on 30- and 90-day mortality from oesophageal perforation, paraoesophageal hernia and perforated peptic ulcer was analysed. RESULTS: Over the study interval, 3707, 12 441 and 56 822 patients with oesophageal perforation, paraoesophageal hernia and perforated peptic ulcer respectively were included. There was a passive centralization to high-volume cancer centres for oesophageal perforation (26·9 per cent increase), paraoesophageal hernia (19·5 per cent increase) and perforated peptic ulcer (23·0 per cent increase). Management of oesophageal perforation in high-volume centres was associated with a reduction in 30-day (HR 0·58, 95 per cent c.i. 0·45 to 0·74) and 90-day (HR 0·62, 0·49 to 0·77) mortality. High-volume cancer centre status did not affect mortality from paraoesophageal hernia or perforated peptic ulcer. Annual emergency admission volume thresholds at which mortality improved were observed for oesophageal perforation (5 patients) and paraoesophageal hernia (11). Following centralization, the proportion of patients managed in high-volume cancer centres that reached this volume threshold was 88·0 per cent for oesophageal perforation, but only 30·3 per cent for paraoesophageal hernia. CONCLUSION: Centralization of low incidence conditions such as oesophageal perforation to high-volume cancer centres provides a greater level of expertise and ultimately reduces mortality.

An observational study of the timing of surgery, use of laparoscopy and outcomes for acute cholecystitis in the USA and UK.

BACKGROUND: Evidence supports early laparoscopic cholecystectomy for acute cholecystitis. Differences in treatment patterns between the USA and UK, associated outcomes and resource utilization are not well understood. METHODS: In this retrospective, observational study using national administrative data, emergency patients admitted with acute cholecystitis were identified in England (Hospital Episode Statistics 1998-2012) and USA (National Inpatient Sample 1998-2011). Proportions of patients who underwent emergency cholecystectomy, utilization of laparoscopy and associated outcomes including length of stay (LOS) and complications were compared. The effect of delayed treatment on subsequent readmissions was evaluated for England. RESULTS: Patients with a diagnosis of acute cholecystitis totaled 1,191,331 in the USA vs. 288 907 in England. Emergency cholecystectomy was performed in 628,395 (52.7% USA) and 45,299 (15.7% England) over the time period. Laparoscopy was more common in the USA (82.8 vs. 37.9%; p < 0.001). Pre-treatment (1 vs. 2 days; p < 0.001) and total ( 4 vs. 7 days; p < 0.001) LOS was lower in the USA. Overall incidence of bile duct injury was higher in England than the USA (0.83 vs. 0.43%; p < 0.001), but was no different following laparoscopic surgery (0.1%). In England, 40.5% of patients without an immediate cholecystectomy were subsequently readmitted with cholecystitis. An additional 14.5% were admitted for other biliary complications, amounting to 2.7 readmissions per patient in the year following primary admission. CONCLUSION: This study highlights management practices for acute cholecystitis in the USA and England. Despite best evidence, index admission laparoscopic cholecystectomy is performed less in England, which significantly impacts subsequent healthcare utilization.

The influence of hospital volume upon clinical management and outcomes of esophageal achalasia: an English national population-based cohort study.

Management of achalasia is potentially complex. Previous studies have identified equivalence between pneumatic dilatation and surgical cardiomyotomy in terms of clinical outcomes. However, previous research has not investigated whether a management strategies and outcomes are different in high-volume achalasia centers. This national population-based cohort study aimed to identify the treatment modalities utilized in centers, which regularly manage achalasia and those which manage it infrequently. This study also assessed rates of re-intervention and complications to establish if a volume-outcome relationship exists for the management of achalasia in England. In this study, the Hospitals Episode Statistics database was used to identify all patients treated for achalasia in England from 2002 to 2012. Primary treatment was defined as surgical cardiomyotomy, sequential pneumatic dilatation, or botulinum toxin therapy. Primary outcome measure was reintervention. Centers were divided into regular achalasia centers (≥5.7 cases per annum) and infrequent achalasia centers (<5.7 cases per annum), and were analyzed according to tertiary cancer center status. In total, there were 7,487 patients treated for achalasia. Out of 1,947 cases (26%) were treated in regular achalasia centers, with 5,540 (74%) treated in infrequent centers. In binary logistic regression modeling regular centers treated a similar proportion of patients with primary surgical cardiomyotomy (OR: 1.11 (95% CI 0.98-1.27)) and had similar rates of re-intervention to infrequent achalasia centers (HR: 1.03 (0.94-1.12)). RA-CUSUM analysis demonstrated no relationship between total hospital volume and reintervention rates. Tertiary cancer centers treated more achalasia patients with primary surgical cardiomyotomy (OR: 1.51 (95% CI 1.31-1.73)) but there was no significant difference in reintervention rates (OR: 1.05 (95% CI 0.95-1.16)). In conclusion, this analysis failed to demonstrate a volume-outcome relationship in the management of achalasia in England. This study highlights that achalasia is treated infrequently by the majority of centers.

Comparison of nutrient intake in adolescents and adults with and without food allergies.

BACKGROUND: Exclusion diets for the management of food allergy pose a risk of nutritional deficiencies and inadequate growth in children, yet less is known about their effect in adolescents and adults. The present study aimed to compare the dietary intake of adolescents and adults with food allergies with that of a control group. METHODS: A food allergic and a control group were recruited from Portsmouth and the Isle of Wight in the UK. Participants were recruited from a food allergy charity, allergy clinics, a local school and university, and previous research studies. Macro and micronutrient intake data were obtained using a 4-day estimated food diary. Sociodemographic and anthropometric data was collected via a constructed questionnaire. RESULTS: This cross-sectional study included 81 adolescents (48 food allergic and 33 controls) aged 11-18 years and 70 adults aged 19-65 years (23 food allergic and 47 controls). Overall, 19 (22.8%) adolescents and 19 (27.1%) adults took dietary supplements, with no difference according to food allergic status. Adolescents with food allergy had higher intakes of niacin and selenium than adolescents without (P < 0.05). This difference persisted when dietary supplements were removed from the analysis. Adults with food allergies had higher intakes of folate and zinc than those without (P < 0.05); however, this difference did not persist when dietary supplements were removed from the analysis. Across all participants, the intake of several micronutrients was suboptimal. There was no difference in protein or energy intake, or body mass index, according to food allergic status. CONCLUSIONS: The dietary intake of food allergic participants was broadly similar and, in some cases, better than that of control participants. However, suboptimal intakes of several micronutrients were observed across all participants, suggesting poor food choices.

Multimodality treatment for esophageal adenocarcinoma: multi-center propensity-score matched study.

Background: The primary aim of this study was to compare survival from neoadjuvant chemoradiotherapy plus surgery (NCRS) versus neoadjuvant chemotherapy plus surgery (NCS) for the treatment of esophageal or junctional adenocarcinoma. The secondary aims were to compare pathological effects, short-term mortality and morbidity, and to evaluate the effect of lymph node harvest upon survival in both treatment groups. Methods: Data were collected from 10 European centers from 2001 to 2012. Six hundred and eight patients with stage II or III oesophageal or oesophago-gastric junctional adenocarcinoma were included; 301 in the NCRS group and 307 in the NCS group. Propensity score matching and Cox regression analyses were used to compensate for differences in baseline characteristics. Results: NCRS resulted in significant pathological benefits with more ypT0 (26.7% versus 5%; P < 0.001), more ypN0 (63.3% versus 32.1%; P < 0.001), and reduced R1/2 resection margins (7.7% versus 21.8%; P < 0.001). Analysis of short-term outcomes showed no statistically significant differences in 30-day or 90-day mortality, but increased incidence of anastomotic leak (23.1% versus 6.8%; P < 0.001) in NCRS patients. There were no statistically significant differences between the groups in 3-year overall survival (57.9% versus 53.4%; Hazard Ratio (HR)= 0.89, 95%C.I. 0.67-1.17, P = 0.391) nor disease-free survival (52.9% versus 48.9%; HR = 0.90, 95%C.I. 0.69-1.18, P = 0.443). The pattern of recurrence was also similar (P = 0.660). There was a higher lymph node harvest in the NCS group (27 versus 14; P < 0.001), which was significantly associated with a lower recurrence rate and improved disease free survival within the NCS group. Conclusion: The survival differences between NCRS and NCS maybe modest, if present at all, for the treatment of locally advanced esophageal or junctional adenocarcinoma. Future large-scale randomized trials must control and monitor indicators of the quality of surgery, as the extent of lymphadenectomy appears to influence prognosis in patients treated with NCS, from this large multi-center European study.

Developing mobile phone text messages for tobacco risk communication among college students: a mixed methods study.

BACKGROUND: Engaging young adults for the purpose of communicating health risks associated with nicotine and tobacco use can be challenging since they comprise a population heavily targeted with appealing marketing by the evolving tobacco industry. The Food and Drug Administration seeks novel ways to effectively communicate risks to warn about using these products. This paper describes the first step in developing a text messaging program delivered by smartphones that manipulate three messaging characteristics (i.e., depth, framing, and appeal). METHODS: Perceptions of community college students were described after previewing text messages designed to inform about risks of using conventional and new tobacco products. Thirty-one tobacco users and nonusers, aged 18-25 participated in five focus discussions held on two community college campuses. Attendees reviewed prototype messages and contributed feedback about text message structure and content. Qualitative data were coded and analyzed using NVivo Version 10. RESULTS: Most participants were female and two-thirds were ethnic minorities. A variety of conventional and new tobacco products in the past month were used by a third of participants. Three identified domains were derived from the qualitative data. These included perceived risks of using tobacco products, receptivity to message content, and logistical feedback regarding the future message campaign. CONCLUSION: Overall, participants found the messages to be interesting and appropriate. A gap in awareness of the risks of using new tobacco products was revealed. Feedback on the prototype messages was incorporated into message revisions. These findings provided preliminary confirmation that the forthcoming messaging program will be appealing to young adults.

National proficiency-gain curves for minimally invasive gastrointestinal cancer surgery.

BACKGROUND: Minimal access surgery for gastrointestinal cancer has short-term benefits but is associated with a proficiency-gain curve. The aim of this study was to define national proficiency-gain curves for minimal access colorectal and oesophagogastric surgery, and to determine the impact on clinical outcomes. METHODS: All adult patients undergoing minimal access oesophageal, colonic and rectal surgery between 2002 and 2012 were identified from the Hospital Episode Statistics database. Proficiency-gain curves were created using risk-adjusted cumulative sum analysis. Change points were identified, and bootstrapping was performed with 1000 iterations to identify a confidence level. The primary outcome was 30-day mortality; secondary outcomes were 90-day mortality, reintervention, conversion and length of hospital stay. RESULTS: Some 1696, 15 008 and 16 701 minimal access oesophageal, rectal and colonic cancer resections were performed during the study period. The change point in the proficiency-gain curve for 30-day mortality for oesophageal, rectal and colonic surgery was 19 (confidence level 98·4 per cent), 20 (99·2 per cent) and three (99·5 per cent) procedures; the mortality rate fell from 4·0 to 2·0 per cent (relative risk reduction (RRR) 0·50, P = 0·033), from 2·1 to 1·2 per cent (RRR 0·43, P < 0·001) and from 2·4 to 1·8 per cent (RRR 0·25, P = 0·058) respectively. The change point in the proficiency-gain curve for reintervention in oesophageal, rectal and colonic resection was 19 (98·1 per cent), 32 (99·5 per cent) and 26 (99·2 per cent) procedures respectively. There were also significant proficiency-gain curves for 90-day mortality, conversion and length of stay. CONCLUSION: The introduction of minimal access gastrointestinal cancer surgery has been associated with a proficiency-gain curve for mortality and major morbidity at a national level. Unnecessary patient harm should be avoided by appropriate training and monitoring of new surgical techniques.

Clinical validity of consultant technical skills assessment in the English National Training Programme for Laparoscopic Colorectal Surgery.

BACKGROUND: The English National Training Programme for Laparoscopic Colorectal Surgery introduced a validated objective competency assessment tool to accredit surgeons before independent practice. The aim of this study was to determine whether this technical skills assessment predicted clinical outcomes. METHODS: Established consultants, training in laparoscopic colorectal surgery, were asked to submit two operative videos for evaluation by two blinded assessors using the competency assessment tool. A mark of 2·7 or above was considered a pass. Clinical and oncological outcomes were compared above and below this mark, including regression analysis. RESULTS: Eighty-five consultant surgeons submitted 171 videos. Of these, 44 (25·7 per cent) were in the fail group (score less than 2·7). This low scoring group had more postoperative morbidity (25 versus 8·7 per cent; P = 0·005), including surgical complications (18 versus 6·3 per cent; P = 0·020) and fewer lymph nodes harvested (median 13 versus 18; P = 0·004). A score of less than 2·7 was an independent predictor of surgical complication, lymph node yield and distal resection margin clearance. Consultants with higher scores had performed similar numbers of laparoscopic colorectal operations (median 37 versus 40; P = 0·373) but more structured training operations (18 versus 9; P < 0·001). CONCLUSION: An objective technical skills assessment provided a discriminatory tool with which to accredit laparoscopic colorectal surgeons.

Risk of bleeding and adverse outcomes predicted by thromboelastography platelet mapping in patients taking clopidogrel within 7 days of non-cardiac surgery.

BACKGROUND: Patients often fail to stop clopidogrel appropriately before non-cardiac surgery. Thromboelastography platelet mapping (TEG-PM) can be used to measure the percentage adenosine 5'-diphosphate platelet receptor inhibition (ADP-PRI) by clopidogrel in these patients. METHODS: This prospective case-control study investigated the risk of bleeding in patients who had taken clopidogrel within 7 days of scheduled operation. Patients underwent TEG-PM to stratify their bleeding risk. Low-risk (ADP-PRI below 30 per cent) and urgent priority high-risk (ADP-PRI 30 per cent or more) patients proceeded to surgery. The outcomes of these patients were compared with those of matched controls. Regression analysis, with bootstrapping validation, was used to identify independent risk factors for bleeding and an optimal cut-off value of ADP-PRI for cancellation of surgery. RESULTS: From May 2008 to October 2013, 182 patients failed to discontinue clopidogrel. No correlation was observed between duration of clopidogrel omission and percentage ADP-PRI; 112 low-risk and 19 high-risk patients proceeded to surgery. High-risk patients had significantly greater intraoperative packed red blood cell (PRBC) transfusion in comparison with their matched controls, and a strong positive correlation between percentage ADP-PRI and units of intraoperative PRBCs transfused (r = 0·749, 95 per cent confidence interval (c.i.) 0·410 to 0·940; P < 0·001). Percentage ADP-PRI was the only independent risk factor for intraoperative PRBC transfusion (odds ratio 1·07, 95 per cent c.i. 1·02 to 1·13; P = 0·005). CONCLUSION: An objective measure of platelet inhibition with TEG-PM, using an ADP-PRI cut-off of 34 per cent, can be used to prevent unnecessary cancellations, while minimizing patient risk.

Treatment with dextroamphetamine decreases the reacquisition of cocaine self-administration: Consistency across social contexts.

RATIONALE: A return to cocaine use following abstinence frequently occurs in a social context, and the presence of other individuals using cocaine may contribute to the likelihood of use. Previous studies have reported that chronic d-amphetamine treatment decreases cocaine self-administration in laboratory animals and reduces a return to cocaine use following abstinence in humans. OBJECTIVE: The purpose of this study was to examine the effects of chronic d-amphetamine treatment on the reacquisition of cocaine use in rats self-administering cocaine in different social contexts. METHODS: Male and female rats were implanted with intravenous catheters and trained to self-administer cocaine during daily 6-hr sessions. After 14 days, cocaine self-administration was extinguished by substituting saline for the cocaine stimulus. At this time, rats were randomized to receive chronic treatment with either d-amphetamine or saline. After 9 days of extinction, cocaine was again made available during daily 6-hr sessions. At this time, rats were further randomized into three social conditions: (1) rats continued self-administering cocaine in isolation, (2) rats self-administered cocaine in the presence of a same-sex partner that also self-administered cocaine, or (3) rats self-administered cocaine in the presence of a same-sex partner that did not have access to cocaine. Daily treatment with d-amphetamine or saline continued for the duration of reacquisition testing. RESULTS: Chronic treatment with d-amphetamine decreased cocaine intake during reacquisition, but these effects were not influenced by the social context. No sex differences were observed. CONCLUSION: These data support previous studies reporting that d-amphetamine decreases cocaine intake and demonstrate its efficacy across social contexts.

Increased iron uptake by splenic hematopoietic stem cells promotes TET2-dependent erythroid regeneration.

Hematopoietic stem cells (HSCs) are capable of regenerating the blood system, but the instructive cues that direct HSCs to regenerate particular lineages lost to the injury remain elusive. Here, we show that iron is increasingly taken up by HSCs during anemia and induces erythroid gene expression and regeneration in a Tet2-dependent manner. Lineage tracing of HSCs reveals that HSCs respond to hemolytic anemia by increasing erythroid output. The number of HSCs in the spleen, but not bone marrow, increases upon anemia and these HSCs exhibit enhanced proliferation, erythroid differentiation, iron uptake, and TET2 protein expression. Increased iron in HSCs promotes DNA demethylation and expression of erythroid genes. Suppressing iron uptake or TET2 expression impairs erythroid genes expression and erythroid differentiation of HSCs; iron supplementation, however, augments these processes. These results establish that the physiological level of iron taken up by HSCs has an instructive role in promoting erythroid-biased differentiation of HSCs.

Serine/arginine-rich splicing factor 7 promotes the type I interferon response by activating Irf7 transcription.

Tight regulation of macrophage immune gene expression is required to fight infection without risking harmful inflammation. The contribution of RNA-binding proteins (RBPs) to shaping the macrophage response to pathogens remains poorly understood. Transcriptomic analysis reveals that a member of the serine/arginine-rich (SR) family of mRNA processing factors, SRSF7, is required for optimal expression of a cohort of interferon-stimulated genes in macrophages. Using genetic and biochemical assays, we discover that in addition to its canonical role in regulating alternative splicing, SRSF7 drives transcription of interferon regulatory transcription factor 7 (IRF7) to promote antiviral immunity. At the Irf7 promoter, SRSF7 maximizes STAT1 transcription factor binding and RNA polymerase II elongation via cooperation with the H4K20me1 histone methyltransferase KMT5a (SET8). These studies define a role for an SR protein in activating transcription and reveal an RBP-chromatin network that orchestrates macrophage antiviral gene expression.

Vitamin D insufficiency and serum levels related to the incidence and stage of cutaneous melanoma: a systematic review and meta-analysis.

Cutaneous melanoma (CM) is the deadliest skin cancer, and vitamin D insufficiency has been suggested as a risk factor. We evaluated the relationship between both vitamin D insufficiency and 25-hydroxy vitamin D levels with the incidence and stage of CM. Five databases were searched from inception until 11 July 2022. Inclusion criteria were cohort and case-control studies that reported mean 25-hydroxy vitamin D levels or the presence of vitamin D insufficiency in CM patients and compared with healthy controls; or those that reported vitamin D insufficiency and Breslow tumor depth or the development of metastasis in CM. Fourteen studies were included in the analysis. Statistically significant relationships were found between vitamin D level <20 ng/dl and incidence of CM [pooled RR 1.45, 95% confidence interval (CI) 1.04-2.02]; lower mean vitamin D level and Breslow depth >1 mm (SMD 0.19, 95% CI 0.11-0.28); and vitamin D level >20 ng/dl and Breslow depth <1 mm (pooled RR 0.69, 95% CI 0.58-0.82). Statistical significance was not found in the relationships between vitamin D levels and the presence of metastasis (pooled SMD -0.13, 95% CI, -0.38 to 0.12); or mean vitamin D level and the incidence of CM (pooled SMD -0.39, 95% CI, -0.80 to 0.01). We identified an association of increased incidence of CM and vitamin D insufficiency, as well as less favorable Breslow tumor depth with lower levels of vitamin D and the presence of vitamin D insufficiency.