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IMPORTANCE: Civilian trauma centers have revived interest in whole-blood (WB) resuscitation for patients with life-threatening bleeding. However, there remains insufficient evidence that the timing of WB transfusion when given as an adjunct to a massive transfusion protocol (MTP) is associated with a difference in patient survival outcome. OBJECTIVE: To evaluate whether earlier timing of first WB transfusion is associated with improved survival at 24 hours and 30 days for adult trauma patients presenting with severe hemorrhage. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used the American College of Surgeons Trauma Quality Improvement Program databank from January 1, 2019, to December 31, 2020, for adult patients presenting to US and Canadian adult civilian level 1 and 2 trauma centers with systolic blood pressure less than 90 mm Hg, with shock index greater than 1, and requiring MTP who received a WB transfusion within the first 24 hours of emergency department (ED) arrival. Patients with burns, prehospital cardiac arrest, deaths within 1 hour of ED arrival, and interfacility transfers were excluded. Data were analyzed from January 3 to October 2, 2023. EXPOSURE: Patients who received WB as an adjunct to MTP (earlier) compared with patients who had yet to receive WB as part of MTP (later) at any given time point within 24 hours of ED arrival. MAIN OUTCOMES AND MEASURES: Primary outcomes were survival at 24 hours and 30 days. RESULTS: A total of 1394 patients met the inclusion criteria (1155 male [83%]; median age, 39 years [IQR, 25-51 years]). The study cohort included profoundly injured patients (median Injury Severity Score, 27 [IQR, 17-35]). A survival curve demonstrated a difference in survival within 1 hour of ED presentation and WB transfusion. Whole blood transfusion as an adjunct to MTP given earlier compared with later at each time point was associated with improved survival at 24 hours (adjusted hazard ratio, 0.40; 95% CI, 0.22-0.73; P = .003). Similarly, the survival benefit of earlier WB transfusion remained present at 30 days (adjusted hazard ratio, 0.32; 95% CI, 0.22-0.45; P < .001). CONCLUSIONS AND RELEVANCE: In this cohort study, receipt of a WB transfusion earlier at any time point within the first 24 hours of ED arrival was associated with improved survival in patients presenting with severe hemorrhage. The survival benefit was noted shortly after transfusion. The findings of this study are clinically important as the earlier timing of WB administration may offer a survival advantage in actively hemorrhaging patients requiring MTP.

IMPORTANCE: Spanish-speaking participants are underrepresented in clinical trials, limiting study generalizability and contributing to ongoing health inequity. The Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial intentionally included Spanish-speaking participants. OBJECTIVE: To describe trial participation and compare clinical and patient-reported outcomes among Spanish-speaking and English-speaking participants with acute appendicitis randomized to antibiotics. DESIGN, SETTING, AND PARTICIPANTS: This study is a secondary analysis of the CODA trial, a pragmatic randomized trial comparing antibiotic therapy with appendectomy in adult patients with imaging-confirmed appendicitis enrolled at 25 centers across the US from May 1, 2016, to February 28, 2020. The trial was conducted in English and Spanish. All 776 participants randomized to antibiotics are included in this analysis. The data were analyzed from November 15, 2021, through August 24, 2022. INTERVENTION: Randomization to a 10-day course of antibiotics or appendectomy. MAIN OUTCOMES AND MEASURES: Trial participation, European Quality of Life–5 Dimensions (EQ-5D) questionnaire scores (higher scores indicating a better health status), rate of appendectomy, treatment satisfaction, decisional regret, and days of work missed. Outcomes are also reported for a subset of participants that were recruited from the 5 sites with a large proportion of Spanish-speaking participants. RESULTS: Among eligible patients 476 of 1050 Spanish speakers (45%) and 1076 of 3982 of English speakers (27%) consented, comprising the 1552 participants who underwent 1:1 randomization (mean age, 38.0 years; 976 male [63%]). Of the 776 participants randomized to antibiotics, 238 were Spanish speaking (31%). Among Spanish speakers randomized to antibiotics, the rate of appendectomy was 22% (95% CI, 17%-28%) at 30 days and 45% (95% CI, 38%-52%) at 1 year, while in English speakers, these rates were 20% (95% CI, 16%-23%) at 30 days and 42% (95% CI 38%-47%) at 1 year. Mean EQ-5D scores were 0.93 (95% CI, 0.92-0.95) among Spanish speakers and 0.92 (95% CI, 0.91-0.93) among English speakers. Symptom resolution at 30 days was reported by 68% (95% CI, 61%-74%) of Spanish speakers and 69% (95% CI, 64%-73%) of English speakers. Spanish speakers missed 6.69 (95% CI, 5.51-7.87) days of work on average, while English speakers missed 3.76 (95% CI, 3.20-4.32) days. Presentation to the emergency department or urgent care, hospitalization, treatment dissatisfaction, and decisional regret were low for both groups. CONCLUSIONS AND RELEVANCE: A high proportion of Spanish speakers participated in the CODA trial. Clinical and most patient-reported outcomes were similar for English- and Spanish-speaking participants treated with antibiotics. Spanish speakers reported more days of missed work. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02800785

Among female victims of violence, pre-existing mental illness is associated with increased risk of violent reinjury and hospital reencounter. Improved efforts at addressing mental illness in trauma patients is critical to ongoing prevention efforts to reduce violent reinjury.

IMPORTANCE: A patient’s belief in the likely success of a treatment may influence outcomes, but this has been understudied in surgical trials. OBJECTIVE: To examine the association between patients’ baseline beliefs about the likelihood of treatment success with outcomes of antibiotics for appendicitis in the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial. DESIGN, SETTING, AND PARTICIPANTS: This was a secondary analysis of the CODA randomized clinical trial. Participants from 25 US medical centers were enrolled between May 3, 2016, and February 5, 2020. Included in the analysis were participants with appendicitis who were randomly assigned to receive antibiotics in the CODA trial. After informed consent but before randomization, participants who were assigned to receive antibiotics responded to a baseline survey including a question about how successful they believed antibiotics could be in treating their appendicitis. INTERVENTIONS: Participants were categorized based on baseline survey responses into 1 of 3 belief groups: unsuccessful/unsure, intermediate, and completely successful. MAIN OUTCOMES AND MEASURES: Three outcomes were assigned at 30 days: (1) appendectomy, (2) high decisional regret or dissatisfaction with treatment, and (3) persistent signs and symptoms (abdominal pain, tenderness, fever, or chills). Outcomes were compared across groups using adjusted risk differences (aRDs), with propensity score adjustment for sociodemographic and clinical factors. RESULTS: Of the 776 study participants who were assigned antibiotic treatment in CODA, a total of 425 (mean [SD] age, 38.5 [13.6] years; 277 male [65%]) completed the baseline belief survey before knowing their treatment assignment. Baseline beliefs were as follows: 22% of participants (92 of 415) had an unsuccessful/unsure response, 51% (212 of 415) had an intermediate response, and 27% (111 of 415) had a completely successful response. Compared with the unsuccessful/unsure group, those who believed antibiotics could be completely successful had a 13–percentage point lower risk of appendectomy (aRD, −13.49; 95% CI, −24.57 to −2.40). The aRD between those with intermediate vs unsuccessful/unsure beliefs was −5.68 (95% CI, −16.57 to 5.20). Compared with the unsuccessful/unsure group, those with intermediate beliefs had a lower risk of persistent signs and symptoms (aRD, −15.72; 95% CI, −29.71 to −1.72), with directionally similar results for the completely successful group (aRD, −15.14; 95% CI, −30.56 to 0.28). CONCLUSIONS AND RELEVANCE: Positive patient beliefs about the likely success of antibiotics for appendicitis were associated with a lower risk of appendectomy and with resolution of signs and symptoms by 30 days. Pathways relating beliefs to outcomes and the potential modifiability of beliefs to improve outcomes merit further investigation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02800785

IMPORTANCE: For adults with appendicitis, several randomized clinical trials have demonstrated that antibiotics are an effective alternative to appendectomy. However, it remains unknown how the characteristics of patients in such trials compare with those of patients who select their treatment and whether outcomes differ. OBJECTIVE: To compare participants in the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) randomized clinical trial (RCT) with a parallel cohort study of participants who declined randomization and self-selected treatment. DESIGN, SETTING, AND PARTICIPANTS: The CODA trial was conducted in 25 US medical centers. Participants were enrolled between May 3, 2016, and February 5, 2020; all participants were eligible for at least 1 year of follow-up, with all follow-up ending in 2021. The randomized cohort included 1094 adults with appendicitis; the self-selection cohort included patients who declined participation in the randomized group, of whom 253 selected appendectomy and 257 selected antibiotics. In this secondary analysis, characteristics and outcomes in both self-selection and randomized cohorts are described with an exploratory analysis of cohort status and receipt of appendectomy. INTERVENTIONS: Appendectomy vs antibiotics. MAIN OUTCOMES AND MEASURES: Characteristics among participants randomized to either appendectomy or antibiotics were compared with those of participants who selected their own treatment. RESULTS: Clinical characteristics were similar across the self-selection cohort (510 patients; mean age, 35.8 years [95% CI, 34.5-37.1]; 218 female [43%; 95% CI, 39%-47%]) and the randomized group (1094 patients; mean age, 38.2 years [95% CI, 37.4-39.0]; 386 female [35%; 95% CI, 33%-38%]). Compared with the randomized group, those in the self-selection cohort were less often Spanish speaking (n = 99 [19%; 95% CI, 16%-23%] vs n = 336 [31%; 95% CI, 28%-34%]), reported more formal education (some college or more, n = 355 [72%; 95% CI, 68%-76%] vs n = 674 [63%; 95% CI, 60%-65%]), and more often had commercial insurance (n = 259 [53%; 95% CI, 48%-57%] vs n = 486 [45%; 95% CI, 42%-48%]). Most outcomes were similar between the self-selection and randomized cohorts. The number of patients undergoing appendectomy by 30 days was 38 (15.3%; 95% CI, 10.7%-19.7%) among those selecting antibiotics and 155 (19.2%; 95% CI, 15.9%-22.5%) in those who were randomized to antibiotics (difference, 3.9%; 95% CI, −1.7% to 9.5%). Differences in the rate of appendectomy were primarily observed in the non-appendicolith subgroup. CONCLUSIONS AND RELEVANCE: This secondary analysis of the CODA RCT found substantially similar outcomes across the randomized and self-selection cohorts, suggesting that the randomized trial results are generalizable to the community at large. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02800785

IMPORTANCE: Social determinants of health have been shown to be key drivers of disparities in access to surgical care and surgical outcomes. Though the concept of social responsibility has received growing attention in the medical field, little has been published contextualizing social responsibility in surgery. In this narrative review, we define social responsibility as it relates to surgery, explore the duty of surgeons to society, and provide examples of social factors associated with adverse surgical outcomes and how they can be mitigated. OBSERVATIONS: The concept of social responsibility in surgery has deep roots in medical codes of ethics and evolved alongside changing views on human rights and the role of social factors in disease. The ethical duty of surgeons to society is based on the ethical principles of benevolence and justice and is grounded within the framework of the social contract. Surgeons have a responsibility to understand how factors such as patient demographics, the social environment, clinician awareness, and the health care system are associated with inequitable patient outcomes. Through education, we can empower surgeons to advocate for their patients, address the causes and consequences of surgical disparities, and incorporate social responsibility into their daily practice. CONCLUSIONS AND RELEVANCE: One of the greatest challenges in the field of surgery is ensuring that surgical care is provided in an equitable and sustainable way. Surgeons have a duty to understand the factors that lead to health care disparities and use their knowledge, skills, and privileged position to address these issues at the individual and societal level.

Supplemental digital content is available in the text.

@PatrickHeindel; @ajordoobadi; @ElmohebM; @garveysha; @AnnieHeyman; @SESanchezMD; @hayfarani; @juanph19; @dnehra_trauma; @CSPH_BWH; @BrighamWomens, @BrighamSurgery; @BMCSurgery; @The_BMC; @MassGeneralNews; @MGHSurgery; @UWSurgerySupplemental digital content is available in the text.

I think it's good to share the successes but also to share the failures and own them so the resident sees that you, too, fail at things, that you have [...]

Many medical students hold negative perceptions about the surgical field that deter them from pursuing surgical training. We hypothesize that these perceptions can be sustainably changed with preclinical surgical education.

There is very limited comprehensive information on disparate outcomes of black and white patients with COVID-19 infection. Reports from cities and states have suggested a discordant impact on black Americans, but no nationwide study has yet been performed. We sought to understand the differential outcomes for black and white Americans infected with COVID-19.

IMPORTANCE: The receipt of surgery in freestanding ambulatory surgery centers (ASCs) is often less costly compared with surgery in hospital-based outpatient departments. Although increasing numbers of surgical procedures are now being performed in freestanding ASCs, questions remain regarding the existence of disparities among patients receiving care at ASCs. OBJECTIVE: To examine the association of patient race, health insurance status, and household income with the location (ASC vs hospital-based outpatient department) of ambulatory surgery. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the State Ambulatory Surgery and Services Databases of the Healthcare Cost and Utilization Project to perform a secondary analysis of patients who received ambulatory surgery in New York and Florida between 2011 and 2013. Patients aged 18 to 89 years who underwent 12 different types of ambulatory surgical procedures were included. Data were analyzed from December 2018 to June 2019. MAIN OUTCOMES AND MEASURES: Receipt of surgery at a freestanding ASC and 30-day unplanned hospital visits after ambulatory surgery. RESULTS: A total of 5.6 million patients in New York (57.4% female; 68.9% aged ≥50 years; and 62.5% White) and 7.5 million patients in Florida (57.3% female; 77.4% aged ≥50 years; 74.3% White) who received ambulatory surgery were included in the analysis. After adjusting for age, comorbidities, health insurance status, household income, location of surgery, and type of surgical procedure, the likelihood of receiving ambulatory surgery at a freestanding ASC was significantly lower among Black patients (adjusted odds ratio [aOR], 0.82; 95% CI, 0.81-0.83; P < .001) and Hispanic patients (aOR, 0.78; 95% CI, 0.77-0.79; P < .001) compared with White patients in New York. This likelihood was also lower among Black patients (aOR, 0.65; 95% CI, 0.65-0.66; P < .001) compared with White patients in Florida. Public health insurance coverage was associated with a significantly lower likelihood of receiving ambulatory surgery at freestanding ASCs in both New York and Florida, particularly among patients with Medicaid (in New York, aOR, 0.22; 95% CI, 0.22-0.22; P < .001; in Florida, aOR, 0.40; 95% CI, 0.40-0.41; P < .001) and Medicare (in New York, aOR, 0.46; 95% CI, 0.46-0.46; P < .001; in Florida, aOR, 0.67; 95% CI, 0.66-0.67; P < .001). CONCLUSIONS AND RELEVANCE: Differences in the use of freestanding ASCs were found among Black patients and patients with public health insurance. Further exploration of the factors underlying these differences will be important to ensure that all populations have access to the increasing number of freestanding ASCs.

IMPORTANCE: Some studies based on proportions of patients with perforated appendicitis (PA) among all patients with acute appendicitis (AA) have found an association between socioeconomic status (SES) and risk of perforation. A potential limitation is their use of proportions, which assumes that incidence of AA is evenly distributed across populations at risk. This assumption may be invalid, and SES may have a more complex association with both AA and PA. OBJECTIVE: To generate population-based incidences of AA and PA and to examine geographic patterns of incidence alongside geographic patterns of SES. DESIGN, SETTING, AND PARTICIPANTS: Retrospective study of data from Washington’s Comprehensive Hospital Abstract Reporting System and the 2010 US census. Geographic methods were used to identify patterns of age- and sex-standardized incidence in Washington State between 2008 and 2012. The study included all patients discharged with International Classification of Diseases, Ninth Revision codes for AA or PA. Data were analyzed between November 2016 and December 2018. EXPOSURES: Location of primary residence. MAIN OUTCOMES AND MEASURES: Age- and sex-standardized incidence for AA and PA was generated for each census tract (CT). Global spatial autocorrelation was examined using Moran index (0.0 = completely random incidence; 1.0 = fully dependent on location). Clusters of low-incidence CTs (cold spots) and high-incidence CTs (hot spots) were identified for AA. Census-based SES data were aggregated for hot spots and cold spots and then compared. RESULTS: Statewide, over the 5-year study period, there were 35 730 patients with AA (including 9780 cases of PA), of whom 16 574 were women (46.4%). Median age of the cohort was 29 years (IQR, 16-48 years). Statewide incidence of AA and PA was 106 and 29 per 100 000 person-years (PY), respectively. Crude incidence was higher within the male population and peaked at age 10 to 19 years. Age- and sex-standardized incidence of AA demonstrated significant positive spatial autocorrelation (Moran index, 0.30; P < .001), but autocorrelation for PA was only half as strong (0.16; P < .001). Median incidence of AA was 118.1 per 100 000 PY among hot spots vs 86.2 per 100 000 PY among cold spots (P < .001). Socioeconomic status was higher in cold spots vs hot spots: mean proportion of college-educated adults was 56% vs 26% (P < .001), and mean per capita income was $44 691 vs $30 027 (P < .001). CONCLUSIONS AND RELEVANCE: Age- and sex-standardized incidence of appendicitis is not randomly distributed across geographic subunits, and geographic clustering of AA is twice as strong as PA. Socioeconomic advantages, such as higher income and secondary education, are strongly associated with lower incidence of AA. These findings challenge conventional views that AA occurs randomly and has no predisposing characteristics beyond age/sex. Socioeconomic status, and likely other geographically circumscribed factors, are associated with incidence of AA.

•Gaps persist in diversity, equity, and inclusion (DEI) efforts in surgery.•Dedicated DEI committees are uncommon in surgical departments.•Joint DEI efforts between trainees and faculty are needed.•A 3-pillar model used to address social support, education, advocacy, and research.

We propose a reduced dynamical system describing the coupled evolution of fluid flow and magnetic field at the top of the Earth's core between the years 1900 and 2014. The flow evolution is modeled with a first‐order autoregressive process, while the magnetic field obeys the classical frozen flux equation. An ensemble Kalman filter algorithm serves to constrain the dynamics with the geomagnetic field and its secular variation given by the COV‐OBS.x1 model. Using a large ensemble with 40,000 members provides meaningful statistics including reliable error estimates. The model highlights two distinct flow scales. Slowly varying large‐scale elements include the already documented eccentric gyre. Localized short‐lived structures include distinctly ageostophic features like the high‐latitude polar jet on the Northern Hemisphere. Comparisons with independent observations of the length‐of‐day variations not only validate the flow estimates but also suggest an acceleration of the geostrophic flows over the last century. Hindcasting tests show that our model outperforms simpler predictions bases (linear extrapolation and stationary flow). The predictability limit, of about 2,000 years for the magnetic dipole component, is mostly determined by the random fast varying dynamics of the flow and much less by the geomagnetic data quality or lack of small‐scale information. The model we propose permits to estimate the reliability of certain patterns the flow at the Earth's core‐mantle boundary is exhibitingThe model we present enables to predict the evolution of the geomagnetic field and to accurately estimate prediction errorsWe show that the discrepancies between the predicted trend in length of day and the observed one can be explained by our flow model

This qualitative analysis sought to explore factors that influenced parent/guardian intentions to vaccinate their children against SARS-CoV-2 in San Francisco, California, USA in order to inform San Francisco Department of Public Health’s (SFDPH) youth vaccine rollout program. 30-minute, semi-structured telephone interviews were conducted with parents and guardians in either Spanish or English. Respondents shared their perspectives on vaccinating their children against SARS-CoV-2. Interviews were conducted over the telephone and recorded on Zoom. Participants (n = 40) were parents/guardians responding on behalf of their adolescent children (age 13+) and parents/guardians identified from the SFDPH COVID-19 testing database who tested for SARS-CoV-2 within the last 2 weeks. Interviews were conducted, audio recorded, transcribed, translated into English as appropriate, and rapidly analyzed in REDCap according to matrix analysis methodology to develop parent study themes. Perspectives on child vaccination were then explored through thematic analysis. Three themes were identified from the thematic analysis: (1) parental desires for children to return to school safely, (2) unclear messaging and information on COVID-19 prevention and vaccination, and (3) consideration of child’s desires or opinions on receiving the vaccine. This study highlights specific factors influencing parent/guardian decisions on whether to vaccinate their children against SARS-CoV-2. The analysis also illustrates a potential role for children to play in influencing household vaccine decision-making.

Recent advances in medical and surgical management have led to improved long-term survival in children with intestinal failure. Yet, limited data exist on their neurodevelopmental and cognitive outcomes. The aim of the present study was to measure neurodevelopmental outcomes in children with intestinal failure. Children enrolled in a regional intestinal failure program underwent prospective neurodevelopmental and psychometric evaluation using a validated scoring tool. Cognitive impairment was defined as a mental developmental index <70. Neurodevelopmental impairment was defined as cerebral palsy, visual or hearing impairment, or cognitive impairment. Univariate analyses were performed using the Wilcoxon rank-sum test. Data are presented as median (range). Fifteen children with a remnant bowel length of 18 (5–85) cm were studied at age 17 (12–67) months. Thirteen patients remained dependent on parenteral nutrition. Twelve (80%) subjects scored within the normal range on cognitive testing. Each child with cognitive impairment was noted to have additional risk factors independent of intestinal failure including cardiac arrest and extreme prematurity. On univariate analysis, cognitive impairment was associated with longer inpatient hospital stays, increased number of surgical procedures, and prematurity (P?

IMPORTANCE: Use of antibiotics for the treatment of appendicitis is safe and has been found to be noninferior to appendectomy based on self-reported health status at 30 days. Identifying patient characteristics associated with a greater likelihood of appendectomy within 30 days in those who initiate antibiotics could support more individualized decision-making. OBJECTIVE: To assess patient factors associated with undergoing appendectomy within 30 days of initiating antibiotics for appendicitis. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study using data from the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) randomized clinical trial, characteristics among patients who initiated antibiotics were compared between those who did and did not undergo appendectomy within 30 days. The study was conducted at 25 US medical centers; participants were enrolled between May 3, 2016, and February 5, 2020. A total of 1552 participants with acute appendicitis were randomized to antibiotics (776 participants) or appendectomy (776 participants). Data were analyzed from September 2020 to July 2021. EXPOSURES: Appendectomy vs antibiotics. MAIN OUTCOMES AND MEASURES: Conditional logistic regression models were fit to estimate associations between specific patient factors and the odds of undergoing appendectomy within 30 days after initiating antibiotics. A sensitivity analysis was performed excluding participants who underwent appendectomy within 30 days for nonclinical reasons. RESULTS: Of 776 participants initiating antibiotics (mean [SD] age, 38.3 [13.4] years; 286 [37%] women and 490 [63%] men), 735 participants had 30-day outcomes, including 154 participants (21%) who underwent appendectomy within 30 days. After adjustment for other factors, female sex (odds ratio [OR], 1.53; 95% CI, 1.01-2.31), radiographic finding of wider appendiceal diameter (OR per 1-mm increase, 1.09; 95% CI, 1.00-1.18), and presence of appendicolith (OR, 1.99; 95% CI, 1.28-3.10) were associated with increased odds of undergoing appendectomy within 30 days. Characteristics that are often associated with increased risk of complications (eg, advanced age, comorbid conditions) and those clinicians often use to describe appendicitis severity (eg, fever: OR, 1.28; 95% CI, 0.82-1.98) were not associated with odds of 30-day appendectomy. The sensitivity analysis limited to appendectomies performed for clinical reasons provided similar results regarding appendicolith (adjusted OR, 2.41; 95% CI, 1.49-3.91). CONCLUSIONS AND RELEVANCE: This cohort study found that presence of an appendicolith was associated with a nearly 2-fold increased risk of undergoing appendectomy within 30 days of initiating antibiotics. Clinical characteristics often used to describe severity of appendicitis were not associated with odds of 30-day appendectomy. This information may help guide more individualized decision-making for people with appendicitis.

Survival of infants with intestinal failure (IF) has increased in the past decade; however, data on their health-related quality of life (HRQOL) are lacking. We hypothesized that HRQOL would be lower among children with IF compared with that of healthy children.

Recent data have demonstrated improved survival in children with intestinal failure. We hypothesized that this trend would also be observed in children with ultrashort bowel syndrome.

Alternative splicing (AS) allows the production of multiple mRNA variants from a single gene, which contributes to increase the complexity of the proteome. There is evidence that AS is regulated not only by auxiliary splicing factors, but also by components of the core spliceosomal machinery, as well as through epigenetic modifications. However, to what extent these different mechanisms contribute to the regulation of AS in response to endogenous or environmental stimuli is still unclear. Circadian clocks allow organisms to adjust physiological processes to daily changes in environmental conditions. Here we review recent evidence linking circadian clock and AS, and discuss the role of Protein Arginine Methyltransferase 5 (PRMT5) in these processes. We propose that the interactions between daily oscillations in AS and circadian rhythms in the expression of splicing factors and epigenetic regulators offer a great opportunity to dissect the contribution of these mechanisms to the regulation of AS in a physiologically relevant context.

Pancreatic cancer is one of the deadliest malignancies, costing the lives of more than 30,000 patients every year. It often presents in advanced stages not amenable to surgery. Gemcitabine is currently considered to be the standard of care for the treatment of advanced pancreatic cancer. Combination of gemcitabine with certain other cytotoxic drugs, including cisplatin, oxaliplatin, capecitabine, and 5-fluorouracil have been undertaken, but all have failed to provide substantial increases in survival benefit. However, neoadjuvant algorithms and targeted therapies, including combinations of gemcitabine with erlotinib suggest more promising results. New targeted therapies in combination with gemcitabine are currently in Phase II and III trials, possibly implicating a primary position for them in future treatment. In this paper we present an overview of the current treatment options for the different presenting stages of pancreatic cancer, including adjuvant, neoadjuvant, and targeted therapies, and attempt to provide a comprehensive analysis of the disparate research indicated on this front.

The IGRF offers an important incentive for testing algorithms predicting the Earth’s magnetic field changes, known as secular variation (SV), in a 5-year range. Here, we present a SV candidate model for the 13th IGRF that stems from a sequential ensemble data assimilation approach (EnKF). The ensemble consists of a number of parallel-running 3D-dynamo simulations. The assimilated data are geomagnetic field snapshots covering the years 1840 to 2000 from the COV-OBS.x1 model and for 2001 to 2020 from the Kalmag model. A spectral covariance localization method, considering the couplings between spherical harmonics of the same equatorial symmetry and same azimuthal wave number, allows decreasing the ensemble size to about a 100 while maintaining the stability of the assimilation. The quality of 5-year predictions is tested for the past two decades. These tests show that the assimilation scheme is able to reconstruct the overall SV evolution. They also suggest that a better 5-year forecast is obtained keeping the SV constant compared to the dynamically evolving SV. However, the quality of the dynamical forecast steadily improves over the full assimilation window (180 years). We therefore propose the instantaneous SV estimate for 2020 from our assimilation as a candidate model for the IGRF-13. The ensemble approach provides uncertainty estimates, which closely match the residual differences with respect to the IGRF-13. Longer term predictions for the evolution of the main magnetic field features over a 50-year range are also presented. We observe the further decrease of the axial dipole at a mean rate of 8 nT/year as well as a deepening and broadening of the South Atlantic Anomaly. The magnetic dip poles are seen to approach an eccentric dipole configuration.

We present a new model of the geomagnetic field spanning the last 20 years and called Kalmag. Deriving from the assimilation of CHAMP and Swarm vector field measurements, it separates the different contributions to the observable field through parameterized prior covariance matrices. To make the inverse problem numerically feasible, it has been sequentialized in time through the combination of a Kalman filter and a smoothing algorithm. The model provides reliable estimates of past, present and future mean fields and associated uncertainties. The version presented here is an update of our IGRF candidates; the amount of assimilated data has been doubled and the considered time window has been extended from [2000.5, 2019.74] to [2000.5, 2020.33].

Background Young children with intestinal failure are at risk for complications from rotavirus gastroenteritis. To date, the safety and immunogenicity of rotavirus vaccines in these children are not known. We hypothesized that rotavirus vaccination would be safe and confer immunity to infants with intestinal failure and a history of abdominal surgery. Methods The study population consisted of infants with early intestinal failure who required abdominal surgery and parenteral nutrition for necrotizing enterocolitis, gastroschisis, jejunoileal atresia, or meconium peritonitis. Subjects received a rotavirus vaccine series at the appropriate age. Safety assessments were performed for the first 5 days after each vaccine dose. Viral stool shedding and serum rotavirus antigen were measured at multiple time points after each dose of the vaccine. A 3-fold increase in rotavirus immunoglobulin A titer at study completion defined seroconversion. Results Fifteen infants were enrolled and 14 infants completed the study protocol. Mild diarrhea, emesis, and fever were noted after vaccination in 33%, 40%, and 7% of subjects, respectively. No subject experienced postvaccine intussusception, viremia, dehydration, or required alterations in nutritional care. Viral stool shedding was noted in 47%, but only 1 child shed virus beyond 2 weeks postvaccination. All subjects who were not considered immune at baseline developed seroconversion to rotavirus after vaccination. Conclusions In infants with intestinal failure, rotavirus vaccination appears to be safe and immunogenic. We found no evidence for altered viral shedding in this population. Given the profound consequences associated with rotavirus infection and potential benefits of rotavirus vaccine in this cohort, multicenter studies focusing on vaccine efficacy are warranted.