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BACKGROUND Merkel cell polyomavirus (MCPyV) is associated with the development of Merkel cell carcinoma (MCC). Antibody (MCPyV-Ab) titers may have prognostic implications. This study evaluated the impact of the presence or absence of MCPyV-Ab on the 2-year overall survival (OS) and disease-free survival (DFS) of MCC patients. METHODS This single-center, IRB-approved, retrospective cohort study evaluated 51 adult patients with MCC from 2014 to 2021 using a prospectively maintained database. Patients were compared by MCPyV-Ab status, and Kaplan-Meier analysis was used to evaluate 2-year OS and DFS. RESULTS Of the 51 patients, 13 (25.4%) were seropositive, 41 (80.4%) underwent wide excision, 40 (80.0%) received radiotherapy, and 43 (84.3%) received multimodal therapy. The median follow-up period was 15.5 months (range 1-69.5 months). The median 2-year OS of the entire cohort was not reached. The median 2-year OS was not reached for either the seronegative or the seropositive patients. The difference in 2-year OS between the groups was not statistically significant (p = 0.37). Eight patients, all seronegative, were never rendered disease-free and were removed from recurrence analysis. The seropositive patients experienced no recurrences. Of the 30 seronegative patients, 9 (30.0%) experienced recurrence. The median 2-year DFS of the entire cohort was not reached. The median 2-year DFS of the seronegative group was 22.2 months. The 2-year DFS was not reached for the seropositive cohort. Seropositivity conferred a significantly better 2-year DFS than seronegativity (p = 0.04). CONCLUSION The MCPyV-Ab seropositive patients demonstrated improved 2-year DFS. The seropositive patients showed a strong trend toward improved 2-year OS, although the difference not statistically significant. This study substantiated the value of MCPyV-Ab assessment for MCC.

Background & Aims The rising incidence of inflammatory bowel disease in regions undergoing Westernization has coincided with the increase in ultra-processed food (UPF) consumption over the past few decades. We aimed to examine the association between consumption of UPFs and the risk of Crohn's disease (CD) and ulcerative colitis (UC). Methods We performed a prospective cohort study of 3 nationwide cohorts of health professionals in the United States—the Nurses' Health Study (1986–2014), the Nurses' Health Study II (1991–2017), and the Health Professionals Follow-up Study (1986–2012). We employed Cox proportional hazards models with adjustment for confounders to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for CD and UC according to self-reported consumption of UPFs. Results The study included 245,112 participants. Over 5,468,444 person-years of follow-up, we documented 369 incident cases of CD and 488 incident cases of UC. The median age at diagnosis was 56 years (range, 29–85 years). Compared with participants in the lowest quartile of simple updated UPF consumption, those in the highest quartile had a significantly increased risk of CD (HR, 1.70; 95% CI, 1.23–2.35; Ptrend = .0008). Among different UPF subgroups, ultra-processed breads and breakfast foods; frozen or shelf-stable ready-to-eat/heat meals; and sauces, cheeses, spreads, and gravies showed the strongest positive associations with CD risk (HR per 1 standard deviation increase in intake, 1.18 [95% CI, 1.07–1.29], 1.11 [95% CI, 1.01–1.22], and 1.14 [95% CI, 1.02–1.27], respectively). There was no consistent association between UPF intake and UC risk. Conclusions Higher UPF intake was associated with an increased risk of incident CD. Further studies are needed to identify specific contributory dietary components.

Nonspecific acute pouchitis is common in patients with ulcerative colitis who undergo IPAA, but there is disagreement about the rate at which this occurs in patients with familial adenomatous polyposis.This study aimed to define the rate at which nonspecific acute pouchitis occurs in patients with familial adenomatous polyposis.This study was conducted at a hereditary colorectal cancer center in a large academic medical center.This is a retrospective cohort study using prospectively gathered data.Patients with familial adenomatous polyposis who have had IPAA were included.Symptoms, pouchoscopy and pouch radiography, and pouch biopsy were evaluated.The primary outcomes measured were the presence of nonspecific acute pouchitis and the alternative diagnosis of pouch dysfunction.There were 250 patients with familial adenomatous polyposis who had undergone IPAA; 38 (15.2%) had been labeled as having "pouchitis": 23 men and 15 women. Median age was 55 years (range, 18-90 years). No patient had nonspecific, acute pouchitis as defined by our criteria. In 9 cases, the diagnosis was derived from benign ulcers common in ileal pouches. Stool frequency was the most common symptom associated with the "pouchitis" label, but actual causes for the frequency included poor pouch emptying, poor eating habits, poor bowel habits, and afferent limb syndrome. Median stool frequency was 9, ranging from 4 to 15 per day. Every patient had at least 1 pouch endoscopy, and the median number was 19 per patient (range, 1-21). Nine patients had pouch biopsies to rule out inflammation; all showed chronic active enteritis, a normal finding in ileal pouches.This study was limited by its retrospective nature.We could not confirm any case of nonspecific acute pouchitis in patients with familial adenomatous polyposis. Those caring for patients with familial adenomatous polyposis who have a pouch should seek causes for pouch-related symptoms other than "pouchitis." See Video Abstract at http://links.lww.com/DCR/B666.POUCHITIS AGUDA INESPECÍFICA EN PACIENTES CON POLIPOSIS ADENOMATOSA FAMILIAR: MENOS COMÚN DE LO QUE PENSAMOSANTECEDENTES:La pouchitis aguda e inespecífica es común en pacientes con colitis ulcerativa, sometidos a anastomosis de bolsa ileoanal, pero no hay acuerdo sobre la frecuencia en que se presenta en pacientes con poliposis adenomatosa familiar (PAF).OBJETIVO:Definir la frecuencia en la que se presenta pouchitis aguda inespecífica en pacientes con poliposis adenomatosa familiar.ENTORNO CLINICO:Centro de cáncer colorrectal hereditario en un gran centro médico académico.DISEÑO:Estudio de cohorte retrospectivo utilizando datos recopilados prospectivamente.PACIENTES:Pacientes con poliposis adenomatosa familiar sometidos a bolsa con anastomosis ileoanal.INTERVENCIONES:Síntomas, proctoscopia, radiografía y biopsia de bolsa ileoanal.PRINCIPALES MEDIDAS DE VALORACION:Presencia de pouchitis aguda inespecífica; diagnósticos alternos de disfunción de la bolsa ileal.RESULTADOS:De 250 pacientes con poliposis adenomatosa familiar sometidos a una anastomosis anal de la bolsa ileal; 38 (15,2%), habían sido etiquetados como "pouchitis", 23 hombres y 15 mujeres. La mediana de edad fue de 55 años (rango de 18 a 90 años). Ningún paciente tuvo pouchitis aguda inespecífica según lo definido por nuestros criterios. En 9 casos el diagnóstico se derivó de úlceras benignas frecuentes en bolsas ileales. La frecuencia de las evacuaciones fue el síntoma más común asociado con la etiqueta "pouchitis", pero las causas reales de la frecuencia, incluyeron un mal vaciado de la bolsa, malos hábitos alimenticios, malos hábitos intestinales y síndrome de asa aferente. La frecuencia media de las evacuaciones fue de 9, con un rango de 4 a 15 por día. A cada paciente se le realizó al menos una endoscopia de la bolsa: la mediana fue de 19 por paciente (rango de 1 a 21). A 9 pacientes se les realizó biopsia de bolsa para descartar inflamación: todos mostraron enteritis activa crónica, un hallazgo normal en las bolsas ileales.LIMITACIONES:Naturaleza retrospectiva del estudio.CONCLUSIONES:No pudimos confirmar ningún caso de pouchitis aguda e inespecífica en pacientes con PAF. Aquellos que atienden a pacientes con PAF con bolsa ileal, deben buscar otras causas para los síntomas relacionados con la bolsa que no sean "pouchitis". Consulte Video Resumen en http://links.lww.com/DCR/B666. (Traducción-Dr. Fidel Ruiz Healy).

Objective To assess the priorities and decisions of gay and bisexual men (GBM) pursuing fatherhood. Design Cross-sectional study. Setting Internet-based survey. Patients GBM who were interested in pursuing or had previously pursued family building options. Interventions None. Main Outcome Measures This study aimed to assess the attitudes of respondents regarding: 1) mode of achieving parenthood and the relative importance of a genetic link to offspring; 2) the relative importance of factors considered when selecting an oocyte donor (OD); and 3) the relative importance of factors associated with selecting a gestational carrier (GC). Access to care and financial considerations were also analyzed. Results The majority (68.2%) of the 110 respondents desired parenthood via OD and GC. This was consistent with 53.2% of respondents reporting that a genetic link to a child was ‘extremely important’ or ‘important.’ Most couples (86.6%) desired to use sperm from both partners. 40.5% of respondents reported that a twin gestation would be the most ideal pregnancy outcome. Medical history was considered the most important factor when selecting an OD (83.5%) while pregnancy history was considered the most important selection criterion for a GC (86.2%). 89.1% of respondents reported the fertility services they desired were available to them, although 33.0% reported they would have to travel to another state for care. Conclusion Understanding the circumstances of GBM pursuing fatherhood allows for individualized care. Since many respondents desired twin pregnancies, it is important to counsel patients regarding risks of multiple gestation and to determine the motivations for this preference.

Background Small airways are known to be affected early in the course of chronic obstructive pulmonary disease (COPD); however, traditional spirometric indices may not accurately identify small airways disease. Research Question Can FEV3/FEV6 identify early airflow abnormalities and predict future clinically important respiratory-related outcomes, including development of COPD? Study Design and Methods We included eight hundred thirty-two current and former smokers with post-bronchodilator FEV1/FVC ≥0.7 from the SPIROMICS cohort. Participants were classified as having a reduced pre-bronchodilator FEV3/FEV6 based on lower limit of normal (LLN) values. Repeatability analysis was performed for FEV3 and FEV6. Regression modeling was used to evaluate the relationship between baseline FEV3/FEV6 and outcome measures including functional small airways disease on thoracic imaging and respiratory exacerbations. Interval censored analysis was used to assess progression to COPD. Results FEV3/FEV6 Interpretation FEV3/FEV6 is a routinely available and repeatable spirometric index which can be useful in the evaluation of early airflow obstruction in current and former smokers without COPD. A reduced FEV3/FEV6 can identify those at risk for future development of COPD and respiratory exacerbations.

Background Ventricular interdependence may account for altered ventricular mechanics in congenital heart disease. The present study aimed to identify differences in load-dependent right ventricular (RV)–left ventricular (LV) interactions in porcine models of pulmonary stenosis (PS) and pulmonary insufficiency (PI) by invasive admittance-derived hemodynamics in conjunction with noninvasive cardiovascular magnetic resonance (CMR). Methods Seventeen pigs were used in the study (7 with PS, 7 with PI, and 3 controls). Progressive PS was created by tightening a Teflon tape around the pulmonary artery, and PI was created by excising 2 leaflets of the pulmonary valve. Admittance catheterization data were obtained for the RV and LV at 10 to 12 weeks after model creation, with the animal ventilated under temporary diaphragm paralysis. CMR was performed in all animals immediately prior to pressure–volume catheterization. Results In the PS group, RV contractility was increased, manifested by increased end-systolic elastance (mean difference, 1.29 mm Hg/mL; 95% confidence interval [CI], 0.57-2.00 mm Hg/mL). However, in the PI group, no significant changes were observed in RV systolic function despite significant changes in RV diastolic function. In the PS group, LV end-systolic volume was significantly lower compared with controls (mean difference, 25.1 mL; 95% CI, -40.5 to -90.7 mL), whereas in the PI group, the LV showed diastolic dysfunction, demonstrated by an elevated isovolumic relaxation constant and ventricular stiffness (mean difference, 0.03 mL−1; 95% CI, -0.02 to 0.09 mL−1). Conclusions The LV exhibits systolic dysfunction and noncompliance with PI. PS is associated with preserved LV systolic function and evidence of some LV diastolic dysfunction. Interventricular interactions influence LV filling and likely account for differential effects of RV pressure and volume overload on LV function.

Background Multiple risk scores claim to predict the probability of postoperative pancreatic fistula (POPF) after pancreatoduodenectomy. However, it is unclear which scores have undergone external validation, and which score is the most accurate. Objective To identify risk scores for POPF, and assess the clinical validity of these scores. Methods Areas under receiving operator characteristic curve (AUROCs) were extracted from studies that performed external validation of POPF risk scores. These were pooled for each risk score, using intercept-only random-effects meta-regression models. Results Systematic review identified 34 risk scores, of which six had been subjected to external validation, and so were included in the meta-analysis, namely the Tokyo (N=2 validation studies), Birmingham (N=5), FRS (N=19), a-FRS (N=12), m-FRS (N=3) and ua-FRS (N=3) scores. The overall predictive accuracies were found to be similar for all six scores, with pooled AUROCs of 0.61, 0.70, 0.71, 0.70, 0.70 and 0.72, respectively. Considerably heterogeneity was observed, with I2 statistics ranging from 52.1-88.6%. Conclusion Most risk scores lack external validation; where this was performed, risk scores were found to have limited predictive accuracy. . Consensus is needed for which score to use in clinical practice. Due to the limited predictive accuracy, future studies to derive a more accurate risk score are warranted.

OBJECTIVE The goal of this study was to assess the social determinants that influence access and outcomes for pediatric neurosurgical care for patients with Chiari malformation type I (CM-I) and syringomyelia (SM). METHODS The authors used retro- and prospective components of the Park-Reeves Syringomyelia Research Consortium database to identify pediatric patients with CM-I and SM who received surgical treatment and had at least 1 year of follow-up data. Race, ethnicity, and insurance status were used as comparators for preoperative, treatment, and postoperative characteristics and outcomes. RESULTS A total of 637 patients met inclusion criteria, and race or ethnicity data were available for 603 (94.7%) patients. A total of 463 (76.8%) were non-Hispanic White (NHW) and 140 (23.2%) were non-White. The non-White patients were older at diagnosis (p = 0.002) and were more likely to have an individualized education plan (p < 0.01). More non-White than NHW patients presented with cerebellar and cranial nerve deficits (i.e., gait ataxia [p = 0.028], nystagmus [p = 0.002], dysconjugate gaze [p = 0.03], hearing loss [p = 0.003], gait instability [p = 0.003], tremor [p = 0.021], or dysmetria [p < 0.001]). Non-White patients had higher rates of skull malformation (p = 0.004), platybasia (p = 0.002), and basilar invagination (p = 0.036). Non-White patients were more likely to be treated at low-volume centers than at high-volume centers (38.7% vs 15.2%; p < 0.01). Non-White patients were older at the time of surgery (p = 0.001) and had longer operative times (p < 0.001), higher estimated blood loss (p < 0.001), and a longer hospital stay (p = 0.04). There were no major group differences in terms of treatments performed or complications. The majority of subjects used private insurance (440, 71.5%), whereas 175 (28.5%) were using Medicaid or self-pay. Private insurance was used in 42.2% of non-White patients compared to 79.8% of NHW patients (p < 0.01). There were no major differences in presentation, treatment, or outcome between insurance groups. In multivariate modeling, non-White patients were more likely to present at an older age after controlling for sex and insurance status (p < 0.01). Non-White and male patients had a longer duration of symptoms before reaching diagnosis (p = 0.033 and 0.004, respectively). CONCLUSIONS Socioeconomic and demographic factors appear to influence the presentation and management of patients with CM-I and SM. Race is associated with age and timing of diagnosis as well as operating room time, estimated blood loss, and length of hospital stay. This exploration of socioeconomic and demographic barriers to care will be useful in understanding how to improve access to pediatric neurosurgical care for patients with CM-I and SM.

OBJECTIVE The primary objective of this trial was to determine if shunt entry site affects the risk of shunt failure. METHODS The authors performed a parallel-design randomized controlled trial with an equal allocation of patients who received shunt placement via the anterior entry site and patients who received shunt placement via the posterior entry site. All patients were children with symptoms or signs of hydrocephalus and ventriculomegaly. Patients were ineligible if they had a prior history of shunt insertion. Patients received a ventriculoperitoneal shunt after randomization; randomization was stratified by surgeon. The primary outcome was shunt failure. The planned minimum follow-up was 18 months. The trial was designed to achieve high power to detect a 10% or greater absolute difference in the shunt failure rate at 1 year. An independent, blinded adjudication committee determined eligibility and the primary outcome. The study was conducted by the Hydrocephalus Clinical Research Network. RESULTS The study randomized 467 pediatric patients at 14 tertiary care pediatric hospitals in North America from April 2015 to January 2019. The adjudication committee, blinded to intervention, excluded 7 patients in each group for not meeting the study inclusion criteria. For the primary analysis, there were 229 patients in the posterior group and 224 patients in the anterior group. The median patient age was 1.3 months, and the most common etiologies of hydrocephalus were postintraventricular hemorrhage secondary to prematurity (32.7%), myelomeningocele (16.8%), and aqueductal stenosis (10.8%). There was no significant difference in the time to shunt failure between the entry sites (log-rank test, stratified by age < 6 months and ≥ 6 months; p = 0.061). The hazard ratio (HR) of a posterior shunt relative to an anterior shunt was calculated using a univariable Cox regression model and was nonsignificant (HR 1.35, 95% CI, 0.98–1.85; p = 0.062). No significant difference was found between entry sites for the surgery duration, number of ventricular catheter passes, ventricular catheter location, and hospital length of stay. There were no significant differences between entry sites for intraoperative complications, postoperative CSF leaks, pseudomeningoceles, shunt infections, skull fractures, postoperative seizures, new-onset epilepsy, or intracranial hemorrhages. CONCLUSIONS This randomized controlled trial comparing the anterior and posterior shunt entry sites has demonstrated no significant difference in the time to shunt failure. Anterior and posterior entry site surgeries were found to have similar outcomes and similar complication rates.

OBJECTIVE There is little research on the effect of social determinants of health on Chiari malformation type I (CM-I). The authors analyzed data on all children evaluated for CM-I at a single institution to assess how socioeconomic factors and race affect the surgical treatment of this population. METHODS Medical records of patients treated for CM-I at the authors’ institution between 1992 and 2017 were reviewed. Area Deprivation Index (ADI) and Rural-Urban Commuting Area (RUCA) codes for each patient were used to measure neighborhood disadvantage. Non-Hispanic White patients were compared to non-White patients and Hispanic patients of any race (grouped together as non-White in this study) in terms of insurance status, ADI, and RUCA. Patients with initially benign CM-I, defined as not having undergone surgery within 9 months of their initial visit, were then stratified by having delayed symptom presentation or not, and compared on these same measures. RESULTS The sample included 665 patients with CM-I: 82% non-Hispanic White and 18% non-White. The non-White patients were more likely to reside in disadvantaged (OR 3.4, p < 0.001) and urban (OR 4.66, p < 0.001) neighborhoods and to have public health insurance (OR 3.11, p < 0.001). More than one-quarter (29%) of patients underwent surgery. The non-White and non-Hispanic White patients had similar surgery rates (29.5% vs 28.9%, p = 0.895) at similar ages (8.8 vs 9.7 years, p = 0.406). There were no differences by race/ethnicity for symptoms at presentation. Surgical and nonsurgical patients had similar ADI scores (3.9 vs 4.2, p = 0.194), RUCA scores (2.1 vs 2.3, p = 0.252), and private health insurance rates (73.6% vs 74.2%, p = 0.878). A total of 153 patients underwent surgery within 9 months of their initial visit. The remaining 512 were deemed to have benign CM-I. Of these, 40 (7.8%) underwent decompression surgery for delayed symptom presentation. Patients with delayed symptom presentation were from less disadvantaged (ADI 3.2 vs 4.2; p = 0.025) and less rural (RUCA 1.8 vs 2.3; p = 0.023) areas than those who never underwent surgery. CONCLUSIONS Although non-White patients were more likely to be socioeconomically disadvantaged, race and socioeconomic disadvantage were not associated with undergoing surgical treatment. However, among patients with benign CM-I, those undergoing decompression for delayed symptom presentation resided in more affluent and urban areas.

BackgroundPatients undergoing surgery for early stage non-small cell lung cancer (NSCLC) may be at high risk for postoperative mortality. Access to stereotactic body radiation therapy (SBRT) may facilitate more appropriate patient selection for surgery.Research questionIs postoperative mortality associated with early stage NSCLC lower at facilities with higher use of SBRT?Study design and methodsPatients with early stage NSCLC reported to the National Cancer Database between 2004 and 2015 were included. Use of SBRT was defined by each facility's SBRT experience (in years) and SBRT to surgery volume ratios. Multivariate logistic regression was used to test for the associations between SBRT use and postoperative mortality.ResultsThe study cohort consisted of 202,542 patients who underwent surgical resection of cT1-T2N0M0 NSCLC tumors. The 90-day postoperative mortality rate declined during the study period from 4.6%to 2.6%(P< .001), the proportion of facilities that used SBRT increased from 4.6%to 77.5%(P< .001), and the proportion of patients treated with SBRT increased from 0.7%to 15.4%(P< .001). On multivariate analysis, lower 90-day postoperative mortality rates were observed at facilities with > 6 years of SBRT experience (OR, 0.84; 95% CI, 0.76-0.94; P= .003) and SBRT to surgery volume ratios of more than 17%(OR, 0.85; 95% CI, 0.79-0.92; P< .001). Ninety-day mortality also was associated with surgical volume, region, year, age, sex, and race, among other covariates. Interaction testing between these covariates showed negative results.InterpretationPatients who underwent resection for early stage NSCLC at facilities with higher SBRT use showed lower rates of postoperative mortality. These findings suggest that the availability and use of SBRT may improve the selection of patients for surgery who are predicted to be at high risk of postoperative mortality.

The incidence of new-onset secondary atrial fibrillation (NOSAF) is as high as 44% in noncardiac critical illness. A systematic review and meta-analysis were performed to evaluate the impact of NOSAF, compared with history of prior atrial fibrillation (AF) and no history of AF in noncardiac critically ill patients. Patients undergoing cardiothoracic surgery were excluded. NOSAF incidence, intensive care unit (ICU)/hospital length of stay (LOS), and mortality outcomes were analyzed. Of 2,360 studies reviewed, 19 studies met inclusion criteria (n = 306,805 patients). NOSAF compared with no history of AF was associated with increased in-hospital mortality (risk ratio [RR] 2.06, 95% confidence interval [CI] 1.76 to 2.41, p0.001), longer ICU LOS (standardized difference in means [SMD] 0.66, 95% CI 0.41 to 0.91, p0.001), longer hospital LOS (SMD 0.31, 95% CI 0.07 to 0.56, p = 0.001) and increased risk of long-term (1 year) mortality (RR 1.76, 95% CI 1.29 to 2.40, p0.001). NOSAF compared with previous AF was also associated with higher in-hospital mortality (RR 1.29, 95% CI 1.12 to 1.49, p0.001), longer ICU LOS (SMD 0.37, 95% CI 0.03 to 0.70, p = 0.03) but no difference in-hospital LOS (SMD -0.18, 95% CI -0.66 to 0.31, p = 0.47). In conclusion, NOSAF, in the setting of noncardiac critical illness is associated with increased in-hospital mortality compared with no history of AF and previous AF. NOSAF (vs no history of AF) is also associated with increased long-term mortality.

Background Delayed biliary strictures (DBS) after cholecystectomy are uncommon and little is known of their aetiology or long-term consequences. The aims of this study were to investigate the clinical and economic impact of DBS after cholecystectomy. Methods Patients who developed DBS after cholecystectomy were identified from a prospectively collected and maintained database. Risk factors for stricture development, quality of life (QoL) and long-term biliary complication rates were explored. Costs of treatment and follow up were determined. The same outcomes among patients with minor or major bile duct injury (BDI) were used as a comparison. Results Among 44 patients, a laparoscopic converted to open procedure or post cholecystectomy bile leak affected some 18 and 12 patients respectively. Most DBS required surgical treatment (40). Over a median follow-up of 8.9 years after DBS treatment, 16 (36%) patients developed biliary complications (similar to minor, 26%, and major BDI, 40%) and 1 patient died of causes related to the biliary stricture. Costs of treating DBS and its follow up (£14,309.26 per patient), were similar to previously reported costs for major BDI (£15,784). Conclusion DBS typically occur after a technically and/or complicated cholecystectomy. Clinical, economic and QoL outcomes are similar to patients with major BDI.

Germinal center B-cell-like diffuse large B cell lymphoma (GCB-DLBCL) at diagnosis is associated with superior long-term outcomes compared to non-GCB-DLBCL in patients treated with conventional chemo-immunotherapy. Whether cell of origin (COO) by Hans algorithm retains its prognostic significance in patients with (R/R) relapsed/refractory DLBCL undergoing autologous hematopoietic cell transplant (auto-HCT) is not well established. Three hundred and fifty-seven patients underwent auto-HCT between 2005 and 2018. The COO status was determined in 284 patients and these were included in the analysis. One hundred ninety-four patients had GCB-DLBCL while 90 had non-GCB-DLBCL. Median follow up was 1.7 (0-13) years. The GCB-DLBCL was associated with inferior 5-year overall survival at 44% (95%CI, 36-52) versus 64% (95%CI, 54-77) (P = .004) and a higher relapse incidence at 67% (95%CI, 58-74) versus 49% (95%CI, 35-60) (P = .01) in the non-GCB-DLBCL. The difference between GCB and non-GCB-DLBCL remained statistically significant in multivariate analysis. Additionally, response at the time of transplant was an independent prognostic factor. GCB-DLBCL was enriched in double-hit and triple hit phenotype based on available fluorescence in situ hybridization data. These results suggest an enrichment of high-risk genetic rearrangements in R/R GCB-DLBCL resulting in limited efficacy of auto-HCT.

OBJECTIVE: It is estimated that childhood ADHD remits by adulthood in approximately 50% of cases; however, this conclusion is typically based on single endpoints, failing to consider longitudinal patterns of ADHD expression. We investigated the extent to which children with ADHD experience recovery and variable patterns of remission by adulthood. METHOD: Children with ADHD (N=558) in the Multimodal Treatment Study of ADHD (MTA) were administered eight assessments from 2-year (M age=10.44) to 16-year follow-up (M age=25.12). We identified participants with fully remitted, partially remitted, and persistent ADHD at each timepoint based on parent, teacher, and self-reports of ADHD symptoms and impairment, treatment utilization, and substance use and mental disorders. Longitudinal patterns of remission and persistence were identified that considered context and timing. RESULTS: Approximately 30% of children with ADHD experienced full remission at some point during the 14-year follow-up period; however, a majority (60% of these) experienced recurrence of ADHD after the initial period of remission. Only 9.1% of the sample demonstrated recovery (sustained remission) by study endpoint and only 10.8% demonstrated stable ADHD persistence across study timepoints. Instead, most participants with ADHD (63.8%) had fluctuating periods of remission and recurrence over time. CONCLUSIONS: The MTA findings challenge the notion that approximately 50% of children with ADHD outgrow the disorder by adulthood. Most cases demonstrated fluctuating symptoms between childhood and young adulthood. Although intermittent periods of remission can be expected in most cases, 90% of children with ADHD continued to struggle with residual ADHD through young adulthood. Clinical Trial Number: NCT00000388, Multimodal Treatment Study of Children with Attention Deficit and Hyperactivity Disorder (MTA). https://clinicaltrials.gov/ct2/show/NCT00000388

Introduction Indocyanine green (ICG) is commonly used to visualize cerebral vasculature, particularly in the management of cerebral aneurysms. There have also been attempts to use ICG for visualization of tumors. Injection of ICG followed by immediate fluorescence microscopy is limited by the short time window for imaging and administration and restricted depth of imaging. Second Window Indocyanine Green (SWIG) addresses these issues by allowing for longer contrast times and the imaging of deeper regions of brain tissue. Biopsy of spinal cord lesions is often difficult for a variety of reasons, including the delicate nature of the tissue and differentiating normal from lesional tissue visually, especially in lesions with heterogeneous enhancement. Methods In this case report, we describe the use of second window ICG to facilitate the visualization of a spinal cord lesion and subsequent biopsy of the lesion. Results This patient is a 24-year-old female who had recurrence of a suprasellar germinoma. An MRI of the rest of the neuraxis was performed to assess for the presence of drop metastases. The spinal cord from C2-5 was expanded with areas of patchy enhancement; however, this lesion was asymptomatic. The patient's oncologist requested a biopsy of this lesion to help direct subsequent care of her recurrent germinoma. The day before surgery, the patient had an intravenous injection of ICG dye. She then underwent a C3-5 laminectomy for biopsy of her cervical intramedullary lesion. After opening of the dura, no visible abnormality of the spinal cord could be identified. A Stryker endoscope showed an area of ICG uptake in the cord at approximately the C3-4 level. A midline myelotomy was centered over the ICG demarcated area and several samples were taken for pathology. Final biopsy results determined the lesion to be spinal cord parenchyma with perivascular and intraparenchymal lymphocytes – not consistent with spinal cord tumor or germinoma. Conclusion Second Window ICG is effective in visualizing otherwise visually unremarkable spinal cord lesions. This technology can facilitate biopsy of these lesions and possibly their surgical resection.

Purpose Radiation therapy (RT) can increase the risk of cardiac events in patients with breast cancer (BC), but biomarkers predicting risk for developing RT-induced cardiac disease are currently lacking. We report results from a prospective clinical trial evaluating early magnetic resonance imaging (MRI) and serum biomarker changes as predictors of cardiac injury and risk of subsequent cardiac events after RT for left-sided disease. Methods Women with node-negative and node-positive (N-/+) left-sided BC were enrolled on 2 institutional review board (IRB)–approved protocols at 2 institutions. MRI was conducted pretreatment (within 1 week of starting radiation), at the end of treatment (last day of treatment ±1 week), and 3 months after the last day of treatment (±2 weeks) to quantify left and right ventricular volumes and function, myocardial fibrosis, and edema. Perfusion changes during regadenoson stress perfusion were also assessed on a subset of patients (n = 28). Serum was collected at the same time points. Whole heart and cardiac substructures were contoured using CT and MRI. Models were constructed using baseline cardiac and clinical risk factors. Associations between MRI-measured changes and dose were evaluated. Results Among 51 women enrolled, mean heart dose ranged from 0.80 to 4.7 Gy and mean left ventricular (LV) dose from 1.1 to 8.2 Gy, with mean heart dose 2.0 Gy. T1 time, a marker of fibrosis, and right ventricular (RV) ejection fraction (EF) significantly changed with treatment; these were not dose dependent. T2 (marker of edema) and LV EF did not significantly change. No risk factors were associated with baseline global perfusion. Prior receipt of doxorubicin was marginally associated with decreased myocardial perfusion after RT (P = .059), and mean MHD was not associated with perfusion changes. A significant correlation between baseline IL-6 and mean heart dose (MHD) at the end of RT (ρ 0.44, P = .007) and a strong trend between troponin I and MHD at 3 months post-treatment (ρ 0.33, P = .07) were observed. No other significant correlations were identified. Conclusions In this prospective study of women with left-sided breast cancer treated with contemporary treatment planning, cardiac radiation doses were very low relative to historical doses reported by Darby et al. Although we observed significant changes in T1 and RV EF shortly after RT, these changes were not correlated with whole heart or substructure doses. Serum biomarker analysis of cardiac injury demonstrates an interesting trend between markers and MHD that warrants further investigation.

Anti–SARS-CoV-2 antibodies have been used in health care and clinical settings to prevent and treat COVID-19. The National Institutes of Health convened a virtual summit on 15 June 2021 to summarize existing knowledge and to identify key unanswered scientific questions to catalyze future development of these antibodies., As the fourth wave of the SARS-CoV-2 pandemic encircles the globe, there remains an urgent challenge to identify safe and effective treatment and prevention strategies that can be implemented in a range of health care and clinical settings. Substantial advances have been made in the use of anti–SARS-CoV-2 antibodies to mitigate the morbidity and mortality associated with COVID-19. On 15 June 2021, the National Institutes of Health, in collaboration with the U.S. Food and Drug Administration, convened a virtual summit to summarize existing knowledge on anti–SARS-CoV-2 antibodies and to identify key unanswered scientific questions to further catalyze the clinical development and implementation of antibodies.

Key Points Isolated and comutated DDX41 myeloid neoplasms have different characteristics.DDX41-mutated AML has a relatively favorable outcome comparable to core binding factor AML., Visual Abstract, DDX41 mutations (germline and somatic) are associated with late onset myelodysplastic syndromes/acute myeloid leukemia (MDS/AML). Myeloid neoplasms (MN) with germline predisposition was identified as a distinct category in the 2016 WHO classification revision, including MN with germline DDX41 mutation. We retrospectively analyzed the molecular findings and clinical characteristics of thirty-three DDX41-mutated (mDDX41) patients at our institution. We identified 14 distinct pathogenic DDX41 variants in 32 patients and 8 DDX41 variants of unknown significance (VUS) in 9 patients. Five (16%) patients had a second DDX41 somatic mutation p.R525H and 13 (40%) had at least one additional oncogenic co-mutation in other genes. The median age at the time of diagnosis was 66 years, with male predominance (72%) and the majority of patients had normal cytogenetics (91%). Two-year overall survival (OS) was 86% and 6 (21%) MDS/AML patients with relatively preserved hematopoietic function were observed without further intervention. In comparison to AML patients with prognostically more favorable subtypes [t(8;21), n=27 and inv(16), n=40], mDDX41 patients in our cohort showed similarly favorable OS. Our study highlights that mDDX41-MN patients often have an indolent course and mDDX41-AML has comparable OS to favorable-risk AML.

Background Histologic analyses of deep vein thrombi (DVTs) have used autopsy samples and animal models. To the best of our knowledge, no previous study has reported on thrombus composition after percutaneous mechanical extraction. Because elements of chronicity and organization render thrombus resistant to anticoagulation and thrombolysis, a better understanding of clot evolution could inform therapy. Methods We performed a histologic evaluation of DVTs from consecutive patients who had undergone mechanical thrombectomy for extensive iliofemoral DVTs using the Clottriever/Flowtriever device (Inari Medical, Irvine, Calif). The DVTs were scored using a semiquantitative method according to the degree of fibrosis (collagen deposition on trichrome staining) and organization (endothelial growth with capillaries and fibroblastic penetration). Results Twenty-three specimens were available for analysis, with 20 presenting as acute DVT (≤14 days from symptom onset). Of the 23 patients, 11 (48%) had had >5% fibrosis (ie, collagen deposition) and 14 (61%) had had >5% organization (ie, endothelial growth, capillaries, fibroblasts). Four patients with acute DVT had had ≥25% organized thrombus and two had had ≥25% collagen deposition. Of the 20 patients with acute DVT, 40% had had >5% fibrosis and 55% had had >5% organization. The acuity of DVT did not correlate with the amount of fibrosis or organizing scores. Conclusions A large proportion of patients with acute DVT will have histologic elements of chronicity and fibrosis. A better understanding of the relationship between such elements and the response to anticoagulant agents and fibrinolytic drugs could inform our approach to therapy.

The sonographic evaluation of early pregnancy has dramatically improved since the introduction of transvaginal sonography. Relatively recent publications highlight the importance of caution in evaluating and intervening in early pregnancy. As a result, new recommendations have been established for identifying milestones in early singleton pregnancy, including a threshold level of hCG = 390–1000 mIU/mL for visualizing a gestational sac, and a discriminatory value of 3000 IU/mL for identifying all normal intrauterine pregnancies. These same values do not apply to multiple gestations, and thus, caution is advised in patients who have undergone assisted reproduction.

Preclinical models propose that increased hippocampal activity drives subcortical dopaminergic dysfunction and leads to psychosis-like symptoms and behaviors. Here, we used multimodal neuroimaging to examine the relationship between hippocampal regional cerebral blood flow (rCBF) and striatal dopamine synthesis capacity in people at clinical high risk (CHR) for psychosis and investigated its association with subsequent clinical and functional outcomes. Ninety-five participants (67 CHR and 28 healthy controls) underwent arterial spin labeling MRI and 18F-DOPA PET imaging at baseline. CHR participants were followed up for a median of 15 months to determine functional outcomes with the global assessment of function (GAF) scale and clinical outcomes using the comprehensive assessment of at-risk mental states (CAARMS). CHR participants with poor functional outcomes (follow-up GAF n = 25) showed higher rCBF in the right hippocampus compared to CHRs with good functional outcomes (GAF ≥ 65, n = 25) (pfwe = 0.026). The relationship between rCBF in this right hippocampal region and striatal dopamine synthesis capacity was also significantly different between groups (pfwe = 0.035); the association was negative in CHR with poor outcomes (pfwe = 0.012), but non-significant in CHR with good outcomes. Furthermore, the correlation between right hippocampal rCBF and striatal dopamine function predicted a longitudinal increase in the severity of positive psychotic symptoms within the total CHR group (p = 0.041). There were no differences in rCBF, dopamine, or their associations in the total CHR group relative to controls. These findings indicate that altered interactions between the hippocampus and the subcortical dopamine system are implicated in the pathophysiology of adverse outcomes in the CHR state.

Objective: The current study used the Canadian Armed Forces Members and Veterans Mental Health Follow-up Survey (CAFVMHS) to (1) examine the incidence and prevalence of mental disorders and (2) estimate the comorbidity of mental disorders over the follow-up period. Method: The CAFVMHS (2018) is a longitudinal study with two time points of assessment. The sample is comprised of 2,941 Canadian Forces members and veterans who participated in the 2002 Canadian Community Health Survey: Canadian Forces Supplement. The World Health Organization Composite International Diagnostic Interview (WHO-CIDI) was utilized to diagnose Diagnostic and Statistical Manual-IV post-traumatic stress disorder (PTSD), major depressive episode (MDE), generalized anxiety disorder, social anxiety disorder (SAD), and alcohol abuse and dependence. Self-report health professional diagnoses were assessed for attention deficit hyperactivity disorder (ADHD), mania, obsessive compulsive disorder (OCD), and personality disorder. We established weighted prevalence of mental disorders and examined the association between mental disorders using logistic regression. Results: In 2018, lifetime prevalence of any WHO-CIDI-based or self-reported mental disorder was 58.1%. Lifetime prevalence of any mood or anxiety disorder or PTSD was 54.0% in 2018. MDE (39.9%), SAD (25.7%), and PTSD (21.4%) were the most common mental disorders. There was a substantial increase in new onset or recurrence/persistence of mental disorders between the two measurement points (16-year assessment gap); 2002–2018 period prevalences were 43.5% for mood and anxiety disorder and 16.8% for alcohol abuse or dependence. The prevalence of self-reported ADHD, OCD, any personality disorder, and mania were 3.3%, 3.0%, 0.8%, and 0.8%, respectively. Comorbidity between mental disorders increased over the follow-up. Conclusions: This study demonstrates a high burden of mental disorders among a large Canadian military and veteran cohort. These findings underscore the importance of prevention and intervention strategies to reduce the burden of mental disorders and alcohol use disorders in these populations.

As prevention trials advance with autosomal dominant Alzheimer disease (ADAD) participants, understanding the similarities and differences between ADAD and "sporadic" late-onset AD (LOAD) is critical to determine generalizability of findings between these cohorts. Cognitive trajectories of ADAD mutation carriers (MCs) and autopsy-confirmed LOAD individuals were compared to address this question. Longitudinal rates of change on cognitive measures were compared in ADAD MCs (n = 310) and autopsy-confirmed LOAD participants (n = 163) before and after symptom onset (estimated/observed). LOAD participants declined more rapidly in the presymptomatic (preclinical) period and performed more poorly at symptom onset than ADAD participants on a cognitive composite. After symptom onset, however, the younger ADAD MCs declined more rapidly. The similar but not identical cognitive trajectories (declining but at different rates) for ADAD and LOAD suggest common AD pathologies but with some differences.

Objectives Single-agent heat shock protein 90 (HSP90) inhibition has demonstrated activity in oncogene-driven non-small cell and small cell lung cancers. SNX-5422 is an oral HSP90 inhibitor with increased activity in vitro with the addition of carboplatin and paclitaxel. Therefore, we conducted a phase 1, open-label, multicenter study to evaluate SNX-5422, carboplatin and paclitaxel followed by SNX-5422 maintenance in patients with advanced lung cancers. Materials and methods In part 1 (3 + 3 dose escalation), SNX-5422 (50/75/100-mg/m2) was dosed every other day (qod) for 21 days (28-day cycle) for ≤4 cycles; carboplatin (AUC 5)-paclitaxel (175 mg/m2) was administered once every 3 weeks for ≤6 courses. In part 2 (maintenance), subjects who achieved at least stable disease in part 1 received 100 mg/m2 SNX-5422 monotherapy qod for 21 days (28-day cycle). Results Twenty-three patients with advanced non-small cell lung cancer (NSCLC, n = 20) and small cell lung cancer (SCLC, n = 3) were enrolled. The median age was 60 years and 61% (n = 14/23) had ≥1 prior treatment regimens. The maximum tolerated dose of SNX-5422 was 100 mg/m2 qod in combination with carboplatin-paclitaxel. The most common treatment-related grade 3/4 adverse events (part 1/part 2) were diarrhea (26%/15%) and nausea (9%/0%). In response-evaluable patients with NSCLC, 33% (6/18) had a partial response, 56% (10/18) stable disease, and 11% (2/18) progressive disease. Patients who remained on single-agent SNX-5422 maintenance therapy ≥2 months (n = 9) had cancers enriched for oncogenic drivers (n = 3 KRAS mutation, n = 1 EGFR exon 20 mutation, n = 1 HER2 mutation, and n = 1 RET fusion). Conclusions The triplet combination of SNX-5422, carboplatin and paclitaxel followed by maintenance SNX-5422 therapy was well-tolerated and showed anti-tumor activity. Cancers for which disease control on single-agent SNX-5422 maintenance was observed were enriched for oncogene-driven NSCLCs.

Lung ultrasound (LUS) has gained considerable acceptance in emergency and critical care medicine but is yet to be fully implemented in cardiology. Standard imaging protocols for LUS in acute care settings have allowed the rapid and accurate diagnosis of dyspnea, respiratory failure, and shock. LUS is greatly additive to echocardiography and is superior to auscultation and chest radiography, particularly when the diagnosis of acute decompensated heart failure is in question. In this review, the authors describe LUS techniques, interpretation, and clinical applications, with the goal of informing cardiologists on the imaging modality. Additionally, the authors review LUS findings associated with various disease states most relevant to cardiac care. Although there is extensive literature on LUS in the acute care setting, there is a dearth of reviews directly focused for practicing cardiologists. Current evidence demonstrates that this modality is an important adjunct to echocardiography, providing valuable clinical information at the bedside.

Background This analysis evaluates the impacts of biologically effective dose (BED) and histology on local control (LC) of spinal metastases treated with highly conformal radiotherapy to moderately-escalated doses. Materials and methods Patients were treated at two institutions from 2010–2020. Treatments with less than 5 Gy per fraction or 8 Gy in 1 fraction were excluded. The dataset was divided into three RPA classes predictive of survival (1). The primary endpoint was LC. Results 223 patients with 248 treatments met inclusion criteria. Patients had a median Karnofsky Performance Status (KPS ) of 80, and common histologies included breast (29.4%), non-small cell lung cancer (15.7%), and prostate (13.3%). A median 24 Gy was delivered in 3 fractions (BED: 38.4 Gy) to a median planning target volume (PTV) of 37.3 cc. 2-year LC was 75.7%, and 2-year OS was 42.1%. Increased BED was predictive of improved LC for primary prostate cancer (HR = 0.85, 95% CI: 0.74–0.99). Patients with favorable survival (RPA class 1) had improved LC with BED ≥ 40 Gy (p = 0.05), unlike the intermediate and poor survival groups. No grade 3–5 toxicities were reported. Conclusions Moderately-escalated treatments were efficacious and well-tolerated. BED ≥ 40 Gy may improve LC, particularly for prostate cancer and patients with favorable survival.

OBJECTIVE Spinal procedures are increasingly conducted as outpatient procedures, with a growing proportion conducted in ambulatory surgery centers (ASCs). To date, studies reporting outcomes and cost analyses for outpatient spinal procedures in the US have not distinguished the various outpatient settings from each other. In this study, the authors used a state-level administrative database to compare rates of overnight stays and nonroutine discharges as well as index admission charges and cumulative 7-, 30-, and 90-day charges for patients undergoing outpatient lumbar decompression in freestanding ASCs and hospital outpatient (HO) settings. METHODS For this project, the authors used the Florida State Ambulatory Surgery Database (SASD), offered by the Healthcare Cost and Utilization Project (HCUP), for the years 2013 and 2014. Patients undergoing outpatient lumbar decompression for degenerative diseases were identified using CPT (Current Procedural Terminology) and ICD-9 codes. Outcomes of interest included rates of overnight stays, rate of nonroutine discharges, index admission charges, and subsequent admission cumulative charges at 7, 30, and 90 days. Multivariable analysis was performed to assess the impact of outpatient type on index admission charges. Marginal effect analysis was employed to study the difference in predicted dollar margins between ASCs and HOs for each insurance type. RESULTS A total of 25,486 patients were identified; of these, 7067 patients (27.7%) underwent lumbar decompression in a freestanding ASC and 18,419 (72.3%) in an HO. No patient in the ASC group required an overnight stay compared to 9.2% (n = 1691) in the HO group (p < 0.001). No clinically significant difference in the rate of nonroutine discharge was observed between the two groups. The mean index admission charge for the ASC group was found to be significantly higher than that for the HO group ($35,017.28 ± $14,335.60 vs $33,881.50 ± $15,023.70; p < 0.001). Patients in ASCs were also found to have higher mean 7-day (p < 0.001), 30-day (p < 0.001), and 90-day (p = 0.001) readmission charges. ASC procedures were associated with increased charges compared to HO procedures for patients on Medicare or Medicaid (mean index admission charge increase $4049.27, 95% CI $2577.87–$5520.67, p < 0.001) and for patients on private insurance ($4775.72, 95% CI $4171.06–$5380.38, p < 0.001). For patients on self-pay or no charge, a lumbar decompression procedure at an ASC was associated with a decrease in index admission charge of −$10,995.38 (95% CI −$12124.76 to −$9866.01, p < 0.001) compared to a lumbar decompression procedure at an HO. CONCLUSIONS These “real-world” results from an all-payer statewide database indicate that for outpatient spine surgery, ASCs may be associated with higher index admission and subsequent 7-, 30-, and 90-day charges. Given that ASCs are touted to have lower overall costs for patients and better profit margins for physicians, these analyses warrant further investigation into whether this cost benefit is applicable to outpatient spine procedures.

As members of the Clinical Practice Committee (CPC) of the Society for General Internal Medicine (SGIM), we support practice innovation and transformation to achieve a more just system by which all people can achieve and maintain optimal health. The COVID-19 pandemic has tested the US healthcare delivery system and sharpened our national awareness of long-standing and ingrained system shortcomings. In the face of crisis, SGIM members innovated and energetically mobilized to focus on the immediate needs of our patients and communities. Reflecting on these experiences, we are called to consider what was learned from the pandemic that applies to the future of healthcare delivery. CPC members include leaders in primary care delivery, practice finance, quality of care, patient safety, hospital practice, and health policy. CPC members provide expertise in clinical practice, serving as primary care doctors, hospitalists, and patient advocates who understand the intensity of care needed for those with severe COVID-19 infections, the disproportionate impact of the pandemic on Black and Brown communities, the struggles created for those with poor access to care, and the physical and emotional impact it has placed on patients, families, and clinicians. In this consensus statement, we summarize lessons learned from the 2020-2021 pandemic and their broader implications for reform in healthcare delivery. We provide a platform for future work by identifying many interactive elements of healthcare delivery that must be simultaneously addressed in order to ensure that care is accessible, equitably provided, patient-centered, and cost-effective.

Purpose of Review The aim of this review is to explore the consequence of emergency general surgery in the elderly, and to summarise recent developments in the pre-, peri- and postoperative management of these patients, in order to improve outcomes. Recent Findings Preoperatively, accurate risk assessment is vital to ensure the right patients undergo emergency surgery. Perioperatively, there are multiple interventions specific to elderly patients that have been shown to improve outcomes. Postoperatively, elderly patients must be cared more in an appropriate setting in order to avoid failure to rescue and promote return to function. Summary This review of contemporary evidence identifies multiple pre-, peri- and postoperative interventions that can improve outcomes for elderly patients after emergency general surgery. These evidence-based recommendations should help direct care of elderly patients undergoing emergency surgery and foster further quality improvement measures and research investigations.

Desmoid disease is a leading cause of morbidity and mortality in patients with familial adenomatous polyposis. Abdominal desmoid disease usually follows total proctocolectomy with IPAA or total abdominal colectomy with ileorectal anastomosis. Sex, extraintestinal manifestations, and a 3'-mutation location have been identified as risk factors, but surgical risk factors are poorly understood. We hypothesized that pouch construction creates a higher risk of desmoid formation due to the increased stretch of the small-bowel mesentery.This study aimed to investigate the surgical risk factors for desmoid formation.This was a retrospective, single-center, registry-based cohort study.This study was conducted at a single academic institution with a prospectively maintained hereditary colorectal cancer database between 1995 and 2015.All patients with familial polyposis (total 345) who underwent either proctocolectomy with a pouch or colectomy with an ileorectal anastomosis during the study period and met inclusion criteria were selected.The development of symptomatic abdominal desmoid disease was the primary end point. Associations between desmoid formation and resection type, surgical approach, and other patient factors were analyzed.A total of 172 (49%) patients underwent proctocolectomy/ileoanal pouch, whereas 173 (51%) underwent total colectomy/ileorectal anastomosis. Overall, 100 (28.9%) developed symptomatic desmoids after surgery. On univariable analysis, open surgery and pouch surgery were associated with desmoid development, along with extracolonic manifestations, family history of desmoids, mutation location, and a high desmoid risk score. On multivarible analysis, proctocolectomy with pouch was most strongly associated with desmoid disease ( p0.01).This study was limited by its retrospective nature, the lack of uniform desmoid screening, and the variable duration of follow-up. Unanalyzed confounding factors include polyposis severity and number of surgeries.Patients with polyposis who underwent total proctocolectomy with pouch by any approach had significantly greater risk of developing desmoid disease than total colectomy with ileorectal anastomosis, even when accounting for other risk factors. See Video Abstract at http://links.lww.com/DCR/B822 .RESULTADOS DE LOS PACIENTES SOMETIDOS A RESECCIÓN INTESTINAL ELECTIVA ANTES Y DESPUÉS DE LA IMPLEMENTACIÓN DE UN PROGRAMA DE DETECCIÓN Y TRATAMIENTO DE ANEMIA.Se sabe que los pacientes anémicos que se someten a una cirugía electiva de cáncer colorrectal tienen tasas significativamente más altas de complicaciones posoperatorias y peores resultados.Mejorar las tasas de detección y tratamiento de la anemia en pacientes sometidos a resecciones electivas de colon y recto a través de una iniciativa de mejora de calidad.Comparamos una cohorte histórica de pacientes antes de la implementación de nuestro programa de detección de anemia y mejora de la calidad del tratamiento con una cohorte prospectiva después de la implementación.Hospital de atención terciaria.Todos los pacientes adultos con un nuevo diagnóstico de cáncer de colon o recto sin evidencia de enfermedad metastásica entre 2017 y 2019.Detección de anemia y programa de mejora de la calidad del tratamiento.El resultado primario fue el costo hospitalario por ingreso.Un total de 84 pacientes se sometieron a resección electiva de colon o recto antes de la implementación de nuestro proyecto de mejora de calidad de la anemia y 88 pacientes se sometieron a cirugía después. En la cohorte previa a la implementación, 44/84 (55,9 %) presentaban anemia en comparación con 47/99 (54,7 %) en la cohorte posterior a la implementación. Las tasas de detección (25 % a 86,4 %) y tratamiento (27,8 % a 63,8 %) aumentaron significativamente en la cohorte posterior a la implementación. El costo total medio por admisión se redujo significativamente en la cohorte posterior a la implementación (costo medio $16 827 vs. $25 796, p = 0,004); esta reducción significativa se observó incluso después de ajustar los factores de confusión relevantes (proporción de medias: 0,74, IC del 95 %: 0,65 a 0,85). El vínculo mecánico entre el tratamiento de la anemia y la reducción de costos sigue siendo desconocido. No hubo diferencias significativas en las tasas de transfusión de sangre, complicaciones o mortalidad entre los grupos.El diseño de antes y después está sujeto a sesgos temporales y de selección.Demostramos la implementación exitosa de un programa de detección y tratamiento de anemia. Este programa se asoció con un costo por admisión significativamente reducido. Este trabajo demuestra el valor y los beneficios posibles de la implementación de un programa de detección y tratamiento de la anemia. Consulte Video Resumen en http://links.lww.com/DCR/C15 . (Traducción- Dr. Francisco M. Abarca-Rendon ).

Objective The objective of the study was to assess the tolerability and safety of galcanezumab in patients with chronic cluster headache (CH) with up to 15 months of treatment. Background Chronic CH is a highly debilitating disease with a substantial and unmet medical need. Methods Patients were randomized to receive placebo or galcanezumab (300 mg) monthly for 12 weeks, followed by an optional 52-week open-label extension and 16-week posttreatment follow-up (washout). This is a secondary analysis and long-term follow-up of a previously conducted clinical trial. The safety analysis included patients who received galcanezumab at any time during the study. Outcomes included adverse events (AEs), discontinuations, laboratory values, vital signs, electrocardiograms (ECGs), and suicidality ratings. Results A total of 233 patients received at least one galcanezumab dose. The mean exposure was 341 days. Galcanezumab-treated patients were mostly male (n = 169/233; 72.5%) with a mean age of 44.9 (±10.9) years. Treatment-emergent adverse events (TEAEs) were reported by 185 patients (n = 185/233; 79.4%), 23 patients (n = 23/233; 9.9%) reported serious adverse events (SAEs), and 18 patients (n = 18/233; 7.7%) discontinued due to AEs. The SAE CH was reported by three patients. The most common TEAEs (>10%) were nasopharyngitis (n = 41/233; 17.6%) and injection site pain (n = 33/233; 14.2%). 27.5% of patients (n = 64/233) had TEAEs related to injection sites. Likely hypersensitivity events, including injection site rash, injection site urticaria, and injection site hypersensitivity were reported (n = 14/233; 6.0%). There were past histories of suicidal ideation (n = 55/237; 23.2%) and suicidal behavior (n = 9/236; 3.8%). During the study, 15 patients (n = 15/230; 6.5%), seven with previous history, reported suicidal ideation. One patient had a nonfatal suicide attempt during the open-label extension and an aborted attempt during the washout. There were no new safety findings compared with the placebo-controlled treatment period in laboratory values, vital signs, or ECGs. Conclusions Galcanezumab 300 mg monthly had a favorable tolerability and safety profile in patients with chronic CH with up to 15 months of treatment.

Schizophrenia has a multifactorial etiology, involving a polygenic architecture. The potential benefit of whole genome sequencing (WGS) in schizophrenia and other psychotic disorders is not well studied. We investigated the yield of clinical WGS analysis in 251 families with a proband diagnosed with schizophrenia (N = 190), schizoaffective disorder (N = 49), or other conditions involving psychosis (N = 48). Participants were recruited in Israel and USA, mainly of Jewish, Arab, and other European ancestries. Trio (parents and proband) WGS was performed for 228 families (90.8%); in the other families, WGS included parents and at least two affected siblings. In the secondary analyses, we evaluated the contribution of rare variant enrichment in particular gene sets, and calculated polygenic risk score (PRS) for schizophrenia. For the primary outcome, diagnostic rate was 6.4%; we found clinically significant, single nucleotide variants (SNVs) or small insertions or deletions (indels) in 14 probands (5.6%), and copy number variants (CNVs) in 2 (0.8%). Significant enrichment of rare loss-of-function variants was observed in a gene set of top schizophrenia candidate genes in affected individuals, compared with population controls (N = 6,840). The PRS for schizophrenia was significantly increased in the affected individuals group, compared to their unaffected relatives. Last, we were also able to provide pharmacogenomics information based on CYP2D6 genotype data for most participants, and determine their antipsychotic metabolizer status. In conclusion, our findings suggest that WGS may have a role in the setting of both research and genetic counseling for individuals with schizophrenia and other psychotic disorders and their families.

Objective To report the 30-day outcomes of patients with perioperative SARS-CoV-2 infection undergoing surgery in the USA. Summary background data Uncertainty regarding the postoperative risks of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exists. Methods As part of the COVIDSurg multicenter study, all patients aged ≥17 years undergoing surgery between January 1 and June 30, 2020 with perioperative SARS-CoV-2 infection in 70 hospitals across 27 states were included. The primary outcomes were 30-day mortality and pulmonary complications. Multivariable analyses (adjusting for demographics, comorbidities, and procedure characteristics) were performed to identify predictors of mortality. Results A total of 1,581 patients were included; more than half of them were males (n= 822, 52.0%) and older than 50 years (n=835, 52.8%). Most procedures (n=1,261, 79.8%) were emergent, and laparotomies (n= 538, 34.1%). The mortality and pulmonary complication rates were 11.0 and 39.5%, respectively. Independent predictors of mortality included age ≥70 years (OR 2.46, 95% CI [1.65-3.69]), male sex (2.26 [1.53-3.35]), ASA grades 3-5 (3.08 [1.60-5.95]), emergent surgery (2.44 [1.31-4.54]), malignancy (2.97 [1.58-5.57]), respiratory comorbidities (2.08 [1.30-3.32]), and higher Revised Cardiac Risk Index (1.20 [1.02-1.41]). While statewide elective cancelation orders were not associated with a lower mortality, a sub-analysis showed it to be associated with lower mortality in those who underwent elective surgery (0.14 [0.03-0.61]). Conclusions Patients with perioperative SARS-CoV-2 infection have a significantly high risk for postoperative complications, especially elderly males. Postponing elective surgery and adopting non-operative management, when reasonable, should be considered in the USA during the pandemic peaks.

FGFR2 genomic alterations are observed in 10–20% of cholangiocarcinoma (CCA). Although FGFR2 fusions are an important actionable target, FGFR2 protein expression has not been thoroughly characterized. To evaluate FGFR2 protein expression in cholangiocarcinoma harboring FGFR2 genomic alterations. FGFR2 protein expression was evaluated in 99 CCA cases with two different antibodies. FGFR2 genomic alterations were confirmed via next-generating sequencing (NGS) or FISH. Primary objective was to determine the specificity and sensitivity of FGFR2 immunohistochemistry staining for detecting FGFR2 genomic alterations. Secondary objectives included overall FGFR2 immunohistochemistry staining in CCA patients, and evaluation of whether FGFR2 expression correlates with clinical outcomes including overall survival (OS), progression-free survival (PFS), and time-to-tumor recurrence (TTR). Immunohistochemistry staining with two antibodies against FGFR2, FPR2-D, and clone 98706 showed high accuracy (78.7% and 91.9%) and specificity (82.9% and 97.7%), and moderate sensitivity (53.9% and 57.1%), respectively, when compared with the standard methods for detecting FGFR2 genomic alterations. In a median follow-up of 72 months, there were no statistically significant differences in OS, PFS, and TTR, for patients with positive or negative FGFR2 staining. FGFR2 protein expression by immunohistochemistry has high specificity and therefore could be used to imply the presence of FGFR2 genomic alterations in the context of a positive test. In the case of a negative test, NGS or FISH would be necessary to ascertain cases with FGFR2 genomic alterations.

Hippocampal hyperactivity driven by GABAergic interneuron deficits and NMDA receptor hypofunction is associated with the hyperdopaminergic state often observed in schizophrenia. Furthermore, previous research in the methylazoxymethanol acetate (MAM) rat model has demonstrated that repeated peripubertal diazepam administration can prevent the emergence of adult hippocampal hyperactivity, dopamine system hyperactivity, and associated psychosis-relevant behaviors. Here, we sought to characterize hippocampal GABAA and NMDA receptors in MAM-treated rats and to elucidate the receptor mechanisms underlying the promising effects of peripubertal diazepam exposure. Quantitative receptor autoradiography was used to measure receptor density in dorsal hippocampus CA1, ventral hippocampus CA1, and in ventral subiculum. Specifically, [3H]-Ro15-4513 was used to quantify the density of α5 GABAA receptors (α5GABAAR), [3H]-flumazenil to quantify α1-3;5GABAAR, and [3H]-MK801 to quantify NMDA receptors. MAM rats exhibited anxiety and schizophrenia-relevant behaviors as measured by elevated plus maze and amphetamine-induced hyperlocomotion (AIH), although diazepam only partially rescued these behaviors. α5GABAAR density was reduced in MAM-treated rats in all hippocampal sub-regions, and negatively correlated with AIH. Ventral hippocampus CA1 α5GABAAR density was positively correlated with anxiety-like behavior. Dorsal hippocampus CA1 NMDA receptor density was increased in MAM-treated rats, and positively correlated with AIH. [3H]-Flumazenil revealed no significant effects. Finally, we found no significant effect of diazepam treatment on receptor densities, potentially related to the only partial rescue of schizophrenia-relevant phenotypes. Overall, our findings provide first evidence of α5GABAAR and NMDA receptor abnormalities in the MAM model, suggesting that more selective pharmacological agents may become a novel therapeutic mechanism in schizophrenia.

PURPOSE The prevalence of germline pathogenic variants (PVs) in established breast cancer predisposition genes in women in the general population over age 65 years is not well-defined. However, testing guidelines suggest that women diagnosed with breast cancer over age 65 years might have < 2.5% likelihood of a PV in a high-penetrance gene. This study aimed to establish the frequency of PVs and remaining risks of breast cancer for each gene in women over age 65 years. METHODS A total of 26,707 women over age 65 years from population-based studies (51.5% with breast cancer and 48.5% unaffected) were tested for PVs in germline predisposition gene. Frequencies of PVs and associations between PVs in each gene and breast cancer were assessed, and remaining lifetime breast cancer risks were estimated for non-Hispanic White women with PVs. RESULTS The frequency of PVs in predisposition genes was 3.18% for women with breast cancer and 1.48% for unaffected women over age 65 years. PVs in BRCA1, BRCA2, and PALB2 were found in 3.42% of women diagnosed with estrogen receptor (ER)–negative, 1.0% with ER-positive, and 3.01% with triple-negative breast cancer. Frequencies of PVs were lower among women with no first-degree relatives with breast cancer. PVs in CHEK2, PALB2, BRCA2, and BRCA1 were associated with increased risks (odds ratio = 2.9-4.0) of breast cancer. Remaining lifetime risks of breast cancer were ≥ 15% for those with PVs in BRCA1, BRCA2, and PALB2. CONCLUSION This study suggests that all women diagnosed with triple-negative breast cancer or ER-negative breast cancer should receive genetic testing and that women over age 65 years with BRCA1 and BRCA2 PVs and perhaps with PALB2 and CHEK2 PVs should be considered for magnetic resonance imaging screening.

PURPOSE: Despite widespread provision of Lynch syndrome (LS) screening programs, questions remain about the most effective and efficient protocol for LS case finding. The purpose of this study was to explore the performance of the two protocols widely shown to be the most efficient and effective, respectively: immunohistochemical (IHC) staining of tumor and direct-to-sequencing (DtS) in endometrial cancer populations. METHODS: Simulation models were developed to explore performance of the IHC and DtS protocols, updated to reflect current evidence. Analyses explicitly account for protocol complexity and failure points, as well as decreased sequencing costs. Key outcomes are percent of LS cases identified, total protocol costs and efficiency, and break-even analyses of sequencing costs. All costs are in 2020 US dollars (USD). RESULTS: Under plausible conditions, the IHC protocol is expected to identify 40%-78% of LS cases and DtS protocol from 49% to 97%. When the key variable success in proceeding to sequencing is fixed for both protocols at 50%, 75%, and 100%, the DtS protocol is 9%, 12%, and 16% better at case finding, respectively, than the IHC protocol. The break-even cost of sequencing is about $488 USD when the outcome is total direct testing protocol costs; it is about $670 USD when the outcome is cost per LS case detected. CONCLUSION: This study quantifies the plausible differences in the clinical effectiveness and cost-effectiveness of the two LS case-finding protocols. We demonstrate the large influence of success in proceeding to sequencing and potential impact of decreasing sequencing prices.

During 2020, Victoria was the Australian state hardest hit by COVID-19, but was successful in controlling its second wave through aggressive policy interventions. We calibrated a detailed compartmental model of Victoria’s second wave to multiple geographically-structured epidemic time-series indicators. We achieved a good fit overall and for individual health services through a combination of time-varying processes, including case detection, population mobility, school closures, physical distancing and face covering usage. Estimates of the risk of death in those aged ≥75 and of hospitalisation were higher than international estimates, reflecting concentration of cases in high-risk settings. We estimated significant effects for each of the calibrated time-varying processes, with estimates for the individual-level effect of physical distancing of 37.4% (95%CrI 7.2−56.4%) and of face coverings of 45.9% (95%CrI 32.9−55.6%). That the multi-faceted interventions led to the dramatic reversal in the epidemic trajectory is supported by our results, with face coverings likely particularly important., The state of Victoria, Australia experienced a substantial second wave of COVID-19 but brought it under control with strict non-pharmaceutical interventions. Here, the authors model the second wave in Victoria to estimate the impacts of the different interventions.

Purpose To report surgical outcomes of combined vitrectomy for vitreous floaters and phacoemulsification surgery with multifocal intraocular lens implantation. Methods Retrospective, interventional, noncomparative case series of five eyes from five patients who underwent same-day combined phacoemulsification surgeries with apodized, diffractive multifocal intraocular lens implantation for cataract and pars plana vitrectomy for symptomatic vitreous opacities, that is, floaters. Primary outcomes were distance and near visual acuities, and resolution of symptoms. Secondary outcomes included intraocular pressure, refractive outcomes, and surgical complications. Results Mean logarithm of the minimum angle of resolution glare distance visual acuity improved from 0.36 (best-corrected Snellen 20/47) preoperatively to an uncorrected distance visual acuity of 0.05 (Snellen 20/23) at 6 months postoperatively (P = 0.042). All but one patient achieved multifocality with a near visual acuity of J2 or better. All patients noted subjective improvement in symptoms from floaters postoperatively. Mean intraocular pressure remained stable during follow-up. Two eyes ultimately required YAG capsulotomies for symptomatic posterior capsular opacification, one of which additionally received LASEK for refractive correction. Conclusion Multifocality and improvement in symptoms from symptomatic vitreous opacities were observed in this pilot series of carefully selected patients who underwent combined phacovitrectomy with multifocal intraocular lens implantation. A high rate of retinal tears was found in these patients. Appropriate caution should be taken in preoperative assessment and patient selection for the combined procedure.

OBJECTIVE: Major negative life events, such as trauma exposure, can play a key role in igniting or exacerbating psychopathology. However, few disorders are diagnosed with respect to precipitating events, and the role of these events in the unfolding of new psychopathology is not well understood. The authors conducted a multisite transdiagnostic longitudinal study of trauma exposure and related mental health outcomes to identify neurobiological predictors of risk, resilience, and different symptom presentations. METHODS: A total of 146 participants (discovery cohort: N = 69; internal replication cohort: N = 77) were recruited from emergency departments within 72 hours of a trauma and followed for the next 6 months with a survey, MRI, and physiological assessments. RESULTS: Task-based functional MRI 2 weeks after a motor vehicle collision identified four clusters of individuals based on profiles of neural activity reflecting threat reactivity, reward reactivity, and inhibitory engagement. Three clusters were replicated in an independent sample with a variety of trauma types. The clusters showed different longitudinal patterns of posttrauma symptoms. CONCLUSIONS: These findings provide a novel characterization of heterogeneous stress responses shortly after trauma exposure, identifying potential neuroimaging-based biotypes of trauma resilience and psychopathology.

Disaster planning is a core facet of modern health care practice. Owing to complex infrastructure requirements, radiology departments are vulnerable to system failures that may occur in isolation or during a disaster event when the urgency for and volume of imaging examinations increases. Planning for systems failures helps ensure continuity of service provision and patient care during an adverse event. Hazards to which a radiology department is vulnerable can be identified by applying a systematic approach with recognized tools such as the Hazard, Risk, and Vulnerability Analysis. Potential critical weaknesses within the department are highlighted by the Failure Mode and Effects Analysis tool. Recognizing the potential latent conditions and active failures that may impact systems allows implementation of strategies to prevent failure or to build resilience and mitigate the effects if they happen. Inherent system resilience to an adverse event can be estimated, and the ability of a department to operate during a disaster and the subsequent recovery can be predicted. The main systems at risk in a radiology department are staff, structure, stuff (supplies and/or equipment), and software, although individual issues and solutions within these are department specific. When medical imaging or examination interpretation needs cannot be met in the radiology department, the use of portable imaging modalities and teleradiology can augment the disaster response. All phases of disaster response planning should consider both sustaining operations and the transition back to normal function.

Background Although the Veterans RAND 12-item Physical Component Survey (VR-12 PCS) has been broadly used to evaluate patient-reported outcome measures (PROMs) in spine surgery, its feasibility for use in patients undergoing minimally invasive lumbar discectomy (MIS LD) has not been well studied. This study aimed to assess the feasibility of VR-12 PCS for use up to 2 years postoperatively for MIS LD by correlation with PROMs for physical function. Methods Patients undergoing primary single-level MIS LD procedures were reviewed retrospectively. Results on the VR-12 PCS, 12-Item Short Form (SF-12) PCS, and Patient-Reported Outcomes Measurement Information System (PROMIS PF) were recorded preoperatively and up to 2 years postoperatively. Improvements in postoperative PROMs were calculated and assessed for significant differences from baseline values. Correlation significance and strength were evaluated between VR-12 PCS and SF-12 PCS or PROMIS PF. Scatterplots were constructed to demonstrate relationships of VR-12 PCS with SF-12 PCS and PROMIS PF at each time point. Results Our cohort comprised 402 patients. Patients improved significantly from preoperative baseline for all 3 PROMs at all postoperative time points. Both Pearson's correlation and time-independent partial correlation revealed statistically significant strong correlations of VR-12 PCS with SF-12 PCS and PROMIS PF through 2-years. Discussion Physical function scores for VR-12, SF-12, and PROMIS PF all demonstrated significant improvements following MIS LD. Strongly statistically significant correlations of VR-12 PCS with SF-12 PCS and PROMIS PF from preoperative measures through 2 years demonstrate the feasibility of VR-12 for assessing patient-reported physical function in MIS LD patients.

Statins remain the drugs of choice in patients at risk of or with atherosclerotic cardiovascular disease (ASCVD). Statins have limitations that drive the development of investigational agents to manage dyslipidemias and/or reduce ASCVD risk. There are a few small-molecule drugs that have the potential to mitigate ASCVD risk either alone or in combination with statins. Most lipid-modifying drugs in clinical development are biologic agents that target specific enzymes or genetic-based protein synthesis. Limitations of the biologic agents include complex mechanisms of action and manufacturing processes with indications in select patients with genetic dyslipidemia or who have failed traditional therapies. The ultimate clinical utility of the new and investigational agents will become established over the next several years.Lay abstract The most common medications that reduce fat (cholesterol) in the blood are called ‘statins.’ Statins reduce the chance of having a heart attack, stroke or cardiac death. Statins do not completely eliminate these risks and some patients cannot tolerate them. New medications are being tested to find out if they reduce the risk of heart problems. Many of the new drugs are called ‘biologics.’ Biologics work through complex mechanisms to reduce the amount of fat produced or by limiting the toxicity of the fat. Many of the new medications are difficult to manufacture and must be given as injections. They are expensive but possibly effective for patients unable to take statins or patients with rare cholesterol disorders.

BACKGROUND Psychological factors have been shown to be consistent predictors of chronic pain in people with musculoskeletal injuries. However, few prognostic studies have considered multiple risk factors including peritraumatic distress. In addition, previous research has not considered that the associations between peritraumatic distress and pain levels can vary across pain outcomes. QUESTION/PURPOSE To determine whether an easily measurable level of baseline distress is associated with pain levels 1 year after noncatastrophic traumatic injuries when the outcome to be assessed is not normally distributed. METHODS This was a prospective cohort study. The data were captured from two cohorts in London, Ontario, Canada, and Chicago, IL, USA. Participants were adults with acute noncatastrophic (that is, not treated with surgery or hospitalization) musculoskeletal injuries of any etiology with various injury locations (60% [145 of 241] spinal and 40% [96 of 241] peripheral) that presented to local urgent care centers. Other inclusion criteria included English/French speakers and having no other disorder that would affect their pain levels. In total, between the years 2015 and 2018, 241 participants were recruited based on the inclusion criteria. Ninety-three percent (225 of 241) of participants provided baseline data, and of these, 48% (109 of 225) were lost to follow-up in 1 year. Based on a complete case approach, this study included 116 participants who ranged in age from 18 to 66 years and 69% (80) of whom were women. The Traumatic Injuries Distress Scale (TIDS) was used to evaluate distress at baseline (within 4 weeks of injury). The TIDS is a validated, reliable 12-item risk prognosis screening tool that takes less than 3 minutes to complete with questions regarding uncontrolled pain, negative affect, and intrusion/hyperarousal. The minimum and maximum possible scores are 0 and 24, with higher scores indicating higher levels of distress. The Numeric Pain Rating Scale (NPRS) was used to assess the pain level at baseline and again 12 months postinjury. To complete the NPRS, participants rate the severity of their pain on a scale of 0 to 10, with 0 indicating no pain and 10 indicating the worst pain imaginable. NPRS scores of 1 to 3 indicate mild pain, 4 to 6 indicate moderate pain and 7 or higher indicate severe pain. As a preliminary analysis, to assess whether the participants as a group experienced recovery, a paired samples t-test was used to compare NPRS scores at baseline and 12 months. In all, 52% (60 of 116) of participants reported no pain (NPRS = 0), and mean pain intensity scores improved from 4.8 ± 2.1 at baseline to 1.6 ± 1.6 at 12-month follow-up (p < 0.001). Quantile regression was used to describe the association between baseline distress and pain levels 1 year after the injury. This technique was used because it reveals the relationships at different quantiles of the pain outcome distribution. RESULTS The results indicate some people (52% [60 of 116]) recovered regardless of their baseline level of distress (30th quantile of the NPRS: β = 0). However, in those with persisting pain, higher levels of baseline distress are associated with greater levels of pain 12 months after the injury (50th quantile of the NPRS: β = 0.11; p = 0.01; 70th quantile of the NPRS: β = 0.27; p < 0.001; 90th quantile of the NPRS: β = 0.31; p = 0.01). According to this model, with a baseline TIDS score of 5, there is 10% probability that patients will report moderate or greater levels of pain (4 or higher of 10) 12 months later. This probability then increases as the TIDS score increases. For instance, at a score of 13 on the TIDS, the probability of a patient reporting moderate or higher levels of pain increases to 30%, and the probability of reporting severe pain (higher than 6 of 10) is 10%. CONCLUSION Clinicians and surgeons in orthopaedic settings can screen for the presence of peritraumatic distress using the TIDS, which is an easily administered tool that does not require extensive knowledge of psychology, and by using it they can identify those with higher levels of distress who are more likely to have persistent, long-term pain. A score of 4 or less indicates a low risk of persistent pain, a score between 5 and 12 (endpoints included) indicates moderate risk, and a score of 13 or higher indicates high risk. Future studies should investigate whether certain immediate interventions for peritraumatic distress in the aftermath of trauma can decrease the likelihood that a patient will develop chronic pain after injury. As an analysis technique, quantile regression is useful to assess complex associations in many orthopaedic settings in which a certain outcome is expected to occur in most patients leading to non-normally distributed data. LEVEL OF EVIDENCE Level II, therapeutic study.

Background and burden Trauma with its early and late consequences disproportionately effects those from poor countries. The availability of effective orthopaedic and trauma care varies significantly across the globe. Challenges The balancing out of quality care is required to reach the health-related UN development goal set out in 2015. A multifactorial approach addressing local, national and international aspects is key to improving the discrepancy seen between high- and low-income countries.

Rationale: Current guidelines recommend patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia receive empirical antibiotics for suspected bacterial superinfection on the basis of weak evidence. Rates of ventilator-associated pneumonia (VAP) in clinical trials of patients with SARS-CoV-2 pneumonia are unexpectedly low. Objectives: We conducted an observational single-center study to determine the prevalence and etiology of bacterial superinfection at the time of initial intubation and the incidence and etiology of subsequent bacterial VAP in patients with severe SARS-CoV-2 pneumonia. Methods: Bronchoscopic BAL fluid samples from all patients with SARS-CoV-2 pneumonia requiring mechanical ventilation were analyzed using quantitative cultures and a multiplex PCR panel. Actual antibiotic use was compared with guideline-recommended therapy. Measurements and Main Results: We analyzed 386 BAL samples from 179 patients with SARS-CoV-2 pneumonia requiring mechanical ventilation. Bacterial superinfection within 48 hours of intubation was detected in 21% of patients. Seventy-two patients (44.4%) developed at least one VAP episode (VAP incidence rate = 45.2/1,000 ventilator days); 15 (20.8%) initial VAPs were caused by difficult-to-treat pathogens. The clinical criteria did not distinguish between patients with or without bacterial superinfection. BAL-based management was associated with significantly reduced antibiotic use compared with guideline recommendations. Conclusions: In patients with SARS-CoV-2 pneumonia requiring mechanical ventilation, bacterial superinfection at the time of intubation occurs in

OBJECTIVE To determine whether childhood maltreatment is associated with immune-mediated inflammatory disorders (IMID; multiple sclerosis [MS], inflammatory bowel disease [IBD] and rheumatoid arthritis [RA]). We further aimed to determine the relationship between maltreatment and psychiatric comorbidity in IMID and whether these relationships differed across IMID. METHODS 681 participants (MS: 232, IBD: 216, RA: 130, healthy controls: 103) completed a structured psychiatric interview to identify psychiatric disorders, and the Childhood Trauma Questionnaire to evaluate five types of maltreatment: emotional abuse, physical abuse, sexual abuse, emotional neglect and physical neglect. We evaluated associations between maltreatment, IMID and psychiatric comorbidity using multivariable logistic regression models. RESULTS The prevalence of having ≥1 maltreatment was similar across IMID, but higher than in controls (MS: 63.8%, IBD: 61.6%, RA: 62.3%, healthy controls: 45.6%). Emotional abuse was associated with having an IMID (adjusted odds ratio [aOR] 2.37; 1.15-4.89). In the sex-specific analysis, this association was only present in women. History of childhood maltreatment was associated with a lifetime diagnosis of a psychiatric disorder in the IMID cohort (OR 2.24; 1.58-3.16), but this association did not differ across diseases. In those with IMID, total types of maltreatments (aOR 1.36; 1.17-1.59) and emotional abuse (aOR 2.64; 1.66-4.21) were associated with psychiatric comorbidity. CONCLUSIONS Childhood maltreatment is more common in IMID than in a healthy population, and is associated with psychiatric comorbidity. Given the high burden of psychiatric disorders in the IMID population, clinicians should be aware of the contribution of maltreatment and the potential need for trauma-informed care strategies.