The Effect of a Tobacco Use Reduction Program on the Prevalence of Smoking and Tobacco Use and Quitting Behavior Among People Living With HIV/AIDS in Michigan.

HIV has evolved from a serious infectious disease to a manageable chronic disease. Tobacco use has a devastating effect on the health of people living with HIV/AIDS (PLWH). The Michigan Tobacco Use Reduction Program for PLWH was established in 2015 to learn about tobacco use among PLWH, gather information on entities that provide health care services to PLWH, and improve tobacco treatment services for this population. The program offers evidence-based treatment interventions to all PLWH who are tobacco users, eligible for the Ryan White HIV/AIDS Program, and served by AIDS service organizations in Michigan. This evaluation had 3 primary outcomes: 1) rates of smoking and tobacco use among program clients, 2) the percentage of clients who made a quit attempt in the previous 12 months, and 3) the types of tobacco cessation methods used by clients. All data were self-reported in 3 surveys, one each in 2015, 2017, and 2021. The rate of cigarette smoking overall among clients decreased significantly from 49.5% in 2015 to 41.5% in 2017. The percentage of clients who made a quit attempt increased from 37.0% in 2015 to 41.9% in 2017; in 2021, this rate was 54.4%. By age, in all 3 survey years, the highest rate of tobacco use was among clients aged 35 to 44 years (range, 48.4%-57.4%). Smoking rates declined significantly from 2015 to 2017 among African American (50.5% to 42.8%) and White clients (49.8% to 39.9%). The most frequently used method of tobacco cessation was medications prescribed by a physician (range, 20%-30%). State tobacco control programs are encouraged to collaborate with their state HIV/AIDS bureaus to create similar programs to treat tobacco use among PLWH.

Regional and bilateral MRI and gene signatures in facioscapulohumeral dystrophy: implications for clinical trial design and mechanisms of disease progression.

Identifying the aberrant expression of DUX4 in skeletal muscle as the cause of facioscapulohumeral dystrophy (FSHD) has led to rational therapeutic development and clinical trials. Several studies support the use of MRI characteristics and the expression of DUX4-regulated genes in muscle biopsies as biomarkers of FSHD disease activity and progression. We performed lower-extremity MRI and muscle biopsies in the mid-portion of the tibialis anterior (TA) muscles bilaterally in FSHD subjects and validated our prior reports of the strong association between MRI characteristics and expression of genes regulated by DUX4 and other gene categories associated with FSHD disease activity. We further show that measurements of normalized fat content in the entire TA muscle strongly predict molecular signatures in the mid-portion of the TA, indicating that regional biopsies can accurately measure progression in the whole muscle and providing a strong basis for inclusion of MRI and molecular biomarkers in clinical trial design. An unanticipated finding was the strong correlations of molecular signatures in the bilateral comparisons, including markers of B-cells and other immune cell populations, suggesting that a systemic immune cell infiltration of skeletal muscle might have a role in disease progression.

Evaluating the safety, tolerability, and immunogenicity of a 24-valent pneumococcal conjugate vaccine (VAX-24) in healthy adults aged 18 to 64 years: a phase 1/2, double-masked, dose-finding, active-controlled, randomised clinical trial.

BACKGROUND: Despite substantial reductions in pneumococcal disease with the availability of pneumococcal conjugate vaccines, a significant burden of pneumococcal disease remains due to the diversity of serotypes combined with serotype replacement. We developed a new vaccine candidate, VAX-24 (24-valent pneumococcal conjugate vaccine), using cell-free protein synthesis to produce a variant of cross-reactive material 197 (eCRM) as the carrier protein, increasing serotype coverage while minimising carrier suppression. The aim of this clinical trial was to assess the safety, tolerability, and immunogenicity of three different doses of VAX-24 compared to pneumococcal 20-valent conjugate vaccine (PCV20). METHODS: This was a phase 1/2, randomised, double-masked study of VAX-24 versus PCV20 conducted in the USA. Key inclusion criteria included being a male or female aged 18 to 64 years in good health; key exclusion criteria included previous history of pneumococcal disease, receipt of a licensed or investigational pneumococcal vaccine, or immunosuppressive therapy. Participants were randomly allocated in a 1:1:1:1 ratio by permuted block to receive one dose of VAX-24 (1·1 µg of each antigen, 2·2 µg of each antigen, or 2·2 µg of 17 antigens mixed with 4·4 µg of seven antigens), or PCV20. The safety population included all participants with safety data. The immunogenicity population was as per-treatment in phase 2. Primary outcome measures included solicited and unsolicited adverse events. Secondary outcomes included serotype-specific opsonophagocytic activity (OPA) geometric mean titres (GMT), and IgG geometric mean concentrations (GMC) were measured 1 month postvaccination. Traditional non-inferiority criteria included OPA geometric mean ratio (GMR), with a lower bound of the two sided 95% CI of greater than 0·5 for shared serotypes. This completed trial is registered at ClinicalTrials.gov, NCT05266456. FINDINGS: Safety profiles were comparable among the treatment groups, with 170 of 209 participants (81%, 95% CI 75·2-86·2) to 178 of 207 participants (86%, 80·5-90·4) reporting at least one solicited adverse event among the three VAX-24 groups. 24 of 207 participants (12%, 7·6-16·8) to 32 of 209 of participants (15%, 10·7-20·9) experiened an unsolicited treatment emergent adverse event within 1 month postvaccination. VAX-24 2·2 µg met traditional OPA GMR non-inferiority criteria for all 20 shared serotypes; 16 serotypes elicited GMR point estimates greater than 1·0, and four reached the lower bound of the two-sided 95% CI greater than 1·0. INTERPRETATION: VAX-24 had a safety profile similar to PCV20 at all doses, with the 2·2 µg dose showing increased serotype coverage with decreased carrier suppression. FUNDING: Vaxcyte.

DUX4 expression in cancer induces a metastable early embryonic totipotent program.

The transcription factor DUX4 regulates a portion of the zygotic gene activation (ZGA) program in the early embryo. Many cancers express DUX4 but it is unknown whether this generates cells similar to early embryonic stem cells. Here we identified cancer cell lines that express DUX4 and showed that DUX4 is transiently expressed in a small subset of the cells. DUX4 expression activates the DUX4-regulated ZGA transcriptional program, the subsequent 8C-like program, and markers of early embryonic lineages, while suppressing steady-state and interferon-induced MHC class I expression. Although DUX4 was expressed in a small number of cells under standard culture conditions, DNA damage or changes in growth conditions increased the fraction of cells expressing DUX4 and its downstream programs. Our demonstration that transient expression of endogenous DUX4 in cancer cells induces a metastable early embryonic stem cell program and suppresses antigen presentation has implications for cancer growth, progression, and immune evasion.

Risk Factors for Postoperative Infections in Cardiac Surgery Patients: A Retrospective Study.

Background and objective Cardiac surgery is one of the most common surgical procedures globally; its incidence has been on the rise due to the faster pace of population aging thanks to technological and epidemiological advances. Patients who undergo cardiac surgeries may face various postoperative complications that might affect their survival, and one of these major complications is infection. Nosocomial pneumonia, surgical site infection (SSI), mediastinitis, bacteremia, and sepsis are common infections encountered after surgeries. In this study, we aimed to determine the common risk factors related to postoperative infections at the King Faisal Cardiac Center from January 2014 to September 2020. Materials and methods  Records from 364 patients who underwent cardiac surgery and were aged above 18 years were assessed for postoperative infections in this retrospective cohort study. Patients who were immunosuppressed or had active systemic infections were excluded. Consent was waived by the Institutional Review Board. All procedures were performed at the King Faisal Cardiac Center, National Guard Hospital, Jeddah. Results Of the total 364 patients, 105 were women and 259 were men. The mean age of the cohort was 59 years (SD = 13) and the mean BMI was 29.1 kg/m2 (SD = 5.3). The study population showed a high prevalence of cardiac risk factors and diseases: diabetes (n = 244, 67%), hypertension (n = 230, 63%), dyslipidemia (n = 144, 40%), smoking (n = 80, 22%), heart failure (n = 41, 11%), and chronic obstructive pulmonary disease (n = 6, 1.6%). The overall rate of postoperative infection was 32.7% (n = 120), and 17 (14%) of these infected patients underwent reoperations for infection. Conclusion Based on a thorough analysis of 364 patients undergoing various cardiac surgical procedures, including a multivariate analysis accounting for preoperative factors, there was a significant association between postoperative infections and hypertension, diabetes, increased preoperative activated partial thromboplastin time, and elevated HbA1c.

The transcription factor DUX4 orchestrates translational reprogramming by broadly suppressing translation efficiency and promoting expression of DUX4-induced mRNAs.

Translational control is critical for cell fate transitions during development, lineage specification, and tumorigenesis. Here, we show that the transcription factor double homeobox protein 4 (DUX4), and its previously characterized transcriptional program, broadly regulates translation to change the cellular proteome. DUX4 is a key regulator of zygotic genome activation in human embryos, whereas misexpression of DUX4 causes facioscapulohumeral muscular dystrophy (FSHD) and is associated with MHC-I suppression and immune evasion in cancer. We report that translation initiation and elongation factors are disrupted downstream of DUX4 expression in human myoblasts. Genome-wide translation profiling identified mRNAs susceptible to DUX4-induced translation inhibition, including those encoding antigen presentation factors and muscle lineage proteins, while DUX4-induced mRNAs were robustly translated. Endogenous expression of DUX4 in human FSHD myotubes and cancer cell lines also correlated with reduced protein synthesis and MHC-I presentation. Our findings reveal that DUX4 orchestrates cell state conversion by suppressing the cellular proteome while maintaining translation of DUX4-induced mRNAs to promote an early developmental program.

A Phase 1 Two-Arm, Randomized, Double-Blind, Active-Controlled Study of Live, Oral Plasmid-Derived Adenovirus Type 4 and Type 7 Vaccines in Seronegative Adults.

PXVX0047 is an investigational vaccine developed for active immunization to prevent febrile acute respiratory disease (ARD) caused by adenovirus serotypes 4 (Ad4) and 7 (Ad7). PXVX0047 consists of a modernized, plasmid-derived vaccine that was generated using a virus isolated from Wyeth Ad4 and Ad7 vaccine tablets. A phase 1 two-arm, randomized, double-blind, active-controlled study was conducted to evaluate the safety profile and immunogenicity of the investigational adenovirus vaccines. The two components of PXVX0047 were administered orally together in a single dose to 11 subjects. For comparison, three additional subjects received the Ad4/Ad7 vaccine that is currently in use by the US military. The results of this study show that the tolerability and immunogenicity of the PXVX0047 Ad7 component are comparable with that of the control Ad4/Ad7 vaccine; however, the immunogenicity of the PXVX0047 Ad4 component was lower than expected. Clinical trial number NCT03160339.

Changes in Healthcare During the Past 30 Years: Can the National Health Service in the United Kingdom Survive?

At the turn of the century, the National Health Service (NHS) in the United Kingdom (UK) was considered one of the top public healthcare systems in the world. Not only was it comprehensive and inclusive, but it was also free at the point of delivery for the entire UK population. It was also largely available to visitors and the families of residents that lived outside the UK. During the past 30 years, the NHS has received more and more funding both in cash terms and as a percentage of the gross national product. Despite this, the general consensus is that the NHS is delivering a poor service. The current government is facing unprecedented strike action from all areas of the workforce including doctors and nurses. This editorial asks the following questions: Where has the money gone? What has caused the current crisis? Can the current NHS model survive in today's highly technological healthcare environment?

Human DUX4 and mouse Dux interact with STAT1 and broadly inhibit interferon-stimulated gene induction.

DUX4 activates the first wave of zygotic gene expression in the early embryo. Mis-expression of DUX4 in skeletal muscle causes facioscapulohumeral dystrophy (FSHD), whereas expression in cancers suppresses IFNγ induction of major histocompatibility complex class I (MHC class I) and contributes to immune evasion. We show that the DUX4 protein interacts with STAT1 and broadly suppresses expression of IFNγ-stimulated genes by decreasing bound STAT1 and Pol-II recruitment. Transcriptional suppression of interferon-stimulated genes (ISGs) requires conserved (L)LxxL(L) motifs in the carboxyterminal region of DUX4 and phosphorylation of STAT1 Y701 enhances interaction with DUX4. Consistent with these findings, expression of endogenous DUX4 in FSHD muscle cells and the CIC-DUX4 fusion containing the DUX4 CTD in a sarcoma cell line inhibit IFNγ induction of ISGs. Mouse Dux similarly interacted with STAT1 and suppressed IFNγ induction of ISGs. These findings identify an evolved role of the DUXC family in modulating immune signaling pathways with implications for development, cancers, and FSHD.

Validation of the association between MRI and gene signatures in facioscapulohumeral dystrophy muscle: implications for clinical trial design.

Identifying the aberrant expression of DUX4 in skeletal muscle as the cause of facioscapulohumeral dystrophy (FSHD) has led to rational therapeutic development and clinical trials. Several studies support the use of MRI characteristics and the expression of DUX4-regulated genes in muscle biopsies as biomarkers of FSHD disease activity and progression, but reproducibility across studies needs further validation. We performed lower-extremity MRI and muscle biopsies in the mid-portion of the tibialis anterior (TA) muscles bilaterally in FSHD subjects and validated our prior reports of the strong association between MRI characteristics and expression of genes regulated by DUX4 and other gene categories associated with FSHD disease activity. We further show that measurements of normalized fat content in the entire TA muscle strongly predict molecular signatures in the mid-portion of the TA. Together with moderate-to-strong correlations of gene signatures and MRI characteristics between the TA muscles bilaterally, these results suggest a whole muscle model of disease progression and provide a strong basis for inclusion of MRI and molecular biomarkers in clinical trial design.

Examining the consequences of dehumanization and adultification in justification of police use of force against Black girls and boys.

OBJECTIVE: Given the greater contact that Black youth have with the legal system compared with White youth, it is important to consider the differential ways that police use of force against these youth is perceived. Black youth may be at greater risk than White youth for animalistic (being seen as animal-like) and mechanistic (being seen as object-like) dehumanization, which, along with a tendency for Black youth to be perceived as older (adultification), may impact observers' perceptions of police use of force toward Black youth. This study examined whether dehumanization and adultification were associated with the perceptions of force used and harm caused by police. HYPOTHESES: We made five hypotheses. First, participants would dehumanize Black individuals more than White individuals, more mechanistically dehumanize Black women than Black men, and more animalistically dehumanize Black men than Black women. Second, dehumanization would be positively associated with adultification. Third, force would be rated as less appropriate and more excessive for White than for Black targets, particularly for males. Fourth, dehumanization, particularly animalistic dehumanization, would be associated with higher participant ratings of force justification and lower participant ratings of force severity and excessiveness. Fifth, participants would perceive girls as more harmed than boys and White individuals as more harmed than Black individuals. METHOD: After completing an implicit dehumanization measure, participants viewed an image (varied on age and gender) of a juvenile, estimated the juvenile's age, and read a vignette in which the juvenile had an altercation with police. Participants rated the amount, severity, and justification of the force used by the officer as well as the physical and emotional harm caused to the juvenile. RESULTS: We found that Black targets were dehumanized more than White targets. Adultification, unrelated to implicit dehumanization, predicted perceiving police use of force against juveniles as more justified and less severe. Black girls were most likely to experience adultification; participants generally perceived them as less victimized than Black boys and White girls. CONCLUSIONS: Adultification is associated with fewer protections for youth. Those with particular intersectional identities, such as Black girls, may be uniquely vulnerable to harm caused by police victimization. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Human DUX4 and porcine DUXC activate similar early embryonic programs in pig muscle cells: implications for preclinical models of FSHD.

Human DUX4 and its mouse ortholog Dux are normally expressed in the early embryo-the 4-cell or 2-cell cleavage stage embryo, respectively-and activate a portion of the first wave of zygotic gene expression. DUX4 is epigenetically suppressed in nearly all somatic tissue, whereas facioscapulohumeral dystrophy (FSHD)-causing mutations result in its aberrant expression in skeletal muscle, transcriptional activation of the early embryonic program and subsequent muscle pathology. Although DUX4 and Dux both activate an early totipotent transcriptional program, divergence of their DNA binding domains limits the use of DUX4 expressed in mice as a preclinical model for FSHD. In this study, we identify the porcine DUXC messenger ribonucleic acid expressed in early development and show that both pig DUXC and human DUX4 robustly activate a highly similar early embryonic program in pig muscle cells. These results support further investigation of pig preclinical models for FSHD.

Identifying Facilitators, Barriers, and Potential Solutions of Adopting Exoskeletons and Exosuits in Construction Workplaces.

Exoskeletons and exosuits (collectively termed EXOs) have the potential to reduce the risk of work-related musculoskeletal disorders (WMSDs) by protecting workers from exertion and muscle fatigue due to physically demanding, repetitive, and prolonged work in construction workplaces. However, the use of EXOs in construction is in its infancy, and much of the knowledge required to drive the acceptance, adoption, and application of this technology is still lacking. The objective of this research is to identify the facilitators, barriers, and corresponding solutions to foster the adoption of EXOs in construction workplaces through a sequential, multistage Delphi approach. Eighteen experts from academia, industry, and government gathered in a workshop to provide insights and exchange opinions regarding facilitators, barriers, and potential solutions from a holistic perspective with respect to business, technology, organization, policy/regulation, ergonomics/safety, and end users (construction-trade professionals). Consensus was reached regarding all these perspectives, including top barriers and potential solution strategies. The outcomes of this study will help the community gain a comprehensive understanding of the potential for EXO use in the construction industry, which may enable the development of a viable roadmap for the evolution of EXO technology and the future of EXO-enabled workers and work in construction workplaces.

Safety and immunogenicity of PXVX0317, an aluminium hydroxide-adjuvanted chikungunya virus-like particle vaccine: a randomised, double-blind, parallel-group, phase 2 trial.

BACKGROUND: Chikungunya virus (CHIKV) disease is an ongoing public health threat. We aimed to evaluate the safety and immunogenicity of PXVX0317, an aluminium hydroxide-adjuvanted formulation of a CHIKV virus-like particle (VLP) vaccine. METHODS: This randomised, double-blind, parallel-group, phase 2 trial was conducted at three clinical trial centres in the USA. Eligible participants were healthy CHIKV-naïve adults aged 18-45 years. Participants were stratified by site and randomly assigned (1:1:1:1:1:1:1:1) to one of the eight vaccination groups using a block size of 16. Group 1 received two doses of unadjuvanted PXVX0317 28 days apart (2 × 20 µg; standard); all other groups received adjuvanted PXVX0317: groups 2-4 received two doses 28 days apart (2 × 6 µg [group 2], 2 × 10 µg [group 3], or 2 × 20 µg [group 4]; standard); group 4 also received a booster dose 18 months after the first active injection (40 µg; standard plus booster); groups 5-7 received two doses 14 days apart (2 × 6 µg [group 5], 2 × 10 µg [group 6], or 2 × 20 µg [group 7]; accelerated); and group 8 received one dose (1 × 40 µg; single). The primary endpoint was the geometric mean titre of anti-CHIKV neutralising antibody on day 57 (28 days after the last vaccination), assessed in the immunogenicity-evaluable population. Additionally, we assessed safety. This trial is registered at ClinicalTrials.gov, NCT03483961. FINDINGS: This trial was conducted from April 18, 2018, to Sept 21, 2020; 468 participants were assessed for eligibility. Of these, 415 participants were randomly assigned to eight groups (n=53 in groups 1, 5, and 6; n=52 in groups 2 and 8; n=51 in groups 3 and 7; and n=50 in group 4) and 373 were evaluable for immunogenicity. On day 57, serum neutralising antibody geometric mean titres were 2057·0 (95% CI 1584·8-2670·0) in group 1, 1116·2 (852·5-1461·4; p=0·0015 vs group 1 used as a reference) in group 2, 1465·3 (1119·1-1918·4; p=0·076) in group 3, 2023·8 (1550·5-2641·7; p=0·93) in group 4, 920·1 (710·9-1190·9; p<0·0001) in group 5, 1206·9 (932·4-1562·2; p=0·0045) in group 6, 1562·8 (1204·1-2028·3; p=0·14) in group 7, and 1712·5 (1330·0-2205·0; p=0·32) in group 8. In group 4, a booster dose increased serum neutralising antibody geometric mean titres from 215·7 (95% CI 160·9-289·1) on day 547 to 10 941·1 (7378·0-16 225·1) on day 575. Durability of the immune response (evaluated in groups 1, 4, and 8) was shown up to 2 years. The most common solicited adverse event was pain at the injection site, reported in 12 (23%) of 53 participants who received the unadjuvanted vaccine (group 1) and 111 (31%) of 356 who received the adjuvanted vaccine. No vaccine-related serious adverse events were reported. INTERPRETATION: PXVX0317 was well tolerated and induced a robust and durable serum neutralising antibody immune response against CHIKV up to 2 years. A single 40 µg injection of adjuvanted PXVX0317 is being further investigated in phase 3 clinical trials (NCT05072080 and NCT05349617). FUNDING: Emergent BioSolutions.

Cerebral oximetry in adult cardiac surgery to reduce the incidence of neurological impairment and hospital length-of-stay: A prospective, randomized, controlled trial.

Background: Cerebral oximetry using near-infrared spectroscopy (NIRS) has been shown to reduce neurological dysfunction and hospital length-of-stay after adult cardiac surgery in some but not all studies. We audited maintaining cerebral saturations at or above baseline and showed improved neurological and length-of-stay outcomes. Our hypothesis for this study was that our NIRS protocol would improve neurological and length-of-stay outcomes. Methods: This prospective, single centre, double-blinded controlled study randomized 182 consecutive patients, scheduled for cardiac surgery using cardiopulmonary bypass. Participants were randomized by concealed envelope prior to anaesthesia. NIRS study group were managed perioperatively using our NIRS protocol of 8 interventions, increase cardiac output, normocapnia, increase mean arterial pressure, increase inspired oxygen, depth of anaesthesia, blood transfusion, correction of bypass cannula, change of surgical plan to restore levels equal to or above baseline. The control group had standard management without NIRS. Primary outcomes were neurological impairment (early and late) and hospital length-of-stay. Secondary outcomes were ventilation times, intensive care length-of-stay, major organ dysfunction and mortality. Results: 91 patients entered each group. There was a significant improvement in self-reported six-month general functionality in the NIRS group (p = 0.016). Early neurological dysfunction and hospital length-of-stay was the same in both groups. Of the secondary outcomes only Intensive Care length-of-stay was statistically significant, being shorter in the NIRS group (p = 0.026). Conclusion: Maintaining cerebral saturations above baseline reduces time spent in Intensive Care and may improve long term functional recovery but not stroke, major organ dysfunction and mortality.

Vasoplegic Syndrome Post-cardiopulmonary Bypass in a Renal Transplant Patient: The Brain Is Not the Index Organ.

Vasoplegia syndrome (VS) is seen in cardiac surgery post-cardiopulmonary bypass (CPB) and defined by increasing requirements for more than one vasoactive agent to which the patient's response is reduced. It is also associated with normal or high cardiac output (CO). Prolonged CPB time is the second commonest precipitating factor. Here, we describe a young adult, with good right ventricular (RV) and left ventricular (LV) function, who previously was a renal transplant recipient with a functioning kidney who developed VS and shock after CPB to replace the mitral and aortic valves. During the first two hours of CPB, his mean arterial blood pressure (MAP) was never lower than 50 mmHg. His brain regional cerebral oxygen saturation (rSO2) remained above baseline, and his body temperature was kept at 33°C. Urine output was constant at 40 ml/hr. He came off CPB requiring two inotropes and two vasoconstrictors. Even so, his systolic blood pressure was low, and his pulse pressure narrows. He was then started on methylene blue which improved his MAP. On arrival to the intensive care unit (ICU), he immediately required continuous veno-veno haemodialysis (CVVHD) and developed acute liver failure. At 16 hours, he showed a clinically fair neurological recovery. Forty-eight hours post-surgery, he suffered multiorgan failure and developed an intractable arrhythmia and died. The unusual components were as follows: he was normally responsive to phenylephrine during CPB; despite normal rSO2 and a clinically neurological recovery, he suffered multiorgan failure; and his serial high-sensitivity (HS) troponin I levels never fell below 500,000 pg/ml (normal <14 pg/ml).

Variations of intestinal malrotation in adults: A case report of midgut volvulus and literature review for the surgeon.

INTRODUCTION: Intestinal malrotation is a rare congenital abnormality occurring in 0.2-1% of the population. Adult presentations comprise only 0.2-0.5% of all cases leading to diagnostic challenges and worse outcomes in adults. We present a rare case of chronic/intermittent midgut volvulus with unique anatomic findings in an adult with intestinal malrotation. PRESENTATION OF CASE: An 18-year-old Caucasian male presented to a community hospital with abdominal pain, nausea, and vomiting. He underwent a CT scan demonstrating concern for small bowel volvulus and subsequently underwent a negative exploratory laparotomy. He was discharged post-operatively with no identified etiology for his presentation. He subsequently had multiple presentations to the ED with recurrent symptoms, review of imaging led to concern for duodenal volvulus resulting in transfer to a tertiary hepatobiliary centre. Repeat CT scan two weeks following initial presentation was consistent with intestinal malrotation with midgut volvulus. Bloodwork was unremarkable and physical exam demonstrated normal vital signs with a tender epigastrium. He underwent an exploratory laparotomy with Ladd's procedure. Intra-operative findings included a midgut volvulus and uniquely positioned Ladd's bands to the transverse colon. Post-operatively he tolerated oral intake and was discharged with three-month follow-up. DISCUSSION: Adults with intestinal malrotation suffer from delays in diagnosis and management. In contrast to the neonatal population, adults often present with vague, or chronic symptoms, which obscures the diagnosis. CONCLUSION: The increased morbidity and mortality observed in adults with intestinal malrotation highlights the need for surgeons to appreciate the challenges associated with this diagnosis in the adult population to ensure early recognition and management.

Upfront Small Bowel Resection for Small Bowel Neuroendocrine Tumors With Synchronous Metastases: A Propensity-score Matched Comparative Population-based Analysis.

OBJECTIVE: We examined the impact of upfront small bowel resection (USBR) for metastatic small bowel neuroendocrine (SB-NET) compared to nonoperative management (NOM) on long-term healthcare utilization and survival outcomes. SUMMARY OF BACKGROUND DATA: The role of early resection of the primary tumor in metastatic SB-NET remains controversial. Conflicting data exist regarding its clinical and survival benefits. METHODS: This is a population-based retrospective matched comparative cohort study of adults diagnosed with synchronous metastatic SB-NET between 2001 and 2017 in Ontario. USBR was defined as resection within 6 months of diagnosis. Primary outcomes were subsequent unplanned acute care admissions and small bowel-related surgery. Secondary outcome was overall survival. USBR and NOM patients were matched 2:1 using a propensity-score. We used time-to-event analyses with cumulative incidencefunctions and univariate Andersen-Gill regression for primary outcomes. E value methods assessed the potential for residual confounding. RESULTS: Of 1000 patients identified, 785 had USBR. The matched cohort included 348 patients with USBR and 174 with NOM. Patients with USBR had lower 3-year risk of subsequent admissions (72.6% vs 86.4%, P < 0.001) than those with NOM, with hazard ratio 0.72 (95% confidence interval 0.570.91). USBR was associated with lower risk of subsequent small bowel-related surgery (15.4% vs 40.3%, P < 0.001), with hazard ratio 0.44 (95% confidence interval 0.29-0.67). E -values indicated it was unlikely that the observed risk estimates could be explained by an unmeasured confounder. Sensitivity analysis excluding emergent resections to define USBR did not alter the results. CONCLUSIONS: USBR for SB-NETs in the presence of metastatic disease was associated with better patient-oriented outcomes of decreased subsequent admissions and interventions, compared to NOM. USBR should be considered for metastatic SB-NETs.

Long-term Dependency Outcomes in Older Adults Following Hepato-Pancreato-Biliary Surgery for Cancer: A Population-based Analysis.

OBJECTIVE: To evaluate healthcare dependency following hepatopancreato-biliary cancer surgery in older adults (OA). SUMMARY BACKGROUND DATA: Functional outcomes are central to decisionmaking by OA, but long-term risks of dependency have not been described beyond 1 year in this population. METHODS: All patients over age 70 undergoing hepatectomy or pancreatec-tomy for cancer between 2007 and 2017 in Ontario were analyzed. Outcomes were 1) receipt of homecare and 2) time at home. Homecare was analyzed with cumulative incidence functions, and time at home with Kaplan-Meier and Cox multivariate models. RESULTS: A total of 902 and 1283 patients underwent hepatectomy and pancreatectomy, respectively. Homecare use was highest (72.3%) in postoperative month-1, decreasing to stabilize between year-1 (25.5%) and year-5 (18.3%). Repeated receipt of homecare was associated with female sex (HR 1.18, 95% CI 1.05-1.32), receipt of adjuvant therapy (HR 1.56, 1.37-1.78), and more recent year of surgery (HR 3.80, 3.05-4.72). The ratio of home nursing care versus personal support services reversed from 68%/26% in year-1, to 29/64% in year-5. High time at home (>350 days) at 1 and 5 years were 40.6% (95% CI 38.5%-42.6%) and 28.1% (25.9%-30.3%), respectively. The ratio of institution-days in acute care versus nursing homes went from 77%/14% in year-1 to 23%/70% in year-5. Low time at home was associated with duodenal (HR 1.45, 1.15-1.70) and pancreas cancer (HR 1.20, 1.02-1.42), and with rural residence (HR 1.24, 1.04-1.48). High time at home was associated with more recent year of surgery (HR 0.84, 0.76-0.93) and perioperative cancer therapy (HR 0.88, 0.78-0.99). Increasing age was neither associated with homecare receipt nor time at home. CONCLUSIONS: Following hepatopancreatobiliary cancer surgery, there is a high rate of long-term healthcare dependency for OA. There is an immediate high need for homecare that reaches a new baseline after 6 months, and the majority of OA will have at least 1 year with low time at home, most commonly the first year. These findings can aid in preoperative preparation and transitional care planning.

Update on CVD 103-HgR single-dose, live oral cholera vaccine.

Cholera remains endemic in >50 countries, putting millions at risk, especially young children for whom killed vaccines offer limited protection. An oral, live attenuated vaccine - CVD 103-HgR (Vaxchora vaccine) - was licensed by the US FDA in 2016 for adults aged 18-64 years traveling to endemic regions, based on clinical trials in human volunteers showing the vaccine was well tolerated and conferred 90% efficacy within 10 days. The evidence base for Vaxchora vaccine has expanded with additional clinical trial data, in older adults (aged 46-64 years) and children (aged 2-17 years), demonstrating that the vaccine produces a strong vibriocidal antibody response. Over 68,000 doses have been administered in the United States, with no new safety signals. The dose volume has been reduced in children to improve acceptability, and cold chain requirements are less st ringent, at +2°C─+8°C. The vaccine has recently been licensed in the Untied States for children aged 2-17 years, in Europe for individuals aged ≥2 years, and for home administration in Europe. Next steps include a Phase 4 study in infants (6-23 months). Additional information is needed regarding duration of immunity, the need for and timing of revaccination, and efficacy data from lower-middle-income countries.