Infectious pathogens and risk of esophageal, gastric and duodenal cancers and ulcers in China: A case-cohort study.

Infection by certain pathogens is associated with cancer development. We conducted a case-cohort study of ~2500 incident cases of esophageal, gastric and duodenal cancer, and gastric and duodenal ulcer and a randomly selected subcohort of ~2000 individuals within the China Kadoorie Biobank study of >0.5 million adults. We used a bead-based multiplex serology assay to measure antibodies against 19 pathogens (total 43 antigens) in baseline plasma samples. Associations between pathogens and antigen-specific antibodies with risks of site-specific cancers and ulcers were assessed using Cox regression fitted using the Prentice pseudo-partial likelihood. Seroprevalence varied for different pathogens, from 0.7% for Hepatitis C virus (HCV) to 99.8% for Epstein-Barr virus (EBV) in the subcohort. Compared to participants seronegative for the corresponding pathogen, Helicobacter pylori seropositivity was associated with a higher risk of non-cardia (adjusted hazard ratio [HR] 2.73 [95% CI: 2.09-3.58]) and cardia (1.67 [1.18-2.38]) gastric cancer and duodenal ulcer (2.71 [1.79-4.08]). HCV was associated with a higher risk of duodenal cancer (6.23 [1.52-25.62]) and Hepatitis B virus was associated with higher risk of duodenal ulcer (1.46 [1.04-2.05]). There were some associations of antibodies again some herpesviruses and human papillomaviruses with risks of gastrointestinal cancers and ulcers but these should be interpreted with caution. This first study of multiple pathogens with risk of gastrointestinal cancers and ulcers demonstrated that several pathogens are associated with risks of gastrointestinal cancers and ulcers. This will inform future investigations into the role of infection in the etiology of these diseases.

Rewiring of the Host Cell Metabolome and Lipidome during Lytic Gammaherpesvirus Infection Is Essential for Infectious-Virus Production.

Oncogenic virus infections are estimated to cause ~15% of all cancers. Two prevalent human oncogenic viruses are members of the gammaherpesvirus family: Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV). We use murine herpesvirus 68 (MHV-68), which shares significant homology with KSHV and EBV, as a model system to study gammaherpesvirus lytic replication. Viruses implement distinct metabolic programs to support their life cycle, such as increasing the supply of lipids, amino acids, and nucleotide materials necessary to replicate. Our data define the global changes in the host cell metabolome and lipidome during gammaherpesvirus lytic replication. Our metabolomics analysis found that MHV-68 lytic infection induces glycolysis, glutaminolysis, lipid metabolism, and nucleotide metabolism. We additionally observed an increase in glutamine consumption and glutamine dehydrogenase protein expression. While both glucose and glutamine starvation of host cells decreased viral titers, glutamine starvation led to a greater loss in virion production. Our lipidomics analysis revealed a peak in triacylglycerides early during infection and an increase in free fatty acids and diacylglyceride later in the viral life cycle. Furthermore, we observed an increase in the protein expression of multiple lipogenic enzymes during infection. Interestingly, pharmacological inhibitors of glycolysis or lipogenesis resulted in decreased infectious virus production. Taken together, these results illustrate the global alterations in host cell metabolism during lytic gammaherpesvirus infection, establish essential pathways for viral production, and recommend targeted mechanisms to block viral spread and treat viral induced tumors. IMPORTANCE Viruses are intracellular parasites which lack their own metabolism, so they must hijack host cell metabolic machinery in order to increase the production of energy, proteins, fats, and genetic material necessary to replicate. Using murine herpesvirus 68 (MHV-68) as a model system to understand how similar human gammaherpesviruses cause cancer, we profiled the metabolic changes that occur during lytic MHV-68 infection and replication. We found that MHV-68 infection of host cells increases glucose, glutamine, lipid, and nucleotide metabolic pathways. We also showed inhibition or starvation of glucose, glutamine, or lipid metabolic pathways results in an inhibition of virus production. Ultimately, targeting changes in host cell metabolism due to viral infection can be used to treat gammaherpesvirus-induced cancers and infections in humans.

An evaluation of isocentre shift magnitude and treatment site on image-guided radiation therapy online decision analysis times.

INTRODUCTION: The ability to capture more anatomical detail in cone-beam computed tomography (CBCT) imaging compared to kilovoltage (kV) and megavoltage (MV) imaging, has seen a documented shift towards CBCT image verification and staff adopting more extensive image analysis processes. The timeframe associated with assessing online CBCT images, termed the online decision analysis time, if drawn out, can affect treatment efficiency and accuracy. This study aimed to determine the current CBCT online decision analysis time at Radiation Oncology Princess Alexandra Ipswich Road (ROPAIR) and investigate the influence of isocentre shift magnitude and treatment site considerations on this timeframe. METHODS: This retrospective clinical audit collected treatment parameters from 202 CBCT images over 2 treatment days. The online decision analysis time was calculated by subtracting the image acquisition timestamp from the image verification shift application timestamp. The quantitative data were analysed using mean, standard deviation, and range in the following categories: all CBCTs, CBCTs grouped by isocentre shift magnitude and CBCTs grouped by treatment site. Content analysis was performed on staff comments made during image analysis. RESULTS: The average online decision analysis time was 2:37 ± 1:28 min. On average approximately, head and neck, spine and extremity treatment sites measured 1 min, pelvis, breast, and chest measured 2-3 min with abdomen measuring 4 min. Common categories reported in staff comments included anatomical changes, repositioning, and organs at risk size. CONCLUSION: The results provide baseline online decision analysis times. Further refinement is required to determine if the image match method, treatment site considerations, and rotational discrepancies influence this timeframe.

Helicobacter pylori multiplex serology and risk of non-cardia and cardia gastric cancer: a case-cohort study and meta-analysis.

BACKGROUND: Helicobacter pylori infection is a major cause of non-cardia gastric cancer (NCGC), but uncertainty remains about the associations between sero-positivity to different H. pylori antigens and risk of NCGC and cardia gastric cancer (CGC) in different populations. METHODS: A case-cohort study in China included ∼500 each of incident NCGC and CGC cases and ∼2000 subcohort participants. Sero-positivity to 12 H. pylori antigens was measured in baseline plasma samples using a multiplex assay. Hazard ratios (HRs) of NCGC and CGC for each marker were estimated using Cox regression. These were further meta-analysed with studies using same assay. RESULTS: In the subcohort, sero-positivity for 12 H. pylori antigens varied from 11.4% (HpaA) to 70.8% (CagA). Overall, 10 antigens showed significant associations with risk of NCGC (adjusted HRs: 1.33 to 4.15), and four antigens with CGC (HRs: 1.50 to 2.34). After simultaneous adjustment for other antigens, positive associations remained significant for NCGC (CagA, HP1564, HP0305) and CGC (CagA, HP1564, HyuA). Compared with CagA sero-positive only individuals, those who were positive for all three antigens had an adjusted HR of 5.59 (95% CI 4.68-6.66) for NCGC and 2.17 (95% CI 1.54-3.05) for CGC. In the meta-analysis of NCGC, the pooled relative risk for CagA was 2.96 (95% CI 2.58-3.41) [Europeans: 5.32 (95% CI 4.05-6.99); Asians: 2.41 (95% CI 2.05-2.83); Pheterogeneity<0.0001]. Similar pronounced population differences were also evident for GroEL, HP1564, HcpC and HP0305. In meta-analyses of CGC, two antigens (CagA, HP1564) were significantly associated with a higher risk in Asians but not Europeans. CONCLUSIONS: Sero-positivity to several H. pylori antigens was significantly associated with an increased risk of NCGC and CGC, with varying effects between Asian and European populations.

Prevalence of Testing for Human Immunodeficiency Virus, Hepatitis B Virus, and Hepatitis C Virus Among Medicaid Enrollees Treated With Medications for Opioid Use Disorder in 11 States, 2016-2019.

BACKGROUND: Limited information exists about testing for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) among Medicaid enrollees after starting medication for opioid use disorder (MOUD), despite guidelines recommending such testing. Our objectives were to estimate testing prevalence and trends for HIV, HBV, and HCV among Medicaid enrollees initiating MOUD and examine enrollee characteristics associated with testing. METHODS: We conducted a serial cross-sectional study of 505 440 initiations of MOUD from 2016 to 2019 among 361 537 Medicaid enrollees in 11 states. Measures of MOUD initiation; HIV, HBV, and HCV testing; comorbidities; and demographics were based on enrollment and claims data. Each state used Poisson regression to estimate associations between enrollee characteristics and testing prevalence within 90 days of MOUD initiation. We pooled state-level estimates to generate global estimates using random effects meta-analyses. RESULTS: From 2016 to 2019, testing increased from 20% to 25% for HIV, from 22% to 25% for HBV, from 24% to 27% for HCV, and from 15% to 19% for all 3 conditions. Adjusted rates of testing for all 3 conditions were lower among enrollees who were male (vs nonpregnant females), living in a rural area (vs urban area), and initiating methadone or naltrexone (vs buprenorphine). Associations between enrollee characteristics and testing varied across states. CONCLUSIONS: Among Medicaid enrollees in 11 US states who initiated medications for opioid use disorder, testing for human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and all 3 conditions increased between 2016 and 2019 but the majority were not tested.

Single molecule studies of the native hair cell mechanosensory transduction complex.

Hearing and balance rely on the conversion of a mechanical stimulus into an electrical signal, a process known as mechanosensory transduction (MT). In vertebrates, this process is accomplished by an MT complex that is located in hair cells of the inner ear. While the past three decades of research have identified many subunits that are important for MT and revealed interactions between these subunits, the composition and organization of a functional complex remains unknown. The major challenge associated with studying the MT complex is its extremely low abundance in hair cells; current estimates of MT complex quantity range from 3-60 attomoles per cochlea or utricle, well below the detection limit of most biochemical assays that are used to characterize macromolecular complexes. Here we describe the optimization of two single molecule assays, single molecule pull-down (SiMPull) and single molecule array (SiMoA), to study the composition and quantity of native mouse MT complexes. We demonstrate that these assays are capable of detecting and quantifying low attomoles of the native MT subunits protocadherin-15 (PCDH15) and lipoma HMGIC fusion partner-like protein 5 (LHFPL5). Our results illuminate the stoichiometry of PCDH15- and LHFPL5-containing complexes and establish SiMPull and SiMoA as productive methods for probing the abundance, composition, and arrangement of subunits in the native MT complex.

Interventions to Support Adherence to Oral Anticancer Medications: Systematic Review and Meta-Analysis.

PROBLEM IDENTIFICATION: This systematic review compared the efficacy of interventions to usual care on adherence to oral anticancer regimens. LITERATURE SEARCH: Embase®, PubMed®, and CINAHL® were searched for eligible comparative studies published between January 2000 and May 2021. Outcomes of interest included adherence, cancer-related morbidity, quality of life, patient satisfaction, and other patient-specific outcomes. DATA EVALUATION: Reviewers assessed risk of bias using the Cochrane Risk of Bias 2 tool and Risk of Bias in Nonrandomized Studies of Interventions. Certainty of evidence was assessed using the GRADE framework. SYNTHESIS: Risk assessment, ongoing or periodic assessment, proactive follow-up, motivational interviewing, or structured programs may improve adherence. Education or coaching interventions may improve or have little to no effect on adherence. Technological interventions may improve adherence, but interactive compared to noninteractive technology may have little to no effect. IMPLICATIONS FOR RESEARCH: As more cancer treatments move to oral formulations, work remains to identify the most effective interventions to support people receiving oral anticancer regimens.

Domains of Structured Oral Anticancer Medication Programs: A Scoping Review.

PROBLEM IDENTIFICATION: An interprofessional approach is necessary to support the multifactorial process of patient adherence to oral anticancer medications (OAMs). This scoping review aims to identify structured OAM programs in published literature, identify components within studies, and propose a framework for institutions developing or maintaining OAM programs. LITERATURE SEARCH: Embase®, PubMed®, and CINAHL® databases were searched for studies published between January 2000 and April 2021. DATA EVALUATION: Two reviewers screened studies and extracted data. Characteristics and specific domains of the OAM programs were captured. Key components of the programs were identified, and a framework was created to guide program development. SYNTHESIS: Components identified among the 21 studies were education; counseling; follow-up; dedicated clinician contact; adverse event and toxicity monitoring; adherence monitoring; drug procurement, delivery, and supply; patient- and system-level cost reduction; information technology; and risk assessment. IMPLICATIONS FOR RESEARCH: Based on the findings, a framework for building and evaluating OAM adherence programs is proposed. Future studies should evaluate the reliability and validity of this framework because further testing may lead to the development of additional components.

Hypoxia shapes the immune landscape in lung injury and promotes the persistence of inflammation.

Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling in the bone marrow. This impaired monopoiesis resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of colony-stimulating factor 1 in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS.

The relative and attributable risks of cardia and non-cardia gastric cancer associated with Helicobacter pylori infection in China: a case-cohort study.

BACKGROUND: Helicobacter pylori infection is a major cause of non-cardia gastric cancer (NCGC), but its causal role in cardia gastric cancer (CGC) is unclear. Moreover, the reported magnitude of association with NCGC varies considerably, leading to uncertainty about population-based H pylori screening and eradication strategies in high-risk settings, particularly in China, where approximately half of all global gastric cancer cases occur. Our aim was to assess the associations of H pylori infection, both overall and for individual infection biomarkers, with the risks of NCGC and CGC in Chinese adults. METHODS: A case-cohort study was done in adults from the prospective China Kadoorie Biobank study, aged 30-79 years from ten areas in China (Qingdao, Haikou, Harbin, Suzhou, Liuzhou, Henan, Sichuan, Hunan, Gansu, and Zhejiang), and included 500 incident NCGC cases, 437 incident CGC cases, and 500 subcohort participants who were cancer-free and alive within the first two years since enrolment in 2004-08. H pylori biomarkers were measured in stored baseline plasma samples using a sensitive immunoblot assay (HelicoBlot 2.1), with adapted criteria to define H pylori seropositivity. Cox regression was used to estimate adjusted hazard ratios (HRs) for NCGC and CGC associated with H pylori infection. These values were used to estimate the number of gastric cancer cases attributable to H pylori infection in China. FINDINGS: Of the 512 715 adults enrolled in the China Kadoorie Biobank between June, 2004, and July, 2008, 500 incident NCGC cases, 437 incident CGC cases, and 500 subcohort participants were selected for analysis. The seroprevalence of H pylori was 94·4% (95% CI 92·4-96·4) in NGCG, 92·2% (89·7-94·7) in CGC, and 75·6% (71·8-79·4) in subcohort participants. H pylori infection was associated with adjusted HRs of 5·94 (95% CI 3·25-10·86) for NCGC and 3·06 (1·54-6·10) for CGC. Among the seven individual infection biomarkers, cytotoxin-associated antigen had the highest HRs for both NCGC (HR 4·41, 95% CI 2·60-7·50) and CGC (2·94, 1·53-5·68). In this population, 78·5% of NCGC and 62·1% of CGC cases could be attributable to H pylori infection. H pylori infection accounted for an estimated 339 955 cases of gastric cancer in China in 2018. INTERPRETATION: Among Chinese adults, H pylori infection is common and is the cause of large numbers of gastric cancer cases. Population-based mass screening and the eradication of H pylori should be considered to reduce the burden of gastric cancer in high-risk settings. FUNDING: Cancer Research UK, Wellcome Trust, UK Medical Research Council, British Heart Foundation, Kadoorie Charitable Foundation, National Key Research and Development Program of China, and National Natural Science Foundation of China.

Optimizing scalable, technology-supported behavioral interventions to prevent opioid misuse among adolescents and young adults in the emergency department: A randomized controlled trial protocol.

Preventing opioid misuse and opioid use disorder is critical among at-risk adolescents and young adults (AYAs). An Emergency Department (ED) visit provides an opportunity for delivering interventions during a rapidly changing opioid landscape. This paper describes pilot data and the protocol for a 2 × 2 factorial randomized controlled trial testing efficacy of early interventions to reduce escalation of opioid (prescription or illicit) misuse among at-risk AYAs. Interventions are delivered using technology by health coaches. AYAs ages 16-30 in the ED screening positive for prescription opioid use (+ ≥ 1 risk factor) or opioid misuse will be stratified by risk severity, sex, and age group. Participants will be randomly assigned to a condition at intake, either a live video health coach-delivered single session or a control condition of an enhanced usual care (EUC) community resource brochure. They are also randomly assigned to one of two post-intake conditions: health coach-delivered portal-like messaging via web portal over 30 days or EUC delivered at 30 days post-intake. Thus, the trial has four groups: health coach-delivered session+portal, health coach-delivered session+EUC, EUC + portal, and EUC + EUC. Outcomes will be measured at 3-, 6-, and 12-months. The primary outcome is opioid misuse based on a modified Alcohol Smoking and Substance Involvement Screening Test. Secondary outcomes include other opioid outcomes (e.g., days of opioid misuse, overdose risk behaviors), other substance misuse and consequences, and impaired driving. This study is innovative by testing the efficacy of feasible and scalable technology-enabled interventions to reduce and prevent opioid misuse and opioid use disorder. Trial Registration:ClinicalTrials.gov University of Michigan HUM00177625 NCT Registration: NCT04550715.

Adherence to Long-Term Follow-up in Patients With Sporadic Vestibular Schwannomas Managed With Serial Observation.

OBJECTIVES: To examine the long-term adherence to serial imaging of patients with sporadic vestibular schwannoma and analyze factors associated with being lost to follow-up. STUDY DESIGN: Retrospective chart review with telephone interview. SETTING: Single tertiary care center. METHODS: Patients with a sporadic vestibular schwannoma and started on observational surveillance management between January 2005 and December 2010 were included. Demographic data, tumor size, hearing and vestibular changes, and follow-up length were recorded. Patient factors were analyzed for association with being lost to follow-up. RESULTS: In total, 122 patients were included with a median length of follow-up of 5 months (range, 0-146). After initial surveillance, 22.1% (n = 27) of patients had a change in management to either microsurgery or radiosurgery. Of the remaining 77.9% (n = 95), nearly half (44.2%, n = 42) never returned for a second visit, and all but 3 were eventually lost to follow-up. There was no association between sex, race, age at diagnosis, initial tumor size, insurance status, household income, or driving distance to hospital and being lost to follow-up. Of 26 interviewed patients initially lost to follow-up, 11 (42.3%) sought care at another institution, 5 (19.2%) chose to no longer receive care, 1 (3.8%) had transportation difficulties, and 9 (36.4%) had poor understanding of their diagnosis or instructions. CONCLUSIONS: The length of follow-up for patients undergoing surveillance of sporadic vestibular schwannoma varies widely, and patients are commonly lost to follow-up. Further efforts should be made to identify at-risk patients and provide adequate education to improve long-term surveillance.

Cerebellar-Subcortical-Cortical Systems as Modulators of Cognitive Functions.

Over the past few decades, research has established that the cerebellum is involved in executive functions; however, its specific role remains unclear. There are numerous theories of cerebellar function and numerous cognitive processes falling under the umbrella of executive function, making investigations of the cerebellum's role in executive functioning challenging. In this review, we explored the role of the cerebellum in executive functioning through clinical and cognitive neuroscience frameworks. We reviewed the neuroanatomical systems and theoretical models of cerebellar functions and the multifaceted nature of executive functions. Using attention deficit hyperactivity disorder and cerebellar tumor as clinical developmental models of cerebellar dysfunction, and the functional magnetic resonance imaging literature, we reviewed evidence for cerebellar involvement in specific components of executive function in childhood, adolescence, and adulthood. There is evidence for posterior cerebellar contributions to working memory, planning, inhibition, and flexibility, but the heterogeneous literature that largely was not designed to study the cerebellum makes it difficult to determine specific functions of the cerebellum or cerebellar regions. In addition, while it is clear that cerebellar insult in childhood affects executive function performance later in life, more work is needed to elucidate the mechanisms by which executive dysfunction occurs and its developmental course. The limitations of the current literature are discussed and potential directions for future research are provided.

Outcomes of surgical mitral valve replacement: A benchmark to assess transcatheter technologies.

BACKGROUND: Clinical trials are underway to evaluate the safety and efficacy of transcatheter mitral valve replacement in intermediate and high surgical risk patients. We analyzed outcomes of surgical mitral valve replacement in a regional consortium to provide benchmark data for emerging alternative therapies. METHODS: All patients undergoing mitral replacement with a Society of Thoracic Surgeons predicted risk of mortality (STS PROM) in a regional consortium from 2001 to 2017 were analyzed. Patients with endocarditis were excluded. Patients were stratified by STS PROM into low (<4%), moderate (4%-8%), and high risk (>8%) cohorts. Mortality, postoperative complications, and resource utilization were evaluated for each group. RESULTS: A total of 1611 patients were analyzed including 927 (58%) low, 370 (23%) moderate, and 314 (20%) high-risk patients. The mean STS PROM was 2%, 5.6%, and 15.4% for each group. Mortality was adequately predicted for all groups while the most common complications included prolonged ventilation, reoperation, and renal failure. Higher risk patients had longer intensive care unit and hospital lengths of stay (2 vs. 3 vs. 5 days, p < .0001 and 7 vs. 8 vs. 10 days, p < .0001) and higher total hospital costs ($38,029 vs. $45,075 vs. $59,171 p < .0001). CONCLUSIONS: Mitral valve replacement is associated with acceptable morbidity and mortality, particularly for low and intermediate-risk patients. These outcomes also serve as a benchmark with which to compare forthcoming results of transcatheter mitral valve replacement trials.

Stress-Related Gastrointestinal Bleeding in Patients with Aneurysmal Subarachnoid Hemorrhage: A Multicenter Retrospective Observational Study.

BACKGROUND/OBJECTIVE: Stress-related mucosal bleeding (SRMB) occurs in approximately 2-4% of critically ill patients. Patients with aneurysmal subarachnoid hemorrhage (aSAH) have a (diffuse) space-occupying lesion, are critically ill, often require mechanical ventilation, and frequently receive anticoagulation or antiplatelet therapy after aneurysm embolization, all of which may be risk factors for SRMB. However, no studies have evaluated SRMB in patients with aSAH. Aims of the study were to determine the incidence of SRMB in aSAH patients, evaluate the effect of acid suppression on SRMB, and identify specific risk factors for SRMB. METHODS: This was a multicenter, retrospective, observational study conducted across 17 centers. Each center reviewed up to 50 of the most recent cases of aSAH. Patients with length of stay (LOS) < 48 h or active GI bleeding on admission were excluded. Variables related to demographics, aSAH severity, gastrointestinal (GI) bleeding, provision of SRMB prophylaxis, adverse events, intensive care unit (ICU), and hospital LOS were collected for the first 21 days of admission or until hospital discharge, whichever came first. Descriptive statistics were used to analyze the data. A multivariate logistic regression modeling was utilized to examine the relationship between specific risk factors and the incidence of clinically important GI bleeding in patients with aSAH. RESULTS: A total of 627 patients were included. The overall incidence of clinically important GI bleeding was 4.9%. Of the patients with clinically important GI bleeding, 19 (61%) received pharmacologic prophylaxis prior to evidence of GI bleeding, while 12 (39%) were not on pharmacologic prophylaxis at the onset of GI bleeding. Patients who received an acid suppressant agent were less likely to experience GI bleeding than patients who did not receive pharmacologic prophylaxis prior to evidence of bleeding (OR 0.39, 95% CI 0.18-0.83). The multivariate regression analysis identified any instance of elevated intracranial pressure, creatinine clearance < 60 ml/min and the incidence of cerebral vasospasm as specific risk factors associated with GI bleeding. Cerebral vasospasm has not previously been described as a risk for GI bleeding (OR 2.5 95% CI 1.09-5.79). CONCLUSIONS: Clinically important GI bleeding occurred in 4.9% of patients with aSAH, similar to the general critical care population. Risk factors associated with GI bleeding were prolonged mechanical ventilation (> 48 h), creatinine clearance < 60 ml/min, presence of coagulopathy, elevation of intracranial pressure, and cerebral vasospasm. Further prospective research is needed to confirm this observation within this patient population.

Using First Principles to Link Silicone Oil/Formulation Interfacial Tension With Syringe Functionality in Pre-Filled Syringes Systems.

Numerous interactions can arise at the interface between the glass barrel/silicone oil coating/aqueous formulation in pre-filled syringes that can affect the functionality of the medical device. In this study, the Young-Dupré equation was applied at these interfaces to correlate the interfacial tension between the silicone oil coating and aqueous formulation to the functionality of the syringe. It was shown that lower silicone oil/drug product formulation interfacial tension led to an increase in the glide force of the syringe. The relationship between glide force profiles and silicone oil thickness after injection was also investigated and the data revealed that the silicone oil was removed at the end of the syringe barrel when the formulation contains polysorbate 80.

Concomitant Left Atrial Appendage Closure Outcomes and Cost: A Multi-institutional Cohort Analysis.

BACKGROUND: Left atrial appendage closure (LAAC) is frequently performed during cardiac operations, but the impact of LAAC on patient outcomes is not fully known. We hypothesized that the addition of LAAC would increase morbidity and resource utilization. METHODS: All patients undergoing cardiac surgery from a multi-institutional Society of Thoracic Surgeons database from 2011 to 2016 were stratified by LAAC. The effect of LAAC on risk-adjusted outcomes was assessed by hierarchical regression modeling accounting for preoperative risk factors, planned surgical procedure, hospital, and year. RESULTS: Concomitant LAAC was performed on 2384 of 28,311 patients (9.3%), who were older, with a greater burden of preoperative atrial fibrillation and heart failure. Although the addition of LAAC increased the risk of new-onset postoperative atrial fibrillation (OR 1.69, P < 0.01), it did not increase rates of major morbidity (OR 1.00, P = 0.970), stroke (OR 0.92, P = 0.787), or mortality (OR 0.93, P = 0.684). Although cardiopulmonary bypass time was not significantly increased by LAAC, patients' total hospitalization costs were $3035 higher (P = 0.018). CONCLUSIONS: Although concomitant LAAC was not associated with major complications, there were higher risk-adjusted rates of new-onset postoperative atrial fibrillation. Furthermore, LAAC added approximately $3000 to a patient's total hospital cost. These short-term risks and costs should be weighed against potential long-term benefits of left atrial appendage closure.

Massive Splenomegaly and Pancytopenia: It's a Hairy Situation.

A 33-year-old previously healthy Middle Eastern male presented to the emergency department with four weeks of progressively worsening fatigue, dyspnea on exertion, night sweats, and a 10-pound weight loss after suffering a self-limiting viral upper respiratory illness. He was found to be profoundly anemic and thrombocytopenic with normal white blood cell count with a lymphocytic predominance. His anemia was refractory to red blood cell transfusions, to which he developed hyperbilirubinemia. A CT scan revealed hepatomegaly and massive splenomegaly associated with multi-station abdominopelvic lymphadenopathy. A peripheral blood smear revealed several lymphocytes with hairy cell features and bone marrow biopsy revealed hypercellularity with interstitial infiltration by mature lymphoid cells. Flow cytometry confirmed the diagnosis of hairy cell leukemia (HCL) and this patient was initiated on cladribine chemotherapy. This case illustrates the uniqueness of this patient presenting within a short time course, at an atypical age, and with uncommon features for HCL including lymphadenopathy, hepatomegaly, and petechial skin rash. This case also highlights an important point regarding the management of severe anemia in the acute setting while undergoing splenic sequestration. His lack of response to red blood cell transfusions highlights the need for more research on the use of transfusions in patients who are not current surgical candidates for splenectomy.