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Employment trends in the hiring of women in business and industry are discussed. A comparison between employer demand for trained women and their supply is made. (Author/EAK)

Background Fluid therapy-the administration of fluids to maintain adequate organ tissue perfusion and oxygenation-is essential in patients admitted to the intensive care unit (ICU) with traumatic brain injury. We aimed to quantify the variability in fluid management policies in patients with traumatic brain injury and to study the effect of this variability on patients' outcomes.Methods We did a prospective, multicentre, comparative effectiveness study of two observational cohorts: CENTER-TBI in Europe and OzENTER-TBI in Australia. Patients from 55 hospitals in 18 countries, aged 16 years or older with traumatic brain injury requiring a head CT, and admitted to the ICU were included in this analysis. We extracted data on demographics, injury, and clinical and treatment characteristics, and calculated the mean daily fluid balance (difference between fluid input and loss) and mean daily fluid input during ICU stay per patient. We analysed the association of fluid balance and input with ICU mortality and functional outcome at 6 months, measured by the Glasgow Outcome Scale Extended (GOSE). Patient-level analyses relied on adjustment for key characteristics per patient, whereas centre-level analyses used the centre as the instrumental variable.Findings 2125 patients enrolled in CENTER-TBI and OzENTER-TBI between Dec 19, 2014, and Dec 17, 2017, were eligible for inclusion in this analysis. The median age was 50 years (IQR 31 to 66) and 1566 (74%) of patients were male. The median of the mean daily fluid input ranged from 1middot48 L (IQR 1middot12 to 2middot09) to 4middot23 L (3middot78 to 4middot94) across centres. The median of the mean daily fluid balance ranged from -0middot85 L (IQR -1middot51 to -0middot49) to 1middot13 L (0middot99 to 1middot37) across centres. In patient-level analyses, a mean positive daily fluid balance was associated with higher ICU mortality (odds ratio [OR] 1middot10 [95% CI 1middot07 to 1middot12] per 0middot1 L increase) and worse functional outcome (1middot04 [1middot02 to 1middot05] per 0middot1 L increase); higher mean daily fluid input was also associated with higher ICU mortality (1middot05 [1middot03 to 1middot06] per 0middot1 L increase) and worse functional outcome (1middot04 [1middot03 to 1middot04] per 1-point decrease of the GOSE per 0middot1 L increase). Centre-level analyses showed similar associations of higher fluid balance with ICU mortality (OR 1middot17 [95% CI 1middot05 to 1middot29]) and worse functional outcome (1middot07 [1middot02 to 1middot13]), but higher fluid input was not associated with ICU mortality (OR 0middot95 [0middot90 to 1middot00]) or worse functional outcome (1middot01 [0middot98 to 1middot03]).Interpretation In critically ill patients with traumatic brain injury, there is significant variability in fluid management, with more positive fluid balances being associated with worse outcomes. These results, when added to previous evidence, suggest that aiming for neutral fluid balances, indicating a state of normovolaemia, contributes to improved outcome. Copyright (C) 2021 Elsevier Ltd. All rights reserved.

Objective To investigate whether epileptiform discharge burden can identify those at risk for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH). Methods Retrospective analysis of 113 moderate to severe grade SAH patients who had continuous EEG (cEEG) recordings during their hospitalization. We calculated the burden of epileptiform discharges (ED), measured as number of ED per hour. Results We find that many SAH patients have an increase in ED burden during the first 3–10 days following rupture, the major risk period for DCI. However, those who develop DCI have a significantly higher hourly burden from days 3.5–6 after SAH vs. those who do not. ED burden is higher in DCI patients when assessed in relation to the onset of DCI (area under the receiver operator curve 0.72). Finally, specific trends of ED burden over time, assessed by group-based trajectory analysis, also help stratify DCI risk. Conclusions These results suggest that ED burden is a useful parameter for identifying those at higher risk of developing DCI after SAH. The higher burden rate associated with DCI supports the theory of metabolic supply-demand mismatch which contributes to this complication. Significance ED burden is a novel biomarker for predicting those at high risk of DCI.

OBJECTIVE: Classification criteria for calcium pyrophosphate deposition disease (CPPD) will facilitate clinical research on this common crystalline arthritis. We report on the first two phases of a four-phase process for developing CPPD classification criteria. METHODS: CPPD classification criteria development is overseen by a 12-member Steering Committee. Item generation (Phase I) included a scoping literature review of five literature databases and contributions from a 35-member Combined Expert Committee and two Patient Research Partners. Item reduction and refinement (Phase II) involved a Combined Expert Committee meeting, discussions among Clinical, Imaging, and Laboratory Advisory Groups, and an item rating exercise to assess the influence of individual items toward classification. The Steering Committee reviewed the modal rating score for each item (range -3 [strongly pushes away from CPPD] to +3 [strongly pushes toward CPPD]) to determine items to retain for future phases of criteria development. RESULTS: Item generation yielded 420 items (312 from the literature, 108 from experts/patients). The Advisory Groups eliminated items they agreed were unlikely to distinguish between CPPD and other forms of arthritis, yielding 127 items for the item rating exercise. Fifty-six items, most of which had a modal rating of +/- 2 or 3, were retained for future phases. As numerous imaging items were rated +3, the Steering Committee recommended focusing on imaging of the knee, wrist, and one additional affected joint for calcification suggestive of CPP crystal deposition. CONCLUSION: A data- and expert-driven process is underway to develop CPPD classification criteria. Candidate items comprise clinical, imaging, and laboratory features.

Objectives This study aimed to characterize the clinical and histopathological features of arrhythmogenic right ventricular cardiomyopathy (ARVC) in English Bulldogs, American Bulldogs, and Bulldog-type mixed breed dogs and assess affected Bulldogs for a striatin gene mutation previously reported in Boxers with ARVC. Animals Seventy-one Bulldogs fit the inclusion criteria. Genetic analysis was performed on five dogs. Cardiac post-mortem evaluations were performed on two dogs. Methods Medical records from a single veterinary cardiology group (CVCA) were retrospectively evaluated. Tissue and blood samples were submitted for histopathological analysis and genetic testing in select patients. Results Presenting complaints included syncope (38%), arrhythmia (81.7%), or murmur (34.2%) documented on examination. On presentation, congestive heart failure (CHF) was diagnosed in 22 (31%) dogs, and 58 (81.7%) had ventricular arrhythmias. On bivariable analyses, the two-dimensional (2D) left atrial-to-aortic root ratio (LA:Ao) was the only prognostic variable significantly associated with survival time. Dogs with 2D LA:Ao below the mean (1.41) had longer median survival to all-cause mortality (12 months; 95% confidence interval [CI] 6.0–15.0 months) than those with 2D LA:Ao above the mean (four months; 95% CI 2.0–6.0 months; p=0.0384). Most dogs (54%) died from cardiac disease, with 42.1% experiencing sudden death. The median time from diagnosis to cardiac death was four months. Conclusions Arrhythmogenic right ventricular cardiomyopathy affects Bulldogs with both arrhythmogenic and dilated-type phenotypes. Despite variable arrhythmia severity and predominantly right-sided involvement in many dogs, an increase in left atrial size was the only significant predictor of mortality in this sample of dogs.

Purpose: International data demonstrate association between clinical trial participation and reduced cancer mortality. Adolescents and young adults (AYA) have low clinical trial enrollment rates. We established a program to understand local barriers and develop targeted solutions that lead to greater AYA clinical trial participation. Methods: A steering committee (SC) with expertise in adult and pediatric oncology, research ethics, and consumer representation was formed. The SC mapped barriers related to AYA trial access and established working groups (WGs) around three themes. Results: The Regulatory Awareness WG identified a lack of understanding of processes that support protocol approval for clinical trials across the AYA age range. A guideline to raise awareness was developed. The Access WG identified challenges for young adults (18-25 years) to access a pediatric hospital to enroll in a pediatric trial. A procedure was developed to streamline applications for access. The first six applications using this procedure have been successful. The Availability WG identified lack of pediatric-adult oncology reciprocal relationships as a barrier to awareness of open trials, and future collaboration. An AYA Craft Group Framework was established to grow relationships within tumor streams across institutions; two craft groups are now operating locally. An additional achievement was a successful request to the Therapeutic Goods Administration for Australian adoption of the Food and Drug Administration Guidance on Considerations for the Inclusion of Adolescent Patients in Adult Oncology Clinical Trials. Conclusion: This multipronged approach to improving AYA clinical trial access has relevance for other health environments. Our knowledge products are available as an online toolkit.

Background: Post-surgical invasive Staphylococcus aureus infections among spinal fusion patients are serious complications that can worsen clinical outcomes and increase healthcare utilization. Ris...

Background Obesity is considered a major cardiovascular risk factor. The excess of pericardial fat (PF) in patients with obesity has been associated with a variety of electrocardiographic alterations. In previous studies, we demonstrated that rapid weight loss and bariatric interventions result in decreased PF. Objectives The aim of this study is to report the changes in PF after bariatric surgery and its effect on ventricular conduction. Setting US hospital, academic institution. Methods A linear measurement of PF thickness on computed tomography scans was obtained for 81 patients, as well as a retrospective review of electrocardiographic changes before and after bariatric surgery. We compared the changes in PF thickness and electrocardiographic components before and after procedures. Common demographics and co-morbidities were collected along with lipid profiles preoperative and postoperative. Results A total of 81 patients had electrocardiograms done before and 1 year after bariatric surgery. Females comprised 67.9% (n = 55), and the average age for our population was 55.07 ± 14.17 years. Pericardial fat thickness before surgery was 5.6 ± 1.84 and 4.5 ± 1.62 mm after surgery (P = .0001). Ventricular conduction (QT and QT corrected [QTc] intervals) showed a significant improvement from 438.7 + 29 before to 426.8 + 25.3 after bariatric surgery (P = .006). We found a statistically significant association between the decrease in PF and the decrease in QTc intervals (P = .002). Conclusion Obesity is a risk factor for arrhythmias and sudden cardiac death. Bariatric surgery and its effect on PF produce an improvement in ventricular conduction, which may reduce the ventricular electrical instability in patients with obesity.

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.

Liver damage in hepatitis B is immune driven and correlates with inflammatory markers in patient serum. There is no comparison of these markers to determine if inflammatory profiles are distinct to different types of liver damage across patients at different stages of disease. We measured 25 inflammatory markers in patients with acute hepatitis B and chronic hepatitis B with hepatitis B e antigen seroconversion and chronic patients stopping nucleoside analogue therapy. Myeloid markers dominated the inflammatory profile in all stages of hepatitis B. More inflammatory markers were detectable in chronic patients, including elevated concentrations of cytotoxic effectors Fas ligand, TRAIL, and TNF-α.

Background We examined the link between increased intra-abdominal pressure, intracranial pressure, and vasopressin release as a potential mechanism. Intra-abdominal pressure, produced by abdominal-cavity insufflation with carbon dioxide (CO2) during laparoscopic abdominal procedures to facilitate visualization, is associated with various complications, including arterial hypertension and oliguria. Methods Mean arterial pressure, optic nerve sheath diameter, measured as a proxy for intracranial pressure, plasma vasopressin, serum and urine osmolarity, and urine output were measured 4 times during laparoscopic sleeve gastrectomy in 42 patients: before insufflation with CO2 (T0); after insufflation to 15 cm water (H2O) pressure, with 5 cm H2O positive end-expiratory pressure (T1); after positive end-expiratory pressure was raised to 10 cm H2O (T2); and after a return to the baseline state (T3). Mean values at T0 to T3 and the directional consistency of changes (increase/decrease/ unchanged) were compared among the 4 data-collection points. Results Statistically significant elevations (all P ≤ .001) were noted from T0 to T1 and from T0 to T2 in mean arterial pressure, optic nerve sheath diameter, and vasopressin, followed by decreases at T3. For optic nerve sheath diameter and vasopressin, the increases at T1 and T2 occurred in 98% and 100% of patients, ultimately exceeding normal levels in 88 and 97%, respectively. Conversely, urine output fell from T0 to T1 and T2 by 60.9 and 73.4%, decreasing in 88.1% of patients (all P Conclusion Increased mean arterial pressure, intracranial pressure, and vasopressin release appear to be intermediary steps between increased intra-abdominal pressure and oliguria. Further research is necessary to determine any causative links between these physiological changes.

Background Considerable evidence documents the effectiveness and efficacy of bariatric surgery (BaS) in reducing the prevalence and severity of obesity-related co-morbidities. Diastolic heart failure (DHF) is a condition with considerable morbidity and mortality, yet recalcitrant to medical therapy. Objective Our objectives were to assess whether BaS is associated with a decrease in hospital admissions for DHF and determine its impact upon DHF hospital admissions among patients with hypertension (HTN) and coronary artery disease (CAD). Setting Academic institution. Methods Data on 296 041 BaS cases and 2 004 804 controls with severe obesity were extracted from the US National Inpatient Sample database for the years 2010 to 2015 and compared. Univariate and multivariable analysis were performed to assess the impact of pre-2010 BaS on the rate of hospital admissions for DHF, adjusting for demographics, co-morbidities, and other risk factors associated with cardiovascular disease (CVD). Results Relative to controls, all baseline CVD risk factors were less common among BaS cases. Nonetheless, even after adjusting for all CVD risk factors, controls exhibited marked increases in the odds of DHF overall (odds ratio = 2.80; 95% confidence interval = 2.52–3.10). Controls with HTN and CAD demonstrated an almost 3-fold increase in odds of DHF admissions. Similarly, controls with no HTN demonstrated a 5-fold increase in odds of admissions for DHF when compared to the surgical group. Conclusions In this retrospective, case control study of a large, representative national sample of patients with severely obesity, BaS was found to be associated with significantly reduced hospitalizations for DHF when adjusted for baseline CVD risk factors. It also reduced DHF incidence in high-risk patients with HTN and CAD.

The UK islet allotransplant program is nationally funded to deliver one or two transplants over 12 months to individuals with type 1 diabetes and recurrent severe hypoglycemia. Analyses were undertaken 10 years after program inception to evaluate associations between transplanted mass; single versus two transplants; time between two transplants and graft survival (stimulated C-peptide >50 pmol/L) and function. In total, 84 islet transplant recipients were studied. Uninterrupted graft survival over 12 months was attained in 23 (68%) single and 47 (94%) (p = .002) two transplant recipients (separated by [median (IQR)] 6 (3–8) months). 64% recipients of one or two transplants with uninterrupted function at 12 months sustained graft function at 6 years. Total transplanted mass was associated with Mixed Meal Tolerance Test stimulated C-peptide at 12 months (p < .01). Despite 1.9-fold greater transplanted mass in recipients of two versus one islet infusion (12 218 [9291–15 417] vs. 6442 [5156–7639] IEQ/kg; p < .0001), stimulated C-peptide was not significantly higher. Shorter time between transplants was associated with greater insulin dose reduction at 12 months (beta −0.35; p = .02). Graft survival over the first 12 months was greater in recipients of two versus one islet transplant in the UK program, although function at 1 and 6 years was comparable. Minimizing the interval between 2 islet infusions may maximize cumulative impact on graft function.

Highlights • The PIRATES protocol is a novel tumor radiation dose-escalation approach. • PIRATES integrates proton therapy, image guided RT and hybrid hyper-fractionation. • It targets only head and neck cancer patients at high risk of treatment failure. • This Phase I trial aims to test the feasibility and safety of PIRATES., Introduction Radiation dose-escalation for head and neck cancer (HNC) patients aiming to improve cure rates is challenging due to the increased risk of unacceptable treatment-induced toxicities. With “Proton Image-guided Radiation Assignment for Therapeutic Escalation via Selection of locally advanced head and neck cancer patients” (PIRATES), we present a novel treatment approach that is designed to facilitate dose-escalation while minimizing the risk of dose-limiting toxicities for locally advanced HPV-negative HNC patients. The aim of this Phase I trial is to assess the safety & feasibility of PIRATES approach. Methods The PIRATES protocol employs a multi-faceted dose-escalation approach to minimize the risk of dose-limiting toxicities (DLTs): 1) sparing surrounding normal tissue from extraneous dose with intensity-modulated proton therapy, 2) mid-treatment hybrid hyper-fractionation for radiobiologic normal tissue sparing; 3) Magnetic Resonance Imaging (MRI) guided mid-treatment boost volume adaptation, and 4) iso-effective restricted organ-at-risk dosing to mucosa and bone tissues. The time-to-event Bayesian optimal interval (TITE-BOIN) design is employed to address the challenge of the long DLT window of 6 months and find the maximum tolerated dose. The primary endpoint is unacceptable radiation-induced toxicities (Grade 4, mucositis, dermatitis, or Grade 3 myelopathy, osteoradionecrosis) occurring within 6 months following radiotherapy. The second endpoint is any grade 3 toxicity occurring in 3–6 months after radiation. Discussion The PIRATES dose-escalation approach is designed to provide a safe avenue to intensify local treatment for HNC patients for whom therapy with conventional radiation dose levels is likely to fail. PIRATES aims to minimize the radiation damage to the tissue surrounding the tumor volume with the combination of proton therapy and adaptive radiotherapy and within the high dose tumor volume with hybrid hyper-fractionation and not boosting mucosal and bone tissues. Ultimately, if successful, PIRATES has the potential to safety increase local control rates in HNC patients with high loco-regional failure risk. Trial registration: ClinicalTrials.gov ID: NCT04870840; Registration date: May 4, 2021. Netherlands Trial Register ID: NL9603; Registration date: July 15, 2021.

Background The incidence of obesity has been steadily increasing, especially in developed countries. Also, obesity is considered one of the modifiable risk factors of kidney cancer. Objectives This study aims to determine the impact of bariatric surgery-induced weight loss on the prevention of kidney cancer. Setting Academic Hospital, United States. Methods The National (Nationwide) Inpatient Sample (NIS) was queried for the period 2010 to 2015 for first-time kidney cancer-related hospitalization, used as a proxy for cancer incidence, in patients with a history of bariatric surgery (cases) and patients with obesity but no history of bariatric surgery (controls). Patients with a previous diagnosis of cancer were excluded from the analysis. In order to identify comparable patients, all controls had to have a body mass index ≥35 kg/m2, as per the existing qualification criteria for bariatric surgery. The International Classification of Diseases-9 codes (ICD-9) was used to identify admissions for kidney cancer. A univariate analysis was conducted to compare demographics and co-morbidities between groups. A multivariate logistic regression model was performed to assess differences between surgical and control groups and adjust for independent variables such as smoking history and family history of malignancy. All percentages and means (with confidence intervals [CIs]) were weighted. Results A total of 2,300,845 were included in the analysis, of which 2,004,804 controls-subjects, with a mean age of 54.4 ± .05 years, and 296,041 treatment-subjects, with a mean age of 51.9 ± .05 years. Demographics and co-morbidities, such as tobacco use, diabetes, and hypertension, were also measured. Patients with a history of bariatric surgery were significantly less likely to experience renal cancer than patients without a history of bariatric surgery, with 5935 cases in the control group and 684 in the case group (P Conclusion Our finding suggests that bariatric surgery-induced weight loss could significantly prevent first-time kidney cancer-related hospitalizations in patients with obesity. Prospective studies are needed to confirm our findings.

Background Ovarian hyperstimulation syndrome (OHSS) is traditionally associated with fertility treatments and results in elevated human chorionic gonadotropin (βhCG) levels and fluid shifts to extravascular compartments. Rarely, spontaneous pregnancies with significant βhCG elevations, such as molar pregnancies, can give rise to OHSS. Case A 24-year-old woman was diagnosed as having a molar pregnancy at approximately 12 weeks gestation following spontaneous conception. Her initial βhCG was over 1 million IU/L. There was no evidence of metastatic disease. She underwent an uncomplicated dilation and curettage. Three days later, she presented with chest pain, shortness of breath, and abdominal discomfort. Massively enlarged ovaries were identified with bilateral pleural effusions requiring repeated thoracentesis. Conclusion This case demonstrates rare sequelae of molar pregnancy. Treatment is mainly supportive, and close observation is required to manage complications. In patients with extremely elevated βhCG levels, clinicians must remain vigilant for signs suggesting OHSS, even following evacuation of the uterus.

Objective and summary of background data Adverse events in surgical patients can occur pre-operatively, intra-operatively and post-operatively. Universally accepted classification systems are not yet available for intra-operative adverse events (iAEs). ClassIntra, has recently been developed and validated as a tool for grading iAEs that occur between skin incision and skin closure irrespective of the origin, i.e. surgery, anesthesia or organizational. The aim of this study is to assess the inter-rater agreement of ClassIntra and assess its predictive value for post-operative complications in elective abdominal surgery. Methods This study is a secondary use of data from the LAParotomy or LAParoscopy and ADhesiolysis (LAPAD) study, with detailed data on incidence and management of intra-operative and post-operative complications. Data were collected in a cohort of elective abdominal surgeries. Two teams graded all recorded events in the LAPAD study according to ClassIntra. Cohen's Kappa coefficient was calculated to determine inter-rater agreement. Uni- and multivariable linear regression was used to assess the predictive value of the ClassIntra grades for post-operative complications. Results IAEs were rated in 333/755 (44%) surgeries by team 1, and in 324/755 (43%) surgeries by team 2. Cohen's kappa coefficient for ClassIntra grades was 0.87 (95% CI 0.84-0.90). Discrepancies in grading were most frequent for intra-operative bleeding and adhesions' associated injuries. At least one post-operative complication was observed in 278 (37%) patients. The risk of a post-operative complications increased with every increase in severity grade of ClassIntra. Intra-operative hypotension (mean difference (MD) 23.41, 95% CI 12.93 - 33.90) and other organ injuries (MD 18.90, 95% CI -4.22 - 42.02) were the strongest predictors for post-operative complications. Conclusions ClassIntra has an almost perfect inter-rater agreement for the classification of iAEs. An increasing grade of ClassIntra was associated with a higher incidence of post-operative complications. Discrepancies in grading related to common complications in abdominal procedures mostly consisted of intra-operative bleeding and adhesion-related injuries. Grading of interoperative events in abdominal surgery might further improve by consensus regarding the definitions of a number of frequent events.

Gleason score, a measure of prostate tumor differentiation, is the strongest predictor of lethal prostate cancer at the time of diagnosis. Metabolomic profiling of tumor and of patient serum could identify biomarkers of aggressive disease and lead to the development of a less-invasive assay to perform active surveillance monitoring. Metabolomic profiling of prostate tissue and serum samples was performed. Metabolite levels and metabolite sets were compared across Gleason scores. Machine learning algorithms were trained and tuned to predict transformation or differentiation status from metabolite data. A total of 135 metabolites were significantly different (Padjusted < 0.05) in tumor versus normal tissue, and pathway analysis identified one sugar metabolism pathway (Padjusted = 0.03). Machine learning identified profiles that predicted tumor versus normal tissue (AUC of 0.82 ± 0.08). In tumor tissue, 25 metabolites were associated with Gleason score (unadjusted P < 0.05), 4 increased in high grade while the remainder were enriched in low grade. While pyroglutamine and 1,5-anhydroglucitol were correlated (0.73 and 0.72, respectively) between tissue and serum from the same patient, no metabolites were consistently associated with Gleason score in serum. Previously reported as well as novel metabolites with differing abundance were identified across tumor tissue. However, a “metabolite signature” for Gleason score was not obtained. This may be due to study design and analytic challenges that future studies should consider. Implications: Metabolic profiling can distinguish benign and neoplastic tissues. A novel unsupervised machine learning method can be utilized to achieve this distinction.