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Non-obstructive azoospermia is reported to affect 1 in 100 men, and despite advances in surgical practice, the succesful sperm retrieval rate for microdissection testicular sperm extraction surgery (mTESE) is only 46%. This article reviews the potential causes for mTESE failure and provides a management strategy to guide the clinicians on how to treat this challenging cohort of patients.

Peripheral T-cell lymphomas (PTCLs) represent a heterogeneous disease group accounting for 10% of non-Hodgkin lymphomas. PTCL patients have typically poorer outcomes compared to aggressive B-cell lymphomas. However, such outcomes are heavily dependent upon subtype. Although anthracycline-based regimens such as cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) remain the standard first-line treatment for most aggressive PTCLs, there are important variations including incorporation of novel agents, use of radiotherapy and judicious consideration of stem cell transplantation. Relapsed or refractory disease represents a significant area of unmet need where chemotherapy intensification has limited efficacy and novel agents such as brentuximab vedotin and pralatrexate provide additional opportunities for attainment of remission and potential stem cell transplant. In the future, pre-therapy prognostic biomarkers including genomic characterisation, may aid in risk stratification and help guide initial patient management to improve survival. There is an urgent need to better understand the pathogenesis of PTCLs to facilitate novel drug combinatorial approaches to improve survival. This position statement represents an evidence-based synthesis of the literature for application in Australian and New Zealand practice. This article is protected by copyright. All rights reserved.

Background Despite years of slow progress, muscle invasive bladder cancer (MIBC) is finally entering the era of molecularly guided targeted therapy. However, tumor heterogeneity is high in MIBC and may impact treatment response and resistance. The objective of this review is to dissect recent insights into inter- and intratumor heterogeneity (ITH) in MIBC, with emphasis on the clinical implications of this heterogeneity for biomarker-driven strategies and the development of new therapies. Methods A nonsystematic review was performed in PubMed and EMBASE using the terms “tumor heterogeneity” and “bladder cancer.” Results Intertumor heterogeneity, as reflected by different clinical phenotypes in different patients, has been partially explained with next generation sequencing and other molecular profiling technologies. RNA-based molecular subtyping, for example, provides a classification of MIBC into distinct categories that can be used for further molecular analysis, biomarker discovery, risk stratification, and treatment selection. Molecular subtyping and specific genomic alterations, especially in DNA damage repair genes, may help explain why some patients respond better to systemic chemotherapy and immunotherapy. Conversely, spatial and temporal ITH threaten to confound attempts to target specific molecular lesions since not all tumor cells within a patient may carry the relevant lesion. Improved understanding and management of ITH is required for the most effective use of biomarker-driven targeted therapies. Conclusion Strategies to assess and overcome intertumor and ITH in MIBC will be critical steps toward realizing the objectives of precision oncology. Novel techniques such as analysis of circulating tumor DNA and single cell sequencing are likely to revolutionize our understanding of tumor heterogeneity.

Introduction : General surgery residents often feel unprepared to perform pediatric surgery procedures since case volume and experience may be low. Previously, we successfully implemented a simulation-based training (SBT) module for placement of a silastic silo for gastroschisis. Therefore, we designed a single institution pilot study to assess whether SBT for placement of a percutaneous peritoneal drain for perforated necrotizing enterocolitis (NEC) was feasible and lead to skill acquisition and increased confidence. Methods : Our newly created NEC module within our pediatric surgery SBT curriculum for general surgery residents was used. Residents completed two simulation sessions three months apart with confidence testing before and after each session. Skill acquisition and performance were assessed using a standardized case scenario and procedure checklist. Changes in residents’ confidence and performance were determined using Wilcoxon Signed-Rank Tests. Results : Nine post-graduate-year three general surgery residents completed this curriculum. Following completion, residents reported improved confidence completing each step of the procedure initially (p = 0.005) and at 3 months (p = 0.008) with improved technical scores (p = 0.011). The number of residents deemed proficient significantly improved (p = 0.031). Conclusion : Implementation of SBT module for perforated NEC was feasible and improved residents’ confidence and proficiency completing the procedure.

STUDY OBJECTIVES: There is a paucity of data on the association between day-to-day variation in sleep pattern and all-cause mortality. We aimed to investigate whether day-to-day variation in sleep duration and onset of sleep are associated with cardiovascular and all-cause mortality. METHODS: We used data belonging to 388 unique patients from the Midlife in the United States 2 Biomarker study (2004–2009). Information on sleep onset, duration, and sleep-wake cycles was collected for 7 consecutive days using the Actiwatch device. Sleep irregularity was assessed using mean and standard deviations in sleep duration and time of onset of sleep over 7 days. Cox proportional regression analysis and the Fine and Gray subdistribution method were used with all-cause and cardiovascular mortality, respectively. RESULTS: Over a median of 8.6 years of follow-up, 37 patients died, including 10 deaths resulting from cardiovascular causes. There was no statistically significant increase in cardiovascular mortality with variation in sleep duration in the highest vs the lowest tertile (hazard ratio, 4.00; 0.45–35.48; P = .21). However, increased all-cause mortality was seen in the highest vs the lowest tertile (hazard ratio, 3.99; 1.33–11.94; P = .01). Multivariable model adjusting for confounders had higher all-cause mortality with increased sleep duration variation in the highest vs the lowest tertile: hazard ratio, 4.85; 1.52–15.49; P

The diagnosis of graft-versus-host-disease (GVHD) after solid organ transplantation is made difficult by its variable clinical presentation and lack of sensitive and specific biomarkers to evaluate the immune state of transplant recipients. Emerging noninvasive diagnostic techniques like the quantification of donor-derived cell-free DNA (dd-cfDNA) for surveillance may improve the current standard-of-care. Herein, we report the use of this methodology in a patient with GVHD and corresponding levels of dd-cfDNA without any evidence of graft injury. Correlation of dd-cfDNA levels with the clinical course and its novel application here could lead to improvements in the rapid diagnosis of GVHD and in monitoring of response to treatment.

Narrative analysis is well established as a means of examining the subjective experience of those who suffer chronic illness and cancer. In a study of perceptions of the outcomes of treatment of cancer of the colon, we have been struck by the consistency with which patients record three particular observations of their subjective experience: (1) the immediate impact of the cancer diagnosis and a persisting identification as a cancer patient, regardless of the time since treatment and of the presence or absence of persistent or recurrent disease; (2) a state of variable alienation from social familiars, expressed as an inability to communicate the nature of the experience of the illness, its diagnosis and treatment; and (3) a persistent sense of boundedness, an awareness of limits to space, empowerment and available time. These subjectivities were experienced in varying degree by all patients in our study. Individual responses to these experiences were complex and variable. The experiences are best understood under the rubric of a category we call "liminality". We believe that all cancer patients enter and experience liminality as a process which begins with the first manifestations of their malignancy. An initial acute phase of liminality is marked by disorientation, a sense of loss and of loss of control, and a sense of uncertainty. An adaptive, enduring phase of suspended liminality supervenes, in which each patient constructs and reconstructs meaning for their experience by means of narrative. This phase persists, probably for the rest of the cancer patient's life. The experience of liminality is firmly grounded in the changing and experiencing body that houses both the disease and the self. Insights into the nature of the experience can be gained from the Existentialist philosophers and from the history of attitudes to death. Understanding liminality helps us to understand what it is that patients with cancer (and other serious illnesses) seek from the system to which they turn for help. Its explication should therefore be important for those who provide health care, those who educate health care workers and those concerned to study and use outcomes as administrative and policy making instruments.

Gastrostomy tube (GT) placement is a common pediatric procedure with high postoperative resource utilization. We aimed to determine if standardized discharge instructions (SDI) reduced healthcare utilization rates.We performed a retrospective cohort study comparing postoperative hospital utilization of patients who underwent initial GT placement pre- and post-SDI protocol implementation from 2014-2019. Statistical analyses included Chi-square tests, multivariable adjusted logistic regression, adjusted Cox proportion hazard regression, and adjusted Poisson regression models when appropriate.197 patients were included, 102 (51.8%) before and 95 (48.2%) after protocol implementation. On primary analysis, SDI patients did not have significantly different total postoperative hospital utilization events at 30-days (48.0% vs. 38.9%, p = 0.25). On secondary analysis, SDI patients had lower rates of ED (8.4% vs. 19.6%, p = 0.026) and office visits (11.6% vs. 25.5%, p = 0.017) at 30-days. Non-SDIs patients had greater odds of ED visits (OR2.7, 95%CI 1.3-5.9, p = 0.01), office visits (OR3.7, 95%CI 1.7-8.1, p = 0.001) and phone calls (OR2.6, 95%CI 1.2-5.7, p = 0.016) at 1-year. The adjusted hazard ratio was 2.0 (95%CI 1.4-3.0, p 0.001). Incident rate ratio were 1.8 (95%CI 1.2-2.5, p = 0.002) at 30-days and 1.9 (95%CI 1.5-2.4, p 0.001) at 1-year post-discharge.SDIs post-GT placement may reduce multiple aspects of postoperative hospital utilization.

A 35-year-old woman presented with a constellation of systemic symptoms: rashes, weight loss, arthralgia and mouth ulcers. Six months afterwards, she experienced bilateral and sequential reduction in vision, and was found to have bilateral vaso-occlusive retinopathy, with critical macular ischaemia in the left eye. Her serological markers were consistent with a diagnosis of lupus. A lymph node biopsy confirmed Kikuchi-Fujimoto disease, a benign condition of unknown cause characterised by fever, cervical and axillary lymphadenopathy. Given that this overlap syndrome was associated with a number of systemic features and had affected the eyes, an immunosuppressive regime with rituximab was considered prudent. This rendered her vasculitis stable and non-progressive, and there were signs of partial retinal microvasculature recovery on optical coherence tomography angiography. There is increasing evidence of an overlap between Kikuchi-Fujimoto disease and systemic lupus erythematosus, which is associated with vaso-occlusive retinopathy. In these instances, a multidisciplinary approach is warranted, with consideration of appropriate treatment in order to prevent harmful sequelae of vasculitis. Our treatment with rituximab abated the disease process, although close follow-up is paramount to monitor results and side-effects of treatment.

BACKGROUND A new bibliometric index called the disruption score was recently proposed to identify innovative and paradigm-changing publications. OBJECTIVE The goal was to apply the disruption score to the colorectal surgery literature to provide the community with a repository of important research papers. DESIGN A bibliometric analysis. SETTINGS The 100 most disruptive and developmental publications in Diseases of the Colon and Rectum, Colorectal Disease, International Journal of Colorectal Disease, and Techniques in Coloproctology were identified from a validated dataset of disruption scores and linked with the iCite NIH tool to obtain citation counts. MAIN OUTCOME MEASURES Disruption score and citation count. RESULTS We identified 12,127 articles published in Diseases of the Colon and Rectum (n=8,109), International Journal of Colorectal Disease (n=1,912), Colorectal Disease (n=1,751), and Techniques in Coloproctology (n=355) between 1954-2014. Diseases of the Colon and Rectum had the most papers in the top 100 most disruptive and developmental lists. The disruptive papers were in the top 1% of the disruption score distribution in PubMed and were cited between 1 and 671 times. Being highly cited was weakly correlated with high disruption scores (r=0.09). Developmental papers had disruption scores that were more strongly correlated with citation count (r=0.18). LIMITATIONS Subject to limitations of bibliometric indices, which change over time. DISCUSSION The disruption score identified insightful and paradigm-changing studies in colorectal surgery. Interestingly, they include a wide range of topics and consistently identified editorials and case reports/case series as important research. This bibliometric analysis provides colorectal surgeons with a unique archive of research that can often be overlooked, but that may have scholarly significance. See Video Abstract at http://links.lww.com/DCR/B639 .

Purpose To evaluate the readability, understandability, and actionability of online patient education materials (OPEM) related to breast cancer risk assessment. Material and methods We queried seven English-language search terms related to breast cancer risk assessment: breast cancer high-risk, breast cancer risk factors, breast cancer family history, BRCA, breast cancer risk assessment, Tyrer-Cuzick, and Gail model. Websites were categorized as: academic/hospital-based, commercial, government, non-profit or academic based on the organization hosting the site. Grade-level readability of qualifying websites and categories was determined using readability metrics and generalized estimating equations based on written content only. Readability scores were compared to the recommended parameters set by the American Medical Association (AMA). Understandability and actionability of OPEM related to breast cancer high-risk were evaluated using the Patient Education Materials Assessment Tool (PEMAT) and compared to criteria set at ≥70%. Descriptive statistics and inter-rater reliability analysis were utilized. Results 343 websites were identified, of which 162 met study inclusion criteria. The average grade readability score was 12.1 across all websites (range 10.8–13.4). No website met the AMA recommendation. Commercial websites demonstrated the highest overall average readability of 13.1. Of the 26 websites related to the search term breast cancer high-risk, the average understandability and actionability scores were 62% and 34% respectively, both below criteria. Conclusions OPEM on breast cancer risk assessment available to the general public do not meet criteria for readability, understandability, or actionability. To ensure patient comprehension of medical information online, future information should be published in simpler, more appropriate terms., Highlights • The average grade readability score of breast cancer risk assessment online education materials was 12.1 • No website met the AMA recommendation of a sixth-grade reading level. • To ensure patient comprehension, future information should be published in simpler, more appropriate terms.

Background: Metastasis is the major cause of mortality in breast cancer; however, the molecular mechanisms remain elusive. In our previous study, we demonstrated that S100A7/RAGE mediates breast cancer growth and metastasis by recruitment of tumor-associated macrophages. However, the downstream S100A7-mediated inflammatory oncogenic signaling cascade that enhances breast tumor growth and metastasis by generating the immunosuppressive tumor microenvironment (iTME) has not been studied. In this present study, we aimed to investigate the S100A7 and cPLA2 cross-talk in enhancing tumor growth and metastasis through enhancing the iTME.Methods: Human breast cancer tissue and plasma samples were used to analyze the expression of S100A7, cPLA2, and PGE2 titer. S100A7-overexpressing or downregulated human metastatic breast cancer cells were used to evaluate the S100A7-mediated downstream signaling mechanisms. Bi-transgenic mS100a7a15 overexpression, TNBC C3(1)/Tag transgenic, and humanized patient-derived xenograft mouse models and cPLA2 inhibitor (AACOCF3) were used to investigate the role of S100A7/cPLA2/PGE2 signaling in tumor growth and metastasis. Additionally, CODEX, a highly advanced multiplexed imaging was employed to delineate the effect of S100A7/cPLA2 inhibition on the recruitment of various immune cells.Results: S100A7 and cPLA2 are highly expressed and positively correlated in malignant breast cancer patients. S100A7/RAGE upregulates cPLA2/PGE2 axis in aggressive breast cancer cells. Furthermore, S100A7 is positively correlated with PGE2 in breast cancer patients. Moreover, cPLA2 pharmacological inhibition suppressed S100A7-mediated tumor growth and metastasis in multiple pre-clinical models. Mechanistically, S100A7-mediated activation of cPLA2 enhances the recruitment of immunosuppressive myeloid cells by increasing PGE2 to fuel breast cancer growth and its secondary spread. We revealed that cPLA2 inhibitor mitigates S100A7-mediated breast tumorigenicity by suppressing the iTME. Furthermore, CODEX imaging data showed that cPLA2 inhibition increased the infiltration of CD4+/CD8+ T cells in the TME. Analysis of metastatic breast cancer samples revealed a positive correlation between S100A7/cPLA2 with CD163+ tumor-associated M2-macrophages.Conclusions: Our study shows that cross-talk between S100A7 and cPLA2 plays an important role in enhancing breast tumor growth and metastasis by generating an immunosuppressive tumor microenvironment and reducing infiltration of T cells. Furthermore, S100A7 could be used as a novel non-invasive prognostic marker and cPLA2 inhibitors as promising drugs against S100A7-overexpressing metastatic breast cancer.

Key Points Somatic UBA1 mutations define VEXAS in men with late-onset systemic inflammatory disease and cytopenia.Features summarizing VEXAS include cytopenia, hypercellularity, lack of hematogones, and vacuoles in myeloid and erythroid precursors., VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is caused by somatic mutations in UBA1 and is identified by a genotype-driven method. This condition affects unrelated men with adultonset inflammatory syndromes in association with hematologic manifestations of peripheral cytopenia and bone marrow myeloid dysplasia. Although bone marrow vacuolization restricted to myeloid and erythroid precursors has been identified in patients with VEXAS, the detailed clinical and histopathological features of peripheral blood and bone marrows remain unclear. The current case report describes the characteristic hematologic findings in patients with VEXAS, including macrocytic anemia, thrombocytopenia, marked hypercellular bone marrow with granulocytic hyperplasia, megaloblastic changes in erythroid precursors, and the absence of hematogones in addition to prominent vacuoles in myeloid and erythroid precursor cells. Characterizing the clinical and hematologic features helps to raise awareness and improve diagnosis of this novel, rare, but potentially underrecognized disease. Prompt diagnosis expands the general knowledgeable and understanding of this disease, and optimal management may prevent patients from developing complications related to this refractory inflammatory syndrome and improve the overall clinical outcome.

PurposeThis qualitative study aimed to construct an observer-reported outcome measure (ObsRO) that evaluates fever distress in young children.MethodsA literature review was conducted to identify fever-related concepts. Clinical experts were interviewed for feedback on these concepts. Parents of young children were interviewed to identify behaviours the child exhibited during a recent fever episode. Fever sign and behaviour concepts endorsed by ≥20% parents were used to create items for the draft ObsRO. Parents of young children who recently had fever completed the ObsRO and gave feedback during two successive rounds of cognitive interviews.ResultsTwenty-five parents participated in the concept elicitation. Mean child age was 2.7 years (range: 0.6‑5.8). Fever sign and behaviour concepts endorsed by ≥20% participants were high temperature (80%), skin hot to touch (32%), skin redness/flushing (32%), reduced appetite/drink (48‑96%), needy/clingy/irritable (48‑92%), less active/interactive (68‑84%) and lethargic (64‑88%). Eighteen items, four in the Fever Signs Module and 14 in the Fever Behaviours Module, were developed for the draft ObsRO. Chosen recall period was 24 hours. Thirty participants (Round 1: n=17; Round 2: n=13), participated in cognitive interviews. Mean child age was 2.4 years (range: 0.3‑5.8). Round 1 feedback resulted in two Fever Signs items being combined. Three Fever Behaviour items were deleted, six revised and four unchanged. No changes were made following Round 2 feedback. Most participants understood all aspects of the ObsRO and found it user-friendly.ConclusionThe ObsRO will undergo further development in validation studies testing measurement properties of each item.

OBJECTIVE The prevalence of chronic kidney disease (CKD) in the United States is 13% of the general population. Among those with CKD, diabetic nephropathy is the leading cause of end-stage renal disease. This is a retrospective study examining the effect of long-term use of dipeptidyl peptidase-4 (DPP-4) inhibitors on all-cause mortality and progression of renal disease in the veteran population. METHODS Data was extracted using the Veterans Administration Informatics and Computing Infrastructure. A large cohort of veterans diagnosed with type 2 diabetes mellitus were used to identify patients on DPP-4 inhibitors and without DPP-4 inhibitors. Groups were compared to determine the effect of DPP-4 inhibitors on the progression of CKD and all-cause mortality. Data were analyzed using SAS. RESULTS Subjects in the treatment group (n = 40 558) had baseline variables (age, body mass index, race) similar to the control group (n = 40 558). Diabetes control improved in the treatment group (HgbA1c, 8.3% [67 mmol/mol] to 7.8% [62 mmol/mol]; P < .001) but not in the control group (HgbA1c, 7.4% [57 mmol/mol] to 7.3% [56 mmol/mol]). New diagnoses of heart failure and coronary artery bypass grafts were clinically significant (odds ratios = 0.66 and 0.52). No change in progression of CKD was seen in either group. All-cause mortality was reduced by 59%. CONCLUSION We conclude that DPP-4 inhibitors are associated with a significant reduction in all-cause mortality independent of glucose control, albeit with no clear cause, including obtainable cardiovascular outcomes. Our data is consistent with prior trials in that DPP-4 inhibitors did not show a significant change in serum creatinine or microalbuminuria.

This study analyzes 2050–2051 grid stability in the 50 U S. states and District of Columbia after their all-sector (electricity, transportation, buildings, industry) energy is transitioned to 100% clean, renewable Wind-Water-Solar (WWS) electricity and heat plus storage and demand response (thus to zero air pollution and carbon). Stability is analyzed in five regions; six isolated states (Texas, California, Florida, New York, Alaska, Hawaii); Texas interconnected with the Midwest, and the contiguous U.S. No blackouts occur, including during summer in California or winter in Texas. No batteries with over 4-h storage are needed. Concatenating 4-h batteries provides long-duration storage. Whereas transitioning more than doubles electricity use, it reduces total end-use energy demand by ∼57% versus business-as-usual (BAU), contributing to the 63 (43–79)% and 86 (77–90)% lower annual private and social (private + health + climate) energy costs, respectively, than BAU. Costs per unit energy in California, New York, and Texas are 11%, 21%, and 27% lower, respectively, and in Florida are 1.5% higher, when these states are interconnected regionally than islanded. Transitioning may create ∼4.7 million more permanent jobs than lost and requires only ∼0.29% and 0.55% of new U.S. land for footprint and spacing, respectively, less than the 1.3% occupied by the fossil industry today.

Purpose: The PARP inhibitor rucaparib is approved in the United States for patients with metastatic castration-resistant prostate cancer (mCRPC) and a deleterious germline and/or somatic BRCA1 or BRCA2 (BRCA) alteration. While sequencing of tumor tissue is considered the standard for identifying patients with BRCA alterations (BRCA+), plasma profiling may provide a minimally invasive option to select patients for rucaparib treatment. Here, we report clinical efficacy in patients with BRCA+ mCRPC identified through central plasma, central tissue, or local genomic testing and enrolled in TRITON2. Patients and Methods: Patients had progressed after next-generation androgen receptor–directed and taxane-based therapies for mCRPC and had BRCA alterations identified by central sequencing of plasma and/or tissue samples or local genomic testing. Concordance of plasma/tissue BRCA status and objective response rate and prostate-specific antigen (PSA) response rates were summarized. Results: TRITON2 enrolled 115 patients with BRCA+ identified by central plasma (n = 34), central tissue (n = 37), or local (n = 44) testing. Plasma/tissue concordance was determined in 38 patients with paired samples and was 47% in 19 patients with a somatic BRCA alteration. No statistically significant differences were observed between objective and PSA response rates to rucaparib across the 3 assay groups. Patients unable to provide tissue samples and tested solely by plasma assay responded at rates no different from patients identified as BRCA+ by tissue testing. Conclusions: Plasma, tissue, and local testing of mCRPC patients can be used to identify men with BRCA+ mCRPC who can benefit from treatment with the PARP inhibitor rucaparib.

Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

Background Pierre Robin Sequence (PRS) is characterized by micrognathia, glossoptosis, and upper airway obstruction. Early recognition and appropriate perinatal management is crucial for optimizing outcomes. This study aimed to evaluate 20-week fetal ultrasounds to determine if specific mandibular measurements could predict PRS diagnosis and disease severity. Methods A retrospective case-control study of 48 patients with PRS and gender-matched controls was performed. Medical records were reviewed for respiratory and surgical interventions. Three parameters to assess micrognathia were measured on mid-sagittal profile ultrasound images: frontal nasal-mental angle (FNMA), facial-maxillary angle (FMA), and alveolar overjet. Student's t-test and univariate logistic regression was performed. P ≤ 0.05 was considered statistically significant. Results Patients with PRS demonstrated a significantly smaller mean FNMA compared to the control group, 129.3 ± 8.6° and 137.4 ± 3.2°, respectively (p Conclusions Mandibular features on the 20-week ultrasound can be measured to predict diagnosis and severity of PRS. This is an important first step to prepare for potential respiratory intervention at delivery to minimize perinatal hypoxia. Alveolar overjet, previously not described in prenatal ultrasound literature, is measurable and has utility in prenatal screening for PRS, as do FMA and FNMA.

Background Cognitive dysfunction after surgery is a major issue in older adults. Here, we determined the effect of APOE4 on perioperative neurocognitive function in older patients. Methods We enrolled 140 English-speaking patients ≥60 yr old scheduled for noncardiac surgery under general anaesthesia in an observational cohort study, of whom 52 underwent neuroimaging. We measured cognition; Aβ, tau, p-tau levels in CSF; and resting-state intrinsic functional connectivity in six Alzheimer's disease-risk regions before and 6 weeks after surgery. Results There were no significant APOE4-related differences in cognition or CSF biomarkers, except APOE4 carriers had lower CSF Aβ levels than non-carriers (preoperative median CSF Aβ [median absolute deviation], APOE4 305 pg ml−1 [65] vs 378 pg ml−1 [38], respectively; P=0.001). Controlling for age, APOE4 carriers had significantly greater preoperative functional connectivity than non-carriers between several brain regions implicated in Alzheimer's disease, including between the left posterior cingulate cortex and left angular gyrus (β [95% confidence interval, CI], 0.218 [0.137–0.230]; PFWE=0.016). APOE4 carriers, but not non-carriers, experienced significant connectivity decreases from before to 6 weeks after surgery between several brain regions including between the left posterior cingulate cortex and left angular gyrus (β [95% CI], –0.196 [–0.256 to –0.136]; PFWE=0.001). Most preoperative and postoperative functional connectivity differences did not change after controlling for preoperative CSF Aβ levels. Conclusions Postoperative change trajectories for cognition and CSF Aβ, tau or p-tau levels did not differ between community dwelling older APOE4 carriers and non-carriers. APOE4 carriers showed greater preoperative functional connectivity and greater postoperative decreases in functional connectivity in key Alzheimer's disease-risk regions, which occur via Aβ-independent mechanisms.

This study extends the understanding of entrepreneurial orientation (EO), vertical knowledge acquisition, and actor collaboration to a “whole of value-chain” perspective in transitional economies by investigating a subsistence smallholder agricultural value-chain. It examines the relationships between EO and vertical knowledge acquisition and the role of value-chain collaboration. It also contributes to the understanding of entrepreneurship as an economic development tool by considering how EO moderates the effect of value-chain actor collaboration on acquiring market and consumer knowledge by subsistence upstream actors within value-chains. Data were collected through a survey of smallholder value-chain shifting from selling to local wet markets to selling to cattle collectors and traders and through a value-chain to retailers. The findings suggest that higher levels of EO by smallholders and SME agribusinesses enhance the acquisition of vertical knowledge such as market and consumer preference information throughout the value-chain, and interfirm collaboration positively moderates this relationship.

Non-human primate (NHP) models are essential for developing and translating new treatments that target neural circuit dysfunction underlying human psychopathology. As a proof-of-concept for treating neuropsychiatric disorders, we used a NHP model of pathological anxiety to investigate the feasibility of decreasing anxiety by chemogenetically (DREADDs [designer receptors exclusively activated by designer drugs]) reducing amygdala neuronal activity. Intraoperative MRI surgery was used to infect dorsal amygdala neurons with AAV5-hSyn-HA-hM4Di in young rhesus monkeys. Invivo microPET studies with [11C]-deschloroclozapine and postmortem autoradiography with [3H]-clozapine demonstrated selective hM4Di binding in the amygdala, and neuronal expression of hM4Di was confirmed with immunohistochemistry. Additionally, because of its high affinity for DREADDs, and its approved use in humans, we developed an individualized, low-dose clozapine administration strategy to induce DREADD-mediated amygdala inhibition. Compared to controls, clozapine selectively decreased anxiety-related freezing behavior in the human intruder paradigm in hM4Di-expressing monkeys, while coo vocalizations and locomotion were unaffected. These results are an important step in establishing chemogenetic strategies for patients with refractory neuropsychiatric disorders in which amygdala alterations are central to disease pathophysiology.

The importance of teams’ and individuals’ non-technical skills in reducing adverse events is well-recognised. We undertook a systematic review of the published literature to assess the research undertaken to date in assessing non-technical skills and behaviours within oral maxillofacial-head and neck (OMFS-H&N) surgery. The aim was to assess the applicability of published studies to current practice, how these studies could guide future research and to assess for areas where further development could be undertaken. The search terms included ‘non technical skills’, ‘nontechnical skills’, ‘NOTSS’, ‘non-technical skills for surgeons’, ‘oral surgery’, ‘oral maxillofacial surgery’, ‘OMFS’, ‘maxillofacial surgery’, ‘head and neck surgery’, ‘microsurgery’, ‘behavioural markers’, ‘behavioural assessment tool’, ‘behavioural ratings system’. Three publications were included in the review, involving 83 participants. Participants consistently achieved the highest scores in ‘situation awareness’ category whilst demonstrating a tendency to achieve their lower mean scores in the ‘communication and teamwork’ and ‘decision making’ categories. The majority of research into surgeons’ non-technical skills has occurred in simulated environments and not the genuine environments where actual surgery is being performed on patients. The research performed in the field of OMFS-H&N involving ‘real’ patients therefore places the specialty in a stronger position than many other surgical specialties.

Field Assessment Stroke Triage for Emergency Destination (FAST-ED) is a simple and accurate prehospital stroke severity scale that has been shown to have comparable accuracy to the gold standard National Institutes of Health Stroke Scale (NIHSS) but requires further field validation for use by emergency medical services (EMS), particularly in rural systems. FAST-ED scores ≥4 are considered high probability for large vessel occlusion (LVO) strokes, while scores4 are low to moderate probability for LVO. The objective of this study was to assess inter-rater reliability of the EMS FAST-ED (EMS) score to the emergency department FAST-ED (ED-MD) scores.EMS calculated FAST-ED scores prior to transport to the emergency department (ED) on patients with a positive prehospital stroke screen. EDMD calculated FAST-ED scores for the same patients upon arrival to the ED. Interrater reliability and test characteristics were calculated.A total of 95 patients were included in this study and 14 were subsequently diagnosed with an LVO. EMS assigned 34 patients (35.8%) a FAST-ED score of ≥4. EDMD assigned 25 patients (26.3%) a FAST-ED score of ≥4. Using the clinical cut-points of FAST-ED scores4 and ≥ 4, a linearly weighted Cohen's kappa coefficient showed moderate interrater reliability when comparing EMS and EDMD scores (kEMS and EDMD FAST-ED scores were moderately comparable in a rural EMS system. Similar NPVs compared to EDMD suggest the use of FAST-ED as an appropriate screening tool for EMS to predict the probability of LVO in the prehospital setting and make destination determinations regarding primary transport to a thrombectomy-capable stroke center.

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

An ecological issue can best be studied by gathering original data that are specifically targeted for that issue. But ascertaining-a priori-whether a novel issue will be worth exploring can be problematic without background data. However, an issue's potential merit can sometimes be evaluated by repurposing legacy or other data that had been gathered for unrelated purposes but that are nonetheless relevant. Our present project was initially motivated by an ecological trade-off-proposed eight decades ago-involving the depth at which desert reptiles overwintered. To address those and related issues, we repurposed our five-decades-old natural history data for 18 species of Kgalagadi lizards and then explored the seasonal ecology of these lizards, emphasizing winter. Our data were not gathered for a study of seasonal ecology but nonetheless inform diverse seasonal patterns for a major community of lizards. However, repurposed data (whether recent or legacy) present challenges and ambiguities, and we suggest targeted, next-step studies of seasonal ecology that can circumvent limitations and ambiguities.

Artificial objects currently populating Earth orbital regimes can be distinguished by comparing remote observational data to that of optical measurements within the visible (VIS) and near infrared (NIR) spectral regions of materials obtained in the laboratory. Careful comparison of spectrally resolved observations with laboratory-based material irradiation experiments can provide a tool for remote diagnosis and anomaly resolution. However, the spectral signatures of many materials change as a function of exposure to radiation in geosynchronous Earth orbit (GEO). In order for remote characterization to be a viable characterization technique, the evolution of material optical properties (VIS-NIR) upon exposure to the GEO environment must be understood. To this end, we have studied the reflectance of several commonly used spacecraft materials including organic polymers, solar cell coverglasses, black thermal control paint, and carbon-carbon (C–C) matrix composite as a function of exposure to high energy electron irradiation in order to mimic the harsh environment of GEO. It was found that different classes of materials exhibit large variation in radiation stability resulting in the development of unique spectral characteristics.

Pain, agitation and delirium are common during critical illness and are associated with many adverse consequences. A key aim of critical care is the facilitation of a calm, comfortable patient who can interact with their family and staff. Intensive care unit (ICU) patients frequently have pain from a variety of sources, many of which are not readily appreciated or actively managed. This article explores the challenges of assessing pain in the ICU and outlines methods that can be used to better identify and manage pain in this patient group. Agitation in ICU is often multifactorial, with many of its sources under-recognized. We will discuss the potential reasons that ICU patients become agitated, methods for measuring agitation and the actions that can be taken to alleviate it. Although the use of sedative and anxiolytic drugs is common in the ICU, their use is not without risks. This article will outline these risks, the variety of drugs available and how to use these drugs to a targeted effect. We will also explore delirium, its risk factors, precipitants and associated morbidity and mortality. This article will discuss how to diagnose delirium and the methods used to prevent and manage it.

PURPOSE The CLL14 study has established one-year fixed-duration treatment of venetoclax and obinutuzumab (Ven-Obi) for patients with previously untreated chronic lymphocytic leukemia. With all patients off treatment for at least three years, we report a detailed analysis of minimal residual disease (MRD) kinetics and long-term outcome of patients treated in the CLL14 study. PATIENTS AND METHODS Patients were randomly assigned to receive six cycles of obinutuzumab with 12 cycles of venetoclax or 12 cycles of chlorambucil (Clb-Obi). Progression-free survival (PFS) was the primary end point. Key secondary end points included rates of undetectable MRD and overall survival. To analyze MRD kinetics, a population-based growth model with nonlinear mixed effects approach was developed. RESULTS Of 432 patients, 216 were assigned to Ven-Obi and 216 to Clb-Obi. Three months after treatment completion, 40% of patients in the Ven-Obi arm (7% in the Clb-Obi arm) had undetectable MRD levels < 10−6 by next-generation sequencing in peripheral blood. Median MRD doubling time was longer after Ven-Obi than Clb-Obi therapy (median 80 v 69 days). At a median follow-up of 52.4 months, a sustained significant PFS improvement was observed in the Ven-Obi arm compared with Clb-Obi (median not reached v 36.4 months; hazard ratio 0.33; 95% CI, 0.25 to 0.45; P < .0001). The estimated 4-year PFS rate was 74.0% in the Ven-Obi and 35.4% in the Clb-Obi arm. No difference in overall survival was observed (hazard ratio 0.85; 95% CI, 0.54 to 1.35; P = .49). No new safety signals occurred. CONCLUSION Appearance of MRD after Ven-Obi is significantly slower than that after Clb-Obi with more effective MRD reduction. These findings translate into a superior long-term efficacy with the majority of Ven-Obi–treated patients remaining in remission.

Refereed/Peer-reviewed In this article, we are primarily concerned with the influence and role of time on an entrepreneurial ecosystem (EE). Hence, the dynamics incorporated into the conception of the EE comes into focus. The recent work on this aspect has generally observed time as an evolutionary element for shaping and forming the context for entrepreneurial outcomes or that time is related to the change in entrepreneur and network profiles within a region. Other scholars have also noted how certain aspects of an EE will be affected by dimensions of size over time or that the profile of resources will alter the EE attractiveness for entrepreneurs. Time itself as a dynamic influence has not been explicitly examined and here we seek to draw out the multiple perceptions of time that influence the different rates of start-up, firm growth, change and evolution. We conclude by drawing attention to the simultaneous interaction of the different perceptions of time and outline the contributions to this Special Issue on the dynamics of the entrepreneurial ecosystem.

ObjectiveTo examine the association between estimated age at first exposure (eAFE) to American football and clinical measures throughout recovery following concussion.MethodsParticipants were recruited across 30 colleges and universities as part of the National Collegiate Athletic Association (NCAA)–Department of Defense Concussion Assessment, Research and Education Consortium. There were 294 NCAA American football players (age 19 ± 1 years) evaluated 24–48 hours following concussion with valid baseline data and 327 (age 19 ± 1 years) evaluated at the time they were asymptomatic with valid baseline data. Participants sustained a medically diagnosed concussion between baseline testing and postconcussion assessments. Outcome measures included the number of days until asymptomatic, Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) composite scores, Balance Error Scoring System (BESS) total score, and Brief Symptom Inventory 18 (BSI-18) subscores. The eAFE was defined as participant's age at the time of assessment minus self-reported number of years playing football.ResultsIn unadjusted regression models, younger eAFE was associated with lower (worse) ImPACT Visual Motor Speed (R2 = 0.031, p = 0.012) at 24–48 hours following injury and lower (better) BSI-18 Somatization subscores (R2 = 0.014, p = 0.038) when the athletes were asymptomatic. The effect sizes were very small. The eAFE was not associated with the number of days until asymptomatic, other ImPACT composite scores, BESS total score, or other BSI-18 subscores.ConclusionEarlier eAFE to American football was not associated with longer symptom recovery, worse balance, worse cognitive performance, or greater psychological distress following concussion. In these NCAA football players, longer duration of exposure to football during childhood and adolescence appears to be unrelated to clinical recovery following concussion.

The COVID-19 pandemic is putting unprecedented pressures on healthcare systems globally. Early insights have been made possible by rapid sharing of data from China and Italy. In the UK, we have rapidly mobilised inflammatory bowel disease (IBD) centres in order that preparations can be made to protect our patients and the clinical services they rely on. This is a novel coronavirus; much is unknown as to how it will affect people with IBD. We also lack information about the impact of different immunosuppressive medications. To address this uncertainty, the British Society of Gastroenterology (BSG) COVID-19 IBD Working Group has used the best available data and expert opinion to generate a risk grid that groups patients into highest, moderate and lowest risk categories. This grid allows patients to be instructed to follow the UK government’s advice for shielding, stringent and standard advice regarding social distancing, respectively. Further considerations are given to service provision, medical and surgical therapy, endoscopy, imaging and clinical trials.

Background. Several large-scale studies suggest that Bacille Calmette–Guerin (BCG) vaccination in early childhood may reduce the risk of atopic diseases, but the findings remain controversial. Here, we aimed to investigate the potential correlation between early childhood BCG vaccination and the risk of developing atopic diseases. Methods. Eligible studies published on PubMed, EMBASE, and Cochrane CENTRAL were systematically sourced from 1950 to July 2021. Studies with over 100 participants and focusing on the association between BCG vaccine and atopic diseases including eczema, asthma, and rhinitis were included. Preliminary assessment of methods, interventions, outcomes, and study quality was performed by two independent investigators. Odds ratio (OR) with 95% confidence interval (CI) was calculated. Random effects of the meta-analysis were performed to define pooled estimates of the effects. Results. Twenty studies with a total of 222,928 participants were selected. The quantitative analysis revealed that administering BCG vaccine in early childhood reduced the risk of developing asthma significantly (OR 0.77, 95% CI 0.63 to 0.93), indicating a protective efficacy of 23% against asthma development among vaccinated children. However, early administration of BCG vaccine did not significantly reduce the risk of developing eczema (OR 0.94, 95% CI 0.76 to 1.16) and rhinitis (OR 0.99, 95% CI 0.81 to 1.21). Further analysis revealed that the effect of BCG vaccination on asthma prevalence was significant especially in developed countries (OR 0.73, 95% CI 0.58 to 0.92). Conclusion. BCG vaccination in early childhood is associated with reduced risk of atopic disease, especially in developed countries.

PURPOSE A dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone plus rituximab (DA-EPOCH-R) regimen has been shown to deliver excellent survival for adults with primary mediastinal large B-cell lymphoma (PMLBL) without the use of radiotherapy. No international prospective evaluation of this regimen has previously been reported in children and adolescents. PATIENTS AND METHODS We conducted an international single-arm phase II trial involving patients younger than age 18 years with PMLBL who were to receive six courses of DA-EPOCH-R. The primary end point was event-free survival (EFS). Overall survival and toxicity were also assessed. This trial was registered (ClinicalTrials.gov identifier: NCT01516567 ). RESULTS Analyses were based on 46 patients. The median age was 15.4 years (interquartile range: 14-16 years). The median follow-up was 59.0 months (interquartile range: 52.6-69.2 months). Fourteen events were observed (eight relapses or progressions (including three parenchymal CNS relapses), four residual lymphoma, and two second malignancies). The 4-year EFS was 69.6% (95% CI, 55.2 to 80.9), which did not differ from the rate observed historically ( P = .59). Seven deaths occurred (six disease-related and one second malignancy). The overall survival was 84.8% (95% CI, 71.8 to 92.4). Twenty-two patients (48%) reached dose levels ≥ 4. Nonhematologic adverse events grade ≥ 3 or cardiac adverse events grade ≥ 2 occurred in 47 of 276 (17%) courses and 30 of 46 patients (65%). CONCLUSION DA-EPOCH-R did not improve the EFS compared with a historical control in this first prospective multisite international study of children and adolescents with PMLBL. Further studies are required to determine the optimum therapy for children and adolescents with this lymphoma.

Background: Many recent studies have focused on the potential hazards of blue light exposure to ocular health. One group with a unique blue light exposure risk is dentists, who use curing lights that emit intense blue light during restorative procedures. During these procedures, dentists often experience brief ocular exposure to these lights. The purpose of the present study was to explore whether such exposures may have an effect on the vision and ocular health of dentists. Methods: A group of 12 dentists who had experienced curing light exposure over a period of 10 or more years were compared to a group of eight control subjects with no such exposure. The subjects were tested for visual acuity and contrast sensitivity. Their retinas were examined using fundus imaging and optical coherence tomography. Macular pigment optical density was measured. The likelihood that brief blue light exposure could lead to ocular effects was further explored by subjecting a retinal pigment epithelial cell (RPE) line to such exposures. Results: Although no visual defects or ocular pathologies were found in either group, the dentist group differed from the control group in having increased macular thickness (P < 0.02), a higher incidence of macular vessel tortuosity (P < 0.05), and greater variance in their macular pigment optical density values (P < 0.01). RPE cells that received blue light exposure similar to those sustained by dentists demonstrated a change in physiology. Conclusions: Retinal changes were found in dentists, which, while not pathological in themselves, are associated with some retinal pathologies. Further studies are necessary to determine whether these signs correlate with the degree of curing light exposure and to determine whether they eventually develop into pathological conditions.

During the COVID-19 pandemic, pressures on clinical services required adaptation to how care was prioritised and delivered for women with gynecological cancer. This document discusses potential ‘salvage’ measures when treatment has deviated from the usual standard of care. The British Gynaecological Cancer Society convened a multidisciplinary working group to develop recommendations for the onward management and follow-up of women with gynecological cancer who have been impacted by a change in treatment during the pandemic. These recommendations are presented for each tumor type and for healthcare systems, and the impact on gynecological services are discussed. It will be important that patient concerns about the impact of COVID-19 on their cancer pathway are acknowledged and addressed for their ongoing care.

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

Purpose Persistent velopharyngeal insufficiency (VPI) following primary palatoplasty remains a difficult problem to treat. This study evaluates speech outcomes following revision palatoplasty with tissue augmentation using buccal myomucosal flaps (BMF) as an alternative to pharyngoplasty for patients with VPI. Methods A retrospective single-center review of revision palatoplasty with tissue augmentation at a tertiary pediatric hospital Cleft-Craniofacial Center between January 2017 and March 2021 was conducted. Patients with a history of previous palatoplasty, a diagnosis of persistent or recurrent VPI, and comprehensive pre- and postoperative speech evaluations who underwent revision palatoplasty with BMF were included. Results Twenty patients met inclusion criteria (35% female, 20% syndromic). Mean age at the time of revision palatoplasty with BMF was 9.7 years. Preoperatively, all patients had stigmatizing speech and received the recommendation for speech surgery; the mean Pittsburgh Weighted Speech Score (PWSS) was 14.3 ± 4.9. The mean postoperative PWSS at the most recent assessment was 4.2 ± 2.3, representing a statistically significant improvement from preoperative scores ( P Conclusion In patients with VPI following primary palatoplasty, revision palatoplasty with tissue augmentation offers an alternative to pharyngoplasty. This approach preserves dynamic velopharyngeal function, improves speech outcomes, and should be considered an option when treating patients with post-primary palatoplasty VPI.

Multiple myeloma (MM) is the second most common hematological cancer and causes significant mortality and morbidity. Knowledge regarding modifiable risk factors for MM remains limited. This analysis of an Australian population-based case-control family study investigates whether smoking or alcohol consumption is associated with risk of MM and related diseases. Incident cases (

Accurate pancreatic and periampullary cancer staging with resectability assessment is vital to optimize surgical management and improve patient outcomes. The aim of this study is to assess the usefulness of a standardized reporting template.Retrospective review of all surgically managed patients with pancreatic or periampullary malignancy between January 2018 and June 2019. Pre-operative CT imaging report was anonymised and audited against a modified NCCN reporting template. The same imaging studies were re-reported by two experienced GI radiologists using the same template.Fifty-nine patients (37 male) with median age of 68 years (36-83) underwent surgery for suspected pancreatic/peri-ampullary malignancy. The median time between pre-operative CT scan and surgery was 56.5 days (14-225). The use of reporting template resulted in significant increase in number of reported key features (p 0.005), interobserver agreed features (p 0.005) and overall k-value assessed interobserver agreement (p 0.005). Template reports correlated closely with key intraoperative findings whilst primary free text reports did not (k-value 0.85-0.96 versus 0.20-0.46, p 0.05).The use of a reporting template resulted in a more complete and accurate pancreatic/peri-ampullary tumour evaluation, improved inter-observer relatability and correlation with intraoperative findings.

In 2003, randomized trials demonstrated potentially improved outcomes when local instead of general anesthesia is used for inguinal hernia repair. Our study aimed to evaluate how the use of local anesthesia for this procedure changed over time following the publication of the trials' level 1 evidence.We used the 1998-2018 Veterans Affairs Surgical Quality Improvement Program database to identify adults who underwent open, unilateral inguinal hernia repair under local or general anesthesia. Our primary outcome was the percentage of cases performed under local anesthesia. We used a time-series design to examine the trend and rate of change of the use of local anesthesia.We included 97,437 veterans, of which 22,333 (22.9%) had hernia surgery under local anesthesia. The median age of veterans receiving local anesthesia remained stable at 64-67 years over time. The use of local anesthesia decreased steadily, from 38.2% at the beginning year to 15.1% in the final year (P 0.0001). The publication of results from randomized trials (in 2003) did not appear to increase the overall use or change the rate of decline in the use of local anesthesia. Overall, we found that the use of local anesthesia decreased by about 1.5% per year.The utilization of local anesthesia for inguinal hernia repair in the VA has steadily declined over the last 20 + years, despite data showing equivalence or superiority to general anesthesia. Future studies should explore barriers to the use of local anesthesia for hernia repair.

Purpose Patients undergoing surgery for trapeziometacarpal (TMC) joint arthritis require preoperative counseling on the expectations of surgery. This study aims to document the objective and functional recovery over the initial 12 months following trapeziectomy and ligament reconstruction with tendon interposition (LRTI). Methods We prospectively followed 55 patients with symptomatic TMC joint osteoarthritis after trapeziectomy and LRTI. Patients were assessed on functional outcome measures, pain, and objective outcomes of grip, tip and key pinch strength, and range of motion. Outcomes were recorded preoperatively and at 3, 6, 9, and 12 months after surgery. Results Outcome measures of Disabilities of the Arm, Shoulder, and Hand (DASH), Patient-Rated Wrist Evaluation (PRWE), and pain, improved significantly after surgery at each 3-month interval up to 9 months. Palmar and radial abduction were significantly improved compared to their preoperative ranges, but opposition was unchanged. Power grip significantly exceeded the preoperative strength at 6 months and further increased at 9 months. Tip pinch significantly exceeded the preoperative strength at 12 months. There was no difference in the key pinch strength compared to the preoperative strength. Conclusions Over a follow-up period of 12 months, trapeziectomy and LRTI is an effective treatment in significantly reducing pain in 80% of patients. Although normal patient-reported outcome measures of DASH and PRWE are not regained, when compared to normative values, these measures are significantly improved; the improvement plateaus at 9 months. Patients can expect to attain 37% and 46% of their eventual measured DASH and PRWE scores, respectively, at 3 months, and 82% and 79% of their eventual measured DASH and PRWE scores, respectively, at 6 months. Grip strength exceeded the preoperative strength by 15% at 6 months and by 30% at 9 months. Tip pinch strength significantly exceeded the preoperative strength by 20% at 9 months. Type of study/level of evidence Therapeutic II.

Background Ferumoxytol is Food and Drug Administration–approved as two 510 mg infusions. Retrospective and prospective reviews have established that a single 1020 mg infusion is as efficacious and safe as two 510 mg infusions. Objectives To transition our preferred intravenous iron infusion practice from two 510 mg infusions to a single 1020 mg ferumoxytol infusion. Practice description This is a prospective process improvement study conducted at Tripler Army Medical Center, a large academic medical center. Practice innovation We set up an evidence-based project to transition and monitor our preferred iron treatment of ferumoxytol from 2 doses to 1 dose. Evaluation methods We collected efficacy and safety data for 188 unique patients receiving 228 infusions, of which 62 were single 1020 mg doses, and 166 were two 510 mg doses. Results Comparing the 1020 mg dose in 62 patients with 166 patients treated with two 510 mg infusions, we found no increase in the rate of infusion reactions (4.8 % vs. 4.8 %) and comparable improvement in ferritin and hemoglobin (144 ng/mL vs. 140 ng/mL; P value = 0.874, and 1.8 g/dL vs. 1.9 g/dL; P value = 0.721, respectively). Conclusion Thus, we were able to successfully transition to total-dose ferumoxytol for iron-deficient anemia, effectively reducing patient treatment visits without any difference in safety or efficacy. Ferumoxytol 1020 mg infused intravenously over 30 minutes in 250 mL normal saline single dose is a viable, safe, and effective treatment for iron-deficiency anemia.

Purpose Through sustained weight loss and improvement in metabolic co-morbidities, bariatric surgery is hypothesized to reduce the risk of severe COVID-19. Small studies have suggested favorable outcomes; however, large population-based studies are lacking. Materials and Methods We conducted a retrospective cohort study utilizing the multi-institutional research network TriNeTx platform. Participants diagnosed with COVID-19 were identified and divided into cohorts based on prior bariatric surgery (BS). Primary study outcome was a composite event of death or requirement for mechanical ventilation up to 30-day following the diagnosis of COVID-19. Other outcomes included death, hospitalization, critical care need, and acute kidney injury in the 30-day follow-up period. Outcomes were compared in BS and non-BS cohorts after propensity score matching. Results There were significant differences in patient demographics and co-morbidities between the BS and non-BS groups. In the propensity score-matched analysis, there was a lower risk of reaching the primary endpoint of mechanical ventilation or mortality at 30 days after COVID-19 diagnosis in the BS cohort compared to the non-BS cohort (risk ratio (RR) 0.40, 95% CI 0.25–0.65). Mortality rate was lower in the BS cohort (RR 0.42, 95% CI 0.22–0.80), and patients in the BS group were less likely to require critical care (RR 0.54, 95% CI 0.38–0.77), mechanical ventilation (RR 0.43, 95% CI 0.24–0.78) or develop acute kidney injury (RR 0.57, 95% CI 0.43–0.76) after COVID-19 diagnosis. Conclusion Prior bariatric surgery is associated with a reduced risk of poor outcomes of COVID-19. Furthermore, large prospective studies are needed. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s11695-021-05803-1.

Traumatic brain injury (TBI) is a complex health problem in military veterans and service members (V/SM) that often co-occurs with psychological and medical conditions such as posttraumatic stress disorder (PTSD) and sleep apnea. We aimed to examine if sleep apnea is associated with the presence and severity of PTSD in V/SM with TBI of all severities.The study examined participants at varying times since their TBI (Almost 32% of the sample stated they had been diagnosed with sleep apnea. In those reporting sleep apnea, 32% also had probable PTSD; 19% of those without sleep apnea had probable PTSD. The regression demonstrated sleep apnea was significantly associated with PTSD symptom severity (TBI, PTSD, and sleep apnea are often comorbid in V/SM. We expand the literature by demonstrating that sleep apnea was associated with PTSD severity. A multipronged approach to TBI rehabilitation that addresses sleep and psychological distress is recommended for enhancing health outcomes in this population. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Clinical Practice Points • Carfilzomib (CFZ) has rarely been associated with atypical hemolytic uremic syndrome (aHUS). • Patients with heterozygous complement factor H related protein 3 (CFHR)/CFHR1 deletions may be predisposed to CFZ-induced aHUS. • The benefit of eculizumab in the treatment of CFZ-induced aHUS that fails to improve with drug withdrawal and supportive care remains uncertain.

Assimilation theories argue that social ties with majority-group members enhance the structural integration of ethnic minority members, whereas under certain conditions, coethnic social ties can also benefit minority members' socioeconomic outcomes. We examine these propositions through a social network perspective, focusing on friendship networks and educational expectations in adolescence, during which peer socialization is crucial. Longitudinal data from 1,992 adolescents in 91 classrooms allow us to investigate co- and interethnic social selection and social influence processes as well as their aggregated outcomes. In terms of friendship selection, we find that Turkishorigin minority adolescents in Germany have distinct preferences for friends with high educational expectations, among both co- and interethnic peers. In contrast, social influence on Turkish-minority adolescents' educational expectations is not uniform: only majority-group friends exert a significant (positive) influence. Our results emphasize that bridging social capital gained from social ties with majority-group members enhances ethnic minority adolescents' educational integration.

Numerous missions are being proposed which involve multiple spacecraft operating in close proximity in harsh charging environments. In such missions, the ability to sense the electrostatic potentia...