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Objective: This study investigated the efficacy of a multimodal analgesia (MMA) with an opioid-sparing strategy, incorporating a parasternal plane block (PPB) within a systematic standardized Enhanced Recovery After Surgery (ERAS) program for patients undergoing elective cardiac surgery. Methods: From 2015 to 2021, 3153 patients underwent elective coronary artery bypass grafting and/or valve procedures. Patients were dichotomized by the presence or absence of an ERAS program including a perioperative MMA with an opioid-sparing approach and PPB protocols. Propensity score matching yielded 1026 well-matched pairs. The primary outcomes were the opioid-free rate and the opioid consumption in morphine milligram equivalents (MME) in the intensive care unit (ICU). The secondary outcomes were postoperative visual analog scale (VAS) scores, mechanical ventilation duration, ileus, delirium, bronchopneumonia, and length of ICU stay. Results: The ICU opioid-free rate was significantly increased in the ERAS group (94.0%) compared with the control group (19.9%; P

Objective: This expert-led consensus aims to provide primary care providers (PCPs) with recommendations for the care of atopic dermatitis (AD) in patients aged

Introduction: Pre-exposure prophylaxis (PrEP) use among transgender women in the U.S. has not reached levels optimal to change the trajectory of the HIV epidemic owing to multilevel barriers. Long-acting injectable PrEP received Food and Drug Administration approval in 2021 and may potentially address some of the barriers experienced in initiating and adhering to daily oral PrEP (e.g., pill fatigue, medication storage). However, preferences for long-acting injectable PrEP compared with daily oral PrEP have not been well studied among transgender women. Methods: The authors analyzed data collected from transgender women not living with HIV in eastern and southern U.S. in 2020–2022. Using multivariable Poisson regression with robust standard errors, the authors estimated prevalence ratios and 95% CIs for factors associated with preference for long-acting injectable PrEP. Results: The study sample (N=789) was racially and ethnically diverse, with 42.6% identifying as Black, Latina, and/or multiracial and 12% using daily oral PrEP. Fifty-eight percent preferred long-acting injectable PrEP to daily oral PrEP. In multivariable regression analyses, preference for long-acting injectable PrEP was associated with residence in Midwest (reference group=Northeast, adjusted prevalence ratio=1.33; 95% CI=1.10, 1.60), current PrEP indications (adjusted prevalence ratio=1.14; 95% CI=1.01, 1.30), and history of gender-affirming hormone injection (adjusted prevalence ratio=1.36; 95% CI=1.18, 1.57). Conclusions: Transgender women may prefer long-acting injectable PrEP to daily oral PrEP, especially those with current PrEP indications and experience with gender-affirming hormone injections. Increasing availability and access to long-acting injectable PrEP may improve PrEP uptake in transgender women, particularly in combination with other interventions to reduce multilevel PrEP barriers.

A 2-stage protocol is standard of care treatment in the United States for chronic periprosthetic joint infection of the knee. While many patients benefit from insertion of an articulating spacer, there are instances in which this is not feasible, and a static spacer is indicated. However, many static spacer techniques risk instability and lack durability. The ideal static spacer construct should provide immediate brace-free weight-bearing to maximize function during the spacer stage and, if needed, permit delayed reimplantation in the case of medically high-risk patients. Here, we describe our surgical technique for a femoral nail and cement static spacer in the treatment of chronic knee periprosthetic joint infection, a reproducible, stable, and durable construct essential to the armamentarium of the arthroplasty surgeon.

Purpose: To validate the performance of the Notal OCT Analyzer (NOA) in processing self-administered OCT images from an OCT system designed for home use (home OCT [HOCT]) as part of a pivotal study aimed at achieving de novo United States Food and Drug Admininstration marketing authorization. Design: A prospective quantitative cross-sectional artificial intelligence study. Participants: The study enrolled adults aged ≥55 years diagnosed with neovascular age-related macular degeneration (nAMD) in ≥1 eligible eye with a best-corrected visual acuity of 20/320 or better. Methods: Participants self-imaged 4 times on each of 2 HOCT devices and once with an in-office OCT (IO-OCT) device during a single visit. Scans were segmented by the NOA and human graders at a certified reading center (RC). Main Outcome Measures: Intradevice and interdevice repeatability and reproducibility of total retinal hyporeflective (TRO) volume estimation by the NOA on HOCT-acquired images as compared with that of RC graders on IO-OCT-acquired images. Additionally, to assess the performance of the NOA in segmentation of TRO over multiple B-scans as compared with RC graders. Results: Self-imaging was performed successfully by 387 participants in 2451 of 2616 attempts (93.7%). For repeatability, the coefficient of variance for NOA was 11.1% for eyes with >10 volume units of TRO imaged with HOCT compared with 16.4% for RC graders segmenting IO-OCT images. The median DICE similarity coefficients for segmentation of TRO by NOA vs. Grader 1, Grader 2, and Grader 3; Grader 1 vs. Grader 2 and Grader 3; and Grader 2 vs. Grader 3 were 0.68, 0.68, 0.61, 0.72, 0.63, 0.70, respectively. Conclusions: The performance of NOA supports the intended use of the system as a tool to monitor TRO at home between routine clinical visits in support of the management of nAMD. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Introduction:. Natural radiation exposure in the general population averages 3 milliSieverts (mSv) annually; however, radiation exposure in orthopaedic residents is not well defined. Despite protective measures, evidence of radiation-related diseases in orthopaedic surgeons is increasing. The purpose of this study was to quantify radiation exposure in orthopaedic residents and to determine the variability of exposure among post graduate year (PGY) of residency. Methods:. Monthly radiation exposure was measured prospectively over a 12-month period in orthopaedic surgery residents from a single program. Participants wore dosimeters above (“exposed”) and beneath (“shielded”) protective lead. The primary outcome measure was the absolute value of radiation exposure in mSv. Repeated measures analysis was used to assess exposure with age, sex, year of training, operating room (OR) days, and height. Results:. Mean annual occupational radiation exposure was 3.30 ± 0.64 mSv over an average of 107 ± 38 OR days. Mean exposure per OR day was 0.033 ± 0.008 mSv. PGY-2 and PGY-3 residents had the highest cumulative exposure, and PGY-5 residents had the highest mean exposure per OR day (0.044 ± 0.009 mSv/d). Number of OR days per month and PGY level were significant predictors of radiation exposure (p < 0.05). Sex, age, and height were not significant in predicting radiation of the exposed dosimeter. Conclusions:. Orthopaedic residents' exposure to radiation is nearly twice the general population's exposure. Given that yearly radiation exposure was highest during early residency years, but exposure based on number of OR days was highest in the final year of training, it is essential for resident education regarding radiation safety and safe clinical practices throughout their training.

ABSTRACT: Background: Is there a statistically significant association between preoperative epidural steroid injections (ESI) and postoperative cervical and lumbar spinal surgery infections (SSI)? Methods: A systematic review and meta-analysis was completed of patients 18 years or older who underwent elective cervical or lumbar spinal surgery. Those who underwent surgery with preoperative ESI were compared to those without. We assessed for differences in postoperative SSI incidence. Electronic literature databases were searched through October 2022. Peer-reviewed publications that included raw data regarding epidural exposure and non-exposure were included. Case reports, case series, abstracts, editorials, or publications that did not include raw data were excluded. Odd's ratios (OR) were calculated from the raw data collected. Meta-analysis was done using RevMan v5 with a fixed effects model. Results: We identified 16 articles for inclusion. When not controlling for the type of surgery and time from ESI to surgery, there was a statistically significant OR between preoperative ESI and postoperative SSI. The association persisted when the ESI was performed within 30 days or 31-90 days of the surgery. No association was discovered when evaluating only cervical spine surgeries. The evidence is assigned a “moderate” GRADE rating. Conclusions: Our analysis shows a small, time-dependent, statistically significant association between preoperative ESI and postoperative lumbar SSI may exist. However, the OR produced, while statistically significant, are close enough to 1.0 that clinically, the effect size is “small.” The number needed to treat for an ESI in the appropriate clinical setting is, at worst, 3. The number needed to harm, meaning the number of patients who undergo an ESI at any time before their spine surgery and then develop a SSI, is 111 patients. Ultimately, the surgical sparing potential from an ESI outweighs the SSI risk based on our findings.

IMPORTANCE:. Pediatric acute kidney injury (AKI) is a prevalent and morbid complication of shock. Its pathogenesis and early identification remain elusive. OBJECTIVES:. We aim to determine whether renal blood flow (RBF) measurements by point-of-care ultrasound (POCUS) and renin-angiotensin-aldosterone system (RAAS) hormones in pediatric shock associate with vasoactive requirements and AKI. DESIGN, SETTING, AND PARTICIPANTS:. This is a single-center prospective, noninterventional observational cohort study in one tertiary PICU in North American from 2020 to 2022 that enrolled children younger than 18 years with shock without preexisting end-stage renal disease. MAIN OUTCOMES AND MEASURES:. RBF was measured by POCUS on hospital days 1 and 3 and plasma RAAS hormone levels were measured on day 1. The primary outcome was the presence of AKI by Kidney Disease Improving Global Outcomes criteria at first ultrasound with key secondary outcomes of creatinine, blood urea nitrogen (BUN), Vasoactive-Inotrope Score (VIS), and norepinephrine equivalent dosing (NED) 48 hours after first ultrasound. RESULTS:. Fifty patients were recruited (20 with AKI, mean age 10.5 yr, 48% female). POCUS RBF showed lower qualitative blood flow (power Doppler ultrasound [PDU] score) and higher regional vascular resistance (renal resistive index [RRI]) in children with AKI (p = 0.017 and p = 0.0007). Renin and aldosterone levels were higher in the AKI cohort (p = 0.003 and p = 0.007). Admission RRI and PDU associated with higher day 3 VIS and NED after adjusting for age, day 1 VIS, and RAAS hormones. Admission renin associated with higher day 3 creatinine and BUN after adjusting for age, day 1 VIS, and the ultrasound parameters. CONCLUSIONS AND RELEVANCE:. In pediatric shock, kidney blood flow was abnormal and renin and aldosterone were elevated in those with AKI. Kidney blood flow abnormalities are independently associated with future cardiovascular dysfunction; renin elevations are independently associated with future kidney dysfunction. Kidney blood flow by POCUS may identify children who will have persistent as opposed to resolving AKI. RAAS perturbations may drive AKI in pediatric shock.

Abstract. Orthopaedic trauma remains a leading cause of patient morbidity, mortality, and global health care burden. Although significant advances have been made in the diagnosis, treatment, and rehabilitation of these injuries, complications such as malunion, nonunion, infection, disuse muscle atrophy and osteopenia, and incomplete return to baseline function still occur. The significant inherent clinical variability in fracture care such as differing patient demographics, injury patterns, and treatment protocols make standardized and replicable study, especially of cellular and molecular based mechanisms, nearly impossible. Hence, the scientists dedicated to improving therapy and treatments for patients with orthopaedic trauma rely on preclinical models. Preclinical models have proven to be invaluable in understanding the timing between implant insertion and bacterial inoculation on the bioburden of infection. Posttraumatic arthritis (PTOA) can take years to develop clinically, but with a porcine pilon fracture model, posttraumatic arthritis can be reliably induced, so different surgical and therapeutic strategies can be tested in prevention. Conversely, the racehorse presents a well-accepted model of naturally occurring PTOA. With preclinical polytrauma models focusing on chest injury, abdominal injury, multiple fractures, and/or head injury, one can study how various injury patterns affect fracture healing can be systemically studied. Finally, these preclinical models serve as a translational bridge to for clinical application in human patients. With selection of the right preclinical model, studies can build a platform to decrease the risk of emerging technologies and provide foundational support for therapeutic clinical trials. In summary, orthopaedic trauma preclinical models allow scientists to simplify a complex clinical challenge, to understand the basic pathways starting with lower vertebrate models. Then, R&D efforts progress to higher vertebrate models to build in more complexity for translation of findings to the clinical practice.

OBJECTIVES:. To assess the in vitro IntelliSep test, a microfluidic assay that quantifies the state of immune activation by evaluating the biophysical properties of leukocytes, as a rapid diagnostic for sepsis. DESIGN:. Prospective cohort study. SETTING:. Five emergency departments (EDs) in Louisiana, Missouri, North Carolina, and Washington. PATIENTS:. Adult patients presenting to the ED with signs (two of four Systemic Inflammatory Response Syndrome criteria, where one must be temperature or WBC count) or suspicion (provider-ordered culture) of infection. INTERVENTIONS:. All patients underwent testing with the IntelliSep using ethylene diamine tetraacetic acid-anticoagulated whole blood followed by retrospective adjudication for sepsis by sepsis-3 criteria by a blinded panel of physicians. MEASUREMENTS AND MAIN RESULTS:. Of 599 patients enrolled, 572 patients were included in the final analysis. The result of the IntelliSep test is reported as the IntelliSep Index (ISI), ranging from 0.1 to 10.0, divided into three interpretation bands for the risk of sepsis: band 1 (low) to band 3 (high). The median turnaround time for ISI results was 7.2 minutes. The ISI resulted band 1 in 252 (44.1%), band 2 in 160 (28.0%), and band 3 in 160 (28.0%). Sepsis occurred in 26.6% (152 of 572 patients). Sepsis prevalence was 11.1% (95% CI, 7.5–15.7%) in band 1, 28.1% (95% CI, 21.3–35.8%) in band 2, and 49.4% (95% CI, 41.4–57.4%) in band 3. The Positive Percent Agreement of band 1 was 81.6% and the Negative Percent Agreement of band 3 was 80.7%, with an area under the receiver operating characteristic curve of 0.74. Compared with band 1, band 3 correlated with adverse clinical outcomes, including mortality, and resource utilization. CONCLUSIONS:. Increasing ISI interpretation band is associated with increasing probability of sepsis in patients presenting to the ED with suspected infection.

Dissection occurring after percutaneous transluminal angioplasty (PTA) is associated with decreased vessel patency and an increased incidence of target lesion revascularization. Management of post-PTA dissection with the Tack Endovascular System (Philips, N.V., Amsterdam, Netherlands) has created an effective and durable treatment strategy for infrainguinal dissections. In this report, we discuss the indications and optimal methods for using Tack devices in post-PTA dissections.

Summary:. Advances in the development of robotic systems have recently enabled the use of robotic technology in reconstructive lymphatic surgery. Although the advantages of microsurgical robots must be weighed carefully against the costs, their use may allow for smaller surgical approaches and easier access to anatomically deeper structures or even smaller vessels. We report on a case of a patient with central lymphatic dilation causing abdominal pain and severely reduced physical capacity. Sonography-assisted intranodal injection of indocyanine green allowed for localization of the lymphatic cyst and anastomosis with the left ovarian vein, applying robotic-assisted microsurgery for the first time on the central lymphatic system. Following the successful reconstruction of lymphatic drainage and decompression of the cyst, the patient reported a complete regression of her preoperative symptoms. From a surgical point of view, the Symani Surgical System improved precision and allowed significantly smaller surgical access. Considering the high morbidity and rarity of pathologies of the central lymphatic system, central lymphatic surgery is to date rarely performed. With improved precision and significantly smaller surgical access, robotic-assisted microsurgery has great potential to expand the treatment options for central lymphatic lesions.

Background:. Multiple studies have compared different pharmacologic thromboprophylaxis agents after hip fracture surgery, including aspirin, unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), direct oral anticoagulants (DOAC), and warfarin, resulting in variability in clinical practice. To guide clinical management, a systematic review and network meta-analysis (NMA), which enables the simultaneous assessment of the effects of multiple interventions for the same patient population, was performed. This study aimed to determine the comparative effectiveness of thromboprophylaxis in reducing venous thromboembolism (VTE) in patients with surgically treated hip fractures. Methods:. The primary outcome was the effect of the treatment on the VTE rate, and the secondary outcome was the treatment effect on the bleeding rate. Relevant studies were identified by a systematic search of Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from January 2000 to February 2022. Title, abstract, and full-text screening; data extraction; and risk-of-bias assessment were performed. All studies examining thromboprophylaxis interventions (DOAC, LMWH, UFH, aspirin, and warfarin) in patients with a surgically treated hip fracture were included. Bayesian NMA was performed, and dichotomous outcome data were pooled using the odds ratio. Interventions were ranked using the surface under the cumulative ranking curve (SUCRA) for each outcome. Results:. A total of 19 studies were included after the screening of 466 citations and 77 full-text articles. Of the included studies, 15 studies had a high overall risk of bias. The NMA of the VTE outcome included 19 studies, 49,409 participants, and 6 thromboprophylaxis interventions. The NMA of the bleeding outcome included 3 studies, 18,163 participants, and 3 interventions. The mean age ranged from 43.5 to 86.2 years among the included studies. No thromboprophylaxis intervention was statistically different from any other intervention in its effect on the VTE or bleeding rate in hip fracture patients. Conclusions:. This NMA demonstrated that there was no difference between the thromboprophylaxis interventions in reducing VTE or bleeding rates in hip fracture patients. More robust randomized controlled trials are needed to determine the most effective thromboprophylaxis interventions for patients with hip fractures. Level of Evidence:. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Purpose: Currently, there is insufficient guidance for standard fractionation lung planning using the Varian Ethos adaptive treatment planning system and its unique intelligent optimization engine. Here, we address this gap in knowledge by developing a methodology to automatically generate high-quality Ethos treatment plans for locally advanced lung cancer. Methods and Materials: Fifty patients previously treated with manually generated Eclipse plans for inoperable stage IIIA-IIIC non-small cell lung cancer were included in this institutional review board–approved retrospective study. Fifteen patient plans were used to iteratively optimize a planning template for the Daily Adaptive vs Non-Adaptive External Beam Radiation Therapy With Concurrent Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Prospective Randomized Trial of an Individualized Approach for Toxicity Reduction (ARTIA-Lung); the remaining 35 patients were automatically replanned without intervention. Ethos plan quality was benchmarked against clinical plans and reoptimized knowledge-based RapidPlan (RP) plans, then judged using standard dose-volume histogram metrics, adherence to clinical trial objectives, and qualitative review. Results: Given equal prescription target coverage, Ethos-generated plans showed improved primary and nodal planning target volume V95% coverage (P < .001) and reduced lung gross tumor volume V5 Gy and esophagus D0.03 cc metrics (P ≤ .003) but increased mean esophagus and brachial plexus D0.03 cc metrics (P < .001) compared with RP plans. Eighty percent, 49%, and 51% of Ethos, clinical, and RP plans, respectively, were “per protocol” or met “variation acceptable” ARTIA-Lung planning metrics. Three radiation oncologists qualitatively scored Ethos plans, and 78% of plans were clinically acceptable to all reviewing physicians, with no plans receiving scores requiring major changes. Conclusions: A standard Ethos template produced lung radiation therapy plans with similar quality to RP plans, elucidating a viable approach for automated plan generation in the Ethos adaptive workspace.

Background:. We aimed to clinically compare needle and cannula techniques in vivo with ultrasound and magnetic resonance imaging, to better understand the best technique and adverse events. Methods:. Ten adults without previous fillers in the area were injected with hyaluronic acid (CPM 22.5 HA mg/mL) with a 25G cannula on one side and a Becton Dickinson syringe needle (31G 0.3 mL) on the other. The product was fractionated among two visits. Assessment was made at time 0d, 14d, 30d, 60d, 90d, 180d, and 365d with standard camera, Vectra H2, ultrasound, and magnetic resonance imaging. Level of satisfaction was also evaluated. Results:. All the patients showed natural results with both techniques and a high satisfaction index. Cannulas were minimally less traumatic in terms of bruises. However, the product was applied in a more superficial layer and in a less precise manner, despite the fact that a deep technique was used with cannulas, depositing the product on the orbital bone. Patients reported a more noticeable change immediately after the procedure on the side treated with cannulas but less edema and a more comfortable procedure on the Becton Dickinson syringe treated side. None of the patients required hyaluronidase to dissolve overcorrection of the area, and no severe complications were observed. The product remained in most of them at day 365. Conclusions:. Cannulas seem to be less traumatic regarding bruises, but less precise in vivo. Thin needles seem to be more precise with minimal trauma. However, this difference disappears during patient’s evolution.

This article reports a rare case of a total knee arthroplasty femoral component fracture. Fractures of early knee systems were attributed to design flaws. Modern design failures have been attributed to poor surgical technique or underlying osteolysis. Here, we report a fracture in the Vanguard prosthesis (Zimmer Biomet, Warsaw, IN) 12 years after implantation in a patient with a persistent flexion contracture. The fracture likely occurred due to fatigue failure of the anterior flange secondary to increased stress from a high riding patella. Although femoral component fractures are rare, they should be considered as a potential complication, especially in patients with special load considerations. For these patients, it is essential that the prosthesis be properly supported with clean cuts and an adequate cement mantle.

Background Purpose: Patient satisfaction has become an increasingly important component of quality measures for both hospital reimbursement and quality assessment. Additionally, patient satisfaction influences patient behavior and patient follow-up. The purpose of this study was to identify preoperative factors associated with patient satisfaction 2 years after shoulder surgery. Methods: Electronic surveys were used to collect patient information including demographic, surgical, and social history, as well as outcome data. Satisfaction was measured 2 years after surgery using the Surgical Satisfaction Questionnaire. Results: Multivariable linear regression identified preoperative Patient-Reported Outcomes Measurement Information System Pain Interference, annual income, and American Society of Anesthesiologists score as independent predictors of lower patient satisfaction, while total shoulder arthroplasty was an independent predictor of greater patient satisfaction. The model accounted for 15% of the variance in satisfaction scores (R2 = 0.15). Conclusion: Patient satisfaction 2 years after shoulder surgery is associated with preoperative patient-reported outcome scores. Lower patient satisfaction is independently predicted by greater preoperative PROMIS PI, income less than $70,000, and ASA score >1, while higher patient satisfaction is predicted by total shoulder arthroplasty.

Background: Knee arthrodesis is predominantly a salvage procedure. In present time, knee arthrodesis is mostly considered for cases of unreconstructable failed total knee arthroplasty after prosthetic joint infection or trauma. Knee arthrodesis has shown better functional outcomes than amputation for these patients but has a high complication rate. The purpose of this study was to characterize the acute surgical risk profile of patients undergoing a knee arthrodesis for any indication. Methods: The American College of Surgeons National Surgical Quality Improvement Program database was queried to determine 30-day outcomes after knee arthrodesis between 2005 and 2020. Demographics, clinical risk factors, and postoperative events were analyzed, along with reoperation and readmission rates. Results: A total of 203 patients that underwent a knee arthrodesis were identified. Forty-eight percent of patients had at least 1 complication. The most common complication was acute surgical blood loss anemia requiring a blood transfusion (38.4%), followed by organ space surgical site infection (4.9%), superficial surgical site infection (2.5%), and deep vein thrombosis (2.5%). Smoking was associated with higher rates of reoperation and readmission (odds ratio 9, P < .01, and odds ratio 6, P < .05). Conclusions: Overall, knee arthrodesis is a salvage procedure that has a high rate of early postoperative complications and is most often performed in patients at higher risk. Early reoperation is strongly associated with a poor preoperative functional status. Smoking places patients at higher risk of early complications.

We consider various curious features of general relativity, and relativistic field theory, in two spacetime dimensions. In particular, we discuss: the vanishing of the Einstein tensor; the failure of an initial-value formulation for vacuum spacetimes; the status of singularity theorems; the non-existence of a Newtonian limit; the status of the cosmological constant; and the character of matter fields, including perfect fluids and electromagnetic fields. We conclude with a discussion of what constrains our understanding of physics in different dimensions.

Background: Pollen allergies are a major public health concern worldwide. An IgE-mediated systemic inflammatory response to pollen allergens causes symptoms of allergic rhinitis or even asthma. They have a significant impact on individual quality of life and cause high socioeconomic strain. The aim of this study was to examine the value of pollen allergy-related web search data for public health. Methods: An in-depth analysis of search volumes and contents, and their correlation with factors of disease activity such as rates of dispensed medicine and pollen concentration, was conducted. In this retrospective longitudinal study, Google Ads Keyword Planner was used to determine the internet search volume of terms related to pollen allergies across Germany and Sweden as a whole and in each of the 16 German federal states and 21 Swedish provinces between January 2017 and December 2020. This search volume was converted into searches per 100,000 inhabitants and categorized qualitatively. Results: A total search volume of 7405 searches per 100,000 inhabitants in Germany and 17,592 searches per 100,000 inhabitants in Sweden was observed, with the total yearly search volume increasing continually in both countries during the study period. Regional search volume correlated with antihistamine dispensation rates (ρ = 0.848–0.960) and pollen concentration (ρ = 0.566–0.922). While overall search interest was higher in Sweden, a higher interest in treatment options was identified in Germany. Conclusion: Internet websearch data is an excellent proxy for disease activity of allergic rhinitis. In the 4-year study period, the interest in pollen allergies has increased and there are unmet medical needs in both countries.

Background. To evaluate clinical characteristics and factors associated with survival among liver transplantation (LT) recipients with Budd-Chiari syndrome (BCS), with or without transjugular intrahepatic portosystemic shunt (TIPS), in the post–Model for End-stage Liver Disease era. Methods. We extracted data from the United Network for Organ Sharing database on all adult (≥18 y old) waitlisted candidates and recipients of LT with BCS in the United States between 2002 and 2019. Multivariable Cox regression was used to determine predictors of mortality and hazard ratios (HRs). Results. A total of 647 BCS patients were waitlisted between 2002 and 2019. BCS was an indication for LT in 378 (0.2%) of all adult LT recipients during the study period. Of BCS patients who received LT, approximately three-fourths (72.3%) were alive for up to 10 y. We found no significant difference in LT outcomes in BCS patients with or without TIPS. Longer length of hospital stay following LT (HR, 1.32; 95% confidence interval [CI], 1.19-1.47), Black/African American race (HR, 2.24; 95% CI, 1.38-3.64), diabetes (HR, 3.17; 95% CI, 1.62-6.21), donor risk index (HR, 1.44; 95% CI, 1.05-1.99), and lower albumin levels at the time of transplantation (HR, 0.66; 95% CI, 0.50-0.88) were negatively associated with survival after LT. Interestingly, neither the Model for End-stage Liver Disease nor prior TIPS showed a significant association with survival after LT. Conclusions. These findings demonstrate good comparable survival among TIPS versus no TIPS in LT recipients with BCS. The decision for TIPS versus LT should be individualized on a case-by-case basis.

We infer gravitational lensing shear and convergence fields from galaxy ellipticity catalogs under a spatial process prior for the lensing potential. We demonstrate the performance of our algorithm with simulated Gaussian-distributed cosmological lensing shear maps and a reconstruction of the mass distribution of the merging galaxy cluster Abell 781 using galaxy ellipticities measured with the Deep Lens Survey. Given interim posterior samples of lensing shear or convergence fields on the sky, we describe an algorithm to infer cosmological parameters via lens field marginalization. In the most general formulation of our algorithm we make no assumptions about weak shear or Gaussian-distributed shape noise or shears. Because we require solutions and matrix determinants of a linear system of dimension that scales with the number of galaxies, we expect our algorithm to require parallel high-performance computing resources for application to ongoing wide field lensing surveys.

Objective:. This Delphi exercise aimed to gather consensus surrounding risk factors, diagnosis, and management of chyle leaks after esophagectomy and to develop recommendations for clinical practice. Background:. Chyle leaks following esophagectomy for malignancy are uncommon. Although they are associated with increased morbidity and mortality, diagnosis and management of these patients remain controversial and a challenge globally. Methods:. This was a modified Delphi exercise was delivered to clinicians across the oesophagogastric anastomosis collaborative. A 5-staged iterative process was used to gather consensus on clinical practice, including a scoping systematic review (stage 1), 2 rounds of anonymous electronic voting (stages 2 and 3), data-based analysis (stage 4), and guideline and consensus development (stage 5). Stratified analyses were performed by surgeon specialty and surgeon volume. Results:. In stage 1, the steering committee proposed areas of uncertainty across 5 domains: risk factors, intraoperative techniques, and postoperative management (ie, diagnosis, severity, and treatment). In stages 2 and 3, 275 and 250 respondents respectively participated in online voting. Consensus was achieved on intraoperative thoracic duct ligation, postoperative diagnosis by milky chest drain output and biochemical testing with triglycerides and chylomicrons, assessing severity with volume of chest drain over 24 hours and a step-up approach in the management of chyle leaks. Stratified analyses demonstrated consistent results. In stage 4, data from the Oesophagogastric Anastomosis Audit demonstrated that chyle leaks occurred in 5.4% (122/2247). Increasing chyle leak grades were associated with higher rates of pulmonary complications, return to theater, prolonged length of stay, and 90-day mortality. In stage 5, 41 surgeons developed a set of recommendations in the intraoperative techniques, diagnosis, and management of chyle leaks. Conclusions:. Several areas of consensus were reached surrounding diagnosis and management of chyle leaks following esophagectomy for malignancy. Guidance in clinical practice through adaptation of recommendations from this consensus may help in the prevention of, timely diagnosis, and management of chyle leaks.

The request for CT (computed tomography) diagnostic in patients with suspected COVID-19 pneumonia has become part of the daily clinical routine. We reported a case of a 61-year-old patient with flu-like symptoms and a suspected COVID-19 pneumonia. After a negative PCR-test (polymerase chain reaction), a non-contrast enhanced CT was performed which revealed a suspicious hyperdensity in the left pulmonary artery and a pneumonia in the left lower lobe. A contrast enhanced CT confirmed a pulmonary embolism. An acute pulmonary embolism is a major complication and a main differential diagnosis of COVID-19. A hyperdense pulmonary artery sign (PAS) is a sensitive sign for a pulmonary embolism. Non-enhanced chest CT scans should be checked for hyperdense PAS in suspected of COVID-19 patients.

Background: The authors performed total hip arthroplasty (THA) using a novel hemispherical dual-mobility (DM) acetabular cup without a protrusive cylindro-spherical rim, intended to reduce risks of iliopsoas impingement without requiring changes to conventional intraoperative positioning as with unipolar cups. We aim to determine clinical scores and rates of dislocations, complications, and revisions of this hemispherical DM cup, with the hypothesis that this novel design would result in clinical scores and dislocation rates comparable to other contemporary DM cups with protrusive cylindro-spherical rims. Methods: We assessed 332 consecutive uncemented THAs performed using a hemispherical DM cup, at a minimum 2-year follow-up, using modified Harris Hip Score (mHHS) and Oxford Hip Score (OHS), and noting complications and revisions. Regression analyses were conducted to determine if mHHS and OHS depended on any independent factors. Results: At 2.8 ± 0.5 years (range, 2–5), 2 patients (0.6%) had stem and cup revisions, 3 patients (1%) had isolated stem revisions, 13 patients (4%) died, and none were lost to follow-up. No dislocations occurred. For the final cohort of 305 patients (314 hips) with their original implants in place, mHHS was 92 ± 12 (range, 46–100), and OHS was 57 ± 5 (range, 34–60). Multivariable analyses revealed that mHHS and OHS decreased significantly with age (β = -0.35, P < .001, and β = -0.15, P < .001, respectively). Conclusions: With no dislocations and satisfactory clinical scores, this sizable cohort confirms that the novel hemispherical DM cup studied is effective at preventing dislocations, although longer-term follow-up remains necessary to ascertain the longevity of clinical outcomes and radiographic stability. Level of Evidence: Level IV, multicentric retrospective case series.

Introduction: The central nervous system (CNS) is a common site of progression among patients with ROS1-rearranged lung cancer receiving crizotinib. We conducted a phase 2 study to evaluate the intracranial efficacy of lorlatinib in patients with ROS1-rearranged lung cancer who developed CNS-only progression on crizotinib. Methods: Patients with metastatic ROS1-rearranged lung cancer with CNS-only progression on crizotinib received lorlatinib 100 mg daily. The primary end point was intracranial disease control rate at 12 weeks per modified Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included intracranial and extracranial progression-free survival, intracranial objective response rate, and safety/tolerability. Results: A total of 16 patients were enrolled between November 2016 and January 2019. Nine patients (56%) had received prior CNS radiation, with a median of 10.9 months between radiation and lorlatinib. At 12 weeks, the intracranial disease control rate was 100% and intracranial objective response rate was 87%. While on study, the complee intracranial response rate was 60%. With median follow-up of 22 months, seven patients experienced disease progression, including five patients with CNS relapse. The median intracranial and extracranial progression-free survivals were 38.8 months (95% confidence interval: 16.9–not reported) and 41.1 months (95% confidence interval: 17.6–not reported), respectively. Molecular analysis of plasma or tissue from patients with extracranial progression on lorlatinib revealed ROS1 G2032R (n = 1), ROS1 L2086F (n = 1), and CCDC6-RET fusion plus ROS1 G2032R (n = 1). The safety profile of lorlatinib was consistent with prior studies. There were 11 patients (69%) who required dose reduction, including one patient who discontinued treatment for grade 3 edema. No grade greater than or equal to 4 adverse events were observed. Conclusions: Lorlatinib induced durable intracranial responses in patients with ROS1-rearranged NSCLC and prior isolated CNS progression on crizotinib.

Background:. There is a paucity of information regarding the use of social media by both orthopaedic residents and applicants. Therefore, this investigation aimed to (1) characterize the use of social media by current orthopaedic surgery residents and applicants to an orthopaedic surgery residency and (2) evaluate the influence of social media on applicants to an orthopaedic surgery residency. Methods:. An anonymous, nationwide survey was conducted among current orthopaedic surgery residents and fourth-year medical students applying to the authors' orthopaedic surgery. Survey data included demographics, social media usage preferences, social media engagement, and the influence of social media on applicants' perception of and decision to apply to residency programs. Results:. Three hundred twelve surveys were completed, which included 170 resident surveys and 142 applicant surveys. Two hundred thirty-seven of the respondents (76%) use social media daily. Two hundred fourteen respondents (72%) have listened to orthopaedic surgery podcasts. Regarding educational social media posts, 81% of the residents and 57% of the applicants preferred case presentations with corresponding imaging; for noneducational posts, 89% of the applicants preferred content involving resident life outside the hospital. When asked how much an orthopaedic residency program's social media presence influenced application decision (on a scale of 0-10, 0 being no influence and 10 being the most influence), the mean response was 3.47 among all respondents. Conclusions:. Most survey respondents use social media daily, have listened to orthopaedic podcasts, find case presentations with corresponding imaging the most useful format for educational posts, and prefer to see residency programs post about resident life outside of the hospital. A residency program's social media presence did not significantly influence applicants' decision to apply to a specific program; however, there was a trend toward increasing influence with more recent applicants. Future research should further investigate social media's impact on the residency application process and the influence of social media on orthopaedic applicants and residents.

We present a tomographic cosmic shear study from the Deep Lens Survey (DLS), which, providing a limiting magnitude rlim ∼ 27 (5s), is designed as a precursor Large Synoptic Survey Telescope (LSST) survey with an emphasis on depth. Using five tomographic redshift bins, we study their auto- and cross-correlations to constrain cosmological parameters. We use a luminosity-dependent nonlinear model to account for the astrophysical systematics originating from intrinsic alignments of galaxy shapes. We find that the cosmological leverage of the DLS is among the highest among existing >10 deg2 cosmic shear surveys. Combining the DLS tomography with the 9 yr results of the Wilkinson Microwave Anisotropy Probe (WMAP9) gives W = m 0.293- +0.014 0.012, s-1 = 0.833 +0.018-0.011, = +- H0 68.6 km s Mpc 1.2+1.4 - - 1 1, and W = b 0.0475 0.0012 for CDM, reducing the uncertainties of the WMAP9- only constraints by ∼50%. When we do not assume flatness for CDM, we obtain the curvature constraint W = - +- k 0.010 0.015+0.013 from the DLS+WMAP9 combination, which, however, is not well constrained when WMAP9 is used alone. The dark energy equation-of-state parameter w is tightly constrained when baryonic acoustic oscillation (BAO) data are added, yielding w = -1.02- +0.090.10 with the DLS+WMAP9+BAO joint probe. The addition of supernova constraints further tightens the parameter to w = - 1.03 ±0.03. Our joint constraints are fully consistent with the final Planck results and also with the predictions of a CDM universe.

Unguarded mitral valve orifice is a rare disease with only 7 described cases in the literature. We describe the first known case of unguarded mitral valve orifice with normal segmental cardiac anatomy, severe left ventricular dilatation and dysfunction, aortic atresia, and atrial flutter. (Level of Difficulty: Advanced.)

We present the case of a 55-year-old female patient with metamizole-induced agranulocytosis after total knee arthroplasty, leading to septic periprosthetic joint infections (PJIs). Owing to metamizole-induced agranulocytosis, the synovial leukocyte count was negative. Here, we discuss the diagnostic challenges evolving from sepsis and neutropenia in patients with suspected PJIs. We suggest an urgent surgical approach, mainly focusing on the clinical presentation preoperatively. Later, our patient developed candidemia and periprosthetic tissue samples were positive for Candida albicans. For fungal PJIs, long-term follow-up studies are lacking and therapeutic recommendations differ. Here, we present our therapeutic approach, including staged revision and 12 weeks of systemic antifungal therapy, and discuss recent findings regarding the therapy of fungal PJIs.

IMPORTANCE:. Myeloperoxidase (MPO)-DNA complexes, biomarkers of neutrophil extracellular traps (NETs), have been associated with arterial and venous thrombosis. Their role in aneurysmal subarachnoid hemorrhage (aSAH) is unknown. OBJECTIVES:. To assess whether serum MPO-DNA complexes are present in patients with aSAH and whether they are associated with delayed cerebral ischemia (DCI). DESIGN, SETTING, AND PARTICIPANTS:. Post-hoc analysis of a prospective, observational single-center study, with de novo serum biomarker measurements in consecutive patients with aSAH between July 2018 and September 2020, admitted to a tertiary care neuroscience ICU. MAIN OUTCOMES AND MEASURES:. We analyzed serum obtained at admission and hospital day 4 for concentrations of MPO-DNA complexes. The primary outcome was DCI, defined as new infarction on brain CT. The secondary outcome was clinical vasospasm, a composite of clinical and transcranial Doppler parameters. We used Wilcoxon signed-rank-test to assess for differences between paired measures. RESULTS:. Among 100 patients with spontaneous subarachnoid hemorrhage, mean age 59 years (sd ± 13 yr), 55% women, 78 had confirmed aSAH. Among these, 29 (37%) developed DCI. MPO-DNA complexes were detected in all samples. The median MPO-DNA level was 33 ng/mL (interquartile range [IQR], 18–43 ng/mL) at admission, and 22 ng/mL (IQR, 11–31 ng/mL) on day 4 (unpaired test; p = 0.015). We found a significant reduction in MPO-DNA levels from admission to day 4 in patients with DCI (paired test; p = 0.036) but not in those without DCI (p = 0.17). There was a similar reduction in MPO-DNA levels between admission and day 4 in patients with (p = 0.006) but not in those without clinical vasospasm (p = 0.47). CONCLUSIONS AND RELEVANCE:. This is the first study to detect the NET biomarkers MPO-DNA complexes in peripheral serum of patients with aSAH and to associate them with DCI. A pronounced reduction in MPO-DNA levels might serve as an early marker of DCI. This diagnostic potential of MPO-DNA complexes and their role as potential therapeutic targets in aSAH should be explored further.

OBJECTIVE:. The CytoSorb hemoadsorption device (CytoSorbents Inc, Monmouth Junction, NJ) is increasingly used in many critical disease states. The potential impact on the pharmacokinetic (PK) of concomitantly administered drugs must be considered in clinical practice. The current review summarizes relevant mechanistic principles, available preclinical and clinical data, and provides general guidance for the management of concomitant drug administration during CytoSorb therapy. DATA SOURCES:. Detailed search strategy using the PubMed and OVID MEDLINE databases, as well as presented congress abstracts for studies on drug removal by the CytoSorb device. STUDY SELECTION:. Human, animal, and bench-top studies with PK or drug-removal data during CytoSorb therapy were selected for inclusion. Publications reporting on CytoSorb treatments for drug overdose were not considered. DATA EXTRACTION:. Relevant PK data were examined and synthesized for narrative review. DATA SYNTHESIS:. To date, PK data during CytoSorb hemoadsorption are available for more than 50 drugs, including analgesics, antiarrhythmics, anticonvulsants, antidepressants, antihypertensives, antiinfectives, antithrombotics, anxiolytics, and immunosuppressants. Based on available PK data, drugs were categorized into low (60%), or, alternatively, according to clearance increase relative to endogenous clearance: negligible (400%). In most reports, additional impact of the extracorporeal platform where CytoSorb was integrated was not available. Based on available data and considering drug, patient, and setup-specific aspects, general dosing guidance for clinical practice was developed. CONCLUSIONS:. CytoSorb therapy may increase drug elimination through active removal. However, the extent of removal is heterogeneous, and its clinical significance, if any, depends on the broader clinical context, including a patient’s specific endogenous drug clearance and the underlying extracorporeal platform used. The available data, although not definitive, allow for general guidance on dosing adjustments during CytoSorb therapy; however, any treatment decisions should always be complemented by clinical judgment and therapeutic drug monitoring, when available.

Background:. Pyogenic flexor tenosynovitis (PFT) is frequently diagnosed by physical examination according to the Kanavel signs. This study proposes a modification of the Kanavel sign “tenderness over the course of the flexor sheath” by including palpation of the A1 pulley to increase specificity for diagnosis. Methods:. A retrospective review was performed over 8 months for patients in the emergency department who received a consult to hand surgery to rule out PFT. Two cohorts, nonPFT infections and PFT infections, were studied for the presence or absence of the four Kanavel signs, as well as tenderness specifically over the A1 pulley on the affected digit(s) or T1 pulley of the thumb. Results:. There were a total of 33 patients in the two cohorts (21 nonPFT, 12 PFT) with statistically significant differences with regard to the presence of all the Kanavel signs. A1 pulley tenderness had the greatest odds ratio, positive predictive value, specificity, and accuracy when compared with all Kanavel signs. When used in conjunction with each Kanavel sign, there was an increase in specificity in all four signs. Receiver operating characteristic analysis revealed increased area under the curve with A1 pulley tenderness added, indicating improved ability to classify hand infections as PFT versus nonPFT. Conclusion:. Although the classic Kanavel signs have shown reliable clinical utility, this study finds that tenderness at the A1 pulley can be a useful specification of “tenderness over the course of the flexor sheath” to help with the diagnosis of PFT.

Background and objectives The evolution of healthcare from 18th-century reductionism to 21st-century postgenomic holism has been described in terms of systems medicine, and the impact of the built environment on human health is the focus of investigation and development, leading to the new specialty of evidence-based, therapeutic architecture. The traditional system of Vāstu architecture—a design paradigm for buildings which is proposed to promote mental and physical health—has been applied and studied in the West in the last 20 years, and features elements absent from other approaches. This review critically evaluates the theory and research of a well-developed, standardized form of Vāstu—Maharishi Vastu® architecture (MVA). MVA’s principles include development of the architect’s consciousness, universal recommendations for building orientation, siting, and dimensions; placement of key functions; and occupants’ head direction when sleeping or performing tasks. The effects of isolated Vāstu elements included in MVA are presented. However, the full value of MVA, documented as a systematic, globally applicable practice, is in the effect of its complete package, and thus this review of MVA includes evaluating the experience of living and working in MVA buildings. Methods The published medical and health-related literature was systematically surveyed for research on factors related to isolated principles applied in MVA as well as on the complete system. Results Published research suggests that incorporating MVA principles into buildings correlates with significant improvements in occupants’ physical and mental health and quality of life: better sleep, greater happiness of children, and the experience of heightened sense of security and reduced stress. The frequency of burglaries, a social determinant of health, also correlates. Potential neurophysiological mechanisms are described. Conclusions Findings suggest that MVA offers an actionable approach for managing a key social determinant of health by using architectural design as preventive medicine and in public health.

Background:. Dual-plate constructs have become an increasingly common fixation technique for midshaft clavicle fractures and typically involve the use of mini-fragment plates. The goal of this technique is to reduce plate prominence and implant irritation. However, limited biomechanical data exist for these lower-profile constructs. The study aim was to compare dual mini-fragment orthogonal plating with small-fragment clavicle plates for biomechanical noninferiority and to determine if an optimal plate configuration could be identified using a cadaveric model. Methods:. Twenty-four cadaveric clavicles were randomized to 1 of 6 groups, stratified by computed tomography-based bone mineral content (BMC): precontoured superior or anterior fixation using a single 3.5-mm Locking Compression Plate (LCP), and 4 different dual-plating constructs utilizing 2.4-mm and 2.7-mm Adaptation plates or LCPs. An inferior butterfly fracture was created. Axial, torsional, and bending (anterior and superior surface loading) stiffnesses were determined through nondestructive cyclic testing, followed by a load-to-failure test in 3-point superior surface bending. Results:. For axial stiffness, the 2 dual-plate constructs with a superior 2.4-mm and anterior 2.7-mm plate (either Adaptation or LCP) were significantly stiffer than the other 4 constructs (p = 0.021 and p = 0.034). For both superior and anterior bending, the superior 2.4-mm and anterior 2.7-mm plate constructs were significantly stiffer when compared with the 3.5-mm superior plate (p = 0.043). No significant differences were found in torsional stiffness or load to failure between the different constructs. Conclusions:. Dual plating using mini-fragment plates is biomechanically superior for the fixation of midshaft clavicle fractures when compared with a single, superior, 3.5-mm plate and has biomechanical properties similar to those of a 3.5-mm plate placed anteriorly. With the exception of axial stiffness, no significant differences were found when different dual-plating constructs were compared with each other. Clinical Relevance:. This study validates the use of dual plating for midshaft clavicle fractures.

Background: Chronic axial neck pain (CANP) due to zygapophysial joint arthropathy is best diagnosed via cervical medial branch block (MBB). However, the paradigm by which MBB is used to select patients for cervical radiofrequency neurotomy (RFN) is contested. Dual diagnostic cervical MBB with a minimum of ≥80% pain relief to diagnose cervical zygapophysial joint pain has been accepted by some Medicare Local Coverage Determinations as the method for selecting patients for cervical RFN. There are some who would argue that the utility of the dual diagnostic MBB and the ≥80% pain relief cut off lacks utility in clinical practice. The suspicion being those who progress from MBB1 to MBB2 will then flow from MBB2 to RFN without fail. Does clinical practice using dual diagnostic MBBs and using an ≥80% pain relief cut off reduce patient eligibility for cervical RFN after both MBB1 and MBB2? Methods: A retrospective clinical audit was carried out at an academic institution spine center from January 1st to December 31st, 2019. Charts were selected based on Current Procedural Terminology codes for MBB, then included if the cervical medial branches were targeted. Charts were then reviewed for procedural progression. Results: 21/51 (24%, 95% Confidence Interval 12-35%) patients progressed from MBB1 to MBB2. Of those 21 patients, 13 patients progressed from MBB2 to RFN (62%, 95% CI 41-83%). In total, 13/51 (14%, 95% CI 14-37%) patients who were initially suspected to have CANP due to zygapophysial joint pain progressed to RFN. Both MBB1 and MBB2 hindered the progression of 30/51 patients (59%, 95% CI 45-72%) and 8/21 patients (38%, 95% CI 17-59%), respectively. Conclusion: Both MBB1 and MBB2 served to filter patients from progression to RFN using dual MBBs with an ≥80% pain relief cutoff.

Introduction: ROS1 fusions are oncogenic drivers in 1% to 3% of NSCLCs. The activity of immune checkpoint inhibitor (ICI) monotherapy or in combination with chemotherapy (chemotherapy with ICI [chemo-ICI]) in these tumors and their immunophenotype have not been systematically described. Methods: In this multi-institutional retrospective study, tumor programmed death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB) were evaluated in patients with ROS1-rearranged NSCLC. Time-to-treatment discontinuation (TTD) and objective response rate (ORR) (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) were calculated for patients treated with ICI or chemo-ICI in the metastatic setting. Results: A total of 184 patients were identified. Among 146 assessable cases, PD-L1 expression was less than 1% in 60 (41%), 1% to 49% in 35 (24%), and greater than or equal to 50% in 51 tumors (35%). Of 100 (92%) TMB-assessable tumors, 92 had less than 10 mutations per megabase. TMB was significantly lower for ROS1-rearranged tumors (n = 97) compared with tumors with EGFR (n = 1250) or KRAS alterations (n = 1653) and all other NSCLC tumors (n = 2753) evaluated with Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (median TMB = 2.6 versus 3.5, 7.0, and 6.1 mutations per megabase, p < 0.001). Among patients treated with ICI, median TTD was 2.1 months (95% confidence interval [CI]: 1.0–4.2 mo; n = 28) and ORR 13% (2 of 16 RECIST-assessable; 95% CI: 2%–38%). Among patients treated with chemo-ICI, median TTD was 10 months (95% CI: 4.7–14.1 mo; n = 11) and ORR 83% (5 of 6 RECIST-assessable; 95% CI: 36%–100%). There was no difference in PD-L1 expression (p = 0.91) or TMB (p = 0.83) between responders and nonresponders. Conclusions: Most ROS1-rearranged NSCLCs have low PD-L1 expression and TMB. The activity of ICI in these tumors is modest. In contrast, chemo-ICI can achieve meaningful activity.

Introduction: Demographic changes have resulted in an increase in injuries among geriatric patients. For these patients, a rigid cervical collar is crucial for immobilizing the cervical spine. However, evidence suggests that patients with a geriatric facial structure require a different means of immobilization than patients with an adult facial structure. This study aimed to analyze the remaining motion of the immobilized cervical spine based on facial structure. Materials and Methods: This study was performed on 8 fresh human cadavers. Facial structure was evaluated via ascertaining the mandibular angle by computer tomography. A mandibular angle below 130°, belongs to the adult facial structure group ( n = 4) and a mandibular angle above 130°, belongs to the geriatric facial structure group ( n = 4). The flexion and lateral bending of the immobilized cervical spine were analyzed in both groups using a wireless motion tracker system. Results: A flexion of up to 19.0° was measured in the adult facial structure group. The mean flexion in the adult vs. geriatric facial structure groups were 14.5° vs. 6.5° (ranges: 9.0-19.0 vs. 5.0-7.0°), respectively. Thus, cervical spine motion was ( p = 0.0286) significantly more reduced in the adult facial structure group. No ( p = 0.0571) significant difference was oberserved in the mean lateral bending of the adult facial structure group (14.5°) compared to the geriatric facial structure group (7.5°). Conclusion: Emergency medical service personnel should therefore follow current guidelines and recommendations and perform cervical spine immobilization with a cervical collar, including in patients with a geriatric facial structure.

Background:. Posttraumatic joint contracture is a debilitating complication following an acute fracture or intra-articular injury that can lead to loss of motion and an inability to complete activities of daily living. In prior studies using an established in vivo model, we found that ketotifen fumarate (KF), a mast cell stabilizer, was associated with a significant reduction in the severity of posttraumatic joint contracture. Our primary research question in the current study was to determine whether a dose-response relationship exists between KF and posttraumatic joint contracture reduction. Methods:. A standardized operative method to create posttraumatic joint contracture in a knee was performed on skeletally mature New Zealand White rabbits. The animals were randomly assigned to 1 of 5 groups (n = 10 per group): a nonoperative control group, an operative control group, or 1 of 3 experimental KF groups (0.01 mg/kg [the KF 0.01 group], 0.1 mg/kg [KF 0.1], or 5.0 mg/kg [KF 5.0]). Flexion contractures were measured following 8 weeks of knee immobilization using a hydraulic material-testing machine. The posterior knee joint capsules were then harvested for quantification of myofibroblast and mast cell numbers with immunohistochemistry analysis. Results:. Forty-five rabbits were used in the final analysis. Contracture severity was significantly reduced in the KF 0.1 group (p = 0.016) and the KF 5.0 group (p = 0.001) compared with the operative control group. When converted to a percent response, posttraumatic joint contracture reduction was 13%, 45%, and 63% for the KF 0.01, KF 0.1, and KF 5.0 groups, respectively. A half-maximal effective concentration (EC50) for KF of 0.22 mg/kg was established. There was also a decrease in myofibroblasts, mast cells, and substance P-containing nerve fiber counts with increasing doses of KF. Conclusions:. Using a preclinical, rabbit in vivo model of posttraumatic joint contracture, increasing doses of KF were associated with decreasing biomechanical estimates of knee posttraumatic joint contracture as well as decreasing numbers of myofibroblasts, mast cells, and substance P-containing nerve fibers. Clinical Relevance:. KF has been used safely in humans for more than 40 years and, to our knowledge, is the first and only agent ready to be potentially translated into an effective treatment for posttraumatic joint contracture.

The data presented here is related to the research article entitled “FERTILITY-SPARING SURGERY AND REPRODUCTIVE-OUTCOMES IN PATIENTS WITH BORDERLINE OVARIAN TUMORS” by Plett et al. in Journal of Gynecologic Oncology [1] and is analysed and discussed in detail. 18 Patients with Recurrent Borderline Ovarian Tumors (BOT) were identified and listed in Table 1. All patients underwent treatment for primary BOT either per radical surgery (RS) or fertility sparing surgery (FSS) by the same team in Horst Schmidt Klinik (HSK) in Wiesbaden and the Department of Gynecology and Gynecologic Oncology at Kliniken Essen-Mitte between January 2000 and December 2018 and were followed up closely. Details on patients` and surgical characteristics are given as well as management of character of recurrent disease. In Table 2 important publications from the last 20 years are listed in order to visualize better the oncologic outcomes (invasive and non-invasive relapses) and calculated risks of recurrence with the purpose to understand better the important findings of the related article cited above.

Abstract. Controversy exists over the optimal management of open fractures as new clinical studies question open fracture management dogma. Open fractures are complex injuries requiring the orthopaedic surgeon to consider both the bone injury as well as associated soft tissue injury. Early intravenous antibiotics and tetanus prophylaxis remain instrumental in infection prevention. However, the “six-hour rule” for initial open fracture debridement and revascularization has come into question. New evidence supports initial debridement within 24 hours with the appropriate surgical team. Additionally, orthopaedic surgeons and vascular surgeons should collaborate on the sequence of management of open fractures with associated vascular injury. Whereas debates on the optimal irrigation pressure and solution have been answered by multicenter randomized controlled trials, further research is required to determine the optimal irrigation volume and timing of wound closure. With advances in management of open fractures, the utility of well-known classification systems including the Gustilo-Anderson classification and Mangled Extremity Severity Score need to be re-evaluated in favor of up-to-date classification systems which better guide management and predict prognosis.

In older persons, the origin of malnutrition is often multifactorial with a multitude of factors involved. Presently, a common understanding about potential causes and their mode of action is lacking, and a consensus on the theoretical framework on the etiology of malnutrition does not exist. Within the European Knowledge Hub “Malnutrition in the Elderly (MaNuEL),” a model of “ D eterminants o f M alnutrition in A ged P ersons” (DoMAP) was developed in a multistage consensus process with live meetings and written feedback (modified Delphi process) by a multiprofessional group of 33 experts in geriatric nutrition. DoMAP consists of three triangle-shaped levels with malnutrition in the center, surrounded by the three principal conditions through which malnutrition develops in the innermost level: low intake, high requirements, and impaired nutrient bioavailability. The middle level consists of factors directly causing one of these conditions, and the outermost level contains factors indirectly causing one of the three conditions through the direct factors. The DoMAP model may contribute to a common understanding about the multitude of factors involved in the etiology of malnutrition, and about potential causative mechanisms. It may serve as basis for future research and may also be helpful in clinical routine to identify persons at increased risk of malnutrition.