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Purpose: The purpose of this study was to determine the association between lens thickness and cataract in participants aged 0 to 5 years. Design: This was a prospective, multicenter, case–control study. Participants: We enrolled 118 participants (171 eyes) aged 0 to 5 years, mean age 14.6 ± 17.0 months, range 0 to 60 months. Methods: Lens thickness was measured on 342 ultrasound biomicroscopy (UBM) images. Main Outcome Measures: Lens thickness; feasibility of lens thickness measurement from UBM images. Results: The mean lens thickness among noncataracts was 3.60 ± 0.17 mm, compared with 3.16 ± 0.61 mm among cataracts (P < 0.0001). Lens thickness

Purpose: The purpose of this study was to analyze the quality and readability of information regarding rotator cuff repair surgery available using an online AI software. Methods: An open AI model (ChatGPT) was used to answer 24 commonly asked questions from patients on rotator cuff repair. Questions were stratified into one of three categories based on the Rothwell classification system: fact, policy, or value. The answers for each category were evaluated for reliability, quality and readability using The Journal of the American Medical Association Benchmark criteria, DISCERN score, Flesch-Kincaid Reading Ease Score and Grade Level. Results: The Journal of the American Medical Association Benchmark criteria score for all three categories was 0, which is the lowest score indicating no reliable resources cited. The DISCERN score was 51 for fact, 53 for policy, and 55 for value questions, all of which are considered good scores. Across question categories, the reliability portion of the DISCERN score was low, due to a lack of resources. The Flesch-Kincaid Reading Ease Score (and Flesch-Kincaid Grade Level) was 48.3 (10.3) for the fact class, 42.0 (10.9) for the policy class, and 38.4 (11.6) for the value class. Conclusion: The quality of information provided by the open AI chat system was generally high across all question types but had significant shortcomings in reliability due to the absence of source material citations. The DISCERN scores of the AI generated responses matched or exceeded previously published results of studies evaluating the quality of online information about rotator cuff repairs. The responses were U.S. 10th grade or higher reading level which is above the AMA and NIH recommendation of 6th grade reading level for patient materials. The AI software commonly referred the user to seek advice from orthopedic surgeons to improve their chances of a successful outcome.

Background: Chronic Spontaneous Urticaria (CSU) is an immune-mediated skin disease that may require prolonged treatments. Currently, there are no recommendations for treatment discontinuation once CSU symptoms are controlled, particularly among patients primarily diagnosed with severe CSU. Objective: In this real-life study we aimed to describe our experience of omalizumab (Oma) treatment withdrawal in CSU and define biomarkers related to these outcomes. Methods: CSU patients followed at our allergy clinic from January 2016 to December 2022 were included. Response to Oma therapy, and Oma-withdrawal outcomes among patients who reached complete remission for >6 months were analyzed. Results: During the study period 192/335(%) CSU patients were categorized as severe-CSU and entitled to receive Oma according to our country's regulations. Of them, 131/192(68%) were considered “Oma-responders”, and 95/131(72.5%) patients underwent gradual treatment withdrawal. Successful Oma-withdrawal was documented in 47/95(49.5%) whereas 48/95(50.5%) patients experienced flare and were defined as unsuccessful OMA-withdrawal. The first was associated with shorter disease duration 7.1 ± 7.4 years vs. 10.7 ± 9.4 (P = 0.042), lower baseline-IgE 81.6 ± 84.1IU/ml vs. 324.7 ± 555.9 (P = 0.005), and lower baseline-eosinophils count 131.4 ± 110.5 vs. 195.6 ± 98.4 (P = 0.043) in comparison to failure of Oma-withdrawal group. Conclusion: OMA may be successfully withdrawn in up to 50% of severe CSU patients following complete remission of disease symptoms, utilizing a gradual withdrawal protocol. Oma-withdrawal failure was linked with longer duration of disease as well as high IgE and eosinophil counts prior to initiation of Oma therapy. These parameters may enable the design of a treatment withdrawal algorithm.

Background: Psychological distress has been associated with declining shoulder function in patients with rotator cuff tears (RCTs). Thus, we aimed to 1) evaluate the absence or presence of differences in shoulder pain, function, or pain-associated psychological distress in patients with increasing RCT severity and 2) assess whether psychological distress is associated with shoulder pain and function while adjusting for RCT severity. Methods: Consecutive patients who underwent rotator cuff repair and completed the optimal screening for prediction of referral and outcome (OSPRO) survey from 2019 to 2021 were included. OSPRO is composed of 3 domains that estimate pain associated psychological distress (negative mood, negative coping, and positive coping). Demographics, tear characteristics, and three patient reported outcomes (PRO), including the visual analog scale (VAS), Single Assessment Numeric Evaluation, and American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) were collected. Patients were analyzed with analysis of variance and chi-square tests and stratified based on severity of RCTs into three groups: partial-thickness, small-to-medium full-thickness, and large-to-massive full-thickness tear. Linear regression analysis was used to evaluate the association between OSPRO scores and PROs, adjusting for severity of RCT. Results: Eighty-four patients were included: 33 (39%) had partial-thickness, 17 (20%) had small-to-medium full-thickness, and 34 (41%) had large-to-massive tears. Regarding PROs and psychological distress, there were no significant differences amongst the three cohorts. In contrast, multiple significant associations between psychological distress and PROs were found. Within the negative coping domain, fear avoidance dimensions demonstrated the strongest correlation to PROs: fear-avoidance behavior for physical activity (ASES Beta −0.592, P

There is a lack of consensus over the description and severity assignment of allergic adverse reactions to immunotherapy, although there seems to be a consensus at least in terms of using the World Allergy Organization (WAO) grading systems to describe local adverse events for Sublingual Immunotherapy (SLIT) and Systemic Allergic Reactions (SARs) to Subcutaneous Immunotherapy (SCIT) amongst the major national/regional allergy societies. In this manuscript, we propose a modification of the previous WAO Grading system for SARs, which aligns with the newly-proposed Consortium for Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions in Food Allergy (version 3.0). We hope this can facilitate a unified grading system appropriate to SARs due to allergen immunotherapy, independent of allergen and route of administration, and across clinical and research practice.

Summary:. Free functional muscle transfer is an attractive option within reconstructive surgery when seeking to restore critical muscle function. The gracilis muscle has long been utilized for this purpose due to its expendability and consistent anatomy. Historically, survival of the skin overlying the distal one-third of the myocutaneous gracilis flap has been unpredictable. To address this, the myofasciocutaneous technique was developed, with prior studies demonstrating improved distal skin paddle viability with this approach; however, the mechanism is poorly defined. This study aimed to understand what factors contribute to survival benefit in myofasciocutaneous gracilis flaps. Using cadaveric dissections followed by latex dye injections, we discuss the creation of a deep fascial sheath that contains a rich vascular network and permits adhesion-free excursion at the recipient site. This study advances our understanding of the myofasciocutaneous gracilis flap and provides wider clinical applicability in free functional muscle transfer.

Background: Chronic spontaneous urticaria (CSU) is a common condition treated by allergist/immunologists, but the only FDA-approved biologic medication, omalizumab, may be underutilized globally. Objective: This study was performed to determine the global prescription of omalizumab for treatment of CSU by allergists/immunologists. Methods: Anonymous questionnaire surveys were distributed online to World Allergy Organization (WAO) members worldwide. Categorical data were analyzed for descriptive analysis using one-way frequency tabulation in SAS 9.4. Results: There were 348 respondents (43 missing data); Average age 51 (range 28–90); M/F 48%/52%. 58% had > 15 years of clinical experience and 10%

Background: The Society of Thoracic Surgeons risk scores are widely used to assess risk of morbidity and mortality in specific cardiac surgeries but may not perform optimally in all patients. In a cohort of patients undergoing cardiac surgery, we developed a data-driven, institution-specific machine learning–based model inferred from multi-modal electronic health records and compared the performance with the Society of Thoracic Surgeons models. Methods: All adult patients undergoing cardiac surgery between 2011 and 2016 were included. Routine electronic health record administrative, demographic, clinical, hemodynamic, laboratory, pharmacological, and procedural data features were extracted. The outcome was postoperative mortality. The database was randomly split into training (development) and test (evaluation) cohorts. Models developed using 4 classification algorithms were compared using 6 evaluation metrics. The performance of the final model was compared with the Society of Thoracic Surgeons models for 7 index surgical procedures. Results: A total of 6392 patients were included and described by 4016 features. Overall mortality was 3.0% (n = 193). The XGBoost algorithm using only features with no missing data (336 features) yielded the best-performing predictor. When applied to the test set, the predictor performed well (F-measure = 0.775; precision = 0.756; recall = 0.795; accuracy = 0.986; area under the receiver operating characteristic curve = 0.978; area under the precision-recall curve = 0.804). eXtreme Gradient Boosting consistently demonstrated improved performance over the Society of Thoracic Surgeons models when evaluated on index procedures within the test set. Conclusions: Machine learning models using institution-specific multi-modal electronic health records may improve performance in predicting mortality for individual patients undergoing cardiac surgery compared with the standard-of-care, population-derived Society of Thoracic Surgeons models. Institution-specific models may provide insights complementary to population-derived risk predictions to aid patient-level decision making.

Humanitarian crises create opportunities for both in-person and remote aid. Durable, complex, and team-based care may leverage a telemedicine approach for comprehensive support within a conflict zone. Barriers and enablers are detailed, as is the need for mission expansion due to initial program success. Adapting a telemedicine program initially designed for critical care during the severe acute respiratory syndrome coronavirus 2 pandemic offers a solution to data transfer and data analysis issues. Staffing efforts and grouped elements of patient care detail the kinds of remote aid that are achievable. A multiprofessional team-based approach (clinical, administrative, nongovernmental organization, government) can provide comprehensive consultation addressing surgical planning, critical care management, infection and infection control management, and patient transfer for complex care. Operational and network security create parallel concerns relevant to avoid geolocation and network intrusion during consultation. Deliberate approaches to address cultural differences that influence relational dynamics are also essential for mission success.

Background: Anaphylaxis is the most severe clinical presentation of acute systemic allergic reactions and can cause death. Given the prevalence of anaphylaxis within healthcare systems, it is a high priority public health issue. However, management of anaphylaxis – both acute and preventative – varies by region. Methods: The World Allergy Organization (WAO) Anaphylaxis Committee and the WAO Junior Members Steering Group undertook a global online survey to evaluate local practice in the diagnosis and management of anaphylaxis across regions. Results: Responses were received from WAO members in 66 countries. While intramuscular epinephrine (adrenaline) is first-line treatment for anaphylaxis, some countries continue to recommend alternative routes in contrast to guidelines. Epinephrine auto-injector (EAI) devices, prescribed to individuals at ongoing risk of anaphylaxis in the community setting, are only available in 60% of countries surveyed, mainly in high-income countries. Many countries in South America, Africa/Middle-East and Asian-Pacific regions do not have EAI available, or depend on individual importation. In countries where EAIs are commercially available, national policies regarding the availability of EAIs in public settings are limited to few countries (16%). There is no consensus regarding the time patients should be observed following emergency treatment of anaphylaxis. Conclusion: This survey provides a global snapshot view of the current management of anaphylaxis, and highlights key unmet needs including the global availability of epinephrine for self-injection as a key component of anaphylaxis management.

Left atrial spontaneous echo contrast is an echocardiographic finding associated with hypercoagulable states and stasis and can be clinically correlated with a thromboembolism in patients with atrial fibrillation, mitral stenosis, or mitral valve repair. Black blood double inversion recovery cardiac magnetic resonance is used to map out cardiac anatomy and demonstrates higher signal in blood flowing at a slower rate, such as at the sites of aortic aneurysms, aortic dissections and vessel occlusions. Here, we present the case of a 66-year-old woman with persistent atrial fibrillation and left atrial findings of spontaneous echo contrast and high signal on black blood double inversion recovery cardiac magnetic resonance imaging, raising concern for a thrombus. However, this was ruled out with subsequent bright blood cardiac magnetic resonance imaging demonstrating high signal with transitory central swirling low signal in the left atrium. Thus, cardiac magnetic resonance imaging can be used to demonstrate non-thrombotic low flow states in cases where contrast is contraindicated.

Summary:. Free flap surgery for limb salvage has become the surgical standard for reconstruction of bone and soft tissue with success rates and flap survivals of 94%–95%. The soft tissue defect dictates the technique of coverage. In many cases, multiple techniques of soft tissue coverage are necessary, ranging from myocutaneous and fasciocutaneous free flaps to split-thickness skin grafts (STSGs). It has been shown that fasciocutaneous free flaps are not inferior to muscle flaps in treatment of lower leg limb salvage. Although a complete flap loss is rare, it is not uncommon to have partial flap necrosis, wound dehiscence, or secondary soft tissue defects, necessitating further minor reconstruction, which we call “touch up” skin grafts. In many of these secondary procedures, split thickness skin grafts are sufficient. We have been using the skin portion of the fasciocutaneous free flap as a donor site for harvesting STSGs for quite some time without disadvantages. We believe that minimizing additional donor site morbidity is of great importance. The free tissue transfer is insensate and readily available at the site of injury, making prepping and draping simple as well as cosmetically acceptable, as the transferred free tissue, unfortunately, is rarely a perfect fit. The associated pain, discomfort, and scar of an additional donor site can be avoided. In our case series, we did not experience any flap loss, infections, or complications. Thus, harvesting an STSG from a fasciocutaneous free flap seems to be a feasible option to be considered in limb salvage.

Background: Recalcitrant or persistent nonunions of the metatarsophalangeal (MTP) joint occur following failed MTP surgery for MTP fusion, failed MTP prosthesis, for hallux rigidus or due to infection and erosion. A deficient soft tissue envelope and compromised vascular supply of tissues in this region compound further attempts to salvage the great toe and preserve function. The medial femoral condyle (MFC) free flap provides vascularized corticocancellous bone and periosteum and has been successfully used for a variety of complex hindfoot and ankle pathologies. We present an additional indication with a small cohort study demonstrating its use in persistent nonunions of the first MTP joint. Methods: A retrospective review was completed of all MFC flaps used for revision of failed first MTP joint fusion from January 2019 to November 2022. Demographic information, comorbidities, as well as clinical and radiologic follow-up was obtained from the patient charts. Results: Three patients were included with MTP nonunion and an average of 7.5 (range, 5-11) failed prior surgeries. Mean age at index surgery was 50 (range, 46-57) years. An osseous union was achieved in all patients after 82 (range, 75-88) days. Hardware removal was possible after 81 (range, 55-98) days. Mean follow-up was 17 (range, 5-31) months. We note a 100% flap success rate without returns to the operating room. The lengths of the bone flaps were 2 to 4 cm, the volumes were 8 to 12 cm 3 . Fixation was performed with 1 intramedullary K-wire. The recipient vessel in all patients was the dorsalis pedis artery or a tributary thereof. All arterial anastomoses were performed under the operating microscope. Conclusion: The MFC free flap is a reasonable option for salvage of complex recalcitrant or persistent nonunions of the first MTP joint. More prospective long-term studies with functional outcomes are necessary to confirm these findings. Level of Evidence: Level IV, retrospective case series.

Background: Cutibacterium acnes is a commensal intradermal microorganism that is commonly isolated at revision shoulder arthroplasty. Standard practice chlorhexidine gluconate (CHG) skin preparation agents have limited effectiveness at eradicating C. acnes in the dermis. Benzoyl peroxide (BPO) has demonstrated effectiveness against C. acnes. This meta-analysis compares the efficacy of at-home shoulder decolonization before surgery using CHG vs. BPO to reduce shoulder C. acnes burden. Methods: This was a Preferred Reporting Items for Systematic Reviews and Meta-Analyses systematic review. PubMed and MEDLINE databases were searched for studies evaluating the effects of CHG and BPO in reducing C. acnes at the shoulder. Trial results were extracted and pooled using a random effects model, separating data from randomized controlled trials (RCTs) and non-RCTs. Methodologic quality of studies was assessed using the Cochrane Risk of Bias Assessment Tools. Results: Ten studies (589 patients) were included. RCTs showed that both BPO and CHG led to significant reductions in culture positivity compared with negative controls (risk ratio [RR] with 95% confidence interval [CI] = 0.20 [0.13, 0.30], P < .0001 and 0.46 [0.37, 0.57], P < .0001, respectively). Non-RCT data demonstrated similar results comparing BPO and CHG to the control (RR with 95% CI = 0.34 [0.21, 0.57], P < .0001 and 0.31 [0.20, 0.49], P < .0001, respectively). Comparing BPO and CHG, RCT data showed a significant reduction in culture positivity with BPO (RR with 95% CI = 0.46 [0.27, 0.77], P < .009). Of RCTs, 5 were low and one was of moderate risk of bias. Of non-RCTs, 3 had low risk of bias, whereas one had moderate risk of bias. Conclusion: This review demonstrated that preoperative CHG and BPO can reduce C. acnes at the shoulder. However, BPO exhibits greater efficacy than CHG, potentially because of the compound’s ability to penetrate the dermis. BPO is a simple and economical agent that may reduce joint exposure to C. acnes in shoulder surgery.

Background:. Patient values may be obscured when decisions are made under the circumstances of constrained time and limited counseling. The objective of this study was to determine if a multidisciplinary review aimed at ensuring goal-concordant treatment and perioperative risk assessment in high-risk orthopaedic trauma patients would increase the quality and frequency of goals-of-care documentation without increasing the rate of adverse events. Methods:. We prospectively analyzed a longitudinal cohort of adult patients treated for traumatic orthopaedic injuries that were neither life- nor limb-threatening between January 1, 2020, and July 1, 2021. A rapid multidisciplinary review termed a “surgical pause” (SP) was available to those who were ≥80 years old, were nonambulatory or had minimal ambulation at baseline, and/or resided in a skilled nursing facility, as well as upon clinician request. Metrics analyzed include the proportion and quality of goals-of-care documentation, rate of return to the hospital, complications, length of stay, and mortality. Statistical analysis utilized the Kruskal-Wallis rank and Wilcoxon rank-sum tests for continuous variables and the likelihood-ratio chi-square test for categorical variables. Results:. A total of 133 patients were either eligible for the SP or referred by a clinician. Compared with SP-eligible patients who did not undergo an SP, patients who underwent an SP more frequently had goals-of-care notes identified (92.4% versus 75.0%, p = 0.014) and recorded in the appropriate location (71.2% versus 27.5%, p < 0.001), and the notes were more often of high quality (77.3% versus 45.0%, p < 0.001). Mortality rates were nominally higher among SP patients, but these differences were not significant (10.6% versus 5.0%, 5.1% versus 0.0%, and 14.3% versus 7.9% for in-hospital, 30-day, and 90-day mortality, respectively; p > 0.08 for all). Conclusions:. The pilot program indicated that an SP is a feasible and effective means of increasing the quality and frequency of goals-of-care documentation in high-risk operative candidates whose traumatic orthopaedic injuries are neither life- nor limb-threatening. This multidisciplinary program aims for goal-concordant treatment plans that minimize modifiable perioperative risks. Level of Evidence:. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Background:. Identifying risk factors for traumatic lower extremity reconstruction outcomes has been limited by sample size. We evaluated patient and procedural characteristics associated with reconstruction outcomes using data from almost four million patients. Methods:. The National Trauma Data Bank (2015–2018) was queried for lower extremity reconstructions. Univariable and multivariable analyses determined associations with inpatient outcomes. Results:. There were 4675 patients with lower extremity reconstructions: local flaps (77%), free flaps (19.2%), or both (3.8%). Flaps were most commonly local fasciocutaneous (55.1%). Major injuries in reconstructed extremities were fractures (56.2%), vascular injuries (11.8%), and mangled limbs (2.9%). Ipsilateral procedures prereconstruction included vascular interventions (6%), amputations (5.6%), and fasciotomies (4.3%). Postoperative surgical site infection and amputation occurred in 2% and 2.6%, respectively. Among survivors (99%), mean total length of stay (LOS) was 23.2 ± 21.1 days and 46.8% were discharged to rehab. On multivariable analysis, vascular interventions prereconstruction were associated with increased infection [odds ratio (OR) 1.99, 95% confidence interval (CI) 1.05–3.79, P = 0.04], amputation (OR 4.38, 95% CI 2.56–7.47, P < 0.001), prolonged LOS (OR 1.59, 95% CI 1.14–2.22, P = 0.01), and discharge to rehab (OR 1.49, 95% CI 1.07–2.07, P = 0.02). Free flaps were associated with prolonged LOS (OR 2.08, 95% CI 1.74–2.49, P < 0.001). Conclusions:. Prereconstruction vascular interventions were associated with higher incidences of adverse outcomes. Free flaps correlated with longer LOS, but otherwise similar outcomes. Investigating reasons for increased complication and healthcare utilization likelihood among these subgroups is warranted.

Background:. The medial femoral condyle free flap serves as an attractive reconstructive option for small- to intermediate-sized bony defects. It is commonly applied in the extremities with limited reports in the head and neck. Methods:. A systematic review of the literature was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results:. Seventeen articles met inclusion criteria, yielding 166 cases for analysis, with a majority of the cohort from a single study (n = 107; 64.4%). However, all included studies represented novel reconstructive sites and surgical indications. Flap components were described in 157 cases; periosteum was used only in four cases (2.5%), whereas all others are composed of cortical bone combined with periosteum, cancellous bone, and/or cartilage (97.5%). Additionally, a skin island was used in 43 cases (25.9%). Flap measurements were reported in 51 cases, averaging 4.5 ± 2.7 cm in length. Seven cases listed skin island dimensions, averaging 20.2 ± 12.8 cm2. The descending genicular artery was the primary pedicle employed (n = 162; 97.6%), while the superior medial genicular was used in the descending genicular artery’s absence (n = 4; 2.4%). Descending genicular artery pedicle length from 15 reporting cases averaged 6.4 ± 1.2 cm. Successful reconstructions totaled 160 cases (96.4%). Recipient complications were seen in 16 cases (9.6%) with six constituting flap failures (3.6%). Donor site complications were minimal (n = 6; 3.6%); however, this included one major complication of femoral shaft fracture. Conclusion:. The medial femoral condyle free flap is an effective reconstructive option for the head and neck due to its versatile nature, low complication profile at both recipient and donor site, ease of harvest, and two-team approach.

Introduction:. Physician shortages across the United States will affect access to orthopaedic care for patients. Orthopaedic surgery is predicted to have one of the largest shortages among surgical subspecialties by 2025, which will disproportionally affect patients in medically underserved areas. This study examines characteristics and experiences of graduating medical students interested in orthopaedic surgery who intend to practice in underserved areas (IPUAs). Methods:. We analyzed deidentified data of AAMC Graduation Questionnaire respondents who matriculated between 2007 to 2008 and 2011 to 2012. Forty-eight thousand ninety-six (83.91%) had complete demographic, financial, and medical school elective data and were included in the study cohort. Multivariable logistic regression was performed to determine the correlation between student characteristics and intention to pursue orthopaedic surgery and IPUAs. Results:. Of the 48,096 students with complete information, 2,517 (5.2%) intended to pursue a career in orthopaedic surgery. Among the orthopaedic students, men were less likely than women to report IPUAs (adjusted odds ratio [aOR], 0.6; 95% CI, 0.4-0.8). Students who identified as Black/African American (aOR, 5.0; 95% CI, 3.0-8.2) or Hispanic (aOR, 2.0; 95% CI, 1.1-3.5) were more likely than White students to report IPUAs. Medical students who intend to pursue orthopaedics and received a scholarship (aOR, 1.5; 95% CI, 1.1-2.0), participated in community research (aOR, 1.8; 95% CI, 1.4-2.3), or had a global health experience (aOR, 1.9; 95% CI, 1.5-2.5) were more likely to report IPUAs. Discussion:. If orthopaedic surgeons who reported as medical students who reported IPUAs actually do so, recruiting and retaining more sex and race/ethnically diverse orthopaedic surgeons could reduce the impact of the impending shortage of orthopaedic surgeons in underserved areas. IPUA is correlated to medical school experiences related to cultural competency including global health experiences and community-based research projects.

Background. Kidney transplant recipients (KTRs) have a diminished response to SARS-CoV-2 vaccination compared with immunocompetent individuals. Deeper understanding of antibody responses in KTRs following third-dose vaccination would enable identification of those who remain unprotected against Omicron. Methods. We profiled antibody responses in KTRs pre- and at 1 and 3 mo post-third-dose SARS-CoV-2 mRNA-based vaccine. Binding antibody levels were determined by ELISA. Neutralization against wild type, Beta, Delta, and Omicron (BA.1) variants was determined using a SARS-CoV-2 spike-pseudotyped lentivirus assay. Results. Forty-four KTRs were analyzed at 1 and 3 mo (n = 26) post-third dose. At 1 mo, the proportion of participants with a robust antibody response had increased significantly from baseline, but Omicron-specific neutralizing antibodies were detected in just 45% of KTRs. Median binding antibody levels declined at 3 mo, but the proportion of KTRs with a robust antibody response was unchanged; 38.5% KTRs maintained Omicron-specific neutralization at 3 mo. No clinical variables were significantly associated with Omicron-neutralizing antibodies, but antireceptor binding domain titers appeared to identify those with Omicron-specific neutralizing capacity. Conclusions. Over 50% of KTRs lack Omicron-specific neutralization capacity 1 mo post-third mRNA-vaccine dose. Antibody levels of responders were well preserved at 3 mo. Anti receptor binding domain antibody titers may identify patients with a detectable Omicron-neutralizing antibody response.

Background. Cardiovascular disease is a major cause of morbidity and mortality in kidney transplant recipients. Trial evidence to improve cardiovascular outcomes is limited by inconsistent reporting of outcomes, which may also lack patient-relevance. This study aimed to assess the range and consistency of cardiovascular outcomes reported by contemporary trials in kidney transplant recipients. Methods. A systematic review of all randomized controlled trials involving adult kidney transplant recipients that reported at least 1 cardiovascular outcome from January 2012 to December 2019 was performed, including Embase, MEDLINE, Cochrane, and ClinicalTrials.gov electronic databases. Trial characteristics were extracted and all levels of specification of the cardiovascular outcome measures reported were analyzed (the measure definition, metric‚ and method of aggregation). Measures assessing a similar aspect of cardiovascular disease were categorized into outcomes. Results. From 93 eligible trials involving 27 609 participants, 490 outcome measures were identified. The outcome measures were grouped into 38 outcomes. A cardiovascular composite was the most common outcome reported (40 trials, 43%) followed by cardiovascular mortality (42%) and acute coronary syndrome (31%). Cardiovascular composite was also the most heterogeneous outcome with 77 measures reported followed by cardiovascular mortality (n = 58) and inflammatory biomarkers (n = 51). The most common cardiovascular composite outcome components reported were major cardiovascular events (18 trials), stroke unspecified (11 trials), and myocardial infarction unspecified (10 trials). Conclusions. There is substantial heterogeneity in cardiovascular outcome reporting in kidney transplant trials.

Background: The historical mortality rate after falling from the Golden Gate Bridge has been approximately 98%. We report on 14 recent survivors treated at Marin Health Medical Center. Methods: We retrospectively reviewed the 22-year experience of treating patients after Golden Gate Bridge falls. Patients with signs of life when recovered by the Coast Guard were included. Results: Marin General Hospital treated 26 patients with an average age of 28.2 years. The mortality rate was 46.2% with an increased survival over the past decade compared to the first 12 years, 61% vs 37%, P = not significant. The average injury severity score was 29.3 and was significantly lower over the past decade (43.9 vs 22.8, P = .004). The leading injuries were hemothorax/pneumothorax (73%), spine fractures (65%), lung contusions (50%), rib fractures (50%), and solid organ injury (46%). Patients with major cardiovascular injuries were significantly more likely to expire, 88% vs 28%, P = .009. Conclusion: The pattern of injury leading to death after an intentional fall from the Golden Gate Bridge has not changed significantly over the decades.

Background: The incidence of shoulder arthroplasty in the United States continues to increase, and while the risk of intraoperative complications such as fracture remains relatively low, there has been little investigation into whether certain patient-specific risk factors predispose to this complication. This study characterizes the incidence of intraoperative fracture during shoulder arthroplasty and additionally hypothesizes that certain risk factors may exist in addition to potentially leading to worsened near-term outcomes. Methods: An institutional database of shoulder arthroplasties (N = 1773; 994 anatomic, 779 reverse) was retrospectively reviewed, and the operative reports for each case were examined for documentation of an intraoperative fracture, including during which surgical step the fracture took place. Various preoperative and intraoperative factors were tested for comparative significance (P

Background: Despite the success of anatomic total shoulder arthroplasty (TSA) and reverse shoulder arthroplasty (RSA), the clinical course of some patients necessitates operative intervention in the acute postoperative period. In this study, we evaluate the risk of subsequent prosthetic joint infection (PJI) in patients who undergo an aseptic reoperation within 90 days of primary shoulder arthroplasty. Method: A retrospective review of patients with primary TSA and RSA was performed using a commercially available national database (PearlDiver Inc., Fort Wayne, IN, USA). Queries were performed with use of International Classification of Diseases, Ninth Revision and Tenth Revision and Current Procedural Technology codes. Patients were divided into cohorts based on undergoing aseptic reoperation, reoperation for PJI, or no reoperations within 90 days of index procedure. Primary outcome was subsequent PJI within 1 year of index procedure. Observed PJI rates were compared using chi-square analysis. Risk factors for PJI were compared using logistic regression. Results: From 2010 to 2018, a total of 96,648 patients underwent primary shoulder arthroplasty: 46,810 underwent TSA and 49,838 underwent RSA. The rate of aseptic reoperation within 90 days was 0.72% and 1.5% in the TSA and RSA cohorts, respectively. At 1 year postoperatively, patients who underwent an aseptic reoperation within 90 days had an elevated risk of subsequent PJI compared with the overall rate of PJI in the TSA (3.54% vs. 0.75%; P

Background: Sesame allergy (SA) is a common cause of life-threatening, persistent food allergy, not only in the Middle East and Asia, but increasingly worldwide. Commercially available tests such as extracts for skin testing or specific IgE for sesame or its components in serum, have very limited predictive values. Therefore the diagnosis is dependent on the performance of oral food challenges (OFC), frequently avoided in children, due to time and resource constraints, as well as the risk of anaphylaxis. In the current study we aimed to develop a simple, readily available, clinical tool, able to predict sesame OFC outcomes in children. Methods: Children with a history of SA were evaluated in the outpatient allergy clinic. All children underwent natural sesame OFC, with an additional baked-sesame challenge offered to children with SA. Clinical data were compared between the sesame tolerant (ST) and SA groups. Machine-learning tools were applied, to create a simple, clinically driven, decision tree analysis (DTA), predicting the outcome of sesame OFCs and the diagnosis of SA. Results: One hundred four children, mean age 47.2 months, 58% boys were included, with a high prevalence of additional food allergies, atopic dermatitis, asthma, and rhinitis. Following OFC, 56 (54%) were diagnosed as ST and 48 (46%) SA. Among SA children, 85% were able to consume baked-sesame in equal or higher protein amounts compared to natural sesame paste. Compared to ST, SA children had a tendency towards a higher incidence of allergic rhinitis (5% Vs 17%, p = 0.062), multiple food allergies (3.6% vs 12.5%, p = 0.09) and requiring medical treatment after the initial SA reaction (27% vs 41%, p = 0.022). As a group, skin tests with both commercial and natural tahini paste differed significantly between ST and SA (mean wheal in mm, for extract 4.2 vs 13.4, p

Background: Angiotensin receptor blockers (ARBs) and/or angiotensin-converting enzyme (ACE) inhibitors could alter mortality from coronavirus disease 2019 (COVID-19), but existing meta-analyses that combined crude and adjusted results may be confounded by the fact that comorbidities are more common in ARB/ACE inhibitor users. Methods: We searched PubMed/MEDLINE/Embase for cohort studies and meta-analyses reporting mortality by preexisting ARB/ACE inhibitor treatment in hospitalized COVID-19 patients. Random effects meta-regression was used to compute pooled odds ratios for mortality adjusted for imbalance in age, sex, and prevalence of cardiovascular disease, hypertension, diabetes mellitus, and chronic kidney disease between users and nonusers of ARBs/ACE inhibitors at the study level during data synthesis. Results: In 30 included studies of 17,281 patients, 22%, 68%, 25%, and 11% had cardiovascular disease, hypertension, diabetes mellitus, and chronic kidney disease. ARB/ACE inhibitor use was associated with significantly lower mortality after controlling for potential confounding factors (odds ratio 0.77 [95% confidence interval: 0.62, 0.96]). In contrast, meta-analysis of ARB/ACE inhibitor use was not significantly associated with mortality when all studies were combined with no adjustment made for confounders (0.87 [95% confidence interval: 0.71, 1.08]). Conclusions: ARB/ACE inhibitor use was associated with decreased mortality in cohorts of COVID-19 patients after adjusting for age, sex, cardiovascular disease, hypertension, diabetes, and chronic kidney disease. Unadjusted meta-analyses may not be appropriate for determining whether ARBs/ACE inhibitors are associated with mortality from COVID-19 because of indication bias. Résumé: Introduction: Les antagonistes des récepteurs de l'angiotensine (ARA) et/ou les inhibiteurs de l'enzyme de conversion de l'angiotensine (IECA) feraient varier la mortalité liée à la COVID-19, mais il est possible que les méta-analyses actuelles qui combinaient les résultats bruts et ajustés soient invalidées du fait que les comorbidités sont plus fréquentes chez les utilisateurs d'ARA/IECA. Méthodes: Nous avons effectué des recherches dans les bases de données PubMed/MEDLINE/Embase pour trouver des études de cohorte et des méta-analyses qui portent sur la mortalité associée à un traitement préexistant par ARA/IECA chez les patients hospitalisés atteints de la COVID-19. Nous avons utilisé la métarégression à effets aléatoires pour calculer les rapports de cotes regroupés de mortalité ajustés en fonction du déséquilibre de l’âge, du sexe, et de la prévalence des maladies cardiovasculaires, de l'hypertension, du diabète sucré et de l'insuffisance rénale chronique entre les utilisateurs et les non-utilisateurs d'ARA/IECA dans le cadre de l’étude durant la synthèse des données. Résultats: Dans les 30 études portant sur 17 281 patients, 22 %, 68 %, 25 % et 11 % avaient respectivement une maladie cardiovasculaire, de l'hypertension, le diabète sucré et de l'insuffisance rénale chronique. L'utilisation des ARA/IECA a été associée à une mortalité significativement plus faible après avoir tenu compte des facteurs confusionnels potentiels (rapport de cotes 0,77 [intervalle de confiance à 95 % : 0,62, 0,96]). En revanche, la méta-analyse sur l'utilisation des ARA/IECA n'a pas été associée de façon significative à la mortalité lorsque toutes les études ont été combinées sans ajustement sur les facteurs confusionnels (0,87 [intervalle de confiance à 95 % : 0,71, 1,08]). Conclusions: L'utilisation des ARA/IECA a été associée à la diminution de la mortalité au sein des cohortes de patients atteints de la COVID-19 après l'ajustement en fonction de l’âge, du sexe, des maladies cardiovasculaires, de l'hypertension, du diabète et de l'insuffisance rénale chronique. Les méta-analyses non ajustées peuvent ne pas permettre de déterminer si les ARA/IECA sont associés à la mortalité liée à la COVID-19 en raison du biais d'indication.

“Brain-predicted age” quantifies apparent brain age compared to normative neuroimaging trajectories. Advanced brain-predicted age has been well established in symptomatic Alzheimer disease (AD), but is underexplored in preclinical AD. Prior brain-predicted age studies have typically used structural MRI, but resting-state functional connectivity (FC) remains underexplored. Our model predicted age from FC in 391 cognitively normal, amyloid-negative controls (ages 18–89). We applied the trained model to 145 amyloid-negative, 151 preclinical AD, and 156 symptomatic AD participants to test group differences. The model accurately predicted age in the training set. FC-predicted brain age gaps (FC-BAG) were significantly older in symptomatic AD and significantly younger in preclinical AD compared to controls. There was minimal correspondence between networks predictive of age and AD. Elevated FC-BAG may reflect network disruption during symptomatic AD. Reduced FC-BAG in preclinical AD was opposite to the expected direction, and may reflect a biphasic response to preclinical AD pathology or may be driven by inconsistency between age-related vs. AD-related networks. Overall, FC-predicted brain age may be a sensitive AD biomarker.

Background: Allergies have long been observed in Inborn Errors of Immunity (IEI) and might even be the first presentation resulting in delayed diagnosis or misdiagnosis in some cases. However, data on the prevalence of allergic diseases among IEI patients are limited and contradictory. Objective: To provide a worldwide view of allergic diseases, across a broad spectrum of IEI, and their impact on the timely diagnosis of IEI. Methods: This is a worldwide study, conceived by the World Allergy Organization (WAO) Inborn Errors of Immunity Committee. A questionnaire was developed and pilot-tested and was sent via email to collect data from 61 immunology centers known to treat pediatric and/or adult IEI patients in 41 countries. In addition, a query was submitted to The United States Immunodeficiency Network (USIDNET) at its website. Results: Thirty centers in 23 countries caring for a total of 8450 IEI patients responded. The USIDNET dataset included 2332 patients. Data from responders showed that a median (IQR) of 16.3% (10–28.8%) of patients experienced allergic diseases during the course of their IEI as follows: 3.6% (1.3–11.3%) had bronchial asthma, 3.6% (1.9–9.1%) atopic dermatitis, 3.0% (1.0–7.8%) allergic rhinitis, and 1.3% (0.5–3.3%) food allergy. As per the USIDNET data, the frequency of allergy among IEI patients was 68.8% (bronchial asthma in 46.9%). The percentage of IEI patients who presented initially with allergic disorders was 8% (5–25%) and diagnosis delay was reported in 7.5% (0.9–20.6%). Predominantly antibody deficiencies had the highest frequency of allergic disease followed by combined immunodeficiency with a frequency of 40.3% (19.2–62.5%) and 20.0% (10–32%) respectively. As per the data of centers, anaphylaxis occurred in 25/8450 patients (0.3%) whereas per USIDNET dataset, it occurred in 249/2332 (10.6%); drugs and food allergy were the main causes in both datasets. Conclusions: This multinational study brings to focus the relation between allergic diseases and IEI. Major allergies do occur in IEI patients but were less frequent than the general population. Initial presentation with allergy could adversely affect the timely diagnosis of IEI. There is a need for policies to raise awareness and educate primary care and other referring specialties on the association of allergic diseases with IEI. This study provides a network among centers for future prospective studies in the field.

Background: Chronic cough management necessitates a clear integrated care pathway approach. Primary care physicians initially encounter the majority of chronic cough patients, yet their role in proper management can prove challenging due to limited access to advanced diagnostic testing. A multidisciplinary approach involving otolaryngologists and chest physicians, allergists, and gastroenterologists, among others, is central to the optimal diagnosis and treatment of conditions which underly or worsen cough. These include infectious and inflammatory, upper and lower airway pathologies, or gastro-esophageal reflux. Despite the wide armamentarium of ancillary testing conducted in cough multidisciplinary care, such management can improve cough but seldom resolves it completely. This can be due partly to the limited data on the role of tests (eg, spirometry, exhaled nitric oxide), as well as classical pharmacotherapy conducted in multidisciplinary specialties for chronic cough. Other important factors include presence of multiple concomitant cough trigger mechanisms and the central neuronal complexity of chronic cough. Subsequent management conducted by cough specialists aims at control of cough refractory to prior interventions and includes cough-specific behavioral counseling and pharmacotherapy with neuromodulators, among others. Preliminary data on the role of neuromodulators in a proof-of-concept manner are encouraging but lack strong evidence on efficacy and safety. Objectives: The World Allergy Organization (WAO)/Allergic Rhinitis and its Impact on Asthma (ARIA) Joint Committee on Chronic Cough reviewed the recent literature on management of chronic cough in primary, multidisciplinary, and cough-specialty care. Knowledge gaps in diagnostic testing, classical and neuromodulator pharmacotherapy, in addition to behavioral therapy of chronic cough were also analyzed. Outcomes: This third part of the WAO/ARIA consensus on chronic cough suggests a management algorithm of chronic cough in an integrated care pathway approach. Insights into the inherent limitations of multidisciplinary cough diagnostic testing, efficacy and safety of currently available antitussive pharmacotherapy, or the recently recognized behavioral therapy, can significantly improve the standards of care in patients with chronic cough.

Abstract. Rationale:. Soft tissue masses are common within the general population with a minority diagnosed as soft tissue neoplasms. Differing between benign and malignant soft tissue processes can be a challenge given the overlapping clinical and imaging characteristics. We present the case of a 69-year-old female referred to the Orthopaedic Oncology Service for evaluation of a suspected soft tissue sarcoma in the upper arm. Patient Concerns:. She reported a mass localized over the deltoid with associated tenderness 1 month after influenza vaccination. Diagnosis:. After thorough consideration of the patient's clinical course, history, advanced imaging, and physical examination, the diagnosis of injection granuloma associated with recent influenza vaccination was considered. Interventions:. Biopsy was deferred and close interval follow-up with clinical and imaging evaluation revealed a resolving process. Outcomes:. The patient was followed until complete resolution of all symptoms, which occurred 5 months after initial presentation. Lessons:. It was hypothesized that due the patient's body habitus, the injection contents intended for intramuscular administration remained in the subcutaneous tissues and elicited a granulomatous reaction. This case highlights several important factors for physicians to consider in the work up of suspicious masses for which injection granuloma is on the differential diagnosis.

The coronavirus disease 2019 (COVID-19) pandemic has prompted rapid restructuring of the health-care system in an effort to stop the spread of the virus and to treat patients who are acutely ill with COVID-19, while continuing to provide outpatient care for the remainder of patients. To help control spread of this pandemic, many centers, including total joint arthroplasty clinics, have boosted telemedicine capability to care for patients who would typically be seen in person in outpatient settings. We review key components relevant to the establishment and effective use of telemedicine, focused on patient education, practice logistics, technological considerations, and sensitive patient health information–associated compliance factors, which are necessary to provide care remotely for total joint arthroplasty patients.

Purpose: The dosimetric parameters used clinically to reduce the likelihood of radiation pneumonitis (RP) for lung cancer radiation therapy have traditionally been V20Gy ≤ 30% to 35% and mean lung dose ≤ 20 to 23 Gy; however, these parameters are derived based on studies from photon therapy. The purpose of this study is to evaluate whether such dosimetric predictors for RP are applicable for locally advanced non-small cell lung cancer (LA-NSCLC) patients treated with proton therapy. Methods and Materials: In the study, 160 (78 photon, 82 proton) patients with LA-NSCLC treated with chemoradiotherapy between 2011 and 2016 were retrospectively identified. Forty (20 photon, 20 proton) patients exhibited grade ≥2 RP after therapy. Dose volume histograms for the uninvolved lung were extracted for each patient. The percent lung volumes receiving above various dose levels were obtained in addition to V20Gy and Dmean. These dosimetric parameters and patient characteristics were evaluated with univariate and multivariate logistic regression tests. Receiver operating characteristic curves were generated to obtain the optimal dosimetric constraints through analyzing RP and non-RP sensitivity and specificity values. Results: The multivariate analysis showed V40Gy and Dmean to be statistically significant for proton and photon patients, respectively. V35Gy to V50Gy were strongly correlated to V40Gy for proton patients. Based on the receiver operating characteristic curves, V35Gy to V50Gy had the highest area under the curve compared with other dose levels for proton patients. A potential dosimetric constraint for RP predictor in proton patients is V40Gy ≤ 23%. Conclusions: In addition to V20Gy and Dmean, the lung volume receiving higher doses, such as V40Gy, may be used as an additional indicator for RP in LA-NSCLC patients treated with proton therapy.

The American Society for Surgery of the Hand (ASSH) was established in 1946. Since then, important advances have been made in the diagnosis and treatment of conditions affecting the upper extremity. However, there has been little documentation regarding how the largest and oldest society dedicated to hand surgery has evolved over time. Furthermore, an understanding of the history of the ASSH and the specialty of hand surgery should be emphasized in resident and fellow education. The authors aim to provide a historical overview of the ASSH through the speeches of ASSH past presidents that sheds light on future directions and long-term goals. Presidential addresses from 1961 to 2018 (courtesy of ASSH Chase Library historical archives) were reviewed. The overall percentage of ASSH presidents by specialty was 67% orthopedic, 25% plastic surgery, and 8% general surgery. The most common speech theme overall was how to be a good hand surgeon (31%). The most common speech themes were, by decade: the 1960s, history and the current state of ASSH; the 1970s and 1980s, assessments of how to be a good surgeon and goals for ASSH; the 1990s, health care and governmental regulation; the 2000s, how to be a better hand surgeon; and the 2010s goals for ASSH. In earlier years, there was more of a focus on education and technical skill development in the ASSH. Work–life balance, introduced in the 1990s, has become more of a focus in the past 20 years. Revisiting the history of the ASSH and its goals allows us to reflect on progress made while recognizing what is important as we look into the future. Furthermore, as we strive to make progress in the field of hand surgery during the current pandemic, valuable tools surface that will allow the specialty to strengthen its education, research, and patient care delivery in the future.

Purpose: Patients with large, high-grade soft tissue sarcomas are commonly treated with aggressive limb preservation regimens. This study aimed to assess cancer control outcomes of patients treated with neoadjuvant chemoradiation (CRT) compared with radiation therapy (RT) alone. Methods: We reviewed records of patients with high-grade extremity or trunk soft tissue sarcomas ≥5 cm who were treated with neoadjuvant radiation with or without chemotherapy. Patient and disease characteristics were compared using t test and χ2 tests. Standardized mortality ratio weighted method was used to compare overall survival (OS), local control, and disease-free (DFS) survival. Acute radiation and surgical toxicity were reported. Results: In the study, 64 patients (34 CRT and 30 RT) treated between 1997 and 2015 were analyzed. In the RT group compared with the CRT group, the patient population was older, with a median age of 65 versus 50 years (P < .001), and more likely to have cardiovascular disease (CVD; 30% vs 0%, P < .001). At a median follow-up of 41 months, after adjusting for propensity score of receiving RT, the 3-year LC was 87.3% versus 86.1%, DFS was 58.5% versus 56.6%, and OS was 75.6% versus 69.0% for the CRT and RT groups, respectively (P > .05). Acute dermatitis occurred in 18% versus 3% and surgical complications occurred in 32% versus 17% of CRT and RT patients, respectively. Conclusions: In this study, patients receiving RT alone were more likely to be older and have comorbid cardiovascular disease. When controlling for baseline differences, neoadjuvant CRT and RT provided similar rates of LC, DFS, and OS.

Bicuspid aortic valve with ascending aortic aneurysm is a common condition encountered in pregnancy. There are limited data on how to manage these patients. To our knowledge, we report the only case of a bicuspid aortic valve and aortic aneurysm with twin gestations. (Level of Difficulty: Intermediate.)

Background: Chronic cough can be triggered by respiratory and non-respiratory tract illnesses originating mainly from the upper and lower airways, and the GI tract (ie, reflux). Recent findings suggest it can also be a prominent feature in obstructive sleep apnea (OSA), laryngeal hyperresponsiveness, and COVID-19. The classification of chronic cough is constantly updated but lacks clear definition. Epidemiological data on the prevalence of chronic cough are informative but highly variable. The underlying mechanism of chronic cough is a neurogenic inflammation of the cough reflex which becomes hypersensitive, thus the term hypersensitive cough reflex (HCR). A current challenge is to decipher how various infectious and inflammatory airway diseases and esophageal reflux, among others, modulate HCR. Objectives: The World Allergy Organization/Allergic Rhinitis and its Impact on Asthma (WAO/ARIA) Joint Committee on Chronic Cough reviewed the current literature on classification, epidemiology, presenting features, and mechanistic pathways of chronic cough in airway- and reflux-related cough phenotypes, OSA, and COVID-19. The interplay of cough reflex sensitivity with other pathogenic mechanisms inherent to airway and reflux-related inflammatory conditions was also analyzed. Outcomes: Currently, it is difficult to clearly ascertain true prevalence rates in epidemiological studies of chronic cough phenotypes. This is likely due to lack of standardized objective measures needed for cough classification and frequent coexistence of multi-organ cough origins. Notwithstanding, we emphasize the important role of HCR as a mechanistic trigger in airway- and reflux-related cough phenotypes. Other concomitant mechanisms can also modulate HCR, including type2/Th1/Th2 inflammation, presence or absence of deep inspiration-bronchoprotective reflex (lower airways), tissue remodeling, and likely cough plasticity, among others.

Background: Cough features a complex peripheral and central neuronal network. The function of the chemosensitive and stretch (afferent) cough receptors is well described but partly understood. It is speculated that chronic cough reflects a neurogenic inflammation of the cough reflex, which becomes hypersensitive. This is mediated by neuromediators, cytokines, inflammatory cells, and a differential expression of neuronal (chemo/stretch) receptors, such as transient receptor potential (TRP) and purinergic P2X ion channels; yet the overall interaction of these mediators in neurogenic inflammation of cough pathways remains unclear. Objectives: The World Allergy Organization/Allergic Rhinitis and its Impact on Asthma (WAO/ARIA) Joint Committee on Chronic Cough reviewed the current literature on neuroanatomy and pathophysiology of chronic cough. The role of TRP ion channels in pathogenic mechanisms of the hypersensitive cough reflex was also examined. Outcomes: Chemoreceptors are better studied in cough neuronal pathways compared to stretch receptors, likely due to their anatomical overabundance in the respiratory tract, but also their distinctive functional properties. Central pathways are important in suppressive mechanisms and behavioral/affective aspects of chronic cough. Current evidence strongly suggests neurogenic inflammation induces a hypersensitive cough reflex marked by increased expression of neuromediators, mast cells, and eosinophils, among others. TRP ion channels, mainly TRP V1/A1, are important in the pathogenesis of chronic cough due to their role in mediating chemosensitivity to various endogenous and exogenous triggers, as well as a crosstalk between neurogenic and inflammatory pathways in cough-associated airways diseases.

OBJECTIVES:. Teleguidance facilitated intubation has recently reemerged during the coronavirus disease 2019 pandemic as a strategy to provide expert airway management guidance and consultation to practitioners in settings where such expertise is not readily available onsite or in-person. We conducted a scoping review to provide a synthesis of the available literature on teleguidance facilitated intubation. Specifically, we aimed to evaluate the feasibility, safety, and efficacy of teleguidance facilitated intubation given existing technology. DATA SOURCES:. A librarian-assisted search was performed using three primary electronic medical databases from January 2000 to November 2020. STUDY SELECTION:. Articles that reported outcomes focused on implementing or evaluating the performance of teleguidance facilitated intubation were included. DATA EXTRACTION:. Two reviewers independently screened titles, abstracts, and full text of articles to determine eligibility. Data extraction was performed using customized fields established a priori within a systematic review software system. DATA SYNTHESIS:. Of 255 citations identified, 17 met eligibility criteria. Studies included prospective investigations and proof of technology reports. These studies were performed in clinical and simulation environments. Five of the prospective investigations that examined time to intubation and intubation success rates. Multiple different commercially available and noncommercial teleconference software systems were used in these studies. CONCLUSIONS:. There is a limited body of literature evaluating the feasibility, safety, and efficacy of teleguidance facilitated intubation. Based on the studies available that examined a variety of technologies within simulation and clinical environments, teleguidance facilitated intubation appears to be feasible, safe, and efficacious. Given the exponential growth in the use of telemedicine technology during the coronavirus disease 2019 pandemic and the evidence supporting teleguidance facilitated intubation, there is a need to critically evaluate the most effective mechanisms to integrate and optimize these technologies across diverse practice settings.

IMPORTANCE:. A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 is hypothesized to play a role in the pathogenesis of invasive infection, but studies in sepsis are lacking. OBJECTIVES:. To study A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 protein level in pediatric sepsis and to study the association with outcome. DESIGN:. Data from two prospective cohort studies. SETTING AND PARTICIPANTS:. Cohort 1 is from a single-center study involving children admitted to PICU with meningococcal sepsis (samples obtained at three time points). Cohort 2 includes patients from a multicenter study involving children admitted to the hospital with invasive bacterial infections of differing etiologies (samples obtained within 48 hr after hospital admission). MAIN OUTCOMES AND MEASURES:. Primary outcome measure was mortality. Secondary outcome measures were PICU-free days at day 28 and hospital length of stay. RESULTS:. In cohort 1 (n = 59), nonsurvivors more frequently had A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels above the detection limit than survivors at admission to PICU (8/11 [73%] and 6/23 [26%], respectively; p = 0.02) and at t = 24 hours (2/3 [67%] and 3/37 [8%], respectively; p = 0.04). In cohort 2 (n = 240), A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels in patients within 48 hours after hospital admission were more frequently above the detection limit than in healthy controls (110/240 [46%] and 14/64 [22%], respectively; p = 0.001). Nonsurvivors more often had detectable A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels than survivors (16/21 [76%] and 94/219 [43%], respectively; p = 0.003), which was mostly attributable to patients with Neisseria meningitidis. CONCLUSIONS AND RELEVANCE:. In children with bacterial infection, detection of A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 within 48 hours after hospital admission is associated with death, particularly in meningococcal sepsis. Future studies should confirm the prognostic value of A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 and should study pathophysiologic mechanisms.

There is a wide time gap between the publication of evidence and the application of new knowledge into routine clinical practice. The consequence is sub-optimal outcomes, particularly concerning for long-term relapsing/remitting conditions such as allergic diseases. In response, there has been a proliferation of published guidelines which systematically review evidence for the gold-standard management of most allergic disorders. However, this has not necessarily been followed by improved outcomes, partly due to a lack of coordination across the patient pathway. This has become known as the ''second translational gap''. A proposed solution is the development and implementation of integrated care pathways (ICPs) to optimize patient outcomes, with the notion that evidence-based medicine requires evidence-based implementation. ICP implementation is shown to improve short-term outcomes for acute conditions and routine surgery, including reduced length of hospital stay, improved documentation and improved patient safety. However, this improvement is not reflected in patient experience or patient-centered functional outcomes. The implementation of life-long, cost-effective interventions within comprehensive pathways requires a deep appreciation for complexity within allergy care.We promote an evidence-based methodology for the implementation of ICPs for allergic disorders in which all stakeholders in allergy care are positioned equally and encouraged to contribute, particularly patients and their caregivers. This evidence-based process commences with scoping the unmet needs, followed by stakeholder mapping. All stakeholders are invited to meetings to develop a common vision and mission through the generation of action/effect diagrams which helps build concordance across the agencies. Dividing the interventions into achievable steps and reviewing with plan/do/study/act cycles will gradually modify the pathway to achieve the best outcomes. While the management guidelines provide the core knowledge, the key component of implementation involves education, training, and support of all healthcare professionals (HCPs), patients and their caregivers.The pathways should define the level of competence required for each clinical task. It may be useful to leave the setting of care delivery or the specific HCP involved undefined to account for variable patterns of health service delivery as well as local socioeconomic, ethnic, environmental, and political imperatives. In all cases, where competence is exceeded, it is necessary to refer to the next stage in the pathway. The success and sustainability of ICPs would ideally be judged by patient experience, health outcomes, and health economics. We provide examples of successful programs, most notably from Finland, but recommend that further research is required in diverse settings to optimize outcomes worldwide.

The increasing prevalence of allergic diseases has placed a significant burden on global healthcare and society as whole. This has necessitated a rapid development of “allergy” as a specialist area. However, as allergy is so common and, for most, relatively easy to diagnose and control, all clinicians need to have basic knowledge and competence to manage mild disease and recognize when referral is required. The allergology specialty has not yet been recognized in many countries and even where allergy is fully recognized as a specialty, the approach to training in allergy differs significantly.In the light of recent developments in allergy diagnosis and management, there is an urgent need to harmonize core competences for physicians, as well as the standardization of core principles for medical education and post-graduate training in allergy. All physicians and allied health professionals must appreciate the multidisciplinary team (MDT) approach to allergy, which is key to achieving the highest standards in holistic care. Due to worldwide variation in resources and personnel, some MDT roles will need to be absorbed by the treating physician or other healthcare professionals. We draw particular attention to the role of psychological input for all allergy patients, dietetic input in the case of food allergy and patient education to support all patients in the supported self-management of their condition on a daily basis. A strong appreciation of these multidisciplinary aspects will help physicians provide quality patient-centered care.We consider that harmonization of allergy components within undergraduate curricula is crucial to ensure all physicians develop the appropriate allergy-related knowledge and skills, particularly in light of inconsistencies seen in the primary care management of allergy. This review from the World Allergy Organization (WAO) Education and Training Committee also outlines allergy-related competences required of physicians working with allergic patients and provides recommendations to promote harmonization of allergy training and practice worldwide.