Common genetic susceptibility loci link PFAPA syndrome, Behçet's disease, and recurrent aphthous stomatitis.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in children. The disease appears to cluster in families, but the pathogenesis is unknown. We queried two European-American cohorts and one Turkish cohort (total n = 231) of individuals with PFAPA for common variants previously associated with two other oropharyngeal ulcerative disorders, Behçet's disease and recurrent aphthous stomatitis. In a metaanalysis, we found that a variant upstream of IL12A (rs17753641) is strongly associated with PFAPA (OR 2.13, P = 6 × 10-9). We demonstrated that monocytes from individuals who are heterozygous or homozygous for this risk allele produce significantly higher levels of IL-12p70 upon IFN-γ and LPS stimulation than those from individuals without the risk allele. We also found that variants near STAT4, IL10, and CCR1-CCR3 were significant susceptibility loci for PFAPA, suggesting that the pathogenesis of PFAPA involves abnormal antigen-presenting cell function and T cell activity and polarization, thereby implicating both innate and adaptive immune responses at the oropharyngeal mucosa. Our results illustrate genetic similarities among recurrent aphthous stomatitis, PFAPA, and Behçet's disease, placing these disorders on a common spectrum, with recurrent aphthous stomatitis on the mild end, Behçet's disease on the severe end, and PFAPA intermediate. We propose naming these disorders Behçet's spectrum disorders to highlight their relationship. HLA alleles may be factors that influence phenotypes along this spectrum as we found new class I and II HLA associations for PFAPA distinct from Behçet's disease and recurrent aphthous stomatitis.

Low Meningococcal Vaccination Rates Among Patients With Newly Diagnosed Complement Component Deficiencies in the United States.

Meningococcal vaccination is recommended for patients with complement component deficiencies (CDs) in the United States. In this retrospective database study, only 4.6% and 2.2% of patients received MenACWY and MenB vaccination, respectively, within 3 years of CD diagnosis. Thus, meningococcal vaccination rates among patients with CDs need to be improved.

Standardized Vaccine-Hesitant Patients in the Assessment of the Effectiveness of Vaccine Communication Training.

OBJECTIVES: To determine if training residents in a structured communication method elicits specific behaviors in a laboratory model of interaction with vaccine-hesitant parents. STUDY DESIGN: Standardized patients portraying vaccine-hesitant parents were used to assess the effectiveness of training in the Announce, Inquire, Mirror, Secure (AIMS) Method for Healthy Conversations. Blinded pediatric residents were pseudorandomized to receive AIMS or control training and underwent pre- and post-training encounters with blinded standardized patients. Encounters were assessed by blinded raters using a novel tool. Participant confidence and standardized patient evaluations of the participants' general communication skills were assessed. RESULTS: Ratings were available for 27 AIMS and 26 control participants. Statistically significant increases in post-training scores (maximum = 30) were detected in AIMS, but not in control, participants (median, 21.3 [IQR, 19.8-24.8] vs 18.8 [IQR, 16.9-20.9]; P < .001). Elements (maximum score = 6) with significant increases were Inquire (0.67 [IQR, 0-1.76] vs -0.33 [IQR, -0.67 to 0.33]; P < .001); Mirror (1.33 [IQR, 0 to 2] vs -0.33 [IQR, -0.92 to 0]; P < .001) and Secure (0.33 [IQR, 0 to 1.67] vs -0.17 [IQR, -0.67 to 0.33]; P = .017). Self-confidence increased equally in both groups. Standardized patients did not detect a difference in communication skills after training and between groups. Internal consistency and inter-rater reliability of the assessment tool were modest. CONCLUSIONS: Standardized patients proved useful in studying the effectiveness of structured communication training, but may have been limited in their ability to perceive a difference between groups owing to the predetermined encounter outcome of vaccine refusal. AIMS training should be studied in real-world scenarios to determine if it impacts vaccine acceptance.

Experts' opinion for improving global adolescent vaccination rates: a call to action.

Worldwide, lifestyle and resource disparities among adolescents contribute to unmet health needs, which have crucial present and future public health implications for both adolescents and broader communities. Risk of infection among adolescents is amplified by biological, behavioral, and environmental factors; however, infectious diseases to which adolescents are susceptible are often preventable with vaccines. Beyond these concerns, there is a lack of knowledge regarding adolescent vaccination and disease risk among parents and adolescents, which can contribute to low vaccine uptake. Promising efforts have been made to improve adolescent vaccination by programs with motivational drivers and comprehensive communication with the public. In May 2017, a multidisciplinary group of experts met in Amsterdam, Netherlands, to discuss adolescent vaccine uptake, as part of an educational initiative called the Advancing Adolescent Health Spring Forum. This article presents consensus opinions resulting from the meeting, which pertain to the burden of vaccine-preventable diseases among adolescents, reasons for low vaccine uptake, and common characteristics of successful strategies for improving adolescent vaccination.Conclusion: There is an urgent "call to action," particularly targeting healthcare providers and public health authorities, for the prioritization of adolescent vaccination as a necessary element of preventive healthcare in this age group.What is Known:• Despite increased risk of certain infectious diseases, adolescent vaccination uptake remains low.What is New:• Barriers to adolescent vaccine uptake include lack of information regarding vaccines and disease risk, health system inadequacies, and insufficient healthcare follow-up.• Successful efforts to improve adolescent vaccine uptake need cohesive leadership and involvement of multiple stakeholders, as well as youth-friendly messaging; healthcare providers and policymakers should prioritize adolescent vaccination and implement proven program strategies to improve adolescent health worldwide.

Functional outcomes after inpatient rehabilitation for trauma-improved but unable to return home.

BACKGROUND: Twenty-five percent of trauma patients are discharged to postacute care, indicating a loss of physical function and need for rehabilitation. The purpose of this study was to quantify the functional improvements in trauma patients discharged from inpatient rehabilitation facility (IRF) and identify predictors of improvement. MATERIALS AND METHODS: A retrospective cohort study of trauma patients aged ≥ 18 years were admitted to an IRF after discharge from a level-1 trauma center. Data included demographics, injury characteristics, hospital, and IRF course. The functional independence measure (FIM) was used to measure change in physical and cognitive function. RESULTS: There were 245 patients with a mean age of 55.8 years and mean injury severity score (ISS) of 14.7. Fall was the leading mechanism of injury (45.7%). On IRF admission, 50.7% of patients required moderate or greater assistance. On discharge, the mean intraindividual change in FIM score was 29.9; 85.4% of the patients improved by ≥1 level of functioning. Before injury, 99.6% of patients were living at home, but only 56.0% were discharged home from the IRF, despite 81.8% requiring minimal assistance at most (23.5% to skilled nursing; 19.7% readmitted). Increasing age and lower ISS were associated with less FIM improvement, and increasing ISS was associated with increased FIM improvement. CONCLUSIONS: More than 80% of the trauma patients experienced meaningful functional improvements during IRF admission. However, only half were discharged home, and a quarter required further institutional care. Further research is needed to identify the additional impediments to return to preinjury functioning.

Subway-Related Trauma: An Urban Public Health Issue with a High Case-Fatality Rate.

BACKGROUND: Between 1990 and 2003, there were 668 subway-related fatalities in New York City. However, subway-related trauma remains an understudied area of injury-related morbidity and mortality. OBJECTIVE: The objective of this study was to characterize the injuries and events leading up to the injuries of all patients admitted after subway-related trauma. METHODS: We conducted a retrospective case series of subway-related trauma at a Level I trauma center from 2001 to 2016. Descriptive epidemiology of patient demographics, incident details, injuries, and outcomes were analyzed. RESULTS: Over 15 years, 254 patients were admitted for subway-related trauma. The mean (standard error of the mean) age was 41 (1.0) years, 80% were male (95% confidence interval [CI] 74-84%) and median Injury Severity Score was 14 (interquartile range [IQR] 5-24). The overall case-fatality rate was 10% (95% CI 7-15%). The most common injuries were long-bone fractures, intracranial hemorrhage, and traumatic amputations. Median length of stay was 6 days (IQR 1-18 days). Thirty-seven percent of patients required surgical intervention. At the time of injury, 55% of patients (95% CI 49-61%) had a positive urine drug or alcohol screen, 16% (95% CI 12-21%) were attempting suicide, and 39% (95% CI 33-45%) had a history of psychiatric illness. CONCLUSIONS: Subway-related trauma is associated with a high case-fatality rate. Alcohol or drug intoxication and psychiatric illness can increase the risk of this type of injury.

The testicular transcriptome associated with spermatogonia differentiation initiated by gonadotrophin stimulation in the juvenile rhesus monkey (Macaca mulatta).

STUDY QUESTION: What is the genetic landscape within the testis of the juvenile rhesus monkey (Macaca mulatta) that underlies the decision of undifferentiated spermatogonia to commit to a pathway of differentiation when puberty is induced prematurely by exogenous LH and FSH stimulation? SUMMARY ANSWER: Forty-eight hours of gonadotrophin stimulation of the juvenile monkey testis resulted in the appearance of differentiating B spermatogonia and the emergence of 1362 up-regulated and 225 down-regulated testicular mRNAs encoding a complex network of proteins ranging from enzymes regulating Leydig cell steroidogenesis to membrane receptors, and from juxtacrine and paracrine factors to transcriptional factors governing spermatogonial stem cell fate. WHAT IS KNOWN ALREADY: Our understanding of the cell and molecular biology underlying the fate of undifferentiated spermatogonia is based largely on studies of rodents, particularly of mice, but in the case of primates very little is known. The present study represents the first attempt to comprehensively address this question in a highly evolved primate. STUDY DESIGN, SIZE, DURATION: Global gene expression in the testis from juvenile rhesus monkeys that had been stimulated with recombinant monkey LH and FSH for 48 h (N = 3) or 96 h (N = 4) was compared to that from vehicle treated animals (N = 3). Testicular cell types and testosterone secretion were also monitored. PARTICIPANTS/MATERIALS, SETTING, METHODS: Precocious testicular puberty was initiated in juvenile rhesus monkeys, 14-24 months of age, using a physiologic mode of intermittent stimulation with i.v. recombinant monkey LH and FSH that within 48 h produced 'adult' levels of circulating LH, FSH and testosterone. Mitotic activity was monitored by immunohistochemical assays of 5-bromo-2'-deoxyuridine and 5-ethynyl-2'-deoxyuridine incorporation. Animals were bilaterally castrated and RNA was extracted from the right testis. Global gene expression was determined using RNA-Seq. Differentially expressed genes (DEGs) were identified and evaluated by pathway analysis. mRNAs of particular interest were also quantitated using quantitative RT-PCR. Fractions of the left testis were used for histochemistry or immunoflouresence. MAIN RESULTS AND THE ROLE OF CHANCE: Differentiating type B spematogonia were observed after both 48 and 96 h of gonadotrophin stimulation. Pathway analysis identified five super categories of over-represented DEGs. Repression of GFRA1 (glial cell line-derived neurotrophic factor family receptor alpha 1) and NANOS2 (nanos C2HC-type zinc finger 2) that favor spermatogonial stem cell renewal was noted after 48 and 96 h of LH and FSH stimulation. Additionally, changes in expression of numerous genes involved in regulating the Notch pathway, cell adhesion, structural plasticity and modulating the immune system were observed. Induction of genes associated with the differentiation of spermatogonia stem cells (SOHLH1(spermatogenesis- and oogenesis-specific basic helix-loop-helix 1), SOHLH2 and KIT (V-Kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog)) was not observed. Expression of the gene encoding STRA8 (stimulated by retinoic acid 8), a protein generally considered to mark activation of retinoic acid signaling, was below our limit of detection. LARGE SCALE DATA: The entire mRNA data set for vehicle and gonadotrophin treated animals (N = 10) has been deposited in the GEO-NCBI repository (GSE97786). LIMITATIONS REASONS FOR CAUTION: The limited number of monkeys per group and the dilution of low abundance germ cell transcripts by mRNAs contributed from somatic cells likely resulted in an underestimation of the number of differentially expressed germ cell genes. WIDER IMPLICATIONS OF THE FINDINGS: The findings that expression of GDNF (a major promoter of spermatogonial stem cell renewal) was not detected in the control juvenile testes, expression of SOHLH1, SOHLH2 and KIT, promoters of spermatogonial differentiation in mice, were not up-regulated in association with the gonadotrophin-induced generation of differentiating spermatogonia, and that robust activation of the retinoic acid signaling pathway was not observed, could not have been predicted. These unexpected results underline the importance of non-human primate models in translating data derived from animal research to the human situation. STUDY FUNDING/COMPETING INTEREST(S): The work described was funded by NIH grant R01 HD072189 to T.M.P. P.A. was supported by an Endocrine Society Summer Research Fellowship Award and CONICET (Argentine Research Council), S.N. by a grant from Vali-e-Asr Reproductive Health Research Center of Tehran University of Medical Sciences (grant #24335-39-92) to Dr Batool Hosseini Rashidi, and M.P.H. by grants from the National Health and Medical Research Council of Australia, and the Victorian State Government's Operational Infrastructure Support Program. The authors have nothing to disclose.

Spermatogonial SOHLH1 nucleocytoplasmic shuttling associates with initiation of spermatogenesis in the rhesus monkey (Macaca mulatta).

As the spermatogenesis- and oogenesis-specific basic helix-loop-helix 1 (SOHLH1) transcription factor has been shown to be essential for spermatogonial differentiation in mice, we examined the immunoexpression of this protein in the testis of the rhesus monkey (Macaca mulatta) during puberty, the stage of development when spermatogonial differentiation is initiated in higher primates. Immunopositive SOHLH1 cells were observed only on the basement membrane of the seminiferous cords and tubules. Prior to puberty, essentially 100% of SOHLH1-positive spermatogonia co-expressed the glial cell line-derived neurotrophic factor family receptor alpha 1 (GFRα1), a marker for undifferentiated spermatogonia, and >80% of the immunopositive SOHLH1 cells exhibited only cytoplasmic staining of this transcription factor. Nuclear-only SOHLH1 was found in <10% of spermatogonia in testes from pre-pubertal animals. Puberty was associated with a dramatic and progressive increase in the percentage of immunopositive SOHLH1 cells with nuclear-only staining, and this was associated with (i) a marked reduction in the fraction (∼100-20%) of SOHLH1-positive germ cells co-expressing GFRα1 and (ii) a significant increase in the proportion of SOHLH1-positive spermatogonia that co-expressed the tyrosine kinase receptor (cKIT). Spermatogonia exhibiting nuclear SOHLH1 staining were found to be cKIT positive, but not all cKIT-positive spermatogonia exhibited nuclear SOHLH1 staining. Taken together, these results suggest that, in the monkey, nuclear location of SOHLH1 is closely associated with spermatogonial differentiation.

United States Physicians' Knowledge, Attitudes, and Practices Regarding Meningococcal Vaccination for Healthy Adolescents and Young Adults.

PURPOSE: The United States Advisory Committee on Immunization Practices (ACIP) recommends vaccination against meningococcal serogroups A, C, W, and Y (MenACWY) for all 11-12-year-olds, with a booster dose for 16-year-olds, and against meningococcal serogroup B (MenB) for 16-23-year-olds under shared clinical decision-making (SCDM). However, uptake of the MenB vaccine and the MenACWY booster dose is low. This study investigated United States physicians' knowledge, attitudes, and practices regarding recommending MenB and MenACWY vaccines to non-high-risk older adolescents and young adults. METHODS: An online survey was conducted in April-May 2022 among pediatricians, family physicians (FPs), general practitioners (GPs), and internists who had recommended the MenB and/or the MenACWY vaccine(s) to at least one 16-23-year-old in the past year. RESULTS: Among 407 participants, 50% correctly identified MenB as the leading cause of meningococcal disease among adolescents and young adults. Furthermore, 46% of physicians (47% of pediatricians, 40% of FPs and GPs, 53% of internists) answered correctly that MenB vaccination is recommended under SCDM, and 82% of physicians (96% of pediatricians, 70% of FPs and GPs, 65% of internists) answered correctly that MenACWY vaccination is routinely recommended. Among MenB-vaccinators, 78% reported having received some training or other information on implementing SCDM, and 65% rated recommending MenB vaccination as very important. DISCUSSION: Knowledge gaps, which varied by specialty, were identified regarding meningococcal disease and vaccine recommendations, particularly regarding MenB. Targeted education of physicians may facilitate discussions about MenB vaccination.

A joinpoint analysis examining trends in firearm injuries at six us trauma centers from 2016 to 2022.

BACKGROUND: There is an epidemic of firearm injuries in the United States since the mid-2000s. Thus, we sought to examine whether hospitalization from firearm injuries have increased over time, and to examine temporal changes in patient demographics, firearm injury intent, and injury severity. METHODS: This was a multicenter, retrospective, observational cohort study of patients hospitalized with a traumatic injury to six US level I trauma centers between 1/1/2016 and 6/30/2022. ICD-10-CM cause codes were used to identify and describe firearm injuries. Temporal trends were compared for demographics (age, sex, race, insured status), intent (assault, unintentional, self-harm, legal intervention, and undetermined), and severity (death, ICU admission, severe injury (injury severity score ≥ 16), receipt of blood transfusion, mechanical ventilation, and hospital and ICU LOS (days). Temporal trends were examined over 13 six-month intervals (H1, January-June; H2, July-December) using joinpoint regression and reported as semi-annual percent change (SPC); significance was p < 0.05. RESULTS: Firearm injuries accounted for 2.6% (1908 of 72,474) of trauma hospitalizations. The rate of firearm injuries initially declined from 2016-H1 to 2018-H2 (SPC = - 4.0%, p = 0.002), followed by increased rates from 2018-H2 to 2020-H1 (SPC = 9.0%, p = 0.005), before stabilizing from 2020-H1 to 2022-H1 (0.5%, p = 0.73). NH black patients had the greatest hospitalization rate from firearm injuries (14.0%) and were the only group to demonstrate a temporal increase (SPC = 6.3%, p < 0.001). The proportion of uninsured patients increased (SPC = 2.3%, p = 0.02) but there were no temporal changes by age or sex. ICU admission rates declined (SPC = - 2.2%, p < 0.001), but ICU LOS increased (SPC = 2.8%, p = 0.04). There were no significant changes over time in rates of death (SPC = 0.3%), severe injury (SPC = 1.6%), blood transfusion (SPC = 0.6%), and mechanical ventilation (SPC = 0.6%). When examined by intent, self-harm injuries declined over time (SPC = - 4.1%, p < 0.001), assaults declined through 2019-H2 (SPC = - 5.6%, p = 0.01) before increasing through 2022-H1 (SPC = 6.5%, p = 0.01), while undetermined injuries increased through 2019-H1 (SPC = 24.1%, p = 0.01) then stabilized (SPC = - 4.5%, p = 0.39); there were no temporal changes in unintentional injuries or legal intervention. CONCLUSIONS: Hospitalizations from firearm injuries are increasing following a period of declines, driven by increases among NH Black patients. Trauma systems need to consider these changing trends to best address the needs of the injured population.

A western trauma association multicenter comparison of mesh versus non-mesh repair of blunt traumatic abdominal wall hernias.

BACKGROUND: Blunt traumatic abdominal wall hernias (TAWH) occur in <1 % of trauma patients. Optimal repair techniques, such as mesh reinforcement, have not been studied in detail. We hypothesize that mesh use will be associated with increased surgical site infections (SSI) and not improve hernia recurrence. MATERIALS AND METHODS: A secondary analysis of the Western Trauma Association blunt TAWH multicenter study was performed. Patients who underwent TAWH repair during initial hospitalization (1/2012-12/2018) were included. Mesh repair patients were compared to primary repair patients (non-mesh). A logistic regression was conducted to assess risk factors for SSI. RESULTS: 157 patients underwent TAWH repair during index hospitalization with 51 (32.5 %) having mesh repair: 24 (45.3 %) synthetic and 29 (54.7 %) biologic. Mesh patients were more commonly smokers (43.1 % vs. 22.9 %, p = 0.016) and had a larger defect size (10 vs. 6 cm, p = 0.003). Mesh patients had a higher rate of SSI (25.5 % vs. 9.5 %, p = 0.016) compared to non-mesh patients, but a similar rate of recurrence (13.7 % vs. 10.5%, p = 0.742), hospital length of stay (LOS), and mortality. Mesh use (OR 3.66) and higher ISS (OR 1.06) were significant risk factors for SSI in a multivariable model. CONCLUSION: Mesh was used more frequently in flank TAWH and those with a larger defect size. Mesh use was associated with a higher incidence and risk of SSI but did not reduce the risk of hernia recurrence. When repairing TAWH mesh should be employed judiciously, and prospective randomized studies are needed to identify clear indications for mesh use in TAWH.

Bone Anchor Fixation in the Repair of Blunt Traumatic Abdominal Wall Hernias: A Western Trauma Association Multicenter Study.

BACKGROUND: Blunt traumatic abdominal wall hernias (TAWHs) are rare but require a variety of operative techniques to repair including bone anchor fixation (BAF) when tissue tears off bony structures. This study aimed to provide a descriptive analysis of BAF technique for blunt TAWH repair. Bone anchor fixation and no BAF repairs were compared, hypothesizing increased hernia recurrence with BAF repair. METHODS: A secondary analysis of the WTA blunt TAWH multicenter study was performed including all patients who underwent repair of their TAWH. Patients with BAF were compared to those with no BAF with bivariate analyses. RESULTS: 176 patients underwent repair of their TAWH with 41 (23.3%) undergoing BAF. 26 (63.4%) patients had tissue fixed to bone, with 7 of those reinforced with mesh. The remaining 15 (36.6%) patients had bridging mesh anchored to bone. The BAF group had a similar age, sex, body mass index, and injury severity score compared to the no BAF group. The time to repair (1 vs 1 days, P = .158), rate of hernia recurrence (9.8% vs 12.7%, P = .786), and surgical site infection (SSI) (12.5% vs 15.6%, P = .823) were all similar between cohorts. CONCLUSIONS: This largest series to date found nearly one-quarter of TAWH repairs required BAF. Bone anchor fixation repairs had a similar rate of hernia recurrence and SSI compared to no BAF repairs, suggesting this is a reasonable option for repair of TAWH. However, future prospective studies are needed to compare specific BAF techniques and evaluate long-term outcomes including patient-centered outcomes such as pain and quality of life.

Expert Perspectives on the Vaccination of Individuals Who Are at Increased Risk of Meningococcal Disease Due to Medical Conditions: A Podcast.

Patients with functional or anatomic asplenia, including sickle cell anemia; complement component deficiency; or human immunodeficiency virus (HIV) infection have a significantly increased risk of developing meningococcal disease. The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) recommends vaccination with a quadrivalent meningococcal conjugate vaccine against serogroups A, C, W, and Y (MenACWY) for individuals 2 months of age or older who are diagnosed with functional or anatomic asplenia, complement component deficiency, or HIV infection. Vaccination with a meningococcal vaccine against serogroup B (MenB) is also recommended for individuals 10 years of age or older who are diagnosed with functional or anatomic asplenia or complement component deficiency. Despite these recommendations, recent studies have shown that vaccination coverage in these populations is low. In this podcast, the authors discuss the challenges for implementing vaccine recommendations for individuals with medical conditions at increased risk of developing meningococcal disease and discuss strategies to increase coverage. Suboptimal vaccination rates could be addressed by better educating healthcare providers about recommendations for MenACWY and MenB vaccines in individuals at increased risk, increasing awareness of low vaccination coverage, and tailoring the education to the needs of particular healthcare providers and their respective patient populations. Barriers to vaccination could also be removed by administering vaccines at alternative sites of care, bundling preventative services, and implementing vaccination reminder systems that are tied to immunization information systems.

Invasive meningococcal disease is rare, but serious. Some people are at increased risk because of their medical conditions, including: People without a working spleen People with reduced immune function due to conditions known as complement component deficiencies People living with human immunodeficiency virus (HIV) infection Vaccines are available to prevent meningococcal disease, and these vaccines are recommended for healthy young people as well as for people at increased risk. Studies have shown that a low proportion of people at increased risk has been vaccinated. Strategies are needed to make sure more people in these groups get vaccinated. We suggest educating healthcare providers about the recommended vaccines and making it easier for people to get vaccinated by, for example, providing vaccines in places they might visit more often than a doctor's office.

The effect of restrictive fluid management on outcomes among geriatric hip fractures: a retrospective cohort study at five level I trauma centers.

Restrictive fluid management (RFM) for hemodynamically unstable trauma patients has reduced mortality rates. The objective was to determine whether RFM benefits geriatric hip fracture patients, who are usually hemodynamically stable. Design: Retrospective propensity-matched study. Setting: Five Level I trauma centers (January 1, 2018-December 12, 2018). Patients: Geriatric patients (65 years or older) with hip fractures were included in this study. Patients with multiple injuries, nonoperative management, and preoperative blood products were excluded. Intervention: Patients were grouped by fluid volume (normal saline, lactated Ringer, dextrose, electrolytes, and medications) received preoperatively or ≤24 hours of arrival; patients with standard fluid management (SFM) received ≥150 mL and RFM <150 mL of fluids. Main Outcome Measurements: The primary outcomes were length of stay (LOS), delayed ambulation (>2 days postoperatively), and mortality. Paired Student t-tests, Wilcoxon paired rank sum tests, and McNemar tests were used; an α value of < 0.05 was considered statistically significant. Results: There were 523 patients (40% RFM, 60% SFM); after matching, there were 95 patients per arm. The matched patients were well-balanced, including no difference in time from arrival to surgery. RFM and SFM patients received a median of 80 mL and 1250 mL of preoperative fluids, respectively (P < 0.001). Postoperative fluid volumes were 1550 versus 2000 mL, respectively, (P = 0.73), and LOSs were similar between the two groups (5 versus 5 days, P = 0.83). Mortality and complications, including acute kidney injuries, were similar. Delayed ambulation rates were similar overall. When stratified by preinjury ambulation status, SFM was associated with delayed ambulation for patients not walking independently before injury (P = 0.01), but RFM was not (P = 0.09). Conclusions: RFM seems to be safe in terms of laboratory results, complications, and disposition. SFM may lead to delayed ambulation for patients who are not walking independently before injury.

A comprehensive review of clinical and real-world safety data for the four-component serogroup B meningococcal vaccine (4CMenB).

INTRODUCTION: Neisseria meningitidis causes invasive meningococcal disease and, globally, significant morbidity, with serogroup B (MenB) being the most common cause of endemic disease and outbreaks in several regions. Extensive use of the four-component serogroup B meningococcal vaccine (4CMenB; Bexsero, GSK) and its inclusion in immunization programs in several countries have generated substantial safety data during the 9 years since its first authorization in 2013. AREAS COVERED: 4CMenB safety data from clinical trials and post-marketing surveillance studies (2011 to 2022), and spontaneously reported adverse events of medical interest from the GSK global safety database. We discuss these safety findings in relation to the benefit of 4CMenB vaccination and implications for further enhancing vaccine confidence. EXPERT OPINION: 4CMenB has been consistently well tolerated across clinical trials and post-licensure surveillance studies, despite a higher incidence of fever reported in infants than with other pediatric vaccines. Surveillance data have not identified any significant safety issues, consistent with an acceptable safety profile of 4CMenB. These findings highlight the need to balance the risk of relatively common, transient, post-immunization fever with the benefit of affording protection that reduces the risk of uncommon but potentially fatal meningococcal infection.

The four-component serogroup B meningococcal vaccine 4CMenB (Bexsero®, GSK) was licensed in 2013 and has acquired substantial safety evidence through clinical trial and real-world data. Availability of real-world and clinical 4CMenB safety evidence is important to help address vaccination hesitancy. This comprehensive review of safety data, from 9 years of 4CMenB use including recent data from the real world, shows no significant safety issues in a variety of age groups. Data show that transient fever may occur after vaccination. Invasive meningococcal disease, although rare, can be life-threatening. Abundant safety data from this review can help reassure individuals and healthcare providers on the use of 4CMenB.

Clinical Features and Follow-up of Referred Children and Young People With Long COVID.

BACKGROUND: Patient-level data on the clinical features and outcomes of children and young people referred for possible long coronavirus disease (COVID) can guide clinicians on what to expect in managing patients and advising families. METHODS: A Post-Acute COVID Clinic for persons <21 years of age was established in October 2020. Intake was standardized and management was tailored to presenting symptoms. Data were abstracted from the charts of all patients evaluated through December 2021, and the study cohort consisted of patients who had a history of confirmed severe acute respiratory syndrome coronavirus 2 infection, had ≥1 symptom persisting for ≥12 weeks and had no pre-existing diagnosis that explained the symptoms. A structured follow-up interview was conducted in early 2022. RESULTS: A total of 104 patients were referred, 81 of whom met inclusion criteria. The median age was 14 years (interquartile range, 13-16), and most were female, White/Caucasian and had commercial health insurance. Patients reported previously good health but over half reported moderate-to-severe disability at their first visit. Two clusters of presenting symptoms-fatigue with multiple symptoms, and fatigue and headache with cardiopulmonary symptoms-were identified. Extensive routine testing did not affirm alternative diagnoses. Incident conditions-most commonly anxiety, depression and/or panic disorder; migraines; and autonomic dysfunction-were diagnosed on clinical grounds. Telephone interviews (N = 55) revealed that 78% of patients were improved by about 6 months. CONCLUSIONS: Within the limits of a single-center, referral-based, observational cohort, this study provides reassurance to patients and parents in that most cases of long COVID were self-limited. Extensive evaluations may be more useful in ruling out alternative diagnoses than in affirming specific physiologic disturbances.

Risk factors for recurrence in blunt traumatic abdominal wall hernias: A secondary analysis of a Western Trauma association multicenter study.

BACKGROUND: Few studies have investigated risk factors for recurrence of blunt traumatic abdominal wall hernias (TAWH). METHODS: Twenty trauma centers identified repaired TAWH from January 2012 to December 2018. Logistic regression was used to investigate risk factors for recurrence. RESULTS: TAWH were repaired in 175 patients with 21 (12.0%) known recurrences. No difference was found in location, defect size, or median time to repair between the recurrence and non-recurrence groups. Mesh use was not protective of recurrence. Female sex, injury severity score (ISS), emergency laparotomy (EL), and bowel resection were associated with hernia recurrence. Bowel resection remained significant in a multivariable model. CONCLUSION: Female sex, ISS, EL, and bowel resection were identified as risk factors for hernia recurrence. Mesh use and time to repair were not associated with recurrence. Surgeons should be mindful of these risk factors but could attempt acute repair in the setting of appropriate physiologic parameters.

Rationale for the Development of a Pentavalent Meningococcal Vaccine: A US-Focused Review.

While invasive meningococcal disease (IMD) is uncommon, it can result in serious sequelae and even death. In 2018 in the United States, the incidence of IMD per 100,000 people was 0.03 among adolescents 11-15 years of age, 0.10 among persons 16-23 years of age, and 0.83 among infants < 1 year of age. Serogroup B accounted for 86%, 62%, and 66% of cases, respectively, in those age groups. Currently, routine meningococcal vaccination covering serogroups ACWY (MenACWY) is recommended in the United States for all adolescents at 11-12 years of age, with a booster dose at 16 years of age, whereas a meningococcal serogroup B (MenB) vaccine series is recommended for persons 16-23 years of age under the shared clinical decision-making paradigm. The MenACWY vaccination program in adolescents has been successful in reducing disease burden, but does not prevent disease caused by serogroup B, which accounts for more than half of IMD cases. There are currently no approved vaccines that cover all of the most common disease-causing meningococcal serogroups, which are A, B, C, W, and Y. A pentavalent MenABCWY vaccine that is constituted from 2 licensed meningococcal vaccines-MenB-FHbp and MenACWY-TT-is being investigated in healthy persons ≥ 10-25 years of age. The addition of a MenABCWY vaccine is the next natural step in the incremental meningococcal immunization program in the United States to improve protection against the most common serogroup causing IMD, with no increase in the number of immunizations needed. With high uptake, routine use of MenABCWY could reduce IMD cases and associated mortality, the rate of long-term physical and psychosocial sequelae in survivors, and costs associated with controlling outbreaks, particularly on college campuses. A MenABCWY vaccine would also reduce the number of injections required for adolescents, potentially improving compliance.