Systematic Review of Gender and Sex Terminology Use in Arthroplasty Research: There is Room for Improvement.

BACKGROUND: There is increasing appreciation of the distinction between gender and sex as well as the importance of accurately reporting these constructs. Given recent attention regarding transgender and gender nonconforming (TGNC) and intersex identities, it is more necessary than ever to understand how to describe these identities in research. This study sought to investigate the use of gender- and sex-based terminology in arthroplasty research. METHODS: The five leading orthopaedic journals publishing arthroplasty research were reviewed to identify the first twenty primary clinical research articles on an arthroplasty topic published after January 1, 2022. Use of gender- or sex-based terminology, whether use was discriminate, and whether stratification or adjustment based on gender or sex was performed, were recorded. RESULTS: There were 98 of 100 articles that measured a construct of gender or sex. Of these, 15 articles used gender-based terminology, 45 used sex-based terminology, and 38 used a combination of gender- and sex-based terminology. Of the 38 articles using a combination of terminology, none did so discriminately. All articles presented gender and sex as binary variables, and two attempted to explicitly define how gender or sex were defined. Of the 98 articles, 31 used these variables for statistical adjustments, though only six reported stratified results. CONCLUSIONS: Arthroplasty articles infrequently describe how gender or sex was measured, and frequently use this terminology interchangeably. Additionally, these articles rarely offer more than two options for capturing variation in sex and gender. Future research should be more precise in the treatment of these variables to improve the quality of results and ensure findings are patient-centered and inclusive.

Impact of age at ivacaftor initiation on pulmonary outcomes among people with cystic fibrosis.

BACKGROUND: Ivacaftor (IVA) improves lung function and other extrapulmonary outcomes in people with cystic fibrosis (CF). However, the effect of initiating IVA at earlier versus later ages has not been studied. METHODS: We conducted an observational cohort study of people in the US CF Foundation Patient Registry aged ≥6 years with ≥1 CF transmembrane conductance regulator-gating mutation to compare the effects of initiating IVA at earlier ages on per cent predicted forced expiratory volume in 1 s (ppFEV1) and pulmonary exacerbation (PEx) outcomes. People with CF were grouped by age at IVA initiation (ages 6-10, 11-15, 16-20 and 21-25 years) to perform three analyses of younger versus older IVA initiation (6-10 vs 11-15, 11-15 vs 16-20 and 16-20 vs 21-25 years). For each analysis, baseline characteristics assessed over 1-year periods at the same age prior to IVA initiation were balanced by standardised mortality/morbidity ratio (SMR) weighting. For each analysis, outcomes were compared over a 5-year outcome assessment period when both groups were in the same age range and receiving IVA. FINDINGS: Baseline characteristics were well balanced between younger and older IVA initiator groups after SMR weighting. In the outcome assessment period, younger IVA initiators had significantly higher mean ppFEV1 than older initiators across all comparisons, and those initiating IVA between ages 6-10 and 11-15 years had significantly lower PEx rates. INTERPRETATION: Study findings showed the importance of early IVA initiation in people with CF.

Comparative Anatomic Analysis of Neuronavigated Transmastoid-Infralabyrinthine Approaches for Jugular Fossa Pathologies: Short Anterior Rerouting Versus Nonrerouting and Tailored Nonrerouting Techniques.

BACKGROUND AND OBJECTIVES: Access to the jugular fossa pathologies (JFPs) via the transmastoid infralabyrinthine approach (TI-A) using the nonrerouting technique (removing the bone anterior and posterior to the facial nerve while leaving the nerve protected within the fallopian canal) or with the short-rerouting technique (rerouting the mastoid segment of the facial nerve anteriorly) has been described in previous studies. The objective of this study is to compare the access to Fisch class C lesions (JFPs extending or destroying the infralabyrinthine and apical compartment of the temporal bone with or without involving the carotid canal) between the nonrerouting and the short-rerouting techniques. Also, some tailored steps to the nonrerouting technique (NR-T) were outlined to enhance access to the jugular fossa (JF) as an alternative to the short-rerouting technique. METHODS: Neuronavigated TI-A was performed using the nonrerouting, tailored nonrerouting, and short-rerouting techniques on both sides of 10 human head specimens. Exposed area, horizontal distance, surgical freedom, and horizontal angle were calculated using vector coordinates for nonrerouting and short-rerouting techniques. RESULTS: The short-rerouting technique had significantly higher values than the NR-T ( P < .01) for the exposed area (169.1 ± SD 11.5 mm 2 vs 151.0 ± SD 12.4 mm 2 ), horizontal distance (15.9 ± SD 0.6 mm vs 10.6 ± SD 0.5 mm 2 ), surgical freedom (19 650.2 ± SD 722.5 mm 2 vs 17 233.8 ± SD 631.7 mm 2 ), and horizontal angle (75.2 ± SD 5.1° vs 61.7 ± SD 4.6°). However, adding some tailored steps to the NR-T permitted comparable access to the JF. CONCLUSION: Neuronavigated TI-A with the short-rerouting technique permits wider access to the JF compared with the NR-T. However, the tailored NR-T provides comparable access to the JF and may be a better option for class C1 and selected class C2 and C3 JFPs.

BREAST-Q REACT: Qualitative Assessment of the Design, Functionality, and Clinical Utility of a New Score Interpretation Tool.

BACKGROUND: The BREAST-Q real-time engagement and communication tool (REACT) was developed to aid with BREAST-Q score interpretation and guide patient-centered care. OBJECTIVE: The purpose of this qualitative study was to examine the perspectives of patients and providers on the design, functionality, and clinical utility of REACT and refine the REACT based on their recommendations. METHODS: We conducted three patient focus groups with women who were at least 6 postoperative months from their postmastectomy breast reconstruction, and two provider focus groups with plastic surgeons, breast surgeons, and advanced practice providers. Focus groups were audio-taped, transcribed verbatim, and analyzed thematically. RESULTS: A total of 18 breast reconstruction patients and 14 providers participated in the focus groups. Themes identified by thematic analysis were organized into two categories: (1) design and functionality, and (2) clinical utility. On the design and functionality of REACT, four major themes were identified: visual appeal and usefulness; contextualizing results; ability to normalize patients' experiences, noting participants' concerns; and suggested modifications. On the clinical utility of REACT, three major themes were identified: potential to empower patients to communicate with their providers; increase patient and provider motivation to engage with the BREAST-Q; and effective integration into clinical workflow. CONCLUSION: Patients and providers in this qualitative study indicated that with some modifications, REACT has a great potential to elevate the clinical utility of the BREAST-Q by enhancing patient-provider communication that can lead to patient-centered, clinically relevant action recommendations based on longitudinal BREAST-Q scores.

When Is Telemedicine Appropriate in the Management of Head and Neck Cancer? A Mixed-Methods Assessment Among Patients and Physicians.

PURPOSE: Evidence suggests that oncology patients are satisfied with and sometimes prefer telemedicine compared with in-person visits; however, data are scarce on when telemedicine is appropriate for specific cancer populations. In this study, we aim to identify factors that influence patient experience and appropriateness of telemedicine use among a head and neck cancer (HNC) population. METHODS: We performed a mixed-methods study at a multisite cancer center. First, we surveyed patients with HNC and analyzed factors that may influence their telemedicine experience using multivariate regression. We then conducted focus groups among HNC oncologists (n = 15) to evaluate their perception on appropriate use of telemedicine. RESULTS: From January to December 2020, we collected 1,071 completed surveys (response rate 24%), of which 551 first unique surveys were analyzed. About half of all patients (56%) reported telemedicine as "same or better" compared with in-person visits, whereas the other half (44%) reported "not as good or unsure." In multivariate analyses, patients with thyroid cancer were more likely to find telemedicine "same or better" (adjusted odds ratio, 2.08 [95% CI, 1.35 to 3.25]) compared with other HNC populations (mucosal/salivary HNC). Consistently, physician focus group noted that patients with thyroid cancer were particularly suited for telemedicine because of less emphasis on in-person examinations. Physicians also underscored factors that influence telemedicine use, including clinical suitability (treatment status, visit purpose, examination necessity), patient benefits (travel time, access), and barriers (technology, rapport-building). CONCLUSION: Patient experience with telemedicine is diverse among the HNC population. Notably, patients with thyroid cancer had overall better experience and were identified to be more appropriate for telemedicine compared with other patients with HNC. Future research that optimizes patient experience and selection is needed to ensure successful integration of telemedicine into routine oncology practice.

Enteric Dysbiosis in Children With Autism Spectrum Disorder and Associated Response to Stress.

Background Microbiome studies in humans, though limited, have facilitated the evaluation of the potential connection between the microbiome and brain function. Children with autism spectrum disorder (ASD) have several behavioral challenges and avoidant/restrictive food intake disorder, which may contribute to gut microbiome dysbiosis. Aim The aim of this study is to examine the extent to which the gut microbiome of children with ASD differs in comparison to children with neurotypical development (CWND) and to assess whether a probiotic intervention has the potential to influence the gut microbiome in mediating positive behavior change and stress regulation. Methods This pilot study collected data from three children with ASD and four CWND before and after a four-week probiotic intervention. Data collection included microbiome diversity screening from stool samples as well as the following biophysiological measures: salivary alpha-amylase (sAA) levels, response to simulated stressor and calming stimulus (behavior), including pulse rate, galvanic skin response, and pupil diameter (PD). In addition, telomere length was assessed. All measures, except for telomere length, were repeated after the four-week intervention on the ASD and CWND groups for pre-/post-comparison. Data analysis consisted of multivariate analyses, including ANOVA. Results While greater heterogeneity in the ASD group was evident in all measures, the gut microbiome of participants who received probiotic intervention differed from pretreatment results within and across the groups investigated. Further, the biophysiological parameter sAA displayed a significant increase between baseline and exposure to stress in both groups, whereas PD increased in both groups from baseline, F(11, 26615) = 123.43, p = 0.00. Conclusion Though gut microbiome diversity is diminished in children with ASD compared to CWND, the gap is narrowed following a brief probiotic intervention. The results suggest that probiotic interventions have the potential to rescue microbiome diversity and abundance, potentially supporting stress regulation in pediatric populations.

A role for TMEM63 in the lung.

Surfactants are essential for breathing. Although major progress has been made in the past half century toward an understanding of surfactant secretion mechanisms, the identity of the mechanosensor that couples breathing to surfactant secretion has remained elusive. In this issue of the JCI, Chen, Li, and colleagues provide evidence that the mechanosensor is the transmembrane 63 (TMEM63) ion channel. These findings open new avenues for future research into lung mechanobiology.

Meta-Analysis of Normal Reference Values for Right and Left Ventricular Quantification by Cardiovascular Magnetic Resonance.

BACKGROUND: Cardiovascular magnetic resonance (CMR) reference values are relied upon to accurately diagnose left ventricular (LV) and right ventricular (RV) pathologies. To date, reference values have been derived from modest sample sizes with limited patient diversity and attention to 1 but not both commonly used tracing techniques for papillary muscles and trabeculations. We sought to overcome these limitations by meta-analyzing normal reference values for CMR parameters stemming from multiple countries, vendors, analysts, and patient populations. METHODS: We comprehensively extracted published and unpublished data from studies reporting CMR parameters in healthy adults. A steady-state free-precession short-axis stack at 1.5T or 3T was used to trace either counting the papillary muscles and trabeculations in the LV volume or mass. We used a novel Bayesian hierarchical meta-analysis model to derive the pooled lower and upper reference values for each CMR parameter. Our model accounted for the expected differences between tracing techniques by including informative prior distributions from a large external data set. RESULTS: A total of 254 studies from 25 different countries were systematically reviewed, representing 12 812 healthy adults, of which 52 were meta-analyzed. For LV parameters counting papillary muscles and trabeculations in the LV volume, pooled normative reference ranges in men and women, respectively, were as follows: LV ejection fraction of 52% to 73% and 54% to 75%, LV end-diastolic volume index of 60 to 109 and 56 to 96 mL/m2, LV end-systolic volume index of 18 to 45 and 16 to 38 mL/m2, and LV mass index of 41 to 76 and 33 to 57 g/m2. For LV parameters counting papillary muscles and trabeculations in the LV mass, pooled normative reference ranges in men and women, respectively, were as follows: LV ejection fraction of 57% to 74% and 57% to 75%, LV end-diastolic volume index of 60 to 97 and 55 to 88 mL/m2, LV end-systolic volume index of 18 to 37 and 15 to 34 mL/m2, and LV mass index of 50 to 83 and 38 to 65 g/m2. For RV parameters, pooled normative reference ranges in men and women, respectively, were as follows: RV ejection fraction of 47% to 68% and 49% to 71%, RV end-diastolic volume index of 64 to 115 and 57 to 99 mL/m2, RV end-systolic volume index of 23 to 52 and 18 to 42 mL/m2, and RV mass index of 14 to 29 and 13 to 25 g/m2. CONCLUSIONS: Our Bayesian hierarchical meta-analysis provides normative reference values for CMR parameters of LV and RV size, systolic function, and mass, encompassing both tracing techniques across a diverse multinational sample of healthy men and women.

The pathogenesis of influenza in intact alveoli: virion endocytosis and its effects on the lung's air-blood barrier.

Lung infection by influenza A virus (IAV) is a major cause of global mortality from lung injury, a disease defined by widespread dysfunction of the lung's air-blood barrier. Endocytosis of IAV virions by the alveolar epithelium - the cells that determine barrier function - is central to barrier loss mechanisms. Here, we address the current understanding of the mechanistic steps that lead to endocytosis in the alveolar epithelium, with an eye to how the unique structure of lung alveoli shapes endocytic mechanisms. We highlight where future studies of alveolar interactions with IAV virions may lead to new therapeutic approaches for IAV-induced lung injury.

A rare case of primary breast lymphoma presenting as calcifications on screening mammography.

Extranodal marginal zone lymphoma (EMZL) is a low-grade subtype of B-cell non-Hodgkin lymphoma that can affect any mucosal tissue, most commonly the GI tract. Primary involvement of the breast, known as primary breast lymphoma (PBL), is a very rare manifestation. We report an unusual case of a 65-year-old woman with primary breast EMZL presenting as calcifications discovered during screening mammography. This represents an exceedingly atypical appearance of primary breast lymphoma that is rarely described in the literature.

New Approaches for the Treatment of AML beyond the 7+3 Regimen: Current Concepts and New Approaches.

Fifty years have passed since the development of the first chemotherapy regimen for treating acute myelogenous leukemia (AML), with the approval in 1973 of the cytarabine daunorubicin (7+3) regimen. Until recently, patients diagnosed with AML had very limited treatment options and depended primarily on chemotherapy in combinations, doses, or schedules of the same drugs. Patients with advanced age, comorbidities, or relapsed or refractory disease were left with no effective options for treatment. New advances in the understanding of the biology and the molecular and genetic changes associated with leukemogenesis, as well as recent advances in drug development, have resulted in the introduction over the last few years of novel therapeutic agents and approaches to the treatment of AML as well as a new classification of the disease. In this article, we will discuss the new classification of AML; the mechanisms, actions, and indications of the new targeted therapies; the chemotherapy combinations; and the potential role of cellular therapies as new treatment options for this terrible disease.

Implementation outcomes of the integrated district evidence to action (IDEAs) program to reduce neonatal mortality in central Mozambique: an application of the RE-AIM evaluation framework.

BACKGROUND: Scarce evidence exists on audit and feedback implementation processes in low-resource health systems. The Integrated District Evidence to Action (IDEAs) is a multi-component audit and feedback strategy designed to improve the implementation of maternal and child guidelines in Mozambique. We report IDEAs implementation outcomes. METHODS: IDEAs was implemented in 154 health facilities across 12 districts in Manica and Sofala provinces between 2016 and 2020 and evaluated using a quasi-experimental design guided by the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. Reach is the proportion of pregnant women attending IDEAs facilities. Adoption is the proportion of facilities initiating audit and feedback meetings. Implementation is the fidelity to the strategy components, including readiness assessments, meetings (frequency, participation, action plan development), and targeted financial support and supervision. Maintenance is the sustainment at 12, 24, and 54 months. RESULTS: Across both provinces, 56% of facilities were exposed to IDEAs (target 57%). Sixty-nine and 73% of pregnant women attended those facilities' first and fourth antenatal consultations (target 70%). All facilities adopted the intervention. 99% of the expected meetings occurred with an average interval of 5.9 out of 6 months. Participation of maternal and child managers was high, with 3076 attending meetings, of which 64% were from the facility, 29% from the district, and 7% from the province level. 97% of expected action plans were created, and 41 specific problems were identified. "Weak diagnosis or management of obstetric complications" was identified as the main problem, and "actions to reinforce norms and protocols" was the dominant subcategory of micro-interventions selected. Fidelity to semiannual readiness assessments was low (52% of expected facilities), and in completing micro-interventions (17% were completed). Ninety-six and 95% of facilities sustained the intervention at 12 and 24 months, respectively, and 71% had completed nine cycles at 54 months. CONCLUSION: Maternal and child managers can lead audit and feedback processes in primary health care in Mozambique with high reach, adoption, and maintenance. The IDEAs strategy should be adapted to promote higher fidelity around implementing action plans and conducting readiness assessments. Adding effectiveness to these findings will help to inform strategy scale-up.

Use of Banked Fibula for Improved Nasal Reconstruction Following Free Fibula Midface Reconstruction.

OBJECTIVE: Anterior maxillary deficiency caused by trauma or oncologic resection presents a complex reconstructive challenge. The authors present a technique for 2-stage midface reconstruction utilizing a vascularized free fibula flap for maxillary reconstruction, followed by nasal reconstruction at a second stage utilizing a banked fibula graft. METHODS: This case series utilizes a 2-stage technique for midface reconstruction. In the first stage, a fibula-free flap was used to reconstruct the maxilla with the excess banked in the abdomen. In the second stage, this bone graft was used to restore the nasal dorsum. RESULTS: Two patients were included in this series. Patient 1 was a 28-year-old man who presented after a remote gunshot wound to his face, resulting in complete loss of his anterior maxilla and nasal support with midface collapse. Patient 2 was a 65-year-old man who presented with squamous cell carcinoma of the hard palate with extension into the maxilla and nasal septum. In both cases, the flaps healed without complication, providing midface restoration. Placement of the banked fibula graft in a second stage resulted in restoration of dorsal nasal projection. CONCLUSION: The authors describe the use of "spare" fibula parts for nasal reconstruction after loss of the maxilla and cartilaginous septum. The use of the fibula bone as a graft to restore the nasal dorsum in a delayed manner allows for a better assessment of the esthetic needs after the massive swelling from the initial surgery has abated. Further, this approach eliminates the need for a second donor site for nasal reconstruction.

Barriers and Facilitators of Colorectal Cancer Screening During the COVID-19 Pandemic.

BACKGROUND: COVID-19 introduced new barriers to health care including cancer screenings. This study evaluated the role of pandemic- and copay-related barriers to colonoscopy and the extent to which home-based testing methods were utilized. METHODS: A cross-sectional survey assessed colorectal cancer (CRC) attitudes and screening early in the COVID-19 pandemic. RESULTS: Respondents (342; 50.37% female) were 62.32 (SD = 6.87) years old. Roughly half were White/Caucasian (329; 48.45%); 29.75% were Black/African American (202); and 21.80% were another race (148). Roughly two-thirds were up-to-date with CRC screening (459; 67.59%). In an adjusted model, those with a higher agreement that concerns about COVID-19 delayed scheduling their colonoscopy (OR = .79; 95% CI: .08, .63; P = .045) and concerns about copays delayed scheduling their colonoscopy (OR = .73; 95% CI: .73, .57; P = .02) were less likely to be up-to-date on screening. In another adjusted model, those screened during the pandemic were significantly more likely to be screened via an at-home test (OR = 10.93; 95% CI: 5.95, 20.27; P < .001). DISCUSSION: During the COVID-19 pandemic, screening copay-related concerns persisted and were significantly higher among those not up-to-date with CRC screening. Increased at-home testing and addressing copay barriers may increase CRC screening adherence now and in future infectious disease outbreaks.

Economic hardship and adolescent behavioral outcomes: Within- and between-family associations.

Understanding how youth perceive household economic hardship and how it relates to their behavior is vital given associations between hardship and behavioral development. Yet, most studies ignore youth's own perceptions of economic hardship, instead relying solely on caregiver reports. Moreover, the literature has tended to treat economic hardship as a stable force over time, rather than a volatile one that varies month-to-month. This study addressed extant limitations by collecting monthly measures of economic hardship, specifically caregiver- and youth-reported material deprivation and youth-reported financial stress, and youth internalizing and externalizing problems from 104 youth-caregiver dyads (youth: 14-16 years, 55% female, 37% Black, 43% White) over nine months. We examined month-to-month variability of these constructs and how youth-reports of material deprivation and financial stress predicted their behavior problems, controlling for caregiver-reports of material deprivation. We found that hardship measures varied month-to-month (ICCs = 0.69-0.73), and youth-reported material deprivation positively predicted internalizing when examining both within- and between-individual variability (ß = .19-.47). Youth-reported financial stress positively predicted within-individual variation in externalizing (ß = .18), while youth reports of material deprivation predicted externalizing when looking between families (ß = .41). Caregiver-reported material deprivation was unrelated to youth behavior when accounting for youth perceptions of economic hardship.

Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques.

The repeat emergence of SARS-CoV-2 variants of concern (VoC) with decreased susceptibility to vaccine-elicited antibodies highlights the need to develop next-generation vaccine candidates that confer broad protection. Here we describe the antibody response induced by the SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine candidate adjuvanted with the Army Liposomal Formulation including QS21 (ALFQ) in non-human primates. By isolating and characterizing several monoclonal antibodies directed against the Spike Receptor Binding Domain (RBD), N-Terminal Domain (NTD), or the S2 Domain, we define the molecular recognition of vaccine-elicited cross-reactive monoclonal antibodies (mAbs) elicited by SpFN. We identify six neutralizing antibodies with broad sarbecovirus cross-reactivity that recapitulate serum polyclonal antibody responses. In particular, RBD mAb WRAIR-5001 binds to the conserved cryptic region with high affinity to sarbecovirus clades 1 and 2, including Omicron variants, while mAb WRAIR-5021 offers complete protection from B.1.617.2 (Delta) in a murine challenge study. Our data further highlight the ability of SpFN vaccination to stimulate cross-reactive B cells targeting conserved regions of the Spike with activity against SARS CoV-1 and SARS-CoV-2 variants.

Ecological modeling, biogeography, and phenotypic analyses setting the tiger cats' hyperdimensional niches reveal a new species.

Recently, the tiger-cat species complex was split into Leopardus tigrinus and Leopardus guttulus, along with other proposed schemes. We performed a detailed analysis integrating ecological modeling, biogeography, and phenotype of the four originally recognized subspecies-tigrinus, oncilla, pardinoides, guttulus-and presented a new multidimensional niche depiction of the species. Species distribution models used > 1400 records from museums and photographs, all checked for species accuracy. Morphological data were obtained from institutional/personal archives. Spotting patterns were established by integrating museum and photographic/camera-trap records. Principal component analysis showed three clearly distinct groups, with the Central American specimens (oncilla) clustering entirely within those of the Andes, namely the pardinoides group of the cloud forests of the southern Central-American and Andean mountain chains (clouded tiger-cat); the tigrinus group of the savannas of the Guiana Shield and central/northeastern Brazil (savanna tiger-cat); and the guttulus group in the lowland forests of the Atlantic Forest domain (Atlantic Forest tiger-cat). This scheme is supported by recent genetic analyses. All species displayed different spotting patterns, with some significant differences in body measurements/proportions. The new distribution presented alarming reductions from the historic range of - 50.4% to - 68.2%. This multidimensional approach revealed a new species of the elusive and threatened tiger-cat complex.