Dispersion of SARS-CoV-2 lineage BA.5.1.25 and its descendants in Peru during two COVID-19 waves in 2022.

During the third year of the pandemic in Peru, the persistent transmission of SARS-CoV-2 led to the appearance of more transmissible and immune-evasive Omicron sublineages; in that context, the National Genomic Surveillance of SARS-CoV-2 performed by the Peruvian National Institute of Health detected spike mutations in the circulating Omicron BA.5.1.25 sublineage which was later designated as DJ.1 and increased during the fourth COVID-19 wave, this eventually branched into new sublineages. The introduction, emergence, and timing of the most recent common ancestor (tMRCA) of BA.5.1.25 and its descendants (DJ.1, DJ.1.1, DJ.1.2, and DJ.1.3) were investigated in this paper as well as the time lags between their emergence and identification by the Peruvian National Institute of Health. Our findings show that ongoing genomic surveillance of SARS-CoV-2 is critical for understanding its phylogenetic evolution and the emergence of novel variations.

Cells Remain Viable When Collected With an In-Line-Suction Tissue Collector From Byproducts of Anterior Cruciate Ligament Reconstruction Surgery.

Purpose: To investigate the viability of cells collected with an in-line-suction autologous tissue collector from the tissue byproducts of arthroscopic anterior cruciate ligament (ACL) reconstruction, to characterize cells from different tissue types, and to identify mesenchymal stem cells. Methods: Patients aged 14 to 50 years with ACL injuries requiring arthroscopic reconstruction surgery were offered enrollment and screened for participation. In total, 12 patients were enrolled in the descriptive laboratory study. Arthroscopic byproduct tissue was collected with an in-line-suction autologous tissue collector from 4 intraoperative collection sites for each patient: ACL stump, ACL fat pad, notchplasty debris, and tunnel drilling debris. All tissue samples were digested using collagenase, and the derived cellular populations were analyzed in vitro, characterizing cellular viability, proliferative potential, qualitative multipotent differentiation capacity, and cell-surface marker presence. Results: An equivalent mass of arthroscopic byproduct tissue was taken from each of the 4 intraoperative collection sites (1.12-1.61 g, P = .433), which all showed an average viability of at least 99.95% and high average total nucleated cells (≥1.37 × 107 cells/mL). No significant differences in collected mass (P = .433), cellular viability (P = .880), or total nucleated cells (P = .692) were observed between the 4 byproduct tissues. The byproduct tissues did exhibit significant differences in monocyte (P = .037) and red blood cell (P = .038) concentrations, specifically with greater values present in the ACL stump tissue. Cells from all byproduct tissues adhered to plastic cell culture flasks. Significant differences were found between colony-forming unit fibroblast counts of the 4 byproduct tissues when plated at 106 (P = .003) and 103 (P = .016) cells as the initial seeding density. There was a significant relationship found between both the starting concentration (χ2 = 32.7, P < .001) and the byproduct tissue type (χ2 = 30.4, P < .001) to the presence of ≥80% confluency status at 10 days. Cells obtained from all 4 byproduct tissues qualitatively showed positive tri-lineage (adipocyte, osteoblast, chondroblast) differentiation potential compared with negative controls under standardized in vitro differentiation conditions. Cells derived from all 4 byproduct tissues expressed cell-surface antigens CD105+, CD73+, CD90+, CD45-, CD14-, and CD19- (>75%), and did not express CD45 (<10%). There were no statistically significant differences in cell-surface antigens between the four byproduct tissues. Conclusions: This descriptive laboratory study demonstrated that cells derived from arthroscopic byproduct tissues of ACL reconstruction remain viable when collected with an in-line-suction autologous tissue collector and these cells meet the ISCT criteria to qualify as mesenchymal stem cells. Clinical Relevance: It is known that viable mesenchymal stem cells reside in byproduct tissue of anterior cruciate ligament reconstruction surgery (ACLR). Practical methods to harvest these cells at the point of care require further development. This study validates the use of an in-line-suction autologous tissue collector for the harvest of viable mesenchymal stem cells after ACLR.

Augmentation of ACL Autograft Reconstruction With an Amnion Collagen Matrix Wrap and Bone Marrow Aspirate Concentrate: A Pilot Randomized Controlled Trial With 2-Year Follow-up.

Background: It is theorized that the lack of a synovial lining after anterior cruciate ligament (ACL) injury and ACL reconstruction (ACLR) contributes to slow ligamentization and possible graft failure. Whether graft maturation and incorporation can be improved with the use of a scaffold requires investigation. Purpose: To evaluate the safety and efficacy of wrapping an ACL autograft with an amnion collagen matrix and injecting bone marrow aspirate concentrate (BMAC), quantify the cellular content of the BMAC samples, and assess 2-year postoperative patient-reported outcomes. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: A total of 40 patients aged 18 to 35 years who were scheduled to undergo ACLR were enrolled in a prospective single-blinded randomized controlled trial with 2 arms based on graft type: bone-patellar tendon-bone (BTB; n = 20) or hamstring (HS; n = 20). Participants in each arm were randomized into a control group who underwent standard ACLR or an intervention group who had their grafts wrapped with an amnion collagen matrix during graft preparation, after which BMAC was injected under the wrap layers after implantation. Postoperative magnetic resonance imaging (MRI) mapping/processing yielded mean T2* relaxation time and graft volume values at 3, 6, 9, and 12 months. Participants completed the Single Assessment Numeric Evaluation Score, Knee injury and Osteoarthritis Outcome Score, and pain visual analog scale. Statistical linear mixed-effects models were used to quantify the effects over time and the differences between the control and intervention groups. Adverse events were also recorded. Results: No significant differences were found at any time point between the intervention and control groups for BTB T2* (95% CI, -1.89 to 0.63; P = .31), BTB graft volume (95% CI, -606 to 876.1; P = .71), HS T2* (95% CI, -2.17 to 0.39; P = .162), or HS graft volume (95% CI, -11,141.1 to 351.5; P = .28). No significant differences were observed between the intervention and control groups of either graft type on any patient-reported outcome measure. No adverse events were reported after a 2-year follow-up. Conclusion: In this pilot study, wrapping a graft with an amnion collagen matrix and injecting BMAC appeared safe. MRI T2* values and graft volume of the augmented ACL graft were not significantly different from that of controls, suggesting that the intervention did not result in improved graft maturation. Registration: NCT03294759 (ClinicalTrials.gov identifier).

Factores individuales e institucionales asociados a la vacunación contra el virus de la hepatitis B en recién nacidos de hospitales de Lima y Callao

Introducción. La vacunación contra el virus de la hepatitis B (VHB) en recién nacidos es crucial para la prevención de la transmisión perinatal. Objetivo. Determinar factores individuales e institucionales asociados a la vacunación contra el VHB en las 12 y 24 primeras horas de vida. Métodos. Se diseñó un estudio transversal y multicéntrico. Los datos sobre la vacunación fueron recogidos de los padres y de la revisión de reportes. Los datos de los variables individuales de los recién nacidos y madres fueron recogidos de las historias clínicas. Los datos institucionales fueron recogidos de registros de atención inmediata y directamente del personal de inmunizaciones. Resultados. Se incluyó 777 recién nacidos en 10 establecimientos. En el análisis multinivel resultó favorable a la vacunación en las primeras 12 horas, el mayor tiempo de atención en los servicios de inmunizaciones (RP: 1,0; IC95%: 0,99 - 1,01). Para la vacunación dentro de las 24 horas de vida fue favorable la mayor cantidad de personal de enfermería en los servicios de vacunación (RP: 1,02; IC95%: 1,01 - 1,03) y desfavorable la mayor cantidad de partos al día de los establecimientos (RP: 0,99; IC95%: 0,99 - 0,997). No se identificó factores individuales. Conclusión. Factores institucionales, como el tiempo de atención, la cantidad de personal de enfermería y la cantidad de partos, estuvieron asociados con la vacunación contra el VHB en recién nacidos. Se requiere estrategias de mejora como la introducción de la vacunación en la atención inmediata del neonato para la prevención de la transmisión perinatal del VHB.

Introduction. Vaccination against hepatitis B Virus (HBV) in newborns is crucial for the prevention of perinatal transmission. Objective. To determine the individual and institutional factors associated with vaccine for HBV in newborns in the first 12 hours and 24 hours of life. Methods. A cross-sectional, multicenter-design study was conducted in high level public and private hospitals in Lima Metropolitana and Callao. Information on vaccination was obtained through consultations with parents and review of health service reports. Individual variables of the newborns and their mothers were obtained from the medical records of the newborns. Institutional data were collected from immediate care records and from health personnel responsible for the immunization program. Results. The study was conducted in 10 health facilities, including 777 newborns. In the multilevel analysis, the longest care time in the vaccination service was favorable for vaccination within 12 hours of life (PR: 1,0; 95% CI: 0,9995-1,01); while for vaccination within 24 hours of life was favorable the greater number of nursing personnel (RP: 1,02; IC95%: 1,01-1,03) and unfavorable the greater number of deliveries per day in the institution (RP:0,99; IC95%: 0,99-0,997). No individual factors related to vaccination were identified. Conclusions. Institutional factors, such as length of care, number of nursing staff, and number of deliveries, were associated with newborn HBV vaccination. Improvement strategies are required, such as the introduction of vaccination in the immediate care of the newborn for the prevention of perinatal transmission of HBV.

Immunogenicity and reactogenicity of a third dose of BNT162b2 vaccine for COVID-19 after a primary regimen with BBIBP-CorV or BNT162b2 vaccines in Lima, Peru.

BACKGROUND: The administration of a third (booster) dose of COVID-19 vaccines in Peru initially employed the BNT162b2 (Pfizer) mRNA vaccine. The national vaccination program started with healthcare workers (HCW) who received BBIBP-CorV (Sinopharm) vaccine as primary regimen and elderly people previously immunized with BNT162b2. This study evaluated the reactogenicity and immunogenicity of the "booster" dose in these two groups in Lima, Peru. METHODS: We conducted a prospective cohort study, recruiting participants from November to December of 2021 in Lima, Peru. We evaluated immunogenicity and reactogenicity in HCW and elderly patients previously vaccinated with either two doses of BBIBP-CorV (heterologous regimen) or BTN162b2 (homologous regimen). Immunogenicity was measured by anti-SARS-CoV-2 IgG antibody levels immediately before boosting dose and 14 days later. IgG geometric means (GM) and medians were obtained, and modeled using ANCOVA and quantile regressions. RESULTS: The GM of IgG levels increased significantly after boosting: from 28.5±5.0 AU/mL up to 486.6±1.2 AU/mL (p<0.001) which corresponds to a 17-fold increase. The heterologous vaccine regimen produced higher GM of post-booster anti-SARS-CoV-2 IgG levels, eliciting a 13% increase in the geometric mean ratio (95%CI: 1.02-1.27) and a median difference of 92.3 AU/ml (95%CI: 24.9-159.7). Both vaccine regimens were safe and well tolerated. Previous COVID-19 infection was also associated with higher pre and post-booster IgG GM levels. CONCLUSION: Although both boosting regimens were highly immunogenic, two doses of BBIBP-CorV boosted with BTN162b2 produced a stronger IgG antibody response than the homologous BNT162b2 regimen in the Peruvian population. Additionally, both regimens were mildly reactogenic and well-tolerated.

The Novel Oxazolidinone TBI-223 Is Effective in Three Preclinical Mouse Models of Methicillin-Resistant Staphylococcus aureus Infection.

Staphylococcus aureus is an important cause of various infections in humans, including bacteremia, skin and soft tissue infections, and infections associated with implanted medical devices. The emergence of hospital- and community-acquired methicillin-resistant Staphylococcus aureus (MRSA) underscores the urgent and unmet need to develop novel, safe, and effective antibiotics against these multidrug-resistant clinical isolates. Oxazolidinone antibiotics such as linezolid have excellent oral bioavailability and provide coverage against MRSA infections. However, their widespread and long-term use is often limited by adverse effects, especially myelosuppression. TBI-223 is a novel oxazolidinone with potentially reduced myelosuppression, compared to linezolid, but its efficacy against MRSA infections is unknown. Therefore, the preclinical efficacy of TBI-223 (80 and 160 mg/kg twice daily) was compared with that of linezolid (40 and 80 mg/kg twice daily) and sham treatment in mouse models of MRSA bacteremia, skin wound infection, and orthopedic-implant-associated infection. The dosage was selected based on mouse pharmacokinetic analysis of both linezolid and TBI-223, as well as measurement of the MICs. In all three models, TBI-223 and linezolid had comparable dose-dependent efficacies in reducing bacterial burden and disease severity, compared with sham-treated control mice. Taken together, these findings indicate that TBI-223 represents a novel oxazolidinone antibiotic that may provide an additional option against MRSA infections. Future studies in larger animal models and clinical trials are warranted to translate these findings to humans. IMPORTANCE Staphylococcus aureus is the predominant cause of bloodstream, skin, and bone infections in humans. Resistance to commonly used antibiotics is a growing concern, making it more difficult to treat staphylococcal infections. Use of the oxazolidinone antibiotic linezolid against resistant strains is hindered by high rates of adverse reactions during prolonged therapy. Here, a new oxazolidinone named TBI-223 was tested against S. aureus in three mouse models of infection, i.e., bloodstream infection, skin infection, and bone infection. We found that TBI-223 was as effective as linezolid in these three models. Previous data suggest that TBI-223 has a better safety profile than linezolid. Taken together, these findings indicate that this new agent may provide an additional option against MRSA infections. Future studies in larger animal models and clinical trials are warranted to translate these findings to humans.

Efficacy and safety of convalescent plasma versus standard care in hospitalized patients with COVID-19 from the Peruvian Social Security Health System: open-label, randomized, controlled clinical trial

OBJECTIVESTo assess the efficacy and safety of convalescent plasma plus standard of care (CP + SoC) compared with standard of care (SoC) alone in patients hospitalized for moderate to severe COVID-19 who do not yet require mechanical ventilation. METHODSPhase 2 randomized, parallel-group, randomized, open-label, controlled, superiority, single-center clinical trial. This clinical trial has been registered in REPEC with the following ID: 013-20. Hospitalized adult patients with moderate to severe COVID-19 were enrolled. The allocation ratio was 1:1 in a variable-size permuted block randomization scheme. The primary outcome was death 28 days after the intervention. Secondary outcomes were mortality at 14 and 56 days, time to death at 56 days, time in the ICU at 28 days, time on a mechanical ventilator at 28 days, frequency of adverse events, and frequency of serious adverse events. RESULTSA total of 64 participants were enrolled, 32 were assigned to CP + SoC, and 32 to SoC. One participant assigned to CP + SoC withdrew his informed consent before applying the treatment. At day 28, there were no statistically significant differences for the primary outcome between the CP + SoC and SoC groups (relative risk: 2.06; 95%CI 0.73 to 7.11; p = 0.190). No differences were found in the incidences of mortality at 56 days (hazard ratio: 2.21; 95%CI 0.66 to 7.33; p = 0.182), admission to the ICU at 28 days (sub-hazard ratio: 2.06; 95%CI 0.57 to 8.55; p = 0.250), admission to mechanical ventilation at 28 days (sub-hazard ratio: 2.19; 95%CI 0.57 to 8.51; p = 0.260). Estimates for days 14 were similar. No infusion-related adverse events were reported during the study. There were no statistically significant differences in the frequency of any adverse events (odds ratio: 2.74; 95%CI 0.90 to 9.10; p = 0.085) or the frequency of serious adverse events (odds ratio: 3.60; 95%CI 0.75 to 26.1; p = 0.75). CONCLUSIONSNo evidence was found that CP had a significant effect in reducing 28-day mortality. There was also no evidence that the frequency of adverse events was higher in those who received CP + SoC than those who received only SoC.

Selected Domains within a Comprehensive Geriatric Assessment in Older Patients with Non-Hodgkin Lymphoma are Highly Associated with Frailty.

Background: The incidence of Non-Hodgkin Lymphoma (NHL) is increasing, particularly among older patients who tend to have worse outcomes and can be predisposed to increased toxicities and less treatment tolerance. Therefore, a thorough pre-treatment assessment is essential. A comprehensive geriatric assessment (CGA) can be used to evaluate the older patient considering chemotherapy and is the preferred evaluation tool. However, a formal CGA is laborious, complex and time-consuming. Objectives: To characterize older adults with NHL and determine the CGA variables with the greatest association to frailty in order to propose a more simplified assessment. Methods: We performed a cross-sectional study using data collected from CGAs in NHL patients > 65 years admitted to our oncology service, from September 2015 to August 2017. Our evaluation parameters included: polypharmacy, a screening tool of older people's prescriptions (STOPP), the Lawton scale, Barthel index, Katz index, gait speed, a Timed Up and Go (TUG) test, a Mini-Mental state examination (MMSE), the Yesavage and Gijon scales, a Mini-nutritional assessment (MNA), a Geriatric Syndromes assessment, and a Cumulative Illness Rating Scale-Geriatric (CIRS-G). The formal CGA was comprised of nine domains; frailty was defined as an impairment in > 2 domains. Each parameter was individually compared with frailty, and the results were used to build different multivariate models using logistic regression analyses to obtain the variables with the highest frailty association. Results: A total of 253 patients were included. Their median age was 75.4 years (range 65-92), and 62.1% had > 1 impaired domain, with 39.9% considered frail. Bivariate analysis showed strong associations with age > 85 and all the geriatric parameters except for STOPP. Our final multivariate analysis resulted in 5 domains (the use of > 5 medications, a Lawton < 7, TUG > 20, Yesavage > 5, and the presence of at least one geriatric syndrome) being significantly associated with frailty and performing similarly to a CGA. Conclusion: In our population of older NHL patients, an abbreviated evaluation based of only five domains, polypharmacy, TUG, Lawton scale, Yesavage scale and the presence of at least one geriatric syndrome, had similar performance to a formal CGA in determining frailty.

Keratinocyte-derived defensins activate neutrophil-specific receptors Mrgpra2a/b to prevent skin dysbiosis and bacterial infection.

Healthy skin maintains a diverse microbiome and a potent immune system to fight off infections. Here, we discovered that the epithelial-cell-derived antimicrobial peptides defensins activated orphan G-protein-coupled receptors (GPCRs) Mrgpra2a/b on neutrophils. This signaling axis was required for effective neutrophil-mediated skin immunity and microbiome homeostasis. We generated mutant mouse lines lacking the entire Defensin (Def) gene cluster in keratinocytes or Mrgpra2a/b. Def and Mrgpra2 mutant animals both exhibited skin dysbiosis, with reduced microbial diversity and expansion of Staphylococcus species. Defensins and Mrgpra2 were critical for combating S. aureus infections and the formation of neutrophil abscesses, a hallmark of antibacterial immunity. Activation of Mrgpra2 by defensin triggered neutrophil release of IL-1ß and CXCL2 which are vital for proper amplification and propagation of the antibacterial immune response. This study demonstrated the importance of epithelial-neutrophil signaling via the defensin-Mrgpra2 axis in maintaining healthy skin ecology and promoting antibacterial host defense.

Genomic surveillance of the Lambda SARS-CoV-2 variant in a global phylogenetic context.

The massive sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and global genomic surveillance strategies allowed the detection of many variants of concern and interest. The variant of interest Lambda (C.37), which originated in South America, has been the most prevalent in Peru and Chile, but its dispersion in other continents still remains unknown. The current study aims to determine the phylogenetic relationship among C.37 isolates worldwide, focusing on spike mutations to understand the spread of Lambda in pandemics. A total of 7441 sequences identified as C.37 were downloaded from the GISAID database; local analysis was carried out to identify spike mutations and phylogenetic analysis was carried out to determine the rate of spread of the virus. Our results showed some spike mutations of Lambda that allowed us to detect small local outbreaks in different countries that occurred in the past and identify several clades that have not yet been designated. Although the lineage C.37 is not epidemiologically relevant in Europe or North America, the endemic behavior of this variant in Peru had a major impact on the second SARS-CoV-2 wave.

Immunogenicity and reactogenicity of a third dose of BNT162b2 vaccine for COVID-19 after a primary regimen with BBIBP-CorV or BNT162b2 vaccines in Lima, Peru.

BackgroundThe administration of a third (booster) dose of COVID-19 vaccines in Peru initially employed the BNT162b2 (Pfizer) mRNA vaccine. The national vaccination program started with healthcare workers (HCW) who received BBIBP-CorV (Sinopharm) vaccine as primary regimen and elderly people previously immunized with BNT162b2. This study evaluated the reactogenicity and immunogenicity of the "booster" dose in these two groups in Lima, Peru. MethodsWe conducted a prospective cohort study, recruiting participants from November to December of 2021 in Lima, Peru. We evaluated immunogenicity and reactogenicity in HCW and elderly patients previously vaccinated with either two doses of BBIBP-CorV (heterologous regimen) or BTN162b2 (homologous regimen). Immunogenicity was measured by anti-SARS-CoV-2 IgG antibody levels immediately before boosting dose and 14 days later. IgG geometric means (GM) and medians were obtained, and modeled using ANCOVA and quantile regressions. ResultsThe GM of IgG levels increased significantly after boosting: from 28.5{+/-}5.0 AU/mL up to 486.6{+/-}1.2 AU/mL (p<0.001) which corresponds to a 17-fold increase. The heterologous vaccine regimen produced higher GM of post-booster anti-SARS-CoV-2 IgG levels, eliciting a 13% fold increase in the geometric mean ratio (95%CI: 1.02-1.27) and a median difference of 92.3 AU/ml (95%CI: 24.9-159.7). Both were safe and well tolerated. Previous COVID-19 infection was also associated with higher pre and post-booster IgG GM levels. ConclusionAlthough both boosting regimens were highly immunogenic, two doses of BBIBP-CorV boosted with BTN162b2 produced a stronger IgG antibody response than the homologous BNT162b2 regimen in the Peruvian population. Additionally, both regimens were mildly reactogenic and well-tolerated.

Preclinical characterization and target validation of the antimalarial pantothenamide MMV693183.

Drug resistance and a dire lack of transmission-blocking antimalarials hamper malaria elimination. Here, we present the pantothenamide MMV693183 as a first-in-class acetyl-CoA synthetase (AcAS) inhibitor to enter preclinical development. Our studies demonstrate attractive drug-like properties and in vivo efficacy in a humanized mouse model of Plasmodium falciparum infection. The compound shows single digit nanomolar in vitro activity against P. falciparum and P. vivax clinical isolates, and potently blocks P. falciparum transmission to Anopheles mosquitoes. Genetic and biochemical studies identify AcAS as the target of the MMV693183-derived antimetabolite, CoA-MMV693183. Pharmacokinetic-pharmacodynamic modelling predict that a single 30 mg oral dose is sufficient to cure a malaria infection in humans. Toxicology studies in rats indicate a > 30-fold safety margin in relation to the predicted human efficacious exposure. In conclusion, MMV693183 represents a promising candidate for further (pre)clinical development with a novel mode of action for treatment of malaria and blocking transmission.

CCR2 contributes to host defense against Staphylococcus aureus orthopedic implant-associated infections in mice.

C-C motif chemokine receptor 2 (CCR2) is an important mediator of myeloid cell chemotaxis during inflammation and infection. Myeloid cells such as monocytes, macrophages, and neutrophils contribute to host defense during orthopedic implant-associated infections (OIAI), but whether CCR2-mediated chemotaxis is involved remains unclear. Therefore, a Staphylococcus aureus OIAI model was performed by surgically placing an orthopedic-grade titanium implant and inoculating a bioluminescent S. aureus strain in knee joints of wildtype (wt) and CCR2-deficient mice. In vivo bioluminescent signals significantly increased in CCR2-deficient mice compared with wt mice at later time points (Days 14-28), which was confirmed with ex vivo colony-forming unit enumeration. S. aureus γ-hemolysin utilizes CCR2 to induce host cell lysis. However, there were no differences in bacterial burden when the OIAI model was performed with a parental versus a mutant γ-hemolysin-deficient S. aureus strain, indicating that the protection was mediated by the host cell function of CCR2 rather than γ-hemolysin virulence. Although CCR2-deficient and wt mice had similar cellular infiltrates in the infected joint tissue, CCR2-deficient mice had reduced myeloid cells and γδ T cells in the draining lymph nodes. Taken together, CCR2 contributed to host defense at later time points during an OIAI by increasing immune cell infiltrates in the draining lymph nodes, which likely contained the infection and prevented invasive spread.

IL-6R/Signal Transducer and Activator of Transcription 3 Signaling in Keratinocytes rather than in T Cells Induces Psoriasis-Like Dermatitis in Mice.

Signal transducer and activator of transcription 3 (STAT3) is important for psoriasis pathogenesis because STAT3 signaling downstream of IL-6, IL-21, IL-22, and IL-23 contributes to T helper type 17 cell development and because transgenic mice with keratinocyte (KC) STAT3 expression (K14-Stat3C mice) develop psoriasis-like dermatitis. In this study, the relative contribution of STAT3 signaling in KCs versus in T cells was evaluated in the imiquimod model of psoriasis-like dermatitis. Mice with STAT3-inducible deletion in KCs (K5-Stat3-/- mice) had decreased psoriasis-like dermatitis and epidermal STAT3 phosphorylation compared with wild-type mice, whereas mice with constitutive deletion of STAT3 in all T cells were similar to wild-type mice. Interestingly, mice with KC-inducible deletion of IL-6Rα had similar findings to those of K5-Stat3-/- mice, identifying IL-6/IL-6R as a predominant upstream signal for KC STAT3-induced psoriasis-like dermatitis. Moreover, psoriasis-like dermatitis inversely associated with type 1 immune gene products, especially CXCL10, whereas CXCL10 limited psoriasis-like dermatitis, suggesting that KC STAT3 signaling promoted psoriasis-like dermatitis by restricting downstream CXCL10 expression. Finally, treatment of mice with the pan-Jak inhibitor, tofacitinib, reduced psoriasis-like dermatitis and epidermal STAT3 phosphorylation. Taken together, STAT3 signaling in KCs rather than in T cells was a more important determinant for psoriasis-like dermatitis in a mechanism that involved upstream KC IL-6R signaling and downstream inhibition of type 1 immunity‒associated CXCL10 responses.

Shoulder Range of Motion Deficits in Youth Throwers Presenting With Elbow Pain.

BACKGROUND: Glenohumeral internal rotation deficit (GIRD) and total arc of motion difference (TAMD) have been associated with elbow injuries in throwing athletes. HYPOTHESIS: Youth pitchers with elbow pain will have greater GIRD and TAMD compared with youth pitchers without elbow pain. STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 3. METHODS: Glenohumeral range of motion of 25 consecutive throwing athletes presenting with elbow pain and that of a matched control group of 18 asymptomatic throwing athletes were compared. Bilateral glenohumeral internal rotation, external rotation, and horizontal adduction at 90° were measured and GIRD and TAMD were then calculated. An analysis of variance was performed to compare range of motion between throwers with and without elbow pain. RESULTS: The average GIRD of the elbow pain group was 32.7° compared with 14.5° in the control group (P < 0.05). The average TAMD in the elbow pain group was 28.3° compared with 6.7° in the control group (P < 0.05). GIRD and TAMD were present in 88% (22 of 25) and 96% (24 of 25) of the elbow pain group versus 33.3% (6 of 18) and 55.6% (10 of 18) of the control group, respectively. CONCLUSION: Compared with asymptomatic youth pitchers, those presenting with elbow pain have a statistically significant GIRD and TAMD. CLINICAL RELEVANCE: This study suggests that a GIRD and TAMD may predispose youth pitchers to present with symptomatic elbow pain.

Successful Outcomes and Return to Sport After Arthroscopic Bankart Repair in National Collegiate Athletic Association and National Football League Football Players.

OBJECTIVE: To characterize recurrent instability, return to sport (RTS), and patient-reported outcomes (PROs) after arthroscopic Bankart repair for acute traumatic anterior shoulder instability in National Collegiate Athletic Association (NCAA) and National Football League (NFL) football players. DESIGN: Case series. SETTING: Orthopaedic and sports medicine clinic. PARTICIPANTS: National Collegiate Athletic Association and NFL football athletes with traumatic anterior shoulder instability who underwent arthroscopic shoulder stabilization at a single institution with at least 2-year follow-up. INTERVENTIONS OR ASSESSMENT OF RISK FACTORS OR INDEPENDENT VARIABLES: Arthroscopic Bankart repair. MAIN OUTCOME MEASURES: Recurrent instability, RTS, patient satisfaction, the visual analog scale (VAS) for pain, American Shoulder and Elbow Surgeons (ASES) score, and Rowe score. RESULTS: Thirty-three players were included with a mean age of 23.8 years (range, 18-33 years) and a mean follow-up of 6.3 years (range, 4.1-9.3 years). One shoulder (3.0%) had a postoperative subluxation event, and 1 shoulder (3.0%) required revision surgery for issues other than instability; 93.3% of players were able to RTS at the same level or higher for at least 1 season. Mean satisfaction was 8.9 ± 2.3. Mean VAS was 1.0 ± 1.7, and mean ASES and Rowe scores were 90.7 ± 18.5 and 89.7 ± 15.2, respectively. CONCLUSION: Arthroscopic Bankart repair is an effective surgical intervention for traumatic anterior shoulder instability in NCAA and NFL football players. At a mean 6-year follow-up, surgery restored stability in 97% of cases and 93.3% returned to their preinjury level of sport.