Eccentric Hamstring Strength Imbalance among Football and Soccer Athletes.

OBJECTIVES: Hamstring strain injuries (HSI) are common among football and soccer athletes. Eccentric strength imbalance is considered a contributing factor for HSI. There is, however, a paucity of data on hamstring imbalances of soccer and American football athletes as they age and advance in skill level. High school athletes will display greater interlimb discrepancies compared with collegiate and professional athletes. In addition, soccer athletes will exhibit greater hamstring asymmetry than American football athletes. METHODS: Hamstring testing was performed on soccer and American football athletes using the NordBord Hamstring Testing System (Vald Performance, Albion, Australia). Age, sex, weight, sport specialization, and sport level were recorded. Maximum hamstring forces (N), torque (N · m), and work (N · s) were measured. Hamstring imbalance (%) was calculated by dividing the absolute value of the difference in leg forces divided by their sum. One-way analysis of variance and independent sample t tests compared measurements between athlete groups. RESULTS: A total of 631 athletes completed measurements, including 88 high school male soccer, 25 college male soccer, 23 professional male soccer, 83 high school female soccer, 28 college female soccer, 288 high school football, and 96 college football athletes. High school soccer players displayed significantly greater imbalances for torque (P = 0.03) and work (P < 0.01) than football athletes. Imbalances for maximum force (P = 0.035), torque (P = 0.018), and work (P = 0.033) were significantly higher for male soccer athletes in high school compared with college- and professional-level athletes. Female high school soccer players had significantly higher imbalance in torque (P = 0.045) and work (P = 0.001) compared with female collegiate soccer players. Football athletes did not experience significant changes in force imbalances between skill levels. CONCLUSIONS: High school soccer athletes exhibit greater hamstring imbalances than football athletes. Higher levels of play in soccer, for both male and female athletes, correlate with less hamstring asymmetry.

The Influence of Psychosocial Factors on Patients Undergoing Anterior Cruciate Ligament Reconstruction.

CONTEXT: Anterior cruciate ligament (ACL) injuries greatly impact patients in terms of future performance, reduced physical activity and athletic participation, and overall economic burden. Decades of research have investigated how to improve ACL reconstruction (ACLR) outcomes. Recently, there has been growing interest to understand the effects of psychosocial factors on patient outcomes. STUDY DESIGN: Clinical review. EVIDENCE ACQUISITION: A search of the PubMed database was performed in March 2023. Articles were reviewed by at least 2 authors to determine relevance. We highlighted publications of the past 5 years while incorporating previous pertinent studies. LEVEL OF EVIDENCE: Level 5. RESULTS: There is no standardization of psychosocial factors regarding ACLR. As such, there is a lack of consensus regarding which psychosocial measures to use and when. There is a need for clarification of the complex relationship between psychosocial factors and physical function. Despite this, psychosocial factors have the potential to help predict patients who are more likely to return to sport: (1) desire/motivation to return; (2) lower levels of kinesiophobia; (3) higher levels of self-efficacy, confidence, and subjective knee function; (4) risk acceptance; and (5) social support. However, there are no standardized interventions to improve psychosocial factors after ACLR. CONCLUSION: Psychosocial factors affect outcomes after ACLR. However, the interplay between psychosocial factors and physical function is complex. There is emerging evidence that testing and interventions may improve ACLR outcomes. There is a lack of standardized interventions to determine or improve psychosocial factors after ACLR. Further research is needed to identify psychosocial factors and to develop standardized interventions for clinicians to implement to improve clinical outcomes.

The Impact of Smoking on Hospital Course and Postoperative Outcomes in Patients With Fracture-Related Infections.

OBJECTIVES: To assess the relationship between patient smoking status and fracture-related infection (FRI) characteristics including patient symptoms at FRI presentation, bacterial species of FRI, and rates of fracture union. DESIGN: Retrospective cohort study. SETTING: Urban level 1 trauma center. PATIENT SELECTION CRITERIA: All patients undergoing reoperation for FRI from January 2013 to April 2021 were identified through manual review of an institutional database. OUTCOME MEASURES AND COMPARISONS: Data including patient demographics, fracture characteristics, infection presentation, and hospital course were collected through review of the electronic medical record. Patients were grouped based on current smoker versus nonsmoker status. Hospital course and postoperative outcomes of these groups were then compared. Risk factors of methicillin-resistant Staphylococcus aureus (MRSA) infection, Staphylococcus epidermidis infection, and sinus tract development were evaluated using multivariable logistic regression. RESULTS: A total of 301 patients, comprising 155 smokers (51%) and 146 nonsmokers (49%), undergoing FRI reoperation were included. Compared with nonsmokers, smokers were more likely male (69% vs. 56%, P = 0.024), were younger at the time of FRI reoperation (41.7 vs. 49.5 years, P < 0.001), and had lower mean body mass index (27.2 vs. 32.0, P < 0.001). Smokers also had lower prevalence of diabetes mellitus (13% vs. 25%, P = 0.008) and had higher Charlson Comorbidity Index 10-year estimated survival (93% vs. 81%, P < 0.001). Smokers had a lower proportion of S. epidermidis infections (11% vs. 20%, P = 0.037), higher risk of nonunion after index fracture surgery (74% vs. 61%, P = 0.018), and higher risk of sinus tracts at FRI presentation (38% vs. 23%, P = 0.004). On multivariable analysis, smoking was not found to be associated with increased odds of MRSA infection. CONCLUSIONS: Among patients who develop a FRI, smokers seemed to have better baseline health regarding age, body mass index, diabetes mellitus, and Charlson Comorbidity Index 10-year estimated survival compared with nonsmokers. Smoking status was not significantly associated with odds of MRSA infection. However, smoking status was associated with increased risk of sinus tract development and nonunion and lower rates of S. epidermidis infection at the time of FRI reoperation. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Novel Use of a Shoulder Spica: Treatment for Midshaft Humerus Fracture in the Presence of Limb Deficiency.

Pediatric midshaft humerus fractures are typically managed with a hanging arm cast, Sarmiento bracing, coaptation splint, or a combination of these treatment options. Here we report a novel use of a shoulder spica cast in the treatment of a midshaft humerus fracture in the presence of limb deficiency. Current treatments proved unsuccessful in maintaining adequate alignment, specifically the varus deformity of the fracture. A shoulder spica was able to successfully maintain acceptable alignment throughout the duration of the patient's healing process. This nontraditional use of a shoulder spica cast shows the practicality of its ability to be utilized for the treatment of unique upper extremity orthopedic obstacles.

Delayed Diagnosis of Pediatric Sternoclavicular Joint Infections and Clavicular Osteomyelitis During the COVID-19 Pandemic: A Report of 3 Cases.

Sternoclavicular joint infections and osteomyelitis of the clavicle are extremely rare infections, especially in the pediatric population. Early signs of these infections are nonspecific and can be mistaken for common upper respiratory infections such as COVID-19 and influenza. Rapid diagnosis and treatment are critical for preventing potentially fatal complications such as mediastinitis. We present three cases of sternoclavicular joint infections in the past year during the COVID-19 pandemic. All three patients had delayed diagnoses likely secondary to COVID-19 workup. Each patient underwent surgical irrigation and débridement. Two of three patients required multiple surgeries and prolonged antibiotic courses. Placement of antibiotic-impregnated calcium sulfate beads into the surgical site cleared the infection in all cases where they were used. All three patients made a full recovery; however, the severity of their situations should not be overlooked. Children presenting to the hospital with chest pain, fever, and shortness of breath should not simply be discharged based on a negative COVID-19 test or other viral assays. A higher index of suspicion for bacterial infections such as clavicular osteomyelitis is important. Close attention must be placed on the physical examination to locate potential areas of concentrated pain, erythema, or swelling to prompt advanced imaging if necessary.

Role of the mitogen-activated protein kinase signaling pathway in the regulation of human melanocytic antigen expression.

Heterogeneous expression of melanocytic antigens occurs frequently in melanomas and represents a potent barrier to immunotherapy. We previously showed that coordinated losses of several melanocytic antigens are generally attributable to down-regulation of antigen gene expression rather than irreversible mutation. Treatment of melanoma cells with mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitors blocks ERK activation and increases steady-state levels of mRNAs and corresponding protein expression for the melanocytic antigens Melan-A/MART-1, gp100, and tyrosinase. Although the degree of MEK inhibitor enhancement of antigen expression varied among different cell lines irrespective of their antigen expression status, all showed detectable responses. Notably, the antigen-enhancing effects of the MEK inhibitors could not be attributed to the master melanocytic regulator MITF-M. Because MAPK pathway activation via constitutively active mutant forms of BRAF is common in melanomas, correlation between BRAF function and antigen expression was investigated. No simple correlation of endogenous BRAF mutational status and antigen levels was observed, but transient overexpression of V600E BRAF increased ERK activation and reduced Melan-A/MART-1 levels in antigen-positive cell lines. These data indicate that whereas multiple factors may regulate antigen expression in melanomas, enhancement of MAPK signaling can act as a negative influence. Blocking such signaling with MEK inhibitors accordingly augments antigen levels, thereby enhancing Melan-A/MART-1-specific cytotoxic T-cell responses to antigen-negative cells following MEK inhibition treatment. Consequently, MAPK inhibition may assist targeting of melanomas for immunotherapy.

Induction of "antigen silencing" in melanomas by oncostatin M: down-modulation of melanocyte antigen expression.

We previously reported that antigen expression in melanoma cell lines is down-regulated by proteins secreted by antigen-negative melanoma cells. Here we report the purification and characterization of one of these down-regulatory factors, the cytokine, oncostatin M (OSM), which transmits its signal via the gp130 cell surface receptor, resulting in the selective down-modulation of the melanocyte lineage antigens: Melan-A/MART-1, gp100, tyrosinase, tyrosinase-related proteins 1 and 2, and the M isoform of microphthalmia transcription factor. Furthermore, we have found that some melanoma cell lines produce as yet uncharacterized factors distinct from OSM which also down-modulate antigen expression via signaling pathways different from that employed by OSM. These data indicate that there may be several regulatory pathways and molecules involved in the antigen-silencing process which may be related to the state of differentiation of the tumor cell and may affect the outcome of antitumor vaccine immunotherapies.

Translocations into human chromosome 14 JH region: factors influencing downstream abortive immunoglobulin class switching.

Bcl-2 translocations in follicular lymphomas (FL) are often associated with downstream immunoglobulin class switch recombination (CSR) on the translocated allele. We studied cell lines with different translocations into the IgH locus to gauge any common features associated with downstream CSR events. CSR associated with chromosomal rearrangements was observed in cells (RL) with translocations similar to those frequently observed in FL (bcl-2-JH), and such CSR was also seen with a myc (near exon 1)-JH5 intron translocation (MC116), but not for far 5'-myc-JH5 intron (P3HR-1) or myc-Smu translocations (Ramos). Both MC116 and P3HR-1 myc translocations showed evidence for an origin from somatic hypermutation. Therefore, the association of JH translocations with CSR on the translocated allele is unlikely to be linked with specific translocation mechanisms, and the P3HR-1 configuration indicated that the downstream class switching is not a necessary consequence of (or precondition for) such a translocation event. MC116 and RL, but not P3HR-1 cells, showed constitutive transcription through the translocated IgH alleles, suggesting that transcription through this region or the processing of such transcripts may promote CSR. However, while CSR events clearly occurred in the precursors of MC116 and RL, neither cell line could undergo complete class switching.

Identification of the bruton tyrosine kinase (BTK) gene mutations in 20 Australian families with X-linked agammaglobulinemia (XLA).

X-linked agammaglobulinemia (XLA) is an immunodeficiency caused by mutations in the Bruton tyrosine kinase (BTK) gene. Twenty Australian patients with an XLA phenotype, from 15 unrelated families, were found to have 14 mutations. Five of the mutations were previously described c.83G>A (p.R28H), c.862C>T (p.R288W), c.904G>A (p.R302G), c.1535T>C (p.L512P), c.700C>T (p.Q234X), while nine novel mutations were identified: four missense c.82C>A (p.R28S), c.494G>A (p.C165Y), c.464G>A (p.C155Y), c.1750G>A (p.G584E), one deletion c.142_144delAGAAGA (p.R48_G50del), and four splice site mutations c.241-2A>G, c.839+4A>G, c.1350-2A>G, c.1566+1G>A. Carrier analysis was performed in 10 mothers and 11 female relatives. The results of this study further support the notion that molecular genetic testing represents an important tool for definitive and early diagnosis of XLA and may allow accurate carrier status and prenatal diagnosis.

Interleukin 12-augmented T cell proliferation of peripheral blood mononuclear cells from HIV-seropositive individuals is associated with interleukin 12 receptor beta 2 upregulation.

Interleukin 12 (IL-12) production is believed to be impaired in individuals with HIV infection and this impairment manifests early in disease, when the CD4(+) cell counts are within normal values. The reduced antigen-specific and mitogen-stimulated T cell-proliferative responses that occur in HIV infection can be corrected by the addition of recombinant human interleukin 12 (rhIL-12). As the IL-12 receptor (IL-12R) is central to the IL-12 signaling pathway, we examined whether the augmentation of antigen-specific proliferation of HIV(+) peripheral blood mononuclear cells (PBMCs) related to altered IL-12R expression. rhIL-12 augmented antigen-specific proliferation of HIV(+) PBMCs but not of HIV(-) PBMCs. Examination of resting PBMCs from HIV(+) and HIV(-) donors showed that neither of these populations expressed IL-12R beta 1 or IL-12R beta 2 chains on their cell surface as detected by flow cytometry. However, examination of mRNA showed that both IL-12R beta 1 and IL-12R beta 2 mRNAs were markedly reduced in HIV(+) PBMCs when compared with HIV(-) PBMCs. After mitogen activation there was an increase in IL-12R beta 1 expression on the cell surface of HIV(+) and HIV(-) PBMCs and this level was not altered by coculture with rhIL-12 or interferon gamma (IFN-gamma). However, coculture of phytohemagglutinin (PHA)-activated HIV(+) or HIV(-) PBMCs with rhIL-12 (but not IFN-gamma) increased IL-12R beta 2 expression on the cell surface of both populations. Examination at the message level showed a correction of IL-12R beta 1 to normal levels with activation that was further enhanced by rhIL-12 coculture for both the HIV(+) and HIV(-) PBMCs. However, although the level of IL-12R beta 2 for the HIV(+) PBMCs was normalized by PHA, rhIL-12 caused a further augmentation. This information provides a strong link between IL-12R upregulation, and the significant improvement in antigen-specific HIV-proliferative responses seen with the addition of rhIL-12. It also reveals that the dysfunction in IL-12R expression seen in cells from HIV(+) patients occurs at the transcriptional level. In addition, we provide further evidence that IL-12R beta 1 and IL-12R beta 2 regulation in human PBMCs is independent of IFN-gamma.

Immunologic manipulation for the threatened fetus.

Management of the pregnant woman with the antiphospholipid syndrome (APLS) has improved over the last 10 years. The recurrent pregnancy loss that is associated with this disease is managed with prophylactic low dose aspirin and heparin therapy. This therapy leads to a 40% absolute risk reduction in pregnancy loss. However, many women still fail to deliver a live infant despite this therapy so immunologic manipulation of the mother's disease in this group needs to be considered. Intravenous immunoglobulin and plasma exchange may have a role. New immunosuppressive drugs such as tacrolimus have yet to be tried. Monoclonal antibodies to B cells, B-cell growth factors, complement proteins and integrin molecules, all of which appear to play a role in the disease process, may also offer patients some hope. Similarly, biologics such as C1 esterase inhibitor protein, cell surface complement regulator proteins or interleukin-3 need to be tried given their efficacy in models of antibody-induced cell injury.

Enhancement of human melanoma antigen expression by IFN-beta.

Although many immunotherapeutic investigations have focused on improving the effector limb of the antitumor response, few studies have addressed preventing the loss of tumor-associated Ag (TAA) expression, associated with immune escape by tumors. We found that TAA loss from human melanomas usually results from reversible gene down-regulation, rather than gene deletion or mutation. Previously, we showed that inhibitors of MAPK-signaling pathways up-regulate TAA expression in melanoma cell lines. We have now identified IFN-beta as an additional stimulus to TAA expression, including Melan-A/MART-1, gp100, and MAGE-A1. IFN-beta (but neither IFN-alpha nor IFN-gamma) augmented both protein and mRNA expression of melanocytic TAA in 15 melanoma lines (irrespective of initial Ag-expression levels). Treatment of low Ag melanoma lines with IFN-beta increased expression of melanocyte-lineage Ags, inducing susceptibility to lysis by specific CTLs. Treatment with IFN-beta also enhances expression of class I HLA molecules, thereby inducing both nominal TAA and the presenting HLA molecule. Data from fluorescent cellular reporter systems demonstrated that IFN-beta triggers promoter activation, resulting in augmentation of Ag expression. In addition to enhancing TAA expression in melanomas, IFN-beta also stimulated expression of the melanocytic Ag gp100 in cells of other neural crest-derived tumor lines (gliomas) and certain unrelated tumors. Because IFN-beta is already approved for human clinical use in other contexts, it may prove useful as a cotreatment for augmenting tumor Ag expression during immunotherapy.

A syndromic rash in patients attending methadone clinics in New South Wales.

We report an outbreak of a "rash" syndrome in patients attending methadone clinics in New South Wales. It presents with a pruritic, exanthematous or purpuric rash involving the trunk, limbs, palms and soles, which develops over a week and proceeds in most patients to desquamation (mainly of palms and soles) persisting for 3-4 weeks. Mucosae are not involved, and patients are generally systemically well. To date, the rash has affected 22% of 316 patients attending one methadone clinic in western Sydney, as well as patients in clinics elsewhere in Sydney and rural NSW. The aetiology is as yet unknown.