Subacromial balloon spacer massive rotator cuff tear treatment systematic review and meta-analysis: Patient selection and physical therapy may be keys to outcome success.

PURPOSE: Subacromial balloon spacer implantation (SBSI) efficacy for massive rotator cuff tear treatment was evaluated based on perceived shoulder function, active shoulder mobility, pain, complications and research study methodological quality. The purpose was to better discern the efficacy of this device from both surgical and rehabilitative perspectives to improve patient outcomes. METHODS: PubMed, EMBASE and Cochrane Library databases were searched (1 January 2010 to 1 June 2024) using 'balloon spacer', 'subacromial spacer', 'subacromial balloon spacer', 'shoulder spacer' and 'inspace' terms. Pre-surgery (baseline), 12-month (12-m) and 24-month (24-m) post-SBSI mean changes were compared using one-way ANOVA and Scheffe post hoc tests, and comparative study effect sizes were calculated (p ≤ 0.05). RESULTS: This review consists of 27 studies with 894 patients (67.8 ± 5 years of age) and 29.4 ± 17-month follow-up. Modified Coleman Methodology Scores (MCMS) revealed fair overall quality (mean = 61.4 ± 11). Constant-Murley scores improved from 34.8 ± 6 (baseline), to 64.2 ± 9 (12-m) and 67.9 ± 8 (24-m) (12-m, 24-m > baseline, p < 0.001). ASES scores improved from 35.1 ± 14 (baseline), to 83.3 ± 7 (12-m) and 81.8 ± 5 (24-m)(12-m, 24-m > baseline, p < 0.001). VAS pain scores improved from 6.6 ± 1 (baseline), to 2.6 ± 1 (12-m) and 2.0 ± 1 (24-m) (12-m, 24-m < baseline, p < 0.001). Flexion increased from 108.5 ± 25° (baseline), to 128.5 ± 30° (12-m) and 151.2 ± 14° (24-m) (24-m > 12-m, baseline, p = 0.01). Abduction increased from 97.7 ± 24° (baseline) to 116.3 ± 23° (12-m) and 142.3 ± 15° (24-m) (24-m > 12-m, baseline, p = 0.02). External rotation (ER) in adduction changed from 33.1 ± 7° (baseline) to 32.5 ± 4° (12-m) and 53.9 ± 9° (24-m)(24-m > 12-m, baseline, p = 0.01). ER at 90° abduction increased from 56.3 ± 3° (baseline) to 83.5 ± 5° (12-m) and 77.1 ± 4° (24-m) (24-m, 12-m > baseline, p = 0.01). Comparison studies, however, displayed insignificant results with small effect sizes. CONCLUSION: Despite overall fair MCMS scores, at 24-m post-SBSI, shoulder function improved and pain decreased. More rigorous comparative studies, however, revealed insignificant findings. Patients with the potential to re-establish the essential glenohumeral joint force couple that depresses the humeral head on the glenoid fossa and who comply with physical therapy may be more likely to achieve success following SBSI. LEVEL OF EVIDENCE: Level IV.

Incidence of Instability Following Primary Total Hip Arthroplasty Continues to Decline in the Medicare Population.

BACKGROUND: Instability has been the primary cause of failure following primary total hip arthroplasty (THA) leading to revision hip surgery. The purpose of this study was to determine if instability rates have further declined following advances in primary THA, including dual mobility articulations, direct anterior approaches, advanced technologies, and improved knowledge of the hip-spine relationships. METHODS: Using the 5% Medicare Part B claims data from 1999 to 2019, we identified 81,573 patients who underwent primary THA for osteoarthritis. Patients who experienced instability at 3 months, 6 months, 1 year, and 2 years were identified. Multivariate cox regression analyses evaluated the effect of patient and procedure characteristics on the risk of instability. RESULTS: Instability at 1 year following primary THA declined from approximately 4% in 2000 to 2.3% in 2010 and 1.6% in 2018. The leading cause of revision surgery was infection (18.6%), followed by periprosthetic fracture (14%), mechanical loosening (11.5%), and instability (9.4%). High-risk groups for instability continue to include increased age, higher Charlson index, obesity, lumbar spine pathology, and neurocognitive disorders. CONCLUSION: Instability is no longer the leading etiology of failure following primary THA with a decline of approximately 40% over the past decade. Infection, periprosthetic fracture, mechanical loosening, and then instability are now the leading causes of failure. Multiple factors may play a role in the decline of instability, including increased use of dual mobility articulations, direct anterior approaches, improved knowledge of the hip-spine relationships, and use of advanced technologies.

Naturally Occurring Subclinical Endotoxemia in Humans Alters Adaptive and Innate Immune Functions through Reduced MAPK and Increased STAT1 Phosphorylation.

Multiple studies have shown correlates of immune activation with microbial translocation and plasma LPS during HIV infection. It is unclear whether this activation is due to LPS, residual viral replication, or both. Few studies have addressed the effects of persistent in vivo levels of LPS on specific immune functions in humans in the absence of chronic viral infection or pathological settings such as sepsis. We previously reported on a cohort of HIV-negative men with subclinical endotoxemia linked to alterations in CD4/CD8 T cell ratio and plasma cytokine levels. This HIV-negative cohort allowed us to assess cellular immune functions in the context of different subclinical plasma LPS levels ex vivo without confounding viral effects. By comparing two samples of differing plasma LPS levels from each individual, we now show that subclinical levels of plasma LPS in vivo significantly alter T cell proliferative capacity, monocyte cytokine release, and HLA-DR expression, and induce TLR cross-tolerance by decreased phosphorylation of MAPK pathway components. Using this human in vivo model of subclinical endotoxemia, we furthermore show that plasma LPS leads to constitutive activation of STAT1 through autocrine cytokine signaling, suggesting that subclinical endotoxemia in healthy individuals might lead to significant changes in immune function that have thus far not been appreciated.

Change in liver, spleen and bone marrow magnetic resonance imaging signal intensity over time in children with solid abdominal tumors.

BACKGROUND: Reticuloendothelial system MRI signal hypointensity is common in pediatric oncology patients with solid abdominal tumors. OBJECTIVE: To assess changes in liver, spleen and bone marrow T2-weighted MRI signal intensity over time and their relationship to blood transfusion history in children with solid abdominal tumors. MATERIALS AND METHODS: In this retrospective study we measured liver, spleen and bone marrow signal intensity on axial T2-weighted MR images obtained December 2009 through February 2016 in children with hepatoblastoma, neuroblastoma, ganglioneuroblastoma and Wilms tumor. All signal intensity measurements were normalized to paraspinal muscle signal intensity. We used linear mixed models (including a day*day quadratic term) to determine whether organ signal intensity changed over time and whether change was associated with blood transfusion volume or tumor type. RESULTS: We included 133 children (mean age at diagnosis =2.9 years); 56 had neuroblastoma, 42 hepatoblastoma, 28 Wilms tumor and 7 ganglioneuroblastoma. Seventy-nine (59.4%) children received transfusions (median: 8 transfusions, range: 1-30; mean volume: 1,148.5 mL). Hepatic, splenic and bone marrow signal intensity ratios changed quadratically over time for the study population, initially decreasing and then increasing (P<0.0001). Children receiving less than the mean blood transfusion volume showed no significant change in tissue signal intensity, while those receiving more than the mean volume showed significant changes in signal intensity over time (P<0.0001). Compared to children with Wilms tumor, those with neuroblastoma exhibited significantly lower hepatic (P=0.03) signal intensity ratios. CONCLUSION: Liver, spleen and bone marrow T2-weighted MRI signal intensity ratios change over time in some pediatric patients with solid abdominal tumors, likely from tissue iron deposition related to blood transfusions and perhaps because of tumor type.

Sex Differences in Plasmacytoid Dendritic Cell Levels of IRF5 Drive Higher IFN-α Production in Women.

Increased IFN-α production contributes to the pathogenesis of infectious and autoimmune diseases. Plasmacytoid dendritic cells (pDCs) from females produce more IFN-α upon TLR7 stimulation than pDCs from males, yet the mechanisms underlying this difference remain unclear. In this article, we show that basal levels of IFN regulatory factor (IRF) 5 in pDCs were significantly higher in females compared with males and positively correlated with the percentage of IFN-α-secreting pDCs. Delivery of recombinant IRF5 protein into human primary pDCs increased TLR7-mediated IFN-α secretion. In mice, genetic ablation of the estrogen receptor 1 (Esr1) gene in the hematopoietic compartment or DC lineage reduced Irf5 mRNA expression in pDCs and IFN-α production. IRF5 mRNA levels furthermore correlated with ESR1 mRNA levels in human pDCs, consistent with IRF5 regulation at the transcriptional level by ESR1. Taken together, these data demonstrate a critical mechanism by which sex differences in basal pDC IRF5 expression lead to higher IFN-α production upon TLR7 stimulation in females and provide novel targets for the modulation of immune responses and inflammation.

Increased frequency and function of KIR2DL1-3⁺ NK cells in primary HIV-1 infection are determined by HLA-C group haplotypes.

The acquisition and maintenance of NK-cell function is mediated by inhibitory killer-cell immunoglobulin-like receptors (KIRs) through their interaction with HLA class I molecules. Recently, HLA-C expression levels were shown to be correlated with protection against multiple outcomes of HIV-1 infection; however, the underlying mechanisms are poorly understood. As HLA-C is the natural ligand for the inhibitory receptors KIR2DL1 and KIR2DL2/3, we sought to determine whether HLA-C group haplotypes affect NK-cell responses during primary HIV-1 infection. The phenotypes and functional capacity of NK cells derived from HIV-1-positive and HIV-1-negative individuals were assessed (N = 42 and N = 40, respectively). HIV-1 infection was associated with an increased frequency of KIR2DL1-3(+) NK cells. Further analysis showed that KIR2DL1(+) NK cells were selectively increased in individuals homozygous for HLA-C2, while HLA-C1-homozygous individuals displayed increased proportions of KIR2DL2/3(+) NK cells. KIR2DL1-3(+) NK cells were furthermore more polyfunctional during primary HIV-1 infection in individuals also encoding for their cognate HLA-C group haplotypes, as measured by degranulation and IFN-γ and TNF-α production. These results identify a novel relationship between HLA-C and KIR2DL(+) NK-cell subsets and demonstrate that HLA-C-mediated licensing modulates NK-cell responses to primary HIV-1 infection.

Antiretroviral-free HIV-1 remission and viral rebound after allogeneic stem cell transplantation: report of 2 cases.

BACKGROUND: It is unknown whether the reduction in HIV-1 reservoirs seen after allogeneic hematopoietic stem cell transplantation (HSCT) with susceptible donor cells is sufficient to achieve sustained HIV-1 remission. OBJECTIVE: To characterize HIV-1 reservoirs in blood and tissues and perform analytic antiretroviral treatment interruptions to determine the potential for allogeneic HSCT to lead to sustained, antiretroviral-free HIV-1 remission. DESIGN: Case report with characterization of HIV-1 reservoirs and immunity before and after antiretroviral interruption. SETTING: Tertiary care center. PATIENTS: Two men with HIV with undetectable HIV-1 after allogeneic HSCT for hematologic tumors. MEASUREMENTS: Quantification of HIV-1 in various tissues after HSCT and the duration of antiretroviral-free HIV-1 remission after treatment interruption. RESULTS: No HIV-1 was detected from peripheral blood or rectal mucosa before analytic treatment interruption. Plasma HIV-1 RNA and cell-associated HIV-1 DNA remained undetectable until 12 and 32 weeks after antiretroviral cessation. Both patients experienced rebound viremia within 2 weeks of the most recent negative viral load measurement and developed symptoms consistent with the acute retroviral syndrome. One patient developed new efavirenz resistance after reinitiation of antiretroviral therapy. Reinitiation of active therapy led to viral decay and resolution of symptoms in both patients. LIMITATION: The study involved only 2 patients. CONCLUSION: Allogeneic HSCT may lead to loss of detectable HIV-1 from blood and gut tissue and variable periods of antiretroviral-free HIV-1 remission, but viral rebound can occur despite a minimum 3-log10 reduction in reservoir size. Long-lived tissue reservoirs may have contributed to viral persistence. The definition of the nature and half-life of such reservoirs is essential to achieve durable antiretroviral-free HIV-1 remission. PRIMARY FUNDING SOURCE: Foundation for AIDS Research and National Institute of Allergy and Infectious Diseases.

Tumor necrosis factor α is associated with viral control and early disease progression in patients with HIV type 1 infection.

Inflammation in early human immunodeficiency virus type 1 (HIV-1) disease progression is not well characterized. Ninety patients with untreated primary HIV-1 infection were studied to determine associations of inflammatory proteins with early disease progression. High plasma tumor necrosis factor α (TNF-α) levels (≥8.5 pg/mL) were significantly associated with an increased viral load set point and shorter times to reaching a CD4(+) T-cell count of <500 cells/mm(3) and initiating antiretroviral therapy. The increased risk of reaching a CD4(+) T-cell count of <500 cells/mm(3) in the group with high TNF-α levels was driven by viral load but was independent of concurrent CD4(+) T-cell count. Thus, TNF-α appears to be an important mediator of inflammation in patients with poor viral control and early HIV-1 disease progression.

Regenerative Anterior Cruciate Ligament Healing in Youth and Adolescent Athletes: The Emerging Age of Recovery Science.

Anterior cruciate ligament (ACL) injuries mainly arise from non-contact mechanisms during sport performance, with most injuries occurring among youth or adolescent-age athletes, particularly females. The growing popularity of elite-level sport training has increased the total volume, intensity and frequency of exercise and competition loading to levels that may exceed natural healing capacity. Growing evidence suggests that the prevailing mechanism that leads to non-contact ACL injury from sudden mechanical fatigue failure may be accumulated microtrauma. Given the consequences of primary ACL injury on the future health and quality of life of youth and adolescent athletes, the objective of this review is to identify key "recovery science" factors that can help prevent these injuries. Recovery science is any aspect of sports training (type, volume, intensity, frequency), nutrition, and sleep/rest or other therapeutic modalities that may prevent the accumulated microtrauma that precedes non-contact ACL injury from sudden mechanical fatigue failure. This review discusses ACL injury epidemiology, current surgical efficacy, the native ACL vascular network, regional ACL histological complexities such as the entheses and crimp patterns, extracellular matrix remodeling, the concept of causal histogenesis, exercise dosage and ligament metabolism, central nervous system reorganization post-ACL rupture, homeostasis regulation, nutrition, sleep and the autonomic nervous system. Based on this information, now may be a good time to re-think primary ACL injury prevention strategies with greater use of modified sport training, improved active recovery that includes well-planned nutrition, and healthy sleep patterns. The scientific rationale behind the efficacy of regenerative orthobiologics and concomitant therapies for primary ACL injury prevention in youth and adolescent athletes are also discussed.

Reamer Irrigator Aspirator Versus Iliac Crest Bone Grafting and Proximal Tibial Curettage: Is There a Difference in Blood Loss and Transfusion Rates?

OBJECTIVES: To compare blood loss and transfusion rates among reamer irrigator aspirator (RIA), iliac crest bone graft (ICBG), and proximal tibial curettage (PTC) for autograft harvest. DESIGN: Retrospective comparative study. SETTING: Level 1 trauma center. PATIENTS/PARTICIPANTS: The study included 139 adult patients treated between 2011 and 2018. INTERVENTIONS: Nonunion repair of the femur or tibia using either RIA (n = 64), ICBG (n = 59), or PTC (n = 16) for autograft. MAIN OUTCOME MEASUREMENTS: Estimated blood loss and transfusion rates. RESULTS: Patient demographics, surgical indications, and medical comorbidities that affect bleeding did not differ among the groups. Estimated blood loss (mL) was significantly higher in the RIA group [RIA: 388 ± 368 (50-2000), ICBG: 286 ± 344 (10-2000), PTC: 196 mL ± 219 (10-700), P < 0.01]. The transfusion rate was also significantly higher in the RIA group (RIA 14%, ICBG 0%, PTC 0%, P < 0.01). The amount of graft obtained was higher in the RIA group (RIA = 48.3 mL, ICBG = 31.0 mL, PTC = 18.8 mL, P < 0.01), and the operative time (hours) was longer in the RIA group (RIA = 2.8, ICBG = 2.6, PTC = 1.9, P = 0.04). CONCLUSION: Estimated blood loss and transfusion rates were significantly higher in patients undergoing RIA compared with those in patients undergoing ICBG and PTC; however, the incidence of transfusion after RIA (14%) was considerably lower than previous reports. These findings suggest that the risk of transfusion after RIA is present and clinically significant but lower than previously believed, and it is likely affected by the amount of graft obtained and complexity of the nonunion repair. The risk of transfusion should be discussed with patients and the choice of RIA carefully evaluated in patients who have anemia or risk factors of bleeding. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Enhanced immune activation linked to endotoxemia in HIV-1 seronegative MSM.

This study assessed cellular and soluble markers of immune activation in HIV-1 seronegative MSM. MSM immune profiles were characterized by an increased expression of CD57 on T cells and endotoxemia. Endotoxin presence was linked to recent high-risk exposure and associated with elevated cytokine levels and decreased CD4+/CD8+ T cell ratios. Taken together, these data show elevated levels of inflammation linked to periods of endotoxemia resulting in a significantly different immune phenotype in a subset of MSM at a high risk of HIV-1 acquisition.