Muscle activation patterns during active external rotation after reverse total shoulder arthroplasty: an electrophysiological study of the teres minor and associated musculature.

BACKGROUND: Preoperative teres minor insufficiency has been identified as a risk factor for poor restoration of external rotation (ER) after reverse total shoulder arthroplasty (RTSA). However, there has been little investigation regarding muscle activation patterns generating ER. This prospective study sought to determine the timing and activation levels of the shoulder girdle musculature during ER in well-functioning RTSAs with an intact teres minor using a lateralized design. METHODS: Patients who underwent RTSA ≥1 year previously with functional ER, an American Shoulder and Elbow Surgeons (ASES) score >70, superior rotator cuff deficiency, and an intact teres minor were identified. Electrophysiological and kinematic analyses were performed during ER in the modified neutral position (arm at side with 90° of elbow flexion) and in abduction (AB) (shoulder abducted 90° with 90° of elbow flexion). Dynamometer-recorded torque and position were pattern matched to electromyography during ER. The root-mean-square and integrated electromyography (in microvolts × milliseconds with standard deviation [SD]), as well as median frequency (MF) (in hertz with SD), were calculated to determine muscle recruitment. Pair-wise t test analysis compared muscle activation (P < .05 indicated significance). RESULTS: After an a priori power analysis, 16 patients were recruited. The average ASES score, visual analog scale pain score, and ASES subscore for ER in AB ("comb hair") were 87.7, 0.5, and 2.75 of 3, respectively. In AB, muscle activation began with the upper trapezius, middle trapezius, and latissimus dorsi, followed by the anterior deltoid activating to neutral. With ER beyond neutral, the teres major (9.6 µV × ms; SD, 9.2 µV × ms) initiated ER, followed by the teres minor (14.1 µV × ms; SD, 18.2 µV × ms) and posterior deltoid (11.1 µV × ms; SD, 9.3 µV × ms). MF analysis indicated equal contributions of the teres major (1.1 Hz; SD, 0.5 Hz), teres minor (1.2 Hz; SD, 0.4 Hz), and posterior deltoid (1.1 Hz; SD, 0.4 Hz) in ER beyond neutral. In the modified neutral position, the upper trapezius and middle trapezius were not recruited to the same level as in AB. For ER beyond neutral, the teres major (9.5 µV × ms [SD, 9 µV × ms]; MF, 1.1 Hz [SD, 0.5 Hz]), teres minor (11.4 µV × ms [SD, 15.1 µV × ms]; MF, 1.1 Hz [SD, 0.5 Hz]), and posterior deltoid (8.5 µV × ms [SD, 8 µV × ms]; MF, 1.2 Hz [SD, 0.3 Hz]) were activated in similar sequence and intensity as AB. No differences in muscle activation duration or intensity were noted among the teres major, teres minor, and posterior deltoid (P > .05). CONCLUSION: Active ER after RTSA is complex and is not governed by a single muscle-tendon unit. This study establishes a sequence, duration, and intensity of muscle activation for ER in well-functioning RTSAs. In both tested positions, the teres major, teres minor, and posterior deltoid function equally and sequentially to power ER.

Comparing maternal substance use and perinatal outcomes before and during the COVID-19 pandemic.

OBJECTIVE: To examine the effect of the COVID-19 pandemic on maternal substance abuse and neonatal outcomes. STUDY DESIGN: Cross-sectional observational study of neonates admitted to the NICU and born to mothers with evidence of substance abuse pre-pandemic compared to during the COVID-19 pandemic. RESULT: We noted a significant increase in fentanyl (12% vs. 0.6%, p < 0.001) and tobacco use (64% vs. 33%, p < 0.001) during the pandemic compared to pre-pandemic, including an increase in fentanyl use among mothers enrolled in opioid maintenance therapy (OMT) during the pandemic (32.3% vs. 1.5%, p < 0.001). There was a significant increase in preterm births (58% vs. 48%, p = 0.022) and lower birth weight (2315 ± 815 vs. 2455 ± 861 g, p = 0.049) during pandemic. CONCLUSION: There was a significant increase in maternal fentanyl use during the pandemic, even with OMT enrollment, with an increase in preterm births and lower birth weights among infants born to mothers with substance use.

Comparing Rates of Fusion and Time to Fusion in Viable Cellular Allograft and Autograft.

BACKGROUND: Autograft or allograft frequently are used to enhance bone union in foot and ankle surgery. Viable cellular bone allograft uses viable cells and bone scaffolding in a gel base, but uncertainty remains around allograft's greater efficacy than autograft regarding rates of fusion (ROF) and time to fusion (TTF). METHODS: Autograft, viable cellular allograft, and viable cellular allograft with autograft were compared in 199 forefoot, midfoot, and hindfoot arthrodeses performed over a 6-year period. Data collected from electronic medical records and radiographs were analyzed to determine ROF and TTF as well as rates of revision surgery for delayed or nonunion and compared among groups. RESULTS: Eighty-seven patients comprised the autograft group, 81 the allograft group, and 31 the combined group. No significant differences were noted in patient demographics among the groups. No statistically significant differences in ROF were noted among the 3 groups, with 86% (75 of 87) fusion in the autograft group, 93% (75 of 81) in the allograft group, and 84% (26 of 31) in the combined group (P = .20). After conducting a multivariate analysis, we found no statistically significant difference for allograft or combined graft on TTF (P = .1379 and .2311, respectively). No significant difference was found in rate of revision surgery for nonunion, which was 1.2% (1 of 81) in the allograft group, 3.4% (3 of 87) in the autograft group, and 6.5% (2 of 31) in the combined group (P = .3). CONCLUSION: No significant difference was found in ROF, TTF, or rate of revision surgery when comparing viable cellular allograft to autograft or combined allograft-autograft. Viable cellular allograft may be a reasonable alternative to the gold standard of autograft and should be considered an option in patients undergoing arthrodesis in foot and ankle surgery. LEVEL OF EVIDENCE: Level III, therapeutic.

Pyeloplasty with ureteral stent placement in children: Do prophylactic antibiotics serve a purpose?

OBJECTIVES: Ureteral stents are commonly used during pyeloplasty to ensure drainage and anastomotic healing. Antibiotic prophylaxis is often used due to concerns for urinary tract infection (UTI). Although many surgeons prescribe prophylactic antibiotics following pyeloplasty, practices vary widely due to lack of clear evidence-based guidelines. We hypothesize that the rate of stent UTI does not significantly vary between children who receive antibiotics and those who do not. METHODS: We reviewed the medical records of 741 patients undergoing pyeloplasty between January 2010 and July 2018 across seven institutions. Exclusion criteria were: age older than 22 years, no stent placed, externalized stents used, and incomplete records. Surgical approach, age, antibiotic use, stent duration, Foley duration, and urine culture results were recorded. Patients were categorized into two groups, those younger than four years of age and those four years and older as proxy for likely diaper use. Univariate logistic regression was conducted to identify variables associated with UTI. Multivariable backward stepwise logistic regression was used to identify the best model with Akaike information criterion as model selection criteria. The selected model was used to calculate odds ratios and 95% confidence intervals summarizing the association between prophylactic antibiotics and stent UTI while controlling for age, gender, and intra-operative urine cultures. RESULTS: 672 patients were included; 338 received antibiotic prophylaxis and 334 did not. These groups differed in mean age (3.91 vs. 6.91 years, P < .001), mean stent duration (38.5 vs. 35.32 days, P < .001), and surgical approach (53.25% vs. 32.04% open vs. laparoscopic, P < .001). The incidence of stent UTI was low overall (7.59%) and similar in both groups: 31/338 (9.17%) in the prophylaxis group and 20/334 (5.99%) in the non-prophylaxis group (P = .119). Although female gender, likely diaper use, and positive intra-operative urine culture were each associated with significantly higher odds of stent UTI, prophylactic antibiotic use was not associated with significant reduction in stent UTI in any of these groups. Surgical approach, stent duration, and Foley duration were not associated with stent UTI. CONCLUSION: Incidence of stent UTI is low overall following pyeloplasty. Prophylactic antibiotics are not associated with lower rates of stent UTI following pyeloplasty even after controlling for risk factors of female gender, likely diaper use, and positive intra-operative urine culture. Routine administration of prophylactic antibiotics after pyeloplasty does not appear to be beneficial, and may be best reserved for those with multiple risk factors for UTI.

Allergic airway recall responses require IL-9 from resident memory CD4+ T cells.

Asthma is a chronic inflammatory lung disease with intermittent flares predominately mediated through memory T cells. Yet, the identity of long-term memory cells that mediate allergic recall responses is not well defined. In this report, using a mouse model of chronic allergen exposure followed by an allergen-free rest period, we characterized a subpopulation of CD4+ T cells that secreted IL-9 as an obligate effector cytokine. IL-9-secreting cells had a resident memory T cell phenotype, and blocking IL-9 during a recall challenge or deleting IL-9 from T cells significantly diminished airway inflammation and airway hyperreactivity. T cells secreted IL-9 in an allergen recall-specific manner, and secretion was amplified by IL-33. Using scRNA-seq and scATAC-seq, we defined the cellular identity of a distinct population of T cells with a proallergic cytokine pattern. Thus, in a recall model of allergic airway inflammation, IL-9 secretion from a multicytokine-producing CD4+ T cell population was required for an allergen recall response.

Predictive biomarker modeling of pediatric atopic dermatitis severity based on longitudinal serum collection.

The pathogenesis of atopic dermatitis (AD) results from complex interactions between environmental factors, barrier defects, and immune dysregulation resulting in systemic inflammation. Therefore, we sought to characterize circulating inflammatory profiles in pediatric AD patients and identify potential signaling nodes which drive disease heterogeneity and progression. We analyzed a sample set of 87 infants that were at high risk for atopic disease based on atopic dermatitis diagnoses. Clinical parameters, serum, and peripheral blood mononuclear cells (PBMCs) were collected upon entry, and at one and four years later. Within patient serum, 126 unique analytes were measured using a combination of multiplex platforms and ultrasensitive immunoassays. We assessed the correlation of inflammatory analytes with AD severity (SCORAD). Key biomarkers, such as IL-13 (rmcorr=0.47) and TARC/CCL17 (rmcorr=0.37), among other inflammatory signals, significantly correlated with SCORAD across all timepoints in the study. Flow cytometry and pathway analysis of these analytes implies that CD4 T cell involvement in type 2 immune responses were enhanced at the earliest time point (year 1) relative to the end of study collection (year 5). Importantly, forward selection modeling identified 18 analytes in infant serum at study entry which could be used to predict change in SCORAD four years later. We have identified a pediatric AD biomarker signature linked to disease severity which will have predictive value in determining AD persistence in youth and provide utility in defining core systemic inflammatory signals linked to pathogenesis of atopic disease.

Granzyme A-producing T helper cells are critical for acute graft-versus-host disease.

Acute graft-versus-host disease (aGVHD) can occur after hematopoietic cell transplant in patients undergoing treatment for hematological malignancies or inborn errors. Although CD4+ T helper (Th) cells play a major role in aGVHD, the mechanisms by which they contribute, particularly within the intestines, have remained elusive. We have identified a potentially novel subset of Th cells that accumulated in the intestines and produced the serine protease granzyme A (GrA). GrA+ Th cells were distinct from other Th lineages and exhibited a noncytolytic phenotype. In vitro, GrA+ Th cells differentiated in the presence of IL-4, IL-6, and IL-21 and were transcriptionally unique from cells cultured with either IL-4 or the IL-6/IL-21 combination alone. In vivo, both STAT3 and STAT6 were required for GrA+ Th cell differentiation and played roles in maintenance of the lineage identity. Importantly, GrA+ Th cells promoted aGVHD-associated morbidity and mortality and contributed to crypt destruction within intestines but were not required for the beneficial graft-versus-leukemia effect. Our data indicate that GrA+ Th cells represent a distinct Th subset and are critical mediators of aGVHD.

Sexually Transmitted Infections and Contraceptive Use in Adolescents.

INTRODUCTION: Although a number of contraception methods exist, long-acting reversible contraceptives have been recommended for female adolescents owing to their low failure rates. However, concern exists that the increasing use of long-acting reversible contraceptive among female adolescents may have unintended consequences of decreasing condom use for the prevention of sexually transmitted infections. Despite this concern, few studies have directly explored the relationship between the use of long-acting reversible contraceptive versus other forms of contraception and diagnosis of sexually transmitted infections in female adolescents. This study compares the rates of sexually transmitted infection diagnosis following various forms of contraceptive use. METHODS: This study was an archival data analysis of single state Medicaid claims retrieved for female adolescents, aged 14-19 years, who received a contraceptive prescription and had 1 year of follow-up data available (n=62,550) between 2011 and 2015. Incidence of sexually transmitted infections was the outcome of interest. Data analysis was conducted in 2018. RESULTS: Compared with the contraceptive pill, hormonal implant (a form of long-acting reversible contraceptives) was associated with significantly lower risk of sexually transmitted infections (hazard ratio=0.81; 95% CI=0.70, 0.93; p=0.004), and hormonal injection was associated with higher risk of sexually transmitted infections (hazard ratio=1.08; 95% CI=1.00, 1.16; p=0.040). CONCLUSIONS: This analysis provides strong evidence that the risk for the acquisition of sexually transmitted infections is no higher for long-acting reversible contraceptives than for other forms of contraception. These results support the use of long-acting reversible contraceptive in female adolescents, as proposed and reaffirmed by the American College of Obstetricians and Gynecologists and American Academy of Pediatrics.

Innate Immunity Induced by the Major Allergen Alt a 1 From the Fungus Alternaria Is Dependent Upon Toll-Like Receptors 2/4 in Human Lung Epithelial Cells.

Allergens are molecules that elicit a hypersensitive inflammatory response in sensitized individuals and are derived from a variety of sources. Alt a 1 is the most clinically important secreted allergen of the ubiquitous fungus, Alternaria. It has been shown to be a major allergen causing IgE-mediated allergic response in the vast majority of Alternaria-sensitized individuals. However, no studies have been conducted in regards to the innate immune eliciting activities of this clinically relevant protein. In this study, recombinant Alt a 1 was produced, purified, labeled, and incubated with BEAS-2B, NHBE, and DHBE human lung epithelial cells. Alt a 1 elicited strong induction of IL-8, MCP-1, and Gro-a/b/g. Using gene-specific siRNAs, blocking antibodies, and chemical inhibitors such as LPS-RS, it was determined that Alt a 1-induced immune responses were dependent upon toll-like receptors (TLRs) 2 and 4, and the adaptor proteins MYD88 and TIRAP. Studies utilizing human embryonic kidney cells engineered to express single receptors on the cell surface such as TLRs, further confirmed that Alt a 1-induced innate immunity is dependent upon TLR4 and to a lesser extent TLR2.

Characterizing and measuring endocytosis of lipid-binding effectors in mammalian cells.

Pathogen-host interactions are mediated in part by secreted microbial proteins capable of exploiting host cells for their survival. Several of these manipulations involve, but are not limited to, suppression of defense responses, alterations in host vesicular trafficking, and manipulation of gene expression. The delivery of such molecules from microbe to host has been of intense interest in several microbe-host systems. Several well-studied bacterial effectors are delivered directly into host cells through a needle injection apparatus. Conversely, there have been several examples of secreted effectors and protein toxins from bacteria and eukaryotic microbes, such as fungi and oomycetes, being internalized into host cells by receptor-mediated endocytosis. In the following chapter, we discuss various techniques utilized to measure these endocytosed lipid-binding effectors that can be delivered in the absence of the pathogen.

Microbe-independent entry of oomycete RxLR effectors and fungal RxLR-like effectors into plant and animal cells is specific and reproducible.

A wide diversity of pathogens and mutualists of plant and animal hosts, including oomycetes and fungi, produce effector proteins that enter the cytoplasm of host cells. A major question has been whether or not entry by these effectors can occur independently of the microbe or requires machinery provided by the microbe. Numerous publications have documented that oomycete RxLR effectors and fungal RxLR-like effectors can enter plant and animal cells independent of the microbe. A recent reexamination of whether the RxLR domain of oomycete RxLR effectors is sufficient for microbe-independent entry into host cells concluded that the RxLR domains of Phytophthora infestans Avr3a and of P. sojae Avr1b alone are NOT sufficient to enable microbe-independent entry of proteins into host and nonhost plant and animal cells. Here, we present new, more detailed data that unambiguously demonstrate that the RxLR domain of Avr1b does show efficient and specific entry into soybean root cells and also into wheat leaf cells, at levels well above background nonspecific entry. We also summarize host cell entry experiments with a wide diversity of oomycete and fungal effectors with RxLR or RxLR-like motifs that have been independently carried out by the seven different labs that coauthored this letter. Finally we discuss possible technical reasons why specific cell entry may have been not detected by Wawra et al. (2013).