Acidic chitinase primes the protective immune response to gastrointestinal nematodes.

Acidic mammalian chitinase (AMCase) is known to be induced by allergens and helminths, yet its role in immunity is unclear. Using AMCase-deficient mice, we show that AMCase deficiency reduced the number of group 2 innate lymphoid cells during allergen challenge but was not required for establishment of type 2 inflammation in the lung in response to allergens or helminths. In contrast, AMCase-deficient mice showed a profound defect in type 2 immunity following infection with the chitin-containing gastrointestinal nematodes Nippostrongylus brasiliensis and Heligmosomoides polygyrus bakeri. The impaired immunity was associated with reduced mucus production and decreased intestinal expression of the signature type 2 response genes Il13, Chil3, Retnlb, and Clca1. CD103(+) dendritic cells, which regulate T cell homing, were also reduced in mesenteric lymph nodes of infected AMCase-deficient mice. Thus, AMCase functions as a critical initiator of protective type 2 responses to intestinal nematodes but is largely dispensable for allergic responses in the lung.

Type 2 Interleukin-4 Receptor Signaling in Neutrophils Antagonizes Their Expansion and Migration during Infection and Inflammation.

Neutrophils are the first immune cells recruited to sites of inflammation and infection. However, patients with allergic disorders such as atopic dermatitis show a paucity of skin neutrophils and are prone to bacterial skin infections, suggesting that allergic inflammation curtails neutrophil responses. Here we have shown that the type 2 cell signature cytokine interleukin-4 (IL-4) hampers neutrophil expansion and migration by antagonizing granulocyte colony-stimulating factor (G-CSF) and chemokine receptor-mediated signals. Cutaneous bacterial infection in mice was exacerbated by IL-4 signaling and improved with IL-4 inhibition, each outcome inversely correlating with neutrophil migration to skin. Likewise, systemic bacterial infection was worsened by heightened IL-4 activity, with IL-4 restricting G-CSF-induced neutrophil expansion and migration to tissues by affecting CXCR2-CXCR4 chemokine signaling in neutrophils. These effects were dependent on IL-4 acting through type 2 IL-4 receptors on neutrophils. Thus, targeting IL-4 might be beneficial in neutropenic conditions with increased susceptibility to bacterial infections.

Venographic classification and long-term surgical treatment outcomes for axillary-subclavian vein thrombosis due to venous thoracic outlet syndrome (Paget-Schroetter syndrome).

OBJECTIVE: We assessed the clinical presentation, operative findings, and surgical treatment outcomes for axillary-subclavian vein (AxSCV) thrombosis due to venous thoracic outlet syndrome (VTOS). METHODS: We performed a retrospective, single-center review of 266 patients who had undergone primary surgical treatment of VTOS between 2016 and 2022. The clinical outcomes were compared between the patients in four treatment groups determined by intraoperative venography. RESULTS: Of the 266 patients, 132 were male and 134 were female. All patients had a history of spontaneous arm swelling and idiopathic AxSCV thrombosis, including 25 (9%) with proven pulmonary embolism, at a mean age of 32.1 ± 0.8 years (range, 12-66 years). The timing of clinical presentation was acute (<15 days) for 132 patients (50%), subacute (15-90 days) for 71 (27%), and chronic (>90 days) for 63 patients (24%). Venography with catheter-directed thrombolysis or thrombectomy (CDT) and/or balloon angioplasty had been performed in 188 patients (71%). The median interval between symptom onset and surgery was 78 days. After paraclavicular thoracic outlet decompression and external venolysis, intraoperative venography showed a widely patent AxSCV in 150 patients (56%). However, 26 (10%) had a long chronic AxSCV occlusion with axillary vein inflow insufficient for bypass reconstruction. Patch angioplasty was performed for focal AxSCV stenosis in 55 patients (21%) and bypass graft reconstruction for segmental AxSCV occlusion in 35 (13%). The patients who underwent external venolysis alone (patent or occluded AxSCV; n = 176) had a shorter mean operative time, shorter postoperative length of stay and fewer reoperations and late reinterventions compared with those who underwent AxSCV reconstruction (patch or bypass; n = 90), with no differences in the incidence of overall complications or 30-day readmissions. At a median clinical follow-up of 38.7 months, 246 patients (93%) had no arm swelling, and only 17 (6%) were receiving anticoagulation treatment; 95% of those with a patent AxSCV at the end of surgery were free of arm swelling vs 69% of those with a long chronic AxSCV occlusion (P < .001). The patients who had undergone CDT at the initial diagnosis were 32% less likely to need AxSCV reconstruction at surgery (30% vs 44%; P = .034) and 60% less likely to have arm swelling at follow-up (5% vs 13%; P < .05) vs those who had not undergone CDT. CONCLUSIONS: Paraclavicular decompression, external venolysis, and selective AxSCV reconstruction determined by intraoperative venography findings can provide successful and durable treatment for >90% of all patients with VTOS. Further work is needed to achieve earlier recognition of AxSCV thrombosis, prompt usage of CDT, and even more effective surgical treatment.

Reliability and validity of the standardized elevated arm stress test in the diagnosis of neurogenic thoracic outlet syndrome.

OBJECTIVE: We developed a standardized elevated arm stress test (sEAST) meter to standardize patients' posture and measure additional grip and fatigue parameters. In the present prospective cohort study, we aimed to determine the reliability and validity of the sEAST in the diagnosis of neurogenic thoracic outlet syndrome (NTOS). METHODS: Patients evaluated for NTOS between October 2018 and February 2020 were included and performed the sEAST. The patients were classified into a proven NTOS group or a symptomatic control group using the reporting standards for NTOS and the outcome of thoracic outlet decompression surgery. Healthy persons were recruited as an asymptomatic control group. The test-retest reliability, area under the receiver operating characteristic curve, and positive and negative predictive values were calculated for each sEAST parameter. RESULTS: A total of 426 patients with suspected NTOS and 147 healthy controls had performed the sEAST. The validity analysis was performed with data from 111 patients with proven NTOS, 94 symptomatic controls, and 147 asymptomatic controls. The reporting standards were inconclusive for 116 patients; 77 patients had been excluded because thoracic outlet decompression surgery had not been performed or was unsuccessful, and 28 because they had arterial or venous thoracic outlet syndrome. The area under the receiver operating characteristic curve for the proven NTOS group compared with the asymptomatic control and symptomatic control groups ranged from 0.59 to 0.77 and 0.54 to 0.63, respectively. The positive predictive value ranged from 46% to 65% and the negative predictive value from 51% to 66%. The test-retest reliability analysis for 80 patients with multiple sEAST measurements showed moderate to good (0.52-0.87) intraclass correlation coefficient values for the duration and grip strength parameters. However, the grip fatigue parameters demonstrated poor (0.46-0.16) intraclass correlation coefficient values. CONCLUSIONS: The sEAST showed good test-retest reliability for the duration and grip strength parameters. However, the discriminative value of all sEAST parameters was low for NTOS diagnostics. The good test-retest reliability of the sEAST parameters indicates that they could be valuable outcome measures for comparison in a diagnostic care pathway.

Reliability and validity of the elevated arm stress test in the diagnosis of neurogenic thoracic outlet syndrome.

OBJECTIVES: The objective of this retrospective analysis of prospectively collected data was to assess the test-retest reliability and validity of the elevated arm stress test (EAST) as measured by the duration in a cohort of patients with suspected neurogenic thoracic outlet syndrome (NTOS). METHODS: Patients evaluated for NTOS between January 2017 and September 2018 were identified. Test-retest reliability by the intraclass correlation coefficient was determined for duration of the EAST. For the validity analysis, patients were classified in a proven NTOS group or a symptomatic control group without NTOS using the Society for Vascular Surgery reporting standards and the outcome of thoracic outlet decompression surgery. A receiver operating characteristic curve was made for the duration of EAST. The area under the curve, and positive and negative predictive values were calculated for the EAST. RESULTS: In total, 428 patients with suspected NTOS were retrospectively analyzed. Of these patients, 61 were excluded because no EAST data was available. Another 101 patients were excluded because of inconclusive reporting standards, arterial or venous TOS, or because thoracic outlet decompression surgery was not performed or had a negative result. The validity analysis in the remaining 266 patients showed an area under the curve for the duration of the EAST of 0.62 (95% confidence interval, 0.55-0.69). The positive predictive value of the duration ranged between 65% and 66%, and the negative predictive value between 53% and 58%. For the test-retest reliability analysis, 118 patients were excluded because they performed only one measurement in a 100-day time period. Analysis in the remaining 148 patients showed an intraclass correlation coefficient value of 0.65 (95% confidence interval, 0.55-0.74) for duration. CONCLUSIONS: The EAST measured by the duration showed a moderate test-retest reliability, but the discriminative value was low in the diagnosis of NTOS. The outcome of the EAST measured by the duration should be used with caution.

Duplex Ultrasound Studies Are Neither Necessary or Sufficient for the Diagnosis of Neurogenic Thoracic Outlet Syndrome.

BACKGROUND: Duplex ultrasound (DU) is used in the diagnosis of neurogenic thoracic outlet syndrome (NTOS) to measure compression of the subclavian artery (SCA) which is thought to strengthen the NTOS diagnosis. However, the value of DU in NTOS remains unclear. METHODS: A retrospective review of a prospectively acquired database from the TOS center of the Catharina Hospital Eindhoven was performed of patients referred between January 2017 and December 2019. Only "proven NTOS" patients, defined as a successful response to thoracic outlet decompression (TOD) surgery based on patient-reported outcomes (NRS pain scale, CBSQ and DASH score) were included to exclude wrongfully diagnosed NTOS patient. The presence of vascular symptoms (defined as discoloration, edema or temperature changes of the hand or fingers), results of provocative maneuvers, and outcome of DU was used for analysis. To assess the link between vascular symptoms and compression on DU, a chi-squared test was performed. Further, we looked for a correlation between vascular symptoms, compression on DU and clinical outcome using a repeated measures analysis of variance (ANOVA). RESULTS: Vascular symptoms were seen in 49 of 133 patients (36.8%). In total, 51 of 133 patients (38.3%) had at least 50% variation in SCA peak systolic velocity (PSV) during DU at the level of SCA stenosis. SCA occlusion was seen in 11 patients (8.3%) during provocative maneuvers. The presence of clinical "arterial symptoms" was not significantly correlated with vascular laboratory findings, neither for alterations in PSV during DU (P = 0.245) nor for positional SCA occlusion (P = 0.540). No statistically significant correlations between the degree of SCA stenosis and postoperative outcomes, as measured with the DASH, CBSQ, or NRS scale for pain were found (P = 0.787). CONCLUSIONS: The role of DU in the work-up of NTOS in patients with vascular complaints is questionable. Changes in flow velocities are seen in NTOS patients and do not correlate with "vascular symptoms" or clinical outcome.

Erector Spinae Plane Block versus Continuous Perineural Local Anesthetic Infusion for Postoperative Pain Control After Supraclavicular Decompression for Neurogenic Thoracic Outlet Syndrome: A Matched Case-Control Comparison.

OBJECTIVE: The purpose of this study was to determine if single injection erector spinae plane blocks are associated with improved pain control, opioid use, numbness, length of stay, or patient satisfaction compared to intraoperatively placed continuous perineural infusion of local anesthetic after decompression of neurogenic thoracic outlet syndrome. METHODS: This is a retrospective cohort study at a tertiary academic center of eighty patients that underwent supraclavicular decompression for thoracic outlet syndrome between May 2019 and January 2020. Forty consecutive patients treated with single-injection preoperative erector spinae plane blocks were retrospectively compared to 40 age- and gender-matched controls treated with continuous perineural infusion. RESULTS: The primary outcome of mean pain scores was not significantly different between the erector spinae and perineural infusion groups over the three-day study period (4.2-5.3 vs 3.0-5.1 P=0.08). On post-operative day 0, mean pain scores were significantly higher in the erector spinae group (4.2 vs 3.0, P=0.02). While statistically significant, the score was still lower in the erector spinae group on day 0 than on day 1,2, or 3 in either group. Opioid use, nausea, length of stay and patient satisfaction were also similar. Upper extremity numbness was significantly less severe in the erector spinae group (36% vs 73% moderate-extreme, P=0.03) at 6-month follow-up. CONCLUSIONS: Seventy-two-hour perineural local anesthetic infusion did not provide superior analgesia compared to preoperative single-injection erector spinae blocks. Furthermore, there was significantly less long-term postoperative numbness associated with erector spinae blocks compared to perineural local anesthetic infusion.

Toll-like receptor-induced arginase 1 in macrophages thwarts effective immunity against intracellular pathogens.

Toll-like receptor (TLR) signaling in macrophages is required for antipathogen responses, including the biosynthesis of nitric oxide from arginine, and is essential for immunity to Mycobacterium tuberculosis, Toxoplasma gondii and other intracellular pathogens. Here we report a 'loophole' in the TLR pathway that is advantageous to these pathogens. Intracellular pathogens induced expression of the arginine hydrolytic enzyme arginase 1 (Arg1) in mouse macrophages through the TLR pathway. In contrast to diseases dominated by T helper type 2 responses in which Arg1 expression is greatly increased by interleukin 4 and 13 signaling through the transcription factor STAT6, TLR-mediated Arg1 induction was independent of the STAT6 pathway. Specific elimination of Arg1 in macrophages favored host survival during T. gondii infection and decreased lung bacterial load during tuberculosis infection.

Evaluation and treatment of thoracic outlet syndrome during the global pandemic due to SARS-CoV-2 and COVID-19.

The global SARS-CoV-2/COVID-19 pandemic has required a reduction in nonemergency treatment for a variety of disorders. This report summarizes conclusions of an international multidisciplinary consensus group assembled to address evaluation and treatment of patients with thoracic outlet syndrome (TOS), a group of conditions characterized by extrinsic compression of the neurovascular structures serving the upper extremity. The following recommendations were developed in relation to the three defined types of TOS (neurogenic, venous, and arterial) and three phases of pandemic response (preparatory, urgent with limited resources, and emergency with complete diversion of resources). • In-person evaluation and treatment for neurogenic TOS (interventional or surgical) are generally postponed during all pandemic phases, with telephone/telemedicine visits and at-home physical therapy exercises recommended when feasible. • Venous TOS presenting with acute upper extremity deep venous thrombosis (Paget-Schroetter syndrome) is managed primarily with anticoagulation, with percutaneous interventions for venous TOS (thrombolysis) considered in early phases (I and II) and surgical treatment delayed until pandemic conditions resolve. Catheter-based interventions may also be considered for selected patients with central subclavian vein obstruction and threatened hemodialysis access in all pandemic phases, with definitive surgical treatment postponed. • Evaluation and surgical treatment for arterial TOS should be reserved for limb-threatening situations, such as acute upper extremity ischemia or acute digital embolization, in all phases of pandemic response. In late pandemic phases, surgery should be restricted to thrombolysis or brachial artery thromboembolectomy, with more definitive treatment delayed until pandemic conditions resolve.

Physical therapy management, surgical treatment, and patient-reported outcomes measures in a prospective observational cohort of patients with neurogenic thoracic outlet syndrome.

OBJECTIVE: To assess the results of physical therapy management and surgical treatment in a prospective observational cohort of patients with neurogenic thoracic outlet syndrome (NTOS) using patient-reported outcomes measures. METHODS: Of 183 new patient referrals from July 1 to December 31, 2015, 150 (82%) met the established clinical diagnostic criteria for NTOS. All patients underwent an initial 6-week physical therapy trial. Those with symptom improvement continued physical therapy, and the remainder underwent surgery (supraclavicular decompression with or without pectoralis minor tenotomy). Pretreatment factors and 7 patient-reported outcomes measures were compared between the physical therapy and surgery groups using t-tests and χ2 analyses. Follow-up results were assessed by changes in 11-item version of Disability of the Arm, Shoulder, and Hand (QuickDASH) scores and patient-rated outcomes. RESULTS: Of the 150 patients, 20 (13%) declined further treatment or follow-up, 40 (27%) obtained satisfactory improvement with physical therapy alone, and 90 (60%) underwent surgery. Slight differences were found between the physical therapy and surgery groups in the mean ± standard error degree of local tenderness to palpation (1.7 ± 0.1 vs 2.0 ± 0.1; P = .032), the number of positive clinical diagnostic criteria (9.0 ± 0.3 vs 10.1 ± 0.1; P = .001), Cervical-Brachial Symptom Questionnaire scores (68.0 ± 4.1 vs 78.0 ± 2.7; P = .045), and Short-Form 12-item physical quality-of-life scores (35.6 ± 1.5 vs 32.0 ± 0.8; P = .019) but not other pretreatment factors. During follow-up (median, 21.1 months for physical therapy and 12.0 months for surgery), the mean change in QuickDASH scores for physical therapy was -15.6 ± 3.0 (-29.5% ± 5.7%) compared with -29.8 ± 2.4 (-47.9% ± 3.6%) for surgery (P = .001). The patient-rated outcomes for surgery were excellent for 27%, good for 36%, fair for 26%, and poor for 11%, with a strong correlation between the percentage of decline in the QuickDASH score and patient-rated outcomes (P < .0001). CONCLUSIONS: The present study has demonstrated contemporary outcomes for physical therapy and surgery in a well-studied cohort of patients with NTOS, reinforcing that surgery can be effective when physical therapy is insufficient, even with substantial pretreatment disability. Substantial symptom improvement can be expected for ∼90% of patients after surgery for NTOS, with treatment outcomes accurately reflected by changes in QuickDASH scores. Within this cohort, it was difficult to identify specific predictive factors for individuals most likely to benefit from physical therapy alone vs surgery.

Influence of Body Weight on Surgical Treatment for Neurogenic Thoracic Outlet Syndrome.

BACKGROUND: Body weight affects outcomes of surgical treatment for various conditions, but its effects on the treatment of neurogenic thoracic outlet syndrome (NTOS) are unknown. The purpose of this study was to evaluate the influence of body weight on technical and functional outcomes of surgical treatment for NTOS. METHODS: A retrospective review of prospectively collected data was conducted for 265 patients who underwent supraclavicular decompression for NTOS between January 1, 2014 and March 31, 2016. Patients were grouped according to 6 standard body mass index (BMI) categories. The influence of BMI on measures of surgical outcome was analyzed using Pearson correlation statistics, analysis of variance (ANOVA), and multivariate logistic regression. RESULTS: Mean patient age was 33.3 ± 0.7 years (range, 12-70), and 208 (78%) patients were women. Mean BMI was 27.2 ± 0.4 (range 16.8-49.9), with 7 underweight (3%), 95 normal (36%), 84 overweight (32%), 47 obese-I (18%), 15 obese-II (6%), and 17 obese-III (6%). There was a slight but significant association between BMI and age (Pearson P < 0.0001, r = 0.264; ANOVA P = 0.0002), but no correlations between BMI and other preoperative variables. There were no differences between BMI groups for intraoperative, immediate postoperative, or 3-month outcomes. Multivariate logistic regression demonstrated that BMI had no significant effect on functional outcome as measured by the extent of improvement in Disability of the Arm, Shoulder, and Hand score at 3 months (P = 0.429). CONCLUSIONS: There was no substantive influence of BMI on preoperative characteristics or intraoperative, postoperative, or 3-month outcomes for patients with NTOS, and no indication of an "obesity paradox" for this condition. Supraclavicular decompression for NTOS achieves similar outcomes across the BMI spectrum.

Role of myeloperoxidase in abdominal aortic aneurysm formation: mitigation by taurine.

Oxidative stress plays a fundamental role in abdominal aortic aneurysm (AAA) formation. Activated polymorphonuclear leukocytes (or neutrophils) are associated with AAA and express myeloperoxidase (MPO), which promotes inflammation, matrix degradation, and other pathological features of AAA, including enhanced oxidative stress through generation of reactive oxygen species. Both plasma and aortic MPO levels are elevated in patients with AAA, but the role of MPO in AAA pathogenesis has, heretofore, never been investigated. Here, we show that MPO gene deletion attenuates AAA formation in two animal models: ANG II infusion in apolipoprotein E-deficient mice and elastase perfusion in C57BL/6 mice. Oral administration of taurine [1% or 4% (wt/vol) in drinking water], an amino acid known to react rapidly with MPO-generated oxidants like hypochlorous acid, also prevented AAA formation in the ANG II and elastase models as well as the CaCl2 application model of AAA formation while reducing aortic peroxidase activity and aortic protein-bound dityrosine levels, an oxidative cross link formed by MPO. Both MPO gene deletion and taurine supplementation blunted aortic macrophage accumulation, elastin fragmentation, and matrix metalloproteinase activation, key features of AAA pathogenesis. Moreover, MPO gene deletion and taurine administration significantly attenuated the induction of serum amyloid A, which promotes ANG II-induced AAAs. These data implicate MPO in AAA pathogenesis and suggest that studies exploring whether taurine can serve as a potential therapeutic for the prevention or treatment of AAA in patients merit consideration.NEW & NOTEWORTHY Neutrophils are abundant in abdominal aortic aneurysm (AAA), and myeloperoxidase (MPO), prominently expressed in neutrophils, is associated with AAA in humans. This study demonstrates that MPO gene deletion or supplementation with the natural product taurine, which can scavenge MPO-generated oxidants, can prevent AAA formation, suggesting an attractive potential therapeutic strategy for AAA.

Clinical presentation and management of arterial thoracic outlet syndrome.

OBJECTIVE: Arterial thoracic outlet syndrome (TOS) is a rare condition characterized by subclavian artery pathology associated with a bony abnormality. This study assessed contemporary clinical management of arterial TOS at a high-volume referral center. METHODS: A prospectively maintained database was used to conduct a retrospective review of patients undergoing primary or reoperative treatment for arterial TOS during an 8-year period (2008 to 2016). Presenting characteristics, operative findings, and clinical and functional outcomes were evaluated. RESULTS: Forty patients underwent surgical treatment for arterial TOS, representing 3% of 1401 patients undergoing operations for all forms of TOS during the same interval. Patients were a mean age of 40.3 ± 2.2 years (range, 13-68 years), and 72% were women. More than half presented with upper extremity ischemia/emboli (n = 21) or posterior stroke (n = 2), including eight that had required urgent brachial artery thromboembolectomy. The presentation in 17 (42%) was nonvascular, with 11 having symptoms of neurogenic TOS and six having an asymptomatic neck mass or incidentally discovered subclavian artery dilatation. All patients underwent thoracic outlet decompression (25 supraclavicular, 15 paraclavicular), of which there were 30 (75%) with a cervical rib (24 complete, 6 partial), 5 with a first rib abnormality, 4 with a clavicle fracture, and 1 (reoperation) with no remaining bone abnormality. Subclavian artery reconstruction was performed in 70% (26 bypass grafts, 1 patch, 1 suture repair), and 30% had mild subclavian artery dilatation (<100%) requiring no arterial reconstruction. Mean postoperative length of stay was 5.4 ± 0.6 days. During a mean follow-up of 4.5 ± 0.4 years (range, 0.9-8.1 years), subclavian artery patency was 92%, none had further dilatation or embolism, and chronic symptoms were present in six (4 postischemic/vasospasm, 2 neurogenic). Functional outcomes measured by scores on the 11-item version of the Disability of the Arm, Shoulder and Hand Outcome Measure improved from 39.1 ± 3.8 to 19.2 ± 2.7 (P < .0001). CONCLUSIONS: This relatively large single-institution series demonstrates the diverse clinical presentation of arterial TOS coincident with a spectrum of bony and arterial pathology. Current surgical protocols can achieve excellent outcomes for this rare and often complicated condition.

Associations between clinical diagnostic criteria and pretreatment patient-reported outcomes measures in a prospective observational cohort of patients with neurogenic thoracic outlet syndrome.

OBJECTIVE: Neurogenic thoracic outlet syndrome (NTOS) is caused by dynamic compression of the brachial plexus at the level of the supraclavicular scalene triangle or the subcoracoid (pectoralis minor) space, or both. The purpose of this study was to characterize relationships between 14 clinical diagnostic criteria (CDC) and seven pretreatment patient-reported outcomes measures (PROMs) in a prospective cohort of patients with NTOS. METHODS: There were 183 new patient referrals between July 1 and December 31, 2015, with 150 (82%) meeting an established set of predefined CDC for NTOS. PROMs were evaluated across five domains: pain severity, functional disability, depression, quality of life, and pain catastrophizing. Linear regression and Pearson correlation statistics were used to analyze associations between CDC and PROMs. RESULTS: Mean ± standard error patient age was 37.1 ± 1.1 years (range, 12-66 years), and 107 (71%) were women. Five (3%) had a cervical rib, and 15 (10%) had recurrent NTOS. The most frequently positive CDC were neck or upper extremity pain (99%), upper extremity or hand paresthesia (94%), symptom exacerbation by arm elevation (97%), localized supraclavicular or subcoracoid tenderness to palpation (96%), and a positive 3-minute elevated arm stress test (94%; mean duration, 102.0 ± 5.1 seconds). The number of positive CDC (mean, 9.6 ± 0.1) correlated with the degree of tenderness to palpation and the duration of elevated arm stress test, as well as with PROMs for pain severity, functional disability, depression, physical quality of life, and pain catastrophizing (all P < .0001). PROMs across multiple domains were also strongly correlated with each other. Patients with clinically significant pain catastrophizing exhibited a greater level of functional disability than noncatastrophizing patients (P < .0001). CONCLUSIONS: This study illustrates the relative strengths of 14 CDC and seven PROMs to evaluate patients with NTOS, helping validate the selected CDC and highlighting the potential role of pain catastrophizing in functional disability. This cohort will provide valuable information on the utility of different CDC and PROMs to predict treatment outcomes.

Performance Metrics in Professional Baseball Pitchers before and after Surgical Treatment for Neurogenic Thoracic Outlet Syndrome.

BACKGROUND: High-performance throwing athletes may be susceptible to the development of neurogenic thoracic outlet syndrome (NTOS). This condition can be career-threatening but the outcomes of treatment for NTOS in elite athletes have not been well characterized. The purpose of this study was to utilize objective performance metrics to evaluate the impact of surgical treatment for NTOS in Major League Baseball (MLB) pitchers. METHODS: Thirteen established MLB pitchers underwent operations for NTOS between July 2001 and July 2014. For those returning to MLB, traditional and advanced (PitchF/x) MLB performance metrics were acquired from public databases for various time-period scenarios before and after surgery, with comparisons made using paired t-tests, Wilcoxon matched-pair signed-rank tests, and Kruskal-Wallis analysis of variance. RESULTS: Ten of 13 pitchers (77%) achieved a sustained return to MLB, with a mean age of 30.2 ± 1.4 years at the time of surgery and 10.8 ± 1.5 months of postoperative rehabilitation before the return to MLB. Pre- and postoperative career data revealed no significant differences for 15 traditional pitching metrics, including earned run average (ERA), fielding independent pitching, walks plus hits per inning pitched (WHIP), walks per 9 innings, and strikeouts to walk ratio (SO/BB). There were also no significant differences between the 3 years before and the 3 years after surgical treatment. Using PitchF/x data for 72 advanced metrics and 25 different time-period scenarios, the highest number of significant relationships (n = 18) was observed for the 8 weeks before/12 weeks after scenario. In this analysis, 54 (75%) measures were unchanged (including ERA, WHIP, and SO/BB) and 14 (19%) were significantly improved, while only 4 (6%) were significantly decreased (including hard pitch maximal velocity 93.1 ± 1.0 vs. 92.5 ± 0.9 miles/hr, P = 0.047). Six pitchers remained active in MLB during the study period, while the other 4 had retired due to factors or injuries unrelated to NTOS. CONCLUSIONS: Objective performance metrics demonstrate that pitchers returning to MLB after surgery for NTOS have had capabilities equivalent to or better than before treatment. Thoracic outlet decompression coupled with an ample period of postoperative rehabilitation can provide effective treatment for professional baseball pitchers with career-threatening NTOS.

Incomplete deletion of IL-4Rα by LysM(Cre) reveals distinct subsets of M2 macrophages controlling inflammation and fibrosis in chronic schistosomiasis.

Mice expressing a Cre recombinase from the lysozyme M-encoding locus (Lyz2) have been widely used to dissect gene function in macrophages and neutrophils. Here, we show that while naïve resident tissue macrophages from IL-4Rαf(lox/delta)LysM(Cre) mice almost completely lose IL-4Rα function, a large fraction of macrophages elicited by sterile inflammatory stimuli, Schistosoma mansoni eggs, or S. mansoni infection, fail to excise Il4rα. These F4/80(hi)CD11b(hi) macrophages, in contrast to resident tissue macrophages, express lower levels of Lyz2 explaining why this population resists LysM(Cre)-mediated deletion. We show that in response to IL-4 and IL-13, Lyz2(lo)IL-4Rα(+) macrophages differentiate into an arginase 1-expressing alternatively-activated macrophage (AAM) population, which slows the development of lethal fibrosis in schistosomiasis. In contrast, we identified Lyz2(hi)IL-4Rα(+) macrophages as the key subset of AAMs mediating the downmodulation of granulomatous inflammation in chronic schistosomiasis. Our observations reveal a limitation on using a LysMCre mouse model to study gene function in inflammatory settings, but we utilize this limitation as a means to demonstrate that distinct populations of alternatively activated macrophages control inflammation and fibrosis in chronic schistosomiasis.

Imaging of the Patient with Thoracic Outlet Syndrome.

Patients with symptoms from compression of the neurovascular bundle in the thoracic outlet are described as having thoracic outlet syndrome (TOS), which is best thought of as three conditions classified according to which structures are involved. The purpose of this article is to review the role of imaging in evaluation of patients with TOS, beginning with diagnosis and extending through postoperative management. While diagnosis of TOS still rests on the patient's presenting history and physical examination, imaging examinations are helpful in supporting the diagnosis, delineating abnormal anatomy, determining which structures are compressed, identifying the site of compression, and excluding other diagnoses. Magnetic resonance imaging is the noninvasive imaging modality of choice in evaluating patients with suspected TOS, but computed tomography also plays an important role, particularly in delineating bone anatomy. Evidence of vascular damage is required to make the diagnosis of TOS at imaging. Dynamic compression of the axillosubclavian vessels at the thoracic outlet can be a finding supportive of the diagnosis of TOS but is not a stand-alone diagnostic criterion, as it can be seen in patients without TOS. As diagnosis and treatment of TOS increase, radiologists will increasingly encounter the TOS patient after decompression surgery. Recognition of the expected postoperative appearance of these patients is critical, as is an understanding of the imaging findings of potential short- and long-term complications. (©)RSNA, 2016.

Fibrinogen-specific antibody induces abdominal aortic aneurysm in mice through complement lectin pathway activation.

Abdominal aortic aneurysm (AAA) is a common vascular disease associated with high mortality rate due to progressive enlargement and eventual rupture. There is currently no established therapy known to alter the rate of aneurysmal expansion. Thus, understanding the processes that initiate and sustain aneurysmal growth is pivotal for the development of medical therapies aimed at halting disease progression. Using an elastase-induced AAA mouse model that recapitulates key features of human AAA, we previously reported that a natural IgG antibody directs alternative pathway complement activation and initiates the inflammatory process that culminates in aneurysmal development. The target of this natural antibody, however, was unknown. Herein we identify a natural IgG that binds to fibrinogen deposited in elastase-perfused aortic tissues, activates the complement lectin pathway (LP), and induces AAA. Moreover, we establish that alterations in the glycosylation patterns of this antibody critically affect its ability to activate the LP in vivo. We find that LP activation precedes the alternative pathway and absence of the LP complement protein mannan-binding lectin abrogates elastase-induced AAA. In human AAA tissues the mouse anti-fibrinogen antibody recognizes epitopes that localize to the same areas that stain positively for mannan-binding lectin, which suggests that the complement LP is engaged in humans as well. Lastly, we demonstrate that circulating antibodies in a subset of AAA patients react against fibrinogen or fibrinogen-associated epitopes in human aneurysmal tissues. Our findings support the concept that an autoimmune process directed at aortic wall self-antigens may play a central role in the immunopathogenesis of AAA.

Antibody directs properdin-dependent activation of the complement alternative pathway in a mouse model of abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a complex inflammatory vascular disease. There are currently limited treatment options for AAA when surgery is inapplicable. Therefore, insights into molecular mechanisms underlying AAA pathogenesis may reveal therapeutic targets that could be manipulated pharmacologically or biologically to halt disease progression. Using an elastase-induced AAA mouse model, we previously established that the complement alternative pathway (AP) plays a critical role in the development of AAA. However, the mechanism by which complement AP is initiated remains undefined. The complement protein properdin, traditionally viewed as a positive regulator of the AP, may also initiate complement activation by binding directly to target surfaces. In this study, we sought to determine whether properdin serves as a focal point for the initiation of the AP complement activation in AAA. Using a properdin loss of function mutation in mice and a mutant form of the complement factor B protein that produces a stable, properdin-free AP C3 convertase, we show that properdin is required for the development of elastase-induced AAA in its primary role as a convertase stabilizer. Unexpectedly, we find that, in AAA, natural IgG antibodies direct AP-mediated complement activation. The absence of IgG abrogates C3 deposition in elastase-perfused aortic wall and protects animals from AAA development. We also determine that blockade of properdin activity prevents aneurysm formation. These results indicate that an innate immune response to self-antigens activates the complement system and initiates the inflammatory cascade in AAA. Moreover, the study suggests that properdin-targeting strategies may halt aneurysmal growth.