Rapid Functional Recovery After Thoracic Outlet Decompression in a Series of Adolescent Athletes With Chronic Atraumatic Shoulder-Girdle Pain, Scapular Winging/Dyskinesis, and Normal Electrodiagnostic Studies.

BACKGROUND: Spontaneous shoulder-girdle pain and scapular winging/dyskinesis can be caused by several neuromuscular disorders identifiable by electrodiagnostic studies (EDX). We describe a group of adolescent athletes with this clinical presentation but normal EDX, followed by later development of neurogenic thoracic outlet syndrome (NTOS). METHODS: We identified patients referred for evaluation of NTOS that had a history of chronic atraumatic shoulder-girdle pain, scapular winging/dyskinesis, and normal EDX. Each was refractory to conservative management and underwent supraclavicular decompression and brachial plexus neurolysis for NTOS. Functional disability was quantified by Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) scores. RESULTS: There were 5 female patients with a mean age at symptom onset of 14.2 ± 0.4 years, including spontaneous severe pain in the shoulder, scapula, and arm, along with prominent scapular winging/dyskinesis, and normal EDX. Symptoms had persisted for 18.9 ± 4.0 months prior to referral, with pronounced upper extremity disability (mean QuickDASH, 54.6 ± 6.9). By 3 months after surgical treatment for NTOS, all 5 patients experienced near-complete symptom resolution, including scapular winging/dyskinesis, with markedly improved function (mean QuickDASH, 2.2 ± 1.3) and a return to normal activity. CONCLUSIONS: A subset of patients with chronic atraumatic shoulder-girdle pain, scapular winging/dyskinesis, and normal EDX may develop dynamic brachial plexus compression characteristic of NTOS, exhibiting an ischemic "Sunderland-zero" nerve conduction block for which surgical decompression can result in rapid and substantial clinical improvement. The presence of surgically treatable NTOS should be considered for selected patients with long-standing scapular winging/dyskinesis who fail conservative management.

Epithelial-intrinsic defects in TGFßR signaling drive local allergic inflammation manifesting as eosinophilic esophagitis.

Allergic diseases are a global health challenge. Individuals harboring loss-of-function variants in transforming growth factor-ß receptor (TGFßR) genes have an increased prevalence of allergic disorders, including eosinophilic esophagitis. Allergic diseases typically localize to mucosal barriers, implicating epithelial dysfunction as a cardinal feature of allergic disease. Here, we describe an essential role for TGFß in the control of tissue-specific immune homeostasis that provides mechanistic insight into these clinical associations. Mice expressing a TGFßR1 loss-of-function variant identified in atopic patients spontaneously develop disease that clinically, immunologically, histologically, and transcriptionally recapitulates eosinophilic esophagitis. In vivo and in vitro, TGFßR1 variant-expressing epithelial cells are hyperproliferative, fail to differentiate properly, and overexpress innate proinflammatory mediators, which persist in the absence of lymphocytes or external allergens. Together, our results support the concept that TGFß plays a fundamental, nonredundant, epithelial cell-intrinsic role in controlling tissue-specific allergic inflammation that is independent of its role in adaptive immunity.

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.

Surgical approaches for thoracic outlet decompression in the treatment of thoracic outlet syndrome.

Thoracic outlet syndrome (TOS) is a controversial and uncommon syndrome. Three different diagnoses can be made based on the compressed structure: arterial TOS, venous TOS, and neurogenic TOS. Diagnosing TOS, especially neurogenic TOS, remains difficult since a single diagnostic tool does not exist. Although this resulted in a lot of confusion, standardization of care and outcome improved daily care practice measures in the last decade. Current treatment algorithms consist of both conservative and surgical treatment approaches, which should be chosen depending on the type of TOS and extend of the complaints. Surgical treatment of TOS is performed via thoracic outlet decompression (TOD). TOD surgery includes complete resection of the first rib (cartilage to cartilage), transection of the scalene muscles and complete neurolysis/venolysis or arteriolysis. Four different approaches can be chosen for TOD surgery: the transaxillary (TA), supraclavicular (SC), paraclavicular (PC), and infraclavicular (IC) approach. The TA, SC, and PC approach can be used for every form of TOS. However, the PC approach is mostly used for treating venous TOS. The IC approach has no role in treating neurogenic or arterial TOS and is only used for venous TOS. Every approach has its own benefits and limitations and literature does not agree on what approach is best. Therefore, the used surgical approach for TOD should be based on the surgeon's preference and experience. The aim of this review is to present an overview of the diagnostic pathway and provide an in-depth description of the surgical approach in each form of TOS.

Reoperative Brachial Plexus Neurolysis After Previous Anatomically Complete Supraclavicular Decompression for Neurogenic Thoracic Outlet Syndrome: A 10-Year Single-Center Case Series.

BACKGROUND: Optimal management of recurrent neurogenic thoracic outlet syndrome (NTOS) remains a considerable challenge. OBJECTIVE: To assess the safety and effectiveness of reoperative brachial plexus neurolysis in patients with recurrent NTOS. METHODS: From 2009 to 2019, 85 patients underwent reoperative supraclavicular brachial plexus neurolysis for recurrent NTOS after a previous anatomically complete supraclavicular decompression. Data from a prospectively maintained database were analyzed retrospectively. RESULTS: The mean patient age at reoperation was 36.9 ± 1.3 (range 15-64) years, 75% were female, and the interval after previous primary operation was 2.5 ± 0.2 years. Intervening injury had precipitated recurrent NTOS in 14 patients (16%), and the mean Disability of the Arm, Shoulder, and Hand (QuickDASH) score before reoperation was 65.2 ± 2.6, reflecting substantial disability. Operative findings consisted of dense fibrous scar tissue surrounding/encasing the brachial plexus. Compared with the previous primary operations, reoperations had a shorter operative time (198 ± 4 vs 161 ± 5 minutes, P < .01) and hospital stay (4.4 ± 0.2 vs 3.6 ± 0.1 days, P < .01), but there were no significant differences in the frequency of prolonged hospitalization (7.1% vs 4.7%), early reoperation (3.5% vs 1.2%), or 30-day hospital readmission (8.2% vs 7.1%). During a median follow-up of 4.8 years, QuickDASH scores improved by 23.3 ± 2.6 (34.2% ± 3.6%; P < .01) and patient-rated outcomes were excellent in 24%, good in 42%, fair in 26%, and poor in 8%. CONCLUSION: Reoperative supraclavicular brachial plexus neurolysis is technically challenging but safe and effective treatment for recurrent NTOS, with significant improvements in symptoms and function. Diminishing perineural scar tissue development and avoiding secondary injury would likely decrease the need for reoperations.

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.

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.

Pilot feasibility study of a simple regenerative peripheral nerve interface designed to diminish cutaneous dysesthesia after supraclavicular operations.

Supraclavicular operations can be associated with postoperative cutaneous dysesthesia and hypersensitivity. Regenerative peripheral nerve interfaces, created by attaching the proximal end of a divided peripheral nerve into a viable muscle target, can promote neurite regrowth and neuromuscular connections to help suppress painful nerve hyperactivity. During 40 consecutive operations for neurogenic thoracic outlet syndrome, we demonstrated that division of at least one of the superficial supraclavicular cutaneous sensory nerve branches was necessary in 98% of cases. We subsequently developed a novel regenerative peripheral nerve interface for supraclavicular operations using the adjacent omohyoid muscle and have described the technical steps involved in this procedure.

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.

Anatomically Complete Supraclavicular Reoperation for Recurrent Neurogenic Thoracic Outlet Syndrome: Clinical Characteristics, Operative Findings, and Long-term Outcomes.

BACKGROUND: The clinical outcomes of reoperations for recurrent neurogenic thoracic outlet syndrome (NTOS) remain undefined. METHODS: From 2009 to 2019, 90 patients with recurrent NTOS underwent anatomically complete supraclavicular reoperation after previous operation(s) performed at other institutions using either supraclavicular (Prev-SC = 48), transaxillary (Prev-TA = 31), or multiple/combination (Prev-MC = 11) approaches. Prospectively maintained data were analyzed retrospectively. RESULTS: The mean patient age was 39.9 ± 1.4 years, 72% were female, and the mean interval after previous operation was 4.1 ± 0.6 years. The mean Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score was 62 ± 2, reflecting substantial preoperative disability. Residual scalene muscle was present in 100% Prev-TA, 79% Prev-SC, and 55% Prev-MC (P < .05). Retained/residual first rib was present in 90% Prev-TA, 75% Prev-SC, and 55% Prev-MC (P < .05). There were no differences in operative time (overall 210 ± 5 minutes), length of hospital stay (4.7 ± 0.2 days), or 30-day readmissions (7%). During follow-up of 5.6 ± 0.3 years, the improvement in QuickDASH scores was 21 ± 2 (36% ± 3%) (P < .01) and patient-rated outcomes were excellent in 10%, good in 36%, fair in 43%, and poor in 11%. CONCLUSIONS: Anatomically complete decompression for recurrent NTOS can be safely and effectively accomplished by supraclavicular reoperation, regardless of the type of previous operation. Residual scalene muscle and retained/residual first rib are more frequently encountered after transaxillary operations than after supraclavicular or multiple/combined operations. Supraclavicular reoperation can achieve significant symptom reduction and functional improvement for approximately 90% of patients with recurrent NTOS.

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.

Heme oxygenase-1 inhibition promotes IFNγ- and NOS2-mediated control of Mycobacterium tuberculosis infection.

Mycobacterium tuberculosis (Mtb) infection induces pulmonary expression of the heme-degrading enzyme heme oxygenase-1 (HO-1). We have previously shown that pharmacological inhibition of HO-1 activity in experimental tuberculosis results in decreased bacterial loads and unexpectedly that this outcome depends on the presence of T lymphocytes. Here, we extend these findings by demonstrating that IFNγ production by T lymphocytes and NOS2 expression underlie this T-cell requirement and that HO-1 inhibition potentiates IFNγ-induced NOS2-dependent control of Mtb by macrophages in vitro. Among the products of heme degradation by HO-1 (biliverdin, carbon monoxide, and iron), only iron supplementation reverted the HO-1 inhibition-induced enhancement of bacterial control and this reversal was associated with decreased NOS2 expression and NO production. In addition, we found that HO-1 inhibition results in decreased labile iron levels in Mtb-infected macrophages in vitro and diminished iron accumulation in Mtb-infected lungs in vivo. Together these results suggest that the T-lymphocyte dependence of the therapeutic outcome of HO-1 inhibition on Mtb infection reflects the role of the enzyme in generating iron that suppresses T-cell-mediated IFNγ/NOS2-dependent bacterial control. In broader terms, our findings highlight the importance of the crosstalk between iron metabolism and adaptive immunity in determining the outcome of infection.

Evaluation and Management of Venous Thoracic Outlet Syndrome.

Venous thoracic outlet syndrome (TOS) is uncommon but occurs in young, healthy patients, typically presenting as subclavian vein (SCV) effort thrombosis. Venous TOS arises through chronic repetitive compression injury of the SCV in the costoclavicular space with progressive venous scarring, focal stenosis, and eventual thrombosis. Diagnosis is evident on clinical presentation with sudden spontaneous upper extremity swelling and cyanotic discoloration. Initial treatment includes anticoagulation, venography, and pharmacomechanical thrombolysis. Surgical management using paraclavicular decompression can result in relief from arm swelling, freedom from long-term anticoagulation, and a return to unrestricted upper extremity activity in more than 90% of patients.

Thoracic Outlet Syndrome in the Overhead Athlete: Diagnosis and Treatment Recommendations.

PURPOSE OF REVIEW: Neurovascular compression in the upper extremity is rare but can affect even those participating in high-level competitive athletics. To assess optimal approaches to treatment, in this review, we evaluate the current literature on neurovascular compressive syndromes affecting the upper extremity, with a special focus on the thoracic outlet syndrome (TOS). RECENT FINDINGS: Neurovascular compression at the thoracic outlet can involve the brachial plexus, subclavian artery, or subclavian vein, each with distinct clinical manifestations. Neurogenic TOS is best treated with surgical decompression, if physical therapy has not improved symptoms. Venous TOS results in acute thrombosis superimposed on chronic venous compression. Treatment is best directed at early anticoagulation, catheter-directed thrombolysis, and surgical decompression, with most patients able to discontinue anticoagulation and return to high-level athletic activity. Arterial TOS is related to aneurysmal degeneration of the subclavian artery with distal embolization, leading to limb-threatening ischemia. This should be aggressively treated with surgery. Similar degenerative changes can occur in the axillary artery and its branches, leading to distal embolization. Prompt recognition of these potential sources of limb-threatening ischemia is critical to limb preservation. TOS includes rare but important conditions in the overhead athlete. Recent advances in physical therapy and image-guided diagnostic techniques have facilitated more accurate diagnosis. Surgical treatment remains the gold standard to maximize function or for limb preservation, and future research is needed to clarify optimal pain and physiotherapy regimens, as well as to examine novel approaches to neurovascular decompression.

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.

False-negative upper extremity ultrasound in the initial evaluation of patients with suspected subclavian vein thrombosis due to thoracic outlet syndrome (Paget-Schroetter syndrome).

OBJECTIVE: To assess the utilization and consequences of upper extremity Duplex ultrasound in the initial diagnostic evaluation of patients with suspected subclavian vein (SCV) thrombosis and venous thoracic outlet syndrome (VTOS). METHODS: A retrospective single-center review was conducted for patients that underwent primary surgical treatment for VTOS between 2008 and 2017, in whom an upper extremity ultrasound had been performed as the initial diagnostic test (n = 214). Clinical and treatment characteristics were compared between patients with positive and false-negative ultrasound studies. RESULTS: There were 122 men (57%) and 92 women (43%) that had presented with spontaneous idiopathic arm swelling, including 28 (13%) with proven pulmonary embolism, at a mean age of 30.7 ± 0.8 years (range 14-69). Upper extremity ultrasound had been performed 23.8 ± 12.2 days after the onset of symptoms, with confirmation of axillary-SCV thrombosis in 169 patients (79%) and negative results in 45 (21%). Of the false-negative ultrasound study reports, only 8 (18%) acknowledged limitations in visualizing the central SCV. Definitive diagnostic imaging (DDI) had been obtained by upper extremity venography in 175 (82%), computed tomography angiography in 24 (11%), and magnetic resonance angiography in 15 (7%), with 142 (66%) undergoing catheter-directed axillary-SCV thrombolysis. The mean interval between initial ultrasound and DDI was 48.9 ± 14.2 days with no significant difference between groups, but patients with a positive ultrasound were more likely to have DDI within 48 hours than those with a false-negative ultrasound (44% vs 24%; P = .02). At the time of surgical treatment, the SCV was widely patent following paraclavicular decompression and external venolysis alone in 74 patients (35%). Patch angioplasty was performed for focal SCV stenosis in 76 (36%) and bypass graft reconstruction for long-segment axillary-SCV occlusion in 63 (29%). Patients with false-negative initial ultrasound studies were significantly more likely to require SCV bypass reconstruction than those with a positive ultrasound (44% vs 25%; P = .02). CONCLUSIONS: Duplex ultrasound has significant limitations in the initial evaluation of patients with suspected SCV thrombosis, with false-negative results in 21% of patients with proven VTOS. This is rarely acknowledged in ultrasound reports, but false-negative ultrasound studies have the potential to delay definitive imaging, thrombolysis, and further treatment for VTOS. Initial false-negative ultrasound results are associated with progressive thrombus extension and a more frequent need for SCV bypass reconstruction at the time of surgical treatment.

Anti-IL-13Rα2 therapy promotes recovery in a murine model of inflammatory bowel disease.

There continues to be a major need for more effective inflammatory bowel disease (IBD) therapies. IL-13Rα2 is a decoy receptor that binds the cytokine IL-13 with high affinity and diminishes its STAT6-mediated effector functions. Previously, we found that IL-13Rα2 was necessary for IBD in mice deficient in the anti-inflammatory cytokine IL-10. Here, we tested for the first time a therapeutic antibody specifically targeting IL-13Rα2. We also used the antibody and Il13ra2-/- mice to dissect the role of IL-13Rα2 in IBD pathogenesis and recovery. Il13ra2-/- mice were modestly protected from induction of dextran sodium sulfate (DSS)-induced colitis. Following a 7-day recovery period, Il13ra2-/- mice or wild-type mice administered the IL-13Rα2-neutralizing antibody had significantly improved colon health compared to control mice. Neutralizing IL-13Rα2 to increase IL-13 bioavailability promoted resolution of IBD even if neutralization occurred only during recovery. To link our observations in mice to a large human cohort, we conducted a phenome-wide association study of a more active variant of IL-13 (R130Q) that has reduced affinity for IL-13Rα2. Human subjects carrying R130Q reported a lower risk for Crohn's disease. Our findings endorse moving anti-IL-13Rα2 into preclinical drug development with the goal of accelerating recovery and maintaining remission in Crohn's disease patients.

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.