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.

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.

The incidence of and risk factors for a repeat obstetric anal sphincter injury (OASIS) in the vaginal birth subsequent to a first episode of OASIS: a hospital-based cohort study.

PURPOSE: To identify the incidence of and risk factors for a repeat obstetric anal sphincter injury (OASIS) in women who sustained an OASIS in their first vaginal delivery and have a subsequent vaginal birth. METHODS: Data were collected retrospectively for women having had singleton cephalic presentation vaginal deliveries between 2007 and 2015. Women with breech deliveries, stillbirths, foetal congenital abnormalities and multiple pregnancies were excluded. RESULTS: Over the study period, we identified 11,191 women who had a first vaginal birth, of which 603 (5.4%) sustained a first episode of OASIS. Of these women, 243 (40.2%) had a subsequent pregnancy with 190 (78.1%) having a second vaginal birth, 13 (5.4%) an emergency caesarean section (CS) delivery while in labour and 40 (16.5%) an elective CS delivery. In those who delivered vaginally, 16 (8.4%) women had a repeat OASIS. After adjusting for several confounding factors, it was found that the risk of a repeat OASIS was associated with the use of epidural analgesia (OR = 3.66; 95% CI: 1.14-11.71) and an episiotomy in the first delivery (OR = 3.93; 95% CI:1. 03-15.02) and a short labour (<2.8 h) in the second delivery (OR = 14.55; 95% CI: 1.83-115.75). The time interval between the two vaginal births was not associated with any increased risk of a repeat OASIS. CONCLUSION: We found that 8.4% of women sustained a repeat OASIS in a subsequent vaginal birth with this risk being associated with the presence of a short second labour and certain features from the first labour.

A randomized, blinded, multicenter trial of a gentamicin vancomycin gel (DFA-02) in patients undergoing abdominal surgery.

BACKGROUND: SI is a significant medical problem. DFA-02 is an investigational bioresorbable modified release gel consisting of both gentamicin (16.8 mg/mL) and vancomycin (18.8 mg/mL). A Phase 2a study, where the drug was applied during surgical incision closure, suggested safety and tolerability but was not designed to assess its efficacy. STUDY DESIGN: In a Phase 2b randomized, blinded trial patients undergoing abdominal, primarily colorectal, surgery were randomized (4:1:1) to one of three study arms: DFA-02, matching placebo gel, or standard of care (SOC) involving irrigation of the wound with normal saline. The DFA-02 and placebo gel groups received up to 20 mL of study drug inserted above the fascia during wound closure, and were treated in a double-blind manner; the SOC group was treated in a single-blind manner. The primary endpoint was SSI (adjudicated centrally by a blinded committee) through postoperative day 30. RESULTS: Overall, 445 subjects (intention-to-treat) were randomized at 35 centers with 425 subjects completing the study and being evaluable. There were 67 SSIs (15.8%): 64.2% superficial, 7.5% deep, and 28.4% organ space. The incidence of SSI was not statistically significantly different between the DFA-02 and the placebo gel/SOC arms combined, 42/287 = 14.6% vs 25/138 = 18.1% (p = 0.36), respectively. Rehospitalization within 30 days was also similar between study groups (DFA-02 28.6%, placebo gel 21.4%, SOC 27.3%). CONCLUSION: In this multicenter, blinded, randomized trial with central adjudication, the gentamicin/vancomycin gel was not associated with a significant reduction in SSI. SUMMARY: Patients undergoing abdominal surgery were randomized to one of three study arms: DFA-02 gel consisting of both gentamicin and vancomycin, matching placebo gel, or standard of care (SOC). Of 425 patients completing the study at 35 sites the gentamicin/vancomycin gel was not associated with a significant reduction in SSI.

Prescriber fidelity to a medication management evidence-based practice in the treatment of schizophrenia.

OBJECTIVE: Medication Management Approaches in Psychiatry (MedMAP) is an evidence-based practice developed to guide the management and monitoring of psychotropic medications for individuals with schizophrenia. This article reports prescriber fidelity to MedMAP principles in a public mental health service system. METHODS: This three-year longitudinal intervention study implemented MedMAP in six community mental health centers in Kentucky. Nine psychiatrists and five advanced practice psychiatric nurses with prescriptive authority participated in the study. Prescribers were trained in the use of MedMAP about one month before implementation, and MedMAP principles were reinforced throughout the study. Four posttraining assessments were conducted at each site at approximately four-month intervals over a period of 30 months. An 18-item scale was used to assess baseline and posttraining prescriber fidelity over a period of 30 months in 900 randomly selected medical records. RESULTS: Average fidelity scores improved significantly over baseline at each of the four postimplementation fidelity assessments. Training effects were most evident at the second posttraining fidelity assessment, but effects persisted over the course of the study. There was considerable variability in scores across items both at baseline and subsequently. Posttraining improvement was greatest in patient education, documentation of illness and medication history, and simplification of medication regimen. CONCLUSIONS: Implementation and monitoring of MedMAP were feasible in these community mental health settings. Additional implementation projects are crucial for advancing evidence-based practice in clinical settings.

AAV8, 9, Rh10, Rh43 vector gene transfer in the rat brain: effects of serotype, promoter and purification method.

We compared adeno-associated virus (AAV) serotypes for expression levels of green fluorescent protein (GFP) in the adult rat hippocampus by biophotonic imaging. Preparations of AAV serotypes 8, 9, Rh10, and Rh43 incorporating cytomegalovirus (CMV) promoter-driven GFP were purified by a CsCl method. Neither AAV Rh10 nor AAV Rh43 produced greater levels of GFP than AAV8, which was used as a reference. For AAV9, there was an increase relative to AAV8. The CsCl-purified AAV8 displayed an astroglial transduction pattern in contrast to the expected neuronal expression of other AAVs. After preparing the same CMV-GFP plasmid in AAV8 with an iodixanol purification method, the expected neuronal pattern resulted. The astroglial expression with the CsCl AAV8 was probably due to relatively high levels of protein impurities. We compared the CMV promoter with the CMV/chicken beta-actin (CBA) promoter in the context of AAV8, both prepared by iodixanol, and found the CBA promoter to produce stronger GFP expression. At two doses of vectors optimized for serotype, promoter and purification, we did not observe serotype differences among AAV8, AAV9, or AAV Rh10. The purification method can therefore impact the transduction pattern as well as the results when comparing serotype strengths.

Parkin is protective for substantia nigra dopamine neurons in a tau gene transfer neurodegeneration model.

Parkin is a ubiquitin ligase involved in the ubiquitin-proteasome system. Elevating parkin expression in cells reduces markers of oxidative stress while blocking parkin expression increases oxidative stress. In parkin gene knock down mouse and fly models, mitochondria function is deficient. Parkin is neuroprotective against a variety of toxic insults, while it remains unclear which of the above properties of parkin may mediate the protective actions. One of the models for which parkin is protective is overexpression of alpha-synuclein, a protein that self-aggregates in Parkinson disease. The microtubule-associated protein tau is another protein that self-aggregates in specific neurodegenerative diseases that also involve loss of dopamine neurons such as frontotemporal dementia with parkinsonism linked to chromosome 17, progressive supranuclear palsy and corticobasal degeneration. We recently developed a tau-induced dopaminergic degeneration model in rats using adeno-associated virus vectors. In this study, we successfully targeted either a mixed tau/parkin vector or mixed tau/control vector to the rat substantia nigra. While there was significant loss of dopamine neurons in the tau/control group relative to uninjected substantia nigra, there was no cell loss in the tau/parkin group. We found no difference in total tau levels between tau/control and tau/parkin groups. Parkin therefore protects dopamine neurons against tau as it does against alpha-synuclein, which further supports parkin as a therapeutic target for diseases involving loss of dopamine neurons.

A novel method for testing learning and preferences in people with minimal motor movement.

Ten individuals with profound multiple impairments were given novel tests for learning and preference with adaptive switches and leisure-oriented devices, such as audio tape players. Typically, tests for learning include a baseline or extinction component in which the adaptive switch and device are not connected as a control for incidental or involuntary switch use. As an alternative, conditions were compared in sets of six sessions each in which switch closure caused (a) Activation of a device, (b) Deactivation of an already operating device, and (c) Deactivation of one of two devices and Activation of the other (Two-Choice). Changes in behavior indicative of learning were observed in eight participants in Activation-Deactivation conditions. The Two-Choice Condition produced indices of learning that also showed a preference for one device over the other with five participants. The preferences observed in the Two-Choice Condition had not been seen in the Activation or Deactivation Condition data. People with profound multiple impairments evinced leisure-device preferences, but such preferences may not lead to differential responding across opportunities with only one device at a time.

Training and support to enable home immunoglobulin therapy.

This article describes the development of an immunoglobulin home therapy and support service. The service provides patients with the education and training that they need to be able to undertake immunoglobulin therapy at home. To facilitate this the trust's competency-based enhanced practice framework was adapted. Evaluation through clinical audit and a patient satisfaction survey has yielded positive results, indicating that the enhanced practice framework provides a robust and effective approach to patient education.

Dynamics of the apical plasma membrane recycling system during cell division.

The members of the family of Rab11 small GTPases are critical regulators of the plasma membrane vesicle recycling system. While previous studies have determined that the Golgi apparatus disperses during mitosis and reorganizes after cytokinesis, the fate of the recycling system during the cell cycle is more obscure. We have now studied in MDCK cells the fate during mitosis of an apical recycling system cargo, the polymeric IgA receptor (pIgAR), and regulators of the recycling system, Rab11a and its interacting proteins myosin Vb, Rab11-FIP1, Rab11-FIP2 and pp75/Rip11. Rab11a, pIgAR and myosin Vb containing vesicles dispersed into diffuse puncta in the cytosol during prophase and then became clustered near the spindle poles after metaphase, increasing in intensity throughout telophase. A similar pattern was observed for Rab11-FIP1 and Rab11-FIP2. However, Rab11-FIP1 lost colocalization with other recycling system markers during late prophase, relocating to the pericentriolar material. During telophase, Rab11-FIP1 returned to recycling system vesicles. Western blot analysis indicated that both Rab11a and pIgAR remained associated with membrane vesicles throughout the cell cycle. This behavior of the Rab11a-containing apical recycling endosome system during division was distinct from that of the Golgi apparatus. These results indicate that critical components of the apical recycling system remain associated on vesicles throughout the cell cycle and may provide a means for rapid re-establishment of plasma membrane components after mitosis.