Research Spotlight

Cox, M., J. Thatcher, R. Mayer, I. Thacker, R. Pearson and K. Layton (2021). “Spontaneous Intracranial Artery Dissection causing Subarachnoid Hemorrhage: Importance of Short-Term Surveillance.” Neurohospitalist 11(4): 379-381.

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Hemorrhagic intracranial artery dissections are unstable lesions, with a high propensity for rebleeding (up to 40%) in the acute period. Imaging plays an important role in the diagnosis and management of intracranial artery dissections. In this paper, we describe 2 cases in which the dissected intracranial artery underwent rapid morphological change within 3 days or less, highlighting the importance of short-term follow-up imaging in patients with these hemorrhagic lesions.

Roberson, D., D. K. Newman, J. B. Ziemba, A. Wein, H. Stambakio, R. G. Hamilton, L. Callender, L. Holderbaum, T. King, A. Jackson, T. Tran, G. Lin and A. L. Smith (2021). “Results of the patient report of intermittent catheterization experience (price) study.” Neurourol Urodyn. [Epub ahead of print].

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AIMS: Patient satisfaction is paramount to health-related quality of life (HR-QoL) outcomes. High quality, quantitative data from the US describing patients’ actual experiences, difficulties, and HR-QoL while on an intermittent self-catheterization (ISC) regimen is very scarce. Our objective was to better understand patient practices with and attitudes towards ISC. METHODS: This is a cross-sectional, multi-centered, clinical study of adult men and women performing ISC in the United States. Data collected included demographics, medical history, catheter characteristics, specific self-catheterization habits and two validated HR-QoL questionnaires: The Intermittent Self-Catheterization Questionnaire (ISC-Q) and the Intermittent Catheterization Difficulty Questionnaire (ICDQ). RESULTS: Two hundred participants were recruited from six sites; 70.0% were male, 73.5% were Caucasian with a median age was 51.0 years (range 19-90 years). The ISC-Q showed that the vast majority of participants reported ease with ISC (82.0% satisfaction score) had confidence in their ability to perform ISC (91.9% satisfaction score); yet, many felt self-conscious about doing so (58.3% satisfaction score) and had concerns about long-term adverse effects (58.1% satisfaction score). The ICDQ indicated little to no difficulty for most participants with all routine ISC practices. A small minority of participants reported some difficulty with a “blocking sensation” during initiation of catheterization, leg spasticity, and painful catheterization. Multivariate linear regression results are also reported. DISCUSSION/CONCLUSION: Participants are confident with ISC and have little overall difficulty, which may be a product of successful education and/or catheter design. urinary tract infections (UTIs) were common (yet variable) and may contribute to the noted long-term ISC concerns. Limitations exist including various selection biases leading to concerns of external validity. Future educational interventions in this population may further improve HR-QoL, optimize UTIs prevention, and diminish concerns with long-term ISC.

Chinitz, N., D. D. Bohl, M. Reddy, S. Tenenbaum, S. Coleman and J. W. Brodsky (2021). “Preoperative Gait Analysis of Peroneal Tendon Tears.” Foot Ankle Int: 10711007211036876.

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BACKGROUND: Little is known regarding the impact of peroneal tendon tears on function. This study quantifies gait changes associated with operatively-confirmed peroneal tendon tears. METHODS: Sixty-five patients with unilateral peroneal tendon tears were prospectively evaluated using preoperative 3D multisegment gait analysis of both limbs. Data were analyzed according to pattern/severity of tears, as confirmed surgically: peroneus brevis tears, reparable (PBR); peroneus brevis tears, irreparable (PBI); peroneus longus tears, irreparable (PLI); and concomitant irreparable tears of both tendons (PBI+PLI). The following parameters were analyzed: ankle sagittal motion, coronal motion, axial rotation, foot progression angle, sagittal power, sagittal moment. RESULTS: Twelve patients (18.5%) had the PBR pattern, 37 (56.9%) PBI, 10 (15.4%) PLI, and 6 (9.2%) PBI+PLI. Compared with the contralateral, nonpathologic extremities, limbs with peroneal tears had diminished ankle sagittal motion (mean 23.14 vs 24.30 degrees, P = .012), ankle/hindfoot axial rotation (6.26 vs 7.23 degrees, P = .001), sagittal moment (1.16 vs 1.29 Nm/kg, P < .001), and sagittal power (1.24 vs 1.47 W/kg, P < .001). The most severe tear patterns had the greatest derangements in multiple parameters of gait (PBI+PLI > PBI or PLI > PBR). For example, all groups except PBR had loss of ankle sagittal moment and/or power in the affected limb, and the greatest losses in moment and power were in the PBI+PLI group (1.22 vs 0.91 Nm/kg, P = .003 for moment; 0.73 vs 1.31 W/kg, P < .001 for power). The PBI+PLI group had a >10-degree varus shift in coronal motion on the affected side (P = .002). CONCLUSION: This is the first study to demonstrate diminished biomechanical function in patients with peroneal tendon tears. In vivo 3-dimensional gait analysis found significant changes in hindfoot motion, ankle motion, and ankle power. Impairments were related to the pattern and severity of the tears, and demonstrated a strong association of peroneal tendon tears with diminished ankle plantarflexion strength. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Ismaeel, A., D. Miserlis, E. Papoutsi, G. Haynatzki, W. T. Bohannon, R. S. Smith, J. L. Eidson, G. P. Casale, Pipinos, II and P. Koutakis (2021). “Endothelial Cell-Derived Pro-fibrotic Factors Increase TGF-β1 Expression by Smooth Muscle Cells in Response to Cycles of Hypoxia-Hyperoxia.” Biochim Biophys Acta Mol Basis Dis: 166278. Oct 1. [Epub ahead of print].

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BACKGROUND: The vascular pathology of peripheral artery disease (PAD) encompasses abnormal microvascular architecture and fibrosis in response to ischemia-reperfusion (I/R) cycles. We aimed to investigate the mechanisms by which pathological changes in the microvasculature direct fibrosis in the context of I/R. METHODS: Primary human aortic endothelial cells (ECs) were cultured under cycles of normoxia-hypoxia (NH) or normoxia-hypoxia-hyperoxia (NHH) to mimic I/R. Primary human aortic smooth muscle cells (SMCs) were cultured and treated with media from the ECs. FINDINGS: The mRNA and protein expression of the pro-fibrotic factors platelet derived growth factor (PDGF)-BB and connective tissue growth factor (CTGF) were significantly upregulated in ECs undergoing NH or NHH cycles. Treatment of SMCs with media from ECs undergoing NH or NHH cycles led to significant increases in TGF-β1, TGF-β pathway signaling intermediates, and collagen expression. Addition of neutralizing antibodies against PDGF-BB and CTGF to the media blunted the increases in TGF-β1 and collagen expression. Treatment of SMCs with PAD patient-derived serum also led to increased TGF-β1 levels. INTERPRETATION: In an in-vitro model of I/R, which recapitulates the pathophysiology of PAD, increased secretion of PDGF-BB and CTGF by ECs was shown to be predominantly driving TGF-β1-mediated expression by SMCs. These cell culture experiments help elucidate the mechanism and interaction between ECs and SMCs in microvascular fibrosis associated with I/R. Thus, targeting these pro-fibrotic factors may be an effective strategy to combat fibrosis in response to cycles of I/R. FUNDING: National Institute on Aging at the National Institutes of Health grant number R01AG064420.

Rolle, C. P., M. Berhe, T. Singh, R. Ortiz, A. Wurapa, M. Ramgopal, P. A. Leone, J. E. Matthews, M. Dalessandro, M. R. Underwood, K. Angelis, B. R. Wynne, D. Merrill, C. Nguyen, J. van Wyk and A. R. Zolopa (2021). “Dolutegravir/lamivudine as a first-line regimen in a test-and-treat setting for newly diagnosed people living with HIV.” Aids 35(12): 1957-1965.

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OBJECTIVES: Dolutegravir/lamivudine (DTG/3TC) is indicated for treatment-naive and experienced people with HIV; however, questions remain about its utility in a test-and-treat setting because of potential transmitted resistance and baseline hepatitis B virus (HBV) co-infection. We present feasibility and efficacy of DTG/3TC in newly diagnosed individuals in a test-and-treat setting. DESIGN: The single-arm STAT study evaluated DTG/3TC in a US test-and-treat setting. METHODS: Eligible adults initiated DTG/3TC 14 days or less after HIV-1 diagnosis without availability of baseline laboratory results. If baseline testing indicated DTG or 3TC resistance, HBV co-infection, or creatinine clearance less than 30 ml/min per 1.73 m2, participants remained on study with treatment modification. Efficacy endpoints included proportions of participants with HIV-1 RNA less than 50 copies/ml at Week 24, regardless of antiretroviral regimen, among all participants (intention-to-treat exposed) and those with available HIV-1 RNA data (observed). RESULTS: Of 131 participants enrolled, 8% were female and 50% were non-white. Through Week 24, treatment was modified in eight participants [five with HBV co-infection, one with baseline M184V, one for adverse event (rash), one participant decision]. At Week 24, 78% (102/131) of all participants and 92% (102/111) of those with available data achieved HIV-1 RNA less than 50 copies/ml. Incidence of drug-related adverse events was low (7%); no drug-related serious adverse events occurred. CONCLUSION: These data demonstrate the feasibility, efficacy, and safety of using DTG/3TC as a first-line regimen in a test-and-treat setting, with therapy adjustments for baseline resistance or HBV co-infection occurring safely via routine clinical care as needed [ClinicalTrials.gov, NCT03945981; see Supplemental Digital Content 1, video abstract (Video abstract summarizing the STAT study design and results), http://links.lww.com/QAD/C189].