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Heart failure contributes to Duchenne muscular dystrophy (DMD), which arises from mutations that ablate dystrophin, rendering the plasma membrane prone to disruption. Cardiomyocyte membrane breakdown in DMD patients yields a serum injury profile similar to other types of myocardial injury with the release of creatinine kinase and troponin isoforms. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are highly useful but can be improved. We generated DMD hiPSC-CMs and subjected these cells to equibiaxial mechanical strain to mimic in vivo stress. Compared to healthy cells, DMD hiPSC-CMs demonstrated greater susceptibility to equibiaxial strain after 2 hours at 10% strain. We generated an aptamer-based profile of proteins released from hiPSC-CMs both at rest and subjected to strain and identified a strong correlation in the mechanical stress-induced proteome from hiPSC-CMs and DMD patient serum. We exposed hiPSC-CMs to recombinant annexin A6, a protein resealing agent, and found reduced biomarker release in DMD and control hiPSC-CMs subjected to strain. Thus, the application of mechanical strain to hiPSC-CMs produces a model that reflects an in vivo injury profile, providing a platform to assess pharmacologic intervention.
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OBJECTIVE: To evaluate whether induction of labor is associated with lower risk of cesarean section compared to expectant management in patients with isolated polyhydramnios. STUDY DESIGN: This is a single-center, retrospective cohort study of patients with pregnancies complicated by idiopathic polyhydramnios, documented between 34 and 38 weeks gestation, who were delivered between July 2012 and February 2020. The primary outcome was cesarean delivery. Secondary outcomes included chorioamnionitis, endometritis, postpartum hemorrhage, preeclampsia/gestational hypertension, and composite neonatal morbidity. RESULTS: There were 194 patients included with idiopathic polyhydramnios - 115 underwent induction and 79 patients were expectantly managed. Planned induction was associated with a lower rate of CD compared with expectant management but did not meet statistical significance (19.1 % vs 30.4 %, aOR 0.51, 95 % CI 0.24, 1.05). A similar effect was seen when stratifying for parity: both nulliparous (9.1 % vs 16.3 %, aOR 0.59, 95 % CI 0.17, 1.98) and multiparous (32.7 % vs 47.2 %, aOR 0.45, 95 % CI 0.18, 1.15) patients had a lower CD rate when there was a planned induction, though neither group met statistical significance. No differences in maternal or fetal secondary outcomes were identified (chorioamnionitis, endometritis, postpartum hemorrhage, preeclampsia/gestational hypertension, composite neonatal morbidity). CONCLUSION: Lower rates of cesarean section were associated with labor induction for patients with isolated polyhydramnios, but confidence intervals did not reach statistical significance.
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BACKGROUND: Polymicrobial colonization and resultant biofilm formation significantly impair the process of wound healing. Stagnant tissue repair processes predispose patients to serious complications including systemic infection and limb amputation. Continuous Low-Irradiance Phototherapy (CLIP) is a novel therapeutic approach that delivers blue light at low irradiance for extended periods of time. Bench and preclinical work in the literature indicates that 405 nm light avoids thermal injury of healthy tissue, promotes a cytokine milieu favoring re-epithelialization and angiogenesis, and prevents bacterial and biofilm growth. Objective: This is the first in-human evaluation of a technology that delivers continuous low-irradiance 405 nm light to chronic wounds. The objective of this study was to determine the safety, feasibility, and ergonomics of this device for the treatment of chronic wounds in adult human subjects. This was not a randomized study to determine device efficacy, although data on outcome were collected. METHODS: In this prospective observational pilot study, participants received the intervention 24 hours per day, 7 days per week, for 4 weeks. Cohort I was conducted from December 2018 to March 2019, with Cohorts II and III ongoing. 25 study participants were recruited by referral (Cohort I: 5 participants, Cohort II: 10 participants, Cohort III: 10 participants). Our primary endpoint was to monitor for safety, assess usability by nurses and physicians, and evaluate patient comfort. The secondary endpoint, although not randomized nor directly compared with standard intervention, was the percentage area reduction (PAR) of the wound. Results: No adverse events or subject discomfort occurred with the CLIP intervention. The staff treating the study participants reported no ergonomic or compliance issues with the use of the device. The device received high scores in categories assessing practicality and ease of use. There was an average PAR of 29% (SD = 0.42). Conclusion: This study serves as the first in-human evaluation of extended low-irradiance 405 nm light for chronic wound therapy. The device appears safe and easy to use and had no compliance issues in the outpatient setting. Study participants who received CLIP without interruption saw either partial or complete reduction in wound area. J Drugs Dermatol. 2023;22(11):1111-1117 doi:10.36849/JDD.7206.
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Luz , Fototerapia , Adulto , Humanos , Projetos Piloto , Estudos Prospectivos , Fototerapia/efeitos adversos , CitocinasRESUMO
INTRODUCTION: Nucleotractotomy is an efficient surgical technique that provides a high pain relief rate for specific clinical indications. There are two main approaches for performing this operation: an open and percutaneous technique. METHODS: In the Federal Center of Neurosurgery (Novosibirsk, Russia) from 2016 to 2022, 13 trigeminal nucleotractotomies (7 open and 6 percutaneous) were performed in 12 patients (5 women and 7 men). The indications for surgery were deafferentation pain and chronic drug-resistant pain syndrome caused by malignancy in the facial region. A neurological examination was done on each patient 1 day before the surgery, right after the surgery, and at the follow-up (examinations were done after 1, 6, and 12 months, or when the patient independently applied to our hospital). In the early postoperative period, patients underwent brain MRI. RESULTS: The average pain intensity score before nucleotractotomy on the 11-point (0-10) visual analog scale (VAS) was 9.3. The effectiveness of open interventions was somewhat higher; the average VAS score in the early postoperative period for the open technique was 1.57, in the group of patients who underwent percutaneous nucleotractotomy were 2.66. Complete regression of the pain syndrome was achieved in 6 patients; in 5 patients, the pain in the face decreased by more than 50%. One case had an unsatisfactory outcome. In the open-surgery group in the early postoperative period, according to MRI, the average length of the visualized area of signal change was longer (21.5 mm, the average diameter was 3.75 mm) than in a percutaneous nucleotractotomy group (16 mm, the average diameter was 3.75 mm). During the postoperative period (average follow-up 40 months), the pain recurred in 3 patients (30%): 2 patients after percutaneous nucleotractotomy (3 and 18 months after surgery) and in 1 patient 4 months after the open surgery. The mean VAS score at the last follow-up was 2.6. CONCLUSION: Trigeminal nucleotractotomy is an effective approach to the treatment of intractable facial pain. Our experience suggests this technique is highly effective in patients with drug-resistant pain caused by craniofacial tumors and deafferentation conditions after treating trigeminal neuralgia.
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Chemical investigation of the antimalarial medicinal plant Clerodendrum polycephalum led to the isolation of five new diterpenoids, including ajugarins VII-X (1-4) and teuvincenone K (5), along with four known compounds, namely, 12,16-epoxy-6,11,14,17-tetrahydroxy-17(15 â 16)-abeo-5,8,11,13,15-abietapentaen-7-one (6), methyl pheophorbide A (7), loliolide (8), and acacetin (9). The chemical structures of the new compounds were elucidated using NMR spectroscopy, mass spectrometry, circular dichroism, as well as density functional theory calculations. All compounds were evaluated for in vitro activity against Plasmodium falciparum 3D7 malaria parasites with methyl pheophorbide A (7) showing the strongest activity (IC50 4.49 µM). Subsequent in vivo testing in a Plasmodium berghei chemosuppression model showed that compound 7 significantly attenuated peripheral blood parasitemia, leading to 79% and 87% chemosuppression following oral doses at 10 and 20 mg/kg, respectively.
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We demonstrate the construction of 7 Tesla and 12 Tesla all high-temperature-superconducting (HTS) magnets, small enough to fit on your wrist. The size of the magnet reduces the cost of fabrication, decreases the fringe field to permit facile siting of magnets, and decreases the stored energy of high field magnets. These small HTS-based magnets are being developed for gyrotron microwave sources for use in high-field nuclear magnetic resonance applications. The 7 Tesla and 12 Tesla magnets employ a no-insulation winding technique and are cooled to 4.2 Kelvin in a liquid helium cryostat. The 7 Tesla magnet is a single pancake coil, made of only 9.4 m of HTS tape, with an inner diameter of 8 mm and an outer diameter of 24 mm. This magnet was charged up to 1168 Amperes, generating a field of 7.3 Tesla. The 12 Tesla magnet is comprised of two pancake coils (inner diameter of 10 mm and outer diameter of 27 mm) connected in series. This magnet reached its maximum field at a current of 850 Amperes.
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OBJECTIVE: We sought to evaluate the association between diet and angiogenic biomarkers in KpB mice, and the association between these markers, body mass index (BMI), and overall survival (OS) in high-grade serous cancers (HGSC). METHODS: Tumors previously obtained from KpB mice subjected to high-fat diets (HFD, n = 10) or low-fat diets (LFD, n = 10) were evaluated for angiogenesis based on CD-31 microvessel density (MVD). Data from prior microarray analysis (Agilent 244 K arrays) conducted in 10 mice were utilized to assess associations between diet and angiogenetic biomarkers. Agilent (mouse) and Affymetrix Human Genome U133a probes were linked to 162 angiogenic-related genes. The associations between biomarkers, BMI, and OS were evaluated in an HGSC internal database (IDB) (n = 40). Genes with unadjusted p < 0.05 were evaluated for association with OS in the TCGA-OV database (n = 339). RESULTS: There was no association between CD-31 and diet in mice (p = 0.66). Sixteen angiogenic-related genes passed the p < 0.05 threshold for association with HFD vs. LFD. Transforming growth factor-alpha (TGFA) demonstrated 72% higher expression in HFD vs. LFD mice (p = 0.04). Similar to the mouse study, in our HGSC IDB, higher TGFA expression correlated with higher BMI (p = 0.01) and shorter survival (p = 0.001). In the TCGA-OV dataset, BMI data was not available and there was no association between TGFA and OS (p = 0.48). CONCLUSIONS: HFD and obesity may promote tumor progression via differential modulation of TGFA. We were unable to confirm this finding in the TCGA dataset. Further evaluation of TGFA is needed to determine if this is a target unique to obesity-driven HGSC.
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There is an urgent need to diversify the physician workforce in obstetrics and gynecology to serve a diverse patient population and mitigate disparities in care. There is a paucity of data on how to improve recruitment of individuals from underrepresented minoritized groups to the field of obstetrics and gynecology. This article outlines important steps for sharing the department's commitment to diversity, equity, and inclusion; addresses ways to attract a diverse applicant pool; and reviews the importance of and need to perform a holistic review of applicants. This commentary also shares some approaches to support faculty and trainees that may lead to sustained increases in diversity. Using this framework, the authors successfully increased the diversity of their obstetrics and gynecology residency program.
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We present an inexpensive, versatile, and robust mounting system for Hester-Dendy (HD) multiplate samplers that are useful in aquatic biological studies and freshwater biomonitoring programs. Detailed instructions are provided outlining the construction and deployment of a concrete block system featuring threaded anchors for screwing in HD columns in a vertical position. Additionally, eye bolts provide a central attachment point for cabling the block securely to the stream or river bank, and for attachment of a buoy or physiochemical data logger if desired. All the components of the block system are inexpensive, readily available, and assembled with no special skills required. The system offers superior ease-of-use and a more standardized sampling device compared to other methods.
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Monitoramento Ambiental , Invertebrados , Animais , Monitoramento Ambiental/métodos , Rios , Monitoramento Biológico , EcossistemaRESUMO
BACKGROUND: Nowadays there still is no sufficient screening tool for ovarian and uterine cancer. OBJECTIVE: The current study aimed to investigate whether cancer antigen 125 (CA-125), tissue polypeptide antigen (TPA) or the combination of both markers are able to act as screening tools for ovarian or uterine cancer. METHODS: A total of 275 blood samples from different cohorts (ovarian cancer, uterine cancer, benign control group) were prospectively drawn and analyzed. RESULTS: Established biomarkers TPA and CA-125 showed elevated serum concentrations in patients with malignant tumors as compared to healthy women and women with benign diseases. In ROC curve analyses, both biomarkers were well able to discriminate between malignant and healthy, benign or overall non-malignant cases in the whole sample, with AUCs of 0.842 and above. While TPA was the best diagnostic marker in patients with uterine cancer, CA 125 was the best in patients with ovarian cancer. CONCLUSIONS: TPA and CA-125 both showed promising results for the detection of gynecologic malignancies. The combination of CA-125 and TPA did not improve sensitivity in comparison to single markers.
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This cross-sectional study examines state-level variability in hospital presumptive eligibility programs to understand discrepancies in access by Medicaid expansion status.
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Definição da Elegibilidade , Hospitais , HumanosRESUMO
Interactive materials are an emerging class of systems that can offer control over response and adaptivity in polymer structures towards the meso- and macroscale. Here, we use enzyme regulated cleavage of peptide crosslinkers in polymer hydrogels to release a cytotoxic therapeutic nanoparticle with an adaptable mechanism. Hydrogel microplates were formed through polyethylene glycol/peptide photoinitiated thiol-ene chemistry in a soft-lithography process to give square plates of 20 by 20 µm with a height of 10 µm. The peptide was chosen to be degradable in the presence of matrix metalloproteinase 2/9 (MMP-2/9). The hydrogel material's mechanical properties, swelling, and protease degradation were characterised. The microfabricated hydrogels were loaded with docetaxel (DTXL) containing poly(dl-lactide-co-glycolide) (PLGA) nanoparticles, and characterised for enzyme responsivity, and toxicity to MMP-2/9 overexpressing brain cancer cell line U87-MG. A 5-fold decrease in EC50 was seen compared to free DTXL, and a 20-fold decrease was seen for the MMP responsive microplates versus a non-degradable control microplate. Potential applications of this system in post-resection glioblastoma treatment are envisioned.
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Most characterised metazoan mitochondrial genomes are compact and encode a small set of proteins that are essential for oxidative phosphorylation, as well as rRNA and tRNA for their expression. However, in rare cases, invertebrate taxa have additional open reading frames in their mtDNA sequences. Here, we sequenced and analysed the mitochondrial genome of a polychaete worm, Polydora cf. ciliata, part of whose life cycle takes place in low-oxygen conditions. In the mitogenome, we found three "ORFan" regions (544, 1060, and 427â bp) that have no resemblance to any standard metazoan mtDNA gene but lack stop codons in one of the reading frames. Similar regions are found in the mitochondrial genomes of three other Polydora species and Bocardiella hamata. All five species share the same gene order in their mitogenomes, which differ from that of other known Spionidae mitogenomes. By analysing the ORFan sequences, we found that they are under purifying selection pressure and contain conservative regions. The codon adaptation indices (CAIs) of the ORFan genes were in the same range of values as the CAI of conventional protein-coding genes in corresponding mitochondrial genomes. The analysis of the Polydora cf. ciliata mitochondrial transcriptome showed that ORFan-544, ORFan-427 and a portion of the ORFan-1060 are transcribed. Together, this suggests that ORFan-544 and ORFan-427 encode functional proteins. It is likely that the ORFans originated when the Polydora/Bocardiella species complex separated from the rest of the Spionidae, and this event coincided with massive gene rearrangements in their mitochondrial genomes and tRNA-Met duplication.
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Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in multimodal pain control following total joint arthroplasty (TJA). However, few studies have assessed the complications associated with the combinations of NSAIDs in this population despite the known risks associated with this class of medications. The Premier Healthcare Database was queried to identify adults who underwent primary total hip or knee arthroplasty from 2005-2014. The following most common inpatient combinations of NSAIDs were chosen for analysis: aspirin + celecoxib (A + C), toradol + aspirin (T + A), toradol + ibuprofen (T + I), celecoxib + ibuprofen (C + I), ibuprofen + aspirin (I + A), and toradol + celecoxib (T + C). Primary outcomes included acute kidney injury (AKI), gastrointestinal bleed, and stroke. Secondary outcomes included periprosthetic joint infection (PJI), deep vein thrombosis, and pulmonary embolism. Univariate and multivariate regression analyses were used to compare differences and address confounds. Overall, 195,833 patients were identified. After controlling for confounds, increased odds of AKI was associated with A + C (adjusted odds ratio [aOR]: 1.20, 95% confidence interval [CI]: 1.09-1.34, p < 0.001) and decreased odds was associated with T + A (aOR 0.76, 95% CI: 0.69-0.83, p < 0.001). Increased odds of stroke was associated with A + C (aOR: 1.80, 95% CI: 1.15-2.84, p = 0.011); T + I (aOR 3.48, 95% CI: 1.25-9.73, p = 0.017); and I + A (aOR 4.29, 95% CI: 1.06-17.9, p = 0.046). Increased odds of PJI was associated with C + I (aOR: 10.3, 95% CI: 1.35-78.3, p = 0.024). In the TJA patient population, NSAID pairings should be regarded as distinct entities. Our results suggest that combinations including A + C, T + I, I + A, and C + I should be used cautiously. With this knowledge, providers should consider tailoring NSAID prescriptions appropriately.
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Irreversible severe bone marrow failure (BMF) is a life-threatening condition in pediatric patients. Most important causes are inherited bone marrow failure syndromes (IBMFSs) and (pre)malignant diseases, such as myelodysplastic syndrome (MDS) and (idiopathic) aplastic anemia (AA). Timely treatment is essential to prevent infections and bleeding complications and increase overall survival (OS). Allogeneic hematopoietic stem cell transplantation (HSCT) provides a cure for most types of BMF but cannot restore non-hematological defects. When using a matched sibling donor (MSD) or a matched unrelated donor (MUD), the OS after HSCT ranges between 60 and 90%. Due to the introduction of post-transplantation cyclophosphamide (PT-Cy) to prevent graft versus host disease (GVHD), alternative donor HSCT can reach similar survival rates. Although HSCT can restore ineffective hematopoiesis, it is not always used as a first-line therapy due to the severe risks associated with HSCT. Therefore, depending on the underlying cause, other treatment options might be preferred. Finally, for IBMFSs with an identified genetic etiology, gene therapy might provide a novel treatment strategy as it could bypass certain limitations of HSCT. However, gene therapy for most IBMFSs is still in its infancy. This review summarizes current clinical practices for pediatric BMF, including HSCT as well as other disease-specific treatment options.
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Methods: We performed a hospital-based prospective cohort study with 1,317 enrolled participants. We compared patients and healthy volunteers according to the main demographic, anthropometric parameters, stroke risk factors, comorbidities, and data of clinical and instrumental examination. In order to balance the study and the control groups for age and sex, the propensity score matching was performed. In order to generate the overall predictive model, a multivariate analysis was performed using the binary logistic regression method. Results: The following predictors of ESUS were identified in current study: arterial hypertension (AH); increased heart rate and pulmonary arterial systolic pressure (PASP); the presence of conduction disturbance; the enlargement of left, right atrium, and left ventricle end-systolic length; increased intima-media thickness (IMT) in right and left common carotid artery (CCA); lowered Montreal Cognitive Assessment (MoСA) cognitive scale score; the presence of subcortical microbleeds; central brain atrophy; the larger size of third ventricle; and the higher medial temporal lobe atrophy (MTA) score. The following risk factors were included in the final predictive model: the presence of AH (p < 0.0005; OR = 12.98 (95% CI: 4.53-37.21)) and PASP (p=0.018; OR = 1.13 (95% CI: 1.02-1.25)) and male sex (p=0.046; OR = 2.771 (95% CI: 1.017-7.555)). The Nagelkerke's pseudo-R-squared value was 0.404 and the significance of the Hosmer-Lemeshow test was 0.733, which indicate the goodness of the final logistic regression model. Conclusions: We propose that AH and its consequences are the main predictors of ESUS. The results of this study emphasize the importance of AH control for primary and secondary prevention of ESUS.
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AVC Embólico , Hipertensão , Acidente Vascular Cerebral , Humanos , Masculino , Espessura Intima-Media Carotídea , Estudos Prospectivos , Acidente Vascular Cerebral/diagnóstico , Fatores de Risco , Hipertensão/complicações , Atrofia/complicaçõesRESUMO
INTRODUCTION: Hospital Presumptive Eligibility (HPE) is a temporary Medicaid insurance at hospitalization which can offset patient costs of care, increase access to post-discharge resources, and provide a path to sustain coverage through Medicaid. Less is known about the implications of HPE programs on trauma centers (TCs). We aimed to describe the association with HPE and hospital Medicaid reimbursement, as well as characterize incentives for HPE participation among hospitals and TCs. We hypothesized there would be financial, operational, and mission-based incentives. METHODS: We performed a convergent mixed methods study of HPE hospitals in California (including all verified TCs). We analyzed Annual Financial Disclosure Reports from California's Department of Health Care Access and Information (HCAI) (2005-2021). Our primary outcome was Medicaid net revenue. We also conducted thematic analysis of semi-structured interviews with hospital stakeholders to understand incentives for HPE participation (n = 8). RESULTS: Among 367 California hospitals analyzed, 285 (77.7%) participate in HPE 77 (21%) of which are TCs. As of early 2015, 100% of trauma centers had elected to enroll in HPE. There is a significant positive association between HPE participation and net Medicaid revenue. The highest Medicaid revenues are in HPE level I and level II trauma centers. Controlling for changes associated with the Affordable Care Act, HPE enrollment is associated with increased net patient Medicaid revenue (b = 6.74, p < 0.001) and decreased uncompensated care costs (b = -2.22, p < 0.05). Stakeholder interviewees' explanatory incentives for HPE participation included: reduction of hospital bad debt, improved patient satisfaction and community benefit in access to care. CONCLUSION: HPE programs are a promising pathway not only for long-term insurance coverage for trauma patients, but also play a role in TC viability. Future interventions will target streamlining the HPE Medicaid enrollment process to reduce resource burden on participating hospitals and ensure ongoing patient engagement in the program. LEVEL OF EVIDENCE: Economic/decision study, Level II.
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BACKGROUND AND OBJECTIVES: Although venous sinus stenting (VSS) improves cerebrospinal fluid reabsorption and decreases intracranial pressure in patients with idiopathic intracranial hypertension (IIH), the underlying pathophysiology of IIH is not well understood. We present a review and meta-analysis of the literature on VSS for IIH treatment, focusing on the rates of restenosis and symptom recurrence. METHODS: We performed a systematic review of PubMed and Embase databases between January 1, 2011, and December 31, 2021. Articles including ≥5 patients with IIH and venous sinus stenosis treated with VSS and post-treatment rates of restenosis (de novo stenosis at a different anatomic location along the dural sinuses or restenosis within or adjacent to the stent) were selected. Demographic, procedural, and outcomes data were collected and analyzed. Mean values for variables collected were pooled, and a mean value was calculated with a 95% CI. RESULTS: Twenty-four articles were included, comprising 694 patients and 781 VSS cases. The mean age was 33.9 (CI, 31.5-36.2) years. The mean body mass index was 35.3 (CI, 32.9-37.7) kg/m2. Before VSS, 98.8% (CI, 96.8%-100.0%) of patients experienced headaches, 87.7% (CI, 80.6%-95.5%) had visual acuity issues, 78.7% (CI, 69.9%-88.5%) had papilledema, 58.3% (CI, 46.0%-73.9%) had tinnitus, and 98.8% (96.4%-100.0%) had symptoms refractory to previous therapies. After VSS, 77.7% (CI, 71.1%-84.95%) experienced symptom improvement and 22.3% (CI, 15.1%-29.0%) had persistent or worsened symptoms. Pooled restenosis rate was 17.7% (CI, 14.9%-20.9%). CONCLUSION: VSS is effective in alleviating IIH signs and symptoms, but the associated high rates of restenosis and persistent symptoms highlight the need for further investigation of this procedure and other adjunctive treatments for IIH.
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Carotid artery elongation (ECA) is widespread in the asymptomatic population and among people with a history of ischemic stroke (IS). There are different points of view on the ways these changes contribute to brain ischemic damage pathogenesis. Materials and Methods: From 2019 to 2021, we included 1171 people who had suffered from IS less than one year before the investigation in the study, 404 (34.5%) women aged 27 to 95 years (64 ± 13 years) and 767 men (21-90; 60 ± 11 years). All patients involved in the study underwent multimodal radiological investigation in addition to assessments of their clinical and neurological data. Results: In this study, we were unable to detect a relationship between ECA localization and acute ischemic lesions. The frequency of ECA detection in patients with IS was the same as that in carotid and vertebral-basilar arterial systems. The prevalence of ECA was the same in patients with different IS subtypes (TOAST). There was no association between the localization of ECA and ischemic lesions; moreover, there were no differences in the IS frequency between anterior and posterior circulation. There were statistically significant decreases in linear peak systolic and end diastolic velocities in the internal carotid and vertebral arteries, as well as in the intracranial arteries in patients with ECA.