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Chorea-acanthocytosis (ChAc) is an extremely rare neurodegenerative disorder characterized by movement disorders and acanthocytosis. Orofacial dyskinesia is a distinct symptom of this disorder that can lead to lip injuries and feeding difficulties. This paper reports the first case of a patient with ChAc presenting with a lip defect, who was managed with surgical and adjuvant onabotulinumtoxinA (BTX-A) therapy. A 43-year-old woman diagnosed with ChAc was referred to our clinic because of a 5× 5 mm lip defect resulting from orofacial dyskinesia. Wedge resection of the scar tissue was carried out, followed by reconstruction by suturing. Postoperatively, BTX-A injections were administered to ameliorate dyskinesia. Thirty units of BTX-A were injected into each masseter muscle, and 40 units were injected into the orbicularis oris muscle. At 1, 2, and 4 weeks after the injections, assessments were performed using the Abnormal Involuntary Movement Scale, and the patient's impression of change was assessed using the Global Rating of Change Scale. Subsequent adjuvant BTX-A treatment yielded subjective and objective improvements in orofacial dyskinesia. In conclusion, lip reconstruction and adjuvant BTX-A injections were effective in treating lip defects associated with orofacial dyskinesia in patients with ChAc, which highlights the need for a multimodal treatment approach. [ABSTRACT FROM AUTHOR]

The severe gummy smile and a skeletal class II profile pose challenges in treatment. This case report outlines an effective alternative for addressing these problems in a patient with skeletal class II division 2, class II molar relationship, retroclination of upper incisors, and lip protrusion. Treatment objectives included normalizing the overjet and overbite, improving the gummy smile, and establishing a satisfactory occlusion. A three-dimensional simulation was performed to consult with the patient, assess possible results, and predict treatment biomechanics. The treatment involved the use of two zygomatic and one inter-radicular temporary anchorage devices, along with botulinum toxin. After the 2-year follow-up, a satisfactory dental occlusion, aesthetic improvement, and adequate function were achieved. This approach offers a viable alternative to orthognathic surgery for adults with skeletal class II malocclusion and a severe gummy smile due to hypermobile lip. [ABSTRACT FROM AUTHOR]

Background: Botulinum toxin type A is widely utilized for both therapeutic and aesthetic purposes, yet concerns regarding its immunogenicity have raised issues related to treatment failure and adverse reactions. Objective: This review aims to evaluate the immunogenicity of commercially available botulinum toxin type A products across various clinical indications and identify the risk factors associated with antibody formation. Methods: A comprehensive search of electronic databases was conducted to find studies that investigated the immunogenicity of botulinum toxin type A in patients treated for different conditions. The studies were classified based on the Oxford Center for Evidence-Based Medicine's evidence hierarchy. Results: The overall incidence of neutralizing antibody formation with botulinum toxin type A treatment is relatively low. However, it varies depending on the indication and is influenced by factors such as the frequency of injections and the cumulative dose. The total cumulative dose and the number of treatment cycles are critical factors in determining the risk of developing antibodies against botulinum toxin type A. Conclusion: This literature review highlights that the immunogenicity of botulinum toxin type A products differs across indications, with repeated injections posing a significant risk for the formation of neutralizing antibodies. The findings underscore the need for further research to better understand antibody formation mechanisms and to develop strategies that minimize their impact on treatment efficacy. [ABSTRACT FROM AUTHOR]

The first-line management of cervical dystonia (CD) symptoms is intramuscular injection of botulinum toxin type A (BoNTA). However, a comparison of safety among BoNTAs is difficult because, per regulatory authorities, units of BoNTA activity are not interchangeable. Dysphagia and muscle weakness are widely considered two key adverse events to monitor closely in the treatment of CD. This integrated analysis compared the safety of BoNTAs approved for CD in the US by evaluating relationships between the incidence of dysphagia and muscle weakness in prescribing information and the core neurotoxin content. Coefficients The coefficients of determination (R2) and trendlines were estimated via regression-based lines of best fit. Adverse drug reaction (ADR) rates were strongly correlated with core neurotoxin amounts for conventional BoNTAs (slope coefficients: dysphagia = 0.048, R2 = 0.74; muscle weakness = 0.096, R2 = 0.82). The published ADR rates at approved doses for conventional BoNTAs were higher compared with DaxibotulinumtoxinA (DAXI; DAXXIFY®, Revance Therapeutics, Inc., Nashville, TN, USA) by core neurotoxin content. The use of a core neurotoxin amount was found to be an effective method for comparing the safety of BoNTA products. Current clinical trials suggest that DAXI, a novel BoNTA formulation, provides a potentially wider safety margin compared with other approved BoNTAs for CD. The lower amount of core neurotoxin administered at approved doses compared with conventional BoNTAs may explain low on-target ADRs like muscle weakness, whereas reduced diffusion from the injection site is thought to be responsible for low off-target ADRs like dysphagia. [ABSTRACT FROM AUTHOR]

BACKGROUND: Olipudase alfa is a recombinant human acid sphingomyelinase enzyme replacement therapy for non-central-nervous-system manifestations of acid sphingomyelinase deficiency (ASMD). The ASCEND randomized placebo-controlled trial in adults with ASMD demonstrated reductions in sphingomyelin storage, organomegaly, interstitial lung disease and impaired diffusion capacity of the lung (DLCO), during the first year of olipudase alfa treatment. In an ongoing open-label extension of the ASCEND trial, individuals in the placebo group crossed over to olipudase alfa, and those in the olipudase alfa group continued treatment. RESULTS: Thirty-five of 36 participants continued in the extension trial, and 33 completed year 2. Change-from-baseline results are presented as least-square mean percent change ± SEM. Improvements in the cross-over group after 1 year of treatment paralleled those of the olipudase alfa group from the primary analysis, while clinical improvement continued for those receiving olipudase alfa for 2 years. In the cross-over group, percent-predicted DLCO increased by 28.0 ± 6.2%, spleen volume decreased by 36.0 ± 3.0% and liver volume decreased by 30.7 ± 2.5%. For those with 2 years of olipudase alfa treatment, the percent predicted DLCO increased by 28.5 ± 6.2%, spleen volume decreased by 47.0 ± 2.7%, and liver volume decreased by 33.4 ± 2.2%. Lipid profiles and elevated liver transaminase levels improved or normalized by 1 year and remained stable through 2 years of treatment. Overall, 99% of treatment-emergent adverse events were mild or moderate, with one treatment-related serious adverse event (extrasystoles; previously documented cardiomyopathy). No individual discontinued due to an adverse event. CONCLUSION: Treatment with olipudase alfa is well tolerated and reduces manifestations of chronic ASMD with sustained efficacy. Trial registration NCT02004691 registered 9 December 2013, https://clinicaltrials.gov/ct2/show/NCT02004691.

Background and Objectives: This is a propensity-matched, single-center study of limited versus extended resection for type A acute aortic dissection (AAAD). Materials and Methods: This study collected retrospective data for 440 patients with acute type A aortic dissection repairs (limited resection, LR-215; extended resection, ER-225), of which 109 pairs were propensity-matched to LR versus ER. Multivariate analysis was performed for inpatient death, long-term survival and the composite outcome of inpatient death/TIA/stroke. Kaplan–Meier survival curves were compared at 1, 3, 5, 10 and 15 years using the log-rank test. Results: Mean age was 66.9 ± 13 years and mean follow-up was 5.3 ± 4.7 years. A total of 48.9% had LR. In-hospital mortality was 10% (LR: 6% vs. ER: 13.8%, p < 0.01). ER, NYHA class, salvage surgery and additional procedures were predictors of increased mortality in unmatched data. Propensity-matched data showed no difference in TIA/stroke rates, LOS, inpatient mortality or composite outcomes. LR had better survival (LR: 77.1% vs. ER: 51.4%, p < 0.001). ER (OR: 1.97, 95% CI: 1.27, 3.08, p = 0.003) was a significant predictor of worse long-term survival. At 15 years, aortic re-operation was 17% and freedom from re-operation and death was 42%. Conclusions: Type A aortic dissection repair has high mortality and morbidity, although results have improved over two decades. ER was a predictor of worse perioperative results and long-term survival. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the safety, efficacy, and short and long-term postoperative results of using BTA. Methods: We conducted a systematic review following the recommendations of the PRISMA method. We systematically reviewed the MEDLINE/PubMed and SCOPUS electronic databases for studies published between January 2010 and September 2021. This systematic review was registered in PROSPERO, with registration number CRD42021252445. Results: After applying the selection criteria, 11 relevant articles were selected. The total sample size was 1058 patients. Most studies aimed to assess the rate of fascial closure, followed by the rate of recurrence and reporting of postoperative complications, as well as the need for the components separation technique (CST). None of the studies reported serious complications from using BTA. Regarding fascial closure, all articles had rates above 75%, except for one. Surgical site events ranged between 19% and 29.4%. No recurrence in the group that used BTA was recorded in five studies. The other articles reported recurrence rates ranging from 6.4 to 11.4% in the groups that received BTA. The studies had varying follow-up times ranging from 1 to 49 months, with a mean of 18.6 months (± 11.2). Conclusion: This review described most of the key points about the preoperative use of BTA in hernia repair. It can be concluded that the use of BTA is a safe and effective practice that promotes good short and long-term results. However, the limitations of the current literature prevent more accurate conclusions on the subject. [ABSTRACT FROM AUTHOR]

Aim: The cost-effectiveness of treatment options (anticholinergics, β3-adrenoceptor agonists, onabotulinumtoxinA, sacral nerve stimulation and percutaneous tibial stimulation [the latter two including new rechargeable neurostimulators]) for the management of overactive bladder (OAB) were compared with best supportive care (BSC) using a previously published Markov model. Materials & methods: Cost-effectiveness was evaluated over a 15-year time horizon, and sensitivity analyses were performed using 2- and 5-year horizons. Discontinuation rates, resource utilization, and costs were derived from published sources. Results: Using Medicare and commercial costs over a 15-year time period, onabotulinumtoxinA 100U had incremental cost-effectiveness ratios (ICERs) gained of $39,591/quality-adjusted life-year (QALY) and $42,255/QALY, respectively, versus BSC, which were the lowest ICERs of all assessed treatments. The sensitivity analyses at 2- and 5-year horizons also showed onabotulinumtoxinA to be the most cost-effective of all assessed treatments versus BSC. Conclusion: OnabotulinumtoxinA 100U is currently the most cost-effective treatment for OAB.

Botulinum neurotoxins (BoNTs) are among the most lethal toxins known to humans, comprising seven established serotypes termed BoNT/A-G encoded in two types of gene clusters (ha and orfX) in BoNT-producing clostridia. The ha cluster encodes four non-toxic neurotoxin-associated proteins (NAPs) that assemble with BoNTs to protect and enhance their oral toxicity. However, the structure and function of the orfX-type NAPs remain largely unknown. Here, we report the crystal structures for OrfX1, OrfX2, and an OrfX1-OrfX3 complex, which are encoded in the orfX cluster of a BoNT/E1-producing Clostridium botulinum strain associated with human foodborne botulism. These structures lay the foundation for future studies on the potential roles of OrfX proteins in oral intoxication and pathogenesis of BoNTs.

According to the facial feedback hypothesis, when we see an angry or happy face, we contract or flex the relevant muscles to recreate the expression to assist in identifying and experiencing the emotion reflected. We investigated the facial feedback hypothesis by using botulinum toxin type A (onabotulinumtoxinA; onabotA) injections to induce temporary paralysis in the glabellar muscles (responsible for frowning) and measured functional brain activity during the processing of emotional faces. Ten females viewed pictures of happy and angry faces during two functional magnetic resonance imaging (fMRI) scan sessions: one prior (Pre) to onabotA and one following (Active) onabotA injections. We found Pre vs. Active onabotA modulation of activity in the amygdala for both happy and angry faces, as well as modulation of activity in the fusiform gyrus for happy faces. Consistent with our predictions, preventing frowning through inhibition of glabellar muscle contraction altered amygdala processing for emotional faces. The modulation of amygdala and fusiform gyrus activity following onabotA may reflect compensatory processes in a neuroanatomical circuit involved in emotional processing that is engaged when facial feedback is impaired. These data contribute to a growing literature suggesting that inhibition of glabellar muscle contraction alters neural activity for emotional processing.Clinical Trials.gov registration number: NCT03373162.

Botulinum neurotoxin E (BoNT/E) is one of the major causes of human botulism and paradoxically also a promising therapeutic agent. Here we determined the co-crystal structures of the receptor-binding domain of BoNT/E (HCE) in complex with its neuronal receptor synaptic vesicle glycoprotein 2A (SV2A) and a nanobody that serves as a ganglioside surrogate. These structures reveal that the protein-protein interactions between HCE and SV2 provide the crucial location and specificity information for HCE to recognize SV2A and SV2B, but not the closely related SV2C. At the same time, HCE exploits a separated sialic acid-binding pocket to mediate recognition of an N-glycan of SV2. Structure-based mutagenesis and functional studies demonstrate that both the protein-protein and protein-glycan associations are essential for SV2A-mediated cell entry of BoNT/E and for its potent neurotoxicity. Our studies establish the structural basis to understand the receptor-specificity of BoNT/E and to engineer BoNT/E variants for new clinical applications.

Equine-derived antitoxin (BAT®) is the only treatment for botulism from botulinum neurotoxin serotype G (BoNT/G). BAT® is a foreign protein with potentially severe adverse effects and is not renewable. To develop a safe, more potent, and renewable antitoxin, humanized monoclonal antibodies (mAbs) were generated. Yeast displayed single chain Fv (scFv) libraries were prepared from mice immunized with BoNT/G and BoNT/G domains and screened with BoNT/G using fluorescence-activated cell sorting (FACS). Fourteen scFv-binding BoNT/G were isolated with KD values ranging from 3.86 nM to 103 nM (median KD 20.9 nM). Five mAb-binding non-overlapping epitopes were humanized and affinity matured to create antibodies hu6G6.2, hu6G7.2, hu6G9.1, hu6G10, and hu6G11.2, with IgG KD values ranging from 51 pM to 8 pM. Three IgG combinations completely protected mice challenged with 10,000 LD50s of BoNT/G at a total mAb dose of 6.25 μg per mouse. The mAb combinations have the potential for use in the diagnosis and treatment of botulism due to serotype G and, along with antibody combinations to BoNT/A, B, C, D, E, and F, provide the basis for a fully recombinant heptavalent botulinum antitoxin to replace the legacy equine product.

BackgroundNiemann-Pick Disease Type C1 (NPC1) is a disorder of intracellular cholesterol and lipid trafficking that leads to the accumulation of cholesterol and lipids in the late endosomal/lysosomal compartment, resulting in systemic manifestations (including hepatosplenomegaly and lung infiltration) and neurodegeneration. Preclinical studies have demonstrated that systemically administered 2-hydroxypropyl-β-cyclodextrin (HPβCD; Trappsol® Cyclo™) restores cholesterol metabolism and homeostasis in peripheral organs and tissues and in the central nervous system (CNS). Here, we assessed the safety, pharmacokinetics, and pharmacodynamics of HPβCD in peripheral tissues and the CNS in adult subjects with NPC1.MethodsA Phase 1, randomized, double-blind, parallel group study enrolled 13 subjects with NPC1 who received either 1500 mg/kg or 2500 mg/kg HPβCD intravenously every 2 weeks for a total of 7 doses (14 weeks). Subjects were 18 years or older, with a confirmed diagnosis of NPC1 and evidence of systemic involvement on clinical assessment. Pharmacokinetic evaluations in plasma and cerebrospinal fluid (CSF) were performed at the first and seventh infusions. Pharmacodynamic assessments included biomarkers of systemic cholesterol synthesis (serum lathosterol) and degradation (serum 4β-hydroxycholesterol), secondary sphingomyelin storage (plasma lysosphingomyelin-509, now more accurately referred to as N-palmitoyl-O-phosphocholineserine [PPCS]), and CNS-specific biomarkers of neurodegeneration (CSF total Tau) and cholesterol metabolism (serum 24(S)-hydroxycholesterol [24(S)-HC]). Safety monitoring included assessments of liver and kidney function, infusion related adverse events, and hearing evaluations.ResultsTen subjects completed the study, with 6 at the 1500 mg/kg dose and 4 at the 2500 mg/kg dose. One subject withdrew following the first infusion after experiencing hypersensitivity pneumonitis, and 2 subjects withdrew after meeting a stopping rule related to hearing loss. Overall, HPβCD had an acceptable safety profile. The observed pharmacokinetic profile of HPβCD was similar following the first and seventh infusions, with a plasma half-life of 2 h, a maximum concentration reached at 6 to 8 h, and no evidence of accumulation. Serum biomarkers of cholesterol metabolism showed reduced synthesis and increased degradation. Compared to Baseline, filipin staining of liver tissue showed significant reductions of trapped unesterified cholesterol at both dose levels at Week 14. Plasma PPCS levels were also reduced. HPβCD was detected at low concentrations in the CSF (maximum, 33 μM) at both dose levels and persisted longer in CSF than in plasma. Total Tau levels in CSF decreased in most subjects. Serum levels of 24(S)-HC, a cholesterol metabolite from the CNS that is exported across the blood-brain barrier and into the circulation, decreased after both the first and seventh doses. Hence, pharmacodynamic assessments in both peripheral and CNS-related tissue show target engagement. While not the aim of the study, subjects reported favorable impacts on their quality of life.ConclusionsThe plasma pharmacokinetics and pharmacodynamics of HPβCD administered at two intravenous dose levels to subjects with NPC1 were comparable to those observed in preclinical models. HPβCD cleared cholesterol from the liver and improved peripheral biomarkers of cholesterol homeostasis. At low CSF concentrations, HPβCD appeared to be pharmacologically active in the CNS based on the increased efflux of 24(S)-HC and reduction in CSF total Tau, a biomarker of CNS neurodegeneration. These data support the initiation of longer-term clinical trials to evaluate the safety and efficacy of intravenous HPβCD in subjects with NPC1. (ClinicalTrials.gov numbers: present trial, NCT02939547; open-label extension of the present trial, NCT03893071; global pivotal trial, NCT04860960).

Copyright of Türkiye Klinikleri Journal of Ophthalmology is the property of Turkiye Klinikleri and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Background Acid Sphingomyelinase Deficiency (ASMD) is an ultra-rare autosomal recessive lysosomal storage disorder characterized by intracellular lipid accumulation resulting from reduced function of acid sphingomyelinase. Olipudase alfa, an enzyme replacement therapy, was recently approved in several countries for the treatment of the non-neurologic manifestations of ASMD. Studies demonstrate improvement in organomegaly, pulmonary function and lipid profiles with olipudase alfa, yet little is known about its impact on quality of life (QoL) for patients and caregivers. The purpose of this study is to better understand the real-life impact of ASMD on patients and caregivers and assess how olipudase alfa impacts QoL for pediatric patients and their caregivers. Methods Caregivers of pediatric patients (≤ 18 years of age) with a confirmed diagnosis of ASMD that received olipudase alfa for at least 12 months were recruited in early 2022 through national patient organizations to participate in a global online questionnaire followed by semi-structured interviews. Ten caregivers of patients with ASMD who utilized olipudase alfa as an experimental therapy for pediatric patients participated in the study. Quantitative analysis of the results was undertaken, and qualitative data was analyzed using an inductive thematic approach. Results Ten eligible participants completed questionnaires, and 8 of the 10 went on to participate in structured interviews. Symptom burden of ASMD and impact on symptomatology and quality of life after olipudase alfa use are reported here. Five themes emerged from analysis: (1) ASMD is a systemic disease with a wide array of manifestations that significantly impact QoL; (2) Olipudase alfa was associated with improvements in all non-neurologic manifestations of ASMD; (3) Participants perceived the risk associated with olipudase alfa to be low and the benefits to greatly outweigh any risk or burden; (4) Participants reported an unmet need to treat the neurologic manifestations of the disease despite the benefits of olipudase alfa in the management of non-neurological symptoms; (5) Participants felt all patients with ASMD need access to olipudase alfa based on the life-changing experience they perceived. Conclusions These findings highlight the sustained positive impact olipudase alfa had in many domains that are deemed important to patients and families living with ASMD and outline the extensive unmet need for patients and families living with ASMD.

Introduction: The aesthetic procedure market is growing exponentially in Brazil. This growth has aroused the interest of several professional categories. The decision to practice in the sector must consider the market opportunities in the location in which you intend to operate. However, the area lacks comparative analyses documenting probable regional differences in the country. The objective of the study is to describe market differences in aesthetic procedures between Brazilian states and regions. An index of potential cosmetic consumption (IPCC) is calculated for such a comparative analysis. Method: Cross-sectional study involving providers of nonsurgical aesthetic procedures in Brazil. Searches on Google Maps® were conducted using key terms, and telephone interviews were conducted to obtain information on professional categories, types of providers, and services offered. Positive predictive values were obtained for all search strategies and used to estimate the total number of providers. Population size and per capita income were considered to calculate the IPCCs for Brazilian states. Results: São Paulo, Minas Gerais, and Rio de Janeiro presented the highest IPCCs, being 524, 210, and 180, respectively. Roraima had an IPCC of 14, the lowest in the country. The Southeast Region presented, on average, the highest IPCC (242) among all Brazilian regions. Conclusion: Considering population size and income, the Southeast Region presents the greatest market opportunities for nonsurgical aesthetic procedures in Brazil. Our findings may be of interest to healthcare professionals and investors who work or intend to work in the sector.

The first-line management of cervical dystonia (CD) symptoms is intramuscular injection of botulinum toxin type A (BoNTA). However, a comparison of safety among BoNTAs is difficult because, per regulatory authorities, units of BoNTA activity are not interchangeable. Dysphagia and muscle weakness are widely considered two key adverse events to monitor closely in the treatment of CD. This integrated analysis compared the safety of BoNTAs approved for CD in the US by evaluating relationships between the incidence of dysphagia and muscle weakness in prescribing information and the core neurotoxin content. Coefficients The coefficients of determination (R2) and trendlines were estimated via regression-based lines of best fit. Adverse drug reaction (ADR) rates were strongly correlated with core neurotoxin amounts for conventional BoNTAs (slope coefficients: dysphagia = 0.048, R2 = 0.74; muscle weakness = 0.096, R2 = 0.82). The published ADR rates at approved doses for conventional BoNTAs were higher compared with DaxibotulinumtoxinA (DAXI; DAXXIFY®, Revance Therapeutics, Inc., Nashville, TN, USA) by core neurotoxin content. The use of a core neurotoxin amount was found to be an effective method for comparing the safety of BoNTA products. Current clinical trials suggest that DAXI, a novel BoNTA formulation, provides a potentially wider safety margin compared with other approved BoNTAs for CD. The lower amount of core neurotoxin administered at approved doses compared with conventional BoNTAs may explain low on-target ADRs like muscle weakness, whereas reduced diffusion from the injection site is thought to be responsible for low off-target ADRs like dysphagia.

Background: Botulinum toxin type A is widely utilized for both therapeutic and aesthetic purposes, yet concerns regarding its immunogenicity have raised issues related to treatment failure and adverse reactions. Objective: This review aims to evaluate the immunogenicity of commercially available botulinum toxin type A products across various clinical indications and identify the risk factors associated with antibody formation. Methods: A comprehensive search of electronic databases was conducted to find studies that investigated the immunogenicity of botulinum toxin type A in patients treated for different conditions. The studies were classified based on the Oxford Center for Evidence-Based Medicine’s evidence hierarchy. Results: The overall incidence of neutralizing antibody formation with botulinum toxin type A treatment is relatively low. However, it varies depending on the indication and is influenced by factors such as the frequency of injections and the cumulative dose. The total cumulative dose and the number of treatment cycles are critical factors in determining the risk of developing antibodies against botulinum toxin type A. Conclusion: This literature review highlights that the immunogenicity of botulinum toxin type A products differs across indications, with repeated injections posing a significant risk for the formation of neutralizing antibodies. The findings underscore the need for further research to better understand antibody formation mechanisms and to develop strategies that minimize their impact on treatment efficacy.

Background: Acute aortic dissection type A (AADA) is a surgical emergency with relevant mortality and morbidity despite improvements in current management protocols. Identifying patients at risk of a fatal outcome and controlling the factors associated with mortality remain of paramount importance. Methods: In this retrospective observational study, we reviewed the medical records of 117 patients with AADA, who were referred to our centre and operated on between 2005 and 2021. Preoperative, intraoperative, and postoperative variables were analysed and tested for their correlation with in-hospital mortality. Results: The overall survival rate was 83%. Preoperatively, factors associated with mortality were age (p = 0.02), chronic hypertension (p = 0.02), any grade of aortic valve stenosis in the patient's medical history (p = 0.03), atrial fibrillation (p = 0.04), and oral anticoagulation (p = 0.04). Non-survivors had significantly longer operative times (p = 0.002). During the postoperative phase, mortality was strongly associated with acute kidney injury (AKI) (p < 0.001), acute heart failure (p < 0.001), stroke (p = 0.02), focal neurological deficits (p = 0.02), and sepsis (p = 0.001). In the multivariate regression analysis, the onset of postoperative focal neurological deficits was the best predictor of a fatal outcome after adjusting for ARDS (odds ratio: 5.8, 95%-CI: 1.2–41.7, p = 0.04). Conclusions: In this retrospective analysis, atrial fibrillation, oral anticoagulation, hypertension, and age were significantly correlated with mortality. Postoperatively, acute kidney injury, acute heart failure, sepsis, and focal neurological deficits were correlated with in-hospital mortality, and focal neurological deficit has been identified as a significant predictor of fatal outcomes. Early detection and interdisciplinary management of at-risk patients remain crucial throughout the postoperative phase. [ABSTRACT FROM AUTHOR]

Background: Acid Sphingomyelinase Deficiency (ASMD) is an ultra-rare autosomal recessive lysosomal storage disorder characterized by intracellular lipid accumulation resulting from reduced function of acid sphingomyelinase. Olipudase alfa, an enzyme replacement therapy, was recently approved in several countries for the treatment of the non-neurologic manifestations of ASMD. Studies demonstrate improvement in organomegaly, pulmonary function and lipid profiles with olipudase alfa, yet little is known about its impact on quality of life (QoL) for patients and caregivers. The purpose of this study is to better understand the real-life impact of ASMD on patients and caregivers and assess how olipudase alfa impacts QoL for pediatric patients and their caregivers. Methods: Caregivers of pediatric patients (≤ 18 years of age) with a confirmed diagnosis of ASMD that received olipudase alfa for at least 12 months were recruited in early 2022 through national patient organizations to participate in a global online questionnaire followed by semi-structured interviews. Ten caregivers of patients with ASMD who utilized olipudase alfa as an experimental therapy for pediatric patients participated in the study. Quantitative analysis of the results was undertaken, and qualitative data was analyzed using an inductive thematic approach. Results: Ten eligible participants completed questionnaires, and 8 of the 10 went on to participate in structured interviews. Symptom burden of ASMD and impact on symptomatology and quality of life after olipudase alfa use are reported here. Five themes emerged from analysis: (1) ASMD is a systemic disease with a wide array of manifestations that significantly impact QoL; (2) Olipudase alfa was associated with improvements in all non-neurologic manifestations of ASMD; (3) Participants perceived the risk associated with olipudase alfa to be low and the benefits to greatly outweigh any risk or burden; (4) Participants reported an unmet need to treat the neurologic manifestations of the disease despite the benefits of olipudase alfa in the management of non-neurological symptoms; (5) Participants felt all patients with ASMD need access to olipudase alfa based on the life-changing experience they perceived. Conclusions: These findings highlight the sustained positive impact olipudase alfa had in many domains that are deemed important to patients and families living with ASMD and outline the extensive unmet need for patients and families living with ASMD. [ABSTRACT FROM AUTHOR]

Purpose: Low anterior resection syndrome (LARS) has had many impacts on the lives of patients and substantial differences in emotional and social functions. The aim of this study was to investigate the correlation analysis of different personality traits in rectal cancer patients with LARS after undergoing curative surgery. Methods: This study was designed as a prospective cohort study. The inclusion criteria included (1) participants diagnosed with rectal cancer who underwent surgical resection of malignant tumors and (2) ECOG 0–1. The primary outcome was the correlation between different personality traits and low anterior resection syndrome in rectal cancer patients after radical surgery. Low anterior resection syndrome incidence rates were estimated by questionnaires and personality groups by the Type A and Type D Scale‐14 Personality Inventory. Results: For all 161 participants in this study, the presence of a tumor at the lower anal verge and the receipt of neoadjuvant CCRT had a statistically significant positive correlation with the LARS score at 1 month, 6 months, and 1 year (Pearson correlation coefficient = −0.283, −0.374, and − 0.205, respectively), with a p value of less than 0.05. Personalities with Type A, Type D, and Type D‐SI scores had a statistically significant positive correlation with LARS score at 1 month (Pearson correlation coefficient = 0.172, 0.162, and 0,164, p value = 0.03, 0.04, and 0.04). Conclusion: Type A and Type D personalities are highly linked to LARS. Personalized support approaches can ultimately assist rectal cancer patients in overcoming difficulties after surgery and recovery and enhance their functional outcomes. [ABSTRACT FROM AUTHOR]

Alluzience (abobotulinumtoxinA RTU; Ipsen, Paris, France and Galderma SA, Lausanne, Switzerland) is the first ready-to-use (RTU) botulinum toxin type A liquid solution approved for the treatment of glabellar lines in Europe. In this article, the authors provide consensus recommendations on the aesthetic usage of abobotulinumtoxinA RTU. Members of the International Board on Alluzience convened to develop consensus on the treatment of glabellar lines as well as other facial wrinkles based on their own extensive experience. Consensus recommendations were developed to provide practical guidelines for injection of abobotulinumtoxinA RTU. General guidance on proper assessment, treatment planning, and patient education is provided, as well as specific injection guidelines per indication. Indications covered include glabellar lines, crow's feet, horizontal forehead lines, lateral eyebrow lift, lower eyelid wrinkles, bunny lines, drooping nasal tip, perioral wrinkles, drooping mouth corners, masseter hypertrophy, hollow cheek lines, dimpled chin, and platysmal bands. These guidelines provide a practical framework to support routine injection of facial muscles with Alluzience. Level of Evidence: 5 [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES There is an ongoing debate regarding whether patients benefit more from root replacement compared to a reconstruction of the sinuses of Valsalva in acute type A aortic dissection (aTAAD). In those with known or suspected connective tissue disorders, root replacement is considered appropriate. However, there are currently no diameter-based guidelines regarding the best approach in patients with minimally to moderately dilated root and no connective tissue disorders. METHODS From January 2005 to December 2022, a two-centre registry of aTAAD was created. Patients were included based on their age (≤60 years), the absence of root entry and dilatation >50 mm and the absence of syndromic hereditable aortic disease. Patients were divided into 2 groups based on the proximal procedure, root reconstruction and root replacement. Propensity score pair matching was performed based on preoperative characteristics. RESULTS Cumulative incidence of reintervention at 10 years was slightly higher after root reconstruction 13% vs 3.9% in the matched group (P  = 0.040). Survival at 10 years was not affected by the procedure independently of the matching 72.1% vs 71.4% (P  = 0.2). Uni- and multivariate Cox regressions showed that a root diameter of >40 mm was associated with a hazard ratio of 7.7 (95% confidence interval 2.6–23) and 5.4 (7–17), respectively, for reoperation for aneurysm and pseudoaneurysm. CONCLUSIONS Rate of reoperation due to proximal pseudoaneurysm and aneurysm could be significantly reduced with a lower threshold of 40 mm to replace the aortic root in aTAAD than in elective cases. [ABSTRACT FROM AUTHOR]

Copyright of Revista Facultad de Medicina de la Universidad Nacional de Colombia is the property of Universidad Nacional de Colombia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The study of personality type and its impact on various facets of life has always generated a great deal of interest among researchers, academicians, and the public in general. This paper specifically explores the relationship between Type A personality and Type B personality with Job Satisfaction and Life Satisfaction. It also attempts to highlight the nature of the relation between Job Satisfaction and Life Satisfaction. The scales used in this study were Jenkins Activity Survey (Jenkins, Hames, Zyzanski, Rosenman, & Friedman, 1969); Job Satisfaction Scale (Spector, 1985); and Satisfaction with Life Scale (Diener, Emmnos, Larsen, & Griffin, 1985). The data was collected from a sample of 60 working individuals in the age range of 25 years to 60 years. Quantitative analysis was carried out involving Descriptive Analysis, Correlation analysis and Independent samples t-test. Descriptive analysis showed that the mean score of Type B was much higher than Type A in Job Satisfaction. Even though a similar trend was observed with regard to Life Satisfaction, the difference was only marginal. t-test showed that Type Aand Type B differed significantly only on Job Satisfaction (p<0.05). Correlational analysis show a moderate positive relation between Job satisfaction and Life satisfaction (p<0.01). It can be inferred that as Personality types have a significant impact on an individual's Job Satisfaction, organizations need to conduct personality assessments of their employees and ensure their optimal placements. This will enhance utilization of full potential of the employees, build-up of positive job-related attitudes, workplace well-being and increase overall productivity. A favourable work environment and high job satisfaction will have a spillover effect on life satisfaction too. Hence, organizations will be benefitted by having employees experience subjective well-being and possess favourable work-related attitudes. [ABSTRACT FROM AUTHOR]

The initial instance of isolated unilateral temporalis muscle hypertrophy (IUTMH) was reported in 1990. Since then, only few cases have been documented. The cause of this condition remains ambiguous; however, it is presumed to be linked to compensatory and stress-induced hypertrophy. We introduce a rare case of the diagnosis and treatment of IUTMH. A 39-year-old woman presented with a steadily enlarging pain-free swelling on the left side of her face, first noticed a month ago. Apart from a hyperthyroidism medication regimen her medical history was unremarkable. She had no history of temporomandibular joint disease, bruxism, surgery, or trauma. However, she complained of having been under substantial stress lately. Contrast-enhanced magnetic resonance imaging revealed asymmetric temporalis muscle hypertrophy. The treatment plan consisted of administering type A botulinum toxin injections into left temporalis muscle, supplemented by lifestyle changes and relaxation techniques. At a follow-up visit 9 months after the injections, the muscle contour was normalized both in physical and in radiologic examinations. While further supportive evidence is needed, it can be anticipated that cosmetic treatment with botulinum toxin, rather than surgical interventions, will become the standard treatment of IUTMH. [ABSTRACT FROM AUTHOR]

Introduction: Visible scars can cause problems, whether aesthetic, psychological, functional, or social, mainly of great extension and volume, such as keloids. The discovery of new treatments for keloids is not easy, given the presence of some methodological and ethical obstacles, and it is an area that is little explored. Botulinum toxin has been presented as a therapeutic alternative in national and international studies, requiring a compilation and highlighting of the main studies that can support clinical practice. Thus, the objective was to present a scoping review on the therapeutic use of botulinum toxin for the treatment of keloid scars. Method: The review was carried out using the PICO strategy and using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. It was carried out in the PubMed/Medline, Virtual Health Library, and SciELO databases, considering studies from 2016 to September 2021. Results: Overall, 34 articles related to the topic were found. After filtering and selection, the review was constructed with the support of 5 articles. The studies varied between cohorts, case reports, randomized clinical trials, and case-control. It was possible to observe as main results of the short-term action of botulinum toxin in reducing keloids, greater effectiveness in reducing symptoms, and possibilities of clinical use for different populations and clinical manifestations. Conclusion: The mechanism of action of botulinum toxin can facilitate the treatment of keloids and reduce symptoms, requiring more robust studies to define effective scar management protocols.

Excess sebum (seborrhea) results in oily skin and is associated with large pore size and acne. Studies in healthy, seborrheic volunteers have reported that intradermal injection of commercial preparations of botulinum neurotoxin type A (BoNT/A) (onabotulinumtoxinA, abobotulinumtoxinA, and incobotulinumtoxinA) reduced sebum production, and thus, skin oiliness and pore size. The mechanism for these effects has not been fully elucidated; however, several theories involving direct or indirect effects of BoNT/A on neuronal and/or dermal cells (e.g., sebocytes) have been proposed. In the present study, we evaluated the direct effect of native research grade BoNT/A complex, a commercial preparation of BoNT/A (onabotA), and BoNT/A variants on sebocyte lipogenesis using an in vitro sebocyte cell model. We show that picomolar concentrations of BoNT/A (BoNT/A complex: half maximal effective concentration [EC50] = 24 pM; BoNT/A 150 kDa: EC50 = 34 pM) modulate sebocyte lipogenesis and reduce oleic acid-induced sebocyte differentiation, lipogenesis, and holocrine-like secretion. Comparative studies with the binding domain of BoNT/A, which lacks enzymatic activity, show that this effect is independent of the enzymatic activity of BoNT/A and likely occurs via sebocyte cell surface receptors (e.g., fibroblast growth factor receptors). Overall, these results shed light on the potential mechanism of action and rationale for use of BoNT/A for treatment of sebum-related conditions.

BackgroundSpasticity is common in cerebral palsy and can result in pain and diminished health-related quality of life.ObjectiveTo evaluate the safety and efficacy of onabotulinumtoxinA for lower limb spasticity treatment in children with cerebral palsy.MethodsIn this registrational phase 3, multinational, randomized, double-blind, placebo-controlled trial (NCT01603628), children (2-

The botulinum neurotoxin serotype A (BoNT/A) cuts a single peptide bond in SNAP25, an activity used to treat a wide range of diseases. Reengineering the substrate specificity of BoNT/A's protease domain (LC/A) could expand its therapeutic applications; however, LC/A's extended substrate recognition (≈ 60 residues) challenges conventional approaches. We report a directed evolution method for retargeting LC/A and retaining its exquisite specificity. The resultant eight-mutation LC/A (omLC/A) has improved cleavage specificity and catalytic efficiency (1300- and 120-fold, respectively) for SNAP23 versus SNAP25 compared to a previously reported LC/A variant. Importantly, the BoNT/A holotoxin equipped with omLC/A retains its ability to form full-length holotoxin, infiltrate neurons, and cleave SNAP23. The identification of substrate control loops outside BoNT/A's active site could guide the design of improved BoNT proteases and inhibitors.

Background and Objectives: This is a propensity-matched, single-center study of limited versus extended resection for type A acute aortic dissection (AAAD). Materials and Methods: This study collected retrospective data for 440 patients with acute type A aortic dissection repairs (limited resection, LR-215; extended resection, ER-225), of which 109 pairs were propensity-matched to LR versus ER. Multivariate analysis was performed for inpatient death, long-term survival and the composite outcome of inpatient death/TIA/stroke. Kaplan–Meier survival curves were compared at 1, 3, 5, 10 and 15 years using the log-rank test. Results: Mean age was 66.9 ± 13 years and mean follow-up was 5.3 ± 4.7 years. A total of 48.9% had LR. In-hospital mortality was 10% (LR: 6% vs. ER: 13.8%, p < 0.01). ER, NYHA class, salvage surgery and additional procedures were predictors of increased mortality in unmatched data. Propensity-matched data showed no difference in TIA/stroke rates, LOS, inpatient mortality or composite outcomes. LR had better survival (LR: 77.1% vs. ER: 51.4%, p < 0.001). ER (OR: 1.97, 95% CI: 1.27, 3.08, p = 0.003) was a significant predictor of worse long-term survival. At 15 years, aortic re-operation was 17% and freedom from re-operation and death was 42%. Conclusions: Type A aortic dissection repair has high mortality and morbidity, although results have improved over two decades. ER was a predictor of worse perioperative results and long-term survival.

Abstract Purpose Low anterior resection syndrome (LARS) has had many impacts on the lives of patients and substantial differences in emotional and social functions. The aim of this study was to investigate the correlation analysis of different personality traits in rectal cancer patients with LARS after undergoing curative surgery. Methods This study was designed as a prospective cohort study. The inclusion criteria included (1) participants diagnosed with rectal cancer who underwent surgical resection of malignant tumors and (2) ECOG 0–1. The primary outcome was the correlation between different personality traits and low anterior resection syndrome in rectal cancer patients after radical surgery. Low anterior resection syndrome incidence rates were estimated by questionnaires and personality groups by the Type A and Type D Scale‐14 Personality Inventory. Results For all 161 participants in this study, the presence of a tumor at the lower anal verge and the receipt of neoadjuvant CCRT had a statistically significant positive correlation with the LARS score at 1 month, 6 months, and 1 year (Pearson correlation coefficient = −0.283, −0.374, and − 0.205, respectively), with a p value of less than 0.05. Personalities with Type A, Type D, and Type D‐SI scores had a statistically significant positive correlation with LARS score at 1 month (Pearson correlation coefficient = 0.172, 0.162, and 0,164, p value = 0.03, 0.04, and 0.04). Conclusion Type A and Type D personalities are highly linked to LARS. Personalized support approaches can ultimately assist rectal cancer patients in overcoming difficulties after surgery and recovery and enhance their functional outcomes.

Objective: Spasticity in children with cerebral palsy can be managed by a spectrum of approaches, from conservative therapy, to temporary botulinum toxin A injections, to permanent transection of sensory nerves with a selective dorsal rhizotomy. This pilot study investigated whether these three tone management approaches are associated with histological and biochemical properties of the medial gastrocnemius. Design: A convenience sample of children with cerebral palsy undergoing gastrocnemius lengthening surgery was enrolled. intraoperative biopsies were obtained from three individuals (one each: minimal tone treatment; frequent gastrocnemius botulinum toxin A injections; previous selective dorsal rhizotomy). All individuals had plantarflexor contractures, weakness, and impaired motor control before the biopsy. Results: Differences between participants were observed for muscle fiber cross-sectional area, fiber type, lipid content, satellite cell density, and centrally located nuclei. The most pronounced difference was the abundance of centrally located nuclei in the botulinum toxin A participants (52%) compared with the others (3-5%). Capillary density, collagen area and content, and muscle protein content were similar across participants. Conclusions: Several muscle properties seemed to deviate from reported norms, although age- and muscle-specific references are sparse. Prospective studies are necessary to distinguish cause and effect and to refine the risks and benefits of these treatment options. [ABSTRACT FROM AUTHOR]

Mice are commonly used to study mandibular dynamics due to their similarity in chewing cycle patterns with humans. Adult mice treated unilaterally with botulinum toxin type A (BoNTA) in the masseter exhibit atrophy of this muscle characterized by an increase in the gene expression of atrophy-related molecular markers, and a reduction in both muscle fiber diameter and muscle mass at 14d. However, the impact of this muscle imbalance on the non-treated masticatory muscles remains unexplored. Here, we hypothesize that the unilateral masseter hypofunction leads to molecular and 3D morphometric signs of atrophy of the masseter and its agonist masticatory muscles in adult mice. Twenty-three 8-week-old male BALB/c mice received a single injection of BoNTA in the right masseter, whereas the left masseter received the same volume of saline solution (control side). Animals were euthanized at 2d, 7d, and 14d, and the masticatory muscles were analyzed for mRNA expression. Five heads were harvested at 14d, fixed, stained with a contrast-enhanced agent, and scanned using X-ray microtomography. The three-dimensional morphometric parameters (the volume and thickness) from muscles in situ were obtained. Atrogin-1/MAFbx, MuRF-1, and Myogenin mRNA gene expression were significantly increased at 2 and 7d for both the masseter and temporalis from the BoNTA side. For medial pterygoid, increased mRNA gene expression was found at 7d for Atrogin-1/MAFbx and at 2d–7d for Myogenin. Both the volume and thickness of the masseter, temporalis, and medial pterygoid muscles from the BoNTA side were significantly reduced at 14d. In contrast, the lateral pterygoid from the BoNTA side showed a significant increase in volume at 14d. Therefore, the unilateral hypofunction of the masseter leads to molecular and morphological signs of atrophy in both the BoNTA-injected muscle and its agonistic non-injected masticatory muscles. The generalized effect on the mouse masticatory apparatus when one of its components is intervened suggests the need for more clinical studies to determine the safety of BoNTA usage in clinical dentistry. [ABSTRACT FROM AUTHOR]

ObjectivesThe objective of this study was to compare efficacy and adverse events between 100 U and 200 U of onabotulinumtoxinA for 6 months in women with nonneurogenic urgency incontinence.MethodsThis is a secondary analysis of 2 multicenter randomized controlled trials assessing efficacy of onabotulinumtoxinA in women with nonneurogenic urgency incontinence; one compared 100 U to anticholinergics and the other 200 U to sacral neuromodulation. Of 307 women who received onabotulinumtoxinA injections, 118 received 100 U, and 189 received 200 U. The primary outcome was mean adjusted change in daily urgency incontinence episodes from baseline over 6 months, measured on monthly bladder diaries. Secondary outcomes included perceived improvement, quality of life, and adverse events. The primary outcome was assessed via a multivariate linear mixed model.ResultsWomen receiving 200 U had a lower mean reduction in urgency incontinence episodes by 6 months compared with 100 U (-3.65 vs -4.28 episodes per day; mean difference, 0.63 episodes per day [95% confidence interval (CI), 0.05-1.20]). Women receiving 200 U had lower perceptions of improvement (adjusted odds ratio, 0.32 [95% CI, 0.14-0.75]) and smaller improvement in severity score (adjusted mean difference, 12.0 [95% CI, 5.63-18.37]). Upon subanalysis of only women who were treated with prior anticholinergic medications, these differences between onabotulinumtoxinA doses were no longer statistically significant. There was no statistically significant difference in adverse events in women receiving 200 U (catheterization, 32% vs 23%; adjusted odds ratio, 1.4 [95% CI, 0.8-2.4]; urinary tract infection, 37% vs 27%; adjusted odds ratio, 1.5 [95% CI, 0.9-2.6]).ConclusionsA higher dose of onabotulinumtoxinA may not directly result in improved outcomes, but rather baseline disease severity may be a more important prediction of outcomes.

Affecting the eccrine glands, granulosis rubra nasi (GRN) is an inherited disorder that manifests itself as redness, sweating, and papules distributed mainly in the center of the face. It is diagnosed clinically and the cornerstone of management is reassurance and education about the benign nature of the condition. A wide array of treatment modalities has been proposed, such as Botox and corticosteroids injections; however curative measures are yet to be discovered. In this paper, we present a case of a 26-year-old man complaining of chronic nose sweating. The case was successfully managed with Botox injections, though we suggested our theory of undercutting the glands through aggressive defatting as part of open rhinoplasty to the patient; he declined our suggested modality. It remains an untested option and caution should be exercised in high-risk patients to avoid compromising blood supply to the skin and risking skin necrosis. [ABSTRACT FROM AUTHOR]

Randomized controlled trials (RCTs) have shown an antidepressant effect of glabellar botulinum toxin (BoNT) injections. In the FDA Adverse Event Reporting System (FAERS) database, BoNT injection is associated with reduced incidence rates of depression across various non-psychiatric indications, which confirms the previous findings independently of specific expectations to an antidepressant effect of BoNT. The rationale of using BoNT to treat depression is to interrupt proprioceptive body feedback that may reinforce negative emotions. Negative emotions also occur in other mental disorders, suggesting a transdiagnostic therapeutic potential of BoNT in psychiatry. Here we report an analysis of the FAERS database, in which we found that, compared to alternative treatments, BoNT injections were associated with lower incidence of anxiety symptoms and related disorders. Among seven indications/injection sites, we found this protective effect of BoNT in cosmetic use/facial muscles, migraine/facial and head muscles, spasms and spasticity/upper and lower limbs, torticollis and neck pain/neck muscles, and sialorrhea/parotid and submandibular glands (reporting odds ratios 0.79-0.27). These findings are encouraging for possible future RCTs on the use of BoNT as a treatment for anxiety and related disorders.

Surgery is the only treatment for parastomal hernia (PH). When possible, stoma closure is the best way to manage this type of hernia, however, whether to perform it in a single approach with abdominal wall reconstruction (AWR) is still debatable. A 58-year-old woman with a type IV PH with loss of domain was submitted to preoperative optimization [botulinum toxin type A and progressive pneumoperitoneum (PPP)], followed by simultaneous stoma closure and AWR. Hospital discharge was on the eighth day with no complications. Six months later, no clinical evidence of recurrence or other complication was observed. Large PHs are technically challenging. Stoma closure and simultaneous AWR increase surgical risk. Preoperative optimization with a combination of adjuvants (including PPP) is feasible in PH and may overcome technical complexity, even though patient selection remains the key when choosing a PH repair with synchronous stoma closure. [ABSTRACT FROM AUTHOR]

IntroductionOpen surgical repair remains the current gold standard for the treatment of acute type A aortic dissection. However, especially elderly patients with relevant comorbidities who are deemed unfit for open surgery may benefit from a minimally invasive endovascular approach.MethodsWe report a case of an 80-year-old male with retrograde acute type A aortic dissection and peripheral malperfusion after receiving thoracic endovascular aortic repair due to thoracic aortic aneurysm. Our individualized endovascular approach consisted of left carotid-subclavian bypass, proximal extension of thoracic endovascular aortic repair using a covered stent graft and a single covered stent graft for the ascending aorta in combination with an uncovered stent for the aortic arch.ResultsPostoperative computed tomographic angiography demonstrated excellent outcome with no signs of endoleak or patent false lumen. Follow-up after 3.5 years showed a stable result with no signs of stent failure or dissection progress. No aortic re-interventions were needed in the further course.DiscussionAn individualized endovascular approach may be justified for acute type A aortic dissection in elderly patients with high surgical risk if performed in specialized aortic centers. Additional short-length stent graft devices are needed to address the anatomical challenges of the ascending aorta. For enhanced remodeling of the dissected aorta, the use of an additional uncovered stent may be advisable.

Objective: Unusual clinical course. Background: Attainment of extremity immobilization in orthopedic trauma patients experiencing psychosis is often uniquely challenging. Many fractures, including those of the distal humerus, require a period of immobilization postoperatively to optimize fracture healing. Patients with Parkinson's disease have also been shown to have lower rates of union after fracture compared to the general population. The combination of Parkinson's disease and associated psychosis requires heightened attention to those parameters that may hinder fracture healing, such as inadequate immobilization of the fracture. Botulinum toxin has previously been described as a potential adjunctive therapy for fracture immobilization but has not yet been described in the setting of distal humerus fractures. Case Report: A 75-year-old woman with Parkinson's disease-associated psychosis presented 2 weeks after open reduction and internal fixation of a distal third humeral shaft fracture due to failure of fixation and episodes of violent hallucinations. The patient underwent irrigation and debridement, and revision open reduction and internal fixation. Given her uncontrolled hallucinations, intramuscular botulinum toxin injections were given to the right triceps, biceps, and brachialis muscles to aid in the immobilization of the right extremity and protect the surgical site during the perioperative period. The patient subsequently followed up at the clinic 3 months postoperatively with ongoing fracture healing, evidenced by bridging callous and bone formation on radiographs, as well as a return of motion to the extremity. Conclusions: Botulinum toxin may be a safe and effective adjunct for fracture immobilization in patients who are difficult to immobilize and have high fixation failure risk. [ABSTRACT FROM AUTHOR]

Botulinum toxin (BTA) is a bacterial-derived extract that can inhibit muscle contraction, acting directly on the absorption of acetylcholine. Thanks to this property, botulinum has been used in aesthetic and general medicine for several years. Nowadays, the use of botulinum toxin is being deepened to address the problem of bruxism. In this scoping review, the results of the studies in the literature of the last 10 years were analyzed. Indeed, 12 reports (found on PubMed, Web of Science, and Scopus, entering the keywords "BRUXISM" and "BOTULINUM TOXIN") were deemed eligible for inclusion in this review. In the studies reviewed, BTA was injected into different muscle groups: masseters, masseter and temporalis or masseter, temporalis, and medial pterygoid. Botulinum toxin injection is a viable therapeutic solution, especially in patients with poor compliance or without improvement in conventional treatment. [ABSTRACT FROM AUTHOR]

Framed oriented n-tangle diagrams in the annulus, subject to the Homfly skein relations, are used to produce an algebra isomorphic to the affine Hecke algebras Ḣn of type A. The use of closed curves and braids gives neat pictures for central elements in the algebras. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of the present study is to determine the prognostic impact of ABO blood types on the survival of a Japanese population of patients with HCC who underwent surgical resection. We retrospectively analyzed 480 patients with HCC who had R0 resection between 2010 and 2020. Outcomes for type A (n = 173) and non-type A (n = 173) groups after surgery were compared using 1-to-1 propensity score matching to control for variables. Recurrence-free survival (RFS; hazard ratio [HR] 0.75, 95% confidence interval [Cl] 0.58–0.98, p = 0.038) and overall survival (OS; HR: 0.67, 95% Cl: 0.48–0.95, p = 0.023) for patients with blood type A were both significantly decreased relative to non-type A patients. Cox proportional hazard analysis demonstrated that patients with HCC who have blood type A had a worse prognosis than those with non-type A blood. ABO blood type may have a prognostic impact for patients with HCC after hepatectomy. Background/Purpose: The effect of the ABO blood group on the survival of patients with hepatocellular carcinoma (HCC) is unclear. The aim of the present study is to determine the prognostic impact of ABO blood types on the survival of a Japanese population of patients with HCC who underwent surgical resection. Methods: Patients with HCC (n = 480) who underwent an R0 resection between 2010 and 2020 were retrospectively analyzed. Survival outcomes were investigated according to ABO blood type (A, B, O, or AB). Outcomes for type A (n = 173) and non-type A (n = 173) groups after surgery were compared using 1-to-1 propensity score matching to control for variables. Results: In the study cohort, 173 (36.0%), 133 (27.7%), 131 (27.3%), and 43 (9.0%) of participants had Type A, O, B, and AB, respectively. Type A and non-type A patients were successfully matched based on liver function and tumor characteristics. Recurrence-free survival (RFS; hazard ratio [HR] 0.75, 95% confidence interval [Cl] 0.58–0.98, p = 0.038) and overall survival (OS; HR: 0.67, 95% Cl: 0.48–0.95, p = 0.023) for patients with blood type A were both significantly decreased relative to non-type A patients. Cox proportional hazard analysis demonstrated that patients with HCC who have blood type A had a worse prognosis than those with non-type A blood. Conclusion: ABO blood type may have a prognostic impact on patients with HCC after hepatectomy. Blood type A is an independent unfavorable prognostic factor for recurrence-free and overall survival (RFS and OS) after hepatectomy. [ABSTRACT FROM AUTHOR]

Botulinum neurotoxins have remarkable persistence (∼weeks to months in cells), outlasting the small-molecule inhibitors designed to target them. To address this disconnect, inhibitors bearing two pharmacophores-a zinc binding group and a Cys-reactive warhead-were designed to leverage both affinity and reactivity. A series of first-generation bifunctional inhibitors was achieved through structure-based inhibitor design. Through X-ray crystallography, engagement of both the catalytic Zn2+ and Cys165 was confirmed. A second-generation series improved on affinity by incorporating known reversible inhibitor pharmacophores; the mechanism was confirmed by exhaustive dialysis, mass spectrometry, and in vitro evaluation against the C165S mutant. Finally, a third-generation inhibitor was shown to have good cellular activity and low toxicity. In addition to our findings, an alternative method of modeling time-dependent inhibition that simplifies assay setup and allows comparison of inhibition models is discussed.

ObjectiveTo examine the safety and efficacy of abobotulinumtoxinA in patients previously treated with botulinum toxin type A (BoNT-A) products other than abobotulinumtoxinA.DesignSecondary analysis from a phase 3, double-blind, single-cycle, randomized, placebo-controlled study.SettingFifty-two centers (11 countries).PatientsAdults with spastic hemiparesis were randomized (1:1:1) to receive abobotulinumtoxinA 1000 U, 1500 U, or placebo in their affected lower limb.Main outcome measurementsMuscle tone (6-point Modified Ashworth Scale [MAS], 0-5) for the gastrocnemius-soleus complex (GSC); proportion of MAS responders (≥1-point improvement); angle of catch (XV3 ) and spasticity grade (Y) for the GSC and soleus. Assessments were at weeks 1, 4, and 12 post-injection. Only descriptive statistics are presented.ResultsOf 388 patients, 84 received previous BoNT-A treatment (abobotulinumtoxinA 1000 U: N = 30; abobotulinumtoxinA 1500 U: N = 28; placebo: N = 26). At week 4, mean (SD) changes in MAS score in the GSC were - 0.8 (1.1), -0.9 (1.0), and - 0.4 (0.7) for abobotulinumtoxinA 1000 U, 1500 U, and placebo, respectively. Greater MAS responder rates were observed for abobotulinumtoxinA versus placebo at all time points. Mean (SD) changes (week 4) for abobotulinumtoxinA 1000 U, 1500 U, and placebo for XV3 were: GSC, 8° (21), 6° (10) and 1° (7); soleus, 11° (21), 5° (9) and 0° (8), respectively; for Y: GSC, -0.4 (0.7), -0.6 (0.8) and - 0.0 (0.9); soleus, -0.5 (0.7), -0.5 (0.7) and - 0.1 (0.6), respectively. Safety data and adverse events were consistent with the overall known profile of abobotulinumtoxinA.ConclusionsPatients previously treated with other BoNT-As showed improved muscle tone and spasticity at week 4 following abobotulinumtoxinA injection versus placebo. These findings suggest that abobotulinumtoxinA, at the recommended doses, has a good safety and efficacy profile in adults with lower limb spasticity who were previously treated with other BoNT-A products.

PURPOSE: Sacral neuromodulation and intradetrusor onabotulinumtoxinA injection are therapies for refractory urgency urinary incontinence. Sacral neuromodulation involves surgical implantation of a device that can last 4 to 6 years while onabotulinumtoxinA therapy involves serial office injections. We assessed the cost-effectiveness of 2-stage implantation sacral neuromodulation vs 200 units onabotulinumtoxinA for the treatment of urgency urinary incontinence. MATERIALS AND METHODS: Prospective economic evaluation was performed concurrent with the ROSETTA (Refractory Overactive Bladder: Sacral NEuromodulation vs. BoTulinum Toxin Assessment) randomized trial of 386 women with 6 or more urgency urinary incontinence episodes on a 3-day diary. Analysis is from the health care system perspective with primary within-trial analysis for 2 years and secondary 5-year decision analysis. Costs are in 2018 U.S. dollars. Effectiveness was measured in quality adjusted life-years (QALYs) and reductions in urgency urinary incontinence episodes per day. We generated incremental cost-effectiveness ratios and cost-effectiveness acceptability curves. RESULTS: Two-year costs were higher for sacral neuromodulation than for onabotulinumtoxinA ($35,680 [95% CI 33,920-37,440] vs $7,460 [95% CI 5,780-9,150], p

PurposeSacral neuromodulation and intradetrusor onabotulinumtoxinA injection are therapies for refractory urgency urinary incontinence. Sacral neuromodulation involves surgical implantation of a device that can last 4 to 6 years while onabotulinumtoxinA therapy involves serial office injections. We assessed the cost-effectiveness of 2-stage implantation sacral neuromodulation vs 200 units onabotulinumtoxinA for the treatment of urgency urinary incontinence.Materials and methodsProspective economic evaluation was performed concurrent with the ROSETTA (Refractory Overactive Bladder: Sacral NEuromodulation vs. BoTulinum Toxin Assessment) randomized trial of 386 women with 6 or more urgency urinary incontinence episodes on a 3-day diary. Analysis is from the health care system perspective with primary within-trial analysis for 2 years and secondary 5-year decision analysis. Costs are in 2018 U.S. dollars. Effectiveness was measured in quality adjusted life-years (QALYs) and reductions in urgency urinary incontinence episodes per day. We generated incremental cost-effectiveness ratios and cost-effectiveness acceptability curves.ResultsTwo-year costs were higher for sacral neuromodulation than for onabotulinumtoxinA ($35,680 [95% CI 33,920-37,440] vs $7,460 [95% CI 5,780-9,150], p

Hypertrophic scar is a dermal fibroproliferative disease characterized by the overproduction and deposition of extracellular matrix, and the hyperproliferation and enhanced angiogenesis of fibroblasts, along with their enhanced differentiation to myofibroblasts. Botulinum toxin type A shows potential for prevention of hypertrophic scar formation; however, its effectiveness in attenuating skin fibrosis and the related mechanism are unclear. In this study, human scar fibroblasts were cultured and stimulated with botulinum toxin type A, and the changes in fibroblast proliferation, migration, and protein expression of pro-fibrotic factors were evaluated with colorimetric, scratch, and enzyme-linked immunosorbent assays and western blotting, respectively. Botulinum toxin type A treatment decreased the proliferation and migration of human scar fibroblasts compared with those of untreated controls. Protein expression levels of pro-fibrotic factors (transforming growth factor β1, interleukin-6, and connective tissue growth factor) were also inhibited by botulinum toxin type A, whereas the JNK phosphorylation level was increased. Activation of the JNK pathway demonstrated the inhibitory effects of the toxin on human scar fibroblast proliferation and production of pro-fibrotic factors, suggesting that the suppressive effects of botulinum toxin type A are closely associated with JNK phosphorylation. Overall, this study showed that botulinum toxin type A has a suppressive effect on extracellular matrix production and scar-related factors in human scar fibroblasts in vitro, and that regulation of JNK signaling plays an important role in this process. Our results provide a theoretical basis, at the cellular level, for the therapeutic use of botulinum toxin type A.