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BACKGROUND: There is unclear added benefit of intravenous thrombolysis (IVT) with endovascular thrombectomy (EVT). We performed a cost-effectiveness analysis to assess the cost-effectiveness of comparing EVT with IVT versus EVT alone. METHODS: We used a decision tree to examine the short-term costs and outcomes at 90 days after the occurrence of index stroke to compare the cost-effectiveness of EVT alone with EVT plus IVT for patients with stroke. Subsequently, we developed a Markov state transition model to assess the costs and outcomes over 1-year, 5-year, and 20-year time horizons. We estimated total and incremental cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio. RESULTS: The average costs per patient were estimated to be $47,304, $49,510, $59,770, and $76,561 for EVT-only strategy and $55,482, $57,751, $68,314, and $85,611 for EVT with IVT over 90 days, 1 year, 5 years, and 20 years, respectively. The cost saving of EVT-only strategy was driven by the avoided medication costs of IVT (ranging from $8,178 to $9,050). The additional IVT led to a slight decrease in QALY estimate during the 90-day time horizon (loss of 0.002 QALY), but a small gain over 1-year and 5-year time horizons (0.011 and 0.0636 QALY). At a willingness-to-pay threshold of $50,000 per QALY gained, the probabilities of EVT only being cost-effective were 100%, 100%, and 99.3% over 90-day, 1-year, and 5-year time horizons. CONCLUSION: Our cost-effectiveness model suggested that EVT only may be cost-effective for patients with acute ischemic stroke secondary to large vessel occlusion.
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Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/cirurgia , Terapia Trombolítica , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/cirurgia , Análise de Custo-Efetividade , Trombectomia , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/cirurgia , Resultado do Tratamento , Análise Custo-BenefícioRESUMO
OBJECTIVE: The larynx is the most common site of localized head and neck amyloidosis. Our study aimed to review the clinical features, treatments, and outcomes associated with localized laryngeal amyloidosis (LA). We also compared these features between two different time periods to evaluate the evolution of LA management. METHODS: A literature search using PubMed, CINAHL, Embase, and Cochrane Library identified cases of LA published between 1891 and 2021. Biopsy-proven cases of localized LA were included. Non-English studies, animal studies, and reviews were excluded. RESULTS: 282 patients (1891-1999: 142 patients, 2000-2021: 140 patients) from 129 studies were included. Results are reported as 1891-2000 vs. 2000-2021: Mean age was 48.5 years (range, 8-90 years) vs. 46.0 years (range, 9-84 years). The most common presenting symptoms were dysphonia (n = 30, 95 % vs. n = 127, 96 %) and difficulty breathing (n = 37, 27 % vs. n = 35, 27 %). A total of 62 (44 %) vs. 46 (33 %) lesions were found in the true vocal folds and 35 (25 %) vs. 59 (42 %) were found in the false vocal folds. 133 (94 %) vs. 137 (98 %) patients underwent surgical interventions to investigate and/or treat LA. Recurrent LA was reported in 27 (19 %) vs. 33 (24 %) patients with a mean time to recurrence of 25.4 months (range, 0.3-132 months) vs. 34.5 months (range, 0.8-144 months). Of cases reporting survival rate, 104 (97 %) vs. 107 (99 %) were alive at source study endpoints. CONCLUSION: LA typically exhibits an indolent course; therefore, early intervention may address longstanding symptoms. Recurrent disease poses a clinical challenge in patients with LA.
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Amiloidose , Doenças da Laringe , Laringe , Amiloidose/diagnóstico , Amiloidose/patologia , Amiloidose/terapia , Rouquidão , Humanos , Doenças da Laringe/diagnóstico , Doenças da Laringe/patologia , Doenças da Laringe/terapia , Laringe/patologia , Prega Vocal/patologiaRESUMO
PURPOSE: Infiltration techniques are used as an adjuvant to regional anesthesia. In this study, we evaluated the efficacy of the superficial cervical plexus nerve block, as an alternative to local infiltration techniques; in the management of mandibular fractures and peri-mandibular space infections. METHODS: A prospective randomized controlled trial was conducted on 24 patients having either mandibular fractures or peri-mandibular space infections; and were scheduled for surgery under regional anesthesia (eg, inferior alveolar nerve block, long buccal nerve block). The control group involved delivering a combination of regional anesthesia along with local infiltration. The experimental group received regional anesthesia with a superficial cervical plexus nerve block. The following parameters were studied: pain, onset and duration of anesthesia, time interval until first analgesic request, pulse rate and blood pressure [at different time intervals]. RESULTS: Intergroup comparison was done using unpaired t-test. Intragroup comparison was done using repeated measures ANOVA (for >2 observations), followed by a post hoc test. The superficial cervical plexus nerve block group showed highly statistically significant (P < .01) improvement in terms of intra-operative pain at 30 minutes, duration of anesthesia, intraoperative anesthetic requirement, time interval until first analgesic request and intraoperative diastolic blood pressure at 10 minutes. CONCLUSION: It can be concluded that the combination of a regional anesthesia technique with a superficial cervical plexus nerve block is an alternative and safe technique for patients undergoing surgery for mandible fractures and perimandibular space infections, with clear advantages over local infiltration.
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Anestesia Dentária , Bloqueio Nervoso , Anestesia Local , Anestésicos Locais , Plexo Cervical , Humanos , Estudos ProspectivosRESUMO
AIMS/HYPOTHESIS: Non-shivering thermogenesis in adipose tissue can be activated by excessive energy intake or following cold exposure. The molecular mechanisms regulating this activation have not been fully elucidated. The Janus kinase (JAK) - signal transducer and activator of transcription (STAT) pathway mediates the signal transduction of numerous hormones and growth factors that regulate adipose tissue development and function, and may play a role in adaptive thermogenesis. METHODS: We analysed mRNA and protein levels of uncoupling protein 1 (UCP1) and JAK2 in different adipose depots in response to metabolic and thermal stress. The in vivo role of JAK2 in adaptive thermogenesis was examined using mice with adipocyte-specific Jak2 deficiency (A-Jak2 KO). RESULTS: We show in murine brown adipose tissue (BAT) that JAK2 is upregulated together with UCP1 in response to high-fat diet (HFD) feeding and cold exposure. In contrast to white adipose tissue, where JAK2 was dispensable for UCP1 induction, we identified an essential role for BAT JAK2 in diet- and cold-induced thermogenesis via mediating the thermogenic response to ß-adrenergic stimulation. Accordingly, A-Jak2 KO mice were unable to upregulate BAT UCP1 following a HFD or after cold exposure. Therefore, A-Jak2 KO mice were cold intolerant and susceptible to HFD-induced obesity and diabetes. CONCLUSIONS/INTERPRETATION: Taken together, our results suggest that JAK2 plays a critical role in BAT function and adaptive thermogenesis. Targeting the JAK-STAT pathway may be a novel therapeutic approach for the treatment of obesity and related metabolic disorders.
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Tecido Adiposo Marrom/fisiologia , Janus Quinase 2/metabolismo , Termogênese , Adipócitos/citologia , Adipogenia , Tecido Adiposo Branco/fisiologia , Adiposidade , Animais , Dieta Hiperlipídica , Feminino , Insulina/fisiologia , Canais Iônicos/fisiologia , Janus Quinase 1/fisiologia , Camundongos , Camundongos Knockout , Proteínas Mitocondriais/fisiologia , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Fator de Transcrição STAT1/fisiologia , Transdução de Sinais , Proteína Desacopladora 1 , Regulação para CimaRESUMO
INTRODUCTION: The National Emergency X-Radiography Utilization Study (NEXUS) clinical decision rule is extremely sensitive for clearance of cervical spine (C-spine) injury in blunt trauma patients with distracting injuries. OBJECTIVES: We sought to determine whether the NEXUS criteria would maintain sensitivity for blunt trauma patients when femur fractures were not considered a distracting injury and an absolute indication for diagnostic imaging. METHODS: We retrospectively analyzed blunt trauma patients with at least 1 femur fracture who presented to our emergency department as trauma activations from 2009 to 2011 and underwent C-spine injury evaluation. Presence of C-spine injury requiring surgical intervention was evaluated. RESULTS: Of 566 trauma patients included, 77 (13.6%) were younger than 18 years. Cervical spine injury was diagnosed in 53 (9.4%) of 566. A total of 241 patients (42.6%) had positive NEXUS findings in addition to distracting injury; 51 (21.2%) of these had C-spine injuries. Of 325 patients (57.4%) with femur fractures who were otherwise NEXUS negative, only 2 (0.6%) had C-spine injuries (95% confidence interval [CI], 0.2%-2.2%); both were stable and required no operative intervention. Use of NEXUS criteria, excluding femur fracture as an indication for imaging, detected all significant injuries with a sensitivity for any C-spine injury of 96.2% (95% CI, 85.9%-99.3%) and negative predictive value of 99.4% (95% CI, 97.6%-99.9%). CONCLUSIONS: In our patient population, all significant C-spine injuries were identified by NEXUS criteria without considering the femur fracture a distracting injury and indication for computed tomographic imaging. Reconsidering femur fracture in this context may decrease radiation exposure and health care expenditure with little risk of missed diagnoses.
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Vértebras Cervicais/lesões , Serviço Hospitalar de Emergência , Fraturas do Fêmur/complicações , Traumatismos da Coluna Vertebral/diagnóstico , Ferimentos não Penetrantes/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Fraturas do Fêmur/diagnóstico , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Traumatismos da Coluna Vertebral/complicações , Ferimentos não Penetrantes/complicações , Adulto JovemRESUMO
Hysterectomy is one of the most common gynecologic procedures performed worldwide. Vaginal cuff dehiscence with resultant bowel evisceration, while rare, is one of the most serious complications of the procedure. We present the case of a 79-year-old female with vaginal cuff dehiscence several decades after hysterectomy. The patient had no significant antecedent symptoms until she experienced bowel evisceration during Valsalva. She underwent a successful reduction of bowel contents with limited resection and transvaginal cuff repair. This case highlights the risk of vaginal cuff dehiscence even decades following the procedure.
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BACKGROUND: The transradial approach (TRA) for neurointerventional procedures is increasingly being used given its technical feasibility and safety. However, catheter trackability and device deliverability are reported barriers to TRA adoption. METHODS: This is the first report describing the technical feasibility and performance of using the Zoom RDL Radial Access System (Imperative Care, Inc., Campbell, CA) in 29 patients who underwent neurointerventional procedures from October 2022 to January 2023 in a single-center institution. RESULTS: Mean age of the study population was 61.9±17.2 years, 79.3% were male (23/29), and 62.1% were black (18/29). The most common procedures were stroke thrombectomy (31.0%, 9/29) and aneurysm embolization (27.6%, 8/29). All the stroke thrombectomy procedures were successfully performed; first-pass effect rate (mTICI≥2 c in one pass) was achieved in 66.7% (6/9) of cases. We used TRA in 86.2% of cases (25/29), including distal radial/snuffbox access in 31.0% (9/29) of cases. The radial diameter was >2 mm for all cases. An intermediate/aspiration catheter was used in 89.7% (26/29) of cases. Access success was achieved in 89.7% of cases (26/29); two cases required conversion from TRA to transfemoral approach (6.9%) and one case required conversion to a different guide catheter (3.4%). There were no access site complications or other Zoom RDL-related complications. One intracerebral hemorrhage, and one procedure-related thrombus were observed. CONCLUSIONS: The use of Zoom RDL Radial Access System is technically feasible and effective for complex neurointerventional procedures with low complication rates.
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Embolização Terapêutica , Acidente Vascular Cerebral , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Artéria Radial/diagnóstico por imagem , Artéria Radial/cirurgia , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/cirurgia , Trombectomia/métodos , Catéteres , Estudos Retrospectivos , Resultado do TratamentoRESUMO
There is limited evidence of N-butyl cyanoacrylate (n-BCA) use in endovascular embolization of traumatic face and neck vessel injuries. We investigated the safety and effectiveness of n-BCA for this purpose. We retrospectively analyzed consecutive patients presenting to a Level 1 trauma center between April 2021 and July 2022. We included patients aged ≥ 18 years old with any vessel injury in the face and neck circulation requiring n-BCA embolization. The primary endpoint was n-BCA effectiveness defined as immediate control of active bleeding post-embolization. In total, 13 patients met the inclusion criteria. The median decade of life was 3 (IQR 3 - 5) with a male predominance (n = 11, 84.6%). Median Glasgow Coma Scale score on presentation was 15 (IQR 3-15). Eleven patients suffered gunshot wound injuries; two patients suffered blunt injuries. Injured vessels included facial artery (n = 6, 46.2%), buccal branch artery (n = 3, 23.1%), internal maxillary (n = 5, 38.5%), cervical internal carotid artery (n = 1, 7.7%), and vertebral artery (n = 1, 7.7%). All patients were treated with 1:2 n-BCA to ethiodol mixture with immediate extravasation control. No bleeding recurrence or need for retreatment occurred. One patient died in-hospital (7.7%). Patients were discharged to home (n = 8, 61.5%), day rehabilitation (n = 1, 7.7%), or acute rehabilitation (n = 3, 23.1%). One patient developed a right posterior cerebral artery infarct with hemorrhagic transformation. To our knowledge, this is the first study demonstrating the safety and effectiveness of n-BCA liquid embolism in traumatic vessel injuries, especially penetrating gunshot wounds.
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BACKGROUND: The use of covered stent grafts for the treatment of carotid rupture is increasingly being used given their ability to preserve the parent artery while simultaneously occluding the fistula or rupture point. METHODS: This case series describes the technical feasibility of using, and the performance of, the PK Papyrus covered coronary stent (Biotronik, Inc., Lake Oswego, Oregon, USA) in six patients with carotid rupture, including carotid cavernous fistulas, between July 2021 and October 2023 in a single-center institution in the USA. RESULTS: The median decade of life was 5 (IQR 3) with a 1:1 male-to-female ratio. The majority were black patients (n=5/6, 83.3%). The most common disease pathology was carotid cavernous fistula (n=4/6, 66.7%), followed by traumatic carotid rupture (n=2/6, 33.3%). All the stent embolization procedures were successfully treated with the PK Papyrus covered coronary stent. None of the patients had any recurrence or re-treatment. The number of stents required ranged from 1 to 3. A balloon guide catheter was used in 66.7% of cases (n=4/6). In-hospital mortality was 0.0% (n=0/6). No in-stent thrombosis was observed, but there was one case of cangrelor-associated hemorrhagic stroke conversion. Transfemoral access was used in all cases with one access site complication. Median follow-up time was 1.8 months (IQR 3.5). CONCLUSIONS: To our knowledge, this is the largest case series in the USA demonstrating the feasibility and safety of using the PK Papyrus covered coronary stent for the treatment of carotid rupture, including carotid cavernous fistulas.
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BACKGROUND: Recent studies indicate endovascular thrombectomy (EVT) as a safe, effective treatment for acute ischemic stroke (AIS) with large ischemic regions. Our study updates an ongoing living systematic review and meta-analysis of randomized controlled trials (RCTs) comparing outcomes of EVT to medical management only. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Library for RCTs comparing EVT to medical management in AIS patients with large ischemic areas. Using fixed-effect models, we conducted a meta-analysis to compare functional independence, mortality, and symptomatic intracranial hemorrhage (sICH) between EVT and standard medical management. We evaluated bias risk with the Cochrane tool and graded the certainty of evidence using the GRADE approach. RESULTS: Of 1363 new citations, we included six RCTs with a total of 1876 patients. We found low-certainty evidence of improved functional independence (risk difference [RD] 29.9%, 95% CI 17.2% to 46.9%), increase in sICH (RD 2.6%, 95% CI 0.3% to 6.4%), and a non-significant decrease in mortality (RD -1.8%, 95% CI -3.9% to 0.6%) for AIS patients with large infarcts who underwent EVT compared to medical management only. CONCLUSION: Our revised meta-analysis suggests low-certainty evidence that there is improved functional independence, a non-significant decrease in mortality, and an increase in sICH among AIS patients with large infarcts who undergo EVT compared to those receiving medical management alone. SYSTEMATIC REVIEW PROTOCOL REGISTRATION: PROSPERO (CRD42023398742).
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Procedimentos Endovasculares , AVC Isquêmico , Ensaios Clínicos Controlados Aleatórios como Assunto , Trombectomia , Humanos , Procedimentos Endovasculares/métodos , AVC Isquêmico/cirurgia , AVC Isquêmico/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Trombectomia/métodosRESUMO
Background: To this date, whether to administer intravenous thrombolysis (IVT) prior to endovascular thrombectomy (EVT) for stroke patients still stirs some debate. We aimed to systematically update the evidence from randomized trials comparing EVT alone vs EVT with bridging IVT. Methods: We searched MEDLINE, EMBASE, and the Cochrane Library to identify randomized controlled trials (RCTs) comparing EVT with or without IVT in patients presenting with stroke secondary to a large vessel occlusion. We conducted meta-analyses using random-effects models to compare functional independence, mortality, and symptomatic intracranial hemorrhage (sICH), between EVT and EVT with IVT. We assessed risk of bias using the Cochrane risk-of-bias tool and certainty of evidence for each outcome using the GRADE approach. Results: Of 11,111 citations, we included 6 studies with a total of 2336 participants. We found low-certainty evidence of possibly a small decrease in the proportion of patients with functional independence (risk difference [RD] -2.0%, 95% CI -5.9% to 2.0%), low-certainty evidence that there is possibly a small increase in mortality (RD 1.0%, 95% CI -2.2% to 4.7%), and moderate-certainty evidence that there is probably a decrease in sICH (RD -1.0%, 95% CI -1.6% to .7%) for patients with EVT alone compared to EVT plus IVT, respectively. Conclusion: Low-certainty evidence shows that there is possibly a small decrease in functional independence, low-certainty evidence shows that there is possibly a small increase in mortality, and moderate-certainty evidence that there is probably a decrease in sICH for patients with EVT alone compared to EVT plus IVT.
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BACKGROUND: Middle meningeal artery (MMA) embolization for subdural hematomas (SDH) and dural arteriovenous fistulas (dAVFs) has gained momentum in the neuroendovascular space. However, there is variability in the technique for safe and effective embolization. The aim of this report is to describe the technical feasibility and clinical performance of using Zoom™ 45 catheter for MMA access to facilitate embolization. METHODS: We analyzed all cases of MMA embolization in which the Zoom™ 45 catheter was used and performed in our institution from February 2021 to March 2023 for SDH and dAVFs. RESULTS: A total of 32 patients were included. Mean age was 64.0 ± 18.0 years, 75.0% (4/32) were male, and 56.7% (17/30), were black. The technical success was achieved in 93.8% (30/32) of cases, with selective embolization utilizing microcatheter directly into frontal and parietal branches for most patients (96.9%, 31/32). Identification of dangerous collaterals, such as lacrimal and petrous branches, prior to embolization, was achieved in most patients (96.9%, 31/32). Bilateral MMA embolization was done in 50.0% (16/32) of patients. The transradial approach and transfemoral approach were used in 53.1% (17/32) and 46.9% (15/32) of patients, respectively. The most common embolization material was n-butyl cyanoacrylate (84.4%, 27/32). There were no access site complications or complications related to the MMA embolization procedures and used devices. CONCLUSIONS: The use of Zoom™ 45 Catheter seems to be technically feasible, safe, and effective for facilitating MMA access for embolization in the context of SDH and dAVFs.
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Background: A 19-year-old male requiring emergency surgery after presenting to the emergency department (ED) as a trauma activation status post-motor vehicle collision. Summary. The patient presented to the ED after a motor vehicle collision. He was taken emergently to the operating room after finding hemoperitoneum on computerized tomography scan without evidence of solid organ injury. Significant small and large bowel injuries were discovered requiring resection and anastomosis. The patient had an uneventful post-operative recovery and was discharged home. He was later re-admitted to the hospital with a large pelvic abscess and a left mid-ureteral stricture causing hydronephrosis. The abscess was treated with antibiotics, and the left ureteral injury was treated with a nephrostomy tube and stent placement. He made a full recovery after hospital re-admission and a delay in diagnosis of blunt ureteral injury. Conclusion: Patients involved in motor vehicle collisions are at risk of multi-system trauma including genito-urinary injuries. A small percentage of these patients may present with blunt ureteral injuries. A high index of suspicion is required to make an early diagnosis. Earlier diagnosis may help to prevent morbidity.
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Introduction: Odontogenic keratocysts (OKC) has a high potential for recurrence. Resection is currently the only fool-proof method to ensure that recurrence does not occur; however, it drastically affects the patient's function and aesthetics. Application of modified Carnoy's solution (MCS) as an adjunct to reduce the recurrence rate is currently in vogue. 5- Flurouracil (5-FU) is an anti-metabolite that has been used in the treatment of basal cell carcinoma and is relatively safer than MCS. The present study aims to compare the effectiveness of 5-UC and MCS in reducing the recurrence rate in OKC.. Material and methods: A total of 42 OKCs were enucleated followed by application of MCS (control group, n = 21) or 5-FU dressing (study group, n = 21) following enucleation. Pain, swelling, temporary and permanent paresthesia paresthesia, bone sequestrum formation, osteomyelitis and recurrence in both groups were evaluated at periodic intervals up to 12 months post-surgery. Results: There was no significant difference in terms of pain, or swelling in both groups. Permanent paresthesia and recurrence rates were higher in patients treated with MC but the difference was not statistically significant. Conclusion: 5-FU is an easy-to-use, feasible, biocompatible and cost-effective alternative for MCS in the management of OKCs. Treatment with 5-FU, therefore, reduces the risk of recurrence and also the post-surgical morbidity associated with other treatment procedures.
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BACKGROUND AND PURPOSE: New studies have shown that endovascular thrombectomy (EVT) is safe and effective for acute ischemic stroke (AIS) patients with large ischemic areas. The aim of our study is to conduct a living systematic review and meta-analysis of randomized trials comparing EVT versus medical management only. METHODS: We searched MEDLINE, Embase, and the Cochrane Library to identify randomized controlled trials (RCTs) comparing EVT versus medical management alone in AIS patients with large ischemic regions. We conducted our meta-analysis using fixed-effect models to compare functional independence, mortality, and symptomatic intracranial hemorrhage (sICH) between EVT and standard medical management only. We assessed the risk of bias using the Cochrane risk-of-bias tool and the certainty of evidence for each outcome using the Grading of Recommendations, Assessment, Development, and Evaluations approach. RESULTS: Of 14,513 citations, we included 3 RCTs with a total of 1,010 participants. We found low-certainty evidence of possibly a large increase in the proportion of patients with functional independence (risk difference [RD] 30.3%, 95% CI 15.0% to 52.3%), low-certainty evidence of possibly a small non-significant decrease in mortality (RD -0.7%, 95% CI -3.8% to 3.5%), and low-certainty evidence of possibly a small non-significant increase in sICH (RD 3.1%, 95% CI -0.3% to 9.8%) for AIS patients with large infarcts who underwent EVT compared to medical management only. CONCLUSION: Low-certainty evidence shows that there is possibly a large increase in functional independence, a small non-significant decrease in mortality, and a small non-significant increase in sICH amongst AIS patients with large infarcts undergoing EVT compared to medical management only.
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We present a 35-year-old male with ulcerative colitis initially admitted for a flare-up who then presented with altered mental status and was found to have extensive cerebral venous sinus thrombosis on computed tomography imaging. The patient underwent successful partial recanalization of the superior sagittal sinus and bilateral transverse sinuses using the Penumbra Indigo® Aspiration System with improved outcomes. To our knowledge, this is the first reported use of this device in the treatment of cerebral venous sinus thrombosis.
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Caspases are cysteine-aspartic proteases that were initially discovered to play a role in apoptosis. However, caspase 8, in particular, also has additional nonapoptotic roles, such as in inflammation. Adipocyte cell death and inflammation are hypothesized to be initiating pathogenic factors in type 2 diabetes. Here, we examined the pleiotropic role of caspase 8 in adipocytes and obesity-associated insulin resistance. Caspase 8 expression was increased in adipocytes from mice and humans with obesity and insulin resistance. Treatment of 3T3-L1 adipocytes with caspase 8 inhibitor Z-IETD-FMK decreased both death receptor-mediated signaling and targets of nuclear factor κ-light-chain-enhancer of activated B (NF-κB) signaling. We generated novel adipose tissue and adipocyte-specific caspase 8 knockout mice (aP2Casp8-/- and adipoqCasp8-/-). Both males and females had improved glucose tolerance in the setting of high-fat diet (HFD) feeding. Knockout mice also gained less weight on HFD, with decreased adiposity, adipocyte size, and hepatic steatosis. These mice had decreased adipose tissue inflammation and decreased activation of canonical and noncanonical NF-κB signaling. Furthermore, they demonstrated increased energy expenditure, core body temperature, and UCP1 expression. Adipocyte-specific activation of Ikbkb or housing mice at thermoneutrality attenuated improvements in glucose tolerance. These data demonstrate an important role for caspase 8 in mediating adipocyte cell death and inflammation to regulate glucose and energy homeostasis. ARTICLE HIGHLIGHTS: Caspase 8 is increased in adipocytes from mice and humans with obesity and insulin resistance. Knockdown of caspase 8 in adipocytes protects mice from glucose intolerance and weight gain on a high-fat diet. Knockdown of caspase 8 decreases Fas signaling, as well as canonical and noncanonical nuclear factor κ-light-chain-enhancer of activated B (NF-κB) signaling in adipose tissue. Improved glucose tolerance occurs via reduced activation of NF-κB signaling and via induction of UCP1 in adipocytes.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Masculino , Feminino , Animais , Camundongos , NF-kappa B/metabolismo , Resistência à Insulina/genética , Caspase 8/genética , Caspase 8/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Camundongos Knockout , Adipócitos/metabolismo , Obesidade/genética , Obesidade/metabolismo , Dieta Hiperlipídica/efeitos adversos , Inflamação/metabolismo , Glucose/metabolismo , Apoptose/genéticaRESUMO
INTRODUCTION: Current published guidelines and meta-analyses comparing endovascular thrombectomy (EVT) alone versus EVT with bridging intravenous thrombolysis (IVT) suggest that EVT alone is non-inferior to EVT with bridging thrombolysis in achieving favourable functional outcome. Because of this controversy, we aimed to systematically update the evidence and meta-analyse data from randomised trials comparing EVT alone versus EVT with bridging thrombolysis, and performed an economic evaluation comparing both strategies. METHODS AND ANALYSIS: We will conduct a systematic review of randomised controlled trials comparing EVT with or without bridging thrombolysis in patients presenting with large vessel occlusions. We will identify eligible studies by systematically searching the following databases from inception without any language restrictions: MEDLINE (through Ovid), Embase and the Cochrane Library. The following criteria will be used to assess eligibility for inclusion: (1) adult patients ≥18 years old; (2) randomised patients to EVT alone or to EVT with IVT; and (3) measured outcomes, including functional outcomes, at least 90 days after randomisation. Pairs of reviewers will independently screen the identified articles, extract information and assess the risk of bias of eligible studies. We will use the Cochrane Risk-of-Bias tool to evaluate risk of bias. We will also use the Grading of Recommendations, Assessment, Development and Evaluation approach to assess the certainty in evidence for each outcome. We will then perform an economic evaluation based on the extracted data. ETHICS AND DISSEMINATION: This systematic review will not require a research ethics approval because no confidential patient data will be used. We will disseminate our findings by publishing the results in a peer-reviewed journal and via presentation at conferences. PROSPERO REGISTRATION NUMBER: CRD42022315608.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Adulto , Humanos , Adolescente , Análise de Custo-Efetividade , Trombectomia , Terapia Trombolítica , Revisões Sistemáticas como AssuntoRESUMO
Background: The optimal antiplatelet therapy regimen for certain neuroendovascular procedures remains unclear. This study investigates the safety and feasibility of intravenous dose-adjusted cangrelor in patients undergoing acute neuroendovascular interventions. Methods: We conducted a retrospective chart review of all consecutive patients on intravenous cangrelor for neuroendovascular procedures between September 1, 2020, and March 13, 2022. We also conducted an updated systematic review and meta-analysis using PubMed, Scopus, Web of Science, Embase and the Cochrane Library up to February 22, 2023. Results: In our cohort, a total of 76 patients were included [mean age (years): 57.2 ± 18.2, males: 39 (51.3), Black: 49 (64.5)]. Cangrelor was most used for embolization and intracranial stent placement (n = 24, 32%). Approximately 44% of our patients had a favorable outcome with a modified Rankin Scale (mRS) score of 0 to 2 at 90 days (n = 25/57); within 1 year, 8% of patients had recurrent or new strokes (n = 5/59), 6% had symptomatic intracranial hemorrhage [sICH] (4/64), 3% had major extracranial bleeding events (2/64), and 3% had a gastrointestinal bleed (2/64). In our meta-analysis, 11 studies with 298 patients were included. The pooled proportion of sICH and intraprocedural thromboembolic complication events were 0.07 [95% CI 0.04 to 1.13] and 0.08 [95% CI 0.05 to 0.15], respectively. Conclusion: Our study found that intravenous cangrelor appears to be safe and effective in neuroendovascular procedures, with low rates of bleeding and ischemic events. However, further research is needed to compare different dosing and titration protocols of cangrelor and other intravenous agents.
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Surgical management of temporomandibular joint (TMJ) ankylosis involves various techniques from which interpositional arthroplasty (IPA) involves using several materials. The objectives of this study were to assess and compare post arthroplasty maximum mouth opening (MMO), symptoms like pain and discomfort in jaw opening and movements, failures such as reankylosis, neurosensory disturbances, and the effect of confounding variables such as age, gender, physiotherapy, etc. The search (conducted in September, 2021) included studies published in English on otherwise healthy individuals (11 months to 88 years) having undergone arthroplasty with a minimum of six months' follow up. We used search engines such as Cochrane database, PubMed, Embase, Scopus, EBSCO host, Pro quest, J gate, Google Scholar, and manual search to include books and grey literature. Randomised clinical (RCT) and non-randomised clinical trials, observational studies, case series and reports meeting the inclusion criteria were selected. Two reviewers (HD and NP) independently extracted the data. Risk of bias was assessed using the Cochrane tool, Rangel checklist, and Joanna Briggs Institute. Data were analysed using RevMan (Version 5.4). Fifty studies with 1524 participants (442 bilateral and 891 unilateral joints) were included; six RCTs, 31 retrospective, 10 prospective, and three case series and reports. Amongst all interpositional materials, the highest increase in mouth opening was seen with dermis fat graft with a mean difference (Pooled MD) being 35.29mm (95% CI [32.36 to 38.22]). Comparison of temporalis myofascial with gap arthroplasty (GA) showed significant increase in MMO (Pooled MD in mm 1.30 95% CI [0.14 to 2.45]). Recurrence was significantly reduced when (IPA) was used, compared with GA (Risk difference 0.08mm 95% CI [-0.15 to -0.02]) and for Temporalis Myofascial Flap (TMF) when compared with GA (Risk difference -0.07mm 95% CI [-0.15 to 0]). Higher odds for developing neurosensory disturbances were seen with Al-Kayat Bramley incision (Pooled OR 0.11 95% CI [0.04 to 0.34]) compared to pre-auricular incision (Pooled OR 0.03 95% CI [0.01 to 0.09]). IPA was superior to GA with respect to maximum mouth opening (MMO) (Pooled MD in mm 1.21 95% CI [0.41 to 2.07]). Dermis fat graft offers the highest MMO. The overall quality of evidence for RCTs is poor while that of observational studies is moderate as per the relevant assessment of quality of evidence. More research with appropriate study designs is needed. Similar to the findings from the previous reviews, outcomes with IPA were superior when compared to GA in terms of mouth opening and less recurrence.