Development and characterization of the mode-of-action of inhibitory and agonist peptides targeting the voltage-gated sodium channel SCN1B beta-subunit.

Cardiac arrhythmia treatment is a clinical challenge necessitating safer and more effective therapies. Recent studies have highlighted the role of the perinexus, an intercalated disc nanodomain enriched in voltage-gated sodium channels including both Nav1.5 and ß1 subunits, adjacent to gap junctions. These findings offer insights into action potential conduction in the heart. A 19-amino acid SCN1B (ß1/ß1B) mimetic peptide, ßadp1, disrupts VGSC beta subunit-mediated adhesion in cardiac perinexii, inducing arrhythmogenic changes. We aimed to explore ßadp1's mechanism and develop novel SCN1B mimetic peptides affecting ß1-mediated adhesion. Using patch clamp assays in neonatal rat cardiomyocytes and electric cell substrate impedance sensing (ECIS) in ß1-expressing cells, we observed ßadp1 maintained inhibitory effects for up to 5 h. A shorter peptide (LQLEED) based on the carboxyl-terminus of ßadp1 mimicked this inhibitory effect, while dimeric peptides containing repeated LQLEED sequences paradoxically promoted intercellular adhesion over longer time courses. Moreover, we found a link between these peptides and ß1-regulated intramembrane proteolysis (RIP) - a signaling pathway effecting gene transcription including that of VGSC subunits. ßadp1 increased RIP continuously over 48 h, while dimeric agonists acutely boosted RIP for up to 6 h. In the presence of DAPT, an RIP inhibitor, ßadp1's effects on ECIS-measured intercellular adhesion was reduced, suggesting a relationship between RIP and the peptide's inhibitory action. In conclusion, novel SCN1B (ß1/ß1B) mimetic peptides are reported with the potential to modulate intercellular VGSC ß1-mediated adhesion, potentially through ß1 RIP. These findings suggest a path towards the development of anti-arrhythmic drugs targeting the perinexus.

Risk factors and consequences of wound complications following sartorius flap reconstruction.

OBJECTIVE: Groin wound complications are common following vascular surgery and can lead to significant patient morbidity. Sartorius muscle flap coverage may help to prevent vascular graft infection in the setting of wound dehiscence or infection. However, risk factors and consequences of wound complications following sartorius flap reconstruction remain incompletely investigated. METHODS: We retrospectively queried all patients who underwent sartorius flap reconstruction at a tertiary academic medical center. Data collected included patient demographics, medical comorbidities, surgical indication, index vascular procedure, and postoperative outcomes. The primary outcome was wound complication following sartorius flap procedure, which was defined as groin wound infection, dehiscence, or lymphocutaneous fistula. RESULTS: From 2012 to 2022, a total of 113 patients underwent sartorius flap reconstruction. Of these, 66 (58.4%) were performed after the development of a prior groin complication, and 47 (41.6%) were prophylactic. A total of 88 patients (77.9%) had a prosthetic bypass graft adjacent to the flap. Twenty-nine patients (25.7%) suffered a wound complication following sartorius flap reconstruction, including 14 (12.4%) with wound dehiscence, 13 (11.5%) with wound infection, and two (1.8%) with lymphocutaneous fistula. Patients with wound complications had a higher body mass index (28.8 vs 26.4 kg/m2; P =.03) and more frequently active smokers (86.2% vs 66.7%; P = .04). Additionally, patients with wound complications had a higher unplanned 30-day hospital readmission rates (72.4% vs 15.5%; P < .001), reintervention rates (75.9% vs 8.3%; P < .001), and re-do flap reconstruction rates (13.8% vs 2.4%; P = .02). On multivariable analysis, higher body mass index was independently associated with post-flap wound complications (adjusted odds ratio [aOR], 1.01; 95% confidence interval [CI], 1.001-1.03; P = .037). Consequently, wound complications were associated with both surgical reintervention (aOR, 35.4; 95% CI, 9.9-126.3; P < .001) and unplanned hospital readmission (aOR, 17.8; 95% CI, 5.9-54.1; P < .001). CONCLUSIONS: Sartorius flap reconstruction is an effective adjunct in facilitating wound healing of groin wounds. However, wound complications are common following sartorius flap reconstruction and may be associated with reintervention and unplanned hospital readmission. These data support the judicious and thoughtful utilization of sartorius flap procedures among high-risk patients.

Breakthrough COVID-19 After Tixagevimab/Cilgavimab Among Patients With Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: To determine the incidence and baseline factors associated with breakthrough coronavirus disease 2019 (COVID-19) after preexposure prophylaxis (PrEP) with tixagevimab/cilgavimab among patients with systemic autoimmune rheumatic diseases (SARDs). METHODS: We performed a retrospective cohort study among patients with SARDs who received tixagevimab/cilgavimab between January 2, 2022, and November 16, 2022. The primary outcome was breakthrough COVID-19 after tixagevimab/cilgavimab. We performed multivariable Cox regression models adjusted for baseline factors to identify risk factors for breakthrough COVID-19. RESULTS: We identified 444 patients with SARDs who received tixagevimab/cilgavimab (mean age 62.0 years, 78.2% female). There were 83 (18.7%) breakthrough COVID-19 cases (incidence rate 31.5/1000 person-months, 95% CI 24.70-38.24), 7 (1.6%) hospitalizations, and 1 (0.2%) death. Older age was inversely associated with breakthrough COVID-19 (adjusted hazard ratio [aHR] 0.86/10 years, 95% CI 0.75-0.99). Higher baseline spike antibody levels were associated with lower risk of breakthrough COVID-19 (aHR 0.42, 95% CI 0.18-0.99 for spike antibody levels > 200 vs < 0.4 units). CD20 inhibitor users had a similar risk of breakthrough COVID-19 (aHR 1.05, 95% CI 0.44-2.49) compared to conventional synthetic disease-modifying antirheumatic drug (DMARD) users. CONCLUSION: We found that patients with SARDs had frequent breakthrough COVID-19, but the proportion experiencing severe COVID-19 was low. DMARD type, including CD20 inhibitors, did not significantly affect risk of breakthrough COVID-19. Evidence of prior humoral immunity was protective against breakthrough infection, highlighting the continued need for a multimodal approach to prevent severe COVID-19 as novel PrEP therapies are being developed.

Factors Associated With an Electronic Health Record-Based Definition of Postacute Sequelae of COVID-19 in Patients With Systemic Autoimmune Rheumatic Disease.

OBJECTIVE: Many individuals with rheumatic disease are at higher risk for severe acute coronavirus disease 2019 (COVID-19). We aimed to evaluate risk factors for postacute sequelae of COVID-19 (PASC) using an electronic health record (EHR)-based definition. METHODS: We identified patients with prevalent rheumatic diseases and COVID-19 within the Mass General Brigham healthcare system. PASC was defined by the International Classification of Diseases, 10th revision (ICD-10) codes, relevant labs, vital signs, and medications at least 30 days following the first COVID-19 infection. Patients were followed until the earliest of incident PASC, repeat COVID-19 infection, 1 year of follow-up, death, or February 19, 2023. We used multivariable Cox regression to estimate the association of baseline characteristics with PASC risk. RESULTS: Among 2459 patients (76.37% female, mean age 57.4 years), the most common incident PASC manifestations were cough (14.56%), dyspnea (12.36%), constipation (11.39%), and fatigue (10.70%). Serious manifestations including acute coronary disease (4.43%), thromboembolism (3.09%), hypoxemia (3.09%), stroke (1.75%), and myocarditis (0.12%) were rare. The Delta wave (adjusted hazard ratio [aHR] 0.63, 95% CI 0.49-0.82) and Omicron era (aHR 0.50, 95% CI 0.41-0.62) were associated with lower risk of PASC than the early pandemic period (March 2020-June 2021). Age, obesity, comorbidity burden, race, and hospitalization for acute COVID-19 infection were associated with greater risk of PASC. Glucocorticoid (GC) use (aHR 1.19, 95% CI 1.05-1.34 compared to no use) was associated with greater risk of PASC. CONCLUSION: Among patients with rheumatic diseases, following their first COVID-19 infection, we found a decreased risk of PASC over calendar time using an EHR-based definition. Aside from GCs, no specific immunomodulatory medications were associated with increased risk, and risk factors were otherwise similar to those seen in the general population.

Surgical Specialty Impacts Quality of Operative Training in Carotid Endarterectomy.

BACKGROUND: Carotid endarterectomy (CEA) is currently performed by multiple surgical specialties. The impact of surgical specialty and operative volume on post-CEA outcomes has been well described. However, it is unclear whether trainees of different surgical specialties have similar quality of operative training. METHODS: Data from Accreditation Council for Graduate Medical Education annual reports were collected and compared between graduating vascular surgery (VS) residents, VS fellows, and neurological surgery (NS) residents. Only cases reported as chief/senior/lead resident, surgeon junior, or surgeon fellow were included in analysis. Linear regression analysis was utilized to evaluate trends in case-mix and volume. RESULTS: From 2013 to 2022, total CEA case volume was higher among VS residents and fellows, compared to NS residents (52.8 ± 0.8 vs. 44.3 ± 1.4 vs. 12.9 ± 0.6, P < 0.0001). Additionally, VS residents and fellows performed other carotid operations including transfemoral or transcarotid artery stenting (11.1 ± 0.9 vs. 11.2 ± 0.8 vs. 0), carotid body tumor resection (0.7 ± 0.1 vs. 0.7 ± 0.0 vs. 0), and extracranial cervical bypass (6.7 ± 0.3 vs. 6.3 ± 0.3 vs. 0) that were not reported by the NS resident cohort (P < 0.0001 each). On linear regression analysis, total CEA procedures did not change for VS residents (R2 = 0.03, P = 0.62), decreased for VS fellows (-1.29 cases/yr, R2 = 0.75, P < 0.0001), and decreased among NS residents (-0.41 cases/yr, R2 = 0.44, P = 0.01) over the study period. CONCLUSIONS: Although residents of multiple surgical specialties are trained in CEA, vascular training offers significantly greater numbers and diversity of extracranial carotid cases. It also appears that CEA volume is decreasing among neurosurgical trainees. In light of recent reports on the volume-outcome effect in carotid surgery, these data may have implications for future practice patterns in the domain of extracranial carotid artery disease.

Prosthetic Conduit Use Does Not Adversely Impact Outcomes after Open Repair of Popliteal Artery Aneurysms.

BACKGROUND: Single segment, greater saphenous vein (GSV) conduit is considered the optimal bypass conduit among patients undergoing bypass surgery for peripheral artery disease (PAD). While this data has been extrapolated to patients undergoing bypass for popliteal artery aneurysms (PAAs), the pathophysiology of PAA is inherently different when compared to PAD, and the impact of conduit type on long-term outcomes after open repair of PAA remains unclear. METHODS: A multicenter database of five regional hospitals was retrospectively reviewed for all patients with PAA undergoing open surgical repair. Data were collected on demographic information, operative details, medications, and postoperative outcomes. Kaplan-Meier curves were used to compare freedom from major adverse limb events (MALE) following GSV versus prosthetic bypass. Cox proportional hazards model was used to identify patient-level characteristics associated with MALE, which was defined as major ipsilateral limb amputation or reintervention for graft patency. RESULTS: From 1999 to 2020, a total of 101 patients with PAA underwent open exclusion and bypass surgery. Median follow-up period was 4.2 years (interquartile range, 1.3-7.4 years), and complete data were available for 99 (98.0%) patients. The majority of patients were male (99.0%) and Caucasian (93.9%). Only 11.1% of procedures were emergent, with the remainder (88.9%) being elective. All patients underwent medial exposure with a below-knee popliteal bypass target (100%). Bypass conduits included GSV (69.7%), prosthetic conduit (28.3%), and 2 (2.0%) alternative conduits (one spliced arm vein, one cryopreserved vein). Patients undergoing prosthetic bypass were older (72 vs. 66 years, P = 0.001) and had similar rates of medical comorbidities. Compared with the GSV group, patients with prosthetic conduits were more frequently placed on postoperative anticoagulation (60.7% vs. 23.2%, P < 0.001). Conduit type did not impact postoperative complication rates (P = NS each). MALE rates were low overall (19.2% at 2 years), and similar when stratified by conduit type (log rank P = 0.47). On multivariable analysis, emergent bypass was associated with MALE (hazard ratio [HR] 5.73, 95% confidence interval [CI] 2.07-15.85, P < 0.001). Prosthetic conduit usage (HR 1.00, 95% CI, 0.40-2.51, P = 0.99) and postoperative anticoagulation (HR 1.02, 95% CI 0.42-2.50, P = 0.97) were not associated with MALE. CONCLUSIONS: Open repair of PAA is associated with excellent long-term outcomes. Prosthetic bypass is a comparable alternative to autogenous conduit for below-knee popliteal bypass targets, and lack of suitable GSV should not prohibit open surgical repair when indicated.

Feasibility and Intermediate Results of Transcarotid Revascularization with a Prosthetic Conduit.

BACKGROUND: Transcarotid artery revascularization (TCAR) is a hybrid technique with excellent initial outcomes. The technical success and safety of TCAR is heavily dependent on an anatomically suitable common carotid artery (CCA). Many patients do not meet anatomic criteria and therefore are not eligible for this therapy. We sought to extend the eligibility of TCAR to patients with unfavorable CCA anatomy via the adoption of a prosthetic arterial conduit. METHODS: A single-center retrospective study of patients with critical carotid artery stenosis who underwent TCAR via a prosthetic conduit between June 2019 and October 2021 was performed. All patients in the study were considered high-risk for carotid endarterectomy based on anatomic features, such as restenosis post-carotid endarterectomy and neck radiation. Unfavorable CCA anatomy was defined as a clavicle to carotid bifurcation distance <5 cm, a CCA diameter <6 mm, and/or significant atherosclerotic disease at the intended arterial access site. The primary outcome of interest was technical success. Secondary outcomes included perioperative complications, intermediate and long-term patency, intermediate and long-term stroke and/or mortality and in-hospital length of stay. Follow-up ranged from 1 to 29 months. RESULTS: Eight patients underwent 10 TCAR procedures via a prosthetic conduit. A total of 2 procedures (20%) were performed on female patients and 8 procedures (75%) were performed on male patients. The mean age was 65 years old (standard deviation 11 years). Technical success was 100%. The 30-day ipsilateral stroke rate was 0%. The 30-day patency was 90%. There was no re-exploration for hemorrhage and 30 day mortality was 0%. CONCLUSIONS: TCAR is an excellent option for carotid artery revascularization. Unfavorable CCA anatomy has limited its applicability. TCAR via a prosthetic conduit has the potential to expand eligibility for this promising therapy.

Attitudes of autistic adults toward genetic testing for autism.

Genetic testing for autism has been a controversial topic within the autistic community. Opinions regarding the benefits, risks, and limitations of genetic testing often differ between autistic people, researchers, and healthcare providers. The present study sought to understand the beliefs, attitudes, and intentions to pursue genetic testing of autistic adults and compare perspectives of autistic people who have had genetic testing with those who have not. An international sample of 173 autistic adults (19 [11%] who had previously undergone autism-related genetic testing) completed an online survey with questions assessing beliefs, attitudes, and intentions to pursue genetic testing. Beliefs and attitudes about genetic testing varied widely across the sample. Autistic individuals who had received prior genetic testing had much more positive beliefs about autism-related genetic testing (d = 0.87, 95% CI [0.37, 1.36]) and attitudes toward genetic testing (d = 1.14, 95% CI [0.66, 1.61]) compared to those who had not received such testing, although there were no meaningful differences between those same groups regarding beliefs about genetic testing unrelated to autism (d = 0.02, 95% CI [-0.45, 0.49], p = 0.93). Intention to genetically test oneself or one's (hypothetical) children was also significantly predicted by autism-specific beliefs, attitudes, and prior genetic testing status. A large majority of the sample (78.6%) also agreed that autistic individuals would benefit from contact with a genetic counselor in certain situations. These findings suggest that the autistic community does not have a singular view of genetic testing, and for those Autistic individuals who are interested in pursuing genetic testing for themselves or a family member, genetic counselors have the potential to play a key role in clinical care.

Parent and Provider Differences in Ratings of Mental Health and Neurodevelopmental Concerns in Children with Neurologic Disorders.

Children with neurologic disorders face increased risks for mental health and neurodevelopmental conditions, with information often limited to parent report. To better understand mental health and neurodevelopmental needs in this population, a retrospective chart review of a convenience sample of children with neurologic disorders referred for a neuropsychological evaluation was conducted in the present study to explore interrater agreement between care team members (referring providers, parents, pediatric neuropsychologist). Qualitative and quantitative data were collected from the evaluation reports of 129 youth (9:0-17:11 years old; 51.2% of female sex) with neurologic disorders (i.e., 38.0% traumatic brain injury, 27.1% epilepsy, 14.7% premature birth, 7.8% pediatric cancer, 3.9% prenatal substance exposure, and 14.7% other) who completed an evaluation in 2019. Over half the youth were flagged for unmet neurodevelopmental and mental health concerns and analyses revealed low interrater agreement for mental health concerns (κ = .324), better agreement for neurodevelopmental concerns (κ = .511), and low sensitivity of referring providers (Se = .326) and parents (Se = .366). One-way analyses of variance uncovered important factors (e.g., symptom severity, adaptive skills) that may account for missed concerns. Findings guide recommendations to strengthen methods for understanding mental health and/or neurodevelopmental concerns in children with neurologic disorders.

Associations of DMARDs with post-acute sequelae of COVID-19 in patients with systemic autoimmune rheumatic diseases: a prospective study.

OBJECTIVE: We investigated the baseline disease-modifying antirheumatic drug (DMARD) use and post-acute sequelae of COVID-19 (PASC) risk among patients with systemic autoimmune rheumatic diseases (SARDs). METHODS: Patients with SARDs and confirmed COVID-19 infection at Mass General Brigham completed a survey ≥28 days after positive PCR/Antigen test to prospectively investigate their COVID-19 courses. We investigated DMARD use at COVID-19 onset and PASC risk. PASC was defined as any COVID-19 symptom that persisted for ≥28 days. We used logistic regression to estimate odds ratios (OR) for PASC by DMARD class. We also used restricted mean survival time to determine the difference in symptom-free days by DMARD class in the 28-day period after infection. RESULTS: We analyzed 510 patients with SARDs and COVID-19 from 11/Mar/2021-17/Jun/2023; 202 (40%) developed PASC. CD20 inhibitor (CD20i) users had significantly higher odds of developing PASC vs csDMARD users (adjusted OR 2.69, 95%CI 1.23-5.88). IL-12/23, IL-17A, or IL-23 inhibitor (IL-12/23i, IL-17Ai, IL-23i) users also had significantly higher odds of PASC (adjusted OR 3.03, 95%CI 1.08-8.49). CD20i users had significantly fewer symptom-free days vs csDMARD users (adjusted -4.12, 95%CI -7.29 to -0.94). CONCLUSION: CD20i users had significantly higher odds of PASC and fewer symptom-free days over the 28 days following COVID-19 diagnosis compared with csDMARD users. Further research is needed to investigate whether PASC risk in CD20i users may be due to prolonged infection or other immune mechanisms. The association of IL-12/23i, IL-17Ai, and IL-23i and PASC calls for additional study.

A national analysis of vascular surgery resident operative experience in peripheral artery disease.

BACKGROUND: Endovascular and hybrid interventions have played an increasingly prominent role in the treatment of peripheral arterial disease (PAD) in the past decade. This shift has prompted concerns about the adequacy of open surgical training for current surgical residents. Moreover, the recent Best Surgical Therapy in Patients With Critical Limb Ischemia trial has further emphasized the importance of open surgical techniques in the treatment of peripheral arterial disease. The purpose of this study was to examine national temporal trends in peripheral operative volume among integrated vascular surgery residents. METHODS: Data was obtained from the Accreditation Council for Graduate Medical Education national data reports for integrated vascular surgery residents. Case volumes for surgeon chief or surgeon junior cases were collected from academic years 2012 to 2013 and 2021 to 2022. Trends in case-mix and volume were evaluated using linear regression analysis. RESULTS: The mean total vascular operative volume increased from 851.2 to 914.3 cases among graduating chief residents, with an annual growth of 8.5 ± 1.7 cases/year (R2 = 0.77; P < .0001). Major vascular case volume also increased at a rate of 5.7 ± 1.2 cases/year (R2 = 0.74; P < .001). Among operative categories, peripheral cases were the most frequent (n = 232.2 [26.6%]) and demonstrated the greatest annual growth (+8.0 ± 0.8 cases/year, R2 = 0.93; P < .001). No changes were seen in volume of open peripheral cases, including suprainguinal bypass (+0.1 ± 0.2 cases/year; R2 = 0.08; P = .40) or femoropopliteal bypass procedures (-0.1 ± 0.2 cases/year; R2 = 0.17; P = .20). Infrapopliteal bypass (+0.4 ± 0.1 cases/year; R2 = 0.48; P = .006), iliac/femoral endarterectomy (+1.3 ± 0.2 cases/year; R2 = 0.82; P < .001), and leg thromboembolectomy (+0.4 ± 0.1 cases/year; R2 = 0.64; P < .001) all demonstrated annual growth. For endovascular peripheral cases, aortoiliac revascularization (+3.4 ± 0.3 cases/year; R2 = 0.94; P < .001), femoropopliteal revascularization (+5.4 ± 0.2 cases/year; R2 = 0.98; P < .001), and tibioperoneal revascularization (+2.0 ± 0.2 cases/year; R2 = 0.92; P < .001) all increased in volume. Lower extremity amputations, including above-knee amputation (+0.6 ± 0.2 cases/year; R2 = 0.65; P < .001) and below-knee amputation (+0.9 ± 0.2 cases/year; R2 = 0.72; P < .001) also demonstrated an increase in volume. CONCLUSIONS: Current graduating residents have higher open and endovascular case volumes for peripheral artery disease on a national level, despite the increasing popularity of endovascular techniques. Further studies are needed to identify how these trends may impact current vascular surgery milestones. These trends may also influence the rising interest in competency-based training programs.

Mechanistic Static Model based Prediction of Transporter Substrate Drug-Drug Interactions Utilizing Atorvastatin and Rifampicin.

OBJECTIVE: An in vitro relative activity factor (RAF) technique combined with mechanistic static modeling was examined to predict drug-drug interaction (DDI) magnitude and analyze contributions of different clearance pathways in complex DDIs involving transporter substrates. Atorvastatin and rifampicin were used as a model substrate and inhibitor pair. METHODS: In vitro studies were conducted with transfected HEK293 cells, hepatocytes and human liver microsomes. Prediction success was defined as predictions being within twofold of observations. RESULTS: The RAF method successfully translated atorvastatin uptake from transfected cells to hepatocytes, demonstrating its ability to quantify transporter contributions to uptake. Successful translation of atorvastatin's in vivo intrinsic hepatic clearance (CLint,h,in vivo) from hepatocytes to liver was only achieved through consideration of albumin facilitated uptake or through application of empirical scaling factors to transporter-mediated clearances. Transporter protein expression differences between hepatocytes and liver did not affect CLint,h,in vivo predictions. By integrating cis and trans inhibition of OATP1B1/OATP1B3, atorvastatin-rifampicin (single dose) DDI magnitude could be accurately predicted (predictions within 0.77-1.0 fold of observations). Simulations indicated that concurrent inhibition of both OATP1B1 and OATP1B3 caused approximately 80% of atorvastatin exposure increases (AUCR) in the presence of rifampicin. Inhibiting biliary elimination, hepatic metabolism, OATP2B1, NTCP, and basolateral efflux are predicted to have minimal to no effect on AUCR. CONCLUSIONS: This study demonstrates the effective application of a RAF-based translation method combined with mechanistic static modeling for transporter substrate DDI predictions and subsequent mechanistic interpretation.

Outcomes Following in Situ Reconstruction for Aortic Infection with the Neo-Aortoiliac System and Aortic Homograft.

BACKGROUND: In situ reconstruction is one of the primary surgical options for primary aortic and graft and endograft infections. One institution's outcomes following aortic reconstruction with femoro-popliteal vein (i.e., the neo-aortoiliac system) and cryopreserved aortic allografts are described. METHODS: A retrospective review was performed of any patient who underwent aortic reconstruction with femoropopliteal vein or cryopreserved aortic allograft from 2013-2022 at a single tertiary-care institution. RESULTS: Twenty four patients underwent in situ reconstruction with the neo-aortoiliac system or with cadaveric allograft for primary or secondary aortic infection from 2013-2022. Short-term (30-day) mortality remains low (3/24 or 12.5%) despite the high incidence of major postoperative complications that necessitated reintervention in 11/24 or 45.8% of the cohort, most often for recurrent intracavitary infection. Gram-negative and drug-resistant pathogens were the most commonly implicated organisms in recurrent intra-abdominal infection. Management of early allograft degeneration is also described with extra-anatomic bypass grafting, conduit/graft embolization, which is then followed by allograft explantation and wide surgical debridement. Despite low short-term (30-day) mortality, all-cause 1-year mortality remains elevated at 38.1% (8/21) in those with an adequate follow-up interval. CONCLUSIONS: In situ reconstruction for primary or secondary aortic infections results in excellent short-term patient outcomes but is characterized by a high incidence of reintervention and an elevated all-cause 1-year mortality.

Restoring Venous Patency with the ClotTriever Following Deep Vein Thrombosis.

BACKGROUND: Although randomized data remain inconclusive, invasive endovenous therapy is increasingly favored in patients with extensive iliocaval or iliofemoral deep vein thrombosis (DVT) to reduce the rates of postthrombotic syndrome. Previously, pharmacomechanical thrombectomy was the therapy of choice, but the Inari ClotTriever device is an appealing, purely mechanical, alternative. It may reduce bleeding risk, intensive care unit admission, and the need for multiple procedures when compared with traditional thrombolysis. We present a series of 18 patients treated with the ClotTriever for extensive iliocaval or iliofemoral DVT. METHODS: The Inari ClotTriever is a percutaneous mechanical thrombectomy system consisting of an expandable nitinol collection bag that is dragged along the vein wall, separating and capturing thrombus for collection into the retrieval sheath. We retrospectively reviewed all patients undergoing ClotTriever thrombectomy since the device became available at our quaternary referral center in June 2019. The review of these patients' records was determined to be exempt by our institutional review board. RESULTS: Eighteen patients underwent ClotTriever thrombectomy between June 2019 and November 2021. Most patients (N = 16, 89%) presented within 2 weeks of symptom onset, and identifiable provoking factors were present in all patients. The most common provoking factor was anatomy, with May-Thurner syndrome present in 8 patients. All patients had restoration of unimpeded venous flow in the treated segments, although 3 had some residual nonflow limiting thrombus. There were no bleeding events or repeat venous procedures. The median postprocedure length of stay of 2 days. Postoperative venous imaging was performed in 15 patients and showed patency of the treated segment in 14 patients. Revised Clinical Venous Severity Scores were available in 14 patients during the course of follow-up. Of these, 9 patients' highest scores were 0, 2 patients' highest scores were 2, 2 patients' highest scores were 4, and 1 patient had a high score of 8. CONCLUSIONS: Venous flow was re-established in all 18 patients treated with the ClotTriever in this series, with no bleeding complications, and median postprocedure length of stay of 2 days. All patients with available follow-up, except 1, retained patency of the treated venous segments, and most had mild postthrombotic syndrome or none at all. These findings suggest that the ClotTriever is a safe and effective way to treat extensive iliocaval/femoral DVT.

Commentary: The construct validity of 'camouflaging' in autism: psychometric considerations and recommendations for future research - reflection on Lai et al. (2020).

Research on the construct of 'camouflaging' in autism and its sociodemographic/clinical correlates has far outpaced the work being done to establish the construct validity of camouflaging and its distinction from other similar constructs. The imprecision with which camouflaging is defined and measured has serious implications for future research on this topic, and unless additional effort is made to produce reliable and valid measurements of this construct, researchers will not be able to meaningfully assess important questions such as whether the effort of camouflaging one's behavior contributes to increased mental health difficulties. By reviewing the psychometric strengths and weaknesses of various operationalizations of camouflaging, this commentary highlights a pressing need for further measure validation in this area. Specific methodological guidance is provided for researchers interested in rigorously testing the validity of putative camouflaging measures.

Barriers and facilitators to the use of survivorship care plans by hematopoietic stem cell transplant survivors and clinicians.

PURPOSE: Survivors of hematopoietic stem cell transplants (HSCT) have complex care needs for the remainder of their lives, known as the survivorship period. Survivorship care plans (SCPs) have been proposed to improve care coordination and ultimately survivorship outcomes. We explored the barriers and facilitators of SCP use among HSCT survivors and their clinicians in order to develop more useful SCPs for the HSCT context. METHODS: Analogous surveys regarding perceived barriers to and facilitators of SCP use based on a sample SCP for a female allogenic HSCT survivor were administered to HSCT survivors and non-transplant oncology and primary care clinicians. RESULTS: Twenty-seven HSCT survivors and 18 clinicians completed the survey. The main barriers to SCP use were lack of awareness of SCP existence, uncertainty regarding where to find SCP, unclear roles and responsibilities among healthcare teams, length of SCP, and difficultly understanding SCPs. The facilitators of SCP use were increased understanding of survivorship care needs, clarified roles and responsibilities of survivors and clinicians, SCPs that are readily available and searchable in electronic health record, increased awareness of SCP existence and provision to all survivors, and if the SCP is survivor-specific and up-to-date. CONCLUSIONS: Much of the work regarding SCPs has looked at barriers to creation and provision; however, our study examines factors influencing use of SCPs. By determining the barriers and facilitators surrounding SCP use for HSCT survivors and their clinicians, we can create SCP templates and clinical workflows to optimize SCP use, ideally leading to better outcomes for HSCT survivors.

Gorillas have been infected with the HERV-K (HML-2) endogenous retrovirus much more recently than humans and chimpanzees.

Human endogenous retrovirus-K (HERV-K) human mouse mammary tumor virus-like 2 (HML-2) is the most recently active endogenous retrovirus group in humans, and the only group with human-specific proviruses. HML-2 expression is associated with cancer and other diseases, but extensive searches have failed to reveal any replication-competent proviruses in humans. However, HML-2 proviruses are found throughout the catarrhine primates, and it is possible that they continue to infect some species today. To investigate this possibility, we searched for gorilla-specific HML-2 elements using both in silico data mining and targeted deep-sequencing approaches. We identified 150 gorilla-specific integrations, including 31 2-LTR proviruses. Many of these proviruses have identical LTRs, and are insertionally polymorphic, consistent with very recent integration. One identified provirus has full-length ORFs for all genes, and thus could potentially be replication-competent. We suggest that gorillas may still harbor infectious HML-2 virus and could serve as a model for understanding retrovirus evolution and pathogenesis in humans.

Cerebral monitoring during transcarotid artery revascularization with flow reversal via transcranial doppler ultrasound examination.

OBJECTIVE: Transcarotid artery revascularization (TCAR) is a hybrid technique for carotid artery revascularization that relies on proximal carotid occlusion with flow reversal for distal embolic protection. The hemodynamic response of the intracranial circulation to flow reversal is unknown. In addition, the rate and pattern of cerebral embolization during flow reversal has yet to be investigated. The aim of this study was to characterize cerebral hemodynamic and embolization patterns during TCAR. METHODS: A single-institution retrospective study of patients with carotid artery stenosis undergoing TCAR with intraoperative transcranial Doppler (TCD) monitoring of the middle cerebral artery (MCA) was performed. Primary outcomes included changes in MCA velocity and MCA embolic signals observed throughout TCAR. RESULTS: Eleven patients underwent TCAR with TCD monitoring of the ipsilateral MCA. The average MCA velocity at baseline was 50.6 ± 16.4 cm/s. MCA flow decreased significantly upon initiation of flow reversal (50.5 ± 16.4 cm/s vs 19.1 ± 18.4 cm/s; P = .02). The reinitiation of antegrade flow resulted in a significant increase in the number of embolic events compared with baseline (P = .003), and embolic events were observed in two patients during flow reversal. CONCLUSIONS: TCD monitoring of patients undergoing TCAR revealed that the initiation of flow reversal results in a decrement in ipsilateral MCA velocity. Furthermore, embolic events can occur during flow reversal and are significantly associated with the reinitiation of antegrade flow in the internal carotid artery. However, both of these hemodynamic events were well-tolerated in our cohort. These findings suggest that TCAR remains a safe neuroprotective strategy for carotid revascularization.

Prevalence of Decreased Sound Tolerance (Hyperacusis) in Individuals With Autism Spectrum Disorder: A Meta-Analysis.

OBJECTIVES: Hyperacusis, defined as decreased tolerance to sound at levels that would not trouble most individuals, is frequently observed in individuals with autism spectrum disorder (ASD). Despite the functional impairment attributable to hyperacusis, little is known about its prevalence or natural history in the ASD population. The objective of this study was to conduct a systematic review and meta-analysis estimating the current and lifetime prevalence of hyperacusis in children, adolescents, and adults with ASD. By precisely estimating the burden of hyperacusis in the ASD population, the present study aims to enhance recognition of this particular symptom of ASD and highlight the need for additional research into the causes, prevention, and treatment of hyperacusis in persons on the spectrum. DESIGN: We searched PubMed and ProQuest to identify peer-reviewed articles published in English after January 1993. We additionally performed targeted searches of Google Scholar and the gray literature, including studies published through May 2020. Eligible studies included at least 20 individuals with diagnosed ASD of any age and reported data from which the proportion of ASD individuals with current and/or lifetime hyperacusis could be derived. To account for multiple prevalence estimates derived from the same samples, we utilized three-level Bayesian random-effects meta-analyses to estimate the current and lifetime prevalence of hyperacusis. Bayesian meta-regression was used to assess potential moderators of current hyperacusis prevalence. To reduce heterogeneity due to varying definitions of hyperacusis, we performed a sensitivity analysis on the subset of studies that ascertained hyperacusis status using the Autism Diagnostic Interview-Revised (ADI-R), a structured parent interview. RESULTS: A total of 7783 nonduplicate articles were screened, of which 67 were included in the review and synthesis. Hyperacusis status was ascertained in multiple ways across studies, with 60 articles employing interviews or questionnaires and seven using behavioral observations or objective measures. The mean (range) age of samples in the included studies was 7.88 years (1.00 to 34.89 years). The meta-analysis of interview/questionnaire measures (k(3) = 103, nASD = 13,093) estimated the current and lifetime prevalence of hyperacusis in ASD to be 41.42% (95% CrI, 37.23 to 45.84%) and 60.58% (50.37 to 69.76%), respectively. A sensitivity analysis restricted to prevalence estimates derived from the ADI-R (k(3) = 25, nASD = 5028) produced similar values. The estimate of current hyperacusis prevalence using objective/observational measures (k(3) = 8, nASD = 488) was 27.30% (14.92 to 46.31%). Heterogeneity in the full sample of interview/questionnaire measures was substantial but not significantly explained by any tested moderator. However, prevalence increased sharply with increasing age in studies using the ADI-R (BF10 = 93.10, R2Het = 0.692). CONCLUSIONS: In this meta-analysis, we found a high prevalence of current and lifetime hyperacusis in individuals with ASD, with a majority of individuals on the autism spectrum experiencing hyperacusis at some point in their lives. The high prevalence of hyperacusis in individuals with ASD across the lifespan highlights the need for further research on sound tolerance in this population and the development of services and/or interventions to reduce the burden of this common symptom.

Retrograde Transamputation Revascularization: A Case Report.

Below-knee amputation remains the most common level of amputation in patients with lower extremity gangrene and critical limb ischemia. Failure to heal, requiring additional operative debridement or conversion to an above-knee amputation remains a significant cause of patient morbidity. There remains no definitive diagnostic test that can accurately predict healing of the amputation site. We report a case utilizing a hybrid technique of retrograde transamputation revascularization via balloon angioplasty. This proximal, retrograde approach allows for relatively easy crossing and treatment of the infrainguinal chronic total occlusions (CTOs), improving arterial inflow for optimal wound healing.