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Type A intramural hematoma (TAIMH) is an acute aortic disease characterized by the presence of hematoma in the aortic media and involving the ascending aorta. Open repair seems to be the first treatment approach, although recent evidence highlights that the best management of TAIMH is controversial. This review will focus on the current concept for TAIMH management and factors affecting the decision making.Recent studies have evaluated the role of open and endovascular repair, as well as conservative management in patients with TAIMH. More specific imaging findings seem to affect decision making for urgent repair.Despite TAIMH's acute nature, conservative management seems to represent a valid option for urgent approach, presenting similar mortality to open and endovascular repair. Comparative data are limited, however, in experienced centers, any approach may be applied with encouraging results. Endovascular management, which is mainly applied to manage retrograde TAIMH, is related to lower mortality and morbidity compared to open repair in this group of patients while aortic remodeling seems beneficial with this approach. Imaging findings, as ulcer-like lesions, hematoma thickness, concomitant dissection and aortic diameter, related to higher complication rate, set the indication for interventional management. Further research, including prospective data and registries, and ideally, randomized data may further clarify the best approach and factors indicating urgent repair.

Connective tissue disease (CTD) syndromes involve the ascending, aortic arch, and thoracoabdominal aorta and are associated with higher risk of aortic aneurysm or dissection. Currently, vascular societies generally recommend open repair as the first option for aortic disease in patients with CTD. However, the implementation of endovascular techniques for patients with CTD with aortic pathologies seems to have increased in recent years, mainly in patients of high surgical risk or in urgent situations. Endovascular treatment of aortic arch pathologies in patients with CTD have been feasible in experienced centers; however, the evidence is scarce. Thoracic endovascular aneurysm repair in patients with CTD is more evident; in 15 studies, 304 patients with CTD were treated with thoracic endovascular aneurysm repair with high technical success rates (88% to 100%) and a low early mortality rate (1.6%). During the median follow-up, 33 patients died and 64 patients underwent a re-intervention. In 6 studies, 26 patients with CTD were treated with fenestrated/branched endovascular aneurysm repair for thoracoabdominal aortic aneurysm, with a technical success rate of 100%, without early mortality and morbidity. The endovascular approach to thoracoabdominal aortic aneurysm, especially in post-dissection patients, mandates adjunctive techniques to achieve false lumen thrombosis with various approaches; in our experience, the Candy-Plug technique has been proven to be technically feasible with good outcomes. Endovascular treatment of aortic pathologies in patients with CTD seems to be feasible and safe in high-risk and urgent patients. Re-intervention remains an issue. The constant development of endovascular techniques and devices may provide improved mortality and morbidity outcomes.

Context: Both isokinetic testing and functional tests are often used during patient rehabilitation programs. Most researchers have assessed the relationship of isokinetic testing and functional tests in parameters such as peak moment, work, or power. However, little information exists regarding the acceleration and deceleration parameters and their relationship to function. Design: The purpose of the study was to investigate the concept of acceleration and deceleration of the knee flexor and extensor muscle groups during isokinetic testing and its relationship to function. Methods: Twenty-six healthy individuals (14 men and 12 women) participated in the study. Isokinetic bilateral concentric knee flexion and extension muscular performance was assessed isokinetically at the angular velocities of 60°/s, 180°/s, and 300°/s. Functional performance was also assessed using (1) single hop for distance, (2) triple hop for distance, and (3) single timed hop. Functional data were normalized to body weight. A P value Results: Fair and moderate to good correlations (r = .396, P = .045 to r = .705, P = .001) were discovered between flexors’ and extensors’ acceleration/deceleration variables and the normalized to body weight functional tests. Conclusions: Appropriate understanding of isokinetic parameters as described in this study, including acceleration/deceleration values, may provide useful information about the functional ability of the lower limb muscular system.

Sarcopenia is the loss of muscle mass and strength. It manifests as decreased core muscle area in axial abdominal computed tomography scans. The predictive value of sarcopenia in outcome research has been widely discussed. A systematic review was conducted to assess sarcopenia as a biomarker in patients undergoing endovascular abdominal aortic aneurysm repair (EVAR) and its association with long-term survival.A systematic search of the English medical literature, published from 1991 to 2021, was conducted, using PubMed, EMBASE, and CENTRAL, as per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA, 2020) guidelines. The study protocol was registered to the International Prospective Register of Systematic Reviews (CRD 42021260192). Observational studies reporting on sarcopenic and nonsarcopenic patients undergoing EVAR were included. The Risk Of Bias In Non-Randomized Studies - of Interventions (ROBINS-I) risk of bias evaluation tool was used for the quality assessment. The outcomes were summarized as odds ratio (OR) along with their 95% confidence intervals (CI), through a paired meta-analysis. The primary outcome was 5-year survival following EVAR.Eleven observational studies, including 2,385 patients (89.6% males) treated with EVAR, between 1999 and 2018, were included in the qualitative synthesis. The mean age was 72.9 years (range 70-76.4 years). Nine of the studies reported on a negative prognostic value of sarcopenia on survival during a long-term follow-up. Six studies stratified their cohorts in sarcopenic versus nonsarcopenic patients (40.3% sarcopenic). The cutoff values (mmThe available data derived from observational studies suggest an association between sarcopenia and worse long-term survival in patients treated with EVAR. There is a lack of a universally accepted definition for sarcopenia and future reporting standards should address this issue. Prospective studies are necessary to establish this negative prognostic value of sarcopenia on long-term survival.

Fenestrated endovascular aneurysm repair (F-EVAR) has allowed successful treatment of patients with complex aortic aneurysms. Custom-made devices (CMDs) are manufactured by companies and tailored to the patient's anatomy to incorporate target vessels, while there is also the "off label" alternative with the devices modified by a surgeon in the operating room: surgeon-modified FEVAR (sm-FEVAR). This study aims to present and compare technical durability of CMDs- and sm-FEVAR for complex abdominal and thoracoabdominal aortic pathologies.A retrospective cohort study was undertaken including all consecutive patients treated with sm- or CMD-FEVAR during a 3-year period in a single center. Only cases with at least 3 reno-visceral target vessels were included. Primary outcomes were technical success, and freedom from endoleak (EL) (Ia or III; all branch related) and re-intervention during follow-up period. Mortality and morbidity were also recorded.Thirty-two sm-FEVAR patients (81,3% male) and 79 CMD-FEVAR patients (77,2% male) were included. Indication for sm-FEVAR was exclusively urgent, while all CMD- FEVAR were elective. Technical success was similar in sm-FEVAR (100%) and CMD-FEVAR (98,7%) (P = 0.523). Mean follow-up was 16.3 ± 13 and 20 ± 17.3 months for sm-FEVAR and CMD- FEVAR, respectively (P = 0.28). The freedom from EL Ia rate was 91.7% [standard error (SE) 5.7%] at 12 months in sm-FEVAR, while it was 97.7% (SE 2.2%) and 92.3% (SE 4.3%) at 12 and 24 months, respectively in CMD-FEVAR (P = 0.69). The freedom from EL III rate was 95.5% (SE 4.4%) and 88% (SE 8.2%) at 12 and 24 months, respectively in sm-FEVAR, while it was 92.1% (SE 3.8%) and 89.2% (SE 4.7%) at 12 and 24 months, respectively in CMD-FEVAR (P = 0.68). The freedom from re-intervention rate was 91.6% (SE 5.7%) and 84.6% (SE 8.6%) at 12 and 24 months, respectively in sm-FEVAR, while it was 91.7% (SE 4%) and 83.4% (SE 5.9%) at 12 and 24 months, respectively in CMD-FEVAR (P = 0.90). The survival rate was 87.5% (5.8%) and 76.3% (7.9%) at 1 and 12 months, respectively in sm-FEVAR, while it was 93.7% (2.7%) at 1 month in CMD-FEVAR without any other death during FU period. No bridging stent occlusions were noted during follow-up period in any patient.Sm-FEVAR offers good technical success and mid-term clinical outcomes in urgent cases of complex aortic pathologies. Its durability is acceptable and comparable to CMD-FEVAR with a relatively low re-intervention rate.

Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling in the bone marrow. This impaired monopoiesis resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of colony-stimulating factor 1 in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS.

Background Asthma epidemics associated with thunderstorms have had catastrophic impacts on individuals and emergency services. Seasonal allergic rhinitis (SAR) is present in the vast majority of people who develop thunderstorm asthma (TA), but there is little evidence regarding risk factors for TA among the SAR population. Objective We sought to identify risk factors for a history of TA and hospital presentation in a cohort of individuals with SAR. Methods This multi-centre study recruited adults from Melbourne (Australia) with a past diagnosis of TA and/or self-reported SAR. Clinical information, spirometry, white blood-cell count, ryegrass pollen specific IgE (RGP-spIgE) and fractional exhaled nitric oxide (FeNO) were measured to identify risk factors for a history of TA in individuals with SAR. Results From a total of 228 individuals with SAR, 35% (80/228) reported SAR only (I-SAR), 37% (84/228) reported TA symptoms but had not attended hospital for treatment (O-TA) and 28% (64/228) had presented to hospital for TA (H-TA). All H-TA patients reported a previous asthma diagnosis. Logistic regression analysis of factors associated with O-TA and H-TA indicated that lower forced expiratory volume in one second (FEV1) and asthma control questionnaire (ACQ) score >1.5 were associated with H-TA. Higher blood RGP-spIgE, eosinophil counts, and FeNO were significantly associated with both O-TA and H-TA. Receiver-operating curve (ROC) analysis showed RGP-spIgE >10·1 kU/L and pre-bronchodilator FEV1 ≤90% to be biomarkers of increased H-TA risk. Conclusion Clinical tests can identify risk for a history of TA in individuals with SAR and thereby inform patient-specific treatment recommendations.

Mutations in GBA1, the gene encoding the lysosomal enzyme β-glucocerebrosidase (GCase), which cause Gaucher’s disease, are the most frequent genetic risk factor for Parkinson’s disease (PD). Here, we employ global proteomic and single-cell genomic approaches in stable cell lines as well as induced pluripotent stem cell (iPSC)-derived neurons and midbrain organoids to dissect the mechanisms underlying GCase-related neurodegeneration. We demonstrate that GCase can be imported from the cytosol into the mitochondria via recognition of internal mitochondrial targeting sequence-like signals. In mitochondria, GCase promotes the maintenance of mitochondrial complex I (CI) integrity and function. Furthermore, GCase interacts with the mitochondrial quality control proteins HSP60 and LONP1. Disease-associated mutations impair CI stability and function and enhance the interaction with the mitochondrial quality control machinery. These findings reveal a mitochondrial role of GCase and suggest that defective CI activity and energy metabolism may drive the pathogenesis of GCase-linked neurodegeneration.

Purpose: The post–endovascular abdominal aortic aneurysm repair (EVAR) inflammatory response, which is very often associated with fever, has been ascribed to a wide range of proinflammatory mediators and operative events. The aim of this study was to evaluate the impact of such factors in the development of fever of noninfectious origin after elective EVAR. Materials and Methods: A retrospective analysis of prospectively collected data of patients treated with standard elective EVAR between February 2017 and December 2020 was undertaken. The database included patients’ demographics and comorbidities, as well as laboratory inflammatory markers (white blood cell count, neutrophils, and C-reactive protein [CRP]) and anatomical characteristics (sac diameter, inferior mesenteric artery [IMA] patency and diameter, number of patent lumbar arteries, internal iliac artery [IIA] patency or occlusion). Intraoperative details, such as type of stent graft material and IIA overstenting, were also analyzed. Patients with infectious postoperative complications or previously receiving systemic anti-inflammatory medication were excluded. Statistical analysis was performed by SPSS 22.0 for Windows software (IBM Corp, Armonk, New York). Results: From 332 patients treated with elective EVAR between 2017 and 2020, 268 patients (all men) were included in the analysis. The mean age was 72.1±7.5 years and the mean aneurysm diameter was 59.1±12.1 mm. Seventeen patients were excluded due to a known infection site. From the study cohort, 114 (42.5%) patients presented with fever. Multivariate regression analysis confirmed that the occlusion of IMA ≥5 mm (pConclusion: Occlusion of an existing wide (≥5 mm) and patent IMA prior to EVAR may contribute to the development of post-EVAR pyrexia. The CRP is a reliable marker for post-EVAR fever. Further prospective studies are needed to corroborate these findings.

Background: Ascending aorta and aortic arch diseases have an increasing interest among cardiovascular specialists regarding diagnosis and management. Innovations in endovascular surgery and evolution of open surgery have extended the indications for treatment in patients previously considered unfit for surgery. The aim of this systematic review of the literature was to present and analyze current cardiovascular guidelines for overlap and differences in their recommendations regarding ascending aorta and aortic arch diseases and the assessment of evidence. Methods: The English medical literature was searched using the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases from January 2009 to December 2020. Recommendations on selected topics were analyzed, including issues from definitions and diagnosis (imaging and biomarkers) and indications for treatment to management, including surgical techniques, of the most important ascending aorta and aortic arch diseases. Results: The initial search identified 2414 articles. After exclusion of duplicate or inappropriate articles, the final analysis included 5 articles from multidisciplinary, cardiovascular societies published between 2010 and 2019. The definition of non-A-non-B aortic dissection is lacking from most of the guidelines. There is a disagreement regarding the class of recommendation and level of evidence for the diameter of ascending aorta as an indication. The indication for treatment of aortic disease may be individualized in specific cases while the growth rate may also affect the decision making. The role of endovascular techniques has not been established in current guidelines except by 1 society. Supportive evidence level in the management of aortic arch diseases remains limited. Conclusion: In current recommendations of cardiovascular societies, the ascending aorta and aortic arch remain a domain of open surgery despite the introduction of endovascular techniques. Recommendations of the included societies are mostly based on expert opinion, and the role of endovascular techniques has been highlighted only from 1 society. The chronological heterogeneity apparent among guidelines and the inconsistency in evidence level should be also acknowledged. More data are needed to develop more solid recommendations for the ascending aorta and aortic arch diseases.

The t-Branch, a standardized off-the-shelf multi-branched stent graft has been used for the treatment of elective and urgent cases in aortic disease. The aim of this study was to assess the early outcomes in terms of technical success, mortality, and morbidity in500 patients being treated with the t-Branch device.A two-center retrospective observational study was undertaken including patients treated using the t-Branch (Cook Medical, Bloomington, IN) in elective or urgent settings for complex abdominal aortic aneurysm and thoraco-abdominal aortic aneurysm between 2014 and 2019 (early experience 2014-2016; late experience 2017-2019). Primary endpoints were technical success and early (30-day) mortality, and secondary endpoints were early morbidity, endoleak, and target vessel patency rates. Multivariable regression models were used to determine the independent association of risk factors with (1) mortality and (2) spinal cord ischemia.A total of 542 patients (mean age, 70.5 ± 8.5 years; 388 men [72%]; mean aneurysm diameter, 7.5 ± 2.5 cm) were included (63% elective; 90% thoraco-abdominal aortic aneurysm). The technical success rate was 97% (526/542) (elective, 96.7% [328/339] vs urgent, 97.6% [208/213]). The total 30-day mortality rate was 12.3% (8.5% in elective, 15% in symptomatic, and 30% in contained rupture). After multivariate regression analysis, the mortality rate was associated with older age (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.03-1.11; P .001) and with lower baseline glomerular filtration rate (OR, 0.98; 95% CI, 0.98-0.99; P .001). In elective cases, the mortality rate was associated with a history of coronary artery disease (OR, 0.26; 95% CI, 0.09-0.73; P .011) and higher body mass index (OR, 0.87; 95% CI, 0.77-0.98; P .027). In urgent cases, the mortality rate was associated with older age, (OR, 1.07; 95% CI, 1.02-1.13; P .010) and lower baseline glomerular filtration rate (OR, 0.97; 95% CI, 0.95-0.99; P .001). The spinal cord ischemia rate was 10.5% (6.5% temporary, 4% permanent) and was associated with the early study period (OR, 2.01; 95% CI, 1.03-3.89; P .038). The renal impairment rate was 13%, the stroke rate was 2.5%, and the myocardial infarction rate was 1.8%, whereas the access complications rate was 7.7%. On early computed tomography angiography, the primary patency rate for the right renal artery was 99.6%, for the left renal artery was 100%, for the superior mesenteric artery was 99.4%, and for the coeliac trunk was 99.8%. The endoleak I and III rates were 2.7% (15/542) and 2.7% (15/542), respectively.Elective and urgent use of the t-Branch multi-branched off-the shelf stent graft showed high technical success and early target vessel patency rates. Early mortality and morbidity rates were acceptable.

Objectives The aim of this study is to assess any relation between spondylitis and aortic aneurysmal disease by reviewing the current literature. Methods A systematic search was undertaken using MEDLINE, EMBASE and CENTRAL databases till May 2019, for articles reporting on patients suffering from spondylitis and aortic aneurysm. Results The most involved aortic segment was infrarenal aorta (56.9%). The lumbar vertebrae were more frequently affected (79.7%). Commonest symptoms were back pain (79.1%), fever (33.7%) and lower limb pain (29.1%). 55.8% of cases were diagnosed using computed tomography. The pathology was attributed to infectious causes in 25.1% of cases. 53.4% of patients were treated only for the aneurysm, 27.9% for both pathologies, while two patients solely for the vertebral disease. Endovascular aneurysm repair was chosen in 12.8% of cases. The 30-day mortality was 8.1% (7/86); mostly from vascular complications. Conclusions A synchronous spondylitis and aortic aneurysm may share common etiopathology, when an infectious or inflammatory cause is presented. The lumbar vertebrae are more frequently affected. Low quality data do not allow safe conclusion to suggest the best treatment option.

Fifty articles comprising 18 randomized controlled trials (RCTs), 16 observational studies, and 16 meta-analyses on the safety and effectiveness of sodium-glucose cotransporter 2 inhibitors were evaluated in the current review. Only one-fourth of the cohorts of recent trials had peripheral arterial disease (PAD), whereas this subgroup was at high risk for amputations. Despite a remarkable heterogeneity of RCTs, only 2 trials on canagliflozin suggested excess amputation rates, whereas several observational studies generated conflicting conclusions and remained short on possible explanations. Preliminary evidence from observational research suggested that patients with PAD may even benefit from SGLT-2 inhibitor treatment due to lower observed heart failure hospitalization rates.

Objective This study aims to determine the outcomes of transcaval embolization (TCE) for type II endoleak after infrarenal endovascular aortic repair (EVAR) and fenestrated/branched EVAR (F/BEVAR). Methods A retrospective single-center cohort study of all consecutive TCE procedures between August 2015 and August 2019 was performed to investigate technical success, in-hospital morbidity, and 30-day mortality as well as clinical success during follow-up. The indication for TCE was an aneurysm sac growth of 5 mm or more owing to a type II endoleak after EVAR for infrarenal or F/BEVAR for juxtarenal and type IV thoracoabdominal aortic aneurysm. Results A total 25 TCE procedures in 24 patients (95.8% male) were included. Technical success was 96.0% (24/25); selective and nonselective TCE were performed in 48% of patients. The in-hospital morbidity and 30-day mortality were 0%. The median follow-up was 23.1 months (interquartile range, 10.9-40.1 months). Freedom from type II endoleak-related reintervention was 84.6% at 12 months. Comparing clinical success after TCE, reintervention was necessary in 16.7% of patients after nonselective and 20% of patients after selective TCE. Regarding TCE after EVAR vs F/BEVAR, reintervention was performed in 12.5% of EVAR and 33.3% of F/BEVAR patients during follow-up. Conclusions TCE is an acceptable treatment alternative for type II endoleak with aneurysm sac enlargement and can be used after EVAR for infrarenal abdominal aortic aneurysms and F/BEVAR for juxtarenal abdominal aortic aneurysms and type IV thoracoabdominal aortic aneurysms.

Purpose: This study describes technical success, feasibility, and early results of fenestrated and branched endovascular aortic repair (F/B-EVAR) for treatment of thoracoabdominal aortic aneurysms (TAAAs) or pararenal aneurysms with more than 4 target visceral vessels (TVs) due to renovisceral arterial anatomical variations. Materials and Methods: Patients with TAAAs or pararenal aortic aneurysms who had more than 4 TVs due to renovisceral arterial anatomical variations of renal, celiac, and/or superior mesenteric arteries and received F/B-EVAR between January 2017 and September 2019 at a single aortic center were included in this study. We analyzed technical success, feasibility, and early outcomes. Results: Twelve patients (mean age 70±10 years, 9 males) were included. The anatomical variations included 6 right accessory renal arteries, 8 left accessory renal arteries, and 1 celiac artery variant. Stent-grafts were fenestrated, branched or combined in 6, 5, or 1 patients, respectively. The mean operating time was 346±120 minutes, the mean fluoroscopy time was 80±29 minutes, and the mean radiation dose area product was 430±219 Gy·cm2. The mean contrast volume was 129±45 mL. The total number of TVs was 64; 5 TVs in 9 patients, 6 in 2 patients, and 7 in 1 patient. Technical success was achieved in all cases. The mean intensive care unit stay was 6±5 days, and the mean total hospital stay was 14±10 days. One patient died early (30-day). Early morbidities included respiratory complication in 1 patient, renal insufficiency in 1 patient, and wound infection in 2 patients. No spinal cord ischemia, stroke, or bowel ischemia occurred. Early computed tomography angiography showed 100% patency of the bridging covered stents and TVs. The mean follow-up was 13±4.3 months. No mortality or adverse major event occurred during the follow-up. Two patients with developed type Ic endoleak related to 1 right renal artery and 1 celiac artery covered stent. Patency of the TVs during follow-up was 100%. Conclusion: The use of F/B-EVAR for the treatment of TAAA with more than 4 TVs due to renovisceral arterial anatomical variations in our own experience is feasible and not related to increased morbidity and mortality.

Objective The aim of our study was to compare three different endovenous thermal ablation (EVTA) modalities in the treatment of great saphenous vein (GSV) incompetence. Methods We performed a single-center, prospective, comparative cohort study that included consecutive patients undergoing EVTA of the GSV. Patients were treated with either segmental radiofrequency ablation (sRFA) or endovenous laser ablation (EVLA) with a 1470-nm dual radial fiber or with a 1470-nm jacket-tip fiber. The clinical classification CEAP (clinical, etiologic, anatomic, pathophysiologic), 10-cm visual analog scale scores for pain, Venous Clinical Severity Scores (VCSSs), and chronic venous insufficiency quality-of-life questionnaire (CIVIQ-20) scores were recorded. The primary outcome was clinical success, which was defined as the absence of reflux or recanalization of the GSV and procedure-related complications, assessed at 7 and 30 days and 1 year postoperatively. The secondary outcomes were the assessment of postoperative pain using the VAS and improvement in the VCSSs and CIVIQ-20 scores. Results A total of 153 patients (160 limbs) had undergone sRFA (sRFA group; n = 53 limbs), 1470-nm radial fiber EVLA (EVLA-R group; n = 55 limbs), or 1470-nm jacket-tip fiber EVLA (EVLA-J group; n = 52 limbs). The patient demographics, CEAP clinical class, and intraoperative details were comparable among the three groups. The GSV occlusion rate at 1 year was 93% in the sRFA group, 93% in the EVLA-R group, and 95% in the EVLA-J group. No major complications were observed postoperatively. Endothermal heat-induced thrombosis was observed in 2 (4.4%), 1 (2.2%), and 2 (4.4%) patients in the sRFA, EVLA-R, and EVLA-J groups, respectively (P > .5). The VCSS showed greater improvement in the EVLA-R group at 1 week compared with that in the sRFA (P = .05) and EVLA-J (P = .002) groups. Changes in the CIVIQ-20 score were in favor of the EVLA-R group at 7 days (−14.3 ± 10.3 vs −7.9 ± 5.9; adjusted difference, 6.06; 95% confidence interval [CI], 1.57-10.55; P = .01) and 30 days (−12 ± 8 vs −11.2 ± 7; adjusted difference, 5.5; 95% CI, 1.21-9.81; P = .02) postoperatively compared with the sRFA group and at 7 days compared with the EVLA-J group (−14.3 ± 10.3 vs −9.6 ± 7.9; adjusted difference, −4.4; 95% CI, −9.06 to 0.22; P = .05). Analyzing the different components of the CIVIQ-20, pain, and physical scores showed a greater reduction in the EVLA-R group in the early postoperative period compared with that in the sRFA and EVLA-J groups. Conclusions All three EVTA modalities showed equal effectiveness and safety for the treatment of GSV reflux. EVLA with the 1470-nm radial fiber showed better outcomes in terms of early postoperative VCSSs and pain and physical CIVIQ scores. The clinical and quality of life benefits were similar for all modalities at 1 year postoperatively.

Objectives The aim of our study was to evaluate the role of flavonoids in the improvement of post-operative symptoms after endovenous thermal ablation (EVTA). Methods A prospective comparative study of 120 consecutive patients undergoing EVTA of the greater saphenous vein associated with phlebectomies was undertaken. Patients were grouped in those receiving micronized purified flavonoid fraction (MPFF- 60 patients) agent 500 mg Bid 7 days pre- and 30 days post- operatively (MPFF group) and those in the control group (60 patients) who did not. Demographics, intra-operative details, Clinical –Etiology- Anatomy- Pathophysiology (CEAP) clinical class, 10-cm Visual Analog Scale (VAS) for pain, Venous Clinical Severity Score (VCSS) and Chronic Venous Insufficiency Quality-of-Life Questionnaire (CΙVIQ-20) were recorded. Primary outcome was the postoperative pain assessement using the VAS scale and CIVIQ pain score. Secondary outcomes included assessement of VCSS and CΙVIQ-20 scores. Results There were no significant differences between the groups regarding demographics, clinical and procedural characteristics. Patients in MPFF group reported significantly lower VAS pain levels than control group at 7- (−3.6 ± 1.2 vs −2.7 ± 1.9, p Conclusions Administration of flavonoids in patients undergoing EVTA associated with phlebectomies reduces pain by a small amount during early postoperative period.

To examine adrenal cortex reserve in patients with rheumatic and musculoskeletal diseases (RMD) who relapse upon tapering of low glucocorticoid dose, despite concomitant treatment with disease-modifying anti-rheumatic drugs (DMARDs).A morning standard dose of 250 mcg tetracosactide (Synacthen test) was given in 25 consecutive patients (13 rheumatoid arthritis, 2 psoriatic arthritis, 5 systemic lupus erythematosus, 2 dermatomyositis, 1 systemic sclerosis, 2 temporal arteritis) at the time of relapse upon small reductions (1-2 mg daily) of low prednisolone dose (7.5 mg daily), while being on stable concomitant treatment with methotrexate, leflunomide, hydroxychloroquine, azathioprine, mycophenolate, tofacitinib, belimumab, anti-TNF, anti-IL-6 or anti-IL-1 regimens (n=14; 3; 9; 1; 2; 1; 1; 5; 2; 1, respectively). Sex-matched apparently healthy individuals (n=45) served as controls.Baseline cortisol levels and time-integrated cortisol response to tetracosactide were lower in patients than controls (12.01±4.47 vs. 15.63±4.16 mcg/dl, p=0.001, and 1050±286 vs. 1284±182, p0.001, respectively). No significant associations were observed between the cortisol response to tetracosactide and age, duration of disease or glucocorticoid treatment. An abnormal Synacthen test, indicative of adrenal insufficiency, presumably secondary to chronic glucocorticoid administration, was noted in 5/25 patients. The remaining 20 patients (80%) had normal Synacthen test demonstrating, however, lower cortisol response than controls, independently of age (β-coefficient=-0.373, p=0.033).Patients with RMD in remission under DMARDs who relapse upon concomitant low glucocorticoid dose tapering should be tested for iatrogenic adrenal insufficiency. Whether a marginally normal Synacthen test should discourage further attempts to withdraw glucocorticoid treatment in these patients warrants further investigation.

Cardiovascular societies have developed recommendations regarding the management of thoracic aortic diseases. While improvements in treatment have been observed during the past decade in regard to patient selection, thoracic endovascular aortic repair (TEVAR) and associated techniques, and high-volume centralization, the broad expansion of TEVAR has raised considerations about its indications, appropriateness, limitations, and application. The aim of this systematic review was to assess the similarities and differences among current cardiovascular societies’ guidelines for the management of thoracic aortic diseases. The MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were searched from January 2009 to May 2020. The initial search identified 990 articles. After exclusion of duplicate or inappropriate articles, the final analysis included 5 articles from cardiovascular societies published between 2010 and 2020. Selected controversial topics were analyzed, including diagnosis, imaging, spinal cord ischemia prevention, and management of the most important thoracic aortic pathologies. The analysis included data concerning the therapeutic approach in acute and chronic type B aortic dissection, penetrating aortic ulcer, intramural hematoma, thoracic aortic aneurysm, and traumatic aortic injury, as well a discussion of inflammatory aneurysms, aortitis, and genetic syndromes. The review presents consistent and controversial recommendations, as well as “gray zone” issues that need further investigation. There was significant overlap and agreement among the 5 societies regarding the management of thoracic aortic diseases. Especially in dissection and aneurysm management, TEVAR has established its role as the treatment of choice. However, robust evidence is still needed in many aspects of the management of thoracic aortic pathologies.

Background Immunotherapy agents are used to treat advanced head and neck lesions. We aim to elucidate relationship between immunotherapy and surgical wound complications. Methods Retrospective multi-institutional case series evaluating patients undergoing ablative and flap reconstructive surgery and immunotherapy treatment. Main outcome wound complications. Results Eight-two (62%) patients received preoperative therapy, 89 (67%) postoperative, and 33 (25%) in both settings. Forty-one (31%) patients had recipient site complications, 12 (9%) had donor site. Nineteen (14%) had major recipient site complications, 22 (17%) had minor. There was no statistically significant difference in complications based on patient or tumor-specific variables. Preoperative therapy alone demonstrated increased major complications (odds ratio [OR] 3.7, p = 0.04), and trend to more donor site complications (OR 7.4, p = 0.06), however treatment in both preoperative and postoperative therapy was not. Conclusions Preoperative immunotherapy may be associated with increased wound complications. Controlled studies are necessary to delineate this association and potential risks of therapy.

BACKGROUND: There are 2 common approaches to assess an individual before commencing of gender-affirming hormone therapy (GAHT); a mental health practitioner assessment and approval or an informed consent model undertaken with a primary care general practitioner (GP). AIM: In a primary care clinic practising an Informed Consent Model of care to initiate GAHT, we aimed to firstly describe the proportion and characteristics of patients referred for secondary consultation to a mental health practitioner (MH referred) and secondly, we aimed to measure patient satisfaction. METHODS: A retrospective audit of all new patients with a transgender or gender diverse identity presenting to a primary care clinic in Melbourne, Australia was performed between March 2017 and March 2019. In those newly seeking GAHT, de-identified data were obtained including presence of secondary mental health practitioner referral, time to GAHT commencement and co-occurring mental health conditions. A separate survey assessed patient satisfaction. OUTCOMES: Mental health conditions and overall patient satisfaction in those referred for secondary mental health consultation (MH referred) were compared with those who were not (GP assessed). RESULTS: Of 590 new consultations, 309 were newly seeking GAHT. Referrals for secondary mental health assessment before GAHT occurred in 8%. The GP-assessed group commenced GAHT at median 0.9 months (0.5-1.8) after initial consultation compared with 3.1 months (1.3-4.0), P

The aim of this study was to analyse the influence of true, false, and combined lumen perfusion of renal arteries on mid- and long-term kidney volume in patients with type B aortic dissection (TBAD).Retrospective analysis of patients diagnosed with a TBAD between 2008 and 2015 in a single high-volume European center. The origin of the renal arteries was evaluated on a dedicated 3D workstation (TeraRecon Inc., San Mateo, CA, USA) and coded as either arising from the true lumen (TL), false lumen (FL) or from a combination of both (CL). Additional evaluated anatomical parameters were renal volume, length, width, and depth of the kidneys. Measurements were recorded at the time of diagnosis (T0) and at 1-month (T1), 6-months (T2), 18-months (T3) and 36-month of follow-up time (T4).A total of 131 renal arteries and kidneys were evaluated in 69 patients. Mean age was 64±13 years and 77% were male. The absolute number and percentage of assessed renal arteries/kidneys was 131 (100%) at T0, 89 (68%) at T1, 73 (56%) at T2, 57 (44%) at T3 and 43 (44%) at T4. At the time of diagnosis, 71.6% renal arteries originated from the TL, 19.1% from the FL and 9.2% from a CL. TEVAR was performed in 92.7% patients and nine patients had additional renal artery stenting. At T0 the mean renal volume was 212.1±70.9cmThere is a significant mid-term renal-volume reduction in patients with TBAD, independent of the origin of the renal arteries. Albeit not statistically significant, combined renal artery perfusion may lead to a greater volume reduction, potentially secondary to a relevant dynamic compression by the dissection membrane. Further multicentre studies are warranted to determine the effect on long-term renal function and on possible preventive strategies.

The cellular response to stress is an important determinant of disease pathogenesis. Uncovering the molecular fingerprints of distinct stress responses may identify novel biomarkers and key signaling pathways for different diseases. Emerging evidence shows that transfer RNA-derived small RNAs (tDRs) play pivotal roles in stress responses. However, RNA modifications present on tDRs are barriers to accurately quantifying tDRs using traditional small RNA sequencing. Here, AlkB-facilitated methylation sequencing is used to generate a comprehensive landscape of cellular and extracellular tDR abundances in various cell types during different stress responses. Extracellular tDRs are found to have distinct fragmentation signatures from intracellular tDRs and these tDR signatures are better indicators of different stress responses than miRNAs. These distinct extracellular tDR fragmentation patterns and signatures are also observed in plasma from patients on cardiopulmonary bypass. It is additionally demonstrated that angiogenin and RNASE1 are themselves regulated by stressors and contribute to the stress-modulated abundance of sub-populations of cellular and extracellular tDRs. Finally, a sub-population of extracellular tDRs is identified for which AGO2 appears to be required for their expression. Together, these findings provide a detailed profile of stress-responsive tDRs and provide insight about tDR biogenesis and stability in response to cellular stressors.

Summary Background Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding UK Medical Research Council and Health Technology Assessment Programme.

RMRP encodes a non-coding RNA forming the core of the RNase MRP ribonucleoprotein complex. Mutations cause Cartilage Hair Hypoplasia (CHH), characterized by skeletal abnormalities and impaired T cell activation. Yeast RNase MRP cleaves a specific site in the pre-ribosomal RNA (pre-rRNA) during ribosome synthesis. CRISPR-mediated disruption of RMRP in human cells lines caused growth arrest, with pre-rRNA accumulation. Here, we analyzed disease-relevant primary cells, showing that mutations in RMRP impair mouse T cell activation and delay pre-rRNA processing. Patient-derived human fibroblasts with CHH-linked mutations showed similar pre-rRNA processing delay. Human cells engineered with the most common CHH mutation (70AG in RMRP) show specifically impaired pre-rRNA processing, resulting in reduced mature rRNA and a reduced ratio of cytosolic to mitochondrial ribosomes. Moreover, the 70AG mutation caused a reduction in intact RNase MRP complexes. Together, these results indicate that CHH is a ribosomopathy, and the first processing-specific human disorder to be described.HighlightsMutations in RMRP lncRNA impair pre-rRNA processing and T cell activationPatient derived fibroblasts show impaired pre-rRNA processingCells with the most common disease-linked mutation have specific processing defectsCytoplasmic ribosomes and intact RNase MRP complexes are also reduced in these cells

The presence and absence of RNA modifications regulates RNA metabolism by modulating the binding of writer, reader, and eraser proteins. For 5-methylcytosine (m5C) however, it is largely unknown how it recruits or repels RNA-binding proteins. Here, we decipher the consequences of m5C deposition into the abundant non-coding vault RNA VTRNA1.1. Methylation of cytosine 69 in VTRNA1.1 occurs frequently in human cells, is exclusively mediated by NSUN2, and determines the processing of VTRNA1.1 into small-vault RNAs (svRNAs). We identify the serine/arginine rich splicing factor 2 (SRSF2) as a novel VTRNA1.1-binding protein that counteracts VTRNA1.1 processing by binding the non-methylated form with higher affinity. Both NSUN2 and SRSF2 orchestrate the production of distinct svRNAs. Finally, we discover a functional role of svRNAs in regulating the epidermal differentiation programme. Thus, our data reveal a direct role for m5C in the processing of VTRNA1.1 that involves SRSF2 and is crucial for efficient cellular differentiation., RNA modifications, including 5-methylcytosines, are known regulators of RNA metabolism affecting protein-RNA binding. Here, the authors reveal the role of m5C in the biogenesis of the non-coding vault-derived small RNAs.

The Hellenic Heart Failure Association has undertaken the initiative to develop a national network of heart failure clinics (HFCs) and cardio‐oncology clinics (COCs). We conducted two questionnaire surveys among these clinics within 17 months and another during the coronavirus disease 2019 outbreak to assess adjustments of the developing network to the pandemic. Out of 68 HFCs comprising the network, 52 participated in the first survey and 55 in the second survey. The median number of patients assessed per week is 10. Changes in engaged personnel were encountered between the two surveys, along with increasing use of advanced echocardiographic techniques (23.1% in 2018 vs. 34.5% in 2020). Drawbacks were encountered, concerning magnetic resonance imaging and ergospirometry use (being available in 14.6% and 29% of HFCs, respectively), exercise rehabilitation programmes (applied only in 5.5%), and telemedicine applications (used in 16.4%). There are 13 COCs in the country with nine of them in the capital region; the median number of patients being assessed per week is 10. Platforms for virtual consultations and video calls are used in 38.5%. Coronavirus disease 2019 outbreak affected provision of HFC services dramatically as only 18.5% continued to function regularly, imposing hurdles that need to be addressed, at least temporarily, possibly by alternative methods of follow‐up such as remote consultation. The function of COCs, in contrast, seemed to be much less affected during the pandemic (77% of them continued to follow up their patients). This staged, survey‐based procedure may serve as a blueprint to help building national HFC/COC networks and provides the means to address changes during healthcare crises.

Purpose: To describe the implantation steps and tips and tricks for the Inner Branch Arch Endograft designed to treat aortic arch aneurysm and chronic type A aortic dissection. Technique: Anatomical suitability criteria should be met in order to use this device. The proximal segment of the graft lands in the ascending aorta distally to the sinotubular junction and the distal segment lands in the descending aorta. The device includes 2 inner branches; the proximal branch is used for a connection to the innominate artery (positioned slightly posterior at 12:30 o’clock), while the second branch is positioned slightly anterior at 11:30 o’clock and is used as a connection to the left common carotid artery. Access, implantation technique, deployment of the device, and catheterization of the branches are described thoroughly. Conclusion: This Inner Branch Arch Endograft is an appealing alternative to treat aortic arch pathology, especially in patients unsuitable for open repair. Nevertheless, complex aortic arch repair is associated with a learning curve. Meticulous preoperative planning and a high level of concentration intraoperatively are mandatory.

The SARS-CoV-2 pandemic has had a deleterious impact on human health since its beginning in 2019. The purpose of this study was to examine the psychosocial impact of the COVID-19 pandemic in the Philippines and determine if there were differential impacts on women compared to men. A web-based survey was conducted in the Luzon Islands of the Philippines, during the pandemic quarantine. A total of 1879 participants completed online surveys between 28 March–12 April 2020. A bivariate analysis of both men and women for each psychological measure (stress, anxiety, depression, and impact of COVID-19) was conducted. Multivariable logistic regression models were built for each measure, dichotomized as high or low, separately for men and women. Younger age (p < 0.001), being married (p < 0.001), and being a parent (p < 0.004) were associated with women’s poor mental health. Marriage and large household size are protective factors for men (p < 0.002 and p < 0.0012, respectively), but marriage may be a risk factor for women (p < 0.001). Overall, women were disproportionately negatively impacted by the pandemic compared to men.

Introduction: AFX is a bifurcated unibody aortic endograft for the treatment of Abdominal Aortic aneurysms. It consists of an inner metallic endoskeleton with multiple metallic struts covered by a polytetrafluoroethylene graft fabric. The endoskeleton is sutured to the outer fabric only at the proximal and distal ends. The unique design of AFX aims at fixation onto the aortic bifurcation while a proximal cuff ensures sealing at the infrarenal level.Areas covered: Since this endograft design by Endologix has undergone significant changes over the last years, the aim of this article is to present its unique structure and deployment method and discuss the relevant clinical results as well as reported complications and associated concerns.Expert commentary: the AFX stent-graft exhibits very satisfactory clinical mid-term results in abdominal aortic aneurysms treated within the instructions-for-use. Its 'active-seal' concept of infrarenal fixation stemming from the loose conjugation of the fabric material to the endoskeleton can accommodate efficiently to challenging necks with thrombus or morphological irregularities, thereby extending the anatomical sealing zone without exerting significant radial outward force. Long-term results are needed to validate the promising performance of AFX.

Chemoradiotherapy (CRT) for locally-advanced head and neck squamous cell carcinoma (LA-HSNCC) yields 5-year survival rates near 50% despite causing significant toxicity. Dichloroacetate (DCA), a pyruvate dehydrogenase kinase metabolic inhibitor, reduces tumor lactate production and has been used in cancer therapy previously. The safety of adding this agent to CRT is unknown. Our randomized, placebo-controlled, double-blind phase II study added DCA to cisplatin-based CRT in patients with LA-HNSCC. The primary endpoint was safety by adverse events (AEs). Secondary endpoints compared efficacy via 3-month end-of-treatment response, 5-year progression-free and overall survival. Translational research evaluated pharmacodynamics of serum metabolite response. 45 participants (21 DCA, 24 Placebo) were enrolled from May 2011-April 2014. Higher rates of all-grade drug related fevers (43% vs 8%, p = 0.01) and decreased platelet count (67% vs 33%, p = 0.02) were seen in DCA versus placebo. However, there were no significant differences in grade 3/4 AE rates. Treatment compliance to DCA/placebo, radiation therapy, and cisplatin showed no significant difference between groups. While end-of-treatment complete response rates were significantly higher in the DCA group compared to placebo (71.4% vs 37.5%, p = 0.0362), survival outcomes were not significantly different between groups. Treatment to baseline metabolites demonstrated a significant drop in pyruvate (0.47, p 0.005) and lactate (0.61, p 0.005) in the DCA group. Adding DCA to cisplatin-based CRT appears safe with no detrimental effect on survival and expected metabolite changes compared to placebo. This supports further investigation into combining metabolic agents to CRT. Trial registration number: NCT01386632, Date of Registration: July 1, 2011.

A persistent endoleak type II (ET II) after endovascular repair for aortic aneurysms is not always a benign condition and has been associated to sac expansion, rupture, and reintervention. A variety of different endovascular approaches are available for ET II treatment. The aim of this systematic review was to assess the currently available literature on transcaval embolization for ET II treatment after standard or complex endovascular aortic aneurysm repair.This systematic review protocol was registered to the PROSPERO (CRD42021289686). The PRISMA guidelines and patient, intervention, comparison, outcome (P.I.C.O.) model was followed. A data search of the literature was conducted, using PubMed, EMBASE via Ovid, and CENTRAL databases, until September 30, 2021. Only studies reporting on ET II embolization using the transcaval approach after endovascular aneurysm repair were included. Studies reporting on different type of endoleak treatment or any other embolization approach were excluded. The quality of studies was assessed using the Newcastle-Ottawa Scale. Primary outcomes were technical success and freedom from ET II persistence during follow-up; secondary outcomes were any postoperative complication associated with the transcaval embolization and need for reintervention.The search yielded 2861 articles in total. Eight articles were included, reporting on 117 patients and 128 transcaval embolizations. The indication for treatment was ET II presence with sac expansion of more than 5 mm; in two studies, the presence of persistent endoleak has set the indication to intervene. The technical success was 91.4% (117/128); a variety of embolic materials were used, including coils, thrombin, and glue. Three cases of deep vein thrombosis were recorded and the remaining morbidity and mortality were null. Follow-up was ranging between 0 and 25 months. Out of 8 studies, persistent ET II rate was 12.8% and 18 reinterventions were performed (14.1%,), including 10 transcaval coil embolizations (56%). Sac expansion was reported in 11 cases, out of 3 studies (17%). Only one case of death, not associated with transcaval embolization, was recorded.Transcaval embolization for ET II treatment presents a high technical success and low mortality in the early and mid-term period. ET II persistence rate is low during the available 12-month follow-up.

Epe1 histone demethylase restricts H3K9-methylation-dependent heterochromatin, preventing it from spreading over, and silencing, gene-containing regions in fission yeast. External stress induces an adaptive response allowing heterochromatin island formation that confers resistance on surviving wild-type lineages. Here we investigate the mechanism by which Epe1 is regulated in response to stress. Exposure to caffeine or antifungals results in Epe1 ubiquitylation and proteasome-dependent removal of the N-terminal 150 residues from Epe1, generating truncated tEpe1 which accumulates in the cytoplasm. Constitutive tEpe1 expression increases H3K9 methylation over several chromosomal regions, reducing expression of underlying genes and enhancing resistance. Reciprocally, constitutive non- cleavable Epe1 expression decreases resistance. tEpe1-mediated resistance requires a functional JmjC demethylase domain. Moreover, caffeine-induced Epe1-to-tEpe1 cleavage is dependent on an intact cell-integrity MAP kinase stress signalling pathway, mutations in which alter resistance. Thus, environmental changes provoke a mechanism that curtails the function of this key epigenetic modifier, allowing heterochromatin to reprogram gene expression, thereby bestowing resistance to some cells within a population. H3K9me-heterochromatin components are conserved in human and crop plant fungal pathogens for which a limited number of antifungals exist. Our findings reveal how transient heterochromatin-dependent antifungal resistant epimutations develop and thus inform on how they might be countered.

Gender-affirming hormone therapy aligns physical characteristics with an individual's gender identity, but sex hormones regulate bone remodeling and influence bone morphology. We hypothesized that trans men receiving testosterone have compromised bone morphology because of suppression of ovarian estradiol production, whereas trans women receiving estradiol, with or without anti-androgen therapy, have preserved bone microarchitecture. We compared distal radial and tibial microarchitecture using high-resolution peripheral quantitative computed tomography images in a cross-sectional study of 41 trans men with 71 cis female controls, and 40 trans women with 51 cis male controls. Between-group differences were expressed as standardized deviations (SD) from the mean in age-matched cisgender controls with 98% confidence intervals adjusted for cross-sectional area (CSA) and multiple comparisons. Relative to cis women, trans men had 0.63 SD higher total volumetric bone mineral density (vBMD; both p = 0.01). Cortical vBMD and cortical porosity did not differ, but cortices were 1.11 SD thicker (p 0.01). Trabeculae were 0.38 SD thicker (p = 0.05) but otherwise no different. Compared with cis men, trans women had 0.68 SD lower total vBMD (p = 0.01). Cortical vBMD was 0.70 SD lower (p 0.01), cortical thickness was 0.51 SD lower (p = 0.04), and cortical porosity was 0.70 SD higher (p 0.01). Trabecular bone volume (BV/TV) was 0.77 SD lower (p 0.01), with 0.57 SD fewer (p 0.01) and 0.30 SD thicker trabeculae (p = 0.02). There was 0.56 SD greater trabecular separation (p = 0.01). Findings at the distal radius were similar. Contrary to each hypothesis, bone microarchitecture was not compromised in trans men, perhaps because aromatization of administered testosterone prevented bone loss. Trans women had deteriorated bone microarchitecture either because of deficits in microstructure before treatment or because the estradiol dosage was insufficient to offset reduced aromatizable testosterone. Prospective studies are needed to confirm these findings. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Purpose: The purpose of this study was to evaluate early and mid-term results of non-standard management of the supraaortic target vessels with the use of the inner branch arch endograft in a single high-volume center. Material and methods: A single-center retrospective study including all patients undergoing implantation of an inner branch arch endograft from December 2012 to March 2021, who presented a non-standard management of the supraaortic target vessels (any bypass other than a left carotid-subclavian or landing in a dissected target vessel). Technical success, mortality, reinterventions, endoleak (EL), and aortic remodeling at follow-up were analyzed. Results: Twenty-four patients were included. In 17 (71%) cases, the non-standard management was related to innominate artery (IA) compromise (12 with IA dissection, 2 with short IA, 2 with short proximal aortic landing zone that required occlusion of IA, 1 with occluded IA after open arch repair). Two (8%) cases were related to an aberrant right subclavian artery (RSA), 1 patient (4%) due to the concomitant presence of a left vertebral artery (LVA) arising from the arch and an occluded left subclavian artery (LSA), and another patient presented with an occluded LSA distal to a dominant vertebral artery. Three (13%) cases were exclusively related to management in patients with genetic aortic syndromes. Twenty (83%) patients had a previous type A aortic dissection. Ten (42%) patients presented a thoracic or thoracoabdominal aortic aneurysm and 8 (33%) patients an arch aneurysm, 6 of them associated to false lumen (FL) perfusion. There were 2 (8%) perioperative minor strokes, and 1 patient with perioperative mortality. Seven patients presented an early type I endoleak, all resolved at follow-up. Seven patients required reinterventions during follow-up (7 reinterventions related to continuous false lumen perfusion, 3 related to Type Ia endoleak, 2 related to surgical bypass). All patients who presented with FL perfusion had complete FL thrombosis at follow-up. No patient presented aneurysm growth at follow-up. Conclusions: The use of the inner branch arch endograft with a non-standard management of the supraaortic target vessels is a possible option. Despite a high reintervention rate, regression or stability of the aneurysmal diameter was achieved in all the patients with follow-up.

The objective of this study was to evaluate renal function and renal parenchymal length changes secondary to the coverage or preservation of accessory renal arteries (ARAs) in complex aortic repair.This was a single-center retrospective study identifying all patients undergoing fenestrated or branched endovascular aortic repair (f-b EVAR) who presented with ARAs. Two groups were created, a preserved ARA group, with incorporation of the vessel as a dedicated fenestration or branch in the endograft plan, and a non-preserved ARA group, without incorporation of them. Early30% decline of glomerular filtration rate (GFR), kidney infarcts, and endoleaks were evaluated. Mid-term results with freedom from kidney shrinkage (defined as length decrease10%) at follow-up, freedom from GFR decrease30%, or need for postoperative dialysis at follow-up were also analyzed. Primary assisted patency of incorporated ARAs was calculated.From 2011 through 2020, 145 patients undergoing complex aortic repair presented with an ARA. After excluding ruptured aneurysms, 33 patients had the ARA preserved with their incorporation into the stent graft (preserved ARA group), and 99 did not have preservation of them (not-preserved ARA group). There were no statistical differences in demographics or type of aneurysm. Patients in the ARA-preserved group had more ARAs (median of two per patient vs one in the non-preserved ARA group; P = .01) and bigger ARAs (median 4 vs 3 mm in the non-preserved ARA group; P = .001). Early postoperative worsening30% of GFR (23% vs 6%; P = .03) as well as postoperative renal infarction (57% vs 6%; P = .001) and ARA-related endoleaks (20% vs 0%; P = .01) were statistically higher for the not-preserved ARA group. Mid-term kidney length showed significant shrinkage in the not-preserved ARA group compared with the ARA preserved group (9.7% vs 0%; P = .001). Freedom from30% GFR decline at 2 years was significantly higher for the preserved ARA group (83% vs 47%; P = .01).Two-year primary assisted patency of incorporated ARA was 94%.Complex aortic repair incorporation of ARA is feasible, with low complications and good primary assisted patency at 2 years. It leads to less postoperative early renal dysfunction as well as higher freedom for mid-term renal disfunction and kidney shrinkage.

Our aim was to compare the safety and efficacy of proximal repair (PR) versus extensive repair (ER) for acute type A aortic dissection (ATAAD).A literature search in three databases was performed according to the PRISMA statement. Studies comparing PR versus ER for ATAAD were included. Random-effects meta-analyses were performed.A total of 27 studies incorporating 7113 patients (PR: 5080; ER: 2033) were included. Patients undergoing PR presented decreased in-hospital mortality (odds ratio [OR]: 0.67 [95% Confidence Interval (95% CI) 0.53-0.85]; p 0.01) and post-operative bleeding (OR 0.75 [95% CI 0.60-0.95]; p = 0.02) compared to ER. Meta-regression analysis revealed that in-hospital mortality was not influenced by differences regarding the extent of dissection (p = 0.43). Cardiopulmonary bypass time (SMD:-0.93 [95% CI - 1.22, - 0.66]; p 0.01) and length of hospital stay (SMD:-0.19 [95% CI - 0.34, - 0.05]; p = 0.01) were also lower in the PR group, while there was no difference in terms of renal failure and permanent neurological deficit. The ER approach demonstrated a lower post-discharge mortality compared to PR (OR 1.46 [95% CI 1.09, 1.97]; p = 0.01), while the post-discharge reoperation rate was comparable between the two groups. 1 and 3-year overall survival (OS) were comparable between PR and ER (OR 1.05, [95% CI 0.77-1.44]; p = 0.76) and (OR 1.27 [95% CI 0.86-1.86]; p = 0.23), respectively. The 5-year OS (OR 1.67 [95% CI 1.16-2.41]; p = 0.01) was in favor of the PR arm.In patients with ATAAD, PR was associated with lower odds of in-hospital mortality but higher odds of late mortality. ER and PR demonstrated similar post-operative complication and reoperation rates.

BACKGROUND: Experimental studies and small clinical trials have suggested that treatment with intranasal oxytocin may reduce social impairment in persons with autism spectrum disorder. Oxytocin has been administered in clinical practice to many children with autism spectrum disorder. METHODS: We conducted a 24-week, placebo-controlled phase 2 trial of intranasal oxytocin therapy in children and adolescents 3 to 17 years of age with autism spectrum disorder. Participants were randomly assigned in a 1:1 ratio, with stratification according to age and verbal fluency, to receive oxytocin or placebo, administered intranasally, with a total target dose of 48 international units daily. The primary outcome was the least-squares mean change from baseline on the Aberrant Behavior Checklist modified Social Withdrawal subscale (ABC-mSW), which includes 13 items (scores range from 0 to 39, with higher scores indicating less social interaction). Secondary outcomes included two additional measures of social function and an abbreviated measure of IQ. RESULTS: Of the 355 children and adolescents who underwent screening, 290 were enrolled. A total of 146 participants were assigned to the oxytocin group and 144 to the placebo group; 139 and 138 participants, respectively, completed both the baseline and at least one postbaseline ABC-mSW assessments and were included in the modified intention-to-treat analyses. The least-squares mean change from baseline in the ABC-mSW score (primary outcome) was −3.7 in the oxytocin group and −3.5 in the placebo group (least-squares mean difference, −0.2; 95% confidence interval, −1.5 to 1.0; P = 0.61). Secondary outcomes generally did not differ between the trial groups. The incidence and severity of adverse events were similar in the two groups. CONCLUSIONS: This placebo-controlled trial of intranasal oxytocin therapy in children and adolescents with autism spectrum disorder showed no significant between-group differences in the least-squares mean change from baseline on measures of social or cognitive functioning over a period of 24 weeks. (Funded by the National Institute of Child Health and Human Development; SOARS-B ClinicalTrials.gov number, NCT01944046.)

Venous thromboembolism (VTE) is a common complication among patients suffering from malignancies, leading to an increased mortality rate. Novel randomized trials have added valuable information regarding cancer-associated thrombosis (CAT) management using direct oral anticoagulants (DOACs). The aim of this study is to present an overview of the current literature and recommendations in CAT treatment. A few randomized control trials (RCTs) have been integrated suggesting that DOACs may be effectively applied in CAT patients compared to low molecular weight heparins (LMWHs) with a decreased mortality and VTE recurrence rate. However, the risk of bleeding is higher, especially in patients with gastrointestinal malignancies. Real-world data are in accordance with these RCT findings, while in the currently available recommendations, DOACs are suggested as a reliable alternative to LMWH during the initial, long-term, and extended phase of treatment. Data retrieved from the current literature, including RCTs and “real-world” studies, aim to clarify the role of DOACs in CAT management, by highlighting their benefits and remarking upon the potential adverse outcomes. Current recommendations suggest the use of DOACs in well-selected patients with an increasing level of evidence through years.