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Dural arteriovenous fistulas (dAVFs) located at craniocervical junction are extremely rare (1%-2% of intracranial/spinal dAVFs). Their angio-architectural complexity renders endovascular embolization to be challenging given multiple small feeders with risk of embolysate reflux into vertebral artery and limited transvenous access. The available literature discussing microsurgery for these lesions is limited to few case reports.To report a multicenter experience assessing microsurgery safety/efficacy.Prospectively maintained registries at 13 North American centers were queried to identify craniocervical junction dAVFs treated with microsurgery (2006-2021).Thirty-eight patients (median age 59.5 years, 44.7% female patients) were included. The most common presentation was subarachnoid/intracranial hemorrhage (47.4%) and myelopathy (36.8%) (92.1% of lesions Cognard type III-V). Direct meningeal branches from V3/4 vertebral artery segments supplied 84.2% of lesions. All lesions failed (n = 5, 13.2%) or were deemed inaccessible/unsafe to endovascular treatment. Far lateral craniotomy was the most used approach (94.7%). Intraoperative angiogram was performed in 39.5% of the cases, with angiographic cure in 94.7% of cases (median imaging follow-up of 9.2 months) and retreatment rate of 5.3%. Favorable last follow-up modified Rankin Scale of 0 to 2 was recorded in 81.6% of the patients with procedural complications of 2.6%.Craniocervical dAVFs represent rare entity of lesions presenting most commonly with hemorrhage or myelopathy because of venous congestion. Microsurgery using a far lateral approach provides robust exposure and visualization for these lesions and allows obliteration of the arterialized draining vein intradurally as close as possible to the fistula point. This approach was associated with a high rate of angiographic cure and favorable clinical outcomes.

Midodrine was effectively used for prophylaxis against hypotensive syndromes such as postural hypotension and intradialytic hypotension, and during the recovery phase of septic shock. In our study, we aimed to assess the efficacy of prophylactic administration of midodrine tablets before spinal anesthesia in reducing the occurrence of hypotension.This randomized placebo-controlled study embraced 67 patients aged 18 to 40 years undergoing elective knee surgery under spinal anesthesia. Patients were randomized to midodrine group (given 10-mg tablets of midodrine) or placebo group (given placebo tablets), and tablets were administered 1 hour before spinal anesthesia (intrathecal injection of 12.5-mg 0.5% hyperbaric bupivacaine and 15-μg fentanyl). The primary outcome was the occurrence of hypotension, defined as a systolic blood pressure90 mm Hg or80% of baseline. Secondary outcomes were hemodynamic characteristics (mean arterial pressure [MAP] and heart rate [HR]) after spinal anesthesia, ephedrine dose, and occurrence of complications including bradycardia, vasovagal attacks, reactive hypertension nausea, vomiting, and shivering.The number of patients who became hypotensive after spinal anesthesia was 5 (14.7%) in midodrine group versus 14 (42.4%) in the placebo group; relative risk (95% confidence interval) was 0.35 (0.14-0.85) ( P = .021). The median (interquartile range) total dose of ephedrine was significantly lower in midodrine group 0 (0-10) mg than in placebo group (0 (0-15) mg; the Hodges-Lehmann median difference (95% confidence interval) was 0 (0-5) mg ( P = .015). For MAP data, the group × time interaction was significant ( P = .038), and the MAP was significantly lower in the placebo group than in the midodrine group after intrathecal injection at 2 minutes ( P = .047), 10 minutes ( P = .045), 15 minutes ( P.001), 20 minutes ( P = .007), 30 minutes ( P =.013), 45 minutes ( P = .029), 60 minutes ( P = .029), and at the end of surgery ( P.001). For HR data, the group × time interaction was nonsignificant ( P = .807), and the difference in means (95% confidence interval) between groups collapsing over time was -1.4 (-3.1 to 0.2) beats/min ( P = .096). There was no significant difference between the 2 groups regarding the occurrence of complications.Prophylactic administration of 10-mg midodrine tablets before spinal anesthesia is an effective method in the prevention of hypotension in young adult patients undergoing elective orthopedic knee surgery.

Holarrhena pubescens seeds are used in the treatment of various diseases, especially diabetes and associated complications, in different parts of the world. The present study was undertaken to determine the hypolipidemic and antihyperlipidemic effects of methanolic extract of H. pubescens seeds in rats. The extract was subjected to LC-MS analysis to determine the chemical constituents. The hypolipidemic action was studied by determining the effect of 28-day oral administration of seed extract on serum cholesterol, serum triglycerides, and serum HDL-cholesterol levels. The antihyperlipidemic action was studied in rats fed with a high-fat diet containing cholesterol and saturated fat, and the same lipid parameters were estimated during 28-day treatment. To elucidate its probable mechanism of action, in vitro studies on the inhibition of lipid accumulation in preadipocytes, DPP-IV inhibitory effect, and lipase enzyme inhibition were studied. The seed extract reduced serum levels of cholesterol and triglycerides in both normal rats and animals fed with a high-fat diet without a significant effect on HDL-cholesterol levels. The seed extract was highly effective in inhibiting lipase enzyme activity but showed a modest effect on the inhibition of lipid accumulation and DPP-IV. The results demonstrated that H. pubescens seed extract has hypolipidemic and antihyperlipidemic effects mediated probably through inhibition of lipase enzyme activity.

Coronavirus disease 19 (COVID-19) is clinically less severe in children, even if the wide variety and degree of severity of symptoms reported in children pose a still-unresolved challenge for clinicians. We performed an in-depth analysis of the immunological profiles of 18 hospitalized SARS-CoV-2-infected children, whose results were compared to those obtained from 13 age- and sex-matched healthy controls (HC). The patients were categorized as paucisymptomatic/moderate (55.6%) or severe/critical (44.5%) according to established diagnostic criteria and further stratified into the categories of infants (1–12 months), children (1–12 years), and adolescents (>12 years). We assessed SARS-CoV-2-specific RBD antibodies (Ab), neutralizing antibodies (nAb), and circulating cytokines/chemokines in the plasma, and the SARS-CoV-2-specific immune response was measured in PBMCs by gene expression and secretome analyses. Our results showed peculiar circulating cytokine/chemokine profiles among patients sharing a similar clinical phenotype. A cluster of patients consisting of infants with severe symptoms presented hyperinflammatory profiles, together with extremely polarized antibody profiles. In a second cluster consisting of paucisymptomatic patients, a less pronounced increase in the level of inflammatory cytokines, together with an association between the selected cytokines and humoral responses, was observed. A third cluster, again consisting of paucisymptomatic patients, showed a circulating cytokine/chemokine profile which overlapped with that of the HC. The SARS-CoV-2-stimulated production of pro-inflammatory proteins, T lymphocyte activation, and migration-specific proteins, were significantly increased in SARS-CoV-2-infected children compared to the HC. Our findings suggest that immune response activation in the course of SARS-CoV-2 infection in children is directly correlated with clinical severity and, to a lesser extent, age.

Background: Bariatric surgery has been an effective safe management for severe obesity. The newly developed single-anastomosis sleeve ileal (SASI) bypass has shown efficacy as a functional as well as mechanical restrictive bariatric procedure, with a neuroendocrine modulation effect. SASI bypass is still an investigational procedure, hence, more evidence is needed till it is declared as a standard bariatric procedure by the IFSO. Aim of the study: The current work aimed to describe our experience regarding the technical steps, the efficacy and the short-term outcome of SASI bypass procedure in patients with severe obesity. Patients and methods: Forty seven patients with severe obesity underwent SASI bypass procedure. They were followed till 1 year postoperatively. The weight loss, comorbidities and laboratory changes were assessed. Results: Patients evaluation at the 1-year postoperative follow up revealed a mean %TWL of 37.55 ± 6.17 and a mean %EBWL of 76.21 ± 9.8. The remission rates of T2DM, hyperlipidemia and hypertension were 85.7%, 94.7% and 89.66%, respectively, with statistically high significant differences between the preoperative and 1-year postoperative comorbidities rate. Stepwise regression analysis demonstrated that only the preoperative HbA1C remained in the model predicting the %TWL, and the preoperative BMI was the remaining factor in the model predicting the %EBWL in the study patients. Conclusion: The present study adds a new evidence to the promising outcome of the newly introduced SASI bypass procedure. After one year, the study patients showed excellent weight loss and comorbidities remission together with acceptable major complication rates.

COVID-19 is a pandemic disease caused by SARS-CoV-2, which is an RNA virus similar to the hepatitis C virus (HCV) in the replication process. Sofosbuvir/ledipasvir is an approved drug to treat HCV infection. This study investigates the efficacy of Sofosbuvir/ledipasvir as a treatment for patients with moderate COVID-19 infection. This is a single-blinded parallel-randomized controlled trial. The participants were randomized equally into the intervention group that received Sofosbuvir/ledipasvir (S.L. group), and the control group received Oseltamivir, Hydroxychloroquine, and Azithromycin (OCH group). The primary outcomes were the cure rate over time and the incidence of serious adverse events. The secondary outcomes included the laboratory findings. 250 patients were divided equally into each group. Both groups were similar regarding gender, but age was higher in the S.L. group (p=0.001). In the S.L. group, 89 (71.2%) patients were cured, while only 51 (40.8%) patients were cured in the OCH group. The cure rate was significantly higher in the S.L. group (RR=1.75, p

The recent Coronavirus Disease 2019 (COVID-19) pandemic made social distancing vital to limiting the spread of infection. As a result many patients postponed their hospital and orthopaedic clinic visits for the fear of contracting the virus, which in turn led to serious complications caused by negligence and lack of follow-up in elbow patients. The pandemic has been an ongoing threat;therefore, establishing an effective virtual assessment technique for patient follow-up has become a valuable option. The authors conducted a systematic approach for proper virtual assessment of patients with elbow disorders using telemedicine.

Telemedicine was originally created as a way to treat patients who were located in remote places far away from local health facilities or in areas with shortages of medical professionals. Telemedicine is still used today to address those problems, and is increasingly becoming a tool for convenient medical care. With the emergence of pandemics, telemedicine became almost a mandatory and valuable option for continuing to provide medical care in various specialties. As the threat of pandemic progress has continued for months and may continue for years, it is essential to validate existing tools to maintain clinical assessment and patient treatment to avoid negative consequences of the lack of medical follow-up. Therefore, the establishment of a virtual assessment technique that can be conducted effectively is of outmost importance as a way of adapting to the current situation. This study evaluated the role of telemedicine in the assessment of various orthopedic pathologies by means of a systematic virtual evaluation.

Fragestellung: Insuffizienzfrakturen des vorderen Beckenringes finden sich gehäuft bei geriatrischen Patienten. Aktuelle Behandlungsalgorithmen empfehlen eine Osteosynthese, wenn keine schmerzfreie Mobilisierung möglich ist. Unter der Vielzahl der Verfahren gilt der supraacetabuläre Fixateur [zum vollständigen Text gelangen Sie über die oben angegebene URL]

The application of cloud computing has increased tremendously in both public and private organizations. However, attacks on cloud computing pose a serious threat to confidentiality and data integrity. Therefore, there is a need for a proper mechanism for detecting cloud intrusions. In this paper, we have proposed a cloud intrusion detection system (IDS) that is focused on boosting the classification accuracy by improving feature selection and weighing the ensemble model with the crow search algorithm (CSA). The feature selection is handled by combining both filter and automated models to obtain improved feature sets. The ensemble classifier is made up of machine and deep learning models such as long short-term memory (LSTM), support vector machine (SVM), XGBoost, and a fast learning network (FLN). The proposed ensemble model’s weights are generated with the CSA to obtain better prediction results. Experiments are executed on the NSL-KDD, Kyoto, and CSE-CIC-IDS-2018 datasets. The simulation shows that the suggested system attained more satisfactory results in terms of accuracy, recall, precision, and F-measure than conventional approaches. The detection rate and false alarm rate (FAR) of different attack types was more efficient for each dataset. The classifiers’ performances were also compared individually to the ensemble model in terms of the false positive rate (FPR) and false negative rate (FNR) to demonstrate the ensemble model’s robustness.

OBJECTIVE Although younger adults have been shown to have better functional outcomes after mechanical thrombectomy (MT) for acute ischemic stroke (AIS), the significance of this relationship in the adolescent and young adult (AYA) population is not well defined given its undefined rarity. Correspondingly, the goal of this study was to determine the prognostic significance of age in this specific demographic following MT for large-vessel occlusions. METHODS A prospectively maintained international multi-institutional database, STAR (Stroke Thrombectomy and Aneurysm Registry), was reviewed for all patients aged 12–18 (adolescent) and 19–25 (young adult) years. Parameters were compared using chi-square and t-test analyses, and associations were interrogated using regression analyses. RESULTS Of 7192 patients in the registry, 41 (0.6%) satisfied all criteria, with a mean age of 19.7 ± 3.3 years. The majority were male (59%) and young adults (61%) versus adolescents (39%). The median prestroke modified Rankin Scale (mRS) score was 0 (range 0–2). Strokes were most common in the anterior circulation (88%), with the middle cerebral artery being the most common vessel (59%). The mean onset-to–groin puncture and groin puncture–to-reperfusion times were 327 ± 229 and 52 ± 42 minutes, respectively. The mean number of passes was 2.2 ± 1.2, with 61% of the cohort achieving successful reperfusion. There were only 3 (7%) cases of reocclusion. The median mRS score at 90 days was 2 (range 0–6). Between the adolescent and young adult subgroups, the median mRS score at last follow-up was statistically lower in the adolescent subgroup (1 vs 2, p = 0.03), and older age was significantly associated with a higher mRS at 90 days (coefficient 0.33, p < 0.01). CONCLUSIONS Although rare, MT for AIS in the AYA demographic is both safe and effective. Even within this relatively young demographic, age remains significantly associated with improved functional outcomes. The implication of age-dependent stroke outcomes after MT within the AYA demographic needs greater validation to develop effective age-specific protocols for long-term care across both pediatric and adult centers.

Patients with type 1 diabetes (T1D) may develop severe outcomes during coronavirus disease 2019 (COVID-19), but their ability to generate an immune response against the SARS-CoV-2 mRNA vaccines remains to be established. We evaluated the safety, immunogenicity, and glycometabolic effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines in patients with T1D. A total of 375 patients (326 with T1D and 49 subjects without diabetes) who received two doses of the SARS-CoV-2 mRNA vaccines (mRNA-1273, BNT162b2) between March and April 2021 at ASST Fatebenefratelli Sacco were included in this monocentric observational study. Local and systemic adverse events were reported in both groups after SARS-CoV-2 mRNA vaccination, without statistical differences between them. While both patients with T1D and subjects without diabetes exhibited a parallel increase in anti-SARS-CoV-2 spike titers after vaccination, the majority of patients with T1D (70% and 78%, respectively) did not show any increase in the SARS-CoV-2-specific cytotoxic response compared with the robust increase observed in all subjects without diabetes. A reduced secretion of the T-cell-related cytokines interleukin-2 and tumor necrosis factor-α in vaccinated patients with T1D was also observed. No glycometabolic alterations were evident in patients with T1D using continuous glucose monitoring during follow-up. Administration of the SARS-CoV-2 mRNA vaccine is associated with an impaired cellular SARS-CoV-2-specific cytotoxic immune response in patients with T1D.

Recent studies have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may induce metabolic distress, leading to hyperglycemia in patients affected by coronavirus disease 19 (COVID-19). We investigated the potential indirect and direct effects of SARS-CoV-2 on human pancreatic islets in 10 patients who became hyperglycemic after COVID-19. Although there was no evidence of peripheral anti-islet autoimmunity, the serum of these patients displayed toxicity on human pancreatic islets, which could be abrogated by the use of anti–interleukin-1β (IL-1β), anti–IL-6, and anti–tumor necrosis factor α, cytokines known to be highly upregulated during COVID-19. Interestingly, the receptors of those aforementioned cytokines were highly expressed on human pancreatic islets. An increase in peripheral unmethylated INS DNA, a marker of cell death, was evident in several patients with COVID-19. Pathology of the pancreas from deceased hyperglycemic patients who had COVID-19 revealed mild lymphocytic infiltration of pancreatic islets and pancreatic lymph nodes. Moreover, SARS-CoV-2–specific viral RNA, along with the presence of several immature insulin granules or proinsulin, was detected in postmortem pancreatic tissues, suggestive of β-cell–altered proinsulin processing, as well as β-cell degeneration and hyperstimulation. These data demonstrate that SARS-CoV-2 may negatively affect human pancreatic islet function and survival by creating inflammatory conditions, possibly with a direct tropism, which may in turn lead to metabolic abnormalities observed in patients with COVID-19.

BackgroundWeight loss in patients with metabolic syndrome has positive effects on cardiovascular and type 2 diabetes risks, but its effects on peripheral cytokines and lipid profiles in patients are still unclear.AimTo determine the effects of diet-induced weight loss on metabolic parameters, lipids and cytokine profiles.MethodsEighteen adult males with metabolic syndrome (defined according to IDF 2009) and Body Mass Index (BMI) between 25 and 35 kg/m2were subjected to a balanced hypocaloric diet for 6 months to reach at least a 5% body weight loss.ResultsAfter weight loss, a significant improvement in BMI, waist circumference, insulin, fasting blood glucose and HOMA-IR (homeostasis model assessment of insulin resistance) was observed. The analysis of LDL (low-density lipoprotein cholesterol) and HDL (high-density lipoprotein cholesterol) lipoproteins showed a change in their composition with a massive transfer of triacylglycerols from HDL to LDL. This was associated with a significant reduction in peripheral pro-inflammatory cytokines such as IL-6, TNF-α, IL-8 and MIP-1β, leading to an overall decreased inflammatory score. An interesting positive correlation was also observed among peripheral cytokines levels after diet and peripheral levels of CETP (cholesteryl ester transfer protein), an enzyme with a key role in lipid change.ConclusionWeight loss through caloric restriction is associated with an improvement in peripheral lipid and cytokine profiles that may play a major role in improving cardiovascular risk.Graphic abstract