Numerous animal and clinical studies have described memory deficits following sleep deprivation. There is also evidence that the absence of sleep increases brain oxidative stress. The present study ...investigates the role of hippocampal oxidative stress in memory deficits induced by sleep deprivation in mice. Mice were sleep deprived for 72 h by the multiple platform method—groups of 4–6 animals were placed in water tanks, containing 12 platforms (3 cm in diameter) surrounded by water up to 1 cm beneath the surface. Mice kept in their home cage or placed onto larger platforms were used as control groups. The results showed that hippocampal oxidized/reduced glutathione ratio as well as lipid peroxidation of sleep-deprived mice was significantly increased compared to control groups. The same procedure of sleep deprivation led to a passive avoidance retention deficit. Both passive avoidance retention deficit and increased hippocampal lipid peroxidation were prevented by repeated treatment (15 consecutive days, i.p.) with the antioxidant agents melatonin (5 mg/kg),
N-tert-butyl-α-phenylnitrone (200 mg/kg) or vitamin E (40 mg/kg). The results indicate an important role of hippocampal oxidative stress in passive avoidance memory deficits induced by sleep deprivation in mice.
Tardive dyskinesia, the most serious iatrogenic movement disorder, has been tentatively associated with nigrostriatal dopaminergic supersensitivity and with oxidative stress. It is also suggested ...that long-term neuroleptic treatment does not cause oral dyskinesia (OD), but interacts with some substrate of brain aging, resulting in the premature emergence of OD, that can occur spontaneously with aging. In order to investigate a possible role of nigrostriatal dopaminergic supersensitivity and of oxidative stress in aging- and reserpine-induced OD, the stereotyped behavior induced by dopaminergic agonists, a functional index of dopaminergic striatal activity, as well as the striatal antioxidant enzymes glutathione peroxidase and catalase were assessed. We demonstrate that, opposite to normotensive Wistar rats (NWR), spontaneously hypertensive rats (SHR) do not develop aging- or reserpine-OD. There were no differences between NWR and SHR in stereotyped behavior or in striatal glutathione peroxidase activity. Adult and old SHR presented higher striatal catalase activity relative to NWR, and aging increased it only in SHR. The catalase inhibitor aminotriazole reverted the absence of aging- and reserpine-induced OD in SHR. Our results suggest an important role of striatal catalase in the development of reserpine- and aging-induced OD.
There is controversy about the outcome of patients with acute myocarditis (AM), and data are lacking on how patients admitted with suspected AM are managed. We report characteristics, in-hospital ...management, and long-term outcome of patients with AM based on a retrospective multicenter registry from 19 Italian hospitals.
A total of 684 patients with suspected AM and recent onset of symptoms (<30 days) were screened between May 2001 and February 2017. Patients >70 years of age and those >50 years of age without coronary angiography were excluded. The final study population comprised 443 patients (median age, 34 years; 19.4% female) with AM diagnosed by either endomyocardial biopsy or increased troponin plus edema and late gadolinium enhancement at cardiac magnetic resonance.
At presentation, 118 patients (26.6%) had left ventricular ejection fraction <50%, sustained ventricular arrhythmias, or a low cardiac output syndrome, whereas 325 (73.4%) had no such complications. Endomyocardial biopsy was performed in 56 of 443 (12.6%), and a baseline cardiac magnetic resonance was performed in 415 of 443 (93.7%). Cardiac mortality plus heart transplantation rates at 1 and 5 years were 3.0% and 4.1%. Cardiac mortality plus heart transplantation rates were 11.3% and 14.7% in patients with complicated presentation and 0% in uncomplicated cases (log-rank P<0.0001). Major AM-related cardiac events after the acute phase (postdischarge death and heart transplantation, sustained ventricular arrhythmias treated with electric shock or ablation, symptomatic heart failure needing device implantation) occurred in 2.8% at the 5-year follow-up, with a higher incidence in patients with complicated forms (10.8% versus 0% in uncomplicated AM; log-rank P<0.0001). β-Adrenoceptor blockers were the most frequently used medications both in complicated (61.9%) and in uncomplicated forms (53.8%; P=0.18). After a median time of 196 days, 200 patients had follow-up cardiac magnetic resonance, and 8 of 55 (14.5%) with complications at presentation had left ventricular ejection fraction <50% compared with 1 of 145 (0.7%) of those with uncomplicated presentation.
In this contemporary study, overall serious adverse events after AM were lower than previously reported. However, patients with left ventricular ejection fraction <50%, ventricular arrhythmias, or low cardiac output syndrome at presentation were at higher risk compared with uncomplicated cases that had a benign prognosis and low risk of subsequent left ventricular systolic dysfunction.
The association between heart rate (HR) and pulmonary embolism (PE) outcomes has not been well studied. Furthermore, optimal cutoffs to identify low-risk and intermediate- to high-risk patients are ...not well known.
Does an association exist between baseline HR and PE outcome across the continuum of HR values?
The current study included 44,331 consecutive nonhypotensive patients with symptomatic PE from the Registro Informatizado de la Enfermedad TromboEmbólica registry between 2001 and 2021. Outcomes included 30-day all-cause and PE-specific mortality. We used hierarchical logistic regression to assess the association between admission HR and outcomes.
A positive relationship was found between admission HR and 30-day all-cause and PE-related mortality. Considering an HR of 80 to 99 beats/min as a reference, patients in the higher HR strata showed higher rates of all-cause death (adjusted OR, 1.5 for HR of 100-109 beats/min; adjusted OR, 1.7 for HR of 110-119 beats/min; adjusted OR, 1.9 for HR of 120-139 beats/min; and adjusted OR, 2.4 for HR of ≥ 140 beats/min). Patients in the lower strata of HR showed significantly lower rates of 30-day all-cause mortality compared with the same reference group (adjusted OR, 0.6 for HR of 60-79 beats/min; and adjusted OR, 0.5 for HR of < 60 beats/min). The findings for 30-day PE-related mortality were similar. For identification of low-risk patients, a cutoff value of 80 beats/min (vs 110 beats/min) increased the sensitivity of the simplified Pulmonary Embolism Severity Index (sPESI) from 93.4% to 98.8%. For identification of intermediate- to high-risk patients, a cutoff value of 140 beats/min (vs 110 beats/min) increased the specificity of the Bova score from 93.2% to 98.0%.
In nonhypotensive patients with acute symptomatic PE, a high HR portends an increased risk of all-cause and PE-related mortality. Modifying the HR cutoff in the sPESI and the Bova score improves prognostication of patients with PE.
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Abstract Background Evidence-based recommendations do not adequately address the treatment of right heart thrombi in patients who present with acute symptomatic pulmonary embolism. Methods This study ...included patients who had acute pulmonary embolism associated with right heart thrombi and participated in the Registro Informatizado de la Enfermedad TromboEmbólica registry. We assessed the effectiveness of anticoagulation versus reperfusion treatment for the outcomes of all-cause mortality, pulmonary embolism–related mortality, recurrent venous thromboembolism, and major bleeding rates through 30 days after initiation of pulmonary embolism treatment. We used propensity score matching to adjust for the likelihood of receiving reperfusion treatment. Results Of 325 patients with pulmonary embolism and right heart thrombi, 255 (78%; 95% confidence interval, 74-83) received anticoagulation and 70 (22%; 95% confidence interval, 17-26) also received reperfusion treatment. Propensity score–matched pairs analyses did not detect a statistically lower risk of all-cause death (6.2% vs 14%, P = .15) or pulmonary embolism–related mortality (4.7% vs 7.8%; P = .47) for reperfusion compared with anticoagulation. Of the patients who received reperfusion treatment, 6.2% had a recurrence during the study follow-up period, compared with 0% of those who received anticoagulation ( P = .049). The incidence of major bleeding events was not statistically different between the 2 treatment groups (3.1% vs 3.1%; P = 1.00). Conclusions In patients with pulmonary embolism and right heart thrombi, no significant difference was found between reperfusion therapy and anticoagulant therapy for mortality and bleeding. The risk of recurrences was significantly higher for reperfusion therapy compared with anticoagulation. Right heart thrombi may not warrant riskier interventions than standard anticoagulation.
Summary
Autoimmune disease is a risk factor for first incident venous thromboembolism (VTE). However, data on the risk of recurrent VTE in people with autoimmune disease is sparse. We explored the ...risk of recurrent VTE using the RIETE registry, comparing people with autoimmune disease (n = 1305) to those without (n = 50608). Overall rates were 6.5 and 5.1 recurrent VTE/100 years for patients with autoimmune disease vs controls, respectively. After adjustment for sex and unprovoked/provoked VTE yielded an adjusted hazard ratio of 1.29 (95%CI 1.03‐1.62). The analysis was limited by short median follow up time (161 days overall), precluding definitive conclusions on recurrent VTE risks.
SUMMARY
The ideal duration of anticoagulation therapy in patients with autoimmune disorders and venous thromboembolism (VTE) is controversial. We used the Registro Informatizado de Enfermedad ...TromboEmbólica (RIETE) database to compare the incidence rate of major bleeding during anticoagulation versus the incidence rate of VTE recurrences after its discontinuation. We included 1061 patients with autoimmune disorders and VTE followed‐up after discontinuing anticoagulant therapy: rheumatoid arthritis, 321; polymyalgia rheumatica, 159; ulcerative colitis, 134; Crohn’s disease, 111; systemic lupus erythematosus (SLE), 82; giant cell arteritis, 58; ankylosing spondylitis, 39; Behcet disease, 17; other vasculitides, 140. During anticoagulation (median, 183 days), 64 patients had major bleeding. After discontinuing anticoagulation (median, 190 days), 112 patients developed symptomatic VTE recurrences. In most subgroups, the incidence rate of major bleeding during therapy was similar to the incidence rate of VTE recurrences after its discontinuation. However, in patients with SLE (10.0 major bleeds, 95% confidence interval CI 4.07–20.9) per 100 patient‐years vs. 3.62 VTE recurrences, 95% CI 1.15–8.74) or ankylosing spondylitis (10.9 major bleeds 95% CI 3.47–26.3 vs. 4.69 VTE recurrences, 95% CI 1.19–12.8) the incidence rates of major bleeding during anticoagulation were over twofold higher than the incidence rates of VTE recurrences after its discontinuation.
Transcatheter aortic valve implantation (TAVI) for aortic stenosis is becoming an appealing alternative to surgical aortic valve replacement in high-risk patients and to medical therapy for ...inoperable ones. Several new-generation TAVI devices have been recently introduced, but comparative analyses are lacking. We aimed to compare 1-month outcomes associated with such five leading new-generation TAVI devices exploiting data collected in the prospective observational RISPEVA (Registro Italiano GISE sull'impianto di Valvola Aortica Percutanea) Study. We queried the dataset of the ongoing RISPEVA study to retrieve baseline, procedural and 1-month outcome details of patients undergoing TAVI with Acurate, Evolut, Portico, Lotus, and Sapien3. Analysis was based on unadjusted and propensity score-adjusted methods. We included 1976 patients, 234 (11.8%) treated with Acurate, 703 (35.6%) with Evolut, 151 (7.6%) with Lotus, 347 (17.6%) with Portico, and 541 (27.4%) with Sapien3. Unadjusted analysis for baseline features highlighted several significant differences, and other discrepancies were found for procedural features. Despite these differences, device and procedural success were similarly high (ranging from 98.0% to 99.4%, p > 0.05). However, procedural valve migration appeared more common with Acurate (p = 0.007), and major bleeding with Sapien3 (p = 0.002). Unadjusted analysis for 1-month outcomes also highlighted significant differences in the composite of death, stroke, myocardial infarction, major vascular complication, major bleeding, or renal failure (favoring Portico, p < 0.001), major vascular complications (favoring Lotus, p < 0.001), renal failure (favoring Portico, p = 0.035), and permanent pacemaker implantation (favoring Acurate, p < 0.001). Propensity score-adjusted analyses showed lower rates of major adverse events with Evolut and Portico (p < 0.05), major vascular complications with Lotus and Portico (p < 0.05), renal failure with Sapien3 (p < 0.05) and permanent pacemaker implantation with Acurate (p < 0.05). In conclusion, new-generation TAVI devices have different profiles of early comparative safety and efficacy. These findings should be taken into account for individualized decision making and patient management.
Introduction
There is still a need to develop a simple algorithm to identify patients likely to need complex Mohs micrographic surgery (MMS) and optimize MMS schedule. The main objectives of this ...study are to identify factors associated with a complex MMS and develop a predictor model of the number of stages needed in surgery and the need for a complex closure.
Materials and Methods
A nationwide prospective cohort study (REGESMOHS, the Spanish Mohs surgery registry) was conducted including all patients with a histological diagnosis of basal cell carcinoma (BCC). Factors related to three or more stages and a complex closure (that needing a flap and/or a graft) were explored and predictive models were constructed and validated to construct the REGESMOSH scale.
Results
A total of 5226 patients that underwent MMS were included in the REGESMOHS registry, with 4402 (84%) having a histological diagnosis of BCC. A total of 3689 (88.9%) surgeries only needed one or two stages and 460 (11.1%) required three or more stages. A model to predict the need for three or more stages included tumour dimension, immunosuppression, recurrence, location in risk areas, histological aggressiveness and previous surgery. Regarding the closure type, 1616 (38.8%) surgeries were closed using a non‐complex closure technique and 2552 (61.2%) needed a complex closure. A model to predict the need for a complex closure included histological aggressiveness, evolution time, patient age, maximum tumour dimension and location.
Conclusion
We present a model to predict MMS needing ≥3 stages and a complex closure based on epidemiological and clinical data validated in a large population (with real practice variability) including different centres that could be easily implemented in clinical practice. This model could be used to optimize surgery schedule and properly inform patients about the surgery duration.
Large prospective studies on the safety of Mohs micrographic (MMS) surgery are scarce, and most focus on a single type of surgical adverse event. Mid-term scar alterations and functional loss have ...not been described.
To describe the risk of MMS complications and the risk factors for them.
A nationwide prospective cohort collected all adverse events on consecutive patients in 22 specialised centres. We used multilevel mixed-effects logistic regression to find out factors associated with adverse events.
5,017 patients were included, with 14,421 patient-years of follow-up. 7.0% had some perioperative morbidity and 6.5% had mid-term and scar-related complications. The overall risk of complications was mainly associated with use of antiaggregant/anticoagulant and larger tumours, affecting deeper structures, not reaching a tumour-free border, and requiring complex repair. Age and outpatient setting were not linked to the incidence of adverse events. Risk factors for haemorrhage (0.9%) were therapy with antiaggregant/anticoagulants, tumour size, duration of surgery, and unfinished surgery. Wound necrosis (1.9%) and dehiscence (1.0%) were associated with larger defects and complex closures. Immunosuppression was only associated with an increased risk of necrosis. Surgeries reaching deeper structures, larger tumours and previous surgical treatments were associated with wound infection (0.9%). Aesthetic scar alterations (5.4%) were more common in younger patients, with larger tumours, in H-area, and in flap and complex closures. Risk factors for functional scar alterations (1.7%) were the need for general anaesthesia, larger tumours that had received previous surgery, and flaps or complex closures.
MMS shows a low risk of complications. Most of the risk factors for complications were related to tumour size and depth, and the resulting need for complex surgery. Antiaggregant/anticoagulant intake was associated with a small increase in the risk of haemorrhage, that probably does not justify withdrawal. Age and outpatient setting were not linked to the risk of adverse events.
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