The Impact of Moderate Chronic Hypoxia and Hyperoxia on the Level of Apoptotic and Autophagic Proteins in Myocardial Tissue

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Evolution of Bariatric Surgery in Italy in the Last 11 Years: Data from the SICOB Yearly National Survey

Background: Bariatric surgery (BS) is a relatively novel surgical field and is in continuous expansion and evolution. Purpose: Aim of this study was to report changes in Italian surgical practice in the last decade. Methods: The Società Italiana di Chirurgia dell'Obesità (SICOB) conducted annual surveys to cense activity of SICOB centers between 2011 and 2021. Primary outcome was to detect differences in frequency of performance of adjustable gastric banding (AGB), sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), one anastomosis gastric bypass (OAGB), bilio-pancreatic diversion (BPD), and gastric plication (GP). Secondary outcome was to detect differences in performance of main non-malabsorptive procedures (AGB + SG) and overall bypass procedures (RYGB + OAGB). Geographical differences were also investigated. Results: Median response rate was 92%. AGB declined from 36% of procedures in 2011 to 5% in 2021 (p < 0.0001). SG increased from 30% in 2011 to 55% in 2021 (p < 0.0001). RYGB declined from 25 to 12% of procedures (p < 0.0001). OAGB rose from 0% of procedures in 2011 to 15% in 2021 (p < 0.0001). BPD underwent decrease from 6.2 to 0.2% in 2011 and 2021, respectively (p < 0.0001). Main non-malabsorptive procedures significantly decreased while overall bypass procedures remained stable. There were significant differences among regions in performance of SG, RYGB, and OAGB. Conclusions: BS in Italy evolved significantly during the past 10 years. AGB underwent a decline, as did BPD and GP which are disappearing and RYGB which is giving way to OAGB. The latter is rising and is the second most-performed procedure after SG which has been confirmed as the preferred procedure by Italian bariatric surgeons

Phosphodiesterase-5 Inhibition Mimics Intermittent Reoxygenation and Improves Cardioprotection in the Hypoxic Myocardium

Although chronic hypoxia is a claimed myocardial risk factor reducing tolerance to ischemia/reperfusion (I/R), intermittent reoxygenation has beneficial effects and enhances heart tolerance to I/R. Aim of the study: To test the hypothesis that, by mimicking intermittent reoxygenation, selective inhibition of phosphodiesterase-5 activity improves ischemia tolerance during hypoxia. Adult male Sprague-Dawley rats were exposed to hypoxia for 15 days (10% O2) and treated with placebo, sildenafil (1.4 mg/kg/day, i. p.), intermittent reoxygenation (1 h/day exposure to room air) or both. Controls were normoxic hearts. To assess tolerance to I/R all hearts were subjected to 30-min regional ischemia by left anterior descending coronary artery ligation followed by 3 h-reperfusion. Whereas hypoxia depressed tolerance to I/R, both sildenafil and intermittent reoxygenation reduced the infarct size without exhibiting cumulative effects. The changes in myocardial cGMP, apoptosis (DNA fragmentation), caspase-3 activity (alternative marker for cardiomyocyte apoptosis), eNOS phosphorylation and Akt activity paralleled the changes in cardioprotection. However, the level of plasma nitrates and nitrites was higher in the sildenafil+intermittent reoxygenation than sildenafil and intermittent reoxygenation groups, whereas total eNOS and Akt proteins were unchanged throughout. Conclusions: Sildenafil administration has the potential to mimic the cardioprotective effects led by intermittent reoxygenation, thereby opening the possibility to treat patients unable to be reoxygenated through a pharmacological modulation of NO-dependent mechanisms

Brain adaptation to hypoxia and hyperoxia in mice

Aims: Hyperoxic breathing might lead to redox imbalance and signaling changes that affect cerebral function. Paradoxically, hypoxic breathing is also believed to cause oxidative stress. Our aim is to dissect the cerebral tissue responses to altered O2 fractions in breathed air by assessing the redox imbalance and the recruitment of the hypoxia signaling pathways. Results: Mice were exposed to mild hypoxia (10%O2), normoxia (21%O2) or mild hyperoxia (30%O2) for 28 days, sacrificed and brain tissue excised and analyzed. Although one might expect linear responses to %O2, only few of the examined variables exhibited this pattern, including neuroprotective phospho- protein kinase B and the erythropoietin receptor. The major reactive oxygen species (ROS) source in brain, NADPH oxidase subunit 4 increased in hypoxia but not in hyperoxia, whereas neither affected nuclear factor (erythroid-derived 2)-like 2, a transcription factor that regulates the expression of antioxidant proteins. As a result of the delicate equilibrium between ROS generation and antioxidant defense, neuron apoptosis and cerebral tissue hydroperoxides increased in both 10%O2 and 30%O2, as compared with 21%O2. Remarkably, the expression level of hypoxia-inducible factor (HIF)−2α (but not HIF-1α) was higher in both 10%O2 and 30%O2 with respect to 21%O2 Innovation: Comparing the in vivo effects driven by mild hypoxia with those driven by mild hyperoxia helps addressing whether clinically relevant situations of O2 excess and scarcity are toxic for the organism. Conclusion: Prolonged mild hyperoxia leads to persistent cerebral damage, comparable to that inferred by prolonged mild hypoxia. The underlying mechanism appears related to a model whereby the imbalance between ROS generation and anti-ROS defense is similar, but occurs at higher levels in hypoxia than in hyperoxia. Keywords: In vivo hypoxia, In vivo hyperoxia, Neurons, Hypoxia-inducible factor, Oxidative injur

The burden of depressive disorders in musculoskeletal diseases: is there an association between mood and inflammation?

Importance: Evidence emerged concerning how inflammatory arthritis and mood disorders can often occur in the same patient and show a similar clinical pattern. An overview of the rheumatological and psychiatric aspects of these diseases can certainly be useful for the improvement of patients' clinical and therapeutic management. Objective: The aim of this narrative review was to summarize existing literature about common pathogenetic and clinical aspects as a means of improving management and therapeutic approach in patients affected by rheumatoid arthritis, psoriatic arthritis and spondyloarthritis. Outcomes such as disease activity indexes and patient reported outcomes (PROs) were considered. Findings: Common pathogenetic pathways emerged between inflammatory arthritis and mood disorders. Pro-inflammatory mechanisms, such as TNFα, IL-6, IL-17 and oxidative stress factors as well as neurotransmitter alterations at the level of CNS and blood-brain barrier (BBB) cells are involved. The activation of these common pathogenetic pathways is, also, affected by the same triggers, such as smoking, stress, lifestyle, and evidence has emerged concerning the possibility of the clinical efficacy of using the same therapeutic approaches. Conclusions: The main causes of the variability in clinical studies outcomes are the rheumatological diseases considered, the prevalence of depression in the general population and in patients with rheumatological diseases and the type of depressive symptom examined. Patients affected by inflammatory arthritis can present symptoms and signs in common with mood disorders, leading to possible clinical overlap. There are still few studies analyzing this concept: they are extremely heterogeneous, both in the characteristics of the population taken into consideration and in the methods used for the definition of depressive disorder, but the suggestions of the data obtained so far are promising and deserve to be pursued

Impact of rehabilitation on mortality and readmissions after surgery for hip fracture

Abstract Background Hip fracture in elderly patients is a rising global public health concern because of population ageing, and increasing frailty. Long-term morbidity related to poor management of hip fracture is associated with decreased quality of life, survival, and increase in healthcare costs. Receiving postoperative rehabilitation is associated with better outcomes and a higher likelihood of returning to pre-existing level of functioning. However little is known about which postoperative rehabilitation pathways are more effective to optimize patient outcomes. Few studies have analyzed postoperative rehabilitation pathways in a universal healthcare system. The aim of this study is to analyze the impact of post-acute rehabilitation pathways on mortality and readmission in elderly patients undergoing surgery for hip fracture in a large metropolitan area in Italy. Methods In this retrospective cohort study, we analyzed 6-month mortality from admission and 6-month readmission after hospital discharge in patients who underwent surgical repair for hip fracture in the hospitals of the Bologna metropolitan area between 1.1.2013 and 30.6.2014. Data were drawn from the regional hospital discharge records database. Kaplan-Meier estimates and multiple Cox regression were used to analyze mortality as a function of rehabilitation pathways. Multiple logistic regression determined predictors of readmission. Results The study population includes 2208 patients, mostly women (n = 1677, 76%), with a median age of 83.8 years. Hospital rehabilitation was provided to 519 patients (23.5%), 907 (41.1%) received rehabilitation in private inpatient rehabilitation facilities (IRF) accredited by the National Health System, and 782 (35.4%) received no post-acute rehabilitation. Compared with patient receiving hospital rehabilitation, the other groups showed significantly higher mortality risks (no rehabilitation, Hazard Ratio (HR) = 2.19, 95%CI = 1.54–3.12, p < 0.001; IRF rehabilitation, HR = 1.66, 95%CI = 1.54–1.79, p < 0.001). The risk of readmission did not differ significantly among rehabilitation pathways. Conclusions Intensive hospital rehabilitation was significantly associated with a lower risk of mortality compared to IRF rehabilitation and no rehabilitation. Our results may help in the development of evidence-based recommendations aimed to improve resource utilization and quality of care in hip fracture patients. Further research is warranted to investigate the impact of the rehabilitation pathway on other outcomes, such as patients’ functional status and quality of life

Hemoglobin extravasation in the brain of rats exchange-transfused with hemoglobin-based oxygen carriers

Haemoglobin (Hb)-based oxygen carriers are under consideration as oxygen therapeutics. Their effect on apoptosis is critical, because the onset of pro-apoptotic pathways may lead to tissue damage. MP4OX, a polyethylene glycol-conjugated human Hb preserves the baseline level of neuron apoptosis with respect to sham. Here we develop a method for measuring Hb extravasation in brain. We exchange transfused rats by haemorrhaging 50% of their blood with simultaneous, isovolemic replacement with Hextend (negative control), MP4OX, or \u3b1\u3b1-cross-linked Hb. Animals were sacrificed 2 h after transfusion, brain tissue was harvested and processed for double-staining immunofluorescence, whereby Hb ? chain and NeuN (a neuron protein) were stained and quantitated. Whereas Hextend did not induce Hb extravasation, in both MP4OX and ??Hb brains Hb molecules were detected outside neurons. The level of extravasated Hb chains was > 3-fold higher in Hb compared to MP4OX. Western blot analysis revealed that the expression levels of protein related to redox imbalance (e.g., Nrf2, iNOS and ERK phosphorylation) were higher in \u3b1\u3b1Hb than MP4OX. In conclusions, higher Hb extravasation in \u3b1\u3b1Hb than MP4OX induces redox imbalance, which causes higher anti-oxidant response. Whereas Nrf2 response may be considered protective, iNOS response appears damaging

CagA positive Helicobacter pylori infection may increase the risk of food allergy development

The aim of this study was to test whether patients with symptomatic food allergy and significant levels of immunoglobulin E (IgE) to alimentary antigens were more likely infected by H. pylori, especially by strains expressing the CagA protein, with respect to controls. A group of 38 patients with symptomatic food allergy and 53 age-matched controls were examined serologically for H. pylori infectious status, and for CagA seropositivity. IgE to alimentary allergens were measured by a commercial kit. The prevalence of H. pylori infection in patients with food allergy and controls was similar (42.1%, and 48.3%, respectively. However, anti-CagA antibodies in H. pylori- infected persons were detected in 62.5% of patients with food allergy, and 28% of controls (P = 0.030, odds ratio = 4.29). The mean level of IgE to the most common alimentary antigens in serum samples from infected patients with anti-CagA antibodies was significantly higher than in CagA-negative infected patients: 3.28 kU/L (SD 3.93), vs. 1.99 kU/L (SD 1.53), P = 0.002, 95% confidence interval = 0.61 to 2.53). Infection by CagA-positive H. pylori increases the risk of developing food allergy