Aging and Parkinson's Disease: Inflammaging, neuroinflammation and biological remodeling as key factors in pathogenesis

In order to better understand the pathogenesis of Parkinson's Disease (PD) it is important to consider possible contributory factors inherent to the aging process, as age-related changes in a number of physiological systems (perhaps incurred within particular environments) appear to influence the onset and progression of neurodegenerative disorders. Accordingly, we posit that a principal mechanism underlying PD is inflammaging, i.e. the chronic inflammatory process characterized by an imbalance of pro- and anti-inflammatory mechanisms which has been recognized as operative in several age-related, and notably neurodegenerative diseases. Recent conceptualization suggests that inflammaging is part of the complex adaptive mechanisms (\ue2\u80\u9cre-modeling\ue2\u80\u9d) that are ongoing through the lifespan, and which function to prevent or mitigate endogenous processes of tissue disruption and degenerative change(s). The absence of an adequate anti-inflammatory response can fuel inflammaging, which propagates on both local (i.e.- from cell to cell) and systemic levels (e.g.- via exosomes and other molecules present in the blood). In general, this scenario is compatible with the hypothesis that inflammaging represents a hormetic or hormetic-like effect, in which low levels of inflammatory stress may prompt induction of anti-inflammatory mediators and mechanisms, while sustained pro-inflammatory stress incurs higher and more durable levels of inflammatory substances, which, in turn prompt a local-to-systemic effect and more diverse inflammatory response(s). Given this perspective, new treatments of PD may be envisioned that strategically are aimed at exerting hormetic effects to sustain anti-inflammatory responses, inclusive perhaps, of modulating the inflammatory influence of the gut microbiota

Secretory breast carcinoma with metastatic sentinel lymph node

BACKGROUND: Secretory mammary carcinoma is a rare breast neoplasia originally described in children but sometimes also found in adults. It presents a more favourable outcome than more common histological types of breast carcinoma; published literature in fact reports only a few cases with axillary lymph node metastases and only four cases with distant metastases. CLINICAL PRESENTATION: In this paper we report a rare case of secretory breast carcinoma with axillary lymph node metastases in a 33-year-old woman. To our knowledge, this is the first case of secretory carcinoma involving biopsy of the sentinel lymph node and investigation of the e-cadherin expression. We found positivity for e-cadherin, which would support the hypothesis that this type of tumour is a variant of the infiltrating ductal carcinoma. CONCLUSION: After a careful analysis of reported data, we have come to the conclusion that the treatment of choice for patients with secretory breast carcinoma should be conservative surgery with sentinel lymph node biopsy, followed by accurate follow-up. We are of the opinion that while post-operative radiotherapy is indicated in adult patients who have undergone quadrantectomy, it should not be used in children. Although several cases of secretory carcinoma have been treated with adjuvant chemotherapy, there are still no reliable data regarding the real value of such a choice

Two cases of monomicrobial intraabdominal abscesses due to KPC - 3 Klebsiella pneumoniae ST258 clone

<p>Abstract</p> <p>Background</p> <p>Knowledge of the etiology of pyogenic liver and pancreatic abscesses is an important factor in determining the success of combined surgical and antibiotic treatment. Literature shows geographical variations in the prevalence and distribution of causative organisms, and the spread of <it>Klebsiella pneumoniae </it>carbapenemase-producing bacteria is an emerging cause of abdominal infections.</p> <p>Case presentation</p> <p>We herein describe two cases of intra-abdominal abscesses due to monomicrobial infection by <it>Klebsiella pneumoniae </it>Sequence Type 258 producing <it>K. pneumoniae </it>carbapenemase 3 (KPC-Kp). In case 1, a 50-year-old HIV-negative Italian woman with chronic pancreatitis showed infection of a pancreatic pseudocystic lesion caused by KPC-Kp. In case 2, a 64-year-old HIV- negative Italian woman with pancreatic neoplasm and liver metastases developed a liver abscess due to KPC after surgery. Both women were admitted to our hospital but to different surgical units. The clonal relationship between the two isolates was investigated by pulsed-field gel electrophoresis (PFGE). In case 2, the patient was already colonized at admission and inter-hospital transmission of the pathogen was presumed. A long-term combination regimen of colistin with tigecycline and percutaneous drainage resulted in full recovery and clearance of the multidrug-resistant (MDR) pathogen.</p> <p>Conclusions</p> <p>Timely microbiological diagnosis, the combined use of new and old antibiotics and radiological intervention appeared to be valuable in managing these serious conditions. The emergence and dissemination of MDR organisms is posing an increasing challenge for physicians to develop new therapeutic strategies and control and prevention frameworks.</p

Appendectomy during the COVID-19 pandemic in Italy: a multicenter ambispective cohort study by the Italian Society of Endoscopic Surgery and new technologies (the CRAC study)

Major surgical societies advised using non-operative management of appendicitis and suggested against laparoscopy during the COVID-19 pandemic. The hypothesis is that a significant reduction in the number of emergent appendectomies was observed during the pandemic, restricted to complex cases. The study aimed to analyse emergent surgical appendectomies during pandemic on a national basis and compare it to the same period of the previous year. This is a multicentre, retrospective, observational study investigating the outcomes of patients undergoing emergent appendectomy in March-April 2019 vs March-April 2020. The primary outcome was the number of appendectomies performed, classified according to the American Association for the Surgery of Trauma (AAST) score. Secondary outcomes were the type of surgical technique employed (laparoscopic vs open) and the complication rates. One thousand five hundred forty one patients with acute appendicitis underwent surgery during the two study periods. 1337 (86.8%) patients met the inclusion criteria: 546 (40.8%) patients underwent surgery for acute appendicitis in 2020 and 791 (59.2%) in 2019. According to AAST, patients with complicated appendicitis operated in 2019 were 30.3% vs 39.9% in 2020 (p = 0.001). We observed an increase in the number of post-operative complications in 2020 (15.9%) compared to 2019 (9.6%) (p &lt; 0.001). The following determinants increased the likelihood of complication occurrence: undergoing surgery during 2020 (+ 67%), the increase of a unit in the AAST score (+ 26%), surgery performed &gt; 24 h after admission (+ 58%), open surgery (+ 112%) and conversion to open surgery (+ 166%). In Italian hospitals, in March and April 2020, the number of appendectomies has drastically dropped. During the first pandemic wave, patients undergoing surgery were more frequently affected by more severe appendicitis than the previous year's timeframe and experienced a higher number of complications. Trial registration number and date: Research Registry ID 5789, May 7th, 202

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Laparoscopic versus robotic right colectomy with extra-corporeal or intra-corporeal anastomosis: a systematic review and meta-analysis

Purpose: The aim of the present systematic review and meta-analysis is to compare laparoscopic right colectomy (LRC) versus robotic right colectomy (RRC) using homogeneous subgroup analyses for extra-corporeal anastomosis (EA) and intra-corporeal anastomosis (IA). Methods: MEDLINE, Scopus, and Web of Science databases were searched up to April 2020 for prospective or retrospective studies comparing LRC versus RRC on at least one short- or long-term outcome. The primary outcome was the length of hospital stay (LOS). The secondary outcomes included operative and pathological results, survival, and total costs. LRC and RRC were compared using three homogeneous subgroups: without distinction by the type of anastomosis, EA only, and IA only. Pooled data analyses were performed using mean difference (MD) and random effects model. Results: Thirty-seven of 448 studies were selected. The included patients were 21,397 for the LRC group and 2796 for the RRC group. Regardless for the type of anastomosis, RRC showed shorter LOS, lower blood loss, lower conversion rate, shorter time to flatus, and lower overall complication rate compared with LRC, but longer operative time and higher total costs. In the EA subgroup, RRC showed similar LOS, longer operative time, and higher costs compared with LRC, the other outcomes being similar. In the IA subgroup, RRC showed shorter LOS and longer operative time compared with LRC, with no difference for the remaining outcomes. Conclusions: Most included articles are retrospective, providing low-quality evidence and limiting conclusions. The more frequent use of the IA seems to explain the advantages of RRC over LRC

Technical details for a robot-assisted hand-sewn esophago-gastric anastomosis during minimally invasive Ivor Lewis esophagectomy

Background: Minimally invasive Ivor Lewis esophagectomy (MIILE) provides better outcomes than open techniques, particularly in terms of post-operative recovery and pulmonary complications. However, in addition to requiring advanced technical skills, thoracoscopic access makes it hard to perform esophagogastric anastomosis safely, and the reported rates of anastomotic leak vary from 5 to 16%. Several minimally invasive esophago-gastric anastomotic techniques have been described, but to date strong evidence to support one technique over the others is still lacking. We herein report the technical details and preliminary results of a new robot-assisted hand-sewn esophago-gastric anastomosis technique. Methods: From January 2018 to December 2020, 12 cases of laparoscopic/thoracoscopic Ivor Lewis esophagectomy with robot-assisted hand-sewn esophago-gastric anastomosis were performed. The gastric conduit was prepared and tailored taking care of vascularization with a complete resection of the gastric fundus. The anastomosis consisted of a robot-assisted, hand-sewn four layers of absorbable monofilament running barbed suture (V-lock). The posterior outer layer incorporated the gastric and esophageal staple lines. Results: The post-operative course was uneventful in nine cases. Two patients developed chyloperitoneum, one patient a Sars-Cov-2 infection, and one patient a late anastomotic stricture. In all cases, there were no anastomotic leaks or delayed gastric conduit emptying. The median post-operative stay was 13&nbsp;days (min 7, max 37&nbsp;days); the longest in-hospital stay was recorded in patients who developed chyloperitoneum. Conclusion: Despite the small series, we believe that our technique looks to be promising, safe, and reproducible. Some key points may be useful to guarantee a low complications rate after MIILE, particularly regarding anastomotic leaks and delayed emptying: the resection of the gastric fundus, the use of robot assistance, the incorporation of the staple lines in the posterior aspect of the anastomosis, and the use of barbed suture. Further cases are needed to validate the preliminary, but very encouraging, results