Rap2, but not Rap1 GTPase is expressed in human red blood cells and is involved in vesiculation

AbstractRecent studies have suggested that Rap1 and Rap2 small GTP-binding proteins are both expressed in human red blood cells (RBCs). In this work, we carefully examined the expression of Rap proteins in leukocytes- and platelets-depleted RBCs, whose purity was established on the basis of the selective expression of the β2 subunit of the Na+/K+-ATPase, as verified according to the recently proposed “β-profiling test” [J.F. Hoffman, A. Wickrema, O. Potapova, M. Milanick, D.R. Yingst, Na pump isoforms in human erythroid progenitor cells and mature erythrocytes, Proc. Natl. Acad. Sci. U. S. A. 99 (2002) 14572-14577]. In pure RBCs preparations, Rap2, but not Rap1 was detected immunologically. RT-PCR analysis of mRNA extracted from highly purified reticulocytes confirmed the expression of Rap2b, but not Rap2a, Rap2c, Rap1a or Rap1b. In RBCs, Rap2 was membrane-associated and was rapidly activated upon treatment with Ca2+/Ca2+-ionophore. In addition, Rap2 segregated and was selectively enriched into microvesicles released by Ca2+-activated RBCs, suggesting a possible role for this GTPase in membrane shedding

Outcomes of endovascular treatment of ruptured abdominal aortic aneurysms

IntroductionThe successful application of endovascular techniques for the elective repair of abdominal aortic aneurysms (AAAs) has stimulated a strong interest in their possible use in dealing with a long-standing surgical challenge: the ruptured abdominal aortic aneurysm (RAAA). The use of a conventional open procedure to repair ruptured aneurysms is associated with a high operative mortality of 45% to 50%. In this study, we evaluated the current frequency of endovascular repair of RAAAs in four large states and the impact of this technique on patient outcome.MethodsWe examined discharge data sets from 2000 through 2003 from the four states of California, Florida, New Jersey, and New York, whose combined population represents almost a third of the United States population. Proportions and trends were analyzed by χ2 analysis and continuous variables by the Student’s t test.ResultsWe found that since the year 2000, endovascular repair has begun to emerge as a viable treatment option for RAAAs, accounting for the repair of 6.2% of cases in 2003. During the same period, the use of open procedures for RAAAs declined. The overall mortality rate for the 4-year period was significantly lower for endovascular vs open repair (39.3% vs. 47.7%, P = .005). Moreover, compared with open repair, endovascular repair resulted in a significantly lower rate of pulmonary, renal, and bleeding complications. Survival after endovascular repair correlated with hospital experience, as assessed by the overall volume of elective and nonelective endovascular procedures. For endovascular repairs, mortality ranged from 45.9% for small volume hospitals to 26% for large volume hospitals (P = .0011). Volume was also a determinant of mortality for open repairs, albeit to a much lesser extent (51.5% for small volume hospitals, 44.3% for large volume hospitals; P < .0001).ConclusionWe observed a benefit to using endovascular procedures for RAAAs in institutions with significant endovascular experience; however, the analysis of administrative data cannot rule out selection bias as an explanation of better outcomes. These data strongly endorse the need for prospective studies to clarify to what extent the improved survival in RAAA patients is to be attributed to the endovascular approach rather than the selection of low-risk patients

Open Versus Laparoscopic Adrenalectomy for Adrenocortical Carcinoma: A Meta-analysis of Surgical and Oncological Outcomes

PURPOSE: This study was designed to determine the role of laparoscopic adrenalectomy (LA) in the surgical management of adrenocortical carcinoma (ACC). METHODS: A systematic literature review was performed on January 2, 2015 using PubMed. Article selection proceeded according to PRISMA criteria. Studies comparing open adrenalectomy (OA) to LA for ACC and including at least 10 cases per each surgical approach were included. Odds ratio (OR) was used for all binary variables, and weight mean difference (WMD) was used for the continuous parameters. Pooled estimates were calculated with the fixed-effect model, if no significant heterogeneity was identified; alternatively, the random-effect model was used when significant heterogeneity was detected. Main demographics, surgical outcomes, and oncological outcomes were analyzed. RESULTS: Nine studies published between 2010 and 2014 were deemed eligible and included in the analysis, all of them being retrospective case-control studies. Overall, they included 240 LA and 557 OA cases. Tumors treated with laparoscopy were significantly smaller in size (WMD -3.41 cm; confidence interval [CI] -4.91, -1.91; p &lt; 0.001), and a higher proportion of them (80.8 %) more at a localized (I-II) stage compared with open surgery (67.7 %) (odds ratio [OR] 2.8; CI 1.8, 4.2; p &lt; 0.001). Hospitalization time was in favor of laparoscopy, with a WMD of -2.5 days (CI -3.3, -1.7; p &lt; 0.001). There was no difference in the overall recurrence rate between LA and OA (relative risk [RR] 1.09; CI 0.83, 1.43; p = 0.53), whereas development of peritoneal carcinomatosis was higher for LA (RR 2.39; CI 1.41, 4.04; p = 0.001). No difference could be found for time to recurrence (WMD -8.2 months; CI -18.2, 1.7; p = 0.11), as well as for cancer specific mortality (OR 0.68; CI 0.44, 1.05; p = 0.08). CONCLUSIONS: OA should still be considered the standard surgical management of ACC. LA can offer a shorter hospital stay and possibly a faster recovery. Therefore, this minimally invasive approach can certainly play a role in this setting, but it should be only offered in carefully selected cases to avoid jeopardizing the oncological outcome.PURPOSE: This study was designed to determine the role of laparoscopic adrenalectomy (LA) in the surgical management of adrenocortical carcinoma (ACC). METHODS: A systematic literature review was performed on January 2, 2015 using PubMed. Article selection proceeded according to PRISMA criteria. Studies comparing open adrenalectomy (OA) to LA for ACC and including at least 10 cases per each surgical approach were included. Odds ratio (OR) was used for all binary variables, and weight mean difference (WMD) was used for the continuous parameters. Pooled estimates were calculated with the fixed-effect model, if no significant heterogeneity was identified; alternatively, the random-effect model was used when significant heterogeneity was detected. Main demographics, surgical outcomes, and oncological outcomes were analyzed. RESULTS: Nine studies published between 2010 and 2014 were deemed eligible and included in the analysis, all of them being retrospective case-control studies. Overall, they included 240 LA and 557 OA cases. Tumors treated with laparoscopy were significantly smaller in size (WMD -3.41 cm; confidence interval [CI] -4.91, -1.91; p &lt; 0.001), and a higher proportion of them (80.8 %) more at a localized (I-II) stage compared with open surgery (67.7 %) (odds ratio [OR] 2.8; CI 1.8, 4.2; p &lt; 0.001). Hospitalization time was in favor of laparoscopy, with a WMD of -2.5 days (CI -3.3, -1.7; p &lt; 0.001). There was no difference in the overall recurrence rate between LA and OA (relative risk [RR] 1.09; CI 0.83, 1.43; p = 0.53), whereas development of peritoneal carcinomatosis was higher for LA (RR 2.39; CI 1.41, 4.04; p = 0.001). No difference could be found for time to recurrence (WMD -8.2 months; CI -18.2, 1.7; p = 0.11), as well as for cancer specific mortality (OR 0.68; CI 0.44, 1.05; p = 0.08). CONCLUSIONS: OA should still be considered the standard surgical management of ACC. LA can offer a shorter hospital stay and possibly a faster recovery. Therefore, this minimally invasive approach can certainly play a role in this setting, but it should be only offered in carefully selected cases to avoid jeopardizing the oncological outcome

Increase of Parkin and ATG5 plasmatic levels following perinatal hypoxic‐ischemic encephalopathy

Brain injury at birth is an important cause of neurological and behavioral disorders. Hypoxic‐ischemic encephalopathy (HIE) is a critical cerebral event occurring acutely or chronically at birth with high mortality and morbidity in newborns. Therapeutic strategies for the prevention of brain damage are still unknown, and the only medical intervention for newborns with moderate‐to‐severe HIE is therapeutic hypothermia (TH). Although the neurological outcome depends on the severity of the initial insult, emerging evidence suggests that infants with mild HIE who are not treated with TH have an increased risk for neurodevelopmental impairment; in the current clinical setting, there are no specific or validated biomarkers that can be used to both correlate the severity of the hypoxic insult at birth and monitor the trend in the insult over time. The aim of this work was to examine the presence of autophagic and mitophagic proteins in bodily fluids, to increase knowledge of what, early at birth, can inform therapeutic strategies in the first hours of life. This is a prospective multicentric study carried out from April 2019 to April 2020 in eight third‐level neonatal intensive care units. All participants have been subjected to the plasma levels quantification of both Parkin (a protein involved in mitophagy) and ATG5 (involved in autophagy). These findings show that Parkin and ATG5 levels are related to hypoxic‐ischemic insult and are reliable also at birth. These observations suggest a great potential diagnostic value for Parkin evaluation in the first 6 h of life

Post-operative acute urinary retention after greenlight laser. Analysis of risk factors from a multicentric database

Purpose: Greenlight laser is a mini-invasive technique used to treat Benign Prostatic Obstruction (BPO). Some of the advantages of GreenLight photoselective vaporization (PVP) are shorter catheterization time and hospital stay compared to TURP. Post-operative acute urinary retention (pAUR) leads to patients' discomfort, prolonged hospital stay and increased health care costs. We analyzed risk factors for urinary retention after GreenLight laser PVP. Materials and methods: In a multicenter experience, we retrospectively analyzed the onset of early and late post-operative acute urinary retention in patients undergoing standard or anatomical PVP. The pre-, intra- and post-operative characteristics were compared betweene patients who started to void and the patients who developed post-operative urinary retention. Results: The study included 434 patients suitable for the study. Post-operative acute urinary retention occurred in 39 (9%). Patients with a lower prostate volume (P &lt; .001), an adenoma volume lower than 40 mL (P &lt; .001), and lower lasing time (P = .013) had a higher probability to develop pAUR at the univariate analysis. The multivariate logistic regression confirmed that lower lasing time (95% CI: 0.86-0.99, OR = 0.93, P = .046) and adenoma volume (95% CI: 0.89-0.98, OR = 0.94, P = .006) are correlated to pAUR. Furthermore IPSS ≥ 19 (95% CI: 1.19- 10.75, OR = 2.27, P = .023) and treatment with 5-ARI (95% CI: 1.05-15.03, OR = 3.98, P = .042) are risk factors for pAUR. Conclusion: In our series, post-operative acute urinary retention was related to low adenoma volume and lasing time, pre-operative IPSS ≥ 19 and 5-ARI intake. These data should be considered in deciding the best timing for urethral catheters removal

Practice patterns and 90-day treatment-related morbidity in early-stage cervical cancer

To evaluate the impact of the Laparoscopic Approach to Cervical Cancer (LACC) Trial on patterns of care and surgery-related morbidity in early-stage cervical cancer

Beta-Blocker Use in Older Hospitalized Patients Affected by Heart Failure and Chronic Obstructive Pulmonary Disease: An Italian Survey From the REPOSI Register

Beta (β)-blockers (BB) are useful in reducing morbidity and mortality in patients with heart failure (HF) and concomitant chronic obstructive pulmonary disease (COPD). Nevertheless, the use of BBs could induce bronchoconstriction due to β2-blockade. For this reason, both the ESC and GOLD guidelines strongly suggest the use of selective β1-BB in patients with HF and COPD. However, low adherence to guidelines was observed in multiple clinical settings. The aim of the study was to investigate the BBs use in older patients affected by HF and COPD, recorded in the REPOSI register. Of 942 patients affected by HF, 47.1% were treated with BBs. The use of BBs was significantly lower in patients with HF and COPD than in patients affected by HF alone, both at admission and at discharge (admission, 36.9% vs. 51.3%; discharge, 38.0% vs. 51.7%). In addition, no further BB users were found at discharge. The probability to being treated with a BB was significantly lower in patients with HF also affected by COPD (adj. OR, 95% CI: 0.50, 0.37-0.67), while the diagnosis of COPD was not associated with the choice of selective β1-BB (adj. OR, 95% CI: 1.33, 0.76-2.34). Despite clear recommendations by clinical guidelines, a significant underuse of BBs was also observed after hospital discharge. In COPD affected patients, physicians unreasonably reject BBs use, rather than choosing a β1-BB. The expected improvement of the BB prescriptions after hospitalization was not observed. A multidisciplinary approach among hospital physicians, general practitioners, and pharmacologists should be carried out for better drug management and adherence to guideline recommendations

The “Diabetes Comorbidome”: A Different Way for Health Professionals to Approach the Comorbidity Burden of Diabetes

(1) Background: The disease burden related to diabetes is increasing greatly, particularly in older subjects. A more comprehensive approach towards the assessment and management of diabetes’ comorbidities is necessary. The aim of this study was to implement our previous data identifying and representing the prevalence of the comorbidities, their association with mortality, and the strength of their relationship in hospitalized elderly patients with diabetes, developing, at the same time, a new graphic representation model of the comorbidome called “Diabetes Comorbidome”. (2) Methods: Data were collected from the RePoSi register. Comorbidities, socio-demographic data, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), and functional status (Barthel Index), were recorded. Mortality rates were assessed in hospital and 3 and 12 months after discharge. (3) Results: Of the 4714 hospitalized elderly patients, 1378 had diabetes. The comorbidities distribution showed that arterial hypertension (57.1%), ischemic heart disease (31.4%), chronic renal failure (28.8%), atrial fibrillation (25.6%), and COPD (22.7%), were the more frequent in subjects with diabetes. The graphic comorbidome showed that the strongest predictors of death at in hospital and at the 3-month follow-up were dementia and cancer. At the 1-year follow-up, cancer was the first comorbidity independently associated with mortality. (4) Conclusions: The “Diabetes Comorbidome” represents the perfect instrument for determining the prevalence of comorbidities and the strength of their relationship with risk of death, as well as the need for an effective treatment for improving clinical outcomes

Antidiabetic Drug Prescription Pattern in Hospitalized Older Patients with Diabetes

Objective: To describe the prescription pattern of antidiabetic and cardiovascular drugs in a cohort of hospitalized older patients with diabetes. Methods: Patients with diabetes aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro POliterapuie SIMI—Società Italiana di Medicina Interna) registry from 2010 to 2019 and discharged alive were included. Results: Among 1703 patients with diabetes, 1433 (84.2%) were on treatment with at least one antidiabetic drug at hospital admission, mainly prescribed as monotherapy with insulin (28.3%) or metformin (19.2%). The proportion of treated patients decreased at discharge (N = 1309, 76.9%), with a significant reduction over time. Among those prescribed, the proportion of those with insulin alone increased over time (p = 0.0066), while the proportion of those prescribed sulfonylureas decreased (p &lt; 0.0001). Among patients receiving antidiabetic therapy at discharge, 1063 (81.2%) were also prescribed cardiovascular drugs, mainly with an antihypertensive drug alone or in combination (N = 777, 73.1%). Conclusion: The management of older patients with diabetes in a hospital setting is often sub-optimal, as shown by the increasing trend in insulin at discharge, even if an overall improvement has been highlighted by the prevalent decrease in sulfonylureas prescription