Regression of Renal Disease by Angiotensin II Antagonism Is Caused by Regeneration of Kidney Vasculature

Chronic renal insufficiency inexorably progresses in patients, such as it does after partial renal ablation in rats. However, the progression of renal diseases can be delayed by angiotensin II blockers that stabilize renal function or increase GFR, even in advanced phases of the disease. Regression of glomerulosclerosis can be induced by angiotensin II antagonism, but the effect of these treatments on the entire vascular tree is unclear. Here, using microcomputed tomography and scanning electron microscopy, we compared the size and extension of kidney blood vessels in untreated Wistar rats with those in untreated and angiotensin II antagonist–treated Munich Wistar Frömter (MWF) rats that spontaneously develop kidney disease with age. The kidney vasculature underwent progressive rarefaction in untreated MWF rats, substantially affecting intermediate and small vessels. Microarray analysis showed increased Tgf-β and endothelin-1 gene expression with age. Notably, 10-week inhibition of the renin-angiotensin system regenerated kidney vasculature and normalized Tgf-β and endothelin-1 gene expression in aged MWF rats. These changes were associated with reduced apoptosis, increased endothelial cell proliferation, and restoration of Nrf2 expression, suggesting mechanisms by which angiotensin II antagonism mediates regeneration of capillary segments. These results have important implications in the clinical setting of chronic renal insufficiency.     

Goal-Directed Fluid Therapy on Laparoscopic Sleeve Gastrectomy in Morbidly Obese Patients

Background

In bariatric surgery, there are no guidelines available for intraoperative fluid administration. Goal-directed fluid therapy (GDFT) is a new concept of perioperative fluid management that has been shown to improve the prognosis of patients undergoing abdominal surgery. The aim of our study is to assess the impact of the implementation of a GDFT protocol in morbidly obese patients who underwent laparoscopic sleeve gastrectomy (LSG).

Methods

A before-after intervention study, in morbidly obese patients who underwent LSG, was conducted at the Obesity Unit of the General University Hospital Elche. Data from the GDFT implementation group (January 2014 to December 2015) were prospectively collected and compared with a preimplementation group (January 2012 to December 2013).

Results

Baseline demographic and comorbidity data between the two groups of patients were similar. The length of stay in the hospital was significantly shortened in GDFT group from 4.5 to 3.44 days (p?<?0.001). Intraoperative fluid administration was significantly lower in the GDFT group (1002.4 vs 1687.2 ml in preimplementation group, p?<?0.001). In the postoperative period, there was a statistically significant reduction in postoperative nausea and vomiting (PONV) after GDFT implementation (48 to 14.3 %, p?<?0.001).

Conclusions

Implementation of GDFT protocols can prevent intraoperative fluid overload in patients undergoing bariatric surgery. It could improve outcomes, for example decreasing PONV or even hospital stay.

     

The Zung's autoscale for depression as predictor of sensorial and autonomic alterations to pain

Clinical and experimental evidence support a relationship between susceptibility to chronic pain and a subjacent depression. Nevertheless, it's not clear if the currently available clinical evaluation instruments for depression allow for linking both disorders. Thus, we evaluated a Zung's autoscale for depression and its different categories: affective, physiological, motor and psychological, as possible predictors of sensorial and autonomic alterations and vulnerability to clinical chronic pain. In 32 healthy controls and 11 subjects with minor depression and free of treatment, ischemic pain was first induced by applying a tourniquet on the dominant arm, and then followed by paresthesias during the reperfusion of arm as the tourniquet is released. Ischemic muscular pain, post-ischemic paresthesias and associated cardiovascular responses were recorded throughout the experimental procedure. The affective category's score was correlated linearly in individual form with the greatest number of variables and it was adjusted to a model of multiple regressions that almost explained the variance in 100% with a contribution of the sensorial and autonomic variables of a 70% and 30%, respectively. In addition, the affective category was 50% greater in subjects with persistent clinical pain. The Zung's index and the other categories had a smaller number of individual linear correlations and models of multiple correlations that only explained between 30-70% of the variance, with a more predominant contribution of the autonomic variables (20-50%), especially in the psychological category. This suggests that the affective category predicts cutaneous-muscular sensorial alterations with greater effectiveness than the Zung's total index.     

Patient education in Parkinson's disease: Formative evaluation of a standardized programme in seven European countries

OBJECTIVE: To evaluate a newly developed education programme for Parkinson's disease (PD) patients. METHODS: The programme consisted of eight sessions and aimed at improving knowledge and skills related to self-monitoring, health promotion, stress management, depression, anxiety, social competence, and social support, all with special reference to PD. The programme was formatively evaluated in seven European countries (Spain, Finland, Italy, The Netherlands, United Kingdom, Estonia, Germany) with 151 patients diagnosed with idiopathic PD. The evaluation included patients' ratings of the comprehensibility and feasibility of the programme as well as mood ratings before and after each session. Patients also completed questionnaires at the beginning and end of the programme to explore possible changes in disease-related psychosocial problems, quality of life, and depression. RESULTS: The programme was feasible to run, and patients were able to understand its elements. Patients reported mood elevations following individual sessions and reduced disease-related psychosocial problems after completing the programme. There were no substantial differences in results between cultures. CONCLUSION: Patient education appears to have potential as a useful and feasible intervention, complementing medical treatment in PD. PRACTICE IMPLICATIONS: The present programme will soon be available in seven European languages and can be tested in different health care systems.     

Protein cellular localization prediction with Support Vector Machines and Decision Trees

Many cellular functions are carried out in specific compartments of the cell. The prediction of the cellular localization of a protein is thus related to its function identification. This paper uses two Machine Learning techniques, Support Vector Machines (SVMs) and Decision Trees, in the prediction of the localization of proteins from three categories of organisms: gram-positive and gram-negative bacteria and fungi. For all categories considered, the localization task has multiple classes, which correspond to the possible protein locations. Since SVMs are originally designed for the solution of two-class problems, this paper also investigates and compares several strategies to extend this technique to perform multiclass predictions.     

Prevalence and correlates of diabetes and metabolic syndrome in a rural indigenous community in Baja California,Mexico

Background

Diabetes is a leading cause of morbidity and mortality in Mexico and understudied among indigenous populations. This study aimed to determine the prevalence and identify correlates of Type 2 diabetes mellitus (Type 2 DM) and metabolic syndrome (MetS) in a rural, indigenous community in Northwestern Mexico.

Methods

A cross-sectional study was conducted in the community of San Quintin, Baja California, Mexico, among a sample of households. A total of 275 participants (≥18?years old) underwent a questionnaire, physical examination, and serologic test. Prevalence and adjusted odds ratio (AOR), using logistic regression modeling, were estimated with 95% confidence intervals (95% CI).

Results

The prevalence of Type 2 DM and MetS was 21.8 and 53.1%, respectively. Mean?±?standard deviation (SD) age and body mass index of study participants was 35.8?±?13.0?years and 28.7?±?5.6?kg/m², respectively. Participants were 75% female and 60.7% self-identified as indigenous. Thirty-seven percent of adults had high blood pressure. After controlling for age, higher educational attainment had a protective effect on Type 2 DM (AOR?=?0.39; 95% CI 0.20, 0.77). Additionally, the presence of MetS was associated with being female (AOR?=?2.27; 95% CI 1.23, 4.14) and having lower educational attainment (AOR?=?0.62; 95% CI 0.37, 0.94).

Conclusions

The prevalence of Type 2 DM and MetS was high in this rural and indigenous population, and education was shown to play a critical role. These findings support the need for community-inclusive health-promoting interventions in rural communities.

     

Dietary Changes and Gut Dysbiosis in Children With Type 1 Diabetes

Objective: Gut dysbiosis in type 1 diabetes (T1D), characterized by high Bacteroides proportion, tends to reverse as T1D progresses, without reaching full recovery. Since diet influences microbiota structure, the aim was to evaluate the impact of dietary changes on Bacteroides proportion the first year of T1D evolution.

Methods: Dietary intake was assessed by 24-hour recalls and Bacteroides proportion by quantitative polymerase chain reaction, in 10 Mexican children (11.6 ± 1.92 years) with T1D at baseline and 3, 6 and 9 months' follow-up. Repeated measures analysis of variance and multiple linear regression were performed to compare ingested nutrients in relation with Bacteroides proportion. Effects over time were evaluated by mixed regression models.

Results: Patients with T1D decreased their energy (2621.89 to 1867.85 kcal, p = 0.028), protein (83.06 to 75.17 g, p = 0.012), and saturated fat consumption (40.83 to 25.23 g, p = 0.031) from baseline to 3 months, without posterior changes. Bacteroides proportion increased in the first months and tended to decrease at around 9 months (p > 0.05) and was positively correlated with saturated fat (β = 3.70, p = 0.009) and total carbohydrates (β = 0.73, p = 0.005) at 3 months. Carbohydrate consumption was related to decreased Bacteroides abundance over time (β = ?14.9, p = 0.004), after adjusting for glycosylated hemoglobin.

Conclusions: Besides autoimmunity, diet appears to have a central role determining the T1D-associated dysbiosis evolution.     

Progressive facial hemiatrophy with associated osseous lesions

Progressive facial hemiatrophy (PFH) is a rare condition characterized by the slow, progressive appearance of a unilateral facial atrophy that affects the skin, subcutaneous tissue, muscle and bone. We report the case of a 60-year-old female patient whose cutaneous symptoms commenced in 1987 in the form of a purplish erythema on the left side of her face and neck, which subsequently remitted giving rise to an indurated region in the left maxillary region. Since 1995 until the present day, she has developed facial hemiatrophy on the left side accompanied by progressive osseous reabsorption of the upper maxilla and left mandible with atrophy of soft tissue. The association of the onset of PFH with progressive osteolysis of the maxilla has not been previously reported in an adult patient.     

The impact of the SARS-CoV-2 pandemic on the management of chronic limb-threatening ischemia and wound care

In the wake of the coronavirus pandemic, the critical limb ischemia (CLI) Global Society aims to develop improved clinical guidance that will inform better care standards to reduce tissue loss and amputations during and following the new SARS-CoV-2 era. This will include developing standards of practice, improve gaps in care, and design improved research protocols to study new chronic limb-threatening ischemia treatment and diagnostic options. Following a round table discussion that identified hypotheses and suppositions the wound care community had during the SARS-CoV-2 pandemic, the CLI Global Society undertook a critical review of literature using PubMed to confirm or rebut these hypotheses, identify knowledge gaps, and analyse the findings in terms of what in wound care has changed due to the pandemic and what wound care providers need to do differently as a result of these changes. Evidence was graded using the Oxford Centre for Evidence-Based Medicine scheme. The majority of hypotheses and related suppositions were confirmed, but there is noticeable heterogeneity, so the experiences reported herein are not universal for wound care providers and centres. Moreover, the effects of the dynamic pandemic vary over time in geographic areas. Wound care will unlikely return to prepandemic practices. Importantly, Levels 2–5 evidence reveals a paradigm shift in wound care towards a hybrid telemedicine and home healthcare model to keep patients at home to minimize the number of in-person visits at clinics and hospitalizations, with the exception of severe cases such as chronic limb-threatening ischemia. The use of telemedicine and home care will likely continue and improve in the postpandemic era.     

Microsatellite and RAS/RAF Mutational Status as Prognostic Factors in Colorectal Peritoneal Metastases Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

Background

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) leads to prolonged survival for selected patients with colorectal (CRC) peritoneal metastases (PM). This study aimed to analyze the prognostic role of micro-satellite (MS) status and RAS/RAF mutations for patients treated with CRS.

Methods

Data were collected from 13 Italian centers with PM expertise within a collaborative group of the Italian Society of Surgical Oncology. Clinical and pathologic variables and KRAS/NRAS/BRAF mutational and MS status were correlated with overall survival (OS) and disease-free survival (DFS).

Results

The study enrolled 437 patients treated with CRS-HIPEC. The median OS was 42.3 months [95% confidence interval (CI), 33.4–51.2 months], and the median DFS was 13.6 months (95% CI, 12.3–14.9 months). The local (peritoneal) DFS was 20.5 months (95% CI, 16.4–24.6 months). In addition to the known clinical factors, KRAS mutations (p = 0.005), BRAF mutations (p = 0.01), and MS status (p = 0.04) were related to survival. The KRAS- and BRAF-mutated patients had a shorter survival than the wild-type (WT) patients (5-year OS, 29.4% and 26.8% vs 51.5%, respectively). The patients with micro-satellite instability (MSI) had a longer survival than the patients with micro-satellite stability (MSS) (5-year OS, 58.3% vs 36.7%). The MSI/WT patients had the best prognosis. The MSS/WT and MSI/mutated patients had similar survivals, whereas the MSS/mutated patients showed the worst prognosis (5-year OS, 70.6%, 48.1%, 23.4%; p = 0.0001). In the multivariable analysis, OS was related to the Peritoneal Cancer Index [hazard ratio (HR), 1.05 per point], completeness of cytoreduction (CC) score (HR, 2.8), N status (HR, 1.6), signet-ring (HR, 2.4), MSI/WT (HR, 0.5), and MSS/WT-MSI/mutation (HR, 0.4). Similar results were obtained for DFS.

Conclusion

For patients affected by CRC-PM who are eligible for CRS, clinical and pathologic criteria need to be integrated with molecular features (KRAS/BRAF mutation). Micro-satellite status should be strongly considered because MSI confers a survival advantage over MSS, even for mutated patients.