Nutritional counselling in adults promoting adherence to the Mediterranean diet as adjuvant in the treatment of major depressive disorder (INDEPT): a randomized open controlled trial study protocol.

BACKGROUND: Major Depressive Disorder (MDD) is a leading cause of disability worldwide. Approximately one-third of patients with MDD do not respond to treatment, and often exhibit elevated inflammation biomarkers, which are associated with worse prognosis. Previous research has linked healthier dietary patterns, such as the Mediterranean Diet (MedDiet), with a lower risk of MDD and symptoms of depression, potentially due to their anti-inflammatory properties. The aim of this study is to evaluate the effectiveness of a nutritional counselling intervention promoting MedDiet to alleviate symptoms of depression in adults recently diagnosed with MDD and presenting with elevated inflammation biomarkers. METHODS: This study is a randomized controlled trial (RCT) that will recruit adults from outpatient clinics, between the ages of 18 and 70 years who have been diagnosed with MDD and are currently receiving treatment with the first prescribed antidepressant, and who exhibit elevated inflammation biomarkers (interleukin-6 and/or C-reactive protein). The control group will receive treatment-as-usual (TAU) only. The primary outcome of the study will be the change in symptoms of depression, as measured by the Beck Depression Inventory 2 (BDI-II), after 12 weeks of intervention. Data analysis will follow an intention-to-treat approach. Secondary outcomes will include changes in inflammation biomarkers, quality of life, adherence to the MedDiet, and cost-effectiveness of nutritional counselling. All outcomes will be assessed at baseline, after the 12-week intervention, and at 6- and 12-months post-baseline. DISCUSSION: This study will be the first RCT to evaluate the effect of a nutritional intervention with anti-inflammatory properties, as an adjuvant in the treatment of MDD, in individuals diagnosed with MDD and elevated inflammation biomarkers. The results of this study may contribute to the development of more effective and personalized interventions for MDD patients with elevated inflammation biomarkers.

Development of a warning score for early detection of colorectal anastomotic leakage: Hype or hope?

BACKGROUND: Colorectal anastomotic leakage (CAL), a severe postoperative complication, is associated with high morbidity, hospital readmission, and overall healthcare costs. Early detection of CAL remains a challenge in clinical practice. However, some decision models have been developed to increase the diagnostic accuracy of this event. AIM: To develop a score based on easily accessible variables to detect CAL early. METHODS: Based on the least absolute shrinkage and selection operator method, a predictive classification system was developed [Early ColoRectAL Leakage (E-CRALL) score] from a prospective observational, single center cohort, carried out in a colorectal division from a non-academic hospital. The score performance and CAL threshold from postoperative day (POD) 3 to POD5 were estimated. Based on a precise analytical decision model, the standard clinical practice was compared with the E-CRALL adoption on POD3, POD4, or POD5. A cost-minimization analysis was conducted, on the assumption that all alternatives delivered similar health-related effects. RESULTS: In this study, 396 patients who underwent colorectal resection surgery with anastomosis, and 6.3% (n = 25) developed CAL. Most of the patients who developed CAL (n = 23; 92%) were diagnosed during the first hospital admission, with a median time of diagnosis of 9.0 ± 6.8 d. From POD3 to POD5, the area under the receiver operating characteristic curve of the E-CRALL score was 0.82, 0.84, and 0.95, respectively. On POD5, if a threshold of 8.29 was chosen, 87.4% of anastomotic failures were identified with E-CRALL adoption. Additionally, score usage could anticipate CAL diagnosis in an average of 5.2 d and 4.1 d, if used on POD3 and POD5, respectively. Regardless of score adoption, episode comprehensive costs were markedly greater (up to four times) in patients who developed CAL in comparison with patients who did not develop CAL. Nonetheless, the use of the E-CRALL warning score was associated with cost savings of €421442.20, with most (92.9%) of the savings from patients who did not develop CAL. CONCLUSION: The E-CRALL score is an accessible tool to predict CAL at an early timepoint. Additionally, E-CRALL can reduce overall healthcare costs, mainly in the reduction of hospital costs, independent of whether a patient developed CAL.

Usefulness of serum C-reactive protein and calprotectin for the early detection of colorectal anastomotic leakage: A prospective observational study.

BACKGROUND: Colorectal anastomotic leakage (CAL) is one of the most dreaded complications after colorectal surgery, with an incidence that can be as high as 27%. This event is associated with increased morbidity and mortality; therefore, its early diagnosis is crucial to reduce clinical consequences and costs. Some biomarkers have been suggested as laboratory tools for the diagnosis of CAL. AIM: To assess the usefulness of plasma C-reactive protein (CRP) and calprotectin (CLP) as early predictors of CAL. METHODS: A prospective monocentric observational study was conducted including patients who underwent colorectal resection with anastomosis, from March 2017 to August 2019. Patients were divided into three groups: G1 - no complications; G2 - complications not related to CAL; and G3 - CAL. Five biomarkers were measured and analyzed in the first 5 postoperative days (PODs), namely white blood cell (WBC) count, eosinophil cell count (ECC), CRP, CLP, and procalcitonin (PCT). Clinical criteria, such as abdominal pain and clinical condition, were also assessed. The correlation between biomarkers and CAL was evaluated. Receiver operating characteristic (ROC) curve analysis was used to compare the accuracy of these biomarkers as predictors of CAL, and the area under the ROC curve (AUROC), specificity, sensitivity, positive predictive value, and negative predictive value (NPV) during this period were estimated. RESULTS: In total, 25 of 396 patients developed CAL (6.3%), and the mean time for this diagnosis was 9.0 ± 6.8 d. Some operative characteristics, such as surgical approach, blood loss, intraoperative complications, and duration of the procedure, were notably related to the development of CAL. The length of hospital stay was markedly higher in the group that developed CAL compared with the group with complications other than CAL and the group with no complications (median of 21 d vs 13 d and 7 d respectively; P < 0.001). For abdominal pain, the best predictive performance was on POD4 and POD5, with the largest AUROC of 0.84 on POD4. Worsening of the clinical condition was associated with the diagnosis of CAL, presenting a higher predictive effect on POD5, with an AUROC of 0.9. WBC and ECC showed better predictive effects on POD5 (AUROC = 0.62 and 0.7, respectively). Those markers also presented a high NPV (94%-98%). PCT had the best predictive effect on POD5 (AUROC = 0.61), although it presented low accuracy. However, this biomarker revealed a high NPV on POD3, POD4, and POD5 (96%, 95%, and 96%, respectively). The mean CRP value on POD5 was significantly higher in the group that developed CAL compared with the group without complications (195.5 ± 139.9 mg/L vs 59.5 ± 43.4 mg/L; P < 0.00001). On POD5, CRP had a NPV of 98%. The mean CLP value on POD3 was significantly higher in G3 compared with G1 (5.26 ± 3.58 µg/mL vs 11.52 ± 6.81 µg/mL; P < 0.00005). On POD3, the combination of CLP and CRP values showed a high diagnostic accuracy (AUROC = 0.82), providing a 5.2 d reduction in the time to CAL diagnosis. CONCLUSION: CRP and CLP are moderate predictors of CAL. However, the combination of these biomarkers presents an increased diagnostic accuracy, potentially decreasing the time to CAL diagnosis.

CBmeter study: protocol for assessing the predictive value of peripheral chemoreceptor overactivation for metabolic diseases.

INTRODUCTION: Early screening of metabolic diseases is crucial since continued undiagnostic places an ever-increasing burden on healthcare systems. Recent studies suggest a link between overactivated carotid bodies (CB) and the genesis of type 2 diabetes mellitus. The non-invasive assessment of CB activity by measuring ventilatory, cardiac and metabolic responses to challenge tests may have predictive value for metabolic diseases; however, there are no commercially available devices that assess CB activity. The findings of the CBmeter study will clarify the role of the CBs in the genesis of-metabolic diseases and guide the development of new therapeutic approaches for early intervention in metabolic disturbances. Results may also contribute to patient classification and stratification for future CB modulatory interventions. METHODS: This is a non-randomised, multicentric, controlled clinical study. Forty participants (20 control and 20 diabetics) will be recruited from secondary and primary healthcare settings. The primary objective is to establish a new model of early diagnosis of metabolic diseases based on the respiratory and metabolic responses to transient 100% oxygen administration and ingestion of a standardised mixed meal. ANALYSIS: Raw data acquired with the CBmeter will be endorsed against gold standard techniques for heart rate, respiratory rate, oxygen saturation and interstitial glucose quantification and analysed a multivariate analysis software developed specifically for the CBmeter study (CBview). Data will be analysed using clustering analysis and artificial intelligence methods based on unsupervised learning algorithms, to establish the predictive value of diabetes diagnosis. ETHICS: The study was approved by the Ethics Committee of the Leiria Hospital Centre. Patients will be asked for written informed consent and data will be coded to ensure the anonymity of data. DISSEMINATION: Results will be disseminated through publication in peer-reviewed journals and relevant medical and health conferences.

Effects of anaesthesia on insulin sensitivity and metabolic parameters in Wistar rats.

We compared the effects of two different anaesthetics, sodium pentobarbital (65 mg/kg) and ketamine (30 mg/kg) plus xylazine (4 mg/kg) (KX) on insulin sensitivity, fasting glycaemia, insulinaemia and free fatty acids (FFA). Four groups of Wistar rats were used: KX group (n=6), pentobarbital group (n=6), high-sucrose diet group (n=6) and the conscious group (n=6). The insulin tolerance test (ITT) was used to measure insulin sensitivity, and metabolic biomarkers were determined using commercial kits. Pentobarbital did not alter plasma insulin, glucose, FFA or the ITT results compared to conscious animals. In contrast, KX anaesthesia induced hyperglycaemia, increased serum FFA and altered the ITT results compared to the conscious animal group. Moreover, under pentobarbital anaesthesia, the ITT proved to be a suitable method to detect insulin resistance in an animal model of diet-induced insulin resistance. We concluded that sodium pentobarbital anaesthesia should be used in metabolic studies since it does not interfere with plasma glucose, insulin, FFA or insulin sensitivity quantification in Wistar rats.

Loss of postprandial insulin sensitization during aging.

With aging, there is a decrease in parasympathetic nervous activity. Since the hepatic parasympathetic nerves (HPNs) are essential to the disposal of nutrients, through the hepatic insulin sensitizing substance (HISS), we tested the hypothesis that aging leads to a lowering of postprandial glucose disposal by a decrease of the HISS-dependent component of insulin action. Insulin sensitivity was quantified in fed or fasted, male and female Wistar rats (from 6 to 52 weeks), using a euglycemic clamp. The HISS-dependent component was quantified by administration of the muscarinic antagonist atropine. Total insulin action decreased gradually up to 52 weeks of age: The HISS-independent component of insulin action decreased until 9 weeks of age and remained unchanged thereafter; the HISS-dependent component decreased from 9 weeks of age throughout aging. The continuous decrease of HISS action, uncovered by blocking the HPN, is the key phenomenon for the gradual decrease of insulin sensitivity with aging.

In vitro nitrosation of insulin A- and B-chains.

The physiological roles of insulin and nitric oxide (NO) have been recently recognized by several studies. A diversity of chemical modifications of insulin is reported both in vivo and in vitro. S-nitrosation, the covalent linkage of NO to cysteine free thiol is recognized as an important post-translational regulation in many proteins. Here we report the in vitro synthesis of an S-nitrosothiol of bovine insulin A- and B-chains. These compounds were characterized by their HPLC chromatographic behavior, monitored by UV visible spectroscopy and electron spray ionization mass spectrometry. The experimental results indicate that each A- and B-chain were S- nitrosated with only one NO group. Stability and solubility of these synthesized derivatives is described for physiological purposes. In this work, nitroso A- and B-chains of insulin were synthesized in vitro in order to better understand the possible interactions between insulin and NO that may be involved in the etiology of insulin resistance.