Adequacy and support of physiological functions in the acutely ill cirrhotic patient

The cirrhotic condition is characterized by a series of changes in physiological functions and of subclinical alterations that imply an abnormal and fragile adaptive pattern with reduced resistance to superimposed distress. In the care of the critically ill cirrhotic patient, the supportive measures aimed at maintaining physiological stability through the control of such debilitating factors have a key role and are not secondary in importance to the more obvious measures needed to treat clinically evident and specific alterations or complications. The relationship between hepatic malfunction and the development of these physiological abnormalities is not fully understood. Our knowledge of the problem, however, has been recently improved and the need for supportive measures motivated by a series of notions on cardiorespiratory and metabolic abnormalities and interactions in hepatic decompensation.

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Resumen La condición cirrótica se caracteriza por una serie de cambios en las funciones fisiológicas y por alteraciones subclinicas que implican un patrón de adaptación anormal y fragil de resistencia reducida al estrés. Estas incluyen disfunción respiratoria con tendencia a la hipoxemia arterial en presencia de elevados indices cardiacos, una situatión crónica de hiperdinamismo cardiovascular pero con precaria eficacia miocárdica y latente riesgo de falla de alto débito, y cambios metabólicos que se traducen en un estado de fallas multisistémicas interrelacionadas características del cirrótico. En el cuidado del paciente cirrótico en estado crítico, las medidas de soporte orientadas al mantenimiento de la estabilidad fisiológica mediante el control de tales factores debilitantes tienen una importancia capital y no son secundarias frente a aquellas muy obvias que se requieren para tratar alteraciones o complicaciones específicas y clínicamente evidentes. La relación entre la disfunción hepática y el desarrollo de las mencionadas anormalidades fisiológicas no está totalmente aclarada, sin embargo, el estado de nuestro conocimiento sobre el problema ha sido enriquecido recientemente y se ha fortalecido la necesidad de establecer medidas de soporte por una serie de nociones relativas a las anormalidades e interacciones cardiorrespiratorias y metabólicas de la descompensación hepática.

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Résumé La cirrhose est caractérisée par des séries de variations des fonctions physiologiques et de modifications cliniques qui impliquent des modalités d'adaptation anormale et fragile se traduisant par une résistance réduite à l'état de détresse ou peut se trouver le cirrhotique. Des mesures appropriées pour maintenir la stabilité physiologique ont un rôle principal en présence de ces facteurs défavorables. Elles ne doivent pas être considérées comme moins importantes que les mesures essentielles qui sont nécessaires pour traiter les complications et les modifications cliniques spécifiques. La relation entre l'altération des fonctions du foie et le développement des anomalies physiologiques précitées n'est pas parfaitement élucidée, cependant, nos connaissances de ce problème ont été récemment améliorées et le besoin de mesures adéquates de soutien est devenu manifeste en raison de séries acquises de notions concernant les anomalies cardio-respiratoires et métaboliques ainsi que les interactions de la décompensation hépatique.

     

Cystometric changes in the early phase of streptozotocin-induced diabetes in rats: evidence for sensory changes not correlated to diabetic neuropathy

Summary 1. The effect of streptozotocin (STZ) induced diabetes on rat urinary bladder function was investigated by means of in vivo cystometry and in vitro recording of bladder strips contractility. A group of sucrose-fed animals was included to determine to what extent the STZ-induced changes were ascribable to the increased diuresis. 2. After 7–9 weeks from STZ injection there was a marked increase in weight of bladder and ureters. Cystometry revealed a marked increase in bladder capacity (volume threshold) although pressure threshold and amplitude of micturition contraction were unaffected. Sucrose-fed animals, having normal blood glucose levels but a similar increase in urine production exhibited cystometric changes identical to those of STZ animals. 3. In vitro experiments indicated that the response to field stimulation (0.1–20 Hz) is reduced in STZ-pretreated but increased in sucrose-fed animals, as compared to controls. 4. The content of urinary bladder and ureters in sensory neuropeptides (substance-P, neurokinin-A and calcitonin-gene related peptide-like immunoreactivity) was increased by STZ diabetes when values were corrected for the increased weight of these organs. 5. The capsaicin-induced contraction of the rat isolated bladder strips, presumably caused by neuropeptides released from intramural sensory nerves, is unaffected by STZ diabetes. 6. These findings indicate that STZ diabetes produces, at an early stage, changes similar to those reported to occur in the human disease, e. g. a greater bladder capacity with unimpaired voiding function. The increased bladder capacity of STZ-rats seems largely, if not solely, ascribable to changes in physical properties of the detrusor muscle, thereby allowing accomodation of greater than normal volumes with similar increase of intraluminal pressure. No sign of diabetic neuropathy of the capsaicin-sensitive sensory nerves can be observed at this stage (7–9 weeks) of STZ diabetes. Send offprint requests to P. Santicioli at the above address     

Component-Resolved Diagnosis of Hazelnut Allergy in Children

Hazelnuts commonly elicit allergic reactions starting from childhood and adolescence, with a rare resolution over time. The definite diagnosis of a hazelnut allergy relies on an oral food challenge. The role of component resolved diagnostics in reducing the need for oral food challenges in the diagnosis of hazelnut allergies is still debated. Therefore, three electronic databases were systematically searched for studies on the diagnostic accuracy of specific-IgE (sIgE) on hazelnut proteins for identifying children with a hazelnut allergy. Studies regarding IgE testing on at least one hazelnut allergen component in children whose final diagnosis was determined by oral food challenges or a suggestive history of serious symptoms due to a hazelnut allergy were included. Study quality was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Eight studies enrolling 757 children, were identified. Overall, sensitivity, specificity, area under the curve and diagnostic odd ratio of Cor a 1 sIgE were lower than those of Cor a 9 and Cor a 14 sIge. When the test results were positive, the post-test probability of a hazelnut allergy was 34% for Cor a 1 sIgE, 60% for Cor a9 sIgE and 73% for Cor a 14 sIgE. When the test results were negative, the post-test probability of a hazelnut allergy was 55% for Cor a 1 sIgE, 16% for Cor a9 sIgE and 14% for Cor a 14 sIgE. Measurement of IgE levels to Cor a 9 and Cor a 14 might have the potential to improve specificity in detecting clinically tolerant children among hazelnut-sensitized ones, reducing the need to perform oral food challenges.     

Associations of Dietary Patterns with Incident Depression: The Maastricht Study

Our aim was to assess the association between a priori defined dietary patterns and incident depressive symptoms. We used data from The Maastricht Study, a population-based cohort study (n = 2646, mean (SD) age 59.9 (8.0) years, 49.5% women; 15,188 person-years of follow-up). Level of adherence to the Dutch Healthy Diet (DHD), Mediterranean Diet, and Dietary Approaches To Stop Hypertension (DASH) were derived from a validated Food Frequency Questionnaire. Depressive symptoms were assessed at baseline and annually over seven-year-follow-up (using the 9-item Patient Health Questionnaire). We used Cox proportional hazards regression analyses to assess the association between dietary patterns and depressive symptoms. One standard deviation (SD) higher adherence in the DHD and DASH was associated with a lower hazard ratio (HR) of depressive symptoms with HRs (95%CI) of 0.78 (0.69–0.89) and 0.87 (0.77–0.98), respectively, after adjustment for sociodemographic and cardiovascular risk factors. After further adjustment for lifestyle factors, the HR per one SD higher DHD was 0.83 (0.73–0.96), whereas adherence to Mediterranean and DASH diets was not associated with incident depressive symptoms. Higher adherence to the DHD lowered risk of incident depressive symptoms. Adherence to healthy diet could be an effective non-pharmacological preventive measure to reduce the incidence of depression.     

Vascular Effects of the Polyphenolic Nutraceutical Supplement Taurisolo®: Focus on the Protection of the Endothelial Function

Preservation of vascular endothelium integrity and functionality represents an unmet medical need. Indeed, endothelial dysfunction leads to decreased nitric oxide biosynthesis, which is prodromic of hypertension and hypercoagulability. In this panorama, the nutraceutical supplement Taurisolo^®, a polyphenolic extract from Aglianico cultivar grape, rich in catechin and procyanidins, was evaluated as a vasoprotective, vasorelaxing, anti-hypertensive and anti-coagulant agent in: cell lines, isolated vessels, in vivo models of chronic hypertension and hypercoagulability, and in clinical tests of endothelial reactivity. Taurisolo^® demonstrated to fully protect vascular cell viability from oxidative stimulus at 100 µg/mL and evoke vasorelaxing effects (Emax = 80.6% ± 1.9 and pEC50 = 1.19 ± 0.03) by activation of the Sirtuins-AMPK-pathway. Moreover, Taurisolo^®, chronically administered at 20 mg/Kg/die in in vivo experiments, inhibited the onset of cardiac hypertrophy (heart weight/rat weight = 3.96 ± 0.09 vs. 4.30 ± 0.03), hypercoagulability (decrease of fibrinogen vs. control: p < 0.01) and hypertension (mean of Psys: 200 ± 2 vs. control 234 ± 2 mmHg) and improved endothelial function (Emax = 88.9% ± 1.5 vs. control 59.6% ± 3.6; flow-mediated dilation in healthy volunteers after 400 mg twice daily for 8 weeks vs. baseline: p = 0.019). In conclusion, Taurisolo^® preserves the vascular function against ox-inflamm-ageing process and the consequent cardiovascular accidents.     

Vitamin D Status in Adolescents during COVID-19 Pandemic: A Cross-Sectional Comparative Study

Vitamin D has been claimed to be effective in the response to infections, including the respiratory syndrome coronavirus 2 (SARS-CoV-2). It is supposed that lockdown measures and fear of SARS-CoV-2 infection might reduce vitamin D levels through the modification of lifestyle. However, very few data exist on the association between lockdown measures and vitamin D status in humans. For this cross-sectional comparative study, adolescents (n = 298) aged 18 to 19 years were enrolled during the compulsory military fitness-for-duty evaluation between July and December 2020 in Southern Switzerland. Beyond anthropometric measurements, participants filled in a structured questionnaire about their lifestyle and a blood specimen was sampled for the determination of total 25-hydroxy-vitamin D. The obtained data were compared with those of 437 adolescents enrolled at the military fitness-for-duty evaluation during the same period of the year in the context of the CENERI study (2014–2016). The anthropometric measures were similar between the two study groups. The levels of vitamin D were also comparable (77 (64–91) vs. 74 (60–92) nmol/L, p = 0.50; median and interquartile range). A total of 38 (13%) and 43 (9.8%) subjects presented insufficient (<50 nmol/L) levels of vitamin D (p = 0.42) during the current pandemic and in the CENERI study, respectively. These data do not support the hypothesis that during the SARS-CoV-2 pandemic, late adolescents are at higher risk of vitamin insufficiency.     

Association of the Chronotype Score with Circulating Trimethylamine N-Oxide (TMAO) Concentrations

Individual differences in the chronotype, an attitude that best expresses the individual circadian preference in behavioral and biological rhythms, have been associated with cardiometabolic risk and gut dysbiosis. Up to now, there are no studies evaluating the association between chronotypes and circulating TMAO concentrations, a predictor of cardiometabolic risk and a useful marker of gut dysbiosis. In this study population (147 females and 100 males), subjects with the morning chronotype had the lowest BMI and waist circumference (p < 0.001), and a better metabolic profile compared to the other chronotypes. In addition, the morning chronotype had the highest adherence to the Mediterranean diet (p < 0.001) and the lowest circulating TMAO concentrations (p < 0.001). After adjusting for BMI and adherence to the Mediterranean diet, the correlation between circulating TMAO concentrations and chronotype score was still kept (r = −0.627, p < 0.001). Using a linear regression analysis, higher chronotype scores were mostly associated with lower circulating TMAO concentrations (β = −0.479, t = −12.08, and p < 0.001). Using a restricted cubic spline analysis, we found that a chronotype score ≥59 (p < 0.001, R² = −0.824) demonstrated a more significant inverse linear relationship with circulating TMAO concentrations compared with knots <59 (neither chronotype) and <41 (evening chronotype). The current study reported the first evidence that higher circulating TMAO concentrations were associated with the evening chronotype that, in turn, is usually linked to an unhealthy lifestyle mostly characterized by low adherence to the MD.     

Do environmental and occupational exposure to pyrethroids and organophosphates affect human semen parameters? Results of a systematic review and meta-analysis

Our purpose was to review and analyse the impact of pyrethroids and organophosphates exposure on human semen parameters. A comprehensive literature search was performed through MEDLINE via PubMed, Scopus and Webscience. Only cohort studies examining semen parameters in workers or general populations exposed to pyrethroids or organophosphates were included. Ejaculate volume, sperm count, concentration, motility, viability, normal morphology and seminal pH alterations were pooled using the Cochran–Mantel–Haenszel Method with the random effect model and expressed as weighted mean difference, risk ratios, 95% confidence intervals and p-values. Seven cross-sectional studies regarding pyrethroids were included. Four of them were eligible for meta-analysis. The only parameter affected by pyrethroid exposure was normal sperm morphology (WMD-7,61%, 95%CI –11,92 to −3,30;p = 0,0,005). Nine studies were selected to evaluate the impact of organophosphates on semen parameters with six of them eligible for meta-analysis. A significant reduction was detected for the following: ejaculate volume (WMD −0,47ml, 95%CI −0,69 to −0,25; p < 0,0001), sperm count (WMD-40,03, 95%CI −66,81 to −13,25;p = 0,003), concentration (WMD-13,69 x10⁶/mL, 95%CI −23, 27 to-4,12;p = 0,005) and motility (WMD −5,70%, 95%CI −12,89 to 1,50;p = 0,12). Despite the increase in sperm abnormality, it has been shown that pyrethroids are unrelated to reduced sperm quality. However, the negative association of organophosphates with spermatogenesis is noteworthy.     

Rehabilitación multimodal en cirugía de urgencias: ¿utopía o realidad?

Enhanced Recovery After Surgery (ERAS) constitutes the application of a series of perioperative measures based on the evidence, in order to achieve a better recovery of the patient and a decrease of the complications and the mortality. These ERAS programs initially proved their advantages in the field of colorectal surgery being progressively adopted by other surgical areas within the general surgery and other surgical specialties. The main excluding factor for the application of such programs has been the urgent clinical presentation, which has caused that despite the large volume of existing literature on ERAS in elective surgery, there are few studies that have investigated the effectiveness of these programs in surgical patients in emergencies. The aim of this article is to show ERAS measures currently available according to the existing evidence for emergency surgery.     

Mechanically Supported Early Graft Failure After Heart Transplantation

BackgroundThe occurrence of early graft failure (EGF) after heart transplantation (Htx) often requires a mechanical circulatory support (MCS) therapy. The aims of our study were to identify risk factors of mechanically supported severe EGF and evaluate their impact on both early and late outcomes.MethodsBetween January 2000 and December 2019, 499 consecutive adult patients underwent Htx at our institution. Severe EGF was defined as the need for extracorporeal life support (ECLS) within 24 hours after surgery. All available recipient and donor variables were retrospectively analyzed.ResultsOverall, EGF occurred in 58 (11.6%) patients. Post-Htx peripheral or central ECLS was necessary in 32 (6.4%) cases. Independent predictors of severe EGF were, in the recipient group, preoperative transpulmonary gradient (TPG) >12 mm Hg (odds ratio [OR] 4.1, P = .013), preoperative inotropic score >10 (OR 7.3, P = .0001), and pre-Htx ECLS support (OR 5.2, P = .015), while in the donors, a Eurotransplant donor score ≥17 (OR 8.5, P = .005). The absence of EGF was related with a better survival at 1 year and 5 years (94% and 85%, respectively) compared with EGF requiring ECLS population (36% and 28% at 1 year and 5 years, respectively; P < .001). A five-year conditional survival rate did not differ significantly (85% no EGF vs 83% EGF requiring ECLS).ConclusionBoth donor and recipient factors may influence EGF occurrence. Post-Htx ECLS may impact negatively early; however, patients weaned from ECLS eventually benefit from such a rescue treatment with outcomes comparable with Htx patients who did not suffer EGF.