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Sepsis and severe sepsis in particular remain a major health problem worldwide. Their cost to society extends well beyond lives lost, as the impact of survivorship is increasingly felt. A review of the medical literature was completed in MEDLINE using the search phrases “severe sepsis” and “septic shock” and the MeSH terms “epidemiology”, “statistics”, “mortality”, “economics”, and “quality of life”. Results were limited to human trials that were published in English from 2002 to 2014. Articles were classified by dominant themes to address epidemiology and outcomes, including quality of life of both patient and family caregivers, as well as societal costs. The severity of sepsis is determined by the number of organ failures and the presence of shock. In most developed countries, severe sepsis and septic shock account for disproportionate mortality and resource utilization. Although mortality rates have decreased, overall mortality continues to increase and is projected to accelerate as people live longer with more chronic illness. Among those who do survive, impaired quality of life, increased dependence, and rehospitalization increase healthcare consumption and, along with increased mortality, all contribute to the humanistic burden of severe sepsis. A large part of the economic burden of severe sepsis occurs after discharge. Initial inpatient costs represent only 30 % of the total cost and are related to severity and length of stay, whereas lost productivity and other indirect medical costs following hospitalization account for the majority of the economic burden of sepsis. Timeliness of treatment as well as avoidance of intensive care unit (ICU)-acquired illness/morbidity lead to important differences in both cost and outcome of treatment for severe sepsis and represent areas where improvement in care is possible. The degree of sophistication of a health system from a national perspective results in significant differences in resource use and outcomes for patients with serious infections. Comprehensive understanding of the cost and humanistic burden of severe sepsis provides an initial practical framework for health policy development and resource use.

Obesity and menopausal hypoestrogenism interact in a way that worsens insulin resistance and increases the risk of metabolic diseases. This study evaluated the effects of a diet composed of liquid chickpea sprouts (CS) on these problems. Sixty-four female Wistar rats were assigned to four experimental groups: a control group (Ctrl); a hypoestrogenic (HE) group, induced by ovariotomy; an obese (Ob) group, fed a high-sucrose diet; and a hypoestrogenic-obese (HE-Ob) group. Each group was subdivided into animals treated with chickpea sprouts (CS, 0.9 g/kg/day) or with a vehicle for four weeks. The results showed that CS significantly improved glucose tolerance and restored insulin sensitivity, normalizing the HOMA-IR index in both the Ob and HE-Ob groups. In addition, CS reduced serum triglycerides, reversed hepatic steatosis, and caused a favorable redistribution of adipose tissue, leading to decreased mesenteric fat accumulation. In conclusion, chickpea sprouts have protective metabolic effects by improving glucose homeostasis, reducing blood lipids, and mitigating liver damage in an estrogen-deficient model of obesity. These findings support the potential of chickpea sprouts as a dietary intervention to help prevent metabolic complications in obese postmenopausal women.

Background Pneumonia is the most common infection after out-of-hospital cardiac arrest (OHCA) occurring in up to 65% of patients who remain comatose after return of spontaneous circulation. Preventing infection after OHCA may (1) reduce exposure to broad-spectrum antibiotics, (2) prevent hemodynamic derangements due to local and systemic inflammation, and (3) prevent infection-associated morbidity and mortality. Methods The ceftriaxone to PRevent pneumOnia and inflammaTion aftEr Cardiac arrest (PROTECT) trial is a randomized, placebo-controlled, single-center, quadruple-blind (patient, treatment team, research team, outcome assessors), non-commercial, superiority trial to be conducted at Maine Medical Center in Portland, Maine, USA. Ceftriaxone 2 g intravenously every 12 h for 3 days will be compared with matching placebo. The primary efficacy outcome is incidence of early-onset pneumonia occurring < 4 days after mechanical ventilation initiation. Concurrently, T cell-mediated inflammation bacterial resistomes will be examined. Safety outcomes include incidence of type-one immediate-type hypersensitivity reactions, gallbladder injury, and C lostridioides difficile -associated diarrhea. The trial will enroll 120 subjects over approximately 3 to 4 years. Discussion The PROTECT trial is novel in its (1) inclusion of OHCA survivors regardless of initial heart rhythm, (2) use of a low-risk antibiotic available in the USA that has not previously been tested after OHCA, (3) inclusion of anti-inflammatory effects of ceftriaxone as a novel mechanism for improved clinical outcomes, and (4) complete metagenomic assessment of bacterial resistomes pre- and post-ceftriaxone prophylaxis. The long-term goal is to develop a definitive phase III trial powered for mortality or functional outcome. Trial registration ClinicalTrials.gov NCT04999592 . Registered on August 10, 2021.

Benign prostatic hyperplasia (BPH) is the most common adenoma in old men. Tomatoes are a rich source of bioactive compounds that, as well as selenium (Se), possess antioxidant and antiproliferative activity. The aim was to evaluate the therapeutic effect of Se in combination with a tomato extract in aged rats with BPH. Aged male Wistar rats were divided in the following groups ( n  = 10 rats/group): Control (C), BPH, BPH + Finasteride (BPH + F), BPH + Tomato Lipidic Extract (BPH + E), BPH + Selenium (BPH + S) and BPH plus E plus S (BPH + E + S). After 4 weeks of treatment, prostate weight, diuresis, antioxidants enzymes, prooxidants and inflammatory markers, growth factors and androgens were determined. BPH + E + S reduced prostate weight by 59.29% and inhibited growth by 99.35% compared to BPH + F which only decreased weight and inhibited growth by 15.31% and 57.54%, respectively. Prooxidant markers were higher with BPH + F (49.4% higher vs. BPH), but BPH + E + S decreased these markers (94.27% vs. BPH) and increased antioxidant activity. Finally, diuresis was higher with the BPH + E + S combination and markers of inflammation and growth factors were significantly lower with respect to BPH + F. Our findings provide a beneficial and protective therapeutic option of E + S directed against androgens, oxidative stress and inflammation that regulates cell proliferation in the prostate gland.

The agent that should be used for light sedation of patients requiring mechanical ventilation is unclear. This randomized trial compared dexmedetomidine with propofol for the light sedation of critically ill patients with sepsis who required mechanical ventilation. No clinically important differences were found.

Background Acute treatment of cerebral edema and elevated intracranial pressure is a common issue in patients with neurological injury. Practical recommendations regarding selection and monitoring of therapies for initial management of cerebral edema for optimal efficacy and safety are generally lacking. This guideline evaluates the role of hyperosmolar agents (mannitol, HTS), corticosteroids, and selected non-pharmacologic therapies in the acute treatment of cerebral edema. Clinicians must be able to select appropriate therapies for initial cerebral edema management based on available evidence while balancing efficacy and safety. Methods The Neurocritical Care Society recruited experts in neurocritical care, nursing, and pharmacy to create a panel in 2017. The group generated 16 clinical questions related to initial management of cerebral edema in various neurological insults using the PICO format. A research librarian executed a comprehensive literature search through July 2018. The panel screened the identified articles for inclusion related to each specific PICO question and abstracted necessary information for pertinent publications. The panel used GRADE methodology to categorize the quality of evidence as high, moderate, low, or very low based on their confidence that the findings of each publication approximate the true effect of the therapy. Results The panel generated recommendations regarding initial management of cerebral edema in neurocritical care patients with subarachnoid hemorrhage, traumatic brain injury, acute ischemic stroke, intracerebral hemorrhage, bacterial meningitis, and hepatic encephalopathy. Conclusion The available evidence suggests hyperosmolar therapy may be helpful in reducing ICP elevations or cerebral edema in patients with SAH, TBI, AIS, ICH, and HE, although neurological outcomes do not appear to be affected. Corticosteroids appear to be helpful in reducing cerebral edema in patients with bacterial meningitis, but not ICH. Differences in therapeutic response and safety may exist between HTS and mannitol. The use of these agents in these critical clinical situations merits close monitoring for adverse effects. There is a dire need for high-quality research to better inform clinicians of the best options for individualized care of patients with cerebral edema.

The prevalence of the metabolic syndrome (MetS) and its cardiac comorbidities as cardiac hypertrophy (CH) have increased considerably due to the high consumption of carbohydrates, such as sucrose and/or fructose. We compared the effects of sucrose (S), fructose (F) and their combination (S + F) on the development of MetS in weaned male Wistar rats and established the relationship between the consumption of these sugars and the degree of cardiac CH development, oxidative stress (OS) and Calcium/calmodulin-dependent protein kinase type II subunit delta oxidation (ox-CaMKIIδ). 12 weeks after the beginning of treatments with S, F or S + F, arterial pressure was measured and 8 weeks later (to complete 20 weeks) the animals were sacrificed and blood samples, visceral adipose tissue and hearts were obtained. Biochemical parameters were determined in serum and cardiac tissue to evaluate the development of MetS and OS. To evaluate CH, atrial natriuretic peptide (ANP), CaMKIIδ and ox-CaMKIIδ were determined by western blot and histological studies were performed in cardiac tissue. Our data showed that chronic consumption of S + F exacerbates MetS-induced CH which is related with a higher OS and ox-CaMKIIδ.

Background Improvements in technology play an important role in caring for critically ill patients. One example is the advance in ventilator design to facilitate triggering of mechanical breaths. Minimal changes in circuit flow unrelated to respiratory effort can trigger a ventilator breath and may mislead caregivers in recognizing brain death. Methods We observed patients with devastating brain injuries in a mixed medical/surgical intensive care unit (ICU) with a high clinical suspicion for brain death including the absence of cranial nerve function with apparent spontaneous breathing during patient-triggered modes of mechanical ventilation. Further clinical observation for spontaneous respirations was assessed upon removal of ventilatory support. Results Nine patients with brain injury due to multiple etiologies were identified and demonstrated no spontaneous respirations when formally assessed for apnea. Length of time between brain death and its recognition could not be determined. Conclusion When brain-dead patients who are suitable organ donors are mistakenly identified as having cerebral activity, the diagnosis of brain death is delayed. This delay impacts resource utilization, impedes recovery and function of organs for donation, and adversely affects donor families, potential recipients of organs, and patient donors who may have testing and treatment that cannot be beneficial. Patients with catastrophic brain injury and absent cranial nerve function should undergo immediate formal apnea testing.

PurposeEvaluate the therapeutic effect of a tomato lipidic extract (STE) in combination with selenium (Se) on rats with prostatic hyperplasia (PH) and to observe its possible mechanisms of action and synergism versus finasteride.Materials and methods54 male Wistar rats of nine weeks old were divided in Control (C), PH, Finasteride (F), STE, Se, F + STE, F + Se, STE + Se and F + STE + Se with testosterone enanthate (except C). After 4 weeks of treatment administration, prostate weight, bladder weight, diuresis, prooxidant and antioxidant activity, dihydrotestosterone (DHT), androgen receptor (AR) expression and anatomopathological analysis were determined.ResultsSTE + Se decreased prostate weight 53.8% versus 28% in F group, also STE + Se decreased significatively glandular hyperplasia, prooxidant activity, DHT and AR expression and increased diuresis and antioxidant activity versus finasteride which increased MDA in prostate.ConclusionsThese results demonstrate a greater therapeutic and beneficial effect of tomato lipidic extract in combination with Se in young rats with PH with respect to finasteride without increase prooxidant activity.

Purpose Tomato is an important source of lycopene, a carotenoid that has been emerging as a natural preventive agent for prostate disease. Moreover, tomato contains other components with a wide range of physiological properties, but their potential beneficial effects on prostatic hyperplasia (PH) during obesity have not been completely established. In this study, we compared the effect of a lipidic extract of tomato saladette (STE) with Serenoa repens ( SR ) on obese rats with PH. Methods Forty-eight Wistar rats were divided in Control (C) and Obese (Ob) treated without ( n  = 12) and with ( n  = 36) testosterone enanthate (TE), once a week for 8 weeks to induce PH. After 4 weeks, SR and STE were administered. Biochemical parameters, oxidative stress markers and inflammatory cytokines production were determined. Results TE increased prostate weight and caused prostatic hyperplasia in C group, and these effects were exacerbated by obesity. SR and STE reverted the increase in prostate weight and hyperplasia caused by TE in C and Ob groups. Obesity increased LDL, TGs, NOx and MAD, but decreased HDLc, GSx, SOD and CAT. SR reverted the effects of obesity, but these were significantly reduced and HDLc increased with STE. Obesity and TE increased TNFα, IL-1β and IL-6 levels, but these were partially reverted by STE compared with SR . Conclusions Excess of fat tissue increases the alterations by PH. STE diminishes these alterations compared with SR , suggesting its beneficial effect to improve prostate function. Whole tomato lipid extract could serve as sole therapy or as an adjunct to pharmacological treatment for PH.