Abstract
Introduction
Fluid challenges are widely adopted in critically ill patients to reverse haemodynamic instability. We reviewed the literature to appraise fluid challenge characteristics in ...intensive care unit (ICU) patients receiving haemodynamic monitoring and considered two decades: 2000–2010 and 2011–2021.
Methods
We assessed research studies and collected data regarding study setting, patient population, fluid challenge characteristics, and monitoring. MEDLINE, Embase, and Cochrane search engines were used. A fluid challenge was defined as an infusion of a definite quantity of fluid (expressed as a volume in mL or ml/kg) in a fixed time (expressed in minutes), whose outcome was defined as a change in predefined haemodynamic variables above a predetermined threshold.
Results
We included 124 studies, 32 (25.8%) published in 2000–2010 and 92 (74.2%) in 2011–2021, overall enrolling 6,086 patients, who presented sepsis/septic shock in 50.6% of cases. The fluid challenge usually consisted of 500 mL (76.6%) of crystalloids (56.6%) infused with a rate of 25 mL/min. Fluid responsiveness was usually defined by a cardiac output/index (CO/CI) increase ≥ 15% (70.9%). The infusion time was quicker (15 min vs 30 min), and crystalloids were more frequent in the 2011–2021 compared to the 2000–2010 period.
Conclusions
In the literature, fluid challenges are usually performed by infusing 500 mL of crystalloids bolus in less than 20 min. A positive fluid challenge response, reported in 52% of ICU patients, is generally defined by a CO/CI increase ≥ 15%. Compared to the 2000–2010 decade, in 2011–2021 the infusion time of the fluid challenge was shorter, and crystalloids were more frequently used.
We aimed to characterise a large population of coronavirus disease 2019 (COVID-19) patients with moderate-to-severe hypoxaemic acute respiratory failure (ARF) receiving continuous positive airway ...pressure (CPAP) outside the intensive care unit (ICU), and to ascertain whether the duration of CPAP application increased the risk of mortality for patients requiring intubation.
In this retrospective, multicentre cohort study, we included adult COVID-19 patients, treated with CPAP outside ICU for hypoxaemic ARF from 1 March to 15 April, 2020. We collected demographic and clinical data, including CPAP therapeutic goal, hospital length of stay and 60-day in-hospital mortality.
The study included 537 patients with a median (interquartile range (IQR) age of 69 (60-76) years. 391 (73%) were male. According to the pre-defined CPAP therapeutic goal, 397 (74%) patients were included in the full treatment subgroup, and 140 (26%) in the do not intubate (DNI) subgroup. Median (IQR) CPAP duration was 4 (1-8) days, while hospital length of stay was 16 (9-27) days. 60-day in-hospital mortality was 34% (95% CI 0.304-0.384%) overall, and 21% (95% CI 0.169-0.249%) and 73% (95% CI 0.648-0.787%) for full treatment and DNI subgroups, respectively. In the full treatment subgroup, in-hospital mortality was 42% (95% CI 0.345-0.488%) for 180 (45%) CPAP failures requiring intubation, and 2% (95% CI 0.008-0.035%) for the remaining 217 (55%) patients who succeeded. Delaying intubation was associated with increased mortality (hazard ratio 1.093, 95% CI 1.010-1.184).
We described a large population of COVID-19 patients treated with CPAP outside ICU. Intubation delay represents a risk factor for mortality. Further investigation is needed for early identification of CPAP failures.
Abstract
Background
Capillary refill time (CRT) has been suggested as a variable to follow during the course of septic shock. We systematically investigated the effects on CRT of volume expansion and ...norepinephrine.
Methods
In 69 septic shock patients, we recorded mean arterial pressure (MAP), cardiac index (CI), and 5 consecutive CRT measurements (video method, standardized pressure applied on the fingertip) before and after a 500-mL saline infusion in 33 patients and before and after an increase of the norepinephrine dose in 36 different patients. Fluid responders were defined by an increase in CI ≥ 15%, and norepinephrine responders by an increase in MAP ≥ 15%.
Results
The least significant change of CRT was 23%, so that changes in CRT were considered significant if larger than 23%. With volume expansion, CRT remained unchanged on average in patients with baseline CRT < 3 s (n = 7) and in all but one patient with baseline CRT ≥ 3 s in whom fluid increased CI < 15% (n = 13 “fluid non-responders”). In fluid responders with baseline CRT ≥ 3 s (n = 13), CRT decreased in 8 patients and remained unchanged in the others, exhibiting a dissociation between CI and CRT responses. The proportion of patients included > 24 h after starting norepinephrine was higher in patients with such a dissociation than in the other ones (60% vs. 0%, respectively). Norepinephrine did not change CRT significantly (except in one patient) if baseline CRT was ≥ 3 s and the increase in MAP < 15% (n = 6). In norepinephrine responders with prolonged baseline CRT (n = 11), it increased in 4 patients and remained unchanged in the other ones, which exhibited a dissociation between MAP and CRT responses.
Conclusions
In septic shock patients with prolonged CRT, CRT very rarely improves with treatment when volume expansion increases cardiac output < 15% and increasing norepinephrine increases MAP < 15%. When the effects of fluid infusion on cardiac output and of norepinephrine on MAP are significant, the response of CRT is variable, as it decreases in some patients and remains stable in others which exhibit a dissociation between changes in macrohemodynamic variables and in CRT. In this regard, CRT behaves as a marker of microcirculation.
Trial registration
: ClinicalTrial.gov (NCT04870892). Registered January15, 2021. Ethics committee approval CE SRLF 21-25.
Rationale. A U-shape relationship should exist between lung volume and pulmonary vascular resistance (PVR), with minimal PVR at functional residual capacity. Thus, positive end-expiratory pressure ...(PEEP) in patients with acute respiratory distress syndrome (ARDS) should increase PVR if it induces significant lung distension compared to recruitment. However, this has never been proven in patients. Objectives. To study the effects of PEEP on PVR according to lung recruitability, evaluated by the recruitment-to-inflation (R/I) ratio. Methods. In patients with ARDS, we measured hemodynamic (pulmonary artery catheter), echocardiographic and ventilatory variables (including esophageal pressure), at both low PEEP and higher PEEP by 10 cmH2O. Preload responsiveness was assessed by the passive leg raising test at high PEEP. Measurements and Main Results. We enrolled 23 patients, including 10 low recruiters (R/I <0.5) and 13 high recruiters (R/I ≥0.5). Raising PEEP from 4 (2-5) to 14 (12-15) cmH2O increased PVR in low recruiters (from 160 (120-297) to 243 (166-380) dyn.s/cm5, p<0.01), while PVR was unchanged in high recruiters (from 224 (185-289) to 235 (168-300) dyn.s/cm5, p=0.55). Right-to-left ventricular end-diastolic areas ratio simultaneously increased in low recruiters (from 0.54 (0.50-0.59) to 0.64 (0.56-0.70), p<0.01), while remaining stable in high recruiters (from 0.70 (0.65-0.79) to 0.68 (0.58-0.80), p=0.48). Raising PEEP decreased cardiac index only in preload responsive patients. Conclusions. PEEP increases PVR only when it induces significant lung distension compared to recruitment according to the recruitment-to-inflation ratio. Tailoring PEEP on this recruitability index should mitigate its hemodynamic effects.Rationale. A U-shape relationship should exist between lung volume and pulmonary vascular resistance (PVR), with minimal PVR at functional residual capacity. Thus, positive end-expiratory pressure (PEEP) in patients with acute respiratory distress syndrome (ARDS) should increase PVR if it induces significant lung distension compared to recruitment. However, this has never been proven in patients. Objectives. To study the effects of PEEP on PVR according to lung recruitability, evaluated by the recruitment-to-inflation (R/I) ratio. Methods. In patients with ARDS, we measured hemodynamic (pulmonary artery catheter), echocardiographic and ventilatory variables (including esophageal pressure), at both low PEEP and higher PEEP by 10 cmH2O. Preload responsiveness was assessed by the passive leg raising test at high PEEP. Measurements and Main Results. We enrolled 23 patients, including 10 low recruiters (R/I <0.5) and 13 high recruiters (R/I ≥0.5). Raising PEEP from 4 (2-5) to 14 (12-15) cmH2O increased PVR in low recruiters (from 160 (120-297) to 243 (166-380) dyn.s/cm5, p<0.01), while PVR was unchanged in high recruiters (from 224 (185-289) to 235 (168-300) dyn.s/cm5, p=0.55). Right-to-left ventricular end-diastolic areas ratio simultaneously increased in low recruiters (from 0.54 (0.50-0.59) to 0.64 (0.56-0.70), p<0.01), while remaining stable in high recruiters (from 0.70 (0.65-0.79) to 0.68 (0.58-0.80), p=0.48). Raising PEEP decreased cardiac index only in preload responsive patients. Conclusions. PEEP increases PVR only when it induces significant lung distension compared to recruitment according to the recruitment-to-inflation ratio. Tailoring PEEP on this recruitability index should mitigate its hemodynamic effects.
Fibromyalgia is a syndrome characterized by chronic and widespread musculoskeletal pain, often accompanied by other symptoms, such as fatigue, intestinal disorders and alterations in sleep and mood. ...It is estimated that two to eight percent of the world population is affected by fibromyalgia. From a medical point of view, this pathology still presents inexplicable aspects. It is known that fibromyalgia is caused by a central sensitization phenomenon characterized by the dysfunction of neuro-circuits, which involves the perception, transmission and processing of afferent nociceptive stimuli, with the prevalent manifestation of pain at the level of the locomotor system. In recent years, the pathogenesis of fibromyalgia has also been linked to other factors, such as inflammatory, immune, endocrine, genetic and psychosocial factors. A rheumatologist typically makes a diagnosis of fibromyalgia when the patient describes a history of pain spreading in all quadrants of the body for at least three months and when pain is caused by digital pressure in at least 11 out of 18 allogenic points, called tender points. Fibromyalgia does not involve organic damage, and several diagnostic approaches have been developed in recent years, including the analysis of genetic, epigenetic and serological biomarkers. Symptoms often begin after physical or emotional trauma, but in many cases, there appears to be no obvious trigger. Women are more prone to developing the disease than men. Unfortunately, the conventional medical therapies that target this pathology produce limited benefits. They remain largely pharmacological in nature and tend to treat the symptomatic aspects of various disorders reported by the patient. The statistics, however, highlight the fact that 90% of people with fibromyalgia also turn to complementary medicine to manage their symptoms.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The innate defense system of the female mucosal genital tract involves a close and complex interaction among the healthy vaginal microbiota, different cells, and various proteins that protect the ...host from pathogens. Vaginal lactobacilli and lactoferrin represent two essential actors in the vaginal environment. Lactobacilli represent the dominant bacterial species able to prevent facultative and obligate anaerobes outnumber in vaginal microbiota maintaining healthy microbial homeostasis. Several mechanisms underlie the protection exerted by lactobacilli: competition for nutrients and tissue adherence, reduction of the vaginal pH, modulation of immunity, and production of bioactive compounds. Among bioactive factors of cervicovaginal mucosa, lactoferrin, an iron-binding cationic glycoprotein, is a multifunctional glycoprotein with antibacterial, antifungal, antiviral, and antiparasitic activities, recently emerging as an important modulator of inflammation. Lactobacilli and lactoferrin are largely under the influence of female hormones and of paracrine production of various cytokines. Lactoferrin is strongly increased in lower genital tract mucosal fluid of women affected by
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infections promoting both innate and adaptive immune responses. In vaginal dysbiosis characterized by low amounts of vaginal lactobacilli and increased levels of endogenous anaerobic bacteria, the increase in lactoferrin could act as an immune modulator assuming the role normally played by the healthy microbiota in vaginal mucosa. Then lactoferrin and lactobacilli may be considered as biomarkers of altered microbial homeostasis at vaginal level. Considering the shortage of effective treatments to counteract recurrent and/or antibiotic-resistant bacterial infections, the intravaginal administration of lactobacilli and lactoferrin could be a novel efficient therapeutic strategy and a valuable tool to restore mucosal immune homeostasis.
Introduction Testicular cancer is one of the most treatable cancers, with a 10-year survival of more than 95%. Many patients will be long-term survivors and this disease strikes men in an important ...phase of their lives, therefore the quality of life (QoL) among these patients is an area of particular interest. We aimed to study whether QoL in testicular cancer survivors depends on the time since cancer diagnosis. Methods Data were collected from the EPSAM (Esposizioni postnatali e salute maschile) study, a case-control study on patients with testicular cancer, diagnosed between 1997 and 2008 in the province of Turin, Northern Italy, and interviewed between 2008 and 2010 (response rate among cases 57%). Patients were contacted through their oncologist at the San Giovanni Batista Hospital in Turin or through their general practitioner (GP) in the rest of the Province of Turin. QoL was assessed cross-sectionally using the short form 12 (SF-12) questionnaire, a generic short-form health survey that produces two summary scores, PCS (physical component score) and MCS (mental component score), to evaluate physical and mental health, respectively. Results Out of 234 study patients, 125 cases were seminomas and 109 cases were nonseminomas. The mean age at diagnosis was 34.5 years. After adjusting for age, time since diagnosis was not associated with PCS and MCS scores. Among nonseminomas, the median PCS slightly increased (adjusted OR (odds ratio) for 5+ vs < 2 years since cancer diagnosis: 1.78 (1.17-2.73), p = 0.008) and MCS slightly decreased (adjusted OR per 1-year increase since cancer diagnosis: 0.92, 95% CI: 0.82-1.05, p = 0.23) with time. Similar findings of no association between time since diagnosis and PCS and MCS were found when the analyses were restricted to the subgroup of cancer patients contacted through their oncologist, whose response proportion was 82%. Conclusion In a study of testicular cancer patients interviewed cross-sectionally at 1 to more than 10 years since diagnosis, time since cancer diagnosis was not associated with QoL when we considered all germ-cell testicular cancer patients together. When stratified by histology type, we found certain evidence that nonseminoma cases report higher PCS over time since cancer diagnosis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Gastric ulcer or peptic ulcer is a common disease worldwide. Basically, it develops when there is an imbalance between the protective and aggressive factors, especially at the luminal surface of ...epithelial cells. Thus, there is a constant interest in research new drugs for treatment of gastric ulcer. The snail secretion is a dense mucous, that covers the external surface of the snails, with important functions for the survival of snails. The biological proprieties of snail Helix Aspersa Muller mucus it has been known for centuries to treat human disorders in particular for skin disease. Recently the use of snail mucus has seen a worldwide increase, as a component in cosmetic product and it has been used in particular for the management of wound and skin disorders. In this study we use a murine model of ethanol intragastric administration which has been widely used to test the drugs efficacies and to explore the underlying mechanism for gastric ulcer development. The intragastric ethanol administration causes several mucosal damages and an induction of a severe inflammatory response. Our results show a significant protective effect of snail secretion filtrate in reducing macroscopic and histological lesions, as well the protective effect on mucus content, oxidative stress and inflammatory response. In conclusion this study demonstrate the protective effect of intragastrical snail secretion filtrate, in a model of ethanol-induced gastric ulcer in mice, suggesting its possible useful use in the treatment or prevention of gastric ulcer.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Concerned about environmental pollution, and aware of the comfort that polyethylene provides for daily human life, this work sought to replace a percentage of high‐density polyethylene (HDPE) with ...human or bovine hair. Hair is natural, abundant, light weight, non‐toxic, and disposed of as garbage. The main disadvantage of natural composites is the interfacial adhesion. To increase the interfacial adhesion between hair and HDPE, stearic acid or oleic acid was chemically anchored on the hair surface, which leads to an improved contact angle hysteresis and hydrophobicity. Dynamic‐mechanical properties of the composites were investigated focusing on the type of carboxylic acid used (stearic or oleic acid), hair length, hair type (human or bovine) and amount of hair used in the composite. Taking 40°C as a reference, using 15% of hair with a length of 1 ± 0.15 mm, the highest storage modulus value was obtained with HDPE with human hair modified with oleic acid, exceeding the value of the storage modulus of HDPE by 67.64%. Increasing storage modulus on composites indicates of interfacial interaction and chemical affinity improvement between hair and polyethylene.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Treatment of breast cancer with trastuzumab is complicated by cardiotoxicity in up to 34% of the patients. In most patients, trastuzumab-induced cardiotoxicity (TIC) is reversible: left ventricular ...ejection fraction (LVEF) improves after trastuzumab withdrawal and with, or sometimes without, initiation of heart failure (HF) therapy. The reversibility of TIC, however, is not foreseeable, and identification of patients at risk and of those who will not recover from cardiac dysfunction is crucial. The usefulness of troponin I (TNI) in the identification of patients at risk for TIC and in the prediction of LVEF recovery has never been investigated.
In total, 251 women were enrolled. TNI was measured before and after each trastuzumab cycle. LVEF was evaluated at baseline, every 3 months during trastuzumab therapy, and every 6 months afterward. In case of TIC, trastuzumab was discontinued, and HF treatment with enalapril and carvedilol was initiated. TIC was defined as LVEF decrease of > 10 units and below 50%. Recovery from TIC was defined as LVEF increase above 50%.
TIC occurred in 42 patients (17%) and was more frequent in patients with TNI elevation (TNI+; 62% v 5%; P < .001). Twenty-five patients (60%) recovered from TIC. LVEF recovery occurred less frequently in TNI+ patients (35% v 100%; P < .001). At multivariate analysis, TNI+ was the only independent predictor of TIC (hazard ratio HR, 22.9; 95% CI, 11.6 to 45.5; P < .001) and of lack of LVEF recovery (HR, 2.88; 95% CI,1.78 to 4.65; P < .001).
TNI+ identifies trastuzumab-treated patients who are at risk for cardiotoxicity and are unlikely to recover from cardiac dysfunction despite HF therapy.
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