Do All Critically Ill Patients with COVID-19 Disease Benefit from Adding Tocilizumab to Glucocorticoids? A Retrospective Cohort Study.

BACKGROUND: Treatment guidelines recommend the tocilizumab use in patients with a CRP of >7.5 mg/dL. We aimed to estimate the causal effect of glucocorticoids + tocilizumab on mortality overall and after stratification for PaO2/FiO2 ratio and CRP levels. METHODS: This was an observational cohort study of patients with severe COVID-19 pneumonia. The primary endpoint was day 28 mortality. Survival analysis was conducted to estimate the conditional and average causal effect of glucocorticoids + tocilizumab vs. glucocorticoids alone using Kaplan-Meier curves and Cox regression models with a time-varying variable for the intervention. The hypothesis of the existence of effect measure modification by CRP and PaO2/FiO2 ratio was tested by including an interaction term in the model. RESULTS: In total, 992 patients, median age 69 years, 72.9% males, 597 (60.2%) treated with monotherapy, and 395 (31.8%), adding tocilizumab upon respiratory deterioration, were included. At BL, the two groups differed for median values of CRP (6 vs. 7 mg/dL; p < 0.001) and PaO2/FiO2 ratio (276 vs. 235 mmHg; p < 0.001). In the unadjusted analysis, the mortality was similar in the two groups, but after adjustment for key confounders, a significant effect of glucocorticoids + tocilizumab was observed (adjusted hazard ratio (aHR) = 0.59, 95% CI: 0.38-0.90). Although the study was not powered to detect interactions (p = 0.41), there was a signal for glucocorticoids + tocilizumab to have a larger effect in subsets, especially participants with high levels of CRP at intensification. CONCLUSIONS: Our data confirm that glucocorticoids + tocilizumab vs. glucocorticoids alone confers a survival benefit only in patients with a CRP > 7.5 mg/dL prior to treatment initiation and the largest effect for a CRP > 15 mg/dL. Large randomized studies are needed to establish an exact cut-off for clinical use.

Risk and Management of Bleeding Complications with Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Venous Thromboembolism: a Narrative Review.

Atrial fibrillation (AF) and venous thromboembolism (VTE) are highly prevalent conditions with a significant healthcare burden, and represent the main indications for anticoagulation. Direct oral anticoagulants (DOACs) are the first choice treatment of AF/VTE, and have become the most prescribed class of anticoagulants globally, overtaking vitamin K antagonists (VKAs). Compared to VKAs, DOACs have a similar or better efficacy/safety profile, with reduced risk of intracerebral hemorrhage (ICH), while the risk of major bleeding and other bleeding harms may vary depending on the type of DOAC. We have critically reviewed available evidence from randomized controlled trials and observational studies regarding the risk of bleeding complications of DOACs compared to VKAs in patients with AF and VTE. Special patient populations (e.g., elderly, extreme body weights, chronic kidney disease) have specifically been addressed. Management of bleeding complications and possible resumption of anticoagulation, in particular after ICH and gastrointestinal bleeding, are also discussed. Finally, some suggestions are provided to choose the optimal DOAC to minimize adverse events according to individual patient characteristics and bleeding risk.

How is hydration assessed and managed in acute stroke? A qualitative study of healthcare staff's knowledge, attitudes and experiences.

AIMS AND OBJECTIVES: To explore healthcare staff's experiences of how dehydration is identified and managed in hospitalised patients after acute stroke, and facilitators and challenges to optimising hydration. BACKGROUND: Optimal hydration post-stroke reduces the risk of neurological deterioration and other complications. Patients are at risk of dehydration in acute stroke, particularly those with dysphagia. DESIGN: A descriptive qualitative study reported following the COREQ guidelines. METHODS: Semi-structured interviews, utilising patient vignettes, were conducted in 2018 (Apr-Oct) with a purposive sample of 30 multidisciplinary staff members from two UK stroke units. Interviews were digitally recorded and transcribed verbatim. Content analysis identified common themes which were mapped to the Theoretical Domains Framework and the Behaviour Change Wheel. RESULTS: The themes were mapped to twelve of the fourteen domains in the Theoretical Domains Framework. Participants believed that inadequate hydration management had potentially serious consequences, and described complex knowledge, skills and cognitive elements to effective hydration care. Participants felt that maintaining hydration was a multidisciplinary responsibility requiring good communication. Although the performance of initial dysphagia screening was reinforced by external audit, other areas of post-stroke hydration management were not; notably, there was no established method of assessing hydration. Barriers to maintaining good hydration included lack of staff, out-of-hours working patterns, low priority given to hydration, patients' comorbidities and complex post-stroke disabilities such as dysphagia, aphasia, inattention and hemiparesis. CONCLUSION: Findings highlighted the importance of assessing and maintaining hydration but identified barriers to, and variation in, clinical practice. To provide optimal care, barriers to the prevention and treatment of dehydration after stroke must be further understood and addressed. RELEVANCE TO CLINICAL PRACTICE: Multidisciplinary teamwork is important in hydration care after stroke, but clarity is required about the specific contributions of each team member. Without this, hydration care becomes 'everybody's and nobody's job'.

First and second waves among hospitalised patients with COVID-19 with severe pneumonia: a comparison of 28-day mortality over the 1-year pandemic in a tertiary university hospital in Italy.

OBJECTIVE: The first COVID-19-19 epidemic wave was over the period of February-May 2020. Since 1 October 2020, Italy, as many other European countries, faced a second wave. The aim of this analysis was to compare the 28-day mortality between the two waves among COVID-19 hospitalised patients. DESIGN: Observational cohort study. Standard survival analysis was performed to compare all-cause mortality within 28 days after hospital admission in the two waves. Kaplan-Meier curves as well as Cox regression model analysis were used. The effect of wave on risk of death was shown by means of HRs with 95% CIs. A sensitivity analysis around the impact of the circulating variant as a potential unmeasured confounder was performed. SETTING: University Hospital of Modena, Italy. Patients admitted to the hospital for severe COVID-19 pneumonia during the first (22 February-31 May 2020) and second (1 October-31 December 2020) waves were included. RESULTS: During the two study periods, a total of 1472 patients with severe COVID-19 pneumonia were admitted to our hospital, 449 during the first wave and 1023 during the second. Median age was 70 years (IQR 56-80), 37% women, 49% with PaO2/FiO2 <250 mm Hg, 82% with ≥1 comorbidity, median duration of symptoms was 6 days. 28-day mortality rate was 20.0% (95% CI 16.3 to 23.7) during the first wave vs 14.2% (95% CI 12.0 to 16.3) in the second (log-rank test p value=0.03). After including key predictors of death in the multivariable Cox regression model, the data still strongly suggested a lower 28-day mortality rate in the second wave (aHR=0.64, 95% CI 0.45 to 0.90, p value=0.01). CONCLUSIONS: In our hospitalised patients with COVID-19 with severe pneumonia, the 28-day mortality appeared to be reduced by 36% during the second as compared with the first wave. Further studies are needed to identify factors that may have contributed to this improved survival.

Guide-wire replacement of a mini-midline catheter with a central venous catheter: A retrospective study on 63 cases.

BACKGROUND: Achieving a reliable venous access in a particular subset of patients and/or in emergency settings can be challenging and time-consuming. Furthermore, many hospitalized patients do not meet the criteria for central venous catheter positioning, unless an upgrade of the treatment is further needed. The mini-midline catheter has already showed to be reliable and safe as a stand-alone device, since it is easily and rapidly inserted and can indwell up to 1 month. METHODS: In this further case series, we retrospectively evaluated data from 63 patients where a previously inserted mini-midline catheter was upgraded to a central venous catheter (the devices inserted in the arm replaced by peripherally inserted central catheter and others inserted "off-label" in the internal jugular replaced by single lumen centrally inserted central catheter), being used as introducer for the Seldinger guidewire. RESULTS: The guidewire replacement was been made even early (after 1 day) or late (more than 10 days), usually following a need for an upgrade in treatment. No early or late complications were reported. CONCLUSION: According to the preliminary data we collected, this converting procedure seems to be feasible and risk-free, since neither infectious nor thrombotic complications were reported.

Direct Oral Anticoagulants in Patients with Liver Disease in the Era of Non-Alcoholic Fatty Liver Disease Global Epidemic: A Narrative Review.

Atrial fibrillation (AF) and venous thromboembolism (VTE) are highly prevalent and relevant healthcare issues. Direct oral anticoagulants (DOACs) are now the first-choice for anticoagulant treatment of these conditions displaying a better efficacy/safety profile than vitamin-K antagonists, mainly due to significantly reduced risk of major bleeding, especially of intracranial haemorrhage. Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in developed countries showing a continuously growing prevalence. Nonalcoholic steatohepatitis (NASH), its evolutive form, will be the leading cause for liver transplantation by 2020. NAFLD is independently associated with an increased risk of abnormalities of cardiac structure and function, including cardiac rhythm disorders (mainly AF). Moreover, data suggest an increased risk of unprovoked VTE associated with NAFLD/NASH. Therefore, a growing number of patients with chronic liver disease (CLD) will be candidate for anticoagulant therapy in the near future. Cirrhosis of any etiology is characterized by an unstable thrombosis/bleeding haemostatic balance, making anticoagulant therapy particularly challenging in this condition. Given that patients with significant active liver disease and cirrhosis were excluded from all pivotal randomized controlled trials on DOACs, this comprehensive review aims at critically discussing real-world evidence, including the latest population studies, regarding the use of DOACs in patients with CLD/cirrhosis.

Direct oral anticoagulants for atrial fibrillation in patients with congenital factor VII deficiency.

The management of anticoagulant therapy (OAT) in patients with factor VII (FVII) deficiency is a very challenging clinical issue, as warfarin further reduces FVII levels, thus potentially increasing bleeding risk. On the other hand, the International Normalized Ratio test is misleading in such patients, as they do not reflect the actual level of global inhibition of the coagulation system. We report here three cases of patients with a moderate FVII deficiency and receiving direct oral anticoagulants (DOAC) for prevention of cardioembolism in atrial fibrillation. Of note, two of them experienced a treatment failure while on warfarin, while DOAC treatment was not associated with thrombotic or hemorrhagic adverse events. DOAC are very attractive for the management of OAT in FVII deficient patients, because they do not require monitoring by tests affected by the inherited defect, and their mechanism of action is FVII-independent.

Is there a role for intervention radiology for the treatment of lower limb deep vein thrombosis in the era of direct oral anticoagulants? A comprehensive review.

Despite recent advances in the treatment of Deep Vein Thrombosis (DVT) provided by Direct Oral Anticoagulants (DOAC), a substantial proportion of lower limb DVT patients will develop some degree of post-thrombotic syndrome (PTS) within 2 years. Systemic thrombolysis, although effective in reducing the risk of PTS and leg ulceration, is associated with a high risk of major bleeding, making it unsuitable for the vast majority of patients. A local approach, aimed at delivering the fibrinolytic drug directly into, or near to, the thrombus surface, is attractive because of the possibility of lowering of the administered drug dose, thus reducing the bleeding risks. However, even after the recent publication of the ATTRACT trial, only weak evidence is available about the efficacy and safety of Catheter Directed Thrombolysis (CDT), either alone (pharmacological technique) or in combination with additional endovascular approaches (pharmacomechanical technique, PMT) including percutaneous mechanical thrombectomy, angioplasty with or without stenting and ultrasound-assisted CDT. The present review is aimed at providing the physicians with a comprehensive evaluation of the current evidence about this relevant topic, in order to build a reliable conceptual framework for a more appropriate use of this resource.

Intermittent gastric outlet obstruction due to a gallstone migrated through a cholecysto-gastric fistula: a new variant of "Bouveret's syndrome".

Bouveret's syndrome, defined as gastric outlet obstruction due to a large gallstone, is still one of the most dramatic biliary gallstone complications. Although new radiological and endoscopic techniques have made pre-surgical diagnosis possible in most cases and the death rate has dropped dramatically, "one-stage surgery" (biliary surgery carried out at the same time as the removal of the gut obstruction) should be still considered as the gold standard for the treatment of gallstone ileus.In this case, partial gastric outlet obstruction resulted in an atypical and insidious clinical presentation that allowed us to perform the conventional one-stage laparatomic procedure that completely solved the problem, thus avoiding any further complications.

[Sport's medicalization]. / La medicalizzazione dello sport.

Medicalization (abuse of sport drinks, supplements and drugs) involves more and more of the sport world, casting doubt on the credibility of results. causes and responsibilities are individuated. Characteristics of two commonly used supplements (creatine, branched-chain amino acids) are analyzed in order to show risks and ambiguities for athletes and the way to come out of it.

A new device for measuring resting energy expenditure (REE) in healthy subjects.

BACKGROUND AND AIM: Lifestyle change targeted towards increasing daily resting energy expenditure (REE) is one of the cornerstones of obesity treatment. Measurements of energy expenditure and substrate utilization are essential to understanding the metabolic basis of obesity, and the physiological responses to perturbations in habitual food intake. REE is the largest part of human energy expenditure (60-70%) and an increase or decrease in REE would have a large impact on total energy. Accurate and easy-to-use methods for measuring REE are needed, to be applied by clinicians in daily clinical settings to assess the validity of a new instrument to estimate REE in normal weight, healthy adults. METHODS: Ninety-nine subjects (52 females and 47 males) (mean+/-SD, age 38+/-14 years; body mass index (BMI) 23+/-3 kg/m(2)) were tested. REE was assessed using a Sensor Medics Vmax metabolic cart with a ventilated canopy and with the SenseWear armband. Body composition, percentage fat mass (%FM) and percentage fat free mass (%FFM) were assessed by skinfold thickness measurements (SF), bio-electrical impedance analysis (BIA) and air displacement plethysmography (BOD-POD). RESULTS: No significant difference was found among measurements of FFM using the three different techniques. Both SenseWear and Sensor Medics Vmax showed a high correlation, r=0.42 and r=0.40 (p<0.0001) respectively, with BMI. No significant difference was found in mean REE between SenseWear (1540+/-280 kcal/day) and Sensor Medics Vmax (1700+/-330 kcal/day) (p=ns) and the correlation between REE measured by SenseWear and Sensor Medics Vmax was high (r=0.86, p<0.0001). Bland-Altman plot showed no difference in REE determination between SenseWear and Sensor Medics Vmax. %FFM determined by BOD-POD correlated with SenseWear (r=0.42, p<0.0001) as well as Sensor Medics Vmax (r=0.38, p<0.001). CONCLUSION: SF, BIA and BOD-POD provide valid and reliable measurements of FFM. Our results suggest that the SenseWear armband is an acceptable device to accurately measure REE in healthy subjects. Its characteristics have the potential to reduce measurement times and make the SenseWear armband useful for epidemiological studies.

[Iron and performance in elite athletes]. / Assetto del ferro e prestazioni negli atleti di alto livello.

The negative relationship between performance and iron deficiency anemia is well known. There is still debate in the literature on the exercise-induced iron loss and if low iron store, even in the absence of frank anemia, can adversely affected performance of elite athletes. We analyse the physiologic changes induced by strong exercise, the diagnostic problems and therapeutic supplementation.

[In search of unknown aetiopathogenesis: from Henry Louis ("Lou") Gehrig to Gianluca Signorini: history of the link between amyotrophic lateral sclerosis and sport]. / Storia del rapporto tra sclerosi laterale amiotrofica e sport: alla ricerca dell'etiopatogenesi sconosciuta.

From "Lou" Gehirg to Gianluca Signorini: the history of almost 70 years of link between amyotrophic lateral sclerosis and sport. From first intuitions and assumptions to late epidemiological evidences supporting the possible relation between Italian soccer and amyotrophic lateral sclerosis; comparison among old and new aetiopathogenetic hypothesis.