Sarilumab use in severe SARS-CoV-2 pneumonia

ImportanceInterleukin-6 signal blockade has shown preliminary beneficial effects in treating aberrant host inflammatory response against SARS-CoV-2 leading to severe respiratory distress. Objectiveto describe the effect of off-label intravenous use of Sarilumab in patients with severe SARS-CoV-2-related pneumonia. DesignObservational clinical cohort study. SettingFondazione Policlinico Universitario A. Gemelli IRCCS as Italian Covid reference center. ParticipantsPatients with laboratory-confirmed SARS-CoV-2 infection and respiratory distress with PaO2/FiO2 ratio<300 treated with Sarilumab between March 23rd - April 4th, 2020. Date of final follow-up was April 18, 2020. Main outcomes and measuresWe describe the clinical outcomes of 53 patients with SARS-CoV-2 severe pneumonia treated with intravenous Sarilumab in terms of pulmonary function improvement or Intensive Care Unit (ICU) admission rate in medical wards setting and of live discharge rate in ICU treated patients as well as in terms of safety. Each patient received Sarilumab 400 mg administered intravenously on day 1, with eventual additional infusion based on clinical judgement, and was followed for at least 14 days, unless previously discharged or dead. No gluco-corticosteroids were used at baseline. ResultsOf the 53 SARS-CoV-2pos patients receiving Sarilumab, 39 (73.6%) were treated in medical wards (66.7% with a single infusion) while 14 (26.4%) in ICU (92.6% with a second infusion). The median PaO2/FiO2 of patients in the Medical Ward was 146(IQR:120-212) while the median PaO2/FiO2 of patients in ICU was 112(IQR:100-141.5), respectively. Within the medical wards, 7(17.9%) required ICU admission, 4 of whom were re-admitted to the ward within 5-8 days. At 19 days median follow-up, 89.7% of medical inpatients significantly improved (46.1% after 24 hours, 61.5% after 3 days), 70.6% were discharged from the hospital and 85.7% no longer needed oxygen therapy. Within patients receiving Sarilumab in ICU, 64.2% were discharged from ICU to the ward and 35.8% were still alive at the last follow-up. Overall mortality rate was 5.7% after Sarilumab administration: 1(2.5%) patient died in the Medical Ward whilst 2(14.2%) patients died in ICU, respectively. Conclusions and relevanceIL-6R inhibition appears to be a potential treatment strategy for severe SARS-CoV-2 pneumonia and intravenous Sarilumab seems a promising treatment approach showing, in the short term, an important clinical benefit and good safety. Key pointsO_ST_ABSQuestionC_ST_ABSSARS-CoV-2 infection remains a disease with many unknown aspects for which there are no therapies with proven efficacy. To date, it is recognized that COVID-19 disease may lead to the development of a cytokine storm for which drugs as IL-6R inhibitors may have beneficial effect. FindingsIn this observational clinical study, we reported the efficacy and safety of intravenous Sarilumab use in SARS-CoV-2 severe pneumonia with a global resolution rate of 83.0% (89.7% in medical wards and 64.3% in ICU) and an overall mortality rate of 5.7%. MeaningIL-6R-inhibition is an effective approach for severe SARS-CoV-2 pneumonia and intravenous Sarilumab is a promising treatment approach leading to an important clinical benefit and good safety in the short term.

High Efficacy and Safety of Flat-Dose Ribavirin Plus Sofosbuvir/Daclatasvir in Genotype 3 Cirrhotic Patients

Background/Aims@#Patients with genotype 3 hepatitis C virus (G3-HCV) cirrhosis are very difficult to treat compared to patients with other HCV genotypes. The optimal treatment duration and drug regimen associated with ribavirin (RBV) remain unclear. To evaluate the efficacy and safety of daclatasvir (DCV)/sofosbuvir (SOF) plus a flat dose of 800 mg RBV (flat dose) compared to DCV/SOF without RBV or DCV/SOF plus an RBV dose based on body weight (weight-based) in G3-HCV patients with compensated or decompensated cirrhosis. @*Methods@#We analyzed data for 233 G3 cirrhotic patients. Of these, 70 (30%), 87(37%) and 76 (33%) received SOF/DCV, SOF/DCV/RBV flat dose, and SOF/DCV/RBV weight-based dose, respectively. Treatment duration was 24 weeks. Sustained virological response (SVR) was evaluated at week 12 posttreatment (SVR12). @*Results@#Overall, SVR12 was achieved in 220 out of 233 patients (94.4%). The SVR12 rate was lower in the DCV/SOF group than in the DCV/SOF/RBV flat-dose group and the DCV/SOF/RBV weight-based group (87.1% vs 97.7% and 97.4%, respectively, p=0.007). A higher incidence of anemia occurred in the DCV/SOF/RBV weight-based group compared to those in the other two groups (p<0.007). @*Conclusions@#We found that the DCV/SOF/RBV flat-dose regimen is an effective treatment in terms of efficacy and safety in patients with G3-HCV compensated or decompensated cirrhosis. Therefore, antiviral regimens without RBV should be restricted only to naïve patients with G3-HCV compensated cirrhosis who have a clear contraindication for RBV.

Understanding the Complex of Suicide in Depression: from Research to Clinics

Objective@#Amongst psychiatric disorders, major depressive disorder (MDD) is the most prevalent, by affecting approximately 15–17% of the population and showing a high suicide risk rate equivalent to around 15%. The present comprehensive overview aims at evaluating main research studies in the field of MDD at suicide risk, by proposing as well as a schematic suicide risk stratification and useful flow-chart for planning suicide preventive and therapeutic interventions for clinicians. @*Methods@#A broad and comprehensive overview has been here conducted by using PubMed/Medline, combining the search strategy of free text terms and exploded MESH headings for the topics of ‘Major Depressive Disorder’ and ‘Suicide’ as following: ((suicide [Title/Abstract]) AND (major depressive disorder [Title/Abstract])). All articles published in English through May 31, 2019 were summarized in a comprehensive way. @*Results@#Despite possible pathophysiological factors which may explain the complexity of suicide in MDD, scientific evidence supposed the synergic role of genetics, exogenous and endogenous stressors (i.e., interpersonal, professional, financial, as well as psychiatric disorders), epigenetic, the hypothalamic-pituitary-adrenal stress-response system, the involvement of the monoaminergic neurotransmitter systems, particularly the serotonergic ones, the lipid profile, neuro-immunological biomarkers, the Brain-derived neurotrophic factor and other neuromodulators. @*Conclusion@#The present overview reported that suicide is a highly complex and multifaceted phenomenon in which a large plethora of mechanisms could be variable implicated, particularly amongst MDD subjects. Beyond these consideration, modern psychiatry needs a better interpretation of suicide risk with a more careful assessment of suicide risk stratification and planning of clinical and treatment interventions.

Alexithymia, Suicide Ideation and Homocysteine Levels in Drug Naïve Patients with Major Depression: A Study in the “Real World” Clinical Practice

OBJECTIVE: This study was performed to elucidate relationships between alexithymia, suicide ideation and homocysteine levels in drug-naïve outpatients with major depressive disorder (MDD). METHODS: Sixty seven outpatients with MDD with melancholic features were evaluated by the means of the Hamilton Depression Rating Scale, the Toronto Alexithymia Scale (TAS–20), the Scale of Suicide Ideation, and homocysteine levels. RESULTS: Alexithymic subjects showed higher scores on all scales and higher homocysteine levels. Regression analysis shown higher homocysteine levels and TAS-20’ “Difficulty in Describing Feelings” dimension, in turn being associated with higher suicide ideation. CONCLUSION: In conclusion, alexithymic MDD outpatients may characterize for homocysteine dysregulation that may be linked to suicide ideation, regardless depression’ severity. However, study limitations are discussed and must be considered.

Hepatic vein transit time of second-generation ultrasound contrast agent: new tool in the assessment of portal hypertension.

PURPOSE: It has been demonstrated that Doppler waveform of the hepatic vein (normally triphasic) is transformed into a biphasic or monophasic waveform in cirrhotic patients. The compressive mechanism of liver tissue has been considered up till now the cause of this change. Moreover, cirrhotics show, after USCA injection, a much earlier HVTT due to intrahepatic shunts. Our aim was to prospectively evaluate the correlation between Doppler pattern of hepatic vein and HVTT of a second-generation USCA; we also correlated HVTT with the most common indexes of portal hypertension. METHODS: We enrolled 38 participants: 33 cirrhotics and 5 healthy controls. Doppler shift signals were obtained from the right hepatic vein. To characterize the hepatic vein pattern, we used the hepatic vein waveform index (HVWI). This index becomes >1 with the appearance of the triphasic waveform. We recorded a clip from 20 s before to 2 min after a peripheral intravenous bolus injection of 2.4 ml of USCA (sulfur hexafluoride).The time employed by USCA to cross the liver from the hepatic artery and portal vein to the hepatic vein was defined as HA-HVTT and PV-HVTT, respectively. RESULTS: Cirrhotics with low HVWI showed an earlier transit time; participants with higher HVWI had a longer transit time (p < 0.001). HVTT was earlier as MELD, Child-Pugh score and spleen diameter increased. Patients with ascites and varices of large size had significantly shorter transit times. CONCLUSIONS: Abnormal hepatic vein Doppler waveform in cirrhotic patients could be due to intrahepatic shunts. HVTT could be useful in the non-invasive evaluation of portal hypertension.

Sensory Processing Disorders are Associated with Duration of Current Episode and Severity of Side Effects

OBJECTIVE: Longer duration of untreated illness, longer duration of current episode, and the severity of medication side effects may negatively impact on the perceived disability and psychosocial impairment of patients with major affective and anxiety disorders. Studies also suggested the involvement of sensory perception in emotional and psychopathological processes. The present study aimed to examine the relationship between Sensory Processing Disorders (SPD), duration of untreated illness and current illness episode, and the severity of side effects related to psychoactive medications. METHODS: The sample included 178 participants with an age ranging from 17 to 85 years (mean=53.84±15.55). Participants were diagnosed with unipolar Major Depressive Disorder (MDD) (50%), Bipolar Disorder (BD) (33.7%), and Anxiety disorders (16.3%). They completed a socio-demographic questionnaire, the Udvalg for Kliniske Undersøgelser (UKU), and Adolescent/Adult Sensory Profile (AASP) questionnaire. RESULTS: Longer duration of current episode correlated with greater registration of sensory input and lower avoidance from sensory input among unipolar patients; with lower registration of sensory input, and higher tendency for sensory sensitivity/avoidance among bipolar participants; with lower sensory sensitivity/avoidance among anxiety participants, respectively. Also, mean UKU total scores correlated with lower sensory sensitivity among bipolar individuals. CONCLUSION: SPD expressed in either hypo/hyper sensitivity may serve to clinically characterize subjects with major affective and anxiety disorders.