SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2)-related pneumonia, referred to as COVID-19 (Coronavirus Disease 19), is a public health emergency as it carries high morbidity, mortality, ...and has no approved specific pharmacological treatments. In this case series, we aimed to report preliminary data obtained with anti-complement C5 therapy with eculizumab in COVID-19 patients admitted to intensive care unit (ICU) of ASL Napoli 2 Nord.
This is a case series of patients with a confirmed diagnosis of SARS-CoV2 infection and severe pneumonia or ARDS who were treated with up to 4 infusions of eculizumab as an off-label agent. Patients were also treated with anticoagulant therapy with Enoxaparin 4000 IU/day via subcutaneous injection, antiviral therapy with Lopinavir 800 mg/day + Ritonavir 200 mg/day, hydroxychloroquine 400 mg/day, ceftriaxone 2 g/day IV, vitamine C 6 g/day for 4 days, and were on Non-Invasive Ventilation (NIV).
We treated four COVID-19 patients admitted to the intensive care unit because of severe pneumonia or ARDS. All patients successfully recovered after treatment with eculizumab. Eculizumab induced a drop in inflammatory markers. Mean C Reactive Protein levels dropped from 14.6 mg/dl to 3.5 mg/dl and the mean duration of the disease was 12.8 days.
Eculizumab has the potential to be a key player in treatment of severe cases of COVID-19. Our results support eculizumab use as an off-label treatment of COVID-19, pending confirmation from the ongoing SOLID-C19 trial.
The potential for Planck to detect clusters of dusty, star-forming galaxies at z > 1 is tested by examining the Herschel-SPIRE images of Planck Early Release Compact Source Catalog sources lying in ...fields observed by the Herschel Multitiered Extragalactic Survey. Of the 16 Planck sources that lie in the ∼90 sq. deg. examined, we find that 12 are associated with single bright Herschel sources. The remaining four are associated with overdensities of Herschel sources, making them candidate clusters of dusty, star-forming galaxies. We use complementary optical/near-IR data for these 'clumps' to test this idea, and find evidence for the presence of galaxy clusters in all four cases. We use photometric redshifts and red sequence galaxies to estimate the redshifts of these clusters, finding that they range from 0.8 to 2.3. These redshifts imply that the Herschel sources in these clusters, which contribute to the detected Planck flux, are forming stars very rapidly, with typical total cluster star formation rates >1000 M yr−1. The high-redshift clusters discovered in these observations are used to constrain the epoch of cluster galaxy formation, finding that the galaxies in our clusters are 1-1.5 Gyr old at z ∼ 1-2. Prospects for the discovery of further clusters of dusty galaxies are discussed, using not only all sky Planck surveys, but also deeper, smaller area, Herschel surveys.
People with balance disorders are characterized as having difficulty with transitional movements, such as the sit-to-stand movement. A valid and feasible tool is needed to help clinicians quantify ...the ability of people with balance disorders to perform transitional movements. The purpose of this study was to describe the concurrent and discriminative validity of data obtained with the Five-Times-Sit-to-Stand Test (FTSST). The FTSST was compared with the Activities-specific Balance Confidence Scale (ABC) and the Dynamic Gait Index (DGI).
Eighty-one subjects without balance disorders and 93 subjects with balance disorders were recruited for the study. Each subject was asked to stand from a 43-cm-high chair 5 times as quickly as possible. The ABC and DGI scores were recorded.
Subjects with balance disorders performed the FTSST more slowly than subjects without balance disorders. Discriminant analysis demonstrated that the FTSST correctly identified 65% of subjects with balance dysfunction, the ABC identified 80%, and the DGI identified 78%. The ability of the FTSST to identify subjects with balance dysfunction was better for subjects younger than 60 years of age (81%).
The FTSST displays discriminative and concurrent validity properties that make this test potentially useful in clinical decision making, although overall the ABC and the DGI are better than the FTSST at discriminating between subjects with and subjects without balance disorders.
Celotno besedilo
Dostopno za:
DOBA, FSPLJ, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Abstract Accelerometry (ACC) shows promise as an easily implemented clinical measure of balance. The purpose of the study was to estimate test–retest reliability of ACC measures and determine the ...relationship between ACC measured at the pelvis and underfoot center of pressure (COP) measures during sensory organization test (SOT) conditions. Eighty-one subjects were recruited from the community with no known orthopedic or vestibular deficits (19–85 years). Subjects completed three consecutive, ninety second trials for each of the six SOT conditions, while wearing the accelerometer. ACC and COP time series were described by calculating the normalized path length, root mean square (RMS), and peak-to-peak values. The test–retest reliability of the three measures within each SOT condition was estimated over three trials using the intraclass correlation coefficient. ACC and COP test–retest reliability were similar, ranging from 0.63 to 0.80 using ACC and 0.42 to 0.81 using COP for the measure of normalized path length. Linear regression between ACC and COP measures showed significant correlation under almost every SOT condition using both single and average measures across trials. The degree of association between COP and ACC was equivalent when using the first trial or the 3-trial average, suggesting that one trial may be sufficient. The use of accelerometry may have value in estimating balance function and minimizing clinical evaluation time.
The Functional Gait Assessment (FGA) is a 10-item gait assessment based on the Dynamic Gait Index. The purpose of this study was to evaluate the reliability, internal consistency, and validity of ...data obtained with the FGA when used with people with vestibular disorders.
Seven physical therapists from various practice settings, 3 physical therapist students, and 6 patients with vestibular disorders volunteered to participate.
All raters were given 10 minutes to review the instructions, the test items, and the grading criteria for the FGA. The 10 raters concurrently rated the performance of the 6 patients on the FGA. Patients completed the FGA twice, with an hour's rest between sessions. Reliability of total FGA scores was assessed using intraclass correlation coefficients (2,1). Internal consistency of the FGA was assessed using the Cronbach alpha and confirmatory factor analysis. Concurrent validity was assessed using the correlation of the FGA scores with balance and gait measurements.
Intraclass correlation coefficients of.86 and.74 were found for interrater and intrarater reliability of the total FGA scores. Internal consistency of the FGA scores was.79. Spearman rank order correlation coefficients of the FGA scores with balance measurements ranged from.11 to.67.
The FGA demonstrates what we believe is acceptable reliability, internal consistency, and concurrent validity with other balance measures used for patients with vestibular disorders.
Celotno besedilo
Dostopno za:
DOBA, FSPLJ, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Summary
Background
In HCV‐infected cirrhotic patients with successfully treated early hepatocellular carcinoma (HCC), the time to HCC recurrence and the effects of sustained viral eradication (SVR) ...by interferon (IFN)‐based or IFN‐free regimens on HCC recurrence remain unclear.
Aim
To perform an indirect comparison of time to recurrence (TTR) in patients with successfully treated early HCC and active HCV infection with those of patients with SVR by IFN‐based and by IFN‐free regimens.
Methods
We evaluated 443 patients with HCV‐related cirrhosis and Barcelona Clinic Liver Cancer Stage A/0 HCC who had a complete radiological response after curative resection or ablation. Active HCV infection was present in 328, selected from the Italian Liver Cancer group cohort; 58 patients had SVR achieved by IFN‐free regimens after HCC cure, and 57 patients had SVR achieved by IFN‐based regimens after HCC cure. Individual data of patients in the last two groups were extracted from available publications.
Results
TTR by Kaplan–Meier curve was significantly lower in patients with active HCV infection compared with those with SVR both by IFN‐free (P = 0.02) and by IFN‐based (P < 0.001) treatments. TTR was similar in patients with SVR by IFN‐free or by IFN‐based (P = 0.49) strategies.
Conclusion
In HCV‐infected, successfully treated patients with early HCC, SVR obtained by IFN‐based or IFN‐free regimens significantly reduce tumour recurrence without differences related to the anti‐viral strategy used.
Summary
Background
Hepatitis C virus (HCV) and alcohol abuse are the main risk factors for hepatocellular carcinoma (HCC) in Western countries.
Aim
To investigate the role of alcoholic aetiology on ...clinical presentation, treatment and outcome of HCC as well as on each Barcelona Clinic Liver Cancer (BCLC) stage, as compared to HCV‐related HCCs.
Methods
A total of 1642 HCV and 573 alcoholic patients from the Italian Liver Cancer (ITA.LI.CA) database, diagnosed with HCC between January 2000 and December 2012 were compared for age, gender, type of diagnosis, tumour burden, portal vein thrombosis (PVT), oesophageal varices, liver function tests, alpha‐fetoprotein, BCLC, treatment and survival. Aetiology was tested as predictor of survival in multivariate Cox regression models and according to HCC stages.
Results
Cirrhosis was present in 96% of cases in both groups. Alcoholic patients were younger, more likely male, with HCC diagnosed outside surveillance, in intermediate/terminal BCLC stage and had worse liver function. After adjustment for the lead‐time, median (95% CI) overall survival (OS) was 27.4 months (21.5–33.2) in alcoholic and 33.6 months (30.7–36.5) in HCV patients (P = 0.021). The prognostic role of aetiology disappeared when survival was assessed in each BCLC stage and in the Cox regression multivariate models.
Conclusions
Alcoholic aetiology affects survival of HCC patients through its negative effects on secondary prevention and cancer presentation but not through a greater cancer aggressiveness or worse treatment result. In fact, survival adjusted for confounding factors was similar in alcoholic and HCV patients.
Multiple sclerosis (MS) is an inflammatory/autoimmune disease of the central nervous system (CNS) mainly mediated by myelin specific T cells. It is widely believed that environmental factors, ...including fungal infections, contribute to disease induction or evolution. Even though Candida infection among MS patients has been described, the participation of this fungus in this pathology is not clear. The purpose of this work was to evaluate the effect of a Candida albicans infection on experimental autoimmune encephalomyelitis (EAE) that is a widely accepted model to study MS. Female C57BL/6 mice were infected with C. albicans and 3 days later, animals were submitted to EAE induction by immunization with myelin oligodendrocyte glycoprotein. Previous infection increased the clinical score and also the body weight loss. EAE aggravation was associated with expansion of peripheral CD4+ T cells and production of high levels of TNF-α, IFN-γ IL-6, and IL-17 by spleen and CNS cells. In addition to yeast and hyphae, fungus specific T cells were found in the CNS. These findings suggest that C. albicans infection before EAE induction aggravates EAE, and possibly MS, mainly by CNS dissemination and local induction of encephalitogenic cytokines. Peripheral production of encephalitogenic cytokines could also contribute to disease aggravation.
The primary purpose of this study was to evaluate acute dose response of different intensities with total volume equalized during the abdominal crunch exercise on muscle thickness, echo-intensity, ...peak force, time under tension, total load lifted, and perception of effort in recreationally-trained participants. Fifteen resistance-trained participants (23 ± 3 years) performed the abdominal crunch exercise in one of two different resistance training (RT) protocols in a randomized order: RT
4×10RM
(4 sets of 10RM / 1-min rest) or RT
1×40RM
(1 set of 40RM). Muscle thickness (MT), echo-intensity (EI), peak force (PF), time under tension (TUT), total load lifted (TLL), and session rating of perceived exertion (sRPE) were measured pre-test and post-test (0-min and 15-min). Two-way repeated-measures ANOVAs (2 × 3) were used to test differences between RT protocols (RT
4×10RM
and RT
1×40RM
) and time (pre-test, post-0, and post-15) for MT, EI, and PF. Paired t-test was used to compare RT protocols for sRPE, TLL, and TUT. For MT, there were significant differences for RT
4×10RM
between pre-x post-0 (
p
= 0.011), pre-x post-15 (
p
< 0.001), and post-0 × post-15 (
p
= 0.02); and for RT
1×40RM
between pre-x post-0 (
p
< 0.001) and pre-x post-15 (
p
= 0.003). For EI, there was a significant difference for RT
4×10RM
between pre-x post-0 (
p
= 0.002). For sRPE, there was no significant difference between RT protocols. For TLL and TUT, there were significant differences between RT protocols (
p
< 0.05). In conclusion, both RT protocols (RT
4×10RM
and RT
1×40RM
) induced similar increases in MT but not for EI. TLL and TUT were higher for RT
4×10RM
. PF and sRPE were similar between RT protocols.
Primary membranoproliferative glomerulonephritis (MPGN) is a rare glomerulopathy characterized by complement dysregulation. MPGN progresses rapidly to kidney failure when it is associated with ...nephrotic syndrome. We assessed the effects of C5 convertase blockade in patients with MPGN and terminal complement activation.
Prospective off-on-off-on open-label clinical trial.
Consenting patients with immune complex–mediated MPGN (n=6) or C3 glomerulonephritis (n=4) with sC5b-9 (serum complement membrane attack complex) plasma levels>1,000ng/mL and 24-hour proteinuria with protein excretion>3.5g identified from the Italian Registry of MPGN and followed up at the Istituto di Ricerche Farmacologiche Mario Negri IRCCS (Bergamo, Italy) between March 4, 2014, and January 7, 2015.
Anti-C5 monoclonal antibody eculizumab administered during 2 sequential 48-week treatment periods separated by one 12-week washout period.
Primary outcome was change in 24-hour proteinuria (median of 3 consecutive measurements) at 24 and 48 weeks.
Median proteinuria decreased from protein excretion of 6.03 (interquartile range IQR, 4.8-12.4) g/d at baseline to 3.74 (IQR, 3.2-4.4) g/d at 24 weeks (P=0.01) and to 5.06 (IQR, 3.1-5.8) g/d (P=0.006) at 48 weeks of treatment, recovered toward baseline during the washout period, and did not significantly decrease thereafter. Hypoalbuminemia, dyslipidemia, and glomerular sieving function improved during the first treatment period. 3 patients achieved partial remission of nephrotic syndrome and all had undetectable C3 nephritic factors before treatment. Mean measured glomerular filtration rate was 69.7±35.2 versus 87.4±55.1 and 75.8±42.7 versus 76.6±44.1mL/min/1.73m2 at the start versus the end of the first and second treatment periods, respectively, among all 10 study participants. Unlike C3, sC5b-9 plasma levels normalized during both treatment periods and recovered toward baseline during the washout in all patients.
Single-arm design, small sample size.
Eculizumab blunted terminal complement activation in all patients with immune complex–mediated MPGN or C3 glomerulonephritis and nephrotic syndrome, but persistently reduced proteinuria in just a subgroup.
Registered in the EU Clinical Trials Register with study no. 2013-003826-10.
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