Mortality reduction in 46 patients with severe COVID-19 treated with hyperimmune plasma. A proof-of-concept,single-arm,multicenter trial

Hyperimmune plasma from patients convalescing from COVID-19 is a potential treatment for severe COVID-19 in other patients. We conducted a multicenter, one-arm, proof-of-concept interventional study. Patients with COVID-19 with moderate-to-severe acute respiratory distress syndrome, elevated C-reactive protein level and need for mechanical ventilation and/or continuous positive airway pressure were enrolled. One to three units (each of 250-300 mL) of hyperimmune plasma (neutralizing antibody titer ≥1:160) were administered. The primary outcome measure was 7-day hospital mortality. Secondary study outcomes were PaO2/FiO2, changes in laboratory and radiological parameters, weaning from mechanical ventilation and safety of the intervention. The study enrolled 46 patients between March 25 and April 21, 2020. The mean age of the patients was 63 years and 61% were male. Thirty of the patients were on continuous positive airway pressure and seven were intubated. The mean PaO2/FiO2 was 128 (standard deviation [SD] 47). Bilateral infiltrates on chest X-ray were present in 36 patients (84%). The mean duration of symptoms and ARDS was 14 (SD 7) and 6 (SD 3) days, respectively. Three patients (6.5%) died within 7 days as compared to an expected 15% according to national statistics and 30% in a small concurrent cohort of 23 patients. The upper one-sided 90% confidence interval (CI) was 13.9%, allowing rejection of the null hypothesis of a 15% mortality. The PaO2/FiO2 increased by 112 units (95% CI: 82-142) in survivors and the severity of the chest X-ray findings decreased in 23% (95% CI: 5%-42%). C-reactive protein, ferritin and lactate dehydrogenase levels decreased by 60%, 36% and 20%, respectively. Weaning from continuous positive airway pressure was achieved in 26/30 patients and it was possible to extubate three of the seven patients who had been intubated. Five serious adverse events occurred in four patients (2 likely and 2 possibly treatment-related). In conclusion, hyperimmune plasma showed promising benefits in COVID-19. Although these benefits need to be confirmed in a randomized controlled trial, this proof-of-concept study could open the way to future developments including hyperimmune plasma banking, standardized pharmaceutical products and monoclonal antibodies.     

Predominant ultrasonographic extracapsular changes in symptomatic psoriatic dactylitis: results from a multicenter cross-sectional study comparing symptomatic and asymptomatic hand dactylitis

Clinical Rheumatology - Despite diffuse digital swelling, dactylitis may sometimes be asymptomatic. The objective of this study was to compare the clinical and ultrasonographic features of...     

Frailty,psychological well-being,and social isolation in older adults with cognitive impairment during the SARS-CoV-2 pandemic: data from the GeroCovid initiative

Background

The containment measures linked to the COVID-19 pandemic negatively affected the phyco-physical well-being of the population, especially older adults with neurocognitive disorders (NCDs). This study aims to evaluate whether the frailty of NCD patients was associated with different changes in multiple health domains, in particular in relation to loneliness and social isolation, pre- and post-lockdown.

Materials and Methods

Patients were recruited from 10 Italian Centers for Cognitive Disorders and Dementia. Data were collected in the pre-pandemic period (T0), during the pandemic lockdown (T1), and 6–9 months post-lockdown (T2). The UCLA Loneliness Scale-3, Activities of Daily Living (ADL), Instrumental ADL (IADL), Mini-Mental State Examination, and Neuropsychiatric Inventory (NPI) were administered. Caregivers' burden was also tested. Patients were categorized as non-frail, pre-frail, and frail according to the Fatigue, Resistance, Ambulation, Illness, and Loss of Weight scale.

Results

The sample included 165 subjects (61.9% women, mean age 79.5 ± 4.9 years). In the whole sample, the ADL, IADL, and NPI scores significantly declined between T0 and T2. There were no significative variations in functional and cognitive domains between the frail groups. During lockdown we recorded higher Depression Anxiety Stress Scales and Perceived Stress Scale scores in frail people. In multivariable logistic regression, frailty was associated with an increase in social isolation, and a loss of IADL.

Conclusions

We observed a global deterioration in functional and neuro-psychiatric domains irrespective of the degree of frailty. Frailty was associated with the worsening of social isolation during lockdown. Frail patients and their caregivers seemed to experience more anxiety and stress disorders during SARS-CoV-2 pandemic.     

An Italian kindred with FALS due to c.149T>C mutation in the SOD1 gene: case report of an affected family member

We report the first Italian kindred with Familial Amyotrophic Lateral Sclerosis (FALS) due to c.149T>C mutation in the exon 5 of superoxide dismutase-1 (SOD1) gene. The proband was a 49-year-old woman who came to our observation because of an history of progressive limbs weakness and gait impairment. She belonged to a family of 24 affected members. The prevalent phenotype of the affected members was characterized by slowly progressive spinal impairment with proximal distribution of weakness, and bulbar involvement in advanced stages. We briefly reviewed the few previous reports about the same SOD1 mutation and discussed the hypothesis that structural instability of the mutant codon 149 protein may underlie some toxic effects significantly involved in FALS pathogenesis.Key words: Familial ALS (FALS), superoxide dismutase 1 (SOD1), mutation     

Prospective screening increases the detection of potentially curable hepatocellular carcinoma: results in 8900 high-risk patients

Objectives

Historically, only 10% of patients with hepatocellular carcinoma (HCC) are diagnosed with early-stage, potentially curable disease. In this study, chronic hepatitis virus-infected patients were prospectively screened to determine: (i) the proportion of patients diagnosed with potentially curable HCC, and (ii) survival following curative therapy.

Methods

The study included 8900 chronic hepatitis virus-infected patients enrolled in a prospective screening programme, of whom 1335 (15.0%) were infected with hepatitis B virus (HBV), 7120 (80.0%) with hepatitis C virus (HCV), and 445 (5.0%) with both HBV and HCV. Screening was conducted every 6 months and included serum alpha-fetoprotein (AFP) measurement and ultrasonography. Curative treatments included liver transplantation, resection, radiofrequency ablation and/or ethanol injection.

Results

Hepatocellular carcinoma was diagnosed in 765 (8.6%) patients. Of 1602 patients with cirrhosis, 758 (47.3%) developed HCC. Curative treatment was possible in 523 (68.4%) of the 765 HCC patients. Two- and 5-year rates of overall survival in the curative treatment group were 65% and 28%, respectively, compared with 10% and 0% in the advanced disease group (P < 0.001).

Conclusions

Prospective screening of patients at high risk for the development of HCC increases the proportion of patients diagnosed with potentially curable disease. This may result in an increase in the number of longterm survivors. Screening strategies should focus on patients with chronic HBV or HCV infection who have progressed to cirrhosis because more than 40% of these patients will develop HCC.     

Spindle cell lipoma: a rare tumor of the mediastinum

Spindle cell lipoma (SCL) is a rare mediastinal tumor hard to be differentiated from myxoid liposarcoma. We report a patient with an expanding fat density in the aorto-pulmonary window and with a previous history of invasive melanoma of the left pectoralis and subsequent pulmonary metastases successfully treated with chemotherapy. Preoperative diagnosis of the mediastinal lesion was difficult but crucial to determine further therapeutic plan.KEY WORDS : Mediastinum, liposarcoma, lipoma, melanoma, thoracoscopy, thoracotomyA 52-year old man was found to have an enlarging lesion in the fat tissue of the anterior mediastinum (Figure 1). Chest magnetic resonance demonstrated mixed density, mainly fat with fibrous septa and confirmed the suspect of infiltration of the aortic adventitia. However, no metabolic activity was proved by total body PET-CT. Eight years earlier this patient had been diagnosed with melanoma of the left pectoral region with positive sentinel lymph node in the ipsilateral axilla. At one year follow-up chest CT scan, three secondary lung lesions were detected which underwent complete regression following six cycles of chemotherapy. In order to obtain cytological diagnosis, a trans-thoracic fine needle biopsy was performed before admission yielding cytologic features of liposarcoma. However, given the previous history of melanoma, confirmatory biopsy of the mediastinal mass through uniportal video-assisted thoracoscopy was requested and indeed revealed only mature lipomatous tissue with no malignant features. It was felt that the diagnostic conundrum could not be solved on limited specimens. Accordingly, a left thoracotomy in the auscultatory triangle became necessary to remove en-bloc the mediastinal lesion. Macroscopically, the 13 cm × 9 cm × 6 cm mass resembled a mature lipoma except for the presence of gray-white gelatinous foci (Figure 2A). Histopathological examination showed a proliferation of small bland spindle cells, in part hypercellular, mixed with mature adipose tissue embedded in a number of birefringent collagen fibers and heterogeneous vascular pattern. The cells were haphazardly distributed but tended to be arranged in short parallel bundles (Figure 2B,C). Immunohistochemically, the cells were strongly and diffusely positive for CD34, but they were negative at immunoreactivity for panCK (Figure 2D). In addition, these were absence of gene amplification at assessment of MDM2 status (band 12q15) by Fluorescence In Situ Hybridization (FISH). Accordingly, the lesion was diagnosed as a spindle cell lipoma (SCL). The patient has been followed clinically for 12 months and remains symptom and disease free to this day.Open in a separate windowFigure 1Chest CT showing an enlarging lesion in the mediastinal fat.Open in a separate windowFigure 2A. Macroscopic view of the surgical specimen; B,C. Proliferation of mesenchymal neoplastic spindle cells at different magnification arranged in short bundles and separated by dense collagen (H&E 10× e 40×); D. Immunostaining positivity for CD34 (IHC 40×).Originally described by Enzinger and Harvey in 1975 (1), SCL is a benign lesion characterized by the replacement of mature fat by collagen-forming spindle cells. As a rule, this lesion is usually found in men aged 45 to 60 years and are located in the subcutaneous tissue of the back, shoulder and posterior neck (2). Conversely, SCLs are rarely seen in the thoracic cavity (3). According to the classification of mediastinal lipomas by Williams and Parsons (4), the current case would be classifed as pure “intrathoracic” type as it was completely situated within the chest.Sakurai et al. reported only one symptomatic case among a total of 10 cases of intrathoracic lipomas observed over a 16-year period (5). In addition, the only one cervico-mediastinal lesion could not be completely resected despite adequate exposure (5). Indeed, irrespective of the benign histology, intrathoracic lipomas may tend to grow and infiltrate surrounding structures (5), a biological aggressiveness also seen in our patient. The differential diagnosis of SCL includes a variety of benign and malignant entities such as dermatofibrosarcoma protuberans, angiomyofibroblastoma, nodular fascitis, and, myxoid liposarcoma (2). By contrast, spindle cell liposarcomas are characterized by bland spindle cells, mature fat, scattered lipoblasts and only rare cells that may stain for CD34. Traditionally, the identification of lipoblasts, fat necrosis, and, fat with atrophic changes, has been crucial to the diagnosis of liposarcoma. In this setting, tumors that consist predominantly of mature fat with a variable number of atypical spindled cells and lipoblasts are diagnosted as well-differentiated liposarcoma. Local excision is the treatment of choice for SCL, and the correct preoperative diagnosis is difficult (5) but important to avoid an unnecessary extensive surgery.     

Hepatocellular carcinoma: preclinical data on a dual-lumen catheter kit for fibrin sealant infusion following loco-regional treatments

Background

Fibrin sealants are currently used in a variety of surgical and endoscopic settings to improve time to haemostasis, reduce blood loss and complications. However, the application of sealants (composed of two essential components: fibrinogen and thrombin) is not without difficulties. These sealants are normally applied to the resected area using dual-chamber delivery systems. Administration of these substances with different viscosities and diverse flow rates through a long catheter means that a certain amount of force needs to be applied and clot formation and clogging at the distal end of the catheter can occur.

Methods

We designed a novel dual-lumen catheter to facilitate the optimal application of fibrin sealant after diagnostic and therapeutic percutaneous procedures and assessed the efficacy and tolerability of this dual-lumen kit when used in a model of hepatic fine needle aspiration (FNA) biopsy and radiofrequency ablation (RFA) in an in vivo, preclinical porcine study.

Results

The experimental was performed on nine pigs (mean body weight 85?±?7 kg) and with the exception of one pig, all animals survived in good conditions until the day of hepatectomy and euthanasia. The premature death of this animal was in the veterinarian’s judgment caused by a common, non-infective disease. In all nine pigs, bleeding was stopped within 3 minutes of the application of the fibrin sealant and no cases of recurrent bleeding occurred.

Conclusions

The new dual aspect catheter increased ease of delivery of the sealant and FNA liver biopsy and RFA procedures were successfully and safely performed.