Application and internal validation of lung ultrasound score in COVID-19 setting: The ECOVITA observational study.

BACKGROUND: The severe acute respiratory syndrome Coronarovirus-2 associated still causes a significant number of deaths and hospitalizations mainly by the development of respiratory failure. We aim to validate lung ultrasound score in order to predict mortality and the severity of the clinical course related to the need of respiratory support. METHODS: In this prospective multicenter hospital-based cohort study, all adult patients with diagnosis of SARS-CoV-2 infection, performed by real-time reverse transcription polymerase chain reaction were included. Upon admission, all patients underwent blood gas analysis and lung ultrasound by expert operators. The acquisition of ultrasound scan was performed on 12 peculiar anatomic landmarks of the chest. Lung ultrasound findings were classified according to a scoring method, ranging 0 to 3: Score 0: normal A-lines. Score 1: multiple separated B-lines. Score 2: coalescent B-lines, alteration of pleural line. Score 3: consolidation area. RESULTS: One thousand and seven patients were included in statistical analysis (male 62.4 %, mean age 66.3). Oxygen support was needed in 811 (80.5 %) patients. The median ultrasound score was 24 and the risk of having more invasive respiratory support increased in relation to higher values score computed. Lung ultrasound score showed negative strong correlation (rho: -0.71) with the P/F ratio and a significant association with in-hospital mortality (OR 1.11, 95 %CI 1.07-1.14; p < 0.001), even after adjustment with the following variables (age, sex, P/F ratio, SpO2, lactate, hypertension, chronic renal failure, diabetes, and obesity). CONCLUSIONS: The novelty of this research corroborates and validates the 12-field lung ultrasound score as tool for predicting mortality and severity clinical course in COVID-19 patients. Baseline lung ultrasound score was associated with in-hospital mortality and requirement of intensive respiratory support and predict the risk of IOT among COVID-19 patients.

Blood lactate in mild and moderate ARDS secondary to SARS COV 2.

BACKGROUND AND OBJECTIVES: Elevated blood lactate levels are associated with poor outcome in several critical conditions. Patients with SARS-CoV-2 rarely develop hyperlactatemia. The purpose of this study is to evaluate the trend of lactatemia in patients affected by mild/moderate SARS-Co V-2-ARDS and if it affected prognosis. METHODS: We analyzed blood lactate levels in thirty-eight patients with severe SARS-CoV-2 infection admitted to COVID Care Unit of Santa Maria delle Grazie Hospital, Pozzuoli. RESULTS: Twenty patients survived and were discharged at home and 18 patients died. Despite severe hypoxia that affected all patients enrolled, T0 lactate was within normal values. All survivors showed a significant increase in lactate concentration the day prior to clinical improvement. In not-survivors levels of lactate did not increase significantly. CONCLUSION: In our study, patients who survive SARS CoV-2 ARDS have a fleeting increase in lactate, which precedes clinical improvement by one day.

Non-invasive CPAP in mild and moderate ARDS secondary to SARS-CoV-2.

BACKGROUND: During the COVID-19 outbreak, a very high number of infected patients developed pneumonia and many of them complicated with acute respiratory distress syndrome. The optimal management of respiratory failure and the role of lung ultrasound imaging in the evaluation of efficacy of treatment are unknown. METHODS: In March 2020 we treated 18 patients with mild and moderate ARDS secondary to SARS-CoV-2 with non-invasive continuous positive airway pressure therapy (NI-CPAP). All patients underwent lung ultrasound imaging to verify the entity of lung recruitment after NI-CPAP initiation. RESULTS: After one hour of treatment we observed a significant improvement in PaO2/FiO2 ratio in 10 patients. Notably, only 50 % of them reached an effective improvement in lung aeration detectable with lung ultrasound. In the other 50 % or patients the improvement in PaO2/FiO2 might be related to blood redistribution and reverse of hypoxic vasoconstriction. CONCLUSION: NI- CPAP is a valid therapeutic option in mild and moderate ARDS secondary SARS-CoV-2. Lung recruitment detected by means of lung ultrasound is a relevant but not the exclusive mechanism that underlies the therapeutic efficacy of NI-CPAP in this clinical setting.

Eculizumab treatment in patients with COVID-19: preliminary results from real life ASL Napoli 2 Nord experience.

OBJECTIVE: 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. PATIENTS AND METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Biochemical markers of bone turnover, serum levels of interleukin-6/interleukin-6 soluble receptor and bisphosphonate treatment in Erdheim-Chester disease.

Erdheim-Chester disease (ECD) is a rare non-Langherans form of histiocytosis characterized radiologically by symmetrical sclerosis of the metaphysis and the diaphysis of long tubular bones. Macrophages are potent interleukin-6 (IL-6) producers and elevated IL-6 serum levels have been described in pathological conditions characterized by increased bone resorption. In a patient with ECD, during the acute phase of the disease we found high serum levels of IL-6 and IL-6 soluble receptor (sIL-6R) and high levels of bone turnover markers. After 5 years of combination therapy with oral prednisone and intravenous clodronate a significant reduction in the above mentioned biological parameters was seen. We suggest that the systemic disorders present in ECD could be related to the high serum levels of IL-6 and sIL-6R. We also propose the use of bisphosphonates in the clinical management of ECD.

Association between vitamin D receptor gene polymorphisms and tubular citrate handling in calcium nephrolithiasis.

OBJECTIVES: Hypocitraturia is a risk factor for calcium nephrolithiasis. 1,25(OH)2D3 influences renal citrate handling and enhances citraturia. The aim of this study was to evaluate the relationship between vitamin D receptor (VDR) allelic variant and urinary citrate excretion in recurrent stone formers (SF) patients. DESIGN: Case-control study. SUBJECTS: A total of 220 recurrent calcium oxalate SF patients and 114 healthy control (C) subjects were enrolled for this study. Subjects with urinary tract infections, hyperparathyroidism, cystinuria >70 micromol/24 h, gouty diathesis, renal tubular acidosis, renal failure, chronic diarrhoeal states, intake of thiazide diuretics, angiotensin-converting enzyme (ACE)-inhibitors, glucocorticoids or oestrogens were excluded. A standard constant diet was given for 7 days. The 24-h urinary citrate excretion and the active tubular reabsorption of filtered citrate (Rcit) were evaluated. Hypocitraturia was defined as a urinary citrate excretion lower than 1.7 mmol day-1. Stone formers patients and C were genotyped for BsmI and TaqI VDR alleles. Contingency table chi-square tests were used to compare genotype frequencies in hypocitraturic SF patients, normocitraturic SF and C. RESULTS: The prevalence of hypocitraturia in SF patients was 32.7% (72 of 200). Hypocitraturia in these patients resulted from excessive Rcit of a normal load of citrate. We found a different distribution (P < 0.05) of BsmI and TaqI VDR genotypes in hypocitraturic SF patients compared with normocitraturic SF and C. In particular, the prevalence of bb and TT VDR genotypes in hypocitraturic SF was significantly higher than in normocitraturic SF and C. CONCLUSIONS: These results point to a genetic association between BsmI and TaqI VDR polymorphisms and idiopathic hypocitraturia in calcium-oxalate recurrent SF patients.

Clodronate treatment reduces serum levels of interleukin-6 soluble receptor in Paget's disease of bone.

OBJECTIVE: Interleukin-6 (IL-6) and its soluble receptor (sIL-6R) stimulate osteoclast formation and activity. The primary cell abnormality in Paget's disease of bone (PDB) involves osteoclasts. Pagetic osteoclasts overproduce IL-6 and IL-6 receptor in vitro. In vivo, IL-6 serum levels are very high in the acute phase of PDB. The aim of this study was to evaluate the modification in the serum levels of IL-6, sIL-6R and osteotropic hormones (parathormone, 25OHD3 and 1,25(OH)2D3) as a in long-term response to clodronate treatment in patients with PDB. METHODS: 16 patients (8 females) with polyostotic PDB were studied. IL-6, sIL-6R and osteotropic hormones serum levels were evaluated in active PDB and after clodronate treatment (300 mg injected intravenously for 5 consecutive days). The sequential changes in total alkaline phosphatase (tALP) serum levels were used to assess the maximal pharmacological response to treatment. RESULTS: In untreated pagetic patients, mean serum levels of IL-6 (3.20+/-1.18 pg/ml) and sIL-6R (35.02+/-8.33 ng/ml) were significantly increased. Serum osteotropic hormone levels fell within the normal range. Eight weeks after treatment, the maximal pharmacological response to clodronate was associated with a significant reduction of sIL-6R serum levels in all patients, without a significant variation in serum IL-6 and osteotropic hormone levels. Moreover, we observed a correlation between lower sIL-6R serum levels before clodronate therapy and complete remission of PBD, defined as a decrease of tALP serum levels within the normal range. CONCLUSION: The decrease in serum sIL-6R levels could be one of the molecular mechanisms that play a role in the clinical response to clodronate treatment in PDB.