Laboratory markers included in the Corona Score can identify false negative results on COVID-19 RT-PCR in the emergency room

After December 2019 outbreak in China, the novel Coronavirus infection (COVID-19) has very quickly overflowed worldwide. Infection causes a clinical syndrome encompassing a wide range of clinical features, from asymptomatic or oligosymptomatic course to acute respiratory distress and death. In a very recent work we preliminarily observed that several laboratory tests have been shown as characteristically altered in COVID-19. We aimed to use the Corona score, a validated point-based algorithm to predict the likelihood of COVID-19 infection in patients presenting at the Emergency rooms. This approach combines chest images-relative score and several laboratory parameters to classify emergency room patients. Corona score accuracy was satisfactory, increasing the detection of positive patients’ rate

Long pentraxin 3 as a marker of COVID-19 severity: evidences and perspectives

Several laboratory tests are characteristically altered in Coronavirus Disease 2019 (COVID-19), but are not totally accurate in predicting the disease outcome. The long pentraxin 3 (PTX3) is quickly released directly at inflammation sites by many immune cell types. Previous studies have shown that PTX3 correlated with disease severity in various inflammatory conditions. Our study investigated the use of PTX3 as a potential marker of COVID-19 severity and compared its performance in detecting a more severe form of the disease with that of routine laboratory parameters. Stored serum samples of RT-PCR confirmed COVID-19 cases that had been obtained at hospital admission were retrospectively analysed. Intensive care unit (ICU) stay was considered a surrogate endpoint of severe COVID-19. Pentraxin 3 was measured by a commercial enzyme-linked immunosorbent assay. A total of 96 patients were recruited from May 1st, 2020 to June 30th, 2020; 75/96 were transferred to ICU. Pentraxin 3 was higher in ICU vs non-ICU patients (35.86 vs 10.61 ng/mL, P 18 ng/mL yielded a sensitivity of 96% and a specificity of 100% in identifying patients requiring ICU. High values of PTX3 predict a more severe COVID-19

Noninvasive ventilation

We used bilevel positive airway pressure ventilation (BiPAP; Respironics, Inc.) through a nasal mask to ventilate 57 consecutive, unselected patients with acute respiratory failure who were unresponsive to oxygen and medical therapy alone. We applied noninvasive positive pressure ventilation for almost 22 hours daily, with a median inspiratory positive airway pressure of 15 cm H2O (maximum, 20 cm H2O; minimum, 8 cm H (2O)) and a median expiratory positive airway pressure of 4 cm H2O (range, 8 cm H2O to 3 cm H2O). Seven patients had hypotension (systolic blood pressure <100 mm Hg; mean, 88 +/-6 mm Hg), 11 had radiologic and clinical findings of pulmonary edema, 20 had edema of the legs; 38 had tachycardia; 21 had hypertension; and 20 had arrhythmias. After 24 hours of BiPAP ventilation, only three patients with initial normal blood pressure and none of those with hypotension showed a decrease of 15 mm Hg or more in their mean blood pressure. None failed to respond to BiPAP. Of the 57 patients, 39 were successfully ventilated with BiPAP, and 18 patients required intubation or died

Prolonged Low-Dose Methylprednisolone in Patients With Severe COVID-19 Pneumonia

Background In hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia, progression to acute respiratory failure requiring invasive mechanical ventilation (MV) is associated with significant morbidity and mortality. Severe dysregulated systemic inflammation is the putative mechanism. We hypothesize that early prolonged methylprednisolone (MP) treatment could accelerate disease resolution, decreasing the need for intensive care unit (ICU) admission and mortality. Methods We conducted a multicenter observational study to explore the association between exposure to prolonged, low-dose MP treatment and need for ICU referral, intubation, or death within 28 days (composite primary end point) in patients with severe COVID-19 pneumonia admitted to Italian respiratory high-dependency units. Secondary outcomes were invasive MV-free days and changes in C-reactive protein (CRP) levels. Results Findings are reported as MP (n = 83) vs control (n = 90). The composite primary end point was met by 19 vs 40 (adjusted hazard ratio [aHR], 0.41; 95% CI, 0.24–0.72). Transfer to ICU and invasive MV were necessary in 15 vs 27 (P = .07) and 14 vs 26 (P = .10), respectively. By day 28, the MP group had fewer deaths (6 vs 21; aHR, 0.29; 95% CI, 0.12–0.73) and more days off invasive MV (24.0 ± 9.0 vs 17.5 ± 12.8; P = .001). Study treatment was associated with rapid improvement in PaO2:FiO2 and CRP levels. The complication rate was similar for the 2 groups (P = .84). Conclusion In patients with severe COVID-19 pneumonia, early administration of prolonged MP treatment was associated with a significantly lower hazard of death (71%) and decreased ventilator dependence. Treatment was safe and did not impact viral clearance. A large randomized controlled trial (RECOVERY trial) has been performed that validates these findings. Clinical trial registration. ClinicalTrials.gov NCT04323592.Peer reviewedFinal Published versio

The role of mean corpuscular volume and red cell distribution width in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors: the MARECAP retrospective study

Background: Tyrosine-kinase inhibitors (TKIs) and immunotherapy represent the backbone treatment for metastatic renal cell carcinoma (mRCC) patients. The aim of the present study was to describe mean corpuscular volume (MCV) and red cell distribution width (RDW) in mRCC patients treated with pazopanib or cabozantinib, and to explore their potential impact on oncological outcomes. Materials and methods: We conducted a multicenter retrospective observational study in mRCC patients treated with pazopanib or cabozantinib between January 2012 and December 2020 in nine Italian centers. Descriptive statistics, univariate, and multivariate analyses were performed. Objectives: The primary endpoints were the incidence and trend over time of anemia, macrocytosis (elevated MCV), and anisocytosis (elevated RDW). The secondary endpoints were the correlations of MCV and RDW with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: A total of 301 patients were enrolled; mean Hb value was 12.5 g/dl, a mean increase of 1 g/dl was observed at day 15 and maintained at 3 months. Most patients had baseline macrocytosis (MCV levels &gt; 87 fl), with a significant mean increase after 3 months of treatment. At univariate analysis patients with macrocytosis had better ORR, longer PFS, and OS. About one third of patients had baseline anisocytosis (RDW &gt; 16%), with a significant mean increase after 3 months of treatment. At univariate analysis, patients with RDW values ⩽ 16% had higher ORR, longer PFS, and OS. At multivariate analysis, baseline macrocytosis was significantly associated with better PFS in patients treated with pazopanib and baseline anisocytosis with shorter OS in all patients. Conclusions: mRCC patients treated with pazopanib or cabozantinib may have baseline macrocytosis and anisocytosis. A significant increase of Hb, MCV, and RDW after TKIs start was observed. Baseline macrocytosis is positively correlated with PFS in patients treated with pazopanib and baseline anisocytosis affects survival of patients treated with TKIs

The impact of proton-pump inhibitors administered with tyrosine kinase inhibitors in patients with metastatic renal cell carcinoma

Tyrosine kinase inhibitors (TKIs) are the backbone of the systemic treatment for patients with metastatic renal cell carcinoma (mRCC). TKIs such as pazopanib and cabozantinib can interact with other drugs concomitantly administered, particularly with proton-pump inhibitors (PPIs), possibly impacting the effectiveness of the anticancer treatment and patients outcome. Few data are available about this interaction. We conducted a multicenter retrospective observational data collection of patients with mRCC treated with pazopanib or cabozantinib between January 2012 and December 2020 in nine Italian centers. Univariate and multivariate analyses were performed. The aim was to describe the impact of baseline concomitant PPIs on the outcome of patients to pazopanib and cabozantinib in terms of response, progression-free survival (PFS) and overall survival (OS), toxicity, and treatment compliance. The use of PPI in our study population (301 patients) significantly influenced the effectiveness of TKIs with worse PFS (16.3 vs. 9.9 months; P &lt; 0.001) and OS (30.6 vs. 18.4 months; P = 0.013) in patients taking PPI at TKI initiation. This detrimental effect was maintained both in the pazopanib and cabozantinib groups. The use of PPI influenced the toxicity and TKI treatment compliance with a reduction of dose or schedule modifications, and treatment interruptions in the population taking PPIs. Our study demonstrates that the use of PPIs can significantly influence the outcome and compliance of patients with mRCC to TKI treatment, suggesting the importance of a more careful selection of patients who need a gastroprotective therapy, avoiding indiscriminate use of PPIs

Tailoring treatment with cabozantinib or pazopanib in patients with metastatic renal cell carcinoma: does it affect outcome?

Background: Metastatic renal cell carcinoma (mRCC) treatment is still largely based on TKI use. Treatment adjustment due to toxicities is often needed. The aim of the present study was to determine the impact of treatment modifications on the outcome of mRCC patients treated with cabozantinib or pazopanib. Research design and methods: This retrospective multicenter study enrolled consecutive patients receiving cabozantinib or pazopanib between January 2012 and December 2020. We evaluated the correlation of TKI treatment modifications with grade 3-4 toxicities and progression-free (PFS) and overall survival (OS). We also performed a landmark analysis excluding patients who did not undergo at least 5 months of therapy. Results: Among 301 patients, 179 (59%) were treated with pazopanib, 122 (41%) with cabozantinib. Treatment modifications were related to grade 3-4 toxicities (p &lt; 0.0001). We observed a statistically significant longer PFS and OS in patients who underwent dose reductions (p &lt; 0.0001 for both PFS and OS), temporary interruption (p &lt; 0.0001 for both PFS and OS) and schedule modifications (p = 0.007 for PFS and p = 0.012 for OS) at univariate analysis. These results were confirmed at multivariable and landmark analyses. Conclusions: Tailoring treatment with pazopanib and cabozantinib was associated with better PFS/OS