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PURPOSE: Adrenal cortical adenomas (ACAs) represent one of the most common endocrine neoplasms. Recently, a genetic syndrome, characterized by tumor-suppressor ARMC5-gene mutations and causing primary macronodular bilateral adrenal hyperplasia with concomitant meningiomas of the central nervous system, has been described. Apart from this rare disorder and despite the well-known influence of steroid hormones on meningiomas, no data are available about the association between ACAs and meningiomas. METHODS: We investigated the prevalence of ACAs in a group of patients with cerebral meningioma undergoing unenhanced chest CT scans before attending surgical treatment. Patients with meningioma were age- and sex-matched in a 1:3 ratio with hospitalized patients for COVID-19. RESULTS: Fifty-six patients with meningioma were included and matched with 168 control patients with COVID-19. One-hundred forty-four (66.1%) were female and the median age was 63 years. Twenty ACAs were detected in the overall population (8.9% of the subjects): 10 in patients with meningioma (18%) and the remaining 10 (6%) in the control group (p = 0.007). Multivariate analysis showed that age and presence of meningioma were statistically associated with the presence of ACAs (p = 0.01, p = 0.008). CONCLUSION: We report, for the first time, a higher prevalence of ACAs in patients with meningioma as compared to age- and sex-matched controls. Larger studies are needed to confirm our data and to clarify the characteristics of the ACAs in patients with meningioma. Whether the detection of ACAs should prompt a neuroimaging evaluation to exclude the presence of meningiomas needs also to be considered.
ABSTRACT
Low Vitamin D (VD) levels in COVID-19 patients have been related to increased disease severity and worse outcomes. However, most of these trials designs were not-controlled and retrospective, including patients with demographic differences and biases potentially influencing the reported associations between lower VD levels and severe COVID-19. Aim of this study was to prospectively evaluate VD levels influence on disease severity in a COVID-19 patients cohort matched for age, sex and comorbidities with control subjects. Patients admitted to San Raffaele University Hospital for COVID-19 from March to June 2021 were consecutively enrolled in this study, which was approved by the local IRB, after giving their informed consent. Severe (i. e. those needing high flow oxygen therapy) and non-severe COVID-19 patients matched for age, sex and comorbidities were recruited at admission in Emergency Department (ED). Control subjects from the outpatient Endocrinology Unit of the same Hospital were enrolled in the same period. We excluded patients with comorbidities and therapies influencing VD metabolism. 25OH-VD levels were evaluated at admission in ED and VD deficiency was defined by serum 25OH-VD below 20 ng/mL. A total of 73 COVID-19 patients and 30 control subjects were included in the study. No differences regarding age, sex and comorbidities were found between patients and control groups, but 25OH-VD levels were statistically lower in COVID-19 patients (13.3 vs 23.6 ng/mL, p<0. 001) with a higher prevalence of VD deficiency (75% vs 43%, p=0. 002). After the ED admission, during the hospitalization, a severe disease occurred in a total of 46 COVID-19 patients, and 27 were affected by a non-severe one. No differences regarding age, sex and comorbidities were found between severe vs non-severe groups, but 25OH-VD was significantly lower in the severe one (11.7 vs 16.7 ng/mL, p=0. 007) with a higher prevalence of VD deficiency (85% vs 59%, p=0. 015). We observed lower 25OH-VD levels at admission in patients with non-invasive mechanical ventilation requirement (n.18) and in those admitted in intensive care unit (n.8) during hospitalization, compared to the other patients (p=0. 003 and p=0. 01), although no differences regarding age and comorbidities were found. Moreover, in patients with VD deficiency we found higher levels of inflammatory markers C-reactive protein and ferritin (69 vs 42 mg/L, p=0. 036;723 vs 414 ng/mL, p=0. 028), and lower SaO2/FiO2 and PaO2/FiO2 ratios (433 vs 447, p=0. 005;261 vs 311;p<0. 001) at hospital admission. In conclusion, our prospective data confirm that low VD levels are widely found in hospitalized COVID-19 patients compared to control subjects and predict increased disease severity independently from age, sex and comorbidities of patients affected. We suggest that tackling VD deficiency may be an effective preventive measure to prevent severe COVID-19.Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
ABSTRACT
Background: The clinical spectrum of COVID-19 ranges from pauci-symptomatic forms to severe disease characterized by respiratory failure requiring mechanical ventilation and intensive care unit (ICU) management, as well as multisystem involvement characterized by sepsis, organ dysfunction and death. Treatment of COVID-19 is not standardized, and respiratory failure from ARDS is the leading cause of mortality;in-hospital mortality at 28-days in our tertiary care center in Lombardia, northern Italy was 23% during the first wave in 2020(Ciceri et al. 2020). Endothelial damage and thrombo-inflammation have been identified as common to both COVID-19 pathophysiology and veno-occlusive disease (VOD/SOS). Defibrotide (DF) has endothelial-protective properties, with pro-fibrinolytic, anti-thrombotic, anti-ischemic, anti-inflammatory, and anti-adhesive activity, but no significant systemic anticoagulant effects and is approved for the treatment of severe VOD/SOS. Aim: A prospective, multicenter, phase II, single-arm, open label trial (DEFI-VID19, NCT04335201) was conducted in patients (pts) with COVID-19 ARDS to evaluate the efficacy of DF in addition to best available therapy per institutional guidelines. The primary endpoint was respiratory-failure rate (RFR) defined as progression of respiratory failure, i.e. severe gas transfer deficit (PaO2/FiO2<200 mmHg), need of ICU or death at day+14 from treatment start. Secondary endpoints included overall survival (OS) at 28 days, duration of hospitalization and safety. A sample size of 50 pts was calculated to detect an absolute reduction of 20% in RFR at day+14, assuming a failure rate in non-treated pts of 70% (alpha=5%, power=90%, two-sided test). Pts received DF intravenously at 6.25 mg/kg/dose by 2-hour infusion repeated every 6 hours. Expected treatment duration was 14 days, with earlier discontinuation if clinical improvement occurred. LMWH at prophylactic dose was allowed. Approval was provided by the National IRB for COVID-19 trials at Institute Spallanzani (Rome) and by the Italian Agency for Drug (AIFA). All patients provided written informed consent. Results: Overall, 52 pts were enrolled from September 2020 to April 2021;48 were evaluated for efficacy and safety;4 pts were excluded due to screen failure (n=2) or withdrawal of informed consent at day 2 after defibrotide was initiated (n=2). Median age was 60.5 years (range 53-71);35 pts (73%) were male and 65% had comorbidities, with high blood pressure, obesity and COPD most common. Two pts had pre-existing diagnoses of non-Hodgkin lymphoma. Median time from onset of COVID-19 symptoms and from Sars-COV2 PCR by nasal swab to enrollment were 8 (range 7-10) and 3 days (range 1-6), respectively. All pts were hospitalized and scale 5 of 8-category ordinal scale by WHO criteria, requiring noninvasive ventilation with CPAP or high-flow oxygen, with a median P/F ratio of 211 (range 134-275) mmHg. At treatment start, the median and (range) lymphocyte counts, LDH, CRP, ferritin, D-dimer and IL-6 were 0.7 (0.5-0.9) x 10e9/L;404 (291-491) U/L;49 (22-97) mg/L;823 (363-1088) ng/ml;0.44 (0.28-1.29) µg/mL and 20 (11-32), respectively. Median treatment duration was 8.5 days (range 6-11). Overall, 13/48 pts (27%) discontinued the treatment due to clinical worsening and/or need of further therapies: 9 pts experienced progressive respiratory failure and 6 of those were transferred to ICU for IOT (one pt required ECMO), and 4 required full anticoagulation due to pulmonary embolism (n=1), ischemic stroke (n=1), and femoral deep venous thrombosis (n=2). All pts who completed the treatment 35/48 (73%) were discharged with no need of oxygen support. Overall, 14 SAEs have been reported in a median time of 6 days (range 2-10): all unrelated to DF. No pts experienced hemorrhagic events. The incidence of RFR at day 14 was 25 (+/- 6)%, and at day 28, 27 (+/- 6) %. Probability of OS at day 28 was 89 (+/-4) %, at day 60 83 (+/- 5)%. Overall, 8 pts died from COVID-19 -related complications. No pts required re-admission after hospital discha ge (median 14 days) or died after discharge. Conclusion: Treatment with DF in pts with grade 5 WHO COVID 19 ARDS does not induce bleeding, and is associated with rapid restoration of respiratory function (73% of pts). Notably, no oxygen support was needed at discharge and a 1-month OS rate of 89% was observed, which is higher than historical controls (77%) treated in the same setting. Disclosures: Richardson: Takeda: Consultancy, Research Funding;AbbVie: Consultancy;Karyopharm: Consultancy, Research Funding;AstraZeneca: Consultancy;Oncopeptides: Consultancy, Research Funding;Jazz Pharmaceuticals: Consultancy, Research Funding;Protocol Intelligence: Consultancy;Secura Bio: Consultancy;Regeneron: Consultancy;Celgene/BMS: Consultancy, Research Funding;GlaxoSmithKline: Consultancy;Janssen: Consultancy;Sanofi: Consultancy. Ciceri: IRCCS Ospedale San Raffaele: Current Employment. Carlo-Stella: Incyte: Honoraria;Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding;Sanofi: Consultancy, Research Funding;AstraZeneca: Honoraria;Celgene: Membership on an entity's Board of Directors or advisory committees;ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding;Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen Oncology: Honoraria;Karyopharm Therapeutics: Membership on an entity's Board of Directors or advisory committees.
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Background: In 2020, in Italy, an estimated 54,976 new diagnoses of breast cancer were made. The State-Regions Agreement has issued the “Guidelines on the organizational and welfare methods of the network on breast unit”, for diagnostic-therapeutic paths in senology. Methods: In the 2018 the Molise Region established a Breast Unit (B.U.);the personalized approach, especially in breast cancer, is more effective by integrating the progress of breast surgery, with staging methods such as MRI, treatment methods, such as neoadjuvant therapy (NACT), able to improve survival and quality of life especially in positive HER2 tumors and typically more aggressive “triple negative” diseases. Every week, in the COVID era on an online platform, the GOM meets to discuss cases;preoperative cases are discussed for which the methods of diagnosis and staging are proposed and the therapeutic hypothesis is discussed. All patients eligible for conservative treatments are stadiated with imaging techniques, in particular MRI, the most accurate tool for the basic evaluation of disease extent, and a biopsy for the evaluation of biological variables. Patological complete response (pCR), defined as the absence of invasive disease in the breast and lymphnodes, should be use to measure response to guide decision making. Results: There were 125 patients diagnosed in 2019, in 2020 there were 157, in 2021 there were 50 (until 18 May). In the year 2019, the B.U. gradually structured. In 2020 the median age was 52 a. (32-72 BC). Of the 157 patients evaluated, 8 or 5.1%, performed neoadjuvant chemotherapy (7 T2 cases, 1 T1c case;5 G3 cases, 3 G2 cases;7 cases with positive RE of which 1 HER-2 score 3+, 1 triple negative). All have undergone quadrantectomy. In 2021 the median age of the 50 patients was 64.5 a. (35-81 BC) and 14 cases, or 28%, performed neoadjuvant chemotherapy (9 T2 cases, 5 T4 cases;13 G3 cases, 1 Case G2;6 HER-2 score 3+ cases;3 triple negative cases and 11 cases with positive RE (all patients are still being treated). Conclusions: In Italy NACT is proposeed to about 20% of women with breast cancer, the European average is about 30% with peaks of 50-60% in Germany and the United Kingdom. The activity data of the B.U. Molise and the systemic treatment with NACT indicate an approach in line with Italian data and with the tendency to improve them since closer to European standards denoting a more modern method and perhaps a real cultural change.
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Background: Secondary bacterial/fungal infection in patients with pandemic strains of Influenza has been well documented in the literature. Little is known about the development of secondary bacterial or fungal infections in patients with COVID- 19. Additionally, COVID patients receiving tocilizumab as treatment may be at higher risk for developing a secondary infection due to theoretical risk of immunosuppression. Table 1 Table 2 Methods: A retrospective analysis of all COVID positive patients admitted to a 128 bed community hospital in Westchester County, NY from March 1 - May 31, 2020. The data was analyzed to determine incidence of secondary infections based on positive cultures in patients and further stratified based on receipt of tocilizumab. Results: Out of 445 COVID positive patients reviewed, 69 (15.5%) had positive bacterial/ fungal cultures. Average age of the patient population reviewed was 64 (range 1 - 106) and 60% of the patients were male. As of May 31, 2020, 114 of the patients had expired, 281 were discharged, 23 were transferred, and 27 were still admitted to the hospital. Of the 445 total patients, 42 received at least 1 dose of tocilizumab. Out of those patients, 6 patients (14.3%) had subsequent positive cultures. (Table 1) This was not statistically significant (p = 0.8185). Most common positive specimens were in urine (n=38), blood (n=33), and respiratory specimens (n=20). Most commonly found co-pathogens were Escherichia coli (n=22), Coagulase-negative staphylococci (n=11), and Pseudomonas aeruginosa (n=9). Of the 69 patients with positive cultures, 27 received ICU level of care. (Table 2) Conclusion: A small retrospective study found that the incidence of bacterial or fungal co-infection for COVID positive patients was high but did not find receipt of tocilizumab was associated with secondary infections. This suggests areas for future study and further investigation as hospitals consider use of immunomodulatory therapies in the treatment of COVID-19.