COVID-19: A complex disease with a unique metabolic signature.

Plasma of COVID-19 patients contains a strong metabolomic/lipoproteomic signature, revealed by the NMR analysis of a cohort of >500 patients sampled during various waves of COVID-19 infection, corresponding to the spread of different variants, and having different vaccination status. This composite signature highlights common traits of the SARS-CoV-2 infection. The most dysregulated molecules display concentration trends that scale with disease severity and might serve as prognostic markers for fatal events. Metabolomics evidence is then used as input data for a sex-specific multi-organ metabolic model. This reconstruction provides a comprehensive view of the impact of COVID-19 on the entire human metabolism. The human (male and female) metabolic network is strongly impacted by the disease to an extent dictated by its severity. A marked metabolic reprogramming at the level of many organs indicates an increase in the generic energetic demand of the organism following infection. Sex-specific modulation of immune response is also suggested.

Profiling metabolites and lipoproteins in COMETA, an Italian cohort of COVID-19 patients.

Metabolomics and lipidomics have been used in several studies to define the biochemical alterations induced by COVID-19 in comparison with healthy controls. Those studies highlighted the presence of a strong signature, attributable to both metabolites and lipoproteins/lipids. Here, 1H NMR spectra were acquired on EDTA-plasma from three groups of subjects: i) hospitalized COVID-19 positive patients (≤21 days from the first positive nasopharyngeal swab); ii) hospitalized COVID-19 positive patients (>21 days from the first positive nasopharyngeal swab); iii) subjects after 2-6 months from SARS-CoV-2 eradication. A Random Forest model built using the EDTA-plasma spectra of COVID-19 patients ≤21 days and Post COVID-19 subjects, provided a high discrimination accuracy (93.6%), indicating both the presence of a strong fingerprint of the acute infection and the substantial metabolic healing of Post COVID-19 subjects. The differences originate from significant alterations in the concentrations of 16 metabolites and 74 lipoprotein components. The model was then used to predict the spectra of COVID-19>21 days subjects. In this group, the metabolite levels are closer to those of the Post COVID-19 subjects than to those of the COVID-19≤21 days; the opposite occurs for the lipoproteins. Within the acute phase patients, characteristic trends in metabolite levels are observed as a function of the disease severity. The metabolites found altered in COVID-19≤21 days patients with respect to Post COVID-19 individuals overlap with acute infection biomarkers identified previously in comparison with healthy subjects. Along the trajectory towards healing, the metabolome reverts back to the "healthy" state faster than the lipoproteome.

Caring for nursing home residents with COVID-19: a "hospital-at-nursing home" intermediate care intervention.

BACKGROUND: Nursing home (NH) residents have been dramatically affected by COVID-19, with extremely high rates of hospitalization and mortality. AIMS: To describe the features and impact of an assistance model involving an intermediate care mobile medical specialist team (GIROT, Gruppo Intervento Rapido Ospedale Territorio) aimed at delivering "hospital-at-nursing home" care to NH residents with COVID-19 in Florence, Italy. METHODS: The GIROT activity was set-up during the first wave of the pandemic (W1, March-April 2020) and became a structured healthcare model during the second (W2, October 2020-January 2021). The activity involved (1) infection transmission control among NHs residents and staff, (2) comprehensive geriatric assessment including prognostication and geriatric syndromes management, (3) on-site diagnostic assessment and protocol-based treatment of COVID-19, (4) supply of nursing personnel to understaffed NHs. To estimate the impact of the GIROT intervention, we reported hospitalization and infection lethality rates recorded in SARS-CoV-2-positive NH residents during W1 and W2. RESULTS: The GIROT activity involved 21 NHs (1159 residents) and 43 NHs (2448 residents) during W1 and W2, respectively. The percentage of infected residents was higher in W2 than in W1 (64.5% vs. 38.8%), while both hospitalization and lethality rates significantly decreased in W2 compared to W1 (10.1% vs 58.2% and 23.4% vs 31.1%, respectively). DISCUSSION: Potentiating on-site care in the NHs paralleled a decrease of hospital admissions with no increase of lethality. CONCLUSIONS: An innovative "hospital-at-nursing home" patient-centred care model based on comprehensive geriatric assessment may provide a valuable contribution in fighting COVID-19 in NH residents.

Management of oral anticoagulation in very old patients with non valvular atrial fibrillation related acute ischemic stroke.

The optimal management of oral anticoagulation (OAC) in the acute phase of non valvular atrial fibrillation (NVAF)-related acute ischemic stroke (AIS) remains controversial, especially in very old patients. Therefore, the aim of our study was to evaluate the practical management of OAC in this context. We conducted an observational retrospective study on patients 85-years old and older admitted to two Italian hospitals for NVAF-related AIS. For each patient, clinical and brain computed tomography data were recorded. Type of OAC (vitamin K antagonists, VKAs or Direct Oral Anticoagulants, DOACs), dosage and starting day after AIS were registered. For each patient 90-day all cause mortality, stroke recurrence, any bleeding and modified Rankin scale (mRS) were reported. One-hundred-seventeen patients, with mean age 89.2 ± 3.4 years, were enrolled. In-hospital and 90-day mortality (out of 109 patients) were 6% and 19.7%, respectively. OAC was started in 93 patients (80.5%), on average after 6 ± 3 days from the acute event. Of them, 88 patients (94.6%) received DOACs, while 5 (5.4%) received VKAs. Patients receiving OAC were significantly younger and suffering from less severe stroke compared with patients who did not receive OAC. Patients receiving OAC presented a reduced in-hospital (2.2% vs. 20.8%, p < 0.004) and 90-day all-cause mortality (9.4% vs. 62.5%, p < 0.001). In patients receiving DOACs, low dosages were used in 87.5% of patients. The use of OAC was not associated with an increased rate of hemorrhagic transformation (HT) during hospitalization (13.2% vs. 9.5%, p = 0.54) or any bleeding at 90-day follow-up. Severe dysphagia and mRS ≥ 4 were found to be independent risk factors for not prescribing OAC. The optimal management of OAC in very old patients suffering from NVAF-related AIS remains a dilemma. In our real world study the majority of patients received OAC as secondary prevention treatment without increase in bleeding risk. Dysphagia and severe disability were independent factors for not prescribing OAC. Further investigations aimed at identifying the optimal approach to OAC during the acute phase of NVAF-related ischemic stroke in this subgroup of patients are warranted.

Direct oral anticoagulants in the early phase of non valvular atrial fibrillation-related acute ischemic stroke: focus on real life studies.

Strong evidence for the use of direct oral anticoagulants (DOACs) in the early phase of non valvular atrial fibrillation (NVAF)-related acute ischemic stroke (AIS) is lacking, because this kind of patients were excluded from phase III randomized clinical trials (RCT) and ad hoc RCTs are ongoing. In the latest years a lot of real life studies on this topic have been published. The aim of our review was to focus on these. We reviewed the PubMed databases searching articles reporting on DOACs starting time within 2 weeks from AIS onset. We selected fifteen studies, eight with retrospective, six with prospective observational and one with a prospective, open-label, single arm design. Overall, 2920 patients (47.8% females) were included. In twelve studies median or mean age of patients was over 75 years. Mean or median NIHSS ad hospital admission was ≤ 12 in all studies. About one-third of patients (32.4%) received urgent reperfusion by systemic thrombolysis or mechanical thrombectomy. About one-fifth of patients (22.8%) had large infarct size. Median starting time of DOACs was reported in thirteen studies and it ranged from 2 to 8 days. About one-half of patients (45.9%) received a low dose of DOACs. In studies reporting on median or mean CHA2DS2-VASC score, it was ≥ 3 in all. In studies reporting on median or mean HAS-BLED score, it was ≥ 2 in all. Ninety-day follow-up was available for nine studies, overall including about 2200 patients. Incidence of 90-day TIA/stroke recurrence, symptomatic haemorrhagic transformation or intracranial bleeding and all cause mortality was 2.25%, 0.90% and 1.5%, respectively. The real life evidence suggests that early starting of DOACs in patients with NVAF-related AIS is safe and associated with low recurrence risk and all-cause mortality.

Therapeutic Efficacy of Autologous Non-Mobilized Enriched Circulating Endothelial Progenitors in Patients With Critical Limb Ischemia　- The SCELTA Trial.

BACKGROUND: The therapeutic efficacy of bone marrow mononuclear cells (BM-MNC) autotransplantation in critical limb ischemia (CLI) has been reported. Variable proportions of circulating monocytes express low levels of CD34 (CD14+CD34lowcells) and behave in vitro as endothelial progenitor cells (EPCs). The aim of the present randomized clinical trial was to compare the safety and therapeutic effects of enriched circulating EPCs (ECEPCs) with BM-MNC administration.Methods and Results:ECEPCs (obtained from non-mobilized peripheral blood by immunomagnetic selection of CD14+and CD34+cells) or BM-MNC were injected into the gastrocnemius of the affected limb in 23 and 17 patients, respectively. After a mean of 25.2±18.6-month follow-up, both groups showed significant and progressive improvement in muscle perfusion (primary endpoint), rest pain, consumption of analgesics, pain-free walking distance, wound healing, quality of life, ankle-brachial index, toe-brachial index, and transcutaneous PO2. In ECEPC-treated patients, there was a positive correlation between injected CD14+CD34lowcell counts and the increase in muscle perfusion. The safety profile was comparable between the ECEPC and BM-MNC treatment arms. In both groups, the number of deaths and major amputations was lower compared with eligible untreated patients and historical reference patients. CONCLUSIONS: This study supports previous trials showing the efficacy of BM-MNC autotransplantation in CLI patients and demonstrates comparable therapeutic efficacy between BM-MNC and EPEPCs.

Confidence in the Use of Direct Oral Anticoagulants in the Acute Phase of Nonvalvular Atrial Fibrillation-Related Ischemic Stroke Over the Years: A Real-World Single-Center Study.

BACKGROUD AND AIM: The use of direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation (NVAF)-related acute ischemic stroke (AIS) is controversial. The aims of our study were to analyze physicians' confidence in prescribing DOACs in NVAF-related AIS, the characteristics of patients receiving DOACs, and their 90-day prognosis. MATERIAL AND METHODS: Clinical records of consecutive patients admitted to our wards for NVAF-related AIS over the years 2014-2016 were reviewed. RESULTS: One hundred forty-seven patients, 72.7% females, mean age ± standard deviation 83.4 ± 8.8 years, were admitted to our ward for atrial fibrillation (AF)-related AIS (38 in 2014, 47 in 2015, 62 in 2016). Of these patients, 141 had NVAF-related AIS. Median length of hospital stay was 8 days (interquartile range [IQR], 6-11). In-hospital mortality was 10.8%. Ninety-eight patients (69.5%) received DOACs for secondary prevention, with increasing percentages from 2014 (62.5%) to 2016 (88%). In 88% of them, DOACs were started during hospital stay, whereas in 12% DOACs were started during ambulatory follow-up. The median time for starting DOACs was 5 days (IQR, 3-8). In patients receiving DOACs, the median National Institutes of Health Stroke Scale score was 6 (IQR, 3-12), and large ischemic lesions were present in 48%; the median modified Rankin Scale score at hospital discharge was 3 (IQR, 1-4), whereas the score at 90 days was 2 (IQR, 1-3). At the 90-day follow-up, in patients receiving DOACs, overall mortality was 3.0%, stroke recurrence was 1%, and no patients had major intracranial or extracranial bleedings. CONCLUSION: Our study suggests that physicians are becoming increasingly confident in the use of DOACs in NVAF-related AIS. The use of DOACs seems effective and safe even when started in the acute phase of stroke.

Epidemiology and outcome of Clostridium difficile infections in patients hospitalized in Internal Medicine: findings from the nationwide FADOI-PRACTICE study.

BACKGROUND: Clostridium difficile (CD) is a leading cause of diarrhoea among hospitalized patients. The objective of this study was to evaluate the rate, the optimal diagnostic work-up, and outcome of CD infections (CDI) in Internal Medicine (IM) wards in Italy. METHODS: PRACTICE is an observational prospective study, involving 40 IM Units and evaluating all consecutive patients hospitalized during a 4-month period. CDI were defined in case of diarrhoea when both enzyme immunoassay for GDH, and test for A/B toxin were positive. Patients with CDI were followed-up for recurrences for 4 weeks after the end of therapy. RESULTS: Among the 10,780 patients observed, 103 (0.96 %) showed CDI, at admission or during hospitalization. A positive history for CD, antibiotics in the previous 4 weeks, recent hospitalization, female gender and age were significantly associated with CDI (multivariable analysis). In-hospital mortality was 16.5 % in CD group vs 6.7 % in No-CD group (p < 0.001), whereas median length of hospital stay was 16 (IQR = 13) vs 8 (IQR = 8) days (p < 0.001) among patients with or without CDI, respectively. Rate of CD recurrences was 14.6 %. As a post-hoc evaluation, 23 out of 34 GDH+/Tox- samples were toxin positive, when analysed by molecular method (a real-time PCR assay). The overall CD incidence rate was 5.3/10,000 patient-days. CONCLUSIONS: Our results confirm the severity of CDI in medical wards, showing high in-hospital mortality, prolonged hospitalization and frequent short-term recurrences. Further, our survey supports a 2-3 step algorithm for CD diagnosis: EIA for detecting GDH, A and B toxin, followed by a molecular method in case of toxin-negative samples.

Simplified PESI score and sex difference in prognosis of acute pulmonary embolism: a brief report from a real life study.

Prognostic stratification of acute pulmonary embolism (PE) remains a challenge in clinical practice. Simplified PESI (sPESI) score is a practical validated score aimed to stratify 30-day mortality risk in acute PE. Whether prognostic value of sPESI score differs according to sex has not been previously investigated. Therefore the aim of our study was to provide information about it. Data records of 452 patients, 180 males (39.8 %) and 272 females (60.2 %) discharged for acute PE from Internal Medicine wards of Tuscany (Italy) were analysed. sPESI was retrospectively calculated. Variables enclosed in sPESI score, all cause in-hospital mortality and overall bleedings were compared between sexes. Moreover, predictive ability of sPESI score as prognosticator of all cause in-hospital mortality was tested and compared between sexes. sPESI score 0 (low risk) was found in 17.7 % of males and 13.6 % of females (p = 0.2323). We didn't find significant difference in sPESI scoring distribution. Age ≥80 years (51.4 vs. 33.8 %, p = 0.0003) and heart rate ≥110 bpm (23.5 vs. 14.4 %, p = 0.0219) were found significantly more prevalent in females, whereas active cancer (23.8 vs. 39.4 %, p = 0.0004) and cardio-respiratory diseases (19.8 vs. 27.7 %, p = 0.0416) were in males. All cause in-hospital mortality was 0 % in both genders for sPESI score 0, whereas it was 5.4 % in females and 13.6 % in males with sPESI score 1-2 (p = 0.0208) and 22 % in females and 19.3 % in males with sPESI score ≥3 (p = 0.7776). Overall bleedings were significantly more frequent in females compared with males (4.77 vs. 0.55 %, p = 0.0189). In females overall bleedings ranged from 2.7 % in sPESI score 0 to 6 % in sPESI score ≥3. Predictive ability of sPESI score as prognosticator of all cause in-hospital mortality was higher in females compared to males (AUC 0.72 vs. 0.67, respectively). In real life different co-morbidity burdens in females compared to males. Females seems to be at lower risk of all cause in-hospital mortality for sPESI score ≤2 but at higher risk of bleeding, irrespective from sPESI scoring. Predictive ability of sPESI score seems better in females.

Diabetic Foot Infection: Preliminary Results of a Fast-Track Program with Early Endovascular Revascularization and Local Surgical Treatment.

BACKGROUND: To demonstrate that a fast-track program consisting in early endovascular revascularization and local surgical treatment saves tissue in patients with diabetic foot infection (DFI). METHODS: Between January and December 2014, 48 patients with DFI underwent early endovascular revascularization and local surgical treatment at our Diabetic Foot Center. In all cases, endovascular revascularization and local surgical treatment were performed within 1 week from the diagnosis of infection and during the same hospital stay. One-year outcomes were evaluated in terms of survival, primary patency, primary-assisted patency, secondary patency, absence of target lesion restenosis (TLR), and limb salvage. RESULTS: The patients were predominantly males (34 of 48, 70.8%) with a mean age of 72.4 years (range, 51-91). The target vessel was a tibial artery in 34 cases (70.8%). Surgical treatment consisted of debridement without bone resection in 27 cases (56.2%), toe and/or ray amputation in 15 cases (31.2%), Lisfranc amputation in 2 cases (4.2%), transmetatarsal amputation in 2 cases (4.2%). In the remaining 2 cases, a leg amputation was necessary with an overall 30-day major amputation rate of 4.2%. During the follow-up (mean duration 6.9 months, range 1-12) healing of the lesions was obtained in 30 cases (62.5%). Estimated 12-month survival, primary patency, primary-assisted patency, secondary patency, absence of TLR, and limb salvage rates were 83.5%, 53.4%, 65%, 65%, 60.7%, and 86.6%, respectively. CONCLUSIONS: A fast-track program consisting in early endovascular revascularization and local surgical treatment contributes to our experience in limiting amputation levels in patients with DFI. A multidisciplinary approach and adoption of diabetic foot triage are essential to achieve these outcomes.

Management of new oral anticoagulants related life threatening or major bleedings in real life: a brief report.

Although new oral anticoagulants (NOAs) have been marketed in many countries, concern exists about the management of bleedings related to these drugs due to the lack of specific antidotes. The aim of our study was to report on real life management of NOAs-related life-threatening or major bleedings. We report data from consecutive cases of NOAs related major bleedings admitted to 4 hospitals since NOAs became marketed in Italy. We treated 8 patients, 4 males, with mean age 84 ± 7 years, 7 of whom were on dabigatran and one on rivaroxaban. The indication for NOA was atrial fibrillation. All bleedings were spontaneous and involving the gastro-intestinal tract. At the time of bleeding all patients had a drop in hemoglobin levels over 20 g/L. Creatinine clearance was ≤30 mL/min in 4 patients. All patients received general supportive measures, 4 of 8 patients were transfused with packed red cells and one patient received platelet transfusion. Three patients were treated with tranexamic acid and one patient on dabigatran received 4-factor prothrombin complex concentrate (PCC) with bleeding cessation, although coagulation parameters were not corrected. The median time for normalization of coagulation parameters was 3 days (range 1-6 days). All patients were discharged alive and NOAs were discontinued. In NOAs related major gastro-intestinal bleeding general supportive measures seem to be effective for the majority of patients. Despite promoting bleeding cessation, 4-factor PCC does not reverse abnormal coagulation parameters.

Effects of the implementation of the dynamic silver code in the emergency department.

BACKGROUND: Older persons accessing the Emergency Department (ED) spend more time and are at increased risk of poor outcomes. The Dynamic Silver Code (DSC), based on administrative data, predicts mortality of 75+ subjects visiting the ED. OBJECTIVE: To evaluate the effects of the implementation of the DSC in the ED. METHODS: A pre-post comparison was conducted in the ED of a community hospital in Florence, Italy before and after the DSC was fully implemented. In the post-DSC phase, a clinical decision tree was applied: patients at low-mild risk (DSC class I and II) were assigned to Internal Medicine, those at moderate risk (class III) to Geriatrics, and those at high risk (class IV) required geriatric consultation before assignment. Outcome measures were ED length of stay (LOS) and, in patients admitted to Geriatrics, weight of the Diagnosis Related Groups (DRG), hospital LOS, and mortality. RESULTS: 7,270 patients were enrolled in the pre-DSC and 4,725 in the post-DSC phase. ED LOS decreased from a median of 380 [206, 958] in the pre-DSC to 318 [178, 655] min in the post-DSC period (p<0.001). Class III represented the largest share of admissions to Geriatrics in the post-DSC period (57.7 % vs. 38.3 %; p<0.001). In patients admitted to Geriatrics, hospital LOS decreased by one day (p = 0.006) between the two study periods, with greater DRG weight and comparable mortality. CONCLUSIONS: Application of the DSC seemed to ease patient flow and to reduce LOS of older patients in the ED and increased appropriateness of admissions to Geriatrics.

Delirium and IL-6 added to clinical scores improves their performance: a prospective analysis of CALL, PREDI-CO, MRS score applied to a population of patients admitted to internal medicine ward.

This study aimed to evaluate the effectiveness of various scoring systems in predicting in-hospital mortality for COVID-19 patients admitted to the internal medicine ward. We conducted a prospective collection of clinical data from patients admitted to the Internal Medicine Unit at Santa Maria Nuova Hospital in Florence, Italy, with confirmed pneumonia caused by SARS-CoV-2. We calculated three scoring systems: the CALL score, the PREDI-CO score, and the COVID-19 in-hospital Mortality Risk Score (COVID-19 MRS). The primary endpoint was in-hospital mortality. : A total of 681 patients were enrolled in the study, with a mean age of 68.8 ± 16.1 years, and 54.8% of them were male. Non-survivors had significantly higher scores in all prognostic systems compared to survivors (MRS: 13 [12- 15] vs. 10 [8-12]; CALL: 12 [10-12] vs. 9 [7-11]; PREDI-CO: 4 [3-6] vs. 2 [1-4]; all p<0.001). The receiver operating characteristic (ROC) analysis yielded the following area under the curve (AUC) values: MRS 0.85, CALL 0.78, PREDI-CO 0.77. The addition of Delirium and IL6 to the scoring systems improved their discriminative ability, resulting in AUC values of 0.92 for MRS, 0.87 for CALL, and 0.84 for PREDI-CO. The mortality rate increased significantly across increasing quartiles (p<0.001). In conclusion the COVID-19 in-hospital Mortality Risk Score (MRS) demonstrated reasonable prognostic stratification for patients admitted to the internal medicine ward with SARS-CoV-2-induced pneumonia. The inclusion of Delirium and IL6 as additional prognostic indicators in the scoring systems enhanced their predictive performance, specifically in determining in-hospital mortality among COVID-19 patients.

Clinical and Personal Predictors of Helmet-CPAP Use and Failure in Patients Firstly Admitted to Regular Medical Wards with COVID-19-Related Acute Respiratory Distress Syndrome (hCPAP-f Study).

Acute Respiratory Distress Syndrome (ARDS) caused by COVID-19 is substantially different from ARDS caused by other diseases and its treatment is dissimilar and challenging. As many studies showed conflicting results regarding the use of Non-invasive ventilation in COVID-19-associated ARDS, no unquestionable indications by operational guidelines were reported. The aim of this study was to estimate the use and success rate of Helmet (h) Continuous Positive Airway Pressure (CPAP) in COVID-19-associated ARDS in medical regular wards patients and describe the predictive risk factors for its use and failure. In our monocentric retrospective observational study, we included patients admitted for COVID-19 in medical regular wards. hCPAP was delivered when supplemental conventional or high-flow nasal oxygen failed to achieve respiratory targets. The primary outcomes were hCPAP use and failure rate (including the need to use Bilevel (BL) PAP or oro-tracheal intubation (OTI) and death during ventilation). The secondary outcome was the rate of in-hospital death and OTI. We computed a score derived from the factors independently associated with hCPAP failure. Out of 701 patients admitted with COVID-19 symptoms, 295 were diagnosed with ARDS caused by COVID-19 and treated with hCPAP. Factors associated with the need for hCPAP use were the PaO2/FiO2 ratio < 270, IL-6 serum levels over 46 pg/mL, AST > 33 U/L, and LDH > 570 U/L; age > 78 years and neuropsychiatric conditions were associated with lower use of hCPAP. Failure of hCPAP occurred in 125 patients and was associated with male sex, polypharmacotherapy (at least three medications), platelet count < 180 × 109/L, and PaO2/FiO2 ratio < 240. The computed hCPAP-f Score, ranging from 0 to 11.5 points, had an AUC of 0.74 in predicting hCPAP failure (significantly superior to Call Score), and 0.73 for the secondary outcome (non-inferior to IL-6 serum levels). In conclusion, hCPAP was widely used in patients with COVID-19 symptoms admitted to medical regular wards and developing ARDS, with a low OTI rate. A score computed combining male sex, multi-pharmacotherapy, low platelet count, and low PaO2/FiO2 was able to predict hCPAP failure in hospitalized patients with ARDS caused by COVID-19.

Efficacy and Safety of Edoxaban in Cancer-Associated Venous Thromboembolism: A Real World Retrospective Study.

Introduction Few data exist on the use of edoxaban in cancer-associated venous thromboembolism (VTE) outside of clinical trials. Aim of this study was to evaluate the characteristics and outcomes of these patients in a real world clinical setting. Methods We retrospectively analyzed the characteristics of patients with cancer-associated VTE who were prescribed edoxaban. Follow-up at 3, 6, and 12 months was performed: VTE recurrences, bleedings, mortality, cancer progression and treatment, edoxaban interruption and its reason were assessed. Results Fifty-four patients, 38 females (70.4%), mean age 71 ± 14 years, were enrolled. In 38 patients (70.4%), the episode of VTE was the first one, in 28 (51.8%) it was an isolated deep vein thrombosis (DVT), in 13 (24.1%) a pulmonary embolism (PE) associated with DVT, in 13 (24.1%) an isolated PE. Median time between cancer and VTE diagnosis was 6 (interquartile range [IQR] 2-47) months. Median time between VTE diagnosis and edoxaban prescription was 36 (IQR 7-117) days. At 3, 6, and 12 months the incidence of all-cause mortality was 16.6, 22.2, and 38.8%, that of VTE recurrence 1.8, 1.8, and 3.7%, and that of major bleeding 7.4, 9.2, and 12.9%, respectively. No bleeding was fatal. Of the 33 patients alive at 12 months, 32 (96.9%) were still on edoxaban therapy, in seven (21.2%) cancer was in progression. Conclusion Our study, conducted on a real world population of patients with cancer-associated VTE, confirms the results of randomized controlled clinical trials, and supports the use of edoxaban as effective and safe treatment in this context.

Long-term effects of SARS-CoV-2 vaccination in the nursing home setting.

BACKGROUND: SARS-CoV-2 vaccination has significantly reduced infection, hospitalization, and lethality rates among nursing home (NH) residents, but durability of vaccine effects remains unknown. This study investigated the long-term impact of BNT162b2 SARS-CoV-2 vaccine on breakthrough infection rates in the NHs of Florence, Italy. METHODS: Participants included residents living in Florence NHs as of April 1st, 2021, who had completed the primary SARS-CoV2 vaccination course by February 15th, 2021. Weekly rates of breakthrough infection were calculated between April 1st and October 31st 2021, with 7-day incidence defined as the number of new confirmed SARS-CoV-2-positive residents over the vaccinated resident census. Hospital admissions and deaths were recorded from local administrative and clinical sources. Patients admitted to NHs after April 1st were excluded to avoid confounding effect of different vaccination timing. RESULTS: Among 2271 vaccinated residents (mean age 86.6, 74% female), we recorded 105 cases of breakthrough infections. Rates of breakthrough infection remained very low in the 6 months after vaccination, but started to rise over the following months, peaking at 0.94%, and then became stable around 0.2%-0.3%. Over the study period, infection rates remained low as compared to the incidence of SARS-CoV-2 infection during pre-vaccination period. Overall hospitalization and lethality rates were 8%. CONCLUSIONS: Among vaccinated NH residents, rates of breakthrough SARS-CoV-2 infection, hospitalization and lethality remained low up to 9 months following primary vaccination course. A mild resurgence of SARS-CoV-2 infection, after 6 months from vaccination, suggests a decline of vaccine effectiveness in preventing transmission.

Early reduction of estimated Glomerular Filtration Rate (eGFR) predicts poor outcome in acutely ill hospitalized COVID-19 patients firstly admitted to medical regular wards (eGFR-COV19 study).

BACKGROUND: Analysis of autopsy tissues obtained from patients who died from COVID-19 showed kidney tropism for SARS-COV-2, with COVID-19-related renal dysfunction representing an overlooked problem even in patients lacking previous history of chronic kidney disease. This study aimed to corroborate in a substantial sample of consecutive acutely ill COVID-19 hospitalized patients the efficacy of estimated GFR (eGFR), assessed at hospital admission, to identify acute renal function derangement and the predictive role of its association with in-hospital death and need for mechanical ventilation and admission to intensive care unit (ICU). METHODS: We retrospectively analyzed charts of 764 patients firstly admitted to regular medical wards (Division of Internal Medicine) for symptomatic COVID-19 between March 6th and May 30th, 2020 and between October 1st, 2020 and March 15th, 2021. eGFR values were calculated with the 2021 CKD-EPI formula and assessed at hospital admission and discharge. Baseline creatinine and GFR values were assessed by chart review of patients' medical records from hospital admittance data in the previous year. The primary outcome was in-hospital mortality, while ARDS development and need for non-invasive ventilation (NIV) and invasive mechanical ventilation (IMV) were the secondary outcomes. RESULTS: SARS-COV-2 infection was diagnosed in 764 patients admitted with COVID-19 symptoms. A total of 682 patients (age range 23-100 years) were considered for statistical analysis, 310 needed mechanical ventilation and 137 died. An eGFR value <60 mL/min/1.73 m2 was found in 208 patients, 181 met KDIGO AKI criteria; eGFR values at hospital admission were significantly lower with respect to both hospital discharge and baseline values (p < 0.001). In multivariate analysis, an eGFR value <60 mL/min/1.73 m2 was significantly associated with in-hospital mortality (OR 2.6, 1.7-4.8, p = 0.003); no association was found with both ARDS and need for mechanical ventilation. eGFR was non-inferior to both IL-6 serum levels and CALL Score in predicting in-hospital death (AUC 0.71, 0.68-0.74, p = 0.55). CONCLUSIONS: eGFR calculated at hospital admission correlated well with COVID-19-related kidney injury and eGFR values < 60 mL/min/1,73 m2 were independently associated with in-hospital mortality, but not with both ARDS or need for mechanical ventilation.