Predictive model for bacterial co-infection in patients hospitalized for COVID-19: a multicenter observational cohort study.

OBJECTIVE: The aim of our study was to build a predictive model able to stratify the risk of bacterial co-infection at hospitalization in patients with COVID-19. METHODS: Multicenter observational study of adult patients hospitalized from February to December 2020 with confirmed COVID-19 diagnosis. Endpoint was microbiologically documented bacterial co-infection diagnosed within 72 h from hospitalization. The cohort was randomly split into derivation and validation cohort. To investigate risk factors for co-infection univariable and multivariable logistic regression analyses were performed. Predictive risk score was obtained assigning a point value corresponding to ß-coefficients to the variables in the multivariable model. ROC analysis in the validation cohort was used to estimate prediction accuracy. RESULTS: Overall, 1733 patients were analyzed: 61.4% males, median age 69 years (IQR 57-80), median Charlson 3 (IQR 2-6). Co-infection was diagnosed in 110 (6.3%) patients. Empirical antibiotics were started in 64.2 and 59.5% of patients with and without co-infection (p = 0.35). At multivariable analysis in the derivation cohort: WBC ≥ 7.7/mm3, PCT ≥ 0.2 ng/mL, and Charlson index ≥ 5 were risk factors for bacterial co-infection. A point was assigned to each variable obtaining a predictive score ranging from 0 to 5. In the validation cohort, ROC analysis showed AUC of 0.83 (95%CI 0.75-0.90). The optimal cut-point was ≥2 with sensitivity 70.0%, specificity 75.9%, positive predictive value 16.0% and negative predictive value 97.5%. According to individual risk score, patients were classified at low (point 0), intermediate (point 1), and high risk (point ≥ 2). CURB-65 ≥ 2 was further proposed to identify patients at intermediate risk who would benefit from early antibiotic coverage. CONCLUSIONS: Our score may be useful in stratifying bacterial co-infection risk in COVID-19 hospitalized patients, optimizing diagnostic testing and antibiotic use.

Preliminary Experience With Low Molecular Weight Heparin Strategy in COVID-19 Patients.

BACKGROUND: Heparin administration in COVID-19 patients is recommended by expert consensus, although evidence about dosage, duration and efficacy are limited. We aim to investigate the association between different dosages of low molecular weight heparin (LMWH) and mortality among COVID-19 hospitalized patients. METHODS AND RESULTS: Retrospective study of 450 laboratory-confirmed COVID-19 patients admitted to Sant'Orsola Bologna Hospital from March 01 to April 10, 2020. Clinical, laboratory and treatment data were collected and analyzed. The in-hospital mortality between COVID-19 patients treated with standard prophylactic LMWH dosage vs. intermediate LMWH dosage was compared. Out of 450 patients, 361 received standard deep vein thrombosis (DVT) prophylaxis enoxaparin treatment (40-60mg daily) and 89 patients received intermediate enoxaparin dosage (40-60 mg twice daily) for 7 days. No significant differences in the main demographic characteristics and laboratory testings at admission were observed in the two heparin regimen subgroups, except for older age and prevalence of hypertension in the group treated with "standard" prophylaxis LMWH dosage. The intermediate LMWH administration was associated with a lower in-hospital all-cause mortality compared to the "standard" prophylactic LMWH dosage (18.8% vs. 5.8%, p = 0.02). This difference remained significant after adjustment with the propensity score for variables that differed significantly between the dosage groups (OR= 0.260, 95% CI 0.089-0.758, p=0.014). CONCLUSIONS: Intermediate LMWH dosage seems to be associated with lower incidence of mortality compared to standard DVT prophylaxys in hospitalized COVID-19 patients. Our study paves the way to further pathophysiological investigations and controlled studies of anticoagulation therapy in Covid-19 disease.

Whole brain radiotherapy with adjuvant or concomitant boost in brain metastasis: dosimetric comparison between helical and volumetric IMRT technique.

BACKGROUND: To compare and evaluate the possible advantages related to the use of VMAT and helical IMRT and two different modalities of boost delivering, adjuvant stereotactic boost (SRS) or simultaneous integrated boost (SIB), in the treatment of brain metastasis (BM) in RPA classes I-II patients. METHODS: Ten patients were treated with helical IMRT, 5 of them with SRS after whole brain radiotherapy (WBRT) and 5 with SIB. MRI co-registration with planning CT was mandatory and prescribed doses were 30 Gy in 10 fractions (fr) for WBRT and 15Gy/1fr or 45Gy/10fr in SRS or SIB, respectively. For each patient, 4 "treatment plans" (VMAT SRS and SIB, helical IMRT SRS and SIB) were calculated and accepted if PTV boost was included in 95 % isodose and dose constraints of the main organs at risk were respected without major deviations. Homogeneity Index (HI), Conformal Index (CI) and Conformal Number (CN) were considered to compare the different plans. Moreover, time of treatment delivery was calculated and considered in the analysis. RESULTS: Volume of brain metastasis ranged between 1.43 and 51.01 cc (mean 12.89 ± 6.37 ml) and 3 patients had double lesions. V95% resulted over 95 % in the average for each kind of technique, but the "target coverage" was inadequate for VMAT planning with two sites. The HI resulted close to the ideal value of zero in all cases; VMAT-SIB, VMAT-SRS, Helical IMRT-SIB and Helical IMRT-SRS showed mean CI of 2.15, 2.10, 2.44 and 1.66, respectively (optimal range: 1.5-2.0). Helical IMRT-SRS was related to the best and reliable finding of CN (0.66). The mean of treatment time was 210 s, 467 s, 440 s, 1598 s, respectively, for VMAT-SIB, VMAT-SRS, Helical IMRT-SIB and Helical IMRT-SRS. CONCLUSIONS: This dosimetric comparison show that helical IMRT obtain better target coverage and respect of CI and CN; VMAT could be acceptable in solitary metastasis. SIB modality can be considered as a good choice for clinical and logistic compliance; literature's preliminary data are confirming also a radiobiological benefit for SIB. Helical IMRT-SRS seems less effective for the long time of treatment compared to other techniques.

Pattern of relapse of glioblastoma multiforme treated with radical radio-chemotherapy: Could a margin reduction be proposed?

To analyse the pattern of recurrence of patients treated with Stupp protocol in relation to technique, to compare in silico plans with reduced margin (1 cm) with the original ones and to analyse toxicity. 105 patients were treated: 85 had local recurrence and 68 of them were analysed. Recurrence was considered in field, marginal and distant if >80 %, 20-80 % or <20 % of the relapse volume was included in the 95 %-isodose. In silico plans were retrospectively recalculated using the same technique, fields angles and treatment planning system of the original ones. The pattern of recurrence was in field, marginal and distant in 88, 10 and 2 % respectively and was similar in in silico plans. The margin reduction appears to spare 100 cc of healthy brain by 57 Gy-volume (p = 0.02). The target coverage was worse in standard plans (pt student < 0.001), especially if the tumour was near to organs at risk (pχ2 < 0.001). PTV coverage was better with IMRT and helical-IMRT, than conformal-3D (pAnova test = 0.038). This difference was no more significant with in silico planning. A higher incidence of asthenia and leuko-encephalopathy was observed in patients with greater percentage of healthy brain included in 57 Gy-volume. No differences in the pattern of recurrence according to margins were found. The margin reduction determines sparing of healthy brain and could possibly reduce the incidence of late toxicity. Margin reduction could allow to use less sophisticated techniques, ensuring appropriate target coverage, and the choice of more costly techniques could be reserved to selected cases.