ABSTRACT
Background: Giant cell arteritis (GCA) is the most common primary systemic vasculitis in western countries with the highest incidence among persons 70-79 years of age. Treatment has been with glucocorticoids (GCs) alone for many decades but recently Tocilizumab (TCZ) has demonstrated efficacy in reducing GC dose and flare rates in patients with GCA. Therefore, both early diagnosis and regular monitoring are necessary for the correct management of GCA. The COVID-19 pandemic has led to decisions by the governments of the countries involved, aimed above all at reducing the contagion. This has also led to reductions in health activities, limiting them to those of urgency by reducing or canceling checkups involving the risk of a time gap which for the GCA meant the interruption of clinical monitoring and therapeutic adjustment. At the same time, the pandemic situation has stimulated remote monitoring activities, through telephone contacts or video calls carried out by the rheumatologist. EULAR identified a minimal data set aimed at research and for clinical use, which includes the main clinical and instrumental data to be taken into consideration in monitoring the patient. For many data a clinical examination is not necessary but an interview is sufficient. We activated the TELEMACOV protocol (TELEmedicine and Management of the patient affected by giant cell arteritis during the COVid-19 pandemic) monitoring the follow-up of patients affected by GCA through telemedicine tools in order to maintain an effective and risk-free follow-up in a pathology with a high risk of relapse. Objectives: The purpose of the study is to evaluate the effectiveness of telemedicine in the follow-up of the patient with GCA. Methods: We evaluated patients (pts) with a clinical diagnosis of GCA (received in previous periods) who were admitted to the our Rheumatology Unit. They were monitored monthly by telephone from 9 March to 9 June 2020 (during lockdown). All patients were asked questions divided according to the sub-groups listed below: -Onset of new symptoms or their recurrence -Exams carried out -Current therapy -Satisfaction of telephone call Results: We performed 148 remote monitoring visits in 37 pts. The cohort was mainly composed by female (77,8%) and had a mean age of 71,85 ± 9,25 years. They were affected by GCA, with a mean duration of 5,3±2,3 months. The characteristics of these pts and the course of the disease are reported in Table 1. Pts treated with TCZ reduced their GC dose more than patients treated with GC alone (p: 0.032). Only one patient (treated with GC alone) had an ocular flare with the need to increase the dosage of the GC with good response and rapid improvement. Furthermore, all patients considered this type of monitoring very satisfactory according to the Likert scale (1-5) with mean 4,4±0,2. Conclusion: Our study has shown how telemedicine can be well used in pts with GCA as a possible alternative, for a limited period, to traditional visits, especially in a fragile population such as the elderly and more exposed to the risk of SARSCOV2 infection.
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Background: Hydroxychloroquine (HCQ) has been used safely for over 60 years in rheumatic patients. However, following its recent use in COVID-19 disease, its safety has been questioned, following controversial reports of cardiac toxicity1, possibly related to a prolongation of the QT interval2. Objectives: To explore the influence of chronic treatment with hydroxychloroquine on QT interval in rheumatic patients, and the possible effects of drug-todrug interference3. Methods: 12-lead electrocardiogram tracings were recorded with standard equipment in 229 ambulatory patients (SLE = 53, RA = 52, SSc = 56, UCTD = 38, Others = 30). The present analysis was performed on corrected QT intervals (QTc) calculated according to Framingham formula (QTc = QT+0.154 (1-RR)), with ULN = 449 ms in males, and 467 ms in females. Estimated glomerular filtrate rate (eGFR) was calculated from serum creatinine with the CKD-EPI equation. The influence on QTc values of demographic variables, chronic (≥3 months) HCQ treatment, and of the use of selected comedications -Statins, Angiotensin Converting Enzyme inhibitors (ACEi), Angiotensin Receptor Blockers (ARBs), Selective Serotonin Reuptake Inhibitors (SSRIs), Proton-Pump Inhibitors (PPI), Calcium Channel Blockers (CCBs) -were evaluated by parametric or non parametric statistical methods, as appropriate. All statistic al analyses were performed with the IBM SPSS statistical package version 25. QTc duration was not associated with the use of Statins, ACEi, ARBs, or SSRIs (p = 0.454, 0.276, 0.475, and 0.131 respectively), but was significantly prolonged in patients treated with HCQ (421.26 ± 19.19 vs 410.55 ± 21.18 msec, p < 0.001), PPIs (420.57 ± 21.45 vs 410.89 ± 18.12 ms, p < 0.001), and CCBs (424.22 ± 25.97 vs 415.59 ± 19.62 ms, p < 0.033). Furthermore, as reported in Fig. 1, our data show a trend -albeit not statistically significant -towards an additive effect on QT prolongation of the association of PPIs and CCBs with HCQ, even more evident in the case of association of the 3 drug classes. Conclusion: In this study, the QTc interval was significantly prolonged in patients treated with hydroxychloroquine as compared to controls, although significant prolongation was extremely infrequent. Furthermore, our data revealed signs of drug-drug interference, suggesting that regular monitoring of the electrocardiogram is advisable in these patients, often undergoing cotreatment with multiple drugs.
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Background: Development of neutralizing antibody (Nab) is crucial for protection from SARS-CoV-2 reinfection. The aim of the study was to analyze Nab titers (NabT) and kinetics over time in a cohort of 85 unselected not hospitalized Italian subjects (pts) with COVID-19 infection, with mild or no symptoms, tested after symptoms onset or for surveillance of healthcare workers. Methods: Two-fold serial dilutions of heat-inactivated sera were incubated with 100 TCID50 of SARS-CoV-2 virus (lineage B) at 37°C for 1 h in 96-wells plates. Then, pre-seeded 10,000 Vero E6 cell lines per well (ATCC CRL-1586) were treated with serum-virus mixtures and incubated at 37°C. After 72h, cell viability was determined through the commercial kit Cell-titer Glo 2.0 (Promega). The NabT was defined as the reciprocal value of the sample dilution that showed a 50% protection of virus cytopathic effect (ID50). NabT ≥5 ID50 were defined as SARS-CoV-2 positive and neutralizing. Chi squared, Wilcoxon, Fisher's exact test and Spearman's correlation coefficient were used. Results: Female were 57 (67.1%) and median age was 48 years. Pts were classified as early tested (ET, <60 days, n=40) and late tested (LT, >60 days, n=45). Overall, 30 (35.3%) pts had low (<10 ID50) NabT, 33 (38.8%) had intermediate NabT (ID50 11 to 50), and 22 (25.9%) had high NabT (ID50 >51, 9 of them >100). The frequency of each NabT class was comparable in ET and LT: low NabT was found in 11 (27.5%) and 19 (42.2%), intermediate in 16 (40%) and 18 (40%) and high in 13 (32.5%) and 8 pts (17.8%), respectively. However, no NabT higher than 200 ID50 was found in LT vs 5 in ET (p=0.04). No correlation between age and gender and NabT was found. At now, 23 pts had 2 NabT available during the follow up (T1 and T2);the interval between the two tests was 117 days (median). Almost all pts (20/23, 87%), showed NabT decrease: the median value of percentage decrease respect to the previous value was 63.2% (IQR 30.8-85.7) (p=0.0006). One pt had undetectable NabT at both times and two pts experienced an increase (Figure 1). No correlation between interval length, T2 value and percentage of decrease was observed. Conclusion: One third of pts had a very low level of NabT regardless of test timing. After 60 days from diagnosis a subset of pts had a value >100 but no >200, differently from the first 60 days, suggesting that NabT level could be a useful tool for dating past infections. The observed decrease of NabT has implications for reinfection and vaccine.
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Background: In Italy the pandemic of COVID-19 infection has placed an enormous burden on health authorities: contact precautions are required to avoid viral transmission and people should be subjected to standard infection control procedures. This is crucial in a country experiencing a high number of confirmed cases of COVID-19 infection in Europe and where multidrug-resistant Gram-negative bacteria (MDR-GN) are endemic.The aim of this study was to compare the prevalence of MDR-GN in surveillance rectal swabs (SRS) and in clinical samples (CS) in the period March 1,2020- April, 24 2020 with respect to the previous 2-month period and to the previous year. Methods: The first SRS and the first CS with a MDR-GN isolate detected from 01/01/2019 to 24/04/2020 were included. Analysis was made by comparing three different study periods in 2019 and 2020 (Jan-Dec 2019, Jan-Feb 2020, and Mar-Apr 2020), for medical department, surgical department and intensive care department. Results: Overall, 612 MDR-GN organisms were identified (399 SRS and 213 CS): carbapenemase-producing Klebsiella pneumoniae and Acinetobacter baumanii (CPAB) were the most frequently detected (Figure 1). We observed an increased relative frequency of patients with MDR-GN detected in CS respect to those found in SRS (32.7% vs 44.5% vs 70.6%, p=0.0005): 5/12 CS detected in the last period were isolated from the respiratory tract (Figure 2). Nine patients with COVID-19 pneumonia had MDR-GN. All but two patients had a previous negative SRS performed 4 days before (median value) and the median interval between COVID-19 positivity and MDR-GN positivity was 7 days.The six patients with CPAB isolation were all hospitalized in the same ward, with partially overlapping hospital stays during the study period. In 5 of them, CPAB was detected in the respiratory tract (Figure 3). Conclusion: The first detection of MDR-GN in CS and the nosocomial MDR-GN acquisition despite cohorting due to COVID-19 infection underline the need to reinforce infection control measures in a high prevalence country during COVID-19 pandemia. A correct antimicrobial policy urged because, according to published data, most patients with COVID-19 infection received antimicrobial therapy: furthermore MDR-GN infection could play a role in the negative outcome of these patients.
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Background: Venetoclax (VEN) and Hypomethylating agents (HMA) have demonstrated remarkable activity in elderly front-line and R/R AML patients. NPM1-mutated (NPM1+) AML seems to benefit most from such therapy. In this patient subset exploring new applications of VEN-HMAs could be an interesting and promising strategy. Methods: We report 3 patients with NPM+ AML treated with VENHMAs in early molecular relapse (EMR) after first line chemotherapy. EMR was evaluated as 1 log increase of NPM1 qRT-PCR transcript, minimal residual disease (MRD) negativity was defined as ratio NPM1+/ABL × 100 transcript < 0.01. Results: From December 2019 to April 2020 we treated three fit AML NPM1+ patients in EMR with Azacitidine (AZA) 75 mg/m2 from days 1-5 in association with VEN at standard dosage of 400 mg. Patientâs characteristics and previous therapy lines are summarized in Table 1. All patients had received an intensive induction chemotherapy-program and, considering the favorable disease risk, had not received a front-line allogeneic stem cell transplant (ASCT). Patient 1 experienced EMR after 1 year from the end of chemotherapy program. Patient 2 and patient 3 developed a log increase of NPM1 transcript during consolidation chemotherapy. In all cases an ASCT could not be performed quickly as first choice due to logistic and concomitant SARS-CoV-2 management complications. In patient 2 and 3 a further chemotherapy approach was contraindicated for recent severe infections occurred during the previous hospitalization. All patients were treated in out-patient setting and VEN full 400 mg dose was reached after a quick 6-days ramp-up. Blood count and chemistry were performed weekly during 1st cycle. Patient 1 received 3 cycles of VEN-AZA and achieved CR MRD- A fter the 1st cycle, confirmed after 3rd cycle. No AEs were reported and patient 1 is now proceeding to ASCT in optimal disease conditions. Patient 2 received 2 cycles of VEN-AZA, 1 cycle of AZA single-agent and achieved CR MRD- A fter 3rd. Patient 2 suspended VEN after 2nd cycle for G3 neutropenia and G2 thrombocytopenia;WBC recovered after 2 weeks of suspension. Patient 2 is now proceeding to consolidation with natural killer (NK) adoptive immunotherapy. Patient 3 received 3 cycles of VEN-AZA and achieved CR MRD- A t 3rd cycle evaluation. AEs reported for patient 3 were G4 neutropenia during cycle 2 for which VEN was suspended from C2 day 21 to day 28. Patient 3 is also now proceeding to ASCT in optimal disease conditions. Conclusions: VEN-HMAs represent a promising approach for the treatment of the unexplored EMR setting in NPM1+ AML patients as bridge to intensified consolidation strategies. This approach allowed to avoid disease expansion, recover from infective complications and even more to achieve MRD-.