Burden of COVID-19 disease and vaccine coverages in Apulian splenectomized patients: A retrospective observational study

Splenectomy/asplenia is a condition associated with immune-compromission and specific vaccines are recommended for these patients, including the anti-COVID-19 vaccine. Among the high-risk group for which vaccination was prioritized in Italy, the immunocompromised patients after therapies or treatments were included. The Apulian regional archive of hospital discharge forms was used to define the list of splenectomized Apulian inhabitants, considering data from 2015 through 2020. The overall vaccination status of asplenic patients was assessed via data collected from the Regional Immunization Database. The history of SARS-CoV-2 infection and the infectious disease outcomes were extracted from the Italian Institute of Health platform “Integrated surveillance of COVID-19 cases in Italy”. 1219 Apulian splenectomized inhabitants were included; the incidence rate of SARS-CoV-2 infection was 15.0 per 100 persons-year with a proportion of re-infection equal to 6.4%; the proportion of hospitalization was 2.9%, with a case-fatality rate of 2.6%. The vaccine coverage (VC) for the anti-COVID-19 vaccine basal routine was 64.2%, for the first booster dose was 15.4%, and for the second booster dose was 0.6%. A multifactorial approach is needed to increase the vaccination uptake in this sub-group population and to increase the awareness of the asplenia-related risks to patients and health personnel.     

In vitro activities of omadacycline,eravacycline, cefiderocol,apramycin, and comparator antibiotics against Acinetobacter baumannii causing bloodstream infections in Greece, 2020–2021: a multicenter study

Resistance of Acinetobacter baumannii to multiple clinically important antimicrobials has increased to very high rates in Greece, rendering most of them obsolete. The aim of this study was to determine the molecular epidemiology and susceptibilities of A. baumannii isolates collected from different hospitals across Greece. Single-patient A. baumannii strains isolated from blood cultures (n = 271), from 19 hospitals, in a 6-month period (November 2020–April 2021) were subjected to minimum inhibitory concentration determination and molecular testing for carbapenemase, 16S rRNA methyltransferase and mcr gene detection and epidemiological evaluation. 98.9% of all isolates produced carbapenemase OXA-23. The vast majority (91.8%) of OXA-23 producers harbored the armA and were assigned mainly (94.3%) to sequence group G1, corresponding to IC II. Apramycin (EBL-1003) was the most active agent inhibiting 100% of the isolates at ≤16 mg/L, followed by cefiderocol which was active against at least 86% of them. Minocycline, colistin and ampicillin-sulbactam exhibited only sparse activity (S <19%), while eravacycline was 8- and 2-fold more active than minocycline and tigecycline respectively, by comparison of their MIC₅₀/₉₀ values. OXA-23-ArmA producing A. baumannii of international clone II appears to be the prevailing epidemiological type of this organism in Greece. Cefiderocol could provide a useful alternative for difficult to treat Gram-negative infections, while apramycin (EBL-1003), the structurally unique aminoglycoside currently in clinical development, may represent a highly promising agent against multi-drug resistant A. baumanni infections, due to its high susceptibility rates and low toxicity.

     

Oral lichen planus in children: An Italian case series

Oral lichen planus usually occurs in adults; there are no clear data regarding the incidence and the clinical features of oral lichen planus in children. This paper reports clinical findings, treatments, and outcomes of 13 Italian patients with oral lichen planus in childhood diagnosed between 2001 and 2021. The most common finding was keratotic lesions with reticular or papular/plaque-like patterns, confined to the tongue in seven patients. Although oral lichen planus in childhood is rare and the malignant transformation index is unknown, specialists must be aware of its characteristics and oral mucosal lesions must be correctly diagnosed and managed.     

Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer: An early exploratory analysis of real-world data

Background

The TOPAZ-1 phase III trial reported a survival benefit with the anti-programmed death cell ligand 1 (anti-PD-L1) durvalumab in combination with gemcitabine and cisplatin in patients with advanced biliary tract cancer. The present study investigated the efficacy and safety of this new standard treatment in a real-world setting.

Methods

The analysed population included patients with unresectable, locally advanced or metastatic adenocarcinoma of the biliary tract treated with durvalumab in combination with gemcitabine and cisplatin at 17 Italian centres. The primary endpoint of the study was progression-free survival (PFS), whereas secondary endpoints included overall survival (OS), overall response rate (ORR) and safety. Unadjusted and adjusted hazard ratios (HRs) by baseline characteristics were calculated using the Cox proportional hazards model.

Results

From February 2022 to November 2022, 145 patients were enrolled. After a median follow-up of 8.5 months (95% CI: 7.9–13.6), the median PFS was 8.9 months (95% CI: 7.4–11.7). Median OS was 12.9 months (95% CI: 10.9–12.9). The investigator-assessed confirmed ORR was 34.5%, and the disease control rate was 87.6%. Any grade adverse events (AEs) occurred in 137 patients (94.5%). Grades 3–4 AEs occurred in 51 patients (35.2%). The rate of immune-mediated AEs (imAEs) was 22.7%. Grades 3–4 imAEs occurred in 2.1% of the patients. In univariate analysis, non-viral aetiology, ECOG PS >0 and NLR ≥3 correlated with shorter PFS.

Conclusion

The results reported in this first real-world analysis mostly confirmed the results achieved in the TOPAZ-1 trial in terms of PFS, ORR and safety.     

Type I spinal muscular atrophy patients treated with nusinersen: 4-year follow-up of motor,respiratory and bulbar function

Background

We report the 4-year follow-up in type I patients treated with nusinersen and the changes in motor, respiratory and bulbar function in relation to subtype, age and SMN2 copy number.

Methods

The study included SMA 1 patients with at least one assessment after 12, 24 and 48 months from the first dose of nusinersen. The assessments used were Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and the Hammersmith Infant Neurological Examination (HINE-II).

Results

Forty-eight patients, with ages ranging from 7 days to 12 years (mean 3.3 years, SD 3.6 years) were included in the study. The CHOP INTEND and HINE-II scores significantly increased between baseline and 48 months (p < 0.001). When age at starting treatment subgroups (<210 days, <2 years, 2–4 years, 5–11 years, ≥12 years) were considered, the CHOP INTEND increased significantly in patients younger than 4 years at treatment, while the HINE-2 increased significantly in patients younger than 2 years at treatment. In a mixed-model analysis, age, nutritional and respiratory status were predictive of changes on both scales while SMN2 copy number and decimal classification were not.

Conclusions

Our results confirm the safety profile previously reported and support the durability of the efficacy of nusinersen at 4 years with an overall stability or mild improvement and no evidence of deterioration over a long period of time.     

Sex-specific differences in myocardial injury incidence after COVID-19 mRNA-1273 booster vaccination

Aims

To explore the incidence and potential mechanisms of oligosymptomatic myocardial injury following COVID-19 mRNA booster vaccination.

Methods and results

Hospital employees scheduled to undergo mRNA-1273 booster vaccination were assessed for mRNA-1273 vaccination-associated myocardial injury, defined as acute dynamic increase in high-sensitivity cardiac troponin T (hs-cTnT) concentration above the sex-specific upper limit of normal on day 3 (48–96 h) after vaccination without evidence of an alternative cause. To explore possible mechanisms, antibodies against interleukin-1 receptor antagonist (IL-1RA), the SARS-CoV-2-nucleoprotein (NP) and -spike (S1) proteins and an array of 14 inflammatory cytokines were quantified. Among 777 participants (median age 37 years, 69.5% women), 40 participants (5.1%; 95% confidence interval [CI] 3.7–7.0%) had elevated hs-cTnT concentration on day 3 and mRNA-1273 vaccine-associated myocardial injury was adjudicated in 22 participants (2.8% [95% CI 1.7–4.3%]). Twenty cases occurred in women (3.7% [95% CI 2.3–5.7%]), two in men (0.8% [95% CI 0.1–3.0%]). Hs-cTnT elevations were mild and only temporary. No patient had electrocardiographic changes, and none developed major adverse cardiac events within 30 days (0% [95% CI 0–0.4%]). In the overall booster cohort, hs-cTnT concentrations (day 3; median 5, interquartile range [IQR] 4–6 ng/L) were significantly higher compared to matched controls (n = 777, median 3 [IQR 3–5] ng/L, p < 0.001). Cases had comparable systemic reactogenicity, concentrations of anti-IL-1RA, anti-NP, anti-S1, and markers quantifying systemic inflammation, but lower concentrations of interferon (IFN)-λ1 (IL-29) and granulocyte-macrophage colony-stimulating factor (GM-CSF) versus persons without vaccine-associated myocardial injury.

Conclusion

mRNA-1273 vaccine-associated myocardial injury was more common than previously thought, being mild and transient, and more frequent in women versus men. The possible protective role of IFN-λ1 (IL-29) and GM-CSF warrant further studies.