High-dose glucocorticoids pulse-therapy for beta-coronaviridae pneumonia: a systematic literature review and case-series of Coronavirus disease-2019.

OBJECTIVES: The results of the RECOVERY trial identified dexamethasone as the first pharmacological therapy that reduces mortality in patients with COVID-19. The aim of this paper is to conduct a systematic literature review on safety and efficacy of pulse glucocorticoid therapy for Severe Acute Respiratory Syndrome (SARS)-CoronaVirus (CoV), Middle East Respiratory Syndrome (MERS)-CoV or SARS-CoV-2 infections and describe a case-series of COVID-19 patients treated with off-label pulse doses of methylprednisolone. METHODS: We performed a systematic literature review on safety and efficacy of pulse therapy for betacoronaviridae infections as described in the protocol registered on PROSPERO (CRD42020190183). All consecutive patients admitted to Arcispedale Santa Maria Nuova di Reggio Emilia or Guastalla Hospital with COVID-19 between March 1st and April 30th, 2020 and treated with methylprednisolone 1 gram/day for at least three days were included in the case series. A retrospective review of available computed tomography (CT) scan and chest x-ray was performed independently by two radiologists blinded to clinical data, and discordances were resolved by consensus. RESULTS: Twenty papers were included for SARS, but only two were comparative and were included in the primary endpoint analysis. Likewise, eleven papers were included for COVID-19, four of which were comparative and were considered for the primary outcome analysis. Included studies for both SARS and COVID-19 are mostly retrospective and highly heterogeneous, with lethality ranging from 0% to 100% and ICU admission rate ranging from 9% to 100%. Fourteen patients were included in our case series, 7 males and 7 females. CONCLUSIONS: No randomised controlled trial is available yet for corticosteroids pulse-therapy defined as at least ≥500mg/day methylprednisolone in patients with emerging coronavirus pneumonia. Lethality among our cohort is high (4/14), but this finding should be interpreted with caution due to the fact that in our setting pulse-steroids were used in patients not eligible for other treatments because of comorbidities or as rescue therapy. The incidence of steroid-related adverse events seems low in our cohort. The quality of the evidence on glucocorticoid pulse-therapy in SARS, MERS and COVID-19 is poor. Randomised controlled trials are greatly needed.

Appropriateness of antibiotic prescribing in paediatrics: retrospective controlled study assessing a multifaceted intervention in Northern Italy in a 7-year period.

BACKGROUND: Academic detailing, audit and feedback, and peer comparison have been advocated as effective ways to promote appropriateness of prescribing and antimicrobial stewardship (AMS). This study explored the effectiveness of a multifaceted intervention aimed at supporting the appropriateness of antibiotic prescribing in paediatrics. METHODS: Over the course of 7 years, all 89 paediatricians of the Local Health Authority (LHA) of Reggio Emilia (530 000 residents) were provided with scientific literature focused on antimicrobial resistance and the appropriateness of use of specific antibiotics, together with local data on antimicrobial resistance and prescribing reports comparing each paediatrician with colleagues in the same district and with local averages. Prescribing rates of specific target antibiotics/classes of antibiotics were evaluated by comparing Reggio-Emilia with the other seven LHAs of the Emilia-Romagna Region (control area), adjusting for prescriptions during a 2-year baseline period. RESULTS: A significant increase in the rate of amoxicillin prescriptions (91 more per 1000 children/year) was observed in the intervention area compared with the control area along with a significant reduction in the rate of amoxicillin+clavulanate prescriptions (70 fewer per 1000 children/year) and a significant increase in the ratio of their prescription rates. No differences were observed in cephalosporin and macrolide prescription rates and overall antibiotic prescriptions. CONCLUSIONS: Improvements in prescribing appropriateness were observed. This study confirms the importance of an audit and feedback approach through small group meetings supported by scientific literature, local resistance data and prescribing reports. Such approach should always be considered as part of multifaceted interventions to promote AMS.

Atypical Presentation of Invasive Aspergillosis during Treatment with Mogamulizumab.

Treatment with CCR-4 antagonists has been shown to be protective against the development of invasive pulmonary aspergillosis in animal models. Herein, we present a case of fatal invasive pulmonary aspergillosis in a patient receiving Mogamulizumab. A 64-year-old man with refractory mycosis fungoides was found to have diffuse bilateral pulmonary nodules during a chest CT in June 2022. Bronchoalveolar lavage (BAL) fungal and bacterial cultures and galactomannan were negative, as well as serum beta-glucan and galactomannan. Histology showed a lymphoid infiltrate with a negative fungal stain, so a presumptive diagnosis of lymphoma infiltration was made, and the patient started the CCR-4 antagonist Mogamulizumab treatment in August 2022. He had no symptoms until November when he presented to the hematology clinic reporting dyspnea. He had neutrophilic leukocytosis (18.610 cells/µL), his c-reactive protein was 27 mg/dL, and his skin lesions from mycosis fungoides were just starting to improve. A CT scan showed large diffuse bilateral severely necrotic cavitated lesions with thick walls and apparently synchronous evolution. Beta-glucan was 31 pg/mL (wako method), while serum galactomannan 3.6. BAL was positive for Aspergillus fumigatus culture and galactomannan. Patient started voriconazole but, despite being in a stable condition, he suddenly died after two days. Discussion: Paradoxically, worsening of the chronic pulmonary aspergillosis has been reported after nivolumab treatment, and immune reconstitution syndromes are usually seen during neutrophil recovery after intensive chemotherapy. Our patient already presented indolent lung lesions from 5 months before and he remained completely asymptomatic until the aspergillosis diagnosis when he quickly passed away. Even if a progression of the lesions was expected in 5 months, this case had an atypical presentation. During the 5-month period, he had no pulmonary symptoms, and his c-reactive protein was negative. Furthermore, in the setting of the natural progression of subacute/chronic aspergillosis, a different radiological picture was expected with a less severe and probably asynchronous evolution. We think that the immune restoration associated with Mogamulizumab (also supported by the concurrent clinical response of the skin lesions) could have been detrimental in this case, exacerbating a catastrophic immune response or alternatively masquerading the clinical progression of aspergillosis. Clinicians should be aware of immune reconstitution syndromes possibly leading to fatal outcomes in immunocompromised patients starting CCR-4 antagonists.

The Endangered Sardinian Grass Snake: Distribution Update, Bioclimatic Niche Modelling, Dorsal Pattern Characterisation, and Literature Review.

The Sardinian grass snake, Natrix helvetica cetti, is an endangered endemic snake subspecies with a restricted and highly fragmented geographic distribution. Information on its ecology and detailed geographic distribution are scarce and may negatively impact on its conservation status. Therefore, a literature review on its taxonomy, morphology, ecology, and conservation is presented here. Moreover, field records from the authors, citizen science and the existing literature provide an updated geographic distribution highlighting its presence within 13 new and 7 historic 10 × 10 km cells. Bioclimatic niche modelling was then applied to explore patterns of habitat suitability and phenotypic variation within N. h. cetti. The geographic distribution of the species was found to be positively correlated with altitude and precipitation values, whereas temperature showed a negative correlation. Taken together, these outcomes may explain the snake's presence, particularly in eastern Sardinia. In addition, analysis of distribution overlap with the competing viperine snake (N. maura) and the urodeles as possible overlooked trophic resources (Speleomantes spp. and Euproctus platycephalus) showed overlaps of 66% and 79%, respectively. Finally, geographical or bioclimatic correlations did not explain phenotypic variation patterns observed in this highly polymorphic taxon. Perspectives on future research to investigate N. h. cetti's decline and support effective conservation measures are discussed.

Aliens Coming by Ships: Distribution and Origins of the Ocellated Skink Populations in Peninsular Italy.

The ocellated skink (Chalcides ocellatus) is a widespread lizard, naturally distributed between the Maghreb and coastal Pakistan, with few insular populations in the Mediterranean coastal area. Some populations of this species have also been recorded in peninsular Italy, Campania and Southern Tuscany due to accidental introductions via touristic and commercial routes. In this work, we conducted genetic analyses on mitochondrial DNA COXI, cytb and 16S mtDNA genes on a sample of Italian insular and peninsular populations. Differently from what previously suggested, the nucleus in Portici (Southern Italy) may have originated from Sardinia. The intense trade and touristic traffic between Sardinia and Southern Tuscany may have been responsible for the introduction of this lizard also to Central Italy.

A surveillance system model for central line-associated bloodstream infections (CLABSI) coordinated at the regional level: a pilot feasibility study.

We describe the methods used to define a surveillance model to incorporate into activities aimed at preventing central line-associated bloodstream infections (CLABSI) in non-critical care units (NCCUs) and designed to be implemented at the regional level. In 2015 we conducted a pilot feasibility study in three NCCUs based in hospitals of the Regional Health System of Emilia Romagna to evaluate the feasibility of the proposed model and to test its accuracy and cost-effectiveness in terms of resources needed to maintain the system. Our results indicate that the system is feasible at the regional level by using the available sources and instruments to collect data in clinical practice context. Observation of device utilization for at least three months in all NCCU wards is needed in order to prioritize the medical area on which to focus costs for surveillance prior to implementing it on a regular basis.

Dysfunction and functional restoration of HCV-specific CD8 responses in chronic hepatitis C virus infection.

UNLABELLED: The functional impairment of HCV-specific T cell responses is believed to be an important determinant of HCV persistence, but the functional T cell defects of patients with chronic hepatitis C (CH-C) are only partially defined. CD8 responses to HLA-A2-restricted epitopes of HCV and other unrelated viruses were studied in 23 HLA-A2-positive patients both ex vivo and after in vitro culture. Degranulation capacity, intracellular perforin, and granzyme-A content and cytokine production (IFN-gamma, TNF-alpha) by HCV- and non-HCV-specific CD8 cells were tested both ex vivo and in vitro, whereas cytolytic activity was studied after 10 days' expansion in vitro. Memory maturation and role of exhaustion were assessed ex vivo by HCV-specific CD8 staining for CD127 and PD-1, and in vitro after peripheral blood mononuclear cells (PBMC) culture in the presence of anti-PD-L1 monoclonal antibodies. IFN-gamma production and cytolytic activity were expressed less efficiently by HCV-specific than by non-HCV specific CD8 cells derived from the same CH-C patients. The amount of stored granzyme-A within single cells was always lower in HCV-specific CD8 cells, which were less efficient also in the release of lytic granules and in the production of TNF-alpha. The CD8 dysfunction was associated with high PD-1 expression by most HCV-specific CD8 cells, and PD-1/PD-L1 blockade by anti-PD-L1 antibodies in vitro was able to improve the HCV-specific CD8 function. CONCLUSION: Our study characterizes CD8 defects that may be important in maintaining HCV persistence; identification of strategies to correct these defects may help to define novel approaches to treat HCV infection.