SARS-CoV-2 infection: use and effectiveness of antigenic swab for the health surveillance of healthcare workers.

BACKGROUND:  The gold standard to identify SARS-CoV-2 infections is the Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) on rhino-pharyngeal swabs, but faster and cheaper methods such as antigenic swabs have been developed. A retrospective observational study on antigenic swabs included in the extraordinary health surveillance protocol of a large Hospital in Turin was aimed to assess their performance validity. Methods: From 30 October 2020 to 4 May 2021, 4000 antigenic swabs were carried out in three groups of healthcare workers (HCWs), respectively (i) asymptomatic, (ii) cohabiting with a positive case, and (iii) not recently exposed to the virus.  Results: Overall sensitivity and specificity associated with a prevalence of 1.30% were 26.9%, 97.2%, respectively, the corresponding positive (PPV) and negative predictive value (NPV) being 11.29% and 99.02% [95% IC (99.00 - 99.04)] respectively; a prevalence of 0.29% was observed in the asymptomatic group, among whom sensitivity and specificity were 25.0% and 98.9%, respectively, the corresponding PPV and NPV being 6.25% and 99.78% [95% IC (99.76 - 99.81)], respectively; the cohabitant group showed a prevalence of 21.11%, sensitivity and specificity were 47.4%, 81.7%, respectively, giving rise to a PPV of 40.91% and NPV of 85.29% [95% IC (85.18 - 85.41)] respectively. The prevalence in the not exposed group was 0.77%, sensitivity and specificity were 29.2%, 97.4%, respectively, and PPV and NPV 8.05% and 99.44% [95% IC (99.42 - 99.46)] respectively. Conclusions: Antigenic swabs reduced costs and provided reliable diagnostic results. In the cohabitant group, the higher-prevalence groups showed poor test performances, likely because of the high prevalence of pre-symptomatic illness in this group. Owing to the relatively low NPV, a negative result would still require confirmation with a molecular test to be acceptable for a surveillance program that effectively reduces the virus's intra-hospital spread.

SARS-CoV-2 infection: efficacy of extensive vaccination of the healthcare workforce in a large Italian hospital.

BACKGROUND: A prospective observational study involved 13,787 Health Care Workers (HCWs) of a large hospital to assess the effectiveness of a SARS-CoV-2 mRNA vaccine. METHODS: The daily incidence of infections was estimated from 1st October 2020 to 30th April 2021 and compared with that of the province of Turin (2.26 million). In the middle of this period, a mass vaccination began among HCW, and its effect was assessed. RESULTS: In the first half-period, 1,163 positive HCWs were observed, the average daily incidence rate per 100,000 being 79.58 (± 15.58; 95% CI) compared to 38.54 (± 5.96; 95% CI) in the general population (p<0.001). The vaccination campaign immunized 9,843 HCWs; among them, the average daily incidence was 14.23 (± 2.73; 95% CI) compared to 34.2 (± 2.95; 95% CI) in the province (p<0.001). Among fully vaccinated HCW, 59 cases were observed, giving rise to an incidence of 6.3 (± 2.66; 95% CI) much lower than in the province (p<0.001). In the second half of the observation period, the RR for HCWs compared to the province dropped from 2.07 (1.96 - 2.18; 95% CI; p<0.001) to 0.5 (0.42 - 0.58; 95% CI; p<0.001) and to 0.17 (0.13 - 0.22; 95% CI; p<0.001) for unvaccinated and vaccinated HCWs, respectively. The RR of vaccinate HCW was 0.43 (0.31 - 0.58; 95% CI; p<0.001) compared to unvaccinated. In the second half of the observation period, unvaccinated HCWs had a RR of 0.21 (0.18 - 0.25; 95% CI; p<0.001) as compared to the first one. A linear regression model (R2 = 0.87) showed that every percent increase in vaccinated HCWs lowered daily incidence by 0.94 (0.86 - 1.02; IC 95%; p<0.001). Vaccinated HCWs had a RR of 0.09 (0.07 - 0.12; 95% CI; p<0.001) compared to unvaccinated HCWs, which led to estimated effectiveness of the two-dose vaccine of 91 % (± 3 %; CI 95%) similar to that reported by the manufacturer.

COVID-19 infection and diffusion among the healthcare workforce in a large university-hospital in northwest Italy.

Backgroud: Since the beginning of the coronavirus disease 2019 (COVID-19) outbreak, healthcare workers (HCWs) have been the workers most likely to contract the disease. Intensive focus is therefore needed on hospital strategies that minimize exposure and diffusion, confer protection and facilitate early detection and isolation of infected personnel. METHODS: To evaluate the early impact of a structured risk-management for exposed COVID-19 HCWs and describe how their characteristics contributed to infection and diffusion. Socio-demographic and clinical data, aspects of the event-exposure (date, place, length and distance of exposure, use of PPE) and details of the contact person were collected. RESULTS: The 2411 HCWs reported 2924 COVID-19 contacts. Among 830 HCWs who were at 'high or medium risk', 80 tested positive (9.6%). Physicians (OR=2.03), and non-medical services -resulted in an increased risk (OR=4.23). Patient care did not increase the risk but sharing the work environment did (OR=2.63). There was a significant time reduction between exposure and warning, exposure and test, and warning and test since protocol implementation. HCWs with management postitions were the main source of infection due to the high number of interactions. DISCUSSION: A proactive system that includes prompt detection of contagious staff and identification of sources of exposure helps to lower the intra-hospital spread of infection. A speedier return to work of staff who would otherwise have had to self-isolate as a precautionary measure improves staff morale and patient care by reducing the stress imposed by excessive workloads arising from staff shortages.

Postictal MRI abnormalities and seizure-induced brain injury: notions to be challenged.

OBJECTIVE: This was a bibliographic search to address the quality of evidence in clinical reports supporting the assertion that brain MRI signal abnormalities are a direct consequence of seizures. METHODS: The search on PubMed was performed by applying the following inclusion criteria: a) original case reports, b) in humans, c) as single case reports or series of patients, d) of visually detected acute MRI signal abnormalities, e) attributable directly to seizures, and f) published in English. Bibliographic references of initially selected publications were reviewed for additional articles. Full texts of selected publications were read for information regarding clinical, EEG, and MRI features. Moreover, claimed evidence supporting seizure-induced excitotoxicity was assessed. RESULTS: The search resulted in 91 publications corresponding to 413 cases. There was a wide range of clinical features and EEG and MRI abnormalities. Premorbid or comorbid conditions were present in many cases, and some of them are potential causes of MRI changes. Claimed evidence for MRI signal abnormalities as a direct consequence of ictal activity was mostly based on the similarity with previous reports, animal models, reversibility, congruent EEG, MRI changes not respecting vascular territories, and ruling out other etiologies. CONCLUSIONS: Evidence supporting the notion of seizure-induced excitotoxicity is questionable in the studied reports of postictal MRI abnormalities.

Síndrome de Menkes: relato de caso em irmãos / Menkes disease: report of two cases in siblings

A Síndrome de Menkes ou tricopoliodistrofia é umadesordem neurodegenerativa de caráter recessivo, ligadaao cromossomo X, caracterizada por um distúrbiono transporte e metabolismo do cobre. O diagnósticoé sugerido pela tríade clássica dos fatores clínicos(atraso no desenvolvimento, degeneração neurológicae má formação dos cabelos) e com a demonstração daredução dos níveis séricos de cobre e ceruloplasmina.Relata-se o caso de dois irmãos, diagnosticados comSíndrome de Menkes, enfatizando-se ainda, a raridadedesse acontecimento e os tratamentos atuais de eficácialimitada.

Menkes syndrome or Twisted Hair Syndromeand trichopolyodistrophy is a rare, X-linked recessiveneurodegenerative disorder, characterized by adisturbance in copper metabolism. The diagnosis isclinically suggested by the classic triad of features(developmental delay, neurological degenerationand malformation of the hair) and with the demonstrationof reduction of serum copper and ceruloplasmin.We report on the case of two brothers, diagnosedwith Menkes syndrome, emphasizing also therarity of this event and the current treatments of limitedeffectiveness.

Leukoencephalopathy with thalamus and brainstem involvement and high lactate 'LTBL' caused by EARS2 mutations.

In the large group of genetically undetermined infantile-onset mitochondrial encephalopathies, multiple defects of mitochondrial DNA-related respiratory-chain complexes constitute a frequent biochemical signature. In order to identify responsible genes, we used exome-next-generation sequencing in a selected cohort of patients with this biochemical signature. In an isolated patient, we found two mutant alleles for EARS2, the gene encoding mitochondrial glutamyl-tRNA synthetase. The brain magnetic resonance imaging of this patient was hallmarked by extensive symmetrical cerebral white matter abnormalities sparing the periventricular rim and symmetrical signal abnormalities of the thalami, midbrain, pons, medulla oblongata and cerebellar white matter. Proton magnetic resonance spectroscopy showed increased lactate. We matched this magnetic resonance imaging pattern with that of a cohort of 11 previously selected unrelated cases. We found mutations in the EARS2 gene in all. Subsequent detailed clinical and magnetic resonance imaging based phenotyping revealed two distinct groups: mild and severe. All 12 patients shared an infantile onset and rapidly progressive disease with severe magnetic resonance imaging abnormalities and increased lactate in body fluids and proton magnetic resonance spectroscopy. Patients in the 'mild' group partially recovered and regained milestones in the following years with striking magnetic resonance imaging improvement and declining lactate levels, whereas those of the 'severe' group were characterized by clinical stagnation, brain atrophy on magnetic resonance imaging and persistent lactate increases. This new neurological disease, early-onset leukoencephalopathy with thalamus and brainstem involvement and high lactate, is hallmarked by unique magnetic resonance imaging features, defined by a peculiar biphasic clinical course and caused by mutations in a single gene, EARS2, expanding the list of medically relevant defects of mitochondrial DNA translation.

Smoking and other pre-gestational risk factors for spontaneous preterm birth / Tabagismo e outros fatores de risco pré-gestacional para nascimento espontâneo prematuro

OBJECTIVES: to investigate pre-gestational risk factors for spontaneous preterm birth and, the role of smoking and its cumulative effects on prematurity. METHODS: a case-control study analyzed a data set of all births occurring in a tertiary maternity hospital between April 2002 and July 2004. Spontaneous preterm births of single and live newborns without malformations were selected as cases. Controls were all the term births of live and single newborns without malformations during the same period. Three outcomes were studied: all preterm births (<37 weeks), less than 35 weeks and less than 32 weeks of gestational age. Logistic regression was used to obtain the independent effect of pre-gestational risk factors. RESULTS: maternal age of less than 20 years, low schooling, low maternal pre-gestational body mass index and smoking showed significant, independent association with spontaneous preterm birth for the three outcomes. For all these risk factors, excepting maternal smoking, odds ratios increased with decreasing gestational age at birth and this trend was significant for low maternal age and low pre-gestational body mass index. CONCLUSIONS: the cumulative effects of smoking calls for the need to encourage smoking cessation among pregnant women, especially those who are underweight and in the older age groups, because of the increased risk of delivering premature babies.

OBJETIVOS: investigar fatores de risco pré-gestacional para nascimento espontâneo prematuro e o papel do tabagismo e seus efeitos cumulativos na prematuridade. MÉTODOS: um estudo transversal baseado em um banco de dados maternos e perinatais, analisou todos os nascimentos ocorridos, em um hospital terciário, no período de abril de 2002 a julho de 2004. Nascimentos prematuros, únicos e espontâneos, de nascidos vivos, sem malformações, foram selecionados como casos. Controles foram selecionados como nascidos vivos e a termo, únicos e sem malformações durante o mesmo período. Três desfechos foram estudados: todos nascimentos prematuros com menos de 37 semanas, aqueles com menos de 35 e 32 semanas de gestação. Regressão Logística foi utilizada na determinação do efeito independente de cada um dos fatores de risco. RESULTADOS: idade materna de menos de 20 anos, baixa escolaridade, baixo índice de massa corporal pré-gestacional e tabagismo se mostraram independente e significativamente associados com nascimento espontâneo e prematuro para os três desfechos. Para todos os fatores de risco, exceto tabagismo materno, as razões de chance aumentaram linearmente com o decréscimo da idade gestacional. O teste para tendência linear se mostrou significante para idade materna de menos de 20 anos e para baixo índice de massa corporal pré-gestacional. CONCLUSÕES: os efeitos cumulativos do tabagismo apontam para a necessidade de incentivar o abandono do hábito de fumar entre as gestantes, especialmente entre aquelas com baixo índice de massa corporal e em idade mais avançada, devido ao risco aumentado de prematuridade neste grupo específico.

tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia.

Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the ventral pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological disorders.

Epstein-Barr virus acute encephalomyelitis in a 13-year-old boy.

The association of acute myelopathy and encephalopathy is reported in a 13-year-old boy. Signs and symptoms of infectious mononucleosis, presence of heterophile antibodies, anticapsid antibodies and Epstein-Barr virus DNA detected in cerebrospinal fluid, disclosed a primary or reactivated infection by Epstein-Barr virus. Outcome was rapid and benign with complete clinical recovery in 1 month, after pulse therapy with methylprednisolone. Epstein-Barr virus is a known agent related to acute disseminated encephalomyelitis, by immune mediated mechanisms. However, in this case, cortical involvement in magnetic resonance imaging, short time between infectious mononucleosis and central nervous system manifestations, and the presence of viral DNA in cerebrospinal fluid, raised the possibility of a direct action of the virus in central nervous system. Acute myelopathy associated to Epstein-Barr virus encephalitis has been rarely reported in children.