Procalcitonina. Utilidad como biomarcador en el diagnóstico de tumores neuroendocrinos

Procalcitonin is used in the day-to-day hospital as a biomarker of bacterial infectious pathology. In recent years, its usefulness for the diagnosis of different neuroendocrine tumors has been described. We present the case of a 73-year-old man with a diagnosis of a high-grade neuroendocrine tumor of unknown origin with single and massive liver involvement being compatible, due to the elevated prostatic antigen (PSA), with a high-grade neuroendocrine tumor of prostate origin with visceral involvement and analytically presenting elevated procalcitonin.La procalcitonina es utilizada en el día a día hospitalario como biomarcador de patología infecciosa bacteriana. En los últimos años se ha descrito su utilidad para el diagnóstico de diferentes tumores neuroendocrinos. Exponemos el caso de un varón de 73 años con diagnóstico de tumor neuroendocrino de alto grado de origen desconocido con afectación única y masiva hepática siendo compatible, por la elevación del antígeno prostático (PSA), con un tumor neuroendocrino de origen prostático de alto grado con afectación visceral y que presentaba analíticamente elevación de procalcitonina

Determinação do trajeto do canal mandibular por meio de tomografia computadorizada em dez mandíbulas de cadáveres de cães mesaticefálicos

Sabe-se que durante qualquer procedimento cirúrgico na região da mandíbula no homem, um dano iatrogênico ao feixe vasculonervoso que percorre o canal mandibular (CM) poderia causar desde parestesia até dor constante. Na odontologia veterinária, diferentes procedimentos cirúrgicos são realizados no tecido ósseo adjacente ao CM, o que implica no conhecimento acurado da localização do mesmo. O objetivo desta pesquisa foi determinar por meio da Tomografia Computadorizada (TC) o trajeto do CM em relação às faces da mandíbula: lingual, vestibular, ventral e crista alveolar em dez mandíbulas de cadáveres de cães mesaticefálicos. Os tomogramas foram realizados no plano transversal, tomando como referência para cada corte o forame mandibular, as raízes dentárias dos dentes molares, pré-molares e forame mentoniano médio. No tomógrafo foram realizadas medidas desde o CM até as diferentes faces. Conclui-se que a partir do dente 3º molar, no sentido rostral, o CM aumenta gradualmente a distância em relação à crista alveolar, alcançando a sua máxima profundidade na região dente 1º molar. Em relação às faces vestibular e lingual, o CM apresentou-se lingualizado na região dos dentes molares. O CM continua rostralmente ocupando a região ventral do corpo da mandíbula, mantendo uma distância similar entre a superfície vestibular e lingual. Já na região do dente 3º pré-molar o canal mandibular aumenta ligeiramente a sua distância com relação à face ventral e lingual da mandíbula, antes do seu fim no forame mentoniano medial na face vestibular da mandíbula.As it is known, during any surgical procedure in the human mandible, an iatrogenic damage to the neurovascular bundle that runs along the mandibular canal (MC) could cause from paresthesia to constant pain. In veterinary dentistry, different surgical procedures are performed on the bone tissue adjacent to the MC, which implies accurate knowledge of its localization. The purpose of this study was to determine by means of computerized tomography (CT) the path of the MC in relation with: lingual surface, vestibular surface, alveolar crest, and ventral mandible surface in ten mesaticephalic dogs. The slices were performed in transverse plane using as reference the mandibular foramen, the medial mental foramen and the tooth roots of molars and premolars; several measures among the MC and the mandibular faces were performed. The conclusion of this study was that from the 3rd molar tooth (following in rostral direction), the MC gradually increases its distance from the alveolar crest, reaching its maximum depth in the 1st molar tooth area. In the molar area, the MC was located nearly of the mandibular lingual surface. The CM continues rostrally occupying the ventral region of the mandible body keeping a similar distance between the buccal and lingual surface. Then in the 3rd premolar area the MC increases slightly its distance from the ventral aspect of the mandible, before its end in the medial mental foramen on the face of the mandible

Clinical and demographical profile of chronic muscleskeletal pain patients assisted at Brazilian Health Public System

The purpose of this study is to determine the demographic and clinical profile of patients with muscle-skeletal chronic pain.  One hundred and fifty patients were evaluated, being divided in three groups according to the clinical setting of origin: Basic Unit of Health (BUH), City Specialty Clinic (CSC) and University Clinic (UC).It was observed a strong female predominance in the three groups.(BUH - 74%; CSC - 66%; UC - 80%). The observed age distribution showed that most of the patients from BUH were above 60 years old (50%) and most patients of the other two units were between 41 and 60 years old. In relation to joint distribution, most part of patients at the BHU presented with involvement of less than 4 joints (60%) and at the UC more than 4 joints (60%). At the CSC, most of the complains were localized at the vertebral spine. Unspecific diagnoses were reported more often at the BUH (40%) than at the CSC (20%) and UC (16%). There were less discontinuation of treatment at the UC in relation to the BUH and CSC. At the BHU 28% of patients reported continuous treatment in comparison to 74% of the CSC and 92% at UC. At worsening of pain, most patients of BHU used self-medication, while at the CSC and UC patients followed medical prescription. It was concluded that the secondary and tertiary levels of health institutions (CSC, UC) are able to treat pain patients with diseases of higher complexity.O objetivo desse estudo é determinar o perfil demográfico e clínico dos pacientes dor crônica.  Avaliou-se 150 pessoas no Centro de Saúde Escola (CSE) (50), na Policlínica Municipal de Sorocaba (50) e no Conjunto Hospitalar de Sorocaba (CHS) (50). Observou-se forte predominância do sexo feminino nas três unidades avaliadas (CSE - 74%; POLICLÍNICA - 66%; CHS - 80%). Em relação a idade houve um predomínio da faixa acima dos 60 anos no CSE (50%) e da faixa entre 41 e 60 anos na Policlínica (52%) e CHS (50%). Quanto à distribuição articular, houve um predomínio da dor oligoarticular no CSE (60%) e de distribuição poliarticular no CHS (60%). Na Policlínica a maioria das queixas se concentrou na coluna vertebral (52%), No CSE (40%) um maior número de pacientes referiu desconhecer um diagnóstico estabelecido em relação aos pacientes da Policlínica (20%) e do CHS (16%).Observa-se, maior continuidade no tratamento no CHS em relação ao CSE e Policlínica. No CSE 28% dos pacientes referiam manter tratamento contínuo em comparação com 74% na POLICLÍNICA e 92% no CHS. Nas agudizações, os pacientes do CSE tomam remédio por conta própria em sua maioria, enquanto que grande parte dos pacientes da Policlínica e do CHS tomam remédio conforme orientação médica. Concluí - se que as unidades secundárias e terciárias de atendimento público a saúde estão aptas a atender casos de maior complexidade e, portanto, em número insuficiente para atender a demanda

Surveillance of Salmonella enterica serovar Typhi in Colombia, 2012-2015.

Salmonella Typhi (S. Typhi) is the causative agent of typhoid fever; a systemic disease affecting ~20 million people per year globally. There are little data regarding the contemporary epidemiology of typhoid in Latin America. Consequently, we aimed to describe some recent epidemiological aspects of typhoid in Colombia using cases reported to the National Public Health Surveillance System (Sivigila) between 2012 and 2015. Over the four-year reporting period there were 836 culture confirmed cases of typhoid in Colombia, with the majority (676/836; 80.1%) of reported cases originated from only seven departments. We further characterized 402 S. Typhi isolates with available corresponding data recovered from various departments of Colombia through antimicrobial susceptibility testing and molecular subtyping. The majority (235/402; 58.5%) of these typhoid cases occurred in males and were most commonly reported in those aged between 10 and 29 years (218/402; 54.2%); there were three (0.74%) reported fatalities. The overwhelming preponderance (339/402; 84.3%) of S. Typhi were susceptible to all tested antimicrobials. The most common antimicrobial to which the organisms exhibited non-susceptibility was ampicillin (30/402;7.5%), followed by nalidixic acid (23/402, 5.7%). Molecular subtyping identified substantial genetic diversity, which was well distributed across the country. Despite the diffuse pattern of S. Typhi genotypes, we identified various geographical hotspots of disease associated with local dominant genotypes. Notably, we found limited overlap of Colombian genotypes with organisms reported in other Latin American countries. Our work highlights a substantial burden of typhoid in Colombia, characterized by sustained transmission in some regions and limited epidemics in other departments. The disease is widely distributed across the country and associated with multiple antimicrobial susceptible genotypes that appear to be restricted to Colombia. This study provides a current perspective for typhoid in Latin America and highlights the importance of pathogen-specific surveillance to add insight into the limited epidemiology of typhoid in this region

A Proposed Approach to Chronic Airway Disease (CAD) Using Therapeutic Goals and Treatable Traits: A Look to the Future

© 2020 Pérez de Llano et al.Chronic airflow obstruction affects a wide range of airway diseases, the most frequent of which are asthma, COPD, and bronchiectasis; they are clearly identifiable in their extremes, but quite frequently overlap in some of their pathophysiological and clinical characteristics. This has generated the description of new mixed or overlapping disease phenotypes with no clear biological grounds. In this special article, a group of experts provides their perspective and proposes approaching the treatment of chronic airway disease (CAD) through the identification of a series of therapeutic goals (TG) linked to treatable traits (TT) – understood as clinical, physiological, or biological characteristics that are quantifiable using biomarkers. This therapeutic approach needs validating in a clinical trial with the strategy of identification of TG and treatment according to TT for each patient independently of their prior diagnosis

The frequency of defective genomes in Omicron differs from that of the Alpha, Beta and Delta variants

Evolution; Genetics; Molecular biologyEvolució; Genètica; Biologia molecularEvolución; Genética; Biología molecularThe SARS-CoV-2 Omicron variant emerged showing higher transmissibility and possibly higher resistance to current COVID-19 vaccines than other variants dominating the global pandemic. In March 2020 we performed a study in clinical samples, where we found that a portion of genomes in the SARS-CoV-2 viral population accumulated deletions immediately before the S1/S2 cleavage site (furin-like cleavage site, PRRAR/S) of the spike gene, generating a frameshift and appearance of a premature stop codon. The main aim of this study was to determine the frequency of defective deletions in prevalent variants from the first to sixth pandemic waves in our setting and discuss whether the differences observed might support epidemiological proposals. The complete SARS-CoV-2 spike gene was deeply studied by next-generation sequencing using the MiSeq platform. More than 90 million reads were obtained from respiratory swab specimens of 78 COVID-19 patients with mild infection caused by the predominant variants circulating in the Barcelona city area during the six pandemic waves: B.1.5, B.1.1, B.1.177, Alpha, Beta, Delta, and Omicron. The frequency of defective genomes found in variants dominating the first and second waves was similar to that seen in Omicron, but differed from the frequencies seen in the Alpha, Beta and Delta variants. The changing pattern of mutations seen in the various SARS-CoV-2 variants driving the pandemic waves over time can affect viral transmission and immune escape. Here we discuss the putative biological effects of defective deletions naturally occurring before the S1/S2 cleavage site during adaption of the virus to human infection.This study was partially supported by Pla Estratègic de Recerca i Innovació en Salut (PERIS) – Direcció General de Recerca i Innovació en Salut (DGRIS), Catalan Health Ministry, Generalitat de Catalunya; the Spanish Network for the Research in Infectious Diseases (REIPI RD16/0016/0003) from the European Regional Development Fund (ERDF); Centro para el Desarrollo Tecnológico Industrial (CDTI) from the Spanish Ministry of Economy and Business, grant number IDI-20200297; Grant PI19/00301 from Instituto de Salud Carlos III cofinanced by the European Regional Development Fund (ERDF), and Gilead’s biomedical research project GLD21/00006. We gratefully acknowledge the authors, originating and submitting laboratories of the sequences from GISAID’s EpiCov Database on which this research is based

The effect of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea and uncontrolled hypertension : study design and challenges during the COVID-19 pandemic

OBJECTIVES: To describe the MORPHEOS (Morbidity in patients with uncontrolled HTN and OSA) trial, and describe the challenges imposed by the COVID-19 pandemic. METHODS: MORPHEOS is a multicenter (n=6) randomized controlled trial designed to evaluate the blood pressure (BP) lowering effects of treatment with continuous positive airway pressure (CPAP) or placebo (nasal strips) for 6 months in adult patients with uncontrolled hypertension (HTN) and moderate-to-severe obstructive sleep apnea (OSA). Patients using at least one antihypertensive medication were included. Uncontrolled HTN was confirmed by at least one abnormal parameter in the 24-hour ABPM and >= 80% medication adherence evaluated by pill counting after the run-in period. OSA was defined by an apnea-hypopnea index >= 15 events/ hours. The co-primary endpoints are brachial BP (office and ambulatory BP monitoring, ABPM) and central BP. Secondary outcomes include hypertension-mediated organ damage (HMOD) to heart, aorta, eye, and kidney. We pre-specified several sub-studies from this investigation. Visits occur once a week in the first month and once a month thereafter. The programmed sample size was 176 patients but the pandemic prevented this final target. A post-hoc power analysis will be calculated from the final sample. ClinicalTrials.gov: NCT02270658. RESULTS: The first 100 patients are predominantly males (n=69), age: 52±10 years, body mass index: 32.7±3.9 kg/m2 with frequent co-morbidities. CONCLUSIONS: The MORPHEOS trial has a unique study design including a run-in period; pill counting, and detailed analysis of hypertension-mediated organ damage in patients with uncontrolled HTN that will allow clarification of the impact of OSA treatment with CPAP

Characteristics of 24 SARS-CoV-2-Sequenced Reinfection Cases in a Tertiary Hospital in Spain

SARS-CoV-2; Clinical features; ReinfectionSARS-CoV-2; Características clínicas; ReinfecciónSARS-CoV-2; Característiques clíniques; ReinfeccióBackground: Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the main concern is whether reinfections are possible, and which are the associated risk factors. This study aims to describe the clinical and molecular characteristics of 24 sequence-confirmed reinfection SARS-CoV-2 cases over 1 year in Barcelona (Catalonia, Spain). Methods: Patients with > 45 days between two positive PCR tests regardless of symptoms and negative tests between episodes were initially considered as suspected reinfection cases from November 2020 to May 2021. Whole-genome sequencing (WGS) was performed to confirm genetic differences between consensus sequences and for phylogenetic studies based on PANGOLIN nomenclature. Reinfections were confirmed by the number of mutations, change in lineage, or epidemiological criteria. Results: From 39 reported suspected reinfection cases, complete viral genomes could be sequenced from both episodes of 24 patients, all were confirmed as true reinfections. With a median age of 44 years (interquartile range [IQR] 32–65), 66% were women and 58% were healthcare workers (HCWs). The median days between episodes were 122 (IQR 72–199), occurring one-third within 3 months. Reinfection episodes were frequently asymptomatic and less severe than primary infections. The absence of seroconversion was associated with symptomatic reinfections. Only one case was reinfected with a variant of concern (VOC). Conclusion: Severe acute respiratory syndrome coronavirus 2 reinfections can occur in a shorter time than previously reported and are mainly found in immunocompetent patients. Surveillance through WGS is useful to identify viral mutations associated with immune evasion.This research was supported by CIBER -Consorcio Centro de Investigación Biomédica en Red- (CB 2021), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea – NextGenerationEU

A year living with SARS-CoV-2: an epidemiological overview of viral lineage circulation by whole-genome sequencing in Barcelona city (Catalonia, Spain)

Catalonia; SARS-CoV-2; Molecular epidemiologyCataluña; SARS-CoV-2; Epidemiología molecularCatalunya; SARS-CoV-2; Epidemiologia molecularHerein, we describe the genetic diversity of circulating SARS-CoV-2 viruses by whole-genome sequencing (WGS) in Barcelona city (Catalonia, Spain) throughout the first four pandemic waves. From weeks 11/2020–24/2021, SARS-CoV-2-positive respiratory samples were randomly selected per clinical setting (80% from primary care or 20% from the hospital), age group, and week. WGS was performed following the ARTICv3 protocol on MiSeq or NextSeq2000 Illumina platforms. Nearly complete consensus sequences were used for genetic characterization based on GISAID and PANGOLIN nomenclatures. From 2475 samples, 2166 (87%) were fully sequenced (78% from primary care and 22% from hospital settings). Multiple genetic lineages were co-circulating, but four were predominant at different periods. While B.1.5 (50.68%) and B.1.1 (32.88%) were the major lineages during the first pandemic wave, B.1.177 (66.85%) and B.1.1.7 (83.80%) were predominant during the second, third, and fourth waves, respectively. Almost all (96.4%) were carrying D614G mutation in the S protein, with additional mutations that define lineages or variants. But some mutations of concern, such as E484K from B.1.351 and P.1 lineages are currently under monitoring, together with those observed in the receptor-binding domain or N-terminal domain, such as L452R and T478K from B.1.617.2 lineage. The fact that a predominant lineage was observed in each pandemic wave suggests advantageous properties over other contemporary co-circulating variants. This genetic variability should be monitored, especially when a massive vaccination campaign is ongoing because the potential selection and emergence of novel antigenic SARS-CoV-2 strains related to immunological escapement events.This work was supported by Spanish Network for the Research in Infectious Diseases: [Grant Number REIPI RD16/0016/0003]; Centro para el Desarrollo Tecnológico Industrial (CDTI) from the Spanish Ministry of Economy and Business [Grant Number IDI-20200297]; Direcció General de Recerca i Innovació en Salut (DGRIS); European Development Regional Fund (ERDF) “A way to achieve Europe” by Spanish Network for Research in Infectious Diseases [REIPI RD16/0016/0003]

Maternal outcomes and risk factors for COVID-19 severity among pregnant women.

Pregnant women may be at higher risk of severe complications associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may lead to obstetrical complications. We performed a case control study comparing pregnant women with severe coronavirus disease 19 (cases) to pregnant women with a milder form (controls) enrolled in the COVI-Preg international registry cohort between March 24 and July 26, 2020. Risk factors for severity, obstetrical and immediate neonatal outcomes were assessed. A total of 926 pregnant women with a positive test for SARS-CoV-2 were included, among which 92 (9.9%) presented with severe COVID-19 disease. Risk factors for severe maternal outcomes were pulmonary comorbidities [aOR 4.3, 95% CI 1.9-9.5], hypertensive disorders [aOR 2.7, 95% CI 1.0-7.0] and diabetes [aOR2.2, 95% CI 1.1-4.5]. Pregnant women with severe maternal outcomes were at higher risk of caesarean section [70.7% (n = 53/75)], preterm delivery [62.7% (n = 32/51)] and newborns requiring admission to the neonatal intensive care unit [41.3% (n = 31/75)]. In this study, several risk factors for developing severe complications of SARS-CoV-2 infection among pregnant women were identified including pulmonary comorbidities, hypertensive disorders and diabetes. Obstetrical and neonatal outcomes appear to be influenced by the severity of maternal disease