Forensic Microbiology: When, Where and How.

Forensic microbiology is a relatively new discipline, born in part thanks to the development of advanced methodologies for the detection, identification and characterization of microorganisms, and also in relation to the growing impact of infectious diseases of iatrogenic origin. Indeed, the increased application of medical practices, such as transplants, which require immunosuppressive treatments, and the growing demand for prosthetic installations, associated with an increasing threat of antimicrobial resistance, have led to a rise in the number of infections of iatrogenic origin, which entails important medico-legal issues. On the other hand, the possibility of detecting minimal amounts of microorganisms, even in the form of residual traces (e.g., their nucleic acids), and of obtaining gene and genomic sequences at contained costs, has made it possible to ask new questions of whether cases of death or illness might have a microbiological origin, with the possibility of also tracing the origin of the microorganisms involved and reconstructing the chain of contagion. In addition to the more obvious applications, such as those mentioned above related to the origin of iatrogenic infections, or to possible cases of infections not properly diagnosed and treated, a less obvious application of forensic microbiology concerns its use in cases of violence or violent death, where the characterization of the microorganisms can contribute to the reconstruction of the case. Finally, paleomicrobiology, e.g., the reconstruction and characterization of microorganisms in historical or even archaeological remnants, can be considered as a sister discipline of forensic microbiology. In this article, we will review these different aspects and applications of forensic microbiology.

The Future Is Now: Unraveling the Expanding Potential of Human (Necro)Microbiome in Forensic Investigations.

The relevance of postmortem microbiological examinations has been controversial for decades, but the boom in advanced sequencing techniques over the last decade is increasingly demonstrating their usefulness, namely for the estimation of the postmortem interval. This comprehensive review aims to present the current knowledge about the human postmortem microbiome (the necrobiome), highlighting the main factors influencing this complex process and discussing the principal applications in the field of forensic sciences. Several limitations still hindering the implementation of forensic microbiology, such as small-scale studies, the lack of a universal/harmonized workflow for DNA extraction and sequencing technology, variability in the human microbiome, and limited access to human cadavers, are discussed. Future research in the field should focus on identifying stable biomarkers within the dominant Bacillota and Pseudomonadota phyla, which are prevalent during postmortem periods and for which standardization, method consolidation, and establishment of a forensic microbial bank are crucial for consistency and comparability. Given the complexity of identifying unique postmortem microbial signatures for robust databases, a promising future approach may involve deepening our understanding of specific bacterial species/strains that can serve as reliable postmortem interval indicators during the process of body decomposition. Microorganisms might have the potential to complement routine forensic tests in judicial processes, requiring robust investigations and machine-learning models to bridge knowledge gaps and adhere to Locard's principle of trace evidence.

Genotypic Findings in Noonan and Non-Noonan RASopathies and Patient Eligibility for Growth Hormone Treatment.

Molecular study has become an invaluable tool in the field of RASopathies. Treatment with recombinant human growth hormone is approved in Noonan syndrome but not in the other RASopathies. The aim of this study was to learn about the molecular base of a large cohort of patients with RASopathies, with particular emphasis on patients with pathogenic variants in genes other than PTPN11, and its potential impact on rGH treatment indication. We reviewed the clinical diagnosis and molecular findings in 451 patients with a genetically confirmed RASopathy. HRAS alterations were detected in only 2 out of 19 patients referred with a Costello syndrome suspicion, whereas pathogenic variants in RAF1 and SHOC2 were detected in 3 and 2, respectively. In 22 patients referred with a generic suspicion of RASopathy, including cardiofaciocutaneous syndrome, pathogenic alterations in classic Noonan syndrome genes (PTPN11, SOS1, RAF1, LZTR1, and RIT1) were found in 7 patients and pathogenic variants in genes associated with other RASopathies (HRAS, SHOC2, and PPPCB1) in 4. The correct nosological classification of patients with RASopathies is critical to decide whether they are candidates for treatment with rhGH. Our data illustrate the complexity of differential diagnosis in RASopathies, as well as the importance of genetic testing to guide the diagnostic orientation in these patients.

Positive airway pressure longer than 24 h is associated with histopathological volutrauma in severe COVID-19 pneumonia-an ESGFOR based narrative case-control review.

Background and Objective: A thorough understanding of the pathogenic mechanisms elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still requires further research. Until recently, only a restricted number of autopsies have been performed, therefore limiting the accurate knowledge of the lung injury associated with SARS-CoV-2. A multidisciplinary European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group of Forensic and Post-mortem Microbiology-ESGFOR team conducted a non-systematic narrative literature review among coronavirus 2019 disease (COVID-19) pneumonia cases assessing the histopathological (HP) effects of positive airways pressure. HP lung features were recorded and compared between mechanically ventilated (>24 hours) and control (ventilation <24 hours) patients. A logistic regression analysis was performed to identify associations between mechanical ventilation (MV) and HP findings. Methods: A PubMed and MEDLINE search was conducted in order to identify studies published between March 1st 2020 and June 30th 2021. Key Content and Findings: Seventy patients (median age: 69 years) from 24 studies were analysed, among whom 38 (54.2%) underwent MV longer than 24 hours. Overall, main HP features were: diffuse alveolar damage (DAD) in 53 (75.7%), fibrosis (interstitial/intra-alveolar) in 43 (61.4%), vascular damage-including thrombosis/emboli- in 41 (58.5%), and endotheliitis in only 8 (11.4%) patients. Association of DAD, fibrosis and vascular damage was detected in 30 (42.8%) patients. Multivariate analysis, adjusted by age and gender, identified MV >24 hours as an independent variable associated with DAD (OR =5.40, 95% CI: 1.48-19.62), fibrosis (OR =3.88, 95% CI: 1.25-12.08), vascular damage (OR =5.49, 95% CI: 1.78-16.95) and association of DAD plus fibrosis plus vascular damage (OR =6.99, 95% CI: 2.04-23.97). Conclusions: We identified that patients mechanically ventilated >24 hours had a significantly higher rate of pulmonary injury on histopathology independently of age and gender. Our findings emphasize the importance of maintaining a protective ventilator strategy when subjects with COVID-19 pneumonia undergo intubation.

Myocarditis Presenting as Sudden Death in Infants and Children: A Single Centre Analysis by ESGFOR Study Group.

BACKGROUND: Acute myocarditis is an inflammatory disease of the heart mostly diagnosed in young people, which can present as sudden death. The etiology includes infectious agents (mostly viruses), systemic diseases and toxins. We aim to characterize infants and children with myocarditis at post-mortem presenting as sudden deaths. METHODS: Retrospective evaluation of 813 post-mortems in infants and children dying suddenly and unexpectedly between 2009-2019. Data retrieved included histological features, microbiology and clinical history. RESULTS: 23 of 813 post-mortems reviewed corresponded to acute myocarditis and 1 to dilated cardiomyopathy related to remote Parvovirus infection. PCR identified enterovirus (7), parvovirus (7 cases, 2 also with HHV6 and 1 case with EVB), Influenza A (1), Parainfluenza type 3 (1). Two cases corresponded to hypersensitivity myocarditis, 1 was Group A Streptococcus and 5 idiopathic myocarditis. Enterovirus was frequent in infants (7/10), and in newborns was associated with meningoencephalitis or congenital myocarditis. More than 50% were less than 2 years of age and all remained clinically unsuspected. CONCLUSION: Myocarditis represents almost 3% of all sudden pediatric deaths. Enterovirus and parvovirus were the most common viruses. This retrospective analysis showed that patients experienced viral symptoms but remained unsuspected, highlighting the need for more clinical awareness of myocarditis.

Forensic evaluation of two nucleic acid extraction systems and validation of a RT-qPCR protocol for identification of SARS-CoV-2 in post-mortem nasopharyngeal swabs.

The COVID-19 outbreak has represented a challenge for the international scientific community and particularly for forensic sciences. The lack of Coronavirus post-mortem testing led the National Institute of Toxicology and Forensic Sciences (INTCF) from Spain to verify the performance and utility of a quantitative reverse transcription PCR (RT-qPCR) clinical diagnosis protocol for SARS-CoV-2 detection (TaqPath™ COVID-19 CE-IVD RT-PCR Kit), to shed light on the cause of death (COD) in potentially COVID-19 cases in judicial autopsies. Two different RNA extraction methods were also tested (EZ1® DSP Virus Kit on the EZ1® Advanced XL robot versus MagMAX™ Viral/Pathogen Nucleic Acid Isolation Kit) regarding extraction efficiency, precision and contamination. RT-qPCR was evaluated for precision, specificity, limit of detection and concordance. Both the automated and the manual RNA extraction procedures showed good efficiency, but the automated virus extraction by bio-robot produced more reproducible results than the manual extraction. The SARS-CoV-2 RT-qPCR assay showed high sensitivity with a detection limit up to 10 copies/reaction and high specificity, as no cross-reactivity was detected between any of the 12 different RNA viruses tested, including three types of coronaviruses (SARS-CoV, NL63 and 229E). Reproducibility and repeatability of the studied method as well as concordance with other SARS-CoV-2 molecular detection protocols were also demonstrated.

Microbiology in minimally invasive autopsy: best techniques to detect infection. ESGFOR (ESCMID study group of forensic and post-mortem microbiology) guidelines.

This manuscript aims to: 1) provide specific guidelines on PMM techniques in the setting of minimally invasive autopsy (MIA), both for pathologists collecting samples and for microbiologists advising pathologists and interpreting the results and 2) introduce standardization in PMM sampling at MIA. Post-mortem microbiology (PMM) is crucial to identify the causative organism in deaths due to infection. MIA including the use of post-mortem (PM) computed tomography (CT) and PM magnetic resonance imaging (MRI), is increasingly carried out as a complement or replacement for the traditional PM. In this setting, mirroring the traditional autopsy, PMM aims to: detect infectious organisms causing sudden unexpected deaths; confirm clinically suspected but unproven infection; evaluate the efficacy of antimicrobial therapy; identify emergent pathogens; and recognize medical diagnostic errors. Meaningful interpretation of PMM results requires careful evaluation in the context of the clinical history, macroscopic and microscopic findings. These guidelines were developed by a multidisciplinary team with experts in various fields of microbiology and pathology on behalf of the ESGFOR (ESCMID - European Society of Clinical Microbiology and Infectious Diseases - Study Group of Forensic and Post-mortem Microbiology, in collaboration with the ESP -European Society of Pathology-) based on a literature search and the author's expertise. Microbiological sampling methods for MIA are presented for various scenarios: adults, children, developed and developing countries. Concordance between MIA and conventional invasive autopsy is substantial for children and adults and moderate for neonates and maternal deaths. Networking and closer collaboration among microbiologists and pathologists is vital to maximize the yield of PMM in MIA.

Cirugía radioguiada de paratiroides / Radioguided parathyroid surgery

El hiperparatiroidismo primario es la principal causa de hipercalcemia en pacientes no hospitalizados, estando causado en el 85-90 % de los casos por un adenoma solitario. La cirugía radioguiada (CRG) es una técnica quirúrgica mínimamente invasiva que emplea medicamentos radiofármacos para facilitar la localización y extirpación de lesiones benignas o malignas. La cirugía radioguiada de paratiroides (CRGP), como técnica GOSTT (Guided intraOperative Scintigraphic Tumor Targeting) y mínimamente invasiva, precisa de una prueba de diagnóstico por la imagen que permita localizar anatómicamente la lesión y establecer su comportamiento funcional. El MIBI-99mTc es el trazador de elección, debiendo siempre incluir estudios tomográficos, especialmente la SPECT-CT. Se emplea durante la CRGP junto con sondas intraoperatorias, gammacámaras y dispositivos SPECT portátiles, herramientas de navegación y sistemas robóticos laparoscópicos. La CRGP disminuye el tiempo quirúrgico, los costes hospitalarios y la morbilidad sobre el paciente, con una elevada efectividad y eficiencia

Primary hyperparathyroidism is the main cause of hypercalcemia in outpatients. It is caused in 85-90 % of cases by a solitary adenoma. Radioguided surgery (RGS) is a minimally invasive surgical technique that uses radiopharmaceutical drugs to facilitate the location and removal of benign or malignant lesions. Radioguided parathyroid surgery (RGPS), as a GOSTT (Guided intraOperative Scintigraphic Tumor Targeting) technique and minimally invasive, requires a diagnostic imaging test to anatomically locate the lesion and establish its functional behavior. The MIBI-99mTc is the tracer of choice, and should always include tomographic studies, especially the SPECT-CT. This radiotracer is used during the RGPS together with intraoperative probes, gammacameras and portable SPECT devices, navigation tools and laparoscopic robotic systems. The RGPS reduces surgical time, hospital costs and patient morbidity with high effectiveness and efficiency

COVID-19 y estudios microbiológicos post mortem / COVID-19 and post-mortem microbiological studies

En este artículo se revisan los aspectos microbiológicos de la infección COVID-19 y se presentan las recomendaciones sobre los análisis que deben realizarse en casos forenses. En primer lugar se analizan las características taxonómicas del virus, su relación con la familia Coronaviridae y su estructura genética. Se presentan brevemente las características clínicas y patológicas de la infección COVID-19, así como las coinfecciones que pueden asociarse a este virus. En el diagnóstico de laboratorio se describen la PCR -técnica de elección en la fase aguda de la infección-, los estudios antigénicos y los estudios serológicos. Finalmente se detallan los principales objetivos para los estudios microbiológicos en fallecidos en relación con la pandemia COVID-19 y se describen los principales análisis microbiológicos post mortem a realizar en fallecidos en el ámbito forense. Los estudios microbiológicos deben estar dirigidos tanto a la detección del SARS-CoV-2 como a la de las coinfecciones, que también podrían contribuir a la causa de muerte

We review the microbiological aspects of COVID-19 infection and present the microbiological studies that should be performed in forensic cases. We describe the taxonomic characteristics of the virus, its relationship with the Coronaviridae family and its genetic structure. We briefly present the clinical and pathological characteristics of COVID-19 infection, as well as the co-infections that could be associated with this virus. In the laboratory, PCR is a first-choice technique in the acute phase of the infection, together with antigen and serological studies. Finally, we describe the main objectives of microbiological studies in the deceased in relation to the COVID-19 pandemic, as well as the main post-mortem microbiological analysis to be carried out in the medico-legal context. The microbiological analysis should aim to detect both SARS-CoV-2 and coinfections, which may also contribute to the cause of death

Growth and metabolic effects of long-term recombinant human growth hormone (rhGH) treatment in short children born small for gestational age: GH-RAST study.

Objectives To study the efficacy and influence on metabolism of recombinant human growth hormone (rhGH) treatment in short children born small for gestational age (SGA). Methods Retrospective, observational, multicenter study in 305 short children born SGA, treated with rhGH during a mean ± SD of 5.03 ± 1.73 years at a mean ± SD dose of 37 ± 8 µg/kg/day. Auxological and metabolic assessment including glucose and lipids profile were collected. Results Mean ± SD age at the start of treatment was 7.11 ± 2.78 years. Height and weight improved significantly until the end of treatment from mean -2.72 (CI95%: -2.81 to -2.63) standard deviation score (SDS) to -1.16 (CI95%: -1.44 to -0.88) SDS and from -1.62 (CI95%: -1.69 to -1.55) SDS to -0.94 (CI95%: -1.14 to -0.74) SDS respectively. Mean height gain was 1.27 (CI95%: 0.99-1.54) SDS. Prepubertal patients showed higher height gain than pubertal children (mean [CI95%] = 1.44 [CI95%: 1.14-1.74] vs. 0.73 [CI95%: 0.22-1.24], p=0.02). Height gain SDS during treatment negatively correlated with chronological age (CA) and bone age (BA) delay and positively correlated with duration of treatment, height gain during first year of treatment, years on prepubertal treatment and height SDS from target height (TH). Glucose, insulin, and triglycerides increased significantly but remained within the normal range. Total and LDL-cholesterol decreased significantly, and HDL-cholesterol remained unchanged. Conclusions rhGH treatment in short SGA children effectively normalized height in most of the patients and showed a safe metabolic profile. Children who benefit the most are those with greater height SDS distance from TH, BA delay, longer duration of treatment and prepubertal treatment initiation.

Linfoma folicular cutáneo agresivo en un estudio 18F-FDG PET/TC / Aggressive cutaneous follicular lymphoma in a 18F-FDG PET/CT study

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Whole-genome sequencing of Neisseria gonorrhoeae in a forensic transmission case.

Molecular epidemiology and phylogenetic analyses are frequently used in the investigation of viral transmission cases in forensic contexts. Here, we present the methods and results of the analysis of a bacterial transmission episode in an alleged child abuse case using complete genome sequences obtained by high-throughput sequencing (HTS) methods. We obtained genomes of Neisseria gonorrhoeae from the victim, the suspect, and 29 unrelated controls. The analysis of the genomes revealed that the victim and suspect isolates had identical sequences in both the bacterial chromosome and the single plasmid present in them. One of the local controls was very similar (differing in only 2 SNPs) to the case sequences, but the remaining controls were very divergent. Additional cases of identity and very high similarity among controls were observed occasionally, pointing at recent transmission cases. These results were more discriminative than the previous molecular epidemiology analyses performed at the hospital's Microbiology Service, as Multi-Locus Sequence Typing (MLST) could not distinguish between the suspect/victim and the controls isolates, and Pulse Field Gel Electrophoresis (PFGE) was not able to distinguish between the suspect/victim and one of the local controls. These results lead us to conclude that complete bacterial genome sequences obtained with HTS technologies may be a valuable tool for establishing recent transmission cases and, although more studies are needed, they have a great potential for being used in forensic analyses.

Influence of fibrin matrices and their released factors on epidermal substitute phenotype and engraftment.

Cultured epithelial autografts (CEAs) represent a life-saving surgical technique for full-thickness skin burns covering more than 60% total body surface area. However, CEAs present numerous drawbacks leading to heavy cosmetic and functional sequelae. In our previous study, we showed that human plasma-based fibrin matrices (hPBM) could improve the reparative potential of CEAs. Therefore, in the present work, we sought to investigate the role of hPBM compared with fibrin from purified fibrinogen (FPF) or plastic support on epidermal substitute formation and engraftment. The use of hPBM for epidermal substitute culture improved keratinocyte migration, proliferation, and epidermal substitute organization to a better extent than FPF in vitro. Both fibrin matrices favored greater dermal-epidermal junction protein deposition and prevented their degradation. Keratinocyte differentiation was also decreased using both fibrin matrices. Basement membrane protein deposition was mainly influenced by matrix whereas growth factors released from fibrin especially by hPBM were shown to enhance in vitro keratinocyte migration, proliferation, and epidermal substitute organization. Ultimately, epidermal substitutes grown on hPBM displayed better engraftment rates than those cultured on FPF or on plastic support in a NOD-SCID model of acute wound with the formation of a functional dermal-epidermal junction. Together, these results show the positive impact of fibrin matrices and their released growth factor on epidermal substitute phenotype and grafting efficiency. Fibrin matrices, and especially hPBM, may therefore be of interest to favor the treatment of full-thickness burn patients.

Postmortem microbiology sampling following death in hospital: an ESGFOR task force consensus statement.

Postmortem microbiology (PMM) is a valuable tool in the identification of the cause of death and of factors contributory to death where death has been caused by infection. The value of PMM is dependent on careful autopsy planning, appropriate sampling, minimisation of postmortem bacterial translocation and avoidance of sample contamination. Interpretation of PMM results requires careful consideration in light of the clinical history, macroscopic findings and the histological appearances of the tissues. This consensus statement aims to highlight the importance of PMM in the hospital setting and to give microbiological and pathological advice on sampling in deaths occurring in hospital.

Mucocele apendicular / Appendiceal mucocele

El mucocele apendicular es una dilatación quística de la luz del apéndice ileocecal de etiología obstructiva que produce un acúmulo retrógrado de sustancia mucoide. Representa un 8-10% de todos los tumores apendiculares, con una incidencia del 0,2-0,3% de todas las apendicectomías. La etiología hace referencia a procesos no neoplásicos o tumorales (cistoadenoma o cistoadenocarcinoma mucinoso). Un incorrecto abordaje terapéutico o un diagnóstico histológico poco definido o incompleto, pueden provocar un síndrome de pseudomixoma peritoneal. El objetivo de este trabajo es describir un caso de mucocele apendicular. Se trata de una paciente de sexo femenino de 68 años de edad, que consultó en el servicio de emergencia por dolor abdominal a nivel de epigastrio, irradiado a la fosa iliaca derecha, con clínica sugerente de proceso inflamatorio apendicular, y tomográficamente se evidenció imagen probable de mucocele apendicular. Luego del tratamiento quirúrgico, la paciente mejoró significativamente. La TC con contraste es más comúnmente utilizada para el diagnóstico prequirúrgico. El objetivo final de la terapéutica es la de evitar la ruptura del mucocele apendicular y el síndrome de pseudomixoma peritoneal, por lo cual es importante contar con la TC simple y contrastada de abdomen y pelvis para la adecuada planeación quirúrgica en los casos sospechosos de mucocele apendicular.

The appendiceal mucocele is cystic dilation light ileocecal appendix obstructive etiology which causes a retrograde accumulation of mucoid substance. A 8-10% of all appendiceal tumors, with an incidence of 0.2 to 0.3% of all appendectomies. The etiology refers to non-neoplastic or tumor (cystadenoma or mucinous cystadenocarcinoma) processes. Incorrect therapeutic approach or poorly defined or incomplete histological diagnosis, can cause peritoneal pseudomixoma syndrome. The aim of this paper is to describe a case of appendiceal mucocele. It is a female patient of 68 years old who consulted in the emergency department for abdominal pain at epigastrium, radiating to the right iliac fossa, with suggestive clinical appendicular inflammatory process, and tomographic image likely was evident appendiceal mucocele. After surgery, the patient improved significantly. Contrast CT is most commonly used for presurgical diagnosis. The ultimate goal of therapeutic is to prevent rupture of the appendiceal mucocele syndrome peritoneal pseudomixoma, so it is important to have the simple and contrast CT of the abdomen and pelvis for proper surgical planning in suspected cases of appendiceal mucocele.

Resonancia Magnética Cardíaca en el diagnóstico de miocarditis / Cardiac Magnetic Resonance in the diagnosis of myocarditis

El uso de la Resonancia Magnética Cardiaca (RMC), se ha convertido en los últimos años en una herramienta fundamental para el diagnóstico de diversas miocardiopatías, entre las cuales sobresale la miocarditis, entidad que cursa con manifestaciones y signos clínicos muy variables y poco específicos en la mayor parte de los casos, lo que la convierte en una patología difícil de reconocer sobre todo en sus episodios de presentación inicial, lo que probablemente conlleve a que sea subdiagnosticada. El desarrollo de nuevas modalidades de imagen ha permitido que ante la sospecha de esta entidad el uso de la RMC se convierta en la técnica ideal para el diagnóstico temprano. A continuación se presenta el caso clínico de un paciente masculino que acude con cuadro de dolor torácico agudo, enzimas cardiacas elevadas, electrocardiograma no concluyente y coronarias normales, mostrando el curso insidioso de esta patología así como de manera resumida el rol de la RMC en su diagnóstico y pronóstico.

The use of cardiac magnetic resonance (CMR) has become in recent years an essential tool for diagnosing various cardiomyopathies, among which stands myocarditis, an entity that presents with demonstrations and highly variable clinical signs and unspecific in most cases, which makes it a difficult disease to recognize especially in its initial filing episodes, which probably lead to be underdiagnosed. The development of new imaging modalities has allowed suspicion of this entity using the RMC becomes the ideal technique for early diagnosis. Next, the case of a male patient presenting with symptoms of acute chest pain, elevated cardiac enzymes inconclusive electrocardiogram and normal coronary showing insidious course of this disease and in summary the role of the RMC in its presented diagnosis and prognosis.

Importancia de la autopsia forense en el diagnóstico del shock séptico: a propósito de un caso / Importance of the forensic autopsy in the diagnosis of septic shock: a case report

El shock séptico en ocasiones se inicia con síntomas inespecíficos que dificultan el diagnóstico clínico y por tanto el tratamiento adecuado. Cuando la evolución es fulminante y el resultado es fatal, el único diagnóstico etiológico posible es el post mortem. Las muertes súbitas e inesperadas en los niños y adultos jóvenes son objeto con frecuencia de las autopsias forenses. Algunas muertes súbitas tienen origen infeccioso, lo que obliga a realizar análisis complementarios, incluidos los microbiológicos, para establecer la causa de la muerte. Se presenta el caso de un varón de 19 meses de edad que, tras sufrir un cuadro banal de una herida en el pie, evolucionó hasta shock séptico y fallecimiento como consecuencia de una sepsis por Streptococcus pyogenes, como se demostró en los estudios post mortem (AU)

Septic shock sometimes starts with unspecific symptoms that hamper the clinical diagnosis and, therefore an appropriate treatment. When the septic shock follows a fulminating course with a fatal outcome, the etiological diagnosis has to be conducted post-mortem. Sudden unexpected deaths in children and young adults are frequently the object of medico-legal autopsies. Some sudden unexpected deaths have an infectious origin, which requires further analyses, including microbiology, to establish the cause of death. Here, the case of a fatal septic shock in a 19-month old male infant is presented. After a mild foot injury, an infection by Streptococcus pyogenes progressed to septic shock with a fatal outcome as post-mortem studies demonstrated (AU)

Recomendaciones para el diagnóstico y tratamiento de pacientes con formas clásicas de hiperplasia suprarrenal congénita por déficit de 21-hidroxilasa / Recommendations for the diagnosis and treatment of classic forms of 21-hydroxylase-deficient congenital adrenal hyperplasia

La hiperplasia suprarrenal congénita debida al déficit de 21-hidroxilasa es una enfermedad autosómica recesiva causada por mutaciones en el gen CYP21A2. En las formas clásicas se produce defecto de cortisol y aldosterona (insuficiencia suprarrenal y pérdida salina) y virilizacion de la recién nacida afecta con ambigüedad genital. En este artículo ofrecemos algunas recomendaciones para el diagnóstico, que debe ser lo más precoz posible, y el tratamiento, adecuado e individualizado. El estudio genético del paciente y su familia es clave en el diagnóstico del propio afectado, y también permite establecer el consejo genético, así como el diagnóstico y tratamiento prenatales en futuros embarazos (AU)

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is an autosomal recessive disorder caused by mutations in the CYP21A2 gene. Cortisol and aldosterone synthesis are impaired in the classic forms (adrenal insufficiency and salt-wasting crisis). Females affected are virilised at birth, and are at risk for genital ambiguity. In this article we give recommendations for an early as possible diagnosis and an appropriate and individualised treatment. A patient and family genetic study is essential for the diagnosis of the patient, and allows genetic counselling, as well as a prenatal diagnosis and treatment for future pregnancy (AU)

[Recommendations for the diagnosis and treatment of classic forms of 21-hydroxylase-deficient congenital adrenal hyperplasia]. / Recomendaciones para el diagnóstico y tratamiento de pacientes con formas clásicas de hiperplasia suprarrenal congénita por déficit de 21-hidroxilasa.

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is an autosomal recessive disorder caused by mutations in the CYP21A2 gene. Cortisol and aldosterone synthesis are impaired in the classic forms (adrenal insufficiency and salt-wasting crisis). Females affected are virilised at birth, and are at risk for genital ambiguity. In this article we give recommendations for an early as possible diagnosis and an appropriate and individualised treatment. A patient and family genetic study is essential for the diagnosis of the patient, and allows genetic counselling, as well as a prenatal diagnosis and treatment for future pregnancy.