Radiological findings in poisoning by synthetic cannabinoids adulterated with brodifacoum.

OBJECTIVES: Severe coagulopathy due to consumption of synthetic cannabinoids adulterated with brodifacoum, a long-acting anticoagulant, is an emerging worldwide hazard. Here, we review the spectrum of imaging findings in adulterated cannabinoid poisoning. MATERIALS AND METHODS: In this retrospective study, we used the Israeli Poison Information Center database to identify patients with cannabinoid-associated coagulopathy who presented to the Rambam Health Care Campus, where most patients were treated during an outbreak in northern Israel between September 2021 and June 2022. All relevant imaging studies for these patients were reviewed. We estimated the sensitivity of findings for cannabinoid-associated coagulopathy. Associations between a continuous variable and a dichotomous outcome were assessed with the Mann-Whitney U test. RESULTS: We identified 48 patients (mean age 40 years ± 9 [SD], 43 males) with 54 hospitalizations due to cannabinoid-associated coagulopathy. Symptomatic hemorrhage was documented in 50 (93%) cases at presentation, most of whom (78%) had hemorrhage from multiple systems. The most common bleeding site was the genitourinary collecting system, with a characteristic sign of suburothelial bleeding in 16/18 of performed abdominal CTs (sensitivity 89% [CI 65-99%] for cannabinoid-associated coagulopathy). Intramural bowel hematomas were noted in 70% (7/10) of CTs of patients with gastrointestinal bleeding. Incidental bleeding sites were identified on imaging in 24% of patients. An increased number of bleeding sites was associated with need for vasopressors (difference in bleeding sites 3.00 [95% CI 0.99-4.00], p = 0.026). CONCLUSION: CT plays a key role in the diagnosis and work-up of adulterated cannabinoid-associated coagulopathy. Characteristic signs include suburothelial hemorrhage and intramural bowel hematomas. CLINICAL RELEVANCE STATEMENT: Recognition of radiological signs of adulterated synthetic cannabinoid-associated coagulopathy is critical for optimizing outbreak control on the public health level and ensuring timely treatment on the individual patient level. KEY POINTS: • Severe coagulopathy due to consumption of synthetic cannabinoids adulterated with brodifacoum, a long-acting anticoagulant, is an emerging worldwide threat. • Characteristic imaging signs include suburothelial bleeding, intramural bowel hematomas, and rare incidental bleeding sites. • Imaging has a pivotal role in optimizing outbreak control and ensuring timely and appropriate treatment.

Improving emergency department care of infants with acute bronchiolitis by reducing the use of unrecommended drugs: a quality-of-care initiative in a Spanish autonomous community. / Iniciativa de mejora para reducir el uso de fármacos no recomendados en el manejo de lactantes con bronquiolitis aguda en los servicios de urgencias de una comunidad autónoma.

OBJECTIVES: To evaluate the impact of a quality-of-care improvement program implemented in emergency departments (EDs) in a Spanish autonomous community with the aim of reducing the use of unrecommended drugs when treating infants for acute bronchiolitis. MATERIAL AND METHODS: Before-after quasi-experimental intervention study. We retrospectively included infants aged 12 months or less who were treated for acute bronchiolitis in 24 Spanish national health system hospital EDs in December during 2 epidemic periods: in 2018, before implementing the program, and in 2019, after implementation. Data collected included epidemiologic information, clinical and care details, and clinical course. The program consisted of providing informative material and training sessions before the epidemic period started. RESULTS: A total of 7717 episodes (4007 in 2018 and 2710 in 2019) were identified. Epidemiologic and clinical characteristics did not differ between the 2 periods. ED use of the following treatments decreased between the 2 periods: salbutamol, from 29.4% (95% CI, 28.8%-30.8%) in 2018 to 10.6% (95% CI, 9.6%-11.6%) in 2019; epinephrine from 6.0% (95% CI, 5.3%-6.8%) to 0.9% (95% CI, 0.7%-1.3%); and hypertonic saline solution fell from 8.2% (95% CI, 7.3%-9.1%) to 2.1% (95% CI, 1.7%-2.6%) (P.001, all comparisons). Prescriptions for salbutamol on discharge fell from 38.7% (95% CI, 36.9%-40.4%) to 10.6% (95% CI, 9.6%-11.6%) (P.001). Admissions and readmissions did not change, and the median time (interquartile range) spent in the ED fell from 81 (44-138) minutes to 66 (37-127) minutes (P.001). CONCLUSION: The quality-of-care improvement initiative was able to decrease the number of unrecommended therapeutic interventions for acute bronchiolitis. However, we identified great variations between EDs, suggesting that training and assessment of impact should continue.

OBJETIVO: Evaluar el impacto de una iniciativa de mejora realizada en los servicios de urgencias (SU) de una comunidad autónoma para reducir el uso de fármacos no recomendados en lactantes con bronquiolitis aguda (BA). METODO: Estudio cuasi-experimental analítico del tipo "antes y después de una intervención". Se incluyeron de forma retrospectiva todas las BA en niños # 12 meses atendidas en los SU de 24 hospitales públicos durante el mes de diciembre de dos periodos epidémicos: 2018 (preintervención) y 2019 (postintervención). Se recogieron variables epidemiológicas, clínicas, asistenciales y evolutivas. La intervención consistió en difundir material informativo y realizar actividades formativas previas al periodo epidémico. RESULTADOS: Se incluyeron 7.717 episodios (2018: 4.007 y 2019: 3.710). No existieron diferencias en las características epidemiológicas y clínicas. El empleo de salbutamol en los SU descendió del 29,4% [intervalo de confianza del 95% (IC 95%): 28,8-30,8] en 2018 al 10,6% (IC 95%: 9,6-11,6) en 2019 (p 0,001), el de adrenalina del 6,0% (IC 95%: 5,3-6,8) al 0,9% (IC 95%: 0,7-1,3) y el de suero salino hipertónico del 8,2% (IC 95%: 7,3-9,1) al 2,1% (IC 95%: 1,7-2,6) (p 0,001). La prescripción al alta de salbutamol se redujo del 38,7% (IC 95%: 36,9-40,4) al 10,6% (IC 95%: 9,6-11,6) (p 0,001). La tasa de ingreso y la tasa de readmisión no cambiaron y la mediana de tiempo de estancia en los SU se redujo 81 minutos [rango intercuartil (RIC) 44-138] a 66 (RIQ: 37-127) (p 0,001). CONCLUSIONES: La iniciativa de mejora ha conseguido disminuir la tasa de intervenciones terapéuticas no indicadas en BA. Sin embargo, existe una gran variabilidad entre los diferentes SU por lo que la estrategia y la medición de su impacto deben mantenerse en el tiempo.

Assessment of heavy metal pollution in marine sediments from southwest of Mallorca island, Spain.

Anthropogenic activities in urban, agrarian, or industrial areas are the main cause of heavy metals in sediments worldwide. Since the 1960s, there have been submarine discharges through outfalls of poorly treated or untreated wastewater on the south coast of Mallorca island (Mediterranean Sea). In this study, the pollution of marine sediments is analyzed at a great number of points on the south of the seacoast. Heavy metal concentrations of As, Ba, Cd, Cr, Cu, Hg, Ni, Pb, Se, V, and Zn, total inorganic carbon (TIC), sulfur, mineralogy, and grain size were analyzed. The objective is to evaluate the concentrations of toxic substances and their spatial distribution and ranges that can negatively affect marine ecosystems and human health. In addition, the results obtained have been compared with standardized indices for marine sediments, and a regional index has been developed with the background values of heavy metals obtained in the sediments of the study area. To obtain consistent conclusions, concentrations of heavy metals were classified with the Igeo Index. The concentrations of heavy metals obtained show that a great number of samples exceeded the limits considered for uncontaminated sediments according to the index applied. Elements such as Hg, Ba, Pb, and Cu showed high concentrations close to the outfalls and lower concentrations in zones far from these points. To support the assessment, chemical processes such as dissolution or chemical precipitation have been studied. The results also show that marine sediments can be a good trap for chemical elements and a good proxy to analyze the impact of anthropogenic activities in areas heavily pressured by humans, and the risk to the environment and human health.

Peripheral T-cell lymphoma: molecular profiling recognizes subclasses and identifies prognostic markers.

Peripheral T-cell lymphoma (PTCL) is a clinically aggressive disease, with a poor response to therapy and a low overall survival rate of approximately 30% after 5 years. We have analyzed a series of 105 cases with a diagnosis of PTCL using a customized NanoString platform (NanoString Technologies, Seattle, WA) that includes 208 genes associated with T-cell differentiation, oncogenes and tumor suppressor genes, deregulated pathways, and stromal cell subpopulations. A comparative analysis of the various histological types of PTCL (angioimmunoblastic T-cell lymphoma [AITL]; PTCL with T follicular helper [TFH] phenotype; PTCL not otherwise specified [NOS]) showed that specific sets of genes were associated with each of the diagnoses. These included TFH markers, cytotoxic markers, and genes whose expression was a surrogate for specific cellular subpopulations, including follicular dendritic cells, mast cells, and genes belonging to precise survival (NF-κB) and other pathways. Furthermore, the mutational profile was analyzed using a custom panel that targeted 62 genes in 76 cases distributed in AITL, PTCL-TFH, and PTCL-NOS. The main differences among the 3 nodal PTCL classes involved the RHOAG17V mutations (P < .0001), which were approximately twice as frequent in AITL (34.09%) as in PTCL-TFH (16.66%) cases but were not detected in PTCL-NOS. A multivariate analysis identified gene sets that allowed the series of cases to be stratified into different risk groups. This study supports and validates the current division of PTCL into these 3 categories, identifies sets of markers that can be used for a more precise diagnosis, and recognizes the expression of B-cell genes as an IPI-independent prognostic factor for AITL.

Towards a Change in the Diagnostic Algorithm of Autism Spectrum Disorders: Evidence Supporting Whole Exome Sequencing as a First-Tier Test.

Autism spectrum disorder (ASD) is a prevalent and extremely heterogeneous neurodevelopmental disorder (NDD) with a strong genetic component. In recent years, the clinical relevance of de novo mutations to the aetiology of ASD has been demonstrated. Current guidelines recommend chromosomal microarray (CMA) and a FMR1 testing as first-tier tests, but there is increasing evidence that support the use of NGS for the diagnosis of NDDs. Specifically in ASD, it has not been extensively evaluated and, thus, we performed and compared the clinical utility of CMA, FMR1 testing, and/or whole exome sequencing (WES) in a cohort of 343 ASD patients. We achieved a global diagnostic rate of 12.8% (44/343), the majority of them being characterised by WES (33/44; 75%) compared to CMA (9/44; 20.4%) or FMR1 testing (2/44; 4.5%). Taking into account the age at which genetic testing was carried out, we identified a causal genetic alteration in 22.5% (37/164) of patients over 5 years old, but only in 3.9% (7/179) of patients under this age. Our data evidence the higher diagnostic power of WES compared to CMA in the study of ASD and support the implementation of WES as a first-tier test for the genetic diagnosis of this disorder, when there is no suspicion of fragile X syndrome.

The presence of a bulky mediastinal mass of 7 cm or greater in diameter confers an adverse prognosis to patients with advanced Hodgkin lymphoma in case of negative interim PET/CT.

In the PET-adapted therapy era, a bulky mediastinal mass (BMM) is not considered a risk factor in patients with advanced-stage Hodgkin lymphoma (HL). The current retrospective study aimed to estimate the prognostic significance of BMM presence and size for disease-free survival (DFS) and determine the most accurate mass size cutoff (among 5 cm, 7 cm, 10 cm) to predict inferior DFS in such patients. The study included 196 advanced-HL patients treated at Rambam (n = 121) and Memorial Sloan Kettering Cancer Center (n = 75) between 2002 and 2016. At a median follow-up of 66.5 (1-222) months, 36 relapses occurred. In multivariate analysis, only the cutoff of 7 cm predicted inferior DFS and PFS (p < 0.007 and <0.038, respectively) in interim PET/CT (PET-2) negative (79%) patients. This study identifies the BMM size cutoff of 7 cm in any plane as most precise in predicting adverse prognosis in PET-2-negative patients with advanced-stage HL. More aggressive initial chemotherapy than ABVD improves such prognosis.

Reactivación silenciosa del virus de la hepatitis B en paciente que reinicia diálisis tras trasplante renal. ¿Cómo podemos prevenirlo o anticiparlo en el diagnóstico? / Reactivation of hepatitis B virus in patient that rests dialysis after renal transplantation. How can we prevent it or anticipate it in diagnosis?

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The HOG MAPK pathway in Candida albicans: more than an osmosensing pathway.

In 1993, Brewster and Gustin described the existence of a kinase whose activity was essential for Saccharomyces cerevisiae to grow in environments with high osmolarity. This led to the discovery of the HOG pathway, a MAP kinase (MAPK) pathway that has been revealed to be crucial to respond to a wide range of stress conditions frequently encountered by fungi in their common habitats. MAPK signaling is initiated at the plasma membrane, where triggering stimuli lead to a phosphorylation cascade that ultimately activates transcription factors to ensure an appropriate adaptive response. In pathogenic fungi, the HOG pathway gains special significance as it is involved in traits related to pathogenicity; these include biofilm formation, adhesion to surfaces, and morphogenetic and epigenetic transitions. It also plays a role in controlling both the pathogen and the commensal state program. Understanding the signals leading to its activation, the elements of the pathways and the targets of the pathway are therefore of primary importance in the design of novel antifungals.

Mycosis Fungoides Associated With Lesions in the Spectrum of Primary Cutaneous CD30+ Lymphoproliferative Disorders: The Same Process or 3 Coexisting Lymphomas?

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, primary cutaneous CD30 lymphoproliferative disorders (pc CD30 LPD) being the second most prevalent. There is evidence that MF and pc CD30 LPD may coexist and share T-cell clonality, suggesting a common origin. These findings were supported by a T-cell receptor clonality assessment by the polymerase chain reaction coupled with capillary electrophoresis, although results produced by this method may be ambiguous. We describe an otherwise healthy 46-year-old man who developed, over the course of 5 months, a tumor consisting of primary cutaneous anaplastic large cell lymphoma and, subsequently, several papules of lymphomatoid papulosis (LyP). Both lymphomas appeared on a single patch of MF, which had been present on the patient's right buttock for at least 2 years. T-cell receptor clonality of the 3 types of neoplastic lesions and apparently non-involved skin were assessed by a next-generation sequencing-based method. We found that MF, primary cutaneous anaplastic large cell lymphoma and LyP harbored the same top 2 clones. Non-involved skin harbored other T-cell clones. In this patient, these findings suggest that MF, LyP and pc CD30 LPD were different clinicopathological manifestations arising from the neoplastic proliferation of the same T-cell clone.

Infarction of the greater omentum. Case report.

The case of a 65 year old woman presented symptoms of acute abdomen secondary to full torsion of the greater omentum is presented, diagnosed preoperatively by CT, thus avoiding emergency surgery due to good evolution with conservative attitude. This disease is a rare cause of abdominal pain, but we include it in the differential diagnosis of acute abdomen. Currently imaging techniques allow preoperative diagnosis to avoid emergency surgery, and maintain an expectant attitude to act on patient evolution. In our case, we chose conservative attitude and the patient is asymptomatic 7 months later.

Infarto de epiplón mayor. Caso clínico / Infarction of the greater omentum. Case report

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Informe del Taller Ibérico de Histocompatibilidad 2013. Componente de análisis de situación de procedimiento de pruebas cruzadas en guardias de trasplante de órganos / Report of the 2013 Iberian Histocompatibility Workshop of 2013. Component analysis of the proceedings of cross-matching procedures in emergency organ transplantation

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Influence of interleukin-10 genetic polymorphism on survival rates in melanoma patients with advanced disease.

Individual ability to produce interleukin-10 (IL-10) may be of relevance in the development and evolution of cutaneous melanoma, probably due to its immunosuppressor and anti-angiogenic properties. Single nucleotide polymorphisms at positions -1082 (G/A), -819 (C/T) and -592 (C/A) in the IL-10 gene promoter were analysed in 100 healthy individuals and 98 melanoma patients using fluorogenic hybridization-specific probes in a 'real-time' thermocycler. Polymorphic frequencies were correlated with various prognostic factors and overall survival. The frequency of IL-10 polymorphic variants was similar in patients and controls. However, high producer genotypes at the -1082 position were over-represented in males with an older age at diagnosis. The analysis of the promoter genotypes in patients stratified according to clinical prognostic factors did not show any associations, although a trend (not statistically significant) towards a prolonged survival in patients genotyped as high IL-10 producers was observed. In addition, the low producer -1082AA genotype was significantly associated with decreased survival in patients with advanced disease. Similarly, the presence of this genotype shortened the overall survival in males after recurrence or metastasis development. In conclusion, the frequency of genetic variants in the IL-10 gene promoter was not associated with melanoma appearance, but conditioned the age at diagnosis in males and the overall survival in patients with advanced disease.

Interindividual variations in constitutive interleukin-10 messenger RNA and protein levels and their association with genetic polymorphisms.

BACKGROUND: Genetic variations in the interleukin (IL)-10 gene promoter have been associated with levels of induced production of IL-10, disease susceptibility, and allograft rejection. Small amounts of this cytokine are constitutively produced and are important in maintaining the physiologic function of the cytokine network. In this study, we evaluated the distribution of IL-10 basal levels and its genetic regulation in a healthy Spanish population. METHODS: Polymorphisms at the -1,082, -819, and -512 positions of the IL-10 promoter were analyzed by polymerase chain reaction amplification and hybridization with fluorescent-labeled allele-specific probes in 183 Spanish people. Levels of IL-10 messenger (m)RNA were tested by real-time reverse transcription-polymerase chain reaction in 123 healthy donors. Serum concentrations of IL-10 were measured by a highly sensitive ELISA, whereas protein amounts in lipopolysaccharide culture supernatants were quantified by an in-house ELISA. RESULTS: The frequency of IL-10 promoter alleles and haplotypes in our population showed remarkable differences from other Caucasian populations. Large interindividual variations were found in mRNA and protein constitutive levels of IL-10, which allowed its classification in low and intermediate/high producers. We found statistical differences in mRNA concentration between the polymorphic variant GCC/GCC and the low producer genotypes. The G allele at position -1082 was the most important genetic factor in the regulation of constitutive IL-10 mRNA levels. Similarly, we also found an association of this polymorphic position with serum concentration greater than 2 pg/mL. CONCLUSIONS: Constitutive levels of IL-10 (mRNA and serum protein) displayed remarkable interindividual variations, which are genetically controlled by polymorphic variants at the cytokine gene promoter.

Optimization of the RT-PCR technique to detect melanoma cells in peripheral blood.

Detection of melanoma cells in the peripheral blood of melanoma patients by reverse transcription polymerase chain reaction techniques has demonstrated varying detection rates. This study examined the sensitivity of the technique by employing a modification of the currently used protocols to detect mRNA markers. RT-PCR of tyrosinase and MART-1 was performed after poly A+-RNA isolation from unmanipulated whole blood lysed in the presence of nuclease inhibitors. We found a preclinical sensitivity of 1 GR-M melanoma cell spiked in 1 ml of blood. The clinical sensitivity was tested by studying 22 melanoma patients with advanced disease. The rate of positivity in all patients was 63.6% for tyrosinase, 50% for MRT-1 and 77.3% for at least one molecular marker. This figure increased to 89.5% when considering only those patients with evident macroscopic disease. We can conclude that the technical modifications introduced in this protocol significantly increased the clinical sensitivity compared with other published methods.