Clinical Utility of Definitive Diagnostic Tests for Choledocholithiasis in Pediatric Patients with Mild Gallstone Pancreatitis.

BACKGROUND: Gallstone pancreatitis was historically considered a risk factor for choledocholithiasis (CD). However, recent studies of adult patients evidenced a weak association between gallstone pancreatitis and CD. The aim of this study was to analyze this association in pediatric patients. METHODS: We conducted a retrospective study on patients with mild gallstone pancreatitis who underwent any definitive testing for CD (MRCP, ERCP, IOC), managed between March 2010 and September 2022. Patients were classified according to the presence or absence of risk factors for CD (total bilirubin ≥2 mg/dl; common bile duct >6 mm on ultrasound; and/or CD on ultrasound). We evaluated the diagnosis of CD on definitive testing in both groups and analyzed the predictive capacity of the presence of risk factors. RESULTS: Eighty-four patients were included in the final analysis. Seventy-nine percent were females. The median age was 13 (4-17) years. Forty-seven (55.9%) patients had one or more risk factors. The definitive testing confirmed 13 (15.5%) cases of CD, 12 (25.5%) in the group of patients with risk factors and 1 (2.7%) in those without risk factors. The sensitivity, specificity, positive predictive value and negative predictive value of the presence of associated risk factors were 92.3, 50.7, 25.5 and 97.3%, respectively. CONCLUSION: Pediatric patients with gallstone pancreatitis without associated risk factors have a very low incidence of CD. In these patients we suggest performing a laparoscopic cholecystectomy without intraoperative cholangiography or any other definitive test for CD. LEVEL OF EVIDENCE: Level II, retrospective study.

Tracking the Emergence and Dissemination of a blaNDM-23 Gene in a Multidrug Resistance Plasmid of Klebsiella pneumoniae.

Since the discovery of blaNDM-1, NDM ß-lactamases have become one of the most widespread carbapenemases worldwide. To date, 43 different NDM variants have been reported but some, such as blaNDM-23, have not been characterized in detail yet. Here, we describe the emergence of a novel blaNDM-23 allele from a blaNDM-1 ancestor and the multidrug resistance plasmid that has disseminated it through a Klebsiella pneumoniae ST437 clone in several Spanish hospitals. Between 2016 and 2019, 1,972 isolates were collected in an epidemiological survey for extended-spectrum-ß-lactamase (ESBL)-producing Klebsiella pneumoniae in the Comunitat Valenciana (Spain). Three carbapenem-resistant strains failed to be detected by carbapenemase-producing Enterobacteriaceae (CPE) screening tests. These isolates carried a blaNDM-23 gene. To characterize this gene, its emergence, and its dissemination, we performed antimicrobial susceptibility tests, hybrid sequencing with Illumina and Nanopore technologies, and phylogenetic analyses. The MICs of the blaNDM-23 allele were identical to those of the blaNDM-1 allele. The blaNDM-23 allele was found in 14 isolates on a 97-kb nonmobilizable, multidrug-resistant plasmid carrying 19 resistance genes for 9 different antimicrobial families. In this plasmid, the blaNDM-23 gene is in the variable region of a complex class 1 integron with a singular genetic environment. The small genetic distance between blaNDM-23-producing isolates reflects a 5-year-long clonal dispersion involving several hospitals and interregional spread. We have characterized the genomic and epidemiological contexts in the emergence and community spread of a new blaNDM-23 allele in a multidrug resistance (MDR) plasmid of Klebsiella pneumoniae. IMPORTANCE At a time when antimicrobial resistance has become one of the biggest concerns worldwide, the emergence of novel alleles and extremely drug-resistant plasmids is a threat to public health worldwide, especially when they produce carbapenem resistance in one of the most problematic pathogens, such as Klebsiella pneumoniae. We used genomic epidemiology to describe the emergence of a novel NDM-23 allele and identify it in a MDR plasmid that has disseminated through a K. pneumoniae ST437 clone in several hospitals in Spain. Using bioinformatic and phylogenetic analyses, we have traced the evolutionary and epidemiological route of the new allele, the hosting plasmid, and the strain that carried both of them from Pakistan to Spain. A better understanding of the NDM-producing K. pneumoniae populations and plasmids has made evident the spread of this clone through the region, enhancing the importance of genomic surveillance in the control of antimicrobial resistance.

Current Technologies for RNA-Directed Liquid Diagnostics.

There is unequivocal acceptance of the variety of enormous potential liquid nucleic acid-based diagnostics seems to offer. However, the existing controversies and the increased awareness of RNA-based techniques in society during the current global COVID-19 pandemic have made the readiness of liquid nucleic acid-based diagnostics for routine use a matter of concern. In this regard-and in the context of oncology-our review presented and discussed the status quo of RNA-based liquid diagnostics. We summarized the technical background of the available assays and benchmarked their applicability against each other. Herein, we compared the technology readiness level in the clinical context, economic aspects, implementation as part of routine point-of-care testing as well as performance power. Since the preventive care market is the most promising application sector, we also investigated whether the developments predominantly occur in the context of early disease detection or surveillance of therapy success. In addition, we provided a careful view on the current biotechnology investment activities in this sector to indicate the most attractive strategies for future economic success. Taken together, our review shall serve as a current reference, at the interplay of technology, clinical use and economic potential, to guide the interested readers in this rapid developing sector of precision medicine.

Reducing sources of variance in experimental procedures in in vitro research.

Background: Lack of reproducibility in preclinical research poses ethical and economic challenges for biomedical science. Various institutional activities by society stakeholders of leading industrialised nations are currently underway with the aim of improving the situation. Such initiatives are usually concerned with high-level organisational issues and typically do not focus on improving experimental approaches per se. Addressing these is necessary in order to increase consistency and success rates of lab-to-lab repetitions. Methods: In this project, we statistically evaluated repetitive data of a very basic and widely applied lab procedure, namely quantifying the number of viable cells. The purpose of this was to assess the impact of different parameters and instrumentations which may constitute sources of variance in this procedure. Conclusion: By comparing the variability of data acquired under two different procedures, featuring improved stringency of protocol adherence, our project attempts to identify the sources and propose guidelines on how to reduce such fluctuations. We believe our work can contribute to tackling the repeatability crisis in biomedical research.

Synthesis and biological evaluation of 2,4,6-functionalized derivatives of pyrido[2,3-d]pyrimidines as cytotoxic agents and apoptosis inducers.

In the search for new derivatives with anticancer activity that are able to induce a selective pro-apoptotic mechanism in cancer cells, we have designed, synthesized, and evaluated a series of new 2-(alkylsulfanyl)-N-alkylpyrido[2,3-d]pyrimidine-4-amine derivatives as cytotoxic and apoptosis inducers. The potential antitumor activity of the compounds was evaluated in vitro by examining their cytotoxic effects against human breast, colon, and bladder cancer-cell lines. The IC(50)values of the compounds that showed cytotoxic activity were calculated. The cytotoxic compounds were then tested for their ability to induce caspase-3 activation and nuclear-chromatin degradation. Some compounds, such as 6c, 6d, 6e, 6j, 6o, and 6p, show significant in-vitro cytotoxicity in at least two of the three tested cell lines, induced apoptosis, and also produced a rapid dose-dependent increase in the caspase-3 level in some of the cell lines tested. In order to test the selectivity of the compounds, two non-tumoral human cell lines were used. Several compounds of the did not show cytotoxicity in these cell lines.

Anetodermia primaria / Primary anetoderma

Mujer de 28 años de edad que presenta máculas y pápulas de aspecto atrófico, asintomáticas, localizadas en tronco y extremidades superiores de 8 años de evolución. Se realizó escisión-biopsia de una de las lesiones que reveló mediante tinción de orceína una disminución y fragmentación de las fibras elásticas en dermis reticular. Se descartaron posibles causas y asociaciones diagnosticándose de anetodermia primaria. Destacamos este caso por ser poco común en la clínica y proponemos la elaboración de un protocolo de actuación ante una anetodermia

A 28 years old woman who complains because the presence of atrophic macules and papules appearing progresivelly in the last 8 years is reported. The lesions were asymptomatic and they were located in the trunk and arms. An excisional biopsy was performed. Ordein stain revealed an important decrease and destruction of the elastical tissue in reticular dermis. Posible related causes and associated conditions were excluded and the diagnose of a primary anetoderma were stablished. We like to emphasize this case report because it is an uncommon disease and at the same time we propose a medical protocol for its study

Linear lichen planus and hepatitis C.

A 23-year-old man with hepatitis C was observed with brownish dome-shaped papules in a linear pattern on the chest. The papules were determined clinically and pathologically to be linear lichen planus. These lesions appeared during an interferon-alpha therapy for his hepatitis and resolved after topical treatment with tacrolimus ointment. Linear lichen planus and hepatitis C have been reported only twice previously. The association between these disorders and the potential role of interferon therapy are discussed.

Granuloma anular generalizado: respuesta al tratamiento con vitamina E / Generalized granuloma annulare: improvement with vitamin E therapy

Presentamos 2 pacientes de sexo femenino con granuloma anular generalizado confirmado histológicamente, sin respuesta a terapéuticas previas con corticoides tópicos, corticoides orales, inmunomoduladores, retinoides e inmunosupresores. En ambos casos se ha instaurado tratamiento con vitamina E, tópica en uno y oral en otro, con evolución favorable. En ningún caso se ha observado recurrencia de la dermatosis. Pensamos que el tratamiento con vitamina E, podría ser una posible alternativa a tener en cuenta ante granulomas anulares generalizados recalcitrantes

We present 2 female patients with generalized granuloma annulare confirmed histopathologically with no improvement after topical and oral steroids, immunomodulators, retinoids and immunosuppressive drugs. Vitamin E therapy was successfully performed in both cases, topical in the first one and oral in the other, with no following recurrence. We think that topical or oral vitamin E are possible alternatives to consider in the treatment of recalcitrant generalized granuloma annulare