Sequencing paired tumor DNA and white blood cells improves circulating tumor DNA tracking and detects pathogenic germline variants in localized colon cancer.

BACKGROUND: In the setting of localized colon cancer (CC), circulating tumor DNA (ctDNA) monitoring in plasma has shown potential for detecting minimal residual disease (MRD) and predicting a higher risk of recurrence. With the tumor-only sequencing approach, however, germline variants may be misidentified as somatic variations, precluding the possibility of tracking in up to 11% of patients due to a lack of known somatic mutations. In this study, we assess the potential value of adding white blood cells (WBCs) to tumor tissue sequencing to enhance the accuracy of sequencing results. PATIENTS AND METHODS: A total of 148 patients diagnosed with localized CC were prospectively recruited at the Hospital Clínico Universitario in Valencia (Spain). Employing a custom 29-gene panel, sequencing was conducted on tumor tissue, plasma and corresponding WBCs. Droplet digital PCR and amplicon-based NGS were performed on plasma samples post-surgery to track MRD. Oncogenic somatic variants were identified by annotating with COSMIC, OncoKB and an internal repository of pathogenic mutations database. A variant prioritization analysis, mainly characterized by the match of oncogenic mutations with the evidence levels defined in OncoKB, was carried out to select specific targeted therapies. RESULTS: Utilizing paired tumor and WBCs sequencing, we identified somatic mutations in all patients (100%) within our cohort, compared to 89% using only tumor tissue. Consequently, the top 10 most frequently mutated genes for plasma monitoring were altered. The sequencing of WBCs identified 9% of patients with pathogenic mutations in the germline, with APC and TP53 being the most frequently mutated genes. Additionally, mutations in genes related to clonal hematopoiesis of indeterminate potential were detected in 27% of the cohort, with TP53, KRAS, and KMT2C being the most frequently altered genes. There were no observed differences in the sensitivity of monitoring MRD using ddPCR or amplicon-based NGS (p = 1). Ultimately, 41% of the patients harbored potentially targetable alterations at diagnosis. CONCLUSION: The germline testing method not only enhanced sequencing results and raised the proportion of patients eligible for plasma monitoring, but also uncovered the existence of pathogenic germline variations, thereby aiding in the identification of patients at a higher risk of hereditary cancer syndromes.

Actualización en carcinoma escamoso orofaríngeo

Resumen El carcinoma escamoso de orofaringe (CEOF) ha tenido un aumento en su incidencia en las últimas décadas, explicándose por el aumento sustancial de su tipo relacionado con el virus papiloma humano (VPH). Existen diferencias clínicas y pronósticas entre los dos grupos de CEOF según su relación etiológica con VPH. Por un lado, los relacionados con VPH se presentan en una población más joven, con menos prevalencia de tabaquismo y consumo de alcohol; además de presentar un tamaño pequeño del tumor primario, con un compromiso linfonodal temprano. Además, aquellos relacionados con VPH presentan un mejor pronóstico que su contraparte no relacionada con el virus, presentando en algunos estudios hasta un 58% menos riesgo de muerte independiente de la modalidad de tratamiento. Actualmente, el sistema de clasificación TNM en su 8va edición presenta un sistema diferente de clasificación y etapificación para ambos grupos. A pesar de aquello, a la fecha el tratamiento habitual no difiere entre ambos, lo que ha llevado a la realización de estudios que buscan responder si la deintensificación de la terapia en aquellos grupos relacionados con VPH y con bajo riesgo de metástasis a distancia, mantendría los buenos resultados oncológicos, disminuyendo las complicaciones a corto y largo plazo asociadas al tratamiento. Sin embargo, aún no existe evidencia que avale consistentemente esta práctica. Finalmente, la prevención primaria a través de la vacuna contra VPH es un elemento prometedor, sin embargo, no existe evidencia que confirme su utilidad.

Abstract Oropharyngeal squamous cell carcinoma (OPSCC) has suffered an increase in its incidence in recent decades, explained by the increase in its type related to the human papilloma virus (HPV). There are clinical and prognostic differences between the two groups of OPSCC according to their etiological relationship with HPV. On the one hand, those related to HPV appear in a younger population, with a lower prevalence of smoking and alcohol consumption; in addition to presenting a small size of the primary tumor, with early lymph node involvement. Furthermore, those related to HPV have a better prognosis than their non-virus counterpart, presenting in some studies up to 58% less risk of death, independent of treatment used. Currently, the TNM classification system in its 8th edition presents a different classification for both groups. Despite this, the treatment does not differ between the two, which has led to studies that seek to answer whether the de-escalation of therapy in the group associated to HPV and with a low risk of distant metastasis would maintain the reported good oncological results, reducing early and long-term complications associated with treatment, however, there is still no evidence to support its use. Finally, primary prevention through the HPV vaccine is a promising element, however there is no evidence to confirm its usefulness.

Mareo postural perceptual persistente: la causa más frecuente de mareo crónico es fácil de tratar / Persistent postural-perceptual dizziness: the most frequent cause of chronic dizziness is easy to manage

RESUMEN Los trastornos vestibulares funcionales se constituyen como una de las causas más frecuentes de consulta por vértigo y trastornos del equilibrio. El mareo postural perceptual persistente (MPPP) es un síndrome recientemente definido, enmarcado en la categoría de síndromes vestibulares crónicos, que agrupa trastornos vestibulares funcionales crónicos como el vértigo postural fóbico, el malestar con el movimiento espacial, el vértigo visual y el mareo subjetivo crónico. El MPPP se manifiesta por síntomas de mareo, inestabilidad y/o vértigo no rotatorio, persistentes, exacerbados por cambios posturales, movimientos y exposición a distintos estímulos visuales. El tratamiento de este cuadro es más sencillo de lo que parece, basado en psicoeducación efectiva respecto a la patología como primer abordaje, adicionando o no rehabilitación vestibular, uso de inhibidores selectivos de la recaptación de serotonina y/o terapia cognitivo conductual. Se presentan dos casos clínicos de pacientes diagnosticados con MPPP y su respuesta a tratamiento.

ABSTRACT Functional vestibular disorders are one of the most frequent causes of consultation due to vertigo and balance disorders. Persistent postural-perceptual dizziness (PPPD) is a recently defined syndrome, categorized as a chronic vestibular syndrome, that includes functional vestibular disorders such as phobic postural vertigo, space-motion discomfort, visual vertigo and chronic subjective dizziness. PPPD manifests with dizziness, unsteadiness and/or non-spinning vertigo, which are persistent, exacerbated by postural changes, movements and exposure to various visual stimuli. PPPD treatment is simpler than it may seem initially. It is based on effective psychoeducation related to the pathology in the first place, followed, or not, by vestibular rehabilitation, use of selective serotonin reuptake inhibitors and/or cognitive behavioral therapy. We present two clinical cases of patients diagnosed with PPPD and their response to treatment.

Indicaciones y cuidados de la traqueostomía en pediatría / Indications and care of the tracheostomy in pediatrics

Tracheostomy in children is an extremely delicate procedure, which consists in the creation of a stoma between the trachea and the skin. Among the most frequent indications are neurological disorders, obstruction of the upper airway or prolonged mechanical ventilation. Pediatric versus adult airway differences should be considered during surgery. In the postoperative period, hemorrhage, pneumothorax, pneumomediatin can occur. In the late postoperative period, accidental decannulation, false pathway, infection of the tracheostomy, and later formation of periostomal or endotracheal granulomas may occur. The care of the tracheostomy in the clinical unit must be with trained personnel and the family environment must be prepared for home care. As long as the tracheostomy persists, control of the airway superior and inferior to the tracheostomy must be maintained by fiber optic. Patients with neurological compromise or cardiopulmonary damage have a lower decannulation rate and a longer hospital stay.

La traqueostomía en niños es un procedimiento extremadamente delicado, que consiste en la creación de un ostoma entre la tráquea y la piel. Entre las indicaciones más frecuentes se encuentran trastornos neurológicos, obstrucción de la vía aérea superior o ventilación mecánica prolongada. Consideraciones a las diferencias de la vía aérea pediátrica versus del adulto deben tenerse en cuenta durante la cirugía. En el postoperatorio se puede presentar hemorragia, neumotórax y neumomediastino. En el postoperatorio tardío puede ocurrir decanulación accidental, falsa vía, infección de la traqueostomía, y más tardíamente formación de granulomas periostomales o endotraqueales. El cuidado de la traqueostomía en la unidad clínica debe ser con personal capacitado y se debe preparar el entorno familiar para el cuidado en el domicilio. Mientras persista la traqueostomía se debe mantener control por fibra óptica de la vía aérea superior e inferior a la traqueostomía. Los pacientes con compromiso neurológico o daño cardiopulmonar tienen menor tasa de decanulación y mayor tiempo en el hospital.

[Validation of the preparation of individual doses of 51Cr-EDTA in syringes]. / Validación de la preparación de dosis individuales de 51Cr-EDTA en jeringas.

The 51Cr-EDTA is one of the radiopharmaceuticals more used in the glomerular filtration rate determination. The necessity to prepare a daily reference dose every time that are prepared the patient's doses can go to a poor exploitation of the multidose vial. One way of improving its use consists on the preparation of individual doses in ready syringes to inject, for several days, employing only one of them as a standard. The aim of this study was to evaluate the storing of 51Cr-EDTA individual doses at room temperature and at 4 degrees C during 4 weeks, analyzing the radiochemical purity, the sterility and the radiopharmaceutical retention into the syringe. The results obtained showed that the radiochemical purity remains stable, always been greater than the value recommended for its use (> 95%). Likewise, there were not microorganism contamination nor 51Cr-EDTA appreciable retention into the syringes. We concluded that the preparation of individual doses of 51Cr-EDTA in syringes and their conservation at room temperature, or at 4 degrees C, during a period of 4 weeks, neither influence in the radiopharmaceutical quality nor increase its retention into the syringe.

Cambios electrocardiográficos perioperatorios en pacientes ancianos sometidos a cirugía de cadera, comparando anestesia general versus Epidural / Perioperative electrocardiographic changes in the elderly patient's following hip surgery. A study comparing general anesthesia versus regional anesthesia

Los ancianos son sometidos a cirugía en mayor proporción que el resto de la población, con una mayor morbi-mortalidad perioperatoria por la alta incidencia de enfermedades coexistentes. Se presenta patología cardiaca hasta en un 50 a 65 por ciento de los pacientes, siendo la principal causa de muerte posterior a anestesia y cirugía. Las arritmias son comunes, encontrándose hasta en un 60 a 80 por ciento de las anestesias. El electrocardiograma ambulatorio o Holter es un método diagnóstico útil para alteraciones de conducción y cambios en el segmento ST. Objetivo: observar los cambios electrocardiográficos perioperatorios en pacientes ancianos, sometidos a cirugía de cadera, comparando anestesia general y anestesia regional. Material y métodos: se estudiaron 21 pacientes ASA I-III sometidos a cirugía de cadera, electiva o de urgencia a los cuales se les colocó un Holter 2 o 3 horas antes de la cirugía, hasta las 7 de la mañana del día siguiente. Se separaron en dos grupos: 1) anestesia epidural y 2) anestesia general. Posteriormente, se hizo una división entre cardiópatas y otras enfermedades. Se analizaron los datos obtenidos en el Holter comparando ambos grupos de anestesia con ambos grupos de patologías por medio de la Pb. U de Mann Whitney considerando como significativa p < 0.051. Las variables paramétricas se contrastaron con la t de Student (p ó 0.05). Resultados: no hubo diferencia significativa en cuanto a la edad, promedio de estancia hospitalaria, tiempo de cirugía y anestesia y sangrado. La presión arterial media fue menor en el grupo 1 (p = 0.001) y la saturación de oxígeno fue mayor en el grupo 2 (p = 0.011). Se contrastaron los hallazgos del Holter en cardiópatas y otras patologías, sin diferencia significativa; mientras que cuando se separaron estos 2, sólo se encontró que la bradicardia se presentó con mayor frecuencia en el grupo 2 (p = 0.041). Conclusión: los cambios electrocardiográficos encontrados en ancianos no son estadísticamante significativos, cuando se compara anestesia general vs epidural

[Stabilization of 99m Tc-HMPAO with methylene blue: its use in leukocyte labelling)]. / Estabilización del 99mTc-HMPAO con azul de metileno: su utilización en el marcaje de leucocitos.

A method to stabilize the 99mTc-HMPAO obtained from Ceretec(R) saline fractions using methylene blue is described. The mean radiochemical purity two hours after the stabilized 99mTc-HMPAO preparation was 92.5% (SD 1.8%), the pH ranged from 7.0 to 7.6 and the osmolality ranged from 305 to 309 mOsm/kg. These features made the stabilized 99mTc-HMPAO suitable for leukocyte labelling. In order to evaluate this method, we performed the labelling of two identical leukocyte samples withdrawn from 10 blood donors. The first sample was labeled using 99mTc-HMPAO non-stabilized and the second one was labelled using 99mTc-HMPAO stabilized 2 hours before with methylene blue. The mean labelling efficiencies we obtained were 70.9% (SD 6.9%) and 66.1% (SD 4.2%) respectively. With the conditions described using the 99mTc-HMPAO stabilized with methylene blue, we had no drawbacks from the stabilizing blue colour and we did not found changes in the cellular viability.