Feasibility and limitations of cultured skin fibroblasts for germline genetic testing in hematologic disorders.

To avoid acquired variants found in the blood, cultured skin fibroblasts are a recommended DNA source for germline genetic testing in patients with hematologic disorders, but data are lacking regarding practicality and limitations. We conducted a retrospective cohort study of 350 subjects with hematologic disorders who underwent skin fibroblast culture for germline genetic testing. We analyzed next-generation sequencing data from the targeted capture of 144 inherited cancer and bonemarrow failure genes to identify variants at heterozygous and subclonal variant allele frequencies. Sixteen (5%) biopsies failed to culture. Culture failure was more likely in samples with delays in culture initiation (OR = 4.3; p < 0.01) or a pathogenic variant in a telomere gene (OR = 42.6; p < 0.01). Median culture time was 28 days (IQR 22-29 days). Culture time was longer for subjects with prior allogeneic stem cell transplantation (+10.7%; p = 0.02) and shorter in subjects with a heterozygous pathogenic variant (-11.9%; p < 0.01), larger biopsy size (-10.6%; p < 0.01), or lymphoid malignancy (-8.4%; p < 0.01). Subclonal variants were identified in 10 (4%) and confirmed in five (56%) of eight with alternate samples available. Subclonal and discordant variants illustrate that germline testing from cultured skin fibroblasts requires phenotypic correlation and, in rare cases, follow-up studies for optimal interpretation.

Targeted mutational analysis of inflammatory bowel disease-associated colorectal cancers.

Inflammatory bowel disease-associated colorectal carcinomas (IBD-CRCs) develop in a background of chronic inflammation, and thus, the molecular landscape of these tumors likely differs from that of sporadic colorectal cancer. To add to emerging data on molecular alterations present in these tumors, we analyzed our institution's cohort of IBD-CRCs. CRCs resected from patients with IBD underwent molecular analysis via a 50-gene hot-spot solid tumor panel (OncoScreen ST2.0). In-house sporadic CRCs and The Cancer Genome Atlas project data were used for comparison. Fifty-five IBD-CRCs from 48 patients were successfully analyzed. Mutations in TP53 were most common and were present in 69% of IBD-CRCs; a similar percentage of TP53 mutations was detected in sporadic colorectal carcinomas (70%). APC and KRAS mutations were significantly less common in IBD-CRCs than in sporadic CRCs (15% versus 53%, P < .001 and 20% versus 38%, P = .02, respectively). Additionally, the potentially targetable IDH1 R132 mutation was present in 7% of IBD-CRCs but only 1% of sporadic CRCs and The Cancer Genome Atlas CRCs; alterations in other genes with potential targeted therapies were very rare. In conclusion, IBD-CRCs exhibit molecular differences when compared to sporadic CRCs, suggesting different pathways of carcinogenesis, although certain alterations are common to both types of tumors. IDH1 mutations are present in a subset of IBD-CRCs, which may expand therapeutic options in the future.

System for Informatics in the Molecular Pathology Laboratory: An Open-Source End-to-End Solution for Next-Generation Sequencing Clinical Data Management.

Next-generation sequencing (NGS) diagnostic assays increasingly are becoming the standard of care in oncology practice. As the scale of an NGS laboratory grows, management of these assays requires organizing large amounts of information, including patient data, laboratory processes, genomic data, as well as variant interpretation and reporting. Although several Laboratory Information Systems and/or Laboratory Information Management Systems are commercially available, they may not meet all of the needs of a given laboratory, in addition to being frequently cost-prohibitive. Herein, we present the System for Informatics in the Molecular Pathology Laboratory (SIMPL), a free and open-source Laboratory Information System/Laboratory Information Management System for academic and nonprofit molecular pathology NGS laboratories, developed at the Genomic and Molecular Pathology Division at the University of Chicago Medicine. SIMPL was designed as a modular end-to-end information system to handle all stages of the NGS laboratory workload from test order to reporting. We describe the features of SIMPL, its clinical validation at University of Chicago Medicine, and its installation and testing within a different academic center laboratory (University of Colorado), and we propose a platform for future community co-development and interlaboratory data sharing.

Postoperative delirium in head and neck cancer patients: a survey of oncologic oral and maxillofacial surgeon practices.

PURPOSE: Effective delirium risk management for head and neck surgical patients has not been investigated. The present study was undertaken to determine oncologic oral and maxillofacial surgeons' postoperative delirium diagnostic and management practices. MATERIALS AND METHODS: Surgeon familiarity with the standard of care for postoperative delirium diagnosis and management was assessed through an electronic survey. Survey results were compared with published guidelines and the results of similar surveys within the critical care medical community. RESULTS: Participation was 87.5%. Although less than one third of respondents used appropriate diagnostic nomenclature to characterize the clinical manifestations of acute postoperative delirium, 89% did recognize delirium as a complication that increased morbidity. Only 58% were aware of methods to identify patients at risk. No surgeon who personally initiated pharmacologic therapy for delirium reported using a validated delirium-screening instrument. The administration of a benzodiazepine occurred more often than any other drug during the treatment of postoperative delirium. CONCLUSION: The present study highlights distinct variations in the medical management of postoperative delirium, with most surgeons prescribing medications that have been shown to potentiate or exacerbate delirium or have not been proved to have superior therapeutic benefit. Haloperidol remains the first-line drug of choice in the management of patients appropriately diagnosed with postoperative delirium. Prospective investigations for risk stratification and postoperative delirium are needed.

Surgical correction of craniosynostosis. A review of 100 cases.

PURPOSE: Provide outcome data for open cranial vault reshaping at a single institution by a single craniofacial surgeon treating 100 patients. METHODS AND SUBJECTS: A total of 100 patient records were reviewed. Criteria for selection included patients less than three years of age undergoing primary surgery with open cranial vault reshaping and a minimum follow up time of 2 years. RESULTS: Of the 100 patients (27 female, 73 male) treated 6 were syndromic and 94 nonsyndromic. Average age and weight were 8.9 months and 9.51 kg, respectively. The oldest child was 30 months and the youngest 5 months at the time of surgery. The estimated blood volume lost was 42.7% of total calculated blood volume ranging from 16.6% to 336%. Average surgical time was 216.7 min. Complications included 2 hematomas, 2 wound infections, 1 subgaleal abscess, 6 dural tears, 3 patients requiring reoperation for residual deformity, 4 cases requiring coronal scar revision, 1 sagittal sinus bleed, and 1 intraoperative death. CONCLUSIONS: Our review of 100 open repairs of patients with craniosynostosis demonstrates good long-term results with an overall low complication rate. The outcome data will assist in developing future prospective studies aimed at improving the multidisciplinary care of these patients.

Conocimientos, conservación y avistamiento del manatí amazónico (Trichechus inunguis), según los pobladores de la cuenca del río Ucayali (Loreto, Perú) / Knowledge of the inhabitants from the Ucayali river basin (Peru) about the Amazonian manatee (Trichechus inunguis)

Identificar conocimientos que poseen los pobladores de la cuenca del río Ucayali sobre la biología, conservación y problemática, asi como avistamientos previos del manatí amazónico Trichechus inunguis. Materiales y métodos: Se encuestaron 421 personas de diferentes edades, sexos y ocupaciones, en diferentes localidades de la cuenca del río Ucayali. Resultados: El 88.8% reconoció a la especie, y el 80.1% conocen al manatí con el nombre de vaca marina. El 65.1% declaran haber consumido su carne de manera poco frecuente y oportunista. La principal razón que justifican para capturarlos fue su buen sabor (46.4%). Así mismo, 51.9% de los encuestados afirmó saber que su caza es ilegal y el 24% refirió haberlo avistado en el área de estudio. Asimismo, 96.7% manifestaron interés para que esta especie animal se conserve. Conclusiones: Los conocimientos de los pobladores encuestados son insuficientes sobre la situación poblacional, las amenazas y la legislación actual que rige la caza del manatí. Actualmente, con poca frecuencia, se siguen avistando ejemplares en vida silvestre dentro del área de estudio, pero también se sigue dando su captura. Se recomienda incluir la educación ambiental en estas comunidades como principal herramienta para la conservación del manatí amazónico...

To collect information about the knowledge of the inhabitants from the Ucayali River basin about the amazonian manateeÆs, Trichechus inunguis, biology, conservation and problematic as well as previous sightings. Materials and methods: 421 people were surveyed without bias of age, sex or occupation, in different localities of the Ucayali River basin. Results: 88.8% of the interviewed recognized species, most of them referring to it as ôsea cowõ (80.1%). The principal use attributed to this animal is the consumption of its meat (65.1%). Also 51.9% of the surveyed are aware that hunting is illegal. According to the surveyed, the consumption of this species is rare and opportunistic, being the good taste of its meat (46.4%) the main reason for its capture. There is a great interest from behalf the population in the conservation of this animal (96.7%). As for the sightings, 24.0% were within the study area. Conclusions: There is a lack of knowledge from the surveyed on the current population, threats and the laws regulating the hunting of the amazonian manatee. Currently, with low frequency, sightings are still occurring within the study area, but also their capture. Environmental education is the main tool required for the conservation of the amazonian manatee in these communities...

Oral maxillary squamous carcinoma: an indication for neck dissection in the clinically negative neck.

BACKGROUND: This multicenter study was undertaken to characterize the metastatic behavior of oral maxillary squamous carcinoma and to determine the role of selective neck dissection. METHODS: A retrospective, multicenter study of patients surgically treated for oral maxillary squamous carcinoma was completed. Data collected included primary tumor location, cervical lymph node status, and neck failure rate. RESULTS: The study included 146 patients. The adjusted regional metastatic rate was 31.4%. Of those N0 (clinically negative) necks treated with or without neck dissection, 14.4% developed cervical metastasis. Within the cohort, 7.5% of patients died with distant disease. The regional salvage rate was 52.9%. None of the patients with locoregional failures were salvaged. CONCLUSIONS: Maxillary palatal, alveolar, and gingival squamous carcinomas exhibit aggressive regional metastatic behavior. Surgical salvage rates for neck failure are low; therefore, selective neck dissection (levels I-III) is recommended at the time of resection of T2, T3, and T4 maxillary squamous carcinomas.

Tolerabilidad y eficacia de morfina versus hidromorfona en analgesia epidural posquirúrgica con bupivacaína: ensayo aleatorizado, doble ciego y controlado / Tolerability and efficacy of morphine vs. hydromorphone in postoperative epidural analgesia: double-blind randomized control trial

Introducción. La tolerabilidad a la analgesia epidural puede comprometerse por efectos adversos derivados del opioide usado. Este estudio compara la tolerabilidad y eficacia de hidromorfona o morfina en combinación con bupivacaína, en analgesia epidural postoperatoria. Métodos. Ensayo prospectivo, aleatorizado y doble ciego en el Hospital Universitario San Vicente de Paul; 147 pacientes fueron aleatorizadosen dos grupos: 73 pacientes del grupo MB recibieron 30 mcg/ml de morfina más bupivacaína 0,1 %, y 74 pacientes del grupo HB recibieron hidromorfona 10 mcg/ml más bupivacaína 0,1 %. Resultados. El desenlace principal fue tolerabilidad, definida por la frecuencia de náusea, vómito, sedación, retención urinaria y prurito entre los grupos a las 24 horas. Se analizaron 142 pacientes: 71 en el grupo MB y 71 en el grupo HB. La frecuencia de náusea fue de 36,6 % y 31 %, (p = 0,54); vómito, 19,7 % y 25,4 % (p = 0,42); sedación 15,5 % y 14,1 % (p = 0,81); retención urinaria 11,3 % y 7 % (p = 0,38); y prurito 43,7 % y 31 % (p = 0,11) para los grupos MB y HB, respectivamente. Cinco pacientes fueron retirados del estudio debido a migración o desconexión del catéter. No se hallaron diferencias estadísticamente significativas entre los grupos. La escala verbal numérica (EVN) de dolor dinámico a las 24 horas fue de 3,42 (+/- 2,8) y 2,82 (+/- 2,5) para los grupos MB y HB, respectivamente (p = 0,16). Conclusión. La escogencia entre morfina 30 mcg/ml o hidromorfona 10 mcg/ml no influye en la tolerabilidad o eficacia de esta técnica.

Introduction. The acceptance (tolerability) of epidural analgesia can be compromised by the side effects of opioids. This study compares theside effects and efficacy of hydromorphone or morphine combined with bupivacaine in postoperativeepidural analgesia. Methods. Double-blind prospective randomizedcontrolled trial at Hospital Universitario San Vicente de Paul; 147 patients were randomized in two groups: 73 patients of the MB Group received 30 μg per ml of morphine with bupivacaine 0.1 % and 74 patients of the HB group received10 μg per ml of hydromorphone with bupivacaine 0.1 %. Results. The main outcome was the tolerability defined by the frequency of nausea and vomitingsedation urinary retention and pruritus between the groups at 24 hours. 142 patients were analyzed: 71 in group MB and 71 in group HB. The incidence of nausea was 36.6 % and 31 % (p = 0.54); vomiting 19.7 % and 25.4 % (p = 0.42); sedation 15.5 % and 14.1 % (p = 0.81); urinary retention 11.3 % and 7 % (p = 0.38); and pruritus 43.7 % and 31 % (p = 0.11) for groups MB and HB respectively. Five patients were excluded either because of catheter migration or disconnection. No statistically significant differences werefound between the groups. The verbal numerical scale (VNS) of dynamic pain at 24 hours was 3.42 (+/- 2.8) y 2.82 (+/- 2.5) for groups MB and HBrespectively (p = 0.16) Conclusions. The choice between 30 μg per ml of morphine or 10 mcg per ml of hydromorphone does not influence the incidence of side effects or the efficacy of this technique.

La omisión de la relajación neuromuscular en pacientes ambulatorios que requieren intubación orotraqueal incrementa temporalmente la incidencia de síntomas laríngeos postoperatorios: estudio cuasi-experimental / The avoidance of neuromuscular paralysis in outpatients requiring endotracheal intubation temporarily increases the incidence of postoperative laryngeal symptoms: quasi-experimental study

Introducción. Las técnicas de intubación endotraqueal sin relajación neuromuscular han crecido en popularidad, pero su impacto en unidades quirúrgicas donde existe personal en entrenamiento es desconocido. Objetivo. Evaluar el impacto de omitir la relajación neuromuscular, en términos de incidencia de disfonía y odinofagia, en pacientes sometidos a procedimientos ambulatorios cortos que requieren intubación endotraqueal en una unidad quirúrgica académica universitaria. Método. Estudio cuasi-experimental, no aleatorizado, doble ciego, en pacientes adultos programados para cirugía ambulatoria que requerían intubación endotraqueal. El grupo de no relajación recibió lidocaína (1,5 mg kg-1), propofol (1,5-2 mg kg-1) y remifentanil 4 mcg kg-1, y el grupo de relajación recibió la misma técnica, y se adicionó rocuronio a dosis de 0,3-0,6 mg kg-1. Los desenlaces primarios se evaluaron a los días 1, 3 y 14 postoperatorios. Resultados. Se incluyeron 287 pacientes. El 51,7 % recibió relajante neuromuscular. La incidencia de disfonía fue estadísticamente mayor a las 24 horas en el grupo de no relajante (26 % frente a 15 %; valor p: 0,016); así, no fue significativa a las 72 horas de seguimiento (0,6 % frente a 0 %; valor de p 0,37). No se encontraron diferencias en la incidencia de odinofagia entre los grupos. Los síntomas habían desaparecido en toda la población estudiada a la semana de seguimiento. Conclusiones. Omitir la relajación neuromuscular se asocia con un incremento transitorio de disfonía a las 24 horas del posoperatorio, pero no de odinofagia. No existen diferencias en la incidencia de síntomas laríngeos en 72 horas. La adición de relajante neuromuscular para disminuir la incidencia de disfonía temprana puede estar justificada.

Introduction. Endotracheal intubation without neuromuscular relaxation has become more common, but its impact on surgical units of teaching hospitals is unknown. Objective. To assess the impact of avoiding neuromuscularrelaxation in terms of incidence ofhoarseness and sore throat in ambulatory surgery patients requiring endotracheal intubation in surgical unit of a teaching hospital. Method. A quasi-experimental, non-randomized, double-blind study in adult patients undergoing outpatient surgery requiring endotracheal intubation. The non muscle relaxant group received lidocaine (1.5 mg kg-1), propofol (1.5 - 2 mg kg-1) and remifentanil 4 mcg * kg-1 and the muscle relaxation group received the same technique and rocuronium 0.3 to 0.6 mg * kg-1. The primary outcomes were assessed at days 1, 3 and 14.Results. We enrolled 287 patients, where 51.7 % received rocuronium. The incidence of hoarseness was significantly higher at 24 hours in the nonrelaxant group (26 % vs. 15 %, p value: 0.016) being not significant after 72 hours of follow up (0.6 % vs. 0 %; p: 0.37). We found no differences inthe incidence of sore throat between the groups. All the study patients were asymptomatic at one week. Conclusions. Avoidance of neuromuscular relaxationis associated with a transient (First 24hours) increase in hoarseness after ambulatory surgery, but no difference in sore throat. We found no differences in the incidence of laryngeal symptoms after 72 hours. The addition of musclerelaxant to reduce the incidence of hoarseness can be justified.

Oral maxillary squamous cell carcinoma: management of the clinically negative neck.

PURPOSE: Squamous cell carcinomas of the hard palate, maxillary gingiva, and maxillary alveolus occur at relatively low rates compared with squamous cell carcinomas in other oral sites. There is little within the surgical literature to guide treatment for maxillary squamous cell carcinoma. To date, only 1 other group has addressed neck management in the oral maxillary squamous cell carcinoma patient presenting with a clinically negative neck. Adequate characterization of maxillary gingival carcinoma behavior with respect to regional cervical metastasis is wanting. PATIENTS AND METHODS: We present a retrospective review of our own clinical experience as well as a review of the existing literature. RESULTS: In our University of California San Francisco patient group, cervical disease was detected in 20% of those individuals with maxillary squamous cell carcinoma presenting for initial consultation. After ablative surgery, those individuals who presented with clinically negative necks had a 21.4% rate of regional node metastasis. Ultimately, 50% of our patients with squamous cell carcinomas of the palate, maxillary gingiva, and maxillary alveolus developed regional or metastatic distant disease; 42.9% of the patients manifested disease to the cervical lymph nodes alone. CONCLUSIONS: The cases of oral maxillary squamous cell carcinomas reviewed herein exhibit aggressive regional metastatic behavior comparable to that of such carcinomas of the tongue, floor of the mouth, and mandibular gingiva. Based on the findings presented herein, we recommend selective neck dissection in the setting of a clinically negative neck as a primary management strategy for patients with oral maxillary squamous cell carcinomas involving the palate, maxillary gingiva, and maxillary alveolus.

Diseases, lesions and malformations in the long-beaked common dolphin Delphinus capensis from the Southeast Pacific.

Miscellaneous lesions of the head, skull, teeth, trunk, appendages, skin and genital tract were observed in 120 of 930 long-beaked common dolphins Delphinus capensis taken in fisheries off Peru between 1985 and 2000. Seven subsamples were defined according to the varying field sampling protocols. Forty-two dolphins showed at least 2 types of injuries or diseases affecting 1 or more organs. The majority (5 of 7) of traumas encountered were diagnosed as caused by violent, fisheries-related interactions, and the skin in 20.4 % of specimens (n = 54) showed healed scars from such interactions. Prevalences of malformations and traumas of crania (n = 103) were 2.9 and 1.9%, respectively. Lytic cranial lesions were present in 31.1% of dolphins (n = 103) and accounted for 84.2% of all bone injuries. Skull damage diagnostic for Crassicauda sp. infestation was encountered in 26.5% of dolphins (n = 98) and did not differ among sex and age classes. Crassicauda sp. and tooth infections were responsible for, respectively, 78.8 and 6.1% of the lytic lesions. Adult dolphins showed a high prevalence of worn and broken teeth (35%, n = 20) as well as damaged alveoli (20%, n = 70). Prevalence of 'paired teeth', a congenital condition, was 9.4% (n = 32). Lesions of the head, body and appendages were present in 10 dolphins and included traumas, deformations (e.g. scoliokyphosis and brachygnathia) and chronic mastitis. Ovarian cysts suggestive of follicular cysts were observed in 1 of 24 females. Chronic orchitis affected 1 of 78 males. Of 12 dolphins 2 had vesicular lesions of the penis. Prevalence of cutaneous lesions, abnormalities and scars ranged between 1.8% (n = 56) and 48.2% (n = 27).