Feasibility of collecting longitudinal patient-reported outcomes in individuals with relapsed or refractory large B-cell lymphoma who received chimeric antigen receptor T-cell (CART) therapy.

PURPOSE: Chimeric antigen receptor T-cell (CART) therapy has shown clinical efficacy in refractory and relapsed large B-cell lymphomas, but is associated with serious acute and long-term toxicities. To understand the patient perspective, we measured a patient-reported outcome (PRO), specifically, health-related quality of life (HRQoL), at multiple time points over one year. METHODS: This was a prospective feasibility study of a cohort of patients who were eligible for standard of care CART therapy, tisagenlecleucel. Demographic data and disease characteristics were collected. HRQoL was measured using FACT-Lym at baseline, and months 1, 3, 6 and 12. FACT-Lym includes FACT-G (physical, social, emotional and functional well-being domains), plus a lymphoma subscale. RESULTS: Thirty-four of 35 patients approached, consented to participate. Two of them did not receive their infusion due to progressive disease. 50% were female and median age was 62 (23-77). Twenty-nine patients (91%) completed baseline FACT-Lym and 20 of 21 (95%) eligible patients completed 12-month FACT-Lym. 52% completed all 4 post-baseline FACT-Lym measures. Exploratory analyses for changes in FACT-Lym scores are reported. CONCLUSION: It is feasible to measure longitudinal PROs in patients who receive CART therapy. This study will inform future studies in evaluating the patient perspective on CART therapy.

Effects of ballistic transport on the thermal resistance and temperature profile in nanowires.

Abstract: Effects of ballistic transport on the temperature profiles and thermal resistance in nanowires are studied. Computer simulations of nanowires between a heat source and a heat sink have shown that in the middle of such wires the temperature gradient is reduced compared to Fourier's law with steep gradients close to the heat source and sink. In this work, results from molecular dynamics and phonon Monte Carlo simulations of the heat transport in nanowires are compared to a radiator model which predicts a reduced gradient with discrete jumps at the wire ends. The comparison shows that for wires longer than the typical mean free path of phonons the radiator model is able to account for ballistic transport effects. The steep gradients at the wire ends are then continuous manifestations of the discrete jumps in the model.

Plasma tryptophan pathway metabolites quantified by liquid chromatography-tandem mass spectrometry as biomarkers in neuroendocrine tumor patients.

A good and accessible biomarker is of great clinical value in neuroendocrine tumor (NET) patients, especially considering its frequently indolent nature and long-term follow-up. Plasma chromogranin A (CgA) and 5-hydroxyindoleacetic acid (5-HIAA) are currently used as biomarkers in NET, but their sensitivity and specificity are restricted. 5-HIAA is the main metabolite of serotonin, an important neurotransmitter of the tryptophan pathway. The aim of this study is to estabish a sensitive and accurate method for the quantification of tryptophan pathway metabolites in plasma. We further aimed to evaluate its utility as a clinical tool in NET disease. We obtained plasma samples from NET patients and healthy controls recruited from the University Hospital of North Norway, Tromsø. Samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and eight metabolites of the tryptophan pathway were quantified. We included 130 NET patients (72/130 small intestinal [SI] NET, 35/130 pancreatic NET, 23/130 other origin) and 20 healthy controls. In the SI-NET group, 26/72 patients presented with symptoms of carcinoid syndrome (CS). We found that combining tryptophan metabolites into a serotonin/kynurenine pathway ratio improved diagnostic sensitivity (92.3%) and specificity (100%) in detecting CS patients from healthy controls compared with plasma 5-HIAA alone (sensitivity 84.6%/specificity 100%). Further, a clinical marker based on the combination of plasma serotonin, 5-HIAA, and 5OH-tryptophan, increased diagnostic capacity identifying NET patients with metastasized disease from healthy controls compared with singular plasma 5-HIAA, serotonin, or CgA. In addition, this marker was positive in 61% of curatively operated SI-NET patients compared with only 10% of healthy controls (p < .001). Our results indicate that simultaneous quantification of several tryptophan metabolites in plasma, using LC-MS/MS, may represent a clinically useful diagnostic tool in NET disease.

Endoscopic Posterior Cervical Foraminotomy Under Lateral Decubitus Position with Local Anesthesia.

BACKGROUND: Endoscopic posterior cervical foraminotomy is gaining popularity among endoscopic spine surgeons for the treatment of radiculopathy caused by foraminal stenosis. METHODS: This study describes a technique using the lateral decubitus position for endoscopic posterior cervical foraminotomy under monitored anesthesia care and local anesthesia only. RESULTS: A total of 10 patients with contraindications to general anesthesia underwent the procedure, resulting in improvement in cervical radicular pain with no perioperative complications. CONCLUSIONS: The findings suggest that this approach is a viable alternative for patients at high risk of general anesthesia care, expanding the surgical options for the treatment of radiculopathy.

A comparison of computed tomography angiography and digital subtraction angiography for the diagnosis of penetrating cerebrovascular injury: a prospective multicenter study.

OBJECTIVE: In this research, the authors sought to characterize the incidence and extent of cerebrovascular lesions after penetrating brain injury in a civilian population and to compare the diagnostic value of head computed tomography angiography (CTA) and digital subtraction angiography (DSA) in their diagnosis. METHODS: This was a prospective multicenter cohort study of patients with penetrating brain injury due to any mechanism presenting at two academic medical centers over a 3-year period (May 2020 to May 2023). All patients underwent both CTA and DSA. The sensitivity and specificity of CTA was calculated, with DSA considered the gold standard. The number of DSA studies needed to identify a lesion requiring treatment that had not been identified on CTA was also calculated. RESULTS: A total of 73 patients were included in the study, 33 of whom had at least 1 penetrating cerebrovascular injury, for an incidence of 45.2%. The injuries included 13 pseudoaneurysms, 11 major arterial occlusions, 9 dural venous sinus occlusions, 8 dural arteriovenous fistulas, and 6 carotid cavernous fistulas. The sensitivity of CTA was 36.4%, and the specificity was 85.0%. Overall, 5.6 DSA studies were needed to identify a lesion requiring treatment that had not been identified with CTA. CONCLUSIONS: Cerebrovascular injury is common after penetrating brain injury, and CTA alone is insufficient to diagnosis these injuries. Patients with penetrating brain injuries should routinely undergo DSA.

Nitric oxide and immune response in infection control of Caseous Lymphadenitis / Óxido nítrico e resposta imune no controle de infecção da Linfadenite Caseosa

This study aimed to evaluate aspects of host immune response using an experimental infection model of Corynebacterium pseudotuberculosis (CP) in C57/Black6 wild-type and knockout for nitric oxide (KO-NO) mice. 28 mice were evaluated: 4 wild-type controls; 10 wild-type infected with CP; 4 KO-NO controls; 10 KO-NO infected with CP. Infection procedures were carried out by intraperitoneal inoculation using 107. Infected C57/Black6 KO-NO mice began to die after the 5° day post-inoculation, up until the 14º day. Neutrophils were found in increased numbers in the infiltrate of KO-NO murine peritoneal cavities. Examination of splenic tissue revealed an accumulation of lymphocytes, predominantly CD8 T-cells, in experimental animal groups. KO-NO animals were found to have a predominance of granulomas 7 days post-inoculation, primarily in the lymph nodes. In addition, greater amounts of bacteria were recovered from the mesenteric lymph nodes of KO-NO mice. There was no statistically significant difference in the levels of total IgG and its subclasses 14 days post-inoculation between KO-NO and wild groups. The results suggest the importance of nitric oxide in the process of controlling CP infection, as KO-NO animals were observed to be markedly more affected by infection with this bacterium.(AU)

O objetivo deste estudo foi avaliar os aspectos da resposta imune do hospedeiro, mediante o uso de um modelo experimental de infecção de Corynebacterium pseudotuberculosis (CP) em camundongos C57/Black6 do tipo selvagem e em C57/Black6 knockout para o óxido nítrico (KO-NO). Foram avaliados 28 camundongos: quatro controles de tipo selvagem; 10 do tipo selvagem infectados com CP; quatro controles KO-NO; e 10 KO-NO infectados com CP. A infecção foi realizada via intraperitoneal, usando-se 107. Os animais C57/Black6 KO-NO infectados começaram a vir a óbito no quinto dia pós-inoculação, o que aconteceu até o 14º dia. Um número maior de neutrófilos foi encontrado na sua cavidade peritoneal. O exame do baço revelou um acúmulo de linfócitos, predominantemente células T CD8, nos grupos de animais experimentais. Nos animais KO-NO, foi observada a presença de granulomas, sete dias pós-inoculação, principalmente nos gânglios linfáticos. Além disso, uma maior quantidade de bactérias foi detectada dos linfonodos mesentéricos desses animais. Não houve diferença estatisticamente significante nos níveis séricos IgG total e em suas subclasses aos 14 dias pós-inoculação nos grupos KO-NO e selvagem. Os resultados obtidos sugerem a importância do óxido nítrico no processo de controle da infecção por CP.(AU)

Transferencia del ácido linoleico conjugado (CLA) de la leche cruda a leche en polvo y condensada / Conjugated linoleic acid transfer (CLA) from raw milk to powdered milk and condensed milk

The objective of this study was to assess the effect of processing fresh milk into dairy products on conjugated linoleic acid (CLA) content of total and individual CLA isomers (cis-9, trans-11; trans-10, cis-12; cis-10. cis-12) of dairy cow products, raw milk powdered and condensed milk. Additionally, samples of raw milk from two regions of southern Chile (Los Angeles and Los Lagos), obtained by a dairy plant were collected and analyzed. The processing of fresh milk dairy products affected the CLA and its isomers, finding a significant interaction between product type and sampling month, with the total average values of 1.35 g CLA / 100g of fatty acids (AG) in fresh milk and 1.45 and 0.93 g/ 100 g AG transferred to the milk powder and condensed respectively. As isomers, the cis-9, trans-11 had higher levels in the powdered milk that fresh milk in 7 months of the 10 months studied with values from 0.50 to 0.84 g/ 100 g AG. The isomer trans-10, cis-1 + cis-10, cis-12 CLA was found in a range of 0, 24 to 0.64 g/ 100 g AG always low in fresh milk. It is concluded that further research is necessary to elucidate the precise effect of processing and storage of milk and milk products on the content of CLA needed.

El objetivo de este estudio fue evaluar la transferencia del ácido linoleico conjugado (CLA) y de sus isómeros (cis-9, trans-1; trans-10, cis-12; cis-10 cis-12) de leche cruda a productos lácteos como la leche en polvo y la leche condensada. Se recogieron y analizaron muestras de leche cruda de dos regiones del sur de Chile (Los Ángeles y Los Lagos), recepcionada por una planta de lácteos. El procesamiento de la leche fresca a productos lácteos afectó al CLA y a sus isómeros, encontrándose una interacción significativa entre el tipo de producto y el mes de muestreo, con valores promedios de CLA total de 1,35 g/100 g AG en la leche fresca y de 1,45 y 0,93 g/100 g AG traspasados a la leche en polvo y condensada respectivamente. En cuanto a los isómeros, el cis-9, trans-11 presentó niveles más altos en leche la en polvo que el leche fresca en 7 meses de los 10 estudiados con valores que fueron de 0,50 a 0,84 g/100 g AG. El CLA trans-10, cis-1+ CLA cis-10, cis-12 se encontró en un rango de 0, 24 a 0,64 a g/100 g AG siempre bajo de la leche fresca en el caso de la leche. Se concluye que es necesario una mayor investigación para dilucidar el efecto exacto del procesamiento y almacenamiento de la leche y los productos lácteos sobre el contenido de CLA.

A description of genes of Corynebacterium pseudotuberculosis useful in diagnostics and vaccine applications

Corynebacterium pseudotuberculosis, a Gram-positive intracellular pathogen, is the etiological agent of caseous lymphadenitis or CLA. This bacterium infects goats and sheep and causes great economic losses worldwide annually, mainly for goat producers. Despite its importance, CLA is still poorly characterized. However, with advances in the genomic field, many C. pseudotuberculosis genes have already been characterized, mainly those related to virulence such as phospholipase D. Here, we examined the use of the several available genes of C. pseudotuberculosis and reviewed their applications in vaccine construction, more efficient diagnostics for CLA, and control of this disease, among other applications.

Surgical treatment of Chagas megacolon. Critical analysis of outcome in operative methods / Tratamento cirúrgico do megacólon chagásico análise crítica dos resultados dos métodos operatórios

PURPOSE: Surgical treatment of chagasic megacolon has suffered innumerable transformations over the years. Poor knowledge of the disease physiopathology is one of the reasons. METHODS: From January 1977 to December 2003, 430 patients were submitted to surgical treatment for chagasic megacolon. Of these procedures, 351 were elective and 79 emergency operations carried out at the University Hospital of Ribeirão Preto. Four elective operations, most frequently used, should be singled out: anterior rectosigmoidectomy (52.71 percent), left hemicolectomy (18.23 percent), Duhamel-Haddad operation(15.95 percent), and total colectomy (5.98 percent). From the 79 exploratory laparotomies performed on an emergency basis, 53 (67.09 percent) required intestinal resection. From the 430 patients operated upon, 268 (62.33 percent) progressed without recurrence of intestinal constipation, and 71 (15.51 percent) had a recurrence. RESULTS AND DISCUSSION: Based on the data collected, left hemicolectomy had the highest constipation recurrence rate compared to other operating procedures; anterior retosigmoidectomy had less complication episodes and a larger recurrence of intestinal constipation in comparison to the Duhamel-Haddad operation. Emergency operations, mainly for the treatment of volvulus and fecaloma, presented high morbidity and mortality and required extensive intestinal resections, stomas and reoperations.

INTRODUÇÃO: O tratamento cirúrgico do megacólon chagásico tem passado por sucessivas modificações ao longo do tempo. A multiplicidade das operações é explicada pelo conhecimento ainda incompleto da fisiopatologia da doença, MÉTODOS: No período de janeiro de 1977 a dezembro de 2003, 430 pacientes chagásicos foram submetidos a tratamento cirúrgico para o megacólon no Hospital das Clínicas de Ribeirão Preto. Foram realizadas 351 operações eletivas e 79 de urgência. Quatro tipos de operações realizadas em caráter eletivo mereceram destaque por terem sido as mais utilizadas: retossigmoidectomia anterior (52,71 por cento), hemicolectomia esquerda (18,23 por cento), abaixamento de cólon à Duhamel-Haddad (15,95 por cento) e colectomia total (5,98 por cento). Das 79 laparotomias exploradoras realizadas em regime de urgência, em 53 (67,09 por cento) houve ressecção intestinal. Dentre os 430 pacientes operados, 268 (62,33 por cento) evoluíram sem recidiva e 71 (16,51 por cento) com recidiva da constipação intestinal. RESULTADOS E DISCUSSÃO: Com base nos resultados obtidos concluiu-se que: a hemicolectomia esquerda, comparada às demais operações, apresentou maior recidiva da constipação intestinal; a retossigmoidectomia anterior comparada à operação de Duhamel-Haddad apresentou menor número de complicações e maior recidiva da constipação intestinal; as operações de urgência para o tratamento do volvo e do fecaloma apresentaram alta morbimortalidade, exigem resseções intestinais, estomas e reoperações.

Construction and partial characterization of a Corynebacterium pseudotuberculosis bacterial artificial chromosome library through genomic survey sequencing

Corynebacterium pseudotuberculosis is a gram-positive bacterium that causes caseous lymphadenitis in sheep and goats. However, despite the economic losses caused by caseous lymphadenitis, there is little information about the molecular mechanisms of pathogenesis of this bacterium. Genomic libraries constructed in bacterial artificial chromosome (BAC) vectors have become the method of choice for clone development in high-throughput genomic-sequencing projects. Large-insert DNA libraries are useful for isolation and characterization of important genomic regions and genes. In order to identify targets that might be useful for genome sequencing, we constructed a C. pseudotuberculosis BAC library in the vector pBeloBAC11. This library contains about 18,000 BAC clones, with inserts ranging in size from 25 to 120 kb, theoretically representing a 390-fold coverage of the C. pseudotuberculosis genome (estimated to be 2.5-3.1 Mb). Many genomic survey sequences (GSSs) with homology to C. diphtheriae, C. glutamicum, C. efficiens, and C. jeikeium proteins were observed within a sample of 215 sequenced clones, confirming their close phylogenetic relationship. Computer analyses of GSSs did not detect chimeric, deleted, or rearranged BAC clones, showing that this library has low redundancy. This GSSs collection is now available for further genetic and physical analysis of the C. pseudotuberculosis genome. The GSS strategy that we used to develop our library proved to be efficient for the identification of genes and will be an important tool for mapping, assembly, comparative, and functional genomic studies in a C. pseudotuberculosis genome sequencing project that will begin this year.

Evolution of tip and columella surgery

It is presented a summary of the historical evolution of tip and columella surgical reconstruction

Integracao ensino/servico numa disciplina clinica. / Teaching and assistence integracion in a clinical discipline.

A avaliacao da integracao estudante/paciente, em uma disciplina clinica, demonstrou uma aprendizagem insuficiente de habilidades basicas que todo medico deve necessariamente dominar, bem como um impacto negativo na qualidade da assistencia. Embora existissem parcos recursos, o problema principal era a utilizacao inadequada dos disponiveis. Com a assessoria pedagogica, exame de literatura e criatividade pessoal, montou-se um sistema para integrar o ensino ao servico de forma que a aprendizagem dos estudantes pudesse ter um impacto mensuravel assistencia aos pacientes. Com este objetivo, varias medidas foram tomadas: o delineamento de um conteudo minimo mais adequado para a formacao geral o aumento dos recursos da disciplina, e principalmente a utilizacao racional do tempo dos professores e alunos.Sao mostrados o planejamento do novo sistema, sua aplicacao durante um ano escolar, a avaliacao da aprendizagem e seu impacto na assistencia.}