Scheduling nab-paclitaxel combined with gemcitabine as first-line treatment for metastatic pancreatic adenocarcinoma.

BACKGROUND: Nab-paclitaxel plus gemcitabine (nabP+gemcitabine) offers modest survival gains for patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Sequential scheduling of nabP+gemcitabine in a PDAC mouse model improved efficacy; this hypothesis was tested in a clinical trial. METHODS: Patients with previously untreated metastatic PDAC were randomised to receive nabP+gemcitabine administered either concomitantly on the same day, or sequentially, with gemcitabine administered 24 h after nabP. The primary outcome measure was progression-free survival (PFS). Secondary outcome measures were objective response rate (ORR), overall survival (OS), safety, quality of life (QoL) and predictive biomarkers. RESULTS: In total, 71 patients received sequential (SEQ) and 75 concomitant (CON) treatment. Six-month PFS was 46% with SEQ and 32% with CON scheduling. Median PFS (5.6 versus 4.0 months, hazard ratio [HR] 0.67, 95% confidence interval [95% CI] 0.47-0.95, p = 0.022) and ORR (52% versus 31%, p = 0.023) favoured the SEQ arm; median OS was 10.2 versus 8.2 months (HR 0.93, 95% CI 0.65-1.33, p = 0.70). CTCAE Grade ≥3 neutropaenia incidence doubled with SEQ therapy but was not detrimental to QoL. Strongly positive tumour epithelial cytidine deaminase (CDA) expression favoured benefit from SEQ therapy (PFS HR 0.31, 95% CI 0.13-0.70). CONCLUSIONS: SEQ delivery of nabP+gemcitabine improved PFS and ORR, with manageable toxicity, but did not significantly improve OS. CLINICAL TRIAL REGISTRATION: ISRCTN71070888; ClinialTrials.gov (NCT03529175).

Morphometry and variations of bony ponticles of the atlas vertebrae (C1) in kenyans / Morfometría y variaciones de puentes óseos de la vértebra atlas (C1) en kenianos

Atlas bridges, the bony outgrowths over the third segment of the vertebral artery are associated with compression of the artery and nerves. There are limited studies comparing morphometry of the complete atlas bridges and that of the ipsilateral transverse foramen. Bilateral and gender differences in the morphometry of the complete bridges remain relatively unexplored. One hundred and two atlas vertebrae (49 male and 53 female) obtained from the Osteology Department of the National Museums of Kenya were used for this study. The presence of complete posterior atlas bridge (retroarticular canal) and lateral bridge (supratransverse foramen) was noted. Measurements were taken for the diameters of foramina, and the ipsilateral transverse foramina and their areas calculated. Complete posterior bridges occurred in 14.6 percent and 13.6 percent on the right and left sides respectively. The lateral bridge was found in 3.9 percent of the cases on the right side only. The complete posterior bridges had a cross-sectional area of 23.44mm2 on the right and 24.98mm2 on the left side. The lateral bridges had a mean cross-sectional area of 27.30mm2. The right and left transverse foramina had mean crosssectional area of 36.30mm2 and 37.20mm2 respectively, which was significantly larger than that of the ipsilateral complete and posterior bridges. The smaller dimensions of the complete atlas bridges compared to the ipsilateral transverse foramen suggest that they may predispose to vertebrobasilar insufficiency, Barre-Lieou and cervicogenic syndromes due to compression of the contents in the foramina.

Puentes del atlas, sobrecrecimientos óseos en el tercer segmento de la arteria vertebral se asocian con la compresión de la arteria y los nervios. Hay pocos estudios que comparan la morfometría de los puentes completos del atlas y el foramen transversal ipsilateral. Diferencias bilaterales y de género en la morfometría de los puentes completos permanecen relativamente inexplorados. Ciento dos vértebras atlas (49 hombres y 53 mujeres) obtenidos del Departamento de Osteología de los Museos Nacionales de Kenya se utilizaron para este estudio. Fueron identificados la presencia de puentes completos posteriores del atlas (canal retroarticular) y puentes laterales (foramen supratransverso). Se realizaron las mediciones de los diámetros del foramen y los forámenes transversos ipsilaterales, y se calcularon sus áreas. Puentes completos posteriores se observaron en el 14,6 por ciento y 13,6 por ciento de los lados derecho e izquierdo, respectivamente. El puente lateral se encontró en el 3,9 por ciento de los casos en el lado derecho solamente. Los puentes completos posteriores tuvieron un área transversal de 23,44mm2 en el lado derecho y 24,98mm2 en el lado izquierdo. Los puentes laterales tuvieron un área media de sección transversal de 27,30mm2. En los lados derecho e izquierdo se encontrron forámenes transversos con un área promedio de sección transversal de 36,30mm2 y 37,20mm2 respectivamente, lo que fue significativamente mayor que el de los puentes completos ipsilaterales y posteriores. Las dimensiones más pequeñas de los puentes atlas completos en comparación con los forámenes transversos ipsilaterales sugieren que pueden predisponer a la insuficiencia vertebrobasilar, síndromes de Barre-Lieou y cervical debido a la compresión de los contenidos en los forámenes.

Regional histomorphometry of the hepatic inferior vena cava; a possible sphincteric mechanism / Histomorfometría regional de la vena cava inferior hepática; un posible mecanismo de esfínter

This study was aimed at identifying the changes in diameter and structural composition of the Hepatic Inferior Vena Cava in its infrahepatic, intrahepatic and suprahepatic portions. Eighty adult liver specimens from the Chiromo and Nairobi City mortuaries were used for morphometry, while twenty of them were processed for light microscopy. A constriction was noted in the mid-portion of the HIVC, while structurally; the intrahepatic portion had thicker fibromuscular adventitia. It is plausible that these are sphincteric apparatus to prevent backflow of blood in the Hepatic Inferior Vena Cava.

Este estudio tiene por objetivo identificar los cambios en el diámetro y la composición estructural de la vena cava inferior hepática en sus porciones infrahepática, intrahepática y suprahepática. Ochenta hígados de especímenes adultos de los depósitos de cadáveres de la ciudad de Nairobi y Chiromo fueron usadas para morfometría, mientras que veinte de ellos fueron procesados para microscopía de luz. Se observó una constricción en el medio de la HIVC, mientras que estructuralmente, la porción intrahepática había una gruesa adventicia fibromuscular. Es posible que este sea un aparato esfinteriano para evitar el reflujo de sangre en la vena cava inferior hepática.