Axicabtagene ciloleucel for the treatment of relapsed/refractory B-cell non-Hodgkin's lymphomas.

B-cell non-Hodgkin's lymphomas are the most common hematological malignancies, which despite improvements in chemo-immunotherapy, carry a uniformly poor prognosis in the relapsed/refractory setting. CD19 is an antigen expressed on the surface of most malignancies arising from the B cells, and adoptive transfer of anti-CD19 chimeric antigen receptor (CAR)-expressing T cells has been shown to be effective in treating these B-cell malignancies. Axicabtagene ciloleucel (axi-cel, KTE-C19) is an autologous anti-CD19 CAR T-cell therapy which has shown high overall response rates and a manageable safety profile in patients with relapsed or refractory B-cell malignancies who lack effective and curative treatment options. Axi-cel is currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy including diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma and DLBCL arising from follicular lymphoma, and is also being evaluated in other B-cell malignancies in ongoing clinical trials. In this review we will discuss the mechanism of action of axi-cel, clinical trials leading to its FDA approval, ongoing clinical trials and its potential adverse effects, and will speculate on the future directions of axi-cel and CAR T-cell therapy in general.

Immune and autoimmune-related adverse events associated with immune checkpoint inhibitors in cancer therapy.

The recent development of monoclonal antibodies that disinhibit the immune system from recognizing and attacking tumor cells has revolutionized the treatment of cancer. Among these agents are drugs that specifically block cytotoxic T-lymphocyte protein 4 (CTLA-4), programmed cell death protein 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) signaling, called immune checkpoint inhibitors (ICIs). While these agents are generally well tolerated, ICI therapy can lead to loss of self-tolerance and the development of autoimmunity, manifesting as immune-related adverse events (IRAEs). Although potentially linked to increased antitumor responses, the morbidity associated with IRAEs can be significant and in rare circumstances, fatal. Virtually any organ can be affected and the patients present with a broad range of signs and symptoms. Moreover, ICIs have varying IRAEs and have distinct toxicity profiles based on their mechanism of action. Fortunately, most of the IRAEs can be managed with immunosuppression and supportive care, but contingent on early recognition and prompt treatment. With increasing advances in drug development, including combination ICI therapy, these agents are becoming one of the most prescribed oncology drugs and clinicians should be knowledgeable about the recognition and management of IRAEs.

Microleakage of Class I and II Composite Resin Restorations Using a Sonic-resin Placement System.

OBJECTIVES: To determine microleakage of posterior Class I and II restorations using the SonicFill composite resin system. METHODS AND MATERIALS: Eighty previously extracted third molars were randomly assigned to four preparation/restoration groups (n=20): Group A: Class I preparations restored with SonicFill system/bulk fill; Group B: Class II preparations restored with SonicFill system/bulk fill; Group C: Class I preparations restored with Herculite Ultra composite resin/incremental technique; and Group D: Class II preparations restored with Herculite Ultra composite resin/incremental technique. Class I preparations were approximately 3.0 mm in width buccolingually and 3.0 mm in depth. Class II preparations were approximately 3.0 mm in width buccolingually, 1.5 mm in axial depth, and 4.0 mm in gingival depth. In all groups, the enamel and dentin surfaces were conditioned with Kerr 37.5% phosphoric acid, followed by application of Optibond Solo Plus adhesive system. Following restoration, the specimens were thermocycled, immersed in methylene blue dye, and embedded in acrylic resin. Specimen blocks were sectioned in the mesiodistal direction, with marginal dye penetration (microleakage) examined using a 20× binocular microscope. Class I and II restoration microleakage was scored separately using a 0-3 ordinal ranking system. Statistical analyses were conducted using nonparametric testing at the p < 0.05 level of significance. RESULTS: Significantly less microleakage was associated with both Class I restorative groups (A and C), SonicFill bulk fill and Herculite Ultra incremental fill, compared to the Class II restorative groups (B and D), SonicFill/bulk fill and Herculite Ultra/incremental fill. CONCLUSIONS: According to the results of this study, the materials (SonicFill vs Herculite Ultra), C-factors, and insertion techniques (bulk vs incremental) did not appear to be significant influences with regard to marginal microleakage; however, the type of preparation cavity (Class I vs Class II) and the subsequent bonding surface (enamel vs dentin [cementum]) proved to be significant factors.

Efectos de la suspensión no convencional de las canales en la palatabilidad de la carne de toretes / Effect of non-conventional of carcass suspension in the palatabilidad of bullock beek

La utilización de un método no convencional de suspender la canal vacuna mejoró significativamente las notas de terneza, y de satisfacción total aumentó el largo de los sarcomeros y disminuyó los valores de fuerza de corte o de cizalla en muestras provenientes de canales de los cuatro grupos de beneficio conciderados. La suspensión por el agujero obturador no mejoró significativamente las notas de terneza o de satisfacción total de las muestras de canales britanicas o sus cruzamientos en los grupos de 9-, 12- ó 18- meses de edad. La suspensión no convencional mejoró todas las notas de terneza y de satisfacción total de muestras provenientes de canales Brahman o sus cruzamientos en los cuatro grupos de edad al beneficio. En algunos casos, el mejoramiento alcanzó hasta 37.9 por ciento. Sin embargo, el mejoramiento mostró la tendencia de disminuir con avances en la edad. La suspensión por el agujero obturador disminuyó significativamente los valores de fuerza de corte o cizalla y aumentó significativamente el largo del sarcomero en tres de los cuatro grupos de edad al beneficio. De acuerdo con los resultados obtenidos, pueden inferirse que la suspensión de la cual por el agujero abjurador mejora significativamente la palatabilidad de la carne de toretes, dentro del rango aquí estudiado (9-18 meses). El mayor efecto de la suspensión no-convencional en mejorar la terneza se logró en aquellas canales que fueron las menos tiernas y menos satisfactorias en palatabilidad total . Además, la suspensión por el agujero obturador tendió a reducir la variabilidad en terneza existente entre los cuatro grupos ..

Infectious jejunitis with stricture after gastrojejunostomy.

Although bacterial overgrowth has often been reported in postgastrectomy patients, inflammatory stricture near the surgical anastomosis is rare. We describe a 36-year-old woman with infectious jejunitis and subsequent jejunal stenosis after gastrojejunostomy.