B cell receptor (BCR)-mediated antigen processing and presentation involves both the BCR-mediated internalization and processing of cognate antigen as well as the formation and expression of antigenic peptide-MHC class II complexes. While BCR signaling is known to result in changes in the biosynthesis and intracellular trafficking of class II molecules, the effect of BCR signaling on the cell biology of antigen endocytosis and processing is less clear. Therefore, the effect of BCR signaling on the cell biology of fluid phase antigen endocytosis, processing and presentation was analyzed in both B cell lines or in normal splenic B cells. The results demonstrate that BCR signaling alters neither the global level of fluid phase antigen endocytosis nor the duration of intracellular persistence of fluid phase internalized antigen. Moreover, while BCR signal does result in an increase in the level of total cell surface MHC class II molecules as well as specific peptide-class II complexes, stimulation failed to alter the fraction of class II molecules loaded with antigen-derived peptide. These results indicate that while BCR-mediated signaling elicits an increase in the expression of antigenic peptide-class II complexes, signaling does not augment antigen presentation by profoundly altering the basic biology of antigen endocytosis and processing. These results also demonstrate that the high efficiency of BCR-mediated antigen processing (when compared to fluid phase antigen processing) is likely to occur independent of BCR signaling-induced global alterations in the biology of endocytosis, processing and presentation. This finding suggests that if BCR signaling augments the efficiency of processing of cognate antigen, it must impact unique aspects of BCR-mediated antigen processing, such as the intracellular persistence of internalized antigen-BCR complexes.

BackgroundVitamin D deficiency is implicated in neoplastic processes in multiple organs, including the pancreas. While animal and human data have established a relationship between serum vitamin D (25(OH)D) and the development of pancreatic cancer, few studies have examined the effects of 25(OH)D on time to progression (TTP) and overall survival (OS) in this patient population. We hypothesize that lower baseline serum concentrations (BSC) of 25(OH)D will be associated with decreased TTP and OS.MethodsThis retrospective analysis of 1222 patients with pancreatic cancer aims to identify potential relationships between 25(OH)D and both TTP and OS, while controlling for the effects of ethnicity and body mass index (BMI). Baseline 25(OH)D was divided into quartiles defined as deficient (<20 ng/mL), insufficient (20–39 ng/mL), sufficient (40–59 ng/mL), and optimal (≥60 ng/ml). Statistical significance was declared if the two-sided p-value was ≤ 0.05.ResultsFor the 627 subjects included for analysis, the median 25(OH)D was 27 ng/mL (range 4 to 114), 30.0 % were 25(OH)D deficient (<20 ng/mL), and 47.2 % were insufficient (20–39 ng/mL). Ethnicity (p < 0.0001) and BMI (p = 0.05) were significantly associated with (BSC)of 25(OH)D, while TTP (p = 0.39) and OS (p = 0.37) were not associated.ConclusionSuboptimal vitamin D levels (<60 ng/mL) occurred in 96 % of patients analyzed. Both ethnicity and BMI were statistically significantly associated with vitamin D deficiency and insufficiency. Similar to results previously reported in the literature, this analysis did not identify a significant association between BSC of 25(OH)D and OS or TTP in patients with pancreatic cancer.

Critical care in the oncology population consists of diverse levels of diseases, syndromes, and emergencies that are not observed in typical medically-ill patients and, with it, comes even more specialized treatment strategies. Therefore, the uncommon or less well-understood pharmacologic considerations in this population must be discussed to better assist any clinician at the bedside. This chapter outlines some of the situations commonly encountered in this setting such as the challenge of treating and preventing infectious diseases when the patient lacks the ability to mount appropriate immune responses to conventional therapy, the paradigm of treating thromboembolism in the group of patients who are at highest risk for both bleeding and clotting and treatment of acute and long-term consequences of cancer or chemotherapy requiring escalation of care to the intensive care unit (ICU).

Abstract"tention has heightened over the last several years to the importance of managing pain, agitation, and delirium in mechanically ventilated patients due to the multiple longterm adverse efects patients experience after an intensive care unit ICU admission. Furthermore, clinical practice is being molded not just by the guidelines and randomized controlled trials, but also by the information gathered from real patient experiences to improve care at the bedside. The literature continues to remain sparse for providing guidance speciically in the oncology population. Therefore, several resources have been combined to beter assist clinicians on making sound decisions for keeping patients comfortable on the ventilator while recognizing the diferences in treatment that may need to be employed due to these patients' medical condition.