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Background: Treating the octogenarian and nonagenarian patients who have acute myeloid leukemia (AML) with intensive chemotherapy is controversial. Several models to predict outcome were proposed, including the use of a comorbidity index. However, it is unclear whether the Charlson comorbidity index (CCI) or the hematopoietic cell transplant comorbidity index (HCTCI) is more sensitive.Methods: The authors analyzed their experience with 92 patients aged >or=80 years who had AML. Patients' pretreatment characteristics and their treatment outcomes were recorded.Results: All patients were offered intensive treatment; 59 patients (64%) were treated intensively with a variety of regimens, whereas 33 patients (36%) elected to receive supportive care. The CCI and the HCTCI had similar predictive ability for outcome in both groups. A multivariate analyses of prognostic factors identified near-normal albumin (48% of patients; 1-year survival rate, >27%) as a favorable factor for the whole cohort, age <83 years (47% of patients; 1-year survival rate, >25%) and nonmonocytic morphology (75% of patients; 1-year survival rate, >26%) as favorable factors for the intensively treated cohort, and bone marrow blasts <46% (50% of patients; 1-year survival rate, >19%) as a favorable factor for patients who received supportive care.Conclusions: This retrospective analysis was developed to assist in treatment decisions for octogenarian and nonagenarian patients with AML. The findings will need validation in a prospective study. [ABSTRACT FROM AUTHOR]

Study Objective: This study investigated race and sex differences in tacrolimus pharmacokinetics and pharmacodynamics in stable kidney transplant recipients., Design and Setting: A cross-sectional, open-label, single center, 12-h pharmacokinetic-pharmacodynamic study was conducted. Tacrolimus pharmacokinetic parameters included area under the concentration-time curve (AUC 0-12 ), AUC 0-4 , 12-h troughs (C 12 h ), maximum concentrations (C max ), oral clearance (Cl), with dose-normalized AUC 0-12 , troughs, and C max with standardized adverse effect scores. Statistical models were used to analyze end points with individual covariate-adjustment including clinical factors, genotypic variants CYP3A5*3, CYP3A5*6, CYP3A5*7(CYP3A5*3*6*7) metabolic composite, and ATP binding cassette gene subfamily B member 1 (ABCB1) polymorphisms., Patients: 65 stable, female and male, Black and White kidney transplant recipients receiving tacrolimus and mycophenolic acid ≥6 months post-transplant were evaluated., Measurements and Main Results: Black recipients exhibited higher tacrolimus AUC 0-12 (Race: p = 0.005), lower AUC* (Race: p < 0.001; Race × Sex: p = 0.068), and higher Cl (Race: p < 0.001; Sex: p = 0.066). Greater cumulative (Sex: p < 0.001; Race × Sex: p = 0.014), neurologic (Sex: p = 0.021; Race × Sex: p = 0.005), and aesthetic (Sex: p = 0.002) adverse effects were found in females, with highest scores in Black women. In 84.8% of Black and 68.8% of White patients, the target AUC 0-12 was achieved (p = 0.027). In 31.3% of White and 9.1% of Black recipients, AUC 0-12 was <100 ng‧h/ml despite tacrolimus troughs in the target range (p = 0.027). The novel CYP3A5*3*6*7 metabolic composite was the significant covariate accounting for 15%-19% of tacrolimus variability in dose (p = 0.002); AUC 0-12 h * (p < 0.001), and Cl (p < 0.001)., Conclusions: Tacrolimus pharmacokinetics and adverse effects were different among stable kidney transplant recipient groups based upon race and sex with interpatient variability associated with the CYP3A5*3*6*7 metabolic composite. More cumulative, neurologic, and aesthetic adverse effects were noted among females. Tacrolimus regimens that consider race and sex may reduce adverse effects and enhance allograft outcomes by facilitating more patients to achieve the targeted AUC 0-12 h ., (© 2022 The Authors. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy published by Wiley Periodicals LLC on behalf of Pharmacotherapy Publications, Inc.)

Objectives/hypothesis: Recent studies have suggested that Staphylococcus aureus secrete exotoxins that may act as superantigens and upregulate the variable beta region of lymphocytes in chronic hyperplasticsinusitis with nasal polyposis (CHSwNP). The aim of this study was to add further information for correlating the presence of staphylococcal species and the upregulation of the V(β) region of both nasal polyp lymphocytes and peripheral blood lymphocytes. Furthermore, IgE-mediated hypersensitivity directed against these exotoxins produces an additional independent immunologic mechanism in upregulating the inflammatory response in the lateral wall of the nose in nasal polyposis., Study Design: Prospective study., Methods: Nasal polyps were harvested from 38 patients with CHSwNP. Eleven patients were studied for the correlation of exotoxin from staphylococcal species and the variable beta region of lymphocytes in both the nasal polyp lymphocytes and corresponding peripheral blood lymphocytes. Eight additional patients with CHSwNP were studied for local and systemic IgE-mediated immunity directed against S aureus exotoxins. Flow cytometry was used to analyze the V(β) repertoire of polyp-derived CD3-positive lymphocytes from 11 patients. S aureus was isolated from nine patients, and coagulase-negative Staphylococcus was isolated from two patients in whom at least 1 × 10(6) T cells could be isolated from their nasal polyps. A quantitative assay for IgE was developed to study the levels of this immunoglobulin directed against S aureus exotoxins in both the nasal polyp and the peripheral blood lymphocytes of 11 patients and in the nasal mucus and serum of eight additional patients., Results: Eleven patients had T-cell V(β) clonal expansion. S aureus exotoxin upregulated the corresponding V(β) region of lymphocytes in both the nasal polyp T cells as well as the T cells from the peripheral blood in nine patients, and two patients with coagulase-negative Staphylococcus also demonstrated upregulation of the V(β) region in the nasal polyps in the absence of exotoxins. In one patient, in vivo exotoxin was isolated, which correlated with the in vitro isolation from the organism itself. IgE directed against staphylococcal enterotoxin B (SEB) and toxic shock syndrome toxin was significantly elevated in the sera of patients with CHSwNP (P < .0001) as compared with the sera of age-related healthy control subjects; IgE directed against staphylococcal enterotoxin A and SEB (P = .0047) was significantly elevated in the mucus of eight patients with CHSwNP as compared with the nasal mucus of healthy controls., Conclusions: This study augments our understanding of the potential role of S aureus exotoxins behaving as superantigens in the lateral wall of the nose in CHSwNP. Furthermore, local nasal IgE directed against these exotoxins may create a local allergic inflammation in the lateral wall of the nose. These two immunologic mechanisms are independent but may be additive in the inflammatory process in CHSwNP., (Copyright © 2010 The American Laryngological, Rhinological, and Otological Society, Inc.)

Background: Wireless pH and pressure motility capsule (wireless motility capsule) technology provides a method to assess regional gastrointestinal transit times., Aims: To analyse data from a multi-centre study of gastroparetic patients and healthy controls and to compare regional transit times measured by wireless motility capsule in healthy controls and gastroparetics (GP)., Methods: A total of 66 healthy controls and 34 patients with GP (15 diabetic and 19 idiopathic) swallowed wireless motility capsule together with standardized meal (255 kcal). Gastric emptying time (GET), small bowel transit time (SBTT), colon transit time (CTT) and whole gut transit time (WGTT) were calculated using the wireless motility capsule., Results: Gastric emptying time, CTT and WGTT but not SBTT were significantly longer in GP than in controls. Eighteen percent of gastroparetic patients had delayed WGTT. Both diabetic and idiopathic aetiologies of gastroparetics had significantly slower WGTT (P < 0.0001) in addition to significantly slower GET than healthy controls. Diabetic gastroparetics additionally had significantly slower CTT than healthy controls (P = 0.0054)., Conclusions: In addition to assessing gastric emptying, regional transit times can be measured using wireless motility capsule. The prolongation of CTT in gastroparetic patients indicates that dysmotility beyond the stomach in GP is present, and it could be contributing to symptom presentation.

Background: Gastric emptying scintigraphy (GES) using a radio-labelled meal is used to measure gastric emptying. A nondigestible capsule, SmartPill, records luminal pH, temperature, and pressure during gastrointestinal transit providing a measure of gastric emptying time (GET)., Aims: To compare gastric emptying time and GES by assessing their correlation, and to compare GET and GES for discriminating healthy subjects from gastroparetics., Methods: Eighty-seven healthy subjects and 61 gastroparetics enrolled with simultaneous SmartPill and GES. Fasted subjects were ingested capsule and [(99m)Tc]-SC radio-labelled meal. Images were obtained every 30 min for 6 h. Gastric emptying time and percentage of meal remaining at 2/4 h were determined for each subject. The sensitivity/specificity and receiver operating characteristic analysis of each measure were determined for each subject., Results: Correlation between GET and GES-4 h was 0.73 and GES-2 h was 0.63. The diagnostic accuracy from the receiver operating characteristic curve between gastroparetics and healthy subjects was GET = 0.83, GES-4 h = 0.82 and GES-2 h = 0.79. The 300-min cut-off time for GET gives sensitivity of 0.65 and specificity of 0.87 for diagnosis of gastroparesis. The corresponding sensitivity/specificity for 2 and 4 h standard GES measures were 0.34/0.93 and 0.44/0.93, respectively., Conclusion: SmartPill GET correlates with GES and discriminates between healthy and gastroparetic subjects offering a nonradioactive, standardized, ambulatory alternative to scintigraphy.