TRAIL Score: A Simple Model to Predict Immunochemotherapy Tolerability in Patients With Diffuse Large B-Cell Lymphoma.

PURPOSE: Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) represents the standard of care for first-line treatment of diffuse large B-cell lymphoma (DLBCL). However, many patients are unable to tolerate R-CHOP and have inferior outcomes. This study aimed to develop a practical tool to help physicians identify patients with newly diagnosed DLBCL unlikely to tolerate a full course of R-CHOP. METHODS: We developed a predictive model (Tolerability of R-CHOP in Aggressive Lymphoma [TRAIL]) on the basis of a training data set from the phase III GOYA trial (obinutuzumab with CHOP v R-CHOP in 1L DLBCL) using a composite binary end point, identifying patients who prematurely stopped or required reductions of R-CHOP. Candidate predictive variables were selected on the basis of known baseline characteristics that contribute to patient frailty, comorbidity, and/or chemotherapy toxicity. TRAIL was developed using an iterative trial-and-error modeling process to fit a logistic regression model. The final model was evaluated for robustness using a GOYA holdout data set and the phase III MAIN (R-CHOP with or without bevacizumab in 1L DLBCL) R-CHOP-21 data set as external validation. RESULTS: TRAIL includes four simple predictors available in the routine clinical setting: Charlson Comorbidity Index, presence of cardiovascular disease or diabetes, serum albumin, and creatinine clearance. Model generalization performance estimated by the area under the curve was around or above 0.70 across GOYA training, GOYA holdout, and MAIN data sets. Classifying patients into low-, intermediate- and high-risk categories, the proportion of patients experiencing a tolerability event was 3.3%, 12.4%, and 32.9%, respectively, in GOYA holdout, and 9.7%, 9.7%, and 34.2%, respectively, in MAIN. CONCLUSION: TRAIL may be useful as a clinical decision support tool for treatment decisions in patients with DLBCL who may not tolerate standard chemoimmunotherapies.

Rapid detection of Enterococcus spp. direct from blood culture bottles using Enterococcus QuickFISH method: a multicenter investigation.

The performance of a diagnostic method for detection and identification of Enterococcus spp. directly from positive blood culture was evaluated in a clinical study. The method, Enterococcus QuickFISH BC, is a second-generation peptide nucleic acid (PNA) fluorescence in situ hybridization (FISH) test, which uses a simplified, faster assay procedure. The test uses fluorescently labeled PNA probes targeting 16S rRNA to differentiate Enterococcus faecalis from other Enterococcus spp. by the color of the cellular fluorescence. Three hundred fifty-six routine blood culture samples were tested; only 2 discordant results were recorded. The sensitivities for detection of Enterococcus faecalis and non-faecalis Enterococcus were 100% (106/106) and 97.0% (65/67), respectively, and the combined specificity of the assay was 100%. The combined positive and negative predictive values of the assay were 100% (171/171) and 98.9% (185/187), respectively.

Systemic immune system alterations in early stages of Alzheimer's disease.

Immune activation and inflammation play significant roles in the pathogenesis of Alzheimer's disease (AD). To test whether AD patients showed systemic manifestations of inflammation, blood from 41 patients with early stages of AD and 31 aged-match elderly controls were evaluated. Cellular markers for monocyte/macrophage (MO) activation and CD8 T lymphocyte were increased in early AD patients. Expression of monocyte CCR2, the receptor for monocyte chemoattractant protein-1 (MCP-1), was decreased; however, plasma MCP-1 levels were significantly increased and were related to the degree of MO activation in AD. These findings suggest that AD pathogenesis may be influenced by systemic immunologic dysfunction and provides potential immunologic targets for therapeutic intervention.

Multicenter evaluation of the Staphylococcus QuickFISH method for simultaneous identification of Staphylococcus aureus and coagulase-negative staphylococci directly from blood culture bottles in less than 30 minutes.

A novel rapid peptide nucleic acid fluorescence in situ hybridization (FISH) method, Staphylococcus QuickFISH, for the direct detection of Staphylococcus species from positive blood culture bottles was evaluated in a multicenter clinical study. The method utilizes a microscope slide with predeposited positive- and negative-control organisms and a self-reporting 15-min hybridization step, which eliminates the need for a wash step. Five clinical laboratories tested 722 positive blood culture bottles containing gram-positive cocci in clusters. The sensitivities for detection of Staphylococcus aureus and coagulase-negative staphylococci (CoNS) were 99.5% (217/218) and 98.8% (487/493), respectively, and the combined specificity of the assay was 89.5% (17/19). The combined positive and negative predictive values of the assay were 99.7% (696/698) and 70.8% (17/24), respectively. Studies were also performed on spiked cultures to establish the specificity and performance sensitivity of the method. Staphylococcus QuickFISH has a turnaround time (TAT) of <30 min and a hands-on time (HOT) of <5 min. The ease and speed of the method have the potential to improve the accuracy of therapeutic intervention by providing S. aureus/CoNS identification simultaneously with Gram stain results.

Diffuse optical tomography activation in the somatosensory cortex: specific activation by painful vs. non-painful thermal stimuli.

BACKGROUND: Pain is difficult to assess due to the subjective nature of self-reporting. The lack of objective measures of pain has hampered the development of new treatments as well as the evaluation of current ones. Functional MRI studies of pain have begun to delineate potential brain response signatures that could be used as objective read-outs of pain. Using Diffuse Optical Tomography (DOT), we have shown in the past a distinct DOT signal over the somatosensory cortex to a noxious heat stimulus that could be distinguished from the signal elicited by innocuous mechanical stimuli. Here we further our findings by studying the response to thermal innocuous and noxious stimuli. METHODOLOGY/PRINCIPAL FINDINGS: Innocuous and noxious thermal stimuli were applied to the skin of the face of the first division (ophthalmic) of the trigeminal nerve in healthy volunteers (N = 6). Stimuli temperatures were adjusted for each subject to evoke warm (equivalent to a 3/10) and painful hot (7/10) sensations in a verbal rating scale (0/10 = no/max pain). A set of 26 stimuli (5 sec each) was applied for each temperature with inter-stimulus intervals varied between 8 and 15 sec using a Peltier thermode. A DOT system was used to capture cortical responses on both sides of the head over the primary somatosensory cortical region (S1). For the innocuous stimuli, group results indicated mainly activation on the contralateral side with a weak ipsilateral response. For the noxious stimuli, bilateral activation was observed with comparable amplitudes on both sides. Furthermore, noxious stimuli produced a temporal biphasic response while innocuous stimuli produced a monophasic response. CONCLUSIONS/SIGNIFICANCE: These results are in accordance with fMRI and our other DOT studies of innocuous mechanical and noxious heat stimuli. The data indicate the differentiation of DOT cortical responses for pain vs. innocuous stimuli that may be useful in assessing objectively acute pain.