Citations

Hodgkin lymphoma (HL) is a B-cell malignancy that typically has a favorable prognosis when treated with chemotherapy, often in combination with radiation therapy. The prognosis for patients whose disease relapses or is refractory, however, is far less favorable and novel therapies are needed for these patients. The unique cellular composition of HL provides a number of opportunities to target either the malignant Reed-Sternberg cell or the inflammatory tumor microenvironment. Antibody-drug conjugates targeting CD30, small molecule inhibitors of cell signaling, and antibodies that inhibit immune checkpoints, have all demonstrated activity in HL. Current and future trials are exploring the use of these agents in combination with each other and with standard chemotherapy.

Clinical trial design strategies have evolved over the past few years as a means to accelerate the drug development process so that the right therapies can be delivered to the right patients. Basket, umbrella, and adaptive enrichment strategies represent a class of novel designs for testing targeted therapeutics in oncology. Umbrella trials include a central infrastructure for screening and identification of patients, and focus on a single tumor type or histology with multiple subtrials, each testing a targeted therapy within a molecularly defined subset. Basket trial designs offer the possibility to include multiple molecularly defined subpopulations, often across histology or tumor types, but included in one cohesive design to evaluate the targeted therapy in question. Adaptive enrichment designs offer the potential to enrich for patients with a particular molecular feature that is predictive of benefit for the test treatment based on accumulating evidence from the trial. This review will aim to discuss the fundamentals of these design strategies, the underlying statistical framework, the logistical barriers of implementation, and, ultimately, the interpretation of the trial results. New statistical approaches, extensive multidisciplinary collaboration, and state of the art data capture technologies are needed to implement these strategies in practice. Logistical challenges to implementation arising from centralized assay testing, requirement of multiple specimens, multidisciplinary collaboration, and infrastructure requirements will also be discussed. This review will present these concepts in the context of the National Cancer Institute's precision medicine initiative trials: MATCH, ALCHEMIST, Lung MAP, as well as other trials such as FOCUS4.

AbstractAcute pain following amputation can be challenging to treat due to multiple underlying mechanisms and variable clinical responses to treatment. Furthermore, poorly controlled preoperative pain is a risk factor for developing chronic pain. Evidence suggests that epidural analgesia and peripheral nerve blockade may decrease the severity of residual limb pain and the prevalence of phantom pain after lower extremity amputation. We present the perioperative analgesic management of a patient with gangrene of the bilateral upper and lower extremities as a result of septic shock and prolonged vasopressor administration who underwent four‐limb amputation in a single procedure. A multimodal analgesic regimen was utilized, including titration of preoperative opioid and neuropathic pain agents, perioperative intravenous, epidural and peripheral nerve catheter infusions, and postoperative oral medication titration. More than 8 months postoperatively, the patient has satisfactory pain control with no evidence for phantom limb pain. To our knowledge, there have been no publications to date concerning analgesic regimens in four‐limb amputation.

BackgroundCommonly used computed tomography (CT) staging systems for chronic rhinosinusitis (CRS) focus on the sinuses and do not quantify disease in the olfactory cleft. The goal of the current study was to determine whether precise measurements of olfactory cleft opacification better correlate with olfaction in patients with CRS.MethodsOlfaction was assessed using the 40‐item Smell Identification Test (SIT‐40) before and after sinus surgery in adult patients. Olfactory cleft opacification was quantified precisely using three‐dimensional (3D), computerized volumetric analysis, as well as via semiquantitative Likert scale estimations at predetermined anatomic sites. Sinus opacification was also quantified using the Lund‐Mackay staging system.ResultsThe overall cohort (n = 199) included 89 (44.7%) patients with CRS with nasal polyposis (CRSwNP) and 110 (55.3%) with CRS without nasal polyposis (CRSsNP). The olfactory cleft opacified volume correlated with objective olfaction as determined by the SIT‐40 (Spearman's rank correlation coefficient [Rs] = −0.461; p < 0.001). The correlation was significantly stronger in the CRSwNP subgroup (Rs = −0.573; p < 0.001), whereas no appreciable correlation was found in the CRSsNP group (Rs = −0.141; p = 0.141). Correlations between sinus‐specific Lund‐Mackay CT scoring and SIT‐40 scores were weaker in the CRSwNP (Rs = −0.377; p < 0.001) subgroup but stronger in the CRSsNP (Rs = −0.225; p = 0.018) group when compared to olfactory cleft correlations. Greater intraclass correlations (ICCs) were found between quantitative volumetric measures of olfactory cleft opacification (ICC = 0.844; p < 0.001) as compared with semiquantitative Likert grading (ICC = 0.627; p < 0.001).ConclusionQuantitative measures of olfactory cleft opacification correlate with objective olfaction, with the strongest correlations seen in patients with nasal polyps.

BACKGROUNDThere is little research regarding characteristics of effective continuing medical education (CME) presentations in hospital medicine (HM). Therefore, we sought to identify associations between validated CME teaching effectiveness scores and characteristics of CME presentations in the field of HM.DESIGN/SETTINGThis was a cross‐sectional study of participants and didactic presentations from a national HM CME course in 2014.MEASUREMENTSParticipants provided CME teaching effectiveness (CMETE) ratings using an instrument with known validity evidence. Overall CMETE scores (5‐point scale: 1 = strongly disagree; 5 = strongly agree) were averaged for each presentation, and associations between scores and presentation characteristics were determined using the Kruskal‐Wallis test. The threshold for statistical significance was set at P < 0.05.RESULTSA total of 277 out of 368 participants (75.3%) completed evaluations for the 32 presentations. CMETE scores (mean [standard deviation]) were significantly associated with the use of audience response (4.64 [0.16]) versus no audience response (4.49 [0.16]; P = 0.01), longer presentations (≥30 minutes: 4.67 [0.13] vs <30 minutes: 4.51 [0.18]; P = 0.02), and larger number of slides (≥50: 4.66 [0.17] vs <50: 4.55 [0.17]; P = 0.04). There were no significant associations between CMETE scores and use of clinical cases, defined goals, or summary slides.CONCLUSIONSTo our knowledge, this is the first study regarding associations between validated teaching effectiveness scores and characteristics of effective CME presentations in HM. Our findings, which support previous research in other fields, indicate that CME presentations may be improved by increasing interactivity through the use of audience response systems and allowing longer presentations. Journal of Hospital Medicine 2015;10:569–573. © 2015 Society of Hospital Medicine

Personalized therapy for the treatment of patients with cancer is rapidly approaching and is an achievable goal in the near future. A substantial number of novel targets have been developed into therapeutic agents. There is a substantial variability to antitumor activity by novel therapeutics because of the unique heterogeneity and biology that exists both between and within lymphoma subtypes. Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL). Approximately 40% of patients have refractory disease or disease that will relapse after an initial response, and the majority of patients with relapsed DLBCL will succumb to the disease. There are two major biologically distinct molecular subtypes of DLBCL: germinal center B-cell (GCB) and activated B-cell (ABC). ABC DLBCL is associated with substantially worse outcomes when treated with standard chemoimmunotherapy. In addition to GCB and ABC subtypes, double-hit lymphomas (approximately 5% to 10% of patients) and double-expressor lymphomas, which overexpress MYC and BCL2 protein, are aggressive DLBCLs and are also associated with a poor prognosis. Double-hit lymphomas have concurrent chromosomal rearrangements of MYC plus BCL2 (or less likely, BCL6). Advances in molecular characterization techniques and the development of novel agents targeting specific subtypes of DLBCL have provided a foundation for personalized therapy of DLBCL based on molecular subtype. A number of early clinical trials evaluating combinations of novel targeted agents with standard chemotherapy (R-CHOP) have been completed and have demonstrated the feasibility of this approach with encouraging efficacy. As such, molecular classification of DLBCL is not only important for prognostication, but moves to center stage for personalization of therapy for DLBCL.

Retraction of ‘N, S co-doped graphene quantum dots from a single source precursor used for photodynamic cancer therapy under two-photon excitation’ by Rijun Gui et al. , Chem. Commun ., DOI: 10.1039/C4CC09280E.

Analysis of the induced stress on undoped and boron-doped diamond (BDD) thin films by confocal Raman microscopy is performed in this study to investigate its correlation with sample chemical composition and the substrate used during fabrication. Knowledge of this nature is very important to the issue of long-term stability of BDD coated neurosurgical electrodes that will be used in fast-scan cyclic voltammetry, as potential occurrence of film delaminations and dislocations during their surgical implantation can have unwanted consequences for the reliability of BDD-based biosensing electrodes. To achieve a more uniform deposition of the films on cylindrically-shaped tungsten rods, substrate rotation was employed in a custom-built chemical vapor deposition reactor. In addition to visibly preferential boron incorporation into the diamond lattice and columnar growth, the results also reveal a direct correlation between regions of pure diamond and enhanced stress. Definite stress release throughout entire film thicknesses was found in the current Raman mapping images for higher amounts of boron addition. There is also a possible contribution to the high values of compressive stress from sp2 type carbon impurities, besides that of the expected lattice mismatch between film and substrate.