Nonspecific Interstitial Pneumonitis after Bortezomib and Thalidomide Treatment in a Multiple Myeloma Patient

Bortezomib, an inhibitor of 26S proteosome, is recently approved treatment option for multiple myeloma. Thalidomide, a drug with immunomodulating and antiangiogenic effects, has also shown promise as an effective treatment in multiple myeloma. Pulmonary complications are believed to be rare, especially interstitial lung disease. Here, we describe a patient with dyspnea and diffuse pulmonary infiltrates while receiving bortezomib and thalidomide in combination with dexamethasone for treatment-naïve multiple myeloma. Bronchoalveolar lavage demonstrated a significant decrease in the ratio of CD4 : CD8 T lymphocytes (CD4/8 ratio, 0.54). Extensive workup for other causes, including infections, was negative. A lung biopsy under video-assisted thorascopic surgery revealed a diagnosis of nonspecific interstitial pneumonitis. The symptoms and imaging study findings improved after initiating steroid treatment. Physicians should be aware of this potential complication in patients receiving the novel molecular-targeted antineoplastic agents, bortezomib and thalidomide, who present with dyspnea and new pulmonary infiltrates and fail to improve despite treatment with broad-spectrum antibiotics

Micro-volume couette flow sample orientation for absorbance and fluorescence linear dichroism

Linear dichroism (LD) can be used to study the alignment of absorbing chromophores within long molecules. In particular, Couette flow LD has been used to good effect in probing ligand binding to DNA and to fibrous proteins. This technique has been previously limited by large sample requirements. Here we report the design and application of a new micro-volume Couette flow cell that significantly enhances the potential applications of flow LD spectroscopy by reducing the sample requirements for flow linear dichroism to 25 μL (with concentrations such that the absorbance maximum of the sample in a 1-cm pathlength cuvette is not, vert, similar1). The micro-volume Couette cell has also enabled the measurement of fluorescence-detected Couette flow linear dichroism. This new technique enables the orientation of fluorescent ligands to be probed even when their electronic transitions overlap with those of the macromolecule and conversely. The potential of flow-oriented fluorescence dichroism and application of the micro-volume Couette LD cell are illustrated by the collection of data for DNA with minor groove and intercalating ligands: DAPI, Hoechst, and ethidium bromide. As with conventional fluorescence, improved sensitivity compared with absorbance LD is to be expected after instrumentation optimization

Intraoperative identification of esophageal sentinel lymph nodes with near-infrared fluorescence imaging

ObjectiveIn esophageal cancer, selective removal of involved lymph nodes could improve survival and limit complications from extended lymphadenectomy. Mapping with vital blue dyes or technetium Tc-99m often fails to identify intrathoracic sentinel lymph nodes. Our purpose was to develop an intraoperative method for identifying sentinel lymph nodes of the esophagus with high-sensitivity near-infrared fluorescence imaging.MethodsSix Yorkshire pigs underwent thoracotomy and received submucosal, esophageal injection of quantum dots, a novel near-infrared fluorescent lymph tracer designed for retention in sentinel lymph nodes. Six additional pigs underwent thoracotomy and received submucosal esophageal injection of CW800 conjugated to human serum albumin, another novel lymph tracer designed for uptake into distant lymph nodes. Finally, 6 pigs received submucosal injection of the fluorophore-conjugated albumin with an endoscopic needle through an esophagascope. These lymph tracers fluoresce in the near-infrared, permitting visualization of migration to sentinel lymph nodes with a custom intraoperative imaging system.ResultsInjection of the near-infrared fluorescent lymph tracers into the esophagus revealed communicating lymph nodes within 5 minutes of injection. In all 6 pigs that received quantum dot injection, only a single sentinel lymph node was identified. Among pigs that received fluorophore-conjugated albumin injection, in 5 of 12 a single sentinel lymph node was revealed, but in 7 of 12 two sentinel lymph nodes were identified. There was no dominant pattern in the appearance of the sentinel lymph nodes either cranial or caudal to the injection site.ConclusionNear-infrared fluorescence imaging of sentinel lymph nodes is a novel and reliable intraoperative technique with the power to assist with identification and resection of esophageal sentinel lymph nodes

Pulsed Electromagnetic Field Stimulates Cellular Proliferation in Human Intervertebral Disc Cells

∙The authors have no financial conflicts of interest. Purpose: The purpose of this study is to investigate the mechanism of cellular proliferation of electromagnetic field (EMF) on human intervertebral disc (IVD) cells. Materials and Methods: Human IVD cells were cultured three-dimensionally in alginate beads. EMF was exposed to IVD cells with 650 Ϊ, 1.8 millitesla magnetic flux density, 60 Hz sinusoidal wave. Cultures were divided into a control and EMF group. Cytotoxicity, DNA synthesis and proteoglycan synthesis were measured by MTT assay, [ 3 H]-thymidine, and [ 35 S]-sulfate incorporation. To detect phenotypical expression, reverse transcription-polymerase chain reactions (RT-PCR) were performed for aggrecan, collagen type I, and type II mRNA expression. To assess action mechanism of EMF, IVD cells were exposed to EMF with N G-Monomethyl-L-arginine (NMMA) and acetylsalicylic acid (ASA). Results: There was no cytotoxicity in IVD cells with the EMF group in MTT assay. Cellular proliferation was observed in the EMF group (p < 0.05). There was no difference in newl

Complete Atrioventricular Block Secondary to Bortezomib Use in Multiple Myeloma

Bortezomib is an inhibitor of 26S proteasome, which is an effective treatment for multiple myeloma. The common adverse effects of bortezomib are asthenic conditions, gastrointestinal disturbances, and peripheral neuropathy. Here we describe a patient with dyspnea and general weakness because of complete atrioventricular block while receiving bortezomib. We immediately stopped bortezomib, and after inserting a permanent VDD pacemaker, the patients' symptoms disappeared

Racial and ethnic differences in internal medicine residency assessments

IMPORTANCE: Previous studies have demonstrated racial and ethnic inequities in medical student assessments, awards, and faculty promotions at academic medical centers. Few data exist about similar racial and ethnic disparities at the level of graduate medical education. OBJECTIVE: To examine the association between race and ethnicity and performance assessments among a national cohort of internal medicine residents. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study evaluated assessments of performance for 9026 internal medicine residents from the graduating classes of 2016 and 2017 at Accreditation Council of Graduate Medical Education (ACGME)-accredited internal medicine residency programs in the US. Analyses were conducted between July 1, 2020, and June 31, 2022. MAIN OUTCOMES AND MEASURES: The primary outcome was midyear and year-end total ACGME Milestone scores for underrepresented in medicine (URiM [Hispanic only; non-Hispanic American Indian, Alaska Native, or Native Hawaiian/Pacific Islander only; or non-Hispanic Black/African American]) and Asian residents compared with White residents as determined by their Clinical Competency Committees and residency program directors. Differences in scores between Asian and URiM residents compared with White residents were also compared for each of the 6 competency domains as supportive outcomes. RESULTS: The study cohort included 9026 residents from 305 internal medicine residency programs. Of these residents, 3994 (44.2%) were female, 3258 (36.1%) were Asian, 1216 (13.5%) were URiM, and 4552 (50.4%) were White. In the fully adjusted model, no difference was found in the initial midyear total Milestone scores between URiM and White residents, but there was a difference between Asian and White residents, which favored White residents (mean [SD] difference in scores for Asian residents: -1.27 [0.38]; P \u3c .001). In the second year of training, White residents received increasingly higher scores relative to URiM and Asian residents. These racial disparities peaked in postgraduate year (PGY) 2 (mean [SD] difference in scores for URiM residents, -2.54 [0.38]; P \u3c .001; mean [SD] difference in scores for Asian residents, -1.9 [0.27]; P \u3c .001). By the final year 3 assessment, the gap between White and Asian and URiM residents\u27 scores narrowed, and no racial or ethnic differences were found. Trends in racial and ethnic differences among the 6 competency domains mirrored total Milestone scores, with differences peaking in PGY2 and then decreasing in PGY3 such that parity in assessment was reached in all competency domains by the end of training. CONCLUSIONS AND RELEVANCE: In this cohort study, URiM and Asian internal medicine residents received lower ratings on performance assessments than their White peers during the first and second years of training, which may reflect racial bias in assessment. This disparity in assessment may limit opportunities for physicians from minoritized racial and ethnic groups and hinder physician workforce diversity

Fabrication of Copper Window Electrodes with ≈10⁸Apertures cm⁻² for Organic Photovoltaics

A powerful approach to increasing the far‐field transparency of copper film window electrodes which simultaneously reduces intraband absorption losses for wavelengths 550 nm is reported. The approach is based on incorporation of a random array of ≈100 million circular apertures per cm2 into an optically thin copper film, with a mean aperture diameter of ≈500 nm. A method for the fabrication of these electrodes is described that exploits a binary polymer blend mask that self‐organizes at room temperature from a single solution, and so is simple to implement. Additionally all of the materials used in electrode fabrication are low cost, low toxicity, and widely available. It is shown that these nanostructured copper electrodes offer an average far‐field transparency of ≥80% and sheet resistance of ≤10 Ω sq−1 when used in conjunction with a conventional solution processed ZnO electron transport layer and their utility in inverted organic photovoltaic devices is demonstrated

Assessing future vent opening locations at the Somma-Vesuvio volcanic complex. 2, probability maps of the caldera for a future Plinian/sub-Plinian event with uncertainty quantification

In this study, we combine reconstructions of volcanological data sets and inputs from a structured expert judgment to produce a first long-term probability map for vent opening location for the next Plinian or sub-Plinian eruption of Somma-Vesuvio. In the past, the volcano has exhibited significant spatial variability in vent location; this can exert a significant control on where hazards materialize (particularly of pyroclastic density currents). The new vent opening probability mapping has been performed through (i) development of spatial probability density maps with Gaussian kernel functions for different data sets and (ii) weighted linear combination of these spatial density maps. The epistemic uncertainties affecting these data sets were quantified explicitly with expert judgments and implemented following a doubly stochastic approach. Various elicitation pooling metrics and subgroupings of experts and target questions were tested to evaluate the robustness of outcomes. Our findings indicate that (a) Somma-Vesuvio vent opening probabilities are distributed inside the whole caldera, with a peak corresponding to the area of the present crater, but with more than 50% probability that the next vent could open elsewhere within the caldera; (b) there is a mean probability of about 30% that the next vent will open west of the present edifice; (c) there is a mean probability of about 9.5% that the next medium-large eruption will enlarge the present Somma-Vesuvio caldera, and (d) there is a nonnegligible probability (mean value of 6–10%) that the next Plinian or sub-Plinian eruption will have its initial vent opening outside the present Somma-Vesuvio caldera