Citations

Abstract A false pituitary tumor describes pituitary enlargement due to intracranial hypotension. Reported previously primarily in the neurological literature, we present this case referred to endocrinology for evaluation of a pituitary mass. A 24-year-old male was referred to endocrinology for evaluation of pituitary enlargement without a hypo-enhancing lesion on magnetic resonance imaging (MRI). The main symptom reported was headache that was worse in the standing position and in the afternoon. He had no symptoms or signs of pituitary mass-effect, or hormone excess or deficiencies. Past medical history was relevant for a history of nerve schwannoma status post resection with subsequent spinal fusion. Biochemical evaluation of pituitary hormones was normal. Upon review of his pituitary MRI, other abnormalities seen were suggestive of intracranial hypotension. Based on his history and imaging findings, he was diagnosed with intracranial hypotension causing a “false pituitary tumor” rather than pituitary enlargement or abnormality. Further evaluation revealed multiple spinal leaks that were patched. His symptoms subsided within a few days of repair. Endocrinologists should be aware of the possible misdiagnosis of a pituitary mass due to intracranial hypotension.

Abstract Background Rifampin-resistant tuberculosis is a leading cause of morbidity worldwide; only one-third of persons start treatment, and outcomes are often inadequate. Several trials demonstrate 90% efficacy using an all-oral, 6-month regimen of bedaquiline, pretomanid, and linezolid (BPaL), but significant toxicity occurred using 1200-mg linezolid. After US Food and Drug Administration approval in 2019, some US clinicians rapidly implemented BPaL using an initial 600-mg linezolid dose adjusted by serum drug concentrations and clinical monitoring. Methods Data from US patients treated with BPaL between 14 October 2019 and 30 April 2022 were compiled and analyzed by the BPaL Implementation Group (BIG), including baseline examination and laboratory, electrocardiographic, and clinical monitoring throughout treatment and follow-up. Linezolid dosing and clinical management was provider driven, and most patients had linezolid adjusted by therapeutic drug monitoring. Results Of 70 patients starting BPaL, 2 changed to rifampin-based therapy, 68 (97.1%) completed BPaL, and 2 of the 68 (2.9%) experienced relapse after completion. Using an initial 600-mg linezolid dose daily adjusted by therapeutic drug monitoring and careful clinical and laboratory monitoring for adverse effects, supportive care, and expert consultation throughout BPaL treatment, 3 patients (4.4%) with hematologic toxicity and 4 (5.9%) with neurotoxicity required a change in linezolid dose or frequency. The median BPaL duration was 6 months. Conclusions BPaL has transformed treatment for rifampin-resistant or intolerant tuberculosis. In this cohort, effective treatment required less than half the duration recommended in 2019 US guidelines for drug-resistant tuberculosis. Use of individualized linezolid dosing and monitoring likely enhanced safety and treatment completion. The BIG cohort demonstrates that early implementation of new tuberculosis treatments in the United States is feasible.

Abstract The Infectious Diseases Society of America (IDSA) has set clear priorities in recent years to promote inclusion, diversity, access, and equity (IDA&E) in infectious disease (ID) clinical practice, medical education, and research. The IDSA IDA&E Task Force was launched in 2018 to ensure implementation of these principles. The IDSA Training Program Directors Committee met in 2021 and discussed IDA&E best practices as they pertain to the education of ID fellows. Committee members sought to develop specific goals and strategies related to recruitment, clinical training, didactics, and faculty development. This article represents a presentation of ideas brought forth at the meeting in those spheres and is meant to serve as a reference document for ID training program directors seeking guidance in this area.

Abstract Background Matrix assisted laser desorption ionization time of flight mass spectrometry coupled to immune enrichment (MASS-FIX) as an alternative to serum immunofixation electrophoresis has demonstrated increased sensitivity in monoclonal protein (MP) detection with improved laboratory workflow. This study explored similar replacement of urine immunofixation electrophoresis (u-IFE) with urine MASS-FIX (u-MASS-FIX) by method comparison. Methods Residual urine (n = 1008) from Mayo Clinic patients with a known plasma cell disease were assayed neat by u-MASS-FIX analysis. Each sample was paired with the following: u-IFE, urine total protein, urine protein electrophoresis, serum κ/λ free light chain (LC) ratio (rFLC), and serum MASS-FIX (s-MASS-FIX). Analytical sensitivities were measured in pooled urine spiked with daratumumab. Results u-IFE and u-MASS-FIX had 91% agreement in determining the presence/absence of MPs (Cohen kappa = 0.8200). In discrepant cases, serum rFLC statistically aligned more closely with positive u-MASS-FIX cases than u-IFE. Patients positive by both s-MASS-FIX and u-MASS-FIX had matching MP masses (±20 daltons) in 94% of cases. The u-MASS-FIX spectra further identified κ/λ LC fragments and glycosylated LCs not appreciated on u-IFE. The unconcentrated u-MASS-FIX limit of detection of 0.156 mg/mL was determined equivalent to 100× concentrated u-IFE. Conclusion u-MASS-FIX is a reliable alternative to u-IFE with the added benefits of LC glycosylation detection and MP mass tracking between serum and urine. Furthermore, u-MASS-FIX is performed using neat urine. Eliminating the need to concentrate urine for u-IFE has potential to increase productivity by decreasing labor minutes per test.

Abstract Background Multiple laboratory tests are employed for detection of monoclonal proteins in patients and include serum protein electrophoresis (SPEP), immunofixation electrophoresis, free light chain (FLC) immunoassay, and mass spectrometry (Mass-Fix). Recently, reports on a drift in FLC quantitation results have been brought to light. Methods We studied a cohort of 16 887 patients whose sera were tested for a monoclonal protein by a FLC assay, serum protein electrophoresis, and Mass-Fix. This is a retrospective study designed to assess the impact of a drift on the performance of FLC ratio (rFLC) in groups of patients with and without detectable plasma cell disorders (PCDs). Results The results demonstrated that 63% of patients with monoclonal protein equal or higher than 2 g/L (by SPEP) had an abnormal rFLC (reference range 0.26–1.65). Conversely, 16% of patients with undetectable monoclonal protein by other methods (i.e., SPEP and Mass-Fix) who also had no record of treated PCD had an abnormal rFLC. In these cases, there was an imbalance in the number of kappa high rFLCs to lambda low rFLCs of 201 to 1. Conclusions The results of this study suggest decreased specificity of rFLC for a monoclonal kappa FLC in the 1.65 to 3.0 range.

Background Intra-procedural characterization of stroke thromboemboli might guide mechanical thrombectomy (MT) device choice to improve recanalization rates. Electrochemical impedance spectroscopy (EIS) has been used to characterize various biological tissues in real time but has not been used in thrombus. Objective To perform a feasibility study of EIS analysis of thrombi retrieved by MT to evaluate: (1) the ability of EIS and machine learning to predict red blood cell (RBC) percentage content of thrombi and (2) to classify the thrombi as “RBC-rich” or “RBC-poor” based on a range of cutoff values of RBC. Methods ClotbasePilot was a multicentric, international, prospective feasibility study. Retrieved thrombi underwent histological analysis to identify proportions of RBC and other components. EIS results were analyzed with machine learning. Linear regression was used to evaluate the correlation between the histology and EIS. Sensitivity and specificity of the model to classify the thrombus as RBC-rich or RBC-poor were also evaluated. Results Among 514 MT,179 thrombi were included for EIS and histological analysis. The mean composition in RBC of the thrombi was 36% ± 24. Good correlation between the impedance-based prediction and histology was achieved (slope of 0.9, R 2 = 0.53, Pearson coefficient = 0.72). Depending on the chosen cutoff, ranging from 20 to 60% of RBC, the calculated sensitivity for classification of thrombi ranged from 77 to 85% and the specificity from 72 to 88%. Conclusion Combination of EIS and machine learning can reliably predict the RBC composition of retrieved ex vivo AIS thrombi and then classify them into groups according to their RBC composition with good sensitivity and specificity.

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by the clonal expansion of myeloid blasts in the peripheral blood, bone marrow, and/or other tissues. It is the most common form of acute leukemia among adults and accounts for the largest number of annual deaths from leukemias in the United States. Like AML, blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a myeloid malignancy. It is a rare malignancy characterized by the aggressive proliferation of precursors of plasmacytoid dendritic cells that frequently involves the bone marrow, skin, central nervous system, and other organs and tissues. This discussion section focuses on the diagnosis and management of BPDCN as outlined in the NCCN Guidelines for AML.

Contrast-induced acute kidney injury (CI−AKI) is manifested by an abrupt decline in kidney function as a consequence of intravascular exposure to contrast media. With the increased applicability of medical imaging and interventional procedures that utilize contrast media for clinical diagnosis, CI−AKI is becoming the leading cause of renal dysfunction. The pathophysiological mechanism associated with CI−AKI involves renal medullary hypoxia, the direct toxicity of contrast agents, oxidative stress, apoptosis, inflammation, and epigenetic regulation. To date, there is no effective therapy for CI−AKI, except for the development of strategies that could reduce the toxicity profiles of contrast media. While most of these strategies have failed, evidence has shown that the proper use of personalized hydration, contrast medium, and high-dose statins may reduce the occurrence of CI−AKI. However, adequate risk predication and attempts to develop preventive strategies can be considered as the key determinants that can help eliminate CI−AKI. Additionally, a deeper understanding of the pathophysiological mechanism of CI−AKI is crucial to uncover molecular targets for the prevention of CI−AKI. This review has taken a step further to solidify the current known molecular mechanisms of CI−AKI and elaborate the biomarkers that are used to detect early-stage CI−AKI. On this foundation, this review will analyze the molecular targets relating to apoptosis, inflammation, oxidative stress, and epigenetics, and, thus, provide a strong rationale for therapeutic intervention in the prevention of CI−AKI.