Long-Term Outcomes of Autologous Hematopoietic Stem Cell Transplant (HSCT) for Multiple Myeloma: While New Horizons Emerge, It Is Still Only a Silver Lining for Resource-Constrained Settings.

Background Significant hurdles impede the optimal implementation of hematopoietic stem cell transplantation (HSCT) in low-middle income countries (LMICs). Herein, we highlight the challenges faced in LMICs while performing HSCT and report the long-term outcomes of patients with newly diagnosed multiple myeloma (MM) who underwent autologous HSCT (AHSCT) at our center. Besides, we provide a comprehensive review of studies reporting long-term outcomes of AHSCT in MM from the Indian subcontinent. Methodology This study was conducted at the State Cancer Institute, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, India. Case records of all patients with MM who received AHSCT from December 2010 to July 2018 were reviewed retrospectively. A non-systematic literature search was performed using PubMed and Google Scholar databases. Data regarding clinicopathological parameters and long-term follow-up were extracted from relevant studies and for patients included in our study. Results At our center, 47 patients (median age 52.0 years) with MM underwent AHSCT. Majority of patients had stage III disease (ISS) and median time to transplant was 11.5 months. The five-year progression free survival (PFS) and overall survival (OS) were 59.1% and 81.2%, respectively. Studies from the Indian subcontinent have observed a five-year OS of ~50% to ~85%. However, a greater variability in the five-year PFS has been reported, ranging from ~20% to ~75%. The median time to transplant has ranged from seven to 17 months (indicating time delays) with median CD34 cell counts of 2.7-6.3×106 cells/kg (lower than developed countries). Conclusions Despite significant resource limitations in LMICs, AHSCT is increasingly been performed in MM with encouraging long-term outcomes.

COVID-19 Infection in Patients with Humoral Immunodeficiency: A Case Series and Literature Review.

Background: The coronavirus 2019 disease (COVID-19) has infected many individuals worldwide and continues to pose a significant threat to those with weakened immune systems. The data evaluating the clinical outcomes of patients with humoral immunodeficiencies that contract COVID-19 is limited and conflicting. Objective: To describe the clinical outcomes of COVID-19 infections in patients with primary humoral immunodeficiency and compare results to current literature. Methods: We conducted a retrospective cohort review on 15 patients with a humoral immunodeficiency defined as Common Variable Immunodeficiency, Specific Antibody Deficiency, or unspecified hypogammaglobulinemia, who contracted COVID-19. Severity scores were determined to evaluate the clinical outcomes of these patients. Results: Of our 15-patient cohort, 33% of individuals with a humoral immunodeficiency infected with COVID-19 had moderate to severe disease, requiring hospitalization or resulting in death. COVID-19 mortality rate was found to be 7%. All 5 of our patients with severe COVID-19 infection had at least 1 comorbidity or risk factor. Conclusion: Within our cohort of humoral immunodeficient patients infected with COVID-19, we found a higher rate of moderate to severe COVID-19 infection and worse clinical outcomes, particularly in patients with comorbidities or risk factors.

Cell Surface N-Glycans Influence Electrophysiological Properties and Fate Potential of Neural Stem Cells.

Understanding the cellular properties controlling neural stem and progenitor cell (NSPC) fate choice will improve their therapeutic potential. The electrophysiological measure whole-cell membrane capacitance reflects fate bias in the neural lineage but the cellular properties underlying membrane capacitance are poorly understood. We tested the hypothesis that cell surface carbohydrates contribute to NSPC membrane capacitance and fate. We found NSPCs differing in fate potential express distinct patterns of glycosylation enzymes. Screening several glycosylation pathways revealed that the one forming highly branched N-glycans differs between neurogenic and astrogenic populations of cells in vitro and in vivo. Enhancing highly branched N-glycans on NSPCs significantly increases membrane capacitance and leads to the generation of more astrocytes at the expense of neurons with no effect on cell size, viability, or proliferation. These data identify the N-glycan branching pathway as a significant regulator of membrane capacitance and fate choice in the neural lineage.

Canadian epileptologists' counseling of drivers amidst guideline inconsistencies.

BACKGROUND: Epilepsy is a common medical condition for which physicians perform driver fitness assessments. The Canadian Medical association (CMA) and the Canadian Council of Motor transportation administrators (CCMTA) publish documents to guide Canadian physicians' driver fitness assessments. OBJECTIVES: We aimed to measure the consistency of driver fitness counseling among epileptologists in Canada, and to determine whether inconsistencies between national guidelines are associated with greater variability in counseling instructions. METHODS: We surveyed 35 epileptologists in Canada (response rate 71%) using a questionnaire that explored physicians' philosophies about driver fitness assessments and counseling practices of seizure patients in common clinical scenarios. Of the nine scenarios, CCMTA and CMA recommendations were concordant for only two. Cumulative agreement for all scenarios was calculated using Kappa statistic. Agreement for concordant (two) vs. discordant (seven) scenarios were split at the median and analyzed using the Wilcoxon signed rank sum test. RESULTS: Overall the agreement between respondents for the clinical scenarios was not acceptable (Kappa=0.28). For the two scenarios where CMa and CCMta guidelines were concordant, specialists had high levels of agreement with recommendations (89% each). A majority of specialists disagreed with CMa recommendations in three of seven discordant scenarios. The lack of consistency in respondents' agreement attained statistical significance (p<0.001). CONCLUSIONS: Canadian epileptologists have variable counseling practices about driving, and this may be attributable to inconsistencies between CMa and CCMta medical fitness guidelines. This study highlights the need to harmonize driving recommendations in order to prevent physician and patient confusion about driving fitness in Canada.

Hemodynamics "au contraire" despite diastolic flow reversal and angiographically severe aortic regurgitation.

One of the commonly used parameters for evaluating aortic regurgitation is the rate of pressure decay data obtained from echocardiographic evaluation or cardiac catheterization. The measurement of the rate of equalization of pressure between the aorta and the left ventricle and its utility in the setting of aortic insufficiency has been validated. Intuitively, the Doppler equivalent, pressure half-time, is inversely related to the severity of regurgitation. However, this is a phenomenon dependent on multiple variables including blood pressure, heart rate, compliance of the receiving chamber, effects of vasopressors and the volume status of the patient. We report a case of unique hemodynamics obtained during cardiac catheterization due to low filling pressures that was further confounded by elevated systemic vascular resistance in a critically ill patient with angiographically severe aortic regurgitation.

The fourth dorsal interosseus pedis muscle: a useful muscle in routine electromyography.

The aim of the study was to assess the utility of needle examination of the fourth dorsal interosseus pedis (FDIP) muscle in routine EMG. FDIP is an easily accessible muscle and may be less prone to blunt trauma as compared with the other foot muscles but despite its potential utility in electrophysiology, little if any data are available on the FDIP muscle. Detailed neurologic examination, nerve conduction, and needle EMG studies were performed in 118 individuals referred to the EMG laboratory of a tertiary referral center. The FDIP was studied by inserting a needle obliquely at an angle of about 30 degrees immediately proximal to the fourth and fifth metatarsal heads. In 44 subjects (patients/volunteers) with normal studies, <5% had increased insertional activity (IA) in the FDIP, but none had sustained spontaneous activity (SA). Among 32 patients with mixed sensorimotor polyneuropathy, FDIP showed abnormal SA in >90%. In patients with S1 root compromise, 66% had sustained SA in FDIP but none with involvement of L3, L4, or L5 nerve root alone. Two of the four patients with tibial and one of five with peroneal neuropathies had increased SA in this muscle; none with other lower limb focal neuropathies. In patients with lumbosacral plexopathy, FDIP showed denervation potentials with diffuse plexus involvement but not with upper plexopathy. Almost all patients tolerated the FDIP needle examination well. End plates were frequently encountered in the FDIP muscle. We concluded that in normal feet, the FDIP muscle has a low incidence of sustained SA. Abnormal SA in FDIP correlates well with the overall neurologic condition, and it may be a useful muscle to include in routine electrodiagnostic evaluation.

Echocardiographic evaluation of hemodynamic parameters.

Hemodynamic assessment is a constant and common task in critically ill and injured patients. Correct interpretation of this data is vital to implement the appropriate intervention, if any. It can be difficult to properly interpret derived and measured data from a pulmonary artery catheter for optimal care of these difficult patients. Catheter use remains controversial because some researchers believe there is no clear benefit to the mortality rate. This conundrum will never be settled without a prospective blinded study. However, echocardiography is a vital and reliable monitoring tool to interrogate pressures, ventricular function, ventricular volumes, ventricular interactions, and diastolic compliance. In some institutions, it is used to construct a pressure/volume curve to measure contractility, which is load-dependent. Echocardiography easily can measure intracardiac pressures accurately but in a static fashion, which is one of its major benefits.

Effect of plasma exchange on carbamazepine levels in a patient with myasthenia gravis and epilepsy.

PURPOSE: Patients taking antiepileptic medications may require plasma exchange (PEX) for treatment of an unrelated condition. METHODS: We studied total serum levels of carbamazepine (CBZ) serially, before and after five PEX cycles, in an epilepsy patient who underwent PEX for myasthenia gravis. RESULTS: A small but consistent reduction in the CBZ levels was noted immediately after each cycle, and a gradual and cumulative increase in the serum levels was observed over the duration of the PEX cycles. CONCLUSIONS: We conclude that alterations in the serum CBZ levels with PEX are not clinically significant to merit adjustment of the CBZ dose.