Clinical outcomes of immune checkpoint inhibitor diabetes mellitus at a comprehensive cancer center.

Introduction: Immune checkpoint inhibitor-associated diabetes mellitus (ICI-DM) is a rare adverse event. In this study, we characterize clinical outcomes of patients with ICI-DM and evaluate survival impact of this complication on melanoma patients. Research design & methods: We conducted a retrospective review of 76 patients diagnosed with ICI-DM from April 2014 to December 2020. Results: 68% of patients presented in diabetic ketoacidosis, 16% had readmissions for hyperglycemia, and hypoglycemia occurred in 70% of patients after diagnosis. Development of ICI-DM did not impact overall survival or progression-free survival in melanoma patients. Conclusion: Development of ICI-DM is associated with long-term insulin dependence and pancreatic atrophy; the use of diabetes technology in this patient population can help improve glycemic control.

Cancer treatment with immune checkpoint inhibitors can cause irreversible side effects. In this study, we describe the clinical presentations of 76 patients who developed immune checkpoint inhibitor diabetes mellitus, a rare complication of checkpoint inhibitor therapy that requires lifelong treatment with insulin therapy. Most patients presented with a life-threatening hyperglycemic emergency and had experienced weight loss and hyperglycemia several weeks prior to diagnosis. After diagnosis, these patients are at risk for high and low blood sugars, but the use of glucose monitoring devices and insulin pumps can help improve blood sugar control. In our study, the development of this complication did not affect survival for melanoma patients. We need to improve awareness of this rare complication to ensure timely treatment for patients.

Impact of intestinal parasites on microbiota and cobalamin gene sequences: a pilot study.

BACKGROUND: Approximately 30% of children worldwide are infected with gastrointestinal parasites. Depending on the species, parasites can disrupt intestinal bacterial microbiota affecting essential vitamin biosynthesis. METHODS: Stool samples were collected from 37 asymptomatic children from a previous cross-sectional Argentinian study. A multi-parallel real-time quantitative PCR was implemented for Ascaris lumbricoides, Ancylostoma duodenale, Necator americanus, Strongyloides stercoralis, Trichuris trichiura, Cryptosporidium spp., Entamoeba histolytica and Giardia duodenalis. In addition, whole-genome sequencing analysis was conducted for bacterial microbiota on all samples and analyzed using Livermore Metagenomic Analysis Toolkit and DIAMOND software. Separate analyses were carried out for uninfected, Giardia-only, Giardia + helminth co-infections, and helminth-only groups. RESULTS: For Giardia-only infected children compared to uninfected children, DNA sequencing data showed a decrease in microbiota biodiversity that correlated with increasing Giardia burden and was statistically significant using Shannon's alpha diversity (Giardia-only > 1 fg/µl 2.346; non-infected group 3.253, P = 0.0317). An increase in diversity was observed for helminth-only infections with a decrease in diversity for Giardia + helminth co-infections (P = 0.00178). In Giardia-only infections, microbiome taxonomy changed from Firmicutes towards increasing proportions of Prevotella, with the degree of change related to the intensity of infection compared to uninfected (P = 0.0317). The abundance of Prevotella bacteria was decreased in the helminths-only group but increased for Giardia + helminth co-infections (P = 0.0262). Metagenomic analysis determined cobalamin synthesis was decreased in the Giardia > 1 fg/µl group compared to both the Giardia < 1 fg/µl and the uninfected group (P = 0.0369). Giardia + helminth group also had a decrease in cobalamin CbiM genes from helminth-only infections (P = 0.000754). CONCLUSION: The study results may provide evidence for an effect of parasitic infections enabling the permissive growth of anaerobic bacteria such as Prevotella, suggesting an altered capacity of vitamin B12 (cobalamin) biosynthesis and potential impact on growth and development in children .

Hypoglycemic risk exposures in relation to low serum glucose values in ambulatory patients.

This study aimed to correlate hypoglycemic risk exposures (HREs) with low blood glucose value (BGV) in ambulatory patients to inform selection of a glucose critical action value (CAV).This was a retrospective study of ambulatory patients with at least 1 serum glucose ≤70 mg/dL obtained at 2 laboratories within the Johns Hopkins Health System over 3.8 years. Multivariable logistic regression was used to evaluate association of BGV cut-offs of <60, <54, <50, and <45 mg/dL with HREs. HREs were classified as "high hypoglycemic risk" (HHR), "moderate hypoglycemic risk" (MHR), "low hypoglycemic risk" (LHR), and "no hypoglycemic risk" (NHR).A total of 5404 patient samples of BG ≤70 mg/dL were analyzed, of which 30.3%, 23.2%, 28.5%, 18.0% occurred in NHR, LHR, MHR, and HHR groups, respectively. An inverse relationship was noted between BGV cut-offs and HHR, but no association was observed for LHR or MHR. After adjusting for age, sex, and race, there was an inverse association between BG thresholds and the odds of HHR. For classification of HHR, BGV cut-offs of <60, <54, <50, and <45 mg/dL correctly classified 71.2%, 69.8%, 68.8%, and 67.2% of BG samples, achieved false-positive rates of 13.6%, 4.7%, 1.7%, and 0.5% and positive likelihood ratios of 3.3, 6.0, 11.2, and 23.4, respectively.Nearly 70% of low BGVs occurred in patients with at least 1 HRE, but only ∼20% occurred in HHR patients. Given their high positive likelihood ratios, BGVs <54 or <50 mg/dL are reasonable candidates for CAVs that would allow sufficient clinician response time while minimizing false-positive alerts.

Development and Implementation of a Subcutaneous Insulin Clinical Decision Support Tool for Hospitalized Patients.

BACKGROUND: Insulin is one of the highest risk medications used in hospitalized patients. Multiple complex factors must be considered in determining a safe and effective insulin regimen. We sought to develop a computerized clinical decision support (CDS) tool to assist hospital-based clinicians in insulin management. METHODS: Adapting existing clinical practice guidelines for inpatient glucose management, a design team selected, configured, and implemented a CDS tool to guide subcutaneous insulin dosing in non-critically ill hospitalized patients at two academic medical centers that use the EpicCare® electronic medical record (EMR). The Agency for Healthcare Research and Quality (AHRQ) best practices in CDS design and implementation were followed. RESULTS: A CDS tool was developed in the form of an EpicCare SmartForm, which generates an insulin regimen by integrating information about the patient's body weight, diabetes type, home and hospital insulin requirements, and nutritional status. Total daily recommended insulin doses are distributed into respective basal and nutritional doses with a tailored correctional insulin scale. Preimplementation, several approaches were used to communicate this new tool to clinicians, including emails, lectures, and videos. Postimplementation, a support team was available to address user technical issues. Feedback from stakeholders has been used to continuously refine the tool. Inclusion of the programming in the EMR vendor's community library has allowed dissemination of the tool outside our institution. CONCLUSIONS: We have developed an EMR-based tool to guide SQ insulin dosing in non-critically ill hospitalized patients. Further studies are needed to evaluate adoption and clinical effectiveness of this intervention.

Human Intestinal Parasite Burden and Poor Sanitation in Rural Alabama.

Hookworm infection affects 430 million people worldwide, causing iron deficiency, impaired cognitive development, and stunting in children. Because of the environmental conditions needed for the hookworm life-cycle, this parasite is endemic to resource-limited countries. Necator americanus was endemic in the southern United States before improvement of sewage disposal systems and eradication programs. With continued poverty, poor sanitation, and an environment suitable for the hookworm life-cycle in some regions of the southern United States, a current prevalence study using modern molecular diagnostics is warranted. Lowndes County, Alabama, was chosen as the study site given previous high hookworm burdens, degree of poverty, and use of open-sewage systems. Participants were interviewed, and stool, serum, and soil samples were tested for nine intestinal parasites using a multiparallel quantitative real-time PCR (qPCR) and enzyme-linked immunosorbent assays. We found that, among 24 households, 42.4% reported exposure to raw sewage within their home, and from 55 stool samples, 19 (34.5%) tested positive for N. americanus, four (7.3%) for Strongyloides stercoralis, and one (1.8%) for Entamoeba histolytica. Stool tested positive for N. americanus contained low levels of parasite DNA (geometric mean 0.0302 fg/µL). Soil studies detected one (2.9%) Cryptosporidium species, and Toxocara serology assay detected one (5.2%) positive in this population. Individuals living in this high-risk environment within the United States continue to have stool samples positive for N. americanus. Gastrointestinal parasites known to be endemic to developing countries are identifiable in American poverty regions, and areas with lower disease burden are more likely to be identified by using qPCR.

Identification of human intestinal parasites affecting an asymptomatic peri-urban Argentinian population using multi-parallel quantitative real-time polymerase chain reaction.

BACKGROUND: In resource-limited countries, stool microscopy is the diagnostic test of choice for intestinal parasites (soil-transmitted helminths and/or intestinal protozoa). However, sensitivity and specificity is low. Improved diagnosis of intestinal parasites is especially important for accurate measurements of prevalence and intensity of infections in endemic areas. METHODS: The study was carried out in Orán, Argentina. A total of 99 stool samples from a local surveillance campaign were analyzed by concentration microscopy and McMaster egg counting technique compared to the analysis by multi-parallel quantitative real-time polymerase chain reaction (qPCR). This study compared the performance of qPCR assay and stool microscopy for 8 common intestinal parasites that infect humans including the helminths Ascaris lumbricoides, Ancylostoma duodenale, Necator americanus, Strongyloides stercoralis, Trichuris trichiura, and the protozoa Giardia lamblia, Cryptosporidium parvum/hominis, and Entamoeba histolytica, and investigated the prevalence of polyparasitism in an endemic area. RESULTS: qPCR showed higher detection rates for all parasites as compared to stool microscopy except T. trichiura. Species-specific primers and probes were able to distinguish between A. duodenale (19.1%) and N. americanus (36.4%) infections. There were 48.6% of subjects co-infected with both hookworms, and a significant increase in hookworm DNA for A. duodenale versus N. americanus (119.6 fg/µL: 0.63 fg/µL, P < 0.001) respectively. qPCR outperformed microscopy by the largest margin in G. lamblia infections (63.6% versus 8.1%, P < 0.05). Polyparasitism was detected more often by qPCR compared to microscopy (64.7% versus 24.2%, P < 0.05). CONCLUSIONS: Multi-parallel qPCR is a quantitative molecular diagnostic method for common intestinal parasites in an endemic area that has improved diagnostic accuracy compared to stool microscopy. This first time use of multi-parallel qPCR in Argentina has demonstrated the high prevalence of intestinal parasites in a peri-urban area. These results will contribute to more accurate epidemiological survey, refined treatment strategies on a public scale, and better health outcomes in endemic settings.