Faculty Bibliography

Introduction: Children and adolescents with pre-existing type 1 diabetes (T1D) diagnosed with COVID-19 are at risk of adverse outcomes such as hospitalizations and diabetic ketoacidosis (DKA). There is limited data on the association between the presence of one or more comorbidities and the risk of adverse outcomes for patients with preexisting T1D and COVID19.
Objective(s): This study's aim is to determine if pediatric and adolescent patients with T1D and other pre-existing comorbidities were more likely to experience adverse outcomes than T1D patients with COVID-19 who did not have any other comorbidities.
Method(s): Data from 592 patients with previously established T1D aged <24 years with COVID-19 were analyzed from the T1Dx COVID-19 Surveillance Registry. Data were collected from 52 endocrinology clinics across the US using an online survey tool. Each clinic completed the survey using electronic medical record (EMR) data between April 2020 and May 2021. Descriptive statistics were used to describe the study population, and multivariate logistic regression models were used to analyze the relationship between age, insurance type, use of diabetes technology, presence of comorbidities, adverse outcomes, and hospitalization.
Result(s): The most frequent comorbidities were obesity (14%), asthma (11%), celiac disease (9%), and hypothyroidism (7%). T1D patients with at least one other comorbidity had a higher DKA presentation (16% vs 12%, p = 0.03) and a higher all-cause hospitalization rate (24% vs 15%, p = 0.02) compared to T1D patients without additional comorbidities. T1D Patients with comorbidities and COVID-19 were almost twice as likely to be hospitalized than those with no comorbidities (Odds Ratio 1.94, 95% CI: 1.23-3.03). The most frequent comorbidities were obesity (14%), asthma (11%), celiac disease (9%), and hypothyroidism (7%). T1D patients with at least one other comorbidity had a higher DKA presentation (16% vs 12%, p = 0.03) and a higher all-cause hospitalization rate (24% vs 15%, p = 0.02) compared to T1D patients without additional comorbidities. T1D Patients with comorbidities and COVID-19 were almost twice as likely to be hospitalized than those with no comorbidities (Odds Ratio 1.94, 95% CI: 1.23-3.03).
Conclusion(s): Our data reveal higher rates of hospitalizations and adverse outcomes among children and adolescents with T1D with at least one more comorbidities and COVID-19 in comparison with T1D patients without additional comorbidities. (Table Presented)

The cancer community understands the value of blood profiling measurements in assessing and monitoring cancer. We describe an effort among academic, government, biotechnology, diagnostic, and pharmaceutical companies called the Blood Profiling Atlas in Cancer (BloodPAC) Project. BloodPAC will aggregate, make freely available, and harmonize for further analyses, raw datasets, relevant associated clinical data (e.g., clinical diagnosis, treatment history, and outcomes), and sample preparation and handling protocols to accelerate the development of blood profiling assays.

Cannabinoid hyperemesis syndrome (CHS) is a rare constellation of clinical findings that includes a history of chronic heavy marijuana use, severe abdominal pain, unrelenting nausea, and intractable vomiting. A striking component of this history includes the use of hot showers or long baths that help to alleviate these symptoms. This is an underrecognized syndrome that can lead to expensive and unrevealing workups and can leave patients self-medicating their nausea and vomiting with the very substance that is causing their symptoms. Long-term treatment of CHS is abstinence from marijuana use-but the acute symptomatic treatment of CHS has been a struggle for many clinicians. Many standard medications used for the symptomatic treatment of CHS (including ondansetron, promethazine, and morphine) have repeatedly been shown to be ineffective. Here we present the use of lorazepam as an agent that successfully and safely treats the tenacious symptoms of CHS. Additionally, we build upon existing hypotheses for the pathogenesis of CHS to try to explain why a substance that has been used for thousands of years is only now beginning to cause this paradoxical hyperemesis syndrome.

Metastatic breast cancer may emerge from latent tumor cells that remain dormant at disseminated sites for many years. Identifying mechanisms regulating the switch from dormancy to proliferative metastatic growth has been elusive due to the lack of experimental models of tumor cell dormancy. We characterized the in vitro growth characteristics of cells that exhibit either dormant (D2.0R, MCF-7, and K7M2AS1.46) or proliferative (D2A1, MDA-MB-231, and K7M2) metastatic behavior in vivo. Although these cells proliferate readily in two-dimensional culture, we show that when grown in three-dimensional matrix, distinct growth properties of the cells were revealed that correlate to their dormant or proliferative behavior at metastatic sites in vivo. In three-dimensional culture, cells with dormant behavior in vivo remained cell cycle arrested with elevated nuclear expression of p16 and p27. The transition from quiescence to proliferation of D2A1 cells was dependent on fibronectin production and signaling through integrin beta1, leading to cytoskeletal reorganization with filamentous actin (F-actin) stress fiber formation. We show that phosphorylation of myosin light chain (MLC) by MLC kinase (MLCK) through integrin beta1 is required for actin stress fiber formation and proliferative growth. Inhibition of integrin beta1 or MLCK prevents transition from a quiescent to proliferative state in vitro. Inhibition of MLCK significantly reduces metastatic outgrowth in vivo. These studies show that the switch from dormancy to metastatic growth may be regulated, in part, through epigenetic signaling from the microenvironment, leading to changes in the cytoskeletal architecture of dormant cells. Targeting this process may provide therapeutic strategies for inhibition of the dormant-to-proliferative metastatic switch.