Faculty Bibliography

Background: Patients with respiratory failure who require prone positioning are not considered good candidates for PD due to the concerns for increased intra-abdominal pressure, impaired diaphragmatic movement, and leaking of peritoneal fluid. We addressed the COVID-related AKI (CRAKI) surge for renal replacement therapy (RRT) by initiating an acute PD program at Bellevue Hospital including prone patients.
Method(s): All patients were in the ICU with COVID related hypoxic respiratory failure and acute kidney injury (AKI). 6/35 patients who received PD were treated for 16 hours per day in the prone position to improve oxygenation. The mean age was 54.6. The average BMI was 35.5. Patients were on mechanical ventilation 12-33 days. 3/6 patients were on CVVH however, switched to PD due to clotting. Patients were on PD for an average of 9.3 days. All PD catheters were placed at the bedside using an open cut down technique. PD was started the same day using manual exchanges. Dwell volume was gradually increased to 2 L. Exchanges were performed q1h while supine and q2h while prone, a total of 4-6 exchanges/day. The PD team coordinated timing with the prone team and ICU nurses to allow the continuation of the PD treatment. Patients were monitored clinically for abdominal distention and changes in respiratory mechanics.
Result(s): All 6 patients remained on PD for the duration of the hospitalization. There were no incidences of bowel injury, hemorrhage, exit-site infections, or peritonitis. None of the patients had any catheter malfunction. Leaking was addressed with temporarily reducing the dwell volume. Patients experienced slow draining which was due to kinking of the tubing during prone positioning. All patients were able to continue receiving PD without interruptions. Either no change or improvement in ABG and ventilator settings was noted after prone positioning and PD.
Conclusion(s): Due to COVID related surge, we saw a significant number of patients in the ICU with severe acute respiratory failure requiring prone positioning who also developed AKI requiring RRT. We were able to successfully provide acute PD in ventilator-dependent prone patients suffering from CRAKI. This required a team effort and some modifications in the conventional PD prescription. (Figure Presented)

<br>Serotonin, a biologically active amine, is related to carcinoid syndrome in functioning neuroendocrine tumors (NETs). Telotristat ethyl is a novel inhibitor of the tryptophan hydroxylase (TPH), a key enzyme in the production of serotonin. While its use in patients with carcinoid syndrome and uncontrolled diarrhea under somatostatin analogs (SSAs) has been recently approved, in vitro data evaluating it effectiveness are lacking. For this reason, we aimed to evaluate the effect of telotristat as monotherapy, and in combination with SSAs, on proliferation and secretion in a NET cell line model. The human pancreatic NET cell lines BON-1/QGP-1 were used as 2D and 3D cultured models; somatostatin receptor and TPH mRNA expression, as well as the potential autocrine effect of serotonin on tumor cell proliferation using a 3D culture system were evaluated. Telotristat decreased serotonin production in a dose-dependent manner at a clinically feasible concentration, without affecting cell proliferation. Its combination with pasireotide, but not with octreotide, had an additive inhibitory effect on serotonin secretion. The effect of telotristat was slightly less potent, when BON-1 cells were co-treated with octreotide. Octreotide and pasireotide had no effect on the expression of TPH. Telotristat did not have an effect on mRNA expression of somatostatin receptor subtypes. Finally, we showed that serotonin did not have an autocrine effect on NET cell proliferation on the 3D cell model. These results suggest that telotristat is an effective drug for serotonin inhibition, but the effectiveness of its combination with SST2-preferring SSA should be evaluated in more detail.<br>.

BACKGROUND:Researchers must often rely on creatinine measurements to assess kidney function because direct glomerular filtration rates (GFR) and cystatin-c are rarely measured in routine clinical settings. However, HIV treatments often include dolutegravir, raltegravir, rilpivirine or cobicistat, which inhibit the proximal tubular secretion of creatinine without impairing kidney function, thus leading to measurement bias when using creatinine-based estimated GFR (eGFR). We developed eGFR correction factors to account for this potential bias. METHODS:(multivariate Cox proportional hazards models) were estimated with and without eGFR correction. RESULTS:compared to efavirenz. CONCLUSIONS:With increasing use of agents that inhibit tubular creatinine secretion, artificially low eGFR values could lead to erroneous conclusions in studies of HIV treatment and kidney outcomes measured with creatinine-based eGFR equations. Sensitivity analyses assessing the potential magnitude of bias arising from creatinine secretion inhibition should be performed.

BACKGROUND:New York City (NYC) bore the greatest burden of COVID-19 in the United States early in the pandemic. In this case series, we describe characteristics and outcomes of racially and ethnically diverse patients tested for and hospitalized with COVID-19 in New York City's public hospital system. METHODS:We reviewed the electronic health records of all patients who received a SARS-CoV-2 test between March 5 and April 9, 2020, with follow up through April 16, 2020. The primary outcomes were a positive test, hospitalization, and death. Demographics and comorbidities were also assessed. RESULTS:22254 patients were tested for SARS-CoV-2. 13442 (61%) were positive; among those, the median age was 52.7 years (interquartile range [IQR] 39.5-64.5), 7481 (56%) were male, 3518 (26%) were Black, and 4593 (34%) were Hispanic. Nearly half (4669, 46%) had at least one chronic disease (27% diabetes, 30% hypertension, and 21% cardiovascular disease). Of those testing positive, 6248 (46%) were hospitalized. The median age was 61.6 years (IQR 49.7-72.9); 3851 (62%) were male, 1950 (31%) were Black, and 2102 (34%) were Hispanic. More than half (3269, 53%) had at least one chronic disease (33% diabetes, 37% hypertension, 24% cardiovascular disease, 11% chronic kidney disease). 1724 (28%) hospitalized patients died. The median age was 71.0 years (IQR 60.0, 80.9); 1087 (63%) were male, 506 (29%) were Black, and 528 (31%) were Hispanic. Chronic diseases were common (35% diabetes, 37% hypertension, 28% cardiovascular disease, 15% chronic kidney disease). Male sex, older age, diabetes, cardiac history, and chronic kidney disease were significantly associated with testing positive, hospitalization, and death. Racial/ethnic disparities were observed across all outcomes. CONCLUSIONS AND RELEVANCE/CONCLUSIONS:This is the largest and most racially/ethnically diverse case series of patients tested and hospitalized for COVID-19 in New York City to date. Our findings highlight disparities in outcomes that can inform prevention and testing recommendations.