Faculty Bibliography

BACKGROUND:Relevant clinical information is often missing when a patient sees a specialist after being referred by another physician in the ambulatory setting. This can result in missed or delayed diagnoses, delayed treatment, unnecessary testing, and drug interactions. Residents' attitudes toward providing clinical information at the time of referral and their perspectives toward training on referral skills are not clear. We sought to assess internal medicine residents' attitudes toward and experiences with outpatient referrals. METHODS:We conducted a cross-sectional survey in October-December 2018 of all internal medicine interns and residents affiliated with a large, urban internal medicine residency program in New York, NY. We used a novel survey instrument that included 13 questions about attitudes toward and experiences with outpatient referrals. We used descriptive statistics to characterize the results. RESULTS:Overall, 122 of 132 residents participated (92% response rate). Respondents were approximately equally distributed across post-graduate years 1-3. Although 83% of residents reported that it is "always" important to provide the clinical reason for a referral, only 11% stated that they "always" provide a sufficient amount of clinical information for the consulting provider when making a referral. Only 9% of residents "strongly agree" that residency provides sufficient training in knowing when to refer patients, and only 8% "strongly agree" that residency provides sufficient training in what information to provide the consulting physician. CONCLUSIONS:These results suggest a substantial discrepancy between the amount of information residents believe they should provide at the time of a referral and the amount they actually provide. Many residents report not receiving adequate training during residency on when to refer patients and what clinical information to provide at the time of referral. Improvements to medical education regarding outpatient referrals are urgently needed.

Twenty patients with carbapenem-resistant Enterobacteriaceae (CRE) infections were treated with meropenem-vaborbactam. Thirty-day clinical success and survival rates were 65% (13/20) and 90% (18/20), respectively. Thirty-five percent of patients had microbiologic failures within 90 days. One patient developed a recurrent infection due to meropenem-vaborbactam non-susceptible, ompK36 porin mutant Klebsiellapneumoniae.

Objectives: To determine links between objectively and subjectively measured physical function and cognitive function among HIV-positive older adults, a growing yet understudied group with elevated risk for multimorbidity. Methods: At a biomedical research visit, 162 participants completed objective tests of gait speed (4-m walk), grip strength (dynamometer), and cognitive function (Montreal Cognitive Assessment, MoCA) and reported their well-being (Medical Outcomes Study-HIV survey). Results: Those with faster gait speed had better overall cognitive function than those with slower gait speed (b = 3.98, SE = 1.30, p = .003) in an adjusted regression model controlling for age, sex, race, height, preferred language, and assistive device use. Grip strength was not significantly associated with overall cognitive function. Self-rated cognitive function was weakly related to MoCA scores (r = .26) and gait speed (r = .14) but was strongly associated with emotional well-being (r = .53). Discussion: These observed, expected connections between physical and cognitive function could inform intervention strategies to mitigate age-related declines for older adults with HIV.

Mycobacterium abscessus (Mab) is a highly drug-resistant nontuberculous mycobacteria (NTM). Efforts to discover new treatments for M. abscessus infections are accelerating with a focus on cell wall synthesis proteins (L, D-transpeptidases, Ldt_Mab1-5, and D,D-carboxypeptidase) that are targeted by β-lactam antibiotics. A challenge to this approach is the presence of chromosomally encoded β-lactamase, Bla_Mab Using a "mechanism based" approach, we show that a novel ceftaroline-imipenem combination effectively lowered the minimal inhibitory concentrations (MICs) of Mab isolates (MIC₅₀ ≤ 0.25, MIC₉₀ ≤ 0.5). Ceftaroline and imipenem combined with a β-lactamase inhibitor, relebactam or avibactam, demonstrated only a modest effect on susceptibility, compared to each of the beta-lactams alone. In steady state kinetic assays, Bla_Mab exhibited a lower K_{i app} (K_{i app} = 0.30 ± 0.03 μM, avibactam; 136 ± 14 μM, relebactam) and a faster acylation rate for avibactam (k₂/K = 3.4 ± 0.4 x 10⁵ M^-1s^-1, avibactam; 6 ± 0.6 x 10² M^-1s^-1, relebactam). The k_cat/K_m was nearly 10-fold lower for ceftaroline fosamil (0.007 ± 0.001 μM^-1s^-1) compared to imipenem (0.056 ± 0.006 μM^-1s^-1). Timed mass spectrometry captured complexes of avibactam and Bla_Mab, Ldt_{Mab1, 2, and 4}, and D,D-carboxypeptidase, whereas relebactam bound only Bla_Mab and Ldt_{Mab1 and 2} Interestingly, Ldt_{Mab1, 2, 4 and 5} and D, D-carboxypeptidase bound only to imipenem when incubated with imipenem and ceftaroline fosamil. We next determined the binding constants of imipenem and ceftaroline fosamil to Ldt_{Mab1, 2, 4 and 5} and showed that imipenem bound > 100 fold more avidly than ceftaroline fosamil for Ldt_Mab1 and Ldt_Mab2 (e.g. K_{i app} or K_m LdtMab1 = 0.01 ± 0.01 μM for imipenem vs 0.73 ± 0.08 μM for ceftaroline fosamil). Molecular modelling indicates that Ldt_Mab2 readily accommodates imipenem, but the active site must widen to ≥ 8Ã… for ceftaroline to enter. Our analysis demonstrates that ceftaroline and imipenem binding to multiple targets (L, D-transpeptidases and D, D-carboxypeptidase) provides mechanistic rationale for the effectiveness of this dual β-lactam combination in Mab infections.

BACKGROUND:We previously identified two acute kidney injury (AKI) sub-phenotypes (AKI-SP1 and AKI-SP2) with different risk of poor clinical outcomes and response to vasopressor therapy. Plasma biomarkers of endothelial dysfunction (tumor necrosis factor receptor-1, angiopoietin-1 and 2) differentiated the AKI sub-phenotypes. However, it is unknown whether these biomarkers are simply markers or causal mediators in the development of AKI sub-phenotypes. METHODS:We tested for associations between single-nucleotide polymorphisms within the Angiopoietin-1, Angiopoietin-2, and Tumor Necrosis Factor Receptor 1A genes and AKI- SP2 in 421 critically ill subjects of European ancestry. Top performing single-nucleotide polymorphisms (FDR < 0.05) were tested for cis-biomarker expression and whether genetic risk for AKI-SP2 is mediated through circulating biomarkers. We also completed in vitro studies using human kidney microvascular endothelial cells. Finally, we calculated the renal clearance of plasma biomarkers using 20 different timed urine collections. RESULTS:A genetic variant, rs2920656C > T, near ANGPT2 was associated with reduced risk of AKI-SP2 (odds ratio, 0.45; 95% CI, 0.31-0.66; adjusted FDR = 0.003) and decreased plasma angiopoietin-2 (p = 0.002). Causal inference analysis showed that for each minor allele (T) the risk of developing AKI-SP2 decreases by 16%. Plasma angiopoietin-2 mediated 41.5% of the rs2920656 related risk for AKI-SP2. Human kidney microvascular endothelial cells carrying the T allele of rs2920656 produced numerically lower levels of angiopoietin-2 although this was not statistically significant (p = 0.07). Finally, analyses demonstrated that angiopoietin-2 is minimally renally cleared in critically ill subjects. CONCLUSION/CONCLUSIONS:Genetic mediation analysis provides supportive evidence that angiopoietin-2 plays a causal role in risk for AKI-SP2.

Addressing patients' social needs is key to helping patients heal from coronavirus disease 2019 (COVID-19), preventing the spread of the virus, and reducing its disproportionate burden on low-income communities and communities of color. New York City Health + Hospitals (NYC H+H) is the city's single largest healthcare provider to Medicaid and uninsured patients. In response to the COVID-19 pandemic, NYC H+H staff developed and executed a strategy to meet patients' intensified social needs during the COVID-19 pandemic. NYC H+H identified food, housing, and income support as patients' most pressing needs and built programming to quickly connect patients to these resources. While NYC H+H was able to build on its existing foundation of strong social work support of patients, all health systems must prioritize the social needs of patients and their families to mitigate the damage of COVID-19. National and local leaders should accelerate change by developing robust policy approaches to redesign the social and economic system that reinforces structural inequity and exacerbates crises like COVID-19. [Editor's Note: This Fast Track Ahead Of Print article is the accepted version of the manuscript. The final edited version will appear in an upcoming issue of Health Affairs.].

The coronavirus disease 2019 (COVID-19) pandemic presented unprecedented challenges to the New York City Health + Hospitals (NYC H+H) system. Besides ramping up capacity and adapting operations quickly to handle the patient surge, NYC H+H had to find new ways to provide emotional and psychological support for patients, families, and staff. To help families keep in touch, dedicated staff provided daily updates by phone and used tablets for virtual visits. An expanded palliative care team held virtual consultations with families to discuss advance care planning and end-of-life decisions. Bereavement hotlines were set up for families who lost loved ones. Enhanced staff support included one-one-one and group sessions with behavioral health specialists, a behavioral health hotline, a webinar series, respite rooms, as well as complimentary lodging and child care. NYC H+H created new rituals to celebrate recoveries and mourn losses. As regular operations resume, NYC H+H plans to sustain and build upon emotional and psychological support initiatives developed during the surge. [Editor's Note: This Fast Track Ahead Of Print article is the accepted version of the manuscript. The final edited version will appear in an upcoming issue of Health Affairs.].

PURPOSE OF REVIEW/OBJECTIVE:To review studies evaluating renal outcomes based on patient adherence to the Mediterranean diet or to the Dietary Approaches to Stop Hypertension (DASH) diet and to determine which diet is most effective in preventing and managing renal disease. RECENT FINDINGS/RESULTS:Both the DASH and Mediterranean diets have shown many health benefits, including reduced risk for chronic kidney disease (CKD), nephrolithiasis, mortality due to all renal causes and composite outcomes. Both diets have shown a decrease in estimated glomerular filtration rates (eGFR) decline with a concomitant improvement in mortality and dialysis initiation. In summary, both diets resulted in similar magnitudes of risk reduction when comparing equivocal levels of adherence to each diet. Review of evidence for renal outcomes shows strikingly similar effects for both DASH and Mediterranean diets. We hypothesize that these results are due to the overlap in nutritional composition. Both encourage whole foods such as fruits, vegetables, beans/legumes, whole grains, and nuts. Additionally, they restrict animal protein consumption and limit processed and fast foods. Determining a nutritional management intervention for renal impairment is clinically important as approximately 1% of the USA annual budget is spent on end stage renal disease (ESRD) treatment. We believe either diet could be incorporated into a patient's management when considering their renal health. In conclusion, we urge physicians to help patients choose either the DASH diet or Mediterranean diet based on the patient preference.