The structure of a haemoglobin-nanobody complex reveals human ß-subunit-specific interactions.

Haemoglobin (Hb) is a vital oxygen carrier in vertebrates. Low blood Hb levels may indicate anaemia or genetic disorders, while its presence in the lower digestive system suggests colon cancer. Detecting and quantifying human Hb is essential for medical diagnostics. A nanobody-based sandwich-ELISA test was recently developed utilising llama-derived nanobodies NbE11 and NbB9. These nanobodies specifically bind to human Hb without cross-reacting with Hb from other vertebrates. Here, we determine the crystal structure of NbE11 in complex with human Hb. NbE11 binds Hb with high affinity, predominantly binding the ß-Hb subunit. Structural differences between human Hb and other vertebrates at the NbE11 binding interface likely explain the assay's lack of cross-reactivity, providing insights for developing Hb binding diagnostics.

Endoscopic and imaging outcomes of PD-1 therapy in localised dMMR colorectal cancer.

BACKGROUND: Neoadjuvant immune checkpoint blockade (IO) is emerging as a therapeutic option for patients with deficient mismatch repair (dMMR) colorectal cancer (CRC) given high pathological response rates. The aim of the study was to characterise imaging and endoscopic response to IO. METHODS: A retrospective analysis of patients with localised dMMR CRC that received at least one cycle of neoadjuvant anti-PD-1 therapy was conducted. Endoscopy, imaging, and pathological outcomes were reviewed to determine response to treatment according to standardised criteria. RESULTS: Thirty-eight patients had received IO for the treatment of localised CRC (median eight cycles). Among evaluable cases (n = 31 for endoscopy and n = 34 for imaging), the best endoscopic response was complete response (CR) in 45% of cases, and the best radiographic response was CR in 23% of cases. Imaging CR rate after ≤4 cycles of IO (n = 1) was 6% compared to 44% after >4 IO cycles (n = 7). Among 28 patients with imaging and endoscopy available, a discrepancy in best response was noted in 15 (54%) cases. At a median follow-up of 28.2 months from IO start, 18 patients underwent surgical resection of which 11 (61%) had pathological CR (pCR). Despite pCR or no evidence of progression ≥6 months after completion of IO among non-operatively managed patients, 72% and 42% of patients had non-CR on imaging and endoscopy, respectively. CONCLUSIONS: Discrepancies between imaging and endoscopy are prevalent, and irregularities identified on these modalities can be identified despite pathological remission. Improved clinical response criteria are warranted.

The Association of the UNOS Heart Allocation Policy Change With Transplant and Left Ventricular Assist Device Access and Outcomes.

In October 2018, the allocation policy for adult orthotopic heart transplant (OHTx) in the United States was changed, with the goal of reducing waitlist mortality and providing broader sharing of donor organs within the United States. This study aimed to assess the association of this policy change with changes in access to OHTx versus left ventricular assist devices (LVADs), overall and in key sociodemographic subgroups, in the United States from 2016 to 2019. We identified all patients receiving OHTx or LVAD between 2016 and 2019 using the National Inpatient Sample. Controlling for medical co-morbidities, prepolicy trends, and within-hospital-year effects, we fit a dynamic logistic regression model to evaluate patient and hospital factors associated with receiving OHTx versus LVAD before versus after policy change. We also examined the frequency of temporary mechanical circulatory support in the same fashion. We identified 2,264 patients who received OHTx and 3,157 who received LVADs during the study period. In its first year of implementation, the United Network for Organ Sharing policy change of 2018 was associated with no overall change utilization of OHTx versus LVAD. In OHTx recipients, the frequency of use of temporary mechanical circulatory support changed from 15.6% in the before period to 42.6% in the after period (p <0.001). Although the policy change was associated with differences in the odds of receiving an OHTx versus LVAD between different regions of the country, there were no significant changes based on age, gender, race/ethnicity, insurance status, or rurality. In conclusion, the United Network for Organ Sharing policy change on access to OHTx was associated with no overall change in OHTx versus LVAD use in its first year of implementation although we observed small changes in relative odds of transplant based on rurality. Shifts in regional allocation were not significant overall, although certain regions appeared to have a relative increase in their use of OHTx.

Variation in the Use of Targeted Temperature Management for Cardiac Arrest.

Targeted temperature management (TTM) is recommended for patients who do not respond after return of spontaneous circulation after cardiac arrest. However, the degree to which patients with cardiac arrest have access to this therapy on a national level is not known. Understanding hospital- and patient-level factors associated with receipt of TTM could inform interventions to improve access to this treatment among appropriate patients. Therefore, we performed a retrospective analysis using National Inpatient Sample data from 2016 to 2019. We used International Classification of Diseases, Tenth Edition diagnosis and procedure codes to identify adult patients with in-hospital and out-of-hospital cardiac arrest and receipt of TTM. We evaluated patient and hospital factors associated with receiving TTM. We identified 478,419 patients with cardiac arrest. Of those, 4,088 (0.85%) received TTM. Hospital use of TTM was driven by large, nonprofit, urban, teaching hospitals, with less use at other hospital types. There was significant regional variation in TTM capabilities, with the proportion of hospitals providing TTM ranging from >21% in the Mid-Atlantic region to <11% in the East and West South Central and Mountain regions. At the patient level, age >74 years (odds ratio [OR] 0.54, p <0.001), female gender (OR 0.89, p >0.001), and Hispanic ethnicity (OR 0.74, p <0.001) were all associated with decreased odds of receiving TTM. Patients with Medicare (OR 0.75, p <0.001) and Medicaid (OR 0.89, p = 0.027) were less likely than patients with private insurance to receive TTM. Part of these differences was driven by inequitable access to TTM-capable hospitals. In conclusion, TTM is rarely used after cardiac arrest. Hospital use of TTM is predominately limited to a subset of academic hospitals with substantial regional variation. Older age, female gender, Hispanic ethnicity, and Medicare or Medicaid insurance are all associated with a decreased likelihood of receiving TTM.

Inequities in Treatments and Outcomes Among Patients Hospitalized With Hypertrophic Cardiomyopathy in the United States.

Background Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiac disease. In small studies, sociodemographic factors have been associated with disparities in septal reduction therapy, but little is known about the association of sociodemographic factors with HCM treatments and outcomes more broadly. Methods and Results Using the National Inpatient Survey from 2012 to 2018, HCM diagnoses and procedures were identified by International Classification of Diseases, Ninth/Tenth Revision, Clinical Modification (ICD-9-CM and ICD-10-CM) codes. Logistic regression was used to determine the association of sociodemographic risk factors with HCM procedures and in-hospital death, adjusting for clinical comorbidities and hospital characteristics. Of 53 117 patients hospitalized with HCM, 57.7% were women, 20.5% were Black individuals, 27.7% lived in the lowest zip income quartile, and 14.7% lived in rural areas. Among those with obstruction (45.2%), compared with White patients, Black patients were less likely to undergo septal myectomy (adjusted odds ratio [aOR], 0.52 [95% CI, 0.40-0.68]), or alcohol septal ablation (aOR, 0.60 [95% CI, 0.42-0.86]). Patients with Medicaid were less likely to undergo each procedure (aOR, 0.78 [95% CI, 0.61-0.99] for myectomy; aOR, 0.54 [95% CI, 0.36-0.83] for ablation). Women (aOR, 0.66 [95% CI, 0.58-0.74]), patients with Medicaid (aOR, 0.78 [95% CI, 0.65-0.93]), and patients from low-income areas (aOR, 0.77 [95% CI, 0.65-0.93]) were less likely to receive implantable cardioverter-defibrillators. Women (aOR, 1.23 [95% CI, 1.10-1.37]) and patients from towns (aOR, 1.16 [95% CI, 1.03-1.31]) or rural areas (aOR, 1.57 [95% CI, 1.30-1.89]) had higher odds of in-hospital death. Conclusions Among 53 117 patients hospitalized with HCM, race, sex, social, and geographic risk factors were associated with disparities in HCM outcomes and treatment. Further research is required to identify and address the sources of these inequities.

Immunity against Moraxella catarrhalis requires guanylate-binding proteins and caspase-11-NLRP3 inflammasomes.

Moraxella catarrhalis is an important human respiratory pathogen and a major causative agent of otitis media and chronic obstructive pulmonary disease. Toll-like receptors contribute to, but cannot fully account for, the complexity of the immune response seen in M. catarrhalis infection. Using primary mouse bone marrow-derived macrophages to examine the host response to M. catarrhalis infection, our global transcriptomic and targeted cytokine analyses revealed activation of immune signalling pathways by both membrane-bound and cytosolic pattern-recognition receptors. We show that M. catarrhalis and its outer membrane vesicles or lipooligosaccharide (LOS) can activate the cytosolic innate immune sensor caspase-4/11, gasdermin-D-dependent pyroptosis, and the NLRP3 inflammasome in human and mouse macrophages. This pathway is initiated by type I interferon signalling and guanylate-binding proteins (GBPs). We also show that inflammasomes and GBPs, particularly GBP2, are required for the host defence against M. catarrhalis in mice. Overall, our results reveal an essential role for the interferon-inflammasome axis in cytosolic recognition and immunity against M. catarrhalis, providing new molecular targets that may be used to mitigate pathological inflammation triggered by this pathogen.

D-methionine administered as late as 36 hours post-noise exposure rescues from permanent threshold shift and dose-dependently increases serum antioxidant levels.

OBJECTIVE: To elucidate D-methionine's (D-met) dose and time rescue parameters from steady-state or impulse noise-induced permanent threshold shift (PTS) and determine D-met rescue's influence on serum and cochlear antioxidant levels. DESIGN: Five D-met doses at 0, 50, 100, or 200 mg/kg/dose administered starting at 1, 24, or 36 hours post steady-state or impulse noise exposure. Auditory brainstem responses at baseline and 21 days post-noise measured PTS. Serum (superoxide dismutase [SOD], catalase [CAT],, glutathione reductaseand glutathione peroxidase [GPx]) and cochlear (Glutathione [GSH] and glutathione disulphide [GSSG]) antioxidant levels measured physiological impact. STUDY SAMPLE: Chinchillas (10/study group; 6-8/confirmatory groups). RESULTS: D-met significantly reduced PTS for impulse noise (100 mg [2, 6, 14 and 20 kHz]; 200 mg [2, 14 and 20 kHz]) and steady-state noise (all dosing groups, time parameters and tested frequencies). PTS reduction did not significantly vary by rescue time. D-met significantly increased serum SOD (100 and 200 mg for 24 hour rescue) and GPx (50 mg/kg at 24 hour rescue) at 21 days post-noise. Cochlear GSH and GSSG levels were unaffected relative to control. CONCLUSION: D-met rescues from steady-state and impulse noise-induced PTS even when administered up to 36 hours post-noise and dose-dependently influences serum antioxidant levels even 21 days post-noise. D-met's broad and effective dose/time window renders it a promising antioxidant rescue agent.

Pathogen-selective killing by guanylate-binding proteins as a molecular mechanism leading to inflammasome signaling.

Inflammasomes are cytosolic signaling complexes capable of sensing microbial ligands to trigger inflammation and cell death responses. Here, we show that guanylate-binding proteins (GBPs) mediate pathogen-selective inflammasome activation. We show that mouse GBP1 and GBP3 are specifically required for inflammasome activation during infection with the cytosolic bacterium Francisella novicida. We show that the selectivity of mouse GBP1 and GBP3 derives from a region within the N-terminal domain containing charged and hydrophobic amino acids, which binds to and facilitates direct killing of F. novicida and Neisseria meningitidis, but not other bacteria or mammalian cells. This pathogen-selective recognition by this region of mouse GBP1 and GBP3 leads to pathogen membrane rupture and release of intracellular content for inflammasome sensing. Our results imply that GBPs discriminate between pathogens, confer activation of innate immunity, and provide a host-inspired roadmap for the design of synthetic antimicrobial peptides that may be of use against emerging and re-emerging pathogens.

Impact of the COVID-19 Pandemic on Patients Without COVID-19 With Acute Myocardial Infarction and Heart Failure.

Background Excess mortality from cardiovascular disease during the COVID-19 pandemic has been reported. The mechanism is unclear but may include delay or deferral of care, or differential treatment during hospitalization because of strains on hospital capacity. Methods and Results We used emergency department and inpatient data from a 12-hospital health system to examine changes in volume, patient age and comorbidities, treatment (right- and left-heart catheterization), and outcomes for patients with acute myocardial infarction (AMI) and heart failure (HF) during the COVID-19 pandemic compared with pre-COVID-19 (2018 and 2019), controlling for seasonal variation. We analyzed 27 427 emergency department visits or hospitalizations. Patient volume decreased during COVID-19 for both HF and AMI, but age, race, sex, and medical comorbidities were similar before and during COVID-19 for both groups. Acuity increased for AMI as measured by the proportion of patients with ST-segment elevation. There were no differences in right-heart catheterization for patients with HF or in left heart catheterization for patients with AMI. In-hospital mortality increased for AMI during COVID-19 (odds ratio [OR], 1.46; 95% CI, 1.21-1.76), particularly among the ST-segment-elevation myocardial infarction subgroup (OR, 2.57; 95% CI, 2.24-2.96), but was unchanged for HF (OR, 1.02; 95% CI, 0.89-1.16). Conclusions Cardiovascular volume decreased during COVID-19. Despite similar patient age and comorbidities and in-hospital treatments during COVID-19, mortality increased for patients with AMI but not patients with HF. Given that AMI is a time-sensitive condition, delay or deferral of care rather than changes in hospital care delivery may have led to worse cardiovascular outcomes during COVID-19.

D-methionine immediate and continued rescue after noise exposure does not prevent temporary threshold shift but alters cochlear and serum antioxidant levels.

OBJECTIVE: Determine if D-methionine (D-met) rescue prevents temporary threshold shift (TTS) from steady-state or impulse noise and determine D-met's impact on serum and cochlear antioxidant levels. DESIGN: D-met at 50, 100 or 200 mg/kg/doses were administered 0, 6 and 18 hours-post noise. ABRs at baseline and 24 hours post-noise measured TTS. Serum (SOD, CAT, GR, GPx) and cochlear (GSH, GSSG) antioxidant levels measured physiological influence. Three control groups, with impulse or steady-state or without noise, were saline-injected. STUDY SAMPLE: Ten Chinchillas/group. RESULTS: D-met rescue did not significantly reduce TTS or impact serum CAT, SOD, GPx or GR levels vs. noise-exposed control groups, but TTS was greater in all groups relative to no-noise controls. D-met significantly elevated CAT at 50 mg/kg vs. steady-state controls and SOD at 200 mg/kg vs. impulse noise controls. D-met significantly reduced cochlear GSH/GSSG ratios in the 100 mg/kg D-met group vs. impulse noise controls. CONCLUSIONS: While D-met rescue has reduced permanent threshold shift in previous studies, it did not reduce TTS in this study. However, D-met rescue did alter selective serum and cochlear oxidative state changes 24 hours post-noise relative to controls. Results demonstrate TTS studies do not always predict PTS protection in otoprotectant experimental designs.

Preloaded D-methionine protects from steady state and impulse noise-induced hearing loss and induces long-term cochlear and endogenous antioxidant effects.

OBJECTIVE: Determine effective preloading timepoints for D-methionine (D-met) otoprotection from steady state or impulse noise and impact on cochlear and serum antioxidant measures. DESIGN: D-met started 2.0-, 2.5-, 3.0-, or 3.5- days before steady-state or impulse noise exposure with saline controls. Auditory brainstem response (ABRs) measured from 2 to 20 kHz at baseline and 21 days post-noise. Samples were then collected for serum (SOD, CAT, GR, GPx) and cochlear (GSH, GSSG) antioxidant levels. STUDY SAMPLE: Ten Chinchillas per group. RESULTS: Preloading D-met significantly reduced ABR threshold shifts for both impulse and steady state noise exposures but with different optimal starting time points and with differences in antioxidant measures. For impulse noise exposure, the 2.0, 2.5, and 3.0 day preloading start provide significant threshold shift protection at all frequencies. Compared to the saline controls, serum GR for the 3.0 and 3.5 day preloading groups was significantly increased at 21 days with no significant increase in SOD, CAT or GPx for any impulse preloading time point. Cochlear GSH, GSSG, and GSH/GSSG ratio were not significantly different from saline controls at 21 days post noise exposure. For steady state noise exposure, significant threshold shift protection occurred at all frequencies for the 3.5, 3.0 and 2.5 day preloading start times but protection only occurred at 3 of the 6 test frequencies for the 2.0 day preloading start point. Compared to the saline controls, preloaded D-met steady-state noise groups demonstrated significantly higher serum SOD for the 2.5-3.5 day starting time points and GPx for the 2.5 day starting time but no significant increase in GR or CAT for any preloading time point. Compared to saline controls, D-met significantly increased cochlear GSH concentrations in the 2 and 2.5 day steady-state noise exposed groups but no significant differences in GSSG or the GSH/GSSG ratio were noted for any steady state noise-exposed group. CONCLUSIONS: The optimal D-met preloading starting time window is earlier for steady state (3.5-2.5 days) than impulse noise (3.0-2.0). At 21 days post impulse noise, D-met increased serum GR for 2 preloading time points but not SOD, CAT, or GpX and not cochlear GSH, GSSG or the GSH/GSSG ratio. At 21 days post steady state noise D-met increased serum SOD and GPx at select preloading time points but not CAT or GR. However D-met did increase the cochlear GSH at select preloading time points but not GSSG or the GSH/GSSG ratio.

Exploring perception and usage of narrative medicine by physician specialty: a qualitative analysis.

BACKGROUND: Narrative medicine is a well-recognized and respected approach to care. It is now found in medical school curricula and widely implemented in practice. However, there has been no analysis of the perception and usage of narrative medicine across different medical specialties and whether there may be unique recommendations for implementation based upon specialty. The aims of this study were to explore these gaps in research. METHODS: Fifteen senior physicians who specialize in internal medicine, pediatrics, or surgery (5 physicians from each specialty) were interviewed in a semi-structured format about the utilization, benefits, drawbacks (i.e., negative consequences), and roles pertaining to narrative medicine. Qualitative content analysis of each interview was then performed. RESULTS: Three themes emerged from our analysis: roles, practice, and outcomes. Through these themes we examined the importance, utilization, barriers, benefits, and drawbacks of narrative medicine. There was consensus that narrative medicine is an important tool in primary care. Primary care physicians (general internists and general pediatricians) also believed that narrative medicine is not as important for non-primary care providers. However, non-primary care providers (surgeons) generally believed narrative medicine is valuable in their practice as well. Within specialties, providers' choice of language varied when trying to obtain patients' narratives, but choice in when to practice narrative medicine did not differ greatly. Among specialties, there was more variability regarding when to practice narrative medicine and what barriers were present. Primary care physicians primarily described barriers to eliciting a patient's narrative to involve trust and emotional readiness, while surgeons primarily described factors involving logistics and patient data as barriers to obtaining patients' narratives. There was broad agreement among specialties regarding the benefits and drawbacks of narrative medicine. CONCLUSIONS: This study sheds light on the shared and unique beliefs in different specialties about narrative medicine. It prompts important discussion around topics such as the stereotypes physicians may hold about their peers and concerns about time management. These data provide some possible ideas for crafting narrative medicine education specific to specialties as well as future directions of study.

Blunt Abdominal Trauma in the Third Trimester: Eight Departments, Two Patients, One Survivor.

Blunt abdominal trauma is one of the leading causes of non-obstetrics-related deaths during pregnancy, with motor vehicle collision, falls, and assaults being the most common etiologies. While a trauma team plays a central role in the care of a pregnant trauma patient, a multidisciplinary involvement is vital to ensure the safety of the fetus and the mother. This case study will follow the step-by-step multidisciplinary approach utilized for a 37-year-old female in her third trimester who suffered blunt trauma and arrived at a Level 1 trauma center that led to maternal survival but fetal demise. She was initially evaluated by Emergency Medicine and Obstetrics/Gynecology departments for maternal and fetal trauma, by Orthopedics for several fractures including the pubic ramus and sacral ala fractures, as well as by Neurosurgery for a subarachnoid hemorrhage and a subdural hematoma. Subsequently, the following departments were brought on after the patient suddenly became hypotensive with abdominal tenderness to assess for internal bleeding: Interventional Radiology, Trauma, Surgery, and Urology. Retroperitoneal and pelvic hematomas were found to be the source of bleeding during an emergency laparotomy and the decision was made for an emergency caesarian section. The neonatal intensive care unit ultimately could not start the fetal heart. In the days that followed, the neurosurgery department monitored the worsening intercranial bleeds while Psychiatry and Social Work attended to the patient. A proper systematic approach towards a patient in this situation necessitates expertise from multiple fields, and the success of this interplay greatly affects patient outcomes.

Changes In Non-COVID-19 Emergency Department Visits By Acuity And Insurance Status During The COVID-19 Pandemic.

Prior studies suggest that the COVID-19 pandemic was associated with decreases in emergency department (ED) volumes, but it is not known whether these decreases varied by visit acuity or by demographic and socioeconomic risk factors. In this study of more than one million non-COVID-19 visits to thirteen EDs in a large St. Louis, Missouri, health system, we observed an overall 35 percent decline in ED visits. The decrease in medical and surgical visits ranged from 40 percent to 52 percent across acuity levels, with no statistically significant differences between higher- and lower-acuity visits after correction for multiple comparisons. Mental health visits saw a smaller decrease (-32 percent), and there was no decrease for visits due to substance use. Medicare patients had the smallest decrease in visits (-31 percent) of the insurance groups; privately insured (-46 percent) and Medicaid (-44 percent) patients saw larger drops. There were no observable differences in ED visit decreases by race. These findings can help inform interventions to ensure that people requiring timely ED care continue to seek it and to improve access to lower-risk alternative settings of care where appropriate.

TM1385 from Thermotoga maritima functions as a phosphoglucose isomerase via cis-enediol-based mechanism with active site redundancy.

Phosphoglucose isomerases (PGIs) belong to a class of enzymes that catalyze the reversible isomerization of glucose-6-phosphate to fructose-6-phosphate. PGIs are crucial in glycolysis and gluconeogenesis pathways and proposed as serving additional extracellular functions in eukaryotic organisms. The phosphoglucose isomerase function of TM1385, a previously uncharacterized protein from Thermotoga maritima, was hypothesized based on structural similarity to established PGI crystal structures and computational docking. Kinetic and colorimetric assays combined with 1H nuclear magnetic resonance (NMR) spectroscopy experimentally confirm that TM1385 is a phosphoglucose isomerase (TmPGI). Evidence of solvent exchange in 1H NMR spectra supports that TmPGI isomerization proceeds through a cis-enediol-based mechanism. To determine which amino acid residues are critical for TmPGI catalysis, putative active site residues were mutated with alanine and screened for activity. Results support that E281 is most important for TmPGI formation of the cis-enediol intermediate, and the presence of either H310 or K422 may be required for catalysis, similar to previous observations from homologous PGIs. However, only TmPGI E281A/Q415A and H310A/K422A double mutations abolished activity, suggesting that there are redundant catalytic residues, and Q415 may participate in sugar phosphate isomerization upon E281 mutation. Combined, we propose that TmPGI E281 participates directly in the cis-enediol intermediate step, and either H310 or K422 may facilitate sugar ring opening and closure.

Bacillus cereus non-haemolytic enterotoxin activates the NLRP3 inflammasome.

Inflammasomes are important for host defence against pathogens and homeostasis with commensal microbes. Here, we show non-haemolytic enterotoxin (NHE) from the neglected human foodborne pathogen Bacillus cereus is an activator of the NLRP3 inflammasome and pyroptosis. NHE is a non-redundant toxin to haemolysin BL (HBL) despite having a similar mechanism of action. Via a putative transmembrane region, subunit C of NHE initiates binding to the plasma membrane, leading to the recruitment of subunit B and subunit A, thus forming a tripartite lytic pore that is permissive to efflux of potassium. NHE mediates killing of cells from multiple lineages and hosts, highlighting a versatile functional repertoire in different host species. These data indicate that NHE and HBL operate synergistically to induce inflammation and show that multiple virulence factors from the same pathogen with conserved function and mechanism of action can be exploited for sensing by a single inflammasome.

Opportunities to Improve Shared Decision Making in Dialysis Decisions for Older Adults with Life-Limiting Kidney Disease: A Pilot Study.

Background: Lack of awareness about the life-limiting nature of renal failure is a significant barrier to palliative care for older adults with end-stage renal disease. Objective: To train nephrologists to use the best case/worst case (BC/WC) communication tool to improve shared decision making about dialysis initiation for older patients with limited life expectancy. Design: This is a pre-/postinterventional pilot study. Setting/Subjects: There were 16 nephrologists and 30 patients of age 70 years and older with estimated glomerular filtration rate (eGFR) <20 mL/min per 1.73 m2 in outpatient nephrology clinics, in Madison, WI. Measurements: Performance of tool elements, content of communication about dialysis, shared decision making, acceptability of the intervention, decisions to pursue dialysis, and palliative care referrals were measured. Results: Fifteen of 16 nephrologists achieved competence performing the BC/WC tool with standardized patients, executing at least 14 of 19 items. Nine nephrologists met with 30 patients who consented to audio record their clinic visit. Before training, clinic visits focused on laboratory results and preparation for dialysis. After training, nephrologists noted that declining kidney function was "bad news," presented dialysis and "no dialysis" as treatment options, and elicited patient preferences. Observer-measured shared decision-making (OPTION 5) scores improved from a median of 20/100 (interquartile range [IQR] 15-35) before training to 58/100 (IQR 55-65). Patients whose nephrologist used the BC/WC tool were less likely to make a decision to initiate dialysis and were more likely to be referred to palliative care. Conclusions: Nephrologists can learn to use the BC/WC tool with older patients to improve shared decision making about dialysis, which may increase access to palliative care.