Autonomy to a fault: The confluence of organ donation, euthanasia, and the dead donor rule.

Five countries now permit organ donation after euthanasia, on the basis of respecting donor autonomy. Some now openly consider performing euthanasia itself via organ extraction to better preserve organ viability, albeit in violation of the dead donor rule. Proponents argue that respect for patient autonomy requires this option; the dead donor rule is inapplicable since it fulfills donors' wishes. Other ethical arguments, not addressed herein, explore issues including dying at home, impact on clinicians, and societal faith in donation enterprise, but these concerns are not insurmountable. This paper instead solely critiques proponents' oversimplified understanding of autonomy with an autonomy-based argument against any linkage of organ donation and euthanasia, regardless of its timing. Respect for patient autonomy does not unilaterally require fulfilling patients' every  wish. Moreover, the very possibility of organ donation with euthanasia limits donor autonomy qualitatively and quantitatively substantially more than by offering it. In fact, organ donation after euthanasia violates the purpose of the dead donor rule, even if not its technicalities.

Cardiac Amyloidosis: Overlooked, Underappreciated, and Treatable.

Cardiac amyloidosis (CA) is an infiltrative and restrictive cardiomyopathy that leads to heart failure, reduced quality of life, and death. The disease has two main subtypes, transthyretin cardiac amyloidosis (ATTR-CA) and immunoglobulin light chain cardiac amyloidosis (AL-CA), characterized by the nature of the infiltrating protein. ATTR-CA is further subdivided into wild-type (ATTRwt-CA) and variant (ATTRv-CA) based on the presence or absence of a mutation in the transthyretin gene. CA is significantly underdiagnosed and increasingly recognized as a cause of heart failure with preserved ejection fraction. Advances in diagnosis that employ nuclear scintigraphy to diagnose ATTR-CA without a biopsy and the emergence of effective treatments, including transthyretin stabilizers and silencers, have changed the landscape of this field and render early and accurate diagnosis critical. This review summarizes the epidemiology, pathophysiology, diagnosis, prognosis, and management of CA with an emphasis on the significance of recent developments and suggested future directions.

Electrical impedance tomography in the adult intensive care unit: clinical applications and future directions.

PURPOSE OF REVIEW: Electrical impedance tomography (EIT) is a novel, noninvasive, radiation-free, bedside imaging and monitoring tool to assess and visualize regional distribution of lung ventilation and perfusion. Although primarily a research tool, rapidly emerging data are beginning to define its clinical role, and it is poised to become a ubiquitous addition to the arsenal of the intensive care unit (ICU). In this review, we summarize the data supporting clinical use of EIT in adult ICUs, with an emphasis on appropriate application while highlighting future directions. RECENT FINDINGS: Recent major studies have primarily focused on the role of EIT in setting correct positive end-expiratory pressure to balance regional overdistention and collapse. Over the last few years, our Lung Rescue Team has demonstrated that incorporating EIT into a multimodal approach to individualizing ventilator management can improve outcomes, particularly in the obese. We also review recent data surrounding EIT use during COVID, as well as other broad potential applications. SUMMARY: As EIT becomes more common and its clinical role more defined, intensivists will benefit from a clear understanding of its applications and limitations.

Risk Factors for 30-day Hospital Readmission for Diverticular Hemorrhage.

INTRODUCTION: The 2010 Affordable Care Act introduced the Hospital Readmissions Reduction Program to reduce health care utilization. Diverticular disease and its complications remain a leading cause of hospitalization among gastrointestinal disease. We sought to determine risk factors for 30-day hospital readmissions after hospitalization for diverticular bleeding. MATERIALS AND METHODS: We utilized the 2013 National Readmission Database sponsored by the Agency for Healthcare Research and Quality focusing on hospitalizations with the primary or secondary discharge diagnosis of diverticular hemorrhage or diverticulitis with hemorrhage. We excluded repeat readmissions, index hospitalizations during December and those resulting in death. Our primary outcome was readmission within 30 days of index hospital discharge. Secondary outcomes of interest included medical and procedural comorbid risk factors. The data were analyzed using logistic regression analysis. RESULTS: In total, 29,090 index hospitalizations for diverticular hemorrhage were included. There were 3484 (12%) 30-day readmissions with recurrent diverticular hemorrhage diagnosed in 896 (3%).Index admissions with renal failure [odds ratio (OR), 1.31; 95% confidence interval (CI), 1.19-1.43], congestive heart failure (OR, 1.30; 95% CI, 1.17-1.43), chronic pulmonary disease (OR, 1.19; 95% CI, 1.09-1.29), coronary artery disease (OR, 1.12; 95% CI, 1.03-1.21), atrial fibrillation (OR, 1.12; 95% CI, 1.02-1.22) cirrhosis (OR, 1.95; 95% CI, 1.29-2.93, performance of blood transfusion (OR, 1.23; 95% CI, 1.15-1.33), and abdominal surgery (OR, 1.24; 95% CI, 1.03-1.49) had increased risk of 30-day readmission. CONCLUSIONS: The 30-day readmission rate for diverticular hemorrhage was 12% with multiple identified comorbidities increasing readmission risk.

Myocardial Contraction Fraction by M-Mode Echocardiography Is Superior to Ejection Fraction in Predicting Mortality in Transthyretin Amyloidosis.

BACKGROUND: Transthyretin amyloidosis (ATTR) is often associated with cardiac involvement manifesting as conduction disease as well as restrictive cardiomyopathy causing heart failure and death. Myocardial contraction fraction (MCF), the ratio of left ventricular stroke volume (SV) to myocardial volume (MV), is a volumetric measure of myocardial shortening that is superior to ejection fraction (EF) in predicting mortality in patients with primary amyloid light chain cardiac amyloidosis. We hypothesized that MCF would be an independent predictor of survival in TTR-CA. METHODS AND RESULTS: MCF was derived from 2-dimensional echocardiography-guided M-mode data for 530 subjects in the Transthyretin Amyloidosis Outcomes Survey (THAOS) database: age 61 ± 16years, 74% male, 158 wild-type (ATTRwt) and 372 mutant (ATTRm), follow-up 1.5 ± 1.7years. Using multivariate Cox proportional hazard regression models, MCF <25% was highly associated with survival (hazard ratio [HR] 8.5, 95% confidence interval [CI] 4.8-14.9,-P < .0001), which was stronger than the association of EF dichotomized at 50% (HR 2.8, 95% CI 1.8-4.4; P < .0001). MCF <25% remained significantly predictive of survival in a multivariate model that included systolic blood pressure, estimated glomerular filtration rate <65 mL·min-1·m-2, New York Heart Association (NYHA) functional class, and health status based on the EuroQol-5D-3L questionnaire (area under the receiver operating characteristic curve [AUC] = 0.83, 95% CI 0.78-0.89). CONCLUSIONS: MCF was superior to EF in predicting mortality in patients with ATTR. A predictive model combining MCF with systolic blood pressure, renal function, NYHA functional class, and health status was strongly associated with survival in patients with ATTR. CLINICALTRIALS. GOV IDENTIFIER: NCT00628745.

Unveiling transthyretin cardiac amyloidosis and its predictors among elderly patients with severe aortic stenosis undergoing transcatheter aortic valve replacement.

AIMS: Transthyretin cardiac amyloidosis (ATTR-CA) has been reported in patients with aortic stenosis (AS) but its prevalence and phenotype are not known. We examine elderly patients with severe symptomatic AS undergoing transcatheter aortic valve replacement (TAVR) and determine the prevalence and phenotype of ATTR-CA non-invasively. METHODS AND RESULTS: We performed technetium-99m pyrophosphate (99mTc-PYP) cardiac scintigraphy prospectively on patients who underwent TAVR, to screen for ATTR-CA. Transthoracic echocardiography and speckle-strain imaging were performed. We assessed the association of several parameters with ATTR-CA using multivariable logistic regression and constructed receiver operating curves to evaluate the best predictors of ATTR-CA. Among 151 patients (mean age 84 ± 6 years, 68% men), 16% (n = 24) screened positive for ATTR-CA with 99mTc-PYP scintigraphy. Compared with patients without ATTR-CA, ATTR-CA patients had a thicker interventricular septum (1.3 vs. 1.1 cm, P = 0.007), higher left ventricular (LV) mass index (130 vs. 98 g/m2, P = 0.002), and lower stroke volume index (30 vs. 36 mL/m2, P = 0.009). ATTR-CA patients had advanced diastolic dysfunction with higher E/A ratio (2.3 vs. 0.9, P = 0.001) and lower deceleration time (176 vs. 257 ms, P < 0.0001); impairment in systolic function with lower ejection fraction (48% vs. 56%, P = 0.011), myocardial contraction fraction (26 vs. 41, P < 0.0001), and average of lateral and septal mitral annular tissue Doppler S' (4.0 vs. 6.6 cm/s, P < 0.0001). While ATTR-CA patients had more impaired global longitudinal strain (-12 vs. -16%, P = 0.007), relative apical longitudinal strain was the same regardless of ATTR-CA diagnosis (0.98 vs. 0.98, P = 0.991). Average S' best predicted ATTR-CA in multivariable logistic regression (odds ratio 16.67 per 1 cm/s decrease with AUC 0.96, 95% confidence interval 0.90-0.99, P = 0.002) with a value ≤6 conferring 100% sensitivity for predicting a positive 99mTc-PYP amyloid scan. CONCLUSIONS: Transthyretin cardiac amyloidosis is prevalent in 16% of patients with severe calcific AS undergoing TAVR and is associated with a severe AS phenotype of low-flow low-gradient with mildly reduced ejection fraction. Average tissue Doppler mitral annular S' of < 6 cm/s may be a sensitive measure that should prompt a confirmatory 99mTc-PYP scan and subsequent testing for ATTR-CA. Prospective assessment of outcomes after TAVR is needed in patients with and without ATTR-CA.

Transthyretin Cardiac Amyloidosis in Older Americans.

Wild-type transthyretin cardiac amyloidosis (ATTRwt), formerly called senile cardiac amyloidosis (SCA), is almost exclusively a disorder of older adults. As the population ages, the diagnosis of ATTRwt will increase, making it the most common form of cardiac amyloidosis. An important precondition to reduce underdiagnosis and misdiagnosis is to maintain a high index of suspicion for cardiac amyloidosis. Several clues can be gleaned from the clinical history, physical exam, electrocardiography, and noninvasive imaging techniques. Nuclear scintigraphy agents using 99mTc-phosphate derivatives combined with assessment for monoclonal proteins are eliminating the need for tissue confirmation in ATTR. Morbidity and mortality from ATTRwt cardiac amyloid is high and the emergence of numerous therapies based on a biologic understanding of the pathophysiology of this condition, including drugs to inhibit the synthesis of TTR, stabilize TTR, and degrade or extract amyloid, provides new hope for those afflicted. This review briefly covers the epidemiology, pathophysiology, and clinical manifestations, as well as diagnostic strategies and treatment, of ATTR in older adults.

Refractory Autoimmune Hepatitis: Beyond Standard Therapy.

Autoimmune hepatitis (AIH) can be difficult to control, particularly in some African-Americans. When standard therapy of prednisone and azathioprine is ineffective or poorly tolerated, alternative therapies are resorted to. We report two patients with AIH who were refractory to or intolerant of standard therapy. They initially responded to a combination of tacrolimus and MMF, but eventually developed acute flares of the disease that had to be managed with sirolimus, and in one case, rituximab, to achieve remission.

Venovenous Extracorporeal Membrane Oxygenation Candidacy Decision-Making: Lessons and Hypotheses From a Single-Center Observational Analysis.

BACKGROUND: Use of venovenous extracorporeal membrane oxygenation (ECMO) is increasing, but candidacy selection processes are variable and subject to bias. RESEARCH QUESTION: What are the reasons behind venovenous ECMO candidacy decisions, and are decisions made consistently across patients? STUDY DESIGN AND METHODS: Prospective observational study of all patients, admitted or outside hospital referrals, considered for venovenous ECMO at a tertiary referral center. Relevant clinical data and reasons for candidacy determination were cross-referenced with other noncandidates and candidates and were assessed qualitatively. RESULTS: Eighty-one consultations resulted in 44 noncandidates (54%), 29 candidates (36%; nine of whom subsequently underwent cannulation), and eight deferred decisions (10%). Fifteen unique contraindications were identified, variably present across all patients. Five contraindications were invoked as the sole reason to deny ECMO to a patient. In patients with three or more contraindications, additional contraindications were cited even if the severity was relatively minor. All but four contraindications invoked to deny ECMO to a patient were nonprohibitive for at least one other candidate. Contraindications documented in noncandidates were present but not mentioned in 21 other noncandidates (47%). Twenty-six candidates (90%) had at least one contraindication that was prohibitive in a noncandidate, including a contraindication that was the sole reason to deny ECMO. Contraindications were proposed as informing three prognostic domains, through which patterns of inconsistency could be understood better: (1) irreversible underlying pulmonary process, (2) unsurvivable critical illness, and (3) clinical condition too compromised for meaningful recovery. INTERPRETATION: ECMO candidacy decisions are inconsistent. We identified four patterns of inconsistency in our center and propose a three-domain model for understanding and categorizing contraindications, yielding five lessons that may improve candidacy decision processes until further research can guide practice more definitively.

Clinical significance of discordant positive hepatitis C virus transcription-mediated amplification following end of treatment response.

BACKGROUND: Polymerase chain reaction (PCR) assays are the standard for detecting hepatitis C virus viremia. The transcription-mediated amplification (TMA)-based assay is more sensitive. METHODS: We retrospectively reviewed the charts of patients with a post-end of treatment (EOT) PCR-/TMA+ result to assess the clinical significance of a positive TMA result after a PCR negative EOT response or sustained viral response (SVR). Patients were divided into Group 1: PCR-/TMA+ after EOT response but during 24 week follow-up (n = 4); and Group 2: PCR-/TMA+ after SVR (n = 11). RESULTS: All Group 1 patients achieved SVR. No Group 2 patients became PCR positive or had a rise in ALT. The TMA subsequently became negative in 6/7 patients with follow-up evaluation. CONCLUSIONS: A discordant positive TMA post-EOT response or SVR did not seem to be clinically significant. This finding supports the possibility that patients with SVR have an acquired immune surveillance that prevents low-level viremia from progressing to clinical relapse.

ARDS With Pneumothorax in a Young Adult.

CASE PRESENTATION: A 19-year-old, previously healthy man presented with 3 days of cough, high-grade fevers (40 °C), and dyspnea. Apart from a resolved history of seizures not requiring medications, he had no medical or surgical history. He had no known drug allergies. He took montelukast for allergies and trimethoprim-sulfamethoxazole (TMP-SMX) for 2 weeks before admission for acne, but no other medications, including over-the-counter medications and supplements. He had animal exposures to a new puppy and a friend's bird. He had no history of smoking, vaping, or recreational drug use. His paternal grandmother had rheumatoid arthritis.

Non-alcoholic fatty liver disease (NAFLD): why you should care, when you should worry, what you should do.

For the diabetologist, non-alcoholic fatty liver disease (NAFLD) is important at both ends of its spectrum. It is an early warning sign of future risk of metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. It may also lead to late life-threatening sequela of diabetes mellitus in the event of progression to liver failure or hepatocellular carcinoma. This review will highlight the recent progress in understanding the natural history of non-alcoholic fatty liver disease and in developing a rational approach to its diagnosis, staging, and management. The pandemic prevalence of non-alcoholic fatty liver disease in Western countries necessitates both a high index of suspicion to identify cases and a non-invasive approach to staging, which is best achieved with clinical/biochemical panels and transient elastography. Lifestyle modification is the cornerstone of management. Recent clinical trials provide support for pharmacologic therapies directed at the metabolic syndrome and at protecting the liver but more data are needed. Bariatric surgery is appropriate for high-risk patients who fail conservative management. Patients with liver failure or hepatocellular carcinoma may be candidates for liver transplantation.

Sump syndrome of the remnant common bile duct following a living donor liver transplant.

Sump syndrome - a collection of digested food, debris, stones, bile, and bacteria in a poorly drained, bile duct reservoir - occurs most commonly after a side-to-side choledochoduodenostomy. As choledochoduodenostomies are now less common, sump syndrome is more often characterized as a complication of Roux-en-Y hepaticojejunostomies; however, most cases occur at the hepaticojejunostomy anastomosis. We report a rare case of sump syndrome in the intra-pancreatic remnant common bile duct in a patient with primary sclerosing cholangitis following living donor liver transplant via Roux-en-Y hepaticojejunostomy. Our patient had a history of end-stage liver disease secondary to primary sclerosing cholangitis but presented with recurrent bacteremia and symptoms of acute cholangitis following her transplant. While this complication has not been reported in this population, we know that those with primary sclerosing cholangitis and those undergoing liver transplantation are at very high risk for biliary complications and strictures. Liver transplant is currently our only treatment for primary sclerosing cholangitis, and more than any other group, they are referred for living donor liver transplantation, preferably via Roux-en-Y hepaticojejunostomy. Thus, our patient's clinical scenario is not uncommon and demonstrates a source of serious infection of which providers must be aware.

Severe Tricuspid Valve Endocarditis: A Tale of 2 Circuits.

A 25-year-old woman with severe tricuspid valve endocarditis and septic pulmonary emboli required VA-ECMO for recurrent hypoxemia-induced cardiac arrest. We present the clinical challenges requiring ECMO circuit reconfiguration and a percutaneous approach for vegetation debulking. (Level of Difficulty: Intermediate.).