Heart-liver-kidney transplantation for AL amyloidosis using normothermic recovery and storage from a donor following circulatory death: Short-term outcome in a first-in-world experience.

AL amyloidosis is a rare condition characterized by the overproduction of an unstable free light chain, protein misfolding and aggregation, and extracellular deposition that can progress to multiorgan involvement and failure. To our knowledge, this is the first worldwide report to describe triple organ transplantation for AL amyloidosis and triple organ transplantation using thoracoabdominal normothermic regional perfusion recovery with a donation from a circulatory death (DCD) donor. The recipient was a 40-year-old man with multiorgan AL amyloidosis with a terminal prognosis without multiorgan transplantation. An appropriate DCD donor was selected for sequential heart, liver, and kidney transplants via our center's thoracoabdominal normothermic regional perfusion pathway. The liver was additionally placed on an ex vivo normothermic machine perfusion, and the kidney was maintained on hypothermic machine perfusion while awaiting implantation. The heart transplant was completed first (cold ischemic time [CIT]: 131 minutes), followed by the liver transplant (CIT: 87 minutes, normothermic machine perfusion: 301 minutes). Kidney transplantation was performed the following day (CIT: 1833 minutes). He is 8 months posttransplant without evidence of heart, liver, or kidney graft dysfunction or rejection. This case highlights the feasibility of normothermic recovery and storage modalities for DCD donors, which can expand transplant opportunities for allografts previously not considered for multiorgan transplantations.

Intravenous acetaminophen associated with acute liver failure.

A woman in her mid-60s, without known liver disease, was admitted to the hospital with a partial malignant colonic obstruction. Over a 6-day course, she received a total of 13 g of intravenous acetaminophen not exceeding 4 g over a 24-hour period. She developed encephalopathy and an international normalised ratio of 6.1 meeting criteria for acute liver failure (ALF). She was treated with intravenous N-acetyl cysteine and other causes of liver failure were excluded. The patient was discharged with subsequent resolution of encephalopathy and improvement of her liver chemistries. Though ALF is rare, in countries where acetaminophen is readily available, almost 50% of ALF cases are acetaminophen-induced hepatotoxicity and most have been documented as oral ingestion of acetaminophen. We present a rare case of intravenous acetaminophen-induced ALF.

Heart failure associated with ustekinumab therapy for treatment of Crohn's Disease.

A man in his 60s with penetrating ileocolonic Crohn's disease (CD), recently started on ustekinumab therapy, presented with new onset dyspnoea, paroxysmal nocturnal dyspnoea and dependent oedema. He was diagnosed with heart failure (HF) 10 months after starting ustekinumab therapy. His symptoms resolved with discontinuation of ustekinumab and he had recovery of his cardiac function. Though initial studies that led to the U.S Food and Drug Administration (FDA)approval for ustekinumab did not detect a signal for HF, postmarketing surveillance has detected rare cases of HF after initiation of the medication. This is one of the few reported cases of HF associated with ustekinumab therapy for CD.

Selective Androgen Receptor Modulator-Induced Liver Injury in Active Duty Male.

Selective androgenic receptor modulators (SARMs) are extensively advertised as safer and more effective analogues to traditional androgenic anabolic steroids, yet there are increasing cases of hepatotoxicity secondary to their use. We present the case of a previously healthy young active duty Marine who presented with cholestatic liver injury secondary to SARM use. This is the first reported case in a service member and contributes to the growing amount of evidence regarding the potential detrimental effects of SARMs. It also illustrates the impact of SARMs on military members and overall mission readiness as his treatment course included hospitalization and placement in a non-deployable status until recovery from his liver injury. Additional steps should be taken to increase awareness in order to protect service members and sustain readiness.

June: open-source individual-based epidemiology simulation.

We introduce June, an open-source framework for the detailed simulation of epidemics on the basis of social interactions in a virtual population constructed from geographically granular census data, reflecting age, sex, ethnicity and socio-economic indicators. Interactions between individuals are modelled in groups of various sizes and properties, such as households, schools and workplaces, and other social activities using social mixing matrices. June provides a suite of flexible parametrizations that describe infectious diseases, how they are transmitted and affect contaminated individuals. In this paper, we apply June to the specific case of modelling the spread of COVID-19 in England. We discuss the quality of initial model outputs which reproduce reported hospital admission and mortality statistics at national and regional levels as well as by age strata.

Volume Resuscitation and Progression to Organ Failure in Shiga Toxin-Producing Escherichia coli Infection in Adults.

Shiga toxin-producing Escherichia coli infection is associated with dysentery and the hemolytic uremic syndrome, marked by the triad of microangiopathic hemolytic anemia, acute kidney failure, and thrombocytopenia. Descriptions of Shiga toxin-producing Escherichia coli outbreaks causing hemolytic uremic syndrome in adults are sparse, and management strategies are largely adapted from pediatric literature where aggressive fluid administration is recommended. However, these may not be ideal for adults. DESIGN: We present a case series of an Shiga toxin-producing Escherichia coli outbreak in U.S. Marine Corps recruits. SETTING: We review the clinical course, laboratory data, and fluid resuscitation used in hospitalized patients during the 2017 Shiga toxin-producing Escherichia coli outbreak at Marine Corps Recruit Depot, San Diego. PATIENTS: Patients admitted to the hospital for complications from Shiga toxin-producing Escherichia coli infection. All were previously healthy men between the ages of 17 and 20 years. INTERVENTIONS: Isotonic crystalloid fluid resuscitation during the first 72 hours. MEASUREMENTS AND MAIN RESULTS: Of 244 identified cases of Shiga toxin-producing Escherichia coli infection, 30 required hospitalization, 15 progressed to hemolytic uremic syndrome, and five required hemodialysis. Patients were admitted and given aggressive IV fluid hydration. Those who progressed to hemolytic uremic syndrome received on average 8.4 L of isotonic crystalloid over the initial 72 hours, with up to 18% of body weight delivered. The six critically ill patients received a mean 12.2 L in the first 72 hours. Those who did not progress to hemolytic uremic syndrome received a mean 3.0 L of crystalloid. If oligoanuria developed, a net-even fluid balance was maintained. The amount of volume infused was not associated with improved outcomes. The patients with the highest fluid balance totals more often required dialysis than those who received less fluid. One hemolytic uremic syndrome patient developed flash pulmonary edema. CONCLUSIONS: The aggressive IV hydration protocols (as a percentage of body weight) in the pediatric literature may not be applicable to adults diagnosed with hemolytic uremic syndrome. A more conservative fluid strategy in adults with hemolytic uremic syndrome merits further investigation.

Reevaluating Goals of Therapy in Primary Biliary Cholangitis: Is Good Enough Is Not Good Enough Anymore?

Primary biliary cholangitis (PBC) is an autoimmune-mediated inflammatory cholestatic liver disease, which can progress to cirrhosis. This issue of The American Journal of Gastroenterology features the results of the GLOBAL PBC Study Group evaluating patients with PBC over a 10-year period. Although biochemical response was evaluated in previous studies, this study showed that bilirubin levels ≤0.6 upper limit of normal or normal levels of alkaline phosphatase are associated with the lowest risk for liver transplantation or death in patients with PBC.

Mass-Discrepancy Acceleration Relation: A Natural Outcome of Galaxy Formation in Cold Dark Matter Halos.

We analyze the total and baryonic acceleration profiles of a set of well-resolved galaxies identified in the eagle suite of hydrodynamic simulations. Our runs start from the same initial conditions but adopt different prescriptions for unresolved stellar and active galactic nuclei feedback, resulting in diverse populations of galaxies by the present day. Some of them reproduce observed galaxy scaling relations, while others do not. However, regardless of the feedback implementation, all of our galaxies follow closely a simple relationship between the total and baryonic acceleration profiles, consistent with recent observations of rotationally supported galaxies. The relation has small scatter: Different feedback implementations-which produce different galaxy populations-mainly shift galaxies along the relation rather than perpendicular to it. Furthermore, galaxies exhibit a characteristic acceleration g_{†}, above which baryons dominate the mass budget, as observed. These observations, consistent with simple modified Newtonian dynamics, can be accommodated within the standard cold dark matter paradigm.

The Association between Sexually Transmitted Infections, Length of Service and Other Demographic Factors in the U.S. Military.

BACKGROUND: Numerous studies have found higher rates of sexually transmitted infections (STIs) among military personnel than the general population, but the cumulative risk of acquiring STIs throughout an individual's military career has not been described. METHODS: Using ICD-9 diagnosis codes, we analyzed the medical records of 100,005 individuals from all service branches, divided in equal cohorts (n = 6,667) between 1997 and 2011. As women receive frequent STI screening compared to men, these groups were analyzed separately. Incidence rates were calculated for pathogen-specific STIs along with syndromic diagnoses. Descriptive statistics were used to characterize the individuals within each accession year cohort; repeat infections were censored. RESULTS: The total sample included 29,010 females and 70,995 males. The STI incidence rates (per 100 person-years) for women and men, respectively, were as follows: chlamydia (3.5 and 0.7), gonorrhea (1.1 and 0.4), HIV (0.04 and 0.07) and syphilis (0.14 and 0.15). During the study period, 22% of women and 3.3% of men received a pathogen-specific STI diagnosis; inclusion of syndromic diagnoses increased STI prevalence to 41% and 5.5%, respectively. In multivariate analyses, factors associated with etiologic and syndromic STIs among women included African American race, younger age and fewer years of education. In the overall sample, increasing number of years of service was associated with an increased likelihood of an STI diagnosis (p<0.001 for trend). CONCLUSION: In this survey of military personnel, we found very high rates of STI acquisition throughout military service, especially among women, demonstrating that STI-related risk is significant and ongoing throughout military service. Lower STI incidence rates among men may represent under-diagnosis and demonstrate a need for enhancing male-directed screening and diagnostic interventions.

Is delayed operative treatment worth the trouble with perforated appendicitis is children?

BACKGROUND: Approximately 30% to 50% of appendicitis in children is already perforated at presentation. The optimal management of these children remains controversial. METHODS: Ninety-six children (aged 2 to 16 years) were treated for perforated appendicitis. Seventy-one underwent immediate appendectomy and drainage of abscess, if present (group I). In the other 25 an attempt was made to treat with intravenous antibiotics, combined with transrectal (4) or percutaneous (2) drainage of abscess. This treatment was successful in 16 patients (group II), who underwent appendectomy 6 to 8 weeks later, and unsuccessful in 9 patients (group III), who underwent appendectomy 3 to 12 days later. RESULTS: The mean length of stay was as follows: group I, 6.7 days; group II, 8.9 days; and group III, 10.9 days (not significant). The white blood cell count (WBC) at presentation was group I, 18.6 K; group II, 17.9 K; group III, 18.8 K. The percent fall of WBC on day 4 was group I, 55%; group II, 25.5%; group III, 17% (P >0.05 versus groups I and II). Twenty of 71 patients in group I (28%) developed wound infection (5), pelvic abscess (14), and pancreatitis (1), while 2 of 16 (12.5%) of group II and 1 of 9 (11%) of group III patients required readmission (both P <0.05 versus group I). CONCLUSIONS: These data show that initial antibiotic treatment of perforated appendicitis in children, followed by interval appendectomy, is useful for a select group who present with little or no peritonitis, slightly elevated temperature, and WBC that falls at least 25% within 3 to 4 days.

The impact of surgery on infants born at extremely low birth weight.

PURPOSE: The aim of this study was to determine the outcome of extremely low-birth-weight infants (ELBW) requiring surgical interventions for the complications of prematurity METHODS: One hundred eighty-seven consecutive infants with a birth weight less than 1,000 g treated over a 5-year period were reviewed. Outcome variables included number and types of surgical procedures; length of stay; survival rate and; pulmonary, neurologic, and gastrointestinal morbidity. RESULTS: Surgical interventions were required in 66 (35%) infants (group S) weighing less than 1,000 g at birth (33% necrotizing enterocolitis/bowel perforation, 36% patent ductus arteriosus, 56% other). Overall mortality rate for group S infants was 23% compared with 22% for those not requiring surgery (group NS; P >.05). Mortality rate rose to 38% for those infants undergoing procedures for necrotizing enterocolitis/bowel perforation (P <.05). Although neurologic and pulmonary morbidity for the entire population were high, there was no difference in their incidence between surgical and nonsurgical groups (29% v 26% and 44% v 65%, group S v group NS, respectively; P >.05). CONCLUSIONS: These data suggest an improving outcome for ELBW infants. Common associated morbidities of prematurity do not appear adversely affected by surgical interventions supporting an aggressive approach to the care of these infants at the extreme of life.