Acute-on-Chronic Liver Failure Incited by Cyclin-Dependent Kinase Inhibitor Therapy for Breast Cancer Effectively Treated With Liver Transplantation.

Cyclin-dependent kinase 4/6 inhibitors are targeted therapies demonstrated to significantly improve overall survival as adjuvant treatment of estrogen receptor-positive breast cancers. Although intended to preferentially arrest cell cycle transitions in tumor cells, these agents can have undesirable systemic side effects, including hepatotoxicity. We report the first case of cyclin-dependent kinase 4/6 inhibitor therapy leading to acute-on-chronic liver failure requiring liver transplantation. Our case highlights the multidisciplinary approach required to manage acute-on-chronic liver failure induced by cancer-directed therapies in those with extrahepatic malignancies.

TEG-based transfusion protocol is associated with decreased blood product use without increased risk of hemoperitoneum.

BACKGROUND: Thromboelastography (TEG) informs the need for blood product transfusions to prevent procedural bleeding complications in patients with cirrhosis. We aimed to evaluate the impact of using a TEG-based transfusion protocol on blood product utilization before paracentesis and the post-paracentesis hemoperitoneum (PPH) incidence. METHODS: We conducted an ambispective analysis of patients with cirrhosis who underwent paracentesis from 2017 to 2021. In May 2019, we enacted a TEG-based transfusion protocol to guide pre-paracentesis blood product use. Patients with platelets < 20,000 or international normalized ratio ≥ 4 underwent TEG and received blood products if r value > 10 min or MA <30 mm. Patients were divided into pre-TEG and post-TEG protocol cohorts based on the date of paracentesis. Pre-paracentesis blood product transfusions in the form of platelets, fresh frozen plasma, and cryoprecipitates were recorded. PPH was defined as a decrease in hemoglobin of ≥1 g and the presence of blood on diagnostic imaging and/or the need for therapeutic intervention. RESULTS: A total of 483 patients underwent 1281 paracenteses. The main etiologies of cirrhosis were alcohol (43%) and NASH (25%), and the mean MELD-sodium was 22±6. Pre-TEG and post-TEG protocol cohort sizes were similar: 253 patients and 607 paracenteses versus 230 patients and 674 paracenteses. After TEG-protocol implementation, blood product transfusions decreased significantly (228 vs. 49 products, p<0.001) with associated cost savings. One patient in each cohort developed PPH. CONCLUSION: Implementation of a pre-paracentesis TEG-based transfusion protocol for patients with cirrhosis successfully resulted in decreased blood product use with no associated increase in incidence of PPH.

Positron emission tomography myocardial perfusion imaging (PET MPI) findings predictive of post-liver transplant major adverse cardiac events.

Positron emission tomography myocardial perfusion imaging (PET MPI) is a noninvasive diagnostic test capable of detecting coronary artery disease, structural heart disease, and myocardial flow reserve (MFR). We aimed to determine the prognostic utility of PET MPI to predict post-liver transplant (LT) major adverse cardiac events (MACE). Among the 215 LT candidates that completed PET MPI between 2015 and 2020, 84 underwent LT and had 4 biomarker variables of clinical interest on pre-LT PET MPI (summed stress and difference scores, resting left ventricular ejection fraction, global MFR). Post-LT MACE were defined as acute coronary syndrome, heart failure, sustained arrhythmia, or cardiac arrest within the first 12 months post-LT. Cox regression models were constructed to determine associations between PET MPI variable/s and post-LT MACE. The median LT recipient age was 58 years, 71% were male, 49% had NAFLD, 63% reported prior smoking, 51% had hypertension, and 38% had diabetes mellitus. A total of 20 MACE occurred in 16 patients (19%) at a median of 61.5 days post-LT. One-year survival of MACE patients was significantly lower than those without MACE (54% vs. 98%, p =0.001). On multivariate analysis, reduced global MFR ≤1.38 was associated with a higher risk of MACE [HR=3.42 (1.23-9.47), p =0.019], and every % reduction in left ventricular ejection fraction was associated with an 8.6% higher risk of MACE [HR=0.92 (0.86-0.98), p =0.012]. Nearly 20% of LT recipients experienced MACE within the first 12 months of LT. Reduced global MFR and reduced resting left ventricular ejection fraction on PET MPI among LT candidates were associated with increased risk of post-LT MACE. Awareness of these PET-MPI parameters may help improve cardiac risk stratification of LT candidates if confirmed in future studies.

The Impact of COVID-19 on Radiotherapy Services in Scotland, UK: A Population-based Study.

AIMS: The effect of the COVID-19 pandemic on cancer radiotherapy services is largely unknown. The aim of the present study was to investigate the impact of the resultant contingency plans on radiotherapy cancer services in Scotland. MATERIALS AND METHODS: Detailed data of radiotherapy activity at our centre were collected from 1 April 2019 to 31 March 2021. Differences in mean weekly radiotherapy courses, dose and fractionation patterns and treatment intent were compared with corresponding pre-pandemic months for all treatment sites. Qualitative data were collected for a subgroup of radical radiotherapy patients. RESULTS: Total radiotherapy courses decreased from 6968 to 6240 (-10%) compared with the previous year, prior to the pandemic. Average weekly radiotherapy courses delivered were 134 (standard deviation ±13), decreasing by 10% to 120 (standard deviation 15) (Welch's t-test, P < 0.001). The greatest decrease in new start treatment courses was observed from May to August 2020 (-7.7%, -24.0%, -16.7% and -18.7%) compared with the corresponding months in 2019. A significant reduction was seen for female patients <70 years (-16%) compared with females >70 years (-8%) or their male counterparts (-7% and -6%, respectively). By diagnosis, the largest reductions between pre- and post-pandemic levels were for anal (-26%), breast (-18%) and prostate (-14%) cancer. Contrarily, a significant increase was found for bladder (28%) and oesophageal (11%) cancers. CONCLUSIONS: Over the first 12 months of the COVID-19 pandemic, radiotherapy activity significantly decreased compared with the 12 months prior. Due to issued guidance, the use of hypofractionated regimens increased, contributing to the reduction in treatments for some tumour sites. An increase in other tumour sites can probably be attributed to the reduction or cancellation of surgical interventions. These results will inform our understanding of the indirect consequences of the pandemic on radiotherapy services.

The closing survival gap after liver transplantation for hepatocellular carcinoma in the United States.

BACKGROUND: Socio-economic inequalities among different racial/ethnic groups have increased in many high-income countries. It is unclear, however, whether increasing socio-economic inequalities are associated with increasing differences in survival in liver transplant (LT) recipients. METHODS: Adults undergoing first time LT for hepatocellular carcinoma (HCC) between 2002 and 2017 recorded in the Scientific Registry of Transplant Recipients (SRTR) were included and grouped into three cohorts. Patient survival and graft survival stratified by race/ethnicity were compared among the cohorts using unadjusted and adjusted analyses. RESULTS: White/Caucasians comprised the largest group (n=9,006, 64.9%), followed by Hispanic/Latinos (n=2,018, 14.5%), Black/African Americans (n=1,379, 9.9%), Asians (n=1,265, 9.1%) and other ethnic/racial groups (n=188, 1.3%). Compared to Cohort I (2002-2007), the 5-year survival of Cohort III (2012-2017) increased by 18% for Black/African Americans, by 13% for Whites/Caucasians, by 10% for Hispanic/Latinos, by 9% for patients of other racial/ethnic groups and by 8% for Asians (All P values<0.05). Despite Black/African Americans experienced the highest survival improvement, their overall outcomes remained significantly lower than other ethnic∕racial groups (adjusted HR for death=1.20; 95%CI 1.05-1.36; P=0.005; adjusted HR for graft loss=1.21; 95%CI 1.08-1.37; P=0.002). CONCLUSION: The survival gap between Black/African Americans and other ethnic/racial groups undergoing LT for HCC has significantly decreased over time. However, Black/African Americans continue to have the lowest survival among all racial/ethnic groups.

Mastering Core Recommendations during HEPAtology ROUNDS in Patients with Advanced Chronic Liver Disease.

Efficient and thorough care of hospitalized patients with advanced chronic liver disease is of utter importance to improve outcomes and optimize quality of life. This requires understanding current evidence and best practices. To facilitate focus on up-to-date knowledge and a practical approach, we have created the HEPA-ROUNDS mnemonic while outlining a practical review of the literature with critical appraisal for the busy clinician. The HEPA-ROUNDS mnemonic provides a structured approach that incorporates critical concepts in terms of prevention, management, and prognostication of the most common complications frequently encountered in patients with advanced chronic liver disease. In addition, implementing the HEPA-ROUNDS mnemonic can facilitate education for trainees and staff caring for patients with advanced chronic liver disease.

Presence of any degree of coronary artery disease among liver transplant candidates is associated with increased rate of post-transplant major adverse cardiac events.

The impact of coronary artery disease (CAD) among liver transplant candidates (LTC) on post-LT clinical outcomes remains unclear. The aim of this study is to determine association of presence and severity of CAD on post-LT major adverse cardiac events (MACE) including cardiac-associated mortality. We conducted a retrospective cohort analysis of 231 patients who underwent diagnostic coronary angiogram (DCA) during their LT evaluation at a tertiary medical center from 2012-2017. Patients were analyzed based on degree of CAD (no CAD, non-obstructive CAD [< 50% stenosis], obstructive CAD [≥50% stenosis]) per DCA results. MACE were noted at 30 days, 1 year, 3 years, and 5 years post-LT, and Kaplan-Meier curves were used to determine post-LT MACE-free probability. LTC with any CAD, including non-obstructive CAD, had lower MACE-free probability at all post-LT time points (0.94 vs 0.65 at 30 days, P = .001; 0.87 vs 0.59 at 1 year, P = .002; 0.87 vs 0.41 at 3 years, P < .001; 0.87 vs 0.37 at 5 years, P < .001). Identification of and medical intervention for non-obstructive CAD should be considered in all LTC, though further studies are necessary to determine optimal medical interventions to mitigate MACE risk in this cohort.

The clinical nurse specialist's role in head and neck cancer care: United Kingdom National Multidisciplinary Guidelines.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. It discusses the role of the clinical nurse specialist in the head and neck cancer patient journey and provides recommendations on the clinical nurse specialist led assessments and interventions for this group of patients receiving cancer care. Recommendations • All cancer patients should meet a clinical nurse specialist at the point of diagnosis. (R) • Clinical nurse specialists must act as gate keeper to the patients' cancer pathway to provide a seamless journey. (R) • Holistic needs assessment should be completed at different stages of the patient's pathway to reflect the changes of the patients' needs. (R) • Clinical nurse specialists to be part of local and national initiatives for health promotion and raising awareness in the public domain. (G) • Clinical nurse specialists should lead in redesigning of services and policies to ensure they are responsive to patient's needs for the future. (G) • Treatment summaries should become part of practice to provide good communication between primary and secondary care to enable continuity of care for the patient. (G).

Neurovascular Interactions in the Neurologically Compromised Neonatal Brain.

Neurological brain injuries such as hypoxic ischaemic encephalopathy (HIE) and associated conditions such as seizures have been associated with poor developmental outcome in neonates. Our limited knowledge of the neurological and cerebrovascular processes underlying seizures limits their diagnosis and timely treatment. Diffuse optical tomography (DOT) provides haemodynamic information in the form of changes in concentration of de/oxygenated haemoglobin, which can improve our understanding of seizures and the relationship between neural and vascular processes. Using simultaneous EEG-DOT, we observed distinct haemodynamic changes which are temporally correlated with electrographic seizures. Here, we present DOT-EEG data from two neonates clinically diagnosed as HIE. Our results highlight the wealth of mutually-informative data that can be obtained using DOT-EEG techniques to understand neurovascular coupling in HIE neonates.

Urban outpost nursing: the nature of the nurses' work in the AIDS prevention street nurse program.

The AIDS Prevention Street Nurse Program in Vancouver, Canada focuses on HIV and sexually transmitted diseases (STD) prevention within a context of harm reduction and health promotion targeted at marginalized, hard to reach, high-risk populations. As part of a large evaluation project that included interviews with street nurses, clients, and other service providers together with document analysis, the nature of the street nurses' work and its fit within the provision of health care were described. The street nurses' work reflected the following themes: reaching the marginalized high-risk populations for HIV/STDs; building and maintaining trust, respect, and acceptance; doing HIV/AIDS and STD prevention, early detection, and treatment work; helping clients connect with and negotiate the health care system; and influencing the system and colleagues to be responsive. The findings and their implications for community health nursing practice are examined.

Harm reduction theories and strategies for control of human immunodeficiency virus: a review of the literature.

AIM: To provide a comprehensive review of the literature on harm reduction theories and strategies related primarily to licit and illicit drug use. BACKGROUND: Although human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) disease transmission is well understood, it continues to spread, particularly among injection drug users (IDUs). Despite early indications that HIV would be contained within the IDU community, it is spreading to non-IDU sexual partners and to children of IDUs, threatening a more widespread epidemic. METHODS: An examination of research studies and theoretical writings including reviews and policy papers published in English between 1990 and 2000. RESULTS: Harm reduction does not seek to eliminate drug use; it focuses on minimizing the personal and social harms and costs associated with drug use and spread of HIV. It seeks to ameliorate conditions surrounding drug use responsible for the spread of HIV in the IDU community: unequal access to health services; sharing of infected needles; racial and social discrimination; poverty; exposure to street violence; inadequate housing; lack of employment; poor general or mental health and other demographic and social determinants. Some controversial harm reduction strategies are described: methadone maintenance programmes, illegal drugs dispensing under controlled conditions, needle exchanges, HIV testing, vein maintenance, safe-sex and would-care programmes. CONCLUSION: The main challenge is to get IDUs to protect themselves against HIV when suffering physical and social privations and addiction needs. Diverse perspectives on harm reduction are problematic with consequences for success of drug use initiatives. Practical, ethical and theoretical complexities exist but further research is needed to build support for a harm-reduction orientation in practice and policy formulation.