The Survival Benefit of Re-abstinence After Harmful Alcohol Use Following Early Liver Transplant for Severe Alcohol-Associated Hepatitis: A Multi-Center ACCELERATE Study.

BACKGROUND AND AIMS: Early (i.e. without mandated period of abstinence) liver transplant (LT) for alcohol-associated hepatitis (AH) is the fastest growing indication for LT in the US and Europe. Harmful alcohol use post-LT is associated with poor outcomes but the distinction of establishing abstinence after return to drinking (i.e. re-abstinence) is understudied. This study aims to characterize the survival outcomes of achieving re-abstinence after post-LT harmful alcohol use. METHODS: We analyzed early LT recipients from 12 US LT centers between 2006-2021. Post-LT alcohol use was characterized as harmful using criteria of "binge" (>5 [men] or >4 [women] drinks in < 24 hours) or "frequent" (>4 days in one week) by interview or phosphatidylethanol >20ng/mL. Re-abstinence was defined as >12 consecutive months without harmful alcohol use following harmful alcohol use. RESULTS: Among 347 LT recipients (64% male, median age 43, median MELD-Na 38) with median post-LT follow-up of 2.2 years (IQI 1.1 - 3.6), 276 (80%) recipients had no evidence of harmful alcohol use, 35 (10%) recipients had re-abstinence, and 36 (10%) recipients had continued harmful alcohol use without re-abstinence. Five-year predicted survival, adjusted for age, sex, MELD-Na score, was lowest among LT recipients with continued harmful alcohol use (77%), but similar among those with no harmful use (93%) and re-abstinence (94%). CONCLUSIONS: Achieving re-abstinence after post-LT harmful alcohol use is associated with similar five-year post-LT survival compared to those without evidence of post-LT harmful alcohol use. Our findings highlight the importance of early detection and treatment of post-LT alcohol use.

Clinical Predictors of Intensive Care Unit Transfer in Admitted Patients with Cirrhosis.

BACKGROUND: Patients with cirrhosis are at high risk of mortality after organ failure that requires ICU care. There have been attempts to predict which patients are at highest risk, with some success found in adapting liver disease-specific scoring systems with clinical variables commonly associated with critical illness. However, the clinical factors predictive of which patients with cirrhosis are most at-risk of needing ICU level care are unknown. AIMS: Our study set out to better understand which clinical variables were associated with need for ICU care in patients with cirrhosis. METHODS: Retrospective analysis of admitted patients with cirrhosis at single tertiary care center. RESULTS: Patients with cirrhosis admitted to our center were categorized into three groups: those without ICU transfer, those admitted to the ICU directly from the emergency department (ED), and those admitted to the ICU from the medicine floor. These groups differed in mortality at 30 days (3.5% vs. 15% vs. 25%, P < 0.001) and at subsequent intervals up to 1 year. These groups differed in indication for ICU transfer, with GI bleed, hemorrhagic shock, hepatic encephalopathy, and hyponatremia occurring more in the ED-to-ICU group, while respiratory failure was more common in the floor-to-ICU group. In multivariable analysis, factors associated with ICU transfer included worsened kidney function, anemia, hyponatremia, leukocytosis, and the decision to obtain a lactate level. Similar analysis with only floor-to-ICU patients found that ICU transfer was associated with hypoalbuminemia, hyponatremia, hypotension, and SIRS score. CONCLUSION: Our study found significant differences in mortality among three distinct groups of patients with cirrhosis. A risk factor model for ICU transfer found that variables both specific and nonspecific to liver disease were associated with ICU transfer, with between-group differences supporting the idea of different clinical phenotypes and suggesting factors that should be considered in early triage and assessment of hospitalized patients with cirrhosis.

Multicentered study of patient outcomes after declined for early liver transplantation in severe alcohol-associated hepatitis.

BACKGROUND: Early liver transplantation for alcohol-associated hepatitis is controversial in part because patients may recover, and obviate the need for liver transplantation. METHODS: In this retrospective study among 5 ACCELERATE-AH sites, we randomly sampled patients evaluated and then declined for liver transplantation for alcohol-associated hepatitis. All had Model of End-Stage Liver Disease (MELD) >20 and <6 months of abstinence. Recompensation was defined as MELD <15 without variceal bleeding, ascites, or overt HE requiring treatment. Multilevel mixed effects linear regression was used to calculate probabilities of recompensation; multivariable Cox regression was used for mortality analyses. RESULTS: Among 145 patients [61% men; median abstinence time and MELD-Na was 33 days (interquartile range: 13-70) and 31 (interquartile range: 26-36), respectively], 56% were declined for psychosocial reasons. Probability of 30-day, 90-day, 6-month, and 1-year survival were 76% (95% CI, 68%-82%), 59% (95% CI, 50%-66%), 49% (95% CI, 40%-57%), and 46% (95% CI, 37%-55%), respectively. Probability of 1-year recompensation was low at 10.0% (95% CI, 4.5%-15.4%). Among patients declined because of clinical improvement, 1-year probability of recompensation was 28.0% (95% CI, 5.7%-50.3%). Among survivors, median MELD-Na at 30 days, 90 days, and 1-year were 29 (interquartile range: 22-38), 19 (interquartile range : 14-29), and 11 (interquartile range : 7-17). Increased MELD-Na (adjusted HR: 1.13, p <0.001) and age (adjusted HR: 1.03, p <0.001) were associated with early (≤90 d) death, and only history of failed alcohol rehabilitation (adjusted HR: 1.76, p =0.02) was associated with late death. CONCLUSIONS: Liver recompensation is infrequent among severe alcohol-associated hepatitis patients declined for liver transplantation. Higher MELD-Na and age were associated with short-term mortality, whereas only history of failed alcohol rehabilitation was associated with long-term mortality. The distinction between survival and liver recompensation merits further attention.

Early Liver Transplantation for Severe Alcohol-Associated Hepatitis and a History of Prior Liver Decompensation.

INTRODUCTION: In the published studies of early liver transplantation (LT) for alcohol-associated hepatitis (AH), patients with a prior liver decompensation are excluded. The appropriateness of this criteria is unknown. METHODS: Among 6 American Consortium of Early Liver Transplantation for Alcohol-Associated Hepatitis sites, we included consecutive early LT for clinically diagnosed AH between 2007 and 2020. Patients were stratified as first vs prior history of liver decompensation, with the latter defined as a diagnosis of ascites, hepatic encephalopathy, variceal bleeding, or jaundice, and evidence of alcohol use after this event. Adjusted Cox regression assessed the association of first (vs prior) decompensation with post-LT mortality and harmful (i.e., any binge and/or frequent) alcohol use. RESULTS: A total of 241 LT recipients (210 first vs 31 prior decompensation) were included: median age 43 vs 38 years ( P = 0.23), Model for End-Stage Liver Disease Sodium score of 39 vs 39 ( P = 0.98), and follow-up after LT 2.3 vs 1.7 years ( P = 0.08). Unadjusted 1- and 3-year survival among first vs prior decompensation was 93% (95% confidence interval [CI] 89%-96%) vs 86% (95% CI 66%-94%) and 85% (95% CI 79%-90%) vs 78% (95% CI 57%-89%). Prior (vs first) decompensation was associated with higher adjusted post-LT mortality (adjusted hazard ratio 2.72, 95% CI 1.61-4.59) and harmful alcohol use (adjusted hazard ratio 1.77, 95% CI 1.07-2.94). DISCUSSION: Prior liver decompensation was associated with higher risk of post-LT mortality and harmful alcohol use. These results are a preliminary safety signal and validate first decompensation as a criterion for consideration in early LT for AH patients. However, the high 3-year survival suggests a survival benefit for early LT and the need for larger studies to refine this criterion. These results suggest that prior liver decompensation is a risk factor, but not an absolute contraindication to early LT.

Innovative Technology Using Virtual Reality in the Treatment of Pain: Does It Reduce Pain via Distraction, or Is There More to It?

Objective: Virtual reality (VR) is an exciting new technology with almost endless possible uses in medicine. One area it has shown promise is pain management. This selective review focused on studies that gave evidence to the distraction or nondistraction mechanisms by which VR leads to the treatment of pain. Methods: The review looked at articles from 2000 to July 29, 2016, focusing on studies concerning mechanisms by which virtual reality can augment pain relief. The data was collected through a search of MEDLINE and Web of Science using the key words of "virtual reality" and "pain" or "distraction." Results: Six studies were identified: four small randomized controlled studies and two prospective/pilot studies. The search results provided evidence that distraction is a technique by which VR can have benefits in the treatment of pain. Both adult and pediatric populations were included in these studies. In addition to acute pain, several studies looked at chronic pain states such as headaches or fibromyalgia. These studies also combined VR with other treatment modalities such as biofeedback mechanisms and cognitive behavioral therapy. Conclusions: These results demonstrate that in addition to distraction, there are novel mechanisms for VR treatment in pain, such as producing neurophysiologic changes related to conditioning and exposure therapies. If these new mechanisms can lead to new treatment options for patients with chronic pain, VR may have the ability to help reduce opioid use and misuse among chronic pain patients. More studies are needed to reproduce results from prospective/pilot studies in large randomized control studies.

Comparative Effectiveness Review of Cooled Versus Pulsed Radiofrequency Ablation for the Treatment of Knee Osteoarthritis: A Systematic Review.

BACKGROUND: Patients suffering from osteoarthritis of the knee and patients post total knee arthroplasty often develop refractory, disabling chronic knee pain. Radiofrequency ablation, including conventional, pulsed, and cooled, has recently become more accepted as an interventional technique to manage chronic knee pain in patients who have failed conservative treatment or who are not suitable candidates for surgical treatment. OBJECTIVE: This systematic review aimed to analyze published studies on radiofrequency ablation to provide an overview of the current knowledge regarding variations in procedures, nerve targets, adverse events, and temporal extent of clinical benefit. STUDY DESIGN: A systematic review of published studies investigating conventional, pulsed, or cooled radiofrequency ablation in the setting of chronic knee pain. METHODS: Medline, Google Scholar, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were reviewed for studies on radiofrequency ablation for patients with chronic knee pain through July 29, 2016. From the studies, the procedural details, outcomes after treatment, follow-up points, and complications were compiled and analyzed in this literature review. Included studies were analyzed for clinical relevance and strength of evidence was graded using either the NHLBI Quality assessment of controlled intervention studies or the NHLBI quality assessment for before-after (pre-post) studies with no control group. RESULTS: Seventeen total publications were identified in the search, including articles investigating conventional, pulsed, or cooled radiofrequency ablation. These studies primarily targeted either the genicular nerves or used an intraarticular approach. Of the studies, 5 were small-sized randomized controlled trials, although one involved diathermy radiofrequency ablation. There were 8 retrospective or prospective case series and 4 case reports. Utilizing the strength of evidence grading, there is a low level of certainty to suggest a superior benefit between targeting the genicular nerve, an intraarticular approach, or targeting the larger nerves such as femoral and tibial nerves. Utilizing the strength of evidence grading, there is a low level of certainty in supporting the superiority of any specific RFA procedure modality. The majority of the studies report positive patient outcomes, but the inconsistent procedural methodology, inconsistent patient assessment measures, and small study sizes limit the applicability of any specific study to clinical practice. LIMITATIONS: While the wide search strategy included a variety of articles, broad conclusions and pooled data could not be obtained based on the studies analyzed. CONCLUSIONS: Overall, the studies showed promising results for the treatment of severe chronic knee pain by radiofrequency ablation at up to one year with minimal complications. Numerous studies, however, yielded concerns about procedural protocols, study quality, and patient follow-up. Radiofrequency ablation can offer substantial clinical and functional benefit to patients with chronic knee pain due to osteoarthritis or post total knee arthroplasty.Key words: Radiofrequency ablation, knee osteoarthritis, knee pain, genicular nerve, total knee arthroplasty (TKA), cooled radiofrequency ablation, pulsed radiofrequency ablation.

Intractable Acute Pain Related to Fluoroquinolone-Induced Peripheral Neuropathy.

Fluoroquinolones are widely prescribed antibiotics, used for various infectious etiologies. These antibiotics carry the possibility of the serious adverse effect of peripheral neuropathy, with a true incidence not known owing to its rare existence. Recently, the Food and Drug Administration (FDA) has required alterations to drug labels to highlight this adverse effect of fluoroquinolones. This is a case report of a single patient at an inpatient neurology service at an urban academic medical center in the United States. The patient is a 20-year-old male, with well-controlled type 1 diabetes mellitus, presenting with a short duration of bilateral lower extremity pain following a 10-day course of levofloxacin for suspected epididymitis. The patient was initially diagnosed with complex regional pain syndrome and treated with a variety of pain medications, including lidocaine infusions, hydromorphone, methadone, and ketamine infusions. After review of the patient's history and limited response to medical management, the patient's condition was reclassified as an adverse effect from fluoroquinolone treatment. Pain of unknown etiology can be perplexing, both for the physician and the patient. Reporting of similar incidents attributed to medication adverse effects will increase the awareness of this type of neuropathy, avoid future cases of misdiagnosis, and enable early detection and treatment.