APASL clinical practice guidelines on the management of acute kidney injury in acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) is a syndrome that is characterized by the rapid development of organ failures predisposing these patients to a high risk of short-term early death. The main causes of organ failure in these patients are bacterial infections and systemic inflammation, both of which can be severe. For the majority of these patients, a prompt liver transplant is still the only effective course of treatment. Kidneys are one of the most frequent extrahepatic organs that are affected in patients with ACLF, since acute kidney injury (AKI) is reported in 22.8-34% of patients with ACLF. Approach and management of kidney injury could improve overall outcomes in these patients. Importantly, patients with ACLF more frequently have stage 3 AKI with a low rate of response to the current treatment modalities. The objective of the present position paper is to critically review and analyze the published data on AKI in ACLF, evolve a consensus, and provide recommendations for early diagnosis, pathophysiology, prevention, and management of AKI in patients with ACLF. In the absence of direct evidence, we propose expert opinions for guidance in managing AKI in this very challenging group of patients and focus on areas of future research. This consensus will be of major importance to all hepatologists, liver transplant surgeons, and intensivists across the globe.

Ammonia is associated with liver-related complications and predicts mortality in acute-on-chronic liver failure patients.

The relationship between ammonia and liver-related complications (LRCs) in acute-on-chronic liver failure (ACLF) patients is not clearly established. This study aimed to evaluate the association between ammonia levels and LRCs in patients with ACLF. The study also evaluated the ability of ammonia in predicting mortality and progression of LRCs. The study prospectively recruited ACLF patients based on the APASL definition from the ACLF Research Consortium (AARC) from 2009 to 2019. LRCs were a composite endpoint of bacterial infection, overt hepatic encephalopathy (HE), and ascites. A total of 3871 cases were screened. Of these, 701 ACLF patients were enrolled. Patients with LRCs had significantly higher ammonia levels than those without. Ammonia was significantly higher in patients with overt HE and ascites, but not in those with bacterial infection. Multivariate analysis found that ammonia was associated with LRCs. Additionally, baseline arterial ammonia was an independent predictor of 30-day mortality, but it was not associated with the development of new LRCs within 30 days. In summary, baseline arterial ammonia levels are associated with 30-day mortality and LRCs, mainly overt HE and ascites in ACLF patients.

Plain language summary of the HIMALAYA study: tremelimumab and durvalumab for unresectable hepatocellular carcinoma (liver cancer).

WHAT IS THIS SUMMARY ABOUT?: This is a summary of results from a phase 3 clinical study called HIMALAYA. HIMALAYA looked at treatment with one dose of a medication called tremelimumab combined with multiple doses of a medication called durvalumab (the STRIDE regimen) or multiple doses of durvalumab alone. These treatments were compared with a medication called sorafenib in participants with unresectable hepatocellular carcinoma (HCC). HCC is a type of liver cancer that is difficult to treat because it is often diagnosed when it is unresectable, meaning it can no longer be removed with surgery. Sorafenib has been the main treatment for unresectable HCC since 2007. However, people who take sorafenib may experience side effects that can reduce their quality of life, so alternative medicines are being trialed. Tremelimumab and durvalumab are types of drugs called immunotherapies, and they both work in different ways to help the body's immune system fight cancer. WHAT WERE THE RESULTS OF THE STUDY?: Participants who took STRIDE lived longer than participants who took sorafenib, whilst participants who took durvalumab alone lived a similar length of time as participants who took sorafenib. Participants who took STRIDE or durvalumab had a lower relative risk of experiencing worsening in their quality of life than participants who took sorafenib. The side effects that participants who received STRIDE or durvalumab experienced were expected for these types of treatments and could mostly be managed. WHAT DO THE RESULTS OF THE STUDY MEAN?: Overall, STRIDE is more effective than sorafenib for people with unresectable HCC.

Secondary hemophagocytic lymphohistiocytosis: an unusual complication in disseminated Mycobacterium tuberculosis.

Tuberculosis-associated hemophagocytic lymphohistiocytosis (TB-HLH) is a rare and life-threatening complication of tuberculosis infection. Early recognition and treatment of TB-HLH is crucial for improving outcomes. Treatment typically involves a combination of antituberculosis therapy and immunosuppressive therapy to control the immune system's overreaction. In this report, we present the case of a 53-year-old ambulance driver who was diagnosed with TB-HLH. His CT scan revealed splenic abscesses, hepatomegaly and bilateral lung consolidation. He subsequently developed multiorgan failure, including acute respiratory distress syndrome (ARDS), transaminitis and bone marrow dysfunction. The clinical course and simultaneous increase in serum ferritin raised the suspicion of HLH. His Hscore was 254, indicating a high probability of hemophagocytic syndrome. TB diagnosis was confirmed by positive endotracheal TB GeneXpert and bone marrow aspiration (BMA) which detected acid-fast bacilli organisms. The patient was promptly started on anti-TB, dexamethasone and IVIG. The patient responded well to treatment and made a full recovery without any lasting complications. This case highlights the importance of promptly recognising HLH and identifying the underlying cause. In critically ill patients, it is crucial not to delay HLH-specific treatment while working up for differential diagnosis.

Symptoms and Satisfaction Levels Associated with Intraocular Lens Implants in the Monofocal and Premium IOL Patient-Reported Outcome Measure Study.

PURPOSE: To develop a questionnaire with standardized questions and images about visual symptoms and satisfaction administered before and after cataract surgery with monofocal and various (premium) intraocular lenses (IOLs). DESIGN: A prospective, observational study of cataract surgery patients completing a self-administered questionnaire preoperatively and postoperatively at 4 to 6 months. PARTICIPANTS: Five hundred fifty-four patients with plans to undergo implantation of the same IOL in both eyes on separate occasions in 20 ophthalmology practices. METHODS: An 86-item questionnaire with standardized images assessed the following 14 symptoms: glare, blurry vision, starbursts, hazy vision, snowballs, halos, floaters, double images, rings and spider webs, light flashes with eyes closed, distortion, light flashes with eyes open, shimmering images, and dark crescent-shaped shadows. MAIN OUTCOME MEASURES: Symptom severity and level of symptom bother, satisfaction with vision, quality of vision, and ability to see without corrective lenses or eyeglasses. RESULTS: Except for dark crescent-shaped shadows, the report of visual symptoms significantly decreased postoperatively. Best uncorrected binocular visual acuity improved from 0.47 (20/59 Snellen visual acuity values) ± 0.35 logarithm of the minimum angle of resolution (logMAR) preoperatively to 0.12 (20/26 Snellen visual acuity values) ± 0.12 logMAR postoperatively. Patients' ratings of intermediate vision as good to excellent improved significantly from 12% preoperatively to 71% postoperatively, and patients' ratings of distance vision improved from 8% preoperatively to 85% postoperatively. After surgery, 84% reported that they were somewhat, very, or completely satisfied with their vision. Most patients (88%) reported that they could see pretty well, very well, or perfectly well without corrective lenses after surgery. CONCLUSIONS: The Assessment of IntraOcular Lens Implant Symptoms questionnaire can be used across a wide variety of IOLs to evaluate visual symptoms and satisfaction with a growing segment of the market, premium IOLs, that target intermediate and near vision, in addition to distance vision. Compared to patients receiving monofocal IOLs, patients receiving premium IOLs appear to be more challenging to satisfy because of their requirements for distance, intermediate, and near vision, and their desire to be free of eyeglasses postoperatively. This instrument provides a structured, uniform tool for regulators, researchers, and ophthalmologists in everyday practice to gain insights into patients' experiences. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Safety and effectiveness comparison of a new cohesive ophthalmic viscosurgical device.

PURPOSE: To evaluate the safety and effectiveness of a new cohesive ophthalmic viscosurgical device (OVD) (StableVisc) compared with a marketed cohesive OVD (ProVisc) in patients undergoing cataract surgery. SETTING: 22 sites in the United States. DESIGN: Prospective multicenter controlled double-masked and randomized 1:1 (StableVisc:ProVisc; stratified by site, age group, and cataract severity). METHODS: Adults (≥45 years) with age-related noncomplicated cataract considered amenable to treatment with standard phacoemulsification cataract extraction and intraocular lens implantation were included. Patients were randomized to receive either StableVisc or ProVisc during standard cataract surgery. Postoperative visits occurred at 6 hours, 24 hours, 7 days, 1 month, and 3 months. The primary effectiveness outcome was the change in endothelial cell density (ECD) from baseline to 3 months. The primary safety endpoint was the proportion of patients who experienced at least 1 intraocular pressure (IOP) measurement ≥30 mm Hg at any follow-up visit. Noninferiority between the devices was tested. Inflammation and adverse events were evaluated. RESULTS: 390 patients were randomized; 187 patients with StableVisc and 193 patients with ProVisc completed the study. StableVisc was noninferior to ProVisc in mean ECD loss from baseline to 3 months (17.5% and 16.9%, respectively). StableVisc was noninferior to ProVisc in the proportion of patients with postoperative IOP ≥30 mm Hg at any follow-up visit (5.2% and 8.2%, respectively). CONCLUSIONS: The StableVisc cohesive OVD, which provides both mechanical and chemical protection, was safe and effective when used in cataract surgery and provides surgeons with a new cohesive OVD.

Development of a Patient-Reported Outcome Measure to Assess Symptoms Associated with Cataract Surgery and Intraocular Lens Implants.

PURPOSE: To develop a standardized patient-reported outcome measure of visual perceptions and symptoms for implanted premium and monofocal intraocular lenses (IOLs). DESIGN: Observational study before and after IOL implants to assess the measure and symptom experience. PARTICIPANTS: Adults scheduled for binocular implantation of the same IOL type completed the survey at baseline prior to surgery (n = 716) and postoperatively (n = 554). Most respondents were female (64%), White (81%), 61 or older (89%), and had some college or more education (62%). METHODS: Administration was by web survey with mail follow-up and phone reminders. MAIN OUTCOME MEASURES: Frequency, severity, and level of symptom bother in the last 7 days for 14 symptoms: (1) glare, (2) hazy vision, (3) blurry vision, (4) starbursts, (5) halos, (6) snowballs, (7) floaters, (8) double images, (9) rings and spider webs, (10) distortion, (11) light flashes with eyes closed, (12) light flashes with eyes open, (13) shimmering images, and (14) dark shadows. RESULTS: The median correlation among having 14 symptoms at baseline was only 0.19. Mean uncorrected binocular visual acuity improved from a preoperative value of 0.47 logarithm of the minimum angle of resolution (logMAR; Snellen 20/59) to a postoperative value of 0.12 (20/26) and best-corrected binocular visual acuity improved from 0.23 logMAR (20/34) preoperative to 0.05 logMAR (20/22) postoperative. The most bothersome symptoms were reduced after surgery: preoperative/postoperative glare (84%/36%), blurry vision (68%/22%), starbursts (66%/28%), hazy vision (63%/18%), snowballs (55%/17%), and halos (52%/22%). All symptoms decreased significantly (P < 0.0001) from before to after surgery except for dark crescent-shaped shadows (4%/4%). The percentage of symptoms rated as quite a bit or extremely bothersome declined from before to after surgery except for dark crescent-shaped shadows (29%/32%): blurry vision (54%/15%), snowballs (52%/14%), glare (49%/15%), and halos (46%/14%). Having monofocal IOL implants was associated with significantly more reduction in halos, starbursts, glare, and rings and spider webs, but less improvement in self-reported general vision. CONCLUSIONS: This study provides support for the 37-item Assessment of IntraOcular Lens Implant Symptoms (AIOLIS) instrument for use to assess symptoms and general perceptions of vision in clinical studies and clinical care. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Efficacy of a One-Piece Aberration Neutral Hydrophobic Acrylic Toric Intraocular Lens.

Purpose: To assess the refractive outcomes, intraocular centration and rotational stability of the enVista toric intraocular lens (IOL). Patients and Methods: This study was a prospective, multi-centre, double-masked, partially randomized and partially controlled clinical trial. A total of 191 participants were implanted with toric IOL (1.25, 2.00, or 2.75D) or non-toric IOL (control). The lowest range of corneal astigmatic eyes were randomized to 1.25D toric or control. Higher astigmatic powers were allocated to the treatment arm. Subjects were assessed immediately postoperatively, 1-2 (V1), 7-14 (V2), 30-60 (V3) and 120-180 (V4) days postoperatively. Unaided (UDVA) and distance corrected visual acuity (CDVA), manifest refraction and corneal curvature were assessed. Vector analysis was used to calculate surgically induced refractive correction (SIRC), correction ratio (CR), error magnitude (EM) and error vector (EV). Slit-lamp photography was used to measure centration and rotational stability. Results: UDVA was better in the low toric IOL group in comparison with the control group at V4 (p<0.001). There was an undercorrection in the control group, whereas the average CR for all toric subjects was 1.00 ± 0.32: V2, 0.98 ± 0.34: V3 and 0.98 ± 0.35: V4. The absolute IOL rotational stability in comparison to the position of the IOL at V1 was 1.35° ± 0.97°: V2, 1.35° ± 1.07°: V3 and 1.38° ± 1.25°: V4. Decentration was generally inferior (V1: 0.04 ± 0.22mm, V2: 0.05± 0.20mm, V3: 0.08 ± 0.22mm, V4: 0.04 ± 0.21mm) and nasal (V1: 0.19 ± 0.23mm, V2: 0.20 ± 0.20mm, V3: 0.20 ± 0.21mm, V4: 0.17 ± 0.22mm). Conclusion: Participants with low levels of corneal astigmatism achieved superior vision and refractive outcomes in the low toric group over the control. Moderate and high levels of astigmatism achieved excellent refractive outcomes. The toric IOL demonstrated high levels of both rotational and centrational stability.

Clinical Conundrums: Differentiating Monkeypox From Similarly Presenting Infections.

Post the coronavirus disease 2019 (COVID-19) pandemic, there arises the concern of a new epidemic as cases of monkeypox are being confirmed, globally. With the initial clinical manifestation of monkeypox resembling that of the common cold or seasonal flu, recognizing alternative differential diagnoses is imperative as a medical health practitioner. The characteristic monkeypox maculopapular rash with the progression to vesicles and pustules before scabbing can be described in several other infections. Understanding the disease progression and distinct clinical presentation of monkeypox in its various stages may allow for a more expedient diagnosis among healthcare providers. Though eradicated, the clinical presentation of smallpox is the most similar to that of monkeypox; however, smallpox is no longer a concern for the general population. Other conditions such as molluscum contagiosum, syphilis, varicella zoster, measles, rickettsialpox, and scabies can present with rashes that may resemble singular or multiple states of the monkeypox rash progression. The ability to correctly diagnose an individual's condition promptly may allow healthcare providers to provide correct supportive therapies or treatments.

Safety and effectiveness of a new ophthalmic viscosurgical device: randomized, controlled study.

PURPOSE: To evaluate the safety and effectiveness of a new dispersive ophthalmic viscosurgical device (OVD) (ClearVisc) compared with an approved dispersive OVD (Viscoat) when used in cataract surgery. SETTING: 16 clinics in the United States. DESIGN: Prospective multicenter controlled randomized 1:1 (ClearVisc:Viscoat; stratified by site, age group, and cataract severity). Patients and examiners masked. METHODS: Patients aged 45 years or older with age-related noncomplicated cataract considered amenable to treatment with standard phacoemulsification cataract extraction and intraocular lens (IOL) implantation were included. Patients were randomized to receive either ClearVisc or Viscoat using standard techniques. 5 postoperative visits occurred at 6 hours, 24 hours, 7 days, 1 month, and 3 months. The primary effectiveness outcome was the change in endothelial cell density (ECD) from baseline to 3 months. The primary safety end point was the proportion of patients who experienced at least 1 intraocular pressure (IOP) measurement ≥30 mm Hg at any follow-up visit. Noninferiority was tested. Inflammation and adverse events were evaluated. RESULTS: 372 patients were randomized: 184 patients in the ClearVisc group and 188 patients in the Viscoat group. ClearVisc was noninferior to Viscoat in mean percentage of ECD loss from baseline to 3 months (8.4% and 6.8%, respectively). ClearVisc was significantly noninferior to Viscoat in the proportion of patients with postoperative IOP ≥30 mm Hg at any follow-up visit (17.4% and 20.3%, respectively, P = .0002). CONCLUSIONS: ClearVisc dispersive OVD provides surgeons with a new option in the continuum of approved dispersive OVDs with beneficial properties as a surgical aid in cataract extraction and IOL implantation.

Impact of compensated cirrhosis on survival in patients with acute-on-chronic liver failure.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is considered a main prognostic event in patients with chronic liver disease (CLD). We analyzed the 28-day and 90-day mortality in ACLF patients with or without underlying cirrhosis enrolled in the ACLF Research Consortium (AARC) database. METHODS: A total of 1,621 patients were prospectively enrolled and 637 (39.3%) of these patients had cirrhosis. Baseline characteristics, complications and mortality were compared between patients with and without cirrhosis. RESULTS: Alcohol consumption was more common in cirrhosis than non-cirrhosis (66.4% vs. 44.2%, p < 0.0001), while non-alcoholic fatty liver disease/cryptogenic CLD (10.9% vs 5.8%, p < 0.0001) and chronic HBV reactivation (18.8% vs 11.8%, p < 0.0001) were more common in non-cirrhosis. Only 0.8% of patients underwent liver transplantation. Overall, 28-day and 90-day mortality rates were 39.3% and 49.9%, respectively. Patients with cirrhosis had a greater chance of survival compared to those without cirrhosis both at 28-day (HR = 0.48; 95% CI 0.36-0.63, p < 0.0001) and 90-day (HR = 0.56; 95% CI 0.43-0.72, p < 0.0001), respectively. In alcohol CLD, non-cirrhosis patients had a higher 28-day (49.9% vs. 23.6%, p < 0.001) and 90-day (58.4% vs. 35.2%, p < 0.001) mortality rate than cirrhosis patients. ACLF patients with cirrhosis had longer mean survival than non-cirrhosis patients (25.5 vs. 18.8 days at 28-day and 65.2 vs. 41.2 days at 90-day). Exaggerated systemic inflammation might be the reason why non-cirrhosis patients had a poorer prognosis than those with cirrhosis after ACLF had occurred. CONCLUSIONS: The 28-day and 90-day mortality rates of ACLF patients without cirrhosis were significantly higher than those with cirrhosis in alcoholic CLD. The presence of cirrhosis and its stage should be evaluated at baseline to guide for management. Thai Clinical Trials Registry, TCTR20191226002.

Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma.

Tremelimumab/Durvalumab for Hepatocellular CarcinomaThis trial examined overall survival (OS) with tremelimumab plus durvalumab, durvalumab alone, or sorafenib in untreated patients with hepatocellular cancer who were not candidates for locoregional therapy. Median OS increased significantly by 2.5 months (16.4 vs. 13.8) with single-dose tremelimumab plus durvalumab treatment every 4 weeks versus sorafenib alone.

Achieving WHO target of HCV control in Hong Kong: challenges and strategies.

With the introduction of effective directly acting antiviral agents (DAAs) therapy, control and elimination of hepatitis C virus (HCV) infection is becoming a feasible goal. In Hong Kong, HCV prevalence in general population is 0.3%-0.5% over the past decades. However, like other high-income areas/countries, high prevalence of HCV infection has been found in several population groups, such as people who inject drugs (PWID), patients undergoing dialysis, and human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/ AIDS) patients. Based on the epidemiological study using data retrieved from the Hong Kong HCV Registry from January 2005 to March 2017, the estimated territory-wide diagnosis rate and treatment rate of HCV infection were only 50.9% and 12.4%, respectively. Although these rates was comparable to many developed countries/areas, the performances remained substantially below 90% and 80%, the 2030 targets proposed by World Health Organization (WHO). In recognition of the challenges, the Hong Kong Government set up the Steering Committee on Prevention and Control of Viral Hepatitis (SCVH) which formulated the Hong Kong Viral Hepatitis Action Plan 2020-2024. The Action Plan adopts four key strategies, as described in the WHO framework for global action, namely, awareness, surveillance, prevention and treatment. With the effective implementation of the Action Plan, especially in targeted screening of high-risk populations and more generalized use of the highly efficacious DAAs for all diagnosed HCV subjects, the goals of reducing HCV transmission and HCV-related morbidity and mortality can be achieved in Hong Kong by 2030.

'First week' is the crucial period for deciding living donor liver transplantation in patients with acute-on-chronic liver failure.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a rapidly progressive illness with high short-term mortality. Timely liver transplant (LT) may improve survival. We evaluated various indices for assessment of the severity of liver failure and their application for eligibility and timing of living donor LT (LDLT). METHODS: Altogether 1021 patients were analyzed for the severity and organ failure at admission to determine transplant eligibility and 28 day survival with or without transplant. RESULTS: The ACLF cohort [mean age 44 ± 12.2 years, males 81%) was of sick patients; 55% willing for LT at admission, though 63% of them were ineligible due to sepsis or organ failure. On day 4, recovery in sepsis and/or organ failure led to an improvement in transplant eligibility from 37% at baseline to 63.7%. Delay in LT up to 7 days led to a higher incidence of multiorgan failure (p < 0.01) contributing to 23% of the first week and 55% of all-cause 28-day mortality. In a matched cohort analysis, the actuarial survival with LT (n = 41) and conditional survival in the absence of transplant (n = 191) were comparable, when the condition, i.e., transplant was adjusted. The comparison curve showed differentiation in survival beyond 7 days (p < 0.01). CONCLUSIONS: ACLF is a rapidly progressive disease and risk stratification within the first week of hospitalization is needed. 'Emergent LT' should be defined in the first week in the ACLF patients; the transplant window for improving survival in a live donor setting.