Clinical and patient-reported outcomes in patients with chronic hepatitis B and C and non-alcoholic fatty liver disease from real-world practices in Saudi Arabia, Turkey and Egypt.

Patients with chronic liver disease (CLD) experience health-related quality of life (HRQoL) and patient-reported outcomes (PROs) impairments. We assessed and identified predictors of HRQoL and PROs in CLD patients from Saudi Arabia (SA), Turkey and Egypt. Patients enrolled in Global Liver Registry™ with chronic hepatitis B (CHB), chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) were included. Clinical data and PRO questionnaires (FACIT-F, CLDQ and WPAI) were compared across countries. Linear regression identified PRO predictors. Of the 4014 included patients, 26.9% had CHB, 26.9% CHC and 46.1% NAFLD/NASH; 19.2% advanced fibrosis. Compared across countries, CHB patients were younger in Egypt (mean age [years] 41.2 ± 11.4 vs. 45.0 ± 10.3 SA, 46.1 ± 12.0 Turkey), most often employed in SA (64.8% vs. 53.2% Turkey) and had the lowest prevalence of obesity in Turkey (26.7% vs. 37.8% SA, 38.5% Egypt). In SA, CHB patients had lowest prevalence of fibrosis and comorbidities (all p < .01). There was a higher frequency of males with NAFLD/NASH in SA (70.0% vs. 49.6% Turkey, and 35.5% Egypt). Among NAFLD/NASH patients, CLDQ-NAFLD/NASH scores were highest in SA (mean total score: 5.3 ± 1.2 vs. 4.8 ± 1.2 Turkey, 4.1 ± 0.9 Egypt, p < .01). Independent predictors of worse PROs included younger age, female sex, advanced fibrosis, non-hepatic comorbidities and lack of regular exercise (all p < .05). Clinical presentation and PRO scores of CLD patients vary across SA, Turkey and Egypt. Impairment of HRQoL is associated with demographic factors, lack of regular exercise, advanced fibrosis and non-hepatic comorbidities.

SERS probing of fungal HET-s fibrils formed at neutral and acidic pH conditions.

Advances in precision medical diagnostics require accurate and sensitive characterization of pathogens. In particular, health conditions associated with protein misfolding require an identification of proteinaceous amyloid fibrils or their precursors. These pathogenic entities express specific molecular structures, which require ultra-sensitive, molecular-level detection methods. A potentially transformative technique termed nanoplasmonics employs electro-optical phenomena in the vicinity of specially engineered metal nanostructures. A signature application of nanoplasmonics exploits enhancement of inelastic scattering of light in specific locations near metallic nanostructures, known as surface-enhanced Raman scattering (SERS). We applied SERS complemented with confocal microscopy imaging for ultra-sensitive, non-invasive, and label-free characterization of the fungal prion HET-s (218-289) as a model for ß-sheet rich amyloid structures. This characterization employed Au-coated dielectric supports as plasmonic substrates. After confirming the formation of HET-s fibrils at both pH 7.5 and 2.8 using negative staining transmission electron microscopy, we subjected the fibril-containing solutions to multimodal analysis using confocal microscopy and SERS. The SERS spectral fingerprints from all HET-s samples expressed vibrational markers for ß-structure, unstructured backbone, and aromatic side-chains. However, relative intensities of major SERS bands were pronouncedly different for the two pH levels. We have analyzed potential origins of the most pronounced SERS bands and proposed hypothetical mechanistic models that could explain the observed SERS fingerprints from HET-s fibrils grown at pH 7.5 and 2.8.

Clinical profiles and mortality rates are similar for metabolic dysfunction-associated steatotic liver disease and non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Recently, the term metabolic dysfunction-associated steatotic liver disease (MASLD) has replaced non-alcoholic fatty liver disease (NAFLD). Concern remains regarding whether the evidence generated under the NAFLD definition can be used for MASLD. We compared the clinical profile and outcomes of NAFLD to MASLD using tertiary care- and population-based data. METHODS: Comparison data were obtained from our NAFLD database and the National Health and Nutrition Examination Survey (NHANES III). Clinical profiles and non-invasive tests (enhanced liver fibrosis [ELF] score, fibrosis-4 index [FIB-4] and vibration-controlled transient elastography) were compared. Mortality data were obtained from NHANES-National Death Index. All-cause mortality was assessed by Cox proportional hazards regression models and cause-specific mortality by competing risk analysis. RESULTS: There were 6,429 patients in the NAFLD database (age: 54 ± 12 years, 42% male, BMI 35.4 ± 8.3, waist circumference 112 ± 17 cm, 52% type 2 diabetes). Average scores for ELF, FIB-4 and liver stiffness were 9.6 ± 1.2, 1.69 ± 1.24,14.0 ± 11.8 kPa, respectively; 99% met MASLD criteria; 95% met MASLD on BMI only. Predictive accuracy of ELF and FIB-4 were identical between MASLD and NAFLD. We included 12,519 eligible participants from NHANES (age 43.00 years, 47.38% male, 22.70% obese, 7.28% type 2 diabetes, 82.51% ≥1 cardiometabolic criteria). Among the NHANES study population, there was excellent concordance between MASLD and NAFLD diagnoses: Cohen's kappa coefficient: 0.968 (95% CI 0.962-0.973) with 5.29% of NAFLD cases not meeting MASLD criteria. After a median follow-up of 22.83 years, there were no mortality differences between MASLD and NAFLD diagnoses (p values ≥0.05). CONCLUSIONS: NAFLD and MASLD are similar except individuals with MASLD seem to be older with slightly higher mortality risk, likely owing to cardiometabolic risk factors. Clinical profiles and non-invasive test thresholds were also identical. These data provide evidence that NAFLD and MASLD terminologies can be used interchangeably. For the small proportion of patients with NAFLD who do not meet MASLD criteria, further consideration is needed. IMPACT AND IMPLICATIONS: In June 2023, new terminology (MASLD) was adopted to replace the term NAFLD as a means to better describe what the liver disease is rather than what it is not, as well as to potentially reduce stigma. Given that MASLD requires at least one cardiometabolic risk factor, questions were raised as to whether this change in the definition would nullify the similarities between NAFLD and MASLD and require new evidence to be generated for MASLD. We used our NAFLD database and a US population-based database to show that the vast majority of patients with NAFLD fulfill criteria for MASLD. Non-invasive tests performed similarly in both groups. Mortality risk was slightly higher in those with MASLD, which is attributed to the presence of cardiometabolic risks. These results provide evidence that data generated in the past three decades for NAFLD can be used interchangeably for MASLD.

The impact of hepatitis B and C positive serologies on the outcomes of non-hepatic solid organ transplantation in the United States.

Chronic viral hepatitis B (HBV) and C (HCV) infection could negatively affect outcomes of non-hepatic solid organ transplantations due to the risk of viral reactivation in the presence of immunosuppression. This study aimed to determine post-transplant outcomes in patients with HBV or HCV positivity receiving non-hepatic solid-state organ transplant. Data was collected from the Scientific Registry of Transplant Recipients (SRTR) 2006-2021 for patients (≥18) who received a lung, heart, or kidney single organ transplant in the U.S. Hepatitis C positivity (HCV+) was determined as positive HCV Ab and hepatitis B positivity (HBV+) as positive HBsAg. We included N = 30,872 lung, N = 36,990 heart and N = 280,162 kidney transplant recipients. The prevalence of HBV+ was 1.3% in lung, 1.5% in heart and 1.7% in kidney patients, HCV+ was 2.2%, 2.2% and 5.0%, respectively. Post-transplant survival of patients with vs. without HBV+ was similar in all solid organ transplants (all p > .05). Similarly, there was no difference in post-transplant survival between lung transplant recipients with vs. without anti-HCV (all p > .05). Heart transplant recipients with HCV+ had higher crude post-transplant mortality (all p < .01). Similarly, there was higher post-transplant mortality in kidney transplant recipients with HCV+ (1-year: 6% vs. 3%; 5-year: 21% vs. 13%; 10-year: 47% vs. 31%; all p < .0001). In multivariate analysis controlling for confounders, only the association of HCV+ with higher post-kidney transplant mortality remained significant: adjusted hazard ratio (aHR) (95% CI) = 1.16 (1.12-1.20), p < .0001. There was no association of viral hepatitis seropositivity with the risk of graft failure in all groups (p > .05). In most cases, the presence of HBV or HCV serologies is not associated with adverse post-transplant outcomes in non-hepatic solid organ transplants. However, kidney transplant recipients who are positive for HCV serology have an increased risk for post-transplant mortality.

The changing epidemiology of adult liver transplantation in the United States in 2013-2022: The dominance of metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease.

BACKGROUND: The high prevalence of obesity in the United States drives the burden of NASH, recently renamed as metabolic dysfunction-associated steatohepatitis (MASH). We assessed the most recent trends in liver transplantation in the United States. METHODS: The Scientific Registry of Transplant Recipients (SRTR 2013-2022) was used to select adult (18 years or above) candidates who underwent liver transplant. RESULTS: There were 116,292 candidates who underwent liver transplant with known etiology of chronic liver disease. In candidates without HCC, the most common etiology was alcohol-associated liver disease (ALD), increasing from 23% (2013) to 48% (2022), followed by NASH/MASH, which increased from 19% to 27%; the rates of viral hepatitis decreased (chronic hepatitis C: 28%-4%; chronic hepatitis B: 1.8%-1.1%) (all trend p<0.01). The proportion of HCC decreased from 25% (2013-2016) to 17% (2021-2022). Among HCC cohort, the proportion of chronic hepatitis C decreased from 60% (2013) to 27% (2022), NASH/MASH increased from 10% to 31%, alcohol-associated liver disease increased from 9% to 24% (trend p<0.0001), and chronic hepatitis B remained stable between 5% and 7% (trend p=0.62). The rapid increase in the proportion of NASH/MASH in HCC continued during the most recent study years [20% (2018), 28% (2020), 31% (2022)]; the trend remained significant after adjustment for age, sex, ethnicity, obesity, and type 2 diabetes. CONCLUSIONS: Liver transplant etiologies in the United States have changed over the last decade. Alcohol-associated liver disease and NASH/MASH remain the 2 most common indications for transplantation among those without HCC, and NASH/MASH is the most common in patients with HCC.

Severe, Persistent, Disruptive Fatigue Post-SARS-CoV-2 Disproportionately Affects Young Women.

Introduction: Post-acute SARS-CoV-2 (PASC) symptoms are often persistent, disruptive, and difficult to treat effectively. Fatigue is often among the most frequently reported symptoms and may indicate a more challenging road to recovery. Purpose: To describe the natural history, symptomology, and risk profile of long-term post-acute SARS-CoV-2. Patients and Methods: Participants treated for SARS-CoV-2 within a large, community health system in the US were enrolled prospectively in a longitudinal, observational PASC study examining participants at enrollment and 6 months. Medical history, symptom reporting, validated measures of cognition, and patient-reported outcomes (PROs), were performed for all participants and repeated during study follow-up visits. Results: A total of 323 participants completed baseline evaluations. Sixty one participants indicated clinically significant fatigue (23.1% at baseline); a representative sample of 141 enrollees also completed a baseline Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) in-depth fatigue reporting questionnaire, 37 had severe fatigue. The severely fatigued (FACIT-F ≤29.7) were significantly younger, female, had more anxiety and depression, had a higher resting heart rate, reported more sick days, and were less physically active post-COVID. They were more likely to have a diagnosis of chronic kidney disease (13.5% vs 2.9%) but less likely to have a history of cancer (8.1% vs 23.1). Participants who were severely fatigued reported health, diet, weight, and sleep were worse than those not severely fatigued post-COVID (p = 0.02 to 0.0002). Fatigue was significantly correlated with impairment of all PROs administered after COVID-19 infection. Conclusion: Fatigue is a common symptom post-COVID-19 infection and is associated with lower reported well-being and function. Those with severe fatigue tended to be younger and female and have a past medical history of anxiety, depression, kidney disease, and more sedentary lifestyles.

Impact of Type 2 Diabetes on the Outcomes of Solid Organ Transplantations in the U.S.: Data From a National Registry.

OBJECTIVE: Type 2 diabetes (T2D) is a major driver of chronic diseases around the globe. The aim was to assess the impact of T2D on the outcomes of solid organ transplantations. RESEARCH DESIGN AND METHODS: We used the Scientific Registry of Transplant Recipients from 2006 to 2021 to collect data for all patients age ≥18 years who received a lung, heart, liver, or kidney transplant in the U.S. RESULTS: We included 462,692 solid organ transplant recipients: 31,503 lung, 38,004 heart, 106,639 liver, and 286,440 kidney transplantations. The prevalence of pretransplantation T2D was 15% in lung, 26% in heart, 25% in liver, and 30% in kidney transplant recipients, increasing over time. Posttransplantation mortality was significantly higher among transplant recipients with T2D versus those without T2D (lung 32.1% vs. 29.3% [3 years], 46.4% vs. 42.6% [5 years]; P < 0.01; heart 11.2% vs. 9.1% [1 year], 24.4% vs. 20.6% [5 years]; P < 0.0001; liver 10.6% vs. 8.9% [1 year], 26.2% vs. 22.0% [5 years]; P < 0.0001; kidney 5.3% vs. 2.5% [1 year], 20.8% vs. 10.1% [5 years]; P < 0.0001). Independent association of pretransplantation T2D with higher posttransplantation mortality was significant after adjustment for clinicodemographic confounders (adjusted hazard ratio in lung transplant recipients 1.08 [95% CI 1.03-1.13]; heart 1.26 [1.20-1.32]; liver 1.25 [1.21-1.28]; kidney 1.65 [1.62-1.68]; P < 0.01). CONCLUSIONS: The prevalence of T2D in solid organ transplantation candidates is increasing. In all solid organ transplantations, pretransplantation T2D was independently associated with higher posttransplantation mortality, most profoundly in kidney transplantations.

Can Frequent Toothbrushing Reduce the Risk of Cirrhosis among Patients with Nonalcoholic Fatty Liver Disease? Hints from a Registry-Based Study.

INTRODUCTION: While poor oral hygiene has been previously associated with an increased risk of nonalcoholic fatty liver disease (NAFLD), its association with hepatic fibrosis remains unclear. Here, we sought to analyze if toothbrushing frequency, an easy-to-assess indicator of oral health habits, would be associated with liver stiffness measurement (LSM) by transient elastography (TE) in patients with an established diagnosis of NAFLD. METHODS: In this registry-based study, LSM was measured in 1,156 patients with NAFLD and analyzed in relation to the self-reported daily frequency of toothbrushing. LSM values ≥12 kPa were considered indicative of cirrhosis. RESULTS: A trend toward a stepwise decrease (cross-sectional p = 0.13) in LSM was found in patients who reported having their teeth brushed more frequently: less than once a day (10.6 ± 8.6 kPa; 13% of the study sample), once a day (9.95 ± 8.40 kPa; 40%), twice a day (9.21 ± 7.63 kPa; 43%), and after every meal (8.91 ± 5.30 kPa; 4%). Patients who brushed their teeth less than once a day had a significantly higher prevalence of LSM values ≥12 kPa (p < 0.05). In multivariable logistic regression analysis, the association of LSM values ≥12 kPa with toothbrushing habits remained statistically significant for less than once a day (odds ratio = 1.69, 95% confidence interval = 1.07-2.66, p = 0.02) with reference to twice a day or after every meal. CONCLUSION: Among patients with NAFLD, there is an independent association between brushing teeth less than once a day and TE-established cirrhosis.

The Growing Economic and Clinical Burden of Nonalcoholic Steatohepatitis (NASH) in the United States.

Background: Nonalcoholic steatohepatitis (NASH) is a cause of chronic liver disease. Aim: Model the burden of NASH in the United States according to obesity. Methods: The discrete-time Markov model comprised adult NASH subjects moving through 9 health states and 3 absorbing death states (liver, cardiac, and other deaths) with 1-year cycles and a 20-year horizon. Given that reliable natural history data for NASH are not available, transition probabilities were estimated from the literature and population-based data. These rates were disaggregated to determine age-obesity group rates by applying estimated age-obesity patterns. The model considers 2019 prevalent NASH cases and new incident NASH cases (2020-2039), assuming that recent trends will continue. Annual per-patient costs by health state were based on published data. Costs were standardized to 2019 US dollars and inflated by 3% annually. Results: NASH cases in the United States are forecasted to increase by +82.6%, from 11.61 million (2020) to 19.53 million (2039). During the same period, cases of advanced liver disease increased +77.9%, from 1.51 million to 2.67 million, while its proportion remained stable (13.46%-13.05%). Similar patterns were observed in both obese and non-obese NASH. Among NASH, 18.71 million overall deaths, 6.72 million cardiac-specific deaths, and 1.71 million liver-specific deaths were observed by 2039. During this period, the projected cumulative direct healthcare costs were $1208.47 billion (obese NASH) and $453.88 billion (non-obese NASH). By 2039, the projected NASH attributable healthcare cost per patient increased from $3636 to $6968. Conclusions: There is a substantial and growing clinical and economic burden of NASH in the United States.

Post-Acute SARS-CoV-2 Symptoms are Fewer, Less Intense Over Time in People Treated with Mono-Clonal Antibodies for Acute Infection.

Introduction: Many with post-acute SARS-CoV-2 (PASC) have persistent symptoms impacting physical and cognitive function, decreased health and health-related life quality. Monoclonal antibody (mAb) treatment was available to acutely infected patients which might improve these outcomes. Purpose: To compare patient perception of PASC symptoms for those receiving bamlanivimab or casirivimab and imdevimab (mAbs) to those not receiving this treatment (non-mAbs). To compare changes between these groups in symptoms, function and quality of life over a 6-month follow-up. Patients and Methods: Consented adults >28 days post-infection with positive SARS-CoV-2 qPCR or antigen test and SARS-CoV-2 infection between March of 2020 and July of 2022 were enrolled. This prospective, repeated measure observational study reports baseline through 6-month follow-up. Extensive sociodemographic data, detailed medical history, COVID-19 symptom history, and standardized measures of well-being, depression, anxiety, stigma, cognition, symptom assessment, distress, and health status were collected. Results: 323 participants [101 mAb, 221 non-mAb, 52.7±15.5 years, 47.7% male, body mass index (BMI) 31.4±8.4] were analyzed. Fewer symptoms at baseline were reported in mAb versus non-mAb participants (1.06±1.31 vs 1.78±2.15, respectively p=0.0177) 6 months: (0.911±1.276 mAb vs.1.75±2.22 non-mAb, p=0.0427). Both groups showed significant within-group decreases in symptom number (52 to 21 mAb, 126 to 63 non-mAb) and symptom burden (p=0.0088 mAb, p<0.00001 non-mAb). mAb patients had significantly shorter infection-to-baseline interval (days) (120.4±55.3 mAb vs 194.0±89.3 non-mAb, p<0.00001); less frequent history of myocardial infarction (0.0 vs 3.9%, p=0.0464); headache (2.0% vs.11.8%, p=0.0046), rash (3.1% vs 9.9%, p=0.0377), and miscellaneous muscle complaints (2.0% vs 12.3%, p=0.0035), plus significantly better 6-month mood. (2.2% vs 13.2%, p=0.0390). Conclusion: mAb treated participants had reduced symptom burden and consistently reported fewer symptoms than non-mAb at all time points despite less time since acute illness. Both groups reported a statistically significant decrease in symptoms by 6-month visit with no statistically significant differences between them at follow-up.

Economic Burden and Patient-Reported Outcomes of Nonalcoholic Fatty Liver Disease.

In addition to adverse clinical outcomes such as liver-related morbidity and mortality, nonalcoholic fatty liver disease (NAFLD) is associated with a substantial public health and economic burden and could also potentially impair health-related quality of life and other patient-reported outcomes. The disease also affects multiple aspects of patients' quality of life which are the most pronounced in physical health-related and fatigue domains as well as work productivity, and get more severe in patients with advanced liver disease or with non-hepatic comorbidities. The economic burden of NAFLD is substantial and is increasing, with the highest costs in those with advanced disease.

The combination of the enhanced liver fibrosis and FIB-4 scores to determine significant fibrosis in patients with nonalcoholic fatty liver disease.

BACKGROUND: The presence of fibrosis in NAFLD is the most significant risk factor for adverse outcomes. We determined the cutoff scores of two non-invasive te sts (NITs) to rule in and rule out significant fibrosis among NAFLD patients. METHODS: Clinical data and liver biopsies were used for NAFLD patients included in this analysis (2001-2020). The enhanced liver fibrosis (ELF) and FIB-4 NITs were calculated. Liver biopsies were read by a single hematopathologist and scored by the NASH CRN criteria. Significant fibrosis was defined as stage F2-F4. RESULTS: There were 463 NAFLD patients included: 48 ± 13 years old, 31% male, 35% type 2 diabetes; 39% had significant fibrosis; mean ELF score was 9.0 ± 1.2, mean FIB-4 score was 1.22 ± 1.05. Patients with significant fibrosis were older, more commonly male, had lower BMI but more components of metabolic syndrome, higher ELF and FIB-4 (p < 0.0001). The performance of the two NITs in identifying significant fibrosis was: AUC (95% CI) = 0.78 (0.74-0.82) for ELF, 0.79 (0.75-0.83) for FIB-4. The combination of ELF score ≥9.8 and FIB-4 ≥ 1.96 returned a positive predictive value of 95% which can reliably rule in significant fibrosis (sensitivity 22%, specificity >99%), while an ELF score ≤7.7 or FIB-4 ≤ 0.30 had a negative predictive value of 95% ruling out significant fibrosis (sensitivity 98%, specificity 22%). CONCLUSIONS: The combination of ELF and FIB-4 may provide practitioners with easily obtained information to risk stratify patients with NAFLD who could be referred to specialists or for enrollment in clinical trials.

Expediting Treatment of Trauma Patients in the Emergency Department: Rapid Trauma Evaluation (RTE).

BACKGROUND: Criteria for trauma determination evolves. We developed/evaluated a Rapid Trauma Evaluation (RTE) process for a trauma patient subset not meeting preestablished trauma criteria. METHODS: Retrospective study (July 2019 - May 2020) for patients either > 65 years with ground level fall within 24 hours or in a motorcycle collision (MCC) arriving by EMS not meeting ACS trauma-criteria. RTE process was immediate evaluation by nurse/EMT, room placement, physician notification, undressing/gowning, vital signs, head-to-toe assessment, upgrade trauma status. Number/type of admissions, discharges, trauma upgrades, LOS obtained via trauma-registry and chart-review. For comparison, historic controls (HC) were used [all patients meeting RTE criteria seen in the ED prior to RTE (Apr- June 2019)]. RESULTS: The RTE cohort (n=755) was 77% falls,23% MCCs, median age 82 [IQR 74-88] years; 42% male-Among falls, 3.2% required a modified-upgrade; 0.7% full-upgrade, 55% admitted [29.4% trauma). HC (n=575) was 92.3% falls, 7.7% MCCs, median age 81 (IQR: 67-88) years, 40.5% males-57.4% admitted (22% trauma). RTE MCC median age 42 (IQR:30-49) years, 84.4% male- 21.9% were upgraded [(6 modified-trauma; 1 full-trauma; 43.8% admitted (85.7% trauma)]. HC MCC median age 29 (IQR: 23-41) years, 95.5% male, 54.5% admitted (75% trauma]. No difference on demographics, admissions or discharges between groups (P>0.05) except HC MCC was younger (P<0.005). RTE median LOS was shorter than HC [203 (IQR: 147-278) minutes vs. 286 (IQR: 205-392) minutes, P<0.001]. CONCLUSIONS: Patients > 65 years with a ground level fall or in a MCC arriving via EMS not meeting ACS trauma criteria may benefit from RTE.

How long is too long: A retrospective study evaluating the impact of the duration of noninvasive oxygenation support strategies (high flow nasal cannula & BiPAP) on mortality in invasive mechanically ventilated patients with COVID-19.

BACKGROUND/AIM: We investigated the association of noninvasive oxygenation support [high flow nasal cannula (HFNC) and BiPAP], timing of invasive mechanical ventilation (IMV), and inpatient mortality among patients hospitalized with COVID-19. METHODS: Retrospective chart review study of patients hospitalized with COVID-19 (ICD-10 code U07.1) and received IMV from March 2020-October 2021. Charlson comorbidity index (CCI) was calculated; Obesity defined as body mass index (BMI) ≥ 30 kg/m2; morbid obesity was BMI ≥ 40 kg/m2. Clinical parameters/vital signs recorded at time of admission. RESULTS: 709 COVID-19 patients underwent IMV, predominantly admitted from March-May 2020 (45%), average age 62±15 years, 67% male, 37% Hispanic, and 9% from group living settings. 44% had obesity, 11% had morbid obesity, 55% had type II diabetes, 75% had hypertension, and average CCI was 3.65 (SD = 3.11). Crude mortality rate was 56%. Close linear association of age with inpatient-mortality risk was found [OR (95% CI) = 1.35 (1.27-1.44) per 5 years, p<0.0001)]. Patients who died after IMV received noninvasive oxygenation support significantly longer: 5.3 (8.0) vs. 2.7 (SD 4.6) days; longer use was also independently associated with a higher risk of inpatient-mortality: OR = 3.1 (1.8-5.4) for 3-7 days, 7.2 (3.8-13.7) for ≥8 days (reference: 1-2 days) (p<0.0001). The association magnitude varied between age groups: 3-7 days duration (ref: 1-2 days), OR = 4.8 (1.9-12.1) in ≥65 years old vs. 2.1 (1.0-4.6) in <65 years old. Higher mortality risk was associated with higher CCI in patients ≥65 (P = 0.0082); among younger patients, obesity (OR = 1.8 (1.0-3.2) or morbid obesity (OR = 2.8;1.4-5.9) (p<0.05) were associated. No mortality association was found for sex or race. CONCLUSION: Time spent on noninvasive oxygenation support [as defined by high flow nasal cannula (HFNC) and BiPAP] prior to IMV increased mortality risk. Research for the generalizability of our findings to other respiratory failure patient populations is needed.

Development and validation of a primary sclerosing cholangitis-specific health-related quality of life instrument: CLDQ-PSC.

OBJECTIVES: To understand the full impact of primary sclerosing cholangitis (PSC) on patients' health, it is important to assess their health-related quality of life (HRQL). Using the Chronic Liver Disease Questionnaire (CLDQ), we aimed to develop and validate a PSC-specific HRQL instrument. METHODS: Previously collected clinical and patient-reported outcome data from PSC patients were used. The original CLDQ with 29 items was subjected to item reduction, followed by factor analysis. A standard HRQL instrument validation pipeline was then applied to the new CLDQ-PSC. RESULTS: There were 100 PSC patients (44±13 y, 32% male, 79% college educated, 39% cirrhosis, 67% inflammatory bowel disease, 66% ulcerative colitis, and 50% on ursodeoxycholic acid After item reduction and exploratory factor analysis, there were 24 items and 5 factors left; based on factor loadings, the factors were named emotional function, fatigue, symptoms, worry, and sleep. Internal consistency assessment returned Cronbach alpha 0.85-0.94, item-to-own domain correlations >0.66 for 22/24 items. Known-groups validity suggests discrimination between PSC patients with and without cirrhosis or its complications, obesity, history of depression, weight loss, and PSC patients on versus not on ursodeoxycholic acid (p<0.05 for all or select CLDQ-PSC domains). Relevant items of Short Form-36 and CLDQ-PSC were highly correlated (all p<0.0001). Matching with items of another PSC-specific instrument (PSC-patient-reported outcome; 42 items) for relevance and redundancy suggests that CLDQ-PSC is a relevant, comprehensive, and short HRQL instrument, which can be used for patients with PSC. CONCLUSIONS: The CLDQ-PSC is a PSC-specific HRQL instrument that was developed using an established methodology and demonstrated good psychometric characteristics.

Utility of public knowledge bases for the interpretation of comprehensive tumor molecular profiling results.

With the growing use of comprehensive tumor molecular profiling (CTMP), the therapeutic landscape of cancer is rapidly evolving. NGS produces large amounts of genomic data requiring complex analysis and subsequent interpretation. We sought to determine the utility of publicly available knowledge bases (KB) for the interpretation of the cancer mutational profile in clinical practice. Analysis was performed across patients who previously underwent CTMP. Independent interpretation of the CTMP was performed manually, and then, the recommendations were compared to ones present in KBs (OncoKB, CIViC, CGI, CGA, VICC, MolecularMatch). A total of 222 CTMP reports from 222 patients with 932 genomic alterations (GA) were identified. For 368 targetable GA identified in 171 (77%) of the patients, 1381 therapy recommendations were compiled. Except for CGA, therapy ESCAT LOE I, II, IIIA and IIIB therapy options were equally represented in the majority of KB. Personalized treatment options with ESCAT LOE I-II were provided for 35 patients (16%); MolecularMatch/CIViC allowed to collect ESCAT I-II treatment options for 34 of them (97%), OncoKB/CGI-for 33 of them (94%). Employing VICC and CGA 6 (17%) and 20 (57%) of patients were left without ESCAT I or II treatment options. For 88 patients with ESCAT level III-B therapy recommendations: only 2 (2%), 3 (3%), 4 (5%) and 6 (7%) of patients were left without options with CIViC, MolecularMatch, CGI and OncoKB, and with VICC-12 (14%). Highest overlap ratio was observed for IIIA (0.81) biomarkers, with the comparable results for LOE I-II. Meanwhile, overlap ratio for ESCAT LOE IV was 0.22. Public KBs provide substantial information on ESCAT-I/R1 biomarkers, but the information on ESCAT II-IV and resistance biomarkers is underrepresented. Manual curation should be considered the gold standard for the CTMP interpretation.

Regular Exercise Is Associated With Low Fatigue Levels and Good Functional Outcomes After COVID-19: A Prospective Observational Study.

OBJECTIVE: The aim of the study is to identify the impact of postacute SARS-CoV-2 infection on patient outcomes. DESIGN: This is a prospective, repeated measure, observational study of consented adults with positive SARS-CoV-2 quantitative polymerase chain reaction or antigen test more than 28 days after infection. Only data from the initial study visit are reported, including disease history, symptoms checklist, patient questionnaires, cognitive tests, social/medical histories, vitals, grip strength, and 2-min walk distance. RESULTS: Two hundred eighteen patients were studied: 100 hospitalized (57.3 ± 15.4 yrs, 62% male, body mass index: 31.3 ± 8.0) and 118 nonhospitalized (46.2 ± 14.6 yrs, 31% male, body mass index: 29.7 ± 7.5). Post-COVID patients reported mean 1.76 symptoms; ≥15% reported fatigue, memory loss, and shortness of breath. Grip strength was 14% lower than norms ( P < 0.0001). Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue), mood (Patient Health Questionnaire), and well-being (EuroQol 5 Dimension 5 Level) scores were lower than the population norms ( P < 0.05). Hospitalized versus nonhospitalized post-COVID patients performed worse on cognitive assessments (processing speed test-Wechsler Adult Intelligence Scale-Fourth Edition Symbol Search) and reported less regular exercise (≥30 mins ≥3× per week; P < 0.05). In addition, 30% had severe fatigue (by the Functional Assessment of Chronic Illness Therapy-Fatigue); those patients reported less exercise ( P < 0.05). In multivariate models, lack of exercise was independently associated with multiple post-COVID-19 impairments. CONCLUSIONS: Low levels of exercise are an independent risk factor for post-COVID sequelae. Patients who report less exercise have low grip strength, higher levels of fatigue, memory loss, shortness of breath, depression, and poorer quality of life.

Clinical and patient-reported outcome profile of patients with hepatitis B viral infection from the Global Liver Registry™.

Chronic hepatitis B (CHB) infection is one of the most common causes of cirrhosis and liver cancer worldwide. Our aim was to assess clinical and patient-reported outcome (PRO) profile of CHB patients from different regions of the world using the Global Liver Registry. The CHB patients seen in real-world practices are being enrolled in the Global Liver Registry. Clinical and PRO (FACIT-F, CLDQ, WPAI) data were collected and compared to baseline data from CHB controls from clinical trials. The study included 1818 HBV subjects (48 ± 13 years, 58% male, 14% advanced fibrosis, 7% cirrhosis) from 15 countries in 6/7 Global Burden of Disease super-regions. The rates of advanced fibrosis varied (3-24%). The lowest PRO scores across multiple domains were in HBV subjects from the Middle East/North Africa (MENA), the highest - Southeast/East and South Asia. Subjects with advanced fibrosis had PRO impairment in 3 CLDQ domains, Activity of WPAI (p < 0.05). HBV subjects with superimposed fatty liver had more PRO impairments. In multivariate analysis adjusted for location, predictors of PRO impairment in CHB included female sex, advanced fibrosis, and non-hepatic comorbidities (p < 0.05). In comparison to Global Liver Registry patients, 242 controls from clinical trials had better PRO scores (Abdominal, Emotional, and Systemic scores of CLDQ, all domains of WPAI) (p < 0.05). In multivariate analysis with adjustment for location and clinicodemographic parameters, the associations of PROs with the enrollment setting (real-life Global Liver Registry vs. clinical trials) were no longer significant (all p > 0.10). The clinico-demographic portrait of CHB patients varies across regions of the world and enrollment settings. Advanced fibrosis and non-hepatic comorbidities are independently associated with PRO impairment in CHB patients.

A Novel Method for Estimating Right Atrial Pressure With Point-of-Care Ultrasound.

BACKGROUND: Current noninvasive estimation of right atrial pressure (RAP) by either bedside jugular venous pressure exam or inferior vena cava measurement during a comprehensive echocardiogram offers imprecise estimates of actual RAP. METHODS: We enrolled 41 patients in a prospective, blinded study to validate a novel point-of-care ultrasound method using direct right atrial depth (RAD) measurement and jugular venous ultrasound to estimate RAP. Two subjects were excluded, and 39 were included in the final analysis. A parasternal long-axis view was obtained, and the depth of the noncoronary cusp attachment to the posterior left ventricular outflow tract was recorded as the RAD. This was added to an estimate of the jugular venous pressure obtained during a jugular vein ultrasound to calculate an estimated RAP (RAPUS). The RAPUS was compared to the RAP measurement during right heart catheterization (RAPcath) both as measured and as corrected for where the catheter was zeroed. RESULTS: The correlation coefficient between RAPcath and RAPUS was +0.75; regression R2, 0.56; and bias, -0.49 mm Hg (95% CI, -1.42 to +0.43 mm Hg), with the limits of agreement -5.56 to +7.24 mm Hg and accuracy of 3 mm Hg or less in 29 (74%) of the subjects. For the RAPUS corrected for the catheter zero point, the correlation coefficient between RAPcath and RAPUS was +0.72; regression R2, 0.52; and bias, -0.60 mm Hg (95% CI, -1.60 to +0.39 mm Hg), with the limits of agreement -5.56 to +7.24 mm Hg and accuracy of 3 mm Hg or less in 26 (67%) of the subjects. CONCLUSION: This simple ultrasound evaluation of RAD and the right jugular vein correlates well with actual RAP and can accurately estimate RAP within 3 mm Hg in most patients. This has the potential to improve our bedside volume status exam, as well as improve the accuracy of RAP estimation during comprehensive echocardiogram.