Lean body mass index is a marker of advanced tumor features in patients with hepatocellular carcinoma.

BACKGROUND: Obesity is an independent risk factor for the development of hepatocellular carcinoma (HCC) and may influence its outcomes. However, after diagnosis of HCC, like other malignancies, the obesity paradox may exist where higher body mass index (BMI) may in fact confer a survival benefit. This is frequently observed in patients with advanced HCC and cirrhosis, who often present late with advanced tumor features and cancer related weight loss. AIM: To explore the relationship between BMI and survival in patients with cirrhosis and HCC. METHODS: This is a retrospective cohort study of over 2500 patients diagnosed with HCC between 2009-2019 at two United States academic medical centers. Patient and tumor characteristics were extracted manually from medical records of each institutions' cancer registries. Patients were stratified according to BMI classes: < 25 kg/m2 (lean), 25-29.9 kg/m2 (overweight), and > 30 kg/m2 (obese). Patient and tumor characteristics were compared according to BMI classification. We performed an overall survival analysis using Kaplan Meier by the three BMI classes and after adjusting for Milan criteria. A multivariable Cox regression model was then used to assess known risk factors for survival in patients with cirrhosis and HCC. RESULTS: A total of 2548 patients with HCC were included in the analysis of which 11.2% (n = 286) were classified as non-cirrhotic. The three main BMI categories: Lean (n = 754), overweight (n = 861), and obese (n = 933) represented 29.6%, 33.8%, and 36.6% of the total population overall. Within each BMI class, the non-cirrhotic patients accounted for 15% (n = 100), 12% (n = 94), and 11% (n = 92), respectively. Underweight patients with a BMI < 18.5 kg/m2 (n = 52) were included in the lean cohort. Of the obese cohort, 42% (n = 396) had a BMI ≥ 35 kg/m2. Out of 2262 patients with cirrhosis and HCC, 654 (29%) were lean, 767 (34%) were overweight, and 841 (37%) were obese. The three BMI classes did not differ by age, MELD, or Child-Pugh class. Chronic hepatitis C was the dominant etiology in lean compared to the overweight and obese patients (71%, 62%, 49%, P < 0.001). Lean patients had significantly larger tumors compared to the other two BMI classes (5.1 vs 4.2 vs 4.2 cm, P < 0.001), were more likely outside Milan (56% vs 48% vs 47%, P < 0.001), and less likely to undergo transplantation (9% vs 18% vs 18%, P < 0.001). While both tumor size (P < 0.0001) and elevated alpha fetoprotein (P < 0.0001) were associated with worse survival by regression analysis, lean BMI was not (P = 0.36). CONCLUSION: Lean patients with cirrhosis and HCC present with larger tumors and are more often outside Milan criteria, reflecting cancer related cachexia from delayed diagnosis. Access to care for hepatitis C virus therapy and liver transplantation confer a survival benefit, but not overweight or obese BMI classifications.

Return-to-Sport Rates After Hip Arthroscopy for Femoroacetabular Impingement Syndrome in Flexibility Sports Athletes: A Systematic Review.

CONTEXT: Femoroacetabular impingement syndrome (FAIS) is a common cause of hip pain in young adults. Flexibility athletes represent an interesting subset due to the extreme range of motion requirements of their sport. OBJECTIVE: The objective of this review was to provide a summary of the outcomes of hip arthroscopy for FAIS in patients who participate in flexibility sports. DATA SOURCES: Three online databases (Medline, Embase, and PubMed) were searched from database inception (1946, 1974, and 1966, respectively) to January 10, 2023. STUDY SELECTION: Studies were screened for literature addressing surgical outcomes for flexibility athletes undergoing hip arthroscopy for FAIS. STUDY DESIGN: Systematic review. LEVEL OF EVIDENCE: Level 4. DATA EXTRACTION: Various patient-reported outcomes that evaluated the efficacy of hip arthroscopy in this patient population were abstracted and presented in descriptive and analytical format. Abstraction was performed by 2 reviewers. RESULTS: Overall, a total of 8 Level 3 or 4 studies and 295 patients (312 hips) were included in this review. The pooled standardized mean differences for the Visual Analog Scale for pain score, Modified Harris Hip Score, Hip Outcome Score - Activity of Daily Living scale, and Hip Outcome Score - Sport-Specific Subscale all demonstrated significant improvement after undergoing arthroscopy for FAIS between 12 and 116 months (N = 175, -1.97, 95% CI -2.5 to -1.4, P < 0.01, I2 = 76%; N = 211, 1.82, 95% CI 1.49 to 2.16, P < 0.01, I2 = 52%; N = 164, 1.75, 95% CI 1.42 to 2.05, P < 0.01, I2 = 28%; N = 211, 1.71, 95% CI 1.38 to 2.04, P < 0.01, I2 = 52%, respectively). Across 289 patients, 75.6% to 98% returned to sport at a similar or higher level than presurgery. CONCLUSION: This review demonstrates a trend of improvement in patient-reported pain, function, quality of life, and return to sport at a minimum of 12 months among flexibility athletes after hip arthroscopy to treat FAIS.

Hip microinstability diagnosis and management: a systematic review.

PURPOSE: The purpose of this systematic review is to present the most common causes, diagnostic features, treatment options and outcomes of patients with hip micro-instability. METHODS: Three online databases (MEDLINE, Embase, and PubMed) were searched from database inception March 2022, for literature addressing the diagnosis and management of patients with hip micro-instability. Given the lack of consistent reporting of patient outcomes across studies, the results are presented in a descriptive summary fashion. RESULTS: Overall, there were a total of 9 studies including 189 patients (193 hips) included in this review of which 89% were female. All studies were level IV evidence with a mean MINORS score of 12 (range: 10-13). The most commonly used features for diagnosis of micro-instability on history were anterior pain in 146 (78%) patients and a subjective feeling of instability with gait in 143 (81%) patients, while the most common feature on physical examination was the presence of anterior apprehension with combined hip extension and external rotation in 123 (65%) patients. The most common causes of micro-instability were iatrogenic instability secondary to either capsular insufficiency or cam over-resection in 76 (62%) patients and soft tissue laxity in 38 (31%) patients. CONCLUSION: The most common symptom of micro-instability on history was anterior hip pain and on physical exam was pain with hip extension and external rotation. There are many treatment options and when managed appropriately based on the precise cause of micro-instability, patients may demonstrate improved outcomes. LEVEL OF EVIDENCE: IV.

Kernel Flow: a high channel count scalable time-domain functional near-infrared spectroscopy system.

SIGNIFICANCE: Time-domain functional near-infrared spectroscopy (TD-fNIRS) has been considered as the gold standard of noninvasive optical brain imaging devices. However, due to the high cost, complexity, and large form factor, it has not been as widely adopted as continuous wave NIRS systems. AIM: Kernel Flow is a TD-fNIRS system that has been designed to break through these limitations by maintaining the performance of a research grade TD-fNIRS system while integrating all of the components into a small modular device. APPROACH: The Kernel Flow modules are built around miniaturized laser drivers, custom integrated circuits, and specialized detectors. The modules can be assembled into a system with dense channel coverage over the entire head. RESULTS: We show performance similar to benchtop systems with our miniaturized device as characterized by standardized tissue and optical phantom protocols for TD-fNIRS and human neuroscience results. CONCLUSIONS: The miniaturized design of the Kernel Flow system allows for broader applications of TD-fNIRS.

Changing Trends of Cirrhotic and Noncirrhotic Hepatocellular Carcinoma in the Era of Directly-Acting Antiviral Agents.

INTRODUCTION: The impact of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) on burden of cirrhotic and noncirrhotic hepatocellular carcinoma (HCC) has not been examined. We assessed recent trends in liver disease etiologies of HCC and proportion of noncirrhotic HCC since DAAs introduction. METHODS: Clinical characteristics including presence or absence of underlying cirrhosis were collected from 2,623 patients diagnosed with HCC between 2009 and 2019 at 2 large US centers. Logistic regression was performed to investigate the annual trends of HCC due to different liver diseases and proportions of noncirrhotic cases. RESULTS: In the DAA era (2014-2019), annual decline in HCV-HCC (odds ratio [OR] = 0.93, 95% confidence interval [CI] 0.88-0.99, P = 0.019), without change in trends of other liver diseases-related HCC, was observed. Annual increase in noncirrhotic HCC (OR 1.13, 95% CI 1.03-1.23, P = 0.009) and decline in cirrhotic HCC (OR 0.89, 95% CI 0.81-0.97, P = 0.009) along with similar trends for HCV-HCC-increase in noncirrhotic cases (OR 1.35, 95% CI 1.08-1.69, P = 0.009) and decrease in cirrhotic cases (OR 0.92, 95% CI 0.86-0.98, P = 0.012)-were observed during the DAA era. Compared with the pre-DAA era, HCC resection rate increased (10.7% vs 14.0%, P = 0.013) whereas liver transplantation rate decreased (15.1% vs 12.0%, P = 0.023) in the DAA era. DISCUSSION: Since introduction of DAAs, proportions of cirrhotic HCC have decreased, whereas proportions of noncirrhotic HCC have increased. These new trends were associated with change in utilization of liver resection and transplantation for HCC. The impact of changing patterns of DAA use on these trends will require further study.

Distinctive Features and Outcomes of Hepatocellular Carcinoma in Patients With Alcohol-Related Liver Disease: A US Multicenter Study.

INTRODUCTION: The burden of hepatocellular carcinoma (HCC) occurring in patients with alcoholic liver disease (ALD) is increasing at an alarming rate. The aims of this study were to compare the patient and tumor characteristics of HCC occurring in ALD-alone relative to and in addition to other chronic liver diseases. METHODS: Patients diagnosed with HCC between 2000 and 2014 were identified at 5 US clinical centers. The patients were categorized as ALD-alone, ALD plus viral hepatitis, or a non-ALD etiology. Clinical and tumor characteristics among the 3 groups were compared, and survival probability was estimated by the Kaplan-Meier method. The frequency of noncirrhotic HCC was compared across the 3 groups. RESULTS: A total of 5,327 patients with HCC were analyzed. Six hundred seventy (12.6%) developed HCC due to underlying ALD. Ninety-one percent of ALD-related HCC arose in men, in contrast to non-ALD etiologies where men accounted for 70% of HCCs cases (P < 0.001). Patients with ALD-alone-related HCC were older at diagnosis and had tumors less likely to be detected as part of routine surveillance. The ALD-alone cohort was least likely to be within the Milan criteria and to undergo liver transplantation. Overall survival in the ALD-alone HCC cohort was lower than the other 2 groups (1.07 vs 1.31 vs 1.41 years, P < 0.001). HCC in the noncirrhotic ALD cohorts occurred in only 3.5% of the patients compared with 15.7% in patients with non-ALD etiologies (P < 0.001). DISCUSSION: HCC occurring in patients with ALD occurred mostly in older men and almost exclusively in a cirrhotic background. They present with advanced tumors, and their survival is lower than HCCs occurring in non-ALD.

Type 2B von Willebrand disease associated with the release of platelet agglutinates from megakaryocytes in the bone marrow.

We report a child with thrombocytopenia since birth, circulating platelet agglutinates, and a tendency to bleed. A bone marrow aspirate revealed large platelet clumps within the bone marrow and megakaryocyte nuclei surrounded by halos of clumped platelets. Laboratory evaluation revealed type 2B von Willebrand disease. Gene sequencing revealed a G to C mutation at base 3923 of the VWF gene. This mutation was previously described in a family with circulating platelet clumps and abnormal megakaryopoiesis with release of clumped platelets in culture. This same mutation was previously described in a family with circulating platelet aggregates and abnormalities of platelet release from megakaryocytes in vitro. Presence of megakaryocytes with halos of clumped platelets in our patient suggests that platelet agglutinate occurs in the bone marrow in some type 2B von Willebrand disease patients.