Evaluation of tumor mutational burden in small early hepatocellular carcinoma and progressed hepatocellular carcinoma.

While researchers know that tumor mutational burden (TMB) is low in hepatocellular carcinoma (HCC), prior studies have not investigated TMB in cirrhosis, small early HCC and progressed HCC. HCC (n = 18) and cirrhosis (n = 6) cases were identified. TMB was determined by a 1.7 megabase, 409-gene next-generation sequencing panel. TMB values were defined as the number of nonsynonymous variants per megabase of sequence. There was no significant difference between cirrhosis versus small early HCC or between cohorts when stratified by size, early versus progressed, differentiation or morphology. There was a significant difference between cirrhosis and small early HCC versus progressed HCC (p = 0.045), suggesting TMB may be related to HCC progression. TMB similarities in small early HCC and background cirrhosis suggest TMB is not a useful tool for diagnosing small early HCC. Additional study is needed to address TMB in histological and molecular subsets of HCC.

Utilization Review of Paraneoplastic Neurological Syndrome Antibody Screening Panels: Experience at a Tertiary Academic Health Center.

BACKGROUND: Pathology departments play a pivotal role in managing laboratory test utilization in healthcare, and inappropriate resource deployment can contribute to unnecessary healthcare costs. Here we share our experience reviewing a send-out test and implementing a utilization strategy. Antibody testing is often considered in the workup for patients with unexplained paraneoplastic syndrome-like neurological presentations. It has been unclear how helpful these antibody tests are. The goal of study is to evaluate diagnostic utility of antibody screening panel results in patients suspicious for paraneoplastic neurological syndrome and possibly underlying occult malignancy. METHODS: We retrospectively reviewed the paraneoplastic neurological syndrome antibody test results. The positive predictive value and negative predictive value were calculated. The proportion of the antibody screening results were compared between groups with and without tumor with 2-sided χ2 test statistics. RESULTS: In total 348 panels were sent to 2 reference laboratories. From ARUP (Associated Regional and University Pathologists; Salt Lake City, Utah), 2 out of 232 screening panels yielded positive results (0.86%) and from the Mayo Clinic (Rochester, Minnesota), 26 out of 116 screening panels yielded positive results (22.4%). The overall positive predictive value was 3.57% (1/28) and the overall negative predictive value was 91.2% (292/320). There were no statistically significant differences between the antibody screening test results between the 2 groups with and without tumor. CONCLUSION: We found the diagnostic utility and yield for the paraneoplastic antibody panel to be low. Following a multidisciplinary team review of the study results, the pathology department has implemented several new utilization strategies.

Outcome of percutaneous sacroiliac joint fixation with porous plasma-coated triangular titanium implants: an independent review.

DESIGN: Independent retrospective review of a single surgeon's experience with a new technique of SI fixation. OBJECTIVE: Examine results of percutaneous fixation of the SI joint with porous coated triangular titanium implants. BACKGROUND: Diagnosis and treatment of a dysfunctional sacroiliac joint is challenging as well as controversial. Recently, percutaneous stabilization techniques have been implemented for fixation. There is minimal literature published on this technique. METHODS: Charts, radiographs, and CT scans of 31 patients operated on by a single surgeon were de-identified and randomized and then reviewed by investigators not involved with the care of the patients. Reviewers had no relationship with the implant manufacturer at the time of the review. OUTCOME MEASURES: intraoperative and postoperative complication, EBL, hospital stays, postoperative image location and number of lucent implants, ingrowth into implants, and bone across SI joint. RESULTS: 27 patients expressed satisfaction, 4 patients did not. Pain relief was noted to be Complete (16 patients), Excellent (5 patients), Good (9 patients), and Fair (1 patients). Four patients had postoperative complications. These were infected hematoma (2), L5 nerve root irritation (1), and L5-S1 discitis (1). One patient required revision. On 6 month postop CT scan, 18/19 patients had radiographic evidence of bone ingrowth and bone into or across the SI joint was evident in 8/19 patients. Lucency was noted around at least one implant in 5/19 patients. CONCLUSIONS: Results are promising for the use of this novel implant for a carefully selected group of patients with disabling SI dysfunction.

Effects of hyaluronic acid on mitochondrial function and mitochondria-driven apoptosis following oxidative stress in human chondrocytes.

Hyaluronic acid is widely used in the treatment of osteoarthritis and exerts significant chondroprotective effects. The exact mechanisms of its chondroprotective action are not yet fully elucidated. Human articular chondrocytes actively produce reactive oxygen and nitrogen species capable of causing cellular dysfunction and death. A growing body of evidence indicates that mitochondrial dysfunction and mitochondrial DNA damage play a causal role in disorders linked to excessive generation of oxygen free radicals. We hypothesized that the chondroprotective effects of hyaluronic acid on oxidatively stressed chondrocytes are due to preservation of mitochondrial function and amelioration of mitochondria-driven apoptosis. When primary human chondrocyte cultures were exposed to reactive oxygen or nitrogen species generators, mitochondrial DNA damage along with mitochondrial dysfunction and mitochondria-driven apoptosis accumulated as a consequence. In addition, cytokine-treated primary human chondrocytes showed increased levels of mitochondrial DNA damage. Pretreatment of chondrocytes with hyaluronic acid caused a decrease of mitochondrial DNA damage, enhanced mitochondrial DNA repair capacity and cell viability, preservation of ATP levels, and amelioration of apoptosis. The results of these studies demonstrate that enhanced chondrocyte survival and improved mitochondrial function under conditions of oxidative injury are probably important therapeutic mechanisms for the actions of hyaluronic acid in osteoarthritis.