Intraprocedural Parenchymal Blood Volume Is a Predictor of Treatment Response for Chemoembolization in Hepatocellular Carcinoma: Results of a Prospective Study.

PURPOSE: To evaluate cone-beam parenchymal blood volume (PBV) before and after embolization as a predictor of radiographic response to transarterial chemoembolization in unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A phase IIa prospective clinical trial was conducted in patients with HCCs > 1.5 cm undergoing chemoembolization; 52 tumors in 40 patients with Barcelona Clinic Liver Criteria stage B disease met inclusion criteria. Pre- and postembolization PBV analysis was performed with a semiquantitative best-fit methodology for index tumors, with a predefined primary endpoint of radiographic response at 3 months. Analyses were conducted with Wilcoxon signed-rank tests and one-way analysis of variance on ranks. RESULTS: Mean tumoral PBV measurements before and after embolization were 170 mL/1,000 mL ± 120 and 0 mL/100 mL ± 130, respectively. Per modified Response Evaluation Criteria In Solid Tumors, 25 tumors (48%) exhibited complete response (CR), 13 (25%) partial response (PR), 3 (6%) stable disease (SD), and 11 (21%) progressive disease (PD). Statistically significant changes in median PBV (ΔPBV) were identified in the CR (P = .001) and PR (P = .003) groups, with no significant difference observed in SD (P = .30) and PD groups (P = .06). A statistically significant correlation between ΔPBV and tumor response was established by one-way analysis of variance on ranks (P = .036; CR, 200 mL/100 mL ± 99; PR, 240 mL/100 mL ± 370; SD, 64 mL/100 mL ± 99; PD, 88 mL/100 mL ± 129). CONCLUSIONS: Intraprocedural PBV can be used as a predictor of response in index HCC tumors of > 1.5 cm.

State of the ablation nation: a review of ablative therapies for cure in the treatment of hepatocellular carcinoma.

Primary liver cancer, mainly hepatocellular carcinoma, is one of the most common malignancies worldwide. Surgical management, either resection or transplantation, is considered definitive treatment, however, less than 20% of patients are ultimately candidates. Thermal ablation modalities such as radiofrequency ablation and microwave ablation have evolved such that these modalities have been applied with curative intent. Moreover, thermal ablation has demonstrated efficacy in treating early-stage tumors and can be offered as first-line treatment in patients with uncomplicated disease. Attributing to refinements in technology and techniques, recent studies evaluating stereotactic ablative body radiotherapy have shown promising results, while irreversible electroporation, an emerging modality, may further expand the role of ablative therapy in treating potentially resectable hepatocellular carcinoma.

Pooled Nucleic Acid Amplification Test for Screening of Stool Specimens for Shiga Toxin-Producing Escherichia coli.

Shiga toxin-producing Escherichia coli (STEC)-associated enteric illness is attributed to O157 and non-O157 serotypes; however, traditional culture-based methods underdetect non-O157 STEC. Labor and cost of consumables are major barriers to implementation of the CDC recommendation to test all stools for both O157 and non-O157 serotypes. We evaluated the feasibility of a pooled nucleic acid amplification test (NAAT) as an approach for screening stool specimens for STEC. For retrospective evaluation, 300 stool specimens were used to create pools of 10 samples each. The sensitivity was 83% for the preenrichment pooling strategy and 100% for the postenrichment pooling strategy compared with those for individual NAAT results. The difference in cycle threshold (CT) between individual and pooled NAAT results for specimens was significantly lower and more consistent for postenrichment pooling (stx1 mean = 3.90, stx2 mean = 4.28) than those for preenrichment pooling (excluding undetected specimens; stx1 mean = 9.34, stx2 mean = 8.96) (P ≤ 0.0013). Cost of consumables and labor time savings of 48 to 81% and 6 to 66%, respectively, were estimated for the testing of 90 specimens by the postenrichment pooled NAAT strategy on the basis of an expected 1 to 2% positivity rate. A 30-day prospective head-to-head clinical trial involving 512 specimens confirmed the sensitivity and labor savings associated with the postenrichment pooled NAAT strategy. The postenrichment pooled NAAT strategy described here is suitable for efficient large-scale surveillance of all STEC serotypes. Comprehensive detection of STEC will result in accurate estimation of STEC burden and, consequently, appropriate public health interventions.

Assessment of birth cohort screening of chronic hepatitis C in colorectal cancer screening patients in British Columbia.

Background: Since 2018, British Columbia (BC) has recommended chronic hepatitis C (HCV) screening for those born between 1945 and 1964, with a provincial prevalence of 2.31%. Combining HCV and colorectal cancer (CRC) screening can facilitate specialist referrals and follow-up. We assessed HCV screening uptake among CRC screening patients following the release of BC's birth cohort guidelines and examined the COVID-19 pandemic's impact on HCV screening practices. Methods: A retrospective review was conducted on patients referred to Vancouver Coastal Health Authority's CRC screening program. Two groups, Cohort A (October-December 2019) and Cohort B (December 2021), were studied to identify pandemic-related changes. Data on demographics, liver disease history, hepatitis B or HIV co-infection rates, and initial anti-hepatitis C and ribonucleic acid (RNA) testing dates were collected. Statistical analyses were performed with Stata 15.1. Results: A total of 579 patients were referred for the CRC screening program, of whom 465 were born between 1945 and 1964 and were included in the study. Among the 348 patients in cohort A, 144 (41%, 95% CI 36%-47%) were screened for HCV infection. Of these, four (1.2%) were positive for anti-hepatitis C, and one patient had positive RNA levels. Similar proportions of screenings were observed in cohort B (47.8%, 95% CI 39%-57%). Of those with liver disease, 66% had been screened for HCV. Conclusion: Birth cohort screening for HCV has been underutilized in British Columbia. Combining HCV and CRC screening could provide a practical approach to linking patients to health care.

The clinical effectiveness of elexacaftor/tezacaftor/ivacaftor (ETI) for people with CF without a F508del variant: A systematic review and meta-analysis.

BACKGROUND: Access to elexacaftor/tezacaftor/ivacaftor (ETI) for people with cystic fibrosis (PwCF) without a F508del variant is limited due to lack of clinical data supporting efficacy. METHODS: In this systematic review and meta-analysis, we examined patient-level data from studies reporting the clinical response to ETI for PwCF with non-F508del CFTR variants. We searched electronic data sources including Embase, MEDLINE, and CENTRAL from January 1st, 2019 to May 14th, 2024. FINDINGS: Our search results identified 4,795 studies and 20 met the eligibility criteria. 120 of 164 (73 %) individuals had a positive clinical response to ETI, defined by a sweat chloride (SwCl) decrease of ≥10 mmol/L or percent-predicted FEV1 (ppFEV1) improvement of ≥5 %. 51 unique ETI-responsive variants were represented across these 120 individuals and 27 of these variants (53 %) have not been previously approved by the U.S. FDA. For variants with at least 10 individuals treated with ETI to date, a consistent positive clinical response was observed for N1303K and G85E. For N1303K (n = 48), the median increase in ppFEV1 was 16 % (IQR: 8 %, 29 %), with a median decrease in SwCl of -9 (IQR: -4, -22) mmol/L. For G85E (n = 16), the median increase in ppFEV1 was 13.5 % (IQR: 8 %, 19 %) with a median decrease in SwCl of -46 (IQR: -39, -66) mmol/L. CONCLUSION: Additional ETI-responsive variants were identified following a comprehensive review of ETI clinical use in PwCF without F508del. This data can be used by the CF community in efforts to expand the labelled indications or to help advocate for off-label ETI reimbursement.

Systemic Air Embolism Complicating Computed Tomography-guided Percutaneous Transthoracic Biopsy of Cavitary Lung Lesions: A Systematic Review.

PURPOSE: Cavitary lung lesions often pose a diagnostic challenge, and tissue sampling can be required to obtain a confident diagnosis. Many authors contend that a computed tomography-guided percutaneous transthoracic lung biopsy (PTLB) of a cavitary lung lesion places a patient at higher risk for systemic air embolism (SAE) compared with biopsy of a noncavitary lesion. MATERIALS AND METHODS: We reviewed the literature for studies of SAE complicating PTLB. We searched English-language articles indexed through PubMed, Embase, and Ovid Medline and included articles published up to March 31, 2020. RESULTS: We identified 10 case reports of SAE complicating PTLB, and 3 case-cohort studies comparing cavitary and noncavitary lesion biopsy. Among the case-cohort studies reviewed, 4 SAE occurred among 145 biopsies of cavitary lesions (2.7%), and 65 SAE occurred among 3050 biopsies of noncavitary lesions (2.1%). The pooled odds ratio of PTLB complicating SAE of cavitary lesions compared with noncavitary lesions was 1.29 (95% confidence interval: 0.47-3.60). No deaths following SAE after computed tomography-guided PTLB of cavitary lesions were reported in recent literature. CONCLUSIONS: On the basis of available evidence, air embolism rates are similar for PTLB of cavitary and noncavitary lesions. Additional research and registry studies are necessary to better understand this topic.

The Extrapulmonary Effects of Cystic Fibrosis Transmembrane Conductance Regulator Modulators in Cystic Fibrosis.

The effects of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators on lung function, pulmonary exacerbations, and quality of life have been well documented. However, CF is a multiorgan disease, and therefore an evidence base is emerging on the systemic effects of CFTR modulators beyond the pulmonary system. This is of great clinical importance, as many of these studies provide proof of concept that CFTR modulators might be used one day to prevent or treat extrapulmonary manifestations stemming from CFTR dysfunction. In this concise review of the literature, we summarize the results of key publications that have evaluated the effects of CFTR modulators on weight and growth, pancreatic function, the gastrointestinal and hepatobiliary systems, sinus disease, bone disease, exercise tolerance, fertility, mental health, and immunity. Although many of these studies have reported beneficial extrapulmonary effects related to the use of ivacaftor (IVA) in patients with CF with at least one gating mutation, most of the evidence is low or very low quality, given the limited number of patients evaluated and the lack of control groups. Based on an even smaller number of studies evaluating the extrapulmonary effects of lumacaftor-IVA, the benefits are less clear. Although limited, these studies may provide the basis for future clinical trials to evaluate CFTR modulators on the extrapulmonary manifestations of CF.

A longitudinal analysis of cannabis use and mental health symptoms among gay, bisexual, and other men who have sex with men in Vancouver, Canada.

BACKGROUND: Cannabis use, anxiety, and depression are common among gay, bisexual, and other men who have sex with men (gbMSM) and some report using cannabis to manage mental health symptoms. METHODS: Sexually-active gbMSM aged ≥16 years were recruited into a longitudinal cohort through respondent-driven sampling and completed study visits every six months. Data on demographics, drug use, and anxiety and depression symptoms were collected via a self-administered computer-based survey. A study nurse determined previous mental health diagnoses and treatment. Using multivariable generalized linear mixed models, we examined factors associated with regular cannabis use (≥weekly in the previous 3 months) and, among individuals who reported anxiety or depression/bipolar diagnoses, factors associated with moderate/severe anxiety or depression symptoms. RESULTS: Of 774 participants (551 HIV-negative, 223 HIV-seropositive), 250 (32.3%) reported regular cannabis use, 200 (26.4%) reported ever being diagnosed with anxiety, and 299 (39.3%) reported ever being diagnosed with depression or bipolar disorder at baseline. Regular cannabis use was positively associated with HIV-seropositivity (aOR = 2.23, 95%CI:1.40-3.54) and previous mental health diagnosis (aOR = 1.52, 95%CI: 1.00-2.31, p = 0.05). Among those previously diagnosed with anxiety or depression/bipolar disorder, regular cannabis use was not associated with moderate/severe anxiety (aOR = 1.16, 95%CI:0.69-1.94) or depression symptoms (aOR = 0.96, 95%CI:0.59-1.58), respectively. LIMITATIONS: Because of observational study design, we are unable to determine absolute effect. CONCLUSIONS: Regular cannabis use was more likely among HIV-positive gbMSM and those previously diagnosed with a mental health disorder. No association was found between regular cannabis use and severity of anxious or depressive symptoms among those diagnosed with these conditions.