Impact of coronary CT angiography in selection of treatment modalities and subsequent cardiovascular events in Thai patients with stable CAD.

BACKGROUND: Coronary computed tomography angiography (CCTA) enables improved diagnosis of subclinical, coronary artery disease (CAD). This retrospective cohort study investigated the association between different treatment modalities guided by CCTA and the prevention of major adverse cardiovascular events (MACEs) in patients with stable CAD. METHODS: From 2005 to 2013, a total of 9338 patients, including both asymptomatic individuals with risk factors and symptomatic patients with suspected CAD, who underwent CCTA were analyzed. The patients were categorized into one of three groups based on results of CCTA: obstructive CAD (≥ 50% stenosis in at least one vessel), non-obstructive CAD (1-49% stenosis in at least one vessel), and no observed CAD (0% stenosis). They were subsequently followed up to assess the treatment they received and the occurrence of MACEs (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or late revascularization). RESULTS: During an average follow-up period of 9.9 ± 2.4 years, patients with obstructive CAD had the highest incidence of MACEs (19.8%), followed by those with non-obstructive CAD and no coronary artery stenosis (10.3 and 5.5%, respectively). After adjusting for confounding variables, it was found that patients treated with statins alone were the least likely to develop MACEs in all three groups, compared to those receiving no treatment, with hazard ratios (95% CI) of 0.43 (0.32, 0.58), 0.47 (0.34, 0.64), and 0.46 (0.31, 0.69), respectively. In patients with obstructive CAD, treatment with a combination of statin and aspirin, or early revascularization was associated with a lower likelihood of experiencing MACEs compared to no treatment with hazard ratios of 0.43 (0.33, 0.58) and 0.64 (0.43, 0.97), respectively. CONCLUSION: CCTA offers useful guidance for the treatment of patients with stable CAD and shows potential for prevention of CV events. However, the full validation of a given strategy utilizing CCTA will require a prospective longitudinal study, utilizing a randomized clinical trial design.

Utility of coronary artery calcium in refining 10-year ASCVD risk prediction using a Thai CV risk score.

Background: Coronary artery calcium (CAC) scanning is a valuable additional tool for calculating the risk of cardiovascular (CV) events. We aimed to determine if a CAC score could improve performance of a Thai CV risk score in prediction of 10-year atherosclerotic cardiovascular disease (ASCVD) risk for asymptomatic patients with CV risk factors. Methods: This was a retrospective cohort study that enrolled asymptomatic patients with CV risk factors who underwent CAC scans between 2005 and 2013. The patients were classified as low-, intermediate-, or high-risk (<10%, 10%-<20%, and ≥20%, respectively) of having ASCVD within 10-years based on a Thai CV risk score. In each patient, CAC score was considered as a categorical variable (0, 1-99, and ≥100) and natural-log variable to assess the risk of developing CV events (CV death, non-fatal MI, or non-fatal stroke). The C statistic and the net reclassification improvement (NRI) index were applied to assess whether CAC improved ASCVD risk prediction. Results: A total of 6,964 patients were analyzed (mean age: 59.0 ± 8.4 years; 63.3% women). The majority of patients were classified as low- or intermediate-risk (75.3% and 20.5%, respectively), whereas only 4.2% were classified as high-risk. Nearly half (49.7%) of patients had a CAC score of zero (no calcifications detected), while 32.0% had scores of 1-99, and 18.3% of ≥100. In the low- and intermediate-risk groups, patients with a CAC ≥100 experienced higher rates of CV events, with hazard ratios (95% CI) of 1.95 (1.35, 2.81) and 3.04 (2.26, 4.10), respectively. Incorporation of ln(CAC + 1) into their Thai CV risk scores improved the C statistic from 0.703 (0.68, 0.72) to 0.716 (0.69, 0.74), and resulted in an NRI index of 0.06 (0.02, 0.10). To enhance the performance of the Thai CV risk score, a revision of the CV risk model was performed, incorporating ln(CAC + 1), which further increased the C statistic to 0.771 (0.755, 0.788). Conclusion: The addition of CAC to traditional risk factors improved CV risk stratification and ASCVD prediction. Whether this adjustment leads to a reduction in CV events and is cost-effective will require further assessment.

Clinical and immunological characteristics for BK polyomavirus-associated nephropathy after kidney transplantation.

INTRODUCTION: BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) can cause a significant risk of allograft impairment after kidney transplantation (KT). Intact BKPyV-specific immunity is associated with viral containment. This study investigated BKPyV-specific immunological factors among KT recipients. METHODS: This prospective study in a single transplant center from January 2019 to August 2019 assessed associations between clinical and immunological characteristics, with a focus on BKPyV-cell-specific immunity and BKPyVAN, among KT recipients aged ≥15 years. The numbers of interferon-gamma (IFN-γ)-producing CD4+  T, CD8+  T, natural killer (NK), and natural killer T (NKT) cells were measured after stimulation with large T antigen and viral capsid protein 1 (VP1). RESULTS: In total, 100 KT recipients were included (mean age ± SD, 42 ± 11 years); 35% of the recipients were female patients, and 70% had received induction immunosuppressive therapy. The 1-year cumulative incidence of high-level BKPyV DNAuria (possible BKPyVAN) and (presumptive BKPyVAN) was 18%. Among 40 patients with immunological factor data, pre-KT %NK cells (hazard ratio [HR], 1.258; 95% confidence interval [CI], 1.077-1.469; p = .004) and %VP1-specific NK cells (HR, 1.209; 95% CI, 1.055-1.386; p = .006) were factors independently associated with possible and presumptive BKPyVAN. KT recipients with possible and presumptive BKPyVAN were more likely to exhibit significant mean coefficients of %NK, %VP1-specific NK, and %NKT cells at 1 month after KT than before KT (all p < .05). CONCLUSION: Individuals with nonspecific and VP1-specific NK cells before KT and increasing numbers of these cells after KT may be at risk for high-level BKPyV DNAuria and presumptive BKPyVAN. Further studies are needed to determine the utility of BKPyV-specific innate immune surveillance in predicting the occurrence of BKPyVAN.

Evaluation of transitions from early hypertension to hypertensive chronic kidney disease, coronary artery disease, stroke and mortality: a Thai real-world data cohort.

Objective: Systemic arterial hypertension (HT) is a major modifiable risk factor for cardiovascular disease (CVDs), associated with all-cause death (ACD). Understanding its progression from the early state to late complications should lead to more timely intensification of treatment. This study aimed to construct a real-world cohort profile of HT and to estimate transition probabilities from the uncomplicated state to any of these long-term complications; chronic kidney disease (CKD), coronary artery disease (CAD), stroke, and ACD. Methods: This real-world cohort study used routine clinical practice data for all adult patients diagnosed with HT in the Ramathibodi Hospital, Thailand from 2010 to 2022. A multi-state model was developed based on the following: state 1-uncomplicated HT, 2-CKD, 3-CAD, 4-stroke, and 5-ACD. Transition probabilities were estimated using Kaplan-Meier method. Results: A total of 144,149 patients were initially classified as having uncomplicated HT. The transition probabilities (95% CI) from the initial state to CKD, CAD, stroke, and ACD at 10-years were 19.6% (19.3%, 20.0%), 18.2% (17.9%, 18.6%), 7.4% (7.1%, 7.6%), and 1.7% (1.5%, 1.8%), respectively. Once in the intermediate-states of CKD, CAD, and stroke, 10-year transition probabilities to death were 7.5% (6.8%, 8.4%), 9.0% (8.2%, 9.9%), and 10.8% (9.3%, 12.5%). Conclusions: In this 13-year cohort, CKD was observed as the most common complication, followed by CAD and stroke. Among these, stroke carried the highest risk of ACD, followed by CAD and CKD. These findings provide improved understanding of disease progression to guide appropriate prevention measures. Further investigations of prognostic factors and treatment effectiveness are warranted.

Is anti-seizure medication the culprit of SUDEP?

BACKGROUND: Heart rate variability (HRV) reduction is a potential biomarker for sudden cardiac death. This study aimed to study the effects of anti-seizure medications (ASMs), adjusted with reported factors associated with sudden unexpected death in epilepsy (SUDEP) on HRV parameters. METHODS: We recruited patients who were admitted in our epilepsy monitoring unit between January 2013 and December 2021. Two 5-min electrocardiogram epochs during wakefulness and sleep were selected in each patient. HRV analysis with Python® software was performed. The imputed datasets were used for linear regression analysis to assess association between each ASM item and all HRV parameters. The effects of ASM on HRV parameters were subsequently adjusted with the significant clinical characteristics and the concomitant use of other ASMs, respectively. RESULTS: Carbamazepine (CBZ), levetiracetam (LEV), lamotrigine (LTG), and clonazepam (CZP) were statistically significantly associated with changes of sleep HRV parameters. Only CBZ showed negative effects with reduction in HRV, evidenced as lower standard deviation of RR interval (SDNN), even when adjusted with concomitant use of other ASMs (p = 0.045) and had a trend of significance when adjusted with significant clinical characteristics of concurrent taking of beta-blocker drug (p = 0.052). LEV and CZP showed opposite effects with increased HRV even when adjusted with significant clinical characteristics and the concomitant use of other ASMs. CONCLUSIONS: CBZ showed negative effects on HRV. We proposed that CBZ should be cautiously used in patients with known risks for SUDEP. In addition, HRV assessment should be performed prior to commencing CBZ and re-performed in follow-up in cases of prolonged use.

Predictive values of coronary artery calcium and arterial stiffness for long-term cardiovascular events in patients with stable coronary artery disease.

BACKGROUND: Subclinical atherosclerosis detected by increased coronary artery calcium (CAC) or arterial stiffness as reflected by cardio-ankle vascular index (CAVI) has been associated with major adverse cardiovascular events (MACEs). However, comparative data from these two assessments in the same population are still limited. METHODS: From 2005 to 2013, patients with stable coronary artery disease (CAD), both asymptomatic and symptomatic who underwent both coronary computed tomography and CAVI were enrolled and followed for occurrence of MACEs (cardiovascular [CV] death, nonfatal myocardial infarction [MI], and nonfatal stroke) until December 2019. A cause-specific hazard model was applied to assess the associations of CAC score, and CAVI with long-term MACEs. RESULTS: A total of 8687 patients participated. Of them, CAC scores were 0, 1-99, 100-399, and ≥400 in 49.7%, 31.9%, 12.3%, and 6.1%, respectively. Arterial stiffness (CAVI ≥ 9.0) was associated with the magnitude of CAC in 23.8%, 36.3%, 44.5%, and 56.2%, respectively. During an average of 9.9 ± 2.4 years follow-up, MACEs occurred in 8.0% (95% CI: 7.4%, 8.6%) of subjects. After adjusting for covariables, CAC scores of 100-399 and ≥400, and CAVIs of ≥9.0 were found to independently predict the occurrence of MACEs with the hazard ratios (95% CI) of 1.70 (1.13, 1.98), 1.87 (1.33, 2.63), and 1.27 (1.06, 1.52), respectively. Other risk predictors were hypertension, diabetes mellitus (DM), chronic kidney disease (CKD), aspirin, and statin therapy. CONCLUSIONS: A CAC score ≥100 or a CAVI ≥ 9.0 predicts the long-term occurrence of MACEs in both asymptomatic and symptomatic patients with stable CAD. These two noninvasive tests can be used as screening tools to guide treatment for the prevention of future CV events.

Causal Relationship of Coronary Artery Calcium on Myocardial Infarction and Preventive Effect of Antiplatelet Therapy.

Background: The role of coronary artery calcium score (CACS) to guide antiplatelet therapy in order to prevent myocardial infarction (MI) is still uncertain. This study aimed to find the causal relationship of CACS on MI and preventive effect of antiplatelet therapy. Methods: From 2005 to 2013, all patients with cardiovascular risk factors or symptoms of suspected CAD underwent coronary computed tomography. CACSs were measured using Agatston method and stratified into 4 groups: 0, 1-99, 100-399, and ≥ 400. Antiplatelet therapy was prescribed following physician discretion. Outcomes of interest were MI and bleeding. A mediation analysis was applied to find association pathways. CACS was considered as an independent variable, whereas antiplatelet therapy was considered as a mediator and MI considered the outcome of interest. Results: A total of 7,849 subjects were enrolled. During an average of 9.9 ± 2.4 years follow-up, MI and bleeding events occurred in 2.24% (n = 176) and 2.82% (n = 221) of subjects, respectively. CACSs 100-399 and CAC ≥ 400 were significantly associated with the development of MI [OR 3.14 (1.72, 5.72), and OR 3.22 (1.66, 6.25), respectively, p < 0.001]. Antiplatelet therapy reduced the risk of MI of these corresponding CAC groups with ORs of 0.60 (0.41, 0.78) and 0.56 (0.34, 0.77), p < 0.001]. A risk of bleeding was associated with antiplatelet therapy (only aspirin), anticoagulant, hypertension, male gender and old age. Conclusion: CACS was associated with the development of future MI. The preventive effect of antiplatelet therapy was clearly demonstrated in subjects with CACSs equal to or above 100, but this benefit was partially offset by an increased risk of bleeding.

Hemoglobin A1c in combination with fasting plasma glucose trumps fasting plasma glucose alone as predictive indicators for diabetes mellitus: an ambidirectional cohort study of Thai people with impaired fasting glucose.

INTRODUCTION: This ambidirectional cohort study aimed to assess the performance of combining hemoglobin A1c (HbA1c) to fasting plasma glucose (FPG) for estimation of progression rate to diabetes mellitus (DM) and to explore the risk factors of DM in patients with impaired fasting glucose (IFG). RESEARCH DESIGN AND METHODS: Patients with IFG were eligible for this study. IFG was defined as FPG of 100-125 mg/dL. Progression rates to DM were estimated using Kaplan-Meier analysis. Risk factors of DM were explored by Cox regression analysis. RESULTS: 3011 patients were enrolled with median follow-up time of 8 years (range: 6 months-29 years). Progression rates to DM in patients with FPG 100-109 mg/dL and 110-125 mg/dL were 2.64 and 4.79 per 100 person-years. After adjusting covariables, compared with patients with FPG 100-109 mg/dL plus normal HbA1c (<5.7%), hazard ratios (95% CI) of patients with FPG 110-125 plus normal HbA1c, FBG 100-109 plus abnormal HbA1c (5.7%-6.49%), and FPG 110-125 plus abnormal HbA1c were 5.89 (2.37 to 14.63), 16.30 (8.59 to 30.92), and 33.84 (16.41 to 69.78), respectively. Body mass index ≥27.5 kg/m2, serum triglyceride level ≥150 mg/dL, family history of DM, and low level of high-density lipoprotein-cholesterol were independently associated with risk of DM in patients with IFG. CONCLUSIONS: Patients with both IFG and abnormal HbA1c had higher risk of DM than patients with IFG alone. Therefore, performing HbA1c in combination with FPG helps to identify subgroups of people with IFG at highest risk of DM. These patients should have the highest priority in diabetes prevention programs, especially in countries with low and limited resources.

Risk and impact of delayed renal impairment in patients with locally advanced head and neck squamous cell carcinoma receiving chemoradiotherapy with cisplatin.

BACKGROUND: An incidence of cisplatin-induced acute kidney injury (AKI) of 34% has been reported in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC). However, delayed cisplatin-induced nephrotoxicity and long-term renal outcomes remain poorly studied. METHODS: Patients with LA-HNSCC who underwent definitive or postoperative cisplatin-based chemoradiotherapy (CRT) were included. Acute kidney disease (AKD) was defined as newly developed estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 for < 3 months, ≥ 35% decrease in eGFR, or > 50% increase in serum creatinine for <3 months from baseline. RESULTS: A total of 509 patients were analyzed. AKD and AKI occurred in 27.9% and 13.4% of patients, respectively. Most patients had primary prophylactic feeding tube (95%) and definitive CRT (83%). More AKD patients had an ECOG status of 0 (p = 0.017), diabetes (p = 0.044), and hypertension (p < 0.001). AKI, but not AKD, was significantly associated with cumulative cisplatin dose, delay, dose reduction, termination, and hospitalization during CRT. GFR percentage in patients with AKD declined significantly during CRT (- 36%), worsened at 3 months (- 39%), and had not recovered to baseline at 12 months after CRT (- 29%). Multivariate analysis identified ECOG status 0 and hypertension as significantly associated with the development of AKD. CONCLUSION: Almost one third of LA-HNSCC patients who underwent CRT with cisplatin developed AKD, and their eGFR did not recover to baseline even after 1 year. ECOG 0 and hypertension were associated with AKD. These findings may have been due to the physician's awareness of AKD and underestimation of its potential complications in fit patients.

Effects of Oral Procaterol for Postinfectious Cough in Adults: Single-Centre, Randomized Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Persistent cough following an upper respiratory tract infection (URTI) is common in clinical practice. We investigated the effects of procaterol on cough-specific quality of life (QoL) and peripheral-airway function among adults suffering from postinfectious cough (PIC). METHODS: This was a prospective, randomized, double-blinded placebo-controlled trial (NCT02349919) conducted at a university hospital. Seventy-four non-asthmatic adults who had persistent post-URTI cough for ≥3 weeks were assessed by a physical examination, chest/paranasal sinus radiographs, spirometry, and impulse oscillometry (IOS) and were allocated to receive procaterol or placebo for 4 weeks. The Thai version of the Leicester Cough Questionnaire (LCQ-T), spirometry and IOS were assessed at baseline, 2 weeks, and 4 weeks. RESULTS: Mean LCQ-T total scores for the procaterol group (10.8) and placebo group (10.9) at baseline were not significantly different (P=0.821). After adjustment for baseline Borg Cough Scale score and post-nasal drip, the mean between-group difference was not significant for LCQ-T total score (-1.26; 95% confidence interval [CI], -2.69 to 0.17), physical domain score (-0.35; 95% CI, -0.76 to 0.06), psychological domain score (-0.53; 95% CI, -1.06 to 0.01), or social domain score (-0.38; 95% CI, -0.92 to 0.16). Large improvements in LCQ-T total score were reported in both groups after 2 weeks (procaterol, 4.21±2.73; placebo, 5.34±3.2), and 4 weeks (procaterol, 5.94±3.68; placebo, 7.07±3.44). No differences between groups were found in the mean changes of spirometry or IOS parameters after 4 weeks. CONCLUSION: Our study shows that procaterol is not effective in the treatment of PIC, in terms of improvement of cough-specific QoL or peripheral-airway function.

Network meta-analysis of management of trigger thumb in children.

To estimate and rank cure and recurrence rates between conservative and operative treatments for trigger thumb in children. A systematic review was conducted by searching PubMed and Scopus. Eligible criteria were comparative studies included non-syndromic trigger thumbs, aged up to 10 years, reported at least 20 thumbs and followed up at least 12 months. Two assessors independently extracted data and appraised for cure, recurrence rates among observation, stretching, splinting, open surgery, and percutaneous surgery. We assessed the risk of bias in non-randomized studies of interventions. A network meta-analysis, and probability of being the best outcomes were estimated with surface under the cumulative ranking curves (SUCRA). From 6853 searched articles, eight studies (799 children and 981 thumbs) were included. Mean age was 1.87-2.83 years and average followed up time was 1-5.7 years. Open surgery, percutaneous release, splinting, and stretching had higher cure rate than observation; pooled risk ratio (95% confidence interval) of 2.06 (1.53-2.78), 1.79 (1.26-2.53), 1.76 (1.30-2.36), and 1.37 (0.93-2.03), respectively. Percutaneous release increased risk of recurrence 3.29 times (1.42-7.60) when compared with open surgery. The best cure rates were open surgery (SUCRA = 95) followed by splint (SUCRA = 63.4), and percutaneous technique (SUCRA= 62.8). The highest recurrence rates were percutaneous (SUCRA = 97.3), and open surgery (SUCRA = 62.4). Splint is the most appropriate intervention for pediatric trigger thumb. After failed conservative methods, open surgery is considered for operative treatment. Level of evidence: Therapeutic study level II-III.

Prevalence of small airways dysfunction in asthma with- and without-fixed airflow obstruction and chronic obstructive pulmonary disease.

BACKGROUND: Small airways dysfunction (SAD) is not uncommon in asthma without fixed airflow obstruction (FAO). OBJECTIVE: We aimed to determine if SAD in non-FAO asthma is different from FAO-asthma and COPD. METHODS: Cases of obstructive airway diseases who underwent spirometry, plethysmography, and impulse oscillometry [resistance at 5 Hz (R5) and at 20 Hz (R20), peripheral resistance (R5-R20), and reactance area (AX)] were reviewed, and classified as; 1) COPD, 2) FAO-asthma, and 3) non-FAO asthma. FAO was defined as post-bronchodilator (post-BD) FEV1/ FVC < 0.7. SAD was considered if 1) RV/TLC ≥ 40%, or 2) post-BD R5-R20 ≥ 0.075 kPa.L-1s. RESULTS: A total of 73 patients (22 COPD, 24 FAO-asthma, and 27 non-FAO asthma) were analyzed. RV/TLC ratio was higher in FAO-asthma and COPD (45 ± 5% and 42 ± 8%) than in non-FAO asthma (32 ± 8%), p < 0.001. Post-BD values of R5-R20 and AX (median; range) were higher in FAO-asthma (0.17; 0.08, 0.47, 13.24; 6.52, 82.11) than in non-FAO asthma (0.11; 0.03, 0.23, 8.63; 2.40, 22.02), p = 0.007 and p = 0.017, respectively. The prevalence of SAD among diagnosis group by RV/TLC criterion was different (95%, 59%, and 15% in FAO-asthma, COPD, and non-FAO asthma, p < 0.001), but those were not observed by R5-R20 criterion (95%, 68%, and 77%, p = 0.052). CONCLUSIONS: SAD in non-FAO asthma was less prevalent than FAO-asthma and COPD.

Tolerability and efficacy of concurrent chemoradiotherapy comparing carboplatin/paclitaxel versus platinum/5-FU regimen for locally advanced esophageal and esophagogastric junction cancers.

Platinum/5-fluorouracil (PF) is commonly used for chemoradiotherapy (CRT) for locally advanced esophageal and esophagogastric junction (EGJ) cancers. Weekly carboplatin and paclitaxel (CP) regimen for preoperative CRT has increased in popularity due to its potentially less toxicity. We retrospectively compared the tolerability and efficacy of these regimens. Patients with esophageal and EGJ squamous cell carcinoma (SCC) or adenocarcinoma who received CRT with curative intent were included. Safety and tolerability during CRT were evaluated using the CTCAE version 4.0. Efficacy was analyzed using pathologic complete response, disease-free survival, and overall survival. One hundred and twenty-four patients were eligible for analysis (CP = 64, PF = 60). Most patients had esophageal cancer (97%) with SCC histology (91%). Preoperative CRT was planned for 43% of patients in the CP group and 34% in the PF group (p = 0.306). The relative dose intensities of cisplatin (67.0%) and 5-fluorouracil (81.4%) were lower than those of carboplatin (86.6%) and paclitaxel (86.2%). No difference in the radiotherapy dose, hospitalization, interruption, or termination was observed between the groups. Dose reduction of chemotherapy was more frequent in the CP group (38 vs. 19%; p = 0.015). Febrile neutropenia was more frequent in the PF group (8 vs. 0%; p = 0.058). All-grade nausea/vomiting was lower in the CP group (20 vs. 38%; p = 0.032). Efficacy was comparable between both regimens. In the multivariate analysis, the CRT regimen was not a significant predictor of survival. The CP regimen had less toxicity than the PF regimen, while efficacy was comparable. A large prospective randomized study is warranted to confirm these results.

The detection of hepatocellular carcinoma (HCC) from patients' breath using canine scent detection: a proof-of-concept study.

Patients with hepatocellular carcinoma (HCC) have poor outcomes as a result of late detection of the disease. We investigated the possibility of using smell detection by dogs for detecting HCC from the breath of patients. Patients whose diagnosis of HCC was confirmed histologically or radiologically according to the American Association for the Study of Liver Diseases criteria had breaths collected using face masks and transported to the study test site. The numbering of the HCC samples was sent in a sealed envelope to blind the dog trainer during testing but allow for correct rewarding of the dog afterwards. One golden retriever was trained to detect HCC with positive feedback using known samples of HCC and healthy controls in a step-wise manner. The controls were selected from hospital staff and relatives of patients who were not involved in the study. They were questioned about the risks of their disease before selection. When the trainer was confident that the dog could recognize the HCC scent, blind testing was performed using 1 HCC : 3 healthy controls per test run. Once the dog signaled on a specimen, it was given a reward. The correct-detection rate was compared to the theoretical detection rate expected based on chance of 25% using the statistical one-sample test of proportions. Thirty-seven HCC patients were tested. The patients had a mean age of 58 years and 21/37 were male. Seventeen patients had hepatitis B and 14 patients had hepatitis C. Twenty-six patients had one HCC lesion; four patients had two lesions in the liver, whilst seven had many lesions. The number of patients in the very early, early, intermediate, advanced, and terminal stages of the Barcelona Clinic Liver Cancer classification was 5, 9, 21, 1, and 1, respectively. The dog detected correctly in 29 runs. The sensitivity for canine detection was 78% (95% CI: 62%-90%). Compared to the 25% correct indication expected based on chance, this was statistically significant (p < 0.001). CONCLUSION: This is the first study to look at the possibility of detecting HCC from breath using canine olfaction. Our results show that this is possible with an accuracy of 78% (p < 0.001 when compared to chance alone), and are thus a proof of concept. Further refinement of the process of detection will be needed before clinical application.