Effect of graft-versus-host disease on outcomes of HLA-haploidentical peripheral blood transplantation using post-transplant cyclophophamide.

There is limited evidence regarding the association between graft-versus-host disease (GVHD) and reduced relapse in patients who undergo allogeneic hematopoietic stem cell transplantation from haploidentical donors (haplo-HSCT) using post-transplant cyclophosphamide (PTCY). We investigated the association between GVHD and transplant outcomes in 938 patients who received haplo-HSCT using PTCY. Overall survival (OS), relapse rate, and non-relapse mortality (NRM) were evaluated using landmark analysis at the landmark points at 100 and 360 days after HSCT for acute and chronic GVHD, respectively. Grade I-II acute GVHD was not associated with OS (adjusted hazard ratio: 1.15, 95% confidence interval: 0.85-1.57), relapse (1.03, 0.74-1.45) and NRM (1.15, 0.74-1.77). Conversely, grade III-IV acute GVHD was associated with higher NRM (3.16, 1.61-6.19), but no other outcomes. Limited chronic GVHD was not associated with OS (1.11, 0.48-1.95), relapse (1.05, 0.30-3.75) and NRM (1.30, 0.45-3.79). Extensive chronic GVHD was associated with higher NRM (2.40, 1.03-5.57), but no other outcome. In conclusion, any GVHD was not associated with a reduced relapse rate and improved OS, and Grade III-IV acute GVHD and extensive chronic GVHD were associated with higher NRM in patients who received haplo-HSCT using PTCY.

Pathophysiological insights into machine learning-based subphenotypes of acute heart failure with preserved ejection fraction.

OBJECTIVE: The heterogeneous pathophysiology of the diverse heart failure with preserved ejection fraction (HFpEF) phenotypes needs to be examined. We aim to assess differences in the biomarkers among the phenotypes of HFpEF and investigate its multifactorial pathophysiology. METHODS: This study is a retrospective analysis of the PURSUIT-HFpEF Study (N=1231), an ongoing, prospective, multicentre observational study of acute decompensated HFpEF. In this registry, there is a predefined subcohort in which we perform multibiomarker tests (N=212). We applied the previously established machine learning-based clustering model to the subcohort with biomarker measurements to classify them into four phenotypes: phenotype 1 (n=69), phenotype 2 (n=49), phenotype 3 (n=41) and phenotype 4 (n=53). Biomarker characteristics in each phenotype were evaluated. RESULTS: Phenotype 1 presented the lowest value of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitive C reactive protein, tumour necrosis factor-α, growth differentiation factor (GDF)-15, troponin T and cystatin C, whereas phenotype 2, which is characterised by hypertension and cardiac hypertrophy, showed the highest value of these markers. Phenotype 3 showed the second highest value of GDF-15 and cystatin C. Phenotype 4 presented a low NT-proBNP value and a relatively high GDF-15. CONCLUSIONS: Distinctive characteristics of biomarkers in HFpEF phenotypes would indicate differential underlying mechanisms to be elucidated. The contribution of inflammation to the pathogenesis varied considerably among different HFpEF phenotypes. Systemic inflammation substantially contributes to the pathophysiology of the classic HFpEF phenotype with cardiac hypertrophy. TRIAL REGISTRATION NUMBER: UMIN-CTR ID: UMIN000021831.

The prognosis and risk factors for patients with complex karyotype myelodysplastic syndrome undergoing allogeneic haematopoietic stem cell transplantation.

Allogeneic haematopoietic stem cell transplantation (HCT) is the curative treatment for myelodysplastic syndrome with a complex karyotype (CK-MDS). However, only a few studies have been limited to patients with CK-MDS undergoing allogeneic HCT. This study aimed to identify the risk factors for patients with CK-MDS undergoing allogeneic HCT. We included 691 patients with CK-MDS who received their first allogeneic HCT. The overall survival (OS) was the primary end-point, estimated using the Kaplan-Meier method. Prognostic factors were identified using a Cox proportional hazards model. The 3-year OS was 29.8% (95% confidence interval [CI]: 26.3-33.3). In the multivariable analysis, older age (hazard ratio [HR]: 1.44, 95% CI: 1.11-1.88), male sex (HR: 1.38, 95% CI: 1.11-1.71), poor haematopoietic cell transplant comorbidity index (HR: 1.47, 95% CI: 1.20-1.81), red blood cell transfusion requirement (HR: 1.58, 95% CI: 1.13-2.20), platelet transfusion requirement (HR: 1.85, 95% CI: 1.46-2.35), not-complete remission (HR: 1.55, 95% CI: 1.16-2.06), a high number of karyotype abnormality (HR: 1.63, 95% CI: 1.18-2.25) and monosomal karyotype (HR: 1.49, 95% CI: 1.05-2.12) were significantly associated with OS. Thus, the 3-year OS of allogeneic HCT was 29.8% in patients with CK-MDS, and we identified risk factors associated with poor OS.

Real-world impact of antifibrotics on prognosis in patients with progressive fibrosing interstitial lung disease.

OBJECTIVE: No studies have demonstrated the real-world efficacy of antifibrotics for progressive fibrosing interstitial lung disease (PF-ILD). Therefore, we evaluated the efficacy of antifibrotics in patients with PF-ILD. METHODS: We retrospectively reviewed the medical records of patients with ILD from January 2012 to July 2021. Patients were diagnosed with PF-ILD if they had ≥10% fibrosis on high-resolution CT (HRCT) and a relative forced vital capacity (FVC) decline of either ≥10% or >5% to <10% with clinical deterioration or progression of fibrosis on HRCT during overlapping windows of 2 years and with a %FVC of ≥45%. We compared FVC changes and overall survival (OS) between patients with and without antifibrotics. FVC changes were analysed using generalised estimating equations. We used inverse probability weighting (IPW) and statistical matching to adjust for covariates. RESULTS: Of the 574 patients, 167 were diagnosed with PF-ILD (idiopathic pulmonary fibrosis (IPF), n=64; non-IPF, n=103). Antifibrotics improved the FVC decline in both IPF (p=0.002) and non-IPF (p=0.05) (IPW: IPF, p=0.015; non-IPF, p=0.031). Among patients with IPF, OS was longer in the antifibrotic group (log-rank p=0.001). However, among patients with non-IPF, OS was not longer in the antifibrotic group (p=0.3263) (IPW and statistical matching: IPF, p=0.0534 and p=0.0018; non-IPF, p=0.5663 and p=0.5618). CONCLUSION: This is the first real-world study to show that antifibrotics improve the FVC decline in PF-ILD. However, among patients with non-IPF, we found no significant difference in mortality between those with and without antifibrotics. Future studies must clarify whether antifibrotics improve the prognosis of non-IPF.

Left ventricle-mitral valve ring size mismatch following ring annuloplasty for nonischemic dilated cardiomyopathy.

BACKGROUND: In patients with ischemic mitral regurgitation (MR) undergoing restrictive mitral annuloplasty (RMA), the ratio of left ventricular (LV) end-systolic dimension (LVESD) to mitral valve (MV) ring size (ie, LV-MV ring mismatch) is associated with postoperative recurrent MR. However, the impact of LV-MV ring mismatch on postoperative recurrent MR, LV function recovery, and long-term survival in patients with nonischemic dilated cardiomyopathy (DCM) remains unknown. METHODS: Sixty-six patients with nonischemic DCM (mean LVESD, 62 mm) underwent RMA (mean ring size, 26 mm) between 2003 and 2014. Recurrent MR was defined as MR grade ≥2+ at a 6-month echocardiographic evaluation. RESULTS: At the 6-month follow-up, 23 patients (35%) had developed recurrent MR. In univariable logistic regression analysis, larger LVESD (P = .012) and LVESD/ring size ratio (P = .008) were associated with recurrent MR. In multivariable models adjusted for age, sex, baseline LV ejection fraction, and severe MR, only LVESD/ring size ratio (odds ratio, 4.65; 95% confidence interval, 1.04-25.0; P = .048) remained significantly associated with MR recurrence. Receiver operating characteristic curve analysis demonstrated an optimal cutoff value for the LVESD/ring size ratio of 2.42. Patients with an LVESD/ring size ratio >2.42 (n = 30; mismatch) had a lower 5-year cumulative survival rate compared with those with an LVESD/ring size ratio ≤2.42 (n = 36; nonmismatch) (52% vs 71%; P = .045). Postoperatively, LV dimensions were significantly reduced in both groups; however, improvements in LVEF were only modest in the mismatched group (P = .091). CONCLUSIONS: LV-MV ring size mismatch was associated with an increased risk of recurrent MR in our series. This finding may aid the formulation of surgical strategies for patients with nonischemic DCM.

Mediation effect of intestinal microbiota on the relationship between fiber intake and colorectal cancer.

Higher fiber intake has been associated with a lower risk of colorectal cancer (CRC) and has been shown to protect against CRC based on probable evidence. Recent studies revealed a possible mechanism whereby the interaction between intestinal microbiota and fiber intake mediates CRC risk. However, the specific intestinal bacteria and the amount of these bacteria involved in this mechanism are not fully known. Therefore, this single-center study aimed to determine whether specific intestinal bacteria mediated the relationship between fiber intake and CRC risk. We enrolled patients who received colonoscopy at National Cancer Center Hospital. This cross-sectional study included 180 patients with clinically diagnosed CRC and 242 controls. We conducted a causal mediation analysis to assess the natural indirect effect and natural direct effect of specific intestinal bacteria on association between fiber intake and CRC risk. The median age was 64 (interquartile range, 54-70) years, and 58% of the participants were males. We used metagenomics for profiling gut microbiomes. The relative abundance of each species in each sample was calculated. Among the candidate, Fusobacterium nucleatum and Gemella morbillorum had a significant natural indirect effect based on their highest fiber intake compared to the lowest fiber intake, with a risk difference (95% confidence interval, proportion of mediation effect) of -0.06 [-0.09 to -0.03, 23%] and -0.03 [-0.06 to -0.01, 10.5%], respectively. Other bacteria did not display natural indirect effects. In conclusion, Fusobacterium nucleatum and Gemella morbillorum were found to mediate the relationship between fiber intake and CRC risk.

Identifying the optimal conditioning intensity for stem cell transplantation in patients with myelodysplastic syndrome: a machine learning analysis.

A conditioning regimen is an essential prerequisite of allogeneic hematopoietic stem cell transplantation for patients with myelodysplastic syndrome (MDS). However, the optimal conditioning intensity for a patient may be difficult to establish. This study aimed to identify optimal conditioning intensity (reduced-intensity conditioning regimen [RIC] or myeloablative conditioning regimen [MAC]) for patients with MDS. Overall, 2567 patients with MDS who received their first HCT between 2009 and 2019 were retrospectively analyzed. They were divided into a training cohort and a validation cohort. Using a machine learning-based model, we developed a benefit score for RIC in the training cohort. The validation cohort was divided into a high-score and a low-score group, based on the median benefit score. The endpoint was progression-free survival (PFS). The benefit score for RIC was developed from nine baseline variables in the training cohort. In the validation cohort, the hazard ratios of the PFS in the RIC group compared to the MAC group were 0.65 (95% confidence interval [CI]: 0.48-0.90, P = 0.009) in the high-score group and 1.36 (95% CI: 1.06-1.75, P = 0.017) in the low-score group (P for interaction < 0.001). Machine-learning-based scoring can be useful for the identification of optimal conditioning regimens for patients with MDS.

Restrictive annuloplasty on remodeling and survival in patients with end-stage ischemic cardiomyopathy.

OBJECTIVES: To elucidate the influence of concomitant restrictive mitral annuloplasty (RMA) on postoperative left ventricular (LV) reverse remodeling and survival in patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting (CABG). METHODS: This study comprised 157 patients with ischemic cardiomyopathy (LV ejection fraction ≤40%) who underwent CABG and completed echocardiographic examination at 1 year after surgery, with 84 (54%) undergoing concomitant RMA for clinically relevant ischemic mitral regurgitation. The primary end point was postoperative reduction in LV end-systolic volume index (LVESVI). The secondary end point was overall survival. Median follow-up was 5.1 years. RESULTS: At baseline, patients who underwent CABG with RMA had a larger LVESVI (83 ± 23 vs 75 ± 24 mm; P = .046). One-year postoperatively, CABG with RMA reduced the LVESVI more than did CABG alone (37% vs 21% from baseline; P < .001), yielding nearly identical postoperative LVESVI (53 ± 27 vs 61 ± 26 mm; P = .065). In multivariable logistic regression analysis, concomitant RMA was associated with significant LV reverse remodeling (odds ratio, 2.79; 95% CI, 1.34-5.78; P = .006). The prevalence in moderate or severe mitral regurgitation was not different between the groups (7% vs 10%; P = .58). Survival rates were similar between the groups (5 years, 78% vs 83%; P = .35). CONCLUSIONS: In patients with ischemic cardiomyopathy undergoing CABG, concomitant RMA was associated with significant reduction in LVESVI. The influence of LV reverse remodeling on survival remains undetermined.

Clustering out-of-hospital cardiac arrest patients with non-shockable rhythm by machine learning latent class analysis.

Aim: We aimed to identify subphenotypes among patients with out-of-hospital cardiac arrest (OHCA) with initial non-shockable rhythm by applying machine learning latent class analysis and examining the associations between subphenotypes and neurological outcomes. Methods: This study was a retrospective analysis within a multi-institutional prospective observational cohort study of OHCA patients in Osaka, Japan (the CRITICAL study). The data of adult OHCA patients with medical causes and initial non-shockable rhythm presenting with OHCA between 2012 and 2016 were included in machine learning latent class analysis models, which identified subphenotypes, and patients who presented in 2017 were included in a dataset validating the subphenotypes. We investigated associations between subphenotypes and 30-day neurological outcomes. Results: Among the 12,594 patients in the CRITICAL study database, 4,849 were included in the dataset used to classify subphenotypes (median age: 75 years, 60.2% male), and 1,465 were included in the validation dataset (median age: 76 years, 59.0% male). Latent class analysis identified four subphenotypes. Odds ratios and 95% confidence intervals for a favorable 30-day neurological outcome among patients with these subphenotypes, using group 4 for comparison, were as follows; group 1, 0.01 (0.001-0.046); group 2, 0.097 (0.051-0.171); and group 3, 0.175 (0.073-0.358). Associations between subphenotypes and 30-day neurological outcomes were validated using the validation dataset. Conclusion: We identified four subphenotypes of OHCA patients with initial non-shockable rhythm. These patient subgroups presented with different characteristics associated with 30-day survival and neurological outcomes.

Sepsis-associated hypoglycemia on admission is associated with increased mortality in intensive care unit patients.

AIM: Hyperglycemia is a common response to acute illness, but it is not often seen in critical conditions. The frequency and cause of hypoglycemia in septic patients have not been well elucidated. In this study, we focused on sepsis-associated hypoglycemia in the early phase and evaluated the impact of hypoglycemia on mortality. METHODS: We performed a retrospective review of 265 patients with sepsis admitted to a tertiary medical center. Blood glucose levels on admission were evaluated and analyzed by a Cox proportional hazard model. RESULTS: We categorized patients with sepsis into five groups according to blood glucose levels. Seven patients (2.6%) were admitted with severe hypoglycemia (≤40 mg/dL), 19 (7.2%) with mild hypoglycemia (41-70 mg/dL), 103 (38.9%) with euglycemia (71-140 mg/dL), 58 (21.9%) with mild hyperglycemia (141-180 mg/dL), and 78 (29.4%) with hyperglycemia (>180 mg/dL). There was a significant difference in 28-day mortality between those with severe hypoglycemia and euglycemia (71.4% versus 8.7%; P < 0.05). We analyzed the hazard ratios for the groups (relative to the reference of euglycemia) adjusted for sex, age, and Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores on admission. The hazard ratios for 28-day mortality in patients with severe hypoglycemia and mild hypoglycemia compared with that in patients with euglycemia were 8.18 (95% confidence interval [CI], 2.39-27.96; P = 0.001) and 7.56 (95% CI, 2.96-19.35; P < 0.001), respectively. CONCLUSION: Septic patients with severe hypoglycemia had significantly higher mortality compared with patients with euglycemia.

Clinical Outcomes After Durable Mitral Valve Repair for Ischemic Mitral Regurgitation.

BACKGROUND: This study aimed to clarify the incidence and determinants of postoperative adverse events in patients with ischemic cardiomyopathy who achieved long-term durable mitral valve repair. METHODS: Between 1999 and 2015, 166 patients with chronic ischemic mitral regurgitation (MR) and a left ventricular ejection fraction ≤40% underwent restrictive mitral annuloplasty. During follow-up (65 ± 34 months), echocardiographic assessments were performed 809 times (mean, 4.9 ± 2.4 times), and 20 patients who had postoperative recurrent MR (moderate or severe) were excluded. Finally, 146 patients (aged 68 [63-75] years) whose MR was well controlled over time were included. RESULTS: A total of 61 deaths or 27 readmissions for heart failure were observed in 76 patients (52%). Among hospital survivors, age (adjusted hazard ratio, 1.05; P = .001) and estimated glomerular filtration rate (adjusted hazard ratio, 0.61; P = .001) were identified as independent predictors of long-term mortality or readmission for heart failure. The degree of postoperative left ventricular function recovery was comparable between patients with and without adverse events. However, the former group showed greater values for systolic pulmonary artery pressure, tricuspid regurgitation severity, inferior vena cava dimension, and plasma brain natriuretic peptide level throughout the follow-up period (group effect P < .05 for all). CONCLUSIONS: Approximately 50% of patients died or were hospitalized for heart failure even in the absence of recurrent MR during the 5-year follow-up, a finding indicating that durable mitral repair does not always lead to favorable clinical outcomes. The adverse events may have been related to volume overload secondary to impaired renal function and less favorable pulmonary hemodynamics.

Clinical evaluation of steroid ointment for the treatment of mucoceles.

OBJECTIVE: We examined whether steroid ointment (0.1% dexamethasone) is an effective treatment for mucoceles. STUDY DESIGN: Using a retrospective cohort study design, a statistical study was conducted of 91 patients diagnosed with mucoceles at the Department of Dental and Oral Surgery, Saga University Hospital, Saga, Japan, between January 2006 and December 2016. The patients' age and sex; shape, size, and site of the lesion; duration; and treatment response rate were evaluated. RESULTS: The most frequent site of mucoceles was the lower labial mucosa, and several were <10 mm in size. The age of onset was often <20 years, with no sex-based differences. The treatment response rate was 65.8% for steroid ointment and 100% for surgical removal. In the subgroup analysis according to each clinical factor, some subgroups showed statistically nonsignificant differences compared with the surgery group. Among them, the older age and short disease duration subgroups showed small risk differences, suggesting that application of ointment may lead to a response in these subgroups. CONCLUSIONS: Although its response rate was lower than that of surgical removal, topical steroid application is a noninvasive and useful treatment method that can be used for patients in whom surgical treatment is infeasible.

Incidence, determinants and clinical impact of left ventricular function recovery after surgical treatments for ischaemic cardiomyopathy.

OBJECTIVES: This retrospective study aimed to clarify the incidence, determinants and clinical impact of left ventricular (LV) function non-recovery after coronary artery bypass grafting (CABG) in patients with ischaemic cardiomyopathy. METHODS: A total of 490 patients with ischaemic cardiomyopathy (LV ejection fraction ≤ 40%) undergoing CABG were analysed. Follow-up echocardiography was performed at 1 month, 1 year, and annually thereafter. LV function recovery was defined as ejection fraction (EF) ≥40% at least once during follow-up. LV function non-recovery was defined as EF <40% at any follow-up. The primary and secondary end points were changes in LV function and all-cause mortality, respectively. Clinical follow-up was completed in 461 patients (94.1%; mean follow-up: 64.5 ± 45.5 months). RESULTS: During follow-up, echocardiographic assessments were performed 1863 times (mean, 3.8 ± 2.4), and 193 patients (39.4%) exhibiting LV function non-recovery were identified. Overall survival was significantly higher in the recovery group (53.9%) than in the non-recovery group (31.4%) at 10 years (P < 0.001). Independent predictors of LV function non-recovery were preoperative LV end-systolic diameter [odds ratio (OR) 1.07, 95% confidence interval (CI) 1.04-1.10; P < 0.001] and bilateral internal thoracic artery grafting (OR 0.61, 95% CI 0.39-0.95; P = 0.028). In a multivariable Cox proportional hazards model, LV function non-recovery was significantly associated with all-cause mortality (hazard ratio 2.14, 95% CI 1.60-2.86; P < 0.001). CONCLUSIONS: Almost 40% of patients with ischaemic cardiomyopathy undergoing CABG did not achieve LV function recovery and were associated with poor prognosis. To achieve LV function recovery, CABG with bilateral internal thoracic artery may be recommended before excessive LV remodelling occurs. CLINICAL TRIAL REGISTRATION NUMBER: Institutional review board of Osaka University Hospital, number 16105.

Surgical Ablation Concomitant With Nonmitral Valve Surgery for Persistent Atrial Fibrillation.

BACKGROUND: Consensus regarding an optimal atrial fibrillation (AF) ablation lesion set concomitant with aortic valve replacement (AVR) and/or coronary artery bypass grafting (CABG) has not been established. METHODS: We enrolled 125 consecutive patients (89 men; 70 ± 8 years old) with persistent AF who underwent radiofrequency-based pulmonary vein isolation (PVI) (PVI group, n = 53) or a Cox-Maze procedure (Maze group, n = 72) with AVR and/or CABG. To reduce the impact of treatment bias and potential confounding in the direct comparisons between patients who underwent Cox-Maze with and those who underwent PVI, we established weighted Cox proportional-hazards regression models with inverse probability of treatment weighting. Mean follow-up was 63 ± 34 months (maximum, 154 months). RESULTS: There was 1 in-hospital death in each group. Patients who underwent Cox-Maze showed a higher freedom from AF at all follow-up examinations. After the operation, there were 32 deaths, 13 thromboembolisms, 8 hemorrhagic events, and 22 heart failure readmissions. The Maze group had higher rates for 5-year survival (88% vs 64%, P = .013) and freedom from composite events (74% vs 42%, P < .001). After adjustment with inverse probability of treatment weighting, the Cox-Maze procedure still showed a lower risk of overall mortality (adjusted hazard ratio, 0.38; 95% confidence interval, 0.21-0.66; P = .001) and composite adverse events (adjusted hazard ratio, 0.52; 95% confidence interval, 0.35-0.76; P = .001). CONCLUSIONS: In patients with persistent AF indicated for nonmitral valve surgery, a concomitant Cox-Maze procedure resulted in superior AF- and event-free survival compared with PVI, without increased risk of early mortality. These findings may assist decision making for surgical management of persistent AF concomitant with AVR and/or CABG.

Multiple percutaneous coronary interventions worsen outcomes for subsequent surgical correction of chronic ischemic mitral regurgitation.

Objective: We investigated whether or not a history of multiple percutaneous coronary interventions (PCIs) is associated with clinical outcomes after surgery for ischemic mitral regurgitation. Methods: A total of 309 patients with chronic ischemic mitral regurgitation and left ventricular ejection fraction ≤40% who underwent restrictive mitral annuloplasty were classified as follows: patients with no or 1 previous PCI (nonmultiple PCI group [n = 211]) and patients with 2 or more previous PCIs (multiple PCIs group [n = 98]). Mean follow-up duration was 53 ± 40 months. Results: Before surgery, there were no intergroup differences in patient demographic characteristics except for lower estimated glomerular filtration rate in patients with multiple PCIs. These patients underwent concomitant coronary artery bypass grafting less frequently with a lower number of distal anastomoses (P < .05 for both). The 30-day mortality was 3.3% and 2.0% in the nonmultiple and multiple PCIs group, respectively (P = .72). During follow-up, there were 157 deaths. Patients with multiple PCIs showed lower 5-year survival rate (44% vs 64%; P = .002). After adjustments with inverse-probability-of-treatment weighting, multiple PCIs history was an independent risk factor for mortality (adjusted hazard ratio, 1.4; 95% confidential interval, 1.1-1.7; P = .002). Patients with multiple PCIs showed less improvement in left ventricular ejection fraction (interaction effect P < .001). Conclusions: In patients with ischemic mitral regurgitation, a history of previous multiple PCIs was associated with increased risk of long-term postoperative mortality, with less improvement in left ventricular ejection fraction.

Circulating tumor HPV DNA complements PET-CT in guiding management after radiotherapy in HPV-related squamous cell carcinoma of the head and neck.

Positron emission tomography and computed tomography (PET-CT) is widely used to assess the response to radiotherapy. However, the ability of PET-CT to predict treatment failure in human papillomavirus (HPV)-related squamous cell carcinoma of the head and neck (HNSCC) is unsatisfactory. We quantified circulating tumor HPV type16 DNA (ctHPV16DNA) using optimized droplet digital PCR in 35 patients with HPV16-related HNSCC, who received radiotherapy with or without chemotherapy, and prospectively correlated ctHPV16DNA and metabolic response with treatment failure. After a median follow-up of 21 months, ctHPV16DNA and PET-CT had similar negative predictive values (89.7% vs 84.0%), whereas the positive predictive value was much higher in ctHPV16DNA than in PET-CT (100% vs 50.0%). Notably, six patients who had detectable posttreatment ctHPV16DNA all had treatment failure irrespective of metabolic response, whereas none of five patients who had partial metabolic response without detectable posttreatment ctHPV16DNA had treatment failure. The risk of treatment failure was high in patients who had incomplete metabolic response with detectable posttreatment ctHPV16DNA (hazard ratio [HR], 138.8; 95% confidence interval [CI], 15.5-3366.4; P < .0001) and intermediate in patients who had discordant results between metabolic response and posttreatment ctHPV16DNA (HR, 4.7; 95% CI, 0.8-36.2, P = .09) as compared with patients who had complete metabolic response without detectable posttreatment ctHPV16DNA. One-year event-free survival rates of each risk group were 0%, 88% (95% CI, 46-98) and 95% (95% CI, 72-99), respectively (P < .0001). In conclusion, posttreatment ctHPV16DNA complements PET-CT and helps guide decisions managing patients with HPV16-related HNSCC after radiotherapy.

Restrictive mitral annuloplasty with or without coronary artery bypass grafting in ischemic mitral regurgitation.

AIMS: In patients with ischaemic mitral regurgitation (MR), the impact of mitral valve surgery with concomitant coronary artery bypass grafting (CABG) on post-operative survival and left ventricular (LV) reverse remodelling remains unknown. Therefore, we investigated these outcomes following restrictive mitral annuloplasty (RMA) with and without CABG in those patients. METHODS AND RESULTS: This study included 309 patients with chronic MR and ischaemic cardiomyopathy for whom concomitant CABG was indicated (n = 225) or not indicated (n = 84) with RMA. The primary endpoint was all cause mortality during the follow-up, and the secondary endpoint was defined as the composite of mortality and re-admission for heart failure. Linear mixed model was used to analyse serial echocardiographic changes in LV function. To reduce the impact of treatment bias and potential confounding in the direct comparisons between patients who underwent RMA with and those who underwent it without CABG, we established weighted Cox proportional-hazards regression models with inverse-probability-of-treatment weighting. Pre-operatively, there were no intergroup differences in age (RMA with CABG, 67 ± 9 vs. RMA without CABG, 68 ± 11, P = 0.409) and logistic EuroSCORE II (16 ± 14 vs. 15 ± 15%, P = 0.496). The 30-day mortalities were 2.7% and 3.6%, respectively (P = 0.67). During follow-up with a mean duration of 72 ± 37 months (range, 5.6-179), there were 157 deaths and 105 re-admissions for heart failure. Overall 1-year and 5-year survival rates were 83 ± 2% and 58 ± 3%, respectively. Patients who did not receive CABG with RMA had a significantly lower 5-year survival rate (45% vs. 63%, P = 0.049) and freedom from adverse events defined as mortality and/or admission for heart failure (19% vs. 43%, P < 0.001) than those who did. After adjustments for clinical covariates with inverse-probability-of-treatment weighting, concomitant CABG was identified as an independent protective factor for adverse events (hazard ratio: 0.53; 95% confidence interval: 0.44-0.64; P < 0.001). Along with significant MR reduction, LV function parameters changed over time after surgery in both groups, with greater improvements in patients who underwent RMA with CABG (time effect, P < 0.001; and interaction effect, P = 0.002). CONCLUSIONS: RMA can be performed with an acceptable operative mortality, irrespective of indications for CABG. Patients with ischaemic MR for whom CABG is indicated with RMA are more likely to show better long-term and event-free survival and greater improvements in LV systolic function. The optimal revascularization strategy should be discussed with a heart team whenever indicated in patients with ischaemic MR; otherwise, they may miss the opportunity to benefit from concomitant CABG during subsequent RMA.

Doubly robust inference procedure for relative survival ratio in population-based cancer registry data.

Cancer registry system has been playing important roles in research and policy making in cancer control. In general, information on cause of death is not available in cancer registry data. To make inference on survival of cancer patients in the absence of cause of death information, the relative survival ratio is widely used in the population-based cancer research utilizing external life tables for the general population. Another difficulty arising in analyzing cancer registry data is informative censoring. In this article, we propose a doubly robust inference procedure for the relative survival ratio under a certain type of informative censoring, called the covariate-dependent censoring. The proposed estimator is doubly robust in the sense that it is consistent if at least one of the regression models for the time-to-death and for the censoring time is correctly specified. Furthermore, we introduced a doubly robust test assessing underlying conditional independence assumption between the time-to-death and the censoring time. This test is model based, but is doubly robust in the sense that at least one of the models for the time to event and for the censoring time is correctly specified, it maintains its nominal significance level. This notable feature entails us to make inference on cancer registry data relying on assumptions, which are much weaker than the existing methods and are verifiable empirically. We examine the theoretical and empirical properties of our proposed methods by asymptotic theory and simulation studies. We illustrate the proposed method with cancer registry data in Osaka, Japan.

Venue of catheter insertion does not significantly impact the event of central line-associated bloodstream infection in patients with haematological diseases.

BACKGROUND: Central line-associated bloodstream infection (CLABSI) is a serious complication of central venous catheter (CVC) placement in patients with haematological diseases associated with neutropenia and immunosuppression. However, whether the venues where CVC are inserted influence CLABSI development remains unclear. METHODS: We investigated whether CVC insertion at venues with different standards of cleanliness altered the occurrence of CLABSI. We evaluated data from 279 patients (545 CVC insertions) with haematological diseases including age, sex, underlying disease, reason for insertion, insertion site, number of lumens, venue, dates of insertion and removal, complete blood counts, percentage of neutrophils and serum albumin concentrations at the time of CVC insertion. FINDINGS: Overall, 55 CLABSI events occurred during a period of 23,434 catheter days (2.35 per 1,000 catheter days). In total, 153 and 190 patients underwent 226 and 305 CVC insertions, respectively in a ward and in an operating room, respectively. Univariate analysis identified the operating room (P = 0.017), allogeneic haematopoietic stem cell transplantation (P < 0.001), triple lumen catheter (P = 0.002), haemoglobin (P = 0.019), white blood cell count (P = 0.012) and percentage of neutrophils (P = 0.012) as significant factors for the development of CLABSI. However, multivariate analysis adjusted for age, reason for insertion, insertion site, number of lumens, haemoglobin, percentage of neutrophils and platelet counts found no significant differences between the venue where CVC were inserted and CLABSI development (P = 0.158). CONCLUSION: The venue of CVC insertion is unlikely to influence CLABSI development in patients with haematological diseases.

Prognostic profile of patients with non-viral hepatocellular carcinoma: A comparative study with hepatitis C virus-related hepatocellular carcinoma using data mining analysis.

Various factors are associated with the prognosis of patients with non-viral hepatocellular carcinoma (HCC). The present study aimed to investigate the prognosis of patients with non-viral HCC compared with that of patients with hepatitis C virus-related (HCV)-HCC and the features associated with prognosis of patients with non-viral HCC using data mining analyses. Patients with non-viral HCC (n=182, age 70.4±8.9 years) and HCV-HCC (n=612, age 70±8.4 years) were enrolled and the overall survival was compared between the non-viral HCC and HCV-HCC groups. The present study performed random forest and decision tree analyses to identify features that distinguish prognosis between the non-viral HCC and HCV-HCC groups. The median survival of the non-viral HCC group was significantly shorter than the HCV-HCC group (1,553 vs. 2,304 days, P<0.01). In the multivariate analysis, the non-viral HCC group was an independent risk factor for survival (HR 1.42, 95% CI 1.08-1.87, P=0.013). In the random forest analysis, the high-ranking distinguishable factors were 'number of tumors' and 'HCC stage' in the non-viral HCC group and 'albumin' and 'total bilirubin' in the HCV-HCC group. The decision tree analysis revealed that, in patients with HCC stage >I, the survival period in the non-viral HCC group was significantly shorter than the HCV-HCC group (HR 1.39, 95% CI 1.07-1.81, P=0.0132). The prognosis of patients with non-viral HCC was poorer than patients with HCV-HCC. In addition, data mining analysis revealed that tumor-related variables had the highest importance for survival in patients with non-viral HCC.