Objective The study objective was to examine the incidence, risk factors, and mortality rate of acute exacerbation of interstitial lung diseases in patients with lung cancer undergoing pulmonary ...resection in a large-scale multi-institutional cohort. Methods We retrospectively analyzed 1763 patients with non–small cell lung cancer who had undergone pulmonary resection and presented with a clinical diagnosis of interstitial lung diseases between January 2000 and December 2009 at 61 hospitals in Japan. The incidence and outcomes of acute exacerbation within 30 days from the operation were investigated. Univariate and multivariate logistic regression analyses were used to identify independent risk factors of acute exacerbation. Results Acute exacerbation occurred in 164 patients (9.3%; 95% confidence interval, 8.0-10.8), with a mortality rate of 43.9%, and was the top cause of 30-day mortality (71.7%). The following 7 independent risk factors of acute exacerbation were identified: surgical procedures, male sex, history of exacerbation, preoperative steroid use, serum sialylated carbohydrate antigen KL-6 levels, usual interstitial pneumonia appearance on computed tomography scan, and reduced percent predicted vital capacity. Surgical procedures showed the strongest association with acute exacerbation (using wedge resection as the reference, lobectomy or segmentectomy: odds ratio, 3.83; 95% confidence interval, 1.94-7.57; bi-lobectomy or pneumonectomy: odds ratio, 5.70; 95% confidence interval, 2.38-13.7; P < .001). The effect of perioperative prophylactics, such as steroids and sivelestat, was not confirmed in this study. Conclusions Pulmonary resection for patients with lung cancer with interstitial lung diseases may provoke acute exacerbation at a substantially high rate and has high associated mortality. Surgical procedures that proved to be a risk factor for acute exacerbation should be chosen cautiously for these high-risk patients.
Objectives Patients with interstitial lung diseases have a poor prognosis and are at increased risk of developing lung cancer. We evaluated the survival and predictors of survival after surgical ...resection in lung cancers in patients with interstitial lung diseases. Methods We retrospectively analyzed data from 1763 patients with non–small cell lung cancer with a clinical diagnosis of interstitial lung disease who underwent pulmonary resection between 2000 and 2009 at 61 Japanese institutions. Results Male patients (90.4%) and smokers (93.8%) were in the majority. The overall 5-year survival was 40%. The 5-year survivals were 59%, 42%, 43%, 29%, 25%, 17%, and 16% for patients with stage Ia, Ib, IIa, IIb, IIIa, IIIb, and IV, respectively. Patients with stage IA had a 5-year survival of 33.2%, 61.0%, and 68.4% in the wedge resection, segmentectomy, and lobectomy groups, respectively (log-rank test, P = .0038). The leading cause of death was cancer recurrence (50.2%), followed by respiratory failure (26.8%). Wedge resection reduced mortality due to respiratory failure when compared with that of lobectomy ( P = .022). Multivariable analysis revealed that the type of surgical procedure, predicted percent vital capacity, and tumor locations were independent predictors for survival. The 5-year survival was 20% for patients with stage Ia with a predicted percent vital capacity of 80% or less, and 64.3% for patients with a predicted percent vital capacity greater than 80% (log-rank test, P < .0001). Conclusions In these patients, there are competing risks of death. Wedge resection reduced death caused by respiratory failure but resulted in poorer long-term prognosis than lobectomy. For patients with poor predictors of survival, such as predicted percent vital capacity of 80% or less, surgical resection should be limited.
IntroductionNecitumumab plus gemcitabine and cisplatin (GCN) is a standard therapy for patients with advanced lung squamous cell carcinoma (LSqCC). However, the efficacy and tolerability of GCN in ...second-line or later treatment for patients previously treated with immune checkpoint inhibitors (ICIs) remain unknown.MethodsThis multicenter, retrospective, cohort study assessed the efficacy and tolerability of GCN initiated between November 1, 2019 and March 31, 2022 as second-line to fourth-line treatment in patients with advanced LSqCC who had been pretreated with ICIs. The primary end point was progression-free survival (PFS).ResultsA total of 93 patients from 35 institutions in Japan were enrolled. The median PFS, median overall survival (OS), and objective response rate were 4.4 months (95% confidence interval CI: 3.8-5.3), 13.3 months (95% CI: 9.6-16.5), and 27.3% (95% CI: 18.3-37.8), respectively. The median PFS, median OS, and objective response rate for second-line, third-line, and fourth-line treatment groups were 4.8 months, 3.8 months, and 4.3 months (p = 0.24); 15.7 months, 11.6 months, and 10.1 months (p = 0.06); and 31.0%, 13.6%, and 37.5% (p = 0.22), respectively. The severity of GCN-related skin disorders was associated with longer PFS (p < 0.05) and OS (p < 0.05). The frequencies of grade ≥3 skin disorders, hypomagnesemia, pneumonitis, and febrile neutropenia were 16.1%, 7.5%, 1.1%, and 4.3%, respectively. There were no treatment-related deaths.ConclusionsGCN for ICI-pretreated patients with LSqCC seems tolerable and offers promising efficacy regardless of treatment line, and ICI pretreatment might enhance GCN efficacy.
Abstract Anhedonia is one of the non-motor symptoms observed in the Parkinson
'
s disease (PD). However, there is no clear relationship between anhedonia and its correlation with other symptoms of ...PD. The aim of this study is to evaluate the characteristics of anhedonia and its correlation with clinical aspects of PD in a relatively large cohort. We enrolled 318 patients with PD and 62 control subjects for this study. Patients and subjects were tested using the Snaith–Hamilton Pleasure Scale Japanese version and the Beck Depression Inventory 2nd edition for the assessment of anhedonia and depression. We also investigated the correlation among clinical aspects of PD, anhedonia, and depression in patients with PD. The Snaith–Hamilton Pleasure Scale Japanese version and the Beck Depression Inventory 2nd edition scores were significantly higher in patients with PD than in control subjects (p = 0.03 and p = 0.0006, respectively). All PD patients with anhedonia had a significantly higher score on the unified Parkinson's disease rating scale (UPDRS) parts I and II compared to PD patients without anhedonia. Additionally, all PD patients with depression scored significantly higher on UPDRS part I
–IV than PD patients without depression. The patients with anhedonia and without depression had mild motor severity and their treatment was relatively low dosage. These results suggest that anhedonia and depression are slightly linked, but not the same. PD patients with only anhedonia may be closely linked apathy found in untreated early stages of PD.
Risk stratification for ventricular fibrillation (VF) in patients with Brugada syndrome (BrS) remains controversial.
The purpose of this study was to construct a novel prediction model for VF risk in ...BrS patients using noninvasive parameters.
A total of 143 Japanese BrS patients with VF (n = 35) and without VF (n = 108) were retrospectively enrolled. We built a logistic regression model predicting VF occurrence and evaluated it by cross-validation.
Frequencies of history of syncope and spontaneous type 1 ECG, r-J interval in V1, QRS duration in V6, and LAS40, Tpeak-Tend dispersion, and max T-wave alternans were significantly associated with VF occurrence in univariate analyses. The history of syncope, r-J interval in V1, QRS duration in V6, and Tpeak-Tend dispersion were identified as independent predictors by multivariate logistic regression analysis. The predictive model was constructed using all these parameters with good discrimination of VF occurrence (area under the curve 0.869 with 97.1% sensitivity and 65.7% specificity). The area under the curve based on leave-one-out cross-validation was 0.845, with 97.1% sensitivity and 63.0% specificity suggesting good performance of the model. Retrospective survival analysis revealed that the cumulative VF event rate was significantly higher in patients at high risk than in those with low risk using the log rank test (P = 2.97 × 10(-8)). Notably, no BrS patient below the cutoff value developed a subsequent VF event.
This novel prediction method may effectively assesses VF risk in BrS patients, especially when determining implantable cardioverter-defibrillator placement for asymptomatic BrS patients.
Background Atrial fibrillation (AF) and chronic kidney disease share risk factors and pathophysiologic mechanisms, suggesting that two conditions have close relationships. Methods This is a ...prospective community-based observational cohort study including 235,818 subjects based upon a voluntary annual health check-up program in Japan. We studied the association of kidney dysfunction at entry with subsequent new-onset AF and the association of AF at entry with the development of kidney disease. Results During a follow-up of 5.9 ± 2.4 years, AF developed in 2947 subjects (1.3%). Baseline serum creatinine and estimated glomerular filtration rate (GFR) were associated with risk of subsequent AF. The HRs (95% CI) for AF were 1.32 (1.08-1.62) and 1.57 (0.89-2.77) for GFR 30 to 59 and <30 mL/min per 1.73 m2 , respectively. The effect of kidney disease on risk of new-onset AF remained significant in subjects without treated hypertension or diabetes. During the follow-up, 7791 subjects (3.3%) developed kidney dysfunction (GFR <60 mL/min per 1.73 m2 ), and 11 307 subjects (4.9%) developed proteinuria. Atrial fibrillation at entry was associated with development of kidney dysfunction (HRs 95% CI, 1.77 1.50-2.10) and proteinuria (HR 95% CI, 2.20 1.92-2.52). The association persisted in subjects without treated hypertension or diabetes. Conclusions Kidney dysfunction increased the risk of new onset of AF, and AF increased the risk of development of kidney disease. This finding supports the concept that the two conditions share common abnormal molecular signaling pathways contributing to their pathogenesis.
Objectives This study evaluated the efficacy and safety of flecainide in addition to conventional drug therapy in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT). ...Background CPVT is an inherited arrhythmia syndrome caused by gene mutations that destabilize cardiac ryanodine receptor Ca2+ release channels. Sudden cardiac death is incompletely prevented by conventional drug therapy with β-blockers with or without Ca2+ channel blockers. The antiarrhythmic agent flecainide directly targets the molecular defect in CPVT by inhibiting premature Ca2+ release and triggered beats in vitro. Methods We collected data from every consecutive genotype-positive CPVT patient started on flecainide at 8 international centers before December 2009. The primary outcome measure was the reduction of ventricular arrhythmias during exercise testing. Results Thirty-three patients received flecainide because of exercise-induced ventricular arrhythmias despite conventional (for different reasons, not always optimal) therapy (median age 25 years; range 7 to 68 years; 73% female). Exercise tests comparing flecainide in addition to conventional therapy with conventional therapy alone were available for 29 patients. Twenty-two patients (76%) had either partial (n = 8) or complete (n = 14) suppression of exercise-induced ventricular arrhythmias with flecainide (p < 0.001). No patient experienced worsening of exercise-induced ventricular arrhythmias. The median daily flecainide dose in responders was 150 mg (range 100 to 300 mg). During a median follow-up of 20 months (range 12 to 40 months), 1 patient experienced implantable cardioverter-defibrillator shocks for polymorphic ventricular arrhythmias, which were associated with a low serum flecainide level. In 1 patient, flecainide successfully suppressed exercise-induced ventricular arrhythmias for 29 years. Conclusions Flecainide reduced exercise-induced ventricular arrhythmias in patients with CPVT not controlled by conventional drug therapy.
Short QT syndrome (SQTS) is characterized by an abnormally short QT interval and sudden death. Due to the limited number of cases, the characteristics of SQTS are not well understood. It has been ...reported recently that early repolarization is associated with idiopathic ventricular fibrillation and the QT interval is short in patients with early repolarization.
The purpose of this study was to study the association between early repolarization and arrhythmic events in SQTS.
The study consisted of three cohorts: SQTS cohort (N = 37), control cohort with short QT interval and no arrhythmic events (N = 44), and control cohort with normal QT interval (N = 185). ECG parameters were compared among the study cohorts.
Heart rate, PR interval, and QRS duration were similar among the three study cohorts. Early repolarization was more common in the SQTS cohort (65%) than in the short QT control cohort (30%) and the normal QT control cohort (10%). Duration from T-wave peak to T-wave end was longer in the SQTS cohort than in the short QT control cohort, although QT and corrected QT intervals were similar. In the SQTS cohort, there were more males among patients with arrhythmic events than in those with a family history but without arrhythmic events. In multivariate models, early repolarization was associated with arrhythmic events in the SQTS cohort. ECG parameters including QT and QTc intervals were not associated with arrhythmic events in the SQTS cohort.
There is a high prevalence of early repolarization in patients with SQTS. Early repolarization may be useful in identifying risk of cardiac events in SQTS.
Abstract Background We investigated features and responses to treatment in patients with febrile and afebrile convulsions with mild gastroenteritis and characterized convulsions with rotavirus and ...norovirus gastroenteritis. Methods We conducted a prospective, observational study to evaluate patients with febrile and afebrile convulsions with mild gastroenteritis who were hospitalized between November 2011 and March 2014 at 13 facilities in the National Hospital Organization. We classified the patients into two groups: presence or absence of fever. We investigated the background, clinical and laboratory characteristics, viral antigen in stool, and efficacy of anticonvulsant drugs. Results Of 126 patients enrolled in this study, 50 were febrile (Fc group) and 76 were afebrile (aFc group). A family history of febrile seizures was significantly more frequent in the Fc group than in the aFc group (28.0% vs 9.2%, P = 0.005). Clinical characteristics were similar between the rotavirus and norovirus groups, but fever was significantly more frequent in the rotavirus group (46.2% vs 8.3%, P < 0.001). Serum sodium levels were significantly negatively related to the number of seizures in the aFc group (β = −0.13; 95% confidence interval, −0.24, −0.03; P = 0.01). Carbamazepine was significantly more efficacious than diazepam suppositories in the aFc group (odds ratio = 49.3, 95% confidence interval, 2.35, 1037; P = 0.01). Conclusion Febrile convulsions with mild gastroenteritis show characteristics of both febrile seizures and convulsions with mild gastroenteritis. Carbamazepine is optimal for convulsions with mild gastroenteritis. Clinical features of convulsions with rotavirus and norovirus gastroenteritis are similar, except for fever. Serum sodium levels may play a major role in the onset of convulsions with mild gastroenteritis.
Abstract Background and Aims The efficacy of endoscopic retrograde cholangiopancreatography (ERCP) for histologic diagnosis of malignant biliary strictures is disappointingly low. The aim of this ...study was to investigate the diagnostic performance of a newly developed endoscopic device with “scraping loops” in combination with conventional biopsy forceps. Methods We performed a multicenter single-arm prospective study. Between February 2013 and December 2014, a total of 123 patients with suspected malignant biliary strictures were enrolled. The new device and conventional biopsy forceps were applied for histologic diagnosis by ERCP. The primary outcome was to evaluate cancer detectability by biopsy forceps, the new device, and their combined use. Results Of the 123 patients, 119 patients were diagnosed with a malignant stricture. Sufficient samples were collected in 83.7% (103/123), 93.5% (115/123), and 95.9% (118/123) of patients using biopsy forceps, the new device, and their combination, respectively. Cancer detectability of forceps biopsy, the new device, and their combination were 51.3% (61/119), 64.7% (77/119), and 74.8% (89/119), respectively. The new device had a significantly higher sample yield and cancer detectability than biopsy forceps (p<0.01 and p=0.018, respectively, McNemar test). Complementary use of the new device with biopsy forceps demonstrated a significantly additive effect in both sample yield and cancer detection (p<0.01 each, McNemar test). The new device detected 48.3% (28/58) of cancers that were not diagnosed as malignant by biopsy forceps. Conclusions The new endoscopic scraper demonstrated a large sample yield and high cancer detectability. It could be a first-line tissue-sampling device for biliary strictures.
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