Clinical manifestations and biomarkers to predict mortality risk in adults with invasive Streptococcus dysgalactiae subsp. equisimilis infections.

PURPOSE: The incidence of invasive Streptococcus dysgalactiae subsp. equisimilis (iSDSE) infections is increasing in developed countries, but studies on the risk factors for death in iSDSE infections are scant. Here, we aimed to clarify risk factors and predictors of mortality in adults with iSDSE infections. METHODS: A multicentre observational study of adults with iSDSE infections was conducted to investigate the effects of host factors, disease severity, biomarkers, and antibiotic regimens, and bacterial factors on 28-day mortality. RESULTS: The overall mortality rate of 588 patients was 10.4%, with a significant increase in those aged ≥ 60 years. Most of the patients (97.4%) had underlying diseases. The mortality rate (70.4%) of patients with severe disease was significantly higher than that of patients with mild-to-moderate disease (4.3%; p < 0.001). The risk factors for death identified using multivariable analysis were age ≥ 60 years (hazard ratio [HR], 3.4; 95% confidence interval [CI], 1.0-11.3, p = 0.042); severe disease (HR, 15.0; 95% CI 7.7-29.2, p < 0.001); bacteraemia without primary focus (HR, 20.5; 95% CI 2.8-152.3, p = 0.003); serum creatinine ≥ 2.0 mg/dL (HR, 2.2; 95% CI 1.2-4.0, p = 0.010); serum creatine kinase ≥ 300 IU/L (HR, 2.1; 95% CI 1.1-3.8, p = 0.019); and macrolide resistance (HR, 1.8; 95% CI 1.0-3.3, p = 0.048). Treatment regimens and emm types were not associated with poor outcomes. CONCLUSION: Evaluation of clinical manifestations and biomarkers on admission is important to predict invasive SDSE infection prognosis.

Risk factors and interventions for developing recurrent pneumonia in older adults.

Background: Pneumonia is common among older adults and often recurrent. Several studies have been conducted on the risk factors for pneumonia; however, little is known about the risk factors for recurrent pneumonia. This study aimed to identify the risk factors for developing recurrent pneumonia among older adults and to investigate methods of prevention. Methods: We analysed the data of 256 patients aged 75 years or older who were admitted for pneumonia between June 2014 and May 2017. Moreover, we reviewed the medical records for the subsequent 3 years and defined the readmission caused by pneumonia as recurrent pneumonia. Risk factors for recurrent pneumonia were analysed using multivariable logistic regression analysis. Differences in the recurrence rate based on the types and use of hypnotics were also evaluated. Results: Of the 256 patients, 90 (35.2%) experienced recurrent pneumonia. A low body mass index (OR: 0.91; 95% CI: 0.83‒0.99), history of pneumonia (OR: 2.71; 95% CI: 1.23‒6.13), lung disease as a comorbidity (OR: 4.73; 95% CI: 2.13‒11.60), taking hypnotics (OR: 2.16; 95% CI: 1.18‒4.01) and taking histamine-1 receptor antagonist (H1RA) (OR: 2.38; 95% CI: 1.07‒5.39) were risk factors. Patients taking benzodiazepine as hypnotics were more likely to experience recurrent pneumonia than patients not taking hypnotics (OR: 2.29; 95% CI: 1.25-4.18). Conclusion: We identified several risk factors for recurrent pneumonia. Among them, restricting the use of H1RA and hypnotics, in particular benzodiazepines, may be useful in preventing the recurrence of pneumonia in adults aged 75 years or older.

Risk factors and pathogen characteristics associated with unfavorable outcomes among adults with pneumococcal meningitis in Japan, 2006 to 2016.

PURPOSE: In this study, we aimed to clarify the risk factors associated with unfavorable outcomes in adults with pneumococcal meningitis (PnM). METHODS: Surveillance was conducted between 2006 and 2016. Adults with PnM (n = 268) were followed up for outcomes within 28 days after admission using the Glasgow Outcome Scale (GOS). After classifying the patients into the unfavorable (GOS1-4) and favorable (GOS5) outcome groups, i) the underlying diseases, ii) biomarkers at admission, and iii) serotype, genotype, and antimicrobial susceptibility for all isolates were compared between both groups. RESULTS: Overall, 58.6% of patients with PnM survived,15.3% died, and 26.1% had sequelae. The number of living days in the GOS1 group was highly heterogeneous. Motor dysfunction, disturbance of consciousness, and hearing loss were the commonest sequelae. Of the underlying diseases identified in 68.9% of the PnM patients, liver and kidney diseases were significantly associated with unfavorable outcomes. Of the biomarkers, creatinine and blood urea nitrogen, followed by platelet and C-reactive protein had the most significant associations with unfavorable outcomes. There was a significant difference in the high protein concentrations in the cerebrospinal fluid between the groups. Serotypes 23F, 6C, 4, 23A, 22F, 10A, and 12F were associated with unfavorable outcomes. These serotypes were not penicillin-resistant isolates possessing three abnormal pbp genes (pbp1a, 2x, and 2b), except for 23F. The expected coverage rate of the pneumococcal conjugate vaccine (PCV) was 50.7% for PCV15 and 72.4% for PCV20. CONCLUSIONS: In the introduction of PCV for adults, the risk factors for underlying diseases should be prioritized over age, and serotypes with unfavorable outcomes should be considered.

Disseminated cryptococcosis in a renal transplant recipient.

Skin cryptococcosis often manifests as an umbilicated papule, and chest computed tomography findings of multiple nodules and cavities are also characteristic. The combination of characteristic cutaneous manifestations and radiological findings can help clinicians make an "at-a-glance" diagnosis of disseminated cryptococcosis.

Endotracheal granulation after tracheostomy in acute respiratory distress syndrome from COVID-19.

Granulation tissue formation is one of the late complications of tracheostomy. It can cause stomal stenosis secondary to chondritis because of disproportionate excision of the anterior cartilage. Clinicians should carefully determine the incision point, which is typically located half way between the cricoid cartilage and the sternal notch.

Multiple comorbidities increase the risk of death from invasive pneumococcal disease under the age of 65 years.

INTRODUCTION: Risk factors for death from invasive pneumococcal disease (IPD) have not been clearly established in patients aged under 65 years. We aimed to evaluate contributions of host and bacterial factors to the risk of death from IPD in patients aged under 65 years in Japan. METHODS: In this prospective, observational, multicenter cohort study, patients with IPD (n = 581) aged 6-64 years were enrolled between 2010 and 2017. We investigated the role of host and bacterial factors in 28-day mortality. RESULTS: The mortality rate increased from 3.4% to 6.2% in patients aged 6-44 years to 15.5%-19.5% in those aged 45-64 years. Multivariable analysis identified the following risk factors for mortality: age 45-64 years (hazard ratio [HR], 3.4; 95% confidence interval [CI], 1.6-6.8, p = 0.001), bacteremia with unknown focus (HR, 2.0; 95% CI, 1.1-3.7, p = 0.024), meningitis (HR, 2.1; 95% CI, 1.1-4.0, p = 0.019), underlying multiple non-immunocompromising conditions (HR, 2.6; 95% CI, 1.1-7.4, p = 0.023), and immunocompromising conditions related to malignancy (HR, 2.4; 95% CI, 1.0-5.2, p = 0.039). Pneumococcal serotype was not associated with poor outcomes. CONCLUSIONS: Host factors, including age of 45-64 years and underlying multiple non-immunocompromising conditions, are important for the prognosis of IPD. Our results will contribute to the development of targeted pneumococcal vaccination strategies in Japan.

Myeloperoxidase anti-neutrophil cytoplasmic antibody-associated vasculitis with a unique imaging presentation of organizing pneumonia: A case report.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) constitutes a group of blood vessel inflammation diseases of autoimmune origin. Myeloperoxidase (MPO) ANCA is closely related to ANCA associated AAV. The MPO-ANCA positive AAV patients have lung involvement at high rates; however, there are only a few reported cases with organizing pneumonia (OP). A 78-year-old man was presented to our hospital due to a fever of 38 °C despite a whole month of antibiotics treatment. Chest computed tomography image revealed restricted consolidations visible in the middle lobe of the right lung and the upper lobe of the left lung, which suggested an OP pattern. MPO-ANCA and urine occult blood tests were positive. Histopathological examination of the transbronchial biopsy revealed OP and mucus plug. Histological findings on renal biopsy showed necrotizing glomerulonephritis related to AAV. The patient was diagnosed with MPO-ANCA positive AAV and was treated with systemic corticosteroid therapy, from which he recovered rapidly. Thus, when diagnosing OP, the possibility of AAV should be considered by ordering patients' serum ANCA and occult hematuria tests.

Safety of bronchoscopy in patients with malignant hematologic disorders.

BACKGROUND: Factors affecting the safety of bronchoscopy in patients with malignant hematologic disorders have not been well described. We evaluated the safety of bronchoscopy and describe factors affecting its complication rate in such patients. METHODS: Between January 2009 and December 2018, 316 bronchoscopies in 282 patients with malignant hematologic disorders and pulmonary infiltrates were performed at our institution. The bronchoscopic procedure used and its complications were evaluated. RESULTS: The most common underlying disease was acute myeloid leukemia (134/282 patients, 47.5%). Platelet transfusion was performed the day before or the day of bronchoscopy in 42.4%, supplemental oxygen was administered before the procedure in 23.1%, and midazolam was used in 74.4%. Thirty-five bronchoscopies (11.1%) were complicated by hemoptysis and 7 patients developed pneumothorax, 4 of whom required thoracic drainage. Two patients (0.6%) were intubated within 48 h of the procedure and prolonged oxygen desaturation (> 48 h) occurred in 3.8%. Multivariate analysis showed that only use of midazolam significantly reduced the risk of prolonged oxygen desaturation (hazard ratio 0.28, 95% confidence interval 0.09-0.85, p = 0.03). Transbronchial lung biopsy significantly increased the risk of hemoptysis (hazard ratio 10.40, 95% confidence interval 4.18-25.90, p = 0.00), while use of midazolam significantly reduced the risk (hazard ratio 0.31, 95% confidence interval 0.14-0.73, p = 0.01). CONCLUSIONS: Bronchoscopy is relatively safe in patients with malignant hematologic disorders. Caution and judicious use of sedatives may improve the patient's procedural tolerance and lower complications.

Clinicoradiological Features of Pulmonary Tuberculosis with Interstitial Pneumonia.

Objective Although rare, pulmonary tuberculosis occasionally develops in patients with interstitial pneumonia (IP). In this study, we aimed to evaluate the clinicoradiological features of pulmonary tuberculosis associated with IP. Methods In this retrospective, observational, single-center study, the medical charts, high-resolution computed tomography (HRCT) findings, and bacteriological test results of patients with IP who also tested positive for Mycobacterium tuberculosis were reviewed. Patients The study included 20 patients with IP out of 329 who tested positive for M. tuberculosis in sputum or bronchoalveolar lavage fluid cultures at Toranomon Hospital between January 2006 and December 2017. Results The HRCT patterns were usual interstitial pneumonia (UIP) in 11 patients and non-UIP in 9 patients. Consolidations (80%) were the most frequent HRCT findings, followed by cavities (60%) and nodules (45%), which are generally characteristic of pulmonary tuberculosis. Consolidations often developed in relation to fibrotic or emphysematous lesions. Tuberculosis lesions could not be identified in one patient. All patients were treated with anti-tuberculosis drugs according to WHO guidelines, and 13 patients achieved a WHO category of "Treatment success." No patient died of tuberculosis, and the median survival time for the 20 patients was 1,196 days. Conclusion Although the HRCT findings for pulmonary tuberculosis associated with IP are atypical, appropriate tuberculosis treatments can lead to favorable outcomes.

Development of a CT image case database and content-based image retrieval system for non-cancerous respiratory diseases: Method and preliminary assessment.

BACKGROUND: To evaluate the benefits of using a CT image case database (DB) with content-based image retrieval system for the diagnosis of typical non-cancerous respiratory diseases. METHODS: Using this DB, which comprised data on 191 cases covering 69 diseases, 933 imaging findings that contributed to differential diagnoses were annotated. Ten test cases were selected. Image similarity between each marked test case lesion and the lesions of the top 10 retrieved cases were assessed and classified as similar, somewhat similar, or dissimilar by two physicians in consensus. Additionally, the accuracy of five internal medicine residents' abilities to interpret CT findings and provide disease diagnoses with and without the proposed system was evaluated by image interpretation experiments involving five test cases. The rates of concordance between the subjects' interpretations and the correct answers prepared in advance by two specialists in consensus were converted into scores. RESULTS: The mean (± SD) of image similarity among the 10 test cases was as follows: 5.1 ± 2.7 (similar), 2.9 ± 1.0 (somewhat similar), and 2.0 ± 2.4 (dissimilar). Using the proposed system, the subjects' mean score for the correct interpretation of CT findings improved from 15.1 to 28.2 points (p = 0.131) and for the correct disease diagnoses, from 9.3 to 28.2 points (p = 0.034). CONCLUSIONS: Although this was a preliminary small-scale assessment, the results suggest that this system may contribute to an improved interpretation of CT findings and differential diagnosis of non-cancerous respiratory diseases, which are difficult to diagnose for inexperienced physicians.

Treatment outcome of patients with unresectable stage III non-small cell lung cancer and interstitial pneumonia.

BACKGROUND: The standard treatment for unresectable stage III non-small cell lung cancer (LC) is chemoradiation therapy (CRT); however, the optimal treatment for LC in patients with interstitial pneumonia (IP) (LC-IP) has not been determined. This study compared the clinical course of LC-IP patients to that of patients without IP (LC without IP) and determined the key factors of survival. METHODS: We retrieved the records of 52 consecutive LC patients treated at our institution between January 2011 and September 2016. The characteristics and outcomes of LC patients with and without IP were compared. Survival was analyzed using the Kaplan-Meier method and univariate and multivariate analyses of two-year survival were also conducted. RESULTS: Forty-two men and 10 women were evaluated. Eleven patients (21%) had IP as their underlying disease. Except for age, the backgrounds of LC patients with and without IP were almost identical. Among LC-IP patients, the median predicted forced vital capacity was 86% and the Gender-Age-Physiology (GAP) index was 3. None of the LC-IP patients received CRT but 32 (78%) of the LC without IP patients underwent CRT. Chemotherapy alone was the main treatment for LC-IP. The median survival times were 485 and 1271 days in LC patients with and without IP, respectively (p=0.419). Multivariate analysis of survival longer than two years revealed CRT as the only predictive factor. CONCLUSIONS: CRT was the only predictive factor for longer survival in LC patients; however, no LC-IP patients received CRT, possibly because of the underlying IP.

Pneumatosis intestinalis induced by osimertinib in a patient with lung adenocarcinoma harbouring epidermal growth factor receptor gene mutation with simultaneously detected exon 19 deletion and T790 M point mutation: a case report.

BACKGROUND: Pneumatosis intestinalis is a rare adverse event that occurs in patients with lung cancer, especially those undergoing treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). Osimertinib is the most recently approved EGFR-TKI, and its usage is increasing in clinical practice for lung cancer patients who have mutations in the EGFR gene. CASE PRESENTATION: A 74-year-old woman with clinical stage IV (T2aN2M1b) lung adenocarcinoma was determined to have EGFR gene mutations, namely a deletion in exon 19 and a point mutation (T790 M) in exon 20. Osimertinib was started as seventh-line therapy. Follow-up computed tomography on the 97th day after osimertinib administration incidentally demonstrated intra-mural air in the transverse colon, as well as intrahepatic portal vein gas. Pneumatosis intestinalis and portal vein gas improved by fasting and temporary interruption of osimertinib. Osimertinib was then restarted and continued without recurrence of pneumatosis intestinalis. Overall, following progression-free survival of 12.2 months, with an overall duration of administration of 19.4 months (581 days), osimertinib was continued during beyond-progressive disease status, until a few days before the patient died of lung cancer. CONCLUSIONS: Pneumatosis intestinalis should be noted as an important adverse event that can occur with administration of osimertinib; thus far, such an event has never been reported. This was a valuable case in which osimertinib was successfully restarted after complete recovery from pneumatosis intestinalis, such that further extended administration of osimertinib was achieved.

Various Bronchiolar Lesions Accompanied by Idiopathic Pleuroparenchymal Fibroelastosis with a Usual Interstitial Pneumonia Pattern Demonstrating Acute Exacerbation.

A 63-year-old man presented with persistent cough and progressive dyspnea. Computed tomography showed irregular pleural thickening and fibrotic changes with volume loss in the upper lobes, and subtle reticulation in the lower lobes. Pleuroparenchymal fibroelastosis (PPFE) was diagnosed based on the findings of a surgical lung biopsy. Bronchiolar lesions, including proliferative bronchiolitis, constrictive bronchiolitis obliterans, and peribronchiolar metaplasia were evident on pathology. A usual interstitial pneumonia (UIP) pattern was also observed in the lower lobes. Three weeks after the biopsy, an acute exacerbation occurred. We herein describe a rare case of idiopathic PPFE with various bronchiolar lesions and a UIP pattern in which an acute exacerbation developed.

Reduced area of the normal lung on high-resolution computed tomography predicts poor survival in patients with lung cancer and combined pulmonary fibrosis and emphysema.

BACKGROUND: This study aimed to determine the radiologic predictors and clarify the clinical features related to survival in patients with combined pulmonary fibrosis and emphysema (CPFE) and lung cancer. METHODS: We retrospectively reviewed the medical chart data and high-resolution computed tomography (HRCT) findings for 81 consecutive patients with CPFE and 92 primary lung cancers (70 men, 11 women; mean age, 70.9 years). We selected 8 axial HRCT images per patient, and visually determined the normal lung, modified Goddard, and fibrosis scores. Multivariate analysis was performed using the Cox proportional hazards regression model. RESULTS: The major clinical features were a high smoking index of 54.8 pack-years and idiopathic pulmonary fibrosis (n = 44). The major lung cancer profile was a peripherally located squamous cell carcinoma (n = 40) or adenocarcinoma (n = 31) adjacent to emphysema in the upper/middle lobe (n = 27) or fibrosis in the lower lobe (n = 26). The median total normal lung, modified Goddard, and fibrosis scores were 10, 8, and 8, respectively. TNM Classification of malignant tumors (TNM) stage I, II, III, and IV was noted in 37, 7, 26, and 22 patients, respectively. Acute exacerbation occurred in 20 patients. Multivariate analysis showed that a higher normal lung score and TNM stage were independent radiologic and clinical predictors of poor survival at the time of diagnosis of lung cancer. CONCLUSIONS: A markedly reduced area of normal lung on HRCT was a relevant radiologic predictor of survival.

Respiratory Viral Infection-Induced Microbiome Alterations and Secondary Bacterial Pneumonia.

Influenza and other respiratory viral infections are the most common type of acute respiratory infection. Viral infections predispose patients to secondary bacterial infections, which often have a more severe clinical course. The mechanisms underlying post-viral bacterial infections are complex, and include multifactorial processes mediated by interactions between viruses, bacteria, and the host immune system. Studies over the past 15 years have demonstrated that unique microbial communities reside on the mucosal surfaces of the gastrointestinal tract and the respiratory tract, which have both direct and indirect effects on host defense against viral infections. In addition, antiviral immune responses induced by acute respiratory infections such as influenza are associated with changes in microbial composition and function ("dysbiosis") in the respiratory and gastrointestinal tract, which in turn may alter subsequent immune function against secondary bacterial infection or alter the dynamics of inter-microbial interactions, thereby enhancing the proliferation of potentially pathogenic bacterial species. In this review, we summarize the literature on the interactions between host microbial communities and host defense, and how influenza, and other acute respiratory viral infections disrupt these interactions, thereby contributing to the pathogenesis of secondary bacterial infections.

Effects of Pneumococcal Conjugate Vaccine on Genotypic Penicillin Resistance and Serotype Changes, Japan, 2010-2017.

To clarify year-to-year changes in capsular serotypes, resistance genotypes, and multilocus sequence types of Streptococcus pneumoniae, we compared isolates collected from patients with invasive pneumococcal disease before and after introductions of 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PVC13, respectively). From April 2010 through March 2017, we collected 2,856 isolates from children and adults throughout Japan. Proportions of PCV13 serotypes among children decreased from 89.0% in fiscal year 2010 to 12.1% in fiscal year 2016 and among adults from 74.1% to 36.2%. Although nonvaccine serotypes increased after introduction of PCV13, genotypic penicillin resistance decreased from 54.3% in 2010 to 11.2% in 2016 among children and from 32.4% to 15.5% among adults. However, genotypic penicillin resistance emerged in 9 nonvaccine serotypes, but not 15A and 35B. Multilocus sequence typing suggested that resistant strains among nonvaccine serotypes may have evolved from clonal complexes 156 and 81. A more broadly effective vaccine is needed.

Gefitinib successfully administered in a lung cancer patient with leptomeningeal carcinomatosis after erlotinib-induced pneumatosis intestinalis.

BACKGROUND: Pneumatosis intestinalis (PI) is a rare complication of chemotherapy, characterized by multiple gas accumulations within the bowel wall. CASE PRESENTATION: A 71-year-old woman with epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma was admitted to our hospital because of reduced consciousness. She was diagnosed as having leptomeningeal carcinomatosis (LM) using lumbar puncture. Because she could not swallow a tablet, erlotinib was administered via a feeding tube. Her state of consciousness gradually improved, but she experienced diarrhea several times a day. After 3 weeks of erlotinib therapy, PI occurred. Erlotinib was discontinued and PI was resolved after treatment with conservative therapies. Erlotinib was re-administrated and PI occurred again. After improvement of erlotinib-induced PI, gefitinib was administered by a feeding tube and the patient did not experience PI or diarrhea. The patient survived 8 months from the diagnosis of LM. CONCLUSION: PI is one of the side effects of erlotinib, and consecutive therapies are useful for the treatment of PI. In this patient, gefitinib was successfully administered after erlotinib-induced PI.

OK-432 pleurodesis for the treatment of pneumothorax in patients with interstitial pneumonia.

BACKGROUND: Pneumothorax occasionally develops in patients with interstitial pneumonia (IP) and is often intractable. As there exists no well-established treatment for pneumothorax with IP, we evaluated the efficacy and safety of pleurodesis with OK-432, a lyophilized preparation of Streptococcus pyogenes Su strain that has been inactivated by benzylpenicillin. METHODS: We retrospectively evaluated the efficacy and safety of pleurodesis using OK-432 in 39 patients treated for IP-related pneumothorax between January 2006 and May 2017. Five to 10 Klinische Einheit (KE) of OK-432 was injected through the chest tube of each patient. Pleurodesis was considered successful if 1) the chest tube was removed without air leaks and 2) there was no recurrence of pneumothorax within 4 weeks after tube removal, and no additional treatment was required. RESULTS: OK-432 pleurodesis was performed 46 times in 39 patients. The median number of OK-432 intrapleural injections received was 1 (range, 1-6), and median dose was 10 KE (range, 5-55 KE). The success rate was 63% (29/46) and recurrence rate was 17.4% (8/46). Grade 5 adverse events were observed in eight patients, including two patients who developed acute exacerbation of IP. Patients in whom the first OK-432 pleurodesis was successful had a significantly longer median survival time than patients in whom it was unsuccessful (322 days vs. 70 days, p = 0.036). CONCLUSIONS: Our results show that OK-432 pleurodesis is an effective treatment for pneumothorax associated with IP; however, clinicians should be aware of the possibility of adverse events, especially in patients who are critically ill.

The Efficacy and Safety of Long-term Pirfenidone Therapy in Patients with Idiopathic Pulmonary Fibrosis.

Objective Pirfenidone (PFD) is often used for years, but the efficacy and safety of long-term PFD therapy in patients with idiopathic pulmonary fibrosis (IPF) are not fully understood. Methods and Patients We retrospectively evaluated 46 patients with IPF who received PFD between February 2009 and August 2014. The efficacy and safety of PFD therapy were compared between 2 groups: long-term therapy patients who received PFD for over 1 year (group L, n=30, 65%) and short-term therapy patients who could not receive PFD for more than 1 year due to worsening of their condition or side effects (group S, n=16, 35%). Results The median age of the 46 patients was 70.5 years, and the median baseline % predicted forced vital capacity (%FVC) was 70.0%. The changes in the FVC in group L were -120 mL and -170 mL at 12 and 24 months after receiving PFD, respectively. The respective median survival times after PFD therapy in groups L and S were 1,612 days and 285 days (p<0.001). The patients in group L experienced a longer time free of acute exacerbation of IPF than those in group S (947 days vs. 145 days, p=0.001). A multivariate analysis revealed that %FVC <60% was a predictor of the inability to receive PFD for over 1 year (odds ratio 0.240, 95% confidence interval 0.060-0.958; p=0.043). With regard to grade 3-5 adverse events, only one patient exhibited grade 3 hyponatremia. Conclusion Long-term PFD therapy is effective, with few severe adverse events.