Tuberculosis survivors and the risk of cardiovascular disease: analysis using a nationwide survey in Korea.

Background: Although the association between tuberculosis (TB) and cardiovascular disease (CVD) has been reported in several studies and is explained by mechanisms related to chronic inflammation, few studies have comprehensively evaluated the association between TB and CVD in Korea. Methods: Using the Korea National Health and Nutrition Survey, we classified individuals according to the presence or absence of previous pulmonary TB was defined as the formal reading of a chest radiograph or a previous diagnosis of pulmonary TB by a physician. Using multivariable logistic regression analyses, we evaluated the association between the 10-year atherosclerotic cardiovascular disorder (ASCVD) risk and TB exposure, as well as the 10-year ASCVD risk according to epidemiological characteristics. Results: Among the 69,331 participants, 4% (n = 3,101) had post-TB survivor group. Comparing the 10-year ASCVD risk between the post-TB survivor and control groups, the post-TB survivor group had an increased 10-year ASCVD risk in the high-risk group (40.46% vs. 24.00%, P < 0.001). Compared to the control group, the intermediate- and high-risk groups had also significantly increased 10-year ASCVD risks (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.04-1.23 and OR 1.69, 95% CI 1.59-1.78, respectively) in the post-TB survivor group. In the association of CVD among post-TB survivors according to epidemiologic characteristics, age [adjusted OR (aOR) 1.10, 95% CI 1.07-1.12], current smoking (aOR 2.63, 95% CI 1.34-5.14), a high family income (aOR 2.48, 95% CI 1.33-4.62), diabetes mellitus (aOR 1.97, 95% CI 1.23-3.14), and depression (aOR 2.06, 95% CI 1.03-4.10) were associated with CVD in the post-TB survivor group. Conclusions: Our study findings suggest a higher 10-year ASCVD risk among TB survivors than healthy participants. This warrants long-term cardiovascular monitoring and management of the post-TB population.

A prospective, open-label, randomized clinical trial to evaluate the efficacy and safety of remimazolam in patients undergoing EBUS-TBNA: REST trial design.

BACKGROUND: Remimazolam is safe and effective for moderate sedation during flexible bronchoscopy, but its safety and efficacy during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) remains undetermined. The REST trial (NCT06275594) will be a prospective randomized study of remimazolam in patients undergoing EBUS-TBNA with conscious sedation. The primary aim is to evaluate whether remimazolam is safe and effective for moderate sedation during EBUS-TBNA compared to real-world midazolam and on-label midazolam. METHODS: The REST trial will recruit 330 patients from four university hospitals with mediastinal lesions suspected of being lung cancer who are eligible for EBUS-TBNA under moderate sedation. The participants will be randomized into groups using remimazolam, real-world midazolam, and on-label midazolam (US prescribing information dosage) to perform EBUS-TBNA for procedural sedation. The primary endpoint will be procedural success using composite measures. DISCUSSION: The REST trial will prospectively evaluate the efficacy and safety of remimazolam during EBUS-TBNA under moderate sedation. It will provide information for optimizing sedation modalities and contribute to practical benefits in patients undergoing EBUS-TBNA. TRIAL REGISTRATION: ClinicalTrials.gov (NCT06275594). Prospectively registered on 15 February 2024.

Safety and efficacy of remimazolam compared with midazolam during bronchoscopy: a single-center, randomized controlled study.

Although remimazolam is an ultra-short-acting benzodiazepine with a shorter elimination half-life and faster recovery time than midazolam, studies evaluating its safety and efficacy during bronchoscopy are limited. This study aimed to compare the safety and efficacy of remimazolam with those of midazolam for bronchoscopy. This prospective randomized parallel-group study was conducted at a single institution. The primary outcome was the time from the end of the procedure to full alertness. Other procedural time parameters, satisfaction profiles, and adverse effects were thoroughly evaluated. The time taken to reach peak sedation and the time from the end of the procedure to full alertness was significantly shorter in the remimazolam group than in the midazolam group (median [interquartile range], 2 min [1-4] vs. 3 min [2-5], P = 0.006; and median, 2 min [1-5] vs. 5 min [1-12], P = 0.035, respectively). In patients with non-biopsy procedures (n = 79), participant satisfaction was significantly higher in the remimazolam group than in the midazolam group (median rated scale, 10 vs. 7, P = 0.042). Physician satisfaction and willingness to repeat the procedure were similar between groups. Although the incidence of adverse effects was similar between the groups and there was no significant difference, the midazolam group had a higher antidote administration rate than the remimazolam group (15.7% vs. 4.1%, P = 0.092). Remimazolam is effective and safe for achieving adequate sedation, with a shorter onset time and faster neuropsychiatric recovery than midazolam. It may be a new option for sedation during bronchoscopy.Trial registration: The trial registration number is NCT05994547, and the date of first registration is 16/08/2023.

Effectiveness of the use of an oscillating positive expiratory pressure device in bronchiectasis with frequent exacerbations: a single-arm pilot study.

Impaired airway clearance in patients with non-cystic fibrosis bronchiectasis causes frequent bacterial infection, chronic inflammation, and progressive tissue destruction. We aimed to evaluate whether an oscillating positive expiratory pressure (OPEP) device could allow effective sputum expectoration and prevent acute exacerbations in patients with bronchiectasis who had frequent acute exacerbations. This open-label, single-arm, prospective study included 17 patients who experienced three or more acute exacerbations in the past year. We evaluated the prevention of acute exacerbations, subjective symptom improvement, and change in sputum amount during the use of the Aerobika (Trudell Medical International, London, ON) OPEP device twice daily for 6 months. Of all enrolled patients, only two acute exacerbations occurred during the study period, indicating a significant decrease compared with the number of acute exacerbations before the device use (p < 0.001). Additionally, Bronchiectasis Health Questionnaire score changed from 58.7 to 66.6, showing significant improvement over the treatment period (p < 0.001). The largest sputum volume was observed 3 months after OPEP device use (baseline: 10 ml, 3rd month 25 ml, p = 0.325). There were no major adverse events related to the use of OPEP devices. Twice-daily physiotherapy with OPEP device in patients with bronchiectasis who have frequent exacerbations may facilitate symptomatic improvement and prevention of acute exacerbations without serious adverse events.

Multidisciplinary team approach on tracheoesophageal fistula in a patient with home ventilator.

A 68-year-old man was transferred to our tertiary hospital. Ten years ago, he received radiation therapy for tonsil cancer, and while there was no evidence of recurrence, he suffered from recurrent aspiration. We treated his aspiration pneumonia in the intensive care unit. Prior to his discharge, he received percutaneous dilatational tracheostomy (PDT) before he was transferred to a nursing hospital. Nine months later, he was readmitted owing to tracheoesophageal fistula (TEF). However, he was considered unsuitable for conservative intervention after a multidisciplinary team discussion. Esophageal stent insertion was impossible due to the high level of TEF in the esophagus. Additionally, the size of the TEF could not be covered by an endosponge and endoluminal vacuum therapy, and there was no tracheal stent that could cover his large trachea. The preceding percutaneous enteral gastrostomy (PEG) procedure was required for the primary closure operation of the esophagus; however, family's consent could not be obtained. After 1month, the patient and his family changed their minds and agreed to the procedure and we attempted to perform PEG procedure. However, we could not proceed with PEG owing to stenosis in the inlet of the esophagus. Then, the patient deteriorated clinically and died due to pneumonia with septic shock.

Clinical characteristics, radiological features, and disease severity of bronchiectasis according to the spirometric pattern.

Bronchiectasis show various ventilatory disorders in pulmonary function. The characteristics and severity of patients with bronchiectasis according to these pulmonary dysfunctions are still very limited. This study aimed to evaluate the clinical, radiologic feature and the disease severity of patients with bronchiectasis according to spirometric patterns. We retrospectively evaluated 506 patients with bronchiectasis who underwent pulmonary lung function test (PFT) at a referral hospital between 2014 to 2021. The results showed that cylindrical type was the most common (70.8%) type of bronchiectasis on chest Computed tomography (CT), and 70% of patients had bilateral lung involvement. On the other hand, obstructive ventilatory disorder was the most common (51.6%), followed by normal ventilation (30%) and restrictive ventilatory disorder (18.4%). The modified Medical Research Council (mMRC) was highest in patients with obstructive ventilatory disorders, Modified Reiff score [median (interquartile range)] [6 (3-10), P < 0.001], FACED (FEV1, Age, Chronic colonization, Extension, and Dyspnea) score [3 (1-4), P < 0.001], and Bronchiectasis Severity (BSI) score [8 (5-11), P < 0.001] showed significantly highest values of obstructive ventilatory disorder rather than restrictive ventilatory disorder and normal ventilation. More than half of patients with bronchiectasis had obstructive ventilatory disorder. Bronchiectasis with obstructive ventilatory disorders has more dyspnea symptom, more disease severity and more radiologic severity. There was no significant association between spirometric pattern and radiologic type, but the more severe the radiologic severity, the more severe the lung function impairment.

A case report of nilotinib-induced irreversible interstitial lung disease.

RATIONALE: Nilotinib is a second line tyrosine kinase inhibitor to treat patients with chronic myeloid leukemia after imatinib resistance or intolerance. Drug related pulmonary complication is known to be rare. We discuss a case of nilotinib-induced interstitial lung disease presenting with nonspecific interstitial pneumonia on the unilateral lung. PATIENT CONCERNS: A 46-year-old man with chronic-phase chronic myeloid leukemia presented with cough and weight loss for 2 months. He had been treated with nilotinib for 52 months. DIAGNOSIS: Computed tomography scan showed right lung dominant consolidations, ground glass opacities and traction bronchiectasis. Bronchoalveolar lavage fluid analysis revealed no evidence of infection or malignancy. Surgical lung biopsy specimen was consistent with fibrosing nonspecific interstitial pneumonia. The patient was diagnosed with nilotinib induced interstitial lung disease. INTERVENTIONS: Corticosteroid treatment was initiated with prednisolone (50 mg daily) and slowly tapered down for 2 months. OUTCOMES: Cough improved after the course of corticosteroid treatment. However, fibrotic lung lesions persisted. Reinitiation of nilotinib resulted in the worsening of lung lesions. LESSONS: We report a case of irreversible interstitial lung disease that caused by nilotinib. Clinicians should have suspicion of this potential pulmonary complication in patients with respiratory symptoms and abnormal radiologic findings during nilotinib treatment, albeit rarely.

Trend of lung cancer surgery, hospital selection, and survival between 2005 and 2016 in South Korea.

BACKGROUND: Studies on the clinical implication of hospital selection for patients with lung cancer are few. Therefore, this study aimed to analyze 2005-2016 data from the Korean national database to assess annual trends of lung cancer surgery and clinical outcomes according to hospital selection. METHODS: Data of 212 554 patients with lung cancer who underwent upfront surgery were screened. Trends according to sex, age, residence, and income were examined. Descriptive statistics were performed, and ptrend values were estimated. The association between survival and hospital selection was assessed using the log-rank test. A multivariate Cox regression analysis was also performed. RESULTS: A total of 49 021 patients were included in this study. Surgery was prevalent among men, patients aged 61-75 years, capital area residents, and high-income patients. However, with the increasing rate of surgery among women, patients aged ≥76 years, city residents, and middle-income patients, the current distribution of lung cancer surgery could change. The rate of lobectomy among these groups increased. All patients, except those in capital areas, preferred a hospital outside their area of residence (HOR); the number of patients with this tendency also increased. However, this trend was not observed among low-income patients and those aged ≥76 years. There were significant differences in survival according to hospital selection. CONCLUSIONS: The trend of lung cancer surgery is changing. The current medical system is effective in providing lobectomy for patients including women, aged ≥76 years, city residents, and middle-income. Increasing tendency to choose an HOR requires further study.

Clinical profiles and outcomes of pulmonary tuberculosis patients with delayed treatment at a tertiary hospital in South Korea.

BACKGROUND: Data on the clinical characteristics of delayed treatment initiation among pulmonary tuberculosis (TB) patients are lacking. Thus, this study aimed to identify the factors associated with delayed treatment in culture-confirmed pulmonary TB and to assess outcomes of delayed treatment. METHODS: We retrospectively evaluated 151 patients with culture-confirmed pulmonary TB between 2015 and 2017. Delayed and timely treatment was defined as initiation of anti-TB treatment after and before the identification of Mycobacterium tuberculosis complex isolate, respectively. Factors related to delayed treatment, such as comorbidities, clinical presentation, and patterns of initial healthcare use, were collected. We analyzed whether delayed treatment was associated with all-cause mortality using a multivariate binary logistic regression model adjusted for age, sex, cardiovascular disease, and malignancy. RESULTS: In total, 55 (36.4%) patients had delayed treatment. The median length between the first medical visit and treatment initiation was 9 days. Compared with timely treatment, delayed treatment was associated with no initial visit to a non-pulmonary department [adjusted odds ratio (aOR) =10.49, 95% confidence interval (CI), 2.56-42.93] and absence of nucleic acid amplification test (aOR =7.54, 95% CI, 2.75-20.67). After adjusting for age, sex, cardiovascular disease, and solid malignancies, delayed treatment was significantly associated with all-cause mortality (aOR =3.79, 95% CI, 1.36-10.58). The most frequent possible cause of delayed treatment was the doctor's low suspicion of active TB disease. CONCLUSIONS: Given that delayed treatment is associated with worse outcomes in South Korea, targeted interventions to increase awareness on TB in the healthcare community are necessary for additional mycobacterial tests and consults of suspicious patients to TB specialists.

Genetic Features of Lung Adenocarcinoma with Ground- Glass Opacity: What Causes the Invasiveness of Lung Adenocarcinoma?

BACKGROUND: Lung adenocarcinoma (LUAD) with ground-glass opacity (GGO) can become aggravated, but the reasons for this aggravation are not fully understood. The goal of this study was to analyze the genetic features and causes of progression of GGO LUAD. METHODS: LUAD tumor samples and normal tissues were analyzed using an Illumina HiSeq 4000 system. After the tumor mutational burden (TMB) was calculated, the identified mutations were classified as those found only in GGO LUAD, those present only in non- GGO LUAD, and those common to both tissue types. Ten high-frequency genes were selected from each domain, after which protein interaction network analysis was conducted. RESULTS: Overall, 227 mutations in GGO LUAD, 212 in non-GGO LUAD, and 48 that were common to both tumor types were found. The TMB was 8.8 in GGO and 7.8 in non-GGO samples. In GGO LUAD, mutations of FCGBP and SFTPA1 were identified. FOXQ1, IRF5, and MAGEC1 mutations were common to both types, and CDC27 and NOTCH4 mutations were identified in the non-GGO LUAD. Protein interaction network analysis indicated that IRF5 (common to both tissue types) and CDC27 (found in the non-GGO LUAD) had significant biological functions related to the cell cycle and proliferation. CONCLUSION: In conclusion, GGO LUAD exhibited a higher TMB than non-GGO LUAD. No clinically meaningful mutations were found to be specific to GGO LUAD, but mutations involved in the epithelial-mesenchymal transition or cell cycle were found in both tumor types and in non-GGO tissue alone. These findings could explain the non-invasiveness of GGO-type LUAD.

Usefulness of CT-Guided Percutaneous Transthoracic Needle Lung Biopsies in Patients with Suspected Pulmonary Infection.

OBJECTIVE: This study aimed to evaluate the clinical benefits and risks of CT-guided percutaneous transthoracic needle lung biopsies (PTNBs) in patients with a suspected pulmonary infection. MATERIALS AND METHODS: This study included 351 CT-guided PTNBs performed in 342 patients (mean age, 58.9 years [range, 17-91 years]) with suspected pulmonary infection from January 2010 to December 2016. The proportion of biopsies that revealed the causative organism for pulmonary infection and that influenced patient's treatment were measured. Multivariate analyses were performed to identify factors associated with PTNB that revealed the causative organism or affected the treatment. Finally, the complication rate was measured. RESULTS: CT-guided PTNB revealed the causative organism in 32.5% of biopsies (114/351). The presence of necrotic components in the lesion (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.1-2.7; p = 0.028), suspected pulmonary tuberculosis (OR, 2.0; 95% CI, 1.2-3.5; p = 0.010), and fine needle aspiration (OR, 2.5; 95% CI, 1.1-5.8; p = 0.037) were factors associated with biopsies that revealed the causative organism. PTNB influenced patient's treatment in 40.7% (143/351) of biopsies. The absence of leukocytosis (OR, 1.9; 95% CI, 1.0-3.7; p = 0.049), presence of a necrotic component in the lesion (OR, 2.4; 95% CI, 1.5-3.8; p < 0.001), and suspected tuberculosis (OR, 1.7; 95% CI, 1.0-2.8; p = 0.040) were factors associated with biopsies that influenced the treatment. The overall complication rate of PTNB was 19% (65/351). CONCLUSION: In patients with suspected pulmonary infection, approximately 30-40% of CT-guided PTNBs revealed the causative organism or affected the treatment. The complication rate of PTNB for suspected pulmonary infection was relatively low.

Clinical Significance of Pleural Attachment and Indentation of Subsolid Nodule Lung Cancer.

PURPOSE: Lung cancers presenting as subsolid nodule commonly have peripheral location, making the cancer-pleura relationship noteworthy. We aimed to evaluate the effect of pleural attachment and/or indentation on visceral pleural invasion (VPI) and recurrence-free survival. MATERIALS AND METHODS: Patients who underwent curative resection of lung cancer as subsolid nodules from April 2007 to January 2016 were retrospectively evaluated. They were divided into four groups according to their relationship with the pleura. Clinical, radiographical, and pathological findings were analyzed. RESULTS: Among 404 patients with malignant subsolid nodule, 120 (29.7%) had neither pleural attachment nor indentation, 26 (6.4%) had attachment only, 117 (29.0%) had indentation only, and 141 (34.9%) had both. VPI was observed in nodules of 36 patients (8.9%), but absent in nonsolid nodules and in those without pleural attachment and/or indentation. Compared to subsolid nodules with concurrent pleural attachment and indentation, those with attachment only (odds ratio, 0.12; 95% confidence interval [CI], 0.02 to 0.98) and indentation only (odds ratio, 0.10; 95% CI, 0.03 to 0.31) revealed lower odds of VPI. On subgroup analysis, the size of the solid portion was associated with VPI among those with pleural attachment and indentation (p=0.021). Such high-risk features for VPI were associated with earlier lung cancer recurrence (adjusted hazard ratio, 3.31; 95% CI, 1.58 to 6.91). CONCLUSION: Concurrent pleural attachment and indentation are risk factors for VPI, and the odds increase with larger solid portion in subsolid nodules. Considering the risk of recurrence, early surgical resection could be encouraged in these patients.

Role of Low-Dose Computerized Tomography in Lung Cancer Screening among Never-Smokers.

INTRODUCTION: The incidence of lung cancer among never-smokers has been increasing rapidly. The U. S. National Lung Screening Trial and the NELSON trial showed that screening using low-dose computerized tomography (LDCT) effectively reduced lung cancer mortality among heavy smokers. However, its effectiveness in never-smokers has not been well investigated. This study investigated the role of LDCT in lung cancer screening among never-smokers. METHODS: The study was designed as a single-center, retrospective cohort study. We analyzed the data on patients who underwent LDCT screening between May 2003 and June 2016. Nodules detected by computerized tomography were classified according to the Lung Imaging Reporting and Data System criteria. The detection rate and lung cancer outcomes (type of cancer, staging of lung cancer, and mortality) according to smoking history were determined. RESULTS: Of the 28,807 enrolled patients, 12,176 were never-smokers; of these patients, 7744 (63.6%) were women and 1218 (10.0%) were found to have lung nodules. Overall, lung cancer was diagnosed in 55 never-smokers (0.45%). In contrast, lung cancer was diagnosed in 143 (0.86%) of the 16,631 ever-smokers. Of the never-smokers with lung cancer, 51 (92.7%) presented with stage I disease, and all patients had adenocarcinomas. CONCLUSIONS: In the never-smoker population, LDCT screening helped to detect a significant number of lung cancers. Most of these lung cancers were detected at a very early stage. The positive results of the National Lung Screening Trial in the United States and the NELSON trial may have established the value of LDCT screening for heavy smokers, but future research should consider the value of using LDCT screening in the never-smoker population.

Characteristics, incidence, and risk factors of immune checkpoint inhibitor-related pneumonitis in patients with non-small cell lung cancer.

OBJECTIVES: Immune checkpoint inhibitors (ICIs) can cause pneumonitis in lung cancer patients. We aimed to identify the clinical and radiologic characteristics, incidence, and risk factors of ICI-related pneumonitis in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Medical records and chest computed tomography scans of NSCLC patients treated with an ICI over a 5-year period at a tertiary hospital were retrospectively analyzed. Clinical characteristics were compared between patients with and without ICI-related pneumonitis to identify risk factors. RESULTS: Data from 167 eligible patients were analyzed. The incidences of all-grade and grade 3-4 pneumonitis were 13.2% and 4.2%, respectively. The presence of preexisting interstitial lung disease [odd ratio (OR), 6.03; 95% confidence interval (CI), 1.19-30.45; P = 0.030] was associated with a higher incidence of ICI-related pneumonitis. The presence of extrathoracic metastasis [OR, 0.34; 95% CI, 0.13-0.92; P = 0.034] was associated with a lower incidence of ICI-related pneumonitis. The dominant radiologic pattern (72.7%) of ICI-related pneumonitis was organizing pneumonia. Half of the patients with pneumonitis completely recovered or improved; however, the mortality rate was 18.2%. CONCLUSION: ICIs should be used with caution when treating lung cancer patients who have underlying chronic lung disease, especially interstitial lung disease.

Solid part size is an important predictor of nodal metastasis in lung cancer with a subsolid tumor.

BACKGROUND: Candidates for preoperative or intraoperative nodal assessment among patients with non-small cell lung cancer (NSCLC) manifesting as a subsolid tumor are not established. The present study was conducted to demonstrate the distribution of nodal metastasis rate according to newly proposed T categories for subsolid tumors, and we further aimed to identify radiologic parameters that can be predictive of nodal metastasis. METHODS: We retrospectively reviewed cases of NSCLC manifesting as a subsolid tumor in computed tomography scans in a university-affiliated tertiary hospital between April 2013 and August 2016. All patients underwent mediastinal lymph node dissection during resection surgery. Multivariate analysis was performed among clinical and radiologic parameters. RESULTS: Of the 269 eligible patients, T-categories were classified as cTis (n = 23, 8.6%), cT1 (n = 203, 75.5%), and cT2 (n = 43, 16.0%). Ten patients (3.7%) had nodal metastasis: pN1 (n = 5, 1.9%), pN2 (n = 5, 1.9%). Nodal metastasis was not observed in tumors with a solid part ≤1.0 cm (cT1mi and cT1a) or in nonsolid tumors ≤3.0 cm (cTis). The nodal metastasis rate in cT1b, cT1c, and cT2 tumors was 6.1% (4/65), 8.3% (1/12), and 11.7% (5/43), respectively. Multivariate analysis showed that a solid part size > 1.5 cm [odds ratio, 5.89; 95% confidence interval, 1.25-27.68, p = 0.025] was significantly associated with nodal metastasis. CONCLUSIONS: We observed nodal metastasis from cT1b tumors (solid part size > 1 cm) among proposed T categories for subsolid tumors and a solid part size is an important radiologic parameter predictive of nodal metastasis in NSCLC manifesting as a subsolid tumor. Considering the low rate of nodal metastasis, pathologic nodal assessment may be unnecessary in early T category tumors with a small solid part size.

Bronchoscopic Improvement of Tracheobronchitis Due to Methicillin-Resistant Staphylococcus aureus After Aerosolized Vancomycin: A Case Series.

BACKGROUND: Ventilator-associated tracheobronchitis (VAT) is an important risk factor for ventilator-associated pneumonia (VAP). The efficacy of aerosolized vancomycin (AV) in treating VAT has not been clearly demonstrated. METHODS: Four mechanically ventilated patients with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia were treated with an additional AV. AV (250 mg twice per day) was administered through a vibrating mesh device for 5 days. All patients were receiving intravenous vancomycin and had severe tracheobronchitis, based on bronchoscopic findings before or soon after additional AV treatment. RESULTS: After several days of AV treatment, follow-up bronchoscopies showed dramatic improvement of tracheobronchitis. All patients achieved microbiological eradication of MRSA. Finally, two of four patients survived through to hospital discharge. CONCLUSION: This case series study suggests a potential role of AV in the treatment of MRSA tracheobronchitis, which were accompanied by VAP. Clinical trial addressing the efficacy of AV in MRSA VAT and/or VAP should be needed.