Ultralow-Dose Dynamic Expiratory CT and Repeated Imaging Enhance Evaluation for Tracheomalacia.

OBJECTIVE: This study aims to determine if a novel imaging protocol (ultralow-dose dynamic expiratory computed tomography [CT] with repeated imaging) identifies tracheomalacia (TM) more reliably than traditional dynamic tracheal CT. METHODS: We performed a retrospective evaluation of 184 consecutive ultralow-dose dynamic CTs for TM during 2017. The protocol obtains images during 1 inspiration and 2 forced expirations. Tracheal narrowing during both expirations (airway narrowing [percentage] during first dynamic expiration CT [DE1], airway narrowing [percentage] during second dynamic expiration CT [DE2]) was reported as a percentage of inspiratory area. We identified maximum narrowing of each patient's sequence (maximum narrowing [percentage] on either dynamic expiration CT [DEmax] = greatest narrowing of DE1 or DE2) and compared DE1, DE2, and DEmax in individual studies and between patients. Outcomes included frequency of TM, tracheal narrowing, and severity. Reliability was assessed by comparing tracheal area narrowing and TM grade. RESULTS: There was significantly more airway narrowing using 2 expiratory image acquisitions. Average DEmax tracheal area was 12% narrower than DE1 alone and 21% worse than DE2 alone (both P < 0.001). Using DEmax, TM was diagnosed 35% more often than DE1 alone and 31% more often than DE2 alone ( P < 0.001). DEmax identified more severe distribution of TM compared with DE1 or DE2 alone ( P < 0.001). Reliability between DE1 and DE2 was good for tracheal narrowing and moderate for TM grade. The mean effective radiation dose was 2.41 millisievert (mSv) for routine inspiration CT and 0.07 mSv for each dynamic expiration CT (total effective radiation, 2.55 mSv). CONCLUSIONS: Dynamic expiration CT with 2 expiratory image acquisitions enhanced evaluation of TM, minimally increased radiation dose, and should be considered as a noninvasive screening option.

Long-term Outcomes After Lung Cancer Resection in Smokers: Analysis of the National Lung Screening Trial.

BACKGROUND: Smoking is a known risk factor for perioperative complications after lung resection; however, little data exists looking at the impact of smoking status (current versus former) on long-term oncologic outcomes after lung cancer surgery. We sought to compare overall survival (OS), progression-free survival (PFS), and cancer-specific mortality (CSM) in current and former smokers using data from the National Lung Screening Trial (NLST). Additionally, we performed subset analysis in current smokers in order to evaluate the effect of modern surgical techniques on long-term outcomes. METHODS: Patients with clinical stage IA or IB NSCLC who underwent upfront resection within 180 days of diagnosis were identified in the NLST database. Cox proportional hazard regression models were used to assess differences in patient and treatment characteristics with respect to OS and PFS, with a cause-specific hazard model used for CSM. RESULTS: A total of 593 patients were included in the study (269 former smokers, 324 current smokers). Lobar resection (LR) was performed more often than sublobar resection (SLR) (481 vs. 112), and thoracotomy was performed more often than thoracoscopy (482 vs. 86). Comparison of current versus former smokers showed no difference in OS or PFS after resection. Higher CSM was seen in current smokers (p = 0.049). Subset analysis of current smokers revealed no difference in OS or PFS between sub-lobar and lobar resection or thoracotomy and thoracoscopy. Although higher CSM was associated with thoracoscopy versus thoracotomy in this group, this finding was limited by a relatively small thoracoscopy sample size of 44 patients (p = 0.026). CONCLUSION: Our analysis of the NLST database shows no significant difference in OS and PFS when comparing current and former smokers undergoing resection for stage I NSCLC. Active smoking status was associated with higher CSM. Subset analysis of current smokers showed no difference in OS or PFS between sub-lobar and lobar resection or thoracotomy and thoracoscopy. Higher CSM was seen in current smokers who underwent thoracoscopy compared to thoracotomy; however, this finding was limited by a small sample size.

Impact of postoperative complications on long-term survival after esophagectomy in older adults: A SEER-Medicare analysis.

BACKGROUND: Esophagectomy is a complex procedure associated with a high rate of postoperative complications. It is not clear whether postoperative complications effect long-term survival. Most studies report the results from single institutions. METHODS: We examined the Surveillance, Epidemiology and End Results (SEER)-Medicare database to assess whether long-term overall and cancer-specific mortality of patients undergoing esophagectomy for cancer is impacted by postoperative complications. RESULTS: Nine hundred and forty patients underwent esophagectomy from 2007 to 2014, of which 50 died, resulting in a cohort of 890 patients. Majority were males (n = 764, 85.8%) with adenocarcinoma of the lower esophagus. Almost 60% of the group had no neoadjuvant therapy. Four hundred and fifty-five patients had no major complications (51.1%), while 285 (32.0%) and 150 (16.9%) patients had one, two, or more major complications, respectively. Overall survival at 90 days was 93.1%. Multivariate analysis of patients followed up for a minimum of 90 days demonstrated that the number of complications was significantly associated with decreased overall survival but no impact on cancer-specific survival. CONCLUSIONS: Our population-based analysis with its inherent limitations suggests that patients undergoing esophagectomy who experience complications have worse overall survival but not cancer-specific survival if they survive at least 90 days from the date of surgery.

Outcomes Following Major Oncologic Operations for Non-AIDS-Defining Cancers in the HIV Population: A Matched Comparison to the General Population.

INTRODUCTION: Human immunodeficiency virus (HIV) patients are living longer due to the availability of antiretroviral therapies, and non-AIDS-defining cancers are becoming more prevalent in this patient population. A paucity of data remains on post-operative outcomes following resection of non-AIDS-defining cancers in the HIV population. METHODS: The National Inpatient Sample was utilized to identify patients who underwent surgical resection for malignancy from 2005 to 2015 (HIV, N = 52,742; non-HIV, N = 11,885,184). Complications were categorized by international classification of disease (ICD)-9 diagnosis codes. Cohorts were matched on insurance, household income, zip code and urban/rural setting. Logistic regression assessed whether HIV was an independent predictor of post-operative complications. RESULTS: Descriptive statistics found HIV patients to have an increased rate of complications following select oncologic surgical resections. Univariate and multivariate logistic regression found HIV to only be an independent predictor of complications following pulmonary lobectomy (p = 0.011; OR 2.93, 95% CI 1.29-6.73). Length of stay was statistically longer following colectomy (2.61 days, 95% CI 1.98-3.44) in those with HIV. CONCLUSIONS: Our findings are hypothesis generating and highlight the potential safety of major cancer surgery in the HIV population. However, care providers need be cognizant of the potential increased risk of post-operative complications following pulmonary lobectomy and the potential for increased length of stay. These findings are an initial insight into quality of care and outcomes metrics on HIV patients undergoing major cancer operations.

Hospital Readmission and Length of Stay Over Time in Patients Undergoing Major Cardiovascular and Orthopedic Surgery: A Tale of 2 States.

BACKGROUND: Readmission and length of stay (LOS) are increasingly accepted as quality measures for surgical care. Centers for Medicare & Medicaid Services will soon assess penalties for excessive readmissions after coronary artery bypass graft (CABG) surgery and hip and knee replacements. OBJECTIVE: To determine and compare population level changes in LOS and relationship with 30-day readmission over time for patients undergoing CABG and hip and knee replacements. Secondary objective was to determine relationship between LOS and discharge disposition as well as mortality. RESEARCH DESIGN: Observational cohort study of patients undergoing CABG and hip and knee replacements in New York and California. Temporal trends in LOS, discharge disposition, 30-day readmission, and mortality were examined. Generalized linear-mixed models, accounting for hospital clustering, were used to assess differences in outcomes. SUBJECTS: Patients undergoing CABG and hip and knee replacements in New York and California between 2005 and 2011. MEASURES: Trends in LOS, discharge disposition, 30-day readmission and mortality, and risk-adjusted odds of all-cause 30-day readmission. RESULTS: We identified 206,784, 336,271, and 416,391 patients who underwent CABG, hip, and knee replacements, respectively, in New York State and California between 2005 and 2011. The risks of readmission within 30 days decreased over time in both states. LOS decreased by 1 day after hip and knee surgery and remained unchanged after CABG. Adjusted analysis confirmed these trends. In secondary analyses patients in New York had higher overall odds of 30-day readmission compared with patients in California. CONCLUSIONS: We found no evidence of inverse relationship between LOS and readmission over time. In hip and knee replacement there is strong evidence that both LOS and readmission have been reduced simultaneously.

National Analysis of Short-Term Outcomes and Volume-Outcome Relationships for Transcatheter Aortic Valve Replacement in the Era of Commercialization.

OBJECTIVES: We queried the 2012 National Inpatient Sample in order to (1) further describe the short-term outcomes for transcatheter aortic valve replacement (TAVR) and (2) characterize possible volume-outcome relationships and other prognostic factors for this procedure. METHODS: Demographics and inhospital outcomes were tabulated for all patients, as were hospital characteristics and procedural-volume data for all centers at which patients underwent TAVR. Logistic regression analyses were performed to identify independent risk factors for mortality or morbidity. RESULTS: 7,635 patients aged ≥ 18 years received TAVR during the study period; 84.5% (n = 6,450) underwent transfemoral TAVR and the rest were treated transapically. The median age was 83 years (IQR 77-88 years) and cardiovascular comorbidities were widespread. Overall inhospital mortality was 5.0% (n = 380), and 1.4% (n = 105) of the patients experienced a stroke. All-cause procedure-related morbidity was 24.7% (n = 1,885). Annual hospital TAVR volume did not predict inhospital mortality or morbidity (OR 1.00, 95% CI 0.99-1.00, p = 0.111 and OR 1.00, 95% CI 0.99-1.00, p = 0.947, respectively). CONCLUSIONS: Our analysis helps to confirm the short-term safety profile of TAVR and further demonstrates that inhospital outcomes have remained acceptable as this procedure has become commercialized.

Techniques of video-assisted thoracoscopic surgery lobectomy and critical review of published data.

Lung cancer resection techniques have gone through many changes and adaptations. Traditional thoracotomy provided sufficient visualization to fully resect the lobe as well as adequate lymph node dissection. Many thought that this allowed for the most accurate surgical staging of a lung cancer, but subjected the patient to longer hospital stays and increased morbidity and mortality. As with many major surgical operations there has been a culture shift toward minimally invasive techniques, but the adoption has been slow. We present the technique of video-assisted thoracoscopic surgery lobectomy and the literature supporting its use in the treatment of early-stage lung cancer.

Predictors of Disease-free Survival and Recurrence in Patients with Resected Bronchial Carcinoid Tumors.

BACKGROUND: Bronchial carcinoids are characterized by neuroendocrine differentiation and have distinct biological behavior, recurrence patterns, and prognosis compared with adenocarcinomas or squamous cell carcinomas. Because of their often indolent nature, it has been suggested that routine postoperative imaging surveillance may not be warranted in the majority of patients. This study aims to define the factors that predict disease-free survival (DFS) and recurrence after resection of these tumors, with the goal of identifying high-risk patients for whom image surveillance may be warranted. METHODS: We conducted a retrospective review of a prospective database to identify patients with completely resected bronchial carcinoid tumors. Surgical procedure, histology, pathological stage, follow-up, tumor recurrence, and survival were assessed. RESULTS: One hundred and forty-two patients were identified. Median age was 62 years and the majority was women (106). Surgical procedures included 20 wedge resections, 10 segmentectomies, 99 lobectomies, 3 bilobectomies, 2 pneumonectomies, 6 sleeve resections, and 2 bronchectomies. Pathologic stages included I (81%), II (10%), III (8%), and IV (1%). With a median follow-up of 31 months, there were seven recurrences. The 5- and 10-year overall survival rates were 92% and 75% and DFS rates were 88% and 72%, respectively. There were 34 patients with atypical carcinoids, and 6 (18%) developed recurrence, compared with 1 recurrence (1%) in the group of 108 patients with typical carcinoids (p = 0.0008). For atypical carcinoid tumors, the 5- and 10-year DFS rates were 72% and 32% versus 92% and 85% in typical carcinoid tumors (p = 0.001). Patients with more advanced tumor stage pT2-4 and pathologic N1/N2 nodal metastases had a significantly decreased 5- and 10-year DFS compared with those with early pT1 stage (p = 0.029) or those without nodal disease (p = 0.043). Multivariate Cox regression analyses showed advancing age (p = 0.001), atypical histology (p = 0.021), and advanced tumor stage (p = 0.047) were significant negative predictors for DFS. CONCLUSION: Long-term survival after resection of bronchial carcinoids is common, especially for patients with typical carcinoid tumors. DFS can be negatively influenced by atypical histology, advanced tumor, and nodal statuses. Efforts at postoperative image surveillance should target those patients with such high-risk factors.

Perioperative Outcomes after Lung Resection in Obese Patients.

BACKGROUND: Obesity is a growing epidemic in the developed world. However, little is known about the impact of obesity on the perioperative morbidity and mortality after lung resection. PATIENTS AND METHODS: We analyzed the American College of Surgeons National Surgical Quality Improvement Program database from 2005 to 2010 to determine whether obesity is a risk factor for perioperative morbidity and mortality after pulmonary resection. Demographic, clinical, intraoperative, and morbidity and mortality data were collected. Multivariable predictors of morbidity and mortality were determined using regression analysis. RESULTS: A total of 5,216 lung resections were identified (1,372 wedges, 3,713 lobectomies, and 131 pneumonectomies). The median age was 66 years and 2,587 (49.6%) were females. The body mass index (BMI, kg/m(2)) of the patients was as follows: 192 (3.7%) < 18.5; 1,727 (33.1%) 18.5 to 24.9; 1,754 (33.6%) 25 to 29.9; and 1,488 (28.5%) > 30. In-hospital mortality and all-cause morbidity was 2.4% (n = 127) and 14.5% (n = 757) for the entire cohort of patients, respectively. BMI was not found to be a predictor of increased mortality or morbidity, even in the morbidly obese (BMI > 35). Rather, age, approach (video-assisted thoracoscopic surgery vs. open), parameters assessing performance status, operative time, and preoperative radiation therapy were the predictors of morbidity and mortality. Conversely, being overweight (BMI 25-30) approached significance as a multivariate predictor for decreased pulmonary complications (odds ratio, 0.77 [0.592-1.004]; p = 0.054) consistent with the "obesity paradox" observed after nonbariatric general surgery. CONCLUSION: Our large national study shows that obesity does not negatively impact perioperative mortality and morbidity in patients undergoing lung resection. Surgical resections should not be denied to obese (BMI > 30) patients.

Outcomes in the management of esophageal cancer.

Esophageal cancer rates have continued to rise in the Western World. Esophageal cancer will be responsible for an estimated 15,450 deaths in the United States in 2014 alone. Esophageal resection with or without preoperative therapy remains the mainstay of treatment. Advances in surgical technique and perioperative care have improved short-term outcomes considerably by decreasing operative mortality. Despite these advances though, esophagectomy remains a procedure associated with considerable morbidity from a wide range of complications. Prompt recognition and treatment of complications can lower overall morbidity and mortality. Unfortunately, long-term outcomes remain poor as the vast majority of patients present with loco-regionally advanced or metastatic disease. Surgery by itself provides poor loco-regional control and fails to address micrometastatic disease. Neoadjuvant chemotherapy or chemoradiation provides a modest survival advantage compared to surgical resection alone. Future gains in understanding the molecular biology of esophageal cancer will hopefully lead to improved therapeutics and resultant outcomes.

Left Thoracoscopic Robot-Assisted Excision of a Left Lower Paratracheal Parathyroid Adenoma for Cure of Primary Hyperparathyroidism.

We present a case of a 38-year-old male patient with symptomatic hypercalcemia secondary to primary hyperparathyroidism. After evaluation, the source of the excess parathyroid hormone was found to be an adenoma localized to the middle mediastinum. Specifically, it was located in the left paratracheal space along the lesser curve of the aortic arch. We discuss this case with a corresponding video to demonstrate the necessary equipment and setup as well as the 5 operative steps recommended to access this paratracheal subaortic location from a minimally invasive transthoracic approach. The pitfalls for this operation are also discussed. The purpose is to make this operation more reproducible for other surgeons.

Evaluating the accuracy of lung-RADS score extraction from radiology reports: Manual entry versus natural language processing.

INTRODUCTION: Radiology scoring systems are critical to the success of lung cancer screening (LCS) programs, impacting patient care, adherence to follow-up, data management and reporting, and program evaluation. LungCT ScreeningReporting and Data System (Lung-RADS) is a structured radiology scoring system that provides recommendations for LCS follow-up that are utilized (a) in clinical care and (b) by LCS programs monitoring rates of adherence to follow-up. Thus, accurate reporting and reliable collection of Lung-RADS scores are fundamental components of LCS program evaluation and improvement. Unfortunately, due to variability in radiology reports, extraction of Lung-RADS scores is non-trivial, and best practices do not exist. The purpose of this project is to compare mechanisms to extract Lung-RADS scores from free-text radiology reports. METHODS: We retrospectively analyzed reports of LCS low-dose computed tomography (LDCT) examinations performed at a multihospital integrated healthcare network in New York State between January 2016 and July 2023. We compared three methods of Lung-RADS score extraction: manual physician entry at time of report creation, manual LCS specialist entry after report creation, and an internally developed, rule-based natural language processing (NLP) algorithm. Accuracy, recall, precision, and completeness (i.e., the proportion of LCS exams to which a Lung-RADS score has been assigned) were compared between the three methods. RESULTS: The dataset includes 24,060 LCS examinations on 14,243 unique patients. The mean patient age was 65 years, and most patients were male (54 %) and white (75 %). Completeness rate was 65 %, 68 %, and 99 % for radiologists' manual entry, LCS specialists' entry, and NLP algorithm, respectively. Accuracy, recall, and precision were high across all extraction methods (>94 %), though the NLP-based approach was consistently higher than both manual entries in all metrics. DISCUSSION: An NLP-based method of LCS score determination is an efficient and more accurate means of extracting Lung-RADS scores than manual review and data entry. NLP-based methods should be considered best practice for extracting structured Lung-RADS scores from free-text radiology reports.

Management and outcomes of patients on preoperative plavix (clopidogrel) undergoing general thoracic surgery.

OBJECTIVES: Plavix (clopidogrel) is a potent antiplatelet agent used to prevent thrombosis in a variety of clinical settings. The perioperative management of thoracic surgery patients who are on clopidogrel at the time of surgery is not well defined. We conducted this review to examine the perioperative management and outcomes of patients undergoing general thoracic surgical procedures. METHODS: From January 2005 to January 2010, 165 patients on clopidogrel underwent 182 operative procedures. Three management strategies were identified: Group I: clopidogrel continued through surgery (n = 17), Group II: clopidogrel discontinued with a bridging agent (n = 44) and Group III clopidogrel discontinued without a bridging agent (n = 121). Propensity score matched cohorts (17 clopidogrel continued; 34 clopidogrel discontinued) were constructed based on age, clopidogrel indication, American Society of Anesthesiology status, and procedure and used to compare the impact of clopidogrel management on postoperative bleeding and cardiovascular morbidity. RESULTS: Unmatched analysis revealed a significantly higher rate of transfusion in the group of patients who continued on clopidogrel throughout the perioperative period, compared with patients who had clopidogrel discontinued. Although there were more cardiovascular events in Groups II and III, there were no significant differences between groups in postoperative mortality, myocardial infarction, stroke, or reoperation for bleeding. In propensity matched patients only the rate of postoperative transfusions was significantly higher in patients continued on clopidogrel compared with patients whose clopidogrel was discontinued (35.3 vs. 2.9%), p < 0.004. CONCLUSIONS: In selected patients, some thoracic surgical procedures can be performed safely on clopidogrel but are associated with higher rates of postoperative transfusion.

Outcomes and Direct Cost of Isolated Nonemergent CABG in Patients With Low Ejection Fraction.

OBJECTIVE: Preoperative left ventricular ejection fraction (LVEF) is one of the main predictors of outcomes in cardiac surgery. We present current era outcomes and associated direct cost in nonemergent isolated coronary artery bypass surgery (CABG) patients with LVEF <20% over the past 6 years and compare it with higher EF subgroups. METHODS: Six-year data from 2016 to 2022 at hospitals sharing Society of Thoracic Surgeons and financial data with Biome Analytics were analyzed based on 3 EF subgroups (EF ≤20%, EF 21% to 35%, and EF >35%). Outcomes and costs were assessed. RESULTS: Overall 30-day mortality of 12,649 patients was 1.9%. The EF ≤20% (n = 248), EF 21% to 35% (n = 1,408), and EF >35 (n = 10,993) cohorts had mortality of 6.9%, 3.7%, and 1.6%, respectively. The EF ≤20% subgroup had higher use of cardiopulmonary bypass, blood products, and mechanical support. In addition, the EF ≤20% subgroup had higher complication rates in almost all measured categories. Also, the EF ≤20% cohort had significantly higher length of stay, intensive care unit (ICU) hours, ICU and hospital readmissions, and lowest discharge to home rate. The strongest factors associated with mortality were postoperative cardiac arrest, renal failure requiring dialysis, extracorporeal membrane oxygenation, sepsis, prolonged ventilation, and gastrointestinal event. The overall median direct cost of care was $37,387.79 ($27,605.18, $51,720.96), with a median direct cost of care in the EF ≤20%, EF 21% to 35%, and EF >35% subgroups of $52,500.17 ($34,103.52, $80,806.79), $44,108.32 ($31,597.58, $63,788.03), and $36,521.80 ($27,168.91, $50,019.31), respectively. CONCLUSIONS: In nonemergent isolated CABG surgery, low EF continues to have higher surgical risks and higher direct cost of care despite advances in cardiovascular care.

Effect of On-Site Cardiac Surgery Program on General Thoracic Surgery Outcomes.

OBJECTIVE: Limited data exist exploring the relationship between multispecialty surgical collaboration and outcomes in general thoracic surgery. To address this, the Nationwide Inpatient Sample (NIS) was analyzed to determine whether the presence of an on-site cardiac surgery program is associated with improved general thoracic surgery outcomes. METHODS: The NIS (1999-2008) was utilized to identify 389,959 patients who had a lobectomy, pneumonectomy, or esophagectomy. Short-term outcomes of patients undergoing these procedures were compared between hospitals with and without an on-site cardiac surgery program. Univariate and multivariate analyses were performed to determine patient and hospital predictors of mortality and morbidity. RESULTS: During the study period, patients undergoing lobectomy (n = 314,130), pneumonectomy (n = 34,860), or esophagectomy (n = 40,969) were identified. Univariate analysis demonstrated lower mortality for lobectomy (P < 0.001) and esophagectomy (P < 0.001) but not pneumonectomy (P = 0.344) in hospitals with a cardiac surgery program. All-cause morbidity was significantly lower for all 3 procedures in hospitals with a cardiac surgery program. However, multivariate analysis demonstrated that a cardiac surgery program was not an independent predictor when adjusted for known confounders, particularly procedure volume and hospital academic teaching status. CONCLUSIONS: The presence of an on-site cardiac surgery program is not in and of itself associated with improved general thoracic surgery outcomes. The presence of a cardiac surgery program is likely a surrogate for other known predictors of improved outcomes such as hospital teaching status and procedure volume.

An unusual case of cardiac tamponade: ruptured subaortic diverticulum.

Cardiac diverticula are rare congenital anomalies found as outpouchings from various chambers of the heart. We present a case of a diverticulum arising from the membranous septum with free rupture into the pericardial space and tamponade.

Modified Blood Patch Used to Treat a High Output Chyle Leak After McKeown Esophagectomy.

Chyle leaks after esophagectomy are associated with significant morbidity and mortality. High-output fistulas are particularly difficult to manage, as the likelihood of spontaneous closure with conservative management is low. Leaks that fail to resolve with conservative management are referred for thoracic duct ligation or embolization. Some patients, however, are not candidates for these procedures or have persistent output despite intervention. We report a case of a post-McKeown esophagectomy patient with a high-output chyle leak despite intraoperative thoracic duct ligation. Treatment was successful with a modified blood patch through a neck drain.

Fibrosing Mediastinitis Requiring Multimodality Treatment to Maintain Pulmonary Vein Patency.

Fibrosing mediastinitis is a rare condition with limited epidemiologic data. We detail a case of a 43-year-old female with no past medical history, who presented with chest pain and dyspnea on exertion. Chest computed tomography revealed a large mediastinal mass that was invading into the anterior chest as well as encasing the pulmonary hilum. Surgical pathology returned as dense hyaline fibrosis tissue with focal histiocytic aggregates and giant cells consistent with fibrosing mediastinitis. Treatment with rituximab and steroids showed a reduction in the size of her mass.

Decrease in Hospital Admissions for Acute Surgical Conditions During the COVID-19 Pandemic.

MINI-ABSTRACT: The nature of emergency room admissions for acute surgical conditions changed during the COVID-19 pandemic with less admissions for potentially life threatening conditions.