Association of decreased estimated glomerular filtration rate with lung cancer risk in the Korean population.

Objectives: Inconsistent results are available regarding the association between low estimated glomerular filtration rate (eGFR) and lung cancer risk. We aimed to explore the risk of lung cancer according to eGFR category in the Korean population. Methods: We included 358,293 adults who underwent health checkups between 2009 and 2010, utilizing data from the National Health Insurance Service-National Sample Cohort. Participants were categorized into 3 groups based on their baseline eGFR, as determined using the Chronic Kidney Disease Epidemiology Collaboration equation: group 1 (eGFR ≥90 mL/min/1.73m2), group 2 (eGFR ≥60 to <90mL/min/1.73m2), and group 3 (eGFR <60 mL/min/1.73m2). Incidences of lung cancer were identified using the corresponding codes from the International Classification of Diseases, 10th Revision. Multivariate Cox proportional hazard models were employed to calculate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer incidence up to 2019. Results: In multivariate analysis, group 2 exhibited a 26.5% higher risk of developing lung cancer than group 1 (HR, 1.265; 95% CI, 1.189 to 1.346). Furthermore, group 3 demonstrated a 72.5% elevated risk of lung cancer relative to group 1 (HR, 1.725; 95% CI, 1.577 to 1.887). Among participants with dipstick proteinuria of 2+ or greater, group 3 faced a significantly higher risk of lung cancer than group 1 (HR, 2.928; 95% CI, 1.375 to 6.237). Conclusion: Low eGFR was significantly associated with increased lung cancer risk within the Korean population. A particularly robust association was observed in individuals with severe proteinuria, emphasizing the need for further investigation.

Decreased estimated glomerular filtration rate increase the risk of pancreatic cancer: A nationwide retrospective cohort study.

BACKGROUND AND AIM: Decreased kidney function is a putative risk factor for various cancers. However, few studies have investigated the association between a decreased estimated glomerular filtration rate (eGFR) and incident pancreatic cancer. We aimed to investigate the risk of incident pancreatic cancer according to eGFR categories. METHODS: In this retrospective cohort study, we included 359 721 adults who underwent health checkups in 2009 or 2010 by using the Korean National Health Insurance Database. The study population was categorized into four groups by eGFR (mL/min/1.73 m2 ) using the Chronic Kidney Disease Epidemiology Collaboration equation: group 1 (eGFR < 45), group 2 (eGFR ≥ 45 to < 60), group 3 (eGFR ≥ 60 to < 90), and group 4 (eGFR ≥ 90). Multivariate Cox proportional hazards models were used to determine the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the incidence of pancreatic cancer until 2019 by comparing the eGFR groups. RESULTS: During the 3 493 589.05 person-years of follow-up, 1702 pancreatic cancer cases were identified. Compared with group 4 (eGFR ≥ 90), HRs and 95% CIs for the incidence of pancreatic cancer were 1.39 (1.24-1.56) for group 3 (eGFR ≥ 60 to < 90), 1.79 (1.47-2.16) for group 2 (eGFR ≥ 45 to < 60), and 2.05 (1.62-2.60) for group 1 (eGFR < 45) in the multivariate adjusted model. CONCLUSIONS: Decreased eGFR was significantly associated with an increased risk of pancreatic cancer in Korean population. Further studies are needed to investigate the relationship between a decreased eGFR and the risk of pancreatic cancer in other ethnic groups.

Predicting severe proximal left anterior descending coronary artery stenosis using proximal left anterior descending coronary artery tortuosity and the angle between the left main and anterior descending coronary arteries: a retrospective cross-sectional study.

Background: Coronary bifurcation angles influence plaque initiation in the coronary artery, and changes in blood flow caused by tortuosity in the coronary arteries can reduce blood pressure distal to the tortuous portion of the coronary artery, leading to myocardial ischemia. We aimed to describe two factors (coronary artery tortuosity and bifurcation angle) as one descriptor for the evaluation of proximal left anterior descending coronary artery (LAD) disease. Methods: We reviewed the medical records of 133 consecutive patients who underwent computed tomography angiography (CTA) for angina symptoms between November 2019 and January 2020. The patients were divided into two groups according to the presence of significant LAD stenosis on CTA (defined as LAD stenosis >50%). The straight length of the vessel was measured using the central luminal line of the flow path, and, calculated using proprietary algorithms in TeraRecon software. We used three-dimensional volume rendering and two-dimensional axial images to measure the left main coronary artery (LM)-LAD angles. Results: In the univariate analysis, there were significant differences in the linear distance between the endpoints of the 20 mm actual curve of the LAD (d20), cosine value for LM-LAD angle (cosθ) <0.8, age, presence of hypertension or diabetes, and number of pack years [hazard ratio (HR): 2.70, 8.04, 1.05, 3.70, 2.82, and 1.04; P=0.029, P<0.001, P=0.020, P=0.024, P=0.021, and P=0.002, respectively]. However, in the multivariate analysis, the cosθ multiplied by d20 (d20*cosθ) <15.5, presence of hypertension and number of pack years (HR: 11.36, 4.54, and 1.04; P<0.001, P=0.019, and P=0.003, respectively) were predictors of significant proximal LAD stenosis. Conclusions: As the tortuosity and LM-LAD angle increased (d20 and cosθ decreased, respectively), the chance of proximal LAD lesions formation increased. d20*cosθ might be useful as a predictor of proximal LAD stenosis.

Conversion to Veno-arteriovenous Extracorporeal Membrane Oxygenation for Differential Hypoxia.

Background: Patients who require initial venoarterial extracorporeal membrane oxygenation (VA ECMO) support may need to undergo veno-arteriovenous ECMO (VAV ECMO) conversion. However, there are no definitive criteria for conversion to VAV ECMO. We report 9 cases of VAV ECMO at Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine. Methods: Of 158 patients who received ECMO support between January 2017 and June 2019, 82 were supported by initial VA ECMO. We retrospectively reviewed the medical records of 9 patients (7 men and 2 women; age, 53.1±19.4 years) who had differential hypoxia and required VAV ECMO support. Percutaneous transaortic catheter venting was used to detect the differential hypoxia. Results: Among the 82 patients who received VA ECMO support, 9 (10.9%) had differential hypoxia and required conversion to VAV ECMO support. The mean time from VA ECMO support to VAV ECMO support and the mean duration of the VAV support were 2.1±2.2 days and 1.9±1.5 days, respectively. The average peak inspiratory pressure before and after VAV ECMO application was 23.89±3.95 cmH2O and 20.67±5.72 cmH2O, respectively, decreasing by an average of 3.2±3.5 cmH2O (p=0.040). The PaO2/FiO2 ratio was kept below 100 mm Hg in survivors and non-survivors for 116±65.4 and 250±124.9 minutes, respectively (p=0.016). Six patients underwent extracorporeal cardiopulmonary resuscitation, of whom 4 survived (67%). The overall survival rate of patients who underwent conversion from VA ECMO to VAV ECMO was approximately 56%. Conclusion: Rapid detection of differential hypoxia is required when VA ECMO is applied, and efficient conversion to VAV ECMO may be critical for patient survival.

Additional Extracorporeal Membrane Oxygenation Pump Without an Oxygenator for Transseptal Left Atrial Decompression: A Case Report.

A 63-year-old man developed chest pain and dyspnea. Venoarterial-venous extracorporeal membrane oxygenation (ECMO) was applied to the patient due to failing heart after percutaneous coronary intervention. We used an additional ECMO pump without an oxygenator for transseptal left atrial (LA) decompression and performed a heart transplant. Transseptal LA decompression with venoarterial ECMO is not always effective for severe left ventricular dysfunction. Here, we report a case of the effective use of additional ECMO pump without an oxygenator for transseptal LA decompression through controlling the blood flow rate of the transseptal LA catheter.

The relationship between visual display terminal usage at work and symptoms related to computer vision syndrome.

Background: Although it is well known that the usage of visual display terminal (VDT) at the workplace causes computer vision syndrome (CVS), previous studies mainly focused on computer use and the health of white-collar workers. In this study, we explored the relationship between the usage of VDT including various devices, and symptoms related to CVS in a large population including pink-collar workers and blue-collar workers. Methods: 21,304 wage workers over the age of 20 years were analyzed from the 6th Korean Working Conditions Survey. To investigate the association between VDT use at work and symptoms related to CVS among wage workers, odds ratios (ORs) and 95% confidence interval (CI) were calculated by multivariate logistic regression models. Results: In the group with the highest VDT usage at work, the OR of headache/eyestrain was 2.16 (95% CI: 1.86-2.52). The OR of suspected CVS patients was significantly increased in the highest group of usage of VDT at work (OR: 1.69; 95% CI, 1.39-2.06). Compare with the reference group, the OR for headache/eyestrain in the highest group of VDT usage was 2.81 (95% CI: 2.13-3.70) in white-collar workers, 1.78 (95% CI: 1.32-2.40) in pink-collar workers, and 1.59 (95% CI: 1.18-2.15) in blue-collar workers. Conclusions: We observed a relationship in which the use of VDT in the workplace increases the risk of headache/eyestrain regardless of occupational classification. Our findings emphasize the importance of paying attention to the health of VDT workers and making plans to improve their working conditions.

Association of metabolites of benzene and toluene with lipid profiles in Korean adults: Korean National Environmental Health Survey (2015-2017).

BACKGROUND: Environmental exposure to benzene and toluene is a suspected risk factor for metabolic disorders among the general adult population. However, the effects of benzene and toluene on blood lipid profiles remain unclear. In this study, we investigated the association between urinary blood lipid profiles and metabolites of benzene and toluene in Korean adults. METHODS: We analyzed the data of 3,423 adults from the Korean National Environmental Health Survey Cycle 3 (2015-2017). We used urinary trans,trans-muconic acid (ttMA) as a biomarker of benzene exposure, and urinary benzylmercapturic acid (BMA) as an indicator of toluene exposure. Multivariate logistic regression analyses were performed to explore the association between blood lipid profiles and urinary metabolites of benzene and toluene. Additionally, we examined the linear relationship and urinary metabolites of benzene and toluene between lipoprotein ratios using multivariate regression analyses. RESULTS: After adjusting for covariates, the fourth quartile (Q4) of ttMA [odds ratio (OR) (95% confidence interval, CI = 1.599 (1.231, 2.077)] and Q3 of BMA [OR (95% CI) = 1.579 (1.129, 2.208)] were associated with an increased risk of hypertriglyceridemia. However, the Q4 of urinary ttMA [OR (95% CI) = 0.654 (0.446, 0.961)] and Q3 of urinary BMA [OR (95% CI) = 0.619 (0.430, 0.889)] decreased the risk of a high level of low-density lipoprotein cholesterol (LDL-C). Higher urinary ttMA levels were positively associated with the ratio of triglycerides to high-density lipoproteins [Q4 compared to Q1: ß = 0.11, 95% CI: (0.02, 0.20)]. Higher urinary metabolite levels were negatively associated with the ratio of low-density lipoprotein to high-density lipoprotein [Q4 of ttMA compared to reference: ß = -0.06, 95% CI: (-0.11, -0.01); Q4 of BMA compared to reference: ß = -0.13, 95% CI: (-0.19, -0.08)]. CONCLUSION: Benzene and toluene metabolites were significantly and positively associated with hypertriglyceridemia. However, urinary ttMA and BMA levels were negatively associated with high LDL-C levels. These findings suggest that environmental exposure to benzene and toluene disrupts lipid metabolism in humans.

Fulminant Giant Cell Myocarditis following Heterologous Vaccination of ChAdOx1 nCoV-19 and Pfizer-BioNTech COVID-19.

A 48-year-old female patient underwent a heart transplantation for acute fulminant myocarditis, following heterologous vaccination with the ChAdOx1 nCoV-19 and Pfizer-BioNTech COVID-19. She had no history of severe acute respiratory syndrome coronavirus-2 infection. She did not exhibit clinical signs or have laboratory findings of concomitant infection before or after vaccination. Heart transplantation was performed because her heart failed to recover with venoarterial extracorporeal oxygenation support. Organ autopsy revealed giant cell myocarditis, possibly related to the vaccines. Clinicians may have to consider the possibility of the development of giant cell myocarditis, especially in patients with rapidly deteriorating cardiac function and myocarditis symptoms after COVID-19 vaccination.

The serial connection of two extracorporeal membrane oxygenators for patient with refractory hypoxemia.

A 34-year-old man developed severe hypoxemia and hypercapnia due to acute respiratory distress during ventilator care after surgery with acute intracranial hemorrhage. Severe hypoxemia had not been corrected even with maximum extracorporeal membrane oxygenation (ECMO) flow and full ventilator settings. We applied a novel technique for the serial connection of two veno-venous ECMO circuits for optimal oxygen delivery and CO2 removal and could wean VV ECMO. The use of serial connection of two VV ECMO circuits may be considered worthwhile when severe hypoxemia or hypercapnia are not improved and the use of protective ventilators is not permitted.

Left Ventricular Decompression by Transaortic Catheter Venting in Extracorporeal Membrane Oxygenation.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been widely applied to patients with cardiogenic shock. Left ventricle (LV) decompression is important when LV distension develops with pulmonary edema. The purpose of this study was to present the results of transaortic catheter venting (TACV) performed during VA-ECMO. We retrospectively reviewed the medical records of 18 patients who underwent both VA-ECMO and TACV between January 2017 and December 2019. Venoarterial extracorporeal membrane oxygenation was applied uneventfully. Lactate level and norepinephrine requirement for patients of weaning success were lower than those of patients of weaning failure after the application of TACV (p = 0.032 and p = 0.015, respectively). The successful weaning rate of ECMO was 77.8% (15/18) and survival rate was 50% (9/18). Transaortic catheter venting may be an easy, safe, and effective technique for LV decompression in patients with VA-ECMO for cardiogenic shock. Also, this technique may be helpful as an alternative or bridge method.

Veno-Arterial-Venous Extracorporeal Membrane Oxygenation in a Critically Ill Patient with Coronavirus Disease 2019.

Patients with cardiopulmonary failure may not be fully supported with typical configurations of extracorporeal membrane oxygenation (ECMO), either veno-arterial (VA) or veno-venous (VV). Veno-arterial-venous (VAV)-ECMO is a technique used to support the cardiopulmonary systems during periods of inadequate gas exchange and perfusion. In the severe case of coronavirus disease 2019 (COVID-19), which simultaneously affects the heart and lung, VAV-ECMO may improve a patient's recovery potential. We report the case of a 72-year-old woman with acute respiratory distress syndrome and circulatory failure following COVID-19, who was treated with VAV-ECMO.

Malignant pulmonary embolism associated with renal sarcoma: A case report.

RATIONALE: The preoperative diagnosis of massive pulmonary tumor embolism associated with renal neoplasms is relatively rare. In most cases, pulmonary tumor embolism is detected intraoperatively during renal tumor resection. Moreover, primary renal sarcoma is rare, and primary renal sarcoma complicated by pulmonary tumor embolism is extremely rare; accordingly, there is no optimal treatment for such cases. Herein, we report a case of renal sarcoma associated with pulmonary tumor embolism. PATIENT CONCERNS: A 39-year-old man was admitted to the emergency room owing to the sudden onset of dyspnea and palpitation. DIAGNOSIS: Contrast-enhanced computed tomography (CT) revealed a large mass in the right kidney involving the infrahepatic inferior vena cava, with massive pulmonary emboli in both the pulmonary arteries. INTERVENTIONS: Emergency pulmonary embolectomy with radical nephrectomy was performed. OUTCOMES: The patient experienced apparent remission of dyspnea, and resolution of right ventricle dysfunction. However, although remnant emboli were detected in the segmental arteries on postoperative CT, complete resolution of pulmonary embolism was observed after adjuvant chemotherapy. LESSONS: Thus, concomitant cytoreductive nephrectomy with pulmonary embolectomy along with chemotherapy may be effective for patients with renal sarcoma with pulmonary tumor embolism.

Perforation of inferior vena cava and duodenum by strut of inferior vena cava filter: A case report.

INTRODUCTION: An Inferior vena cava (IVC) filter is an intravascular filter that is implanted into the IVC to prevent pulmonary embolism in medical, surgical, and trauma patients. The insertion of an IVC filter is a relatively safe procedure, but rarely may be associated with symptomatic perforation of the IVC wall, particularly in the long term. PATIENT CONCERNS AND DIAGNOSIS: A 74-year-old-woman with a medical history of IVC filter insertion visited the emergency department complaining of abdominal pain. A computed tomography scan showed perforation of the IVC wall and penetration into the duodenum by one of the filter's struts. INTERVENTIONS: We performed a laparotomy to remove the IVC filter. OUTCOMES: Postoperatively, the patient was admitted to the general ward. On hospital day 12, she was discharged without any complications. We followed her up and computed tomography did not show any abnormal findings six months after discharge. LESSONS: There is currently no evidence testifying to the benefits of IVC filter removal. Detailed, evidence-based guidelines on the indications, timing and procedure for IVC filter removal are needed. Documenting cases of long-term complications of IVC filter s such as in this patient serve to accelerate the publication of updated guidelines and are aimed at improving outcomes of similar cases in the future.

Management of acute type A aortic dissection with acute lower extremities malperfusion.

BACKGROUND: Acute type A aortic dissection complicated by malperfusion is a life - threatening emergency. The optimal management strategy for malperfusion remains controversial. CASE PRESENTATION: A 46-year-old man presented to another institution with acute type A aortic dissection with abdominal aorta occlusion. Motor and sensory grade of both lower extremities were zero. Immediate antegrade distal perfusion of both lower extremities was achieved, and total arch replacement with left axillo-bifemoral bypass was performed. At the time of discharge, motor and sensory grades of both lower extremities were 2 and 3, respectively. CONCLUSION: This case demonstrates many of the techniques in the management of acute type A aortic dissection with abdominal aorta occlusion. In this case, direct antegrade perfusion of both lower extremities and axillo-bifemoral bypass may be helpful for patients presenting with severe malperfusion of both lower extremities with acute type A aortic dissection.

Sternal reconstruction with bone cement block using the rigid plate fixation technique.

Chest computed tomography demonstrated a suspected primary tumor in the upper sternal body of a 48-year-old woman who presented with sternal pain. After being diagnosed with chondrosarcoma, she underwent sternal resection. Subsequent chest wall reconstruction was performed after careful planning using a bone cement block made of polypropylene mesh and polymethylmethacrylate. The block was fixed to the manubrium and ribs using the SternaLock System. She was discharged following an uneventful postoperative recovery, and is currently undergoing follow-up.

Heparin-free veno-venous ECMO applied to a patient with severe lung contusion and hypovolemic shock due to trauma.

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) plays a crucial role when the lung is extensively damaged and when conventional management has failed. ECMO provides adequate tissue oxygenation and an opportunity for lung recovery. However, ECMO remains contraindicated in patients with a risk of bleeding because of systemic anticoagulation during the treatment. A 26-yearold female experienced polytrauma due to a traffic accident 1 h before arrival. Simple chest radiography and chest computed tomography showed a large right hemopneumothorax with atelectasis of the right lung and severe contusion of the left lung. Heparin-free VV-ECMO was applied peripherally via both femoral veins. Under the ECMO support, right lower lobectomy was successfully performed. Although contraindicated in polytraumatic patients with hemorrhagic shock, surgical repair with the application of ECMO may be feasible if bleeding is well controlled. The patient was discharged without significant complications.

Diquafosol Sodium Inhibits Apoptosis and Inflammation of Corneal Epithelial Cells Via Activation of Erk1/2 and RSK: In Vitro and In Vivo Dry Eye Model.

Purpose: To evaluate the effect of diquafosol on corneal epithelium in a dry eye model using Transwell culture and a scopolamine-induced dry eye rat model. Methods: Desiccation stress induced in an in vitro dry eye model using human corneal epithelial cells was used, and the cells were incubated with or without diquafosol media diluted at 1:100. Reactive oxygen species (ROS) generation was measured using 2',7'-dichlorofluorescein diacetate (DCFH-DA). Apoptosis was analyzed, and levels of phosphorylated Erk1/2, phosphorylated p90RSK, phosphorylated Akt, IκB-α, and NF-κB-p65 were determined. Levels of IL-1ß, TNF-α, IL-6, IL-8, and GM-CSF were quantified. To investigate the in vivo effects of diquafosol, we induced dry eye in Wistar rats using scopolamine hydrobromide. The rats were divided into three groups: control, dry eye, and dry eye diquafosol; topical DIQUAS was applied four times daily for 28 days. We used immunohistochemistry to detect the levels of phosphorylated Erk1/2, phosphorylated p90RSK, and IL-1ß, and used the TUNEL assay in corneal tissue. Results: The distribution of highly fluorescent dichlorofluorescein and the proportion of annexin V- and PI-positive cells decreased in the diquafosol medium. Diquafosol increased the levels of phospho-Erk1/2, phospho-90RSK, phospho-Akt, and IκB-α, whereas it significantly decreased the levels of NF-κB-p65, IL-1ß, and TNF-α. In vivo, apoptosis was enhanced in dry eye group. This response was markedly reduced and the level of phosphorylated p90RSK and phosphorylated ERK1/2 were upregulated and IL-1ß was downregulated by DIQUAS. Conclusions: Diquafosol treatment reduced intracellular ROS levels, apoptosis, and inflammation, all of which were increased in the dry eye model through desiccation.

Clinical usefulness of the angle between left main coronary artery and left anterior descending coronary artery for the evaluation of obstructive coronary artery disease.

BACKGROUND: A wider angle between the left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCX) has been suggested to induce plaque formation in the arterial system via changes in shear stress. However, the relationship between the left main coronary artery (LM)-LAD angle and LAD stenosis has not been investigated. Therefore, we aimed to evaluate the associations between the LM-LAD and LAD-LCX angles and LAD stenosis. METHODS: Coronary computed tomography angiographies (CTAs) of 201 patients with suspected coronary artery disease were analyzed. Angle measurements were performed twice by experts using CTA images, and the values were averaged. The patients were divided into two groups, based on the presence of significant LAD stenosis (luminal diameter narrowing ≥50%) on CTA. RESULTS: The mean LM-LAD and LAD-LCX angles were 37.46° and 63.04°, respectively. The LM-LAD and LAD-LCX angles of the group with significant LAD stenosis were significantly wider than that of the group with nonsignificant LAD stenosis (P<0.001; P = 0.020, respectively). In a multivariate analysis, an LAD-LCX angle greater than 60° showed a trend toward predicting significant LAD stenosis (HR, 3.14; 95% CI: 0.96-1026; P = 0.058). In contrast, an LM-LAD angle greater than 40° was a significant predictor of significant LAD stenosis (HR, 12.2; 95% CI: 2.60-56.52; P = 0.001). CONCLUSIONS: The results of the present study may suggest that a wider LM-LAD angle could be used to identify patients at higher risk for coronary artery disease (CAD). Thus, close follow-up and preventive management of other risk factors may be needed in such cases.

Invasive thymoma with multiple ring calcifications and osseous metaplasia: A case report.

An 8.0 × 7.0 × 3.0 cm calcified anterior mediastinal mass was found in a 57-year-old man during a regular health checkup. The tumor had invaded the pericardium and phrenic nerve. The Masaoka-Koga classification was stage III. Multiple ring calcifications were present in the gross feature, and osseous metaplasia was observed in the histologic examination. World Health Organization histologic classification of the tumor was type B2. The patient is currently undergoing chemotherapy and radiation therapy to prevent tumor recurrence. To our knowledge, this is the first case of multiple ring calcifications and osseous metaplasia in invasive thymoma.

A case report of pseudoaneurysm of left sinus of Valsalva invaded into the left ventricle with severe aortic regurgitation.

BACKGROUND: The pseudoaneurysms of sinus of Valsalva is an uncommon and serious complication of an infection, trauma, or after cardiac surgery or procedure. Pseudoaneurysms of sinus of Valsalva from left is rare. We describe a case of pseudoaneurysm of the left coronary sinus of Valsalva invaded into the left ventricle (LV) diagnosed by transthoracic echocardiography (TTE), transesophageal ecoccardiography (TEE), and multiple detector computed tomography (MDCT). CASE PRESENTATION: A 44-year-old male patient had New York Heart Association (NYHA) class II / III dyspnea during 4 months. He underwent surgery including aortic valve replacement using mechanical prosthesis, and he was discharged well without significant complications on follow - up TTE and chest computed tomography (CT) post-operative 7 days. CONCLUSIONS: We report this rare case in which a ruptured pseudoaneurysm of sinus of Valsalva into LV with severe AR due to perforation of LCC was successfully-treated.