Impact of neutrophil-to-lymphocyte ratio in patients with EGFR-mutant NSCLC treated with tyrosine kinase inhibitors.

Background Exon 19 deletion and L858R point mutation in exon 21 of the epidermal growth factor receptor (EGFR) are the most commonly encountered mutations in patients with non-small cell lung cancer (NSCLC) and predict better clinical outcomes following treatment with EGFR-tyrosine kinase inhibitors (TKIs). The inflammatory indicator neutrophil-to-lymphocyte ratio (NLR) in peripheral blood serves as a predictive factor for NSCLC patients treated with chemotherapy. Here, we aimed to evaluate the correlation between NLR and clinical efficacy of EGFR-TKIs in NSCLC patients harboring EGFR mutations. Methods We retrospectively collected information of 205 patients with advanced NSCLC harboring exon 19 deletion or L858R point mutation and receiving gefitinib or erlotinib. The clinical outcomes in the NSCLC patients were evaluated based on NLR level before EGFR-TKI therapy. Results The optimal cut-off value for NLR was 3.55. The response rates in the low-NLR and high-NLR groups were 69.2% and 51.5%, respectively. The median progression-free survival (PFS) in the low-NLR and high-NLR groups were 15.7 months and 6.7 months, respectively. The median overall survival (OS) in the low-NLR and high-NLR groups were 37.6 months and 19.2 months, respectively. The multivariate analysis identified performance status (PS), NLR, stage, and smoking status as independent predictors of PFS. Moreover, the PS and NLR were identified as independent predictors of OS. Conclusions NLR was a significant predictor of clinical efficacy and OS in NSCLC patients harboring EGFR mutations treated with gefitinib or erlotinib.

Preoperative Implementation of Transverse Thoracic Muscle Plane Block and Rectus Sheath Block Combination for Pediatric Cardiac Surgery.

Systemic intravenous administration of opioids is the main treatment strategy for intraoperative and postoperative pain management in patients undergoing cardiac surgery with sternotomy. However, using lower doses of opioids may achieve the well-established benefits of the fast-track approach, with minimal opioid-related side effects. Postoperative pain is coupled with a long stay in the intensive care unit. Although neuraxial anesthesia has some benefits, its use remains controversial due to the potential development of epidural hematoma after anticoagulation for cardiopulmonary bypass and coagulopathy after cardiac surgery. Therefore, there is a need for other effective postoperative analgesic strategies, such as peripheral nerve blocks other than neuraxial anesthesia, for cardiac surgery with sternotomy. The effects of real-time ultrasound-guided transverse thoracic muscle plane (TTP) block on postoperative pain after sternotomy have been reported; however, the pain and discomfort in the epigastric area caused by chest drainage tubes placed through the rectus abdominis muscle also are major postoperative problems after cardiac surgery. Herein, the authors report on a preoperative combination of TTP block and rectus sheath block (RSB) for postoperative pain management after cardiac surgery with sternotomy that addresses pain in both the chest and epigastric areas. Considering previous studies, it is presumed that preemptive analgesic effects can be expected via a combination of the TTP block and RSB, and indeed, the preemptive effect was observed in the present study's patients. In this article, the procedure and tips for combining the TTP block and RSB are introduced.

Efficacy of Platinum-Based Chemotherapy for Relapsed Small-Cell Lung Cancer after Amrubicin Monotherapy in Elderly Patients and Patients with Poor Performance Status.

BACKGROUND: Previous studies have shown amrubicin to be an effective first- or second-line treatment option for small-cell lung cancer (SCLC). However, there have been few studies reporting the efficacy of platinum-based chemotherapy after amrubicin therapy. We aimed to evaluate the efficacy of platinum-based chemotherapy as second-line treatment for elderly patients and those with SCLC with poor performance status (PS) previously treated with amrubicin monotherapy. METHODS: The records of SCLC patients who received platinum-based chemotherapy as a second-line chemotherapy after first-line treatment with amrubicin monotherapy were retrospectively reviewed and the treatment outcomes were evaluated. RESULTS: A total of 48 patients were enrolled in this study. Forty-one patients (85%) received carboplatin plus etoposide. The overall response rate was 39.6%. The median progression-free survival and overall survival were 3.7 and 7.6 months, respectively. The efficacy of the platinum-based regimen did not differ with the type of relapse after amrubicin monotherapy. The most common adverse events were hematological toxicities, including grade 3 or 4 neutropenia (38%), leukopenia (33%), and thrombocytopenia (10%). CONCLUSIONS: Platinum-based chemotherapy is potentially a valid treatment option for elderly patients or those with extensive-stage SCLC with poor PS as second-line chemotherapy, who progressed after first-line treatment with amrubicin monotherapy.

Pulmonary haemorrhage due to an aortopulmonary collateral artery after arterial switch.

A neonate with transposition of the great arteries and intact ventricular septum presented without pulmonary over-circulation, and subsequently developed pulmonary haemorrhage after corrective surgery. Postoperative CT revealed an aortopulmonary collateral artery arising from the descending aorta, and we performed successful embolisation on postoperative day 9. Aggressive imaging modalities such as angiography and/or CT imaging with contrast can detect unexpected extra-pulmonary blood supply and guide further management.

Surgical outcomes of the systemic-to-pulmonary artery shunt: risk factors of post-operative acute events and effectiveness of regulation of pulmonary blood flow with metal clips.

OBJECTIVES: The aim of this study was to analyze the risk factors for acute events after systemic-to-pulmonary shunt (SPS) and to investigate the effectiveness of pulmonary blood flow regulation with a metal clip. METHODS: The case histories of 116 patients (78 biventricular [BV] and 38 single ventricle [SV] physiology) who underwent SPS between 2010 and 2021 were retrospectively reviewed. Our strategy was to delay SPS until 1 month of age; pulmonary blood flow (PBF) regulation by partial clipping of the graft, if needed. Cases of aortic cross-clamping were excluded from this study. RESULTS: CPB was used in 49 (42%) patients: the median age at SPS was 1 month (2 days to 16 years), and the sternotomy approach in 65. Discharge survival was 98.3% (114/116); hospital death occurred in 1.7% due to coronary ischemia. Inter-stage mortality occurred in 1.7% (shunt thrombosis, 1; pneumonia, 1). Pre-discharge acute events occurred in 7 patients (6.0%): thrombosis 3, pulmonary over-circulation 2, and coronary ischemia 2. Multiple logistic regression analysis revealed that pulmonary atresia with intact ventricular septum (PA/IVS) (p = 0.0253) was an independent risk factor for acute events. Partial clipping of the graft was performed in 24 patients (pulmonary atresia 15) and clip removal was performed by catheter intervention in 9 patients; no coronary ischemic events and graft injury occurred in these patients. CONCLUSION: Surgical outcomes after SPS were acceptable and metal clip regulation of pulmonary blood flow appears to be safe and effective. PA/IVS was still a significant risk factor for acute events.

Divergent synthesis of trans-fused polycyclic ethers by a convergent oxiranyl anion strategy.

Octacyclic polyethers that correspond to the CDEFGHIJ-ring system of yessotoxin as well as G- and/or I-ring-modified analogues were synthesized in a divergent manner, starting from a common intermediate, using an [X + 2 + Y]-type convergent method. Reaction of a triflate with the oxiranyl anion generated from an epoxy sulfone, followed by ring expansion, allowed for the incorporation of medium-sized ring ethers into the key intermediate. Subsequent acetal formation and reductive etherification afforded various octacycles containing seven- and eight-membered ether rings.

Contemporary surgical management of complete atrioventricular septal defect with tetralogy of Fallot in Japan.

OBJECTIVES: Complete atrioventricular septal defect with tetralogy of Fallot is a rare and complex heart disease. This study aimed to describe contemporary management approaches for this heart disease and the outcomes. METHODS: Data were obtained from 46 domestic institutions in the Japan Cardiovascular Database (2011-2018). Patients with a fundamental diagnosis of complete atrioventricular septal defect with tetralogy of Fallot, without other complex heart diseases, were included. The primary outcome was operative mortality (30-day or in-hospital mortality). RESULTS: A total of 119 patients underwent initial surgery for a complete atrioventricular septal defect with tetralogy of Fallot during this study period. Primary repair was performed in 40 (34%) patients (primary repair group), and palliative procedure was performed in 79 (66%) patients as part of a planned staged approach (staged group). Forty institutions (87%) experienced at least one case of staged repair. No institution experienced more than or equal to two cases/year on average during the study period. Overall, 11 operative mortalities occurred (9.2%). Operative mortality rates in the primary and staged groups were comparable (p = 0.5). Preoperative catecholamine use, repeat palliative surgeries, and emergency admission were significant risk factors for operative mortality in multivariate analysis (odds ratio, 95% confidence interval: 8.58, [0-0.11]; 12.65, [1.28-125.15]; 8.64, [1.87-39.32, respectively]). CONCLUSIONS: Staged approach for complete atrioventricular septal defect with tetralogy of Fallot was the preferred option. The outcomes of this complex disease were favorable for patients in centers with low cases of complete atrioventricular septal defect with tetralogy of Fallot.

Gravity assistance enables liver stiffness measurements to detect liver fibrosis under congestive circumstances.

BACKGROUND: As survival has been prolonged owing to surgical and medical improvements, liver failure has become a prognostic determinant in patients with congestive heart diseases. Congestive hepatopathy, an abnormal state of the liver as a result of congestion, insidiously proceed toward end-stage liver disease without effective biomarkers evaluating pathological progression. Regular measurements of shear wave elastography cannot qualify liver fibrosis, which is a prognosticator in any type of chronic liver disease, in cases of congestion because congestion makes the liver stiff without fibrosis. We hypothesized that the effects of congestion and fibrosis on liver stiffness can be dissociated by inducing architectural deformation of the liver to expose structural rigidity. AIM: To establish a strategy measuring liver stiffness as a reflection of architectural rigidity under congestion. METHODS: Two-dimensional shear wave elastography (2dSWE) was measured in the supine (Sp) and left decubitus (Ld) positions in 298 consecutive cases as they were subjected to an ultrasound study for various liver diseases. Regions of interest were placed at twelve sites, and the median and robust coefficient of variation were calculated. Numerical data were compared using the Mann-Whitney U or Kruskal-Wallis test followed by Dunn's post-hoc multiple comparisons. The inferior vena cava (IVC) diameters at different body positions were compared using the Wilcoxon matched pairs signed rank test. The number of cases with cardiothoracic ratios greater than or not greater than 50% was compared using Fisher's exact test. A correlation of 2dSWE between different body positions was evaluated by calculating Spearman correlation coefficients. RESULTS: The IVC diameter was significantly reduced in Ld in subjects with higher 2dSWE values in Ld (LdSWE) than in Sp (SpSWE) (P = 0.007, (average ± SD) 13.9 ± 3.6 vs 13.1 ± 3.4 mm) but not in those with lower LdSWE values (P = 0.32, 13.3 ± 3.5 vs 13.0 ± 3.5 mm). In 81 subjects, SpSWE was increased or decreased in Ld beyond the magnitude of robust coefficient of variation, which suggests that body postural changes induced an alteration of liver stiffness significantly larger than the technical dispersion. Among these subjects, all 37 with normal SpSWE had a higher LdSWE than SpSWE (Normal-to-Hard, SpSWE - LdSWE (∆2dSWE): (minimum-maximum) -0.74 - -0.08 m/sec), whereas in 44 residual subjects with abnormal SpSWE, LdSWE was higher in 27 subjects (Hard-to-Hard, -0.74 - -0.05 m/sec) and lower in 17 subjects (Hard-to-Soft, 0.04 - 0.52 m/sec) than SpSWE. SpSWE was significantly correlated with ∆2dSWE only in Hard-to-Soft (P < 0.0001). ∆2dSWE was larger in each lobe than in the entire liver. When Hard-to-Hard and Hard-to-Soft values were examined for each lobe, fibrosis-4 or platelet counts were significantly higher or lower only for Hard-to-Soft vs Normal-to-Hard cases. CONCLUSION: Gravity alters the hepatic architecture during body postural changes, causing outflow blockage in hepatic veins. A rigid liver is resistant to structural deformation. Stiff-liver softening in the Ld position suggests a fibrous liver.

A case of rectal obstruction caused by bilateral internal iliac artery aneurysms.

In this article, we report a rare case of rectal obstruction caused by bilateral internal iliac artery aneurysms that required open surgical repair. A 73-year-old man was admitted to our hospital complaining of abdominal pain and persistent constipation for >1 month. Computed tomography demonstrated bilateral internal iliac artery aneurysms, 5.0 and 7.0 cm each in diameter, which occupied the intrapelvic space. An urgent surgery was performed to reduce the volume of the aneurysms and release the obstructed rectum. The postoperative course was uneventful, in which he had good evacuation. Aneurysms in the iliac region can be a good indication for the use of newly developed endovascular devices; however, open surgery should be considered without delay to avoid ileus or subileus symptoms when the aneurysms cause space-occupying complications.

[Efficacy of vacuum-assisted closure therapy for various non-healing wounds after cardiovascular and thoracic surgery].

Vacuum-assisted closure (VAC) therapy is an efficacious modality for treating chronic and difficult wounds. We present 3 cases that responded well to VAC therapy after cardiovascular and thoracic surgery: 1 methicillin-resistant Staphylococcus aureus (MRSA) wound infection after Stony's incision, 1 inguinal lymphorrhea, and 1 empyema after a traffic accident The duration of VAC therapy was 9, 18, and 90 days, respectively, and all 3 wounds healed completely. Familiar equipment and supplies available on the hospital ward were used, and patients were able to leave their beds. In this report, the efficacy of VAC therapy, the problems encountered, and the steps that could be taken to address them are discussed.

[Pacemaker infection on the neonate with congenital heart disease].

A 6-day-old girl underwent pacemaker implantation for complete atrioventricular block through a subxiphoid incision. Epicardial leads were sutured on the right ventricle, and the pulse generator was buried in a subcutaneous pocket on the abdomen. After 3 days, the pacemaker site became infected. The whole pacing system was extracted immediately and replaced by temporary pacing leads. After the infection was controlled, a new pacemaker was implanted through a left thoracotomy during which an original Blalock-Taussig shunt was established. The new pulse generator was buried in a subcutaneous pocket in the left precordial area. The patient's postoperative course was uneventful, and there have been no signs of lead problems or re-infection. Using temporary pacing leads as a bridge to implant a new system and choosing a precordial subcutaneous pocket for the implantation site following suturing of the leads on the left ventricle through a left thoracotomy were useful in this case.

Adverse impact of univentricular pacing for the patient with functional single ventricle: successful conversion to cardiac resynchronization therapy.

BACKGROUND: In a Fontan candidate, univentricular pacing may cause delay in interventricular conduction, which induces asynchronous contraction. Cardiac resynchronization therapy is expected to be an effective mode of therapy in such a case. CASE PRESENTATION: A 7-month-old girl, diagnosed with dextrocardia, congenitally corrected transposition of the great artery [situs solitus, L-loop, and L-transposition], ventricular septal defect, infundibular and pulmonary valvular stenosis, and straddling of the tricuspid valve, was considered as a candidate for the Fontan procedure. She had undergone Blalock-Taussig shunt, and epicardial univentricular pacemaker implantation for persistent complete atrioventricular block. She underwent a bidirectional cavopulmonary shunt concomitant with ventricular lead translocation from the morphological left ventricle to the morphological right ventricle. After discharge, ventricular dyssynchrony was noted and cardiac failure persisted. She was converted to cardiac resynchronization therapy (CRT) at 13 months of age. Two-dimensional speckle tracking imaging was used by cardiologists to determine the most suitable pacing site. CRT rapidly corrected the heart failure; thus, she underwent the Fontan procedure after 1.5 years. Five years have passed since the cardiac resynchronization therapy; her interventricular synchrony is maintained well and the level of brain natriuretic peptide remains within normal range. CONCLUSION: We describe the successful conversion from single ventricular pacing to CRT, in a case of congenitally corrected transposition of the great artery indicated for the Fontan procedure. The long-term prognosis of cardiac resynchronization therapy is undetermined in the pediatric population; therefore, further follow-up is required.

A Case Report of Reconstruction of the Left Superior Vena Cava Using the Right Superior Vena Cava Autograft at Bilateral Bidirectional Superior Cavopulmonary Anastomosis.

The choice of graft material for reconstruction of the vena cava in pediatric patients remains controversial. We successfully treated an eight-month-old female patient with single ventricle physiology and long segment obstruction of the left superior vena cava using the right superior vena cava autograft at the time of bilateral bidirectional superior cavopulmonary anastomosis. Postoperative computed tomography confirmed the patency of the reconstruction.

Swing-back and trap-door technique repair for interrupted aortic arch with right-sided descending aorta.

A right-sided descending aorta with a left aortic arch is a rare congenital anomaly in which the aortic arch crosses the midline from the left side of the trachea coursing to the descending aorta in the right thoracic cavity. The surgical repair of an interrupted aortic arch with a right-sided descending aorta carries great risks of bronchial and oesophageal obstruction. Herein, we describe a case of successful surgical repair of an interrupted aortic arch with a right-sided descending aorta using the swing-back and trap-door techniques.

Superior Vena Cava Flap to Reroute Partial Anomalous Pulmonary Venous Connection.

A 46-year-old man who had undergone atrial septal defect closure during childhood was referred for surgery for residual partial anomalous pulmonary venous connection. The anomalous pulmonary veins were connected to the higher (cephalad) segment of the superior vena cava. As the usual caval division technique was not applicable, we chose to utilize the anterior wall of the superior vena cava as a flap for anomalous pulmonary vein rerouting. Bovine pericardium was used to reconstruct the systemic venous pathway. Systemic or pulmonary venous stenosis was not detected. The patient was discharged with a sinus rhythm.

A novel parameter for pulmonary blood flow during palliative procedures: velocity time integral of the pulmonary vein†.

OBJECTIVES: The main goal of palliative procedures for congenital heart defects is adequate pulmonary blood flow (PBF), but precise intraoperative PBF evaluation is sometimes difficult. The purpose of this preliminary study was to investigate the usefulness of velocity time integral of the pulmonary vein (PV-VTI) measured by transoesophageal echocardiography (TOE) at the time of palliative procedure as a parameter for PBF. METHODS: Case histories of 63 patients who underwent palliative procedures (bilateral pulmonary artery banding in 18 patients, main pulmonary artery banding in 22 patients and systemic-to-pulmonary artery shunt in 23 patients) and whose intraoperative PV-VTI was measured by TOE from 2011 to 2017 at our centre were retrospectively reviewed. Low-body-weight infants, cases in which cardiopulmonary bypass was used and cases that were anatomically difficult to measure were excluded. RESULTS: PV-VTIs measured at 4 orifices of the pulmonary veins were all significantly decreased in both the bilateral pulmonary artery banding and main pulmonary artery banding groups and increased in the systemic-to-pulmonary artery shunt group immediately after the procedure. There were significant correlations between the velocity time integrals of both right and left pulmonary veins and arterial oxygen saturation (r = 0.564 and 0.703). Nine patients (6 bilateral pulmonary artery banding and 3 systemic-to-pulmonary artery shunt) required unplanned early reoperation due to inadequate PBF; their PV-VTIs were significantly different from those of patients not requiring reoperation. No major complications related to TOE occurred postoperatively. CONCLUSIONS: The PV-VTI measured by TOE during palliative procedures reflected the change of PBF and could help identify patients at higher risk of early reoperation due to inadequate PBF. This parameter may be a useful additional tool for evaluating intraoperative PBF.

Comparison of carboplatin plus etoposide with amrubicin monotherapy for extensive-disease small cell lung cancer in the elderly and patients with poor performance status.

BACKGROUND: Carboplatin plus etoposide (CE) is a standard treatment for elderly patients with extensive-disease small cell lung cancer (ED-SCLC). However, amrubicin monotherapy (AMR) may be a feasible alternative. We compared the efficacies and safety profiles of CE and AMR for ED-SCLC in elderly patients and chemotherapy-naive patients with poor performance status (PS). METHODS: The records of SCLC patients who received CE or AMR as first-line chemotherapy were retrospectively reviewed and their treatment outcomes evaluated. RESULTS: Eighty-four patients (median age 72 years; 42 each received CR and AMR) were analyzed; 34 patients had a PS score of 2. There were no significant differences in patient characteristics between the treatment groups. The median progression-free survival rates of patients in the CE and AMR groups were 5.8 and 4.8 months, respectively (P = 0.04); overall survival was 14.0 and 8.5 months, respectively (P = 0.089). Twenty-three CE group patients received AMR as second-line chemotherapy; their median overall survival from first-line chemotherapy was 18.5 months. Grade 3 or higher neutropenia occurred more frequently in patients treated with AMR (64% vs. 40%; P = 0.02), as did febrile neutropenia (14% vs. 7%). CONCLUSIONS: CE remains a suitable first-line treatment for ED-SCLC in elderly patients or those with poor PS in comparison with AMR.

Predictors of ventricular tachyarrhythmia occurring late after intracardiac repair of tetralogy of Fallot: combination of QRS duration change rate and tricuspid regurgitation pressure gradient.

BACKGROUND: To determine potential predictors of ventricular tachyarrhythmia and sudden cardiac death (SCD) occurring late after repair of tetralogy of Fallot (TOF). METHODS: Since 1964, 415 patients had undergone total repair for TOF at Niigata University Hospital. Of these, 89 patients who were followed for more than 10 years at our institute were retrospectively reviewed. RESULTS: The mean follow-up period was 24.3 years. During the study period, one patient died of cerebral bleeding, and two patients had SCD. The overall survival rates at 20, 30, and 40 years were 100%, 94.6%, and 94.6%, respectively. Eight (9.0%) patients required re-intervention during the late period associated with right ventricular outflow (n=4), tricuspid valve (n=3), aortic valve (n=2), and others (n=2). Ten (11.2%) patients had a history of ventricular tachycardia (VT) or ventricular fibrillation (VF), and six underwent implantation of an implantable cardiac defibrillator. Multivariate analysis selected the change rate of QRS duration [ms/year; odds ratio (OR), 2.44; 95% confidence interval (CI): 1.28-4.65; P=0.007] and the pressure gradient at tricuspid valve regurgitation on echocardiography (OR, 1.12; 95% CI: 1.02-1.22; P=0.017) as risk factors for VT/VF or SCD. Trans-annular patch (TAP) repair was not an independent risk factor for ventricular arrhythmia. CONCLUSIONS: The combination of rapid change rate of QRS duration and higher-pressure gradient at tricuspid regurgitation were risk factors for ventricular tachyarrhythmia late after TOF repair. Adequate surgical or catheter intervention for pressure and volume load in the right ventricle might decrease the prevalence of VT/VF and SCD.

Pulmonary root translocation for borderline complex coarctation of aorta and multiple ventricular septal defects.

We describe a case of complex left ventricular outflow tract obstruction, multiple muscular ventricular septal defects, aortic coarctation and a hypoplastic aortic arch, where staged biventricular repair was performed successfully using pulmonary root translocation.

Pneumocephalus and subcutaneous scalp emphysema in a neonate on a low-flow nasal cannula.

A 15-day-old boy after intracardiac repair was discharged from the intensive care unit with a low-flow nasal cannula for oxygen administration. The cannula was a 4-Fr multi-purpose tube with a side hole that was inserted into his left nostril. Next day, he suddenly developed pneumocephalus emerging from the right periorbital swelling and extending to his face and subcutaneous scalp over the next 6 h. A computed tomography (CT) scan revealed massive air pockets in the orbit, subdural space, subcutaneous scalp, and face. The nasal cannula was found to have been inserted deeper than we thought and was thus presumed to be the source of the air pockets. We immediately removed the cannula. Follow-up CTs revealed rapid resolution of the intracranial and subcutaneous air. The subcutaneous emphysema completely disappeared over the next 4 days, and he was discharged without any incident.