Establishment of acquired tracheoesophageal fistula using a modified magnetic compression technique in rabbits and its postmodeling evaluation

BACKGROUND Previous studies have validated the efficacy of both magnetic compression and surgical techniques in creating rabbit tracheoesophageal fistula(TEF)models.Magnetic compression achieves a 100%success rate but requires more time,while surgery,though less frequently successful,offers rapid model establishment and technical maturity in larger animal models.AIM To determine the optimal approach for rabbit disease modeling and refine the process.METHODS TEF models were created in 12 rabbits using both the modified magnetic compression technique and surgery.Comparisons of the time to model establishment,success rate,food and water intake,weight changes,activity levels,bronchoscopy findings,white blood cell counts,and biopsies were performed.In response to the failures encountered during modified magnetic compression modeling,we increased the sample size to 15 rabbit models and assessed the repeatability and stability of the models,comparing them with the original magnetic compression technique.RESULTS The modified magnetic compression technique achieved a 66.7%success rate,whereas the success rate of the surgery technique was 33.3%.Surviving surgical rabbits might not meet subsequent experimental requirements due to TEF-related inflammation.In the modified magnetic compression group,one rabbit died,possibly due to magnet corrosion,and another died from tracheal magnet obstruction.Similar events occurred during the second round of modified magnetic compression modeling,with one rabbit possibly succumbing to aggravated lung infection.The operation time of the first round of modified magnetic compression was 3.2±0.6 min,which was significantly reduced to 2.1±0.4 min in the second round,compared to both the first round and that of the original technique.CONCLUSION The modified magnetic compression technique exhibits lower stress responses,a simple procedure,a high success rate,and lower modeling costs,making it a more appropriate choice for constructing TEF models in rabbits.

Pathogenesis and drug resistance mechanism of Burkholderia pseudomallei

Burkholderia pseudomallei is the pathogen that causes melioidosis.Melioidosis has a long duration of chronic infection,atypical clinical manifestations at acute onset,and is prone to life-threatening complications and poor prognosis.Understanding the pathogenesis and drug resistance mechanism of Burkholderia pseudomallei will effectively help the diagnosis and treatment of the disease and improve the prognosis.This review focuses on the extracellular movement of Burkholderia pseudomallei in host cells,the way of infecting host cells,virulence factors,and drug resistance mechanisms(efflux pumps,changes in target sites,etc.).This study provides a possible direction for the early diagnosis,treatment and control of melioidosis caused by this bacterium.

Feasibility Study for Biweekly Administration of Cisplatin plus Vinorelbine as Adjuvant-Chemotherapy for Completely Resected Non-Small Cell Lung Cancer Patients in a Japanese Population

Purpose: To evaluate the feasibility of biweekly administration of cisplatin and vinorelbine as adjuvant chemotherapy for patients with completely resected non-small cell lung cancer (NSCLC). Patients and Methods: This was a single-arm, single-institutional study. Patients with completely resected NSCLC (p-Stage IB-IIIA) with no previous chemotherapy or radiotherapy were eligible. Simon’s optimal two-stage design was applied. Both cisplatin (50 mg/m2) and vinorelbine (25 mg/m2) were given on days 1 and 15, every 28 days. The primary endpoint of this study was the feasibility of this combination in the four cycles of treatment. Results: Twenty patients (19 lobectomies and 1 pneumonectomy) were enrolled in this study. 10 (50%) of patients had grade 3/4 neutropenia, and 3 (15%) had grade 3/4 anemia. Severe non-hematologic toxicities were uncommon in this series. No treatment-related death was encountered. 18 (90%) patients completed the planned 4 cycles of chemotherapy. The median intensity was 24.3 (range 18.1 to 25) mg/m2/week with an average of 23.6 (21 - 25) mg/m2/week cisplatin and 12.5 (range 10 to 12.5) mg/m2/week with an average of 12.3 (10 - 12.5) mg/m2/week vinorelbine. The median relative dose intensity of cisplatin was 97.5% (range 72.5% to 100%) with an average of 94.6% (72.5% - 100%) and that of vinorelbine was 100% (range 80% to 100%) with an average of 97.8% (80% - 100%). Conclusion: This regimen is feasible in the treatment of patients with completely resected NSCLC. A phase III trial is warranted to assess the efficacy of this regimen at promoting survival and preventing recurrence.

Congenital tracheoesophageal fistula successfully diagnosed by CT esophagography

Tracheoesophageal fistula （TEF） or bronchoesophageal fistula may be congenital, inflammatory, neoplastic, or secondary to trauma. Congenital TEF or bronchoesophageal fistula is usually associated with esophageal atresia and is readily diagnosed in infancy. But if it is not associated with esophageal atresia, it may persist until adulthood. Some theories have been proposed to explain this delay in diagnosis. We present a case of a 70-year-old man with congenital TEF. The TEF was successfully diagnosed by multidetector-row CT esophagography.

Trauma and syncope-evidence for further sleep study? A case report

We report on an 83-year-old male with traumatic brain injury after syncope with a fall in the morning. He had a history of seizures, coronary artery disease and paroxysmal atrial fibrillation(AF). No medical cause for seizures and syncope was determined. During rehabilitation, the patient still complained of seizures, and also reported sleepiness and snoring. Sleep apnea diagnostics revealed obstructive sleep apnea(SA) with an apnea-hypopnoea index of 35/h, and sudden onset of tachycardia with variations of heart rate based on paroxysmal atrial fibrillation. Additional tests showed nocturnal AF which spontaneously converted to sinus rhythm mid-morning with an arrest of 5 s(sick sinus syndrome) and seizures. A DDD-pacer was implanted and no further seizures occurred. SA therapy with nasal continuous positive airway pressure was refused by the patient. Our findings suggests that screening for SA may offer the possibility to reveal causes of syncope and may introduce additional therapeutic options as arrhythmia and SA often occur together which in turn might be responsible for trauma due to syncope episodes.

Surgical Treatment of Idiopathic Multiple Pulmonary Arteriovenous Malformation Identified at the Onset of Cerebral Infarction: A Case Report

Pulmonary arteriovenous malformation (PAVM), which is asymptomatic in most cases, is often identified in patients with central nervous system disorders such as brain abscesses and/or cerebral infarctions. We have reported a patient with idiopathic multiple PAVM identified at the onset of cerebral infarction. A 69-year-old woman visited the Department of Neuropathic Internal Medicine at our hospital with chief complaints of numbness in her left hand and a feeling of weakness. The patient was given a diagnosis of subacute cerebral infarction. Multiple old lacunar infarctions were also observed in the deep white matter of the left frontal lobe. Chest computed tomography showed multiple nodular structures, mainly in the right lower lung field (S8), as well as continuous arteries and veins at the site;thus, the patient was finally diagnosed with multiple PAVM. Right lower thoracoscopic lobectomy was performed, as is typical surgical practice in such cases. The patient had a favorable postoperative course, and had no recurrence of cerebral infarction. Although the patient’s lesions were mainly restricted to S8, the fact that there were multiple lesions deemed a lobectomy as the appropriate course of treatment. This case emphasizes that attention should be paid to cases of multiple PAVM since cerebral infarction may arise from the disease.

Relapse of both small cell lung cancer and Lambert-Eaton myasthenic syndrome after a 13-year disease-free survival period

Lambert-Eaton myasthenic syndrome(LEMS) is a paraneoplastic syndrome and only 3%of small cell lung carcinoma(SCLC) patients have LEMS.Moreover,the recurrence of SCLC after a disease-free survival(DFS) of more than 10 years is rare.We report a patient who had a recurrence of both SCLC and LEMS after a 13-year DFS period.A 69-year-old man was diagnosed with LEMS and SCLC(cT0N2M0,stage ⅢA) 13 years ago.Chemoradiotherapy was performed and a complete response was achieved.With anticancer treatment,the LEMS symptoms was alleviated.At the age of 82 years,gait disturbance appeared followed by left supraclavicular lymphadenopathy and further examination revealed the recurrence of SCLC.Careful screening for the recurrence of SCLC might be needed when the patient has recurrent or secondary paraneoplastic neurological syndrome even after a long DFS period.

Severe Mediastinal Emphysema and Tension Pneumothorax Caused by Cough-Induced Intercostal Lung Herniation

We report a case of cough-induced intercostal lung herniation with severe mediastinal emphysema and pneumothorax. A 60-year-old overweight man was admitted with dyspnea, chest pain, and chest wall bulging. Imaging confirmed left pneumothorax, fractures of the 8th to 10th ribs, and a defect in the 8th intercostal muscles. The presence of protrusion of lung parenchyma outside the intercostal space was unclear. Although the symptoms of tension pneumothorax disappeared after drainage, the subcutaneous emphysema was uncontrollable. Emergency surgery revealed lung injury near the 8th rib wedge not directly related to the rib fracture, and lung herniation was observed. We performed direct approximation of the ribs, and the lung parenchymal surface was encased by absorbable materials, avoiding infection risk. Although the lung herniation recurred 5 months later, the patient did not desire additional surgical repair. Non-absorbable materials should be considered for repair of lung herniation, excluding patients at high infection risk.

Relationship between metabolic syndrome and hypercapnia among obese patients with sleep apnea Relationship between metabolic syndrome and hypercapnia among obese patients with sleep apnea

BACKGROUND In the obese patient population,some patients have severe obstructive sleep apnea(OSA)with daytime hypoventilation.Such patients are generally identified on the basis of the presence or absence of daytime hypercapnia,and the condition is called obesity hypoventilation syndrome.However,mechanisms for such daytime hypoventilation remain unclear.AIM To investigate metabolic syndrome and daytime hypercapnia association based on hypercapnia prevalence in obese OSA patients in a nested case-control study.METHODS Consecutive obese patients(body mass index≥30 kg/m2)who underwent polysomnography due to suspected OSA were included.Among them,patients with severe OSA(apnea hypopnea index≥30/h)were divided into two groups according to the presence or absence of hypercapnia during wakefulness(arterial partial pressure of carbon dioxide≥or<45 Torr,respectively).The characteristics and clinical features of these two groups were compared.RESULTS Among 97 eligible patients,25 patients(25.8%)had daytime hypercapnia.There were no significant differences in age,gender,body mass index,apnea-hypopnea index,and Epworth Sleepiness Scale scores between the two groups.However,patients with hypercapnia had a significantly lower arterial partial pressure of oxygen level(75.8±8.2 torr vs 79.9±8.7 torr,P=0.042)and higher arterial partial pressure of carbon dioxide level(46.6±2.5 torr vs 41.0±2.9 torr,P<0.001).Additionally,patients with hypercapnia were more likely to have metabolic syndrome(72.0%vs 48.6%,P=0.043)and a higher metabolic score(the number of satisfied criteria of metabolic syndrome).In multivariate logistic regression analysis,the presence of metabolic syndrome was associated with the presence of hypercapnia(OR=2.85,95%CI:1.04-7.84,P=0.042).CONCLUSION Among obese patients with severe OSA,26%of patients had hypercapnia during wakefulness.The presence of metabolic syndrome was independently correlated with the presence of daytime hypercapnia.

Sodium-glucose cotransporter 2 inhibitors in Asian patients with heart failure

To the Editor:Sodium-glucose cotransporter 2(SGLT-2)inhibitors are recognized as one of the essential drugs for the treatment of heart failure(HF).Recent randomized controlled trials(RCTs)have shown that the SGLT-2 inhibitors significantly reduced the occurrence of HF hospitalizations or cardiovascular mortality in HF patients.

Curcumin Inhibits Lipopolysaccharide-lnduced Mucin 5AC Hypersecretion and Airway Inflammation via Nuclear Factor Erythroid 2-Related Factor 2

Background： Excess mucus production is an important pathophysiological feature of chronic inflammatory airway diseases. Effective therapies are currently lacking. The aim of the study was to evaluate the effects ofcurcumin （CUR） on lipopolysaccharide （LPS）-induced mucus secretion and inflammation, and explored the underlying mechanism in vivo and in vitro. Methods： For the in vitro study, human bronchial epithelial （NCI-H292） cells were pretreated with CUR or vehicle for 30 min, and then exposed to LPS for 24 h. Next, nuclear factor erythroid 2-related factor 2 （Nrf2） was knocked down with Nrf2 small interfering RNA （siRNA） to confirm the specific role of Nrf2 in mucin regulation of CUR in NCI-H292 cells. In vivo, C57BL/6 mice were randomly assigned to three groups （n = 7 for each group）： control group, LPS group, and LPS ＋ CUR group. Mice in LPS and LPS ＋ CUR group were injected with saline or CUR （50 mg/kg） intraperitoneally 2 h before intratracheal instillation with LPS （ 100 μg/ml） for 7 days. Cell lysate and lung tissue were obtained to measured Mucin 5AC （MUC5AC） and Nrf2 mRNA and protein expression by a real-time polymerase chain reaction and Western blotting. Bronchoalveolar lavage fluid （BALF） was collected to enumerate total cells and neutrophils. HistopathologicaI changes of the lung were observed. Data were analyzed by one-way analysis of variance. Student＇s t-test was used when two groups were compared. Results： CUR significantly decreased the expression ofMUC5AC mRNA and protein in NCI-H292 cells exposed to LPS. This effect was dose dependent （2.424 ± 0.318 vs. 7.169 ± 1.785, t = 4.534, and 1.060 ± 0.197 vs. 2.340 ± 0.209, t = 7.716; both P 〈 0.05, respectively） and accompanied by increased mRNA and protein expression of Nrf2 （1.952 ± 0.340 vs. 1.142 ± 0.176, t = -3.661, and 2.010 ± 0.209 vs. 1.089 ±0. 132, t = -6.453; both P 〈 0.05, respectively）. Furthermore, knockdown of Nrf2 with siRNA increased MUC5A C mRN A expression by 47.7%, compared with levels observed in the siRNA-negative group （6.845 ± 1.478 vs. 3.391 ± 0.517, t = -3.821, P 〈 0.05）. Knockdown of Nrf2 with siRNA also markedly increased MUC5A C protein expression in NCI-H292 cells. CUR also significantly decreased LPS-induced mRNA and protein expression of MUC5A C in mouse lung （ 1.672 ± 0.721 vs. 5.961 ± 2.452, t = 2.906, and 0.480 ± 0.191 vs. 2.290 ± 0.834, t = 3.665, respectively; both P 〈 0.05）. Alcian blue/periodic acid-Schiff staining also showed that CUR suppressed mucin production. Compared with the LPS group, the numbers of inflammatory cells （247 ± 30 vs. 334 ± 24, t = 3.901, P 〈 0.05） and neutrophils （185 ± 22 vs. 246 ± 20, t = 3.566, P 〈 0.05） in BALF decreased in the LPS ＋ CUR group, as well as reduced inflammatory cell infiltration in lung tissue. Conclusion： CUR inhibits LPS-induced airway mucus hypersecretion and inflammation through activation of Nrf2 possibly.

Massive hemoptysis and hemothorax： a rare but fatal complication of intralobar sequestration

Intralobar sequestration （ILS） is an uncommon abnormality that accounts for 75% of all pulmonary sequestrations. Over the years there have been several reports of various presenting signs of which hemoptysis was commonly described, however, massive hemoptysis and hemothorax is extremely rare in literature. We present a case of a 45-year-old man who died of fatal complication from an ILS. This case report shows an uncommon presentation of ILS with massive hemoptysis and hemothorax resulting in a dramatic course of disease and a fatal outcome, and for this reason in the absence of trauma or other causes for massive hemoptysis, hemothorax, or lung hematoma, this possibility should be kept in mind so as to avoid misdiagnosis, and resection of the sequestered tissue should be considered in all patients.

Lung cancer biopsy dislodges tumor cells into circulating blood

Aim:A“seed”of lung cancer metastasis is circulating tumor cells(CTCs),which may be dislodged from a tumor during biopsy.This possibility was assessed among patients who underwent lung tumor biopsy using flexible fiber-topic bronchoscopy(FFB).Methods:The study involved six patients with non-small cell lung cancer who underwent FFB biopsy to diagnose a lesion pathologically(5 males and 1 female,median age 63 years,6 adenocarcinomas,of 4 clinical-stage IA,1 stage IB,and 1 stage IIIA),CTCs were extracted from the peripheral vein blood at pre-FFB and at post-FFB using a size selection method.Results:No t umor c ell was d etected a t p re-a nd p ost-FFB was i n t hree c ases(50%);no tumor cells were detected pre-FFB while CTCs were detected at post-FFB in two cases(33.3%);and CTCs were detected at pre-FFB with numerous CTCs detected at post-FFB in one case(17.7%).In addition,similar tendencies were observed in each analysis of single-cell and clustered-cell categories.Conclusion:These results suggest that a FFB biopsy of lung cancer may potentially dislodge CTCs from a tumor into the circulating peripheral blood.