Comparative aspects of targeted sentinel lymph node mapping in veterinary and human medicine: opportunities for future research.

There is a significant overlap in the genetic, metabolic and epigenetic alterations between human and companion animal cancers, including those of the oral cavity, breast, bladder, skin, lungs and pancreas. In many cancer types, the identification and removal of affected lymph nodes are essential for accurate cancer management, including treatment and prognosis. Historically, lymphadenectomy and subsequent radical resection based on regional anatomy, palpation and lymph node aspirates were considered sufficient; however, modern approaches with sentinel lymph node mapping (SLN) mapping have increased the accuracy of surgical decision-making. Preoperative and intraoperative SLN mapping techniques in veterinary patients parallel those used in human medicine. While many of these techniques are highly successful, the main challenges with current methodologies are their sensitivity and specificity for the presence of cancer, which can be overcome via precision medicine and targeted SLN mapping agents. Given the large population of dogs and cats with cancer, the crossover of knowledge between species can help to deepen our understanding of many of these cancers and can be useful in evaluating new drugs and/or therapies. In this review, we discuss SLN mapping techniques in veterinary medicine and the concept of precision medicine as it relates to targeted SLN mapping imaging agents. The large number of companion animals affected by cancer is an underutilized resource to bridge the translational gap and we aim to provide a reference for the use of dogs and cats as a comparative model for human SLN mapping.

Effect of volume and methylene blue on fluorescence intensity and transit of indocyanine green for sentinel lymph node mapping in a simulated feline tumor model.

OBJECTIVE: To compare the effect of volume and solution on transit time and fluorescence intensity (FI) using near-infrared fluorescence imaging (NIRF) in a simulated tumor model in cats. Secondarily, to describe SLN mapping with indocyanine green (ICG) NIRF and report any adverse effects of intradermally injected ICG in cats. ANIMALS: 7 healthy purpose-bred domestic shorthaired male cats. METHODS: Cats were randomly divided into 2 groups (ICG or ICG + methylene blue [MB]). Transit time and FI were determined for 1 or 2 mL solutions injected intradermally in 4 quadrants around a simulated tumor. Following massage, fluorescence intensity was quantified by calculating the corrected total ROI fluorescence using ImageJ software. Cats were monitored for adverse effects up to 4 weeks post-injection. RESULTS: A larger solution volume had decreased transit times to the SLN (P = .001). There was no significant difference in transit times between ICG and ICG-MB. ICG demonstrated a greater FI (P = .001) in the SLN compared to ICG-MB. Methylene blue did not percutaneously fluoresce under NIRF. The volume of the solution did not significantly affect FI. No adverse reactions were reported. CLINICAL RELEVANCE: Increased volume of ICG may aid in rapid percutaneous lymphatic tracking from tumor to SLN. Indocyanine green alone may be preferred over ICG-MB for greater visualization of the SLN. Intradermal injections of ICG and ICG-MB were well-tolerated in healthy cats with no significant complications. Clinical evaluation of this technique in an impaired lymphatic system, as seen in cancer patients, should be assessed in future research.

Evaluation of complications and long-term outcomes associated with 101 dogs and cats discharged with and without subcutaneous active closed-suction drains (2014-2022).

OBJECTIVE: To retrospectively evaluate complications reported in dogs and cats with a closed suction subcutaneous drain that were either managed completely in hospital (Group ND) or discharged home for ongoing outpatient care (Group D). ANIMALS: 101 client-owned animals involving 94 dogs and 7 cats with a subcutaneous closed suction drain placed during a surgical procedure. PROCEDURES: Electronic medical records (January 2014 to December 2022) were reviewed. Signalment, reason for drain placement, surgical procedure, location and duration of drain placement, drain discharge status, antimicrobial usage, culture and sensitivity results, and intraoperative and postoperative complications were recorded. Associations among variables were evaluated. RESULTS: There were 77 animals in Group D and 24 animals in Group ND. Majority (n = 21/26) of complications were classified as minor and were all from Group D. Length of hospitalization in Group D (1 day) was significantly shorter than Group ND (3.25 days). Duration of drain placement was significantly longer in Group D (5.6 days) than Group ND (3.1 days). There were no associations between drain location, drain duration, or surgical site contamination with risk of complications. CLINICAL RELEVANCE: There is a higher risk of complications associated with discharging an animal from hospital (37%) with a subcutaneous closed suction drain than removing it prior to discharge (4%). These complications, however, were primarily minor and easily managed. Discharging an otherwise stable animal to home with a subcutaneous closed suction drain may be feasible to decrease duration of hospitalization, cost to the owner, and stress for the animal.

Implantation of 125I radioactive seeds via c-TBNA combined with chemotherapy in an advanced non-small-cell lung carcinoma patient.

BACKGROUND: The critical management of advanced non-small-cell lung carcinoma (NSCLC), especially when complicated by severe airway stenosis, is difficult and often leads to high clinical risks and medical costs. CASE PRESENTATION: A 51-year-old previously healthy male was admitted to the Department of Respiratory and Critical Care Medicine, Taizhou People's Hospital, in November 2018 for haemoptysis and difficulty breathing during a 15-d period. Following admission, chest computed tomography (CT) showed a large mass in the left hilum with atelectasis in the left upper lobe and obstructive pneumonia in the left lower lobe. Bronchoscopy revealed that the lesions occurred in the distal segment of the left main trachea, with occlusion of the left upper bronchus and significant narrowing of the lower bronchus. A basal mucosal biopsy of the lump tissue was performed after haemostasis treatment with sub-plasma coagulation (APC), and squamous lung carcinoma was confirmed. Following the final diagnosis, the patient was successfully treated with implantation of 125I radioactive seeds via transbronchial needle aspiration (c-TBNA) combined with chemotherapy. CONCLUSION: We believe that implantation of 125I radioactive seeds via c-TBNA is an effective treatment for patients with advanced lung cancer and those presenting with severe and mixed main bronchus stenosis.

Long non-coding RNA EPIC1 promotes human lung cancer cell growth.

Long non-coding RNA (LncRNA) EPIC1 (Lnc-EPIC1) is a MYC-interacting LncRNA. In the present study, the expression and potential function of Lnc-EPIC1 in human lung cancer cells are tested. We show that Lnc-EPIC1 expression is significantly higher in established/primary human lung cancer cells than that in human lung epithelial cells. Lnc-EPIC1 is also elevated in human lung cancer tissues. Silencing of Lnc-EPIC1 by targeted siRNA significantly inhibited human lung cancer cell growth, survival and proliferation, whiling inducing G1-S cell cycle arrest and cell apoptosis. MYC targets, including Cyclin A1, CDC20 and CDC45, were downregulated by Lnc-EPIC1 siRNA. MYC knockout by CRISPR/Cas-9 gene-editing method mimicked actions by Lnc-EPIC1 siRNA in A549 cells. Conversely, forced overexpression of Lnc-EPIC1 by a lentiviral construct increased expression of MYC targets to promote A549 cell growth. Lnc-EPIC1 directly associated with MYC protein in the nuclei of A549 cells. Significantly MYC knockout abolished Lnc-EPIC1 silencing- or overexpression-induced actions in human lung cancer cells. Together, our results show that Lnc-EPIC1 promotes human lung cancer cell growth possibly by targeting MYC.

k-RAS mutations in non-small cell lung cancer patients treated with TKIs among smokers and non-smokers: a meta-analysis.

AIM OF THE STUDY: Recent studies have suggested that k-RAS mutations are related to the response to epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitions (TKIs) in advanced non-small cell lung cancer (NSCLC) treatment. The aim of this meta-analysis was to assess the relationship between smoking history and k-RAS mutations in NSCLC treated with TKIs. MATERIAL AND METHODS: We searched MEDLINE and Web of Science up to 15 March 2014. The pooled relative risk (RR) was estimated by using fixed effect model or random effect model, according to heterogeneity between studies. We also carried out power analyses. RESULTS: We identified 12 studies with 1193 patients, including 196 patients (16.4%) with k-RAS mutations. The pooled k-RAS mutations incidence was 22.8% (174/764) in patients with smoke expose vs. 5.4% (23/429) in those with no smoke exposure. The pooled RR was 2.991 (95% CI: 1.884-4.746; Z = 4.65, p = 0.000). No publication bias was found (Begg's test: z = 1.09, p = 0.274 and Egger's test: t = 1.38, p = 0.201). In subgroup analyses, the pooled RR was 3.336 (95% CI: 1.925-5.779; Z = 4.30, p = 0.000) in the Caucasian subgroup, while in the Asian subgroup the pooled RR was 2.093 (95% CI: 0.909-4.822; Z = 1.73, p = 0.083), but the sample size was underpowered (0.465). CONCLUSIONS: The current meta-analysis found that smoking was related to increased incidence of k-RAS mutations in non-small cell lung cancer treated with TKIs. This may be further evidence that smoking will lead to a worse prognosis in NSCLC patients treated with TKIs.

Primary pulmonary synovial sarcoma presenting with a large lump mass in the left upper mediastinum: A case report.

Primary pulmonary synovial sarcoma is a rare lesion that occurs in 0.5% cases of lung malignancies. Chest computed tomography (CT) reveals a heterogeneously enhancing mass in the lobe or hilum of the lungs, frequently calcified and with pleural invasion. Involvement of the mediastinum in the course of primary pulmonary synovial sarcoma, in particular detection of a large mass in the mediastinum as the sole initial imaging manifestation, is extremely rare, which may contribute to a delayed diagnosis or misdiagnosis. The present case report describes an extremely rare case of a patient with primary pulmonary synovial sarcoma presenting with a large mass in the left upper mediastinum. A 59-year-old patient was admitted to the Department of Respiratory Medicine of Taizhou People's Hospital in May 2014, complaining of a persistent cough and blood sputum for 2 weeks. Following admission, a chest CT showed a large mass in the left upper mediastinum. Thoracoscopy was performed and revealed that the left pulmonary artery was engulfed by the mass, and thus surgical resection of the tumor was abandoned. The patient was definitively diagnosed with primary pulmonary synovial sarcoma following the histopathological and immunohistochemical analysis of biopsy specimens obtained via thoracoscopy. Following the final diagnosis, the patient was transferred to the Department of Oncology for chemotherapy treatments with ifosfamide and doxorubicin. Unfortunately, no partial regression was achieved after two rounds of chemotherapy, and the patient was lost to follow-up 3 months after the diagnosis was confirmed. The present case may promote the consideration of primary pulmonary synovial sarcoma in the differential diagnosis of patients who present with a large mass in the mediastinum.

siRNA targeting of Trop2 suppresses the proliferation and invasion of lung adenocarcinoma H460 cells.

The aim of the present study was to investigate the effect of the small interfering RNA (siRNA)-induced inhibition of the Trop2 gene on the proliferation and invasion of lung adenocarcinoma H460 cells. A recombinant adenovirus expression vector, which contained siRNA targeting open reading frames for Trop2 (rAd5-siTrop2), was transfected into lung adenocarcinoma H460 cells. Three groups were included in the study, namely the Ctrl (non-transfected control), rAd5-siCtrl (native control) and rAd5-siTrop2 (knockdown Trop2 gene) groups. The mRNA and protein expression levels of Trop2 were detected using quantitative polymerase chain reaction and western blot analysis, respectively. In addition, the expression levels of cyclin Dl and phospho-extracellular signal regulated kinase (p-ERK)-1 were detected using western blot analysis. The effects of Trop2 inhibition on the proliferation and invasion of lung adenocarcinoma H460 cells were investigated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assay. Trop2-targeted siRNA recombinant plasmids were successfully constructed. The recombinant adenovirus vector, rAd5-siTrop2, significantly downregulated the mRNA and protein expression levels of Trop2 in the lung adenocarcinoma H460 cells, with cyclin D1 and p-ERK-1 expression downregulated simultaneously. In addition, following the silencing of Trop2, the proliferation and invasion rates of the lung adenocarcinoma H460 cells were reduced. Therefore, the results indicated that Trop2 serves a key function in the proliferation and invasion of lung adenocarcinoma H460 cells in vitro.

Sporadic lymphangioleiomyomatosis with bloody sputum as an initial symptom: A case report and review of the literature.

Lymphangioleiomyomatosis (LAM) is an extremely rare lung disease affecting females of a childbearing age. The condition occurs sporadically or in association with tuberous sclerosis complex. The diagnosis of LAM is often delayed since the clinical symptoms and signs are non-specific. The present study reports the a case of a patient with LAM, in which bloody sputum was presented as the initial symptom. The 43-year-old female had experienced a small amount of bloody sputum over the previous five years. The patient was admitted to the Department of Respiratory Medicine at Taizhou People's Hospital (Taizhou, China) in 2012, reporting symptoms of a cough, shortness of breath and bloody sputum over the previous 10 days. A high-resolution computed tomography scan revealed multiple small circular thin-walled translucent areas in both lung fields. The initial diagnosis of the patient was LAM. A biopsy was performed using a video-assisted thoracoscopy. In conclusion, increased awareness and early diagnosis and treatment were determined to be key factors in ensuring a satisfactory prognosis.

The relationship between Glasgow Prognostic Score and serum tumor markers in patients with advanced non-small cell lung cancer.

BACKGROUND: Glasgow Prognostic Score (GPS) has been reported as a powerful prognostic tool for patients with advanced non-small cell lung cancer (NSCLC). The aim of this study was to assess the relationship between GPS and prognosis related tumor markers in patients with advanced NSCLC. METHODS: We included 138 advanced NSCLC patients and twenty healthy controls in the study. GPS was calculated by combined serum C-reactive protein (CRP) and albumin. Three serum tumor markers, which included cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), carcinoembryonic antigen (CEA) and tissue polypeptide specific antigen (TPS), were detected by enzyme-linked immunosorbent assay (ELISA). GPS and tumor markers were all assessed before chemotherapy. All patients received at least 2 courses of cisplatin-based chemotherapy. After that, 2 to 5 years follow-up was conducted. RESULTS: Median levels of CYFRA21-1 were 1.5 ng/ml (0.1-3.1 ng/ml) in healthy controls, and 4.6 ng/ml (0.7-35.2 ng/ml) in GPS 0 advanced NSCLC, 11.2 ng/ml (0.4-89.2) ng/ml in GPS 1 advanced NSCLC, and 15.7 ng/ml (2.9-134.6 ng/ml) in GPS 2 advanced NSCLC, respectively. Median levels of CYFRA21-1 were higher in NSCLC patients than in healthy controls, and CYFRA21-1 increased gradually according to GPS category in NSCLC patients (P< 0.05). Similar results were found for median levels of CEA and TPS in healthy controls and NSCLC patients (P < 0.05). In NSCLC patients, positive correlations were found between CYFRA21-1 and GPS, CEA and GPS, TPS and GPS. The Spearman's rank correlation coefficient were 0.67 (P < 0.05), 0.61 (P < 0.05) and 0.55 (P < 0.05), respectively. Survival analyses showed GPS was an independent prognostic factor for advanced NSCLC. CYFRA21-1(>3.3 ng/ml) and TPS (>80 U/l) were related with the prognosis of advanced NSCLC by univariate analyses, but multivariate analyses showed CYFRA21-1, TPS and CEA were not the independent prognostic factors for advanced NSCLC. CONCLUSIONS: Our results showed GPS were positive correlated with CYFRA21-1, CEA and TPS in patients with advanced NSCLC. However, GPS was more efficient in predicting prognosis of advanced NSCLC than these three single prognosis related tumor markers.

Short hairpin RNA targeting AKT1 and PI3K/p85 suppresses the proliferation and self-renewal of lung cancer stem cells.

The aim of the present study was to investigate the effect of short hairpin (sh)RNA targeting AKT1 and phosphatidylinositol 3-kinase (PI3K)/p85 on the proliferation and self-renewal of lung cancer stem cells (LCSCs). The recombinant adenovirus expression vector, which contained shRNA targeting open reading frames of AKT1 and PI3K/p85, was transfected into LCSCs. It was found that AKT1 and PI3K/p85 expression was upregulated in LCSCs compared with that in the primary lung cancer cells. Recombinant adenovirus vector rAd5-siAKT1-siPI3K/p85 significantly downregulated AKT1 and PI3K/p85 mRNA and protein expression in LCSCs. The downstream factors, proliferating cell nuclear antigen (PCNA) and cyclin D1 were also downregulated, while p53 was upregulated. Following silencing of AKT1 and PI3K/p85, cell proliferation, tumor sphere formation and tumor formation in NOD/SCID mice were also reduced. According to the present results, it was hypothesized that the PI3K/Akt signaling pathway is important in the self­renewal and proliferation of LCSCs, and that targeting the PI3K/Akt signaling pathway decreases the rate of tumor formation in vivo.

Bilateral pleural effusion as an initial manifestation of multiple myeloma: A case report and literature review.

Multiple myeloma (MM) is a rare type of malignant hematological neoplasm. Although primarily involving the bone marrow, MM has a significant risk of metastasizing to other organs and may present with various clinical symptoms. However, the involvement of the respiratory system in the course of MM is extremely uncommon, particularly presenting with bilateral pleural effusion as the sole initial manifestation, which may result in a delayed diagnosis of MM. The present study describes the extremely rare case of a patient with MM presenting with myelomatous pleural effusion (MPE). The 78-year-old patient was admitted to the Department of Respiratory Medicine, Taizhou People's Hospital (Taizhou, China) in March 2014, complaining of persistent dyspnea. Following admission, chest computed tomography scans revealed bilateral pleural effusion and a small amount of pericardial effusion, but no evident mass lesion. Thoracentesis was performed and the resulting pleural effusion was exudative and slightly bloody. In the following cytological examination, myeloma cells were identified in the pleural effusion. The patient was diagnosed definitively with MM following a histopathological study of the bone marrow aspiration. Therefore, the observations of the present case report may promote the consideration of MM in the differential diagnosis of patients with unexplained and refractory pleural effusion. The present study also reviewed the literature with regard to the association between MM and pleural effusion.

The Glasgow prognostic score as a prognostic factor in patients with advanced non-small cell lung cancer treated with cisplatin-based first-line chemotherapy.

OBJECTIVES: The aim of this study was to assess the predictive value of survival in patients with advanced non-small cell lung cancer (NSCLC) treated with cisplatin-based first-line chemotherapy. METHODS: In this study, 138 consecutive patients with advanced NSCLC were included in this study. Glasgow prognostic score (GPS) was calculated before the onset of treatment. The outcome indicators were progression free survival (PFS) and overall survival (OS). RESULTS: Univariate log-rank test showed that GPS was significantly associated with both PFS (P  =  0.01) and OS (P  =  0.02). Multivariate Cox model revealed that the hazard ratios (HRs) for PFS were 0.8(0.5-0.9) for GPS 1 versus GPS 0 and 0.5(0.3-0.8) for GPS 2 versus GPS 0, respectively. The HRs for OS were 0.8(0.4-0.9) for GPS 1 versus GPS 0 and 0.5(0.2-0.8) for GPS 2 versus GPS 0, respectively. CONCLUSIONS: The GPS can be used as an independent predictor for survival in patients with advanced NSCLC.

Comparison of Glasgow prognostic score and prognostic index in patients with advanced non-small cell lung cancer.

OBJECTIVES: Previous studies have shown that Glasgow prognostic score (GPS) and prognostic index (PI) are also powerful prognostic tool for patients with advanced non-small cell lung cancer (NSCLC). The aim of this study was to compare the prognostic value between GPS and PI. METHODS: We enrolled consecutive patients with advanced NSCLC in this prospective cohort. GPS and PI were calculated before the onset of chemotherapy. The prognosis outcomes included 1-, 3-, and 5-year progression-free survival and overall survival (OS). The performance of two scores in predicting prognosis was analyzed regarding discrimination and calibration. RESULTS: 138 patients were included in the study. The area under the receiver operating characteristic curve for GPS predicting 1-year DFS was 0.62 (95 % confidence interval (CI) 0.56-0.68, P < 0.05), and the area under curve for PI predicting 1-year DFS was 0.57 (95 % CI 0.52-0.63). Delong's test showed that GPS was more accurate than PI in predicting 1-year DFS (P < 0.05). Similar results of discriminatory power were found for predicting 3-year DFS, 1-year OS, and 3-year OS. The predicted 1-year DFS by GPS 0, GPS 1, and GPS 2 were 62.5, 42.1, and 23.1 %, respectively, while actual 1-year DFS by GPS 0, GPS 1, and GPS 2 were 61.1, 43.8, and 27.2 %, respectively. Calibration of the Hosmer and Lemeshow statistic showed good fit of the predicted 1-year DFS to the actual 1-year DFS by GPS (χ(2) = 4.326, P = 0.462), while no fit was found between the predicted 1-year DFS and the actual 1-year DFS by PI (χ(2) = 15.234, P = 0.091). Similar results of calibration power were found for predicting 3-year DFS, 5-year DFS, 1-year OS, 3-year OS, and 5-year OS by GPS and PI. CONCLUSIONS: GPS is more accurate than PI in predicting prognosis for patients with advanced NSCLC. GPS can be used as a useful and simple tool for predicting prognosis in patients with NSCLC. However, GPS only can be used for preliminary assessment because of low predicting accuracy.

Isolation, cultivation and identification of human lung adenocarcinoma stem cells.

Recently, an increasing number of studies have demonstrated that lung cancer is a stem cell disease. However, ideal cell surface markers for isolating stem cells in lung cancer are yet to be identified. In the present study, a cell population with a cluster of differentiation (CD)133+ phenotype was successfully isolated from a single cell suspension of lung adenocarcinoma tissue using magnetic-activated cell sorting (MACS) and enriched in a serum-free culture. In comparison to CD133- cells, the CD133+ cells exhibited an enhanced capacity for self-renewal and differentiation, and a greater potential for in vivo tumor formation, in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. Tumors could be induced in NOD/SCID mice by the transplantation of 102 stem-like cells per mouse. The results of the present study demonstrated that CD133 may serve as a specific cell surface marker for lung adenocarcinoma stem cells, and that MACS combined with serum-free culture is an effective method for isolating and enriching lung cancer stem cells.

Diagnosis and management of a patient with primary pulmonary diffuse large B-cell lymphoma: A case report and review of the literature.

Primary pulmonary lymphoma (PPL) is an uncommon type of non-Hodgkin's lymphoma. The majority of PPLs are of low-grade, mucosa-associated lymphoid tissue type. Primary pulmonary diffuse large B-cell lymphoma (DLBCL) is extremely rare, and prompt diagnosis may be challenging since its clinical symptoms and signs are nonspecific. Although the clinical features, diagnostic procedures, optimal management and prognostic factors of this disease have not yet been well defined, open thoracotomy and chest computed tomography (CT)-guided percutaneous biopsy are the preferred methods used in previous studies. In the present case report, the diagnosis and management of a patient with primary pulmonary DLBCL is reported. A 68-year-old patient was admitted to hospital in May 2013, with complaints of shortness of breath and intermittent wheezing and a cough associated with the production of small amounts of phlegm. Following admission, chest CT scans revealed a mass in the right middle lobe with ground-glass opacities at the lesion margins, as well as air bronchograms in the areas of consolidation. Bronchoscopy was performed and revealed an endobronchial lesion and partial stenosis in the distal end of the middle segment bronchus. Transbronchial needle aspiration (TBNA) of the right hilar lymph node, as well as endobronchial biopsy, was performed. The patient was diagnosed with primary pulmonary DLBCL by subsequent histopathological and immunohistochemical analysis of biopsy specimens collected via TBNA. Following the final diagnosis, standard treatment with CHOP chemotherapy resulted in significant clinical and radiological response and the patient remained in remission 8 months later. These results indicate that TBNA may be an effective method for the diagnosis of primary pulmonary DLBCL.

Diagnosis and management of an elderly patient with severe tracheomalacia: A case report and review of the literature.

Severe adult tracheomalacia is a dangerous disease that is difficult to manage, particularly at the time of airway infection, and has a high mortality rate. The present study reports the diagnosis and treatment of an elderly patient with severe adult tracheomalacia. In March 2012, the 59-year-old patient presented with progressive dyspnea to the Department of Respiratory Medicine, Taizhou People's Hospital (Jiangsu, China). Following admission, chest radiography revealed symptoms consistent with chronic obstructive pulmonary disease (COPD) and chest computed tomography (CT) demonstrated an evident stenosis of the tracheal lumen at the end of expiration. Bronchoscopy revealed a 91% reduction in the cross-sectional area of the tracheal lumen at the end of expiration. Following the final diagnosis, the patient was successfully treated with nasal continuous positive airway pressure (CPAP) combined with implantation of a temporary Chinese Li's metallic stent. These treatment methods appeared to be temporarily effective in alleviating the symptoms of the disease.

Agnogenic massive pulmonary embolism with syncope as initial symptom: A case report and review of the literature.

Pulmonary embolism may escape prompt diagnosis since clinical symptoms and signs are nonspecific. The occurrence of syncope as the sole initial symptom in a previously healthy patient with no predisposing factors to embolism and no hemodynamic instability is extremely rare, which may have been a factor in the delayed diagnosis. We describe a case of agnogenic massive pulmonary embolism with syncope as the initial symptom. A 41-year-old previously healthy female was admitted to the Department of Neurology, Taizhou People's Hospital in March 2012, for two transitory episodes of syncope during a 5-h period. Following admission, chest computed tomography demonstrated embolism in the right main pulmonary and left inferior pulmonary arteries. Color ultrasonography revealed a dilated right ventricle and right heart overload, severe tricuspid regurgitation and severe pulmonary hypertension. Following the final diagnosis, the patient was successfully treated with interventional mechanical thrombectomy combined with thrombolytic therapy with local and systemic low-dose urokinase. We consider that raised awareness and early diagnosis and treatment were key factors in ensuring a satisfactory prognosis.

[Efficacy and safety of cyclosporine A in treatment of refractory nephrotic syndrome in children: a systematic review of randomized controlled trials].

OBJECTIVE: To evaluate the efficacy and safety of cyclosporine A(CsA) in the treatment of refractory nephrotic syndrome (RNS) in children. METHODS: The Cochrane library, PubMed, EMBASE, CBMdisk, CNKI and VIP were searched from the time when the databases were established to December 31, 2008. Reports on RCTs on treating RNS in children with CsA were collected. Data were extracted and assessed independently by three reviewers. The methodological quality of included RCTs was assessed by the revised Jadad-scale (including randomization, allocation concealment, blinding method and withdrawal). Meta-analysis of homogenous RCTs was managed by using RevMan4.2.3. RESULT: Nine RCTs involving 293 participants were included. Six RCTs were assessed as high-quality studies with scores from 4 to 7 and 3 RCTs were assessed as low-quality studies with scores from 1 to 3. Sub-category meta-analysis was based on different clinical types and interventions of RNS in children. Meta-analysis based on included RCTs showed the following results. (1) In children with steroid-dependent or frequent relapse nephrotic syndrome: the short-term efficacy of CsA plus prednisone was better than that of prednisone alone [OR 0.14, 95% CI (0.03, 0.71)]; the short-term efficacy of CsA, cyclophosphamide (CTX) and mycophenolate mofetil had no significant differences, but compared with chlorambucil, CsA had a worse short-term efficacy [OR 6.93, 95% CI (1.53, 31.38)] and a higher relapse rate [OR 0.06, 95% CI (0.01, 0.58)]; maintaining a blood level of CsA between 60 and 80 microg/L during remission period could reduce the long term relapse rate [OR 6.43, 95% CI (1.21, 34.19)]; the incidence of end-stage renal disease (ESRD) or mortality was zero in both groups. (2) In children with steroid-resistant nephrotic syndrome, the short-term efficacy of CsA was better than that of placebo or supportive treatment and CTX, OR and 95% CI were 0.15 (0.02, 0.96) and 0.41 (0.03, 5.00), respectively, but no significant differences were found in the relapse rate and the incidence of ESRD or mortality. (3) Side effects of CsA: the incidence of nephrotoxicity, hypertrichosis and gum hypertrophy was higher in the CsA group than in that of control group, OR and 95% CI were 0.19 (0.05, 0.79), 0.06 (0.02, 0.19), 0.05 (0.02, 0.18), respectively, but no significant differences were found in the incidence of hypertension and liver toxicity. CONCLUSIONS: Available evidence showed that CsA could improve short term efficacy in RNS in children, but could not improve long term and endpoint efficacy, therefore CsA could be one of the ideal second-line drugs for RNS in children. There was a trend that the effect of CsA on steroid-dependent or frequent relapse nephrotic syndrome was superior to that on steroid-resistant nephrotic syndrome.