Objectives The aim of this study was to test the hypothesis that angiotensin (Ang)-converting enzyme-2 (ACE2) overexpression may inhibit myocardial collagen accumulation and improve left ventricular ...(LV) remodeling and function in diabetic cardiomyopathy. Background Hyperglycemia activates the renin-Ang system, which promotes the accumulation of extracellular matrix and progression of cardiac remodeling and dysfunction. Methods Ninety male Wistar rats were divided randomly into treatment (n = 80) and control (n = 10) groups. Diabetes was induced in the treatment group by a single intraperitoneal injection of streptozotocin. Twelve weeks after streptozotocin injection, rats in the treatment group were further divided into adenovirus-ACE2, adenovirus–enhanced green fluorescent protein, losartan, and mock groups (n = 20 each). LV volume; LV systolic and diastolic function; extent of myocardial fibrosis; protein expression levels of ACE2, Ang-converting enzyme, and Ang-(1-7); and matrix metalloproteinase–2 activity were evaluated. Cardiac myocyte and fibroblast culture was performed to assess Ang-II and collagen protein expression before and after ACE2 gene transfection. Results Four weeks after ACE2 gene transfer, the adenovirus-ACE2 group showed increased ACE2 expression, matrix metalloproteinase–2 activity, and LV ejection fractions and decreased LV volumes, myocardial fibrosis, and ACE, Ang-II, and collagen expression in comparison with the adenovirus–enhanced green fluorescent protein and control groups. ACE2 was superior to losartan in improving LV remodeling and function and reducing collagen expression. The putative mechanisms may involve a shift in balance toward an inhibited fibroblast-myocyte cross-talk for collagen and transforming growth factor–beta production and enhanced collagen degradation by matrix metalloproteinase–2. Conclusions ACE2 inhibits myocardial collagen accumulation and improves LV remodeling and function in a rat model of diabetic cardiomyopathy. Thus, ACE2 provides a promising approach to the treatment of patients with diabetic cardiomyopathy.
Abstract Background Acute-on-chronic liver failure (ACLF) is a severe clinical condition for which liver transplantation (LT) is the only curative option. However, there are little published data on ...risk factors and outcomes of LT for ACLF. Methods The objective of this study was to analyze preoperative, intraoperative, postoperative, and overall survival data on 100 consecutive cases with ACLF in order to try to determine for which patients LT are futile. Results One hundred consecutive patients with pathology-confirmed ACLF who underwent LT from June 2004 to September 2012 were enrolled. The preoperative data showed that all patients were in a serious condition with a median high model for end-stage liver disease (MELD) score of 32, total bilirubin of 440.20 umol/L, international normalized ratio (INR) of 3.012, and at least one organ dysfunction as assessed by a Sequential Organ Failure Assessment (SOFA) score of ≥9. The patients had either deceased or a living donor LT with an overall mortality of 20%. The 1-, 3-, and 5-year cumulative survival rates were 76.8%, 75.6%, and 74.1%, respectively, and graft 1-, 3-, and 5-y accumulative survival rates were 73.3%, 72.1%, and 70.6%, respectively. However, the area under receiver operating characteristic of SOFA score, MELD score, as well as Child-Pugh score were 0.552, 0.547, and 0.547, respectively. Conclusions Both deceased and living donor LT are effective therapeutic options for patients with ACLF and the short- and long-term survival rates are encouraging. It is important to conduct more prospective and multi-center studies to define preoperatively which patients would benefit from LT.
BACKGROUND:Although the mechanisms and pathways mediating ARDS have been studied extensively, less attention has been given to the mechanisms and pathways that counteract injury responses. This study ...found that the apelin-APJ pathway is an endogenous counterinjury mechanism that protects against ARDS. METHODS:Using a rat model of oleic acid (OA)-induced ARDS, the effects of ARDS on apelin and APJ receptor expressions and on APJ receptor binding capacity were examined. The protective effect of activating the apelin-APJ pathway against OA- or lipopolysaccharide (LPS)-induced ARDS was evaluated. RESULTS:ARDS was coupled to upregulations of the apelin and APJ receptor. Rats with OA-induced ARDS had higher lung tissue levels of apelin proprotein and APJ receptor expressions; elevated plasma, BAL fluid (BALF), and lung tissue levels of apelin-36 and apelin-12/13; and an increased apelin-APJ receptor binding capacity. Upregulation of the apelin-APJ system has important pathophysiologic function. Stimulation of the apelin-APJ signaling using receptor agonist apelin-13 alleviated, whereas inhibition of the apelin-APJ signaling using receptor antagonist Ala-apelin-13 exacerbated, OA-induced lung pathologies, extravascular lung water accumulation, capillary-alveolar leakage, and hypoxemia. The APJ receptor agonist inhibited, and the APJ receptor antagonist augmented, OA-induced lung tissue and BALF levels of tumor necrosis factor-α and monocyte chemoattractant protein-1, and plasma and lung tissue levels of malondialdehyde. Postinjury treatment with apelin-13 alleviated lung inflammation and injury and improved oxygenation in OA- and LPS-induced lung injury. CONCLUSIONS:The apelin-APJ signaling pathway is an endogenous anti-injury and organ-protective mechanism that is activated during ARDS to counteract the injury response and to prevent uncontrolled lung injury.
Purpose This study was performed to gain some knowledge on the possible relation between surgical site infection (SSI) and geriatric patients who undergo surgical treatment of oral squamous cell ...carcinoma and to identify the risk factors in this specific population. Patients and Methods A retrospective study from 2004 through 2010 at the Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine was conducted. The primary outcome variable was the presence of SSIs. Twenty-seven variables of the patients concerning general characteristics, comorbidities, disease information, and treatment options were investigated. A multivariate analysis using logistic regression was implemented to find SSI risk factors. Results The data of 376 patients (183 men, 48.7%; 193 women, 51.3%) older than 65 years with the diagnosis of oral squamous cell carcinoma were included in the present analysis. In multivariate logistic regression analysis, 6 parameters were identified for a significant and independent association with the development of SSI: body mass index ( P = .0086); diabetes ( P < .0001); American Society of Anesthesiologists score ( P = .0127); Adult Comorbidity Evaluation-27 score ( P = .0392); operation time ( P = .0003); and reconstruction with pectoralis major myocutaneous flaps or free flaps ( P < .0001). Conclusions Special attention to SSIs should be given to elderly patients with oral squamous cell carcinoma. The authors advocate a preoperative evaluation of comorbidities and the selection of high-risk elderly patients for a more effective prevention of SSIs.
Objectives: To investigate the dosimetric advantages of the voluntary deep inspiration breath-hold technique assisted by optical surface monitoring system for whole breast irradiation in left breast ...cancer after breast-conserving surgery and verify the reproducibility and acceptability of this technique. Methods: Twenty patients with left breast cancer receiving whole breast irradiation after breast-conserving surgery were enrolled in this prospective phase II study. Computed tomography simulation was performed during both free breathing and voluntary deep inspiration breath-hold for all patients. Whole breast irradiation plans were designed, and the volumes and doses of the heart, left anterior descending coronary artery, and lung were compared between free breathing and voluntary deep inspiration breath-hold. Cone beam computed tomography was performed for the first 3 treatments, then weekly during voluntary deep inspiration breath-hold treatment to evaluate the accuracy of the optical surface monitoring system technique. The acceptance of this technique was evaluated with in-house questionnaires completed by patients and radiotherapists. Results: The median age was 45 (27-63) years. All patients received hypofractionated whole breast irradiation using intensity-modulated radiation therapy up to a total dose of 43.5 Gy/2.9 Gy/15f. Seventeen of the 20 patients received concomitant tumor bed boost to a total dose of 49.5 Gy/3.3 Gy/15f. Voluntary deep inspiration breath-hold showed a significant decrease in the heart mean dose (262 ± 163 cGy vs 515 ± 216 cGy, P < .001) and left anterior descending coronary artery (1191 ± 827 cGy vs 1794 ± 833 cGy, P < .001). The median delivery time of radiotherapy was 4 (1.5-11) min. The median deep breathing cycles were 4 (2-9) times. The average score for acceptance of voluntary deep inspiration breath-hold by patients and radiotherapists was 8.7 ± 0.9 (out of 12) and 10.6 ± 3.2 (out of 15), respectively, indicating good acceptance by both. Conclusions: The voluntary deep inspiration breath-hold technique for whole breast irradiation after breast-conserving surgery in patients with left breast cancer significantly reduces the cardiopulmonary dose. Optical surface monitoring system–assisted voluntary deep inspiration breath-hold is reproducible and feasible and showed good acceptance by both patients and radiotherapists.
Background Previous studies have shown that individuals with schizophrenia have a greater risk for psoriasis than a typical person. This suggests that there might be a shared genetic etiology between ...the 2 conditions. We aimed to characterize the potential shared genetic susceptibility between schizophrenia and psoriasis using genome-wide marker genotype data. Methods We obtained genetic data on individuals with psoriasis, schizophrenia and control individuals. We applied a marker-based coheritability estimation procedure, polygenic score analysis, a gene set enrichment test and a least absolute shrinkage and selection operator regression model to estimate the potential shared genetic etiology between the 2 diseases. We validated the results in independent schizophrenia and psoriasis cohorts from Singapore. Results We included 1139 individuals with psoriasis, 744 with schizophrenia and 1678 controls in our analysis, and we validated the results in independent cohorts, including 441 individuals with psoriasis (and 2420 controls) and 1630 with schizophrenia (and 1860 controls). We estimated that a large fraction of schizophrenia and psoriasis risk could be attributed to common variants ( h2SNP = 29% ± 5.0%, p = 2.00 × 10−8 ), with a coheritability estimate between the traits of 21%. We identified 5 variants within the human leukocyte antigen ( HLA ) gene region, which were most likely to be associated with both diseases and collectively conferred a significant risk effect (odds ratio of highest risk quartile = 6.03, p < 2.00 × 10−16 ). We discovered that variants contributing most to the shared heritable component between psoriasis and schizophrenia were enriched in antigen processing and cell endoplasmic reticulum. Limitations Our sample size was relatively small. The findings of 5 HLA gene variants were complicated by the complex structure in the HLA region. Conclusion We found evidence for a shared genetic etiology between schizophrenia and psoriasis. The mechanism for this shared genetic basis likely involves immune and calcium signalling pathways.
Early stage peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is rare. The purpose of this study was to evaluate the outcome of treatment as well as the potential role of radiation ...therapy in PTCL-NOS.
Thirty-five patients with early stage PTCL-NOS were included. There were 13 patients with stage I disease and 22 with stage II. All patients except 1 received doxorubicin-based chemotherapy alone (n=13) or a combination of chemotherapy and radiation therapy (CMT) (n=21).
The 3-year overall survival (OS) and progression-free survival (PFS) rates for the entire group were 41.3% and 25.7%, respectively. The addition of radiation therapy to chemotherapy significantly improved OS and PFS in early stage PTCL-NOS. The 3-year OS and PFS rates were 49.7% and 33.3% for CMT, compared with 23.1% (P=.042) and 15.4% (P=.035) for chemotherapy alone, respectively. The prognosis for patients who achieved a complete response (CR) was significantly better than that observed in those who did not achieve a CR.
Despite the aggressive clinical course of early stage PTCL-NOS, additional radiation therapy has a significant impact on outcome. The integration of local radiation therapy into more effective systemic therapies may further improve survival.
To assess the technical safety, adverse events, and efficacy of computed tomography (CT)-guided interstitial high-dose-rate (HDR) brachytherapy in combination with regional positive lymph node ...intensity modulated radiation therapy in patients with locally advanced peripheral non-small cell lung cancer (NSCLC).
Twenty-six patients with histologically confirmed NSCLC were enrolled in a prospective, officially approved phase 1 trial. Primary tumors were treated with HDR brachytherapy. A single 30-Gy dose was delivered to the 90% isodose line of the gross lung tumor volume. A total dose of at least 70 Gy was administered to the 95% isodose line of the planning target volume of malignant lymph nodes using 6-MV X-rays. The patients received concurrent or sequential chemotherapy. We assessed treatment efficacy, adverse events, and radiation toxicity.
The median follow-up time was 28 months (range, 7-44 months). There were 3 cases of mild pneumothorax but no cases of hemothorax, dyspnea, or pyothorax after the procedure. Grade 3 or 4 acute hematologic toxicity was observed in 5 patients. During follow-up, mild fibrosis around the puncture point was observed on the CT scans of 2 patients, but both patients were asymptomatic. The overall response rates (complete and partial) for the primary mass and positive lymph nodes were 100% and 92.3%, respectively. The 1-year and 2-year overall survival (OS) rates were 90.9% and 67%, respectively, with a median OS of 22.5 months.
Our findings suggest that HDR brachytherapy is safe and feasible for peripheral locally advanced NSCLC, justifying a phase 2 clinical trial.
Abstract Background Allograft with wire techniques showed low fusion rate in pediatric atlantoaxial fusions (AAF) in early studies. Using allograft in pediatric AAF with screw/rod constructs has not ...been reported. Thus, we compared the fusion rate and clinical outcomes in pediatric patients who underwent atlantoaxial fusions (AAF) with screw/rod constructs using either a structural autograft or allograft. Methods Pediatric patients (aged ≤12 years) who underwent AAF between 2007 and 2015 were retrospectively evaluated. Patients were divided into two groups (allograft or autograft). Clinical and radiographic results were collected from hospital records and compared. Results A total of 32 patients were included (18 allograft, 14 autograft). There were no significant group differences in age, sex, weight, diagnosis, or duration of follow-up. A similar fusion rate was achieved (allograft: 94%, 17/18; autograft: 100%, 14/14); however, the average fusion time was 3 months longer in the allograft group. Blood loss was significantly lower in the allograft group (68±8.5 ml) than in the autograft group (116±12.5 ml). Operating time and length of hospitalization were slightly (non-significantly) shorter for the allograft group. A significantly higher overall incidence of surgery-related complications was seen in the autograft group, including a 16.7% (2/14) rate of donor site-related complications. Conclusions The use of allograft for AAF was safe and efficacious when combined with rigid screw/rod constructs in pediatric patients, with a similar fusion rate to autografts and an acceptable complication rate. Furthermore, blood loss was less when using allograft and donor-site morbidity was eliminated; however, the fusion time was increased.
Radiation-induced lymphopenia is a well-recognized factor for tumor control and survival in patients with cancer. This study aimed to determine the role of radiation dose to the thymus and thoracic ...duct on radiation-induced lymphopenia.
Patients with primary lung cancer treated with thoracic radiation therapy between May 2015 and February 2020 with whole blood count data were eligible. Clinical characteristics, including age, gender, histology, stage, chemotherapy regimen, radiation dosimetry, and absolute lymphocyte count (ALC) were collected. The thymus and thoracic duct were contoured by one investigator for consistency and checked by one senior physician. The primary endpoint was radiation-induced decrease in lymphocytes, defined as the difference in ALC (DALC) before and after radiation therapy.
The data of a total of 116 consecutive patients were retrospectively retrieved. Significant correlations were found between DALC and several clinical factors. These factors include stage, chemotherapy or concurrent chemoradiation, biologically effective dose (BED), mean lung dose, mean body dose, effective dose to immune cells (EDIC), mean thymus dose (MTD), and mean thoracic duct dose (MTDD) (all P < .05). Ridge regression showed that DALC = 0.0063 × BED + 0.0172 × EDIC + 0.0002 × MTD + 0.0147 × MTDD + 0.2510 (overall P = .00025 and F = 5.85). The combination model has the highest area under the curve of 0.77 (P < .001) when fitting the logistic regression model on DALC categorized as binary endpoint. The sensitivity and specificity of the combined model were 89% and 58%, respectively.
This study demonstrated for the first time that radiation doses to the thymus and thoracic duct are strongly associated with radiation-induced lymphopenia patients with lung cancer. Further validation studies are needed to implement thymus and thoracic duct as organs at risk.
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