Combined measurements of N-terminal pro-brain natriuretic peptide and cardiac troponins in potential organ donors

Objective Brain death may induce cardiac dysfunction. In potential organ donors measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP) and circulating cardiac troponins T and I (cTnT and cTnI), alone or in combination, are performed to investigate the accuracy of these biomarkers for early diagnosis of left ventricular systolic dysfunction. Design and setting Prospective study in a multidisciplinary intensive care unit of an university hospital. Patients 63 brain-dead patients scheduled for multiple organ harvesting. Measurements and results We measured NT-proBNP, cTnT, and cTnI and determined fractional area change (FAC) using transesophageal echocardiography. Forty-five patients had normal FAC, 9 a moderate decrease in FAC (30–50), and 9 a severe decrease in FAC (≤ 30%). NT-proBNP and cTnT concentrations were significantly higher in patients with a severe decrease in FAC than in those with a moderate decrease. Combining measurements of these two biomarkers, the sensitivity of the test to predict severe decrease in FAC increased significantly to reach 1.00 compared with the sensitivities of individual measurements. The ROC curve area of combined measurements of NT-proBNP and cTnT was significantly higher than single measurements: 0.87 vs. 0.82 for NT-proBNP, 0.78 for cTnT, and 0.72 for cTnI. Conclusions In potential organ donors the combined measurement of NT-proBNP and cTnT concentrations is more accurate than individual measurement of NT-proBNP, cTnT, and cTnI in the early diagnosis of severe left ventricular systolic dysfunction. These findings may lead to improve the quality of cardiac care of the potential organ donors.     

Differentiated Thyroid Cancer With Liver Metastases: Lessons Learned From Managing a Series of 14 Patients

Liver metastases from differentiated thyroid carcinoma (LMDTC) are rare and usually occur in disseminated metastatic disease. The aim of this study was to review the diagnosis and management of LMDTC. Between 1995 and 2011, 14 patients with a mean age of 59.7 years (+/-10.2) were treated for LMDTC. Data were retrospectively reviewed and analyzed. Seven patients had distant metastases at diagnosis, including 2 with synchronous liver lesions. The average time of onset of LMDTC from initial diagnosis was 52.2 months (+/49.5). All LMDTC were discovered during routine radiologic monitoring. Histologic analysis confirmed LMDTC in 5 patients. Eight patients received tyrosine kinase inhibitors, 1 patient underwent resection of their LMDTC after chemotherapy. Six patients (disseminated metastases, significant comorbidities) did not receive any specific treatment. The median survival after diagnosis of LMDTC was 17.4 months (+/-3.3): 23.6 months (+/-2.9) for patients who underwent chemotherapy versus 3.9 months (+/-0.9) for patients who did not receive any specific treatment (P < 0.001). Developing DTC liver metastasis is a very poor prognostic sign. Chemotherapy by TKIs, especially, hold promise in the cure of LMDTC for selected patients.Key words: Liver metastasis, Thyroid carcinomaDifferentiated thyroid carcinoma, encompassing follicular and papillary carcinomas, has a good prognosis and long-term survival rates. Indeed, the 10-year survival rate is 80–95%. The incidence of distant metastases at the time of initial presentation of differentiated thyroid carcinoma (DTC) is 4%. During the course of treatment and follow-up, the prevalence of distant metastases ranges from 2% in low-risk patients, to 33% in high-risk patients. Distant metastases occur primarily in the lungs and, to a lesser extent, in bones. The presence of distant metastases is the most significant prognostic factor and is associated with poor outcomes. Only 50% of patients survive 10 years after a diagnosis of the metastatic DTC.^1–3Liver metastases from differentiated thyroid carcinoma (LMDTC) are rare, with a reported frequency of 0.5%. They tend to occur during the terminal phase of the disease are a grave event. Survival ranges from 1 to 60 months after diagnosis of LMDTC in the largest series of 11 cases.⁴Because of this rarity, there is little information available on the diagnosis and management of LMDTC. We have therefore undertaken a retrospective, multicenter study on LMDTC and analyzed factors affecting survival.     

Risk factors for surgical site infection after groin hernia repair: does the mesh or technique matter?

Hernia - Surgical site infections (SSIs) following groin hernia repair (GHR) are getting rarer in high income countries despite a wider use of meshes. Among the risk factors for SSIs, those related...     

Use of a Smartphone Self-assessment App for a Tobacco-Induced Disease (COPD,Cardiovascular Diseases,Cancer) Screening Strategy and to Encourage Smoking Cessation: Observational Study

BackgroundPatient self-assessment via a mobile app detects actionable symptoms and has been shown to detect lung cancer relapses early, thereby lengthening survival.ObjectiveThe purpose of this study was to assess the incidence of chief symptoms associated with the main tobacco-induced pathologies in both current and ex-smokers through a self-assessment smartphone app and to evaluate the app’s capacity to encourage users to quit smoking or reduce consumption, as well as its impact on early lung cancer stages at the time of diagnosis.MethodsCurrent and ex-smokers were recruited through an advertising campaign in Sarthe county (France) proposing the free download of a smartphone app. App users were asked to answer 13 questions related to symptoms associated with tobacco-induced diseases (chronic obstructive pulmonary disease [COPD], cardiovascular diseases, cancer). In the event of any positive answer, a message was displayed recommending the user to consult a physician. In addition, they were asked about smoking cessation intention before and after answering these 13 questions. Finally, incidence of stage 1 or 2 lung cancers diagnosed during the launch period of our application was evaluated by comparing data from various sources to those from the same period during the previous year.ResultsOf the 5671 users who were eligible for evaluation, an alert was sent to the majority (4118/5671, 72.6%), with a higher incidence for current smokers (2833/3679, 77.0% vs 1298/1992, 65.2%; P<.001). The most frequent symptoms triggering the notifications were fatigue (2023/5671, 35.7%), cough (1658/5671, 29.2%), dyspnea (1502/5671, 26.5%), and persistent chest pain (1286/5671, 22.7%). Of the current smokers, 14.0% (515/3679) showed symptoms suggesting COPD, 15.5% (571/3679) showed symptoms suggesting stable angina, 12.4% (455/3679) probably had lower extremity artery disease, and 6.8% (249/3679) had possible cancer. Of the users, 36.5% (1343/3679) claimed that they thought about quitting smoking, and 48.7% (1795/3679) had thought about reducing their consumption. Surgery-eligible stage 1 and 2 lung cancer incidence was 24% (14/58) during the study period versus 9% (5/54) during the previous year in Sarthe county (P=.04), whereas it remained unchanged in the neighboring county of Maine-et-Loire.ConclusionsA majority of current and ex-smokers showed worrying symptoms, and the use of a self-assessment smartphone app may drive a majority of smokers toward the intention of smoking cessation or decreasing consumption. A randomized study should be performed to confirm this intention and to support the potential increase of symptomatic lung cancer detection at early, surgery-accessible stages.Trial RegistrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT04048954","term_id":"NCT04048954"}}NCT04048954; https://www.clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT04048954","term_id":"NCT04048954"}}NCT04048954     

Conjunctival epithelial cells from patients with Sjögren's syndrome inappropriately express major histocompatibility complex molecules,La(SSB) antigen,and heat-shock proteins

The La(SSB) antigen has been detected within the cytoplasm and on the membrane of conjunctival cells (CC) from patients with Sjögren's syndrome, whereas it was weakly expressed in the nucleus of normal cells. The diseased CC were shown to overproduce major histocompatibility complex (MHC) class I antigens and express MHC class II antigens. Anti-heat-shock protein monoclonal antibody bound to the cell membrane in patients but not in normal controls.On sabbatical leave from Department of Internal Medicine, Medical School, Ioannina, Greece.     

Spontaneous vitiligo in an animal model for human melanoma: role of tumor-specific CD8+ T cells

Tumor antigen-reactive T cells can be detected in a large proportion of melanoma patients, but their efficacy on tumor control in vivo remains unclear. On the other hand, vitiligo, a skin disorder characterized by patchy depigmented macules, may occur spontaneously or after antitumor therapies. Moreover, vitiligo is significantly associated with positive clinical response, but the mechanism is not understood. Therefore, the establishment of a relevant animal model in which melanoma and vitiligo spontaneously develop stepwise may be useful for better understanding of the parameters involved in the destruction of both benign and malignant melanocytes. In a previous work, we established a mouse model for melanoma in which MT/ret transgenic mice express the ret oncogene fused to the metallothionein promoter. Here we report that melanoma leads to spontaneous vitiligo. We further investigate, for the first time in this model, the natural antitumor T-cell response and evaluate the role of cellular immunity in the development of the disease. Interestingly, the occurrence of spontaneous tumor nodules in MT/ret mice with melanoma-associated vitiligo is significantly delayed when compared in melanoma mice without vitiligo. Moreover, a significant proportion of mice with melanoma-associated vitiligo resisted a challenge with syngeneic melanoma cells in contrast to animals without vitiligo. Our results confirm that vitiligo is associated with clinical benefit and further demonstrate the crucial role of CD8+ T cells for tumor control in melanoma-associated vitiligo.     

The tumor invasion inhibitor dihydromotuporamine C activates RHO, remodels stress fibers and focal adhesions, and stimulates sodium-proton exchange

The motuporamines are macrocyclic alkaloids that inhibit tumor cell invasion by an, as yet, unknown mechanism. A structure-activity study recently identified dihydromotuporamine C (dhMotC) as a highly active and readily synthesized analogue. Here, we show that dhMotC causes subtle cytoskeletal alterations in highly invasive MDA231 breast tumor cells that include an increase in the thickness and number of cytoplasmic actin stress fibers. Experiments with serum-starved Swiss 3T3 fibroblasts showed that micromolar concentrations of dhMotC that inhibit tumor cell invasion induce the formation of new stress fibers and large focal adhesion complexes that are dispersed around the entire cell periphery. dhMotC treatment of Swiss 3T3 cells also initiates a strong, long-lived activation of the small GTP-binding protein Rho, and it stimulates Rho kinase-dependent sodium-proton exchanger activity. Liposome-mediated cell loading of C3 exoenzyme prevents dhMotC-mediated Rho activation and stress fiber formation in 3T3 cells. C3 exoenzyme loading also reestablishes elongated MDA231 breast tumor cell invasion in the presence of dhMotC. Taken together, these results indicate that the ability to activate Rho is one important determinant of the anti-invasive activity of dhMotC.     

Combination of DNA repair gene single nucleotide polymorphisms and increased levels of DNA adducts in a population-based study.

Inherited single nucleotide polymorphisms (SNPs) of DNA repair genes may contribute to variations in DNA repair capacity and susceptibility to cancer. We investigated the role of SNPs in three DNA repair genes (X-ray repair cross-complementing group 1-Arg399Gln, exon 10; X-ray repair cross-complementing group 3-Thr241Met, exon 7; and xeroderma pigmentosum-D-Lys751Gln, exon 23) and their combination, in modulating the levels of "bulky" DNA adducts in a population sample of 628 Italian healthy individuals belonging to the prospective European project "European Prospective Investigation into Cancer and Nutrition." DNA-adduct levels were measured as relative adduct level per 10(9) nucleotides by (32)P-post DNA labeling assay in WBCs from peripheral blood. Genotyping was performed by PCR-RFLP analysis or primer extension/denaturing high-performance liquid chromatography technique. We found a dose-response relationship between the number of at-risk alleles and levels of adducts (P = 0.0046). Individuals with at least three variant alleles had a statistically significant odds ratio (OR) for being in the highest tertile of adducts compared with those with undetectable adducts [three alleles, adjusted OR = 5.07, 95% confidence interval (CI) = 1.29-19.9; four alleles, adjusted OR = 5.03, 95% CI = 1.18-21.45; five alleles, adjusted OR = 7.65, 95% CI = 0.94-62.2]. Our study suggests that the combined effect of multiple variant alleles may be more important than the investigation of single SNP in modulating DNA repair capacity.     

Sarcoidosis of the upper respiratory tract in children

Sarcoidosis is a multisystemic granulomatosis of unknown etiology which mainly affects young adults. It is characterized primarily by bilateral hilar adenopathies, a pulmonary infiltrate and cutaneous and ocular lesions. It rarely occurs in children under the age of 16. Localization in the upper respiratory tract (URT) is infrequent and sarcoidosis of the URT in children is exceptional, with only 13 cases reported in the literature. In the present report we describe the clinical, diagnostic explorations, histological and therapeutic aspects of 2 new cases in children.