Usefulness of the N-Terminal Fraction of Brain Natriuretic Peptide for Deciding When to Refer Patients With Sleep Apnea-Hypopnea Syndrome to the Cardiologist

Introduction and objectiveWhen sleep apnea-hypopnea syndrome (SAHS) and cardiovascular disease occur concurrently, prognosis is affected. Echocardiography can detect structural cardiac abnormalities but using this technique in all patients would place a heavy burden on resources. The objective of this study was to investigate whether the N-terminal fraction of brain natriuretic peptide (NT-proBNP) can be used as a marker for silent heart disease.Patients and methodsNT-proBNP concentration was measured in the 114 consecutive patients with SAHS who underwent echocardiography before starting treatment. Left and right ventricular systolic and diastolic function, as well as structural abnormalities, were studied. Correlations between NT-proBNP concentration and the abnormalities detected were investigated. A receiver operating characteristics (ROC) curve was plotted for NT-proBNP concentration and cardiac abnormalities.ResultsData for 98 patients were finally analyzed. NT-proBNP concentration was significantly correlated with ventricular septal thickness (r=0.63), posterior wall thickness (r=0.45), and left ventricular enddiastolic diameter (r=0.51) (P<.0001 for all correlations). The area under the ROC curve was significant (0.870; 95% confidence interval, 0.801-0.939; P<.0001). Assuming that specificity would be more useful for clinical practice, we calculated that NT-proBNP concentrations below 100 and 200 pg/mL could rule out structural abnormalities with a reliability of 90% and 100%, respectively.ConclusionsNT-proBNP concentration was strongly correlated with echocardiographic abnormalities and so could be a useful tool for identifying patients who should be referred to the cardiologist.     

Multidimensional approach to the differences between muscular and articular temporomandibular patients: coping, distress, and pain characteristics.

OBJECTIVE: This study analyzes the differences in psychological variables and symptomatology between temporomandibular disorder diagnosis subgroups. STUDY DESIGN: The sample included 114 temporomandibular disorder patients that were evaluated in coping, distress, and temporomandibular characteristics. Diagnostic muscular (n = 58) and articular (n = 56) subgroups were compared in these variables through a MANCOVA. RESULTS: Muscular patients show a higher level of general distress, specifically in the anxiety and somatization subscales and a more active coping style, with a tendency of a minor use of humor and a higher number of parafunctional habits, specifically, biting nails, hangnails, and lips. CONCLUSION: We discuss the differences found in order to design the targets of the psychological intervention of temporomandibular patients.     

Mature eosinophils stimulated to develop in human-cord blood mononuclear cell cultures supplemented with recombinant human interleukin-5. II. Vesicular transport of specific granule matrix peroxidase, a mechanism for effecting piecemeal degranulation.

The mechanism of piecemeal degranulation by human eosinophils was investigated. Mature eosinophils that developed in rhIL-5-containing conditioned media from cultured human cord blood mononuclear cells were prepared for ultrastructural studies using a combined technique to image eosinophil peroxidase by cytochemistry in the same sections on which postembedding immunogold was used to demonstrate Charcot-Leyden crystal protein. Vesicular transport of eosinophil peroxidase from the specific granule matrix compartment to the cell surface was associated with piecemeal degranulation. This process involved budding of eosinophil peroxidase-loaded vesicles and tubules from specific granules. Some eosinophil peroxidase that was released from eosinophils remained bound to the cell surface; some was free among the cultured cells. Macrophages and basophils bound the released eosinophil peroxidase to their plasma membranes, internalized it in endocytotic vesicles, and stored it in their respective phagolysosomes and secretory granules. Charcot-Leyden crystal protein was diffusely present in the nucleus and cytoplasm of IL-5-stimulated mature eosinophils. Extensive amounts were generally present in granule-poor and subplasma membrane areas of the cytoplasm in contrast to eosinophil peroxidase, which was secreted and bound to the external surface of eosinophil plasma membranes. These studies establish vesicular transport as a mechanism for emptying the specific eosinophil granule matrix compartment during IL-5-associated piecemeal degranulation.     

Pharmacophore Selection and Redesign of Non-nucleotide Inhibitors of Anthrax Edema Factor

Antibiotic treatment may fail to protect individuals, if not started early enough, after infection with Bacillus anthracis, due to the continuing activity of toxins that the bacterium produces. Stable and easily stored inhibitors of the edema factor toxin (EF), an adenylyl cyclase, could save lives in the event of an outbreak, due to natural causes or a bioweapon attack. The toxin’s basic activity is to convert ATP to cAMP, and it is thus in principle a simple phosphatase, which means that many mammalian enzymes, including intracellular adenylcyclases, may have a similar activity. While nucleotide based inhibitors, similar to its natural substrate, ATP, were identified early, these compounds had low activity and specificity for EF. We used a combined structural and computational approach to choose small organic molecules in large, web-based compound libraries that would, based on docking scores, bind to residues within the substrate binding pocket of EF. A family of fluorenone-based inhibitors was identified that inhibited the release of cAMP from cells treated with EF. The lead inhibitor was also shown to inhibit the diarrhea caused by enterotoxigenic E. coli (ETEC) in a murine model, perhaps by serving as a quorum sensor. These inhibitors are now being tested for their ability to inhibit Anthrax infection in animal models and may have use against other pathogens that produce toxins similar to EF, such as Bordetella pertussis or Vibrio cholera.     

A phase 1/2 trial of ibrutinib in combination with pembrolizumab in patients with mismatch repair proficient metastatic colorectal cancer

Background MMR proficient (pMMR) colorectal cancer (CRC) is usually unresponsive to immunotherapy. Recent data suggest that ibrutinib may enhance the anti-tumour activity of anti-PD-1 immunotherapy. In this study, we evaluated the safety and efficacy of ibrutinib plus pembrolizumab in refractory metastatic CRC.Methods This was a phase 1/2 study in patients with refractory metastatic pMMR CRC. The primary endpoints for phases 1 and 2 were maximum tolerated dose (MTD) and disease control rate, respectively. The secondary endpoints were safety, progression-free survival (PFS) and overall survival (OS).Results A total of 40 patients were enrolled. No dose-limiting toxicity was observed, and MTD was not identified. The highest tested dose of ibrutinib, 560 mg once daily, was combined with a fixed dose of pembrolizumab 200 mg every 3 weeks for the phase 2 portion. The most common grade 3/4 treatment-related adverse events were anaemia (21%), fatigue (8%) and elevated alkaline phosphatase (8%). Among 31 evaluable patients, 8 (26%) achieved stable disease, and no objective response was observed. The median PFS and OS were 1.4 and 6.6 months, respectively.Conclusion Ibrutinib 560 mg daily plus pembrolizumab 200 mg every 3 weeks appears to be well tolerated with limited anti-cancer activity in metastatic CRC.ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT03332498","term_id":"NCT03332498"}}NCT03332498.Subject terms: Cancer immunotherapy, Colorectal cancer     

Disseminated adiaspiromycosis: case report of a liver transplant patient with human immunodeficiency infection,and literature review

I. Pelegrín, J. Ayats, X. Xiol, M. Cuenca‐Estrella, A. Jucglà, S. Boluda, N. Fernàndez‐Sabé, A. Rafecas, F. Gudiol, C. Cabellos. Disseminated adiaspiromycosis: case report of a liver transplant patient with human immunodeficiency infection, and literature review.
Transpl Infect Dis 2011: 13: 507–514. All rights reserved Abstract: Disseminated adiaspiromycosis is a rare infection that is sometimes associated with immunocompromised situations. We report the case of a patient, infected with human immunodeficiency virus and receiving highly active antiretroviral therapy, who had a liver transplant for hepatocellular carcinoma. The patient presented skin and pulmonary lesions due to adiaspiromycosis during immunosuppressive therapy. A review of >60 cases in the literature shows that adiaspiromycosis is a rare infection and Emmonsia is a dimorphic fungus that is difficult to grow. It should be considered a possible diagnosis in case of fungal infection and pulmonary granulomatosis. We should be aware of emerging adiaspiromycosis in patients with risk factors of immunosuppression, particularly transplant recipients. In these patients in particular, liposomal amphotericin B therapy should be considered.     

A Web-Based Survey of Oculoplastic Surgeons Regarding the Management of Lower Lid Retraction

Purpose: To survey the opinion of oculoplastic surgeons on the assessment and management of lower eyelid retraction (LLR).

Methods: A web-based survey queried oculoplastic surgeon members of Ojoplast, Spanish and Brazilian Oculoplastic Societies on the management of LLR. The frequency and percentage proportions of the responses were analyzed.

Results: One hundred ninety-six oculoplastic surgeons participated in the survey. The main cause of LLR is post-blepharoplasty (62;31.6%). The most used sign to detect LLR is scleral show. The most common approaches to managing LLR are lateral canthal surgery (164/593;27.6%), autogenous spacers (148/593; 24.9%) and retractor release (131/593;22.1%). The preferred autogenous graft material includes ear cartilage (102/260;39.2%). The majority of surgeons (161/314; 51.3%) recommend massage or steroids injection (80/314;25.5%) for early post-blepharoplasty LLR, while, 54.1% (106/196) of participants suggested waiting for at least six months prior to surgical intervention. Frost suture is used after most LLR surgeries (154/196;91.1%). Incomplete correction is the main complication (111/310;35.8%) of LLR surgery. For mild LLR, 48% of the responders prefer clinical treatment; conversely, severe cases routinely require combined surgical techniques.

Conclusions: Oculoplastic surgeons frequently diagnose LLR based on scleral show. LLR management depends on the cause and severity of lid retraction. Mild cases, in general, receive clinical treatment and severe cases need a combination of surgical techniques and grafts.     

Ethical Concerns of Congresses and Joint Winter Meetings of the Spanish Society of Pneumology and Thoracic Surgery

The pharmaceutical industry contributes to the development of new drugs, provides funding for research and collaborates in continuing medical education. Although this relationship with medical practice is beneficial and desirable, commercial interests could potentially eclipse patient benefits and compromise professional integrity. Congresses and meetings of the Spanish Society of Pneumology and Thoracic Surgery (SEPAR) agglutinate different spheres of knowledge, including aspects such as bioethics, management and communication, always centered on patient and their well-being. SEPAR congresses and meetings should provide sufficient economic benefits to be reinvested in research and other purposes which are reflected in SEPAR statutes in order to ensure the solvency, sustainability and economic independence of the Society. SEPAR has developed strict regulations governing the sponsorship and accreditation of training activities while striving for a balance between the interests of the industry and its own necessary independence, which results from the constant concern for maintaining good medical practice and complying with ethical aspects. This regulation is useful from an organizational and logistical standpoint, and it is necessary to prevent or resolve any possible conflicts of interest. Scientific societies should regulate common practices that could potentially result in conflicts of interest.