FXa inhibition by rivaroxaban modifies mechanisms associated with the pathogenesis of human abdominal aortic aneurysms.

AIMS: To evaluate if rivaroxaban, an oral factor Xa (FXa) inhibitor, could modify the expression in vitro of inflammatory and oxidative stress biomarkers in abdominal aortic aneurysmal (AAA) sites showing intraluminal thrombus. METHODS: AAA sites with intraluminal mural thrombus were obtained from six patients undergoing elective AAA repair. In addition, control abdominal aortic samples were obtained from six organ donors. AAA sites were incubated in the presence and absence of 50 nmol l-1 rivaroxaban. RESULTS: AAA sites showing thrombus demonstrated higher content of FXa than control. Interleukin-6 levels released from AAA [Control: median: 23.45 (interquartile range: 16.17-37.15) vs. AAA: median: 153.07 (interquartile range: 100.80-210.69) pg ml-1  mg tissue-1 , P < 0.05] and the expression levels of nitric oxide synthase 2 were significantly higher in AAA than in control. The protein expression level of NADPH oxidase subunits gp67-and gp91-phox, but did not gp47-phox, were also significantly higher in the AAA sites than in control. Addition of rivaroxaban to AAA sites explants significantly reduced the release of interleukin-6 [median: 51.61 (interquartile range: 30.87-74.03) pg ml-1  mg tissue-1 , P < 0.05 with respect to AAA alone] and the content of nitric oxide synthase 2, gp67 and gp91-phox NADPH subunits. The content of matrix metallopeptidase 9 was significantly higher in the AAA sites as compared to control. Rivaroxaban also reduced matrix metallopeptidase 9 content in AAA sites to similar levels to control. CONCLUSIONS: FXa inhibition by rivaroxaban exerted anti-inflammatory and antioxidative stress properties in human AAA sites, suggesting a role of FXa in these mechanisms associated with the pathogenesis of AAA.

Clinical standards for the management of adverse effects during treatment for TB.

BACKGROUND: Adverse effects (AE) to TB treatment cause morbidity, mortality and treatment interruption. The aim of these clinical standards is to encourage best practise for the diagnosis and management of AE.METHODS: 65/81 invited experts participated in a Delphi process using a 5-point Likert scale to score draft standards.RESULTS: We identified eight clinical standards. Each person commencing treatment for TB should: Standard 1, be counselled regarding AE before and during treatment; Standard 2, be evaluated for factors that might increase AE risk with regular review to actively identify and manage these; Standard 3, when AE occur, carefully assessed and possible allergic or hypersensitivity reactions considered; Standard 4, receive appropriate care to minimise morbidity and mortality associated with AE; Standard 5, be restarted on TB drugs after a serious AE according to a standardised protocol that includes active drug safety monitoring. In addition: Standard 6, healthcare workers should be trained on AE including how to counsel people undertaking TB treatment, as well as active AE monitoring and management; Standard 7, there should be active AE monitoring and reporting for all new TB drugs and regimens; and Standard 8, knowledge gaps identified from active AE monitoring should be systematically addressed through clinical research.CONCLUSION: These standards provide a person-centred, consensus-based approach to minimise the impact of AE during TB treatment.

Clinical standards for diagnosis, treatment and prevention of post-COVID-19 lung disease.

BACKGROUND: The aim of these clinical standards is to provide guidance on 'best practice' care for the diagnosis, treatment and prevention of post-COVID-19 lung disease.METHODS: A panel of international experts representing scientific societies, associations and groups active in post-COVID-19 lung disease was identified; 45 completed a Delphi process. A 5-point Likert scale indicated level of agreement with the draft standards. The final version was approved by consensus (with 100% agreement).RESULTS: Four clinical standards were agreed for patients with a previous history of COVID-19: Standard 1, Patients with sequelae not explained by an alternative diagnosis should be evaluated for possible post-COVID-19 lung disease; Standard 2, Patients with lung function impairment, reduced exercise tolerance, reduced quality of life (QoL) or other relevant signs or ongoing symptoms ≥4 weeks after the onset of first symptoms should be evaluated for treatment and pulmonary rehabilitation (PR); Standard 3, The PR programme should be based on feasibility, effectiveness and cost-effectiveness criteria, organised according to local health services and tailored to an individual patient's needs; and Standard 4, Each patient undergoing and completing PR should be evaluated to determine its effectiveness and have access to a counselling/health education session.CONCLUSION: This is the first consensus-based set of clinical standards for the diagnosis, treatment and prevention of post-COVID-19 lung disease. Our aim is to improve patient care and QoL by guiding clinicians, programme managers and public health officers in planning and implementing a PR programme to manage post-COVID-19 lung disease.

TB in the elderly: clinical features and outcomes.

BACKGROUND: TB in low-incidence countries is characterised by changes in age distribution towards larger numbers of cases among the elderly.OBJECTIVES: To investigate clinical features and outcomes of TB treatment in older patients and identify predictors of poor outcome.METHODS: Multicentre retrospective study of new TB cases from 53 hospitals included in the registry of the Integrated Tuberculosis Research Programme of the Spanish Society of Pulmonology and Thoracic Surgery (Sociedad Española de Neumología y Cirugía Torácica) between 2006 and 2020.RESULTS: We identified 731 patients aged ≥75 years from a cohort of 7,505 patients with TB. In the elderly, weight loss, disseminated disease and normal X-rays or infiltrates without cavitation were more common. All-cause mortality was 16% (5% of deaths due to TB). The elderly had higher rates of toxicity (6.7%) and hospital admissions (36%). In the multivariate analysis of predictors of TB mortality in ≥75-year-olds, only weight, age and treatment with non-standard regimens remained significant.CONCLUSIONS: TB in older patients needs more attention and remains a challenge because of a lack of specific clinical and radiological features. Standard treatment is effective, although mortality is higher than in young patients. Low weight, non-standard regimens and age are significant predictors of TB mortality.

Clinical standards for drug-susceptible pulmonary TB.

BACKGROUND: The aim of these clinical standards is to provide guidance on 'best practice´ for diagnosis, treatment and management of drug-susceptible pulmonary TB (PTB).METHODS: A panel of 54 global experts in the field of TB care, public health, microbiology, and pharmacology were identified; 46 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all 46 participants.RESULTS: Seven clinical standards were defined: Standard 1, all patients (adult or child) who have symptoms and signs compatible with PTB should undergo investigations to reach a diagnosis; Standard 2, adequate bacteriological tests should be conducted to exclude drug-resistant TB; Standard 3, an appropriate regimen recommended by WHO and national guidelines for the treatment of PTB should be identified; Standard 4, health education and counselling should be provided for each patient starting treatment; Standard 5, treatment monitoring should be conducted to assess adherence, follow patient progress, identify and manage adverse events, and detect development of resistance; Standard 6, a recommended series of patient examinations should be performed at the end of treatment; Standard 7, necessary public health actions should be conducted for each patient. We also identified priorities for future research into PTB.CONCLUSION: These consensus-based clinical standards will help to improve patient care by guiding clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment for PTB.

Clinical standards for the assessment, management and rehabilitation of post-TB lung disease.

BACKGROUND: Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR).METHODS: A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement).RESULTS: Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR.CONCLUSION: This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD.

Tuberculosis, COVID-19 and migrants: Preliminary analysis of deaths occurring in 69 patients from two cohorts.

Little is known about the relationship between the COVID-19 and tuberculosis (TB). The aim of this study is to describe a group of patients who died with TB (active disease or sequelae) and COVID-19 in two cohorts. Data from 49 consecutive cases in 8 countries (cohort A) and 20 hospitalised patients with TB and COVID-19 (cohort B) were analysed and patients who died were described. Demographic and clinical variables were retrospectively collected, including co-morbidities and risk factors for TB and COVID-19 mortality. Overall, 8 out of 69 (11.6%) patients died, 7 from cohort A (14.3%) and one from cohort B (5%). Out of 69 patients 43 were migrants, 26/49 (53.1%) in cohort A and 17/20 (85.0%) in cohort B. Migrants: (1) were younger than natives; in cohort A the median (IQR) age was 40 (27-49) VS. 66 (46-70) years, whereas in cohort B 37 (27-46) VS. 48 (47-60) years; (2) had a lower mortality rate than natives (1/43, 2.3% versus 7/26, 26.9%; p-value: 0.002); (3) had fewer co-morbidities than natives (23/43, 53.5% versus 5/26-19.2%) natives; p-value: 0.005). The study findings show that: (1) mortality is likely to occur in elderly patients with co-morbidities; (2) TB might not be a major determinant of mortality and (3) migrants had lower mortality, probably because of their younger age and lower number of co-morbidities. However, in settings where advanced forms of TB frequently occur and are caused by drug-resistant strains of M. tuberculosis, higher mortality rates can be expected in young individuals.

Prevention and treatment of tuberculosis infection in candidates for biologic therapy: A multidisciplinary consensus statement adapted to the dermatology patient. / Consenso multidisciplinar sobre prevención y tratamiento de la tuberculosis en pacientes candidatos a tratamiento biológico. Adaptación al paciente dermatológico.

Patients with chronic inflammatory diseases being treated with immunosuppressive drugs, and with tumor necrosis factor inhibitors in particular, have an increased risk of infection by Mycobacterium tuberculosis. Screening for latent tuberculosis infection and preventive therapy to reduce the risk of progression to active tuberculosis are mandatory in this group of patients. This updated multidisciplinary consensus document presents the latest expert opinions on the treatment and prevention of tuberculosis in candidates for biologic therapy and establishes recommendations based on current knowledge relating to the use of biologic agents.

Factors Associated with Fatality during the Intensive Phase of Anti-Tuberculosis Treatment.

OBJECTIVE: To determine the case-fatality rate (CFR) at the end of the intensive phase of tuberculosis (TB) treatment, and factors associated with fatality. METHODS: TB patients diagnosed between 2006 and 2013 were followed-up during treatment. We computed the CFR at the end of the intensive phase of TB treatment, and the incidence of death per 100 person-days (pd) of follow-up. We performed survival analysis using the Kaplan-Meier method and Cox regression, and calculate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: A total of 5,182 patients were included, of whom 180 (3.5%) died; 87 of these deaths (48.3%) occurred during the intensive phase of treatment, with a CFR of 1.7%. The incidence of death was 0.028/100 pd. The following factors were associated with death during the intensive phase: being >50 years (HR = 36.9;CI:4.8-283.4); being retired (HR = 2.4;CI:1.1-5.1); having visited the emergency department (HR = 3.1;CI:1.2-7.7); HIV infection (HR = 3.4;CI:1.6-7.2); initial standard treatment with 3 drugs (HR = 2.0;CI:1.2-3.3) or non-standard treatments (HR = 2.68;CI:1.36-5.25); comprehension difficulties (HR = 2.8;CI:1.3-6.1); and smear-positive sputum (HR = 2.3-CI:1.0-4.8). CONCLUSION: There is a non-negligible CFR during the intensive phase of TB, whose reduction should be prioritised. The CFR could be a useful indicator for evaluating TB programs.

Clinical utility of hyaluronic acid values in serum and bronchoalveolar lavage fluid as tumor marker for bronchogenic carcinoma.

Various authors have proposed the use of hyaluronic acid (HA) as a tumor marker. In order to analyze its usefulness as a marker in bronchogenic carcinoma, the most common carcinoma in men, we determined the HA values in serum and bronchoalveolar lavage fluid (BAL). We performed prospective studies on two groups of patients: 81 diagnosed as having bronchial carcinoma and 34 with benign respiratory diseases. HA values were higher in patients with cancer than in those with benign diseases (serum: 79.8 ng/ml vs 63.7 ng/ml; BAL: 927 ng/mg vs 522 ng/mg). Also, the percentage of patients with levels exceeding the established cutoff was greater in the group with cancer than in the group with benign disease (serum: 24.6 vs 17.6; BAL: 25.3 vs 3). Statistically significant differences in these percentages were found in BAL (p<0.01). Patients with extended small cell carcinoma had higher HA values (p =0.04) than those with limited disease, and the percentage of patients with abnormal HA values was larger in the group with extended disease than in the group with limited disease (p = 0.004). The serial determinations of HA values in serum reflected the clinical evolution after treatment in 73% of the small cell carcinomas. Most of the patients with benign diseases whose HA values exceeded the cutoff level suffered from acute infectious dis-eases. Once these cases were excluded, the specificity of HA value determination in the diagnosis of carcinoma was very high (serum 96%, BAL 100%). The determination of HA levels in serum or BAL did not have any prognostic value in this study. We conclude that the HA levels in serum and BAL could be of interest as a tumor marker, especially in patients with small cell carcinoma.

[Acute pericarditis as the initial presentation of a primary cardiac angiosarcoma. The anatomicoclinical correlations]. / Pericarditis aguda como presentación inicial de un angiosarcoma primario cardíaco. Correlaciones anatomoclínicas.

We report the clinic and postmortem pathologic examination of a 38-years-old man with a primary angiosarcoma of right atrium and many widespread metastatic. Both his presentation, a clinical course of acute pericarditis self-limited, as the negatives complementary examination, give at case unusual characteristics, for his high malignancy.

[Aortic prosthetic endocarditis and periprosthetic abscess caused by Staphylococcus aureus]. / Endocarditis protésica aórtica y absceso periprotesico por Staphylococcus aureus.

Prosthetic endocarditis with annular abscess formation is a severe complication of cardiac valve replacement fortunately uncommon, though highly lethal. Increasing surgical experience and the high mortality with medical management have led to a widespread recommendation for early prosthetic replacement. We report a case of a 49 year old man with infective endocarditis due to Staphylococcus aureus in aortic ascendens prosthetic and aortic valve prosthetic complicated with periaortic abscess which was as successful treatment by drain of abscess without prosthetic replacement.

[Localized tracheobronchial amyloidosis. The usefulness of computed tomography]. / Amiloidosis traqueobronquial localizada. Utilidad de la tomografía computarizada.

Tracheobronchial amyloidosis is the most common form of localized bronchopulmonary amyloidoses, although its diagnosis is rare in daily practice. We describe two new cases of localized tracheobronchial amyloidosis, one in the form of a single node and one diffuse. We discuss in particular the contribution of computed axial tomography, mainly for diagnosing the diffuse form, in which a finding of a thickened tracheobronchial wall and intraluminal nodes should lead to the suspicion of this entity. The treatment of choice in most cases is resection with an Nd-YAG laser.

[Pulmonary interstitial disease due to hemochromatosis as a presenting sign of disease]. / Afectación intersticial pulmonar por hemocromatosis como forma de presentación de la enfermedad.

We present a patient with hemochromatosis whose first sign of disease was an accidental finding of interstitial patterns on a chest film and whose transbronchial biopsy showed traces of iron (Fe) in alveolar macrophages and septal matter. We then looked for deposits in other locations, finding Fe ([+]: 6.964 micrograms) in the dry weight of a cylindrical sample of liver tissue. A Medline search on CD-ROM for 1989 through May of 1994 revealed no references to similar cases.

[Primary angiosarcoma of the spleen]. / Angiosarcoma primitivo de bazo.

Primary spleen angiosarcoma is a malignant neoplasia based on vascular tissue and it is a rare tumor (65 cases published). The clinical aspects are obscure and the specific diagnosis is made by laparotomy. The prognosis is very poor in any case and survival isn't more than two years, whenever the spleen undergoes spontaneous rupture in which case the survival should be less than six months. The splenectomy before rupture could increase survival. Patients with or without metastatic disease may be treated by chemotherapy but with poor results. Radiotherapy is used for relief the pain produced for bone metastasis.

[Angina-like chest pain due to gastric anisakiasis]. / Dolor torácico como manifestación inicial de anisakiasis gástrica.

The chest pain is one of the most common reasons for consultation of the patients seen in the emergency services of hospitals. Still being the acute coronary syndrome one of the first causes to confirmed by its important repercussions, we do not have to forget other reasons. We report a case of acute anginalike chest pain due to gastric anisakiasis. The larvae of Anisakis in the gastric mucosa were found and extracted endoscopically. Gastric anisakiasis should be included in the differential diagnosis of acute chest pain.

[Spontaneous pneumothorax as the only initial manifestation of bronchogenic carcinoma]. / Neumotórax espontáneo como única manifestación inicial del carcinoma broncogénico.

We present the case of a patient with spontaneous pneumothorax associated to pulmonary epidermoid carcinoma, which was not radiologically visible after pulmonary reexpansion. Neither it was macroscopically detected in the first thoracotomy performed for the treatment of the pneumothorax, being diagnosed after the histological study of the resected blisters. The association between pneumothorax and lung cancer is very rare, especially in the absence of other radiological disorders suggesting neoplasia after the pulmonary reexpansion. In these cases, the diagnosis is extremely difficult and it must be always suspected in patients with spontaneous pneumothorax and risk factors for pulmonary cancer.

[Results and complications of pertrochanteric hip fractures using an intramedullary nail with a helical blade (proximal femoral nail antirotation) in 200 patients]. / Resultados y complicaciones de la osteosíntesis de fracturas pertrocantéreas de fémur mediante clavo endomedular con espiral cefálica (clavo femoral proximal antirrotación) en 200 pacientes.

OBJECTIVES: Evaluation of the surgical management, outcome and complications in patients with pertrochanteric fractures treated with PFNA nail. MATERIAL AND METHOD: A retrospective study was conducted on 200 patients treated consecutively between April 2010 and February 2012. Radiological assessments were performed before and after the surgery, and during the follow-up (fracture reduction, blade position, consolidation or collapse signs). A clinical evaluation was performed as regards walking capabilities. The results were compared with those of a previous study on 700 patients treated with gamma 3 and TFN nails. RESULTS: The blade position was centre-centre in 64% of patients, and decreased to 53% in the mechanical complications group. Tip-apex distance was less than 25mm in 91.5%. The average hospital stay was 9.17 days, with a mean post-surgery stay of 5.95 days. Complications (7.5%): 2 cut out (1%), one cut through (0.5%), 4 cases of helical blade sliding (2%), one failure in distal locking procedure (0.5%), 2 cases with painful fasciae latae (1%), one union delay (0.5%), 2 cases of non-union with hardware failure (1%), one case of intense bleeding related to distal locking of the nail (0.5%), and one case of avascular necrosis (0.5%). CONCLUSIONS: The PFNA helical blade system seems to reduce the incidence of cut out and cut through in osteoporotic bone. Blade position was one of the main parameters associated with mechanical complications.

Novel poly(hydroxyalkanoates)-based composites containing Bioglass® and calcium sulfate for bone tissue engineering.

Three different poly(hydroxyalkanoates) (PHAs), copolymers of poly(3-hydroxybutyrate) (P3HB), have been used to make composites using two different fillers, bioactive glass (type 45S5 Bioglass®) and calcium sulfate dihydrate. The PHAs used were poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [PHBHV] and two copolymers of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) [PHBHHx]. The aim of the study was the fabrication and characterization of the new composites and the assessment of the influence of the particular filler combination on the physical properties and bioactivity of the films. The thermal behaviour was studied using differential scanning calorimetry while mechanical properties were evaluated using dynamic mechanic thermal analysis and tensile strength test. The mechanical and thermal properties were affected by particles addition. The distribution of the particles in the polymer matrix, observed by scanning electron microscopy, was directly related to the mechanical properties. The surface characteristics were investigated by contact angle measurements and Raman spectroscopy. The extent of formation of hydroxyapatite (HA) upon immersion in simulated body fluid (SBF) depended on the polymer used, the amount of fillers employed and the time of immersion in SBF. Bioactivity was enhanced in the composites with a rise of hydrophilicity. The HA formation was controllable with time in the case of PHBHHx composites.