Position statement: asthma in Latin America. IS short-acting beta-2 agonist helping or compromising asthma management?

In Latin-America, with 603 million inhabitants, the average prevalence of asthma is estimated at 17%, but with wide fluctuations, ranging from 5% in some cities (Mexico) to 30% in Costa Rica. The risk of severe exacerbations seems to be higher in Latin America compared with other regions. A majority of patients uses daily quick-relief medication, with the belief that it is the most important treatment because of its rapid onset of action; without treating the underlying inflammation. Overuse of short-acting beta2 agonists (SABAs) is associated with increased risk of asthma deaths in a dose-response manner. Beta2 agonists increase the severity of asthma through enhanced bronchial hyperresponsiveness and reduced lung function. Also, it has been shown that overreliance on SABA delays recognition of a potentially life-threatening asthma attack. We believe that overreliance on SABA in asthma is also an important public health issue. The fact that SABA use in GINA is not supported by a randomized trial but by an anonymous paper; makes us guess that we use SABA just because we are used to do so. In 2019 GINA strategy introduces one of the most important changes in the management of Asthma in the past 30 years, highlighting anti-inflammatory reliever therapy. A combination of low dose ICS/fast action bronchodilator will not only treat symptoms, but more importantly the underlying inflammation, protecting patients from preventable asthma attacks. After 50 years of a SABA centric approach in asthma management, it is time to leave behind a treatment based just on the bronchodilation and tackle the inflammation.

Tratamiento quirúrgico de las fracturas periprotésicas de húmero y algoritmo de actuación / Surgical treatment of periprosthetic humerus fractures and algorithm

INTRODUCCIÓN: Las fracturas periprotésicas de húmero son infrecuentes y su manejo, difícil. La bibliografía es limitada y no existe consenso sobre su tratamiento. MATERIAL Y MÉTODO: Hemos realizado un estudio observacional retrospectivo de 10pacientes con fractura periprotésica de húmero con un seguimiento de 25,1 meses (6-87). Valoramos los resultados clínicos, radiológicos y funcionales, como las complicaciones. Utilizamos el cuestionario Quick-DASH y UCLA Shoulder Score (UCLASS). Realizamos una búsqueda sistemática para comparar la serie presentada y los protocolos de tratamiento publicados. RESULTADOS: Diez pacientes con una media de edad de 69,4 años (37-91) fueron intervenidos quirúrgicamente: 8 mediante reducción abierta y fijación interna (RAFI), en otro se realizó un recambio protésico colocando una nueva prótesis con un vástago más largo, y en el último se retiró la prótesis y se realizó una osteosíntesis con un clavo endomedular. Nueve de 10 pacientes consolidaron en un tiempo de 6,2 meses (rango 5-12); el restante sufrió una nueva fractura 5 meses después, siendo reintervenido, realizándole una nueva osteosíntesis, con aporte de aloinjerto óseo, que consolidó a los 8meses de la última fractura. En relación con la situación previa a la fractura, los pacientes tenían como promedio un descenso notable de la función, que era de 10,66 puntos en el test de UCLASS y un ascenso de 27,3 puntos en el cuestionario Quick-DASH. CONCLUSIONES: Nuestra serie tiene similitudes con las publicadas en relación con los aspectos demográficos, las complicaciones y el tiempo de consolidación. Sin embargo, en otros aspectos, como el dolor y los resultados funcionales, encontramos gran variabilidad

INTRODUCTION: Periprosthetic humerus fractures are infrequent and sometimes difficult to treat. There is limited literature and no consensus on the handling of these fractures. The objective of this study was to compare our results with those published in the literature, in order to improve our care and propose a management algorithm. MATERIAL AND METHOD: Observational study of 10 cases of periprosthetic humerus fractures with a mean follow-up of the patients of 23 months. An analysis of sociodemographic, radiological and surgical variables was performed. They were reviewed clinically and by telephone using the UCLA Shoulder Score and Quick-DASH scales. A systematic search was made in Pubmed for periprosthetic humerus fractures, for a literature review with which to compare our series. RESULTS: We analysed 10 patients with an average age of 69.4 years (37-91). Of the patients, 90% underwent surgery through open reduction and internal fixation. Nine of the ten patients consolidated in a mean time of 6.2months (range 5-12), the remaining suffered a new fracture 5 months after the intervention, who were reoperated and a new osteosynthesis performed with bone allograft. In the UCLA scale there was a decrease of 10.66 points, and an increase of 27.3 points in the Quick-DASH, at the end of the follow-up. CONCLUSIONS: In our series of cases we found similarities in the literature, in relation to demographic aspects and obtaining good radiographic results, which do not correspond to the functional outcome of patients

Surgical treatment of periprosthetic humerus fractures and algorithm. / Tratamiento quirúrgico de las fracturas periprotésicas de húmero y algoritmo de actuación.

INTRODUCTION: Periprosthetic humerus fractures are infrequent and sometimes difficult to treat. There is limited literature and no consensus on the handling of these fractures. The objective of this study was to compare our results with those published in the literature, in order to improve our care and propose a management algorithm. MATERIAL AND METHOD: Observational study of 10cases of periprosthetic humerus fractures with a mean follow-up of the patients of 23months. An analysis of sociodemographic, radiological and surgical variables was performed. They were reviewed clinically and by telephone using the UCLA Shoulder Score and Quick-DASH scales. A systematic search was made in Pubmed for periprosthetic humerus fractures, for a literature review with which to compare our series. RESULTS: We analysed 10patients with an average age of 69.4years (37-91). Of the patients, 90% underwent surgery through open reduction and internal fixation. Nine of the ten patients consolidated in a mean time of 6.2months (range 5-12), the remaining suffered a new fracture 5months after the intervention, who were reoperated and a new osteosynthesis performed with bone allograft. In the UCLA scale there was a decrease of 10.66points, and an increase of 27.3points in the Quick-DASH, at the end of the follow-up. CONCLUSIONS: In our series of cases we found similarities in the literature, in relation to demographic aspects and obtaining good radiographic results, which do not correspond to the functional outcome of patients.

Real-world prevalence of programmed death ligand 1 expression in locally advanced or metastatic non-small-cell lung cancer: The global, multicenter EXPRESS study.

OBJECTIVES: Tumor programmed death ligand 1 (PD-L1) expression is associated with improved clinical benefit from immunotherapies targeting the PD-1 pathway. We conducted a global, multicenter, retrospective observational study to determine real-world prevalence of tumor PD-L1 expression in patients with NSCLC. MATERIALS AND METHODS: Patients ≥18 years with histologically confirmed stage IIIB/IV NSCLC and a tumor tissue block (≤5 years old) obtained before treatment were identified in 45 centers across 18 countries. Tumor samples from eligible patients were selected consecutively, when possible. PD-L1 expression was evaluated at each center using the PD-L1 IHC 22C3 pharmDx kit (Agilent, Santa Clara, CA, USA). RESULTS: Of 2617 patients who met inclusion criteria, 2368 (90%) had PD-L1 data; 530 (22%) patients had PD-L1 TPS ≥ 50%, 1232 (52%) had PD-L1 TPS ≥ 1%, and 1136 (48%) had PD-L1 TPS < 1%. The most common reason for not having PD-L1 data (n = 249) was insufficient tumor cells (<100) on the slide (n = 170 [6%]). Percentages of patients with PD-L1 TPS ≥ 50% and TPS ≥ 1%, respectively were: 22%/52% in Europe; 22%/53% in Asia Pacific; 21%/47% in the Americas, and 24%/55% in other countries. Prevalence of EGFR mutations (19%) and ALK alterations (3%) was consistent with prior reports from metastatic NSCLC studies. Among 1064 patients negative for both EGFR mutation and ALK alteration, the percentage with PD-L1 TPS ≥ 50% and TPS ≥ 1%, respectively, were 27% and 53%. CONCLUSIONS: This is the largest real-world study in advanced NSCLC to date evaluating PD-L1 tumor expression using the 22C3 pharmDx kit. Testing failure rate was low with local evaluation of PD-L1 TPS across a large number of centers. Prevalence of PD-L1 TPS ≥ 50% and TPS ≥ 1% among patients with stage IIIB/IV NSCLC was similar across geographic regions and broadly consistent with central testing results from clinical trial screening populations.

HIN-1: a New Epigenetic Biomarker Crucial for Therapy Selection in Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most common brain tumor in adults. The role of high in normal-1 (HIN-1) as a potential biomarker in combating this disease is being described for the first time in this study. A combination of O6-methylguanine DNA methyltransferase (MGMT) and HIN-1 methylation could be a possible biomarker in therapy choice. Interestingly, survival data shows a similar trend for the methylation of MGMT and for unmethylation of HIN-1 and vice versa. Eighty-eight paraffin-embedded brain tumors were analyzed to screen methylation rates of different genes and evaluate the association between genes methylation and clinicopathologic variables. Our study is the first of its kind to indicate that MGMT and HIN-1 methylation status are inverted (97.7% of methylated ones) and could be new markers in the study of GBM prognosis, especially in the therapy selection.

Recommendations of a gropu of experts for the pathological assessment of tumor regression of liver metastases of colorectal cancer and damage of non-tumour liver tissue after neoadjuvant theray

Colorectal cancer (CRC) incidence has increased during the past decades in Spain, being the first malignant tumour in incidence. Observed mortality for CRC is mainly due to liver and lung metastases. The only curative treatment is surgery; new surgical techniques and neoadjuvant treatments have increased the number of surgery candidate patients. Patients should be managed with a multidisciplinary approach that includes imaging techniques, chemotherapy, surgery and pathological assessment. As an answer to this approach, a group of pathology experts interested on CRC liver metastases aimed to review the diagnosis and prognosis of liver mestastases and developed practical recommendations for its assessment. The expert group revised the current literature and prepared questions to be discussed based on available evidence and on their clinical practise. As a result, recommendations for the assessment of tumour regression of liver metastases are proposed, which could be implemented in oncology centres allowing assessment standardisation for these patients. Prospective multi-center studies to evaluate these recommendations validity will further contribute to improve the standard care of CRC liver metastases patients (AU)

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Recommendations of a group of experts for the pathological assessment of tumour regression of liver metastases of colorectal cancer and damage of non-tumour liver tissue after neoadjuvant therapy.

Colorectal cancer (CRC) incidence has increased during the past decades in Spain, being the first malignant tumour in incidence. Observed mortality for CRC is mainly due to liver and lung metastases. The only curative treatment is surgery; new surgical techniques and neoadjuvant treatments have increased the number of surgery candidate patients. Patients should be managed with a multidisciplinary approach that includes imaging techniques, chemotherapy, surgery and pathological assessment. As an answer to this approach, a group of pathology experts interested on CRC liver metastases aimed to review the diagnosis and prognosis of liver mestastases and developed practical recommendations for its assessment. The expert group revised the current literature and prepared questions to be discussed based on available evidence and on their clinical practise. As a result, recommendations for the assessment of tumour regression of liver metastases are proposed, which could be implemented in oncology centres allowing assessment standardisation for these patients. Prospective multi-center studies to evaluate these recommendations validity will further contribute to improve the standard care of CRC liver metastases patients.

Whether to determine HER2 status for breast cancer in the primary tumour or in the metastasis.

Trastuzumab has substantially changed the prognosis of breast carcinomas. As HER2 over-expression/amplification is a prerequisite for treatment with trastuzumab, an accurate assessment of HER-2 status is the first step for successful treatment. In metastatic breast cancer, we routinely assess HER2 expression in the primary tumour, assuming that HER2 status remains stable through cancer progression. However, it is frequent to find reports that describe discordance between HER2 expression in primary and metastatic tumours. The aim of this paper was to verify whether HER2 status of breast carcinomas is maintained in the corresponding axillary metastasis. Immunohistochemistry was performed on 52 breast carcinomas and their matched axillary metastasis. HercepTest results were concordant in 46 out of 52 cases (88.5%). FISH proved that the differences observed were clinically relevant in only one of the 52 cases studied (98% concordance). We concluded that HER2 status was stable during axillary metastatic progression. Evaluation of gene HER2 status in axillary metastasis rather than in the primary can be useful in certain situations, e.g., small invasive component intimately mixed with in situ component and difficult to recognize in dark field, no tumor after biopsy, or axillary relapse (in this case we can find occasional de novo amplifications susceptible to trastuzumab treatment).

Primary extramedullary myeloid tumor of the breast: a case report and review of the literature.

Primary extramedullary myeloid tumors (PEMMT) are extramedullary proliferations of myeloid cells occurring in the absence of an antecedent myeloproliferative disorder. They have predilection for the skin, lymph nodes, central nervous system, and small intestine. Breast is an uncommon location for PEMMT and only a few cases have been reported so far in the medical literature. Many of these cases have been initially misdiagnosed. We reviewed all the reported cases of PEMMT of the breast in the English-language literature since 1965. In addition, we present a new case of PEMMT of the breast who presented with a mass in her right breast mimicking a breast malignancy and was initially misdiagnosed as non-Hodgkin's lymphoma. A careful histologic examination with immunohistochemical studies revealed the presence of PEMMT of the breast. Treatment with systemic chemotherapy and local radiotherapy rendered a complete remission. Seventeen cases of PEMMT of the breast were reported in the English literature from 1965 to 2003. Most of the cases were misdiagnosed initially as lymphomas, breast carcinomas, or malignant melanomas. PEMMT of the breast is a poorly recognized entity whose diagnosis frequently challenges both the pathologist and the oncologist. Given the small number of patients reported no optimal treatment has been defined, but systemic chemotherapy similar to that given for acute myeloid leukemia with or without local radiotherapy may result in long remissions and avoid the progression to overt acute myeloid leukemia.

Reseña de dos casos de tumor rabdoide originados en el intestino delgado / Malignant rhabdoid tumours arising in the small bowel. Report of two cases

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Colon-specific delivery of budesonide from microencapsulated cellulosic cores: evaluation of the efficacy against colonic inflammation in rats.

Budesonide (BDS) is a potent corticosteroid that has important implications in the pharmacotherapy of inflammatory bowel disease, especially in the treatment of ulcerative colitis and Crohn's disease. BDS is available on the market in the form of enteric-coated preparations. However these products, similar to other available site-specific dosage forms, are not sufficiently selective to treat colonic inflammatory bowel disease. The objective of this study was to evaluate the efficacy of a new microparticulate system containing BDS, to treat experimentally induced colitis in rats. This microparticulate system consisted of BDS-containing hydrophobic cores, microencapsulated within an enteric polymer, which solubilizes at above pH 7, thus combining pH-sensitive and controlled-release properties. Colonic injury and inflammation were assessed by measuring colon/bodyweight ratio, myeloperoxidase (MPO) activity, and by scoring macroscopic and histological damage in colitic rats. Rats were treated orally with BDS, included in the developed system, once a day for 4 days after the induction of inflammation. A BDS suspension and BDS-containing enteric microparticles were included as control formulations in the experimental design. The administration of the new BDS delivery system significantly reduced the colon/bodyweight ratio compared with the administration of control formulations. Similarly, MPO activity and macroscopic and histological damage of the inflamed colonic segments decreased significantly when the BDS formulation was administered, compared with the results obtained after oral administration of the drug suspension. There were no significant differences, however, when the new treatment was compared with the control formulation consisting of simple enteric microparticles.

Bronchiolitis obliterans organizing pneumonia secondary to amiodarone: a rare aetiology.

Bronchiolitis obliterans organizing pneumonia (BOOP) is a clinicopathological entity with well-defined diagnostic criteria, the aetiology of which is generally unknown. Among the adverse pulmonary effects of the drug amiodarone, BOOP is the least commonly reported in the literature. In this article we describe a case of amiodarone-induced BOOP.

A comparative immunohistochemical study of phaeochromocytomas and paragangliomas.

There is no definite morphological distinction between phaeochromocytomas and paragangliomas. We, therefore, attempted to determine the universality and differential utility of a panel of tumour markers for diagnosis in formalin-fixed, paraffin-embedded specimens. Antibodies to neuron-specific enolase (NSE), chromogranin, synaptophysin, Leu-7, neurofilaments, cytokeratins, carcinoembryonic antigen (CEA), melanoma antigen HMB-45, S-100 protein and glial fibrillary acid protein (GFAP), were used on 11 phaeochromocytomas and 8 paragangliomas. NSE reactivity was detected in 10 phaeochromocytomas and in all paragangliomas. Chromogranin reactivity was found in all but two cases (one phaeochromocytoma and one paraganglioma). Synaptophysin reactivity was present in 10 phaeochromocytomas and in the 8 paragangliomas. Ten phaeochromocytomas stained for Leu-7, but none of the paragangliomas did. S-100-positive cells (sustentacular or type II cells) were found in 8 phaeochromocytomas and 7 paragangliomas. GFAP stained sustentacular cells of only one paraganglioma. Only in 5 phaeochromocytomas was there a focal reaction by neurofilaments. Cytokeratins, CEA and HMB-45 were never detected. We conclude that NSE, chromogranin, synaptophysin and S-100 protein are useful markers of both types of tumour, whereas GFAP staining is limited to a small number of these neoplasms. Leu-7 reactivity seems to favour diagnosis of phaeochromocytoma rather than paraganglioma, but further studies with larger series are needed to confirm this. Unlike previous reports, we did not find cytokeratin or HMB-45 immunostaining in any case.

[Alagille's syndrome: a family case and its association with hepatocellular carcinoma]. / Síndrome de Alagille: presentación familiar y asociación con carcinoma de células hepáticas.

Two cases of Alagille syndrome are reported, father and son. This, a 6-year-old boy, presented with neonatal cholestasis but thereafter evolved with progressively decreasing jaundice and persisting pruritus. A liver biopsy confirmed the absence of intrahepatic bile ducts with preservation of hepatic architecture and no fibrosis. The patient had a characteristic phenotype: short stature, triangular face, deep eyes with hypertelorism, partial embryotoxon and data of peripheral pulmonary artery stenosis. His father died 43-year-old by a hepatocarcinoma. His liver biopsy showed also absence of intrahepatic bile ducts. In addition to the association Alagille's syndrome hepatocarcinoma (previously reported in six cases, three into the same family), it should be stressed in this case the long survival and the fact he had many children: the case with Alagille's syndrome, five children in good health, and one who died shortly after birth.