Chemo-radiotherapy integration in unresectable locally advanced non-small-cell lung cancer: a review.

Approximately one-third of all non-small-cell lung cancer (NSCLC) are locally-advanced at diagnosis, and 15-17% of these tumors are unresectable at presentation. Definitive chemo-radiotherapy (CRT) represents the standard therapeutic approach. However, the literature has shown that only 15% of patients are alive at 5 years and this percentage has remained unchanged despite various attempts of improvement. The recent introduction of immunotherapy has not only strongly changed the clinical scenario but has also drawn attention to a stage of disease apparently forgotten for decades. Stage III NSCLC can represent an interesting setting for the combined use of chemo-radiation and immunotherapy, due to the potential synergistic effect between radiation and immune checkpoint inhibitors. We reviewed the available literature in order to report the state of art of stage III NSCLC, by focusing on trials that evaluate different combinations of CRT and new drugs of PD-1/PD-L1 axis, and anti-CTLA-4. The future goal in the management of unresectable stage III NSCLC will be the optimal patients' selection combined with the use of individualized immuno/chemotherapies that could potentially improve clinical outcomes.

Benefit of ablative versus palliative-only radiotherapy in combination with nivolumab in patients affected by metastatic kidney and lung cancer.

PURPOSE: Here, we present the results from a retrospective analysis, with the purpose of evaluating the safety and feasibility of nivolumab and radiotherapy (RT) concomitant association in metastatic kidney and lung cancer patients. MATERIALS AND METHODS: From August 2015 until September 2017, we retrospectively observed 20 patients with metastatic lung and renal cell carcinoma who had been initiated therapy with nivolumab and underwent concomitant RT. RT was administered either as an ablative therapy in the oligometastatic/oligoprogressive setting or as palliative-only treatment for symptomatic patients. Data on progression-free and overall survival (PFS and OS), treatment response and adverse events were collected and reported. Comparison between palliative-only and ablative treatments was performed. RESULTS: PFS and OS were 7 and 12.5 months in the entire population, respectively. Oligoprogressive patients treated with ablative intent, compared to patients undergoing RT with palliative-only intent, had statistically longer PFS (11.5 vs 5.2 months, HR 0.42, CI 0.18-0.98, p 0.03) and OS (17.9 vs 10.31 months, HR 0.41 CI 0.16-1.02, p 0.04). Considering only patients treated with ablative intent, 87.5% showed response to treatment, and complete response was reported in 37.5% of cases. Adverse G2-G3 related to combination treatment were reported as follows: 1 gastrointestinal (nausea), 4 breakthrough pain. CONCLUSIONS: Our data showed significant advantage for oligoprogressive patients treated with RT during nivolumab therapy. No safety alert emerged. These results underline the potential synergistic effects of RT and Immune therapy combination. Our analysis prompts further prospective studies exploring the benefit of integrated treatment strategies.

Work productivity loss and indirect costs associated with new cardiovascular events in high-risk patients with hyperlipidemia: estimates from population-based register data in Sweden.

OBJECTIVES: To estimate productivity loss and associated indirect costs in high-risk patients treated for hyperlipidemia who experience cardiovascular (CV) events. METHODS: Retrospective population-based cohort study conducted using Swedish medical records linked to national registers. Patients were included based on prescriptions of lipid-lowering therapy between 1 January 2006 and 31 December 2011 and followed until 31 December 2012 for identification of CV events and estimation of work productivity loss (sick leave and disability pension) and indirect costs. Patients were stratified into two cohorts based on CV risk level: history of major cardiovascular disease (CVD) and coronary heart disease (CHD) risk equivalent. Propensity score matching was applied to compare patients with new events (cases) to patients without new events (controls). The incremental effect of CV events was estimated using a difference-in-differences design, comparing productivity loss among cases and controls during the year before and the year after the cases' event. RESULTS: The incremental effect on indirect costs was largest in the CHD risk equivalent cohort (n = 2946) at €3119 (P value <0.01). The corresponding figure in the major CVD history cohort (n = 4508) was €2210 (P value <0.01). There was substantial variation in productivity loss depending on the type of event. Transient ischemic attack and revascularization had no significant effect on indirect costs. Myocardial infarction (€3465), unstable angina (€2733) and, most notably, ischemic stroke (€6784) yielded substantial incremental cost estimates (P values <0.01). CONCLUSIONS: Indirect costs related to work productivity losses of CV events are substantial in Swedish high-risk patients treated for hyperlipidemia and vary considerably by type of event.

Predicting bottlenose dolphin distribution along Liguria coast (northwestern Mediterranean Sea) through different modeling techniques and indirect predictors.

Habitat modeling is an important tool to investigate the quality of the habitat for a species within a certain area, to predict species distribution and to understand the ecological processes behind it. Many species have been investigated by means of habitat modeling techniques mainly to address effective management and protection policies and cetaceans play an important role in this context. The bottlenose dolphin (Tursiops truncatus) has been investigated with habitat modeling techniques since 1997. The objectives of this work were to predict the distribution of bottlenose dolphin in a coastal area through the use of static morphological features and to compare the prediction performances of three different modeling techniques: Generalized Linear Model (GLM), Generalized Additive Model (GAM) and Random Forest (RF). Four static variables were tested: depth, bottom slope, distance from 100 m bathymetric contour and distance from coast. RF revealed itself both the most accurate and the most precise modeling technique with very high distribution probabilities predicted in presence cells (90.4% of mean predicted probabilities) and with 66.7% of presence cells with a predicted probability comprised between 90% and 100%. The bottlenose distribution obtained with RF allowed the identification of specific areas with particularly high presence probability along the coastal zone; the recognition of these core areas may be the starting point to develop effective management practices to improve T. truncatus protection.

Pleomorphic adenoma of the nasal septum.

INTRODUCTION: Pleomorphic adenoma is the most common benign tumour of the salivary glands. The major salivary glands are most commonly involved, or more rarely accessory salivary glands, especially the oral cavity. Other locations, such as the nasal cavity, paranasal sinuses or upper aerodigestive tract, are exceptional. CASE REPORT: A 26-year-old female presented with right-sided nasal obstruction. Radiology found a lesion involving the anterior third of the nasal septum. The patient underwent complete surgical resection of the tumour via an endonasal approach. Histological examination found a mixed cellular component (epithelial and myoepithelial) and mesenchymatous tissue with chondromyxoid stroma, enabling diagnosis of a typical pleomorphic adenoma. DISCUSSION/CONCLUSION: Pleomorphic adenoma is exceptional in the nasal cavity, with only a few cases reported in the literature. Although benign, the risk of local recurrence, malignant transformation and metastasis requires close long-term follow-up.

[Important of off loading in the treatment of foot diabetic ulcers]. / Importance de la décharge dans le traitement des lésions du pied diabétique.

Foot ulcers are a frequent complication and develop in 15% of patient with diabetes. Ulceration is caused by several factor including neuropathy, arterial insufficiency and infection. Neuropathy results in a loss of the protective sensation and foot deformation. Off loading is an important part of the treatment permitting to reduce pressure and improve healing. Total casting is the gold standard and healing is observed in 90%, but there are several contraindications and limitations. Alternatives include removal devices that must be evaluated to improve off-loading and patient observance. Prevention with specific follow-up and shoes adaptation is recommended to prevent recurrent ulcer.

Persistent primitive trigeminal artery in monochorial twins. A case report.

The trigeminal artery is one of the arterial structures that constitute anastomosis between the carotid and the posterior circulation during fetal life and usually regress. However these arterial structures may persist in adult life and the trigeminal artery is the one that most frequently show such behaviour. We describe the case of two monochorial female twins with a persistent primitive trigeminal artery revealed by magnetic resonance angiography.

Plaque surface and microembolic signals in moderate carotid stenosis.

We performed Transcranial Doppler Monitoring to detect microembolic signals (MES) in 47 patients with moderate (30%-69%) carotid stenosis proven by selective angiography. We compared the occurrence of MES with the clinical characteristics of stenosis (symptomatic or asymptomatic) and the angiographic plaque features (nonulcerated, deep ulceration, superficial ulceration, ulceration with flap, or ulceration without flap). For these cases there was no indication for endarterectomy, nevertheless we thought it would be useful to identify risk subgroups that might benefit from surgical treatment. MES were detected in 17.9% of the stenoses with a prevalence (p <. 01) in symptomatic cases (25%) compared to asymptomatic cases (14. 3%). There was a significant correlation of MES with plaque ulceration (p <.01) and particularly with ulceration without flap (p <.01). No difference between deep and superficial ulceration was observed. The availability of prospective data on this topic might be useful to select subgroups of patients with moderate carotid stenosis at risk for embolism.

[High-intensity transcranial Doppler signals in patients wearing heart valve prostheses: a prospective study]. / Segnali Doppler transcranici ad alta intensità in portatori di protesi valvolari cardiache: studio prospettico.

BACKGROUND: Transcranial Doppler sonography (TCD) of the middle cerebral arteries in patients with prosthetic heart valves reveals high-intensity transient signals (HITS) and can detect asymptomatic cerebrovascular microemboli. Both the nature of the underlying embolic material (either gaseous or corpuscular) and its clinical significance remain uncertain. METHODS: Seventy-one patients undergoing heart valve replacement (n = 63) or repair (n = 8) from June 1996 to June 1998 were prospectively evaluated preoperatively and one week, 3 months and 12 months after valve replacement using TCD. At each follow-up interval, clinical assessment was aimed at detecting neurological events. Furthermore, continuous echo-Doppler study of the carotid arteries and TCD of the middle cerebral arteries for a 30-minute period during each following visit was carried out. RESULTS: No HITS were recorded preoperatively in any patient. At one week, HITS were detected in 25 patients (35%): 22 (65%) of these had received a mechanical prosthesis and three (10%) a bioprosthesis. No HITS were recorded in patients with mitral repair. HITS were subsequently detected only in patients with mechanical prosthesis with a positive TCD at one week, the mean number of HITS per patient being 7 +/- 18 at 3 months and 8 +/- 24 at 12 months. No neurological symptoms were evident in any patients during the postoperative evaluation. Multivariate analysis showed mechanical prosthetic valve to be the only independent predictive risk factor for HITS development. CONCLUSIONS: The role of a mechanical prosthetic valve as a risk factor in the pathogenesis of HITS appears evident. However, HITS appear to be unrelated to possible postoperative neurological events. TCD could have more specific clinical applications if associated with methods that would make it possible to ascertain the nature of various embolic materials.

Diagnóstico de hipertensäo arterial sistêmica: evidências de que os critérios contemporâneos devem ser revistos / Diagnosis of systemic hypertension: evidences that current criteria should be revised

Diversos comitês normativos em hipertensäo arterial recomendam considerar a média de várias aferiçöes da pressäo arterial com esfigmomanômetro para diagnosticar hipertensäo. Näo há consenso sobre o número de medidas a serem consideradas. OBJETIVO. Descrever o comportamento da pressäo arterial obtida em três dias diferentes, utilizando-se a média de seis aferiçöes para o diagnóstico de hipertensäo. MÉTODOS. No ambulatório de hipertensäo da Unidade de Farmacologia Clínica do Hospital de Clínicas de Porto Alegre, emprega-se a média de seis determinaçöes, obtidas em três dias diferentes, para diagnosticar e classificar a hipertensäo, exceto nos pacientes com valores muito baixos ou elevados nas duas primeiras aferiçöes. Cinqüenta e oito pacientes foram submetidos a essa rotina. RESULTADOS. As médias das pressöes sistólica (PS) e diastólica (PD) decresceram da primeira à sexta determinaçäo (ANOVA para medidas repetidas: F = 4,45, p = 0,001 para PS e F = 5,54, p < 0,001 para PD). Os pacientes foram divididos em grupos com PS e PD obtidas na primeira aferiçäo superiores e inferiores à média de todo grupo. A diminuiçäo de ambas as pressöes ao longo das seis aferiçöes ficou restrita aos grupos com valores da primeira determinaçäo superiores à média de todo o grupo (ANOVA: F = 8.03; p < 0,0001 para PS e F = 6,33, p < 0,0001 para PD). A regressäo à média e uma reaçäo de alerta inicial säo explicaçöes aventadas para esse fenômeno. CONCLUSÄO. Esses dados demonstram que o diagnóstico de hipertensäo arterial näo deve ser feito com base em uma única aferiçäo e sugerem que a recomendaçäo de diagnosticar hipertensäo severa baseando-se em altos valores das duas primeiras medidas pode classificar erroneamente alguns pacientes.

[Diagnosis of systemic hypertension: evidences that current criteria should be revised]. / Diagnóstico de hipertensão arterial sistêmica: evidências de que os critérios contemporâneos devem ser revistos.

UNLABELLED: It has been recommended to take the average of several blood pressure (BP) determinations with a sphygmomanometer to diagnose hypertension, but there is no agreement on the reading numbers. PURPOSE: Describing the behavior of BP readings taken in three different days to establish the classificatory BP in an outpatient hypertension clinic. METHOD: In the outpatient hypertension clinic of the Clinical Pharmacology Division of the Hospital de Clínicas de Porto Alegre, we use the mean of six readings taken in three different days to establish the classificatory blood pressure, except for those with very high or low values in the first day. In this report we describe the behavior of BP in 58 patients submitted to this routine. RESULTS: The mean of systolic (SBP) and diastolic (DBP) blood pressures decreased from the first to the 6th reading (ANOVA for repeated measurements: F = 4.45, P = 0.001 for SBP and F = 5.54, P < 0.001 for DBP). Afterward, the patients were classified into two groups according their first SBP and DBP reading. The decreasing in both SBP and DBP was confined to those with the first measurement in the upper half of the entire group (ANOVA: F = 8.03; P < 0.0001 for SBP and F = 6.33, P < 0.0001 for DBP). Regression to the mean and some reactiveness in the first day are possible explanations for this. CONCLUSION: These data corroborate that the hypertension diagnosis should not be based in an single blood pressure determination and suggest that the recommendation to diagnose severe hypertension based on high values in the first two readings could misclassify some patients.

Evaluation of a competitive enzyme immunoassay in screening for syphilis.

A competitive immunoenzymatic method has been developed and evaluated for the serological screening of syphilis. The method detects both anti-Treponema Pallidum IgG and IgM. The kit, commercially known as "Syphilis Screen", is produced by DIESSE Diagnostica Senese (Siena, Italy); all the required reagents are included and are ready for use. The test is performed on undiluted serum and a single incubation step is necessary. The method can be easily automated, and the results do not require a subjective interpretation. A good correlation was found with the Treponema Pallidum Haemagglutination (TPHA) technique: only 14 out of 2350 samples tested (2090 non reactive and 260 reactive) were found to be in disagreement. This test can be considered an alternative to the TPHA method in screening for syphilis.

[Neuroendocrine carcinoma of the larynx with secretion of calcitonin: primary tumor or metastasis of the medullary thyroid carcinoma?]. / Carcinome neuroendocrine laryngé avec sécrétion de calcitonine: cancer primitif ou métastase d'un cancer médullaire de la thyroïde?

Neuroendocrine carcinomas of the larynx are rare and their links with thyroid neoplastic lesions are not specified in most reported cases. We report such a case secondary to medullary thyroid carcinoma. In a 63-year-old man, a supra glottic laryngeal carcinoma confirmed by biopsy was initially treated by chemotherapy. A second biopsy of the laryngeal lesion after incomplete remission displayed a neuroendocrine carcinoma with calcitonin in neoplastic cells. Laryngectomy, cervical bilateral neck dissection and thyroid isthmic adenoma dissection were performed. Numerous neoplastic cells from these tissues contained calcitonin revealed by immunohistochemical method. Calcitoninemia was highly increased and multiple bone metastases were discovered. Secondary total thyroidectomy was not possible and the patient died 6 months after. In this case the neuroendocrine laryngeal carcinoma was probably secondary to a latent medullary thyroid carcinoma. Medullary thyroid carcinoma is most often unknown in similar previously reported cases of neuroendocrine laryngeal carcinoma. Thus a neuroendocrine tumour of the larynx should require search for extra thyroid and over all thyroid neuroendocrine carcinoma, even limited to a small and latent lesion.