How do ultrafine particles in urban air affect ambulatory blood pressure?

INTRODUCTION: Air in urban areas is usually contaminated with particle matter. High concentrations lead to a rise in the risk of cardiovascular and respiratory diseases. Some studies have reported that ultrafine particles (UFP) play a greater role in cardiovascular diseases than other particle matter, particularly regarding hypertensive crises and DBP, although in the latter such effects were described concerning clinical blood pressure (BP). In this study, we evaluate the relationship between 24-h ambulatory BP monitoring (ABPM) and atmospheric UFP concentrations in Barcelona. METHODS: An observational study of individual patients' temporal and geographical characteristics attended in Primary Care Centres and Hypertensive Units during 2009-2014 was performed. RESULTS: The participants were 521 hypertensive patients, mean age 56.8 years (SD 14.5), 52.4% were women. Mean BMI was 28.0 kg/m and the most prominent cardiovascular risk factors were diabetes (N = 66, 12.7%) and smoking (N = 79, 15.2%). We describe UFP effects at short-term and up to 1 week (from lag 0 to 7). For every 10 000 particle/cm UFP increase measured at an urban background site, a corresponding statistically significant increase of 2.7 mmHg [95% confidence interval = (0.5-4.8)] in 24-h DBP with ABPM for the following day was observed (lag 1). CONCLUSION: We have observed that a rise in UFP concentrations during the day prior to ABPM is significantly associated with an increase in 24 h and diurnal DBP. It has been increasingly demonstrated that UFP play a key role in cardiovascular risk factors and, as we have demonstrated, in good BP control.

Urinary transferrin pre-emptively identifies the risk of renal damage posed by subclinical tubular alterations.

Nephrotoxicity is an important limitation to the clinical use of many drugs and contrast media. Drug nephrotoxicity occurs in acute, subacute and chronic manifestations ranging from glomerular, tubular, vascular and immunological phenotypes to acute kidney injury. Pre-emptive risk assessment of drug nephrotoxicity poses an urgent need of precision medicine to optimize pharmacological therapies and interventional procedures involving nephrotoxic products in a preventive and personalized manner. Biomarkers of risk have been identified in animal models, and risk scores have been proposed, whose clinical use is abated by their reduced applicability to specific etiological models or clinical circumstances. However, our present data suggest that the urinary level of transferrin may be indicative of risk of renal damage, where risk is induced by subclinical tubular alterations regardless of etiology. In fact, urinary transferrin pre-emptively correlates with the subsequent renal damage in animal models in which risk has been induced by drugs and toxins affecting the renal tubules (i.e. cisplatin, gentamicin and uranyl nitrate); whereas transferrin shows no relation with the risk posed by a drug affecting renal hemodynamics (i.e. cyclosporine A). Our experiments also show that transferrin increases in the urine in the risk state (i.e. prior to the damage) precisely as a consequence of reduced tubular reabsorption. Finally, urinary transferrin pre-emptively identifies subpopulations of oncological and cardiac patients at risk of nephrotoxicity. In perspective, urinary transferrin might be further explored as a wider biomarker of an important mechanism of predisposition to renal damage induced by insults causing subclinical tubular alterations.

Chronic kidney disease in Spain: Prevalence and impact of accumulation of cardiovascular risk factors. / Prevalencia de enfermedad renal crónica en España: impacto de la acumulación de factores de riesgo cardiovascular.

BACKGROUND: Chronic kidney disease (CKD) is a public health problem worldwide. We aimed to estimate the CKD prevalence in Spain and to examine the impact of the accumulation of cardiovascular risk factors (CVRF). MATERIAL AND METHODS: We performed a nationwide, population-based survey evaluating 11,505 individuals representative of the Spanish adult population. Information was collected through standardised questionnaires, physical examination, and analysis of blood and urine samples in a central laboratory. CKD was graded according to current KDIGO definitions. The relationship between CKD and 10CVRF was assessed (age, hypertension, general obesity, abdominal obesity, smoking, high LDL-cholesterol, low HDL-cholesterol, hypertriglyceridaemia, diabetes and sedentary lifestyle). RESULTS: Prevalence of CKD was 15.1% (95%CI: 14.3-16.0%). CKD was more common in men (23.1% vs 7.3% in women), increased with age (4.8% in 18-44 age group, 17.4% in 45-64 age group, and 37.3% in ≥65), and was more common in those with than those without cardiovascular disease (39.8% vs 14.6%); all P<.001. CKD affected 4.5% of subjects with 0-1CVRF, and then progressively increased from 10.4% to 52.3% in subjects with 2 to 8-10CVRF (P trend <.001). CONCLUSIONS: CKD affects one in seven adults in Spain. The prevalence is higher than previously reported and similar to that in the United States. CKD was particularly prevalent in men, older people and people with cardiovascular disease. Prevalence of CKD increased considerably with the accumulation of CVRF, suggesting that CKD could be considered as a cardiovascular condition.

Spontaneous nasal perforation in a bevacizumab-treated patient with metastatic breast cancer.

Nasal septum perforation in patients with cancer receiving systemic therapy is rare, and its association with bevacizumab use has described recently in the literature. Here, we report the case of a 34-year-old woman with hormone-sensitive, HER-2/neu negative, metastatic breast cancer who develope a nasal septum perforation during the treatment with paclitaxel and bevacizumab.

Could the Addition of Cetuximab to Conventional Radiation Therapy Improve Organ Preservation in Those Patients With Locally Advanced Larynx Cancer Who Respond to Induction Chemotherapy? An Organ Preservation Spanish Head and Neck Cancer Cooperative Group Phase 2 Study.

PURPOSE: To evaluate the efficacy and safety of induction chemotherapy (IC) followed by bioradiotherapy (BRT) to achieve functional larynx preservation in the setting of locally advanced head and neck tumors. METHODS AND MATERIALS: This was a phase 2, open-label, multicenter study of patients with stage III and IVA laryngeal carcinoma who were candidates for total laryngectomy. The primary endpoint was the rate of survival with functional larynx (SFL) at 3 years, with a critical value to consider the study positive of SFL >59%. Patients received 3 cycles of IC with TPF (docetaxel, cisplatin, and 5-fluorouracil), and those who responded received conventional BRT with cetuximab. In patients with residual nodal disease after BRT, neck dissection was planned 2 months after BRT. Patients who did not respond to IC underwent total laryngectomy plus neck dissection and radiation therapy. RESULTS: A total of 93 patients started TPF. Responses to IC on larynx target lesion were as follows: 37 patients (40%) showed a complete response; 38 patients (41%) showed a partial response; 8 patients (9%) showed stabilization; 2 patients (2%) showed progressive disease, and 8 patients (9%) were not evaluated (2 deaths, 5 adverse events, and 1 lost to follow-up). Seventy-three patients (78%) received BRT: 72 as per protocol, but 1 with only stable disease. Median follow-up was 53.7 months. Three-year actuarial rates were as follows: SFL: 70% (95% confidence interval [CI] 60%-79%); laryngectomy-free survival: 72% (95% CI 61%-81%); overall survival: 78% (95% CI: 63%-82%). The acute toxicity observed during both IC and BRT was as expected, with only 1 toxicity-related death (local bleeding) during BRT. CONCLUSIONS: According to this protocol, the SFL rate was clearly higher than the critical value, with acceptable levels of toxicity. The use of cetuximab added to radiation therapy in patients with stage III and IVA laryngeal cancer who respond to TPF could improve functional larynx preservation. A phase 3 trial is warranted.

Social support and ambulatory blood pressure in older people.

OBJECTIVE: Social support has been associated with greater nocturnal decline (dipping) in blood pressure (BP) in younger and middle-aged individuals. However, it is uncertain if aggregated measures of social support are related to ambulatory SBP in older adults, where high SBP is frequent and clinically challenging. METHODS: We studied 1047 community-living individuals aged at least 60 years in Spain. Twenty-four-hour ambulatory BP was determined under standardized conditions. Social support was assessed with a seven-item questionnaire on marital status, cohabitation, frequency of contact with relatives, or with friends and neighbors, emotional support, instrumental support, and outdoor companionship. A social support score was built by summing the values of the items that were significantly associated with SBP variables, such that the higher the score, the better the support. RESULTS: Participants' mean age was 71.7 years (50.8% men). Being married, cohabiting, and being accompanied when out of home were the support items significantly associated with SBP variables. After adjustment for sociodemographic (age, sex, education), behavioral (BMI, alcohol, tobacco, salt consumption, physical activity, Mediterranean diet score), and clinical variables [sleep quality, mental stress, comorbidity, BP medication, and ambulatory BP levels and heart rate (HR)], one additional point in the social support score built with the abovementioned three support variables, was associated with a decrease of 0.93 mmHg in night-time SBP (P = 0.039), totaling 2.8 mmHg decrease for a score of 3 vs. 0. The three-item social support score was also inversely associated with the night/day SBP ratio (ß = -0.006, P = 0.010). CONCLUSION: In older adults, social support is independently associated with lower nocturnal SBP and greater SBP dipping. Further research is needed in prospective studies to confirm these results.

Quality Indicators to Assure and Improve Cancer Care in Spain Using the Delphi Technique.

BACKGROUND: The quality of cancer care has become a priority for health care systems. The goal of this research was to develop a set of evidence-based quality indicators (QIs) for organization, palliative care, and colorectal, breast, and lung cancers for introducing a system of benchmarking in Spain. METHODS: A comprehensive evidence-based literature search was performed to identify potential QIs. An expert panel (the health care quality promotion group) of 9 oncologists identified indicators and evaluated them. A Delphi process involving 58 physicians was used to rank QIs by clinical relevance (validity). The expert panel then evaluated the selected indicators in terms of the feasibility of measuring them in Spanish hospitals, their usefulness for comparisons, their degree of clinical relevance, and their sensitivity to the impact of health care improvements. RESULTS: From the literature review, 99 potential QIs were identified. The Delphi process shortened the list to 72 QIs. A final set of 57 QIs was established by the health care quality promotion group: 12 related to organizational issues, 11 to colorectal cancer, 11 to breast cancer, 12 to lung cancer, and 11 to palliative care. This final set included structure (n=2), process (n=36), and outcome (n=19) indicators. CONCLUSIONS: A set of QIs has been developed using a validated Delphi method, meaning that we can be confident of their validity, feasibility, sensitivity, and acceptability. These QIs are to serve as the basis of a strategy for benchmarking across oncology services in Spanish hospitals and should enable us to assure and improve the quality of cancer care.

Spanish consensus on the risks and detection of antipsychotic drug-related hyperprolactinaemia. / Consenso español sobre los riesgos y detección de la hiperprolactinemia iatrogénica por antipsicóticos.

INTRODUCTION: Iatrogenic hyperprolactinaemia (IHPRL) has been more frequently related to some antipsychotic drugs that provoke an intense blockade of dopamine D2 receptors. There is a wide variation in clinical practice, and perhaps some more awareness between clinicians is needed. Due to the high frequency of chronic treatment in severe mental patients, careful attention is recommended on the physical risk. IHPRL symptoms could be underestimated without routine examination. METHODOLOGY: An intense scientific literature search was performed in order to draw up a multidisciplinary consensus, including different specialists of psychiatry, endocrinology, oncology and internal medicine, and looking for a consensus about clinical risk and detection of IHPRL following evidence-based medicine criteria levels (EBM I- IV). RESULTS: Short-term symptoms include amenorrhea, galactorrhoea, and sexual dysfunction with decrease of libido and erectile difficulties related to hypogonadism. Medium and long-term symptoms related to oestrogens are observed, including a decrease bone mass density, hypogonadism, early menopause, some types of cancer risk increase (breast and endometrial), cardiovascular risk increase, immune system disorders, lipids, and cognitive dysfunction. Prolactin level, gonadal hormones and vitamin D should be checked in all patients receiving antipsychotics at baseline although early symptoms (amenorrhea-galactorrhoea) may not be observed due to the risk of underestimating other delayed symptoms that may appear in the medium term. Routine examination of sexual dysfunction is recommended due to possible poor patient tolerance and low compliance. Special care is required in children and adolescents, as well as patients with PRL levels >50ng/ml (moderate hyperprolactinaemia). A possible prolactinoma should be investigated in patients with PRL levels >150ng/ml, with special attention to patients with breast/endometrial cancer history. Densitometry should be prescribed for males >50 years old, amenorrhea>6 months, or early menopause to avoid fracture risk.

A Phase 2 Open Label, Single-Arm Trial to Evaluate the Combination of Cetuximab Plus Taxotere, Cisplatin, and 5-Flurouracil as an Induction Regimen in Patients With Unresectable Squamous Cell Carcinoma of the Head and Neck.

PURPOSE: Despite treatment, prognosis of unresectable squamous cell carcinoma of the head and neck (SCCHC) is dismal. Cetuximab therapy has proven to increase the clinical activity of radiation therapy and chemotherapy in patients with locoregional advanced disease with an acceptable toxicity profile. We designed a phase 2 trial to evaluate the efficacy of docetaxel, cisplatin, and 5-fluorouracil (TPF) plus cetuximab (C-TPF) as an induction regimen in patients with unresectable SCCHN. METHODS AND MATERIALS: A single-arm phase 2 trial was conducted. Eligible patients included those with untreated unresectable SCCHC, World Health Organization performance status of 0 to 1, 18 to 70 years of age. Treatment consisted of four 21-day cycles of TPF (docetaxel, 75 mg/m(2) day 1; cisplatin, 75 mg/m(2) day 1; 5-fluorouracil [5-FU], 750 mg/m(2) day 1-5) and cetuximab, 250 mg/m(2) weekly (loading dose of 400 mg/m(2)). Prophylactic granulocyte colony-stimulating factor and antibiotic support were given. After induction, sequential accelerated radiation therapy with concomitant boost (69.9 Gy) and weekly cetuximab therapy were delivered in the absence of disease progression. The primary endpoint was objective response rate (ORR) to C-TPF. RESULTS: Fifty patients were enrolled across 8 centers. Median age was 54 years; disease was stage IV; oropharynx and hypopharynx were the most common primary sites. Eighty-two percent received 4 cycles of C-TPF, and 86% started sequential treatment based on radiation therapy and cetuximab. ORR after C-TPF was 86% (95% confidence interval [CI]: 73%-94%) and 24% had complete response (CR). With a median follow-up of 40.7 months, median overall survival (OS) was 40.7 months. The 2-year actuarial locoregional control (LRC) rate was 57%. The most common drug-related grade 3 or 4 toxicities during induction were neutropenia (24%), neutropenic fever (24%), and diarrhea (20%). There were 3 treatment-related deaths (6%). CONCLUSIONS: C-TPF yields high ORR and CR as induction treatment in unresectable SCCHN. However, hematologic toxicity is too high to recommend this regimen at the current dose.

Outcomes of Estrogen Receptor Negative and Progesterone Receptor Positive Breast Cancer.

PURPOSE: To describe the clinical features and outcomes of estrogen receptor negative (ER-) and progesterone receptor positive (PgR+) breast cancer. METHODS: We retrospectively reviewed a well-characterized database of sequential patients diagnosed with early stage invasive breast carcinoma. Outcomes of interest were time to relapse (TTR) and overall survival (OS). Multivariable Cox proportional hazards analysis was conducted to assess the association of ER-/PgR+ with TTR and OS in comparison to ER+ and to ER- and PgR negative (ER-/PgR-) tumors irrespective of HER2 status. ER and PgR expression was conservatively defined as 10% or greater staining of cancer cells. RESULTS: 815 patients were followed for a median of 40.5 months; 56 patients (7%) had ER-/PgR+, 624 (77%) had ER+ and 136 (17%) had ER-/PgR- phenotypes. Compared with ER+ tumors, ER-/PgR+ tumors were associated with younger age (50 versus 59 years, p=0.03), high grade (50% versus 24%, p<0.001) and more frequent HER2 overexpression/amplification (43% versus 14%, p<0.001). TTR for ER-/PgR+ was intermediate between ER+ and ER-/PgR- tumors, but was not significantly different from ER+ tumors. Recurrences in the ER-/PgR+ and ER-/PgR- groups occurred early in follow-up while in ER+ tumors recurrences continued to occur over the duration of follow-up. OS of ER-/PgR+ was similar to ER+ tumors and better than that of ER-/PgR- tumors. CONCLUSIONS: The ER-/PgR+ phenotype is associated with higher grade with HER2 overexpression/amplification and occurs more commonly in younger women. Risk of relapse and death more closely resembles ER+ than ER-/PgR- tumors suggesting this phenotype represents a group of more aggressive hormone receptor positive tumors.

Trends in hypertension control among the older population of Spain from 2000 to 2001 to 2008 to 2010: role of frequency and intensity of drug treatment.

BACKGROUND: The use of antihypertensive medication and hypertension control has significantly increased during recent decades in some developed countries, but the impact of improved drug treatment on blood pressure (BP) control in the population is unknown. METHODS AND RESULTS: Data were taken from 2 surveys representative of the population aged ≥ 60 years in Spain conducted with the same methodology in 2000 to 2001 and in 2008 to 2010. BP was measured 6×. The first BP reading was discarded, and the average of the remaining 3 to 5 BP readings was taken for analysis. Hypertension prevalence was 68.7% in 2000 to 2001 and 66.0% in 2008 to 2010. Between both time periods there was an improvement in hypertension awareness (63.6%-67.7%), drug treatment among those aware (84.5%-87.5%), and BP control among treated hypertensives (30.3%-42.9%). Overall, BP control among all hypertensives increased from 16.3% to 25.4%. After adjustment for age, sex, education, hypertension duration, smoking, alcohol consumption, body mass index, sedentary behavior, diabetes mellitus, cardiovascular disease, and visits to the physician through logistic regression, ≈ 7% of the improvement in BP control among all hypertensives was explained by higher hypertension awareness, and 36.2% was explained by a higher treatment rate. Among the treated hypertensives, 22.6% of the progress in BP control was because of the increase in the number of BP medications used in each patient. CONCLUSIONS: BP control among the older hypertensive population in Spain has improved from 2000 to 2001 to 2008 to 2010 because of a higher treatment rate and more intense antihypertensive drug treatment.

Night-time heart rate cut-off point definition by resting office tachycardia in untreated hypertensive patients: data of the Spanish ABPM registry.

OBJECTIVE: Epidemiological studies have shown that an elevated resting heart rate (HR) is a risk factor for both total and cardiovascular mortality. Our aim was to estimate the night-time HR cut-off point that best predicts cardiovascular risk office tachycardia in hypertensive patients. DESIGN AND METHOD: Untreated hypertensive patients without concomitant cardiovascular diseases were included. Office and ambulatory HRs were measured. Cardiovascular risk office tachycardia was defined by office HR at least 85 beats per minute (bpm). Different night-time HR cut-offs were estimated by receiver operating characteristic curve analyses to predict cardiovascular risk office tachycardia. The best cut-off was selected on the basis of its combined sensitivity and specificity. RESULTS: A total of 32 569 hypertensive patients were included: 46.5% women, mean age (SD) 52 (14) years, office blood pressure 146 (16)/89 (11) mmHg, diabetes 10.3%, smoking 19.2%, BMI 29 (6.8) kg/m, office HR 77 (11.2) bpm, and night-time HR 64.9 (9.3) bpm. A total of 7070 (21.7%) patients were found to have cardiovascular risk office tachycardia. The night-time HR value that better predicted cardiovascular risk office tachycardia was more than 66 bpm. In comparison with patients with night HR below this value, those with night-time tachycardia were predominantly women, younger, with higher ambulatory blood pressure, greater BMI, and higher prevalence of diabetes and smoking. All comparisons were statistically significant (P less than 0.001). CONCLUSION: A mean night-time HR more than 66 bpm is a good predictor of cardiovascular risk office tachycardia in untreated hypertensive patients and could be considered a variable associated with an increased cardiovascular risk.

Nocturnal hypertension or nondipping: which is better associated with the cardiovascular risk profile?

BACKGROUND: Both increased night blood pressure (BP) and nondipping are associated with worse cardiovascular risk and prognosis. However, as they are often related features, their relative importance has been difficult to assess separately. In this study we address separate associations of nocturnal hypertension and nondipping with cardiovascular risk profile in treated and untreated hypertensive patients. METHODS: A total of 37,096 untreated patients and 62,788 patients receiving antihypertensive treatment from the Spanish Ambulatory Blood Pressure Monitoring Registry were included. Each cohort was separated into 4 groups: group 1, night systolic blood pressure (SBP) <120 mm Hg and normal dipping (>10%); group 2, night SBP <120 mm Hg and nondipping (≤10%); group 3, nocturnal hypertension (SBP ≥120 mm Hg) and normal dipping; and group 4, nocturnal hypertension and nondipping. RESULTS: The smallest proportion of patients with additional cardiovascular risk factors, organ damage, and history of previous events was observed in the group with both normal night SBP and dipping, whereas those with both nocturnal hypertension and nondipping showed the largest proportion of cardiovascular risk factors and diseases. When groups showing only 1 abnormality were compared, nondipping was associated with female sex, reduced renal function, and previous cardiovascular events, whereas nocturnal hypertension was associated with male sex, smoking, and increased urinary albumin excretion. In treated patients, it was also associated with the presence of diabetes. CONCLUSION: Nondipping is related to more advanced disease (reduced renal function and clinical evidence of cardiovascular disease), whereas nocturnal hypertension is associated with albuminuria. The worst cardiovascular risk profile is present in patients exhibiting both nocturnal hypertension and nondipping.

Clinical features of 8295 patients with resistant hypertension classified on the basis of ambulatory blood pressure monitoring.

We aimed to estimate the prevalence of resistant hypertension through both office and ambulatory blood pressure monitoring in a large cohort of treated hypertensive patients from the Spanish Ambulatory Blood Pressure Monitoring Registry. In addition, we also compared clinical features of patients with true or white-coat-resistant hypertension. In December 2009, we identified 68 045 treated patients with complete information for this analysis. Among them, 8295 (12.2% of the database) had resistant hypertension (office blood pressure ≥140 and/or 90 mm Hg while being treated with ≥3 antihypertensive drugs, 1 of them being a diuretic). After ambulatory blood pressure monitoring, 62.5% of patients were classified as true resistant hypertensives, the remaining 37.5% having white-coat resistance. The former group was younger, more frequently men, with a longer duration of hypertension and a worse cardiovascular risk profile. The group included larger proportions of smokers, diabetics, target organ damage (including left ventricular hypertrophy, impaired renal function, and microalbuminuria), and documented cardiovascular disease. Moreover, true resistant hypertensives exhibited in a greater proportion a riser pattern (22% versus 18%; P<0.001). In conclusion, this study first reports the prevalence of resistant hypertension in a large cohort of patients in usual daily practice. Resistant hypertension is present in 12% of the treated hypertensive population, but among them more than one third have normal ambulatory blood pressure. A worse risk profile is associated with true resistant hypertension, but this association is weak, thus making it necessary to assess ambulatory blood pressure monitoring for a correct diagnosis and management.

Maintenance of target hemoglobin level in stable hemodialysis patients constitutes a theoretical task: a historical prospective study.

Maintenance of target hemoglobin (Hb) values in hemodialysis patients treated with erythropoiesis-stimulating agents (ESAs) remains difficult. We examined Hb variability in the clinical setting in hemodialysis patients. Hemodialysis patients treated with ESAs who maintained the recommended Hb range of 11-13 g per 100 ml over 3 months and were not admitted to hospital, did not require transfusion, and did not experience any major clinical event during this period were followed prospectively for 1 year. Anemia events, Hb variation events (any value out of +/-1.5 g per 100 ml of the median Hb level in the total follow-up period for the individual patient), risk factors for anemia, and Hb variation events were assessed. We studied 420 patients (63% males, mean age 61 years), 222 received short-acting erythropoietin (EPO) and 198 long-acting darbepoetin. A total of 4654 blood samples (mean 11.1 per patient-year) were analyzed. Only 3.8% of patients were maintained within the target Hb levels (11-13 g per 100 ml) during 1 year. Hb variation events occurred in 20.8% of laboratory values and anemia events in 14.7%, with a median time to the first event of 3 months. Treatment with short-acting EPO (vs long-acting darbepoetin), change of ESA dose in the previous visit, resistance index, and hospitalization were significant risk factors for both anemia events and Hb variation events. Our results show that Hb values are rarely maintained within the recommended guidelines even in more stable hemodialysis patients. Hb variability is frequently associated with clinical events or ESA dose changes. Long-acting darbepoetin achieved better Hb stability than short-acting EPO.

New options in the treatment of locally advanced head and neck cancer: role for induction chemotherapy.

Advanced locoregional disease is the most frequent clinical situation in Head and Neck cancer. The standard of care for most clinicians is a multidisciplinary treatment with concomitant chemotherapy plus radiotherapy (CRT). However, retrospective studies have shown that in patients treated with CRT there was a relative increase in systemic relapse due to a lack of systemic control. For this reason a renewed interest has appeared for the incorporation of induction chemotherapy in the treatment of locally advanced Head and Neck Cancer. Furthermore new combination regimens with taxanes have shown to be more active than the classical cisplatin and 5-fluorouracil induction regimen. For these reasons ongoing trials are comparing induction chemotherapy followed by chemoradiotherapy with chemoradiotherapy alone. In this review, we will discuss the currently available data that support the design of these clinical trials as well as the future role of new agents in this clinical situation.

Percutaneous fixation of displaced proximal humeral fractures: indications based on the correlation between clinical and radiographic results.

We evaluated 74 patients with displaced proximal humeral fractures (mean age, 70.9 years) treated with closed reduction and percutaneous pinning. Fractures were classified radiographically following Neer's system, and the quality of reduction was assessed according to Kristiansen and Kofoed. Patients were also evaluated clinically with the Constant scale. Overall, the reduction was good in 72% of fractures, but the probability of obtaining a satisfactory reduction of displaced tuberosities was significantly lower in comparison to the humeral head. Four-part fractures obtained the worst radiographic results. The mean Constant scores were 65.8 +/- 18 points for the injured shoulder and 79.5 +/- 9.1 points for the opposite shoulder. Clinical results correlated with the quality of reduction. Closed reduction and percutaneous pinning should be reserved for 2-part fractures, but the technique can also be used in 3-part fractures in elderly patients, in whom an incomplete reduction can yield satisfactory clinical results.

Neuregulin expression modulates clinical response to trastuzumab in patients with metastatic breast cancer.

PURPOSE: Human epidermal growth factor receptor 2 (HER-2) overexpression has been associated with the genesis and progression of a subset of breast cancers. The function of HER-2 may be upregulated by overexpression or by the availability of neuregulins (NRGs), a group of transmembrane growth factors. Transmembrane NRGs strongly activated HER-2 and cell proliferation in breast cancer cells that did not overexpress HER-2, and treatment with trastuzumab prevented the proliferative action of transmembrane NRG. This raised the relevant clinical question of whether patients considered as HER-2 negative, but expressing transmembrane NRG, may benefit from treatment with trastuzumab. PATIENTS AND METHODS: MCF7 cells expressing transmembrane NRG (MCF7-NRG2c) were injected into mice, and their sensitivity to trastuzumab was assessed. A retrospective study of 124 patients with early-stage or metastatic breast cancer was conducted. Expression of transmembrane NRG was evaluated by immunohistochemistry. In 11 patients, Western blot for NRGs was also carried out. Statistics were performed to analyze possible correlations between NRG expression and response to trastuzumab-based therapies, event-free survival, and overall survival (OS). RESULTS: Trastuzumab inhibited tumor growth in mice injected with MCF7-NRG2c cells. Transmembrane NRG was frequently expressed in breast cancer patients. Overexpression of transmembrane NRG significantly correlated with a longer event-free survival and OS in patients with low or normal HER-2 expression who were treated with trastuzumab-based therapies but not in patients with HER-2 overexpression. CONCLUSION: We suggest that the spectrum of patients who may benefit from trastuzumab-based therapies may be widened to include patients with metastatic breast cancer without HER-2 amplification but who express transmembrane NRGs.