[Isolated nocturnal hypertension in individuals with human immunodeficiency virus]. / Hipertensión nocturna aislada en individuos con el virus de la inmunodeficiencia humana.

INTRODUCTION: Isolated nocturnal hypertension is associated with a greater number of cardiovascular events and target organ damage due to arterial hypertension. It has been observed that patients in the general population with this entity do not have high blood pressure figures in the office; and it is necessary to perform an outpatient measurement to unmask it. The prevalence in special populations is not fully described. The objective of the following study is to describe the prevalence of isolated nocturnal hypertension in a population living with the human immunodeficiency virus and to observe its relationship with the categories of office blood pressure and the phenotypes of the 24-hour ambulatory blood pressure measurement. METHODOLOGY: A retrospective cohort was carried out in a population with human immunodeficiency virus in a public hospital in Spain, clinical epidemiological characteristics, office blood pressure measurements and 24-hour ambulatory blood pressure measurement (ABPM) were recorded. An analysis was performed based on the different ABPM blood pressure phenotypes, as well as based on the different office blood pressure categories, the risks for isolated nocturnal hypertension were calculated. RESULTS: One hundred and sixteen individuals, without antihypertensive medication or history of established cardiovascular disease, were included in the analysis. A prevalence of nocturnal hypertension of 23.3% was described. It was not possible to demonstrate significant differences between phenotypes by ABPM of any variable specific to HIV. There were no adjusted risk differences between the different categories of office normotensives. CONCLUSIONS: Isolated nocturnal hypertension is more frequent in patients with HIV and office blood pressure values in normotensive patients are not sufficient to predict isolated nocturnal hypertension.

SEOM clinical guideline for the management of cutaneous melanoma (2020).

Melanoma affects about 6000 patients a year in Spain. A group of medical oncologists from Spanish Society of Medical Oncology (SEOM) and Spanish Multidisciplinary Melanoma Group (GEM) has designed these guidelines to homogenize the management of these patients. The diagnosis must be histological and determination of BRAF status has to be performed in patients with stage ≥ III. Stage I-III resectable melanomas will be treated surgically. In patients with stage III melanoma, adjuvant treatment with immunotherapy or targeted therapy is also recommended. Patients with unresectable or metastatic melanoma will receive treatment with immunotherapy or targeted therapy, the optimal sequence of these treatments remains unclear. Brain metastases require a separate consideration, since, in addition to systemic treatment, they may require local treatment. Patients must be followed up closely to receive or change treatment as soon as their previous clinical condition changes, since multiple therapeutic options are available.

SEOM clinical guideline for the management of immune-related adverse events in patients treated with immune checkpoint inhibitors (2019).

The use of immune checkpoint inhibitors has emerged as an effective treatment option for patients with several tumor types. By increasing the activity of the immune system, they can induce inflammatory side effects, which are often termed immune-related adverse events. These are pathophysiologically unique toxicities, compared with those from other anticancer therapies. In addition, the spectrum of the target organs is very broad. Immune-inflammatory adverse events can be life threatening. Prompt diagnosis and pharmacological intervention are instrumental to avoid progression to severe manifestations. Consequently, clinicians require new skills to successfully diagnose and manage these events. These SEOM guidelines have been developed with the consensus of ten medical oncologists. Relevant studies published in peer-review journals were used for the guideline elaboration. The Infectious Diseases Society of America grading system was used to assign levels of evidence and grades of recommendation.

A retrospective chart review study describing metastatic melanoma patients profile and treatment patterns in Spain.

PURPOSE: To describe patient characteristics by disease stage, resectability status and current treatment management after first diagnosis of IIIB to IV1c advanced (AM)/metastatic melanoma (MM). METHODS/PATIENTS: Multicentre, retrospective study based on data from medical charts of patients > 18 years at MM first diagnosis, visited by oncologists at 4 reference centres in Spain: Hospital Universitario Gregorio Marañón (Madrid), Hospital General de Valencia (Valencia), Clínica Universidad de Navarra (Pamplona), and Hospital Clínic (Barcelona). RESULTS: Metastatic non-visceral melanoma (IIIB, IIIC, IV M1a) was reported in 139 (48.6%) patients and 40.9% (n = 117) were diagnosed with IV-M1c disease. 160 (55.9%) metastases were resectable. Available therapies under clinical practice were used in 210 patients; 74 were treated under clinical trials (CT). Intention-to-cure surgery (47.6%) was the most common treatment at time of MM diagnosis. Systemic (45.1% overall) therapy included chemo-, targeted- and immunotherapy (19.6%, 14.3%, 8.4%, respectively). At time of data collection, 26 patients were still alive and 120 had progressed to IV-M1c. Median overall survival (OS) was significantly larger in IIIB patients, 28.9 m (25.2-32.7); the shortest for IV-M1c patients, 11.0 m (8.7-13.3). CONCLUSIONS: Novel treatments are undoubtedly a major step forward in AM/MM, however these are often only available in the CT setting because early stages of development or country-specific regulations. Further prospective studies and multifactorial analysis should be performed to clearly identify possible clinical associations for outcome in Spanish patients with AM/MM.

Delay in starting radiotherapy due to neoadjuvant therapy does not worsen survival in unresected glioblastoma patients.

PURPOSE: We retrospectively examined the potential effect on overall survival (OS) of delaying radiotherapy to administer neoadjuvant therapy in unresected glioblastoma patients. PATIENTS AND METHODS: We compared OS in 119 patients receiving neoadjuvant therapy followed by standard treatment (NA group) and 96 patients receiving standard treatment without neoadjuvant therapy (NoNA group). The MaxStat package of R identified the optimal cut-off point for waiting time to radiotherapy. RESULTS: OS was similar in the NA and NoNA groups. Median waiting time to radiotherapy after surgery was 13 weeks for the NA group and 4.2 weeks for the NoNA group. The longest OS was attained by patients who started radiotherapy after 12 weeks and the shortest by patients who started radiotherapy within 4 weeks (12.3 vs 6.6 months) (P = 0.05). OS was 6.6 months for patients who started radiotherapy before the optimal cutoff of 6.43 weeks and 19.1 months for those who started after this time (P = 0.005). Patients who completed radiotherapy had longer OS than those who did not, in all 215 patients and in the NA and NoNA groups (P = 0.000). In several multivariate analyses, completing radiotherapy was a universally favorable prognostic factor, while neoadjuvant therapy was never identified as a negative prognostic factor. CONCLUSION: In our series of unresected patients receiving neoadjuvant treatment, in spite of the delay in starting radiotherapy, OS was not inferior to that of a similar group of patients with no delay in starting radiotherapy.

This is a call to oncologists for action.

Cancer cases are growing in an exponential way, likewise the prices of new cancer drugs. Continuing in this way, in the near future, it will be impossible to provide optimum care for all cancer patients. Therefore, it is important to establish mechanisms that enable the National Health Systems to provide the best options of treatment, either through the elaboration of decision-binding frameworks or through other initiatives that guarantee the best quality care for all oncology patients to overcome, in the best possible way, this difficult illness. Here, we review current proposals that have been established by different cancer organizations worldwide, their similarities, their differences and whether they are helpful in a real clinical setting. Facing present reality and despite these organizations' huge efforts, these proposals are not being implemented at all and it does not seem feasible that they will in the short run. In the same way, we support and argue why oncologists should have a crucial and a preponderant role to establish the best way of guaranteeing an equal access to the latest oncology care.

SEOM clinical guideline for the management of malignant melanoma (2017).

All melanoma suspected patients must be confirmed histologically and resected. Sentinel node biopsy must be done when tumor is over 1 mm or if less with high-risk factors. Adjuvant therapy with interferon could be offered for patients with high-risk melanoma and in selected cases radiotherapy can be added. Metastatic melanoma treatment is guided by mutational BRAF status. BRAF wild type patients must receive anti-PD1 containing therapy and BRAF mutated patients BRAF/MEK inhibitors or anti-PD1 containing therapy. Up to 10 years follow up is reasonable for melanoma patients with dermatologic examinations and physical exams.

Pembrolizumab for advanced melanoma: experience from the Spanish Expanded Access Program.

BACKGROUND: The programmed death (PD-1) inhibitor pembrolizumab has been recently approved for the treatment of advanced melanoma. We evaluated the clinical activity of pembrolizumab in melanoma patients treated under the Spanish Expanded Access Program. METHODS: Advanced melanoma patients who failed to previous treatment lines were treated with pembrolizumab 2 mg/kg every three weeks. Patients with brain metastases were not excluded if they were asymptomatic. Data were retrospectively collected from 21 centers in the Spanish Melanoma Group. RESULTS: Sixty-seven advanced melanoma patients were analyzed. Most patients were stage M1c (73.1%), had high LDH levels (55.2%) and had ECOG PS 1 or higher (59.7%). For cutaneous melanoma patients, median overall survival was 14.0 months; the 18-month overall survival rate was 47.1%. Overall response rate was 27%, including three patients with complete responses (6.5%). Median response duration was not reached, with 83.3% of responses ongoing (3.5 m+ to 20.4 m+). From ten patients included with brain metastases, four (40%) had an objective response, two (20%) of them achieved a complete response. Significant prognostic factors for overall survival were LDH level, ECOG PS and objective response. There were no serious adverse events. CONCLUSION: Although this was a heavily pretreated cohort, pembrolizumab activity at the approved dose and schedule was confirmed in the clinical setting with long-term responders, also including patients with brain metastases.

Safety of vemurafenib in patients with BRAF V600 mutated metastatic melanoma: the Spanish experience.

OBJECTIVES: Vemurafenib tolerability was assessed in a large, open-label, multicentre study in patients with BRAF V600 mutated advanced melanoma. We investigated safety, tolerability and efficacy of vemurafenib in Spanish patients participating in that study. METHODS: Patients with previously treated or treatment-naive, unresectable stage IIIC or stage IV, BRAF V600 mutation-positive melanoma received vemurafenib 960 mg twice daily until disease progression, unacceptable toxicity, withdrawal of consent or death. The primary endpoint was safety; secondary endpoints included overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). RESULTS: 301 Spanish patients were included, 70 % with M1c disease, 22 % with brain metastases and 51 % with prior systemic therapy for metastatic disease. Most frequent adverse events included fatigue (48 %), arthralgia (45 %), rash (41 %), photosensitivity (34 %) and skin neoplasms (21 %). Grade 3/4 adverse events occurred in 156 patients (52 %), including cutaneous squamous cell carcinoma (including keratoacanthoma; 16 %), fatigue (6 %) and arthralgia (5 %). The ORR was 28 % (95 % CI 23-34 %). Responses occurred in patients with brain metastases (18 %), elevated baseline lactate dehydrogenase (19 %) and poor performance status (15 %), and elderly patients (22 %). Median PFS was 5.8 (95 % CI 5.0-6.4) months; median OS was 10.5 (95 % CI 9.5-13.5) months. CONCLUSION: Our results for Spanish patients in the vemurafenib safety study indicate similar efficacy and a comparable safety profile in Spanish patients with no new safety signals compared with the overall population. Clinical benefit was demonstrated in poor-prognosis patients and in those with favourable baseline characteristics, suggesting that poor-prognosis patients may also benefit from vemurafenib treatment.

SEOM guidelines for the management of Malignant Melanoma 2015.

All melanoma patients must be confirmed histologically and resected according to Breslow. Sentinel node biopsy must be done when tumor is over 1 mm or if less with high-risk factors. Adjuvant therapy with interferon must be offered for patients with high-risk melanoma and in selected cases radiotherapy can be added. Metastatic melanoma treatment is guided by mutational BRAF status. BRAF wild type patients must receive anti-PD1 therapy and BRAF mutated patients BRAF/MEK inhibitors or anti-PD1 therapy. Up to 10 years follow up is recommended for melanoma patients with dermatologic examinations and physical exams.

A phase II study of feasibility and toxicity of bevacizumab in combination with temozolomide in patients with recurrent glioblastoma.

PURPOSE: The aim of this prospective and multicentric phase II study was to evaluate the efficacy and safety of temozolomide (TMZ) and bevacizumab (BV) in patients (pts) with recurrent glioblastoma (GB), previously treated with chemoradiotherapy and at least three cycles of adjuvant TMZ. PATIENTS AND METHODS: Patients with GB at first relapse received BV 10 mg/kg day every 2 weeks and TMZ 150 mg/m(2) days 1-7 and 15-21, every 28 days. Patients underwent brain magnetic resonance imaging every 8 weeks. RESULTS: Thirty-two evaluable pts were recruited in 8 sites. Fourteen pts (44%) had gross total resection. O(6)-methylguanine-DNA methyltransferase (MGMT) promoter was methylated in 12 pts, unmethylated in 6 pts, and missing in 14 pts. The estimated 6-month progression free survival (PFS) rate was 21.9% (95% CI 9.3-40.0%). The median PFS and overall survival (OS) were 4.2 months (95% CI 3.6-5.4 months) and 7.3 months (95% CI 5.8-8.8 months), respectively. No significant association with MGMT status was found in terms of OS or PFS. Six of 32 pts (19%; 95% CI 7.2-36.4) were long-term survivors, with a median PFS and OS (50% events) of 9.5 months (95% CI 7.9-23.6) and 15.4 (95% CI 8.9-NA), respectively: no differences in baseline characteristics were identified in comparison with total population. No unexpected toxicities or treatment-related deaths were observed. CONCLUSIONS: This regimen showed to be feasible and well tolerated in pts with recurrent GB pretreated with TMZ. Further investigation is warranted to identify subpopulations that are more likely to benefit from addition of BV to GB therapy.

Management of high-risk and advanced basal cell carcinoma.

Despite that basal cell carcinoma (BCC) is curative in the vast majority of cases, some patients are at high risk of recurrence and, in a few patients, lesions can progress to a point unsuitable for local therapy and prognosis is quite poor. The aim of the present work is to review clinical and pathologic characteristics as well as classical and new treatment options for high-risk, metastatic and locally advanced BCC. Surgery and radiotherapy remain the selected treatments for the majority of high-risk lesions. However, some patients are located on a blurry clinical boundary between high-risk and locally advanced BCC. Treatment of these patients is challenging and need an individualized and highly specialized approach. The treatment of locally advanced BCC, in which surgery or radiotherapy is unfeasible, inappropriate or contraindicated, and metastatic BCC has changed with new Hedgehog pathway inhibitors of which vismodegib is the first drug approved by FDA and EMA.

Guidelines for biomarker testing in metastatic melanoma: a National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology.

This consensus statement, conceived as a joint initiative of the Spanish Society of Pathology (SEAP) and the Spanish Society of Medical Oncology (SEOM), makes diagnostic and treatment recommendations for the management of patients with advanced or metastatic melanoma based on the current scientific evidence on biomarker use. This document thus provides an opportunity to improve healthcare efficiency and resource use, which will benefit these patients. Based on the data available so far, this expert group recommends routinely testing patients with metastatic melanoma for BRAF mutation status, as the result affects the subsequent therapeutic management of these patients. The analysis of genetic alterations in KIT may be reasonable in patients with primary tumours in acral or mucosal sites or on chronically sun-exposed skin, in an advanced condition, but not in patients with other types of melanomas. This panel believes that testing for other genetic alterations, such as NRAS mutation status in patients not carrying BRAF mutations, GNAQ/GNA11 mutational analysis or genetic alterations in PTEN, is not currently indicated as routine clinical practice, because the results do not influence treatment planning in these patients at the present time. Other important issues addressed in this document are the organisational requirements and quality controls needed for proper testing of these biomarkers, and the legal implications to be borne in mind.

Quorum sensing activity in Ophiostoma ulmi: effects of fusel oils and branched chain amino acids on yeast-mycelial dimorphism.

AIMS: For Ophiostoma (Ceratocystis) ulmi, the ability to undergo morphological change is a crucial factor for its virulence. To gain an understanding of quorum-sensing activity in O. ulmi as it relates to yeast-mycelium dimorphism control, this study examines the effects of branched-chain amino acids as well as their fusel alcohols and fusel acids as quorum sensing molecules. METHODS AND RESULTS: In a defined medium containing glucose, proline and salts, O. ulmi grew as yeasts when the culture was inoculated with a high density of spores (2 × 10(7) CFU ml(-1) ) and as mycelia when inoculated with a low spore density (4 × 10(5) CFU ml(-1) ). The cultures displaying yeast morphology secreted a quorum-sensing factor that shifted the morphology from mycelia to yeast. This quorum-sensing molecule was lipophilic and extractable by organic solvents from the spent medium. Using GC/MS analysis, it was determined that the major compound in the extract was 2-methyl-1-butanol. A similar effect was observed when the branched-chain amino acids (fusel alcohol precursors) were used as the nitrogen source. E, E-farnesol had no effect on the morphology of O. ulmi. CONCLUSIONS: Addition of the branched-chain amino acids or one of the compounds detected in the spent medium, 2-methyl-1-butanol or 4-hydroxyphenylacetic acid, or methylvaleric acid, decreased germ tube formation by more than 50%, thus demonstrating a quorum sensing molecule behaviour in O. ulmi cultures. SIGNIFICANCE AND IMPACT OF THE STUDY: This study presents advances in the investigation of dimorphism in O. ulmi, complementing the existing scientific basis, for studying, understanding and controlling this phenomenon.

Clinical and pathological findings of a sac-like formation in the tunica vaginalis of a Nelore (Bos indicus) bull.

A seven-month-old purebred Nelore calf was diagnosed with a bilateral finger-shaped swelling although more prominent at the left side of the scrotum, located longitudinal and parallel to epididymis corpus. The finding was present from 7 months of age up to castration (performed at 25 months of age). Scrotal circumference, testicular and epididymis consistency and symmetry as well as seminal quality were normal during the follow-up period. The ultrasonographic appearance of the scrotal wall, pampiniform plexus, gonad and epididymis was normal. However, an anechoic region surrounded by a wall forming a sac-like structure with a blind end at its dorsal pole was seen on the swelling area. The examination of fluid aspirated from the saccular contents revealed the presence of mononuclear cells mainly from lymphocytic and histiocytic type as well as some loosing degenerated mesothelial cells. Gross examination at castration revealed a blind sac-like appendix derived from an evagination in the parietal layer of the tunica vaginalis. The structure of approximately 5.0 cm in length extended from the dorsal edge of the epididymis cauda. No adherences with surrounded tissues were observed. Histopathology of the sac wall showed a smooth inner surface composed by scarce mesothelial cells forming in some areas papillary-like projections protruding to the vaginal cavity. Underneath, a thick layer of fibrous tissue mixed with collagen fibres and mononuclear inflammatory cells were seen. The potential consequences of this saccular formation at an older age in a bull are unknown.

A joint myxoma in a dog.

Myxomas of the joints are extremely rare in domestic animals, only four cases, all in dogs, having been reported previously. This paper describes a myxoma originating from the synovium of the right radiocarpal joint of a mature female Dobermann pinscher with right front limb lameness. The tumour was excised surgically and no recurrence was detected during a 2-year follow-up period. Immunohistochemically, the tumour cells reacted with antibodies to vimentin and S100 protein but not with antibodies to cytokeratins (high and low molecular weight) or human callus keratin.

Leukoencephalitis and vasculitis with perivascular demyelination in a Weimaraner dog.

Aseptic and noninfectious diseases of the central nervous system are being recognized with increasing frequency. After multiple episodes of neurologic illness, this 7-year-old Weimaraner dog was euthanatized and submitted for postmortem examination. Lesions in the central nervous system were found mainly in the white matter of the cerebral cortex and cervical spinal cord and represented acute and more chronic injury. Necrotizing vasculitis with fibrinoid change and a marked neutrophilic infiltrate dominated the acute lesions. More chronic changes consisted of perivascular demyelination and accumulation of foamy macrophages with positive staining for myelin. An immune-complex (Arthus-type) vasculitis is suspected.

[Determination of serologic markers of hepatitis B virus in high risk areas at the Central Air Force Hospital of Peru]. / Determinación de marcadores serológicos del virus de la hepatitis B en áreas de alto riesgo del Hospital Central Fuerza Aérea del Perú.

In the present paper, the serologic markers of Hepatitis B virus were studied in 123 people belonging to the Hospital Central de la Fuerza Aérea del Perú that had been working in areas of high risk to get contact with this virus. The determination was done with the enzimo inmuno assay (EIA Abbot) and the results were the following: In 15 individuals (12.1%), at least one positive marker was found, evidence which proved to have been in contact with the virus in some moment of his life. Only one carrier (0.8%) was found, in 6 (4.8%) the presence of anti-HBc as only marker was found and in 8 (6.5%) the presence of Anti-HBc and Anti-HBs was observed which means post infection immunity. The great number of the individuals in which the markers were found, were male: 13 (16.0%) against only 2 (4.7%) female. There wasn't great difference with relation to the prevalency of markers according to the years of work like there has been observed in other greater series. It can be concluded that in this group the incidence of infection due to VHB was no greater than that of general population, which indicates us the little contact that they have had with the contaminating material during their professional life.

[The determination of serological markers of the hepatitis B virus in high-risk areas of the Central Air Force Hospital of Peru]. / Determinación de marcadores serológicos del virus de la hepatitis B en áreas de alto riesgo del Hospital Central Fuerza Aérea del Perú.

In the present paper, the serologic markers of Hepatitis B virus were studied in 123 people belonging to the Hospital Central de la Fuerza Aérea del Perú that had been working in areas of high risk to get contact with this virus. The determination was done with the enzyme immunoassay (EIA Abbot) and the results were the following: In 15 individuals (12.1%), at least one positive marker was found, evidence which proved to have been in contact with the virus in some moment of his life. Only one carrier (0.8%) was found, in 6 (4.8%) the presence of anti-HBc as only marker was found and in 8 (6.5%) the presence of anti-HBc and anti-HBs was observed which means post infection immunity. The great number of the individuals in which the markers were found, were male: 13 (16.0%) against only 2 (4.7%) female. There wasn't great difference with relation to the prevalence of markers according to the years of work like there has been observed in other greater series. It can be concluded that in this group the incidence of infection due to VHB was no greater than that of general population, which indicates us the little contact that they have had with the contaminating material during their professional life.