68Ga-PSMA PET/CT-based metastasis-directed radiotherapy for oligometastatic prostate cancer recurrence after radical prostatectomy.

PURPOSE: The aim of this communication was to assess the efficacy of directed oligometastatic radiotherapy (RT) based on 68Ga-PSMA PET/CT in patients with prostate cancer (PCa) biochemical relapse (BCR) after primary treatment with curative intent. METHODS: This is a retrospective analysis of a monocentric cohort of PCa patients diagnosed with oligometastatic disease on 68Ga-PSMA PET/CT and treated with metastasis-directed RT. Inclusion criteria were: histologically proven PCa, BCR after primary treatment with curative intent, oligometastatic disease defined as ≤ 3 metastatic lesions. To evaluate the efficacy of the therapy, biochemical response defined as a decrease of > 50% of PSA (PSA50) was measured at 1 and 4 months. Patients were followed up until progression and start of androgen deprivation therapy (ADT). BCR-free survival and ADT-free survival were calculated. RESULTS: 20 patients met the inclusion criteria. Median PSA value: 1.4 ng/ml (IQR, 0.3-2.3 ng/ml). A total of 30 PSMA-positive lesions were treated: 18 lymph nodes (60%), nine bone (30%) and three visceral lesions (10%). Median follow-up was 15 months (range 4-33 months). Biochemical response at 1 and 4 months was found in 3/20 patients (15%) and 14/20 (70%), respectively. BCR-free survival rate at 1 year was 79% and 53% at 2 years. ADT-free survival at 2 years was 74%. CONCLUSION: This retrospective study suggests that metastasis-directed RT based on 68Ga-PSMA PET/CT may be a valuable treatment in patients with PCa oligometastatic disease, providing promising BCR-free survival rates and potentially postponing ADT for at least 2 years in 74% of the patients. Response assessment should not be measured before 4 months after treatment.

Outcome of uterine sarcoma patients treated with pazopanib: A retrospective analysis based on two European Organisation for Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group (STBSG) clinical trials 62043 and 62072.

BACKGROUND: Uterine sarcomas are a group of mesenchymal tumours comprising several histologies. They have a high recurrence rate following surgery, modest outcome to systemic therapy, and poor overall survival. Pazopanib is a multi-targeted tyrosine kinase inhibitor approved for non-adipocytic advanced soft tissue sarcomas (STS). Here we investigated whether response to pazopanib in patients with uterine sarcomas differs from that of patients with non-uterine sarcomas. PATIENTS AND METHODS: Uterine sarcoma patients were retrieved from all soft tissue sarcoma patients treated with pazopanib in EORTC Phase II (n=10) and Phase III (PALETTE) (n=34) studies. Patient and tumour characteristics, response, progression free and overall survival data were compared. RESULTS: Forty-four patients with uterine sarcoma were treated with pazopanib. The majority of patients had uterine leiomyosarcoma (LMS) (n=39, 88.6%) with high grade tumours (n=37, 84.1%) compared to 54.8% (n=164) in the non-uterine population. The median age was 55years (range 33-79) and median follow up was 2.3years. Uterine patients were heavily pre-treated, 61.3% having ≥2 lines of chemotherapy prior to pazopanib compared to 40.8% in the non-uterine population. Five patients (11%), all LMS, had a partial response (95% CI 3.8-24.6). Median progression free survival (PFS) 3.0months (95% CI 2.5-4.7) in uterine versus 4.5 (95% CI 3.7-5.1) in non-uterine STS. Median overall survival (OS) was 17.5months (95% CI 11.1-19.6), longer than the non-uterine population, 11.1months (95% CI 10.2-12.0) (p=0.352). CONCLUSIONS: Despite heavy pre-treatment, pazopanib shows signs of activity in patients with uterine sarcoma with the similar outcomes to patients with non-uterine STS.

Role of corticosteroids in prostate cancer progression: implications for treatment strategy in metastatic castration-resistant patients.

Corticosteroid agents (CA) are widely used in the treatment of metastatic castration-resistant prostate cancer (mCRPC) either as concomitant treatment with active agents such as docetaxel, cabazitaxel and abiraterone or in a palliative setting, predominantly due to their anti-inflammatory activity. However, the chronic use of CA has numerous side effects, especially in case of steroid-induced adrenal insufficiency. Furthermore, the latest clinical and preclinical data demonstrate that CA themselves are likely to promote tumour progression in certain populations of patients with mCRPC. Therefore, the role of CA in advanced disease should be carefully weighed for each patient and their withdrawal should be considered in some patients. This is necessary, especially in clinical trials that need good performance status patients to evaluate the activity and the safety of emerging drugs in mCRPC that do not require the concurrent use of CA. In oncology, there is no consensus on an algorithm of gradual steroid tapering and frequently the approach to this procedure is empirical. An algorithm is presented in this article based on clinical observations. Prospective studies are necessary to evaluate the efficacy and safety of the above-proposed algorithm in metastatic castration-resistant prostate cancer.

International study on nurses' views and experiences of compassion.

BACKGROUND: Compassion is considered the cornerstone of nursing practice. However, the recent failures in delivering high-quality compassionate nursing care in the UK's National Health Service have brought the topic of compassion to the attention of the public, service providers, policy makers and academics. AIM: The aim of this study was to explore the nurses' views and experiences of a number of compassion-related issues in nursing and describe similarities and differences at an international level as well as from the different nursing roles of the participating nurses. METHODS: An exploratory, cross-sectional descriptive study, using the International Online Compassion Questionnaire. A total of 1323 nurses from 15 countries completed the questionnaire. RESULTS: The majority of participants (59.5%) defined compassion as "Deep awareness of the suffering of others and wish to alleviate it" but definitions of compassion varied by country. Of participants, 69.6% thought compassion was very important in nursing and more than half (59.6%) of them argued that compassion could be taught. However, only 26.8% reported that the correct amount and level of teaching is provided. The majority of the participants (82.6%) stated that their patients prefer knowledgeable nurses with good interpersonal skills. Only 4.3% noted that they are receiving compassion from their managers. A significant relationship was found between nurses' experiences of compassion and their views about teaching of compassion. CONCLUSION: Our study is unique in identifying the views and experiences of nurses from 15 different countries worldwide. The findings reveal that compassion is neither addressed adequately in nursing education nor supported in the practice environment by managers. LIMITATIONS: Self-report bias was inherent to our survey study design. Furthermore, the individual cultural differences and similarities in the findings are difficult to extrapolate owing to the fact that our analysis was at country level, as well as at the level of the participating nurses. IMPLICATIONS FOR NURSING POLICY: Understanding the influence of culture on nurses' views about compassion is critical in the current multicultural healthcare environment and merits further research. This will potentially drive changes in nursing education (ensuring that compassion is taught to nurses) and in the way healthcare leaders and managers foster a compassionate culture within their organizations (e.g. by leading by example and compassionate to their staff).

A prospective case-control study of non-healing wounds of the lower limbs - the value of biopsies for ulcerating carcinoma.

BACKGROUND: In some leg ulcer patients there is cancer that is responsible for lack of healing of such a wound. AIM: This study was aimed at prospective analysis of histopathology of non-healing wounds (NHWs) in the patient presenting with high and low suspicion for ulcerating carcinoma. MATERIAL AND METHODS: Forty patients with NHWs were enrolled and had been prospectively divided into two groups: 25 patients with high suspicion for ulcerating carcinoma according to their medical history and physical examination, and the second group of 15 patients without suspicion for malignancy (control group). All NHWs were photographed and underwent biopsies. RESULTS: In the control group biopsies did not reveal cancers. On the contrary, in 10 patients (40%) from high suspicion group biopsies revealed cancers: seven basal cell carcinomas (BCCs), one - malignant melanoma, one - Bowen's disease and one - squamous cell carcinomas. Histopathology of six of seven BCCs suggested that non-healing benign wound might have preceded malignancy. We found that leg ulcers which were small (wound area less than 3 cm(2) ), longstanding (duration 24 ≤ weeks), presenting with granulation tissue covering ≥75% of the wound area, with a dull pink appearance of the granulation tissue, or an atypical clinical presentation, can actually be an ulcerating carcinoma. Dull pink granulation tissue or an atypical clinical presentation of ulceration, as a single clinical finding, suggested an underlying malignancy with a statistical significance (71.5% vs. 0%; P = 0.001 and 27.8% vs. 0%; P = 0.0049 respectively). CONCLUSIONS: Prevalence of malignancy, primarily: BCCs in NHWs, may be higher than expected and clinical features suggestive of such a nature of ulcer are an indication for diagnostic biopsy.

Phase I trial combining temozolomide plus lapatinib for the treatment of brain metastases in patients with HER2-positive metastatic breast cancer: the LAPTEM trial.

BACKGROUND: Brain metastases (BMs) pose a clinical challenge in breast cancer (BC). Lapatinib or temozolomide showed activity in BM. Our study assessed the combination of both drugs as treatment for patients with HER2-positive BC and BM. METHODS: Eighteen patients were enrolled, with sixteen of them having recurrent or progressive BM. Any type of previous therapy was allowed, and disease was assessed by gadolinium (Gd)-enhanced magnetic resonance imaging (MRI). The primary end points were the evaluation of the dose-limiting toxicities (DLTs) and the determination of the maximum-tolerated dose (MTD). The secondary end points included objective response rate, clinical benefit and duration of response. RESULTS: The lapatinib-temozolomide regimen showed a favorable toxicity profile because the MTD could not be reached. The most common adverse events (AEs) were fatigue, diarrhea and constipation. Disease stabilization was achieved in 10 out of 15 assessable patients. The estimated median survival time for the 16 patients with BM reached 10.94 months (95% CI: 1.09-20.79), whereas the median progression-free survival time was 2.60 months [95% confidence interval (CI): 1.82-3.37]. CONCLUSIONS: The lapatinib-temozolomide combination is well tolerated. Preliminary evidence of clinical activity was observed in a heavily pretreated population, as indicated by the volumetric reductions occurring in brain lesions.

Sexual violence in post-conflict Liberia: survivors and their care.

Using routine data from three clinics offering care to survivors of sexual violence (SV) in Monrovia, Liberia, we describe the characteristics of SV survivors and the pattern of SV and discuss how the current approach could be better adapted to meet survivors' needs. There were 1500 survivors seeking SV care between January 2008 and December 2009. Most survivors were women (98%) and median age was 13 years (Interquartile range: 9-17 years). Sexual aggression occurred during day-to-day activities in 822 (55%) cases and in the survivor's home in 552 (37%) cases. The perpetrator was a known civilian in 1037 (69%) SV events. Only 619 (41%) survivors sought care within 72 h. The current approach could be improved by: effectively addressing the psychosocial needs of child survivors, reaching male survivors, targeting the perpetrators in awareness and advocacy campaigns and reducing delays in seeking care.

Pain evaluation and control during and following the treatment of hypertrophic scars and keloids by contact and intralesional cryosurgery--a preliminary study.

BACKGROUND: Intralesional cryosurgery effectively treats hypertrophic scars and keloids (HSK), but pain experienced by the patient during treatment can limit the application of cryosurgery. OBJECTIVES: To characterize the pain response during cryosurgical treatment of HSK, and to evaluate the pain experienced during contact and intralesional cryosurgery that employs a pain-control protocol. METHODS: Twenty-nine patients (17 women, 12 men) aged 17 years and older (mean ages 31.9±12.5 and 38.9±18.6 years, respectively, P=0.24), who were treated for a total of 36 HSKs by intralesional (n=20; 22 cryotreatments) or contact (n=9; 14 cryotreatments) cryosurgery were evaluated. The pain-control protocol involved oral pain-relief tablets (Dipyrone) and translesional local anaesthesia with Bupivacaine hydrochloride 0.5%. Pain evaluation according to the Visual Analogue Scale (VAS) (0-10 cm) was compared between the two groups at three time points: during cryosurgery, immediately after it, and 4 h later. Scores ≤3 cm were considered to define the 'zone of analgesic success'. These results were compared with control data (contact cryosurgery without a pain-control protocol; n=56). RESULTS: Pain in the intralesional group was significantly lower than that in the contact group during and immediately after cryotreatment. During: mean VAS=1.68±2.21 vs. 5.07±4.01 cm; median VAS=0.5 vs. 5.5 cm, respectively; P<0.0001. Immediately after: mean VAS=1.22±1.77 vs. 5.38±3.81 cm; median VAS=0 vs. 6.0 cm, respectively; P=0.001. The control group had more pain during treatment (mean VAS=5.34±2.31, median=6.0) and 4 h later (mean=3.79±2.35, median=4.0) than the intralesional group (P<0.0001 and P=0.988, respectively). The pain level in the control group during the cryotreatment did not differ from that in the contact group (P=0.988). In the intralesional, contact and control groups analgesic success (VAS ≤3 cm) was achieved in 77.3%, 35.7% and 33.9%, respectively, of cases (P=0.002) during cryotreatment, and in 54.5%, 42.9% and 33.9%, respectively, of cases 4 h after treatment (P=0.24). CONCLUSIONS: The pain-control protocol significantly reduced pain severity to tolerable levels (VAS ≤3 cm) during and following intralesional and contact cryosurgery. Intralesional cryosurgery caused the least pain during and immediately after treatment.

[Electronic calendar as an organization element in Internal Medicine services]. / Los calendarios electrónicos como herramientas de organización de los servicios de Medicina Interna.

The growing volume of information and introduction of new technologies in the Internal Medicine hospital department mare making the traditional updating «methods¼ of knowledge and organization obsolete. The development of new tools could help the management of information and organization of the medical departments is outdated. Electronic calendar such as the Google calendar facilitate adequate coordination among health care professionals. Our experience suggests that the Google calendar is a simple and useful tool that helps planning and organization of the clinical, educational, and research activities of the different medical departments, limits loss of information and improves efficacy with a close to zero cost of infrastructure.

[Phenotypic and genotypic detection of the production of carbapenemases type NDM-1 and KPC in isolated Enterobacteriaceae in a clinical laboratory in Maracay, Venezuela]. / Detección fenotípica y genotípica de la producción de carbapenemasas tipo NDM-1 y KPC en enterobacterias aisladas en un laboratorio clínico en Maracay, Venezuela.

BACKGROUND: The production of carbapenem-hydrolyzing ß-lactamases is one of the most concerning resistance mechanisms since it eliminates the last therapeutic option against multidrug resistant microorganisms. AIM: To determine the production of KPC and NDM-1 type carbapenemases, using phenotypic and genotypic methods, in isolated enterobacteria in a clinical laboratory in the city of Maracay, Venezuela. METHODS: The production of carbapenemases was determined by phenotypic (according to the Malbrán algorithm) and genotypic methods (amplification of the blaNDM-1 and blaKPC genes by PCR) in clinical isolates of Enterobacteriaceae during the period March-August 2018. RESULTS: 605 Enterobacteriaceae of different species were identified, being Escherichia coli the strain with the highest percentage of isolation (61.3%), followed by Klebsiella pneumoniae (14.9%). Sixteen strains (2.64%) were positive for carbapenemases production: 13 strains of K. pneumoniae and three of the Enterobacter cloacae complex. PCR showed that 14 strains (87.5%) carry the blaNDM-1 gene and two strains (12.5%) the blaKPC gene; 100% agreement was observed between phenotypic determination and PCR for both groups of enzymes. CONCLUSIONS: The results of this study showed a higher incidence of metallo-ß-lactamase type NDM-1, which rapid dissemination and consequently difficult control has been cause of epidemiological alert. The identification of the type of enzyme would allow establishing more accurate management and control strategies in order to eradicate these pathogens.

Spontaneous retroperitoneal hemorrhage in dialysis: a presentation of 5 cases and review of the literature.

BACKGROUND: Spontaneous retroperitoneal hemorrhage (SRH) is a rare but potentially fatal entity. Despite published case reports of SRH in dialysis, little systematic information is available. METHODS: Report of 5 cases and review of MEDLINE database from 1971 until 2008. RESULTS: Incidence of SRH in our unit was 0.86 cases per 100 patients; annual incidence rate 8/10,000 patients. We identified 34 publications, comprising 55 cases. The existing cases and the 5 reported were analyzed: 74.5 % male, average age 53.3 years (range 27-78), average time on dialysis 7.1 years (range 3 weeks-27.5 years), 95% on hemodialysis and 5% on peritoneal dialysis. There was significant heterogeneity in clinical presentation. The kidney was the most commonly reported origin (87.8%), and acquired cystic kidney disease (ACKD) was the most frequent underlying cause. 91.8% received some kind of anticoagulation. Treatment was conservative, included angioembolization or surgery in 33.3%, 17.6% and 49% of the cases respectively. Mortality rate was 18.3%. CONCLUSIONS: More than 85% of SRH in dialysis had a renal cause, ACKD being predominant. The complication occurs mainly in the HD modality, possibly in relation to anticoagulation. There is no evidence that screening of ACKD is of benefit predicting SRH. Therefore, awareness of ACKD as a manifestation of ESRD patients and its risk of bleeding is necessary. Because of the summation of risk factors that appears in the population on dialysis, SRH should be considered in the differential diagnosis of unexplained pain before drop in blood pressure or hematocrit occurs.

Docetaxel plus oblimersen sodium (Bcl-2 antisense oligonucleotide): an EORTC multicenter, randomized phase II study in patients with castration-resistant prostate cancer.

BACKGROUND: This randomized, phase II study assessed the activity of oblimersen sodium, a Bcl-2 antisense oligonucleotide, administered before docetaxel (Taxotere) to patients with castration-resistant prostate cancer. PATIENTS AND METHODS: Chemotherapy-naive patients with prostate-specific antigen (PSA) progression and testosterone < or = 0.5 ng/ml received docetaxel 75 mg/m2 on day 1 or oblimersen 7 mg/kg/day continuous i.v. infusion on days 1-7 with docetaxel 75 mg/m2 on day 5 every 3 weeks for < or = 12 cycles. Primary end points were confirmed PSA response (Bubley criteria) and major toxic events. RESULTS: Confirmed PSA response was observed in 46% and 37% of 57 and 54 patients treated with docetaxel and docetaxel-oblimersen, respectively. Partial response (RECIST) was achieved in 18% and 24%, respectively. Oblimersen added to docetaxel was associated with an increase in the incidence of grade > or = 3 fatigue, mucositis, and thrombocytopenia. Major toxic events were reported in 22.8% and 40.7% of patients with docetaxel and docetaxel-oblimersen, respectively. CONCLUSIONS: The primary end points of the study were not met: a rate of confirmed PSA response >30% and a major toxic event rate <45% were not observed with docetaxel-oblimersen.

Contribution of molecular diagnosis of allergy to the management of pediatric patients with allergy to pollen.

BACKGROUND: Component-resolved diagnosis based on recombinant allergens facilitates treatment of multiple sensitization and/or crossreactivity in allergic patients. OBJECTIVE: To assess the usefulness of molecular diagnosis in childhood allergies. METHODS: A total of 162 children aged 4-16 years diagnosed with allergic rhinitis or asthma/rhinitis caused by pollen were referred for recombinant allergen-based diagnosis in 2006. Specific immunoglobulin (Ig) E against pollen allergens and purified recombinant Phleum pratense pollen allergens were measured using an in vitro quantitative assay, and considering the recombinant allergens Phl p 1+Phl p 5 as P pratense--specific allergens and Phl p 7+Phl p 12 as cross-reacting allergens. Conditional probability was calculated to determine the relationship between values for specific IgE against major allergens and those for cross-reacting allergens. RESULTS: Specific IgE antibodies against P pratense were detected in 99.4% of serum samples, and cross-reacting allergens in 46%. Multiple sensitization to pollen was documented in 38% of patients, with Plantago lanceolata as the main cause. Conditional probability calculations showed that patients with specific IgE values of 75-80 kU(A)/L to Phl p 1+Phl p 5 were 75% (95% confidence interval) more likely to present values > or = 2 kUA/L to Phl p 7+Phl p 12. CONCLUSIONS: Our results show that recombinant DNA technology can help diagnose allergy in cases of multiple sensitization and crossreactivity, and is therefore a promising option for improving prognosis and management of allergic pediatric populations.