Anticancer Activity and Tolerance of Treatments Received Beyond Progression in Men Treated Upfront with Androgen Deprivation Therapy With or Without Docetaxel for Metastatic Castration-naïve Prostate Cancer in the GETUG-AFU 15 Phase 3 Trial

Background

Androgen deprivation therapy (ADT) plus docetaxel is the standard of care in fit men with metastatic castration-naive prostate cancer (mCNPC) following results from GETUG-AFU 15, CHAARTED, and STAMPEDE. No data are available on the efficacy of treatments used for metastatic castration-resistant prostate cancer (mCRPC) in men treated upfront with ADT plus docetaxel for mCNPC.

Astrocytic high-mobility group box 1 promotes endothelial progenitor cell-mediated neurovascular remodeling during stroke recovery

Crosstalk between the brain and systemic responses in blood is increasingly suspected of playing critical roles in stroke. However, how this communication takes place remains to be fully understood. Here, we show that reactive astrocytes can release a damage-associated molecular-pattern molecule called high-mobility-group-box-1 (HMGB1) that promotes endothelial progenitor cell (EPC)-mediated neurovascular remodeling during stroke recovery. Conditioned media from reactive astrocytes increase EPC proliferation in vitro. siRNA suppression of HMGB1 in astrocytes or blockade of the HMGB1 receptor for advanced glycation endproducts in EPCs prevents this effect. In a mouse model of focal cerebral ischemia, reactive astrocytes in the peri-infarct cortex up-regulate HMGB1 at 14 d poststroke, along with an accumulation of endogenous EPCs. In vivo siRNA suppression of HMGB1 blocks this EPC response, reduces peri-infact angiogenesis, and worsens neurological deficits. Taken together, these molecular and in vivo findings support a previously undescribed mechanism of crosstalk between reactive astrocytes and EPCs wherein HMGB1 promotes neurovascular remodeling and functional recovery after stroke and brain injury.     

Risk factors for developing nosocomial infections among pediatric patients

BACKGROUND: Nosocomial infections (NIs) are important causes of morbidity and mortality in pediatric hospitals. Multiple factors contribute towards exposing children to the risk of infection when hospitalized, and some of them differ from those in adults. METHODS: This was a prospective study in a tertiary-level teaching pediatric hospital in Salvador, Bahia, Brazil, conducted from January to July, 2003, to describe the epidemiologic characteristics of NIs. Centers for Disease Control's standard definitions were used and the data recorded included intrinsic and extrinsic risk factors. RESULTS: We evaluated 808 patients. There were 143 episodes of NI in 124 patients (15.4%). The overall incidence of NI cases was 9.2 per 1,000 patient-days, with higher rates among children aged less than 1 year (P < 0.001) and those with nonsurgical clinical diseases (P < 0.001). Gastrointestinal infections (39.2%) and eye, ear, nose, throat or mouth infections (29.4%) were most common. The factors most closely associated with higher incidence of NI were respiratory disease on admission (incidence density ratio [IDR], 4.0; 95% confidence interval [CI], 2.83-5.72), another disease associated with admission diagnosis (IDR, 3.5; 95% CI, 2.41-5.02), nonsurgical clinical disease (IDR, 5.9; 95% CI, 3.92-8.85) and pediatric intensive care unit residence (IDR, 3.5; 95% CI, 1.91-6.28). The lengths of hospital stay for patients with and without nosocomial infection were, respectively, 14.1 days (SD, 20.5 days) and 5.1 days (SD, 6.6 days) (t = 121.76; P < 0.001). CONCLUSIONS: Nosocomial infections are a frequent complication in pediatrics. They are not necessarily related to invasive procedures but certainly are related to a group of factors that have particular characteristics in the pediatric age group.     

Gender effects on cardiac valvular function in hyperprolactinaemic patients receiving cabergoline: a retrospective study

Background Ergot‐derived dopamine agonists are associated with increased risk of valvular dysfunction in Parkinson’s disease. The risk of valvular disease associated with lower doses of cabergoline used to treat prolactinomas remains controversial. Objective To determine whether there is an association of cabergoline and valvular function in patients with hyperprolactinaemia according to gender. Design Case‐record retrospective study. Setting Outpatient neuroendocrine clinical centre at a tertiary care hospital. Study participants One hundred patients (48 men and 52 women) with hyperprolactinaemia who had an echocardiogram while receiving cabergoline for at least 6 months. Controls One hundred controls (48 men and 52 women) selected from Massachusetts general hospital (MGH) database of echocardiograms without clinically significant findings, matched to patients for age, gender, body mass index (BMI) and hypertension. Main outcome measure Echocardiogram. Results There were no significant differences in valvular function in patients compared with controls. However, women patients had a higher prevalence of mild tricuspid regurgitation (TR) than female controls (15·4%vs. 1·9%, P = 0.03). Among men only, patients had more trace TR than controls (68·8%vs. 45·8%, P = 0.02). The mild valvular regurgitation in patients was not clinically significant and did not correlate with dose, duration or cumulative dose. Conclusions Overall cabergoline was not associated with valvulopathy. However, subdivided by gender, hyperprolactinaemic men and women had higher prevalence of trace or mild TR, respectively, compared with gender matched controls. There may be gender differences in valvular dysfunction associated with cabergoline. Longer term, larger studies are necessary to evaluate definitively an effect of cabergoline on valvular function in hyperprolactinaemic patients.     

The use of tibial Less Invasive Stabilization System (LISS) plate [AO-ASIF] for the treatment of paediatric supracondylar fracture of femur: a case report

Paediatric supracondylar fractures of the femur are not common. The treatment options depend on the age of child, the site of the fracture, the pattern of injury and the surgeon's preference. We report a case of an 11-year old boy who sustained a comminuted displaced supracondylar fracture of the femur and was treated with indirect reduction and internal fixation with the Less Invasive Stabilization System (LISS) tibial plate.     

Sensorineural hearing loss in very low birth weight infants with histological chorioamnionitis

Objective: Histological chorioamnionitis (HCAM) has been associated with inflammatory diseases of preterm infants. Recently we have observed that it increased the risk of speech delay and hearing loss. So the aim of this study was to evaluate the relationship between sensorineural hearing loss (SNHL) of VLBW infants and HCAM.

Methods: We performed an observational study on VLBW infants admitted to the NICU of Padua. Each patient with HCAM was matched with one control without HCAM. All infants underwent hearing screening before discharge by means of automated transient–evoked otoacustic emissions and automated auditory brainstem responses, which were repeated at 3 and 6 months of age with tympanometry measurement. Incidence of SNHL at 6 months of age was compared in the 2 groups and risk factors for hearing loss were studied.

Results: Two of 77 (2.6%) newborns with HCAM e 6/73 (8.2%) without it presented SNHL at 6 months of corrected age (p?=?0.16). Multivariable logistic regression analysis identified surgical ligation of patent ductus arteriosus (PDA) as independent predictors of SNHL (OR: 5.75, 95% CI 1.34–24.84, p?=?0.02), whereas the effect of HCAM on SNHL was only near to statistical significance level.

Conclusions: Surgical ligation of PDA is associated with an increased risk of SNHL in VLBW infants, regardless of HCAM.     

Is aortic lymphadenectomy necessary in the management of endometrial carcinoma?

OBJECTIVE: To evaluate the role of aortic lymphadenectomy in the management of endometrial carcinoma. METHODS: Clinical notes of 163 patients with endometrial carcinoma were reviewed. All patients had peritoneal cytology, total abdominal hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy with or without aortic lymphadenectomy. RESULTS: Seventy-five (46.0%) patients had pelvic lymphadenectomy alone whereas 88 (54.0%) had both pelvic and aortic lymphadenectomy. Thirty-five (21.5%) patients had nodal metastases with positive pelvic and aortic nodes in 26 (16.0%) and 24 (27.3%) patients, respectively. Isolated aortic metastases were found in 17 cases (19.3%). Among 35 patients with nodal metastases, recurrence developed in 15 (42.9%) patients and all except one died within five to 50 months. The remaining patients had a median disease-free period of 55 months (13-93 months). The recurrence rate was higher (63.6%) among patients with upper aortic lymph node metastases, and all those who recurred died of disease within seven to 28 months. CONCLUSIONS: Our data suggest that aortic lymphadenectomy provides both diagnostic and therapeutic value in the management of endometrial carcinoma with high metastatic risk. After surgical removal and adjuvant radiotherapy, patients with nodal metastases achieved a better survival chance.     

Cushing's disease in children: report of three cases

Cushing's disease is rare in children and adolescents. We report the clinical presentations of three children with Cushing's disease. All three exhibited the typical symptoms and signs of weight gain and growth retardation. Tw o also demonstrated personality changes, hypertension and hypokalemia, the last of these being rarely reported in patients with Cushing's disease. Lack of diurnal changes in serum cortisol levels was the most common biochemical finding. Serum cortisol levels were suppressed by low-dose dexamethasone in one patient, which is not typical for patients with Cushing's disease. Imaging studies are essential for localizing the tumor. Transsphenoidal surgery remains the treatment of choice, and pituitary irradiation should be considered for those patients whose tumors cannot be totally removed. Careful follow-up of these patients with awareness of the possibilities of relapse and the complications of hypopituitarism is indicated.