Prospective Assessment of Bone Metabolism Biomarkers and Survival in Metastatic Castration-resistant Prostate Cancer Patients Treated with Radium-223: The PRORADIUM Study.

BACKGROUND: Radium-223 is an active therapy option for bone metastatic castration-resistant prostate cancer (mCRPC). The lack of adequate biomarkers for patient selection and response assessment are major drawbacks for its use. OBJECTIVE: To assess the prognostic value of bone metabolism biomarkers (BMBs) in ra-223-treated mCRPC patients. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of mCRPC patients treated with Ra-223 (PRORADIUM study: NCT02925702) was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The main objective of the study was to evaluate the association between high (≥median) baseline values in at least three bone formation (bone alkaline phosphatase [BAP] and C-terminal type-I collagen propeptide) and bone resorption (N-terminal telopeptide and pyridinoline) biomarkers, and survival. The independent prognostic value of each BMB was also assessed. The association with time to radiographic, clinical, and prostate-specific antigen (PSA) progression; time to skeletal-related events; and PSA response were secondary objectives. Multivariable (MV) Cox-regression models were evaluated. RESULTS AND LIMITATIONS: A total of 169 patients were included. Of the patients, 70.4% received Ra-223 in second/third line; 144 (85.2%) were Eastern Cooperative Oncology Group 0-1, 126 (74.6%) were in pain, and 80 (47.5%) had more than ten bone metastases. Sixty-seven (39.6%) patients had elevation in at least three BMBs. The median overall survival was 12.1 mo (95% confidence interval [CI]: 10-14.7). No association was observed with other treatment-related secondary outcome parameters. Patients with high values in three or more BMBs had significantly worse survival (9.9 vs 15.2 mo; hazard ratio [HR]: 1.8 [95% CI: 1.3-2.5]; p < 0.001) in the univariate analysis, but not independent in the MV analysis (HR: 1.33; 95% CI: 0.89-2; p = 0.181). High baseline BAP was the only biomarker associated with survival in the MV model (HR: 1.89; 95% CI: 1.28-2.79; p = 0.001). Addition of BAP to the MV clinical model increased the area under the receiver operating characteristic curve 2-yr value from 0.667 to 0.755 (p = 0.003). CONCLUSIONS: Biomarkers of bone formation, especially BAP, have prognostic value in mCRPC patients treated with radium-223. Its predictive value remains to be assessed, ideally in prospective, adequately powered, randomised clinical trials. PATIENT SUMMARY: In this study, we evaluate the role of bone metabolism biomarkers to help improve the use of radium-223 as therapy for advanced prostate cancer. We found that bone alkaline phosphatase may be a suitable tool.

A systematic review and meta-analysis on the efficacy of topical povidone iodine in adenoviral conjunctivitis.

PURPOSE: To evaluate if topical povidone iodine (alone (PI) or combined with dexamethasone (PI-DXM)) is superior to placebo for treating adenoviral conjunctivitis (AC). METHODS: A systematic review was performed according to Preferred Reporting Items for the Systematic Review and Meta-Analyses (PRISMA) Statement. An electronic search was made on PubMed, Embase and Cochrane Library. Randomized control studies that compared PI or PI-DXM with placebo were included. At least three researchers were involved in all phases. Primary outcomes were AC duration and the number of clinical resolutions during the first week. Secondary outcomes were conjunctival redness and serous discharge one week after starting treatment and the rate of AC complications. RESULTS: Only five studies met the inclusion criteria. PI-DXM reduced the duration of the disease by 2.4 days (IC95% 4.09-0.71), however this result was based only in one study. PI and PI-DXM did not modify the probability of clinical resolution during the first week; relative risk (RR) = 1.77 (IC95% 0.63-4.96) and 1.70 (IC95% 0.67-4.36). The impact of PI on the probability of pseudomembranes could not be estimated. PI-DXM did not influence the risk of developing subepithelial infiltrates RR = 0.73 (IC95% 0.02-33.38). CONCLUSIONS: At this time there is great uncertainty about the usefulness of PI on the course of adenoviral conjunctivitis. PI-DXM may have a small effect on AC duration. To make future reviews possible, it is important to standardize the way in which these results are reported. Futures studies should include etiological confirmation, unit of study (eyes vs patients) and report on those aspects that are more relevant for patient quality of life (duration of the disease, development of complications: pseudomembranes and subepithelial infiltrates).

Impact of concurrent tumour events on the prostate cancer outcomes of germline BRCA2 mutation carriers.

BACKGROUND: Several studies have reported the association of germline BRCA2 (gBRCA2) mutations with poor clinical outcomes in prostate cancer (PCa), but the impact of concurrent somatic events on gBRCA2 carriers survival and disease progression is unknown. PATIENTS AND METHODS: To ascertain the role of frequent somatic genomic alterations and histology subtypes in the outcomes of gBRCA2 mutation carriers and non-carriers, we correlated the tumour characteristics and clinical outcomes of 73 gBRCA2 and 127 non-carriers. Fluorescent in-situ hybridisation and next-generation sequencing were used to detect copy number variations in BRCA2, RB1, MYC and PTEN. Presence of intraductal and cribriform subtypes was also assessed. The independent impact of these events on cause-specific survival (CSS), metastasis-free survival and time to castration-resistant disease was assessed using cox-regression models. RESULTS: Somatic BRCA2-RB1 co-deletion (41% versus 12%, p < 0.001) and MYC amplification (53.4% versus 18.8%, p < 0.001) were enriched in gBRCA2 compared to sporadic tumours. Median CSS from diagnosis of PCa was 9.1 versus 17.6 years in gBRCA2 carriers and non-carriers, respectively (HR 2.12; p = 0.002), Median CSS in gBRCA2 carriers increased to 11.3 and 13.4 years in the absence of BRCA2-RB1 deletion or MYC amplification, respectively. Median CSS of non-carriers decreased to 8 and 2.6 years if BRCA2-RB1 deletion or MYC amplification were detected. CONCLUSIONS: gBRCA2-related prostate tumours are enriched for aggressive genomic features, such as BRCA2-RB1 co-deletion and MYC amplification. The presence or absence of these events modify the outcomes of gBRCA2 carriers.

Poppers maculopathy: A quantitative review of previous literature.

AIM: To review the available literature on poppers maculopathy (PM). MATERIAL AND METHODS: Sixty-four patients (60 with bilateral and 4 with unilateral involvement), for a total of 124 eyes were reported in PubMed, Google Scholar and Embase. Patterns were analyzed according to country, age, gender, sexual orientation, HIV status, consumption habits, visual acuity at presentation (VAP), final visual acuity (VAF) and optical coherence tomography (OCT). RESULTS: Most cases (110 eyes) of PM were reported in European countries and affected middle-aged men (only 8 eyes from female users). The median age was 38.7 years (SD = 10.5 years). Final visual acuity (Median = 0.8; Interquartile range: 0.67-1) was higher than visual acuity at presentation (Median = 0.67; Interquartile range: 0.4-0.8). Many articles lack data on sexual orientation and HIV status as this is considered very personal information. One third of the eyes (40 eyes) developed PM after a single exposure. No significant differences were found between eyes that developed PM after a single exposure and those which developed the condition after several exposures. The most commonly reported pattern was an interruption of the ellipsoid line (68 eyes). CONCLUSION: PM is more prevalent in Europe or European ophthalmologists are more likely to diagnose PM. PM usually affects middle-aged men given that this condition generally appears with chronic exposure to poppers. VAF was higher than VAP, suggesting that this toxicity is in part reversible. Information about HIV status was not provided in most recent articles, thus it is not possible to make inferences about the possible implication of HIV drugs as cofactors for the development of this retinal toxicity.

Impact of the COVID-19 Lockdown on Ophthalmological Assistance in the Emergency Department at a Spanish Primary Level Hospital.

PURPOSE: To analyze the changes in ophthalmological emergencies during the COVID-19 pandemic lockdown at a Spanish primary level hospital. METHODS: The number and type of emergencies attended in the emergency department of Hospital Universitario del Henares between March 10 and August 31, 2020 (COVID-19 cohort) were compared with the emergencies attended during the same period of 2019 (pre-COVID-19 cohort). Data on the diagnosis, patient age, and gender was retrospectively collected from the electronic medical records of the hospital. The different diagnoses were organized into "clusters," which include those conditions that affect the same ocular tissue and that have similar clinical expression. RESULTS: The number of ophthalmological emergencies during the study period was 841, compared to 1343 during the same month of 2019, which represents a reduction of 37.4%. The percentage reduction in each cluster was as follows: conjunctiva (-65.4%), cornea (-35.8%), uveitis (-3.6%), eyelid and orbital and lacrimal (-35.5%), strabismus (-60%), neuro-ophthalmology (-11.8%), retina (-10.6%), cataract (+16.4%), glaucoma (-37%), and miscellaneous (-45.1%). The number of people seen with viral conjunctivitis decreased by -87.1% compared to 2019. Patients with complications due to conjunctivitis also decreased: patients with pseudomembranes dropped from 16 to 4 cases and patients with corneal subepithelial infiltrates from 9 to 3 cases. CONCLUSIONS: Most diagnostic clusters showed a similar decrease. Clusters that included vision-threating conditions (retina, neuro-ophthalmology, and uveitis) remained mostly stable. During the COVID-19 lockdown, the diagnosis of adenoviral conjunctivitis decreased nearly 10 times. This fact may represent a decrease in the transmission of these infections.

Survival analysis of time to SARS-CoV-2 PCR negativisation to optimise PCR prescription in health workers: the Henares COVID-19 healthcare workers cohort study.

OBJECTIVES: Reverse transcriptase PCR (RT-PCR) is considered the gold standard in diagnosing COVID-19. Infected healthcare workers do not go back to work until RT-PCR has demonstrated that the virus is no longer present in the upper respiratory tract. The aim of this study is to determine the most efficient time to perform RT-PCR prior to healthcare workers' reincorporation. MATERIALS AND METHODS: This is a cohort study of healthcare workers with RT-PCR-confirmed COVID-19. Data were collected using the medical charts of healthcare workers and completed with a telephone interview. Kaplan-Meier curves were used to determine the influence of several variables on the time to RT-PCR negativisation. The impact of the variables on survival was assessed using the Breslow test. A Cox regression model was developed including the associated variables. RESULTS: 159 subjects with a positive RT-PCR out of 374 workers with suspected COVID-19 were included. The median time to negativisation was 25 days from symptom onset (IQR 20-35 days). Presence of IgG, dyspnoea, cough and throat pain were associated with significant longer time to negativisation. Cox logistic regression was used to adjust for confounding variables. Only dyspnoea and cough remained in the model as significant determinants of prolonged negativisation time. Adjusted HRs were 0.68 (0.48-096) for dyspnoea and 0.61 (0.42-0.88) for dry cough. CONCLUSIONS: RT-PCR during the first 3 weeks leads to a high percentage of positive results. In the presence of respiratory symptoms, negativisation took nearly 1 week more. Those who developed antibodies needed longer time to negativisate.

Open-globe-injury: A single center Spanish retrospective 5-year cohort study.

PURPOSE: To review and analyze the epidemiological profile, clinical characteristics and visual outcomes in patients attended for traumatic open globe injury (OGI) at our hospital over a 5-year period. DESIGN: Retrospective chart review study. METHODS: Retrospective analysis of all patients attended at Fundación Jiménez Díaz University Hospital for OGI between 2011 and 2015. Data from 104 patients including demographics, ocular examination, medical and surgical treatment, visual outcomes, and complications were analyzed. RESULTS: Most patients were male (79.8%) and the median age at the time of injury was 41 years (interquartile range 31.5-58 years). Work-related accidents represent more than half of the cases and their main mechanism was penetrating trauma or foreign body. This type of accident had good prognosis (median final visual acuity in decimal scale 0.8; interquartile range 0.4-1). Falls were the second most common cause of OGI, predominantly affecting senior women (50%), with a high incidence of ocular rupture (50%) and associating a poor visual prognosis (median final visual acuity 0.01; interquartile range 0-0.5). There was a strong correlation (0.75; p < 0.001) between ocular trauma score (OTS) and final best corrected visual acuity. CONCLUSIONS: Two different patterns of OGI were identified in our sample. Work-related trauma in young males was the most common form of OGI and was associated with good prognosis. However, falls in senior women were associated with poor prognosis.

Clinical Applications of Molecular Biomarkers in Prostate Cancer.

There is clinically relevant molecular heterogeneity in prostate cancer (PCa), but this biological diversity has had only a minimal impact on clinical practice. Treatment outcomes in patients with localised PCa are often highly variable, even among patients stratified to the same risk group or disease state based on standard clinical and pathological parameters. In recent years, the development of gene panels has provided valuable data on the differential expression of genes in patients with PCa. Nevertheless, there is an urgent need to identify and validate prognostic and predictive biomarkers that can be applied across clinical scenarios, ranging from localised disease to metastatic castration-resistant PCa. The availability of such tools would allow for precision medicine to finally reach PCa patients. In this review, we evaluate current data on molecular biomarkers for PCa, with an emphasis on the biomarkers and gene panels with the most robust evidence to support their application in routine clinical practice.

Cytomegalovirus infection associated with severe intraocular inflammation in an HIV patient: a case report.

This is a report of a case of severe intraocular inflammation associated with cytomegalovirus in an untreated HIV+ patient with a marked CD4+ T-cell depletion. The atypical presentation shown could confuse and delay the diagnosis. Early suspicion and appropriate treatment (ganciclovir, valganciclovir, HAART) increase the likelihood of a favourable outcome.

Factores pronósticos en el cáncer de mama en estadio inicial / Prognostic factors of early breast cancer

La decisión de administrar un tratamiento adyuvante del cáncer de mama en estadio inicial se fundamenta en la evaluación de varios factores pronósticos. El estado de los ganglios axilares, el tamaño del tumor y el grado de diferenciación histológico son las variables consideradas como clásicas, que se ven complementadas con el estado de los receptores hormonales y la expresión de HER2. Estos factores pueden combinarse con índices pronósticos para tener una estimación más precisa sobre el riesgo de recaída o de muerte asociada a la neoplasia. Otros parámetros individuales tienen una importancia secundaria. En los últimos años, a los factores clásicos se les han añadido los perfiles de expresión de genes, que permiten definir qué pacientes pueden prescindir de la quimioterapia adyuvante cuando el riesgo de recaída estimado es bajo. Se encuentran comercializados diferentes perfiles y se emplean de forma rutinaria en casos seleccionados. En el futuro, los perfiles génicos servirán para seleccionar grupos de pacientes que se beneficien de nuevos tratamientos dirigidos (AU)

Decision about the administration of adjuvant therapy for early breast cancer depends on the evaluation of prognostic factors. Lymph node status, tumor size and grade of differentiation are classical variables in this regard, and can be complemented by hormonal receptor status and HER2 expression. These factors can be combined into prognostic indexes to better estimate the risk of relapse or death. Other factors are less important. Gene profiles have emerged in recent years to identify low-risk patients who can forgo adjuvant chemotherapy. A number of profiles are available and can be used in selected cases. In the future, gene profiling will be used to select patients for treatment with new targeted therapies (AU)

[Prognostic factors of early breast cancer]. / Factores pronósticos en el cáncer de mama en estadio inicial.

Decision about the administration of adjuvant therapy for early breast cancer depends on the evaluation of prognostic factors. Lymph node status, tumor size and grade of differentiation are classical variables in this regard, and can be complemented by hormonal receptor status and HER2 expression. These factors can be combined into prognostic indexes to better estimate the risk of relapse or death. Other factors are less important. Gene profiles have emerged in recent years to identify low-risk patients who can forgo adjuvant chemotherapy. A number of profiles are available and can be used in selected cases. In the future, gene profiling will be used to select patients for treatment with new targeted therapies.

The role of anthracyclines in small cell lung cancer.

Small cell lung cancer (SCLC) represents the 15% of the totally of lung cancer. The percentage of cases in women is arising due to the differences in smoking patterns; it occurs almost exclusively in smokers and appears to be most common in heavy smokers. The stage of disease at presentation is the most important prognostic factor in patients with SCLC; for patients with extended stage disease, the median survival is around 10 months, and the five-year survival rate is 1 to 2 percent. The standard regimen for patients with extensive disease is cisplatin based chemotherapy. Second line chemotherapy is generally less effective than the initial treatment but it can provide significant palliation for many patients. We make a review here of the different options of second line chemotherapy and the role of anthracyclines in it.