Prostate-specific Antigen at 3 Months as a Predictor of Radiologic Progression-free Survival in Metastatic Hormone-sensitive Prostate Cancer Treated with Apalutamide: Analysis of 633 Patients in a Real-world Database.

Background and objective: The depth of the prostate-specific antigen (PSA) decline after androgen receptor pathway inhibitor (ARPI) treatment combined with androgen deprivation therapy for patients with metastatic hormone-sensitive prostate cancer (mHSPC) may affect prognosis. The primary objective in our study was the correlation between the PSA response at 3 mo and radiologic progression-free survival (rPFS) at 24 mo. Three groups were defined according to the PSA decline: complete response (PSA ≤0.02 ng/ml), partial response (PSA >0.02 and ≤0.2 ng/ml), and incomplete response (PSA >0.2 ng/ml). Secondary objectives were correlation between the PSA response at 3 mo and overall survival, and the development of a model predicting complete PSA response. Methods: We conducted a retrospective multicenter study of patients with mHSPC treated with apalutamide from May 2018 to September 2023 registered in the Real-World Evidence APA registry across 20 centers. Key findings and limitations: We included 633 patients with mHSPC. The median age at diagnosis was 68 yr (interquartile range [IQR] 63-75) and median PSA was 16 ng/ml (IQR 7.5-64). Some 63% of the short had low-volume disease, 51% had de novo disease, 48% had recurrent disease. At 3 mo, 27% had a complete response, 42% a partial response, and 31% an incomplete response, with corresponding rRFS rates at 24 mo of 92%, 86%, and 63%. According to the predictive model, a complete PSA response at 3 mo was associated with the use of next-generation imaging and PSA <50 ng/ml at diagnosis. Study limitations include heterogeneity among the groups and variations in data quality and assessment methods. Conclusions and clinical implications: Patients with a complete PSA response after 3 mo of apalutamide treatment face a very low risk of progression within 2 yr. Conversely, nearly 50% of patients with an incomplete PSA response will experience disease progression. Patient summary: For patients with metastatic prostate cancer that is still responsive to hormone therapy, a complete response after treatment with a drug called apalutamide is associated with a very low risk of progression within 2 years. However, nearly half of patients with an incomplete response to apalutamide will experience progression of their cancer.

Case Series of Acral and Mucosal Melanoma in a Diverse Patient Population.

Melanomas affecting acral and mucosal sites have distinct features and are associated with poorer prognosis. Patients of color may be disproportionately affected. Herein we discuss six ethnically diverse cases of acral and mucosal melanoma (AMM). More data on clinical, genetic, and environmental features of AMM are needed, but thorough physical examination can reduce the burden of disease now. J Drugs Dermatol. 2024;23(8):683-685. doi:10.36849/JDD.8311.

A systematic review and meta-analysis on glycemic control in traumatic brain injury.

BACKGROUND: Hyperglycemia is associated with adverse outcomes in patent with traumatic brain injury. There is convincing evidence of the deleterious effects of early systemic hyperglycemia on neurological outcomes and guides management toward intensive glycemic control. The purpose of this systematic review and meta analysis is to evaluate and summarize the level of evidence on the role of glycemic control in traumatic brain injury. METHODS: A systematic review and meta-analysis were performed following PRISMA guidelines. This review involved studies conducted in humans covering glycemic control in traumatic brain injury. A systematic literature search was performed in PubMed, Embase, EBSCO Host, Scopus, ScienceDirect, Medline, and LILACS from database inception to October 2020. The risk of bias was evaluated with the GRADE quality Scale. RESULTS: The results of this meta-analysis that involved 1236 patients included in 10 studies suggest that intensive glycemic control did not show significant differences in mortality compared with conservative management (RR 0.99 [95 % CI 0.81-1.21] p = 0.92). Intensive glycemic control reduced the risk of unfavorable clinical outcomes compared to standard management (RR 0.87 [95 % CI 0.78-0.96] p = 0.007) and increased favorable clinical outcomes compared to standard neurocritical care (RR 1.19 [95 % CI 1.02-138] p = 0.003). CONCLUSIONS: The possible effect of glycemic control could be associated with silent hypoglycemic episodes during intensive care. Further studies evaluating the impact of glycemic control in traumatic brain injury are necessary.

Treatment of Bullous Pemphigoid With Dupilumab: A Case Series of 30 Patients.

Bullous pemphigoid is often difficult to treat with the limited therapies available. Here, we describe clinical outcomes among 30 adults with bullous pemphigoid patients treated with dupilumab. We performed a multicenter, retrospective case series between March 2020 to August 2022. Patients received a loading dose of dupilumab 600 mg, followed by 300 mg maintenance dose with varying administration frequency tailored to individual patient response. All patients experienced at least some improvement in blister formation and pruritus, with 23 (76.7%) of patients demonstrating either complete clearance of blistering or marked response. Complete clearance of pruritus or marked response was noted in 25 (83.3%) of patients. Eight patients were effectively maintained solely on dupilumab. One (3.3%) patient reported an injection site reaction. Thirty patients represent a small sample, however, to our knowledge, this is the second largest group of BP treated with dupilumab. Furthermore, we provide an understandable framework for clinicians outside of academics to follow and assess treatment responses in their BP patients treated with dupilumab. Dupilumab should be considered as a therapeutic option in patients with bullous pemphigoid given its ability to induce sustained blistering and pruritus response in both typical and refractory cases while maintaining a favorable safety profile. J Drugs Dermatol. 2024;23(6):e144-e148. doi:10.36849/JDD.8258e.

Hidradenitis Suppurativa Found Associated With Cytokine Storm.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease that generates multiple cytokines. Here, we present an example of the cytokines forming a cytokine storm and its effects on the patient. CASE PRESENTATION: We report the case of a 55-year-old man who had severe but stable HS. Serum samples were collected from the patient and extraordinarily elevated cytokine concentrations were identified in the patient's serum.  Conclusion: Cytokine storms may be a condition associated with HS posing additional risk to patient survival. J Drugs Dermatol. 2024;23(5):e134-e136.     doi:10.36849/JDD.7860R1e.

First-line Avelumab plus Chemotherapy in Patients with Advanced Solid Tumors: Results from the Phase Ib/II JAVELIN Chemotherapy Medley Study.

PURPOSE: Chemotherapy can potentially enhance the activity of immune checkpoint inhibitors by promoting immune priming. The phase Ib/II JAVELIN Chemotherapy Medley trial (NCT03317496) evaluated first-line avelumab + concurrent chemotherapy in patients with advanced urothelial carcinoma or non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Avelumab 800 or 1,200 mg was administered continuously every 3 weeks with standard doses of cisplatin + gemcitabine in patients with urothelial carcinoma, or carboplatin + pemetrexed in patients with nonsquamous NSCLC. Dual primary endpoints were dose-limiting toxicity (DLT; phase Ib) and confirmed objective response (phase Ib/II). RESULTS: In phase Ib, urothelial carcinoma and NSCLC cohorts received avelumab 800 mg (n = 13 and n = 6, respectively) or 1,200 mg (n = 6 each) + chemotherapy. In evaluable patients with urothelial carcinoma treated with avelumab 800 or 1,200 mg + chemotherapy, DLT occurred in 1/12 (8.3%) and 1/6 (16.7%), respectively; no DLT occurred in the NSCLC cohort. In phase II, 35 additional patients with urothelial carcinoma received avelumab 1,200 mg + chemotherapy. Across all treated patients, safety profiles were similar irrespective of avelumab dose. Objective response rates (95% confidence internal) with avelumab 800 or 1,200 mg + chemotherapy, respectively, across phase Ib/II, were 53.8% (25.1-80.8) and 39.0% (24.2-55.5) in urothelial carcinoma, and 50.0% (11.8-88.2) and 33.3% (4.3-77.7) in NSCLC. CONCLUSIONS: Preliminary efficacy and safety findings with avelumab + chemotherapy in urothelial carcinoma and NSCLC were consistent with previous studies of similar combination regimens. Conclusions about clinical activity are limited by small patient numbers. SIGNIFICANCE: This phase Ib/II trial evaluated avelumab (immune checkpoint inhibitor) administered concurrently with standard first-line chemotherapy in patients with advanced urothelial carcinoma or advanced nonsquamous NSCLC without actionable mutations. Efficacy and safety appeared consistent with previous studies of similar combinations, although patient numbers were small.

Real-world prostate-specific antigen reduction and survival outcomes of metastatic hormone-sensitive prostate cancer patients treated with apalutamide: An observational, retrospective, and multicentre study.

Background: Metastatic hormone-sensitive prostate cancer (mHSPC) treatment has changed drastically during the last years with the emergence of androgen receptor-targeted agents (ARTAs). ARTA combined with androgen deprivation therapy has demonstrated better oncological and survival outcomes in these patients. However, the optimal choice among different ARTAs remains uncertain due to their analogous efficacy. Objectives: The objective of this study was to describe prostate-specific antigen (PSA) response and oncological outcomes of patients with mHSPC treated with apalutamide. Material and methods: Medical records from three different hospitals in Spain were used to conduct this study. Patients diagnosed with mHSPC and under apalutamide treatment were included between March 2021 and January 2023. Data regarding PSA response, overall survival (OS), and radiographic progression-free survival (rPFS) were collected and stratified by metastasis volume, timing, and stating. Results: 193 patients were included; 34.2% of patients were de novo mHSPC, and the majority was classified as m1b. The 18-month OS and rPFS were 92.5% and 88.9%, respectively. Patients with PSA levels ≤0.2 ng/ml showcased an 18-month OS rate of 98.7%, contrasting with 65.3% for those with PSA >0.2 ng/ml. Similar trends emerged for rPFS (97.4% and 53.7%, respectively). When differentiating between low-volume and high-volume metastasis, the OS rate stood at 98.4% and 80.7%, respectively, while the rPFS rates were 93% and 81.6%, respectively. No significant differences were found between groups stratified by metastasis timing. Conclusion: This real-world study on patients with mHSPC treated with apalutamide plus androgen deprivation therapy revealed robust oncological outcomes, aligning with the emerging evidence. The study's hallmark finding highlights the significance of rapid and deep PSA response as a predictor of improved oncological and survival outcomes.

Avelumab First-line Maintenance for Advanced Urothelial Carcinoma: Analysis from JAVELIN Bladder 100 by Duration of First-line Chemotherapy and Interval Before Maintenance.

BACKGROUND: In the JAVELIN Bladder 100 phase 3 trial, avelumab first-line maintenance + best supportive care (BSC) prolonged overall survival (OS) and progression-free survival (PFS) versus BSC alone in patients with advanced urothelial carcinoma (advanced UC) without progression after first-line platinum-based chemotherapy. OBJECTIVE: To report post hoc analyses of subgroups defined by the duration of first-line chemotherapy and interval before maintenance. DESIGN, SETTING, AND PARTICIPANTS: Patients with advanced UC without progression after four to six cycles of platinum-based chemotherapy and a 4-10-wk interval after chemotherapy (n = 700) were randomized to receive avelumab + BSC or BSC alone. Subgroups were defined by duration (quartile [Q]) and estimated number of cycles of chemotherapy, and interval between chemotherapy and maintenance. The median follow-up was >19 mo in both arms. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: OS (primary endpoint), PFS, and safety were assessed. RESULTS AND LIMITATIONS: Hazard ratios (95% confidence interval) for OS with avelumab + BSC versus BSC alone were as follows: by chemotherapy duration-Q3: 0.63 (0.39-1.00); by number of cycles-four cycles: 0.69 (0.48-1.00), five cycles: 0.98 (0.57-1.71), and six cycles: 0.66 (0.47-0.92); and by interval-4-<6 wk: 0.75 (0.54-1.04), 6-<8 wk: 0.67 (0.43-1.06), and 8-10 wk: 0.69 (0.47-1.02). Results were similar for PFS. Safety was similar across subgroups. All analyses were exploratory. CONCLUSIONS: Post hoc analyses of OS and PFS in subgroups defined by first-line chemotherapy duration and interval before maintenance were generally consistent with the results in the overall population, with similar safety findings. Prospective trials are warranted to confirm these findings. PATIENT SUMMARY: Avelumab maintenance treatment helped patients with advanced urothelial cancer without disease progression after at least four cycles of prior chemotherapy, and who started maintenance treatment at least 4 wk after chemotherapy, to live longer.

Patient-reported Outcomes from JAVELIN Bladder 100: Avelumab First-line Maintenance Plus Best Supportive Care Versus Best Supportive Care Alone for Advanced Urothelial Carcinoma.

BACKGROUND: In JAVELIN Bladder 100, avelumab first-line maintenance plus best supportive care (BSC) significantly prolonged overall survival (OS; primary endpoint) versus BSC alone in patients with advanced urothelial carcinoma (aUC) without disease progression with first-line platinum-containing chemotherapy. OBJECTIVE: To evaluate patient-reported outcomes (PROs) with avelumab plus BSC versus BSC alone. DESIGN, SETTING, AND PARTICIPANTS: A randomized phase 3 trial (NCT02603432) was conducted in 700 patients with locally advanced or metastatic urothelial carcinoma that had not progressed with first-line gemcitabine plus cisplatin or carboplatin. PROs were a secondary endpoint. INTERVENTION: Avelumab plus BSC (n = 350) or BSC alone (n = 350). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Bladder Symptom Index-18 (FBlSI-18) and EuroQol five-level EQ-5D (EQ-5D-5L) assessments were analyzed using descriptive statistics and mixed-effect models. Time to deterioration (TTD; prespecified definition: a ≥3-point decrease from baseline in the FBlSI-18 disease-related symptoms-physical subscale for two consecutive assessments) was evaluated via Kaplan-Meier analyses. RESULTS AND LIMITATIONS: Completion rates for scheduled on-treatment PRO assessments were >90% (overall and average per assessment). Results from descriptive analyses and mixed-effect or repeated-measures models of FBlSI-18 and EQ-5D-5L were similar between arms. TTD was also similar, both in the prespecified analysis (hazard ratio 1.26 [95% confidence interval: 0.90, 1.77]) and in the post hoc analyses including off-treatment assessments and different event definitions. Limitations included the open-label design and limited numbers of evaluable patients at later time points. CONCLUSIONS: Addition of avelumab first-line maintenance to BSC in patients with aUC that had not progressed with first-line platinum-containing chemotherapy prolonged OS, with a relatively minimal effect on quality of life. PATIENT SUMMARY: In this trial of people with advanced urothelial carcinoma who had benefited from first-line chemotherapy (ie, had stable disease or reduced tumor size), treatment with avelumab maintenance plus best supportive care (BSC) versus BSC alone improved survival significantly, without compromising quality of life, as reported by the patients themselves.

Evolución clínica de trabajadores con fractura de radio distal Fernández III. Tratamiento no complicado quirúrgico y no quirúrgico.

ANTECEDENTES: Las fracturas de radio distal Fernández III (FRDF III) son una urgencia muy frecuente. Las indicaciones quirúrgicas y no quirúrgicas persisten controversiales, así como el impacto funcional. OBJETIVO: Comparar la evolución clínica de los trabajadores con FRDF III, con manejo quirúrgico frente a no quirúrgico, no complicados, en un hospital especializado. MÉTODO: Estudio comparativo, observacional y longitudinal en trabajadores con FRDF III unilateral cerrada, de ambos sexos, con evolución menor de 5 días. Se excluyeron pacientes con comorbilidad afectante de consolidación ósea y polifracturados. Se eliminaron aquellos con información incompleta, con complicaciones, con aparato de yeso modificado 5 días después de su colocación, con mala reducción-estabilización acorde a la AO. Se aplicó la Escala Funcional de Mayo para Muñeca (EFMM) a los 3 y 6 meses del tratamiento. Se utilizó la prueba t de Student. RESULTADOS: 159 pacientes, 34% mujeres, 66% hombres. Edad promedio 40.18 años. Manejo quirúrgico 42,5% (placa 8.7%, fijador 29%, fijador + clavillo 8.7%); no quirúrgico 33%. Diferencias significativas (p ≤ 0.05): EFMM 3 y 6 meses; a 3 meses: dolor, prensión; a 6 meses: movilidad; y días totales de incapacidad. CONCLUSIONES: El tratamiento quirúrgico muestra mejores resultados funcionales, destacando el dolor y la prensión a 3 meses, y la movilidad a 6 meses, con reincorporación laboral en menos tiempo. BACKGROUND: This fracture is a very frequent emergency. Surgical and non-surgical management are still controversial, such as functional impact. OBJECTIVE: To compare clinical evolution of Fernandez III distal radius fractures, managed with surgically vs no surgical treatment, in a specialized hospital. METHOD: Comparative, observational, longitudinal study, released on workers with unilateral Fernandez III closed distal radius fractures, both sex, with evolution less than 5 days. Those patients with pathologies getting difficult in bone consolidation, and with several fractures were excluded. Those with incomplete information, complicated, and whom paste were modified after 5 days, and with bad reduction or stabilization fracture according AO were eliminated. Mayo Functional Wrist Scale (EFMM) was applied at 3 and 6 months. Student-t test was applied. RESULTS: 159 patients recruited, 34% females, 66% males. Medium age 40 years old. Surgical treatment 42.5% (plaque 8.7%, external fixation 29%, external fixation and nails 8.7%). Non-surgical treatment 33%. Significative differences (p≤0.05): EFMM at 3 and 6 months; pain, grasp at 3 months; mobility at 6 months; total laboral inhability days. CONCLUSIONS: Surgical treatment shows better functional results, specially pain and grasp at 3 months, mobility at 6 months, and faster returning to work.

Una revisión sistemática de la terapia endovascular en pacientes con accidente cerebrovascular isquémico / A systematic review of endovascular therapy in patients with ischemic stroke

Objetivo: Revisar sistemáticamente la evidencia de la terapia endovascular comparado con el manejo estándar. Criterios de inclusión: Ensayos clínicos aleatorizados que incluyan a: pacientes adultos mayores de 18 años, haber sufrido accidente cerebrovascular isquémico manejados con terapia endovascular en comparación con manejo médico. Métodos: Se realizó la búsqueda en las siguientes bases de datos: MEDLINE, the Central Register of Controlled Trials (CENTRAL); PubMed, HINARI, EMBASE; Cochrane Injuries group y lista de referencia de los artículos. Resultados: La trombectomía se asoció con disminución de la mortalidad (OR 0,78, IC del 95%: 0,63-0,95 p= 0,01), aumento de la tasa de revascularización (OR 6,16, IC del 95%: 4,39-8,64 p= <0,0001), mejoría de desenlace funcional (OR 1,78, IC del 95%: 1,52 ­ 2,08 p= <0,0001). No hubo diferencia en cuanto a la recurrencia de isquemia cerebral ni de la aparición de hemorragia intracerebral (OR 0,86, IC del 95%: 0,51 ­ 1,47 p= 0,59; OR 1,13, IC del 95%: 0,79 ­ 1,62 p= 0,5, respectivamente). Conclusiones: La terapia endovascular comparada con la fibrinólisis endovenosa mejora el pronóstico funcional, aunque se necesitan más estudios.

Objective: Systematically review the evidence of endovascular therapy compared with standard management. Inclusion criteria: Randomized clinical trials that include adult patients older than 18 years, have suffered an ischemic stroke managed with endovascular therapy compared to medical management. Methods: The search is performed in the following databases: MEDLINE, the Central Registry of Controlled Trials (CENTRAL); PubMed, HINARI, EMBASE; Cochrane Injury Group and reference list of articles. Results: Thrombectomy was associated with decreased mortality (OR 0.78, 95% CI 0.63-0.95 p = 0.01), increased revascularization rate (OR 6.16, CI 95%: 4.39-8.64 p = <0.0001), improvement in functional outcome (OR 1.78, 95% CI: 1.52 - 2.08 p = <0.0001). There was no difference in the recurrence of cerebral ischemia or the appearance of intracerebral hemorrhage (OR 0.86, 95% CI 0.51 - 1.47 p = 0.59, OR 1.13, 95% CI %: 0.79 - 1.62 p = 0.5, respectively). Conclusions: Endovascular therapy compared with the treatment of fibrinolysis improves functional prognosis

Hipotermia para la hipertensión intracraneana refractaria después de un trauma craneoencefálico severo / Hypothermia for refractory intracranial hypertension after severe head trauma

Objetivo: Revisar sistemáticamente la evidencia que tiene la inducción de hipotermia en la hipertensión endocraneana traumática refractaria. Criterios de inclusión: Ensayos clínicos aleatorizados que incluyan a: pacientes mayores de 12 años, haber sufrido un traumatismo craneal grave (Glasgow < 8) con hipertensión intracraneana y que se les haya inducido hipotermia terapéutica. Métodos: Se realizó la búsqueda en las siguientes bases de datos: MEDLINE, the Central Register of Controlled Trials (CENTRAL); PubMed, HINARI, EMBASE; Cochrane Injuries group y lista de referencia de los artículos. Resultados: La mortalidad disminuyó en los pacientes en que se usó la inducción de hipotermia comparados con el grupo control (RR 0,82, IC del 95%: 0,7-0,95 p= 0,008), el grupo inducción de hipotermia muestra una disminución de los desenlaces neurológicos no favorables (estado vegetativo y coma, GOS-E 1-3) frente al control (RR 0,81, IC del 95%: 0,75 a 0,88 p= <0,00001). Conclusiones: Los pacientes con trauma craneoencefálico e hipertensión endocraneana refractaria se beneficiarían con el uso de hipotermia terapéutica, aunque se necesitan más estudios de buena calidad para extraer conclusiones definitivas.

Objectives: To systematically review published evidence on the induction of mild hypothermia for refractory traumatic intracranial hypertension. Methods: A thorough search was conducted of MEDLINE, the Central Register of Controlled Trials (CENTRAL); PubMed, HINARI, EMBASE; Cochrane Injuries group and the reference lists of articles, looking for randomized clinical trials that assessed mortality and morbidity in patients, 12 years old and older, who had suffered a severe traumatic brain injury (Glasgow coma scale < 8), had intracranial hypertension, and had mild hypothermia intentionally induced. Results: Mortality was reduced in patients treated with mild hypothermia relative to controls (RR 0.82, 95% CI: 0.70- 0.95; p = 0.008). Similarly, hypothermia induction was associated with a decreased rate of unfavorable neurological outcomes (vegetative state, coma, GOS-E 1-3) (RR 0.81, 95% CI 0.75 to 0.88; p < 0.001). Conclusions: Available evidence suggests that traumatic brain injury patients with refractory intracranial hypertension may benefit from therapeutic hypothermia. However, more methodologically-robust studies are needed.

Geminivirus Replication Protein Impairs SUMO Conjugation of Proliferating Cellular Nuclear Antigen at Two Acceptor Sites.

Geminiviruses are DNA viruses that replicate in nuclei of infected plant cells using the plant DNA replication machinery, including PCNA (proliferating cellular nuclear antigen), a cofactor that orchestrates genome duplication and maintenance by recruiting crucial players to replication forks. These viruses encode a multifunctional protein, Rep, which is essential for viral replication, induces the accumulation of the host replication machinery, and interacts with several host proteins, including PCNA and the SUMO E2 conjugation enzyme (SCE1). Posttranslational modification of PCNA by ubiquitin or SUMO plays an essential role in the switching of PCNA between interacting partners during DNA metabolism processes (e.g., replication, recombination, and repair, etc.). In yeast, PCNA sumoylation has been associated with DNA repair involving homologous recombination (HR). Previously, we reported that ectopic Rep expression results in very specific changes in the sumoylation pattern of plant cells. In this work, we show, using a reconstituted sumoylation system in Escherichia coli, that tomato PCNA is sumoylated at two residues, K254 and K164, and that coexpression of the geminivirus protein Rep suppresses sumoylation at these lysines. Finally, we confirm that PCNA is sumoylated in planta and that Rep also interferes with PCNA sumoylation in plant cells.IMPORTANCE SUMO adducts have a key role in regulating the activity of animal and yeast PCNA on DNA repair and replication. Our work demonstrates for the first time that sumoylation of plant PCNA occurs in plant cells and that a plant virus interferes with this modification. This work marks the importance of sumoylation in allowing viral infection and replication in plants. Moreover, it constitutes a prime example of how viral proteins interfere with posttranslational modifications of selected host factors to create a proper environment for infection.

Una revisión sistemática del monitoreo de la presión intracraneana en adultos con trauma craneoencefálico severo / A systematic review of intracranial pressure monitoring in adults with severe traumatic brain injury

Objetivos: Revisar sistemáticamente la evidencia relacionada con el monitoreo de la presion intracraneana en unidades de cuidado neurocrítico en el contexto de trauma craneoencefálico severo. Criterios de elección: Ensayos clínicos aleatorizados que comparen el uso del monitoreo de la presión intracraneana (PIC) que muestren un estimado de mortalidad/discapacidad a 6 meses, en pacientes mayores de 12 años de edad con trauma craneoencefálico severo (escala de Glasgow menor a 8). Método de búsqueda: En Medline, el Registro Central de Ensayos Controlados (CENTRAL); PubMed, HINARI, EMBASE; Grupo Cochrane de Lesiones y las listas de referencias de artículos. De acuerdo con el Manual Cochrane para meta-análisis y revisión sistemática. Resultados: No hubo diferencias entre el grupo de PIC y el control en el pronóstico de discapacidad (RR [Riesgo Relativo]1.01, 95 por ciento CI 0.87 to 1.18). Sin embargo, el monitoreo de la PIC reduce la estancia en UCI en comparación con otros métodos. La estancia en UCI con tratamiento cerebral específico también se redujo en comparación con grupo control. Conclusiones: En pacientes con trauma craneoencefálico, no hubo diferencia entre el monitoreo de la PIC y el examen clínico sin embargo, para mantener una PIC baja, hubo una sustancial reducción de requerimiento de solución salina hipertónica y un descenso en la hiperventilación trayendo consigo beneficios para pacientes en UCI.

Objectives: To systematically review the evidence of intracranial pressure monitoring in neuro critical care unit in the context of a severe head injury. Study eligibility criteria: Patients were older than 12 years ,had a severe traumatic brain injury (Glasgow coma scale < 8), that compared the use of ICP monitoring with control, that presented an estimate of mortality/ disability prognosis 6 months after injury.only randomized clinical trials. Methods: Searched MEDLINE, the Central Registerof Controlled Trials (CENTRAL); PubMed, HINARI,EMBASE; Cochrane Injuries group and the reference lists of articles. In accordance with the Cochrane handbook for meta-analysis and systematic review. Results: In the ICP and control groups there was no difference in the prognosis of disability (RR [Relative Risk]1.01, 95 percent CI 0.87 to 1.18). However, ICP monitoring reduced the duration of stay in ICU compared to other surveillance methods. The stay in the ICU with specific medical support for brain injury was also reduced compared to the control group. Conclusions: In patients with severe traumatic brain injury, the ICP monitoring was not difference to imaging and clinical examination. However, by keeping the ICP low there was a substantial reduction in the requirement for hypertonic saline and a decrease in hyperventilation providing benefits to thepatient in the ICU.

Tromboprofilaxis con heparinas de bajo peso molecular en trauma craneoencefálico severo: una revisión sistemática / Low-molecular-weight heparin thromboprophylaxis in severe cranioencephalic trauma: a systematic review

Objetivo: Revisar sistemáticamente la evidencia de la tromboprofilaxis con heparinas de bajo peso molecular en trauma craneoencefálico severo. Criterios de inclusión: Ensayos clínicos aleatorizados que incluyan: pacientes mayores de 15 años, que hayan sufrido un traumatismo craneal grave (Glasgow < 8), que comparen el uso de heparinas de bajo peso molecular (HBPM) con grupo control (otras medidas farmacológicas y mecánicas o la no profilaxis), que evalúe mortalidad a 6 meses, riesgo de sangrado y de eventos trombóticos. Métodos: Se buscó en las siguientes bases de datos MEDLINE, the Central Register of Controlled Trials (CENTRAL); PubMed, HINARI, EMBASE; Cochrane Injuries group y lista de referencia de los artículos. Resultados: En el grupo de HBPM y el control no hubo diferencia significativa en el pronóstico de mortalidad (RR [Riesgo Relativo] 0,88, 95% CI 0.34 to 2.26). No aumentó el riesgo de sangrados. No hubo diferencias relacionadas con el riesgo tromboembólico comparado con el grupo control. Conclusiones: En pacientes con trauma craneoencefálico severo la tromboprofilaxis con HBPM fue similar con otros métodos de profilaxis antitrombótica. Faltan estudios que demuestren la eficacia y seguridad de la profilaxis antitrombótica con HBPM.

Objective: To systematically review the evidence of thromboprophylaxis tos with Low Molecular Weight Heparin (LMWH) in severe traumatic brain injury. Study eligibility criteria: Randomized clinical Trials with Patients older than 15 years, had a severe traumatic brain injury (Glasgow coma scale < 8), that compared the use of LMWH with control group (no prophylaxis and other pharmacologic and/ or mechanical methods, that presented an estimate of mortality/disability prognosis 6 months after injury, risk of bleeding and thromboembolic events (PE, DTV). Methods: Searched MEDLINE, the Central Register of Controlled Trials (CENTRAL); PubMed, HINARI, EMBASE; Cochrane Injuries group and the reference lists of articles. Results: In the LMWH and control groups there was no difference in the prognosis of mortality (RR [Relative Risk] 0,88, 95% CI 0.34 to 2.26). Don’t rise the risk of bleeding. There was no difference in the risk from thromboembolic events compared to the control group. Conclusions: In patients with severe traumatic brain injury, the use of LMWH is similarly with other thromboprophylactics methods. There aren’t studies that demonstrate the efficacy and safety of antithrombotic prophylaxis with LMWH.

Impact on clinical practice of the implementation of guidelines for the toxicity management of targeted therapies in kidney cancer. The protect-2 study.

BACKGROUND: The impact of such recommendations after their implementation of guidelines has not usually been evaluated. Herein, we assessed the impact and compliance with the Spanish Oncology Genitourinary Group (SOGUG) Guidelines for toxicity management of targeted therapies in metastatic renal cell carcinoma (mRCC) in daily clinical practice. METHODS: Data on 407 mRCC patients who initiated first-line targeted therapy during the year before and the year after publication and implementation of the SOGUG guideline program were available from 34 Spanish Hospitals. Adherence to SOGUG Guidelines was assessed in every cycle. RESULTS: Adverse event (AE) management was consistent with the Guidelines as a whole for 28.7% out of 966 post-implementation cycles compared with 23.1% out of 892 pre-implementation cycles (p = 0.006). Analysis of adherence by AE in non-compliant cycles showed significant changes in appropriate management of hypertension (33% pre-implementation vs. 44.5% post-implementation cycles; p < 0.0001), diarrhea (74.0% vs. 80.5%; p = 0.011) and dyslipemia (25.0% vs. 44.6%; p < 0.001). CONCLUSIONS: Slight but significant improvements in AE management were detected following the implementation of SOGUG recommendations. However, room for improvement in the management of AEs due to targeted agents still remains and could be the focus for further programs in this direction.

Fingering in a channel and tripolar Loewner evolutions.

A class of Laplacian growth models in the channel geometry is studied using the formalism of tripolar Loewner evolutions, in which three points, namely, the channel corners and the point at infinity, are kept fixed. Initially, the problem of fingered growth, where growth takes place only at the tips of slitlike fingers, is revisited and a class of exact solutions of the corresponding Loewner equation is presented for the case of stationary driving functions. A model for interface growth is then formulated in terms of a generalized tripolar Loewner equation and several examples are presented. It is shown that the growing interface evolves into a steadily moving finger and that tip competition arises for nonsymmetric initial configurations with multiple tips.

Interaction between geminivirus replication protein and the SUMO-conjugating enzyme is required for viral infection.

Geminiviruses are small DNA viruses that replicate in nuclei of infected plant cells by using plant DNA polymerases. These viruses encode a protein designated AL1, Rep, or AC1 that is essential for viral replication. AL1 is an oligomeric protein that binds to double-stranded DNA, catalyzes the cleavage and ligation of single-stranded DNA, and induces the accumulation of host replication machinery. It also interacts with several host proteins, including the cell cycle regulator retinoblastoma-related protein (RBR), the DNA replication protein PCNA (proliferating cellular nuclear antigen), and the sumoylation enzyme that conjugates SUMO to target proteins (SUMO-conjugating enzyme [SCE1]). The SCE1-binding motif was mapped by deletion to a region encompassing AL1 amino acids 85 to 114. Alanine mutagenesis of lysine residues in the binding region either reduced or eliminated the interaction with SCE1, but no defects were observed for other AL1 functions, such as oligomerization, DNA binding, DNA cleavage, and interaction with AL3 or RBR. The lysine mutations reduced or abolished virus infectivity in plants and viral DNA accumulation in transient-replication assays, suggesting that the AL1-SCE1 interaction is required for viral DNA replication. Ectopic AL1 expression did not result in broad changes in the sumoylation pattern of plant cells, but specific changes were detected, indicating that AL1 modifies the sumoylation state of selected host proteins. These results established the importance of AL1-SCE1 interactions during geminivirus infection of plants and suggested that AL1 alters the sumoylation of selected host factors to create an environment suitable for viral infection.

Interface growth in two dimensions: a Loewner-equation approach.

The problem of Laplacian growth in two dimensions is considered within the Loewner-equation framework. Initially the problem of fingered growth is revisited and an exact solution for a three-finger configuration is reported. Then a general class of growth models for an interface growing in the upper half-plane is introduced and the corresponding Loewner equation for the problem is derived. Several examples are given including interfaces with one or more tips as well as multiple growing interfaces. A generalization of our interface growth model in terms of "Loewner domains," where the growth rule is specified by a time evolving measure, is briefly discussed.