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In 2021, the Food and Drug Administration Oncology Center of Excellence announced Project Optimus focusing on dose optimization for oncology drugs. The Methodology for the Development of Innovative Cancer Therapies (MDICT) Taskforce met to review and discuss the optimization of dosage for oncology trials and to develop a practical guide for oncology phase I trials. Defining a single recommended phase II dose based on toxicity may define doses that are neither the most effective nor the best tolerated. MDICT recommendations address the need for robust non-clinical data which are needed to inform trial design, as well as an expert team including statisticians and pharmacologists. The protocol must be flexible and adaptive, with clear definition of all endpoints. Health authorities should be consulted early and regularly. Strategies such as randomization, intrapatient dose escalation, and real-world eligibility criteria are encouraged whereas serial tumor sampling is discouraged in the absence of a strong rationale and appropriately validated assay. Endpoints should include consideration of all longitudinal toxicity. The phase I dose escalation trial should define the recommended dose range for later testing in randomized phase II trials, rather than a single recommended phase II dose, and consider scenarios where different populations may require different dosages. The adoption of these recommendations will improve dosage selection in early clinical trials of new anticancer treatments and ultimately, outcomes for patients.

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Introducción: La hernia lumbar es un tipo muy infrecuente de hernia de la pared abdominal con un reducido número de casos publicados. Puede producirse a través de dos triángulos anatómicos: uno superior o triángulo de Grynfelt-Lesshaft y uno inferior o triángulo de Petit. Presentación del caso: Presentamos el caso de una mujer de 64 años con una tumoración blanda y reductible en la región posterolateral izquierda de la pared abdominal. La tomografía computarizada confirmó la existencia de una hernia lumbar a través del triángulo superior o Grynfelt-Lesshaft. Fue intervenida mediante un abordaje laparoscópico transabdominal en el que tras la reducción del contenido herniario (tejido graso) se colocó una malla de doble capa en posición intraperitoneal. Fue dada de alta a las 24 horas de la intervención sin observarse complicaciones inmediatas. Discusión: Se trata de un tipo muy infrecuente de hernia de la pared por lo que su diagnóstico requiere una alta sospecha clínica y a menudo una confirmación radiológica mediante tomografía computarizada. Conclusiones: La reparación de la hernia lumbar está indicada para evitar posibles complicaciones y puede realizarse tanto por vía abierta como laparoscópica, debiendo incluir la colocación de material prótesico en forma de malla para reducir el riesgo de recidiva.

Introduction: Lumbar hernia is a very rare type of abdominal wall hernia with a small number of published cases. It can occur through two anatomical triangles: an upper one or Grynfelt-Lesshaft triangle and a lower one or Petit triangle. Case presentation: We present the case of a 64-year-old woman with a soft and reducible tumor in the left posterolateral region of the abdominal wall. Computerized tomography confirmed the existence of a lumbar hernia through the superior triangle or Grynfelt-Lesshaft triangle. Patient was operated through a transabdominal laparoscopic approach in which after reduction of hernial content (fatty tissue) a double-layer mesh was placed in an intraperitoneal position. She was discharged 24 hours after the intervention and no immediate complications were observed. Discussion: Lumbar hernia is a very rare type of abdominal wall hernia and its diagnosis requires high clinical suspicion and often radiological confirmation by computerized tomography. Conclusion: Lumbar hernia repair is indicated to avoid possible complications and can be performed with an open or laparoscopic approach. Repair should include a mesh to reduce the risk of recurrence.

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Discovery and clinical development of monoclonal antibodies with the ability to interfere in the regulation of the immune response have significantly changed the landscape of oncology in recent years. Among the active agents licensed by the regulatory agencies, nivolumab and pembrolizumab are paradigmatic as the most relevant ones according to the magnitude of available data derived from the extensive preclinical and clinical experience. Although in both cases the respective data sheets indicate well-defined dosage regimens, a review of the literature permits to verify the existence of many issues still unresolved about dosing the two agents, so it must be considered an open question of potentially important consequences, in which to work to improve the effectiveness and efficiency of use.

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The measurement of circulating tumour markers (TMs) for the diagnosis or monitoring of breast cancer has sometimes been considered of limited utility. In addition to the overinterpretation of irrelevant changes in marker levels, the characteristics of the patient, the disease or other pathologies that can modify them are often not considered in their evaluation. On the other hand, there are recent data on the relationship of TMs with molecular subtypes and on their prognostic value, the knowledge of which may improve their clinical utility. This consensus article arises from a collaboration between the Spanish Society of Laboratory Medicine (SEQCML) and the Spanish Society of Medical Oncology (SEOM). It aims to improve the use and interpretation of circulating TMs in breast cancer. The text summarizes the current knowledge and available evidence on the subject and proposes a series of recommendations mainly focussed on the indication, the frequency of testing and the factors that should be considered for correctly interpreting changes in the levels of TMs.

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PURPOSE: Non-epithelial ovarian cancers (NEOCs) are rare diseases. Despite their overall good prognosis, the best management and current prognostic factors remain unclear. The objective of our study was to assess the clinical and pathological features of NEOC patients treated in our institution in the last 15 years and to explore risk factors for relapse and survival. METHODS/PATIENTS: All patients with a pathological diagnosis of NEOC referred to the medical oncology department at Hospital Universitario Virgen del Rocio between 1999 and 2014 were included. Demographics, tumor characteristics, treatment procedures, and clinical follow-up were retrospectively collected. Risk factors for disease-free survival (DFS) and overall survival (OS) were assessed. RESULTS: Fifty-seven patients were included, 33 (58 %) had a sex cord-stromal tumor (SCST) and 24 (42 %) had a germ-cell tumor (GCT). Median age, non-conservative surgery rates and DFS were lower in the GCT cohort; however, salvage chemotherapy led to a high proportion of complete responses in this group translating into a 90 % 3-year OS rate in both NEOC subtypes. The only identified risk factors statistically significant were stage and tumour relapse that associated, respectively, with DFS (HR = 8.84; 95 % CI 1.85-42) and OS (HR = 11.02; 95 % CI 1.76-68.7). CONCLUSIONS: Despite their rarity, NEOCs remain a highly curable group of neoplasm. In our series, a more conservative treatment approach in ovarian GCTs revealed comparable OS outcomes to SCST. No new risk factors that would help in patient stratification were identified.

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Dengue disease statistics is mainly based on consulting patients with febrile illness, but misdiagnosed and asymptomatic cases are important to measure dengue epidemiology in endemic areas. The main objective of this work was to determine the prevalence of IgM and IgG antibodies or NS1 antigen and viral RNA in a group of healthy volunteers from an isolated village in Colombian Chocó rain forest. It found 51.7% of virologically PCR confirmed asymptomatic cases, despite low IgM seroprevalence. It was confirmed that all four serotypes are in the circulation and in 17.2% of individuals it detected natural coinfections of two or three different serotypes simultaneously. This is the first report in Colombia evaluating viremia in asymptomatic volunteers. These findings pose a big concern about the transmission of dengue virus by asymptomatic individuals because they can spread the virus without take appropriate control measures.

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The O2/Li2O2 electrode reaction has been studied on low surface area Au electrodes in three solvent-electrolyte pairs (0.1 M LiPF6/DMSO, LiPF6/ACN, and LiBF4/ACN) using an electrochemical cell coupled to UHV XPS spectrometer, EQCM, AFM, and DEMS. The XPS spectra of the surfaces after treatment at selected electrode potentials for the O2 reduction and reoxidation of the surface show the presence of C and S from solvent decomposition and of F and P from electrolyte decomposition. Furthermore, Li 1s and O 1s peaks due to Li2O2 and decomposition products such as carbonate, organics, LiF, high oxidation sulfur, and phosphorus compounds were also observed. Using ACN instead of DMSO results in less solvent decomposition, whereas using LiBF4 results in less electrolyte decomposition. XPS, AFM, and EQCM show that O2 reduction products removal only takes place at very high overpotentials. In agreement with XPS which shows removal of carbonate surface species, DEMS confirms evolution of CO2 and consumption of O2 at 4.5 V, but LiF cannot be removed completely in a round trip of the Li-O2 battery cathode.

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Sequential adsorption of PdCl4(2-) within weak polyelectrolyte layer-by-layer (LbL) self-assembled multilayer films with further electrochemical reduction to yield Pd(0) nanoparticles (Pd-NPs) has been demonstrated. The electrocatalytic hydrogenation (ECH) of model molecules such as acetophenone and benzophenone on Pd-NPs of different sizes (6 to 35 nm) and bulk Pd crystal surface in hydroalcoholic acid solution has been investigated. Distribution of reaction products (secondary alcohols and alkanes) and faradaic yield was systematically investigated. While the polyelectrolyte multilayers act as nanoreactors by confining PdCl4(2-) ions and preventing the formation of large crystals, their presence also alters the hydrogenation reaction and therefore heat treated surfaces showed only the effect of nanocrystal size on the reaction selectivity and faradaic yield.

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Osmium pyridine-bipyridine redox centers have been tethered to Au electrodes by chemical modification through Au-S and Au-C bonds respectively. 4-Mercapto benzoic acid and the reduction product of the aryl diazonium salt of 4-amino benzoic acid were reacted on Au surfaces, with further post-functionalization by chemical reaction of the osmium complex amino-pyridine derivative with the surface carboxylates. The resulting modified Au surfaces were characterized by polarization modulated infrared reflection absorption spectroscopy (PM-IRRAS), scanning tunneling microscopy (STM), X-ray photoelectron spectroscopy (XPS), resonant raman spectroscopy and cyclic voltammetry.

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Seventeen striped dolphins (Stenella coeruleoalba) displaying swimming disorders compatible with neurological syndromes were investigated for Brucella infection. Sixteen dolphins had meningoencephalomyelitis. Serum antibody against Brucella antigen was detected in all 14 animals tested and Brucella ceti was isolated from eight out of nine animals. Brucella antigen was detected in the brain by immunofluorescence, but not by immunohistochemical labelling. By contrast, Brucella antigen was demonstrated by immunohistochemistry in the trophoblast of animals with severe placentitis and in the mitral valve of animals with myocarditis. The microscopical lesions observed in the tissues of the infected dolphins were similar to those of chronic brucellosis in man. The severity of brucellosis in S. coeruleoalba indicates that this dolphin species is highly susceptible to infection by B. ceti.

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