Real-World Evidence of Ribociclib Plus Aromatase Inhibitors as First-Line Treatment in Advanced Breast Cancer: The BrasiLEEira Study.

PURPOSE: Cyclin inhibitors plus endocrine therapy represent the reference standard for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) locally advanced or metastatic breast cancer (ABC). Efficacy results on hard end points such as overall survival come from well-designed randomized clinical trials (RCTs). However, a limitation of RCTs is the low external results validity, and their extrapolation to a broader population may not be appropriate. Real-world studies can overcome these limitations, also increasing the reliability of RCTs. MATERIALS AND METHODS: The BrasiLEEira was an observational, longitudinal, retrospective, multicenter study to evaluate the effectiveness and safety of ribociclib plus nonsteroidal aromatase inhibitors in Brazilian women age 18 years or older with HR+/HER2- ABC. The study was approved by the institutional review boards of all 11 hospitals. Data were collected anonymously from medical records using an electronic case report form designed by an independent academic research organization, which conducted the study considering all recommendations of international guidelines. The primary end point was 1-year progression-free survival (PFS) rate. Secondary end points included mortality, dose reduction, and safety. RESULTS: The mean age of 76 patients was 57 years, and 28.9% were Black/Brown. The most prevalent comorbidity was arterial hypertension (34.7%). About 26.0% had endocrine-resistant disease, and 54.1% had more than three metastatic sites. The PFS rate was 77.6%. Three patients died (3.9%). Dose reductions occurred in 37.7% of patients. The most common adverse event was neutropenia (68.4%). CONCLUSION: The high-quality evidence from the BrasiLEEira study corroborates the RCTs' findings, expanding its validity to a broader spectrum and underrepresented population who may benefit from ribociclib treatment.

Advantages of Intraoperative Neuromonitoring Over Direct Visualization of the Recurrent Laryngeal Nerve During Thyroidectomy.

BACKGROUND: The well-recognized risk of injury to the recurrent laryngeal nerve (RLN) during thyroidectomy has instigated various preventive measures. One such measure involves directly visualizing the RLN, but this is not always feasible in practice. A more recent approach involves using intraoperative neuromonitoring to identify and preserve the RLN. This study aims to evaluate the effectiveness of intraoperative neuromonitoring compared to single visualization of the RLN in averting nerve injury. METHODS: We conducted a retrospective, observational, and descriptive study on a cohort of 218 patients. A Chi-square test was employed to determine the influence of intraoperative neuromonitoring on the incidence of nerve injury, with P < 0.05 considered statistically significant. We used Jamovi software version 2.3.18 to analyze the data. RESULTS: Of the 218 patients, intraoperative neuromonitoring was used in 150 (68.8%) cases; none of which resulted in nerve injury. Conversely, 68 (31.2%) patients underwent surgery without the use of neuromonitoring, with two (2.9%) patients in this group experiencing nerve injury (p=0.037). In comparison, the risk of nerve injury was 0% in the group monitored intraoperatively and 2.94% in the group that did not undergo intraoperatively neuromonitoring. Further, the relative risk of complications was 0.66% in patients operated with neuromonitoring, while it was 5.88% in the group operated without neuromonitoring, thus demonstrating a clinically significant protective against vasculonervous complications. CONCLUSION: The results advocate for the use of intraoperative neuromonitoring, whenever available, as it is a safe method for significantly decreasing the incidence of RLN injury during thyroidectomy compared with only visualization.

Effect of the aniline fragment in Pt(II) and Pt(IV) complexes as anti-proliferative agents. Standard reduction potential as a more reliable parameter for Pt(IV) compounds than peak reduction potential.

The problems of resistance and side effects associated with cisplatin and other chemotherapeutic drugs have boosted research aimed at finding new compounds with improved properties. The use of platinum(IV) prodrugs is one alternative, although there is some controversy regarding the predictive ability of the peak reduction potentials. In the work described here a series of fourteen chloride Pt(II) and Pt(IV) compounds was synthesised and fully characterised. The compounds contain different bidentate arylazole heterocyclic ligands. Their cytotoxic properties against human lung carcinoma (A549), human breast carcinoma (MCF7) and human colon carcinoma (HCT116 and HT29) cell lines were studied. A clear relationship between the type of ligand and the anti-proliferative properties was found, with the best results obtained for the Pt(II) compound that contains an aniline fragment, (13), thus evidencing a positive effect of the NH2 group. Stability and aquation studies in DMSO, DMF and DMSO/water mixtures were carried out on the active complexes and an in-depth analysis of the two aquation processes, including DFT analysis, of 13 was undertaken. It was verified that DNA was the target and that cell death occurred by apoptosis in the case of 13. Furthermore, the cytotoxic derivatives did not exhibit haemolytic activity. The reduction of the Pt(IV) compounds whose Pt(II) congeners were active was studied by several techniques. It was concluded that the peak reduction potential was not useful to predict the ability for reduction. However, a correlation between the cytotoxic activity and the standard reduction potential was found.

Ozonoterapia como adyuvante en el tratamiento periodontal no quirúrgico y quirúrgico / Ozonoterapia as adjuvant in the non-surgical and surgical periodontal treatment

Introducción: El ozono (O3) presenta múltiples acciones biológicas, entre ellas su efecto antimicrobiano, lo que ha sido beneficioso en odontología, siendo la presentación acuosa la más utilizada (20 µg/ mL), la cual presenta efectos similares a la clorhexidina. Reporte de caso: Paciente masculino de 76 años de edad, diagnosticado con periodontitis crónica moderada localizada, el cual fue tratado mediante ozonoterapia acuosa durante la fase inicial periodontal y la fase quirúrgica en colgajo por debridación. 12 semanas posteriores al acto quirúrgico se obtuvo la eliminación de las bolsas periodontales, encontrándose un surco de 3 y 2 mm y un buen control de placa dentobacteriana. Conclusión: No existen reportes acerca del uso de ozonoterapia acuosa durante un colgajo por debridación. El éxito del tratamiento periodontal consiste en la eliminación del factor causal así como en establecer y mantener un control de placa dentobacteriana adecuado (AU)

Introduction: Ozone (O3) has multiple biological actions, including its antimicrobial effect, which has been beneficial in dentistry, the aqueous presentation being the most used (20 µg/mL), which has similar effects to chlorhexidine. Case report: Male patient of 76 years of age, diagnosed with localized moderate chronic periodontitis, which was treated by aqueous ozone therapy during the initial periodontal phase and surgical phase in debridement flap. Twelve weeks after surgery, the periodontal pockets were eliminated, finding a 3 and 2 mm groove and good control of dentobacterial plaque. Conclusion: There are no reports about the use of aqueous ozone therapy during a debridement flap. The success of the periodontal treatment consists in the elimination of the causal factor, as well as establishing and maintaining an adequate control of plaque (AU)

Checkpoint Blockade Strategies in the Treatment of Breast Cancer: Where We Are and Where We Are Heading.

OPINION STATEMENT: Immunotherapy has become one of the greatest advances in medical oncology over the last century; however, the optimal application for the treatment of breast cancer remains an active area of investigation. Modern immunotherapy strategies augment the immune system and ideally, permit durable tumor-specific immune memory. In fact, several monoclonal antibodies that mediate the immune checkpoint receptors have provided the most clinically meaningful improvement for breast cancer patients to date, particularly for the triple negative subtype. Checkpoint blockade as monotherapy has demonstrated some encouraging results, although some combination strategies appear to augment those responses and may be particularly effective when administered earlier in the course of disease. For example, the combination of atezolizumab and nab-paclitaxel as first-line therapy for metastatic triple negative breast cancer demonstrated significant improvements in progression-free survival when compared with chemotherapy alone. Herein, we review the data for immune therapy in breast cancer and highlight promising future directions.

Taste disorders following cancer treatment: report of a case series.

PURPOSE: To present the findings of combined oral assessment and gustometry testing of a series of head and neck and hematologic malignancies in patients with self-reported taste change after cytotoxic therapies. METHODS: Patients with acute myeloid leukemia (AML), multiple myeloma (MM), and head and neck cancer (HNC) were evaluated for taste function. Chemical gustometry was conducted assessing chemosensory qualities that included sweet, sour, salty, bitter, umami, and spicy. NCI Common Terminology Criteria for Adverse Events (CTCAE) 4.0 and the Scale of Subjective Total Taste Acuity (STTA) were used to describe taste symptoms. Saliva flow rates were measured to determine the presence of hyposalivation. Patients were provided treatment trials for taste dysfunction, including zinc supplements, or medications that included clonazepam, megestrol acetate, and the cannabinoid dronabinol. RESULTS: According to STTA, hematology cases reported the incidence of grades 2 and 3 taste disturbances as 60% and 40%, respectively. For HNC patients, the incidence of grades 2 and 3 was 44% each. Gustometry tests confirmed dysgeusia in all patients evaluated. In the hematology group, 80% of patients exhibited a decrease in sweet taste perception, and no patients correctly identified umami taste. In the HNC group, most patients could not identify salt taste, 66% of patients reported "no sensation" with spicy taste, bitter taste was reduced in some, and increased or altered in others, while only one patient could identify umami taste. In the hematologic and HNC patient groups, 80% and 66% reported grade 2 dry mouth, respectively, according to CTCAE 4.0. After treatment for taste dysfunction, 71% of all patients in the present study reported improvements in taste function. CONCLUSIONS: Persisting dysgeusia in cancer survivors may be assessed by patient report and taste testing. The taste most affected in our patients was umami. Treatment trials with current interventions for dysgeusia appeared effective and should be considered in cancer survivors. Understanding taste and flavor function during and following cancer treatment is important in developing rational prospective preventive and interventional strategies.

Role of Seroalbumin in the Cytotoxicity of cis-Dichloro Pt(II) Complexes with (N

Given the potent anticancer properties of cis-diamminedichloroplatinum(II) and knowing its mode of action, we synthesized four new cis-[PtCl2(N^N)] organoplatinum complexes, two with N-substituted pbi ligands (pbiR = 1-R-2-(2-pyridyl)benzimidazole) (namely, 1 and 2) and two more with 4,4'-disubstituted bpy ligands (bpy = 2,2'-bipyridine) (namely, 3 and 4). We explored their cytotoxicity and ability to bind to deoxyguanosine monophosphate (dGMP), DNA, and albumin models. By 1H NMR and UV-vis spectroscopies, circular dichroism, agarose gel electrophoresis, differential scanning calorimetry measurements, and density functional theory calculations, we verified that only 3 can form aquacomplex species after dimethyl sulfoxide solvation; surprisingly, 1, 2, and 3 can bind covalently to DNA, whereas 4 can form a noncovalent complex. Interestingly, only complexes 1 and 4 exhibit good cytotoxicity against human ovarian carcinoma (HeLa) cell line, whereas 2 and 3 are inactive. Although lung carcinoma (A549) cells are more resistant to the four platinum complexes than HeLa cells, when the protein concentration in the extracellular media is lower, the cytotoxicity becomes substantially enhanced. By native electrophoresis of bovine seroalbumin (BSA) and inductively coupled plasma mass spectrometry uptake studies we bear out, on one hand, that 2 and 3 can interact strongly with BSA and its cellular uptake is negligible and, on the other hand, that 1 and 4 can interact with BSA only weakly, its cellular uptake being higher by several orders. These results point up the important role of the protein binding features on their biological activity and cellular uptake of cis-"PtCl2" derivatives. Our results are valuable in the future rational design of new platinum complexes with improved biological properties, as they expose the importance not only of their DNA binding abilities but also of additional factors such as protein binding.

Cryptococcus gattii aislado de un guepardo (Acinonyx jubatus) del Parque Zoológico Nacional de Cuba / Cyptococcus gattii isolated from a cheetah (Acinonyx jubatus) in the National Zoo of Cuba

INTRODUCCIÓN: la criptococosis, micosis sistémica causada por especies del género Cryptococcus, ha elevado considerablemente su incidencia en los últimos años, asociada sobre todo a la infección por el virus de la inmunodeficiencia humana. También ha sido descrita en animales, aunque con baja frecuencia. MÉTODOS: se presentó el caso de una hembra de guepardo (Acinonyx jubatus) mantenida en cautiverio en el Parque Zoológico Nacional, en La Habana. El animal, procedente de Sudáfrica, comenzó con súbita pérdida de peso, astenia, anorexia y dificultad respiratoria con abundante secreción nasal. RESULTADOS: mediante exámenes micológicos de esas secreciones se demostró la presencia de Cryptococcus gattii serotipo B. Por el origen del animal y su permanencia en cautiverio, se estima que la infección se mantuvo latente por un período no menor de 16 meses. CONCLUSIONES: en Cuba, hasta el momento, todos los aislamientos clínicos de Cryptococcus corresponden a C. neoformans var. grubii, por lo que se estima que la infección fue adquirida en el país de origen del animal. Este representa el primer aislamiento de C. gattii en Cuba a partir de un animal importado de Sudáfrica, donde este hongo es endémico.

INTRODUCTION: Cryptoccosis systemic mycosis caused by Cryptococcus species- has considerably raised its incidence in the last years, mainly associated with the human immunodeficiency virus infection. It has also been described in animals, but rare cases. METHODS: a case of a female cheetah (Acinonyx jubatus) kept in the Nacional Zoo of Havana was presented. The animal came from South Africa. She began losing weight, and suffering asthenia, anorexia and breathing problems with abundant nasal secretion. RESULTS: mycological testing of these secretions disclosed the presence of serotype B Cryptococcus gattii. Because of the origin and captive condition of the animal, it was believed that the infection had been latent for 16 months at least. CONCLUSIONS: up to the present, in Cuba, all clinical Cryptococcus isolates were C. neoformans var. grubii, so it is considered that the infection was caught in the country of origin of the female cheetah. This is the first C. gattii isolate in Cuba from an animal coming from South Africa where this fungus is endemic.

Hormonioterapia paliativa em câncer de mama: aspectos práticos e revisão da literatura / Palliative hormonal therapy for breast cancer: a practical review literature

JUSTIFICATIVA E OBJETIVOS: O câncer de mama é uma doença altamente prevalente em todo o mundo e com elevada taxa de mortalidade. Na doença metastática, o principal objetivo é a paliação dos sintomas, com benefício em qualidade de vida e aumento da sobrevida do paciente. O objetivo deste estudo foi revisar a literatura relacionada à hormonioterapia no tratamento do câncer de mama avançado, com ênfase nos ensaios clínicos com maior impacto científico, além de contextualizar estes estudos com a prática clínica diária. CONTEÚDO: Dentre os diversos tipos de tratamento, a hormonioterapia tem papel fundamental, pois tem bom perfil de toxicidade, elevada eficácia e diversas opções terapêuticas. CONCLUSÃO: A hormonioterapia é um recurso altamente eficaz para o tratamento paliativo do câncer de mama e seu uso mais difundido será certamente encontrado por clínicos gerais que participem do cuidado destas pacientes.

BACKGROUND AND OBJECTIVES: Breast cancer is a frequent disease worldwide with a high mortality rate. Care of patients with metastatic disease is mainly focused in palliating symptoms and improving the quality of life of patients. This study has evaluated the most important evidence regarding horMédicamonal therapy in metastatic breast cancer in order to come up with a practical approach to the care of these patients. CONTENTS: Among the therapeutic options at this stage, hormonal therapy is very important because of its efficacy, favorable toxicity profile and for the multiple choices of different medications of this type currently available. CONCLUSION: Hormonal therapy is highly effective for the palliative care of breast cancer patients and because of its more widespread use, general internists who also care for these patients may certainly use these medications.

Utilidad de la D-prolina en la diferenciación de las variedades de Cryptococcus neoformans / Usefulness of D-proline in the differentiation of varieties of Cryptococcus neoformans

Se realizó un estudio comparativo entre la asimilación de la D-prolina y el crecimiento en medio canavanina-glicina-azul de bromotimol (CGB) utilizados para la clasificación de las variedades de Cryptococcus neoformans. En las 86 cepas estudiadas, 100 por ciento de coincidencia entre ambos métodos, permitió afirmar que 95,34 por ciento pertenecían a la var. neoformans y el resto (4,65 por ciento) a la var. gattii. Los resultados obtenidos corroboraronn que todos los aislamientos clínicos autóctonos, hasta el presente, corresponden a la var. neoformans y permitieron sugerir el uso de la D-prolina para la evaluación inicial de las cepas, como un método alternativo y sencillo que presentó, en estas condiciones, alta coincidencia con el método de referencia (crecimiento en CGB)

Imágenes angiográficas posangioplastia: pronóstico de la dilatación coronaria intraluminal / Postangioplasty angiographic images: prognosis of intraluminal coronary dilation

Estudiamos consecutivamente 17 enfermos (14 hombres y tres mujeres) entre 39 y 68 años de edad (x=57.11 ñ 8.48 años), con estenosis de una sola arteria coronaria: 12 tipo B y cinco tipo A. El promedio de estenosis coronaria fue 89.59 ñ 5.2 por ciento (límites entre 78 y 96 por ciento) antes de la angioplastia intraluminal y 37.29 ñ 13.06 por ciento (límites entre 18 y 60 por ciento) después de la angioplastia. La clase funcional (según la Sociedad Canadiense Cardiovascular) fue en promedio 2.41 ñ 0.5 antes de la angioplastia y 1.7 ñ 0.68 varios meses después de ella (5.11 ñ 2.61, límites tres a siete meses): El tipo de estenosis coronaria anterior a la angioplastia no predice el grado de complejidad de las imágenes coronariográficas observadas después de efectuada (tersas, brumosas, con disección o aneurisma). En cambio, se encontró fuerte relación (r=0.89) entre el grado de complejidad de las coronariografías posteriores a la angioplastia y el deterioro de la clase funcional del paciente varios meses después de realizada. También se observó que el mayor grado de complejidad de las imágenes coronariográficas inmediatas a la plastia estaba relacionado con la mayor frecuencia de electrocardiograma de esfuerzo positivo obtenido meses después. En conclusión, la apariencia de las coronariografías predice la evolución clínica del paciente a corto y mediano plazos.

Leptospirosis humana en Yucatán: presentación de dos nuevos casos y revisión clínica / Human leptospirosis in Yucatan: report of 2 new cases and clinical review

Se presentan los dos últimos casos de leptospirosis registrados en el Estado de Yucatán. Ambos casos cursaron con el cuadro clínico correspondiente a la forma ictérica grave o "Síndrome de Weil". Uno de ellos presentó compromiso pulmonar intenso y falleció. Los títulos máximos de reactividad serológica fueron de 1:800 y 1:1600 en uno y otro paciente respectivamente y en ambos contra el serotipo icterohaemorragiae. En la biopsia de hígado del paciente muerto se observó leptospiras. Se hace una revisión clínica y epidemiológica de los casos diagnosticados hasta ahora en la región y se insiste sobre la necesidad de incluirla en el diagnóstico diferencial de otros procesos infecciosos, para tener un mejor conocimiento de su importancia epidemiológica en México