Real world evidence of adjuvant trastuzumab in HER2 positive early breast cancer.

Adjuvant trastuzumab in HER2+ breast cancer reduces recurrence and mortality, and has been the standard treatment since 2006. The objective was to analyze health outcomes in the real world. Observational, retrospective study of patients with HER2+ breast cancer, stages I-III, treated with adjuvant trastuzumab in the past 15 years in only one center and for the first time in Spain. Survival was analyzed according to the number of cycles and cardiotoxicity. Two hundred and seventy-five HER2positive patients (18.60%) out of 1479 received adjuvant (73%) or neoadjuvant/adjuvant (26%) trastuzumab, concomitantly (90%) or sequentially (10%) with chemotherapy. The probability of overall and disease-free survival (OS and DFS) at 5 years was 0.93 (95% CI 0.89-0.96), and 0.88 (95% CI 0.83-0.92). The number of cases with a significant and asymptomatic decrease in ventricular ejection fraction and heart failure were 54 (19.64%) and 12 (4.36%), respectively. Sixty-eight patients (24.70%) received 16 or fewer cycles, especially those older than 65 (OR 0.371, 95% CI 0.152-0.903; p = 0.029) and with cardiotoxicity (OR 15.02, 95% CI 7.437-30.335; p < 0.001). The risk of cardiotoxicity was associated with having received radiotherapy (OR 0.0362, 95% CI 0.139-0.938; p = 0.037). Arterial hypertension (HR 0.361, 95% CI 0.151-0.863, p = 0.022), neoadjuvant treatment (HR 0.314, 95% CI 0.132-0.750, p = 0.009) and cardiotoxicity (HR 2.755, 95% CI 1.235-6.143, p = 0.013) maintained significant association with OS. Only neoadjuvant treatment maintained a significant association with DFS (HR 0.437, 95% CI 0.213-0.899, p = 0.024). The effectiveness of neoadjuvant and adjuvant trastuzumab can be considered comparable to those of clinical trials. In the real world, factors such as age, hypertension, radiotherapy, neoadjuvant treatment, and cardiotoxicity should be taken into consideration to optimize outcomes.

Lithium salts as a treatment for COVID-19: Pre-clinical outcomes.

INTRODUCTION: Identifying effective drugs for Coronavirus disease 2019 (COVID-19) is urgently needed. An efficient approach is to evaluate whether existing approved drugs have anti-SARS-CoV-2 effects. The antiviral properties of lithium salts have been studied for many years. Their anti-inflammatory and immune-potentiating effects result from the inhibition of glycogen synthase kinase-3. AIMS: To obtain pre-clinical evidence on the safety and therapeutic effects of lithium salts in the treatment of COVID-19. RESULTS: Six different concentrations of lithium, ranging 2-12 mmol/L, were evaluated. Lithium inhibited the replication of SARS-CoV-2 virus in a dose-dependent manner with an IC50 value of 4 mmol/L. Lithium-treated wells showed a significantly higher percentage of monolayer conservation than viral control, particularly at concentrations higher than 6 mmol/L, verified through microscopic observation, the neutral red assay, and the determination of N protein in the supernatants of treated wells. Hamsters treated with lithium showed less intense disease with fewer signs. No lithium-related mortality or overt signs of toxicity were observed during the experiment. A trend of decreasing viral load in nasopharyngeal swabs and lungs was observed in treated hamsters compared to controls. CONCLUSIONS: These results provide pre-clinical evidence of the antiviral and immunotherapeutic effects of lithium against SARS-CoV-2, which supports an advance to clinical trials on COVID-19's patients.

Evaluation of waiting times for breast cancer diagnosis and surgical treatment

Purpose: To analyse any delays in breast cancer diagnosis and surgical treatment, influence of clinical and biological factors and influence of delays on survival. Methods/patients: A descriptive, observational, and retrospective study was conducted between 2006 and 2016 on stages I-III breast cancer patients. This is a retrospective review of health records to collect data on delays, patients’ clinical data, biological features of the tumour and information on treatment. Mortality data from the National Death Index. Results: In 493 evaluable patients, the median of days from the first symptom to mammography, biopsy, and surgery was 41, 57, and 92, respectively. The median of days from screening mammography to biopsy and surgery was 10 and 51, respectively. From biopsy to surgery, the median was 34 days in every case. Over the last 5 years, an increase in biopsy-surgery delay has been observed (p = 0.0001). Tumour stages I and II vs. stage III (RR 1.74. 95% CI 1.08-2.80, p = 0.027), diagnosis in screening (RR 0.66. 95% CI 0.45-0.96, p = 0.030), and use of magnetic resonance imaging (RR 2.08. 95 CI 1.21-3.56, p = 0.008) condition a greater biopsy-surgery delay. No influence of delays on survival has been identified. Conclusions: Delays in diagnosis and surgery in the case of women diagnosed on the basis of symptoms may be improved. There is a temporary tendency to a greater delay in surgery. Some clinical and biological factors must be taken into account to optimise delays. Survival results are not adversely affected by delays

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Evaluation of waiting times for breast cancer diagnosis and surgical treatment.

PURPOSE: To analyse any delays in breast cancer diagnosis and surgical treatment, influence of clinical and biological factors and influence of delays on survival. METHODS/PATIENTS: A descriptive, observational, and retrospective study was conducted between 2006 and 2016 on stages I-III breast cancer patients. This is a retrospective review of health records to collect data on delays, patients' clinical data, biological features of the tumour and information on treatment. Mortality data from the National Death Index. RESULTS: In 493 evaluable patients, the median of days from the first symptom to mammography, biopsy, and surgery was 41, 57, and 92, respectively. The median of days from screening mammography to biopsy and surgery was 10 and 51, respectively. From biopsy to surgery, the median was 34 days in every case. Over the last 5 years, an increase in biopsy-surgery delay has been observed (p = 0.0001). Tumour stages I and II vs. stage III (RR 1.74. 95% CI 1.08-2.80, p = 0.027), diagnosis in screening (RR 0.66. 95% CI 0.45-0.96, p = 0.030), and use of magnetic resonance imaging (RR 2.08. 95 CI 1.21-3.56, p = 0.008) condition a greater biopsy-surgery delay. No influence of delays on survival has been identified. CONCLUSIONS: Delays in diagnosis and surgery in the case of women diagnosed on the basis of symptoms may be improved. There is a temporary tendency to a greater delay in surgery. Some clinical and biological factors must be taken into account to optimise delays. Survival results are not adversely affected by delays.

A C60-aryne building block: synthesis of a hybrid all-carbon nanostructure.

The synthesis of a [60]fullerene-benzyne building block and its further chemical cycloaddition reaction with graphene has resulted in a new all-carbon hybrid material which has been characterized by TGA, FTIR and Raman spectroscopies, XPS as well as AFM and TEM. Based on computational studies, the formation of both [2+2] and [4+2] cycloadducts on the graphene surface is feasible.

Chirality transfer from graphene quantum dots.

Chiral graphene quantum dots were prepared by acidic exfoliation and oxidation of graphite, dialysis, and esterification with enantiomerically pure (R) or (S)-2-phenyl-1-propanol. Circular dichroism studies support the formation of supramolecular aggregates with pyrene molecules, where a transfer of chirality occurs from the chiral graphene quantum dots to the pyrene.

Frequency of Toxoplasma gondii in pork meat in Ocotlán, Jalisco, Mexico.

Toxoplasmosis is an infection caused by Toxoplasma gondii, an intracellular obligate parasite. Its transmission has usually been attributed to ingestion of undercooked or raw meat. The frequency of T. gondii in pork, the most common meat for human consumption in Jalisco, Mexico, is unknown; in Guadalajara city high prevalence of human toxoplasmosis has been documented. Forty-eight samples of pork meat from butcher shops in Ocotlán city were analyzed. Through bioassay, 50 g of tissue was homogenized in an acidic pepsin solution and inoculated subcutaneously to previously immunosuppressed mice. Blood samples from the mice tail vein were obtained before inoculation and 7, 14, 28, and 45 days postinoculation to analyze anti-Toxoplasma immunoglobulin (Ig) M and IgG antibody kinetics by indirect enzyme-linked immunosorbent assay. For histopathology, small fragments of the brain, lungs, heart, and skeletal muscle were extracted on day 45 and were stained with hematoxylin and eosin. Also, DNA was extracted from the pork meat for PCR amplification of the B1 gene. Even though all pork samples were negative by histopathology and PCR, IgG and IgM antibodies against T. gondii were detected in 1 of the 48 inoculated mice, reflecting a frequency of 2.1% positive pork meat, which is lower than expected but similar to that found in other regions.

Acute infection of Toxoplasma gondii and cytomegalovirus reactivation in a pediatric patient receiving liver transplant.

A 7-year-old Mexican boy with end-stage cirrhosis underwent liver transplantation and was maintained with cyclosporine and prednisolone. No specific data about Toxoplasma gondii or cytomegalovirus (CMV) infections in the cadaver donor were available. The recipient was seronegative for Toxoplasma, but CMV-IgG positive before transplantation. Ganciclovir was administered for prophylaxis during 3 months, but 5 months later he presented with icterus and increased transaminases. Acute transplant rejection was ruled out by biopsy. A seroconversion for T. gondii IgM and IgG and a small increase in CMV-IgM antibodies were observed, although the CMV-polymerase chain reaction (PCR) was negative. Ganciclovir was re-started, and the patient improved, but 6 months later he relapsed, and chorioretinitis lesions compatible both with T. gondii and CMV infections appeared. Pyrimethamine, sulfadiazine, folinic acid, and ganciclovir were administered. The boy showed favorable clinical improvement and remained stable for 12 months. Then, new retinal CMV lesions appeared in both eyes and the PCR for CMV became positive; therefore, the patient received a new regimen of ganciclovir, and clinically improved. From these data we concluded that the child presented a reactivation of CMV and a primary infection with T. gondii after transplantation.

Riesgo de caries en los niños de tercer grado de la escuela "Fernando Cuesta Piloto".

Se realizó un estudio epidemiológico descriptivo transversal para determinar el riesgo de caries mediante el empleo de un modelo de predicción (tabla de riesgo) en 64 infantes que cursan el tercer grado en la escuela "Fernando Cuesta Piloto" en Santa Clara, en el período comprendido de septiembre a mayo del 2006. Para la estimación del riesgo de caries en niños se utilizó un modelo que emplea predictores factibles de medir en nuestros servicios estomatológicos, garantizando la identificación de factores de riesgo asociados con la enfermedad. La recogida de la información se llevó a cabo por el método de encuesta, mediante examen clínico, observación, mediciones y entrevistas individuales. Se pudo observar que el 19,4 % de los examinados se encontró en la categoría de alto riesgo. Se destaca que el factor de riesgo que más se asoció con otros de manera significativa o muy significativa fue el de hábitos nocivos, seguido por antecedentes de caries y caries en familiares. Consideramos que el empleo de este modelo de predicción resulta de vital importancia para garantizar la identificación de factores asociados con la enfermedad y favorecer la proyección estratégica en función de prevenir el inicio de esta. (AU)

Immunocytochemical characterisation of the wall of the bovine lateral ventricle.

The cytoarchitecture of the walls of the bovine lateral ventricles was investigated by the use of immunocytochemistry. We defined three types of walls. Type 1 lined regions of white matter and had ciliated cuboidal ependyma, a few subependymal cells and a narrow subjacent glial layer. Type 2 lined the striatum and possessed ependymal cells with conspicuous basal processes that extended through a wide subependyma containing many subependymal cells and a wide subjacent glial network. Type 3 lined the rostral horn and displayed ependymal cells with the longest basal processes and wider subependymal and glial layers. Ependymal cells of type 2 and 3 walls were labelled with antibodies against S-100beta protein, vimentin, GFAP, BLBP and nestin. Anti-betaIII-tubulin stained small cells in the subependyma and inside the GFAP- and vimentin-positive subjacent glial network. Anti-PCNA-positive nuclei were abundant in the subependymal and glial layers of type 2 and 3 walls. DiI in vitro tracing studies revealed small bipolar cells in the glial layer at a distance from the site of the label deposit. These results suggest that neurogenesis takes place in adult bovine subependyma mostly in the walls of the striatum and the rostral horn, and that young neuroblasts may migrate in a rostro-ventral direction through the glial network.

[Neurologic development of children at age two who had been treated at a neonatal intensive care unit]. / El neurodesarrollo a los dos años de vida de neonatos tratados en una unidad de cuidados intensivos neonatales.

The principal objective of this study was to evaluate, at 2 years of age, the neurological development of a group of children who had been treated in the neonatal intensive care unit (NICU) of the National Institute of Perinatology of Mexico. All the children born between 1 January 1992 and 31 December 1993 who had entered the NICU and stayed for 3 or more days were studied from the neurological, psychological, auditory, linguistic, motor, and neuromuscular standpoint. This group included 134 patients, who had had an average gestational age of 32 weeks and an average birth-weight of 1,677 g. They had stayed in the hospital an average of 51 days, and 75% of them had undergone artificial respiration. In the examination done at age 2, 66.5% of the children were normal and 8.2% had serious impairments. There were statistically significant associations between their neurological condition and the days of artificial respiration (P < 0.0001), the days spent in the NICU (P < 0.000004), and the gestational age in weeks (P < 0.03). There was no association between the children's sex and the results of the assessments. The study results showed a decrease in neural abnormalities in comparison with the results obtained in similar studies 10 years earlier.

[Subependymal/intraventricular hemorrhage in preterm newborn infants. Neurodevelopmental course during the first year of life]. / Hemorragia subependimaria/intraventricular en neonatos pretérmino. Evolución del neurodesarrollo durante el primer año de vida.

Subependymal/intraventricular hemorrhage (SE/IVH) is the most frequently encountered type of hemorrhage in the neonatal period. Premature infants often develop SE/IVH which remains is one of most serious neonatal events. We studied a group of 96 premature newborn infants: half of which were diagnosed with SE/IVH. We evaluated the babies at six and 12 months of age which++ a battery of neurobehavioral exams, including neurological, psychological, motor an audiological test. In 52 of infants with SE/IVH showed some type of neurobehavioral abnormality, compared with 13% of non-SE/IVH infants. In 56% of SE/IVH infants had neurological abnormalities at 12 months (P < 0.0001) difference with non-SE/IVH), predominantly in areas of muscle tone and reflex. Motor abnormalities were encountered in 42% of SE/IVH children, and in 4% of non-SE/IVH children at 12 months. Psychometric abnormalities at 12 months were noted in 53% of the SE/IVH group. Hypocusis were noted in 38% of the SE/IVH group and in 15% of the non-SE/IVH group.

[Alterations in neuro-development in the 1st year of life in newborn infants weighing 2000 grams or less at birth]. / Alteraciones del neurodesarrollo en el primer año de vida en neonatos que pesaron 2.000 gramos o menos al nacer.

The infants with low weight at birth have great chance of exhibiting early death or neurodevelopmental sequelae. We prospectively evaluated the neurological and psychological development during the first year of life in 118 infants who weighted less than 2,000 g at birth. All patients were examined with the Amiel Tison and Grenier test (neurologic evaluation), Gesell test (psychological) and Brunette-Lezine test (Psychomotor scale). Mean gestational age was 33 weeks (SD = 3.1) and birth mean weight was 1495 g (SD = 291). Seventy per cent were delivered by cesarean section. Neurological abnormalities were found in 20 infants (alteration of muscular tone in all and motor deficit in 50%). Twenty five per cent had abnormal Gesell test and 17% psychomotor retardation (13% mild and 4% severe).

[A follow-up during the first year of life of newborn infants with very low weight at birth]. / Seguimiento durante el primer año de vida, de neonatos con muy bajo peso al nacer.

Groups of low-weight neonates, especially those under 1,500 g, discharged from the Intensive Care Unit, have a greater frequency of having psychoneurologic, audiologic, language and ophthalmologic scars in comparison with those neonates who suffered no complications. These frequencies vary considerably depending on different authors, the type of sequela and the duration of the follow-up. It is difficult to identify early on, which of these children will be affected in his later development. The currently used prognostic indexes have shown the importance of combining the child's psychoneurologic and biologic evolution as well as his surrounding environmental factors. Thirty-eight newborns were studied. Each weighted 1,500 g or less and were discharged from the Neonatal Intensive Care Unit. All of the patients were subsequently evaluated by specialists in Neurology, Psychology, Social Communication, Neuromotor Rehabilitation and Ophthalmology at 3, 6, 9 and 12 months of age (37 weeks) and included in a study conducted by the Program for Pediatric Follow-up at the National Institute of Perinatology. In general, the number of abnormalities found in each of the specialties during the first months of life was notorious, which later decreased as the child got older. For example, Neurology found abnormalities at 3 months in a proportion of 0.61 and at 12 months, it decreased to 0.19 (P less than 0.001). During neuromotor stimulation something similar was seen at three months a proportion of 0.39 abnormalities were recorded while at 12 months this decreased to 0.18. The human communication tests showed a proportion of 0.32 at 3 months and 0.10 at 12 months (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)