"Very early" intrahepatic cholangiocarcinoma in cirrhotic patients: should liver transplantation be reconsidered in these patients?

A retrospective cohort multicenter study was conducted to analyze the risk factors for tumor recurrence after liver transplantation (LT) in cirrhotic patients found to have an intrahepatic cholangiocarcinoma (iCCA) on pathology examination. We also aimed to ascertain whether there existed a subgroup of patients with single tumors ≤2 cm ("very early") in which results after LT can be acceptable. Twenty-nine patients comprised the study group, eight of whom had a "very early" iCCA (four of them incidentals). The risk of tumor recurrence was significantly associated with larger tumor size as well as larger tumor volume, microscopic vascular invasion and poor degree of differentiation. None of the patients in the "very early" iCCA subgroup presented tumor recurrence compared to 36.4% of those with single tumors >2 cm or multinodular tumors, p = 0.02. The 1-, 3- and 5-year actuarial survival of those in the "very early" iCCA subgroup was 100%, 73% and 73%, respectively. The present is the first multicenter attempt to ascertain the risk factors for tumor recurrence in cirrhotic patients found to have an iCCA on pathology examination. Cirrhotic patients with iCCA ≤2 cm achieved excellent 5-year survival, and validation of these findings by other groups may change the current exclusion of such patients from transplant programs.

Intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma in patients undergoing liver transplantation: a Spanish matched cohort multicenter study.

OBJECTIVE: To evaluate the outcome of patients with hepatocellular-cholangiocarcinoma (HCC-CC) or intrahepatic cholangiocarcinoma (I-CC) on pathological examination after liver transplantation for HCC. BACKGROUND: Information on the outcome of cirrhotic patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study is limited. METHODS: Multicenter, retrospective, matched cohort 1:2 study. STUDY GROUP: 42 patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study; and control group: 84 patients with a diagnosis of HCC. I-CC subgroup: 27 patients compared with 54 controls; HCC-CC subgroup: 15 patients compared with 30 controls. Patients were also divided according to the preoperative tumor size and number: uninodular tumors 2 cm or smaller and multinodular or uninodular tumors 2 cm or larger. Median follow-up: 51 (range, 3-142) months. RESULTS: The 1-, 3-, and 5-year actuarial survival rate differed between the study and control groups (83%, 70%, and 60% vs 99%, 94%, and 89%, respectively; P < 0.001). Differences were found in 1-, 3-, and 5-year actuarial survival rates between the I-CC subgroup and their controls (78%, 66%, and 51% vs 100%, 98%, and 93%; P < 0.001), but no differences were observed between the HCC-CC subgroup and their controls (93%, 78%, and 78% vs 97%, 86%, and 86%; P = 0.9). Patients with uninodular tumors 2 cm or smaller in the study and control groups had similar 1-, 3-, and 5-year survival rate (92%, 83%, 62% vs 100%, 80%, 80%; P = 0.4). In contrast, patients in the study group with multinodular or uninodular tumors larger than 2 cm had worse 1-, 3-, and 5-year survival rates than their controls (80%, 66%, and 61% vs 99%, 96%, and 90%; P < 0.001). CONCLUSIONS: Patients with HCC-CC have similar survival to patients undergoing a transplant for HCC. Preoperative diagnosis of HCC-CC should not prompt the exclusion of these patients from transplant option.

Emotional and Cognitive Preservice Science Teachers' Engagement While Living a Model-Based Inquiry Science Technology Engineering Mathematics Sequence About Acid-Base.

Science inquiry and modeling activities have been proved to heighten emotional situations; therefore, research about emotions should aim to identify which activities promote student engagement with Science, Technology, Engineering and Mathematics fields through multidimensional models that include emotional and cognitive engagement. This research is focused on science teachers' need to carefully review their classroom instructions to ensure that students are provided with opportunities to develop appropriate understandings of acid/base models (and their concepts). To achieve this, we have implemented a short model-based inquiry acid-base instructional sequence in the context of a TV-spot about chewing gum. A descriptive, non-experimental quantitative methodology with a heuristic (emotional: self-report questionnaire; and cognitive: self-regulation questionnaire) has been used to analyze what Pre-Service Secondary Education Teachers from several Spanish universities recognize to have learned and felt in each activity. Differences regarding knowledge declared by the participants were identified in all the tasks from before to after carrying them out. Furthermore, the results seem to indicate that there are significant relationships between the knowledge and the emotions, being different depending on the skill involved. Significant correlations between emotions have been found. However, there were no significant correlations with either rejection and knowledge or with other emotions, which points to emotional engagement. Generally, no significant differences were identified between emotions and gender or universities, with some exceptions between genders in two tasks. Thus, the results led us to reflect on the instructional sequence implementation's ability to bring awareness to the learning process and how it produces multidimensional engagements.

COVID-19 Cliff Notes: A COVID-19 Multidisciplinary Care Compendium.

As we pass the nearly 9 month mark of the coronavirus virus disease 2019 (COVID-19) pandemic in the United States, we sought to compile a brief multi-disciplinary compendium of COVID-19 information learned to date. COVID-19 is an active viral pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that confers high morbidity and mortality. COVID-19 has been associated with: pulmonary compromise and acute respiratory distress syndrome, thrombotic events, inflammation and cytokine, and post-infectious syndromes. Mitigation of these complications and expeditious therapy are a global urgency; this is brief summary of current data and management approaches synthesized from publications, experience, cross-disciplinary expertise (Figure 1).

Modulation of immunodominant sites in influenza hemagglutinin compromise antigenic variation and select receptor-binding variant viruses.

The regions of antigenic variation in influenza hemagglutinin (HA) are located on surface-accessible regions in the three-dimensional structure of the HA1 monomer. The aim of this study was to establish whether a novel variant virus, IMUT4, in which we had mutated specific amino acid residues (HA1 63, 144, 158, and 193) in these regions, previously shown to be immunodominant for CBA/Ca mice, would either (a) establish holes in the antibody (ab) repertoire or (b) preclude further antigenic variation in IMUT4. CBA/Ca mice were able to mount a neutralizing ab response to IMUT4 infection and molecular recognition sites were established by sequencing of the HA genes of monoclonal antibody (mAb)-selected laboratory variants of wild-type X31 virus (HA1 131, 145, 155, and 196). However, each of these mAbs failed to select further antigenic variants of IMUT4, in ovo, but rather a receptor binding mutant (HA1 190 Glu-->Asp; 226 Leu-->Gln) that was still recognized by the selecting mAb, specific for HA1 155 of X31 virus. The facility for antigenic variation in influenza would appear to be compromised, therefore, by targeted mutation of immunodominant sites, as initially proposed by S. Fazekas de St. Groth (Fazekas de St. Groth, S. 1977. Antigenic, adaptive and adsorptive variants of the influenza haemagglutinin. In Topics in Infectious Diseases. Vol. 3. R.G. Laver, H. Bachmayer, and R. Weil, editors. Springer-Verlag, Vienna. 25-48.). It is interesting to note that recent isolates of the H3 subtype, (e.g., A/Beijing/92) obtained between 1991 and 1993, contain the same substitutions at HA1 190 and 226, which may indicate similar constraints to immune evasion and the relevance of our findings to antigenic variation in the human population.

Structural assignment of novel and immunodominant antigenic sites in the neutralizing antibody response of CBA/Ca mice to influenza hemagglutinin.

Information on the antigenic structure of influenza hemagglutinin (HA) has been deduced previously from sequence analyses of laboratory mutant viruses selected, in vitro, with neutralizing monoclonal antibody (mAb) established exclusively from BALB/c (H-2d) mice; and there has been no attempt to investigate the influence of host genetic background, or natural route of infection, on the protective antibody repertoire. CBA/Ca mice are extremely sensitive to X31 virus infection, and in the present study a structural analysis was made of the antibody repertoire, by direct sequencing of the HA genes of laboratory mutant viruses selected, in ovo with mAb from CBA/Ca mice primed by natural infection with X31 virus at two different infectious doses. Single nucleotide substitutions in the HA genes of mutant viruses identified both novel and immunodominant antigenic sites on the HA1 subunit: a majority of mAbs, from different donors, were of the IgG2a isotype and were specific for HA1 158 Gly. In addition, novel laboratory mutants were obtained containing substitutions in the HA1 subunit that had not been reported previously for H3 subtype viruses, either natural variants or laboratory mutants, at residues: HA1 62 Ile----Arg; HA1 165 Asn----Ser (resulting in the loss of a N-glycosylation site); and HA1 273 Pro----Leu. Our findings suggest that host genetic background and/or a natural route of infection may be significant factors in the selection of different and distinct neutralizing antibody responses to influenza HA and therefore be of some relevance in our further understanding of the immune pressure for antigenic drift, and the immunogenic features of a protective antigen.

[Phenotype proposal for early diagnosis of possibility of metabolic syndrome in school children aged 6 to 15 years]. / Propuesta de fenotipo para diagnóstico temprano de posibilidad de síndrome metabólico en escolares de seis a 15 años.

INTRODUCTION AND OBJECTIVES: Obesity and metabolic syndrome (MS) continue to be a problem at a socioeconomic level, causing high morbidity and mortality in the adult population. Prevention of risk factors should be carried out from an early age. Currently, there is no consensus on the opportune moment to start an intervention or treatment, regarding metabolic syndrome. The objective of the study is to describe the phenotype to predict early diagnosis of metabolic syndrome in schoolchildren. MATERIAL AND METHODS: Observational, prospective, cross-sectional and analytical study in schoolchildren from 6 to 15 years old, conducted in Guayaquil. Anthropometric measurements and a survey were performed, obtaining signing informed consent. The IBM Watson artificial intelligence (AI) platform with its software Modeler Flow, were used for the analysis. RESULTS: A population of 1025 students between 6 and 15 years old (mean of 12 years for men and 13 years for women) was examined, of whom 62.3% were men and 37.7% women. 23.9% of the population was overweight and 14% obese. A greater tendency to weight alteration was observed in men than in women (51.37% vs 47.79%), and a lower waist circumference in men (85 cm vs 87 cm, respectively). Males had a higher level of systolic blood pressure (SBP), being within the 90th percentile (mean SBP of 123 mmHg) 61.2%, compared to 38.8% of women, with a p < 0.001. Sedentary lifestyle is similar in both groups, with an average of 4.79 hours in front of the screen and/or video games. A statistically significant correlation was demonstrated between SBP and the waist/height ratio (WHtR) in the 90th percentile and 95th percentile (X2 9.075, p < 0.028, and X2 23,54, p < 0,000 respectively), as well as a relationship between 95th percentile and sex (X2 11.57, p < 0.001). The Modeler Flow software showed us that if WHtR, > 0.46, weight > 56.1 kg and height > 1.61 m, the probability of presenting metabolic syndrome, was of 82.4%. The statistic of this study has a predictive accuracy of 90% (error deviation of 0.009). The importance in the predictors of metabolic syndrome, range from 97.57% to 100%. CONCLUSIONS: A prevalence of 33.9% of metabolic syndrome was observed in schoolchildren from 6 to 15 years old, with pathological cut-off points of: WHtR > 0.46, weight > 56.1 kg, pure sedentary lifestyle > 3 hours in front of the screen/playing video games, and SBP within the 90th percentile (> 123 mmHg). With these four indicators, we can predict a probability of early diagnosis of metabolic syndrome of 97% to 100%.

Mammary hamartoma.

INTRODUCTION: Mammary hamartomas are rare benign breast lumps. They are usually painless, wellcircumscribed, mobile and with no adherence to skin or muscle, composed of varying amounts of fat, glandular and fibrous tissue. Mammary hamartoma has been classically considered as an underdiagnosed pathology, but with the increasing use of diagnostic procedures in breast tumours, the number of hamartomas has increased in the last years. Because there is no distinct pathological feature, a correlation with the clinical findings and image techniques is necessary in order to achieve a correct diagnosis of the pathology. MATERIALS AND METHODS: The clinicopathological features of 8 mammary hamartomas are reported here. RESULTS: The patients are ranged in age from 34 to 67 years. The initial manifestation was in all cases a well-circumscribed, soft, palpable breast lump. Mammography was performed in all patients. Other diagnostic procedures used in the diagnosis were Ultrasound, Fine Needle Aspiration Cytology and Needle Core Biopsy. Treatment was tumorectomy. We describe a case of recurrence after excision of the lump in a more aggressive histological form and one patient who presented the coexistence of a mammary hamartoma and an invasive ductal carcinoma. CONCLUSION: Mammary hamartoma is an uncommon breast tumour. It is necessary the correlation between pathology and clinical and radiological findings. We express our management plan for these lesions.

Inflammation and perforation of a solitary diverticulum of the cecum. A report of 5 cases and literature review.

Solitary diverticulum of the cecum is a benign condition uncommon in the Western world, and with a higher incidence in Asian population. They are usually asymptomatic, and manifest clinically only with complications such as inflammation, perforation, or bleeding. They are a rare cause of acute abdominal pain, clinically similar to acute appendicitis, with tenderness in the right lower quadrant, fever, and leukocytosis. In spite of the information provided by ultrasonography or CT scans, a correct preoperative diagnosis is still difficult to reach, and is usually arrived at in the operating theater; differentiation from a neoplasm may be also sometimes complicated, and a wide surgical resection is usually required for such cases. We report on 5 cases of inflammation and perforation of a solitary cecal diverticulum, and perform a literature review.

Tendencia de la mortalidad no relacionada con Covid-19 en la región del Bio-Bio, periodo 2016-2020 / Mortality trand not related to Covid-19 in the Bio-Bio, period 2016-2020

INTRODUCCIÓN: La pandemia por SARS-COV-2 ha generado mortalidad por exceso, aun así, se deben revisar la mortalidad atribuida a otras enfermedades. El siguiente trabajo pretende identificar la tendencia de mortalidad no relacionada con COVID-19 en la región del Bio-bio, periodo 2016-2020. Material y Método: Estudio descriptivo, ecológico, longitudinal. Se estudió la población de la región del Biobío, periodo 2016-2020. Los datos se obtuvieron del departamento de estadística e información en Salud. Se estudió: Distribución etaria, sexo, tasa de mortalidad general y específica, y promedio anual del número de muertos en el periodo 2016-2019; excluyendo la causa de muerte por enfermedad COVID-19 o sospechosa de COVID-19. Se realizó un análisis descriptivo. Se utilizó el programa Microsoft Excel 365® para análisis. Resultados: 2016-2019 fallecieron más hombres (n=19.110; 53,00%), siendo el principal grupo etario de 75-79 años (n=2.433; 12,73%), en el caso de las mujeres fue el grupo de 90-99 años (n=2.832; 16,71%). En 2020, fallecieron más hombres que mujeres, de los mismos grupos etarios respectivamente. Tasa de mortalidad general 2020 fue 544,39 x100.000 hbts., inferior a la de otros años, excepto en 2016. Sin embargo, el periodo Enero-abril 2020, la tasa de mortalidad es mayor comparado con los años anteriores. El promedio de muertes 2016-2019 fue 9.016,0 ±186,5, siendo el total en 2020 n=9.057. Discusión: La pandemia ha afectado a pacientes con patologías que han presentado una atención poco efectiva u inoportuna, falleciendo por el SARS-COV-2 o por sus comorbilidades, camuflándose sus registros. Lo cual dificultará interpretar dichos valores.

INTRODUCTION: The SARS-COV-2 pandemic has generated excess mortality, even so, the mortality attributed to other diseases should be reviewed. The study objective was to identify the mortality trend unrelated to COVID-19 in the Bio-bio Region between 2016-2020. Material and Method: Descriptive, ecological, longitudinal study. The population of the Biobío region was studied between the years 2016-2020. Data were obtained from the Department of Statistics and Health Information, DEIS. It was studied: Age distribution, sex, general and specific mortality rate, annual average of the number of deaths between 2016-2020, excluding mortality from (or suspected) COVID-19 disease. A descriptive analysis was performed. Microsoft Excel 365® software was used for the analysis. Results: 2016-2019 mortality rate was higher for men (n=19,110; 53.00%), with the highest rates in the 75-79 years group (n=2,433; 12.73%); women 90- 99 years (n=2,832; 16.71%) presented the highest mortality rates. In 2020 more men than women continued to die in the same age groups, respectively. The general mortality rate 2020 was 544,39 x 100,000 inhabitants, which is lower than that of any other year, except for 2016. However, from January to April 2020, the mortality rate was higher when compared to the previous years. The average of deaths 2016-2019 was 9,016.0 ± 186.5, meanwhile in the same period in 2020 was 9,057. Discussion: The pandemic has affected patients with pathologies who have presented ineffective or untimely care, dying from SARS-COV-2 or its comorbidities, then their records get camouflaged, which will make it difficult to interpret these values.

Activation of the PI3K/AKT pathway by microRNA-22 results in CLL B-cell proliferation.

Chronic lymphocytic leukemia (CLL) is characterized by accumulation of clonal B cells arrested in G0/G1 stages that coexist, in different proportions, with proliferative B cells. Understanding the crosstalk between the proliferative subsets and their milieu could provide clues on CLL biology. We previously identified one of these subpopulations in the peripheral blood from unmutated patients that appears to be a hallmark of a progressive disease. Aiming to characterize the molecular mechanism underlying this proliferative behavior, we performed gene expression analysis comparing the global mRNA and microRNA expression of this leukemic subpopulation, and compared it with their quiescent counterparts. Our results suggest that proliferation of this fraction depend on microRNA-22 overexpression that induces phosphatase and tensin homolog downregulation and phosphoinositide 3-kinase (PI3K)/AKT pathway activation. Transfection experiments demonstrated that miR-22 overexpression in CLL B cells switches on PI3K/AKT, leading to downregulation of p27(-Kip1) and overexpression of Survivin and Ki-67 proteins. We also demonstrated that this pathway could be triggered by microenvironment signals like CD40 ligand/interleukin-4 and, more importantly, that this regulatory loop is also present in lymph nodes from progressive unmutated patients. Altogether, these results underline the key role of PI3K/AKT pathway in the generation of the CLL proliferative pool and provide additional rationale for the usage of PI3K inhibitors.

Different immunoreactivity of endothelial markers in well and poorly differentiated areas of angiosarcomas.

This study evaluated the immunohistochemical staining of four endothelial cell markers in well differentiated and poorly differentiated areas of angiosarcomas. Formaldehyde-fixed, paraffin-embedded sections from eight angiosarcomas were studied using the antibodies anti-factor VIII-related antigen (FVIII-RA), Ulex europaeus I agglutinin, anti-CD34 (QBEND/10) and anti-CD31 (JC70). The immunostaining of the angiomatous (well differentiated) and solid (poorly differentiated) areas was separately analysed and specificity was evaluated in 20 non-vascular tumours. The antibody anti-CD31 and Ulex europaeus were the most sensitive markers staining well differentiated vasoformative structures and poorly differentiated solid areas. Anti-FVIII-RA and anti-CD34 did not stain undifferentiated malignant endothelial cells from solid areas. Ulex europueus and anti-CD34 showed very low specificity; in contrast, none of the non-vascular tumours expressed CD31 or FVIII-RA. JC70 (anti-CD31) appears to be the most useful marker in elucidating the vascular nature of angiosarcomas. Is important to emphasize the lack of specificity of Ulex europaeus and the low sensitivity of anti-CD34 and anti-FVIII-RA for poorly differentiated lesions.

Lobular carcinoma of the male breast associated with the use of cimetidine.

A case of carcinoma in the breast of a male patient with a chronic gastric ulcer is described. The patient had received cimetidine for 17 years. Histological examination of an excisional biopsy showed lobular in situ and infiltrating carcinoma. In our review of the English literature, this is the 18th case of lobular carcinoma of the male breast to be reported; it is also the first report of lobular carcinoma associated with the use of cimetidine, and the second in a man with documentation of genotype.

Adsorptive stripping voltammetric determination of cefepime at the mercury electrode in human urine and cerebrospinal fluid, and differential pulse polarographic determination in serum.

The cephalosporin cefepime has been studied by adsorptive stripping voltammetric on the hanging mercury drop electrode, followed by linear sweep voltammetry (staircase). The adsorptive stripping response was evaluated with respect to preconcentration dependence and other variables. The drug is strongly adsorbed in acid media, with maximum adsorption at pH 5.8. The detection limit found was 4.8 x 10(-10) M, with 120-s preconcentration. The relative standard deviation at the 10(-7) M level was 0.93%. This method was applied to the determination of cefepime in human urine and cerebrospinal fluid. Differential pulse polarography has been applied to determination in human serum.

Fuzzy logic in a patient supervision system.

A patient supervision system in progress for intensive and coronary care units, focused on patients with acute myocardial infarct is briefly described particularly regarding the role that fuzzy logic is playing in its design, and why this is so.

A problem-solving method for 'unprotocolised' therapy administration task in medicine.

This paper describes a problem-solving method for modelling the 'unprotocolised' treatment administration task in medicine. We argue that there are medical domains in which no well-established standard treatment protocols exist, and the physician has to decide on the therapy that is to be applied to each patient, in function of a set of therapeutic objectives to be fulfilled. For this reason, we propose the modelling of this type of task adapting the generic class of problem resolution methods for design task, labelled as Propose-Critique-Modify (PCM). In this paper, we are presenting a model of expertise which has been developed using the basic modelling components of the CommonKADS methodology.

Simultaneous determination of cefepime and grepafloxacin in human urine by high-performance liquid chromatography.

A liquid chromatographic method with UV detection for simultaneous determination of cefepime and grepafloxacin has been developed. The method uses a C18 column, equipped with a pre-column of the same material, and acetonitrile-0.1 M phosphoric acid/sodium hydroxide buffer (pH 3.0)-0.01 M n-octylamine (pH 3.0) as mobile phase in gradient mode. Mobile flow rate and sample volume injected were 1.3 mL min(-1) and 20 microL, respectively. Detection wavelengths were 259 nm for cefepime and 278 nm for grepafloxacin. The retention times were 4.03 min for cefepime and 8.85 min for grepafloxacin, with detection limits of 1.0 and 1.1 microg mL(-1), respectively. The method was applied to the determination of both antibiotics in spiked samples of human urine.

Wavelet transform analysis of heart rate variability during myocardial ischaemia.

Analysis of heart rate variability (HRV) is a valuable, non-invasive method for quantifying autonomic cardiac control in humans. Frequency-domain analysis of HRV involving myocardial ischaemic episodes should take into account its non-stationary behaviour. The wavelet transform is an alternative tool for the analysis of non-stationary signals. Fourteen patients have been analysed, ranging from 40 to 64 years old and selected from the European Electrocardiographic ST-T Database (ESDB). These records contain 33 ST episodes, according to the notation of the ESDB, with durations of between 40s and 12 min. A method for analysing HRV signals using the wavelet transform was applied to obtain a time-scale representation for very low-frequency (VLF), low-frequency (LF) and high-frequency (HF) bands using the orthogonal multiresolution pyramidal algorithm. The design and implementation using fast algorithms included a specially adapted decomposition quadrature mirror filter bank for the frequency bands of interest. Comparing a normality zone against the ischaemic episode in the same record, increases in LF (0.0112 +/- 0.0101 against 0.0175 +/- 0.0208 s2 Hz(-1); p<0.1) and HF (0.0011 +/- 0.0008 against 0.00 17 +/- 0.0020 s2 Hz(-1); p<0.05) were obtained. The possibility of using these indexes to develop an ischaemic-episode classifier was also tested. Results suggest that wavelet analysis provides useful information for the assessment of dynamic changes and patterns of HRV during myocardial ischaemia.

Breast carcinoma in situ in a male. Report of a case diagnosed by nipple discharge cytology.

BACKGROUND: Cytologic evaluation of abnormal nipple secretion is a well-established method for the rapid diagnosis of breast carcinoma in females. However, less attention has been focused on male patients presenting with nipple discharge. CASE: A case of intraductal carcinoma of the male breast was diagnosed by nipple discharge cytology alone. CONCLUSION: This report illustrates the usefulness of nipple discharge cytology in the diagnosis of early breast carcinoma in males.