Detección de novedad y codificación predictiva en el sistema auditivo: Impacto clínico en disfunciones auditivas y vestibulares. Revisión de la literatura

Una propiedad fundamental de los sistemas sensoriales es su capacidad para detectar estímulos novedosos en el entorno. El sistema nervioso posee neuronas que disminuyen su respuesta a los estímulos sonoros que se repiten a lo largo del tiempo y otras neuronas que aumentan su frecuencia de disparo ante estímulos novedosos, siendo la diferencia entre ambas respuestas conocida como adaptación-específica a estímulos. En las últimas décadas, se ha propuesto que el cerebro establece, continuamente, predicciones de los estímulos novedosos y del entorno basándose en sus experiencias previas y en modelos de representación internos, teoría denominada codificación predictiva. En esta revisión, abordaremos algunos conceptos de la adaptación-específica a estímulos y codificación predictiva, centrándonos principalmente en el sistema auditivo. Por último, propondremos una explicación teórica basada en el marco de la codificación predictiva para algunas disfunciones neuropsiquiátricas, auditivas y vestibulares.

A fundamental property of sensory systems is their ability to detect novel stimuli in the environment. The nervous system possesses neurons that decrease their response to sound stimuli that are repeated over time and other neurons that increase their firing rate to novel stimuli, the difference between the two responses being known as stimulus-specific adaptation. In recent decades, it has been proposed that the brain continuously makes predictions of novel stimuli and the environment based on its previous experiences and internal representational models, a theory called predictive coding. In this review, we will address some concepts of stimulus-specific adaptation and predictive coding, focusing mainly on the auditory system. Finally, we will propose a theoretical explanation based on the predictive coding framework for some neuropsychiatric, auditory, and vestibular dysfunctions.

Is there an Electro-Angiographic Correlation in RD Infarction?

Introduction: Coronary angiography is the examination of choice in the evaluation of coronary anatomy during acute myocardial infarction, particularly of the right ventricle (RV), whose diagnosis remains difficult. The electrocardiogram reflects the pathophysiology of myocardial ischemia, thus allowing prediction of the culprit lesion. Objective: To investigate the correlation between electrical and coronary data and to judge the reproducibility of the electrocardiogram in identifying the culprit lesion in RV infarction. Materials and Methods: Retrospective study of patients hospitalized in the Cardiology Department of the Mohammed VI University Hospital in Marrakech over a period of 24 months for MDI extended to the RV. Results: During the study period, 120 patients were hospitalized for MI with RV extension. Inferior MI represented 70% of all cases of infarction extended to the RV. It is represented electrically by isolated ST-segment elevation in V3R found in 76%, as well as in association with an elevation in V4R in 45% of cases. Conduction disorders were noted in 38% of cases, presented essentially by first degree atrioventricular block, without any electrical specificity. Coronary angiography was performed in 91% of patients, half of whom underwent coronary angioplasty. A bi-truncular involvement (RC + VIA) was found in 40% of cases, the middle DC is the culprit lesion in almost half of the cases of VD infarction. The presence of an ST elevation in the isolated V3R shunt is a specific criterion of right middle coronary involvement, found in 48% of patients. Conclusion: The ECG remains an essential tool in the early prediction of the artery responsible for the infarction. Because of its complementary nature, the combination of ECG and coronary angiography is essential for a better evaluation of acute myocardial infarction.

'Oasis' in 'death desert': attach importance to the diagnosis and treatment for pancreatic cancer with microsatellite instability-high/deficient mismatch repair / 中华消化外科杂志

Pancreatic cancer (PC) is a malignant digestive tract tumor with poor prognosis. Most of patients with PC are insensitive to traditional strategies of chemotherapy, targeted therapy and immunotherapy. PC with microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) is rare in clinic, which has distinctive clinicopathological characteristics and better prognosis from conventional PC. Reasonable acquisition of pancreatic tumor biopsy and accurate assessment of MSI-H/dMMR status are helpful for accurate diagnosis of such patients. Individualized treatment strategy based on immunotherapy can significantly improve the prognosis of patients with MSI-H/dMMR PC. Based on relevant literatures of domestic and foreign, the authors discuss the current status and research hotspots of diagnosis and treatment for MSI-H/dMMR PC.

Pathological Types,Expression of Mismatch Repair Protein,Human Epidermal Growth Factor Receptor 2,and Pan-TRK,and Eostein-Barr Virus Infection in Patients With Colorectal Cancer Resected in Tibet / 中国医学科学院学报

Objective To study the pathological types,expression of mismatch repair protein,human epidermal growth factor receptor 2(HER2),and Pan-TRK,and Epstein-Barr virus(EBV)infection in patients with colorectal cancer resected in Tibet. Methods A total of 79 patients with colorectal cancer resected in Tibet Autonomous Region People's Hospital from December 2013 to July 2021 were enrolled in this study.The clinical and pathological data of the patients were collected.The expression of mismatch repair protein,HER2,and Pan-TRK was detected by immunohistochemical(IHC)staining,and detection of HER2 gene by fluorescence in situ hybridization(FISH)in the patients with HER2 IHC results of 2+ or above.EBV was detected by in situ hybridization with EBV-encoded small RNA. Results A total of 79 colorectal cancer patients were included in this study,with the male-to-female ratio of 1.26:1 and the mean age of(57.06±12.74)years(24-83 years).Among them,4 patients received preoperative neoadjuvant therapy.Colonic cancer and rectal cancer occurred in 57(57/79,72.15%,including 31 and 26 in the right colon and left colon,respectively)and 22(22/79,27.85%)patients,respectively.The maximum diameter of tumor varied within the range of 1-20 cm,with the mean of(6.61±3.33)cm.Among the 79 colorectal cancer patients,75(75/79,94.94%)patients showed adenocarcinoma.Lymph node metastasis occurred in 12(12/21,57.14%)out of the 21 patients with severe tumor budding,13(13/23,56.52%)out of the 23 patients with moderate tumor budding,and 2(2/31,6.45%)out of the 31 patients with mild tumor budding,respectively.The lymph node metastasis rate showed differences between the patients with severe/moderate tumor budding and the patients with mild tumor budding(all P<0.001).The IHC staining showed that mismatch repair protein was negative in 10(10/65,15.38%)patients,including 5 patients with both MSH2 and MSH6 negative,4 patients with both MLH1 and PMS2 negative,and 1 patient with MSH6 negative.Pan-TRK was negative in 65 patients.The IHC results of HER2 showed 0 or 1+ in 60 patients and 2+ in 5 patients.FISH showed no positive signal in the 5 patients with HER2 IHC results of 2+.The detection with EBV-encoded small RNA showed positive result in 1(1/65,1.54%)patient. Conclusions Non-specific adenocarcinoma of the right colon is the most common in the patients with colorectal cancer resected in Tibet,and 15% of the patients showed mismatch repair protein defects.EBV-associated colorectal carcer is rare,Pan-TRK expression and HER2 gene amplification are seldom.The colorectal cancer patients with moderate and severe tumor budding are more likely to have lymph node metastasis.

Mismatch repair gene germline mutations in patients with prostate cancer / 浙江大学学报·医学版

OBJECTIVES@#To investigate the prevalence of pathogenic germline mutations of mismatch repair (MMR) genes in prostate cancer patients and its relationship with clinicopathological characteristics.@*METHODS@#Germline sequencing data of 855 prostate cancer patients admitted in Fudan University Shanghai Cancer Center from 2018 to 2022 were retrospectively analyzed. The pathogenicity of mutations was assessed according to the American College of Medical Genetics and Genomics (ACMG) standard guideline, Clinvar and Intervar databases. The clinicopathological characteristics and responses to castration treatment were compared among patients with MMR gene mutation (MMR+ group), patients with DNA damage repair (DDR) gene germline pathogenic mutation without MMR gene (DDR+MMR－ group) and patients without DDR gene germline pathogenic mutation (DDR－ group).@*RESULTS@#Thirteen (1.52%) MMR+ patients were identified in 855 prostate cancer patients, including 1 case with MLH1 gene mutation, 6 cases with MSH2 gene mutation, 4 cases with MSH6 gene mutation and 2 cases with PMS2 gene mutation. 105 (11.9%) patients were identified as DDR gene positive (except MMR gene), and 737 (86.2%) patients were DDR gene negative. Compared with DDR－ group, MMR+ group had lower age of onset (P<0.05) and initial prostate-specific antigen (PSA) (P<0.01), while no significant differences were found between the two groups in Gleason score and TMN staging (both P>0.05). The median time to castration resistance was 8 months (95%CI: 6 months-not achieved), 16 months (95%CI: 12-32 months) and 24 months (95%CI: 21-27 months) for MMR+ group, DDR+MMR－ group and DDR－ group, respectively. The time to castration resistance in MMR+ group was significantly shorter than that in DDR+MMR－ group and DDR－ group (both P<0.01), while there was no significant difference between DDR+MMR－ group and DDR－ group (P>0.05).@*CONCLUSIONS@#MMR gene mutation testing is recommended for prostate cancer patients with early onset, low initial PSA, metastasis or early resistance to castration therapy.

A case of Constitutional Mismatch Repair Deficiency (CMMRD)

@#Constitutionalmismatch repair deficiency(CMMRD) is a hereditary predisposition of malignancy evident in childhood leukemias, lymphomas, and malignant tumors of the brain, GI tract. It is a very rare condition that affects 1 per 1 million patients. Patients with CMMRD syndrome may also manifest with Neurofibromatosis Type 1 (NF1) phenotypic features, and benign masses, particularly in the gastrointestinal tract. This is a case of a 12-year old male who presented with phenotypic features of NF1, developed Acute Lymphoblastic Leukemia at 7 years old and went into remission. He subsequently developed synchronous Glioblastoma and Poorly differentiated Adenocarcinoma of the rectum.This report aims to raise awareness regarding the possibility of a CMMRD syndrome in pediatric patients who present with phenotypic features of NF1, and in those patients who present with two or more malignancies in their lifetime.

Progress of Lynch syndrome associated endometrial cancer / 肿瘤研究与临床

Lynch syndrome (LS) is a common hereditary tumor syndrome. Gynecological malignancy is usually the first tumor of LS in women, and endometrial cancer (EC) is the most closely associated with LS. Most patients with LS are unaware of this risk, and it is possible to cause misdiagnosis. Thus, early diagnosis helps patients to start tumor surveillance timely, as well as a cascade of family surveillance. This paper reviews the progress of LS associated with EC.

Progress and prospect of heart transplantation in children / 器官移植

Pediatric heart transplantation is the standard treatment for children complicated with refractory heart failure which is difficult to be treated by conventional surgery or drugs. At present, an increasing quantity of pediatric heart transplantation is being performed worldwide, whereas relevant experience is still lacking in China. In recent 10 years, significant progress has been achieved in pediatric heart transplantation. On one hand, the number of pediatric heart transplantation has been increased year by year. On the other hand, ABO-incompatible heart transplantation, application of ventricular assist device in children, and recipient-donor weight mismatch transplantation have been widely employed to resolve the shortage of donor heart in pediatric heart transplantation. However, relevant experience of pediatric heart transplantation is lacking in China, especially in understanding the indications of pediatric heart transplantation and the application of specific strategies for pediatric heart transplantation, etc. In this article, the development history, advances in therapeutic strategy and clinical prognosis of pediatric heart transplantation were reviewed.

Recorrência do ameloblastoma: análise de fatores clínicoradiográficos e imunoexpressão de hMSH2, hMLH1 e KI-67 / Ameloblastoma recurrence: analysis of clinical-radiographic factors and immunoexpression of hMSH2, hMLH1 and KI-67

Introdução: O ameloblastoma é uma neoplasia odontogênica benigna, que apresenta altas taxas de recorrência pós-operatória. Diversos estudos mostram a relação entre as características clínico-patológicas e as modalidades de tratamento na recorrência do ameloblastoma. Os mecanismos moleculares envolvidos com a etiopatogenia deste tumor são pouco conhecidos, e apesar de alterações no Sistema Mismatch favorecerem o desenvolvimento de diferentes neoplasias humanas, a importância destes no desenvolvimento do ameloblastoma ainda permanece pouco compreendido. Objetivo: Identificar os fatores clínico-patológicos associados à recorrência do ameloblastoma, bem como investigar o papel da imunoexpressão das proteínas hMLH1, hMSH2 e Ki-67 na recidiva desses tumores odontogênicos. Metodologia: Tratou-se de um estudo descritivo, transversal e restrospectivo, com uma amostra constituída por 22 casos de ameloblastomas recidivantes e 22 casos não-recidivantes. A análise imunoistoquímica foi realizada de forma quantitativa, considerando a localização celular (nuclear) das proteínas estudadas. O teste de McNemar foi utilizado para comparar as variáveis entre lesões da 1ª biópsia e recorrentes de AMB. A sobrevida livre de recorrência foi analisada pelo método de Kaplan-Meier e as funções de sobrevida foram comparadas de acordo com as variáveis pelo teste log-rank. Resultados: O gênero mais acometido foi o feminino (n=24; 54,5%), com média de idade de acometimento de 39,1 ± 19,8 anos, sendo 45,5% (n=20) leucodermas. A região posterior de mandíbula foi a mais frequente no grupo recidivante (n=18, 81,8%) e também para os casos que não apresentaram recidivas (n=16, 72,8%). O tempo livre de recorrência foi de 50,0 (34,5 ­ 63,6) meses. Foram fatores significativamente associadas à recorrência dos ameloblastomas: presença de expansão da cortical (p=0,0089), ausência de reconstrução óssea (p=0,018), tratamento conservador (p=0,021), perda de imunoexpressão de hMSH2 (p=0,006) e hMLH1 (p=0,038) e forte imunoexpressão de Ki-67 (p=0,029). Conclusão: Baseado nos achados desta pesquisa, aspecto radiográfico, modalidade do tratamento e imunoexpressão de proteínas do Sistema Mismatch e Ki-67 podem ser utilizados como indicadores para a recorrência em ameloblastomas (AU).

Introduction: Ameloblastoma is a benign odontogenic neoplasm, which has high rates of postoperative recurrence. Several studies show the relationship between clinicopathological characteristics and treatment modalities in ameloblastoma recurrence. The molecular mechanisms involved in the etiopathogenesis of this tumor are little known, and although changes in the Mismatch System favor the development of different human neoplasms, their importance in the development of ameloblastoma still remains poorly understood. Objective: To identify clinical and pathological factors associated with ameloblastoma recurrence, as well as to investigate the role of immunoexpression of hMLH1, hMSH2 and Ki-67 proteins in the recurrence of these odontogenic tumors. Methodology: This was a descriptive, cross-sectional and retrospective study, with a sample consisting of 22 cases of recurrent ameloblastoma and 22 non-recurrent cases. Immunohistochemical analysis was performed quantitatively, considering the cellular (nuclear) location of the studied proteins. McNemar's test was used to compare variables between 1st biopsy and recurrent AMB lesions. Recurrence-free survival was analyzed using the Kaplan-Meier method and survival functions were compared according to variables using the log-rank test. Results: The most affected gender was female (n=24; 54.5%), with a mean age of involvement of 39.1 ± 19.8 years, 45.5% (n=20) being white. The posterior region of the mandible was the most frequent in the relapsed group (n=18, 81.8%) and also for the cases that did not present recurrences (n=16, 72.8%). Recurrence-free time was 50.0 (34.5 ­ 63.6) months. Factors significantly associated with recurrence of AMBs were: presence of cortical expansion (p=0.0089), absence of bone reconstruction (p=0.018), conservative treatment (p=0.021), loss of hMSH2 immunoexpression (p=0.006) and hMLH1 (p=0.038) and strong Ki-67 immunoexpression (p=0.029). Conclusion: Based on the findings of this research, radiographic appearance, treatment modality and immunoexpression of proteins from the Mismatch System and Ki-67 can be used as indicators for recurrence in ameloblastomas (AU).

Expression of mismatch repair proteins in urothelial carcinoma of the urinary bladder

Background: Urothelial carcinoma of the urinary bladder (UCUB) is a frequently diagnosed malignancy. Mismatch repair (MMR), a proofreading machinery of the DNA, prevents tumorigenesis. The role of MMR deficiency in UCUB in eastern Indian population is not known. Methods: Immunohistochemistry panel for MLH1, PMS2, MSH2, and MSH6 (MMR proteins) was performed on the biopsy specimens of UCUB (N=100). Results: MMR deficiency by immunohistochemistry was demonstrated in two cases (2%). One case showed deficiency of MSH2 and MSH6 and the other case showed the deficiency of all four mismatch proteins. Both cases showed high?grade invasive urothelial carcinoma by histomorphology. Conclusion: The prevalence of MMR deficiency by immunohistochemistry is 2% in eastern Indian population. Immunohistochemistry

Potencial de disparidad o Mismatch negativity y P3a en pacientes con esquizofrenia / Mismatch negativity and P3a in patients with Schizophrenia

Resumen Antecedentes: la esquizofrenia es una enfermedad crónica que genera gran discapacidad, para la cual se han reportado biomarcadores potenciales, pero sin suficiente validez clínica. El mismatch negativity (MMN) y el P3a son potenciales relacionados con eventos que han demostrado ser indicadores neurofisiológicos del procesamiento auditivo pre-atencional y potenciales biomarcadores. Objetivo: evaluar el MMN y P3a en pacientes con diagnóstico de esquizofrenia y su relación con variables sociodemográficas y clínicas. Método: estudio cuantitativo transversal de 23 sujetos con esquizofrenia (ESQ) y 22 controles sanos (SN). Las amplitudes promedio y latencias del MMN/P3a para la condición infrecuente en duración y frecuencia fueron obtenidas mediante un paradigma oddball auditivo en un EEG de 32 canales. Resultados: se encontraron diferencias para la condición frecuencia en la amplitud del MMN (p=0.046; CI 95% 0.009; 0.87) y la amplitud del P3a (p=0.042; CI 95% 0.025; 1.24) entre los grupos; la amplitud del MMN fue menor en el grupo ESQ (-0.36 DE 0.51 µV) en comparación con los participantes del grupo de SN (-0.81 DE 0.89 µV), mientras que la amplitud del P3a fue menor en el grupo SN (0.18 DE 0.97 µV) versus el grupo ESQ (0.82 DE 1.05 µV). En relación con las variables sociodemográficas y clínicas, las asociaciones con el P3a fueron moderadas y con el MMN débiles. Conclusiones: la reducción de la amplitud del MMN a la condición frecuencia exhibe mayor utilidad que el P3a como medida de alta estabilidad en pacientes con esquizofrenia, lo que reitera su posible uso como biomarcador.

Abstract Background: schizophrenia is a chronic disease that generates great disability, which currently has potential biomarkers but without sufficient clinical validity. Mismatch negativity (MMN) and P3a are event-related potentials that have been shown to be neurophysiological indicators of pre-attentional auditory processing and potential biomarkers. Objective: to evaluate MMN and P3a in patients with a diagnosis of schizophrenia and their relationship with sociodemographic and clinical variables. Method: a quantitative cross-sectional study of 23 subjects with schizophrenia and 22 healthy controls was performed. The average amplitudes and latencies of the MMN/P3a for the condition infrequent in duration and infrequent in frequency were obtained using an auditory oddball paradigm on a 32-channel EEG. Results: differences were found for the frequency condition in the amplitude of the MMN (p=0.046; 95% CI 0.009; 0.87) and the amplitude of the P3a (p=0.042; 95% CI 0.025; 1.24) between the groups; MMN amplitude was lower in schizophrenia (-0.36 SD 0.51 µV) compared to healthy controls (-0.81 SD 0.89 µV), while P3a amplitude was lower in healthy controls (0.18 SD 0.97 µV) versus the group with schizophrenia (0.82 SD 1.05 µV). In regard to sociodemographic and clinical variables, the associations with P3a were moderate, and showed weak MMN. Conclusions: MMN amplitude reduction to the frequency condition exhibits greater utility than P3a as a measure of high stability in schizophrenia, restating its potential use as a biomarker.

Evaluation of microsatellite instability in routine examinations of surgical samples

Context: Approximately 20%–30% of colon cancer cases have a hereditary basis. The genetic defect may involve mismatch repair (MMR) genes, which results in microsatellite instability (MSI). MMR-deficient colorectal cancer may occur due to germline mutation (Lynch syndrome) or be a sporadic one. A tumor's histological features, supported by a panel of immunohistochemistry stains, enables pathologists to assess the MMR status, which in turn has beneficial effects on clinical management. Aims: We aimed to show the relations between histopathological features identified during routine examinations and MMR genes' mutations. Methods and Material: We reviewed retrospectively the material of the Department of Pathology fulfilling the revised Bethesda Guidelines. Statistical Analysis Used: We used Chi-square test, Spearman test, and epidemiological analysis. Results: For the PMS2 gene, the positive predictive value (PPV) indicates that 91% of cases neither present any histological lesions nor have genetic abnormalities. The negative predictive value (NPV) indicates that only 50% of cases have both histological and genetic changes. For the MSH6 gene, the PPV indicates that 85% of tumors without specific histological features do not have genetic abnormalities. Conclusions: We advise universal staining for MLH1, MSH2, MSH6, and PMS2 in every newly diagnosed colon cancer, but due to costly analyses we suggest a protocol for the selection of cases for MMR examinations.

Does mismatch negativity have utility for NMDA receptor drug development in depression?

Rapid antidepressant effects associated with ketamine have shifted the landscape for the development of therapeutics to treat major depressive disorder (MDD) from a monoaminergic to glutamatergic model. Treatment with ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, may be effective, but has many non-glutamatergic targets, and clinical and logistical problems are potential challenges. These factors underscore the importance of manipulations of binding mechanics to produce antidepressant effects without concomitant clinical side effects. This will require identification of efficient biomarkers to monitor target engagement. The mismatch negativity (MMN) is a widely used electrophysiological signature linked to the activity of NMDA receptors (NMDAR) in humans and animals and validated in pre-clinical and clinical studies of ketamine. In this review, we explore the flexibility of the MMN and its capabilities for reliable use in drug development for NMDAR antagonists in MDD. We supplement this with findings from our own research with three distinct NMDAR antagonists. The research described illustrates that there are important distinctions between the mechanisms of NMDAR antagonism, which are further crystallized when considering the paradigm used to study the MMN. We conclude that the lack of standardized methodology currently prevents MMN from being ready for common use in drug discovery. Clinical trial registration: This manuscript describes data collected from the following National Institutes of Health (NIH) and Veterans Affairs (VA) studies: AV-101, NCT03583554; lanicemine, NCT03166501; ketamine, NCT02556606.

Pre-attentive processing in autism spectrum disorder / 中华行为医学与脑科学杂志

Autism spectrum disorder (ASD) is a neurodevelopmental disorder.Its typical symptoms include social disorder, stereotyped behavior and restrictive interest.In addition, sensory abnormality is also a common symptom of ASD individuals.Pre-attentive processing is an automatic cognitive process that takes place before attention and is independent of consciousness, which reflects the ability to automatically detect changes in the environment of brain.Many researches show that the sensory abnormality and social ability disorder in ASD patients may be related to the defects in the pre-attentive processing stage.Mismatch negativity (MMN) is the most commonly used indicator of pre-attentive processing.ASD individuals show abnormal MMN in response to both social and non-social stimulus.Among them, the pre-attentive processing defect of non-social stimuli in ASD individuals is manifested as the amplitude or latency of MMN induced by single tones, voice or visual stimuli, which is different from that of normal people.The pre-attentive processing defect of social stimuli in ASD individuals is manifested as the amplitude or latency of MMN induced by emotional voice and emotional face, which is different from that of normal people.This result not only helps to find the physiological mechanism of sensory and social disorders in ASD individuals, but also provides theoretical support for MMN as an auxiliary diagnostic index of ASD.Future research on the pre-attentive processing of ASD individuals should pay more attention to enriching the research paradigms of MMN and adopting more kinds of social stimuli.At the same time, the influence of ASD genetic factors on MMN can also be one of the concerns of future research.

Research and Prospect of Visual Event-Related Potential in Traumatic Brain Injury and Visual Function Evaluation / 法医学杂志

Visual event-related potential (ERP) is an electrophysiological technique that objectively reflects the cognitive processing of stimulus from the perspective of detecting and recording neural electrophysiology responses using different paradigms of visual stimuli. Its endogenous components are closely related to advanced psychological activities. This article introduces the characteristics of main endogenous components including visual mismatch negativity (vMMN), N200 and P300, reviews the research progress of visual ERP in the sequelae of brain injury and objective evaluation of visual function, and prospects the application prospect of visual ERP in the field of forensic medicine.

Fisiología respiratoria: relación ventilación/perfusión / Respiratory fisiology: ventilation/perfusion relationship

Las alteraciones de la relación entre la ventilación y el flujo sanguíneo (V/Q) en diversas regiones del pulmón alteran el aporte de oxígeno (O2) y remoción del dióxido de carbono (CO2) al organismo. Fisiológicamente existen diferencias regionales en la relación V/Q. Determinadas patologías pueden alterar esta relación, produciendo tres escenarios distintos: Cortocircuito (Shunt), Alteración V/Q y aumento del espacio muerto. Para evaluar estos escenarios y realizar una aproximación diagnostica son de utilidad el estudio de los gases arteriales y venosos, la diferencia alveolo arterial y la respuesta al suministrar O2

Alterations in the ventilation perfusion relationship (V/Q) in various lung regions alter the supply of oxygen (O2) and the removal of carbon dioxide (CO2) in the body. Physiologically, there are regional differences in the V/Q ratio. Certain pathologies can alter this relationship, producing three different scenarios: Shunt, V/Q mismach and dead space increased. To evaluate these scenarios and carry out a diagnostic approach, it is useful to study arterial and venous gasometry, the alveolar arterial difference and the response to oxygen supplying.

Nicardipine versus nitroglycerin for hypertensive acute heart failure syndrome: a single-center observational study / Journal of Rural Medicine

Objective: Nitroglycerin is a first-line treatment for hypertensive acute heart failure syndrome (AHFS). However, nicardipine is frequently used to treat hypertensive emergencies, including AHFS. In this study, we compared the effectiveness of nicardipine and nitroglycerin in patients with hypertensive AHFS.Patients and Methods: This single-center, retrospective, observational study was conducted at the intensive care unit of a Japanese hospital. Patients diagnosed with AHFS and systolic blood pressure 140 mmHg on arrival between April 2013 and March 2021 were included. The outcomes were the time to optimal blood pressure control, duration of continuous infusion of antihypertensive agents, duration of positive pressure ventilation, need for additional antihypertensive agents, length of hospital stay, and body weight changes. Outcomes were compared between the nicardipine and nitroglycerin groups. We also compared these outcomes between the groups after excluding patients who received renal replacement therapy.Results: Fifty-eight patients were enrolled (26 and 32 patients were treated with nitroglycerin and nicardipine, respectively). The nicardipine group had a shorter time to optimal blood pressure control (2.0 [interquartile range, 2.0–8.5] h vs. 1.0 [0.5–2.0] h), shorter duration of continuous anti-hypertensive agent infusion (3.0 [2.0–5.0] days vs. 2.0 [1.0–2.0] days), less frequent need for additional anti-hypertensive agents (1 patients [3.1%] vs. 11 patients [42.3%]), and shorter length of hospital stay (17.5 [10.0–33.0] days vs. 9.0 [5.0–15.0] days) than the nitroglycerin group. The duration of positive pressure ventilation and body weight changes were similar between the groups. The outcomes were similar after excluding patients who received renal replacement therapy.Conclusion: Nicardipine may be more effective than nitroglycerin for treating hypertensive AHFS.

Analysis of HLA-Ⅰ antibody specificity and estimation of antigen immunogenicity: 96 patients recieved genotype-matched platelet transfusions / 中国输血杂志

【Objective】 To analyze the specificity of HLA class-Ⅰ antibody in the patients received HLA-matched platelet transfusions and estimate the relative immunogenicity of HLA-Ⅰ antigens. 【Methods】 The samples from 96 patients who suffered from platelet transfusion refractorines(PTR) and applied for transfusion with genotype-matched platelet were collected. The specificity of HLA I antibody was detected by Luminex technique, and the antibody expression level was analyzed according to MFI. The mismatch rate of HLA antigen and relative immunogenicity of the population were estimated according to the allele frequency distribution of HLA-A and B loci as well as the yielding frequency of antibody. 【Results】 HLA-Ⅰ antibodies were detected in all 96 patients, with varied species of antibodies. The average positive yielding rates of antibodies corresponding to HLA-A, -B and -C magnetic bead coated antigens (97 in total) were 0.38, 0.47 and 0.28, respectively. Among the HLA-A and -B loci in the Zhejiang population, HLA-A2, A11, A24 and HLA-B60, B46, B58 were the antigens with higher frequency, and their relative immunogenicity was 0.403, 0.283, 0.342, and 0.100, 0.067, 0.178, respectively. 【Conclusion】 The specificity of HLA-Ⅰ antibodies in PTR patients is different, which confirms that the relative immunogenicity differs by HLA-A and -B antigens.

Neoadjuvant immunotherapy in microsatellite stability or mismatch repair proficient colorectal cancer / 中华胃肠外科杂志

Immunotherapy has become an important treatment option for microsatellite instability-high (MSI-H) and mismatch repair deficient (dMMR) colorectal cancer. From late-line to first-line treatment, and even in neoadjuvant setting for early stage colorectal cancer, promising efficacy was observed with immunotherapy. In microsatellite stability (MSS) or mismatch repair proficient (pMMR) colorectal cancer, the researches of neoadjuvant immunotherapy have been conducted constantly. This paper focuses on the recent researches and progress of neoadjuvant immunotherapy for MSS or pMMR colorectal cancer. Neoadjuvant immunotherapy alone led to a good pathological response in a subset of patients. Studies of induction or consolidation immunotherapy before or after neoadjuvant chemoradiotherapy or concurrent immunotherapy during radiotherapy showed higher pathological complete remission (pCR) rates as compared to standard chemoradiotherapy. Studies on sequential dual immunotherapy after radiochemotherapy and targeted therapy combined with neoadjuvant immunotherapy are ongoing. At present, most of these are pilot studies with small sample size. More researches and long-term follow-up are needed to prove the efficacy of neoadjuvant immunotherapy in MSS or pMMR colorectal cancer.

Short-term outcome of programmed cell death protein1 (PD-1) antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer with high risk factors / 中华胃肠外科杂志

Objective: Total neoadjuvant chemoradiotherapy is one of the standard treatments for locally advanced rectal cancer. This study aims to investigate the safety and feasibility of programmed cell death protein 1 (PD-1) antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer with high-risk factors. Methods: A descriptive cohort study was conducted. Clinicopathological data of 24 patients with locally advanced middle-low rectal cancer with high-risk factors receiving PD-1 antibody combined with neoadjuvant chemoradiotherapy in Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital between January 2019 and April 2021 were retrospectively analyzed. Inclusion criteria: (1) rectal adenocarcinoma confirmed by pathology; patient age of ≥ 18 years and ≤ 80 years; (2) the distance from low margin of tumor to anal verge ≤ 10 cm under sigmoidoscopy; (3) ECOG performance status score 0-1; (4) clinical stage T3c, T3d, T4a or T4b, or extramural venous invasion (EMVI) (+) or mrN2 (+) or mesorectal fasciae (MRF) (+) based on MRI; (5) no evidence of distant metastases; (6) no prior pelvic radiation therapy, no prior chemotherapy or surgery for rectal cancer; (7) no systemic infection requiring antibiotic treatment and no immune system disease. Exclusion criteria: (1) anticipated unresectable tumor after neoadjuvant treatment; (2) patients with a history of a prior malignancy within the past 5 years, or with a history of any arterial thrombotic event within the past 6 months; (3) patients received other types of antitumor or experimental therapy; (4) women who were pregnant or breast-feeding; (5) patients with any other concurrent medical or psychiatric condition or disease; (6) patients received immunotherapy (PD-1 antibody). The neoadjuvant therapy consisted of three stages: PD-1 antibody (sintilimab 200 mg, IV, Q3W) combined with CapeOx regimen for three cycles; long-course intensity modulated radiation therapy (IMRT) with gross tumor volume (GTV) 50.6 Gy/CTV 41.8 Gy/22f; CapeOx regimen for two cycles after radiotherapy. After oncological evaluation following the end of the third stage of treatment, surgery or watch and wait would be carried out. Surgical safety, histopathological changes and short-term oncological outcome were analyzed. Results: There were 15 males and 9 females with a median age of 65 (47-78) years. Median distance from the lower margin of the tumor to the anal verge was 4 (3-7) cm. The median maximal diameter of the tumor was 5.1 (2.1-7.5) cm. Twenty patients were cT3, 4 were cT4, 8 were cN1, 5 were cN2a, 11 were cN2b. Ten cases were MRF (+) and 10 were EMVI (+). All the patients were mismatch repair proficient (pMMR). During the neoadjuvant treatment period, 6 patients (25.0%) developed grade 1-2 treatment-related adverse events, including 3 immune-related adverse events. As of April 30, 2021, 20 patients (83.3%, 20/24) had received surgical resection, including 19 R0 resections and 16 sphincter-preservation operations. Morbidity of postoperative complication was 25.0% (5/20), including 2 cases of Clavien-Dindo grade II (1 of anastomotic bleeding and 1 of pseudomembranous enteritis), 3 cases of grade I anastomotic stenosis. Pathological complete response (pCR) rate was 30.0% (6/20) and major pathological response rate was 20.0% (4/20). None of Ras/Raf mutants had pCR or cCR (0/5), while 6 of 17 Ras/Raf wild-type patients had pCR and 3 had cCR, which was significantly higher than that of Ras/Raf mutants (P<0.01). Nine of 16 patients with Ras/Raf wild-type and differentiated adenocarcinoma had pCR or cCR. Among other 4 patients without surgery, 3 patients preferred watch and wait strategy because their tumors were assessed as clinical complete response (cCR), while another one patient refused surgery as the tumor remained stable. After a median follow-up of 11 (6-24) months, only 1 patient with signet ring cell carcinoma had recurrence. Conclusions: PD-1 antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced rectal cancer has quite good safety and histopathological regression results. Combination of histology and genetic testing is helpful to screen potential beneficiaries.