Search

PDF file - 284KB, CONSORT study diagram.

PDF file - 61KB

PDF file - 2804KB, Association of antibody response with patient's survival.

Purpose: Racotumomab-alum is an anti-idiotype vaccine targeting the NeuGcGM3 tumor-associated ganglioside. This clinical trial was conducted to provide a preliminary estimate of efficacy and safety of racotumomab as switch maintenance for patients with advanced non–small cell lung cancer (NSCLC).Experimental design: Patients with stage IIIb/IV NSCLC who have at least stable disease after first-line chemotherapy were randomized 1:1 to racotumomab-alum (5 immunizations every 2 weeks and re-immunizations every 4 weeks) or placebo. Treatment was administered beyond progressive disease, until severe performance status worsening or toxicity. At progression, only five patients per group received further anticancer therapy. The primary endpoint was overall survival (OS).Results: One-hundred and seventy-six patients were randomized to racotumomab-alum (n = 87) and placebo (n = 89). Median OS was 8.23 and 6.80 months, respectively [HR, 0.63; 95% confidence interval (CI), 0.46–0.87; P = 0.004]. Median progression-free survival (PFS) in vaccinated patients was 5.33 versus 3.90 months for placebo (HR, 0.73; 95% CI 0.53–0.99; P = 0.039). The most common adverse events in the racotumomab-alum arm were burning and pain at the injection site, bone pain, and asthenia. A high antibody response of IgM and IgG isotype against the NeuGcGM3 ganglioside was obtained. Hyperimmune sera were able to specifically recognize and kill the NeuGcGM3-expressing L1210 cell line. Patients who developed anti-NeuGcGM3 antibodies capable to bind and kill ≥30% L1210 cells showed longer median survival times.Conclusions: Switch maintenance with racotumomab-alum is an effective and a well-tolerated treatment option for patients with advanced NSCLC. Clin Cancer Res; 20(14); 3660–71. ©2014 AACR.

PDF file - 47KB, Adverse event severity.

PDF file - 132KB, Number of doses received, maximal titer and isotype analysis against Racotumomab-mAb and NeuGcGM3, percentages of binding and cytotoxicity against L1210 cells, and survival times in vaccinated NSCLC patients.

PDF file - 66KB, Summary of adverse events.

PDF file - 137KB, Association of functional capacity of elicited anti-NeuGcGM3 antibodies with patient's survival.

PDF file - 144KB, Overall survival HRs (racotumomab over placebo) in subgroups according to baseline characteristics.

Introducción: La conexión venosa pulmonar anómala total (CVPAT) es un defecto relativamente poco frecuente, con una prevalencia de 0.8 por cada 10 000 nacimientos vivos, mientras que la forma parcial, tiene una mayor prevalencia, que oscila entre un 0.4 y 0.7% de la población. En Panamá, la CVPAT representa un 9% de los nacimientos con defectos cardíacos. Este estudio tuvo como objetivo evaluar las características por tomografía computada de los niños con este diagnóstico que fueron atendidos entre los años 2010 y 2020 en el Hospital del Niño Dr. José Renán Esquivel. Método: Se realizó un estudio descriptivo, retrospectivo, de corte transversal en la población sometida a tomografía computarizada por cardiopatía congénita en el Hospital del Niño Dr. José Renán Esquivel de la Ciudad de Panamá, en el período comprendido entre enero de 2010 y diciembre de 2020. Se realizaron 615 tomografías computarizadas por malformación cardíaca. De estas, 51 tenían diagnóstico de conexión venosa pulmonar anómala (CVPA) Resultados: Se encontró un predominio de esta patología en el sexo masculino (57.5%). Un 76.2% de los pacientes cursaban con otra malformación cardíaca asociada, siendo la comunicación interauricular (CIA) la más frecuente (54.5%). Los tipos más frecuentes fueron el supracardíaco (50.0%) y el infracardíaco (28.5%). Conclusión: La tomografía computada con contraste endovenoso es un método útil, que permite evaluar con detalle la anatomía cardíaca y de los grandes vasos en pacientes con malformaciones cardíacas y que además brinda información valiosa sobre otras patologías asociadas.

Purpose Informal caregivers play an important supportive care role for patients with cancer. This may be especially true for pancreatic cancer which is often diagnosed late, has a poor prognosis and is associated with a significant symptom burden. We systematically reviewed the evidence on caregiver burden, unmet needs and quality-of-life of informal caregivers to patients with pancreatic cancer. Method PubMed, Medline, CINAHL and Embase databases were systematically searched on 31 August 2021. Qualitative and quantitative data on informal caregivers’ experiences were extracted and coded into themes of burden, unmet needs or quality-of-life with narrative synthesis of the data undertaken. Results Nine studies (five qualitative, four quantitative), including 6023 informal caregivers, were included in the review. We categorised data into three key themes: caregiver burden, unmet needs and quality-of-life. Data on caregiver burden was organised into a single subtheme relating to symptom management as a source of burden. Data on unmet needs was organised into three subthemes need for: better clinical communication; support and briefings for caregivers; and help with navigating the health care system. Data on quality-of-life indicate large proportions of informal caregivers experience clinical levels of anxiety (33%) or depression (12%-32%). All five qualitative studies were graded as good quality; three quantitative studies were poor quality, and one was fair quality. Conclusion High-quality pancreatic cancer care should consider the impacts of informal caregiving. Prospective longitudinal studies examining multiple dimensions of caregiver burden, needs, and quality-of-life would be valuable at informing supportive care cancer delivery to pancreatic cancer informal caregivers.

Background Preoperative Obstructive Sleep Apnoea (OSA) screening, followed by sleep studies as indicated, is commonly performed for patients undergoing bariatric surgery in our hospital but not for patients with similar weight undergoing other surgeries such as laparoscopic cholecystectomy. The purpose of this audit was to understand if laparoscopic cholecystectomy can be performed safely in patients with a Body Mass Index (BMI) ≥35 kg/m2 without such screening. Methods Patients with a BMI ≥ 35 kg/m2 undergoing elective laparoscopic cholecystectomy between 2nd May 2014 and 4th April 2022 were included. Patients with known OSA were excluded and no patients were referred for sleep studies. Data on patient demographics, co-morbidities, and any intraoperative or postoperative surgical complications were extracted and analysed. Univariate associations between different preoperative and operative variables and 30-day morbidity were studied using the Fisher's exact test. Results A total of 434 patients were included in the audit (64 male, 370 female). The mean age was 49 +/- 15 years. The mean weight and BMI were 110 +/- 20 kg (range 70–79kg) and 37 +/- 6 kg/m2 respectively. The mean operating time was 70 +/- 31 minutes (median=62). Approximately, 92% (398/434) had a day case procedure. The readmission rate at 30-day was 1% (5/434). There were no intraoperative complications. 17 patients had post-operative complications including deep vein thrombosis (n=2), leak in transverse colon secondary to cholecysto-colic fistula (n=1), wound infection (n=9), bile leak and post-op ERCP (n=3), common bile duct stone requiring ERCP (n=1) and pneumonia (n=1). No patients required ITU or HDU admission for further organ support. The 30-day mortality rate was 0% (0/434) while the 30-day morbidity rate was 3.9% (17/434). ASA grade, previous abdominal surgery, hypertension, diabetes, dyslipidemia, smoking history, chronic obstructive pulmonary disease, ischemic heart disease, fatty liver disease, preoperative liver reducing diet, number of ports, and conversion to laparotomy were not associated with increased 30-day morbidity rate (p Conclusions This audit demonstrated that laparoscopic cholecystectomy can be performed safely without the need for preoperative sleep studies in patients with BMI ≥35 kg/m2.

Background The present systematic review aimed to compare survival outcomes of invasive intraductal papillary mucinous neoplasms (IIPMNs) treated with adjuvant chemotherapy versus surgery alone and to identify pathologic features that may predict survival benefit from adjuvant chemotherapy. Method A systematic search of MEDLINE, PubMed, Scopus, and EMBASE was performed using the PRISMA framework. Studies comparing adjuvant chemotherapy and surgery alone for patients with IIPMNs were included. Primary endpoint was overall survival (OS). A narrative synthesis was performed to identify pathologic features that predicted survival benefits from adjuvant chemotherapy. Results Eleven studies and 3393 patients with IIPMNs were included in the meta-analysis. Adjuvant chemotherapy significantly reduced the risk of death in the overall cohort (HR 0.57, 95% CI 0.38–0.87, p = 0.009) and node-positive patients (HR 0.29, 95% CI 0.13–0.64, p = 0.002). Weighted median survival difference between adjuvant chemotherapy and surgery alone in node-positive patients was 11.6 months (95% CI 3.83–19.38, p = 0.003) favouring chemotherapy. Adjuvant chemotherapy had no impact on OS in node-negative patients (HR 0.53, 95% CI 0.20–1.43, p = 0.209). High heterogeneity (I2 > 75%) was observed in pooled estimates of hazard ratios. Improved OS following adjuvant chemotherapy was reported for patients with stage III/IV disease, tumour size > 2 cm, node-positive status, grade 3 tumour differentiation, positive margin status, tubular carcinoma subtype, and presence of perineural or lymphovascular invasion. Conclusion Adjuvant chemotherapy was associated with improved OS in node-positive IIPMNs. However, the findings were limited by marked heterogeneity. Future large multicentre prospective studies are needed to confirm these findings and explore additional predictors of improved OS to guide patient selection for adjuvant chemotherapy.

This article aims to generate a better understanding of Hong Kong teachers’ perception of national education as implemented in the Hong Kong Special Administrative Region (hereafter referred to as Hong Kong SAR) and the interrelationship between their perception and the methods they adopt to teach the topic. We outline the Hong Kong context relevant to our research and review the relevant literature to consider typologies and teaching methods about and for national education. Questionnaire data focused on the seven typologies of nationalism and the three teaching methods of national education identified in the literature review. A total of 601 questionnaires were returned from 198 schools. The typologies of cultural nationalism, civic and peripheral nationalism, authoritarian nationalism, unification nationalism and cosmopolitan nationalism, and the teaching methods of group discussion and an affective approach characterize the views of Hong Kong secondary school teachers about national education. We suggest that teachers’ diverse views about nationalism and their varied use of teaching methods to achieve their goals suggest the powerful influence of current initiatives from the Chinese mainland and the need to reflect on established academic literature that proposes the decolonization of the curriculum and interactive and critical teaching methods.

La malformación congénita de las vías aéreas respiratorias (MCVAP), anteriormente conocida como malformación adenomatoidea quística (MAQ) es una malformación congénita poco frecuente, que forma parte de las lesiones quísticas pulmonares. Puede ser diagnosticada de manera prenatal o bien ser de presentación tardía como hallazgo casual o manifestarse por neumonías recurrentes. Se clasifica en cinco tipos en relación a condiciones anatomopatológicas y al tamaño de las lesiones. Se presentan dos casos de pacientes con malformación congénita de las vías aéreas respiratorias tipo 1 y una revisión de la literatura. En uno de los casos se realizó el diagnóstico prenatal por ecografía durante el control del embarazo y, en el otro, el diagnóstico fue tardío como hallazgo casual.

Literature describing recovery of left ventricular (LV) function post sacubitril/valsartan treatment and the optimal management of heart failure (HF) patients receiving sacubitril/valsartan remain sparse.We recruited 437 consecutive chronic HF patients with baseline left ventricular ejection fraction (LVEF) less than 40%, who were treated with sacubitril/valsartan. All patients underwent routine echocardiographic measurement.During treatment period, recovery of LVEF to 50% or greater was observed in 77 (17.6%) patients. After multivariate analysis, recovery of LV dysfunction was associated with non-ischemic etiology of HF, smaller baseline LV end-diastolic diameter (LVEDD), and higher initial dosage of sacubitril/valsartan. Compared to those without recovery of LV dysfunction, death from cardiovascular causes or first unplanned hospitalization for HF (CVD/HFH) were significantly lower in patients with LVEF recovery [11.7% vs. 24.4%, hazard ratio (HR) 0.42, p = 0.014]. Among patients with recovery of LVEF, 51 patients continued to receive the same dosage of sacubitril/valsartan had higher LVEF and were less likely to have deterioration of LVEF than the other 26 patients who received either tapering dose of sacubitril/valsartan or switching from sacubitril/valsartan to renin-angiotensin-system blockers (LVEF 56.4 ± 5.3% vs. 45.0 ± 12.8%, p 0.001; ΔLVEF 1.2 ± 5.1% vs. -9.3 ± 12.0%, p 0.001). CVD/HFH occurred more frequently in the taper group than the maintenance group (23.1% vs. 5.9%, HR 0.22, p = 0.035).Non-ischemic etiology of HF, smaller baseline LVEDD, and higher initial dosage of sacubitril/valsartan could predict better recovery of LV function. Among patients with functional recovery, tapering sacubitril/valsartan dose was associated with deterioration of recovered heart function and had less favorable prognosis during follow-up.

Acute pancreatitis (AP) is an inflammatory disease, and NLRP3 inflammasome activation is involved in the pathogenesis of AP. Previous research showed that inhibition of NLRP3 inflammasome may exert protective effects on animal models of AP and reduces disease severity. The aim of this systematic review and meta-analysis is to evaluate the effects of drug treatment of NLRP3 inflammasome on the outcomes of experimental AP. PubMed, Embase, Medline, and Web of Science databases were searched for relevant articles without language restrictions. The main outcomes for this study included local pancreatic injury, the incidence of systemic inflammatory responses, and the incidence of organ failure. Twenty-eight animal studies including 556 animals with AP were included in the meta-analysis. Compared with controls, inhibition of NLRP3 inflammasome significantly reduced the pancreatic histopathological scores, serum amylase, and lipase levels. In addition, inhibition of NLRP3 inflammasome reduced the levels of circulating inflammatory cytokines, as well as mitigating severity of AP-associated acute lung injury and acute intestinal injury. To conclude, inhibition of NLRP3 inflammasome has protective effects on AP by mitigating organ injury and systemic inflammation in animal studies, indicating that NLRP3 inflammasome holds promise as a target for specific AP therapy.

Canine atopic dermatitis (AD) is a complex multifactorial disease characterised by an exaggerated immunological response. Little is known about the role that cutaneous and circulating chemokines play in disease severity.To evaluate the messenger (m)RNA and protein levels of selected chemokines in skin and serum of healthy and atopic dogs, and in the atopic group to determine whether there is a correlation with disease severity.Skin biopsies and blood samples were taken from 12 privately owned atopic [lesional (AD-L) and nonlesional (AD-NL) skin] and 12 privately owned healthy dogs. Circulating exosomes were extracted from the serum. Cutaneous and exosomal mRNA levels of CCL17, CCL22, CCL27 and CCL28 were quantified using quantitative real-time PCR. Protein levels were evaluated using canine-specific ELISA kits. The severity and extent of the clinical signs also were assessed in the atopic dogs using Canine Atopic Dermatitis Extent and Severity Index, 4The expression of CCL28 exosomes in skin was greater in AD-L when compared to healthy (P = 0.019) and AD-NL (P = 0.002) samples. However, serum expression was lower in dogs with AD compared to healthy dogs (P = 0.03). A higher expression of CCL17 and CCL22 was seen in AD-L when compared to healthy skin (P = 0.018 and P = 0.019, respectively). There also was a positive correlation between clinical scores and CCL22 (AD-NL; r = 0.6, P = 0.05) and between the pruritus score and CCL22 (AD-L; r = 0.6, P = 0.05). Differences in CCL27 concentrations were not observed.This study suggests that CCL17, CCL22 and CCL28 may play a role in the cutaneous inflammatory response in atopic dogs. They may be considered as markers of disease severity, although further studies are needed to validate these findings.La dermatite atopique canine (DA) est une maladie multifactorielle complexe caractérisée par une réponse immunologique exagérée. On sait peu de choses sur le rôle des chimiokines cutanées et circulantes dans la gravité de la maladie.Évaluer les niveaux d'ARNm (messager) et de protéines de chimiokines sélectionnées dans la peau et le sérum de chiens sains et atopiques, et dans le groupe atopique afin de déterminer s'il existe une corrélation avec la gravité de la maladie. MATÉRIELS ET MÉTHODES: Des biopsies cutanées et des échantillons de sang ont été prélevés sur 12 chiens atopiques [peau lésionnelle (AD-L) et non lésionnelle (AD-NL)] et 12 chiens sains de propriétaires privés. Les exosomes circulants ont été extraits du sérum. Les niveaux d'ARNm cutanés et exosomaux de CCL17, CCL22, CCL27 et CCL28 ont été quantifiés à l'aide d'une PCR quantitative en temps réel. Les niveaux de protéines ont été évalués à l'aide de kits ELISA spécifiques canins. La gravité et l'étendue des signes cliniques ont également été évaluées chez les chiens atopiques à l'aide de l'indice d'étendue et de gravité de la dermatite atopique canine, 4e itération (CADESI-04) et d'une échelle visuelle analogue de prurit validée (pVAS). RÉSULTATS: L'expression des exosomes CCL28 dans la peau était supérieure dans AD-L par rapport aux échantillons sains (P = 0,019) et AD-NL (P = 0,002). Cependant, l'expression sérique était plus faible chez les chiens atteints de MA par rapport aux chiens sains (P = 0,03). Une expression plus élevée de CCL17 et CCL22 a été observée dans AD-L par rapport à la peau saine (respectivement P = 0,018 et P = 0,019). Il y avait également une corrélation positive entre les scores cliniques et CCL22 (AD-NL ; r = 0,6, P = 0,05) et entre le score de prurit et CCL22 (AD-L ; r = 0,6, P = 0,05). Aucune différence dans les concentrations de CCL27 n'a été observée.Cette étude suggère que CCL17, CCL22 et CCL28 pourraient jouer un rôle dans la réponse inflammatoire cutanée chez les chiens atopiques. Ils peuvent être considérés comme des marqueurs de la gravité de la maladie, bien que d'autres études soient nécessaires pour valider ces résultats.INTRODUCCIÓN: La dermatitis atópica canina (AA) es una enfermedad multifactorial compleja caracterizada por una respuesta inmunológica exagerada. Poco se sabe sobre el papel que juegan las quimioquinas cutáneas y circulantes en la severidad de la enfermedad. OBJETIVO: evaluar los niveles de proteína y RNA mensajero (mRNA) de quimioquinas seleccionadas en la piel y el suero de perros sanos y atópicos, y en el grupo atópico para determinar si existe una correlación con la gravedad de la enfermedad. MATERIALES Y MÉTODOS: se tomaron biopsias de piel y muestras de sangre de 12 perros atópicos de propietarios particulares [piel lesionada (AD-L) y no lesionada (AD-NL)] y 12 perros sanos también de particulares. Los exosomas circulantes se extrajeron del suero. Los niveles cutáneos y exosómicos de RNAm de CCL17, CCL22, CCL27 y CCL28 se cuantificaron mediante PCR cuantitativa en tiempo real. Los niveles de proteína se evaluaron utilizando kits ELISA específicos para caninos. La gravedad y el alcance de los signos clínicos también se evaluaron en los perros atópicos utilizando el índice de extensión y gravedad de la dermatitis atópica canina, cuarta revisión (CADESI-04) y una escala análoga visual de prurito validada (pVAS). RESULTADOS: la expresión de exosomas de CCL28 en la piel fue mayor en AD-L en comparación con muestras sanas (P = 0,019) y AD-NL (P = 0,002). Sin embargo, la expresión sérica fue menor en perros con DA en comparación con perros sanos (P = 0,03). Se observó una mayor expresión de CCL17 y CCL22 en AD-L en comparación con la piel sana (P = 0,018 y P = 0,019, respectivamente). También hubo una correlación positiva entre las puntuaciones clínicas y CCL22 (AD-NL; r = 0,6, P = 0,05) y entre la puntuación de prurito y CCL22 (AD-L; r = 0,6, P = 0,05). No se observaron diferencias en las concentraciones de CCL27. CONCLUSIONES E IMPORTANCIA CLÍNICA: este estudio sugiere que CCL17, CCL22 y CCL28 pueden desempeñar un papel en la respuesta inflamatoria cutánea en perros atópicos. Pueden considerarse como marcadores de la gravedad de la enfermedad, aunque se necesitan más estudios para validar estos hallazgos.Die atopische Dermatitis des Hundes (AD) ist eine komplexe multifaktorielle Erkrankung, die durch eine übertriebene Immunantwort charakterisiert wird. Es ist wenig bekannt über die Rolle, die kutane und zirkulierende Chemokine beim Schweregrad der Erkrankung spielen. ZIEL: Eine Evaluierung der Messenger (m) RNA und der Proteinwerte von selektierten Chemokinen in der Haut und im Serum von gesunden und atopischen Hunden, sowie eine Untersuchung, ob in der atopischen Gruppe eine Korrelation mit dem Schweregrad der Erkrankung besteht.Hautbiopsien und Blutproben wurden von 12 privaten atopischen Hunden [(Läsionale (AD-L) und nichtläsionale (AD-NL) Haut] und 12 privaten gesunden Hunden genommen. Es wurden zirkulierende Exosome aus dem Serum extrahiert. Kutane und exosomale mRNA Werte von CCL17, CCL22, CCL27 und CCL28 wurden mittels quantitativer real-time PCR quantifiziert. Proteinwerte wurden mittels Hunde-spezifischer ELISA Kits evaluiert. Der Schweregrad und das Ausmaß der klinischen Zeichen wurden bei den atopischen Hunden ebenfalls mittels Canine Atopic Dermatitis Extent and Severity Index, 4te Auflage (CADESI-04) und einer validierten Juckreiz Visual Analog Scale (pVAS) beurteilt.Die Exprimierung von CCL28 Exosomen in der Haut war bei AD-L größer im Vergleich zu gesunden (P = 0,019) und AD-NL (P = 0,002) Proben. Nichtsdestotrotz war die Exprimierung im Serum bei Hunden mit AD im Vergleich zu gesunden Hunden (P = 0,03) niedriger. Eine höhere Exprimierung von CCL17 und CCL22 wurde bei AD-L im Vergleich zu gesunder Haut (P = 0,018 bzw P = 0,019) gefunden. Es bestand auch eine positive Korrelation zwischen klinischen Werten und CCL22 (AD-NL; r = 0,6; P = 0,05) und zwischen den Juckreizwerten und CCL22 (AD-L; r = 0,6; P = 0,05). Es wurden keine Unterschiede bei den CCL27 Konzentrationen beobachtet.Diese Studie liefert Hinweise, dass CCL17, CCL22 und CCL28 eine Rolle bei der Entzündungsantwort der Haut atopischer Hunde spielen könnte. Sie könnten als Marker für den Schweregrad der Erkrankung betrachtet werden, obwohl noch weitere Studien nötig sind, um diese Ergebnisse zu validieren.要約 背景: 犬アトピー性皮膚炎(AD)は、免疫反応の亢進を特徴とする多因子複合疾患である。皮膚および血中ケモカインが疾患の重症化に果たす役割については、ほとんど知られていない。 目的: 本研究の目的は、健常犬とアトピー犬の皮膚および血清中の選択したケモカインのメッセンジャー(m)RNAおよびタンパク質レベルを評価し、アトピーグループにおいては、疾患の重症度と相関があるかどうかを判断することであった。 材料と方法: アトピー[病変皮膚(AD-L)および非病変皮膚(AD-NL)]のオーナー所有犬12頭と健常オーナー所有犬12頭から皮膚生検および血液サンプルを採取した。血清から循環エクソソームを抽出した。CCL17、CCL22、CCL27、CCL28の皮膚およびエクソソームmRNAレベルは、定量的リアルタイムPCRを用いて定量化した。タンパク質レベルは、犬特異的ELISAキットを用いて評価した。臨床症状の重症度および程度も、犬アトピー性皮膚炎重症度指数(CADESI-04)および有効なかゆみのVisual Analog Scale(pVAS)を用いて評価された。 結果: 皮膚におけるCCL28エクソソームの発現は、健常(P = 0.019)およびAD-NL(P = 0.002)サンプルと比較して、AD-Lでより大きかった。しかし、血清中の発現は、健常犬と比較してAD犬で低かった(P = 0.03)。健常皮膚と比較した場合、AD-LではCCL17とCCL22の高い発現が見られた(それぞれP = 0.018とP = 0.019)。また、臨床スコアとCCL22(AD-NL；r=0.6、P=0.05)およびそう痒スコアとCCL22(AD-L；r=0.6、P=0.05)の間に正の相関が見られた。CCL27濃度の差は観察されなかった。 結論と臨床的重要性: 本研究は、CCL17、CCL22およびCCL28がアトピー犬の皮膚炎症反応に関与している可能性を示唆するものである。これらの所見を検証するためにさらなる研究が必要であるが、これらは疾患の重症度マーカーとして考えられるかもしれない。.摘要 背景: 犬特应性皮炎(AD)是一种复杂的多因素疾病，表现为过度的免疫应答。我们对皮肤和循环趋化因子在疾病严重程度中的作用知之甚少。 目的: 评价健康和特应性犬皮肤和血清中选定趋化因子的信使(m)RNA和蛋白水平，并在特应性组中确定是否与疾病严重程度存在相关性。 材料和方法: 从12只私家特应性犬[病变(AD-L)和非病变(AD-NL)皮肤]和12只私家健康犬中采集皮肤活检和血液样本。从血清中提取循环外泌体。使用定量实时PCR定量CCL17、CCL22、CCL27和CCL28的皮肤和外泌体mRNA水平。使用犬特异性ELISA试剂盒评价蛋白水平。还使用犬特应性皮炎程度和严重指数第4版(CADESI-04)和经验证的瘙痒视觉模拟量表(pVAS)评估特应性皮炎犬中临床体征的严重程度和范围。 结果: 与健康(P = 0.019)和AD-NL(P = 0.002)样本相比，AD-L皮肤中CCL28外泌体的表达更高。然而，与健康犬相比，AD犬的血清表达较低(P = 0.03)。与健康皮肤相比，在AD-L中观察到CCL17和CCL22的较高表达(分别为P = 0.018和P = 0.019)。临床评分与CCL22(AD-NL；r = 0.6，P = 0.05)、瘙痒评分与CCL22(AD-L；r = 0.6，P = 0.05)也呈正相关。未观察到CCL27浓度的差异。 结论和临床重要性: 本研究表明CCL17、CCL22和CCL28可能在特应性犬的皮肤炎症反应中发挥作用。它们可被认为是疾病严重程度的标志物，尽管还需要进一步的研究来验证这些发现。.Resumo CONTEXTO: A dermatite atópica canina (DA) é uma doença multifatorial complexa caracterizada por uma resposta imunológica exagerada. Pouco se sabe sobre o papel das quimiocinas cutâneas e circulantes na gravidade da doença. OBJETIVO: Avaliar os níveis de RNA mensageiro (mRNA) e de proteínas de quimiocinas selecionadas na pele e soro de cães saudáveis e atópicos, e, no grupo atópico, determinar se há correlação com a gravidade da doença. MATERIAIS E MÉTODOS: Biópsias cutâneas e amostras de sangue foram coletadas de doze cães atópicos de proprietários [pele lesional (DA-L) e não lesional (DA-N)] e doze cães saudáveis de proprietários. Exossomos circulantes foram extraídos do soro. Os níveis cutâneos e exossômicos de mRNA de CCL17, CCL22, CCL27 e CCL28 foram quantificados utilizando o PCR real-time quantitativo. Os níveis de proteínas foram avaliados utilizando kits de ELISA específico canino. A gravidade e a extensão dos sinais clínicos foram também avaliadas nos cães atópicos utilizando o Canine Atopic Dermatitis Extent and Severity Index, 4

Background Angiotensin receptor and neprilysin inhibition (ARNI) has been shown to reduce cardiovascular mortality by 20% as compared with enalapril in a randomized controlled trial. However, there is a paucity of real-world data on the effects of ARNI in heart failure patients with reduced ejection fraction (HFrEF), especially those with concurrent renal impairment or hypotension. Methods Between 2016 and 2017, we recruited 466 HFrEF patients treated with sacubitril/valsartan (Group A) and 466 patients managed with standard HF treatment without ARNI (Group B) in a HF referral center. Baseline characteristics and clinical outcomes were collected between both groups. Results Baseline characteristics were comparable between the two groups. During a follow-up period of 15 months, death from cardiovascular causes or first unplanned hospitalization for HF occurred in 100 patients in Group A (21.5%) and 144 in Group B (30.9%, hazard ratio 0.66; 95% CI 0.51–0.85; p = 0.001). The incidences of deaths from any causes, cardiovascular death, sudden death, and HF re-hospitalization were all significantly lower in Group A than Group B patients. Among patients with different chronic kidney disease stages and normotensive patients, treatment with sacubitril/valsartan showed more favorable outcomes than treatment with standard HF care without ARNI. However, in patients with baseline systolic blood pressure lower than 100 mmHg, there were no significant differences of outcomes in both groups. Among Group A patients, escalation of sacubitril/valsartan was associated with better outcomes. Conclusions Our study demonstrated the effectiveness of sacubitril/valsartan on HFrEF patients in real world practice, including those with advanced renal impairment.

Background Disconnected pancreatic duct syndrome (DPDS) is a complication of acute necrotizing pancreatitis in the neck and body of the pancreas often manifesting as persistent pancreatic fluid collection (PFC) or external pancreatic fistula (EPF). This systematic review and pairwise meta-analysis aimed to review the definitions, clinical presentation, intervention, and outcomes for DPDS. Methods The PubMed, EMBASE, MEDLINE, and SCOPUS databases were systematically searched until February 2020 using the PRISMA framework. A meta-analysis was performed to assess the success rates of endoscopic and surgical interventions for the treatment of DPDS. Success of DPDS treatment was defined as long-term resolution of symptoms without recurrence of PFC, EPF, or pancreatic ascites. Results Thirty studies were included in the quantitative analysis comprising 1355 patients. Acute pancreatitis was the most common etiology (95.3%, 936/982), followed by chronic pancreatitis (3.1%, 30/982). DPDS commonly presented with PFC (83.2%, 948/1140) and EPF (13.4%, 153/1140). There was significant heterogeneity in the definition of DPDS in the literature. Weighted success rate of endoscopic transmural drainage (90.6%, 95%-CI 81.0–95.6%) was significantly higher than transpapillary drainage (58.5%, 95%-CI 36.7–77.4). Pairwise meta-analysis showed comparable success rates between endoscopic and surgical intervention, which were 82% (weighted 95%-CI 68.6–90.5) and 87.4% (95%-CI 81.2–91.8), respectively (P = 0.389). Conclusions Endoscopic transmural drainage was superior to transpapillary drainage for the management of DPDS. Endoscopic and surgical interventions had comparable success rates. The significant variability in the definitions and treatment strategies for DPDS warrant standardisation for further research.

The prognostic significance and the optimal treatment strategy for patients with atrial fibrillation (AF) and heart failure (HF) remain controversial.We extracted data from a large prospective national database involving Taiwanese patients with AF who were hospitalized for acute HF with reduced ejection fraction. Baseline characteristics, AF types, medications, and 1-year outcomes of the patients were analyzed.At baseline, 393 (26%) patients had AF, including 117 (29.8%) patients with paroxysmal AF (PAF) and 276 (70.2%) with nonparoxysmal AF (N-PAF). Patients with PAF were more likely to have ischemic cardiomyopathy (47.3% vs 29.7%, p = 0.021), chronic kidney disease (46.2% vs 29.0%, p = 0.001), and higher CHA2DS2-VASc score (4.0 vs 3.6, p = 0.033) compared with patients with N-PAF; however, patients with N-PAF had larger left atrial diameter (50.5 vs 47.3 mm, p = 0.004) than patients with PAF. Patients with PAF were more likely to receive treatment with amiodarone (31.6% vs 13.8%, p0.001) and antiplatelet agents (54.1% vs 42.5%, p = 0.041) but less likely to receive treatment with renin-angiotensin system blockers (52.3% vs 64.9%, p = 0.021) and anticoagulants (33.3% vs 50%, p = 0.003) compared with patients with N-PAF at discharge. The 1-year mortality (26.2% vs 16.5%, p = 0.024) and non-HF-related death rates (13.1% vs 5%, p = 0.005) were significantly higher in patients with PAF, whereas HF and arrhythmic death rates were similar in both groups (13.1% vs 11.5%).Among patients with HF complicated with AF, those with PAF were more likely to receive antiarrhythmic agents, less likely to receive guideline-recommended therapy, but developed worse 1-year outcome compared with patients with N-PAF. These findings further emphasize the importance of optimal guideline-recommended medical therapy in patients with HF.

Aims Acute myocardial infarction (AMI) and stroke are important causes of mortality and morbidity. Our aims are to determine the comparative epidemiology of AMI and ischaemic stroke; and examine the differences in cardiovascular outcomes or mortality occurring after an AMI or stroke. Methods and results The Singapore National Registry of Diseases Office collects countrywide data on AMI, stroke, and mortality. Index events of AMI and ischaemic stroke between 2007 and 2012 were identified. Patients were then matched for occurrences of subsequent AMI, stroke, or death within 1-year of the index event. There were 33 222 patients with first-ever AMI and 20 982 with first-ever stroke. AMI patients were significantly more likely to be men (66.3% vs. 56.9%), non-Chinese (32.1% vs. 24.1%), and smokers (43.1% vs. 38.6%), but less likely to have hypertension (65.6% vs. 79%) and hyperlipidaemia (61.1% vs. 65.5%), compared with stroke patients. In total 6.8% of the AMI patients had recurrent AMI, whereas 4.8% of the stroke patients had recurrent stroke within 1 year; 31.7% of the AMI patients died, whereas 17.1% of the ischaemic stroke patients died within 1 year. Older age, Malay ethnicity, and diabetes mellitus were statistically significant risk factors for all-cause mortality and for the composite endpoint of AMI, stroke, and all-cause mortality, at 1 year. Conclusions Risk profiles of patients with AMI and stroke are significantly different. Patients suffer recurrent events in vascular territories similar to the index event. Age and diabetes mellitus are significant predictors of recurrent vascular events and mortality.

INTRODUCTION Rhodiola, a popular plant in Tibet, has been proven to decrease arrhythmia. The aim of this study was to elucidate the molecular mechanism and electrophysiological properties of rhodiola in the suppression of atrial fibrillation. METHODS This study consisted of 3 groups as follows: Group 1: normal control rabbits (n = 5); Group 2: rabbits with heart failure (HF) created by coronary ligation and who received 2 weeks of water orally as a placebo (n = 5); and Group 3: rabbits with HF who received 2 weeks of a rhodiola 270 mg/kg/day treatment orally (n = 5). The monophasic action potential, histology, and real-time polymerase chain reaction (RT-PCR) analysis of ionic channels and PI3K/AKT/eNOS were examined. RESULTS Compared with the HF group, attenuated atrial fibrosis (35.4 ± 17.4% vs. 16.9 ± 8.4%, P = 0.05) and improved left ventricular (LV) ejection fraction (51.6 ± 3.4% vs. 68.0 ± 0.5%, P = 0.001) were observed in the rhodiola group. The rhodiola group had a shorter ERP (85.3 ± 6.8 vs. 94.3 ± 1.2, P = 0.002), APD90 (89.3 ± 1.5 vs. 112.7 ± 0.7, P < 0.001) in the left atrium (LA), and decreased AF inducibility (0.90 ± 0.04 vs. 0.42 ± 0.04, P < 0.001) compared with the HF group. The mRNA expressions of Kv1.4, Kv1.5, Kv4.3, KvLQT1, Cav1.2, and SERCA2a in the HF LA were up-regulated after rhodiola treatment. The rhodiola-treated HF LA demonstrated higher mRNA expression of PI3K-AKT compared with the HF group. CONCLUSIONS Rhodiola reversed LA electrical remodeling, attenuated atrial fibrosis and suppressed AF in rabbits with HF. The beneficial electrophysiological effect of rhodiola may be related to upregulation of Kv1.4, Kv1.5, Kv4.3, KvLQT1, Cav1.2, SERCA2a, and activation of PI3K/AKT signaling.

Atrial fibrillation (AF) can be associated with an increased risk of developing coronary artery disease (CAD) due to mechanisms of inflammation, endothelial dysfunction and adverse atrial remodelling. It is unclear if adverse coronary events can be further reduced after successful catheter ablation of AF. We hypothesise that AF ablation and sinus maintenance could reduce future adverse cardiac events in patients with underlying CAD.A total of 310 patients with drug-refractory paroxysmal AF and prior history of percutaneous coronary intervention (PCI) for underlying CAD were recruited in the retrospective case control study. Of these, 155 patients underwent AF ablation (the Ablation Group), while 155 patients received medical treatment (the Medical Group). All patients were followed up for major adverse cardiac events, including acute coronary syndrome requiring hospitalisation, stroke, pulmonary embolism and mortality.The clinical characteristics were comparable between the two groups, except for higher antiarrhythmic drug use in the Medical Group. During a follow-up duration of 61±32 months, all-cause mortality (8.4% vs. 1.3%, p=0.004) and the overall major adverse events (47.7% vs. 12.3%, p0.001) were significantly higher in the Medical Group than the Ablation Group. There were also more instances of stroke (10.3% vs. 3.2%, p=0.013) and acute coronary syndrome requiring hospitalisation (29% vs. 7.1%, p0.001) in the Medical Group than the Ablation Group. Multivariate analysis confirmed that non-ablation was an independent risk factor for major adverse events (p0.001, HR 3.4, 95% confidence interval 1.9-5.9).In PAF patients with established CAD who underwent PCI, catheter ablation could lead to fewer major adverse cardiac events compared to medical therapy.

Background Radiofrequency ablation of ventricular arrhythmias (VAs) originating from the continuum between the aortic sinus of Valsalva (ASV) and the left ventricular (LV) summit is a challenge. Objectives The objectives of this study were to investigate the electrocardiographic, electrophysiological, and anatomical characteristics of VAs and to develop an algorithm for predicting the successful ablation site. Methods We recruited 66 patients (mean age, 47 ± 15 years; 42 male patients) with symptomatic VAs originating from the continuum between the ASV and the LV summit who underwent radiofrequency ablation. Patients were classified into 4 groups (group 1: ASV, n=20; group 2: subvalvular region, n=15; group 3: great cardiac vein/anterior interventricular vein [GCV/AIV], n=16; group 4: epicardium requiring pericardial access, n=15). The QRS morphological characteristics of VAs were compared between the 4 groups. Results Electrocardiographic analysis revealed that the aVL/aVR Q-wave ratio is useful in the prediction of successful ablation sites in the ASV, subvalvular area, GCV/AIV, and epicardium requiring pericardial access at cutoff values of ≤1.415, 1.416–1.535, 1.536–1.740, and >1.740, respectively. The aVL/aVR Q-wave ratio was well correlated with the distance between the successful ablation site and the tip of the LV summit. A distance of >18.9 mm and an LV myocardial thickness of >9.1 mm predicted the need for the epicardial or GCV/AIV approaches. There were no major procedural complications. Eight patients (12.1%) developed VA recurrence during a mean follow-up of 15.9 months (interquartile range 9.2–24.2 months). Conclusion The aVL/aVR Q-wave ratio is a useful parameter for predicting the successful ablation sites of VAs originating from the continuum between the ASV and the LV summit.

Hyperthyroidism is a known reversible cause of atrial fibrillation (AF). However, some patients remain in AF despite restoration of euthyroid status.The purpose of this study was to compare the electrophysiologic characteristics and long-term ablation outcome in AF patients with and without history of hyperthyroidism.The study enrolled 717 consecutive patients with AF who underwent first AF ablation, which involved pulmonary vein (PV) isolation in paroxysmal AF and additional substrate modification in nonparoxysmal AF patients. Eighty-four patients (12%) with hyperthyroidism history were compared to those without. Euthyroid status was achieved for ≥3 months before ablation in hyperthyroid patients.Patients with hyperthyroid history were associated with older age, more female gender, lower mean right atrial voltage, higher number of PV ectopic foci (1.3 ± 0.4 vs 1.0 ± 0.2, P.01), and higher prevalence of non-PV foci (42% vs 23%, P.01). Ectopic foci from ligament of Marshall were demonstrated more often in hyperthyroid patients (7.1% vs 1.6%, P.01) in whom alcohol ablations were required. After propensity score matching for potential covariates, history of hyperthyroidism was an independent predictor of AF recurrence after single procedure (hazard ratio 2.07, 95% confidence interval 1.27-3.38). AF recurrence rates after multiple procedures were not different between patients with and those without hyperthyroid history.Patients with hyperthyroid history had a significantly higher number of PV ectopies and higher prevalence of non-PV ectopic foci compared to euthyroid patients, which resulted in a higher AF recurrence rate after a single procedure.

A 44 year old male with idiopathic dilated cardiomyopathy was undergoing persistent atrial fibrillation (AF) ablation. Following antral ablation, AF terminated into a regular narrow complex rhythm. Earliest activation was mapped to a focus in the superior vena cava (SVC) which was conducted in a 2:1 ratio to the atria which in turn was conducted with 2:1 ratio to the ventricles, resulting in an unusual 4:2:1 conduction of the SVC tachycardia. 1:1 conduction of the SVC tachycardia to the atrium preceded initiation of AF. During AF, SVC tachycardia continued unperturbed. Sinus rhythm was restored following catheter ablation of the focus.

Substrate Modification in Persistent Atrial Fibrillation Introduction The optimal substrate ablation approach in patients with persistent atrial fibrillation (Per AF) remains unclear. This was a prospective randomized study comparing the efficacy of limited (continuous complex fractionated atrial electrogram, CFAE