Partial Stent-in-Stent Method with an Uncovered Self-Expandable Metallic Stent for Unresectable Malignant Hilar Bile Duct Obstruction.

(1) Background: There is controversy regarding stent placement for unresectable malignant hilar biliary obstruction (UMHBO). We mainly use the partial stent-in-stent (PSIS) method with an uncovered self-expandable metallic stent (UCSEMS) based on the drainage area and patency period. In this study, we investigated the usefulness and safety of the PSIS method. (2) Methods: In total, 59 patients who underwent the PSIS method for UMHBO at our hospital were included in the study. The technical success rate, clinical success rate, time to recurrent biliary obstruction (TRBO) and overall survival (OS) from the first placement, factors affecting TRBO and OS, and early complications within 30 days after the procedure were evaluated retrospectively. (3) Results: The technical and clinical success rates were 100% and 96.6%, respectively, with a TRBO of 121 days [95% confidence interval: 82-231] and an OS of 194 days [95% confidence interval: 113-305] after the first placement. Early complications occurred in nine patients (15.3%), including five cases of cholangitis, three cases of pancreatitis, and one case of cholecystitis. (4) Conclusions: The PSIS method for UMHBO is safe and useful with high technical and clinical success rates.

Safety and Diagnostic Yield of Endoscopic Ultrasound-Guided Fine-Needle Biopsy for Hypervascular Pancreatic Lesions.

Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) is a common technique for diagnosing pancreatic lesions with high accuracy and a low incidence of procedural adverse events. However, occasional adverse events, particularly bleeding, may occur. Procedures for hypervascular lesions are considered important, but their risks are unknown. We aimed to evaluate the safety and diagnostic yield of EUS-FNB for hypervascular pancreatic solid lesions. This study included 301 patients with 308 solid pancreatic lesions who underwent EUS-FNB between May 2011 and December 2018. We performed propensity-score matching to balance clinical differences between hypervascular and hypovascular lesions and analyzed 52 lesions. We compared the safety and diagnostic performance of propensity score-matched cohorts. The sensitivity, specificity, and accuracy rates of EUS-FNB for hypervascular lesions were 94.7%, 100%, and 96.2%, and those for hypovascular lesions were 80.0%, 100%, and 84.6%, respectively. There was no difference in diagnostic performance between hypervascular and hypovascular lesions. Furthermore, adverse events occurred in only one patient (pancreatitis) in the hypovascular group. There were no significant differences in the occurrence of adverse events between hypervascular and hypovascular lesions (0% vs. 3.8%, p = 1.000). Therefore, EUS-FNB may be safe with a high diagnostic yield, even for hypervascular solid pancreatic lesions.

Pancreatic Juice Cytology Evaluations Using Synthetic Secretin and Serial Pancreatic Juice Aspiration Cytological Examination for the Diagnosis of Pancreatic Ductal Adenocarcinoma.

Pathological examination by endoscopic ultrasound-fine needle aspiration is not possible in approximately 10% of pancreatic tumor cases. Pancreatic juice cytology (PJC) is considered an alternative diagnostic method. However, its diagnostic capability is insufficient, and PJC has been repeatedly redevised. Serial pancreatic juice aspiration cytological examination (SPACE) and secretin-loaded PJC (S-PJC) have been recently introduced as alternative diagnostic methods. This study aimed to determine the diagnostic capacity and safety of SPACE and S-PJC using a propensity score-matched analysis. The sensitivity, specificity, and accuracy were 75.0%, 100%, and 92.3% for S-PJC, respectively, and 71.4%, 100%, and 92.3% for SPACE, respectively, meaning that there was no significant difference between the groups. Four patients (15.4%) each in the S-PJC and SPACE groups experienced complications, including postendoscopic retrograde cholangiopancreatography, pancreatitis, and cholangitis. Overall, there was no difference in efficacy and safety between the SPACE and S-PJC groups.

Comparison between Target Sample Check Illuminator and White Light Observation in Discriminating the Presence of Target Specimen for Endoscopic Ultrasound-Guided Fine Needle Aspiration Sample.

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is an essential endoscopic tissue sampling method for diagnosing pancreatobiliary diseases; however, determining the presence of target specimens mixed in the blood by conventional observation is challenging due to the small size of the obtained sample. This study investigated the usefulness of a target sample check illuminator (TSCI) that emits a specific wavelength of light to determine the presence of target specimens. Twenty-seven patients who underwent EUS-FNA at our hospital were included. Conventional white light observation was performed for the collected samples, followed by TSCI; six people evaluated the presence of the target specimen on a 5-point scale. The target specimen discrimination score using TSCI (median: 5) was significantly higher than that using conventional white light observation (median: 1) (p < 0.001). No significant difference was observed in the discrimination score between the evaluator (novice vs. expert, p = 0.162) and puncture needle (22G vs. 25G, p = 0.196). The discriminability of TSCI in the samples obtained using EUS-FNA was significantly higher than that of conventional observation. TSCI does not depend on the evaluator or puncture needle for the identification of the target specimen; hence, it can provide a good pathological specimen and may contribute to the improvement of the diagnostic ability.

Citrate Synthase Insufficiency Leads to Specific Metabolic Adaptations in the Heart and Skeletal Muscles Upon Low-Carbohydrate Diet Feeding in Mice.

A decrease in TCA cycle activity may lead to impaired nutrition metabolism and cellular energy shortage. Herein, we aimed to characterize the detailed metabolic changes that compensate for energy shortages in energy-consuming organs (heart and skeletal muscles) in mice with knockout of citrate synthase (CS), an important enzyme in the TCA cycle. CS hetero knockout (CS +/-) mice and wild-type mice were fed a low-carbohydrate ketogenic diet (LCKD) or high-fat, high-carbohydrate diet (HFHCD) to induce metabolic changes. Body weight, blood serum parameters, metabolic gene expression, and adenosine triphosphate (ATP) levels were measured in the heart and skeletal muscles. Glycogen content, anabolic and catabolic biomarkers, and morphological changes were also assessed in the skeletal muscles. After diet feeding, there were no differences observed in the body weight and blood serum parameters between wild-type and CS +/- mice. The cardiac expression of genes related to the utilization of fatty acids, monocarboxylates, and branched amino acids increased in LCKD-fed CS +/- mice. In contrast, no significant differences in gene expression were observed in the muscles of LCKD-fed mice or the heart and muscles of HFHCD-fed mice. ATP levels decreased only in the skeletal muscles of LCKD-fed CS +/- mice. Additionally, the decrease in glycogen content, suppression of p70 S6 kinase, and presence of type I fiber atrophy were observed in the muscles of LCKD-fed CS +/- mice. These results suggest that the energy-consuming organs with CS insufficiency may undergo tissue-specific adaption to compensate for energy shortages when the carbohydrate supply is limited.

Review on acute pancreatitis attributed to COVID-19 infection.

The coronavirus disease 2019 (COVID-19) is known to cause gastrointestinal symptoms. Recent studies have revealed COVID-19-attributed acute pancreatitis (AP). However, clinical characteristics of COVID-19-attributed AP remain unclear. We performed a narrative review to elucidate relation between COVID-19 and AP using the PubMed database. Some basic and pathological reports revealed expression of angiotensin-converting enzyme 2 and transmembrane protease serine 2, key proteins that aid in the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the pancreas. The experimental and pathological evaluation suggested that SARS-CoV-2 infects human endocrine and exocrine pancreas cells, and thus, SARS-CoV-2 may have a direct involvement in pancreatic disorders. Additionally, systemic inflammation, especially in children, may cause AP. Levels of immune mediators associated with AP, including interleukin (IL)-1ß, IL-10, interferon-γ, monocyte chemotactic protein 1, and tumor necrosis factor-α are higher in the plasma of patients with COVID-19, that suggests an indirect involvement of the pancreas. In real-world settings, some clinical features of AP complicate COVID-19, such as a high complication rate of pancreatic necrosis, severe AP, and high mortality. However, clinical features of COVID-19-attributed AP remain uncertain due to insufficient research on etiologies of AP. Therefore, high-quality clinical studies and case reports that specify methods for differential diagnoses of other etiologies of AP are needed.

Efficacy and Safety of Pancreatic Juice Cytology with Synthetic Secretin in Diagnosing Malignant Intraductal Papillary Mucinous Neoplasms of the Pancreas.

The risk of malignant transformation of intraductal papillary mucinous neoplasm (IPMN) is presently assessed using imaging, which remains unsatisfactory. Given the high viscosity of pancreatic juice, pancreatic juice cytology (PJC) is considered an investigational procedure. We previously demonstrated that the diagnostic performance of PJC was improved via synthetic secretin loading in pancreatic ductal carcinoma. This study aimed to evaluate the efficacy of synthetic secretin-loaded PJC (S-PJC) for IPMN. The usefulness and safety of S-PJC were prospectively evaluated in 133 patients with IPMN. Overall, 92, 12, and 26 patients had branch duct, main duct, and mixed-type lesions, respectively. The risk classifications based on the 2017 international consensus guidelines were high-risk stigmata, worrisome features, and no risk in 29, 59, and 45 patients, respectively. Synthetic secretin loading improved the sensitivity of PJC from 50.0% to 70.8%. Complications included 13 (9.8%) cases of mild pancreatitis, 1 (0.8%) case of acute cholangitis, and 1 (0.8%) case of Mallory-Weiss syndrome, all of which resolved with conservative treatment. In conclusion, synthetic secretin-loaded PJC improved the diagnostic performance of cytology for malignant IPMN. We recommend using synthetic secretin-loaded PJC for the preoperative pathological diagnosis of malignant IPMN in clinical settings.

Large Gallstones Stacked Together in the Common Bile Duct after Choledochojejunostomy.

A 65-year-old man had a history of cholecystectomy and treatment for cholelithiasis with a common bile duct incision. Owing to frequent cholangitis, he underwent choledochojejunostomy. Twenty years after the surgery, he was hospitalized for cholangitis and was suspected of having hilar cholangiocarcinoma based on imaging findings. Percutaneous transhepatic cholangioscopy using a SpyGlass™ DS (Boston Scientific, Marlborough, USA) showed gallstones and bile sludge in the bile ducts, but no tumors were noted. Electrohydraulic shockwave lithotripsy with double-balloon enteroscopy enabled complete stone removal; a direct visual biopsy with peroral cholangioscopy showed no malignancy in the bile duct.

Peroral Cholangioscopy-Guided Forceps Mapping Biopsy for Evaluation of the Lateral Extension of Biliary Tract Cancer.

BACKGROUND: Peroral cholangioscopy (POCS)-guided forceps mapping biopsy (FMB) is a method for the accurate preoperative identification of the extent of the disease of biliary tract cancer (BTC). However, the diagnostic value of POCS-FMB is still uncertain. OBJECTIVES: We evaluated the diagnostic utility of POCS-FMB for the identification of lateral extension-superficial intraductal spread longitudinally and continuously from the main lesion-of BTC. METHODS: In the retrospective study, patients who received POCS-FMB and surgery for curative resection of BTC between September 2016 and August 2019 at our medical institution were enrolled. The diagnostic accuracy of POCS-FMB for the identification of lateral extension of BTC was evaluated. Furthermore, we also evaluated the factors affecting the diagnostic accuracy of POCS-FMB. RESULTS: A total of 23 patients with BTC were enrolled, and 24 procedures of POCS-FMB from 96 sites of biliary tracts were performed. The sensitivity, specificity, and accuracy of POCS-FMB were 53.8%, 63.9%, and 63.1%, respectively. In the multivariate logistic regression analyses, the biopsy from the bifurcation of biliary tracts was a significant factor affecting the diagnostic accuracy of POCS-FMB (odds ratio 3.538, 95%; confidence interval 1.151-10.875, p = 0.027). CONCLUSIONS: The diagnostic accuracy of POCS-FMB for the identification of lateral extension of BTC was insufficient. The biopsy from the bifurcation of biliary tracts was a positive factor affecting the diagnostic accuracy of POCS-FMB.

Peroral cholangioscopy-guided forceps biopsy versus fluoroscopy-guided forceps biopsy for extrahepatic biliary lesions.

BACKGROUND AND AIM: Endoscopic retrograde cholangiopancreatography (ERCP)-related tissue acquisition, including fluoroscopy-guided forceps biopsy (F-FB), is a common technique in diagnosing indeterminate biliary lesions. Recently, peroral cholangioscopy (POCS) and POCS-guided forceps biopsy (POCS-FB) has also been used for the diagnosis of indeterminate biliary lesions. However, it is uncertain which of those techniques were superior for the diagnosis of extrahepatic cholangiocarcinoma (ECC). We aimed to evaluate the diagnostic yield and safety of F-FB for indeterminate biliary lesions compared with POCS-FB. METHODS: Patients who underwent F-FB or POCS-FB to evaluate indeterminate biliary lesions between October 2011 and August 2019 were enrolled retrospectively. We carried out propensity score matching to balance these clinical differences between the F-FB group and POCS-FB group. In the propensity score-matched cohort, we compared the diagnostic performance of F-FB with that of POCS-FB based on the pathological evaluation. We also evaluate adverse events associated with F-FB and POCS-FB. RESULTS: We enrolled 113 patients with biliary diseases, and 62 patients were analyzed in the propensity score-matched cohort. Sensitivity, specificity, and accuracy of F-FB were 82.4, 100, and 90.3%, and for POCS-FB, those values were 83.3, 100, and 90.3%, respectively. There were no significant differences in the diagnostic performance between F-FB and POCS-FB. There were also no significant differences in the occurrence of adverse events between F-FB and POCS-FB (41.9 vs 29.0%, P = 0.289). CONCLUSIONS: The diagnostic yield of F-FB for ECC is similar to that of POCS-FB. POCS-FB is not necessary for the initial pathological diagnosis of indeterminate biliary lesions.

Adequate tissue acquisition rate of peroral cholangioscopy-guided forceps biopsy.

BACKGROUND: Peroral cholangioscopy (POCS)-guided forceps biopsy is a method for diagnosing indeterminate biliary strictures and for the preoperative identification of the exact perihilar and distal margins of biliary tract cancer (BTC). However, POCS-guided forceps biopsy may result in an insufficient amount of specimen at times. Therefore, we evaluated the adequate tissue acquisition rate and the factors affecting the adequate tissue acquisition of POCS-guided forceps biopsy for the biliary tract. METHODS: Patients who underwent POCS-guided forceps biopsy for biliary disease between September 2016 and October 2018 at our hospital were enrolled retrospectively. We evaluated the adequate tissue acquisition rate of POCS-guided forceps biopsy for the biliary lesion and that for non-stenotic bile duct. In addition, the factors affecting the adequate tissue acquisition rate of POCS-guided forceps biopsy were evaluated. RESULTS: We enrolled 47 patients with biliary disease and performed POCS-guided forceps biopsy for biliary lesion and POCS-guided forceps mapping biopsy for non-stenotic bile duct in 40 and 36 patients, respectively. The adequate tissue acquisition rates of POCS-guided forceps biopsy for biliary lesions and that for non-stenotic bile duct were 86.4%, and 68.9%, respectively. In the multivariate logistic regression analyses, age, and previous biliary stenting before POCS were factors affecting the adequate tissue acquisition rate of POCS-guided forceps biopsy for the biliary lesion. For non-stenotic bile duct, the location of the biliary lesion, endoscopic sphincterotomy (EST), and procedure time of POCS were factors affecting the adequate tissue acquisition rate of POCS-guided forceps mapping biopsy. CONCLUSIONS: Previous biliary stenting was a factor affecting a low tissue acquisition rate of POCS-guided forceps biopsy for the biliary lesion. In the POCS-guided forceps mapping biopsy, the location of the biliary lesion, EST, and procedure time were factors affecting tissue acquisition rates.

Programmed cell death-1 inhibitor-related sclerosing cholangitis: A systematic review.

BACKGROUND: Programmed cell death-1 (PD-1) inhibitor has been indicated for many types of malignancies. However, these inhibitors also cause immune-related adverse events. Hepatobiliary disorder is a phenotype of immune-related adverse event affecting 0%-4.5% of patients treated with PD-1 inhibitors. Recent studies have reported PD-1 inhibitor-related sclerosing cholangitis (SC); however, the associated clinical and pathological features are unclear. AIM: To evaluate the clinical and pathological features of PD-1 inhibitor-related SC through a systematic review of the literature. METHODS: The review, conducted using electronic databases in PubMed, was restricted to the period from January 2014 to September 2019 and focused on case reports/series on PD-1 inhibitor-related SC published in English. We scanned the references of the selected literature to identify any further relevant studies. Six cases previously studied by us, including three that have not yet been published, were included in this review. RESULTS: Thirty-one PD-1 inhibitor-related SC cases were evaluated. Median age of patients was 67 years (range, 43-89), with a male to female ratio of 21:10. The main disease requiring PD-1 inhibitor treatment was non-small cell lung cancer. Agents that caused PD-1 inhibitor-related SC were nivolumab (19 cases), pembrolizumab (10 cases), avelumab (1 case), and durvalumab (1 case). The median number of cycles until PD-1 inhibitor-related SC onset was 5.5 (range, 1-27). Abdominal pain or discomfort (35.5%, 11/31) was the most frequent symptom. Blood serum tests identified liver dysfunction with a notable increase in biliary tract enzymes relative to hepatic enzymes, and a normal level of serum immunoglobulin G4. Biliary dilation without obstruction (76.9%, 20/26), diffuse hypertrophy of the extrahepatic biliary tract (90.5%, 19/21), and multiple strictures of the intrahepatic biliary tract (30.4%, 7/23) were noted. In 11/23 (47.8%) cases, pathological examination indicated that CD8+ T cells were the dominant inflammatory cells in the bile duct or peribiliary tract. Although corticosteroids were mainly used for PD inhibitor-related SC treatment, the response rate was 11.5% (3/26). CONCLUSION: Some clinical and pathological features of PD-1 inhibitor-related SC were revealed. To establish diagnostic criteria for PD-1 inhibitor-related SC, more cases need to be evaluated.

Daidzein promotes the expression of oxidative phosphorylation- and fatty acid oxidation-related genes via an estrogen-related receptor α pathway to decrease lipid accumulation in muscle cells.

Estrogen-related receptor (ERR)α regulates genes involved in fatty acid oxidation (FAO) and oxidative phosphorylation (OXPHOS) in muscle. The soy isoflavone daidzein was reported to be a putative ERRα activator, but little is known about its effects on gene expression and FA metabolism. This study aimed to clarify whether daidzein affects FAO- and OXPHOS-related genes thereby modulating intracellular FA metabolism in muscle cells. For this purpose, we used the C2C12 murine muscle cell line. ERRα-expressing C2C12 myotubes were treated with 50 µM daidzein, and gene expression was examined. The expression of FAO genes such as pyruvate dehydrogenase kinase 4 (Pdk4) and acyl-coenzyme A dehydrogenase (Acadm) and that of OXPHOS genes such as ATP synthase F1 subunit beta (Atp5b) and cytochrome c (Cycs) was significantly increased by daidzein, and these effects were partially blocked by an ERRα inhibitor. Using a reporter assay, we showed that daidzein enhanced the promoter activity of these genes and that ERRα responsive elements in the promoter region were necessary for the action of daidzein. Finally, daidzein significantly decreased lipid accumulation in C2C12 myotubes associated with increased oxygen consumption. In conclusion, daidzein decreases lipid deposition in muscle cells by regulating the expression of genes related to FAO and OXPHOS via an ERRα-associated pathway at least in part. These results suggest that daidzein would be a beneficial tool to protect against various diseases caused by muscle lipotoxicity.

Peroral Cholangioscopy-Guided Forceps Biopsy and Endoscopic Scraper for the Diagnosis of Indeterminate Extrahepatic Biliary Stricture.

BACKGROUND: Peroral cholangioscopy (POCS) has become a widely-used technique in diagnosing indeterminate biliary strictures, enabling optical viewing of the biliary system and targeted biopsies under direct vision. The diagnostic utility of the new endoscopic scraper, Trefle®, for extrahepatic cholangiocarcinoma (ECC) has also been reported. However, the diagnostic utility of POCS-guided and Trefle®-assisted tissue acquisition for ECC has never been compared empirically. We evaluated the efficacy and safety of Trefle®-assisted tissue acquisition for diagnosing ECC compared with POCS-guided tissue sampling. METHODS: Patients who underwent Trefle®-assisted tissue acquisition or POCS-guided forceps biopsy to differentiate ECC from benign biliary disease between April 2014 and March 2018 were enrolled retrospectively. We evaluated the diagnostic performance of Trefle®-assisted tissue acquisition and POCS-guided forceps biopsy based on pathological evaluation. We also compared adverse events associated with Trefle®-assisted tissue acquisition with those of POCS-guided forceps biopsy. RESULTS: We enrolled 34 patients with biliary disease and performed Trefle®-assisted tissue acquisition and POCS-guided forceps biopsy in 14 and 20 patients, respectively. Sensitivity, specificity, and accuracy of Trefle®-assisted tissue acquisition were 87.5%, 83.3%, and 85.7%, respectively, and for POCS-guided forceps biopsy, these were 90.0% each. Statistical values of Trefle®-assisted tissue acquisition and POCS-guided tissue acquisition were not significantly different. There were no significant differences in the occurrence of adverse events between the Trefle®-assisted tissue acquisition and the POCS-guided forceps biopsy (35.7% vs. 25.0%, p = 0.770). Compared with patients who underwent POCS procedure, endoscopic sphincterotomy was performed for fewer patients who underwent Trefle®-assisted tissue acquisition (p < 0.001). CONCLUSIONS: The diagnostic ability of Trefle®-assisted tissue acquisition for ECC is similar to that of POCS-guided tissue acquisition. Trefle®-assisted tissue acquisition might also help to preserve the sphincter of Oddi and its digestive function.

Prevalência da apneia obstrutiva do sono em trabalhadores de turno: uma revisão sistemática / Prevalence of obstructive sleep apnea in shift workers: a systematic review

Resumo A apneia obstrutiva do sono (AOS) é um dos distúrbios do sono mais frequentes, associada ao risco aumentado para obesidade, hipertensão e evento cardiovascular. O presente estudo buscou investigar a prevalência da AOS em trabalhadores de turno. Foi realizada a revisão sistemática da literatura, utilizando-se os descritores "sleep apnea" AND "shift work", nas bases de dados do PubMed Central, Biblioteca Virtual em Saúde, Web of Science e Scopus, incluindo-se artigos que apresentaram a frequência da AOS em trabalhadores de turno, publicados entre 2004 e 2014, em inglês, português ou espanhol, apenas com seres humanos, maiores de 18 anos, utilizando polissonografia. Artigos de revisão ou com participantes com comorbidades prévias (exceto sobrepeso/obesidade), tratados para doença do sono ou gestantes foram excluídos. Dos 1.428 artigos identificados, quatro foram incluídos para análise, totalizando 819 participantes, com predomínio do sexo masculino. A prevalência da AOS em trabalhadores de turno variou de 14,3% a 38,1%, superior à estimada para a população geral, sugerindo associação importante com o trabalho de turno e a necessidade de prevenção, diagnóstico e intervenção sobre possíveis impactos negativos da escala de trabalho na saúde desses trabalhadores.

Abstract The obstructive sleep apnea (OSA) is one of the most common sleep disorders and is associated with increased risk for obesity, hypertension and cardiovascular event. The present study aimed to investigate the prevalence of OSA in shift workers. The systematic literature review was performed using the descriptors "sleep apnea" and "shift work", in the databases PubMed, PubMed Central, Biblioteca Virtual em Saúde, Web of Science and Scopus, including studies that presented the frequency of OSA in shift workers; published between 2004 and 2014; in English, Portuguese or Spanish; only with human beings, older than 18 years old; using the polysomnography. Review articles or those including participants with previous comorbidities (except overweight/obesity), treated for sleep disorders or pregnant women were excluded. From 1,428 studies identified, four were included in the analysis, resulting in 819 participants, with a predominance of men. The prevalence of OSA in shift workers varied from 14.3% to 38.1%, higher than that estimated for the general population, suggesting an important association with shift work and the need for prevention, diagnostic and intervention on the possible negative impacts of working range on the health of shift workers.

Association between Obstructive Sleep Apnea and Myocardial Infarction: A Systematic Review / Associação entre Apneia Obstrutiva do Sono e Infarto do Miocárdio: Uma Revisão Sistemática

Abstract Obstructive sleep apnea (OSA) has been associated to cardiovascular risk factors. However, the association between OSA and cardiovascular disease is still controversial. The objective of the present study was to verify the association between OSA and myocardial infarction (MI). This is a systematic review of the literature performed through electronic data sources MEDLINE/PubMed, PubMed Central, Web of Science and BVS -Biblioteca Virtual em Saúde (Virtual Health Library). The descriptors used were: 'obstructive sleep apnea' AND 'polysomnography' AND 'myocardial infarction' AND 'adults NOT 'treatment.' The present work analysed three prospective studies, selected from 142 articles. The studies followed a total sample of 5,067 OSA patients, mostly composed by male participants. All patients underwent night polysomnography, and all studies found an association between OSA and fatal and non-fatal cardiovascular outcomes. Thus, we were able to observe that 644 (12.7%) of the 5,067 patients suffered MI or stroke, or required a revascularization procedure, and 25.6% of these cardiovascular events were fatal. MI was responsible for 29.5% of all 644 analysed outcomes. There is an association between OSA and MI, in male patients, and apnea and hypopnea index (AHI) are the most reliable markers.

Resumo A apneia obstrutiva do sono (AOS) tem sido associada a fatores de risco cardiovascular, porém a relação entre a AOS e doença cardiovascular ainda é controversa. O objetivo do presente estudo foi verificar a associação entre AOS e infarto do miocárdio (IM). Revisão sistemática de literatura por meio das fontes de dados eletrônicas MEDLINE/PubMed, PubMed Central, Web of Science e Biblioteca Virtual em Saúde (BVS). Os descritores utilizados foram: "obstructive sleep apnea" AND "polysomnography" AND "myocardial infarction" AND "adults" NOT "treatment".O presente trabalho analisou três estudos prospectivos, selecionados dentre 142 artigos encontrados. Os estudos acompanharam uma amostra total de 5.067 pacientes diagnosticados com AOS, composta majoritariamente por participantes do sexo masculino. Todos os pacientes realizaram polissonografia noturna, e todas as pesquisas encontraram associação entre AOS e desfechos cardiovasculares fatais e não fatais. Assim, foi possível observar que 644 (12,7%) dos 5.067 pacientes sofreram IM ou acidente vascular cerebral, ou precisaram de procedimento de revascularização, sendo que 25,6% desses eventos cardiovasculares foram fatais. O IM foi responsável por 29,5% do total de 644 desfechos analisados. Existe associação entre AOS e IM, no sexo masculino, sendo o índice de apneia e hipopneia (IAH) um dos marcadores mais fidedignos.

The Dietary Isoflavone Daidzein Reduces Expression of Pro-Inflammatory Genes through PPARα/γ and JNK Pathways in Adipocyte and Macrophage Co-Cultures.

Obesity-induced inflammation caused by adipocyte-macrophage interactions plays a critical role in developing insulin resistance, and peroxisome proliferator-activated receptors (PPARs) regulate inflammatory gene expression in these cells. Recently, the soy isoflavone daidzein was reported to act as a PPAR activator. We examined whether daidzein affected adipocyte-macrophage crosstalk via the regulation of PPARs. Co-cultures of 3T3-L1 adipocytes and RAW264 macrophages, or palmitate-stimulated RAW264 macrophages were treated with daidzein in the presence or absence of specific inhibitors for PPARs: GW6471 (a PPARα antagonist), and GW9662 (a PPARγ antagonist). Inflammatory gene expression was then determined. Daidzein significantly decreased chemokine (C-C motif) ligand 2 (Ccl2, known in humans as monocyte chemo-attractant protein 1 (MCP1)) and interleukin 6 (Il6) mRNA levels induced by co-culture. In 3T3-L1 adipocytes, daidzein inversed the attenuation of adiponectin gene expression by co-culture, and these effects were inhibited by the PPAR-γ specific inhibitor. Daidzein also decreased Ccl2 and Il6 mRNA levels in RAW264 macrophages stimulated with palmitate or conditioned medium (CM) from hypertrophied 3T3-L1 adipocytes. This inhibitory effect on Il6 expression was abrogated by a PPAR-α inhibitor. Additionally, we examined the activation of nuclear factor-kappa B (NF-κB) and c-Jun N-terminal kinase (JNK) pathways and found that daidzein significantly inhibited palmitate-induced phosphorylation of JNK. Our data suggest that daidzein regulates pro-inflammatory gene expression by activating PPAR-α and -γ and inhibiting the JNK pathway in adipocyte and macrophage co-cultures. These effects might be favorable in improving adipose inflammation, thus, treatment of daidzein may be a therapeutic strategy for chronic inflammation in obese adipose tissue.

Milk-derived peptide Val-Pro-Pro (VPP) inhibits obesity-induced adipose inflammation via an angiotensin-converting enzyme (ACE) dependent cascade.

SCOPE: This study aimed to examine the effects of Val-Pro-Pro (VPP), a food-derived peptide with an angiotensin-converting enzyme (ACE) inhibitory property, on obesity-linked insulin resistance, and adipose inflammation in vivo and in vitro. METHODS AND RESULTS: C57BL/6J mice were fed high-fat high-sucrose diet and VPP (0.1% in water) for 4 months. For in vitro analysis, coculture of 3T3-L1 adipocytes overexpressing either ACE (3T3-ACE) or green fluorescent protein (3T3-GFP) and RAW264 macrophages was conducted with VPP. In diet-induced obese mice, VPP improved insulin sensitivity, concomitant with a significant decrease in tumor necrosis factor α (TNF-α) and IL-1ß expression in adipose tissue, with a tendency (p = 0.06) toward decreased CC chemokine ligand 5 expression. Additionally, VPP administration inhibited macrophage accumulation and activation in fat tissues. In vitro, VPP attenuated TNF-α mRNA induced by ACE overexpression in 3T3-L1 adipocytes. TNF-α and IL-1ß expression decreased following VPP treatment of RAW264 macrophage and 3T3-ACE adipocyte cocultures, but not in RAW264-3T3-GFP adipocyte cocultures. CONCLUSION: Our data suggest that VPP inhibits adipose inflammation in the interaction between adipocytes and macrophages, acting as an ACE inhibitor, thereby improving obesity-related insulin resistance. Thus, ingestion of VPP may be a viable protective and therapeutic strategy for insulin resistance and obesity-associated adipose inflammation.

Dietary isoflavone daidzein promotes Tfam expression that increases mitochondrial biogenesis in C2C12 muscle cells.

Mitochondrial dysfunction in muscles leads to a wide range of metabolic and age-related disorders. Recently, it has been reported that a natural polyphenol, resveratrol, affects mitochondrial biogenesis. This study aimed to identify other natural polyphenolic compounds that regulate mitochondrial biogenesis in muscles. For this purpose, we used the C2C12 murine muscle cell line. Screening involved a reporter assay based on the promoter of mitochondrial transcription factor A (Tfam). We found that several polyphenols exhibited the ability to increase Tfam promoter activity and that the soy isoflavone daidzein was a most potent candidate that regulated mitochondrial biogenesis. When C2C12 myotubes were treated with 25-50 µM daidzein for 24h, there were significant increases in the expression of Tfam and mitochondrial genes such as COX1 and Cytb as well as the mitochondrial content. Using several mutant Tfam promoter fragments, we found that the transcription factor, nuclear respiratory factor (NRF) and its coactivator, PGC1α, were necessary for the effect of daidzein on Tfam expression. Finally, silencing of sirtuin-1 (SIRT1) by shRNA resulted in inhibition of the daidzein effects on mitochondrial gene expression. In conclusion, daidzein regulates mitochondrial biogenesis in muscle cells by regulating transcriptional networks through a SIRT1-associated pathway. These results suggest that daidzein would be beneficial to protect against a wide range of diseases caused by muscle mitochondrial dysfunction.