Involvement of BCR::ABL1 in laminin adhesion of Philadelphia chromosome-positive acute lymphoblastic leukemia through upregulation of integrin α6.

BACKGROUND: Adhesion of cancer cells to extracellular matrix laminin through the integrin superfamily reportedly induces drug resistance. Heterodimers of integrin α6 (CD49f) with integrin ß1 (CD29) or ß4 (CD104) are major functional receptors for laminin. Higher CD49f expression is reportedly associated with a poorer response to induction therapy in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Moreover, a xenograft mouse model transplanted with primary BCP-ALL cells revealed that neutralized antibody against CD49f improved survival after chemotherapy. AIMS: Considering the poor outcomes in Philadelphia chromosome (Ph)-positive ALL treated with conventional chemotherapy without tyrosine kinase inhibitors, we sought to investigate an involvement of the laminin adhesion. METHODS AND RESULTS: Ph-positive ALL cell lines expressed the highest levels of CD49f among the BCP-ALL cell lines with representative translocations, while CD29 and CD104 were ubiquitously expressed in BCP-ALL cell lines. The association of Ph-positive ALL with high levels of CD49f gene expression was also confirmed in two databases of childhood ALL cohorts. Ph-positive ALL cell lines attached to laminin and their laminin-binding properties were disrupted by blocking antibodies against CD49f and CD29 but not CD104. The cell surface expression of CD49f, but not CD29 and CD104, was downregulated by imatinib treatment in Ph-positive ALL cell lines, but not in their T315I-acquired sublines. Consistently, the laminin-binding properties were disrupted by the imatinib pre-treatment in the Ph-positive ALL cell line, but not in its T315I-acquired subline. CONCLUSION: BCR::ABL1 plays an essential role in the laminin adhesion of Ph-positive ALL cells through upregulation of CD49f.

A technique for reconstruction of a giant extracranial internal carotid artery aneurysm: A technical note.

Background: Surgery is effective for extracranial internal carotid artery (EICA) aneurysms. However, the risk of cranial nerve injury associated with surgical repair, such as graft-assisted resection and extracranial-intracranial bypass techniques, is relatively high. Here, we report two cases of surgical treatment for EICA aneurysms and describe the surgical techniques and strategies to avoid cranial nerve injury. Methods: Two patients presented to our facility with an increasing cervical pulsatile mass and no neurological symptoms. Angiography showed a large aneurysm in the cervical internal carotid artery. Surgical treatment was performed to prevent rupture of the aneurysm. In both patients, the aneurysm was strongly attached to the vagus nerve. The aneurysm and vagus nerve were carefully dissected using a low-power bipolar (20 Malis; 3 watts), leaving connective tissue on the vagus nerve side. Results: The aneurysm was detached from the vagus nerve without injury. Based on intraoperative findings, one patient underwent clipping, and the other underwent aneurysmectomy and primary closure for aneurysm obliteration and angioplasty. Both patients were discharged without any cranial nerve dysfunction. Conclusion: The selection of a strategy based on intraoperative findings and low-power bipolar cutting is important for the treatment of extracranial carotid artery aneurysms to preserve cranial nerves.

Utility of bronchoscopically obtained frozen cytology pellets for next-generation sequencing.

BACKGROUND: Next-generation sequencing (NGS) is essential for lung cancer treatment. It is important to collect sufficient tissue specimens, but sometimes we cannot obtain large enough samples for NGS analysis. We investigated the yield of NGS analysis by frozen cytology pellets using an Oncomine Comprehensive Assay or Oncomine Precision Assay. METHODS: We retrospectively enrolled patients with lung cancer who underwent bronchoscopy at Kobe University Hospital and were enrolled in the Lung Cancer Genomic Screening Project for Individualized Medicine. We investigated the amount of extracted DNA and RNA and determined the NGS success rates. We also compared the amount of DNA and RNA by bronchoscopy methods. To create the frozen cytology pellets, we first effectively collected the cells and then quickly centrifuged and cryopreserved them. RESULTS: A total of 132 patients were enrolled in this study between May 2016 and December 2022; of them, 75 were subjected to frozen cytology pellet examinations and 57 were subjected to frozen tissue examinations. The amount of DNA and RNA obtained by frozen cytology pellets was nearly equivalent to frozen tissues. Frozen cytology pellets collected by endobronchial ultrasound-guided transbronchial needle aspiration yielded significantly more DNA than those collected by transbronchial biopsy methods. (P < 0.01) In RNA content, cytology pellets were not inferior to frozen tissue. The success rate of NGS analysis with frozen cytology pellet specimens was comparable to the success rate of NGS analysis with frozen tissue specimens. CONCLUSIONS: Our study showed that frozen cytology pellets may have equivalent diagnostic value to frozen tissue for NGS analyses. Bronchial cytology specimens are usually used only for cytology, but NGS analysis is possible if enough cells are collected to create pellet specimens. In particular, the frozen cytology pellets obtained by endobronchial ultrasound-guided transbronchial needle aspiration yielded sufficient amounts of DNA. TRIAL REGISTRATION: This was registered with the University Medical Hospital Information Network in Japan (UMINCTR registration no. UMIN000052050).

Reversed-Image Mechanical Thrombectomy for Acute Ischemic Stroke in a Situs Inversus Totalis Patient.

An 85-year-old female with situs inversus totalis presented with right hemiplegia, right facial nerve palsy, eye deviation to the left, and aphasia. Magnetic resonance imaging revealed acute ischemic lesions in the left insular cortex and the frontal lobe. Magnetic resonance angiography revealed an occlusion of the left internal carotid artery. Reversed-image mechanical thrombectomy achieved complete reperfusion in three passes within 54 minutes. Six months post-intervention, the patient could walk indoors independently. Our technique, which replicates the normal arterial anatomy by inversion and angulation, was adapted to situs inversus totalis.

Genomic insights into familial adenomatous polyposis: unraveling a rare case with whole APC gene deletion and intellectual disability.

A young patient diagnosed with advanced colon cancer and liver metastasis was found to have familial adenomatous polyposis (FAP) through comprehensive genomic analysis. Whole-genome array comparative genomic hybridization (aCGH) revealed germline deletions at chromosome 5q22.1-22.2 encompassing the entire APC gene. The patient and her son exhibited mild intellectual disability without developmental delay. This case highlights the need for further exploration of the characteristics associated with whole APC deletions. aCGH is a valuable tool for studying FAP and provides a detailed analysis of large deletions.

New gel immersion endoscopic ultrasonography technique for accurate periampullary evaluation.

BACKGROUND: Visualization of the pancreatobiliary junction is one of the challenges faced by endoscopic ultrasonography (EUS). The water-filling technique, which allows for the observation of the ampulla at a suitable distance by injecting water into the lumen of the duodenum, was used for this purpose. However, a new gel immersion technique has recently been introduced for visualizing the gastrointestinal tract. This study investigated the effectiveness of visualizing the pancreatobiliary junction in EUS by comparing both water filling and the new gel immersion technique in identical cases. METHODS: The study ran from June to December 2021. Ten images from each technique were retrospectively compared by three independent researchers. The primary result of the study was the number of images depicting the "Pancreatic and Biliary Ducts Penetrating the Duodenal Muscularis Propria" (defined as Excellent observation) in each technique. The secondary outcome was defined as gel immersion technique's safety and impact on duodenal lumen distension. RESULTS: Ten patients used the gel immersion technique. All patients underwent the water-filling technique first, followed by gel injection after the water was completely aspirated. The average number of pictures rated as "Excellent observation," which is the primary outcome, was significantly higher with the gel immersion technique than with water filling, and no adverse events were observed. The subanalysis revealed that both convex and radial echoendoscopes are equally effective at depicting the ampulla with the gel immersion technique. CONCLUSIONS: The ability to depict the pancreatobiliary junction using the gel immersion technique is superior to that of the water-filling method, which may allow for a more detailed assessment of the ampullary region with both radial and convex echoendoscopes. This can be a useful EUS technique for diagnosing pancreaticobiliary maljunction or periampullary tumors.

Small Insulinoma Followed-up as an Indolent Pancreatic Tumor: A Case Report.

A woman in her 60s presented with a small pancreatic head tumor. Imaging studies revealed a 13-mm well-defined pancreatic head tumor. A neuroendocrine neoplasm was suspected, and the patient opted for observation at that time. After 8 months, the patient began experiencing sweating while fasting, and blood tests during regular follow-up visits showed hypoglycemia. Hypoglycemia was induced during fasting test. The tumor exhibited clear features of an insulinoma during follow-up observation. While small neuroendocrine neoplasms are often managed through observation, caution should be exercised regarding their transformation into functional neuroendocrine tumors.

Frontal Sinus Mucosa Bacteriological Features: Evaluation after Unintentional Opening in Neurosurgery.

Objectives The bacteriological features of the frontal sinus mucosa may impose significant complications in neurosurgery, when breached unintentionally. This study aimed to investigate the bacterial flora in patients undergoing frontal craniotomy for cerebrovascular substrate surgery. Design This is a single-center prospective study. Setting When mucosal laceration occurred, the patients underwent frontal sinus reconstruction with mucosa reconstruction, preserving the nasofrontal duct. Participants We enrolled eight consecutive patients who underwent bifrontal craniotomy associated with frontal sinus mucosa laceration. Main Outcome Measures A portion of the mucosa was extracted during the reconstructive procedure and was sent for microbiological analysis. Results None of the patients presented with the bacterial flora in the mucosal cultures. No patient experienced postoperative cerebrospinal fluid leakage or meningitis. One patient with a clinical history of chronic maxillary sinusitis presented with a subcutaneous abscess around the forehead at 9 months postoperatively. The patient rapidly recovered after receiving oral administration of antibiotics. Conclusions Our findings demonstrated that the frontal sinuses were maintained in an aseptic environment in all cases. The results may encourage the development and wider use of transfrontal sinus approaches.

A novel prediction tool for mortality in patients with acute lower gastrointestinal bleeding requiring emergency hospitalization: a large multicenter study.

The study aimed to identify prognostic factors for patients with acute lower gastrointestinal bleeding and to develop a high-accuracy prediction tool. The analysis included 8254 cases of acute hematochezia patients who were admitted urgently based on the judgment of emergency physicians or gastroenterology consultants (from the CODE BLUE J-study). Patients were randomly assigned to a derivation cohort and a validation cohort in a 2:1 ratio using a random number table. Assuming that factors present at the time of admission are involved in mortality within 30 days of admission, and adding management factors during hospitalization to the factors at the time of admission for mortality within 1 year, prognostic factors were established. Multivariate analysis was conducted, and scores were assigned to each factor using regression coefficients, summing these to measure the score. The newly created score (CACHEXIA score) became a tool capable of measuring both mortality within 30 days (ROC-AUC 0.93) and within 1 year (C-index, 0.88). The 1-year mortality rates for patients classified as low, medium, and high risk by the CACHEXIA score were 1.0%, 13.4%, and 54.3% respectively (all P < 0.001). After discharge, patients identified as high risk using our unique predictive score require ongoing observation.

Liquid Biopsy for Pancreatic Cancer by Serum Extracellular Vesicle-Encapsulated Long Noncoding RNA HEVEPA.

OBJECTIVES: The role of long noncoding RNAs (lncRNAs) in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Extracellular vesicle (EV)-encapsulated RNAs could be effective targets for liquid biopsy. We aimed to identify previously unknown EV-encapsulated lncRNAs in PDAC and establish highly accurate methods for isolating EVs. MATERIALS AND METHODS: Extracellular vesicles were isolated using existing and newly developed methods, namely, PEViA-UC and PEViA-IP, from serum samples of 20 patients with PDAC, 22 patients with intraductal papillary mucinous neoplasms, and 21 healthy individuals. Extracellular vesicle lncRNA expression was analyzed using digital PCR. RESULTS: Gene expression analysis using cDNA microarray revealed a highly expressed lncRNA, HEVEPA, in serum EVs from patients with PDAC. We established PEViA-UC and PEViA-IP using PEViA reagent, ultracentrifugation, and immunoprecipitation. Although detection of EV-encapsulated HEVEPA using existing methods is challenging, PEViA-UC and PEViA-IP detected EV HEVEPA, which was highly expressed in patients with PDAC compared with non-PDAC patients. The detection sensitivity for discriminating PDAC from non-PDAC using the combination of HEVEPA and HULC, which are highly expressed lncRNAs in PDAC, and carbohydrate antigen 19-9 (CA19-9), was higher than that of HEVEPA, HULC, or CA19-9 alone. CONCLUSIONS: Extracellular vesicle lncRNAs isolated using PEViA-IP and CA19-9 together could be effective targets in liquid biopsy for PDAC diagnosis.

High risk stigmata and treatment strategy for acute lower gastrointestinal bleeding: a nationwide study in Japan.

BACKGROUND: The rebleeding risks and outcomes of endoscopic treatment for acute lower gastrointestinal bleeding (ALGIB) may differ depending on the bleeding location, type, and etiology of stigmata of recent hemorrhage (SRH) but have yet to be fully investigated. We aimed to identify high risk endoscopic SRH and to propose an optimal endoscopic treatment strategy. METHODS: We retrospectively analyzed 2699 ALGIB patients with SRH at 49 hospitals (CODE BLUE-J Study), of whom 88.6 % received endoscopic treatment. RESULTS: 30-day rebleeding rates of untreated SRH significantly differed among locations (left colon 15.5 % vs. right colon 28.6 %) and etiologies (diverticular bleeding 27.5 % vs. others [e. g. ulcerative lesions or angioectasia] 8.9 %), but not among bleeding types. Endoscopic treatment reduced the overall rebleeding rate (adjusted odds ratio [AOR] 0.69; 95 %CI 0.49-0.98), and the treatment effect was significant in right-colon SRH (AOR 0.46; 95 %CI 0.29-0.72) but not in left-colon SRH. The effect was observed in both active and nonactive types, but was not statistically significant. Moreover, the effect was significant for diverticular bleeding (AOR 0.60; 95 %CI 0.41-0.88) but not for other diseases. When focusing on treatment type, the effectiveness was not significantly different between clipping and other modalities for most SRH, whereas ligation was significantly more effective than clipping in right-colon diverticular bleeding. CONCLUSIONS: A population-level endoscopy dataset allowed us to identify high risk endoscopic SRH and propose a simple endoscopic treatment strategy for ALGIB. Unlike upper gastrointestinal bleeding, the rebleeding risks for ALGIB depend on colonic location, bleeding etiology, and treatment modality.

The BAP1 nuclear deubiquitinase is involved in the nonhomologous end-joining pathway of double-strand DNA repair through interaction with DNA-PK.

BRCA1-associated protein 1 (BAP1) has emerged as a major tumor suppressor gene in diverse cancer types, notably in malignant pleural mesothelioma (DPM), and has also been identified as a germline cancer predisposition gene for DPM and other select cancers. However, its role in the response to DNA damage has remained unclear. Here, we show that BAP1 inactivation is associated with increased DNA damage both in Met-5A human mesothelial cells and human DPM cell lines. Through proteomic analyses, we identified PRKDC as an interaction partner of BAP1 protein complexes in DPM cells and 293 T human embryonic kidney cells. PRKDC encodes the catalytic subunit of DNA protein kinase (DNA-PKcs) which functions in the nonhomologous end-joining (NHEJ) pathway of DNA repair. Double-stranded DNA damage resulted in prominent nuclear expression of BAP1 in DPM cells and phosphorylation of BAP1 at serine 395. A plasmid-based NHEJ assay confirmed a significant effect of BAP1 knockdown on cellular NHEJ activity. Combination treatment with X-ray irradiation and gemcitabine (as a radiosensitizer) strongly suppressed the growth of BAP1-deficient cells. Our results suggest reciprocal positive interactions between BAP1 and DNA-PKcs, based on phosphorylation of BAP1 by the latter and deubiquitination of DNA-PKcs by BAP1. Thus, functional interaction of BAP1 with DNA-PKcs supports a role for BAP1 in NHEJ DNA repair and may provide the basis for new therapeutic strategies and new insights into its role as a tumor suppressor.

Non fire-adapted dry forest of Northwestern Madagascar: Escalating and devastating trends revealed by Landsat timeseries and GEDI lidar data.

Ankarafantsika National Park (ANP), the last significant remnant of Northwestern Madagascar's tropical dry forests, is facing rapid degradation due to increased incidences of fire. This poses severe threats to biodiversity, local livelihoods, and vital ecosystem services. Our study, conducted on 3,052-ha of ANP's pristine forests, employed advanced remote-sensing techniques to assess fire impacts during the past 37 years. Our aims were to understand historical fire patterns and evaluate forest recovery and susceptibility to repeated fires following initial burns. Using data from multiple Landsat satellite sensors, we constructed a time series of fire events since 1985, which revealed no fire activity before 2014. The Global Ecosystem Dynamics Investigation (GEDI) lidar sensor data were used to observe forest structure in both post-fire areas and undisturbed zones for comparison. We recorded six fire incidents from 2014-2021, during which the fire-affected area exponentially grew. A significant fire incident in October 2021 impacted 1,052 hectares, 59% of which had experienced at least one fire in two-to-four years prior, with 60% experiencing two preceding incidents: one in 2017 and another in 2019. The initial fire drastically reduced plant cover and tree height, with subsequent fires causing minor additional loss. Post-fire recovery was negligible within the initial four years, even in patches without recurrent fires. The likelihood for an initial burn to trigger subsequent fires within a few years was high, leading to larger, more severe fires. We conclude that ANP's dry forests exhibit high vulnerability and low resilience to anthropogenic fires. Prompt preventive measures are essential to halt further fire spread and conserve the park's unique and invaluable biodiversity.

The Lambda stenting technique: a new approach to address EUS-guided biliary drainage-associated adverse events.

Background and Aims: EUS-guided biliary drainage (EUS-BD) has been performed increasingly worldwide, especially in patients with malignant tumors in which ERCP is difficult, patients with surgically altered GI tracts, and older patients who are at high risk for surgery. EUS-BD requires high-level skills and has limited options for managing adverse events, particularly when stent migration and cholangitis occur. Adverse events, such as persistent bile leakage from the fistula and continuous reflux from the GI tract, are believed to always have a risk of severe exacerbation that could threaten the patient's life. Methods: We encountered 2 cases of stent migrations and 1 case with repeated cholangitis in patients with malignant tumors among the patients who underwent EUS-BD. The migrated stent was visualized under EUS in 2 patients with stent migration, and an EUS-guided FNA needle was used to puncture the mesh of the stent. The cannulation catheter was directly inserted into the mesh of the stent in 1 case with repeated retrograde cholangitis, while the stent was visualized with an endoscope. Subsequently, a guidewire was inserted through the puncture site, and a second metal stent was deployed between the meshes of the first stent, bridging the GI wall again (Lambda stenting technique). All procedures were performed with the patient under general anesthesia, and the patients safely completed the intervention. Results: Patients' conditions significantly improved after the second stent insertion, allowing for chemotherapy resumption while maintaining their activities of daily living. The second stent remained in place without any migration, and the stent successfully prevented further cholangitis. Conclusions: The Lambda stenting technique is considered highly effective for managing stent migration and repeated cholangitis, which is a major EUS-BD adverse event. This procedure helps avoid more invasive surgeries when stent migration and cholangitis occur and contributes to expanding EUS-BD applicability.

Impact of the COVID-19 Pandemic on the Long-Term Prognosis of Acute Myocardial Infarction in Japan.

Background During the early phase of the coronavirus disease 2019 (COVID-19) pandemic, a global reduction in hospitalizations for acute myocardial infarction (AMI) was observed. Generally, patients experienced increased severity of AMI with delays in time from symptom onset to treatment during the pandemic. However, the impact of the COVID-19 pandemic on in-hospital mortality among patients with AMI remains unclear. This study aimed to compare the long-term prognosis of patients with AMI during the COVID-19 pandemic to that observed in the pre-pandemic period and to evaluate the influence of the COVID-19 pandemic on the prognosis of patients with AMI. Methods We reviewed the data of patients admitted to our hospital for AMI treatment between April 1, 2018, and March 31, 2021. The time from admission to major adverse cardiac events (MACE), as well as the time from admission to all-cause death, were examined between the pandemic period (April 1, 2020, to March 31, 2021) and the pre-pandemic period (April 1, 2018, to March 31, 2020). Results Eighty patients were included in the study, and those admitted during the pandemic exhibited a higher likelihood of advanced age, lower levels of LDL-cholesterol, and a reduced prevalence of hypertension. The 2.5-year MACE-free survival and overall survival rates between the patients during the pre-pandemic and pandemic periods were not significantly different. Conclusion The long-term prognosis of patients with AMI during the COVID-19 pandemic remains unclear. In this study, we reported that the 2.5-year MACE-free survival and overall survival rates of the patients with AMI admitted during the COVID-19 pandemic were not significantly different from those during the pre-pandemic period. The impact of the COVID-19 pandemic on the prognosis of patients with AMI appears to vary according to the study population.

Corrigendum: Use of the index of pulmonary vascular disease for predicting longterm outcome of pulmonary arterial hypertension associated with congenital heart disease.

[This corrects the article DOI: 10.3389/fcvm.2023.1212882.].

Pharmacological Inhibition of Epidermal Growth Factor Receptor Prevents Intracranial Aneurysm Rupture by Reducing Endoplasmic Reticulum Stress.

BACKGROUND: Multiple pathways and factors are involved in the rupture of intracranial aneurysms. The EGFR (epidermal growth factor receptor) has been shown to mediate inflammatory vascular diseases, including atherosclerosis and aortic aneurysm. However, the role of EGFR in mediating intracranial aneurysm rupture and its underlying mechanisms have yet to be determined. Emerging evidence indicates that endoplasmic reticulum (ER) stress might be the link between EGFR activation and the resultant inflammation. ER stress is strongly implicated in inflammation and apoptosis of vascular smooth muscle cells, both of which are key components of the pathophysiology of aneurysm rupture. Therefore, we hypothesized that EGFR activation promotes aneurysmal rupture by inducing ER stress. METHODS: Using a preclinical mouse model of intracranial aneurysm, we examined the potential roles of EGFR and ER stress in developing aneurysmal rupture. RESULTS: Pharmacological inhibition of EGFR markedly decreased the rupture rate of intracranial aneurysms without altering the formation rate. EGFR inhibition also significantly reduced the mRNA (messenger RNA) expression levels of ER-stress markers and inflammatory cytokines in cerebral arteries. Similarly, ER-stress inhibition also significantly decreased the rupture rate. In contrast, ER-stress induction nullified the protective effect of EGFR inhibition on aneurysm rupture. CONCLUSIONS: Our data suggest that EGFR activation is an upstream event that contributes to aneurysm rupture via the induction of ER stress. Pharmacological inhibition of EGFR or downstream ER stress may be a promising therapeutic strategy for preventing aneurysm rupture and subarachnoid hemorrhage.

Vitamin D deficiency promotes intracranial aneurysm rupture.

Intracranial aneurysm rupture causes severe disability and high mortality. Epidemiological studies show a strong association between decreased vitamin D levels and an increase in aneurysm rupture. However, the causality and mechanism remain largely unknown. In this study, we tested whether vitamin D deficiency promotes aneurysm rupture and examined the underlying mechanism for the protective role of vitamin D against the development of aneurysm rupture utilizing a mouse model of intracranial aneurysm. Mice consuming a vitamin D-deficient diet had a higher rupture rate than mice with a regular diet. Vitamin D deficiency increased proinflammatory cytokines in the cerebral arteries. Concurrently, vitamin D receptor knockout mice had a higher rupture rate than the corresponding wild-type littermates. The vitamin D receptors on endothelial and vascular smooth muscle cells, but not on hematopoietic cells, mediated the effect of aneurysm rupture. Our results establish that vitamin D protects against the development of aneurysmal rupture through the vitamin D receptors on vascular endothelial and smooth muscle cells. Vitamin D supplementation may be a viable pharmacologic therapy for preventing aneurysm rupture.

Direct sac puncture embolization for a left subclavian aneurysm with Marfan syndrome: A case report.

Subclavian artery aneurysms, occasionally related to connective tissue diseases, including Marfan syndrome, are rare and conventionally managed with surgery or endovascular treatment. However, in some cases, both interventions are challenging because of the inability to reach an aneurysm through a safe route or postoperative adhesion. This report describes the case of a 43-year-old patient with a left subclavian artery aneurysm and Marfan syndrome. In this case, the patient's 5 previous surgeries related to Marfan syndrome made surgery and endovascular treatment difficult. Therefore, an alternative was researched, and we decided to perform a method of percutaneous embolization with coils and N-butyl cyanoacrylate using the direct puncture technique, which succeeded in eliminating the blood flow in the left subclavian artery aneurysm. No severe complications were associated with the procedure. The patient was free from the risk of an aneurysm rupture post-treatment, and the left back pain improved. Follow-up computed tomography 2 years postsurgery revealed the aneurysm being under control without re-enlarging. Our method is considered an effective and safe therapeutic option for cases in which surgical approach and transarterial access routes are limited.

Dose-Response Relationship of Physical Activity with All-Cause Mortality among Older Adults: An Umbrella Review.

OBJECTIVES: To examine the dose-response relationship between physical activity (PA) and all-cause and cardiovascular disease (CVD) mortality, specifically among older adults. DESIGN: Umbrella review. SETTING AND PARTICIPANTS: Eligible studies included systematic reviews with meta-analyses that investigated the association of aerobic PA, muscle-strengthening activity, and multicomponent PA, including exercise programs (such as aerobic, muscle strengthening, and balance training), with all-cause and CVD mortality among older adults aged ≥60 years. METHODS: We performed a literature search in PubMed, CINAHL, and the Cochrane Library for eligible studies published between January 2017 and March 2023 to update an umbrella review initially conducted by the United States 2018 PA Guidelines Advisory Committee. Studies included in the 2018 US PA and 2020 World Health Organization (WHO) Guidelines were also reviewed. In addition, meta-analyses that reported effect sizes stratified by age and recruiting older adults (aged ≥60 years) were included. RESULTS: Overall, 16 relevant systematic reviews (10 from our review and 6 from the US and WHO guidelines) met the inclusion criteria. All these reviews showed that 7.5 to 15.0 metabolic equivalents (METs)-hours/week (around the recommended PA levels outlined in the US and WHO guidelines) substantially reduced mortality risks among older adults (approximately 19%-30% for all-cause mortality and 25%-34% for CVD mortality). Moreover, 15.0 to 22.5 MET-hours/week, exceeding the guideline-recommended PA levels, resulted in greater reductions in mortality risks by 35% to 37% and 38% to 40%, respectively. CONCLUSIONS AND IMPLICATIONS: PA substantially reduced all-cause and CVD mortality risks among older adults. Larger risk reductions may be achieved by engaging in PA levels higher than those recommended by the current international PA guidelines. Our findings suggest that recommending higher PA levels beyond the current guidelines may benefit older adults when developing future international PA guidelines.