Association of cardiometabolic multimorbidity with all-cause and cardiovascular disease mortality among Chinese hypertensive patients.

BACKGROUND: Hypertension usually clusters with multiple comorbidities. However, the association between cardiometabolic multimorbidity (CMM) and mortality in hypertensive patients is unclear. This study aimed to investigate the association between CMM and all-cause and cardiovascular disease (CVD) mortality in Chinese patients with hypertension. METHODS: The data used in this study were from the China National Survey for Determinants of Detection and Treatment Status of Hypertensive Patients with Multiple Risk Factors (CONSIDER), which comprised 5006 participants aged 19-91 years. CMM was defined as the presence of one or more of the following morbidities: diabetes mellitus, dyslipidemia, chronic kidney disease, coronary heart disease, and stroke. Cox proportional hazard models were used to calculate the hazard ratios (HR) with 95% CI to determine the association between the number of CMMs and both all-cause and CVD mortality. RESULTS: Among 5006 participants [mean age: 58.6 ± 10.4 years, 50% women (2509 participants)], 76.4% of participants had at least one comorbidity. The mortality rate was 4.57, 4.76, 8.48, and 16.04 deaths per 1000 person-years in hypertensive patients without any comorbidity and with one, two, and three or more morbidities, respectively. In the fully adjusted model, hypertensive participants with two cardiometabolic diseases (HR = 1.52, 95% CI: 1.09-2.13) and those with three or more cardiometabolic diseases (HR = 2.44, 95% CI: 1.71-3.48) had a significantly elevated risk of all-cause mortality. The findings were similar for CVD mortality but with a greater increase in risk magnitude. CONCLUSIONS: In this study, three-fourths of hypertensive patients had CMM. Clustering with two or more comorbidities was associated with a significant increase in the risk of all-cause and cardiovascular mortality among hypertensive patients, suggesting more intensive treatment and control in this high-risk patient group.

METTL3-mediated m6 A methylation of TRAF5 inhibits lung adenocarcinoma cell metastasis via activation of the PI3K/AKT/NF-κB signaling pathway.

Tumor necrosis factor receptor-associated factor 5 (TRAF5) has been implicated in the pathogenesis of human malignancies. This work aimed to clarify the role of TRAF5 in lung adenocarcinoma (LUAD) progression. Herein, we uncovered that TRAF5 level was reduced in LUAD tissues. Low TRAF5 expression correlated with dismal prognosis in LUAD patients. Moreover, upregulated TRAF5 impeded cell viability, migration, and invasion, induced apoptosis in vitro, as well as impaired tumorigenicity in vivo. However, depletion of TRAF5 revealed opposing results. Moreover, TRAF5 was identified as the downstream target of methyltransferase-like 3 (METTL3)-elicited N6 -methyladenosine (m6 A) modification. METTL3 stabilized TRAF5 mRNA and positively modulated TRAF5 level. Further, TRAF5 depletion relieved the repressive phenotype caused by METTL3 addition. In addition, it was manifested that the METTL3/TRAF5 axis served as an inhibitor in LUAD through the PI3K/AKT/Nuclear Factor-Kappa B (NF-κB) signaling. Collectively, we propose that METTL3-mediated TRAF5 m6 A modification exerted as a vital tumor inhibitory function in LUAD development. The METTL3/TRAF5 axis may be a critical effector of LUAD progression.

Efficacy and safety comparison of infrared laser moxibustion and traditional moxibustion in knee osteoarthritis: study protocol for a Zelen-design randomized controlled non-inferiority clinical trial.

BACKGROUND: Knee osteoarthritis (KOA) is the most common chronic degenerative joint disease and places a substantial burden on the public health resources in China. The purpose of this study is to preliminarily evaluate whether infrared laser moxibustion (ILM) is non-inferior to traditional moxibustion (TM) in the treatment of KOA. MATERIALS AND METHODS: In the designed Zelen-design randomized controlled non-inferiority clinical trial, a total of 74 patients with KOA will be randomly allocated to one of two interventions: ILM treatment or TM treatment. All participants will receive a 6-week treatment and a follow-up 4 weeks after treatment. The primary outcomes will be the mean change in pain scores on the numeric rating scale (NRS) measured at baseline and the end of last treatment at week 6. The secondary outcomes will be the pain scores on the NRS from weeks 1 to 5 after the start of treatment and the changes from baseline to endpoints (weeks 6 and 10) in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), SF-36, knee circumference, and 6-min walking test. In addition, safety assessment will be performed throughout the trial. CONCLUSION: The results of our study will help determine whether a 6-week treatment with ILM is non-inferior to TM in patients with KOA, therefore providing evidence to verify if ILM can become a safer alternative for TM in clinical applications in the future. TRIAL REGISTRATION: Clinical Trial Registration Platform (ChiCTR2200065264); Pre-results. Registered on 1 November 2022.

Low-dose decitabine for previously untreated acute myeloid leukemia ineligible for intensive chemotherapy aged 65 years or older: a prospective study based on comprehensive geriatric assessment.

Background: The outcome of patients with acute myeloid leukemia (AML) aged ⩾65 years is poor. Effective treatment options are limited for patients with AML who cannot tolerate intensive chemotherapy. Objectives: We aimed to evaluate the efficacy of low-dose decitabine in previously untreated patients with AML aged ⩾65 years who were ineligible for intensive chemotherapy based on a comprehensive geriatric assessment. Design: We performed a prospective, multicenter, open-label, and non-randomized study. Methods: Patients were enrolled at four centers in Beijing between 1 January 2017 and 31 December 2020. They were treated with decitabine at a dose of 6 mg/m2 for 10 days. The treatment was repeated every 28 days for one cycle for a total of six cycles. The primary endpoint of our study was overall survival (OS) at the end of the first year after enrolment. The secondary endpoints included overall response rate, leukemia-free survival, relapse rate, treatment-related mortality (TRM), quality of life, safety, and transfusion dependence. Patients were continuously monitored for toxicity. Results: Overall, 47 patients (30 males and 17 females) participated in this study. The median age of the enrolled patients was 78 (range, 65-90) years. The median follow-up time was 22.2 (range, 4.6-38.8) months. Fifteen (31.9%) patients achieved complete remission (CR), 11 (23.4%) patients achieved partial remission, 3 (6.4%) patients achieved hematological improvement only, and 18 (38.3%) patients did not achieve remission. The median time to obtain CR was 2 months. The median CR was 8.5 months. Of the patients, 36 (76.6%) patients completed six cycles of treatment with low-dose decitabine, and the 1-year OS was 36.1%. According to instrumental activities of daily living scales, age, comorbidities, and albumin (IACA) scores, the median survival was 11.2 months in the unfit group and 6 months in the frail group. The 1-year OS rates in the unfit and frail groups were 49.2% and 23.4%, respectively. Grade ⩾3 non-hematological toxicity was observed in 70.2% (33/47) of the patients. TRM occurred in three patients. No early deaths occurred after treatment. Conclusion: In newly diagnosed older patients with AML whose IACA assessment was unfit or frail for standard chemotherapy, treatment with low-dose decitabine demonstrated clinical activity and good security in our study.

Vascular endothelial growth factor protein and gene delivery by novel nanomaterials for promoting liver regeneration after partial hepatectomy.

Partial hepatectomy (PH) can lead to severe complications, including liver failure, due to the low regenerative capacity of the remaining liver, especially after extensive hepatectomy. Liver sinusoidal endothelial cells (LSECs), whose proliferation occurs more slowly and later than hepatocytes after PH, compose the lining of the hepatic sinusoids, which are the smallest blood vessels in the liver. Vascular endothelial growth factor (VEGF), secreted by hepatocytes, promotes LSEC proliferation. Supplementation of exogenous VEGF after hepatectomy also increases the number of LSECs in the remaining liver, thus promoting the reestablishment of the hepatic sinusoids and accelerating liver regeneration. At present, some shortcomings exist in the methods of supplementing exogenous VEGF, such as a low drug concentration in the liver and the reaching of other organs. More-over, VEGF should be administered multiple times and in large doses because of its short half-life. This review summarized the most recent findings on liver regeneration and new strategies for the localized delivery VEGF in the liver.

Systemic Inflammation Response Index Predicts Clinical Outcomes in Patients With Acute Ischemic Stroke (AIS) After the Treatment of Intravenous Thrombolysis.

BACKGROUND: Intravenous thrombolysis (IVT) is one of the most important means of therapy for patients with acute ischemic stroke (AIS). After cerebral infarction, the inflammatory response fulfills an essential role in the pathobiology of stroke, affecting the process of recanalization. Hence, we evaluated the usefulness of the systemic inflammatory response index (SIRI) for the prognosis of patients with AIS. METHODS: A total of 161 patients suffering from AIS were retrospectively analyzed. SIRI was introduced and calculated using the absolute neutrophil, monocyte, and lymphocyte numbers from the admission blood work. The study outcomes were determined using a modified Rankin Scale (mRS) at the 3-month timepoint, and a favorable clinical outcome was calculated in the mRS score range of 0 to 2. The analysis of receiver operating characteristic (ROC) curves was performed to determine the values of the optimal cutoff of SIRI for the prediction of clinical outcomes. In addition, multivariate analyses were performed to investigate the association between clinical outcomes and SIRI. RESULTS: The ROC curve analysis revealed that the ideal SIRI cutoff was at 2.54 [area under the curve, 78.85%; 95% CI, 71.70% to 86.00%; sensitivity, 70.89%; and specificity, 84.14%]. Multivariate analysis indicated that SIRI ≤2.54 (odds ratio, 1.557, 95% CI, 1.269 to 1.840; P =0.021) was an independent predictor of favorable clinical outcomes in patients suffering from AIS after treatment with IVT. CONCLUSIONS: We preliminary speculate that SIRI may serve as an independent predictor of clinical outcomes with AIS following IVT.

[Behavioral and physiological responses to hypoxia stress in male and female Macrobrachium rosenbergii]. / 雌雄罗氏沼虾应对低氧胁迫的行为生理响应.

To explore the physiological and behavioral responses of male and female Macrobrachium rosenbergii under hypoxia stress, an experiment with three dissolved oxygen (DO) levels (6.46, 4.48 and 3.27 mg·L-1, 6.46 mg·L-1 as control) was conducted. The enzyme activities of energy metabolism in hepatopancreas and muscles of male and female M. rosenbergii were measured after six days of hypoxia stress. The results showed that the enzyme activities of aerobic metabolism in muscles and swimming abilities were significantly decreased as DO decreased from 6.46 mg·L-1 to 4.48 mg·L-1, with the decreases being less in males than females. There was no significant difference in enzyme activities of anaerobic metabolism. When DO was further decreased to 3.27 mg·L-1, the enzyme activities of aerobic metabolism and anaerobic metabolism in muscles significantly decreased. The activity of lactate dehydrogenase (LDH) in anaerobic metabolism of hepatopancreas and tail-flipping speeds significantly decreased in males and females, with less decrease in females than that in males for LDH activity of hepatopancreas. The swimming ability was positively correlated with the enzyme activities of aerobic metabolism in pleopods muscles. There was significant correlation between tail-flipping abilities and enzyme activities of anaerobic metabolism. M. rosenbergii could reduce its reliance on energy metabolism during hypoxia stress, but with negative consequences on locomotor abilities. The muscles were preferentially powered to meet energy requirements of locomotion in males, while females gave priority to energy supply for hepatopancreas under insufficient oxygen conditions.

Solitary fibrous tumor of the liver: A case report and review of the literature.

BACKGROUND: Hepatic solitary fibrous tumor (SFT) is a rare neoplasm. Up to now, only 90 cases have been reported in the English language literature. This report describes a case of SFT of the liver misdiagnosed as hepatocellular carcinoma. CASE SUMMARY: A 42-year-old male had a two-year history of a gradually enlarging intrahepatic nodule. The preoperative imaging revealed a mass with a size of 2.7 cm × 2.3 cm located in the segment IV of the liver. The patient was subjected to the resection of the segment IV, such as the medial segment of the left lobe of the liver. The histological examination of the mass showed various spindled cells irregularly arranged in the stroma. The immunohistochemistry of this mass revealed a positive staining for CD34 and STAT6. The history of intracranial tumor and postoperative pathological results led to the diagnosis of SFT of the liver (SFTL) due to a metastasis from the brain. CONCLUSION: SFTL is an uncommon mesenchymal neoplasm that can be easily overlooked or misdiagnosed. The best treatment choice is the complete surgical resection of the mass. A regular follow-up after the surgery should be performed due to the poor prognosis of metastatic or recurrent SFT.

Intrahepatic sarcomatoid cholangiocarcinoma: A case report of the youngest patient on record and a review of the condition's characteristics.

As a rare disease, intrahepatic sarcomatoid cholangiocarcinoma (s-CCC) represents less than 1% of malignancies of the hepatobiliary system and its main clinical symptoms include abdominal pain and fever. Results of pathological examinations, despite being the "gold standard", can easily be confused with hepatocellular carcinoma (HCC). This report is about a 32-year-old male patient who was hospitalized due to occupancy of segment V of the liver for three days and had a history of chronic hepatitis B (CHB) over a 20-year span. Magnetic resonance imaging (MRI) showed a 43 mm × 52 mm-sized liver mass in the V segment, with patchy peripheral enhancement during the arterial phase and rapid wash-out during the portal and late phases. A laparoscopic hepatectomy of segment V, along with cholecystectomy, was performed. Histopathological and immunohistochemical examinations indicated a malignant neoplasm that was positive for vimentin and cytokeratin, with these features providing a positive diagnosis for intrahepatic sarcomatoid cholangiocarcinoma. After surgery, an adjuvant therapy of albumin-paclitaxel combined with gemcitabine regimen was given. No recurrence was found six months after the surgery, with follow-up still ongoing. This report aims to improve the awareness, diagnosis, and treatment of s-CCC.

Preoperative prediction of intrahepatic cholangiocarcinoma lymph node metastasis by means of machine learning: a multicenter study in China.

BACKGROUND: Hepatectomy is currently the most effective modality for the treatment of intrahepatic cholangiocarcinoma (ICC). The status of the lymph nodes directly affects the choice of surgical method and the formulation of postoperative treatment plans. Therefore, a preoperative judgment of lymph node status is of great significance for patients diagnosed with this condition. Previous prediction models mostly adopted logistic regression modeling, and few relevant studies applied random forests in the prediction of ICC lymph node metastasis (LNM). METHODS: A total of 149 ICC patients who met clinical conditions were enrolled in the training group. Taking into account preoperative clinical data and imaging features, 21 indicators were included for analysis and modeling. Logistic regression was used to filter variables through multivariate analysis, and random forest regression was used to rank the importance of these variables through the use of algorithms. The model's prediction accuracy was assessed by the concordance index (C-index) and calibration curve and validated with external data. RESULT: Multivariate analysis shows that Carcinoembryonic antigen (CEA), Carbohydrate antigen19-9 (CA19-9), and lymphadenopathy on imaging are independent risk factors for lymph node metastasis. The random forest algorithm identifies the top four risk factors as CEA, CA19-9, and lymphadenopathy on imaging and Aspartate Transaminase (AST). The predictive power of random forest is significantly better than the nomogram established by logistic regression in both the validation group and the training group (Area Under Curve reached 0.758 in the validation group). CONCLUSIONS: We constructed a random forest model for predicting lymph node metastasis that, compared with the traditional nomogram, has higher prediction accuracy and simultaneously plays an auxiliary role in imaging examinations.

Metagenomics Reveals Dominant Unusual Sulfur Oxidizers Inhabiting Active Hydrothermal Chimneys From the Southwest Indian Ridge.

The deep-sea hydrothermal vents (DSHVs) in the Southwest Indian Ridge (SWIR) are formed by specific geological settings. However, the community structure and ecological function of the microbial inhabitants on the sulfide chimneys of active hydrothermal vents remain largely unknown. In this study, our analyses of 16S rRNA gene amplicons and 16S rRNA metagenomic reads showed the dominance of sulfur-oxidizing Ectothiorhodospiraceae, Thiomicrorhabdus, Sulfurimonas, and Sulfurovum on the wall of two active hydrothermal chimneys. Compared with the inactive hydrothermal sediments of SWIR, the active hydrothermal chimneys lacked sulfur-reducing bacteria. The metabolic potentials of the retrieved 82 metagenome-assembled genomes (MAGs) suggest that sulfur oxidation might be conducted by Thiohalomonadales (classified as Ectothiorhodospiraceae based on 16S rRNA gene amplicons), Sulfurovaceae, Hyphomicrobiaceae, Thiotrichaceae, Thiomicrospiraceae, and Rhodobacteraceae. For CO2 fixation, the Calvin-Benson-Bassham and reductive TCA pathways were employed by these bacteria. In Thiohalomonadales MAGs, we revealed putative phytochrome, carotenoid precursor, and squalene synthesis pathways, indicating a possible capacity of Thiohalomonadales in adaptation to dynamics redox conditions and the utilization of red light from the hot hydrothermal chimneys for photolithotrophic growth. This study, therefore, reveals unique microbiomes and their genomic features in the active hydrothermal chimneys of SWIR, which casts light on ecosystem establishment and development in hydrothermal fields and the deep biosphere.

Stereoselective intermolecular radical cascade reactions of tryptophans or ɤ-alkenyl-α-amino acids with acrylamides via photoredox catalysis.

The radical cascade reaction is considered as one of the most powerful methods to build molecular complexity. However, highly stereoselective intermolecular radical cascade reactions that can produce complex cyclic compounds bearing multiple stereocenters via visible-light-induced photocatalysis have been challenging yet desirable. Herein we report a facile and efficient synthesis of multi-substituted trans-fused hexahydrocarbazoles via a stereoselective intermolecular radical cascade reaction of readily available tryptophans and acrylamides enabled by visible-light-induced photoredox catalysis. The trans-fused hexahydrocarbazoles with up to five stereocenters including two quaternary ones can be accessed in up to 82% yield, >20/1 diastereoselectivity, and 96% ee. Interestingly, the tetrahydrocarbazoles are favorably formed when the reaction is performed under air. Moreover, by simply switching the starting material from tryptophans to ɤ-alkenyl substituted α-amino acids, this protocol can be further applied to the stereoselective syntheses of 1,3,5-trisubstituted cyclohexanes which are otherwise challenging to access. Preliminary mechanistic studies suggest that the reaction goes through radical addition cascade and radical-polar crossover processes.

Evolving Treatment of Advanced Hepatocellular Carcinoma in the Asia-Pacific Region: A Review and Multidisciplinary Expert Opinion.

Hepatocellular carcinoma (HCC) is the fourth most common driver of cancer-related death globally, with an estimated 72% of cases in Asia. For more than a decade, first-line systemic treatments for advanced or unresectable HCC were limited to the multi-targeted kinase inhibitors sorafenib and, more recently, lenvatinib. Now, treatment options have expanded to include immunotherapy, as exemplified by the immune checkpoint inhibitor (ICI) atezolizumab combined with the antiangiogenic agent bevacizumab. Additional combinations of ICIs with kinase inhibitors, other ICIs, or antiangiogenic agents are under investigation, further supporting the new era of immunotherapy for first-line treatment of advanced or unresectable HCC. We describe this evolving landscape and provide expert opinion on therapeutic best practices in the Asia-Pacific region, where different costs of, and patient access to, treatment are a challenge. With the combination of atezolizumab plus bevacizumab likely to become the clinical standard of care, optimising treatment sequence and ensuring patient access to newer therapies remain priorities. Cost containment and treatment sequencing may be facilitated by characterisation of predictive positive and negative biomarkers. With these considerations in mind, this review and expert opinion focused on advanced HCC in the Asia-Pacific region offers perspectives of multiple stakeholders, including physicians, payer systems, and patients.

Holographic Optical Tweezers and Boosting Upconversion Luminescent Resonance Energy Transfer Combined Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas12a Biosensors.

Taking advantage of outstanding precision in target recognition and trans-cleavage ability, the recently discovered CRISPR/Cas12a system provides an alternative opportunity for designing fluorescence biosensors. To fully exploit the analytical potential, we introduce here some meaningful concepts. First, the collateral cleavage of CRISPR/Cas12a is efficiently activated in a functional DNA regulation manner and the bottleneck which largely applicable to nucleic acids detection is broken. After selection of a representative aptamer and DNAzyme as the transduction pathways, the sensing coverage is extended to a small organic compound (ATP) and a metal ion (Na+). The assay sensitivity is significantly improved by utilizing a bead-supported enrichment strategy wherein emerging holographic optical tweezers are used to enhance imaging stability and simultaneously achieve multiflux analysis. Last, a sandwich-structured energy-concentrating upconversion nanoparticle triggered boosting luminescent resonance energy transfer mode is comined to face with complicated biological samples by skillfully confining the emitters into a very limited inner shell. Following the above attempts, the developed CRISPR/Cas12a biosensors not only present an ultrasensitive assay behavior toward these model non-nucleic acid analytes but also can serve as a formidable toolbox for determining real samples including single cell lysates and human plasma, proving a good practical application capacity.

Patient-centered developments in colon- and rectal cancer with a multidisciplinary international team: From translational research to national guidelines.

Rarely, scientific developments centered around the patient as a whole are published. Our multidisciplinary group, headed by gastrointestinal surgeons, applied this research philosophy considering the most important aspects of the diseases "colon- and rectal cancer" in the long-term developments. Good expert cooperation/knowledge at the Comprehensive Cancer Center Ulm (CCCU) were applied in several phase III trials for multimodal treatments of primary tumors (MMT) and metastatic diseases (involving nearly 2000 patients and 64 centers), for treatment individualization of MMT and of metastatic disease, for psycho-oncology/quality of life involving the patients' wishes, and for disease prevention. Most of the targets initially were heavily rejected/discussed in the scientific communities, but now have become standards in treatments and national guidelines or are topics in modern translational research protocols involving molecular biology for e.g., "patient centered individualized treatment". In this context we also describe the paths we had to tread in order to realize our new goals, which at the end were highly beneficial for the patients from many points of view. This description is also important for students and young researchers who, with an actual view on our recent developments, might want to know how medical progress was achieved.

Catalytic Enantioselective Synthesis and Switchable Chiroptical Property of Inherently Chiral Macrocycles.

We report herein a strategy to construct enantiopure inherently chiral macrocycles, ABCD-type heteracalix[4]aromatics, through a catalytic enantioselective intramolecular C-N bond forming reaction. A chiral ligand-palladium complex was found to efficiently induce the inherent chirality of molecules during the macrocyclization process with ee values up to >99%. The resulting ABCD-type heteracalix[4]aromatics displayed excellent and pH-triggered switchable electronic circular dichroism and circularly polarized luminescence properties.

Comprehensive Geriatric Assessment (CGA): A Simple Tool for Guiding the Treatment of Older Adults with Diffuse Large B-Cell Lymphoma in China.

BACKGROUND: We aimed to validate a simple Comprehensive Geriatric Assessment (CGA) in older adults with diffuse large B-cell lymphoma (DLBCL) in China and to evaluate the tolerability and efficacy of CGA-driven therapy. MATERIALS AND METHODS: In total, 78 patients with DLBCL aged ≥60 years were evaluated using CGA with the following parameters: age ≥ 80 years, activities of daily living (ADL), instrumental ADL, and modified cumulative illness rating score for geriatrics. Patients were grouped as fit, unfit, or frail. Patients classified as fit received standard-dose rituximab plus CHOP, whereas patients in the latter two groups received reduced-dose or reduced-agent therapy. The overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and toxicities in the three groups were evaluated. RESULTS: According to the CGA, 45 (57.5%) patients were classified as fit, 5 (6.4%) as unfit, and 28 (35.9%) as frail. The ORR was 82.1% (64/78) among all the patients, including 55 patients (70.6%) who achieved complete response and 9 patients (11.5%) who achieved partial response. In the fit and unfit + frail groups, it achieved 97.8% and 60.6%, respectively. In total, 26 (33.3%) patients (10/45 [22.2%] fit and 16/33 [48.5%] unfit + frail) showed disease progression or recurrence. The median follow-up time was 18 months (range, 5-62). The 3-year OS and PFS rates were 82% and 58%, respectively. There were no treatment-related deaths. CONCLUSION: A simple CGA in older adults with DLBCL may be an effective tool for guiding therapeutic strategies in China. IMPLICATIONS FOR PRACTICE: Diffuse large B-cell lymphoma (DLBCL) is the most common malignant lymphoma in older adults. The simple tool, Comprehensive Geriatric Assessment (CGA), is proved to be an effective method to identify older adults with DLBCL who are suitable for standard-dose R-CHOP regimen therapy. This is the first prospective trial in China to evaluate the tolerability and efficacy of CGA-driven therapy for older adults with DLBCL, and the result showed that this simple CGA may be an effective tool for guiding therapeutic strategies.

Malignant solitary fibrous tumor of the pancreas with systemic metastasis: A case report and review of the literature.

BACKGROUND: Pancreatic solitary fibrous tumor (SFT) is a rare neoplasm of intermediate biological potential. So far, only 22 cases have been reported since 1999. All the cases, except one, exhibited benign features. Here, we report the first case of malignant pancreatic SFT with typical Doege-Potter syndrome, along with the clinical and pathologic evidence of its systemic metastasis. CASE SUMMARY: The patient was a 48-year-old man with a 1-year history of pancreatic and liver masses and refractory hypoglycemia. Increased uptake of the tracer fluorodeoxyglucose (FDG) was found in the liver and bones by fluorine-18 FDG positron emission tomography/computed tomography. After multidisciplinary discussion, a distal pancreatectomy procedure was performed, and histological examination showed a lesion composed of abundant heterogeneous spindle cells with localized necrosis. On immunohistochemistry evaluation, STAT6 was found to be diffusely expressed in the tumor. Based on the overall evidence, the patient was diagnosed with malignant pancreatic SFT with liver and bone metastases. CONCLUSION: The diagnosis of malignant SFT requires comprehensive evidence including clinical, immunohistochemistry, and histological features. This case may be presented as a reference for diagnoses and management of malignant pancreatic SFTs with systemic metastasis.

A new tool for comprehensive geriatric assessment in elderly patients with acute myeloid leukemia: a pilot study from China.

BACKGROUND: Acute myeloid leukemia (AML) is a common type of hematological malignancy in elderly people. Geriatricians have developed comprehensive geriatric assessment (CGA) methods for elderly patients; however, the tools used for CGA in AML are not uniform. Thus, we aimed to validate the instrumental activities of daily living (IADL) scales, age, comorbidities (Charlson Comorbidity Index), and albumin (IACA) index, which is a new tool for CGA, in elderly patients with AML. METHODS: Patients aged ≥60 years who had been diagnosed with AML were screened for eligibility. Among the IACA low-, intermediate-, and high-risk groups, continuous variables were compared using the Mann-Whitney U test, and categorical variables were compared using χ and Fisher exact tests. In addition, probabilities of overall survival (OS) were estimated using the Kaplan-Meier method. RESULTS: A total of 21, 34, and 6 patients were categorized into IACA low-risk (0 point), intermediate-risk (1-2 points), and high-risk (≥3 points) groups, respectively. The rates of relapse/progression-related mortality were 23.8%, 58.8%, and 100.0% in the IACA low-, intermediate-, and high-risk groups, respectively (χ = 12.81, P < 0.001). The 2-year probabilities of OS were 47.7% (95% confidence interval [CI] 22.8%-72.6%) and 20.2% (95% CI 5.9%-34.5%) in the IACA low- and intermediate-risk groups, respectively (χ = 5.99, P = 0.014), which were significantly higher than those in the high-risk group (low-risk [47.7% (95% CI 22.8%-72.6%)] vs. high-risk [0], χ = 20.80, P < 0.001; intermediate-risk [20.2% (95% CI 5.9%-34.5%)] vs. high-risk [0], χ = 7.56, P = 0.006; respectively). In the IACA low-risk group, the 2-year probability of OS in patients receiving induction chemotherapy (50.8% [95% CI 24.1%-77.5%]) was significantly higher than that in those receiving best supportive care (0, χ = 25.74, P < 0.001). CONCLUSION: We suggest that the IACA index might be a simple and effective tool for comprehensive geriatric assessment in elderly AML patients.

Intraperitoneal Administration of Monoclonal Antibody Against Pathologic Aß42 Aggregates Alleviated Cognitive Deficits and Synaptic Lesions in APP/PS1 Mice.

Alzheimer's disease (AD) is the most common form of dementia, characterized by amyloid-ß peptide (Aß) aggregates, phosphorylated tau protein (p-tau), and progressive neurodegeneration. Amyloid-ß peptide 42 (Aß42) is considered an early trigger of AD pathogenesis. We have previously reported that Aß N-terminus monoclonal antibody (mAb) A8 alleviated cognitive dysfunction and reduced the abundance of soluble Aß in the brains of the senescence-accelerated mouse prone 8 (SAMP8) mouse model. To confirm the efficacy of mAb A8 in the double-transgenic APPswe/PS1ΔE9 (APP/PS1) mice, here we reported the related findings. The Morris water maze (MWM) data showed that the A8 treatment group had a shorter escape latency than the control groups in the place navigation test and the probe trial (p < 0.05). Moreover, immunohistochemistry showed decreased levels of both Aß and p-tau in the brains of APP/PS1 mice. Regarding Aß levels, western blot results showed that Aß42 oligomer (p < 0.01) but not Aß40 levels were diminished in brains of A8-treated APP/PS1 mice. Western blot results showed that phospho-tau (pSer231) (p < 0.01) but not tau levels were reduced in A8-treated mouse brains. Furthermore, transmission electron microscopy images indicated ultrastructural improvements, including an increased (p < 0.01) density of synapses and a reduction of abnormally enlarged mitochondria (p < 0.01), in the brains of A8-treated mice. Taken together, our data showed that mAb A8 is highly efficacious in APP/PS1 mice as a treatment for AD, and the underlying mechanism may target synaptic pathology by inhibiting the amyloid cascade.