The small-molecule alkaloid halofuginone (HF) is obtained from febrifugine. Recent studies on HF have aroused widespread attention owing to its universal range of noteworthy biological activities and therapeutic functions, which range from parasite infections and fibrosis to autoimmune diseases. In particular, HF is believed to play an excellent anticancer role by suppressing the proliferation, adhesion, metastasis, and invasion of cancers. This review supports the goal of demonstrating various anticancer effects and molecular mechanisms of HF. In the studies covered in this review, the anticancer molecular mechanisms of HF mainly included transforming growth factor-β (TGF-β)/Smad-3/nuclear factor erythroid 2-related factor 2 (Nrf2), serine/threonine kinase proteins (Akt)/mechanistic target of rapamycin complex 1(mTORC1)/wingless/integrated (Wnt)/β-catenin, the exosomal microRNA-31 (miR-31)/histone deacetylase 2 (HDAC2) signaling pathway, and the interaction of the extracellular matrix (ECM) and immune cells. Notably, HF, as a novel type of adenosine triphosphate (ATP)-dependent inhibitor that is often combined with prolyl transfer RNA synthetase (ProRS) and amino acid starvation therapy (AAS) to suppress the formation of ribosome, further exerts a significant effect on the tumor microenvironment (TME). Additionally, the combination of HF with other drugs or therapies obtained universal attention. Our results showed that HF has significant potential for clinical cancer treatment.

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• Journal Article MeSH
• Review MeSH

An increasing number of studies have characterized the bone as an endocrine organ, and that bone secreted factors may not only regulate local bone remodeling, but also other tissues and whole-body metabolic functions. The precise nature of these regulatory factors and their roles at bridging the bone, bone marrow adipose tissue, extramedullary body fat and whole-body energy homeostasis are being explored. In this study, we report that KIAA1199, a secreted factor produced from bone and bone marrow, previously described as an inhibitor of bone formation, also plays a role at promoting adipogenesis. KIAA1199-deficient mice exhibit reduced bone marrow adipose tissue, subcutaneous and visceral fat tissue mass, blood cholesterol, triglycerides, free fatty acids and glycerol, as well as improved insulin sensitivity in skeletal muscle, liver and fat. Moreover, these mice are protected from the detrimental effects of high-fat diet feeding, with decreased obesity, lower blood glucose and glucose tolerance, as well as decreased adipose tissue inflammation, insulin resistance and hepatic steatosis. In human studies, plasma levels of KIAA1199 or its expression levels in adipose tissue are positively correlated with insulin resistance and blood levels of cholesterol, triglycerides, free fatty acids, glycerol, fasting glucose and HOMA-IR. Mechanistically, KIAA1199 mediates its effects on adipogenesis through modulating osteopontin-integrin and AKT / ERK signaling. These findings provide evidence for the role of bone secreted factors on coupling bone, fat and whole-body energy homeostasis.

• MeSH
• Adipogenesis * physiology   MeSH
• Diet, High-Fat MeSH
• Energy Metabolism * MeSH
• Hyaluronoglucosaminidase MeSH
• Insulin Resistance MeSH
• Humans MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Obesity metabolism   MeSH
• Proteins * metabolism   MeSH
• Adipose Tissue metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

BACKGROUND AND OBJECTIVE: Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCOGC) is a rare variant of malignant pancreatic tumor. There is still no standardized treatment for this uncommon subtype, as surgical resection with lymphadenectomy is the only potentially curative treatment so far. In this paper, we describe the current knowledge of this very rare specific subtype of pancreatic cancer (PC) as a narrative review. METHODS: For this review, we did not specify the time range of studies referred to due to limited data availability. Our inclusion criteria comprised previous studies, which specifically focused on the rare UCOGC subtype of PC as a confirmed histopathology, either pure or present together with other subtypes. We disregarded the studies involving any other PC subtype but not UCOGC, including undifferentiated and anaplastic carcinomas without osteoclast-like giant cell components. KEY CONTENT AND FINDINGS: The limited available data precludes a definitive assessment of the efficacy of both neoadjuvant and adjuvant chemotherapy in the treatment of UCOGC. Monoclonal antibody pembrolizumab has been proven to be effective in metastatic cases. Multiple cases demonstrate a better overall survival rate for patients with UCOGC only versus those having UCOGC as a component with a pancreatic ductal adenocarcinoma (PDAC) histopathological subtype. The same conclusion can be also drawn comparing the survival rate of patients having pure UCOGC versus UCOGC with associated PDAC. Programmed cell death ligand-1 expression has been shown to be an important determinant, which shortens the survival period of patients diagnosed with UCOGC. CONCLUSIONS: The rarity of UCOGC limits data for clinical courses and treatment plans. We need more data to better understand the relationship between pathogenic mutations, histological subtypes, and prognosis in PC, including UCOGC. Understanding UCOGC's molecular, clinical, radiological, and pathological characteristics can lead to earlier, more accurate diagnoses and better management.

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• Journal Article MeSH
• Review MeSH

BACKGROUND: The diagnostic accuracy of prostate magnetic resonance imaging (MRI) is highly dependent on image quality. Although the effects of spasmolytics and rectal preparation have been previously studied, the findings remain inconsistent and fail to address other critical modifiable factors. This study aimed to evaluate the impact of various modifiable factors on prostate MRI image quality and their subsequent influence on Prostate Imaging Reporting and Data System (PI-RADS) scoring. METHODS: Fifty-six consecutive patients who underwent 3T multiparametric MRI (mpMRI) with the administration of hyoscine butylbromide (HB+) and at least one 3T mpMRI without HB (HB-) ≤3 years earlier were retrospectively evaluated. Two radiologists performed morphometry of the prostate, bladder, rectum, and abdomen and evaluated image quality, artifacts, and motion on a five-point scale and T2 and diffusion-weighted imaging (DWI) PI-RADS v2.1 scores. The influence of HB, rectum and bladder distension, breathing motion, and examination hour were analyzed. RESULTS: The sharpness and overall image quality of T2 images were significantly better in HB+ compared to HB- (P=0.0047 and P=0.013). T2 motion artifacts were reduced earlier in the day (ρ=0.32, P=0.017). DWI susceptibility artifact correlated with patient diameter (ρ=0.40, P=0.002), but not with rectum diameter (ρ=0.09, P=0.51) or gas content (ρ=0.13, P=0.33). Examinations later in the day were associated with increased motion artifacts on T2 [hazard ratio (HR) =1.36]. T2 and DWI scores were influenced by bladder volume, breathing motion, and rectal air, but not by HB. Breathing motion negatively impacted overall image quality (HR =1.24), and DWI susceptibility artifacts (HR =1.22). CONCLUSIONS: HB administration, daytime, and breathing motion have significant influence on image quality of prostate MRI. The gas content of the rectum influences T2 image quality and T2 scores. Bladder filling is associated with reduced breathing motion, subsequently affecting DWI scores.

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OBJECTIVE: To evaluate the benefits of surgical repair acute type A aortic dissection (ATAAD) on survival of octogenarians. METHODS: Patients who underwent surgery for acute ATAAD from the multicenter European Registry of Type A Aortic Dissection (ERTAAD) were the subjects of the present analysis. RESULTS: 326 (8.4%) patients were aged ≥ 80 years. Among 280 propensity score matched pairs, in-hospital mortality was 30.0% in patients aged ≥ 80 years and 20.0% in younger patients (P = 0.006), while 10-year mortality were 93.2% and 48.0%, respectively (P < 0.001). The hazard of mortality was higher among octogenarians up to two years after surgery, but it became comparable to that of younger patients up to 5 years. Among patients who survived 3 months after surgery, 10-year relative survival was 0.77 in patients aged < 80 years, and 0.46 in patients aged ≥ 80 years. Relative survival of octogenarians decreased markedly 5 years after surgery. Age ≥ 85 years, glomerular filtration rate, preoperative invasive ventilation, preoperative mesenteric mal-perfusion and aortic root replacement were independent predictors of in-hospital mortality among octogenarians (AUC = 0.792; E:O ratio = 0.991; CITL = 0.016; slope = 1.096). An additive score was developed. A risk score ≤ 1 was observed in 68.4% of patients, and their in-hospital mortality was 20.9%. CONCLUSIONS: Provided a thoughtful patient selection, surgery may provide a survival benefit in patients aged ≥ 80 years with ATAAD that, when compared to younger patients and the general population, may last up to 5 years after the procedure. These findings have significant epidemiologic and clinical relevance because of the increasing longevity of the population of the Western countries.

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• Journal Article MeSH

BACKGROUND: Over 55 million people worldwide are living with dementia. The rate of cognitive decline increases with age, and loss of senses may be a contributing factor. OBJECTIVES: This study aimed to analyze hearing, olfactory function, and color vision in patients with dementia. MATERIALS AND METHODS: The sample comprised 40 patients with dementia and 37 cognitively normal controls aged 41-85 years. All participants underwent conventional pure-tone audiometry and a screening version of the Hearing Handicap Inventory for Adults, the Odorized Markers Test of olfactory function and the Ishihara color vision test. The effects of comorbidities and lifestyle factors were also assessed. RESULTS: Patients with dementia had significantly worse hearing at almost all frequencies tested and significantly greater olfactory impairment than cognitively normal controls. Color vision impairment was found in less than 8% of the sample, with no significant difference between the groups. Impairment of two senses (hearing and olfaction) was significantly more common in patients with dementia than in controls. CONCLUSION: Individuals with dementia were found to have sensory decline, namely hearing and olfactory impairment. Color vision was rarely impaired in the sample. Participants with dementia tended to have more multisensory impairments than controls.

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• Journal Article MeSH

BACKGROUND: Chest wall sarcomas are rare and pose significant technical challenges in surgical management, particularly in patients with advanced disease. In this study, we examined the extent of resection, reconstruction techniques, and oncological outcomes of patients with chest wall soft tissue and bone sarcomas. METHODS: This retrospective single-center series included patients who underwent surgery at our center between May 2014 and February 2022 for deep-seated/subfascial primary and recurrent soft tissue or bone sarcomas of the chest wall requiring significant resection and extensive reconstruction. We analyzed clinical and operative data, including extent of resection, reconstruction techniques, and oncological outcomes. Additionally, we compared survival outcomes between patients with primary and recurrent tumors, and examined how these were influenced by clinical factors using Cox proportional hazards regression analysis. RESULTS: Of the 38 patients included, 22 were treated for primary or recurrent soft tissue sarcoma (STS) and 16 for bone sarcoma. En bloc microscopic radical resection (R0) was achieved in 95.45% and 93.75% of patients with soft tissue and bone sarcomas, respectively. Nonetheless, local recurrence or distant metastases occurred in 40%, 58.33%, and 40% of patients with primary soft tissue, recurrent soft tissue, and bone sarcomas, respectively. Adherence to clinical guidelines and treatment in the reference center was high for bone sarcoma (93.75%), but notably low for STS, resulting in 54.55% of these patients requiring re-resection. Compared with those who underwent only one surgery, patients who underwent re-resection had poorer postoperative outcomes, more severe complications, and longer hospital stay. CONCLUSIONS: Chest wall sarcomas often require extensive resection and complex reconstruction. Although surgical treatment at reference sarcoma centers has significantly improved oncological and clinical outcomes, the prognosis of these patients remains guarded, necessitating further related research and continued refinement in surgical techniques, adjuvant therapies, and follow-up strategies.

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• Journal Article MeSH

BACKGROUND: Improved prediction of prognosis among lung cancer patients could facilitate better clinical management. We aimed to study the prognostic significance of circulating proteins at the time of lung cancer diagnosis, among patients with and without smoking history. METHODS: We measured 91 proteins using the Olink Immune-Oncology panel in plasma samples that were collected at diagnosis from 244 never smoking and 742 ever smoking patients with stage I-IIIA non-small cell lung cancer (NSCLC). Patients were recruited from nine centres in Russian Federation, Poland, Serbia, Czechia, and Romania, between 2007-2016 and were prospectively followed through 2020. We used multivariable Survey-weighted Cox models to assess the relationship between overall survival and levels of proteins by adjusting for smoking, age at diagnosis, sex, education, alcohol intake, histology, and stage. RESULTS: The 5-year survival rate was higher among never than ever smoking patients (63.1% vs. 46.6%, P<0.001). In age- and sex-adjusted survival analysis, 23 proteins were nominally associated with overall survival, but after adjustment for potential confounders and correcting for multiple testing, none of the proteins showed a significant association with overall survival. In stratified analysis by smoking status, IL8 [hazard ratio (HR) per standard deviation (SD): 1.40, 95% confidence interval (CI): 1.18-1.65, P=1×10-4] and hepatocyte growth factor (HGF) (HR: 1.45, 95% CI: 1.18-1.79, P=5×10-4) were associated with survival among never smokers, but no protein was found associated with survival among ever smokers. Integrating proteins into the models with clinical risk factors did not improve the predictive performance of NSCLC prognosis [C-index of 0.63 (clinical) vs. 0.64 (clinical + proteins) for ever smokers, P=0.20; C-index of 0.68 (clinical) vs. 0.72 (clinical + proteins) for never smokers, P=0.28]. CONCLUSIONS: We found limited evidence of a potential for circulating immune- and cancer-related protein markers in lung cancer prognosis. Whereas some specific proteins appear to be uniquely associated with lung cancer survival in never smokers.

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• Journal Article MeSH

Robotic coronary and intra-cardiac surgery has been available for more than 25 years. In this period, multiple studies have demonstrated the beneficial effects of robotic surgery over conventional open surgery. Throughout the years, technical developments have enabled us to perform totally endoscopic coronary artery bypass (TECAB) grafting. But these techniques remained in the hands of a small group of pioneers because of a lack of structured training programs and the absence of long-term results at that time. Currently, a renewed interest and a wide dispersion of robotic platforms, thanks to use of robotics in other disciplines, has led to an exponential increase in robotic cardiac centers both in Europe and USA. Nonetheless, this increase was slowed down in Europe as a result of the uncertainty introduced by the implementation of a revised regulatory framework for medical devices [Regulation 2017/745, 'Medical Device Regulation' ('MDR')]. The MDR was introduced with the goal of increasing patient safety and supporting innovation. Implementing the MDR has proven to be exceptionally challenging and risks to the supply of essential devices have been identified. Changes to both regulatory and market dynamics led to a circumstance where the only available robotic platform for cardiac surgery decided to cease marketing of essential accessories for conducting surgery. This resulted in the disappearance of dedicated tools such as the Endowrist stabilizer, essential for TECAB, and the atrial retractor which is essential for intra-cardiac surgery. In the mean-time, further clinical evidence was published demonstrating the superiority of robotic cardiac surgery over other minimally invasive approaches. This has demonstrated the need to better define the clinical evidence requirements for regulatory purposes to ensure that dedicated tools for evidence-based interventions in robotic coronary surgery remain available such that TECAB can continue in Europe.

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• Journal Article MeSH
• Review MeSH

This state-of-the-art review aimed to synthesize evidence from various sex-stratified studies on aortic stenosis (AS), focusing on the difference in clinical presentation, anatomical characteristics, pathophysiology, and management of AS. In comparison to men, women with AS are present at later stages, are older, more symptomatic, frailer, and exhibit higher operative risk [Society of Thoracic Surgeons (STS) score]. Women tend to have smaller aortic valve (AV) areas and left ventricular (LV) outflow tract, leading to lower stroke volumes (SVs) than men and have a higher prevalence of paradoxical, low-flow, low-gradient AS. In women, chronic pressure overload due to AS results in concentric LV remodelling and hypertrophy, characterized by reduced LV cavities, higher filling pressures, lower wall stress, and more diastolic dysfunction. Conversely, men exhibit more dilated eccentric LV remodelling and hypertrophy. AVs in women are less calcified but more fibrotic. Moreover, women are often underdiagnosed, have severity underestimated, and experience delays or receive fewer referrals for AV replacement (AVR). However, women tend to benefit from transcatheter AVR (TAVR) with a long-term survival advantage over men, although the incidence of vascular complications and bleeding events in 30 days after TAVR is higher in women. Surgical AVR (SAVR) in women has high operative risk, is technically demanding and has poorer outcomes with increased mortality at 30 days compared to men. According to the STS score and EuroSCORE, the female sex itself is considered a risk factor for SAVR. Therefore, addressing sex-related disparities in AS and increasing awareness among physicians promises improved diagnosis and treatment, facilitating equitable care and the development of sex-specific personalized medicine.

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• Journal Article MeSH
• Review MeSH