Intercostal Lung Hernias Presenting After Minimally Invasive Cardiac Surgery.

INTRODUCTION: With the introduction of minimally invasive cardiac surgery, more commonly cases of lung herniation are starting to appear. Acquired lung hernias are classified as postoperative, traumatic, pathologic, and spontaneous. Up to 83% of lung hernias are intercostal. Herein, we describe patients presenting with intercostal lung hernias following minimally invasive cardiac surgery at a single center in Medellín, Colombia. METHODS: We conducted a retrospective search of all patients presenting with intercostal lung hernias secondary to minimally invasive cardiac surgery at our clinic in Medellín since the beginning of our program, from 2010 to 2022. Mini-sternotomies were excluded from our study. We reviewed the incision type and other possible factors leading to intercostal lung hernia development. We also describe the approach taken for these patients. RESULTS: From 2010 up until 2022, 803 adult patients underwent minimally invasive cardiac surgeries through a mini-thoracotomy. At the time of data retrieval, nine patients presented with intercostal lung hernias at the previous incision site. Five hernias (55%) were from right 2nd intercostal parasternal mini-thoracotomies for aortic valve surgeries. Four hernias (45%) were from right 4th intercostal lateral mini-thoracotomies for mitral valve surgeries. Our preferred repair technique is a video-assisted thoracoscopic mesh approach. CONCLUSION: Minimally invasive cardiac surgical approaches are becoming more routine. Proper wound closure is critical in preventing lung hernias. Additionally, timely diagnosis and opportune hernia surgery using video-assisted thoracoscopic mesh repair can prevent further complications.

Identification of PRMT5 as a therapeutic target in cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma (CCA) is a very difficult-to-treat cancer. Chemotherapies are little effective and response to immune checkpoint inhibitors is limited. Therefore, new therapeutic strategies need to be identified. OBJECTIVE: We characterised the enzyme protein arginine-methyltransferase 5 (PRMT5) as a novel therapeutic target in CCA. DESIGN: We evaluated the expression of PRMT5, its functional partner MEP50 and methylthioadenosine phosphorylase (MTAP)-an enzyme that modulates the sensitivity of PRMT5 to pharmacological inhibitors-in human CCA tissues. PRMT5-targeting drugs, currently tested in clinical trials for other malignancies, were assessed in human CCA cell lines and organoids, as well as in two immunocompetent CCA mouse models. Transcriptomic, proteomic and functional analyses were performed to explore the underlying antitumoural mechanisms. RESULTS: PRMT5 and MEP50 proteins were correlatively overexpressed in most CCA tissues. MTAP was absent in 25% of intrahepatic CCA. PRMT5-targeting drugs markedly inhibited CCA cell proliferation, synergising with cisplatin and gemcitabine and hindered the growth of cholangiocarcinoma organoids. PRMT5 inhibition blunted the expression of oncogenic genes involved in chromatin remodelling and DNA repair, consistently inducing the formation of RNA loops and promoting DNA damage. Treatment with PRMT5-targeting drugs significantly restrained the growth of experimental CCA without adverse effects and concomitantly induced the recruitment of CD4 and CD8 T cells to shrinking tumourous lesions. CONCLUSION: PRMT5 and MEP50 are frequently upregulated in human CCA, and PRMT5-targeting drugs have significant antitumoural efficacy in clinically relevant CCA models. Our findings support the evaluation of PRMT5 inhibitors in clinical trials, including their combination with cytotoxic and immune therapies.

Emergency laparotomy and endoscopic gastrostomy in patients on extra-corporeal membrane oxygenation (ECMO) support.

INTRODUCTION: An infrequent yet known complication of ECMO is abdominal compartment syndrome requiring emergency laparotomy. Also, the need for prolonged enteral nutrition while on ECMO may require endoscopic gastrostomy to maintain adequate nutritional status. Here we describe our experience with emergency laparotomy and endoscopic gastrostomy in patients on ECMO support. METHODS: We retrieved patient histories from our clinical archives and performed a retrospective description of all patients taken to an emergency laparotomy or endoscopic gastrostomy while on ECMO support at our cardiovascular referral center from July 2019 through June 2024. RESULTS: During the research period of 5 years a total of 401 patients were placed on ECMO support for either cardiogenic shock or respiratory failure. A total of 27 (7%) patients required an abdominal intervention while on ECMO. 14 (3.5%) patients required emergency laparotomy and 13 (3.2%) of patients required endoscopic gastrostomy tube placement. Overall 30-day mortality of all patients requiring a general surgery procedure while on ECMO support was 33%. CONCLUSION: ECMO support can result in many complications despite its many benefits. Patients who require emergency laparotomy while on ECMO have lower survival-to-discharge and higher mortality at 30 days. Endoscopic gastrostomy however, can be safely performed on ECMO with little to no bleeding complications despite anticoagulation.

Tunable SIM properties in a family of 3D anilato-based lanthanide-MOFs.

By reacting a 3,6-ditriazolyl-2,5-dihydroxybenzoquinone (H2trz2An) anilato linker with LnIII ions (LnIII = Dy, Tb, Ho), two different series of polymorphs, formulated as [Ln2(trz2An)3(H2O)4] n ·10H2O (DyIII, 1a; TbIII, 2a, HoIII, 3a) and [Ln2(trz2An)3(H2O)4] n ·7H2O (DyIII, 1b, TbIII, 2b, HoIII, 3b) have been obtained. In these series the two DyIII-coordination networks (1a and 1b) and the TbIII-coordination polymer (2b) show a Single Ion Magnet (SIM) behavior. 1-3a MOFs show reversible structural flexibility upon removal of a coordinated water molecule from a distorted hexagonal 2D framework to a distorted 3,6-brickwall rectangular 3D structure in [Ln2(trz2An)3(H2O)2] n ·2H2O (DyIII, 1a_des; TbIII, 2a_des, HoIII, 3a_des) involving shrinkage/expansion of the hexagonal-rectangular networks. Noteworthy, 2b represents the first example of a TbIII-anilate-based coordination polymer showing SIM behaviour to date and the best SIM properties within the polymorphs. Theoretical investigation via ab initio CASSCF calculations supports this behavior, since 2b shows less mixing between the m J states of the ground state among all the studied complexes.

Non-mitogenic FGF19 mRNA-based therapy for the treatment of experimental metabolic dysfunction-associated steatotic liver disease (MASLD).

Metabolic dysfunction-associated steatohepatitis (MASH), represents a global health threat. MASH pathophysiology involves hepatic lipid accumulation and progression to severe conditions like cirrhosis and, eventually, hepatocellular carcinoma. Fibroblast growth factor (FGF)-19 has emerged as a key regulator of metabolism, offering potential therapeutic avenues for MASH and associated disorders. We evaluated the therapeutic potential of non-mitogenic (NM)-FGF19 mRNA formulated in liver-targeted lipid nanoparticles (NM-FGF19-mRNAs-LNPs) in C57BL/6NTac male mice with diet-induced obesity and MASH (DIO-MASH: 40% kcal fat, 20% kcal fructose, 2% cholesterol).  After feeding this diet for 21 weeks, NM-FGF19-mRNAs-LNPs or control (C-mRNA-LNPs) were administered (0.5 mg/kg, i.v.) weekly for another six weeks, in which diet feeding continued. NM-FGF19-mRNAs-LNPs treatment in DIO-MASH mice resulted in reduced body weight, adipose tissue depots, and serum transaminases, along with improved insulin sensitivity. Histological analyses confirmed the reversal of MASH features, including steatosis reduction without worsening fibrosis. NM-FGF19-mRNAs-LNPs reduced total hepatic bile acids (BA) and changed liver BA composition, markedly influencing cholesterol homeostasis and metabolic pathways as observed in transcriptomic analyses. Extrahepatic effects included the downregulation of metabolic dysfunction-associated genes in adipose tissue. This study highlights the potential of NM-FGF19-mRNA-LNPs therapy for MASH, addressing both hepatic and systemic metabolic dysregulation. NM-FGF19-mRNA demonstrates efficacy in reducing liver steatosis, improving metabolic parameters, and modulating BA levels and composition. Given the central role played by BA in dietary fat absorption, this effect of NM-FGF19-mRNA may be mechanistically relevant. Our study underscores the high translational potential of mRNA-based therapies in addressing the multifaceted landscape of MASH and associated metabolic perturbations.

Anelosimuseximius bioinspired ZnO nano cobwebs for environmental remediation of drugs and endocrine disruptors from water.

The pollution of wastewater with pharmaceuticals and endocrine-disrupting chemicals (EDCs) in populated areas poses a growing threat to humans and ecosystems. To address this serious problem, various one-dimensional (1D) hierarchical ZnO-based nanostructures inspired by Anelosimus eximius cobwebs were developed and successfully grown on a glass substrate through simple hydrothermal synthesis. The nanorods (nr) obtained during primary growth were chemically etched with KOH (ZnOnr-KOH), followed by the secondary growth of nano cobweb-like (ncw) structures using polyethyleneimine (ZnOnr/ncw). These structures were further decorated by the photoreduction of Ag nanoparticles (ZnOnr/ncw/Ag). The feasibility of ZnO-based 1D nanostructures to remove pollutants was demonstrated by degrading commonly prescribed pharmaceutical drugs (diclofenac and carbamazepine) in a miniature cuvette reactor. The photocatalytic activities for drug degradation generally decreased in the order ZnOnr/ncw/Ag > ZnOnr/ncw > ZnOnr-KOH. Additionally, the suitability of the samples for scaling up and practical application was demonstrated by photocatalytic degradation of the hormone estriol (E3) in a flow-through photoreactor. The photocatalytic degradation efficiency of E3 followed the same trend observed for drug degradation, with the complete elimination of the endocrine disruptor achieved by the best-performing ZnOnr/ncw/Ag within 4 h, due to optimized charge transfer and separation at the heterostructure interface.

Selective Agonism of Liver and Gut FXR Prevents Cholestasis and Intestinal Atrophy in Parenterally Fed Neonatal Pigs.

BACKGROUND & AIMS: We aimed to investigate the relative efficacy of feeding different bile acids in preventing PNALD in neonatal pigs. METHODS: Newborn pigs given total parenteral nutrition (TPN) combined with minimal enteral feeding of chenodeoxycholic acid (CDCA), or increasing doses of obeticholic acid (OCA) for 19 days. RESULTS: Enteral OCA (5 and 15 mg/kg), but not CDCA (30 mg/kg) reduced blood cholestasis markers compared to TPN controls and increased bile acids in the gallbladder and intestine. Major bile acids in the liver and distal intestine were CDCA, HCA, HDCA and OCA, and their relative proportions were increased by the type of bile acid (CDCA or OCA) given enterally. High doses of OCA increased the total NR1H4-agonistic bile acid profile in the liver and intestine above 50% total bile acids. Both CDCA and OCA treatments suppressed hepatic cyp7a1 expression, but only OCA increased hepatobiliary transporters, ABCB11, ABCC$ and ABCB1. Plasma phytosterol levels were reduced and biliary levels were increased by CDCA and OCA and hepatic sterol transporters, abcg5/8, expression were increased by OCA. Both CDCA and OCA increased plasma FGF19 and OCA increased intestinal FGF19, FABP6, and SLC51A. Both CDCA and OCA increased intestinal mucosal growth, whereas CDCA increased the plasma GLP-2, GLP-1 and GIP. CONCLUSIONS: Enteral OCA prevented cholestasis and phytosterolemia by increased hepatic bile acid and sterol transport via induction of hepatobiliary transporter FXR target genes and not by suppression of bile acid synthesis genes. We also showed an intestinal trophic action of OCA that demonstrates a dual clinical benefit of FXR agonism in the prevention of PNALD in piglets.

Vision loss and diabetic retinopathy prevalence and risk among a cohort of Indigenous and non-Indigenous Australians with type 2 diabetes receiving renal haemodialysis treatment: The retinopathy in people currently on renal dialysis (RiPCORD) study.

AIMS: Diabetic nephropathy, vision loss and diabetic retinopathy (DR) are frequent comorbidities among individuals with type 2 diabetes (T2D). The Retinopathy in People Currently On Renal Dialysis (RiPCORD) study sought to examine the epidemiology and risk of vision impairment (VI) and DR among a cohort of Indigenous and non-Indigenous Australians with T2D currently receiving haemodialysis for end-stage renal failure (ESRF). METHODS: A total of 106 Indigenous and 109 non-Indigenous Australians were recruited in RiPCORD across five haemodialysis centres in urban and remote settings. Clinical assessments, questionnaires and medical record data determined the rates of ocular complications and risk factor profiles. RESULTS: Prevalence rates include unilateral VI, 23.5 %; bilateral VI, 11.7 %; unilateral blindness, 14.2 %; and bilateral blindness, 3.7 %, with no significant differences between sub-cohorts (p=0.30). DR prevalence rates were 78.0 % among non-Indigenous Australians and 93.1 % among Indigenous Australians (p=<0.001). Non-Indigenous ethnicity (OR: 0.28) and pre-dialysis diastolic blood pressure (OR: 0.84 per 10-mmHg) were protective, while peripheral vascular disease (OR: 2.79) increased DR risk. CONCLUSIONS: Ocular complications among individuals with T2D and ESRF are disproportionately high, especially for Indigenous Australians, and beyond what can be accounted for by risk factor variation. Findings suggest a need to improve screening and preventative efforts within this high-risk population group.

Genome-wide association analysis and admixture mapping in a Puerto Rican cohort supports an Alzheimer disease risk locus on chromosome 12.

Introduction: Hispanic/Latino populations are underrepresented in Alzheimer Disease (AD) genetic studies. Puerto Ricans (PR), a three-way admixed (European, African, and Amerindian) population is the second-largest Hispanic group in the continental US. We aimed to conduct a genome-wide association study (GWAS) and comprehensive analyses to identify novel AD susceptibility loci and characterize known AD genetic risk loci in the PR population. Materials and methods: Our study included Whole Genome Sequencing (WGS) and phenotype data from 648 PR individuals (345 AD, 303 cognitively unimpaired). We used a generalized linear-mixed model adjusting for sex, age, population substructure, and genetic relationship matrix. To infer local ancestry, we merged the dataset with the HGDP/1000G reference panel. Subsequently, we conducted univariate admixture mapping (AM) analysis. Results: We identified suggestive signals within the SLC38A1 and SCN8A genes on chromosome 12q13. This region overlaps with an area of linkage of AD in previous studies (12q13) in independent data sets further supporting. Univariate African AM analysis identified one suggestive ancestral block (p = 7.2×10-6) located in the same region. The ancestry-aware approach showed that this region has both European and African ancestral backgrounds and both contributing to the risk in this region. We also replicated 11 different known AD loci -including APOE- identified in mostly European studies, which is likely due to the high European background of the PR population. Conclusion: PR GWAS and AM analysis identified a suggestive AD risk locus on chromosome 12, which includes the SLC38A1 and SCN8A genes. Our findings demonstrate the importance of designing GWAS and ancestry-aware approaches and including underrepresented populations in genetic studies of AD.

Ocular Albinism, Telecanthus, and Skin Depigmentation: A Phenotypic Conundrum.

This case report details the clinical manifestations observed in a 22-year-old male diagnosed with ocular albinism (OA). The patient underwent a comprehensive eye examination by one of the authors, revealing clinical features such as skin depigmentation, telecanthus, iris transillumination, nystagmus, and foveal hypoplasia. This report underscores the importance of a thorough clinical examination and genetic testing for accurate diagnosis, effective management, and appropriate counseling of patients with OA.

Impact of high-risk and low-risk human papillomavirus infections on the male genital tract: effects on semen inflammation and sperm quality.

Human Papillomavirus (HPV), a prevalent sexually transmitted infection, comprises high-risk (HR-HPV) and low-risk (LR-HPV) viruses, the former posing a high risk for developing malignancies whereas the latter mainly for benign warts. Despite increasing awareness of HPV's impact on men's health, the influence of HR-HPV and LR-HPV urogenital infections on male fertility potential remains uncertain. This study aimed to investigate whether male urogenital infection with HR- or LR-HPV associates with impaired sperm quality, oxidative stress, and inflammation. A total of 205 male patients attending an urology clinic were enrolled. Semen samples were analyzed for HPV using PCR and genotyped by RFLP. Semen quality was evaluated following WHO guidelines. Semen leukocytes, reactive oxygen species (ROS), and sperm viability were analyzed using flow cytometry. HPV was detected in 19% (39/205) of semen samples. HR-HPV infections were more prevalent, with HPV-16 being the most frequent genotype. Neither HR-HPV nor LR-HPV were associated with significant alterations in routine sperm quality parameters. However, HR-HPV+ individuals showed significantly higher levels of sperm necrosis and exhibited increased proportions of ROS+ spermatozoa compared to LR-HPV+ or control individuals. Furthermore, no significant semen inflammation was detected in patients infected with either HR-HPV or LR-HPV, and unexpectedly reduced semen leukocytes and inflammatory cytokines (IL-6 and IL-1ß) were observed in HR-HPV+ patients compared to controls. These observations underscore the importance of comprehensive HPV screening, including genotyping, in urology and fertility clinics to understand the progression of the infection, potential adverse effects on reproductive health, and the oncogenic risks involved.

Opening the Hysteresis Loop in Ferromagnetic Fe3GeTe2 Nanosheets Through Functionalization with TCNQ Molecules.

Ferromagnetic metal Fe3GeTe2 (FGT), whose structure exhibits weak van-der-Waals interactions between 5-atom thick layers, was subjected to liquid-phase exfoliation (LPE) in N-methyl pyrrolidone (NMP) to yield a suspension of nanosheets that were separated into several fractions by successive centrifugation at different speeds. Electron microscopy confirmed successful exfoliation of bulk FGT to nanosheets as thin as 6 nm. The ferromagnetic ordering temperature for the nanosheets gradually decreased with the increase in the centrifugation speed used to isolate the 2D material. These nanosheets were resuspended in NMP and treated with an organic acceptor, 7,7,8,8-tetracyano-quinodimethane (TCNQ), which led to precipitation of FGT-TCNQ composite. The formation of the composite material is accompanied by charge transfer from the FGT nanosheets to TCNQ molecules, generating TCNQ•- radical anions, as revealed by experimental vibrational spectra and supported by first principles calculations. Remarkably, a substantial increase in magnetic anisotropy was observed, as manifested by the increase in the coercive field from nearly zero in bulk FGT to 1.0 kOe in the exfoliated nanosheets and then to 5.4 kOe in the FGT-TCNQ composite. The dramatic increase in coercivity of the composite suggests that functionalization with redox-active molecules provides an appealing pathway to enhancing magnetic properties of 2D materials.

Effect of the basilar invagination (type B) on cervical spine: a case-control study at MRI.

OBJECTIVE: To evaluate the effect of the basilar invagination (BI) type B on cervical spine. METHODS: The research protocol used head magnetic resonance imaging (MRI) exams from 41 participants with BI type B and 158 controls. The criterion for BI was the distance of the odontoid apex to Chamberlain's line (DOCL) equal to or greater than 7 mm. The clivus length (CLI), clivus canal angle (CCA), Welcker's basal angle (WBA), Boogaard's angle (BOA), upper cervical lordosis angle (UCL), and total cervical lordosis angle (CL) were evaluated. The descriptive analysis, group comparisons, and correlations between skull base and cervical spine parameters were performed at the 95% confidence interval. RESULTS: Participants with BI type B showed shorter clivus length (CLI: 25.7mm±7.3); greater angulation of the skull base (WBA: 126.5±10.4); greater inclination foramen magnum (BOA: 151.5±14.5); decrease in the value of the (CCA: 131.6±15); and greater angulations of UCL (17.9 ±13.8) and CL (29.7 ±19.9) in comparison to the control group (P < 0.05). Clivus length and CCA correlated inversely with UCL and CL, while BOA correlated directly with UCL and CL. The WBA did not correlate with CL (P < 0.05). CONCLUSION: The deformation of skull base in the BI of type B caused, on average, a hyperlordosis of almost 30 degrees in the C2-C6 segment. This change was approximately 17º in the C2-C4, with the clivus hypoplasia being a risk factor for cervical hyperlordosis.

Cross-sex hormonal replacement: Some effects over mitochondria.

Transgender is a term for people whose gender identity or expression differs from their natal sex. These individuals often seek cross-hormonal therapy to simulate the individual´s desired gender. However, the use of estrogens and testosterone has side effects such as a higher propensity to cancer, weight changes and cardiovascular diseases. Testosterone has also been linked with hypertension. Still, little is known about the outcomes and prevalence of metabolic perturbations in the trans community. Here we aim to analyze if cross-administering sexual hormones affects heart mitochondrial function. Mitochondria produces the ATP needed for heart function. In fact, different studies show that mitochondrial dysfunction precedes cardiac damage. In this work we used either female rats castrated and injected with testosterone or male rats castrated and injected with estrogens for 4 months. We performed an electrocardiogram, and then we isolated heart mitochondria to measure the rate of oxygen consumption, calcium fluxes, membrane potential, superoxide dismutase activity, lipoperoxidation and cytokines. We detected wide modifications in all parameters associated to cross-hormonal administration.

Multiplex spatial omics reveals changes in immune-epithelial crosstalk during inflammation and dysplasia development in chronic IBD patients.

Patients with long-standing inflammatory bowel disease (IBD) face an increased risk of developing colitis-associated cancer (CAC). Although IBD-induced prolonged inflammation seems to be involved in CAC pathogenesis, the specific molecular changes that contribute remain unknown. Here, we applied digital spatial RNA profiling, RNAscope, and imaging mass cytometry to examine paired uninflamed, inflamed, and early dysplastic mucosa of patients with IBD. We observed robust type 3 (IL-17) responses during inflammation, accompanied by elevated JAK-STAT signaling and phosphorylated STAT3 (P-STAT3) levels, with both inflamed and dysplastic mucosa displaying immune cell activation. Higher stromal P-STAT3 was detected in uninflamed and inflamed mucosa of patients who eventually developed dysplasia. CD8a+ T cells did not infiltrate inflamed or dysplastic epithelial regions in these patients, while control patients showed elevated CD8a in inflamed mucosa. Our study reveals distinct inflammatory patterns throughout CAC development, marked by an activated IL-17 pathway, engaged STAT3, and diminished cytotoxic T cell infiltration.

Co-morbid sarcopenia and low bone mineral density in young paediatric cancer survivors.

BACKGROUND: Sarcopenia and low areal bone mineral density (aBMD) are prevalent musculoskeletal complications after paediatric cancer treatment. However, their relationship has not been examined in young paediatric cancers survivors. This study aimed to evaluate aBMD differences according to sarcopenia status and the risk of low aBMD Z-score in young paediatric cancer survivors with sarcopenia confirmed/probable. METHODS: This cross-sectional study included 116 paediatric cancer survivors (12.1 ± 3.3 years old; 42.2% female). Handgrip strength was used to assessed muscle strength. Dual-energy X-ray absorptiometry estimated aBMD (g/cm2) and appendicular lean mass index (ALMI, kg/m2). 'No sarcopenia' was defined when muscle strength was >decile 2. 'Sarcopenia probable' was defined when muscle strength was ≤ decile 2 and ALMI Z-score was > -1.5 standard deviation (SD). 'Sarcopenia confirmed' was defined when muscle strength was ≤ decile 2 and ALMI Z-score ≤ -1.5 SD. Analysis of covariance and logistic regression, adjusted for time from treatment completion, radiotherapy exposure, calcium intake, and physical activity, was used to evaluate aBMD and estimate the odds ratios (ORs) of low aBMD (aBMD Z-score < -1.0). RESULTS: Survivors with sarcopenia confirmed had significantly lower aBMD than those without sarcopenia at total body (-1.2 [95% CI: -1.5 to -0.8] vs. 0.2 [-0.2 to 0.6], P < 0.001), lumbar spine (-0.7 [-1.1 to -0.3] vs. 0.4 [0.0 to 0.8], P < 0.001), total hip (-0.5 [-0.9 to -0.2] vs. 0.4 [0.1 to 0.8], P < 0.001), and femoral neck (-1.0 [-1.4 to -0.6] vs. 0.1 [-0.3 to 0.4], P = 0.001). Compared with survivors with sarcopenia probable, survivors with sarcopenia confirmed had significantly lower aBMD Z-score at total body (-1.2 [-1.5 to -0.8] vs. -0.2 [-0.7 to 0.4], P = 0.009), total hip (-0.5 [-0.9 to -0.2] vs. 0.5 [-0.1 to 1.0], P = 0.010), and femoral neck (-1.0 [-1.4 to -0.6] vs. 0.1 [-0.5 to 0.7], P = 0.014). Survivors with sarcopenia confirmed were at higher risk of low aBMD Z-score at the total body (OR: 6.91, 95% CI: 2.31-24.15), total hip (OR: 2.98, 1.02-9.54), and femoral neck (OR: 4.72, 1.72-14.19), than those without sarcopenia. Survivors with sarcopenia probable were at higher risk of low aBMD Z-score at the total body (OR: 4.13, 1.04-17.60) than those without sarcopenia. CONCLUSIONS: Young paediatric cancer survivors with sarcopenia present higher risk of low aBMD. Resistance training-based interventions designed to mitigate osteosarcopenia in this population should be implemented at early stages.

Impact of genetic variants in the solute carrier (SLC) genes encoding drug uptake transporters on the response to anticancer chemotherapy.

Cancer drug resistance constitutes a severe limitation for the satisfactory outcome of these patients. This is a complex problem due to the co-existence in cancer cells of multiple and synergistic mechanisms of chemoresistance (MOC). These mechanisms are accounted for by the expression of a set of genes included in the so-called resistome, whose effectiveness often leads to a lack of response to pharmacological treatment. Additionally, genetic variants affecting these genes further increase the complexity of the question. This review focuses on a set of genes encoding members of the transportome involved in drug uptake, which have been classified into the MOC-1A subgroup of the resistome. These proteins belong to the solute carrier (SLC) superfamily. More precisely, we have considered here several members of families SLC2, SLC7, SLC19, SLC22, SLCO, SLC28, SLC29, SLC31, SLC46, and SLC47 due to the impact of their expression and genetic variants in anticancer drug uptake by tumor cells or, in some cases, general bioavailability. Changes in their expression levels and the appearance of genetic variants can contribute to the Darwinian selection of more resistant clones and, hence, to the development of a more malignant phenotype. Accordingly, to address this issue in future personalized medicine, it is necessary to characterize both changes in resistome genes that can affect their function. It is also essential to consider the time-dependent dimension of these features, as the genetic expression and the appearance of genetic variants can change during tumor progression and in response to treatment.

The Search for Risk, Diagnostic, and Prognostic Biomarkers of Cholangiocarcinoma and Their Biological and Clinicopathologic Significance.

Cholangiocarcinomas (CCAs) are a heterogeneous group of malignant tumors that originate from the biliary tract. They are usually diagnosed in advanced stages, leading to a dismal prognosis for affected patients. As CCA often arises as a sporadic cancer in individuals lacking specific risk factors or with heterogeneous backgrounds, and there are no defined high-risk groups, the implementation of effective surveillance programs for CCA is problematic. The identification and validation of new biomarkers useful for risk stratification, diagnosis, prognosis, and prediction of treatment response remains an unmet need for patients with CCA, even though numerous studies have been conducted lately to try to discover and validate CCA biomarkers. In this review, we overview the available information about the different types of biomarkers that have been investigated in recent years using minimally invasive biospecimens (blood, serum/plasma, bile, and urine) and their potential usefulness in diagnosis, prognosis, and risk stratification. It is widely accepted that early detection of CCA will impact patients' outcomes, by improving survival rates, quality of life, and the possibility of less invasive and/or curative treatments; however, challenges to its translation and clinical application for patients with CCA need to be resolved.