Adverse outcomes related to morcellation in Total Laparoscopic Hysterectomy.

OBJECTIVE: This study aimed to comprehensively evaluate the complications associated with morcellation in Total Laparoscopic Hysterectomy (TLH) procedures, providing evidence-based insights to enhance patient safety and surgical efficacy. DATA SOURCES: A comprehensive literature search was conducted using multiple databases, including PubMed, EMBASE, Google Scholar, and Cochrane Central Register of Controlled Trials. The inclusion criteria were Studies that focused on morcellation and morcellation-related complications were included. The risk of bias in the included studies was assessed using established evaluation scales. METHODS OF STUDY SELECTION: Thirteen studies investigating complications associated with morcellation in TLH (Total Laparoscopic Hysterectomy) were included in this review.This review covers intraoperative blood loss, length of hospital stay, loss of bag integrity, mean uterine specimen and weight, morcellation time, operation time, and TLH morcellation complications. TABULATION, INTEGRATION, AND RESULTS: The selected studies covered different approaches and aspects related to this procedure, providing valuable insights into the factors associated with complications and efficacy of the technique in various clinical settings.This review highlights the importance of evaluating and considering complications associated with morcellation in TLH. CONCLUSION: The findings of this review provide valuable insights into complications associated with morcellation in TLH. Clinicians could use this information to make informed decisions, implement safe protocols, and improve patient care. Addressing these complications will enhance the safety and efficacy of morcellation for TLH. Ethical Compliance: All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Elevated α-Ketoglutaric Acid Concentrations and a Lipid-Balanced Signature Are the Key Factors in Long-Term HIV Control.

Long-term elite controllers (LTECs) are a fascinating small subset of HIV individuals with viral and immunological HIV control in the long term that have been designated as models of an HIV functional cure. However, data on the LTEC phenotype are still scarce, and hence, the metabolomics and lipidomics signatures in the LTEC-extreme phenotype, LTECs with more than 10 years of viral and immunological HIV control, could be pivotal to finding the keys for functional HIV remission. Metabolomics and lipidomics analyses were performed using high-resolution mass spectrometry (ultra-high-performance liquid chromatography-electrospray ionization-quadrupole time of flight [UHPLC-(ESI) qTOF] in plasma samples of 13 patients defined as LTEC-extreme, a group of 20 LTECs that lost viral and/or immunological control during the follow-up study (LTEC-losing) and 9 EC patients with short-term viral and immunological control (less than 5 years; no-LTEC patients). Long-term viral and immunological HIV-1 control was found to be strongly associated with elevated tricarboxylic acid (TCA) cycle function. Interestingly, of the nine metabolites identified in the TCA cycle, α-ketoglutaric acid (p = 0.004), a metabolite implicated in the activation of the mTOR complex, a modulator of HIV latency and regulator of several biological processes, was found to be a key metabolite in the persistent control. On the other hand, a lipidomics panel combining 45 lipid species showed an optimal percentage of separation and an ability to differentiate LTEC-extreme from LTEC-losing, revealing that an elevated lipidomics plasma profile could be a predictive factor for the reignition of viral replication in LTEC individuals.

Adipokines as New Biomarkers of Immune Recovery: Apelin Receptor, RBP4 and ZAG Are Related to CD4+ T-Cell Reconstitution in PLHIV on Suppressive Antiretroviral Therapy.

A significant proportion of people living with HIV (PLHIV) who successfully achieve virological suppression fail to recover CD4+ T-cell counts. Since adipose tissue has been discovered as a key immune organ, this study aimed to assess the role of adipokines in the HIV immunodiscordant response. This is a multicenter prospective study including 221 PLHIV starting the first antiretroviral therapy (ART) and classified according to baseline CD4+ T-cell counts/µL (controls > 200 cells/µL and cases ≤ 200 cells/µL). Immune failure recovery was considered when cases did not reach more than 250 CD4+ T cells/µL at 144 weeks (immunological nonresponders, INR). Circulating adipokine concentrations were longitudinally measured using enzyme-linked immunosorbent assays. At baseline, apelin receptor (APLNR) and zinc-alpha-2-glycoprotein (ZAG) concentrations were significantly lower in INRs than in immunological responders (p = 0.043 and p = 0.034), and they remained lower during all ART follow-up visits (p = 0.044 and p = 0.028 for APLNR, p = 0.038 and p = 0.010 for ZAG, at 48 and 144 weeks, respectively). ZAG levels positively correlated with retinol-binding protein 4 (RBP4) levels (p < 0.01), and low circulating RBP4 concentrations were related to a low CD4+ T-cell gain (p = 0.018 and p = 0.039 at 48 and 144 weeks, respectively). Multiple regression adjusted for clinical variables and adipokine concentrations confirmed both low APLNR and RBP4 as independent predictors for CD4+ T cells at 144 weeks (p < 0.001). In conclusion, low APLNR and RBP4 concentrations were associated with poor immune recovery in treated PLHIV and could be considered predictive biomarkers of a discordant immunological response.

The Small GTPases in Fungal Signaling Conservation and Function.

Monomeric GTPases, which belong to the Ras superfamily, are small proteins involved in many biological processes. They are fine-tuned regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Several families have been identified in organisms from different kingdoms. Overall, the most studied families are Ras, Rho, Rab, Ran, Arf, and Miro. Recently, a new family named Big Ras GTPases was reported. As a general rule, the proteins of all families have five characteristic motifs (G1-G5), and some specific features for each family have been described. Here, we present an exhaustive analysis of these small GTPase families in fungi, using 56 different genomes belonging to different phyla. For this purpose, we used distinct approaches such as phylogenetics and sequences analysis. The main functions described for monomeric GTPases in fungi include morphogenesis, secondary metabolism, vesicle trafficking, and virulence, which are discussed here. Their participation during fungus-plant interactions is reviewed as well.

High circulating SDF-1and MCP-1 levels and genetic variations in CXCL12, CCL2 and CCR5: Prognostic signature of immune recovery status in treated HIV-positive patients.

BACKGROUND: The underlying mechanisms of incomplete immune reconstitution in treated HIV-positive patients are very complex and may be multifactorial, but perturbation of chemokine secretion could play a key role in CD4+T-cell turnover. METHODS: We evaluated the circulating baseline and 48-week follow-up concentrations of SDF-1/CXCL12, fractalkine/CX3CL1, MCP-1/CCL2, MIP-α/CCL3, MIP-ß/CCL4 and RANTES/CCL5, and we estimated their association with CXCL12, CX3CR1, CCR2, CCL5 and CCR5 single nucleotide polymorphisms (SNPs) to investigate multiple chemokine-chemokine receptor signatures associated with immune dysregulation preceding poor immune recovery. FINDINGS: The circulating concentrations and gene expression patterns of SDF-1/CXCL12 (CXCL12 rs1801157) and MCP-1/CCL2 (CCR2 rs1799864_814) were associated with immune recovery status. CCR2 rs1799864_814 and CCR5 rs333_814 (Δ32) determine the baseline plasma RANTES and MIP-α concentrations, respectively, in participants with poor immune response. INTERPRETATION: SDF-1/CXCL12 and MCP-1/CCL2 could be considered prognostic markers of immune failure despite suppressive antiretroviral therapy. The strong linkage disequilibrium (LD) between CCR2 rs1799864_814 and CCR5 rs1800024 indicated that the alleles of each gene are inherited together more often than would be expected by chance. FUNDING: This work was supported by Fondo de Investigacion Sanitaria and SPANISH AIDS Research Network (ISCIII-FEDER); AGAUR and Gilead Fellowship. FV and YMP are supported by grants from the Programa de Intensificación (ISCIII) and Servicio Andaluz de Salud, respectively. JVG,EY and LR are supported by the Instituto de Salud Carlos III (ISCIII). AR is supported by Departament de Salut, Generalitat de Catalunya and by the Instituto de Salud Carlos III (ISCIII).

IL-7/IL-7R gene variants impact circulating IL-7/IL-7R homeostasis and ART-associated immune recovery status.

A relationship between polymorphisms in genes encoding interleukin 7 (IL-7) and its cellular receptor (IL-7R) and antiretroviral therapy (ART)-associated immune recovery in HIV subjects has been previously reported. However, details of this relationship remain unclear, and the association of these polymorphisms with circulating IL-7/IL-7R levels is scarce. Here, we explored whether IL-7/IL-7R axis was associated with quantitative CD4+ T-cell recovery in HIV-infected subjects. IL-7/IL-7R polymorphisms were assessed by genotyping, and multiple inheritance models were used to estimate both, their association with low pre-ART CD4+ T-cell counts and incomplete immune recovery status after 48 weeks of suppressive ART. Integrated data from genetic variants association and soluble plasma IL-7/IL-7R quantification suggest that IL-7/IL-7R genotype expression could alter the homeostatic balance between soluble and membrane-bound receptors. The haplotype analyses indicates that allele combinations impacts pre-ART circulating CD4+ T-cell counts, immune recovery status and the absolute increment of CD4+ T-cell counts. The knowledge about how IL-7/IL-7R axis is related to quantitative CD4+ T-cell recovery and immune recovery status after initiating ART could be useful regarding T-cell reservoirs investigations in HIV subjects.

Circulating metabolomic profile can predict dyslipidemia in HIV patients undergoing antiretroviral therapy.

BACKGROUND AND AIMS: Dyslipidemia in HIV-infected patients is unique and pathophysiologically associated with host factors, HIV itself and the use of antiretroviral therapy (ART). The use of nuclear magnetic resonance spectroscopy (NMR) provides additional data to conventional lipid measurements concerning the number of lipoprotein subclasses and particle sizes. METHODS: To investigate the ability of lipoprotein profile, we used a circulating metabolomic approach in a cohort of 103 ART-naive HIV-infected patients, who were initiating non-nucleoside analogue transcriptase inhibitor (NNRTI)-based ART, and we subsequently followed up these patients for 36 months. Univariate and multivariate analyses were performed to evaluate the predictive power of NMR spectroscopy. RESULTS: VLDL-metabolism (including VLDL lipid concentrations, sizes, and particle numbers), total triglycerides and lactate levels resulted in good classifiers of dyslipidemia (AUC 0.903). Total particles/HDL-P ratio was significantly higher in ART-associated dyslipidemia compared to ART-normolipidemia (p = 0.001). Large VLDL-Ps were positively associated with both LDL-triglycerides (ρ 0.682, p < 0.001) and lactate concentrations (ρ 0.416, p < 0.001), the last one a marker of mitochondrial low oxidative capacity. CONCLUSIONS: Our data suggest that circulating metabolites have better predictive values for HIV/ART-related dyslipidemia onset than do the biochemical markers associated with conventional lipid measurements. NMR identifies changes in VLDL-P, lactate and LDL-TG as potential clinical markers of baseline HIV-dyslipidemia predisposition. Differences in circulating metabolomics, especially differences in particle size, are indicators of important derangements of mitochondrial function that are linked to ART-related dyslipidemia.

Causas de no aptitud en examen de salud inicial de trabajadores expuestos a citostáticos / Causes of no aptitude in initial health examination of workers exposed to cytostatics

Resumen: Los fármacos citostáticos son terapias que se utilizan específicamente para causar daño celular no selectivo, poseen características genotoxicas, carcinogénicas, teratogénicos, entre otras. La exposición de los trabajadores a sustancias citotóxicas ha sido identificada como un problema de preocupación creciente para la salud. Material y métodos: Estudio descriptivo entre los años 2008-2012, basado en la revisión de historias clínico-laborales de todos los trabajadores expuesto a citostáticos al inicio de su actividad laboral. Resultados: Se revisaron un total de 434 historias clínico-laborales. no aptos en los 5 años de 37 trabajadores, que corresponde al 8,5 % del total de valorados. Los criterios de no aptitud se tomaron de los propuestos por el Protocolo de Vigilancia Especifica de los trabajadores expuestos a citostáticos, de la comisión de salud pública, consejo interterritorial del sistema nacional de salud del 2003. La causa mas frecuente de no aptitud fue el tratamiento previo con citostáticos, inmunosupresores y antecedentes de enfermedad neoplásica con un 28 % de frecuencia, seguidas por un 16 % de inmunodepresión y voluntad de reproducción (16%), patología dermatológica (16%). las causas menos comunes fueron historia de abortos previos (8%), actividad laboral asociada a radiación ionizantes (5%), daño genético (3%) y otras causas (5%). Conclusiones: La mayoría de trabadores expuesto a citostáticos en nuestro hospital en el periodo antes mencionado son mujeres, en edad fértil, donde la causa mas frecuente de no aptitud se debe a enfermedad neoplásica y tratamiento previo con citostáticos e inmunosupresores, no hay datos de alergias a citostáticos (AU)

Abstract: Cytostatic drugs are therapies that are used specifically to cause cellular damage nonselective possess genotoxic properties, carcinogenic, teratogenic, among others. The worker exposure to cytotoxic substances has been identified as an issue of growing concern for health. Material and Methods: A descriptive study between the years 2008- 2012, based on review of clinical and work histories of all workers exposed to cytostatics at the beginning of their employment. Results: A total of 434 clinical and labor records were reviewed. Unfit within 5 years of 37 workers, which corresponds to 8.5% of rated. No fitness criteria were taken from those proposed by the Monitoring Protocol Specifies workers exposed to cytostatic, the public health commission, council interregional national health system in 2003 The most frequent cause of no aptitude was pretreatment with cytostatic, immunosuppressive and history of neoplastic disease with 28% frequency, followed by 16% and will play immunosuppression (16%), dermatological pathology (16%). Less common causes were history of previous abortions (8%), work activity associated with ionizing radiation (5%), genetic damage (3%) and other causes (5%). Conclusions: The majority of workers exposed to cytostatic in our hospital in the period mentioned above are women of childbearing age, where the most frequent cause of no aptitude due to neoplastic disease and prior treatment with cytostatic and immunosuppressants, no details of allergies cytostatics (AU)

Zinc alpha-2 glycoprotein is implicated in dyslipidaemia in HIV-1-infected patients treated with antiretroviral drugs.

OBJECTIVES: Treated HIV-1-infected patients with lipodystrophy often develop insulin resistance and proatherogenic dyslipidaemia. Zinc alpha-2 glycoprotein (ZAG) is a recently characterized adipokine which has been shown to be involved in the development of obesity and metabolic syndrome in uninfected subjects. We assessed the relationship between circulating ZAG levels and metabolic derangements in HIV-1-infected patients receiving antiretroviral drugs. METHODS: Plasma ZAG levels were assessed in 222 individuals: 166 HIV-1-infected patients treated with antiretroviral drugs (77 with lipodystrophy and 89 without lipodystrophy) and 56 uninfected controls. Plasma ZAG levels were assessed by enzyme-linked immunosorbent assay (ELISA) and were correlated with fat distribution abnormalities and metabolic parameters. RESULTS: HIV-1-infected patients had lower plasma ZAG levels compared with uninfected controls (P < 0.001). No differences were found in ZAG plasma levels according to the presence of lipodystrophy, components of the metabolic syndrome or type of antiretroviral treatment regimen. Circulating ZAG levels were strongly determined by high-density lipoprotein cholesterol (HDLc) in men (B = 0.644; P < 0.001) and showed a positive correlation with total cholesterol (r = 0.312; P < 0.001) and HDLc (r = 0.216; P = 0.005). CONCLUSIONS: HIV-1-infected patients have lower plasma ZAG levels than uninfected controls. In infected patients, plasma ZAG levels are in close relationship with total cholesterol and HDLc.