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Considering the divergent biological behaviors of certain histological subtypes of urothelial carcinoma, it would be of great importance to examine the impact of variant histology and to predict its presence in patients with bladder cancer. A single-center cohort study included 459 patients who underwent radical cystectomy for urothelial carcinoma between 2017 and 2021. Patients were followed up with until July 2022. We compared clinical, laboratory, and histopathologic characteristics and the overall survival between patients with pure urothelial carcinoma and variant histologies. Our results showed that the patients with variant histology were older and preoperatively more frequently had hydronephrosis and higher values of leukocytes and neutrophils. Also, we found a significant association between variant histology and an advanced stage of tumor disease, the presence of lymphovascular invasion, positive surgical margins, and metastases in surgically resected lymph nodes. The number of neutrophils was identified as an independent preoperative predictor of the presence of variant histology after a radical cystectomy. The overall survival of the patients with variant histology was significantly lower compared to the patients with pure urothelial carcinoma. According to our results, the presence of variant histology represents a more aggressive form of the disease. Preoperative neutrophil counts may indicate the presence of variant histology of urothelial carcinoma in patients with bladder cancer.

Innate and adaptive immune responses exert their role in CIDP pathogenesis through cytokine production. Single-nucleotide polymorphisms (SNPs) may alter cytokine gene expression, with a potential influence on the pathogenesis of autoimmune diseases. However, cytokine gene SNPs have not been assessed in CIDP patients yet. We assessed functional SNPs in the genes encoding IL-10 (rs1800896, rs1800871, rs1800872 and rs3024505), IL-6 (rs1800795), TNF (rs1800629 and rs361525), IL-12B (rs3212227), IFN-γ (rs2430561), GM-CSF (rs25882) and IL-17F (rs11465553) in a cohort of 88 CIDP patients and 486 healthy controls (HCs) via qPCR. We found an association of SNP in the IL10 promotor and CIDP occurrence. Major homozygotes (AA) were more frequent in the HCs compared to CIDP patients ( p = 0.049), but the GA genotype prevailed among the patients ( p = 0.032). A lower frequency of the C allele was observed for rs1800871 and rs1800872 in CIDP patients compared to the HCs ( p = 0.048). A higher proportion of A carriers at position -1082 (rs1800896) (presumed to be a low IL-10 producer) was noted in patients with milder disability (low INCAT). All mild-INCAT patients were C carriers for rs1800871 and rs1800872 in IL10 ( p = 0.038). Furthermore, the IL6 rs1800795 GG genotype was more frequent in patients ( p = 0.049) and the CG heterozygote in the HCs ( p = 0.013). Among the CIDP patients, being a G carrier for this SNP was associated with a higher frequency of type 2 diabetes (T2D) compared to being a non-carrier ( p = 0.032). Our data indicate a possible association of the IL10 and IL6 SNPs with CIDP, but also with disease severity and T2D occurrence. Given the paucity of CIDP patients, multicentric studies are necessary to draw definite conclusions on these associations.

In recent years, the focus of numerous studies has been the predictive value of inflammatory and nutritional parameters in oncology patients. The aim of our study was to examine the relationship between the inflammatory and nutritional parameters and the histopathological characteristics of patients with bladder cancer. A retrospective study included 491 patients who underwent radical cystectomy for bladder cancer between 2017 and 2021. We calculated the preoperative values of the neutrophil-to-lymphocyte ratio (NLR), the derived neutrophil-to-lymphocyte ratio (dNLR), the systemic immune-inflammation index (SII), the systemic inflammatory response index (SIRI), the platelet-to-lymphocyte ratio (PLR), the lymphocyte-to-monocyte ratio (LMR), the prognostic nutritional index (PNI), and the geriatric nutritional risk index (GNRI). Statistically significant positive correlations were observed between NLR, dNLR, SII, SIRI, and PLR and the pathological stage of the tumor. We observed statistically significant inverse correlations for LMR, PNI, and GNRI with the tumor stage. SIRI was identified as an independent predictor of the presence of LVI. dNLR was identified as an independent predictor of positive surgical margins. GNRI was identified as an independent predictor of the presence of metastases in the lymph nodes. We noticed the predictive value of SIRI, dNLR, and GNRI in the pathology of bladder cancer patients.

AMP-activated protein kinase (AMPK) is an intracellular energy sensor that regulates metabolic and immune functions mainly through the inhibition of the mechanistic target of rapamycin (mTOR)-dependent anabolic pathways and the activation of catabolic processes such as autophagy. The AMPK/mTOR signaling pathway and autophagy markers were analyzed by immunoblotting in blood mononuclear cells of 20 healthy control subjects and 23 patients with an acute demyelinating form of Guillain-Barré syndrome (GBS). The activation of the liver kinase B1 (LKB1)/AMPK/Raptor signaling axis was significantly reduced in GBS compared to control subjects. In contrast, the phosphorylated forms of mTOR activator AKT and mTOR substrate 4EBP1, as well as the levels of autophagy markers LC3-II, beclin-1, ATG5, p62/sequestosome 1, and NBR1 were similar between the two groups. The downregulation of LKB1/AMPK signaling, but not the activation status of the AKT/mTOR/4EBP1 pathway or the levels of autophagy markers, correlated with higher clinical activity and worse outcomes of GBS. A retrospective study in a diabetic cohort of GBS patients demonstrated that treatment with AMPK activator metformin was associated with milder GBS compared to insulin/sulphonylurea therapy. In conclusion, the impairment of the LKB1/AMPK pathway might contribute to the development/progression of GBS, thus representing a potential therapeutic target in this immune-mediated peripheral polyneuropathy., Competing Interests: The authors declare no conflict of interest. The sponsors had no role in the design, execution, interpretation, or writing of the study.