Background: Two unique biomarkers, soluble form of the urokinase-type plasminogen activator receptor (suPAR) and neopterin, play a crucial role in inflammatory processes. This study aimed to reveal whether it is possible to utilize these biomarkers in predicting tumor prognosis in patients with lung cancers.
Methods: The present study was designed as a single center, prospective, and controlled research. The study was conducted with forty patients with lung cancer (case group) and 41 healthy individuals (control group) in Kırıkkale University, Faculty of Medicine between 2016-2020. The case group was also divided into two of the early and advanced stages. The blood samples were drawn to evaluate suPAR and neopterin levels, and these parameters were compared between the case and control groups. Also, the prognostic effects of age, stage of the tumor, and the levels of mentioned parameters were investigated with the survival analysis.
Results: The median duration of the follow-up was 32 (4-75) months. suPAR and neopterin levels were found to be higher in the case group than in the control group. Cox regression showed that the high levels of neopterin and suPAR increased mortality risk [p=0.002, HR: 1.25 (1.08-1.45 95%CI) and p=0.023, HR:1.07 (1.01-1.13), respectively]. Finally, age and stage of the tumor were found to have no relationship with survival.
Conclusion: suPAR and neopterin as members of the inflammatory pathway were found to be higher in cancer cases. Furthermore, both suPAR and neopterin levels were found to be predictive for the mortality of patients with lung cancers; therefore, they are thought to be used for the management of cancer.
In this review, a series of experiments is presented, in which γ-amino butyric acid (GABA)ergic and glutamatergic effects on dopamine function in the rat nigrostriatal and mesolimbic system was systematically assessed after pharmacological challenge with GABAA receptor (R) and and N-methyl d-aspartate (NMDA)R agonists and antagonists. In these studies, [123I]iodobenzamide binding to the D2/3R was mesured in nucleus accumbens (NAC), caudateputamen (CP), substantia nigra/ventral tegmental area (SN/VTA), frontal (FC), motor (MC) and parietal cortex (PC) as well as anterior (aHIPP) and posterior hippocampus (pHIPP) with small animal SPECT in baseline and after injection of either the GABAAR agonist muscimol (1 mg/kg), the GABAAR antagonist bicuculline (1 mg/kg), the NMDAR agonist d-cycloserine (20 mg/kg) or the NMDAR antagonist amantadine (40 mg/kg). Muscimol reduced D2/3R binding in NAC, CP, SN/VTA, THAL and pHIPP, while, after amantadine, decreases were confined to NAC, CP and THAL. In contrast, d-cycloserine elevated D2/3R binding in NAC, SN/VTA, THAL, frontal cortex, motor cortex, PC, aHIPP and pHIPP, while, after bicuculline, increases were confined to CP and THAL. Taken together, similar actions on regional dopamine levels were exterted by the GABAAR agonist and the NMDAR antagonist on the one side and by the GABAAR antagonist and the NMDAR agonist on the other, with agonistic action, however, affecting more brain regions. Thereby, network analysis suggests different roles of GABAARs and NMDARs in the mediation of nigrostriatal, nigrothalamocortical and mesolimbocortical dopamine function.
Endothelins are powerful vasoconstrictor peptides that play numerous other roles. Endothelin-1 (ET1) is the principal isoform produced by the endothelium in the human cardiovascular system. Endothelin-3 (ET3) and its rPptor affinity have been demonstrated to support neuronal repair mechanisms throughout life. In multiple sclerosis (MS), the role of vasoactive peptides are not well defined. Here we focus on ET3, specifically the plasma levels between MS patients and healthy subjects. Furthermore, we evaluated the changes in ET1 and ET3 plasma levels during different disease phases, the correlation between ET3 and cerebral circulation time, and the relationship between ET1 and ET3. In MS patients, the ET3 plasma levels were altered in a time-dependent manner. These results could support a putative role of ET3 in neuroprotection and/or neuroimmune modulation over time.
Major depressive disorder (MDD) is a highly prevalent and disabling condition for which the currently available treatments are not fully effective. Existing unmet needs include rapid onset of action and optimal management of concurrent agitation. Dexmedetomidine (DEX) is a selective and potent α2-adrenergic receptor (α2-AR) agonist, with unique pharmacokinetic and pharmacodynamic properties. In this review, we discuss pre-clinical and clinical studies which focused on DEX in the context of its putative antidepressant effects for the management of MDD. Preliminary data support DEX as an antidepressant with fast onset of action, which would be especially helpful for patients experiencing treatment resistant depression, and agitation. We further explore the mechanistic and clinical implications of considering DEX as a putative antidepressant agent, and the next steps to explore the efficacy of low dose DEX infusion among patients with treatment resistant depression.
Invasive fungal disease (IFD) is one of the most serious complications of therapy in patients with immune suppression. It particularly concerns patients treated for malignant hematological diseases, immune deficiencies, or undergoing hematopoietic cell transplantation (HCT). Development of IFD can abrogate the effect of previous therapy and contributes to dismal outcome of the underlying disease. The Working Group consisting of members of the Polish Society of Hematology and Blood Transfusion, the Polish Society of Pediatric Oncology and Hematology, and the Polish Adult Leukemia Study Group has prepared recommendations for the diagnostic and therapeutic management of IFD in adults and children. This paper presents the current recommendations for patients in immune suppression treated in Polish pediatric and adult hematology and HCT centers, based on the guidelines of the European Conference on Infections in Leukaemia (ECIL) 2015–2019. Levels of diagnosis of IFD (possible, probable, and proven) and antifungal management (prophylaxis, as well as empirical and targeted therapies) are declared according to updated international criteria of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSG) 2019. Patients with primary diagnosis of acute lymphoblastic leukemia, acute myeloblastic leukemia, severe aplastic anemia, chronic granulomatous disease, and severe combined immunodeficiency, as well as patients after allogeneic HCT, are included in the high-risk groups for development of IFD. For these patients, antifungal prophylaxis based on azoles or micafungin is recommended. In empirical therapy, caspofungin or liposomal/lipid formulas of amphotericin B are recommended. The Working Group has discouraged the use of itraconazole in capsules and amphotericin deoxycholate. Detailed guidelines for first- and second-line targeted therapies for invasive candidiasis, aspergillosis, mucormycosis, fusariosis, and scedosporiosis, as well as the principles of the recommended dosing of antifungals, are presented in this paper.
Proton pump inhibitors (PPIs) are drugs commonly used for many diseases of the gastrointestinal tract, such as gastroesophageal reflux disease, erosive esophagitis, and peptic ulcers of the stomach and duodenum. Used for about 30 years, they are currently the most effective drugs that reduce the gastric secretion of hydrochloric acid. However, a dramatic increase in their consumption has been recently observed. Very often, they are used not in accordance with the guidelines. The consequences of the long-term use of PPIs may be various, with the most common side effects being bone fractures, cardiovascular events, recurrent infections, and vitamin and mineral deficiencies. Case report: An 82-year-old and a 58-year-old patients who had been taking omeprazole, a PPI for several years, developed vitamin B12 and iron deficiency anemia. Both patients were administered PPI orally for nonspecific dyspeptic symptoms. An evaluation of the gastrointestinal tract did not reveal the evident causes of gastrointestinal blood loss. They were also screened negative for Helicobacter pylori infection. Conclusions: There are no definitive pieces of evidence that the long-term use of PPIs can induce anemia, but our cases strongly suggest this thesis. Physicians should be aware of this potential side effect and consider monitoring in high-risk patients.
Hemoglobin/red cell distribution width (RDW) ratio (HRR) and lymphocyte-to-monocyte ratio (LMR) are two novel bio-markers associated with overall survival (OS) and prognosis in several types of cancers. The aim of this study is to investigate the value of HRR and LMR in newly diagnosed multiple myeloma (MM) patients.
A total of 180 patients were included in this study. Patients diagnosed with MM between May 2013 and May 2019 at a single center were evaluated. HRR was calculated by dividing hemoglobin to RDW, both measured from the same sample. LMR was calculated by dividing absolute lymphocyte count (ALC) to absolute monocyte count (AMC).
The cutoff value for HRR was taken as 0.61, and the cutoff value for LMR was taken as 3.28. Patients were divided into low HRR, high HRR, low LMR, and high LMR groups. OS of the patients with low HRR was found lower compared with high HRR (36.7 months for low HRR and 53.2 months for high HRR, p < 0.001). Also, OS was found lower in the low LMR group (39.4 months for low LMR and 51.7 months for high LMR, p = 0.016). On multivariate analysis, low HRR and low LMR were predictive factors of OS (hazard ratio (HR) 2.08, 95% confidence intervals (CI) 1.31–3.03, and p = 0.002 for low HRR; HR 1.47, 95% CI 0.92–2.29, and p = 0.010 for low LMR).
Combining both HRR and LMR could be a prognostic biomarker and it reflects the status of the immune system in newly diagnosed MM patients.