Shedding Light on Colorectal Cancer: An In Vivo Raman Spectroscopy Approach Combined with Deep Learning Analysis.

Raman spectroscopy has emerged as a powerful tool in medical, biochemical, and biological research with high specificity, sensitivity, and spatial and temporal resolution. Recent advanced Raman systems, such as portable Raman systems and fiber-optic probes, provide the potential for accurate in vivo discrimination between healthy and cancerous tissues. In our study, a portable Raman probe spectrometer was tested in immunosuppressed mice for the in vivo localization of colorectal cancer malignancies from normal tissue margins. The acquired Raman spectra were preprocessed, and principal component analysis (PCA) was performed to facilitate discrimination between malignant and normal tissues and to highlight their biochemical differences using loading plots. A transfer learning model based on a one-dimensional convolutional neural network (1D-CNN) was employed for the Raman spectra data to assess the classification accuracy of Raman spectra in live animals. The 1D-CNN model yielded an 89.9% accuracy and 91.4% precision in tissue classification. Our results contribute to the field of Raman spectroscopy in cancer diagnosis, highlighting its promising role within clinical applications.

Decreased Levels of Soluble Developmental Endothelial Locus-1 Are Associated with Thrombotic Microangiopathy in Pregnancy.

HELLP (Hemolysis, Elevated Liver enzymes and Low Platelets) syndrome is a life-threatening complication of pregnancy, which is often secondary to preeclampsia. To date, there is no biomarker in clinical use for the early stratification of women with preeclampsia who are under increased risk of HELLP syndrome. Herein, we show that the levels of circulating developmental endothelial locus-1 (DEL-1), which is an extracellular immunomodulatory protein, are decreased in patients with HELLP syndrome compared to preeclampsia. DEL-1 levels are also negatively correlated with the circulating levels of kidney injury molecule-1 (KIM-1), which is a biomarker for disorders associated with kidney damage. Receiver-operating characteristic curve analysis for DEL-1 levels and the DEL-1 to KIM-1 ratio demonstrates that these values could be used as a potential biomarker that distinguishes patients with HELLP syndrome and preeclampsia. Finally, we show that placental endothelial cells are a source for DEL-1, and that the expression of this protein in placenta from patients with HELLP syndrome is minimal. Taken together, this study shows that DEL-1 is downregulated in HELLP syndrome both in the circulation and at the affected placental tissue, suggesting a potential role for this protein as a biomarker, which must be further evaluated.

Eugenol Reduced ΜPO, CD45 and HMGB1 Expression and Attenuated the Expression of Leukocyte Infiltration Markers in the Intestinal Tissue in Biliopancreatic Duct Ligation-Induced Pancreatitis in Rats.

Background and Objectives: Inflammation and dysregulation in the intestinal barrier function in acute pancreatitis (AP) trigger pancreatic lesions, systemic inflammatory response, and multiple organ dysfunction. Eugenol, as the main component of clove (Syzygium aromaticum), is known for its antioxidant and anti-inflammatory properties. We studied the potentially beneficial effect of eugenol in a rodent model of biliopancreatic duct ligation-induced AP. Materials and Methods: Rats were randomly divided into three groups: Sham, AP, and AP + eugenol (15 mg/kg/day). Serum TNFα, IL-6, IL-18, and resistin levels, as well as IL-6, TNFα, MPO, HMGB1, and CD45 tissue expression, were determined at various timepoints after the induction of AP. Results: Eugenol attenuated hyperemia and inflammatory cell infiltration in the intestinal mucosal, submucosal, and muscular layers. IL-6 and resistin serum levels were significantly reduced in the AP + eugenol group, while serum TNFα and IL-18 levels remained unaffected overall. TNFα pancreatic and intestinal expression was attenuated by eugenol at 72 h, while IL-6 expression was affected only in the pancreas. MPO, CD45, and HMGB1 intestinal expression was significantly reduced in eugenol-treated rats. Conclusions: Eugenol managed to attenuate the inflammatory response in the intestine in duct ligation-induced AP in rats.

Three-year pollen and fungi calendar in a Mediterranean region of the Northeast Greece.

INTRODUCTION AND OBJECTIVES: Pollen calendars have been proved clinically important in allergic disease management, as differences in airborne allergens exist not only between different countries but also between regions of the same country as well. This study aims to provide new data regarding the atmospheric pollen and fungi content of a Mediterranean region (Western Thrace/North-East Greece) and discuss seasonal trends, differences in pollen grains and fungi spores' circulation over the years, and correlations with climate parameters. MATERIAL AND METHODS: A 7-day continuously running volumetric trap was used to collect circulating pollen grains and fungi spores. Pollen taxa and fungi were characterized by standard protocols and counted as grains /m3 and average total grains and spores. The primary allergenic pollen season was discovered, and their 10-day averages were measured over time. Correlations with temperature, rain, and humidity were assessed by single linear regression analysis. RESULTS: Pollen grains from nine pollen families were identified, including five arboreal, two nonarboreal taxa, and spores from two fungi species. The three most prevalent taxa were Oleaceae, Poaceae, Pinaceae, and Cladosporium in the fungi. Peak pollen concentrations were detected during April and May, with daily averages exceeding 170 grains/m3. Poaceae presented the longest pollen season of 342 days and Oleaceae the shortest, extending to only 110 days, during the 3years. Cladosporium was the fungus with the highest spore concentration (180,129.9 spores) compared with Alternaria (28,026.1 spores). Correlations with meteorological parameters showed variable associations among different taxa, with rainfall and relative humidity being the most significant determinants. CONCLUSION: In this study, the pollenic and fungal spectrum of a Mediterranean region and information that can be proved clinically significant for the appropriate diagnostic and therapeutic approach of allergic patients was presented.

The Role of Interleukins in Recurrent Implantation Failure: A Comprehensive Review of the Literature.

Recurrent implantation failure (RIF) is a multifactorial condition affecting 10-15% of in vitro fertilization (IVF) couples. Data suggest that functional dysregulation of the endometrial immune system constitutes one of the main pathophysiological mechanisms leading to RIF. The aim of this article is to provide a thorough presentation and evaluation of the role of interleukins (ILs) in the pathogenesis of RIF. A comprehensive literature screening was performed summarizing current evidence. During implantation, several classes of ILs are secreted by epithelial and stromal endometrial cells, including IL-6, IL-10, IL-12, IL-15, IL-18, and the leukemia inhibitory factor. These ILs create a perplexing network that orchestrates both proliferation and maturation of uterine natural killer cells, controls the function of regulatory T and B cells inhibiting the secretion of antifetal antibodies, and supports trophoblast invasion and decidua formation. The existing data indicate associations between ILs and RIF. The extensive analysis performed herein concludes that the dysregulation of the ILs network indeed jeopardizes implantation leading to RIF. This review further proposes a mapping of future research on how to move forward from mere associations to robust molecular data that will allow an accurate profiling of ILs in turn enabling evidence-based consultancy and decision making when addressing RIF patients.

Effect of laparoscopic liver resection versus the open technique on hepatocyte regenerating activity in the rat.

BACKGROUND: Laparoscopic liver resection offers a safe and feasible option primarily for the excision of hepatic neoplasms. Timely recovery of liver volume is a key factor for improving prognosis and post-operative mortality of patients undergone liver resection. The aim of the present study was to compare liver regeneration after laparoscopic over open partial hepatectomy. METHODS: Wistar rats were subjected to laparoscopic 70% hepatectomy (group LAP-HEP), open 70% hepatectomy (group HEP), sham operation (group Sham) or no intervention (group Control). At various timepoints following operation (1 h-2 weeks), the liver was excised to assess relative liver weight, thiobarbituric acid reactive substances (TBARS) levels, mitotic activity, tissue expression of Nuclear Factor-κB (NFκB), Intercellular Adhesion Molecule-1 (ICAM-1) and Vascular Cell Adhesion Molecule-1 (VCAM-1) and the histopathologic profile. RESULTS: No differences were seen in relative liver weight between hepatectomy groups. Mitotic index was increased in all operative study groups, being higher in group LAP-HEP than in group HEP. TBARS levels were higher in group LAP-HEP compared to group HEP. NFκB and VCAM-1 tissue expression scores were increased in all operative study groups with VCAM-1 being higher in group HEP, while ICAM-1 was overexpressed only in hepatectomy groups. Mild histopathologic lesions were noted in hepatectomy groups with the histopathologic score being higher in group HEP (24 h). CONCLUSIONS: Laparoscopic liver resection enhanced hepatocyte mitotic activity which was accompanied by mild oxidative stress and a less pronounced local inflammatory response and tissue injury to that of the open technique.

Postponing Pregnancy Through Oocyte Cryopreservation for Social Reasons: Considerations Regarding Clinical Practice and the Socio-Psychological and Bioethical Issues Involved.

Oocyte freezing for 'social reasons' refers to women of reproductive age who are aiming to prolong, protect and secure their fertility. The term emerged to describe application of the highly promising technique, namely vitrification on oocytes retrieved through controlled ovarian stimulation (COS) from women intending to preserve their fertility for social reasons. These women opt to cryopreserve their oocytes at a point in their life when they need to postpone childbearing on the grounds of so called 'social' reasons. These reasons may include a highly driven career, absence of an adequate partner, financial instability, or personal reasons that make them feel unprepared for motherhood. This is a sensitive and multifaceted issue that entails medical, bioethical and socio-psychological components. The latest trend and the apparent increase noted on oocyte freezing for 'social reasons' has prompted our team of fertility specialists, embryologists, obstetricians, gynecologists and psychologists to proceed with a thorough, critical and all-inclusive comprehensive analysis. The wide range of findings of this analysis involve concerns of embryology and epigenetics that shape decisions made in the IVF laboratory, issues regarding obstetric and perinatal concerns on the pregnancy concluding from these oocytes and the respective delivery management and neonatal data, to the social and bioethical impact of this trend's application. This literature review refers to matters rising from the moment the 'idea' of this option is 'birthed' in a woman's thoughts, to proceeding and executing it clinically, up until the point of the pediatric follow up of the children born. We aim to shed light to the controversial issue of oocyte freezing, while objectively exhibit all aspects regarding this complex matter, as well as to respectfully approach how could the prospect of our future expectations be shaped from the impact of its application.

KISS1 and KISS1R expression in primary and metastatic colorectal cancer.

PURPOSE: Kisspeptins are produced by the KISS1 gene and have tumor-suppressing and anti-metastatic properties. Our aim was to study the expression of KISS1 and its receptor, KISS1R, in colorectal cancer. METHODS: KISS1 and KISS1R expression was detected using immunohistochemistry in malignant tissue samples from 66 patients (34 men, 32 women) with colorectal adenocarcinoma. In total, 74 tumor samples were studied, 57 samples from primary tumors and 17 samples from liver metastases. KISS1 and KISS1R levels were associated with various clinicopathological parameters and survival data. RESULTS: KISS1 expression was higher in primary tumors with advanced stage (III or IV) and in those with infiltrated lymph nodes. KISS1R expression was higher in primary tumors with distant metastases. No significant differences were detected between primary and metastatic tumors regarding KISS1 and KISS1R levels. Furthermore, patients with high KISS1R levels had longer overall survival. CONCLUSIONS: KISS1 and KISS1R expression is higher in advanced colorectal cancers and high KISS1R levels are associated with better prognosis in colorectal cancer.

Gene promoter methylation and protein expression of BRMS1 in uterine cervix in relation to high-risk human papilloma virus infection and cancer.

Cervical cancer is strongly related to certain high-risk types of human papilloma virus infection. Breast cancer metastasis suppressor 1 (BRMS1) is a tumor suppressor gene, its expression being regulated by DNA promoter methylation in several types of cancers. This study aims to evaluate the methylation status of BRMS1 promoter in relation to high-risk types of human papilloma virus infection and the development of pre-cancerous lesions and describe the pattern of BRMS1 protein expression in normal, high-risk types of human papilloma virus-infected pre-cancerous and malignant cervical epithelium. We compared the methylation status of BRMS1 in cervical smears of 64 women with no infection by high-risk types of human papilloma virus to 70 women with proven high-risk types of human papilloma virus infection, using real-time methylation-specific polymerase chain reaction. The expression of BRMS1 protein was described by immunohistochemistry in biopsies from cervical cancer, pre-cancerous lesions, and normal cervices. Methylation of BRMS1 promoter was detected in 37.5% of women with no high-risk types of human papilloma virus infection and was less frequent in smears with high-risk types of human papilloma virus (11.4%) and in women with pathological histology (cervical intraepithelial neoplasia) (11.9%). Methylation was detected also in HeLa cervical cancer cells. Immunohistochemistry revealed nuclear BRMS1 protein staining in normal high-risk types of human papilloma virus-free cervix, in cervical intraepithelial neoplasias, and in malignant tissues, where staining was occasionally also cytoplasmic. In cancer, expression was stronger in the more differentiated cancer blasts. In conclusion, BRMS1 promoter methylation and aberrant protein expression seem to be related to high-risk types of human papilloma virus-induced carcinogenesis in uterine cervix and is worthy of further investigation.

Tissue injury of the remnant liver following radiofrequency-assisted partial hepatectomy.

PURPOSE: To evaluate remnant liver tissue damage in a pig model of radiofrequency (RF)-assisted liver resection employing either the sequential coagulate cut (SCC) Belgrade technique using a monopolar RF electrode or the one using the bipolar Habib-4x device. METHODS: Sixteen pigs underwent either a) resection of part of the left lateral and left median hepatic lobes employing the SCC (SCC group), the Habib-4X (H group) or the "crushclamp" technique (CC group) or b) sham operation (Sham group). Forty-eight hours later, tissue specimens were excised from the right lateral hepatic lobe for histopathological examination and immunohistochemical assessment of tissue injury, mitosis and inflammation. RESULTS: Histopathologic lesions, apoptotic activity, HSP 40 and TNFα expression were more intense, while mitotic activity was less prominent in the SCC group technique compared to H group. Comparison between CC and H groups suggested the pivotal role of partial hepatectomy (PH) per se in the changes noted in H group. CONCLUSION: The Habib-4X liver resection technique proved to be less injurious in the remnant liver tissue after PH compared to the SCC technique.

Room air versus carbon dioxide pneumoperitoneum: effects on oxidative state, apoptosis and histology of splanchnic organs.

BACKGROUND: Although CO2 is the insufflation gas of choice in laparoscopic procedures, room air is usually used in natural orifice transluminal endoscopic surgery. The aim of the present study was to compare the safety of room air versus CO2 pneumoperitoneum in terms of their effect on the oxidative state, apoptosis and tissue injury of splanchnic organs. METHODS: Eighteen Wistar rats were assigned to three groups (n = 6 per group) and were subjected to 8 mm Hg room air (group Pne-Air) or CO2 pneumoperitoneum (group Pne-CO2) or sham operation for 60 min. Forty-five minutes postdeflation, tissue samples were excised from the liver, stomach, ileum and kidneys for reduced glutathione-to-glutathione disulfide (GSH/GSSG) ratio, caspase-8 and caspase-3 and hypoxia-inducible factor-1α (HIF-1α) immunohistochemical assessment and histopathologic examination. RESULTS: GSH/GSSG ratio substantially declined in both pneumoperitoneum groups. No change was noted in HIF-1α expression. Mild upregulation of caspase-8 and caspase-3 was noted in both pneumoperitoneum groups being less pronounced in group Pne-Air. Histopathologic score was increased in all organs studied, but the stomach, in both pneumoperitoneum groups. CONCLUSION: Pneumoperitoneum established by either room air or CO2 induced substantial oxidative stress, mild apoptosis and mild tissue injury in splanchnic organs. While air pneumoperitoneum conferred a less pronounced apoptotic effect, the oxidative state and histopathologic profile of splanchnic organs did not differ between insufflation gases.

Intravenous Heroin Abuse and Acute Myocardial Infarction: Forensic Study.

OBJECTIVE: The purpose of this study was to investigate chronic intravenous heroin abuse and its potential to induce acute myocardial infarction (AMI). It also aims to examine the causative factors and the incidence of heroin-induced myocardial infarction. MATERIAL AND METHODS: The hearts of 113 intravenous heroin abusers were studied for a duration exceeding 3 years. The parameters studied included sex, age, time of intravenous heroin abuse, medical history, and body and heart weight. Macroscopic histological studies of the heart were also performed. RESULTS: The histological examination revealed only 1 case of AMI. The victim was an intravenous heroin abuser for the last 7 years. The age and the medical history of the victim do not act as dissuading factors for the potential of an AMI. CONCLUSIONS: The incidence of heroin-induced myocardial infarction is rare, and the actual mechanism remains unclear. The increased heart weight in relation to the increased thickness of the heart walls may be an aggravating factor, and thus, it is a fact that should be investigated.

Early hemodynamic effects after extended liver radiofrequency ablation.

BACKGROUND: The purpose of the present study was to assess early intestinal and systemic hemodynamic effects after extended radiofrequency ablation (RFA) of the liver in terms of investigating their potential contribution to gut barrier disruption. MATERIALS AND METHODS: Ten rabbits were assigned to two groups of five animals each and were subjected to either 30% liver RFA (group RFA-1) or sham operation (group sham-1). Blood flow rate at the superior mesenteric artery (SMA) was monitored for 90 min after operation. Ileal tissue was excised at 48 h for histomorphometric and histopathologic analysis. Eight pigs were assigned to two groups of four animals each and were also subjected to either 30% liver RFA (group RFA-2) or sham operation (group sham-2). A panel of systemic hemodynamic parameters was serially measured up to 90 min after operation. RESULTS: In group RFA-1, SMA blood flow rate was lower than that in group sham-1 throughout the study period. Intestinal mucosa atrophy and a deterioration of histopathologic profile were noted in group RFA-1. In group RFA-2, diastolic pulmonary artery pressure was lower (60-90 min), central venous pressure was gradually decreased, arterial pressure was higher (30-90 min), and systemic vascular resistance was higher (30-90 min) than those in group sham-2. No change was noted in the cardiac output. CONCLUSIONS: In conclusion, SMA blood flow was reduced during the early post-RFA period, justifying an ischemic insult at the intestine. In addition, a gradual decrease of the preload was counterbalanced by an increase of systemic vascular resistance leaving the cardiac output unaffected.

Regenerated Nerve Defects with a Nerve Conduit Containing Dental Pulp Stem Cells in Pigs: An Immunohistochemical and Electrophysiological Evaluation.

BACKGROUND: Dental pulp stem cells (DPSCs) present an exciting new tool in the field of peripheral nerve regeneration due to their close embryonic origin. In this study, we examined their potential in pigs, using biodegradable collagen conduits filled with DPSCs. To our knowledge, this is the first time DPCSs are tested for peripheral nerve regeneration in such large animal model. MATERIALS AND METHODS: The second lateral incisor was extracted from every animal's lower jaw and stem cells were isolated and cultured. The collagen nerve conduits containing the DPSCs were subsequently transplanted into the transected fifth and sixth intercostal nerves, while the seventh intercostal nerve was used as a control and no stem cells were added on the respective collagen conduit. RESULTS: A histological examination was performed on the 3rd and 6th postoperative months and showed the gradual development of neural tissue and immunohistochemical expression of neuron-specific enolase. An electrophysiological study was performed on the 6th postoperative month and showed similar potentials between the stem cell infusion region (5 ± 0.04 units) and their proximal stumps (5 ± 0.05 units) and slightly smaller potentials in the respective distal stumps (4 ± 0.045 units). CONCLUSION: The nerves where DPSCs were injected exhibited morphological and functional recovery, in contrast to the control nerves where no recovery was detected; thus, there is a first evidence of the therapeutic potential of DPSCs in peripheral nerve regeneration.

The role of apigenin in an experimental model of acute pancreatitis.

AIM: The aim of the present study is to evaluate pathologic changes in the pancreatic parenchyma in an experimental model of acute pancreatitis (AP) following bilio-pancreatic duct ligation. An effort was made to clarify the role of apigenin, a substance that is well-known for its antioxidant and anti-inflammatory role and its likely beneficial activity to the pancreatic parenchyma following AP in rats. MATERIAL AND METHOD: One hundred twenty-six male Wistar rats 3-4 mo old and weighing 220-350 g were used. At time 0, the following groups were randomly assigned: group sham: rats were subjected to virtual surgery; group control: rats were subjected to surgery for induction of AP, by ligation of the bilio-pancreatic duct; group apigenin: rats were subjected to surgery for induction of AP and enteral feeding with apigenin. Pathologic changes of the pancreatic parenchymal and myeloperoxidase activity were measured at predetermined time intervals 6, 12, 24, 48, and 72 h. RESULT: From the pathologic reports, by comparing the control group with the apigenin group, an improvement of pancreatic tissue architecture following apigenin administration was observed. Inflammatory infiltration, edema, ductal dilation, and necrosis were reduced following apigenin administration over time (P = 0.049, P = 0.228, P = 0.387, P = 0.046). Treatment with apigenin significantly reduced the bilio-pancreatic duct ligation and evoked an increase in pancreatic myeloperoxidase activity (P = 0.030). CONCLUSION: Oral apigenin administration in rats, following experimentally induced pancreatitis, seems to protect the pancreatic tissue. Thus, apigenin administration to humans could potentially ameliorate the damages to the pancreas.

Assessment of SOX17 DNA methylation in cell free DNA from patients with operable gastric cancer. Association with prognostic variables and survival.

BACKGROUND: DNA methylation represents one of the most common epigenetic changes in human cancer providing important information regarding carcinogenesis. A possible role as a prognostic indicator has also been proposed. The aim of our study was to evaluate the prognostic significance of SOX17 promoter methylation status in patients with operable gastric cancer. METHODS: Using methylation-specific PCR (MSP) we examined the incidence and prognostic significance of SOX17 methylation status in cell free circulating DNA in the serum of 73 patients with operable gastric cancer. Fifty-one patients were male (69.9%), their median age was 65 years, 43 patients (58.9%) had regional lymph node involvement and all had a Performance Status (WHO) of 0-1. RESULTS: SOX17 promoter was found to be methylated in 43 out of 73 gastric cancer serum samples examined (58.9%). All 20 control serum samples from healthy individuals were negative. Overall survival (OS) was found to be significantly associated with SOX17 methylation (p=0.049). A significant correlation between methylation status and differentiation (p=0.031) was also observed. No other significant associations between different tumor parameters examined and SOX17 methylation status were observed. CONCLUSIONS: SOX17 promoter methylation in cell free DNA of patients with operable gastric cancer is a frequent event and may provide important information regarding prognosis in this group of patients.

Tumor Microenvironment and Immune Response in Lip Cancer.

Tumor-infiltrating lymphocytes (TILs) play a significant role in cancer progression and prognosis of patients. The tumor microenvironment (TME) may affect the anti-tumor immune response. We examined the TIL and tertiary lymphoid structure (TLS) density in the invading front and inner tumor stroma, and the lymphocyte subpopulation (CD8, CD4, FOXP3) density in 60 squamous cell carcinomas of the lip. Analysis was performed in parallel with markers of hypoxia (hypoxia-inducible factor (HIF1α), lactate dehydrogenase (LDHA)) and angiogenesis. Low TIL density in the invading tumor front was related with larger tumor size (p = 0.05), deep invasion (p = 0.01), high smooth-muscle actin (SMA) expression (p = 0.01), and high HIF1α and LDH5 expression (p = 0.04). FOXP3+ TILs infiltration and FOXP3+/CD8+ ratios were higher in inner tumor areas, linked with LDH5 expression, and higher MIB1 proliferation index (p = 0.03) and SMA expression (p = 0.001). Dense CD4+ lymphocytic infiltration in the invading front is related to high tumor-budding (TB) (p = 0.04) and angiogenesis (p = 0.04 and p = 0.006, respectively). Low CD8+ TIL density, high CD20+ B-cell density, high FOXP3+/CD8+ ratio and high CD68+ macrophage presence characterized tumors with local invasion (p = 0.02, 0.01, 0.02 and 0.006, respectively). High angiogenic activity was linked with high CD4+, FOXP3+, and low CD8+ TIL density (p = 0.05, 0.01 and 0.01, respectively), as well as high CD68+ macrophage presence (p = 0.003). LDH5 expression was linked with high CD4+ and FOXP3+ TIL density (p = 0.05 and 0.01, respectively). Further research is needed to explore the prognostic and therapeutic value of TME/TIL interactions.

The Clinical Significance of Pollen and Fungi Concentrations for Allergic Rhinitis: A Three-Year Study.

INTRODUCTION: The relationship between disease severity and exposure to allergens in allergic rhinitis (AR) patients is not fully clarified presently. We aimed to detect the correlation between airborne pollen and fungi concentrations in a Mediterranean region with symptom scores. METHODS: A total of 98 patients suffering from AR rated their symptoms at the time of exacerbation using the Total 5 Symptoms Score (T5SS) and the Visual Analogue Scale (VAS). Patients' quality of life (QoL) was estimated by using either disease-specific (Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and mini-RQLQ) or generic (Short-Form 36 (SF-36) and Beck Depression Inventory (BDI)) questionnaires. All patients' responses were correlated with aerobiological data. Skin prick tests (SPTs) were used to detect sensitivities to the most common registered pollen and fungi species. RESULTS: A significant positive correlation between total pollen and fungi counts and disease-specific questionnaires was found only for the RQLQ. Accordingly, a significant positive correlation was found between total pollen and fungi counts and T5SS (r = 0.655, p = 0.021), with breathing (r = 0.620, p = 0.032) and sneezing (r = 0.660, p = 0.020) being strongly affected. Moreover, a tendency toward a higher VAS score was found as total pollen and fungi counts increased (r = 0.523, p = 0.081). CONCLUSION: We found a significant correlation between patients' symptoms and pollen and fungal air concentrations. Our results emphasize the clinical significance of pollen and fungi maps in everyday clinical practice.

Development and validation of a prognostic nomogram for overall and disease-specific survival in patients with sarcomatoid urothelial carcinoma.

INTRODUCTION: Sarcomatoid urothelial carcinoma (SUC) is a rare and aggressive variant of bladder cancer with limited data guiding prognosis. In this study, we present the first prognostic nomograms in the literature for 3- and 5-year overall survival (OS) and disease-specific survival (DSS), for patients with SUC derived from the surveillance, epidemiology and end results database (SEER). MATERIALS AND METHODS: Patients with SUC were identified by using the ICD-10 topography codes C67.0-C67.9 (bladder cancer), and the morphologic code 8122 (SUC). Patients were randomly divided into a training cohort (TC) and a validation cohort (VC) (7:3 ratio). Variables significantly associated with OS and DSS were identified with multivariate Cox regression and were used to build the nomograms. Harrel's C-statistic with bootstrap resampling and calibration curves were used for internal (TC) and external (VC) validation. Clinical utility of the nomograms was assessed with the decision curve analysis (DCA). Goodness of fit between the nomograms and the AJCC 8th edition staging system was compared with the likelihood ratio test. RESULTS: A total of 741 patients with SUC were included (507 TC, 234 VC). No statistically significant differences in baseline characteristics were identified between the 2 cohorts. Sex, SEER stage, radical cystectomy and chemotherapy were common variables for the OS and the DSS nomograms with the addition of age in the former. Optimism-corrected C-statistic for the nomograms was 0.68 and 0.67 for OS and DSS respectively. In comparison, C-statistic for AJCC was 0.59 for OS and 0.60 for DSS (P < 0.001). Calibration curves constructed for the nomograms showed appropriate consistency between predicted and actual survival. The nomograms demonstrated optimal clinical utility in the DCA, outperforming the AJCC staging system, by maintaining a higher clinical net benefits than treat all, treat none and AJCC curves, across threshold probabilities. CONCLUSION: We present the first prognostic nomograms developed in patients with SUC. Our models demonstrated superior prognostic performance to the AJCC system, by utilizing a set of variables readily available in daily practice and may serve as useful tools for the individualized risk assessment of these patients.