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Background: The impact of pathogen reduction technology (PRT) such as Mirasol, and the effect of platelet additive solutions (PAS) on the activity and hemostatic profile of transfused apheresis platelets remain largely unknown. The aim of this study was to assess the in vitro hemostatic and metabolic profile of Mirasol treated platelets in PAS during a 7-day storage period., Material and Methods: Ten split bags containing apheresis platelets stored in PAS were split into two groups; control platelets (No.=10 units) and PRT-treated platelets (No.=10 units). In vitro evaluation of the platelet components was performed on the 1 st , 3 rd , 5 th , and 7 th days of the storage period. Several metabolic parameters including pH, glucose, and lactate levels were evaluated, while assessment of their hemostatic capacity was performed using light transmission aggregometry (LTA) and viscoelastic studies such as rotational thromboelastometry (ROTEM) and thromboelastography (TEG). Last, Annexin V levels were measured though flow cytometry for evaluation of platelet activation., Results: Clot strength, as reflected by the maximum clot firmness (MCF) and the maximum amplitude (MA) parameters of the viscoelastic studies was significantly decreased in the PRT-treated platelets compared to the control platelets (p<0.05). Clot strength based on MCF and MA values was also found to be decreasing over storage time in PRT-treated platelets (p<0.001), while this was not evident in control platelets. Moreover, the comparison between pH, glucose, and lactate levels were indicative of increased metabolic activity in PRT-treated platelets compared to control platelets (p<0.001). Last, Annexin-V was significantly higher in PRT-treated platelets compared to control platelets on the 7 th day of the storage period (p<0.001)., Discussion: The results of this study indicate that increased PSL induced by PRT treatment leads to a decreased in vitro platelet hemostatic efficacy and increased metabolic activity. However, the clinical impact of these alterations needs further investigation.

Background: This study aimed to explore the hemostatic profile of neonates with necrotizing enterocolitis (NEC) using Rotational Thromboelastometry (ROTEM) and to investigate if ROTEM parameters have the capacity to play a role in the differentiation of NEC from sepsis at the disease onset., Methods: This observational study included 62 neonates (mean gestational age 31.6 weeks and mean birth weight 1620g) hospitalized in a neonatal intensive care unit. The neonates were categorized in three groups: neonates with NEC (Bell stage II and above), neonates with sepsis and healthy neonates and they were matched 1:1:1 with regards to gestational age, delivery mode, and sex. Clinical, laboratory data as well as measurements of ROTEM parameters at disease onset were recorded., Results: ROTEM parameters differed between neonates with NEC and neonates with sepsis, indicating that NEC results in accelerated clot formation and higher clot strength compared to sepsis. The EXTEM CFT and A10 parameters demonstrated the highest diagnostic performance for NEC in terms of discrimination between NEC and sepsis (AUC, 0.997; 95% CI: 0.991-1.000 and 0.973; 95% CI: 0.932-1.000, respectively)., Conclusions: Neonates with NEC manifested accelerated clot formation and higher clot strength compared to septic and healthy neonates, as these were expressed by ROTEM parameters., Impact: This work reports data on the hemostatic profile of neonates with necrotizing enterocolitis (NEC) using Rotational Thromboelastometry (ROTEM) and the capacity of ROTEM parameters in differentiating of NEC from sepsis at the disease onset. Neonates with NEC present acceleration of coagulation and exhibit a hypercoagulable profile, as this is expressed by ROTEM parameters, in comparison to septic and healthy neonates. ROTEM parameters demonstrated a good diagnostic capacity in differentiating NEC from sepsis at the disease onset., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background/Objectives: There is a lack of reliable biomarkers for diagnosis of infection eradication prior to second-stage reimplantation in two-stage exchange arthroplasty for periprosthetic joint infections (PJIs). The aim of this study was to assess the diagnostic accuracy of rotational thromboelastometry (ROTEM) for persistent infection in two-stage exchange arthroplasties. Methods: A pilot, retrospective analysis was performed including 70 patients who underwent a two-stage exchange arthroplasty for PJI. They were categorized as patients without ( n = 64) or patients with persistent infection ( n = 6) prior to reimplantation. Definition of persistent infection prior to reimplantation was based on the 2018 ICM criteria. Conventional coagulation biomarkers and ROTEM parameters were compared between groups. Results: Higher FIBTEM MCF values were associated with persistent infection (odds ratio [OR], 1.30, 95% confidence interval [CI], 1.04-1.63; p = 0.020), and FIBTEM MCF had the highest diagnostic accuracy for persistent infection prior to second-stage reimplantation (AUC, 0.907; 95% CI, 0.812-1.000). A cut-off value ≥ 18 mm for FIBTEM MCF was found to have 100.0% sensitivity and 73.4% specificity for diagnosing persistent infection prior to second-stage reimplantation. Moreover, the diagnostic accuracy of FIBTEM MCF was higher than that of fibrinogen levels ( p = 0.036) and D-dimer ( p = 0.006). Conclusions: Our findings indicate that ROTEM parameters have the potential to identify persistent infections before reimplantation in two-stage exchange arthroplasties for PJI. Such coagulation biomarkers could provide guidance regarding the optimal timing for reimplantation. Further studies in larger populations are warranted to validate the diagnostic accuracy of ROTEM parameters for persistent PJI.

Background: Teledermatology is employed in the diagnosis and follow-up of skin cancer and its use was intensified during and after the COVID-19 pandemic. At the same time, demographic changes result in an overall increase in non-melanoma skin cancer and skin precancerous lesions. The aim of this study was to elucidate the role of teledermatology in comparison to conventional face-to-face dermatology for such lesions and determine the advantages and limitations of this workflow for patients and physicians., Methods: Research was performed using relevant keywords in MEDLINE and CENTRAL. Relevant articles were chosen following a predetermined standardized extraction form., Results: Diagnostic accuracy and interrater/intrarater agreement can be considered comparable-although lower-than in-person consultation. Improvement of particular features such as image quality, medical history availability, and teledermoscopy can further increase accuracy. Further aspects of limitations and advantages (mean time-to-assessment, time-to-treatment, cost-effectiveness) are discussed., Conclusions: Teledermatology has comparable diagnostic accuracy with face-to-face dermatology and can be utilized both for the effective triage of non-melanocytic epithelial tumors and precancerous lesions, as well as the follow-up. Easy access to dermatologic consultation with shorter mean times to diagnostic biopsy and/or treatment coupled with cost-effectiveness could compensate for the lower sensitivity of teledermatology and offer easier access to medical care to the affected populations.

Background: Psoriasis and psoriatic arthritis are chronic inflammatory skin and joint diseases requiring effective therapies. Although clinical studies have shown the efficacy of IL-23 inhibitors, real-world data are limited., Methods: We conducted a single-center retrospective Greek study enrolling patients with psoriatic arthritis and moderate-to-severe plaque psoriasis being treated at our multidisciplinary psoriasis outpatient clinic. Our aim was to investigate the efficacy and safety of IL-23 inhibitors guselkumab and risankizumab. Additionally, we sought to determine the clinical characteristics affecting treatment response. Primary endpoints were the evaluation of absolute Psoriasis Area and Severity Index (aPASI) and Disease Activity Index for Psoriatic Arthritis (DAPSA) at week 24., Results: Fifty-nine patients (55.9% male, 69.5% early onset) with a mean age of 51.7 years were included. Twenty-four patients (40.7%) had a concomitant psoriatic arthritis. Obesity was the main comorbidity (49.2%) with a mean body mass index (BMI) of 31.3 kg/m 2 . Additional comorbidities were hypertension (44.1%), dyslipidemia (32.2%), and diabetes (18.6%). Only eight patients (13.6%) were naïve to previous systemic treatments, whereas 40 patients (67.8%) were bio-experienced. A statistically significant improvement of aPASI and DAPSA was demonstrated after 4, 16, and 24 weeks of treatment (P < 0.05). IL23 blockers were also efficacious in difficult-to-treat areas. Clinical outcome was affected from previous treatment with biologics. Treatment response was the same between guselkumab and risankizumab (P > 0.05)., Conclusion: This real-world study confirms the efficacy and safety of guselkumab and risankizumab in psoriatic arthritis and psoriasis reported from clinical trials., (© 2023 The Authors. International Journal of Dermatology published by Wiley Periodicals LLC on behalf of the International Society of Dermatology.)

Significant cross talk occurs between inflammation and coagulation. Thus, coagulopathy is common in sepsis, potentially aggravating the prognosis. Initially, septic patients tend to exhibit a prothrombotic state through extrinsic pathway activation, cytokine-induced coagulation amplification, anticoagulant pathways suppression, and fibrinolysis impairment. In late sepsis stages, with the establishment of disseminated intravascular coagulation (DIC), hypocoagulability ensues. Traditional laboratory findings of sepsis, including thrombocytopenia, increased prothrombin time (PT) and fibrin degradation products (FDPs), and decreased fibrinogen, only present late in the course of sepsis. A recently introduced definition of sepsis-induced coagulopathy (SIC) aims to identify patients at an earlier stage when changes to coagulation status are still reversible. Nonconventional assays, such as the measurement of anticoagulant proteins and nuclear material levels, and viscoelastic studies, have shown promising sensitivity and specificity in detecting patients at risk for DIC, allowing for timely therapeutic interventions. This review outlines current insights into the pathophysiological mechanisms and diagnostic options of SIC.

(1) Background: Although invasive fungal infections are a major cause of neonatal morbidity and mortality, data on the incidence and outcomes of localized abscesses in solid organs due to fungal infections are scarce. The aim of this study was to consolidate evidence and enhance our understanding on neonatal liver abscesses due to invasive fungal infections. (2) Methods: An electronic search of the PubMed and Scopus databases was conducted, considering studies that evaluated fungal liver abscesses in the neonatal population. Data on the epidemiology, clinical course, treatment, and outcome of these infections were integrated in our study. (3) Results: Overall, 10 studies were included presenting data on 19 cases of neonatal fungal liver abscesses. Candida spp. were the most common causative pathogens (94.7%). Premature neonates constituted the majority of cases (93%), while umbilical venous catheter placement, broad spectrum antibiotics, and prolonged parenteral nutrition administration were identified as other common predisposing factors. Diagnosis was established primarily by abdominal ultrasonography. Medical therapy with antifungal agents was the mainstay of treatment, with Amphotericin B being the most common agent (47%). Abscess drainage was required in four cases (21%). Eradication of the infection was achieved in the majority of cases (80%). (4) Conclusions: Even though fungal liver abscess is a rare entity in the neonatal population, clinicians should keep it in mind in small, premature infants who fail to respond to conventional treatment for sepsis, particularly if an indwelling catheter is in situ. A high index of suspicion is necessary in order to achieve a timely diagnosis and the initiation of the appropriate treatment.

Background: We aimed to develop and validate a diagnostic model for sepsis among neonates evaluated for suspected sepsis, by incorporating thromboelastometry parameters, maternal/neonatal risk factors, clinical signs/symptoms and laboratory results., Methods: This retrospective cohort study included 291 neonates with presumed sepsis, hospitalized in a NICU, from 07/2014 to 07/2021. Laboratory tests were obtained on disease onset and prior to initiating antibiotic therapy. Τhromboelastometry extrinsically activated (EXTEM) assay was performed simultaneously and Tοllner and nSOFA scores were calculated. Sepsis diagnosis was the outcome variable. A 10-fold cross-validation least absolute shrinkage and selection operator logit regression procedure was applied to derive the final multivariable score. Clinical utility was evaluated by decision curve analysis., Results: Gestational age, CRP, considerable skin discoloration, liver enlargement, neutrophil left shift, and EXTEM A10, were identified as the strongest predictors and included in the Neonatal Sepsis Diagnostic (NeoSeD) model. NeoSeD score demonstrated excellent discrimination capacity for sepsis and septic shock with an AUC: 0.918 (95% CI, 0.884-0.952) and 0.974 (95% CI, 0.958-0.989) respectively, which was significantly higher compared to Töllner and nSOFA scores., Conclusions: The NeoSeD score is simple, accurate, practical, and may contribute to a timely diagnosis of sepsis in neonates with suspected sepsis. External validation in multinational cohorts is necessary before clinical application., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Sokou, Ioakeimidis, Piovani, Parastatidou, Konstantinidi, Tsantes, Lampridou, Houhoula, Iacovidou, Kokoris, Vaiopoulos, Gialeraki, Kopterides, Bonovas and Tsantes.)

Background:  Hip fracture surgeries are associated with considerable blood loss, while the perioperative coagulopathy is associated with the bleeding risk of these patients. We aimed to evaluate the ability of rotational thromboelastometry (ROTEM) to detect patients at high risk for excessive bleeding and increased transfusion requirements., Methods:  We conducted a prospective observational study of 221 patients who underwent hip fracture surgeries. ROTEM analysis was performed preoperatively and immediately postoperatively. Blood loss parameters including blood loss volume, number of transfused red blood cell (RBC) units, and drop in hemoglobin levels were recorded. ROTEM parameters were compared between patients with and without excessive bleeding, and between patients with and without increased transfusion requirements (i.e., ≥2 RBC units)., Results:  The postoperative FIBTEM MCF value ≤15 mm had 66.6% (95% confidence interval [CI]: 59.7-74.1%) sensitivity and 92.0% (95% CI: 80.7-97.7%) specificity to prognose excessive bleeding, and preoperative FIBTEM MCF value ≤15 mm had 80.4% (95% CI: 73.5-86.2%) sensitivity and 91.2% (95% CI: 80.7-97.0%) specificity to prognose increased transfusion requirements. Preoperative FIBTEM MCF ≤11 mm and postoperative FIBTEM MCF ≤15 mm were associated with considerably increased risks of excessive bleeding (odds ratio [OR]: 44.8, 95% CI: 16.5-121.3, p  < 0.001; and OR: 23.0, 95% CI: 7.8-67.0, p  < 0.001, respectively)., Conclusion:  ROTEM parameters demonstrated high prognostic accuracy for excessive bleeding and increased transfusion requirements. This can enable implementation of blood sparing strategies in high-risk patients, while blood banks could be better prepared to ensure adequate blood supply., Competing Interests: None declared., (Thieme. All rights reserved.)

Introduction: Coronavirus disease 2019 (COVID-19) in patients with hip fractures is associated with increased incidence of venous thromboembolism (VTE). The purpose of this study was to evaluate the hemostatic alterations of COVID-19 that are associated with a higher thrombotic risk using rotational thromboelastometry (ROTEM)., Methods: A retrospective observational study was performed including 20 COVID-19 patients with hip fractures. To compare the coagulopathy of patients with mild COVID-19 and hip fractures with the coagulopathy associated with each of these two conditions separately, we used two previously recruited groups of patients; 198 hip fracture patients without COVID-19 and 21 COVID-19 patients without hip fractures. The demographics, clinical parameters, conventional coagulation parameters and ROTEM findings of the three groups were analyzed and compared., Results: COVID-19 hip fracture patients had higher amplitude of clot firmness at 10 min ( p < 0.001), higher alpha angle ( p < 0.001), higher lysis index at 60 min ( p < 0.001), and shorter clot formation time ( p < 0.001) than non-COVID-19 hip fracture patients, indicating increased clot strength and impaired fibrinolysis due to COVID-19. The value of lysis index at 60 min (99%) in COVID-19 patients with hip fractures was consistent with fibrinolysis shut down. Multivariable linear regression analysis further confirmed that COVID-19 resulted in increased amplitude of clot firmness at 10 min ( p < 0.001), increased maximum clot firmness ( p < 0.001), increased lysis index at 60 min ( p < 0.001) and increased alpha angle ( p < 0.001), but significantly shortened clot formation time ( p < 0.001)., Discussion: The higher thrombotic risk in COVID-19 patients with hip fractures is characterized by increased clot strength and fibrinolysis shutdown, as shown by ROTEM findings. Further prospective studies are warranted to evaluate the need for modification of thromboprophylaxis to balance the hemostatic derangements of COVID-19 patients with hip fractures.

A 69-year-old man presented with a 12-month history of unilateral eczematous changes of the left nipple and areola without any signs of systemic inflammation. His main complaints were mild, intermittent itching, and occasionally local pain or burning. An external initial treatment with topical corticosteroids combined with disinfectants/antibiotics did not lead to an improvement. Triggering factors or any other conditions that could affect the diagnosis could not be detected. Histopathological examination of a biopsy from the left nipple performed at admission confirmed the suspected diagnosis of Paget disease. Radical left breast mastectomy was performed and the patient is under regular follow-up.

Background: There is growing evidence that (certain) hidradenitis suppurativa (HS) comorbidities comprise syndromes including HS as a key cutaneous manifestation. These apparently autoinflammatory syndromes and their diagnostic delay might have detrimental effects on affected patients., Methods: A systematic review was performed on the databases MEDLINE, EMBASE, and CENTRAL utilizing a standardized extraction form according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines., Results: Sixty-four eligible articles on syndromic HS were retrieved. The identified syndromes included already described ones (pyoderma gangrenosum-acne-suppurative hidradenitis, pyogenic arthritis-pyoderma gangrenosum-acne-suppurative hidradenitis, psoriatic arthritis-pyoderma gangrenosum-acne-suppurative hidradenitis, pyoderma gangrenosum-acne vulgaris-hidradenitis suppurativa-ankylosing spondylitis, synovitis-acne-pustulosis-hyperostosis-osteitis) and further novel symptom constellations. Cutaneous signs, including HS lesions, usually precede signs from other organs. The cutaneous signs of a considerable proportion of patients appear refractory to conventional treatment, and monotherapy with biologics does not suffice to sustain remission., Conclusion: The results are subsequently discussed with focus on the pathophysiology and treatment of the detected syndromes. The dermatologist's role in the precise diagnosis and early treatment administration of HS is pivotal. The purpose of the treatment should be the effective prevention or delay of the autoinflammatory march and its irreversible consequences., (© 2020 S. Karger AG, Basel.)

Hidradenitis suppurativa (HS) is a chronic, recurrent cutaneous disease of the terminal hair follicle which manifests with deep-seated, painful nodules, abscesses, and sinus tract formation. The pathophysiology of the disease includes among various factors also dermatoendocrinologic variables: Correlations with metabolic syndrome, obesity, sex steroid hormones, and the improvement after antiandrogen therapy are some of the key points presented in this review. Hormonal treatment of HS can be an effective and inexpensive alternative or add-on therapy to classic HS treatments, especially in cases where antibiotics and/or biologics are ineffective or contraindicated.

Background: Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle affecting apocrine glands-rich areas of the body. The disease usually occurs after puberty leading to painful nodules, abscesses, tunnels and scarring. Although uncommonly, HS can also occur in children and adolescents., Objective: Our objective was to describe the epidemiology, characteristics, predisposing factors and clinical course of HS in paediatric patients., Methods: The retrospective cohort study included patients with HS, who have been diagnosed in Dessau Medical Center and reported development of HS during childhood or adolescence, fulfilled the diagnostic criteria for HS and had a follow-up period of at least one year. A systematic review was conducted on MEDLINE, EMBASE and CENTRAL on 19 March 2020 using the terms 'hidradenitis' or 'acne inversa' together with the terms 'children', 'paediatric' and 'adolescence'., Results: Twenty paediatric patients [1 child (0.22%), 19 adolescents (4.25%)] were detected out of 447 patients evaluated (4.5%) with a male to female ratio of 1.86 : 1. The median age at diagnosis was 17 years [interquartile range (IQR) 16-18] and the median age at onset 15 years (IQR: 14-16.5). The majority of the patients suffered from moderate disease were overweight or obese and non-smokers. The most common comorbid disorder was acne vulgaris. The systematic review revealed reports with data heterogeneity and lack of systematic documentation of specific demographic characteristics. Most paediatric patients were female, obese and non-smokers, with considerable comorbid disorders., Conclusions: Hidradenitis suppurativa in Germany may affect children and adolescents exhibiting a particular phenotype of mainly male non-smokers., (© 2020 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background/objectives: Musculoskeletal manifestations are frequent in Adamantiades-Behçet's disease (ABD) but only represent non-specific clinical findings. They have not been included in the two commonly used sets of classification criteria. The occurrence of musculoskeletal manifestations at ABD onset may even delay or obscure the diagnosis; therefore, detailed knowledge of the different musculoskeletal manifestations is essential. Our objective was to describe musculoskeletal signs and their clinical course in Greek ABD patients., Methods: We conducted a retrospective cohort study, which included all patients with ABD, who had been examined in our Rheumatology Outpatient Division from 1995 to 2010. The study included 224 ABD patients (140 male, 84 female) that fulfilled the International Criteria for the diagnosis of BD. For statistical analysis, we have used chi-square and Fisher's exact tests., Results: Arthritis as a presenting sign was seen in 10.2% of our patients. During the follow-up period, the frequency of arthritis was 58.4%. Monoarthritis was found in 32.8% and 22.6% of male and female patients, respectively (ns). During the follow-up period, polyarthritis was only occasionally observed in male patients (2.14%). Oligoarthritis was assessed in 20.0% and 41.6% of male and female patients, respectively (P < 0.001), and was the only significantly different manifestation between sexes., Conclusions: Musculoskeletal manifestations are common in ABD both at presentation and during the disease course. The most frequent sign is mooarthritis. Oligoarthritis was the only significantly different articular manifestation between sexes (more common in women) in our study group., (© 2018 European Academy of Dermatology and Venereology.)

Purpose: To study the diagnostic and/or prognostic role of preoperative blood tests in colorectal cancer., Methods: Preoperative complete blood count tests and lactate dehydrogenase (LDH) serum levels of 167 patients with colorectal adenocarcinoma were examined for associations with clinicopathological parameters, disease-specific survival (DSS) and relapse-free survival (RFS)., Results: The following parameters showed high sensitivity (≥85%) in detecting these features: platelet to lymphocyte ratio (PLR) for T4 tumors, white blood cell count (WBC) and neutrophil count (NC) for distant metastases and lymphocyte count (LC) for high-grade tumors. The following parameters showed high specificity (≥85%) in excluding these features: lymphocyte percentage (LP) for tumors larger than 5 cm, LP, neutrophil to lymphocyte ratio (NLR), neutrophil to monocyte ratio (NMR), lymphocyte to monocyte ratio (LMR) and LDH for T4 tumors, platelet to monocyte ratio (PMR) for T2-T4 tumors, LDH for more than three infiltrated regional lymph nodes and distant metastases, LMR for high-grade tumors and neutrophil percentage (NP) for lymphovascular invasion. WBC and NLR were independent prognostic factors for DSS, whereas WBC, NP, LP and NLR were independent prognostic factors for RFS., Conclusions: Preoperative complete blood count and LDH serum levels can provide valuable information about diagnosis and prognosis in colorectal cancer.

We report the case of a 53-year-old healthy man, presenting with confusion. The patient had been clinically diagnosed with cat-scratch disease (CSD) and prescribed a 10-day course of doxycycline orally. Approximately a week after he had completed the treatment, he was admitted to our department with confusion. Neurological examination revealed expressive dysphasia with no motor or sensory deficits. Cerebrospinal fluid (CSF) examination showed only increased content. Imaging with CT and MRI of the brain did not reveal any abnormalities, and funduscopy was normal. Serology confirmed Bartonella henselae infection. CSD-associated encephalopathy was confirmed based on the clinical manifestations, CSF findings and positive serology. The patient was treated with a combination of doxycycline and rifampin and he rapidly improved with complete neurological recovery within 7 days. Encephalopathy is an unusual manifestation of CSD in adults with excellent prognosis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: Kisspeptins, which are derived from the gene KISS1, supress tumor progression. We intended to investigate the production of KISS1 and its receptor (KISSR) in gastric cancer., Methods: The expression of KISS1 and KISS1R in both normal and cancer tissue was examined with immunohistochemistry in tissue specimens of 40 cases of gastric adenocarcinoma., Results: KISS1 expression in normal gastric mucosa was much higher than in malignant mucosa. KISS1 expression was higher in early stages (stage I or II) than in advanced stages (stage III or IV), in tumors with intestinal histological type than in those with diffuse histological type, in tumors without lymphovascular invasion than in those with and in cancers of older patients (≥70 years) than in younger patients. No significant differences were found regarding other clinicopathological parameters. There was no KISS1R expression in cancer tissues, while only low levels of KISS1R were detected in normal gastric epithelium., Conclusions: KISS1 expression is decreased during carcinogenesis in gastric mucosa. More advanced tumors and more aggressive histological types produce lower KISS1 levels. In addition, no KISS1R is produced in malignant gastric epithelium, while KISS1R is only weakly expressed in normal gastric epithelium.

Behçet's disease is a chronic, recurrent, inflammatory disorder characterized by orogenital ulcers and skin lesions; serious manifestations also include ocular, large vessel, gastrointestinal and neurological involvement. Genetic and unknown environmental factors modify the wide clinical spectrum of the disease. During the long clinical course of the disease, testicular and epididymal involvement has been reported, with scrotal pain and swelling being the most common symptoms. In this review, we discuss the various aspects of epididymo-orchitis in Behcet's disease patients, and we evaluate the diagnostic approaches as well as the empirical therapeutic modalities of this entity.

Adamantiades-Behçet disease (ABD) is a chronic, multisystemic, recurrent, inflammatory vascular disorder of unknown etiology. Patients with symptoms initially appearing at the age of 16 or less are considered as cases of juvenile-onset ABD (JABD). JABD is relatively rare compared to ABD of adults, and only case reports and case studies have been published regarding this subtype of the disease. Epidemiology, clinical features, diagnosis and treatment of JABD are discussed in this review., (© 2016 S. Karger AG, Basel.)

Kisspeptins, the products of the KISS1 gene have tumor suppressing and antimetastatic properties. We aimed to study KISS1 and KISS1R expression in colorectal cancer. We analyzed KISS1 and KISS1R expression using immunohistochemistry and image analysis in normal and malignant tissue samples from 111 patients with colorectal adenocarcinoma. KISS1 expression was much higher in the normal than in the malignant colonic mucosa. Regarding malignant tissues, KISS1 levels were higher in larger tumors, in stage III and IV cancers, in cancers with lymph node metastasis and in tumors located in the distal part of the large intestine. Patients with greater KISS1 levels had worse prognosis. No KISS1R expression was detected in normal or malignant tissues or in liver metastases. KISS1 expression is reduced during the malignant transformation of the colonic mucosa. However, larger and advanced colorectal cancers express more KISS1, without reaching the former normal levels, and increased KISS1 levels are associated with worse prognosis. Finally, neither the normal nor the malignant colonic epithelial cells produce KISS1R., (© 2015 APMIS. Published by John Wiley & Sons Ltd.)

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease, which affects a wide variety of organs including the spleen. Splenic involvement in SLE includes conditions such as splenomegaly, hyposplenism, infarction, and spontaneous rupture. However, only a few cases of splenic calcifications in patients with SLE have been reported. Herein, we present a case of a 24-year-old female diagnosed with SLE, in which we found diffuse splenic calcifications. The unique pattern of splenic calcifications in SLE contributes to the differential diagnosis from other conditions such as infections and other connective tissue diseases, which also cause calcifications in the spleen.

Rheumatoid arthritis (RA) synovial fibroblasts hyperexpress the mesenchymal cadherin-11, which is involved also in tumor invasion/metastasis, whereas anti-cadherin-11 therapeutics prevent and reduce experimental arthritis. To test the hypothesis that cadherin-11 is aberrantly expressed in RA peripheral blood, 100 patients (15 studied serially) and 70 healthy controls were analyzed by real-time reverse transcription-PCR. Cadherin-11 mRNA transcripts were detected in 69.2% of moderately/severely active RA, versus 31.8% of remaining patients (p=0.001), versus 17.1% of controls (p<0.0001). Notably, cadherin-11 positivity correlated significantly and independently only with established (>1year) polyarthritis (>4 swollen tender joints), by multivariate logistic regression analysis including various possible clinical/laboratory factors. Rare cells of undefined nature, detected by flow cytometry following CD45(-) enrichment, strongly expressed surface cadherin-11 (estimated 10-50cells/ml of blood) in 5/6 patients with polyarticular established disease versus 1/6 patients with early RA. Studies on the potential pathogenic role of circulating cells expressing cadherin-11 in RA are warranted., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Behçet's disease is a chronic, recurrent, inflammatory disorder characterized by orogenital ulcers and skin lesions; serious manifestations also include ocular, large vessel, gastrointestinal and neurological involvement. Genetic and unknown environmental factors customise the wide clinical expression of the disease. Gastrointestinal involvement is not unusual, albeit with a highly variable frequency among different ethnic populations. However, given the fact that gastrointestinal symptoms such as reflux, bleeding, diarrhoea are common in the general population, their clinical significance needs to be carefully interpreted. Apart from mouth the ileocecal area is typically involved, but inflammatory and/or vasculitic lesions may affect any part of the gastrointestinal tract. Complications such as perforation carry high morbidity rates and even mortality. Herein, we review all available information pertinent to gastrointestinal involvement of Behçet's disease and discuss the published advances in evaluation and its empirical management, including anti-TNF biologic therapies.

Colorectal cancer, a leading cause of mortality worldwide, is a multistep disorder that results from the alteration of genetic and epigenetic mechanisms under contextual influence. Epigenetic aberrations, including DNA methylation, histone modifications, chromatin remodeling and non-coding RNAs, affect every aspect of tumor development from initiation to metastasis. Cancer stem cell promotion is also included in the wide spectrum of epigenetic dysregulations. Elucidation of this complex crosstalk network may offer new insights in the molecular interactions involved in the pathogenesis of colorectal carcinogenesis. In the era of translational medicine new horizons are opened for the pursuit of personalized therapeutic approaches and the development of novel and accurate diagnostic, prognostic and therapy-assessment markers. This review discusses the implications of epigenetic mechanisms in tumor biology and their applications "from bench to bedside"., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Survivin, a member of the inhibitor of apoptosis protein family, has been associated with protection from cell apoptosis and regulation of mitosis. Survivin exhibits low to undetectable expression in most finally differentiated adult tissues but is abundantly over-expressed in almost all cancers. The aberrant high expression of survivin in cancers is associated with advanced disease, increased rate of tumor recurrence, abbreviated overall survival and resistance to chemo- and radio- therapy. Survivin touches nearly every aspect of cancer and is involved in the initiation, maintenance and development of tumor. Therefore, its significance in cancer dictates the pursuit for anti-survivin cancer therapies., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Aim: The aim of this study was the development of a multiplex-PCR assay for the detection of circulating tumor cells in patients with colorectal and gastric cancer., Patients and Methods: Peripheral blood samples were collected from 81 patients with colorectal cancer, 16 with gastric cancer and 38 healthy blood donors, as controls. The samples were processed for RNA extraction and cDNA synthesis and were subsequently analyzed for the expression of cytokeratin 19 (CK19), cytokeratin 20(CK20) and epidermal growth factor receptor (EGFR) with multiplex PCR., Results: Statistical analysis revealed that the combination of CK19 and CK20 could be useful in the exclusion of colorectal cancer, as well as the diagnosis and exclusion of gastric cancer. Furthermore, the expression of EGFR was correlated with the presence of systemic disease in patients with colorectal cancer., Conclusion: Multiplex-PCR-based detection of circulating tumor cells could serve as a useful tool for the diagnosis, and monitoring of patients with colorectal and gastric cancer., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Kisspeptins, the products of the KISS1 gene, are involved in cancer invasion, migration, metastasis and angiogenesis, while they induce apoptosis in various cancers. Herein, we studied KISS1 expression in colorectal cancer. We analyzed KISS1 expression using immunohistochemistry and image analysis in normal and malignant tissue samples from 60 patients with colorectal adenocarcinoma. The results correlated with various clinicopathological parameters. The expression of KISS1 was much higher in normal than in malignant colonic mucosa. However, among malignant tissues, KISS1 expression was higher in larger tumors (>4 cm) than in smaller ones (≤4 cm) and in stages III and IV than in stages I and II. In addition, it was higher in patients with lymph node metastases. Moreover, KISS1 levels in the normal mucosa and their difference from those in the malignant mucosa were higher in the right part of the large intestine than in the left one. KISS1 expression is reduced during the malignant transformation of the colonic mucosa and there is a difference in the expression pattern between the right and the left part of the large intestine. However, larger and advanced colorectal tumors express higher KISS1 levels than smaller and localized ones., (© 2013 APMIS. Published by John Wiley & Sons Ltd.)

Colorectal cancer (CRC) is a leading cause of morbidity and mortality worldwide, responsible for more than half a million deaths annually. CRC is a multistep process that entails the accumulation of genetic/epigenetic aberrations, which lead to the simultaneous failure of protective mechanisms and the activation of tumorigenic pathways. In most cases of CRC a deregulation of the Wnt-signaling pathway is required. The transcription factor nuclear factor κB (NF-κB) has been recognized as a key player in the initiation and propagation of CRC. Under physiological conditions, NF-κB orchestrates the inflammatory process and participates in the modulation of various steps of cell cycle and survival. It is normally kept in an inactive state in the cytoplasm by binding to a group of inhibitory proteins. Upon receipt of a signal, its inhibitor is phosphorylated and proteolytically degraded and NF-κB is actively translocated to the nucleus, where it facilitates target-gene transcription. Recent experimental data reveal the important role of NF-κB in tumor cells as well as in the surrounding "cancerous" and reactive microenvironment. Various tumor cell-derived and contextual cues feed constantly this vicious circuitry sustaining inflammation and promoting proliferation, angiogenesis, invasion and eventually metastasis. Therefore NF-κB along with its upstream and downstream network presents a rational target for therapeutic interventions. Numerous small molecules, inhibitory peptides, antisense RNAs, natural compounds, as well as gene therapy strategies interfere with multiple steps of the NF-κΒ signaling cascade. The design of NF-κΒ-targeted treatment may aid the efforts towards the pursuit of more efficient therapeutic measures devoid of severe systemic side-effects.

Patients with antiphospholipid syndrome may develop various lung manifestations. The lung complications that have been described so far are pulmonary thromboembolic disease, pulmonary hypertension, acute respiratory distress syndrome, primary thrombosis of large and small lung vessels, diffuse alveolar haemorrhage, fibrosing alveolitis and postpartum syndrome. Clinicians should be aware of these conditions as in most of these cases, timely diagnosis and treatment is needed.

The invasive procedures amniocentesis and chorionic villus sampling are routinely applied in pregnancies at risk for fetal genetic disorders and the results obtained are the gold standard for prenatal diagnosis. These procedures have an approximately 0.5-1% risk for fetal loss and are mainly used in cases at risk for fetal chromosomal abnormalities and single-gene disorders. Identification of cell-free fetal nucleic acids (DNA and RNA) in maternal plasma and the recognition that they represent a useful source of fetal genetic material for prenatal diagnosis has led to intensive efforts to develop non-invasive prenatal testing. This review summarizes recent developments in the field of non-invasive prenatal diagnosis through the use of cell-free fetal nucleic acids in maternal circulation during pregnancy and provides an overview of the possibilities for future clinical applications.

Aim: To reveal correlations between serum lactate dehydrogenase (LDH) levels and various clinicopathological parameters in colorectal and gastric cancer., Materials & Methods: A hospital-based case-control study was conducted by measuring serum LDH levels in 140 patients with colorectal cancer, 40 patients with gastric cancer and 20 hospital controls., Results: LDH levels did not differ between patients with colorectal or gastric cancer and hospital controls. In colorectal cancer, LDH values were significantly higher in T4, N2 and/or M1 cases, with high specificities and negative predictive values, but low sensitivities and positive predictive values. On the other hand, there were no significant associations in gastric cancer., Conclusion: Serum LDH levels are increased in T4, N2 and/or M1 colorectal cancer. Most patients with early-stage cancer have normal LDH values, whereas in advanced stages, some patients have increased LDH values and others have normal values.

Background: Inflammatory bowel disease frequently begins during childhood or adolescence. Current tests and procedures for diagnosing and monitoring inflammatory bowel disease are invasive, uncomfortable and costly. Fecal calprotectin is an inflammatory marker tested in several studies including pediatric patients with inflammatory bowel disease., Methods: A search for articles published up to October 2011 was conducted using MEDLINE and EMBASE databases. We included original English-written articles referred to pediatric patients with inflammatory bowel disease and measured fecal calprotectin levels. We extracted data concerning fecal calprotectin levels in patients with inflammatory bowel disease and in the controls groups, sensitivity, specificity, positive and negative likelihood ratio., Results: Thirty-four studies were included. Fecal calprotectin levels of patients with inflammatory bowel disease are much higher than those of healthy controls or patients with functional disorders or other gastrointestinal diseases. The results vary greatly when taking all studies into consideration. Nevertheless, in cases of newly diagnosed and/or active inflammatory bowel disease, the results are more homogeneous, with high sensitivity and positive likelihood ratio, low negative likelihood ratio, but moderate specificity. Moreover, 50 μg/g seems to be the most proper cut-off point for the fecal calprotectin test., Conclusions: The fecal calprotectin test could be used for supporting diagnosis or confirming relapse of inflammatory bowel disease in pediatric patients. A positive result could confirm the suspicion of either inflammatory bowel disease diagnosis or inflammatory bowel disease relapse, due to the high sensitivity of the test, but a negative result should not exclude these conditions, due to its moderate specificity.

Pulmonary aspergilloma is a fungus ball developed in a pre-existing lung cavity, generally in the superior lobes. Its size remains stable in most cases and it is usually asymptomatic. Herein, we present a case of a 64-year-old male with pulmonary aspergilloma, which was developed in an emphysematous cyst of the right inferior lobe, increased in size, and fluorodeoxyglucose positron emission tomography scan was positive. There are only a few reported cases of pulmonary aspergilloma with a false positive fluorodeoxyglucose positron emission tomography scan.

By being the "integration" center of transcriptional control as they move and target transcription factors, corepressors fine-tune the epigenetic status of the nucleus. Many of them utilize enzymatic activities to modulate chromatin through histone modification or chromatin remodeling. The clinical and etiological relevance of the corepressors to neoplastic growth is increasingly being recognized. Aberrant expression or function (both loss and gain of) of corepressors has been associated with malignancy and contribute to the generation of transcriptional "inflexibility" manifested as distorted signaling along certain axes. Understanding and predicting the consequences of corepressor alterations in tumor cells has diagnostic and prognostic value, and also have the capacity to be targeted through selective epigenetic regimens. Here, we evaluate corepressors with the most promising therapeutic potential based on their physiological roles and involvement in malignant development, and also highlight areas that can be exploited for molecular targeting of a large proportion of clinical cancers and their complications.

Adiponectin (ApN) is an adipose tissue-derived hormone which is involved in a wide variety of physiological processes including energy metabolism, inflammation, and vascular physiology via actions on a broad spectrum of target organs including liver, skeletal muscle, and vascular endothelium. Besides possessing insulin sensitizing and anti-inflammatory properties ApN also exerts a pivotal role in vascular protection through activation of multiple intracellular signaling cascades. Enhancement of nitric oxide generation and attenuation of reactive oxygen species production in endothelial cells along with reduced vascular smooth muscle cell proliferation and migration constitute some of ApN's vasoprotective actions. Additionally, recent data indicate that ApN has direct myocardio-protective effects. Decreased plasma ApN levels are implicated in the pathogenesis of the metabolic syndrome and atherosclerosis and may serve as a diagnostic and prognostic biomarker as well as a rational pharmaco-therapeutic target to treat these disorders. This review article summarizes recent work on the cardiovascular actions of ApN., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Colorectal cancer (CRC) is one of the most commonly diagnosed and lethal cancers worldwide. It is a multistep process that requires the accumulation of genetic/epigenetic aberrations. There are several issues concerning colorectal carcinogenesis that remain unanswered, such as the cell of origin and the type of cells that propagate the tumor after its initiation. There are two models of carcinogenesis: the stochastic and the cancer stem cell (CSC) model. According to the stochastic model, any kind of cell is capable of initiating and promoting cancer development, whereas the CSC model suggests that tumors are hierarchically organized and only CSCs possess cancer-promoting potential. Moreover, various molecular pathways, such as Wingless/Int (Wnt) and Notch, as well as the complex crosstalk network between microenvironment and CSCs, are involved in CRC. Identification of CSCs remains controversial due to the lack of widely accepted specific molecular markers. CSCs are responsible for tumor relapse, because conventional drugs fail to eliminate the CSC reservoir. Therefore, the design of CSC-targeted interventions is a rational target, which will enhance responsiveness to traditional therapeutic strategies and reduce local recurrence and metastasis. This review discusses the implications of the newly introduced CSC model in CRC, the markers used up to now for CSC identification, and its potential implications in the design of novel therapeutic approaches., (Copyright © 2012 AlphaMed Press.)

Colorectal cancer (CRC) is among the most common types of cancer attributed to genetic alterations. Its manifestation implicates NF-kappaB and AP-1 signaling pathways by virtue of their regulative role on the genetic control of cell cycle and apoptosis as well as by their capacity to be constitutively activated or exogenously induced by growth factors, cytokines, stress signals and oncoproteins. In CRC, the positive impact of NF-kappaB and AP-1 on the transcription of angiogenic and invasive factors strongly implicates these transcription factors in the transition of benign carcinomas towards a metastatic phenotype. Furthermore, the deregulated function of NF-kappaB and AP-1 in CRC cells affects inflammatory cascades, manifested by the ample production of inflammatory mediators. In this perspective, inhibition of NF-kappaB and AP-1 signaling mechanisms has become a rational target in the development of novel therapeutic approaches against CRC., (Copyright 2010 Elsevier Ltd. All rights reserved.)