Enthesitis in a European registry-based cohort of patients with psoriatic arthritis treated with tumour necrosis factor inhibitors: clinical burden, patient-reported outcomes, and treatment response.

OBJECTIVE: To explore the registration of enthesitis among biologic-naïve patients with psoriatic arthritis (PsA) initiating tumour necrosis factor inhibitor (TNFi) treatment across 12 European registries, compare the disease burden and patient-reported outcomes (PROs) between patients with and without enthesitis, and assess the enthesitis treatment response. METHOD: Demographics, clinical characteristics, and PROs at first TNFi (TNFi-1) initiation (baseline) were assessed in patients with PsA, diagnosed by a rheumatologist, with versus without assessment of entheses and between those with versus without enthesitis. Enthesitis scores and resolution frequency were identified at follow-up. RESULTS: Of 10 547 patients in the European Spondyloarthritis (EuroSpA) Research Collaboration Network initiating TNFi, 1357 underwent evaluation for enthesitis. Eight registries included a validated scoring system for enthesitis. At baseline, 874 patients underwent entheses assessment [Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) 485 patients, Spondyloarthritis Research Consortium of Canada (SPARCC) 389 patients]. Enthesitis was detected by MASES in 170/485 (35%, mean score ± sd 3.1 ± 2.4) and by SPARCC in 236/389 (61%, 4 ± 3.4). Achilles enthesitis was most frequent, by both MASES (unilateral/bilateral 28%/9%) and SPARCC (48%/18%). MASES/SPARCC baseline and follow-up scores for TNFi-1 were available for 100/105 patients. Of these, 63 patients (63%) (MASES) and 46 (43.8%) (SPARCC) achieved resolution of enthesitis. The site-specific enthesitis resolution was overall lower at SPARCC sites (peripheral; 63-80%) than at MASES sites (mainly axial; 82-100%) following TNFi-1. Disease activity and PROs were worse in patients with versus without enthesitis. CONCLUSION: Entheseal assessments are only registered in a minority of patients with PsA in routine care. When assessed, enthesitis was common, and a substantial proportion demonstrated resolution following treatment with TNFi-1.

Characteristics of 1555 childhood-onset lupus in three groups based on distinct time intervals to disease diagnosis: a Brazilian multicenter study.

Objective The objective of this study was to compare demographic data, clinical/laboratorial features and disease activity at diagnosis in three different groups with distinct time intervals between onset of signs/symptoms and disease diagnosis. Methods A multicenter study was performed in 1555 childhood-onset systemic lupus erythematosus (American College of Rheumatology criteria) patients from 27 pediatric rheumatology services. Patients were divided into three childhood-onset systemic lupus erythematosus groups: A: short time interval to diagnosis (<1 month); B: intermediate time interval (≥1 and <3 months); and C: long time interval (≥3 months). An investigator meeting was held to define the protocol. Demographic data, SLICC classification criteria and SLEDAI-2 K were evaluated. Results The number of patients in each group was: A = 60 (4%); B = 522 (33.5%); and C = 973 (62.5%). The median age at diagnosis (11.1 (4.2-17) vs. 12 (1.9-17.7) vs. 12.5 (3-18) years, P = 0.025) was significantly lower in group A compared with groups B and C. The median number of diagnostic criteria according to SLICC (7 (4-12) vs. 6 (4-13) vs. 6 (4-12), P < 0.0001) and SLEDAI-2 K (18 (6-57) vs. 16 (2-63) vs. 13 (1-49), P < 0.0001) were significantly higher in group A than the other two groups. The frequency of oral ulcers in the palate (25% vs. 15% vs. 11%, P = 0.003), pleuritis (25% vs. 24% vs. 14%, P < 0.0001), nephritis (52% vs. 47% vs. 40%, P = 0.009), neuropsychiatric manifestations (22% vs. 13% vs. 10%, P = 0.008), thrombocytopenia (32% vs. 18% vs. 19%, P = 0.037), leucopenia/lymphopenia (65% vs. 46% vs. 40%, P < 0.0001) and anti-dsDNA antibodies (79% vs. 66% vs. 61%, P = 0.01) were significantly higher in group A compared with the other groups. In contrast, group C had a less severe disease characterized by higher frequencies of synovitis (61% vs. 66% vs. 71%, P = 0.032) and lower frequencies of serositis (37% vs. 33% vs. 25%, P = 0.002), proteinuria >500 mg/day (48% vs. 45% vs. 36%, P = 0.002) and low complement levels (81% vs. 81% vs. 71%, P < 0.0001) compared with groups A or B. Conclusions Our large Brazilian multicenter study demonstrated that for most childhood-onset systemic lupus erythematosus patients, diagnosis is delayed probably due to mild disease onset. Conversely, the minority has a very short time interval to diagnosis and a presentation with a more severe and active multisystemic condition.

Droplet-based logic gates simulation of viscoelastic fluids under electric field.

Nano and microfluidic technologies have shown great promise in the development of controlled drug delivery systems and the creation of microfluidic devices with logic-like functionalities. Here, we focused on investigating a droplet-based logic gate that can be used for automating medical diagnostic assays. This logic gate uses viscoelastic fluids, which are particularly relevant since bio-fluids exhibit viscoelastic properties. The operation of the logic gate is determined by evaluating various parameters, including the Weissenberg number, the Capillary number, and geometric factors. To effectively classify the logic gates operational conditions, we employed a deep learning classification to develop a reduced-order model. This approach accelerates the prediction of operating conditions, eliminating the need for complex simulations. Moreover, the deep learning model allows for the combination of different AND/OR branches, further enhancing the versatility of the logic gate. We also found that non-operating regions, where the logic gate does not function properly, can be transformed into operational regions by applying an external force. By utilizing an electrical induction technique, we demonstrated that the application of an electric field can repel or attract droplets, thereby improving the performance of the logic gate. Overall, our research shows the potential of the droplet-based logic gates in the field of medical diagnostics. The integration of deep learning classification algorithms enables rapid evaluation of operational conditions and facilitates the design of complex logic circuits. Additionally, the introduction of external forces and electrical induction techniques opens up new possibilities for enhancing the functionality and reliability of these logic gates.

Pre-analytical parameters associated with unsuccessful karyotyping in myeloid neoplasm: a study of 421 samples.

Cytogenetics is essential in myeloid neoplasms (MN) and pre-analytical variables are important for karyotyping. We assessed the relationship between pre-analytical variables (time from collection to sample processing, material type, sample cellularity, and diagnosis) and failures of karyotyping. Bone marrow (BM, n=352) and peripheral blood (PB, n=69) samples were analyzed from acute myeloid leukemia (n=113), myelodysplastic syndromes (n=73), myelodysplastic syndromes/myeloproliferative neoplasms (n=17), myeloproliferative neoplasms (n=137), and other with conclusive diagnosis (n=6), and reactive disorders/no conclusive diagnosis (n=75). The rate of unsuccessful karyotyping was 18.5% and was associated with the use of PB and a low number of nucleated cells (≤7×103/µL) in the sample. High and low cellularity in BM and high and low cellularity in PB samples showed no metaphases in 3.9, 39.7, 41.9, and 84.6% of cases, respectively. Collecting a good BM sample is the key for the success of karyotyping in MN and avoids the use of expensive molecular techniques.

Hepatic and cardiac and iron overload detected by T2* magnetic resonance (MRI) in patients with myelodisplastic syndrome: A cross-sectional study.

INTRODUCTION: Transfusion-dependent anemia and iron overload are associatedwith reduced survival in myelodysplastic syndrome (MDS). This cross-sectional study aimed to evaluate the prevalence of hepatic and cardiac overload in patients with MDS as measured by T2* magnetic resonance imaging (MRI), and its correlation with survival. METHODS: MDS or chronic myelomonocytic leukemia patients had iron overload evaluated by T2* MRI. HIO was considered when hepatic iron concentration ≥ 2 g/mg. Cardiac iron overload was considered with a T2*-value < 20 ms. RESULTS: Among 71 patients analyzed, median hepatic iron concentration was 3.9 g/mg (range 0.9-16 g/mg), and 68%of patients had hepatic iron overload. Patients with hepatic iron overload had higher mean ferritin levels (1182 ng/mL versus 185 ng/mL, p < 0.0001), transferrin saturation (76% versus 34%, p < 0.0001) and lower survival rates. Median cardiac T2*value was 42 ms (range 19.7-70.1 ms), and only one patienthad a T2* value indicative of cardiac iron overload. CONCLUSIONS: Hepatic iron overload is found in two thirds of patients, even in cases without laboratory signs of iron overload. Hepatic iron overload by T2* MRI is associated with a decreased risk of survival in patients with MDS.

Haploidentical BMT and post-transplant Cy for severe aplastic anemia: a multicenter retrospective study.

Patients with refractory severe aplastic anemia (SAA) who lack a matched sibling or unrelated donor need new therapeutic approaches. Hematopoietic SCT (HSCT) using mismatched or haploidentical related donors has been used in the past, but was associated with a significant risk of GVHD and mortality. Recently, the use of post-transplant cyclophosphamide (Cy) has been shown to be an effective strategy to prevent GVHD in recipients of haploidentical HSCT, but the majority of reports have focused on patients with hematology malignancies. We describe the outcome of 16 patients who underwent haploidentical transplantation using a reduced-intensity conditioning regimen with post-transplant Cy. Stem cell sources were BM (N=13) or PBSCs (N=3). The rate of neutrophil engraftment was 94% and of platelet engraftment was 75%. Two patients had secondary graft failure and were successfully salvaged with another transplant. Three patients developed acute GVHD being grades 2-4 in two. Five patients have died and the 1-year OS was 67.1% (95% confidence interval: 36.5-86.4%). In our small series, the use of a reduced-intensity conditioning with post-transplant Cy in haploidentical BMT was associated with high rates of engraftment and low risk of GVHD in patients with relapsed/refractory SAA.

Pre-analytical parameters associated with unsuccessful karyotyping in myeloid neoplasm: a study of 421 samples

Cytogenetics is essential in myeloid neoplasms (MN) and pre-analytical variables are important for karyotyping. We assessed the relationship between pre-analytical variables (time from collection to sample processing, material type, sample cellularity, and diagnosis) and failures of karyotyping. Bone marrow (BM, n=352) and peripheral blood (PB, n=69) samples were analyzed from acute myeloid leukemia (n=113), myelodysplastic syndromes (n=73), myelodysplastic syndromes/myeloproliferative neoplasms (n=17), myeloproliferative neoplasms (n=137), and other with conclusive diagnosis (n=6), and reactive disorders/no conclusive diagnosis (n=75). The rate of unsuccessful karyotyping was 18.5% and was associated with the use of PB and a low number of nucleated cells (≤7×103/µL) in the sample. High and low cellularity in BM and high and low cellularity in PB samples showed no metaphases in 3.9, 39.7, 41.9, and 84.6% of cases, respectively. Collecting a good BM sample is the key for the success of karyotyping in MN and avoids the use of expensive molecular techniques.

Characterization of Bacillus thuringiensis isolates with potential for control of Aedes aegypti (Linnaeus, 1762) (Diptera: Culicidae).

Aedes aegypti (Linnaeus) is the vector of dengue virus in Brazil. Bioinsecticides based on Bacillus thuringiensis have shown satisfactory results in the control of Diptera, due to the production of proteins called Cry and Cyt. The aim of the present study was to select B. thuringiensis isolates carrying the cry and cyt genes, which are efficient in the control of Ae. aegypti. A collection of 27 isolates of B. thuringiensis, derived from various regions in Brazil, was evaluated using selective bioassays against A. aegypti larvae. Of the 27 isolates, five showed 100% larval mortality at a concentration of 0.05 ppm and the toxicity of these isolates in quantitative bioassays did not differ significantly at temperatures of 15, 25 and 35 °C. In addition, these isolates showed statistical differences for the LC50 values only above pH 9, which indicates a maintenance in insecticide potential in a wide range of alkaline pH values. This result is promising, considering that waste treatment reservoirs generally show an acid pH and higher temperatures. These isolates were also evaluated by PCR using specific primers for the genes cry4A, cry4B, cry10A, cry11, cyt1 and cyt2. The analyses demonstrated that all the five isolates showed amplification products for all the studied genes showing four different Cry proteins, besides Cyt proteins. The obtained results of bioassays and PCR demonstrates the great potential for the use of these isolates in controlling populations of Ae. Aegypti and perhaps other species of mosquitoes in a wide range of environments.

Histone deacetylase inhibitors for the treatment of myelodysplastic syndrome and acute myeloid leukemia.

Epigenetic changes have been identified in recent years as important factors in the pathogenesis of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Histone deacetylase inhibitors (HDACIs) regulate the acetylation of histones as well as other non-histone protein targets. Treatment with HDACIs results in chromatin remodeling that permits re-expression of silenced tumor suppressor genes in cancer cells, which, in turn, can potentially result in cellular differentiation, inhibition of proliferation and/or apoptosis. Several classes of HDACIs are currently under development for the treatment of patients with MDS and AML. Although modest clinical activity has been reported with the use of HDACIs as single-agent therapy, marked responses have been observed in selected subsets of patients. More importantly, HDACIs appear to be synergistic in vitro and improve response rates in vivo when combined with other agents, such as hypomethylating agents. Furthermore, HDACIs are also being investigated in combination with non-epigenetic therapies. This article synthesizes the most recent results reported with HDACIs in clinical trials conducted in patients with MDS and other myeloid malignancies.

Experimental analysis of lateral impact on planar brittle material: spatial properties of cracks.

The breakup of alkaline glass and alumina plates due to planar impacts on one of their lateral sides is studied. Particular attention is given to investigating the spatial location of the cracks within the plates. Analysis based on a phenomenological model suggests that bifurcations along the cracks' paths are more likely to take place closer to the impact region than far away from it, i.e., the bifurcation probability seems to lower as the perpendicular distance from the impacted lateral increases. It is also found that many observables are not sensitive to the plate material used in this work, as long as the fragment multiplicities corresponding to the fragmentation of the plates are similar. This gives support to the universal properties of the fragmentation process reported in previous experiments. However, even under the just mentioned circumstances, some spatial observables are capable of distinguishing the material of which the plates are made, which therefore suggests that this universality should be carefully investigated.

Co-operative signalling through DP(1) and DP(2) prostanoid receptors is required to enhance leukotriene C(4) synthesis induced by prostaglandin D(2) in eosinophils.

BACKGROUND AND PURPOSE: Prostaglandin (PG) D(2) has emerged as a key mediator of allergic inflammatory pathologies and, particularly, PGD(2) induces leukotriene (LT) C(4) secretion from eosinophils. Here, we have characterized how PGD(2) signals to induce LTC(4) synthesis in eosinophils. EXPERIMENTAL APPROACH: Antagonists and agonists of DP(1) and DP(2) prostanoid receptors were used in a model of PGD(2) -induced eosinophilic inflammation in vivo and with PGD(2) -stimulated human eosinophils in vitro, to identify PGD(2) receptor(s) mediating LTC(4) secretion. The signalling pathways involved were also investigated. KEY RESULTS: In vivo and in vitro assays with receptor antagonists showed that PGD(2) -triggered cysteinyl-LT (cysLT) secretion depends on the activation of both DP(1) and DP(2) receptors. DP(1) and DP(2) receptor agonists elicited cysLTs production only after simultaneous activation of both receptors. In eosinophils, LTC(4) synthesis, but not LTC(4) transport/export, was activated by PGD(2) receptor stimulation, and lipid bodies (lipid droplets) were the intracellular compartments of DP(1) /DP(2) receptor-driven LTC(4) synthesis. Although not sufficient to trigger LTC(4) synthesis by itself, DP(1) receptor activation, signalling through protein kinase A, did activate the biogenesis of eosinophil lipid bodies, a process crucial for PGD(2) -induced LTC(4) synthesis. Similarly, concurrent DP(2) receptor activation used Pertussis toxin-sensitive and calcium-dependent signalling pathways to achieve effective PGD(2) -induced LTC(4) synthesis. CONCLUSIONS AND IMPLICATIONS: Based on pivotal roles of cysLTs in allergic inflammatory pathogenesis and the collaborative interaction between PGD(2) receptors described here, our data suggest that both DP(1) and DP(2) receptor antagonists might be attractive candidates for anti-allergic therapies.

Experimental analysis of lateral impact on planar brittle material.

The fragmentation of alumina and glass plates due to lateral impact is studied. A few hundred plates have been fragmented at different impact velocities and the produced fragments are analyzed. The method employed in this work allows one to investigate some geometrical properties of the fragments, besides the traditional size distribution usually studied in former experiments. We found that, although both materials exhibit qualitative similar fragment size distribution function, their geometrical properties appear to be quite different. A schematic model for two-dimensional fragmentation is also presented and its predictions are compared to our experimental results. The comparison suggests that the analysis of the fragments' geometrical properties constitutes a more stringent test of the theoretical models' assumptions than the size distribution.

Clinical and histopathological features of myocarditis in dogs with visceral leishmaniasis / Aspectos clínicos e histopatológicos da miocardite em cães com leishmaniose visceral

Visceral leishmaniasis (VL) is a cosmopolitan parasitic zoonosis that can promote myocarditis and heart rate changes in canine and human hosts. Thus, histopathological aspects of the myocardium and clinical, hematological, biochemical, radiological and electrocardiographic data were evaluated in a group of 36 dogs naturally infected with VL (VLG) and compared to data from 15 non-infected dogs (CG=Control Group). A prevalence of asymptomatic dogs was present in the CG (100%) and polysymptomatic dogs in the VLG (66%). In addition, two dogs in the VLG demonstrated systolic murmurs in the mitral valve region: one with a II/VI intensity and the other with a III/VI intensity. The mean values of RBC, hemoglobin and hematocrit were lower in dogs in VLG and were associated with higher values of total protein, total leukocytes, neutrophils, creatine kinase overall (CK) and the CK-MB fraction (CK-MB). The absence of radiographic changes was accompanied by a predominance of respiratory sinus arrhythmia associated with episodes of migratory pacemaker and sinus arrest in dogs in VLG (75%), sinus rhythm in dogs in CG (60%) and decreased P wave amplitude in VLG electrocardiography. Mononuclear cell infiltration was detected in the myocardium of 77,8% of dogs in GVL and classified primarily as mild multifocal lymphohistioplasmacytic. Amastigotes were detected in only one dog, which did not allow the association between myocarditis and parasitism, although the myocardial lesions that were found constitute irrefutable evidence of myocarditis in the VLG dogs, accompanied by lenient electrocardiographic changes compared to CG.

A leishmaniose visceral (LV) é uma zoonose parasitária cosmopolita capaz de promover miocardite e alterações no ritmo cardíaco em cães e seres humanos. Dessa forma, os aspectos clínicos, hematimétricos, bioquímicos, radiográficos, eletrocardiográficos e histopatológicos do miocárdio foram avaliados em 36 cães naturalmente infectados com LV (GLV) e comparados a 15 cães não infectados (GC). Houve predomínio de cães assintomáticos no GC (100%) e polissintomáticos no GLV (66%). Dois cães do GLV apresentaram sopro sistólico de intensidade II/VI e III/VI, em região de foco mitral. Os valores médios de hemácia, hemoglobina e hematócrito foram inferiores nos cães do GLV, associados a maiores valores de proteína total, leucócitos totais, neutrófilos, creatinina quinase total (CK) e fração MB (CK-MB). Ausência de alterações radiográficas foi acompanhada de predomínio de arritmia sinusal respiratória associada a episódios de marcapasso migratório e sinus arrest nos cães do GLV (75%), ritmo sinusal nos cães do GC (60%) e diminuição da amplitude da onda P no GLV à eletrocardiografia. Infiltrado inflamatório mononuclear foi detectado no miocárdio de 77,8% dos cães do GLV, classificados, em sua maioria, como linfoistioplasmocitário multifocal leve. A forma amastigota foi detectada em apenas um cão, não permitindo a associação entre a miocardite e a parasitose, ainda que as lesões miocárdicas encontradas constituam prova irrefutável da miocardite nos cães do GLV, acompanhadas por alterações eletrocardiográficas brandas em comparação ao GC.

Desempenho de vacas em lactação alimentadas com dietas contendo torta de macaúba / Performance of dairy cows fed diets containing macauba meal

Avaliaram-se o consumo de nutrientes e a produção e composição do leite de vacas da raça Holandesa alimentadas com dietas contendo diferentes quantidades de inclusão de torta de macaúba. Oito animais foram distribuídos em dois quadrados latinos 4x4, sendo quatro tratamentos, 0, 100, 200 e 300g kg-1 de TM na matéria seca da dieta, e quatro períodos experimentais de 21 dias, 14 de adaptação e sete de avaliações. A adição de quantidades crescentes de torta de macaúba à dieta alterou o consumo de matéria seca, matéria orgânica, proteína bruta, extrato etéreo, fibra em detergente neutro, carboidratos não fibrosos, produção e os teores de lactose, extrato seco desengordurado e sólidos totais do leite, bem como a eficiência alimentar e a digestibilidade da matéria seca. Por outro lado, não foi verificada diferença nos teores de gordura do leite. A adição da TM em até 300g kg-1 da dieta comprometeu o consumo e o desempenho produtivo dos animais.

We evaluated nutrient intake, production and composition of milk from Holstein cows fed feedlot diets with different inclusion levels of macauba meal. Eight animals were divided into two 4x4 latin square designs, four treatments, 0, 100, 200 and 300g kg-1 macauba meal in the dry matter diet, and four experimental periods of 21 days, 14 adaptation and seven evaluation The addition of increasing levels of macauba meal diet alter the intake of dry matter, organic matter, crude protein, ether extract, neutral detergent fiber, non-fiber carbohydrates, production and concentration of lactose, nonfat dry and total solids in milk, as well as the feed efficiency and digestibility of dry matter. Moreover, there was no difference in the levels of milk fat. The addition of macaúba meal up to 300g kg-1 diet compromised the consumption and production performance of animals.

Adult acute erythroleukemia: an analysis of 91 patients treated at a single institution.

Acute erythroleukemia (AML-M6) is an uncommon subtype of acute myeloid leukemia (AML); it is considered to have a poor prognosis. From 1 January 1980 to 21 May 2008, 91 patients with newly diagnosed AML-M6 were seen at the University of Texas-M.D. Anderson Cancer Center (UT-MDACC). Forty-five patients (50%) had a history of myelodysplatic syndrome (MDS), compared with 41% in our control group (patients with other AML subtypes) (P=0.08). Poor-risk cytogenetics were more common in patients with AML-M6 (61% versus 38%, P=0.001). Complete remission rates were 62% for patients with AML-M6, comparing with 58% for the control group (P=0.35). Median disease free survival (DFS) for patients with AML-M6 was 32 weeks, versus 49 weeks for the control group (P=0.05). Median overall survival (OS) of patients with AML-M6 was 36 weeks, compared with 43 weeks for the control group (P=0.60). On multivariate analysis for DFS and OS, AML-M6 was not an independent risk factor. AML-M6 is commonly associated with a previous diagnosis of MDS and poor-risk karyotype. The diagnosis of AML-M6 does not impart by itself a worse prognosis, and treatment decisions on this disease should be guided by well known AML prognostic factors.

Whole body and regional bone mineral density in ankylosing spondylitis.

OBJECTIVE: To study the regional distribution of bone mass and look for factors leading to bone loss in ankylosing spondylitis (AS). METHODS: Thirty-nine patients, all men, aged 20 to 55 years and presenting with AS were studied. Four hundred sixteen gendarmes, all men aged 20 to 55 years, formed an age matched control population used to define standard values for bone mineral density (BMD) in men. The patients with AS and the controls underwent measurement of whole body BMD and regional BMD by dual-energy x-ray absorptiometry. RESULTS: AS was associated with spinal bone loss, with lumbar spine BMD (LSBMD) 1.085 +/- 0.178 g/cm2 in the AS group compared with 1.232 +/- 0.136 g/cm2 in the control group (p < 0.01). Whole body BMD and regional BMD of head, whole spine, pelvis, and legs were reduced, although this was not statistically significant. Using standard values for LSBMD from the controls, we found that 46% (18/39) of patients with AS had Z score < -1.5 SD. Biological markers of disease activity were higher in the subgroup of patients with low LSBMD than in the subgroup with normal LSBMD, with an erythrocyte sedimentation rate of 29.4 +/- 23.4 mm/h versus 12.1 +/- 10.8 mm/h (p < 0.05) and C-reactive protein at 24.8 +/- 18 mg/l versus 12.7 +/- 14.2 mg/l (p < 0.05). CONCLUSION: AS is associated with bone loss, mainly concerning the lumbar spine, in patients whose disease is biologically most active.

Colorectal cancer screening.

Colorectal cancer (CRC) is the third most common cancer in the world, and mortality has remained the same for the past 50 years, despite advances in diagnosis and treatment. Because significant numbers of patients present with advanced or incurable stages, patients with pre-malignant lesions (adenomatous polyps) that occur as result of genetic inheritance or age should be screened, and patients with long-standing inflammatory bowel disease should undergo surveillance. There are different risk groups for CRC, as well as different screening strategies. It remains to be determined which screening protocol is the most cost-effective for each risk catagory. The objective of screening is to reduce morbidity and mortality in a target population. The purpose of this review is to analyze the results of the published CRC screening studies, with regard to the measured reduction of morbidity and mortality, due to CRC in the studied populations, following various screening procedures. The main screening techniques, used in combination or alone, include fecal occult blood tests, flexible sigmoidoscopy, and colonoscopy. Evidence from the published literature on screening methods for specific risk groups is scanty and frequently does not arise from controlled studies. Nevertheless, data from these studies, combined with recent advances in molecular genetics, certainly lead the way to greater efficacy and lower cost of CRC screening.