Seasonal Patterns of Enteric Pathogens in Colombian Indigenous People-A More Pronounced Effect on Bacteria Than on Parasites.

Enteric pathogens, which are frequently food- and waterborne transmitted, are highly abundant in Indigenous people living in remote rural areas of Colombia. As the frequency of gastroenteritis in the tropics shows seasonal differences, we analyzed variations of pathogen patterns in the stool samples of a Colombian Indigenous tribe called Wiwa during the dry (n = 105) and the rainy (n = 227) season, applying real-time PCR from stool samples and statistical analysis based on a multi-variable model. Focusing on bacterial pathogens, increased detection rates could be confirmed for enteropathogenic, enterotoxigenic and enteroaggregative Escherichia coli with a tendency for an increase in Campylobacter jejuni detections during the rainy season, while there was no seasonal effect on the carriage of Tropheryma whipplei. Salmonellae were recorded during the rainy season only. A differentiated pattern was seen for the assessed parasites. Entamoeba histolytica, Necator americanus and Trichuris trichiura were increasingly detected during the rainy season, but not Ascaris lumbricoides, Giardia duodenalis, Hymenolepis nana, Strongyloides stercoralis, and Taenia solium, respectively. Increased detection rates during the dry season were not recorded. Negative associations were found for Campylobacter jejuni and Giardia duodenalis with age and for Tropheryma whipplei with the body mass index, respectively. Positive associations of enteropathogenic Escherichia coli and Taenia solium detections were observed with age. In conclusion, facilitating effects of the tropical rainy season were more pronounced on bacterial enteric pathogens compared to enteropathogenic parasites.

Dengue virus detection in Lao PDR and Colombia: Comparative evaluation of PCR tests.

OBJECTIVES: Dengue virus (DENV) detection by polymerase chain reaction (PCR) facilitates diagnosis of dengue fever, which is the most frequent arboviral disease globally. Two studies were performed in countries with high dengue incidence, to assess the diagnostic performance of different PCR techniques. METHODS/RESULTS: Two hundred and seventy-nine acute phase blood samples from febrile patients were analyzed for DENV by the RealStar Dengue RT-PCR kit (Altona Diagnostics) as gold standard in comparison with the Tropical Fever Core multiplex PCR (Fast Track Diagnostics). In total, 102 samples collected in Savannakhet Province (Lao PDR, Southeast Asia) in 2013 and 35 samples from Valledupar (Colombia, South America) tested positive for DENV by RealStar RT-PCR. In comparison, the Tropical Fever Core multiplex PCR detected 65.0% (65/102) and 68.6% (24/35) of these samples as positive for DENV in Savannakhet and Valledupar, respectively. Diagnostic sensitivity of the multiplex PCR strongly correlated with viral load. A subset of DENV PCR-confirmed samples was additionally tested by BNITM in house Dengue Type RT-PCR in comparison with two commercial test kits (RealStar Dengue Type RT-PCR [Altona Diagnostics], Dengue differentiation PCR [Fast Track Diagnostics]). The leading dengue serotype in Savannakhet was DENV-3 (58% [29/50]), while DENV-1 (53.8% [14/26]) was the predominant serotype found in samples collected in Valledupar by BNITM-type PCR. However, three DENV serotypes were circulating in Valledupar and in Savannakhet. In 2015, additional studies found predominantly DENV-4 (71% [12/17]) in Savannakhet. CONCLUSIONS: Both studies emphasized that routine diagnostics in both regions will benefit from an expanded use of highly sensitive pan-dengue PCRs.

Seasonal Differences in Cyclospora cayetanensis Prevalence in Colombian Indigenous People.

Fecal-orally transmitted cyclosporiasis is frequent in remote resource-limited settings in Central and South America with poor hygiene conditions. In this study, we aimed at assessing seasonal effects on the epidemiology of colonization or infection with C. cayetanensis in Colombian indigenous people living under very restricted conditions. In the rainy season between July and November and in the dry season between January and April, stool samples from indigenous people with and without gastrointestinal symptoms were collected and screened for C. cayetanensis applying in-house real-time polymerase chain reaction (PCR). In the rainy season and in the dry season, positive PCR results were observed for 11.8% (16/136) and 5.1% (15/292), respectively, with cycle threshold (Ct) values of 30.6 (±3.4) and 34.4 (±1.6), respectively. Despite higher parasite loads in the rainy season, fewer individuals (2/16, 12.5%) reported gastrointestinal symptoms compared to the dry season (6/15, 40%). In conclusion, considerable prevalence of C. cayetanensis in Colombian indigenous people persists in the dry season. Low proportions of gastrointestinal symptoms along with higher parasite loads make colonization likely rather than infection.

Haemophilia early arthropathy detection with ultrasound and haemophilia joint health score in the moderate haemophilia (MoHem) study.

INTRODUCTION: Detection of early arthropathy is crucial for the management of haemophilia, but data on moderate haemophilia are limited. Therefore, we evaluated joint health and treatment modalities in Nordic patients with moderate haemophilia A (MHA) and B (MHB). AIM: To explore and compare the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) and Haemophilia Joint Health Score (HJHS) to detect early arthropathy in moderate haemophilia. METHODS: A cross-sectional, multicentre study covering Nordic patients with MHA and MHB. Arthropathy was evaluated by HEAD-US and HJHS 2.1. RESULTS: We assessed 693 joints in 118 patients. HEAD-US scores (medians [interquartile ranges]) were as follows: elbows 0 points (0-0), knees 0 (0-0) and ankles 0 (0-1). Respectively, by HJHS: elbows 0 (0-1), knees 0 (0-1) and ankles 0 (0-1). Cartilage (14%) and bone (13%) were most commonly affected by HEAD-US. Frequent HJHS findings were crepitus on motion in knees (39%), and loss of flexion (23%) and extension (13%) in ankles. HEAD-US correlated strongly with HJHS (elbows r = .70, knees r = .60 and ankles r = .65), but 24% had discordant scores. Joints with HJHS zero points, 5% captured HEAD-US ≥1 point. Moreover, 26% had HJHS findings without HEAD-US pathology. Notably, 31% of knees had crepitus on motion and normal HEAD-US. CONCLUSION: Overall, the joints attained low scores implying good joint health. HEAD-US correlated strongly with HJHS. In 5%, HEAD-US detected subclinical pathology. Crepitus on motion was frequently reported despite normal HEAD-US, thus not necessarily reflecting arthropathy. HEAD-US therefore improves the joint assessment in moderate haemophilia.

High Prevalence of Intestinal Pathogens in Indigenous in Colombia.

BACKGROUND: Intestinal infections remain a major public health burden in developing countries. Due to social, ecological, environmental, and cultural conditions, Indigenous peoples in Colombia are at particularly high risk. MATERIALS: 137 stool samples were analyzed by microscopy and real-time-Polymerase Chain Reaction (RT-PCR), targeting protozoan parasites (Giardia intestinalis, Entamoeba histolytica, Cryptosporidium spp., and Cyclospora cayetanensis), bacteria (Campylobacter jejuni, Salmonella spp., Shigella ssp./enteroinvasive E. coli (EIEC), Yersinia spp., enterohemorrhagic E. coli (EHEC), enteropathogenic E. coli ( EPEC), enterotoxin-producing E. coli (ETEC), enteroaggregative E. coli (EAEC), and Tropheryma whipplei), and helminths (Necator americanus, Strongyloides stercoralis, Ascaris lumbricoides, Ancylostoma spp., Trichuris. trichiura, Taenia spp., Hymenolepis nana, Enterobius vermicularis, and Schistosoma spp.). Microscopy found additional cases of helminth infections. RESULTS: At least one pathogen was detected in 93% of the samples. The overall results revealed protozoa in 79%, helminths in 69%, and bacteria in 41%. G. intestinalis (48%), Necator/hookworm (27%), and EAEC (68%) were the most common in each group. Noteworthy, T. whipplei was positive in 7% and T. trichirua in 23% of the samples. A significant association of one infection promoting the other was determined for G. intestinalis and C. jejuni, helminth infections, and EIEC. CONCLUSIONS: The results illustrate the high burden of gastrointestinal pathogens among Indigenous peoples compared to other developing countries. Countermeasures are urgently required.

Chagas Disease: Detection of Trypanosoma cruzi by a New, High-Specific Real Time PCR.

BACKGROUND: Chagas disease (CD) is a major burden in Latin America, expanding also to non-endemic countries. A gold standard to detect the CD causing pathogen Trypanosoma cruzi is currently not available. Existing real time polymerase chain reactions (RT-PCRs) lack sensitivity and/or specificity. We present a new, highly specific RT-PCR for the diagnosis and monitoring of CD. MATERIAL AND METHODS: We analyzed 352 serum samples from Indigenous people living in high endemic CD areas of Colombia using three leading RT-PCRs (k-DNA-, TCZ-, 18S rRNA-PCR), the newly developed one (NDO-PCR), a Rapid Test/enzyme-linked immuno sorbent assay (ELISA), and immunofluorescence. Eighty-seven PCR-products were verified by sequence analysis after plasmid vector preparation. RESULTS: The NDO-PCR showed the highest sensitivity (92.3%), specificity (100%), and accuracy (94.3%) for T. cruzi detection in the 87 sequenced samples. Sensitivities and specificities of the kDNA-PCR were 89.2%/22.7%, 20.5%/100% for TCZ-PCR, and 1.5%/100% for the 18S rRNA-PCR. The kDNA-PCR revealed a 77.3% false positive rate, mostly due to cross-reactions with T. rangeli (NDO-PCR 0%). TCZ- and 18S rRNA-PCR showed a false negative rate of 79.5% and 98.5% (NDO-PCR 7.7%), respectively. CONCLUSIONS: The NDO-PCR demonstrated the highest specificity, sensitivity, and accuracy compared to leading PCRs. Together with serologic tests, it can be considered as a reliable tool for CD detection and can improve CD management significantly.

Auditory and Visual External Cues Have Different Effects on Spatial but Similar Effects on Temporal Measures of Gait Variability.

Walking synchronized to external cues is a common practice in clinical settings. Several research studies showed that this popular gait rehabilitation tool alters gait variability. There is also recent evidence which suggests that alterations in the temporal structure of the external cues could restore gait variability at healthy levels. It is unknown, however, if such alterations produce similar effects if the cueing modalities used are different; visual or auditory. The modality could affect gait variability differentially, since there is evidence that auditory cues mostly act in the temporal domain of gait, while visual cues act in the spatial domain of gait. This study investigated how synchronizing steps with visual and auditory cues that are presented with different temporal structures could affect gait variability during treadmill walking. Three different temporal structured stimuli were used, invariant, fractal and random, in both modalities. Stride times, length and speed were determined, and their fractal scaling (an indicator of complexity) and coefficient of variation (CV) were calculated. No differences were observed in the CV, regardless of the cueing modality and the temporal structure of the stimuli. In terms of the stride time's fractal scaling, we observed that the fractal stimulus induced higher values compared to random and invariant stimuli. The same was also observed in stride length, but only for the visual cueing modality. No differences were observed for stride speed. The selection of the cueing modality seems to be an important feature of gait rehabilitation. Visual cues are possibly a better choice due to the dependency on vision during walking. This is particularly evident during treadmill walking, a common practice in a clinical setting. Because of the treadmill effect on the temporal domain of gait, the use of auditory cues can be minimal, compared to visual cues.

Assessment of diagnostic and analytic performance of the SD Bioline Dengue Duo test for dengue virus (DENV) infections in an endemic area (Savannakhet province, Lao People's Democratic Republic).

BACKGROUND: Rapid tests detecting both dengue virus (DENV) NS1 antigen and anti-DENV IgM and IgG antibodies facilitate diagnosis of dengue fever (DF) in resource-poor settings. METHODOLOGY/PRINCIPAL FINDINGS: 92 acute phase serum samples from patients with a PCR-confirmed DENV infection collected in Lao People's Democratic Republic (Lao PDR) in 2013 and 2015 were analyzed with the SD Bioline Dengue Duo test. A subset of 74 samples was additionally tested with the Platelia NS1 antigen test, the Panbio DENV µ-capture ELISA and the Panbio DENV IgG ELISA. IgM seroconversion was assayed using follow-up samples of 35 patients collected in the convalescent phase. 57.6%, 22.8% and 44.6% of acute phase serum samples tested positive in the SD Bioline Dengue Duo NS1, IgM, and IgG test, respectively. Diagnostic sensitivity of the SD Bioline Dengue Duo NS1 test strongly correlated with viral load, decreased rapidly over the acute phase of the disease, and was significantly reduced in presence of high anti-DENV IgG antibody titers resulting from secondary DENV infection. While a good concordance (Cohen's kappa 0.78) was found between the SD Bioline Dengue Duo NS1 test and the Platelia NS1 antigen ELISA, both the SD Bioline Dengue Duo IgM and IgG test displayed a significantly lower sensitivity than the corresponding ELISA tests. CONCLUSIONS/SIGNIFICANCE: The SD Bioline Dengue Duo test is a valuable tool for diagnosis of DENV infections especially when analyzing early acute phase samples with high viral load. Nevertheless, in endemic areas, where secondary flavivirus infections are common, diagnostic sensitivity of the NS1 and IgM test components may be compromised.

Source apportionment of metallic elements in urban atmospheric particulate matter and assessment of its water-soluble fraction toxicity.

Clean air is essential for the maintenance of human life and environmental balance. The atmospheric particulate matter (PM) is one of the main air pollutants and is characterized by the heterogeneity of its composition, being able to accumulate numerous components, such as metallic elements, which contribute to increasing its toxicity. The objectives of this study were to assess of the air quality in two urban environments, to carry out the source apportionment of the metallic elements Al, Ba, Cd, Pb, Cu, Cr, Fe, Mn, Ni, and Zn in the PM2.5 and PM2.5-10, and evaluate the toxicity of PM2.5 and PM2.5-10 water-soluble fractions using Lactuca sativa as bioindicator. The collection of PM2.5 and PM2.5-10 was performed using a dichotomous stacked filter unit (SFU) sampler. The source apportionment was carried out using the EPA PMF 5.0 receptor model and the toxicity tests followed the EPA Ecological Effects Test Guidelines OPPTS 850.4200: Seed Germination/Root Elongation Toxicity Test. The source apportionment demonstrated that vehicular and industrial emissions are the main anthropogenic sources contributing to the concentration of metallic elements to thePM2.5 and PM2.5-10. The studied sites did not show statistically significant differences in terms of phytotoxicity to the Lactuca sativa seeds. Cd and Cu were identified as the main metallic elements which able to cause negative effects on seed germination and root elongation, respectively. The presence of cadmium and copper in the atmospheric particulate matter is one of the main causes of the phytotoxicity affecting the Lactuca sativa seed germination and root elongation.

E-Library of Authentic Patient Videos Improves Medical Students' Mental Status Examination.

OBJECTIVE: During psychiatric rotation, clerkship students must learn the clinical skill of recording an accurate Mental Status Examination (MSE). The authors built a video e-library consisting of 23 authentic patient videos that were accessible on a secure website during the rotation period, aimed at assisting students' acquisition of MSE skills. METHODS: The authors conducted a prospective case comparison study investigating the impact of the video e-library as "add-on" intervention, on acquisition of MSE skills, as measured by a test consisting of three videos with adjoining forced choice questionnaires. Eighty-five clerkship students had instructions and access to the video e-library whereas 82 did not. A group of clinicians, unfamiliar with the video e-library, was also subjected to the new MSE skills test and they served as a reference group. Outcome was defined as scores of MSE skills measured by the purpose made MSE skills test and entailed evaluation questions on the students' use of the e-library. RESULTS: The MSE skill test score differed between the three groups, and the clinicians scored higher than both student groups (clinicians mean score (M) 12.6; p < 0.001). However, the students with video access scored higher compared to students without access (M 10.7 versus M 9.9, p = 0.04). The e-library was appreciated by the students as helpful (83.6%) and they used it not only for practicing the MSE but also for observation of interviewing techniques. CONCLUSION: The e-library with video vignettes of authentic patients strengthens MSE skills as "add-on" to the psychiatric rotation, and evaluations by the students were positive.

The effect of melatonin on depressive symptoms and anxiety in patients after acute coronary syndrome: The MEDACIS randomized clinical trial.

BACKGROUND: Depression following acute coronary syndrome is prevalent and associated with increased mortality and morbidity. Melatonin may function as a primary prophylactic antidepressant substance and alleviate depressive symptoms. The study was undertaken to determine if melatonin administered following an acute coronary syndrome (ACS) could prevent development of depression. METHODS: The study was a double-blinded, placebo-controlled, multicenter, randomized clinical trial performed in five primary care cardiology departments at Zealand, Denmark. Included patients were adults patients, free of depression at baseline, included at the latest 4 weeks after acute coronary syndrome. Twenty-five mg melatonin or placebo was administered 1 h before participants' bedtime for 12 weeks. The primary outcome is Major Depression Inventory (MDI) measured every two weeks throughout the trial. Incidence of depression was apriori defined as MDI score ≥ 21 during the trial. Reported exploratory outcomes were patterns of dropout and safety outcomes. RESULTS: 1220 patients were screened and 252 participants were randomized in a 1:1 ratio. Baseline MDI score in the melatonin and placebo group were, respectively, 6.18 (CI 5.32-7.05) and 5.98 (CI 5.19-6.77). No significant intergroup differences were found during the study in the intention-to-treat analysis or per-protocol analysis. Cumulative events of depressive episodes during the 12 weeks were six in the melatonin group and four in the placebo group. A significant drop in depressive symptoms were present throughout the study period. No intergroup differences were present in dropouts or adverse events. CONCLUSIONS: Melatonin showed no prophylactic antidepressant effect following acute coronary syndrome. The non-significant results might be due to a type II error or melatonin might not be able to prevent development of depressive symptoms following ACS.

Red blood cells mediate the onset of thrombosis in the ferric chloride murine model.

Application of ferric chloride (FeCl(3)) to exposed blood vessels is widely used to initiate thrombosis in laboratory mice. Because the mechanisms by which FeCl(3) induces endothelial injury and subsequent thrombus formation are little understood, we used scanning electron and brightfield intravital microscopy to visualize endothelial damage and thrombus formation occurring in situ. Contrary to generally accepted belief, FeCl(3) does not result in appreciable subendothelial exposure within the time frame of thrombosis. Furthermore, the first cells to adhere to FeCl(3)-treated endothelial surfaces are red blood cells (RBCs) rather than platelets. Energy dispersive x-ray spectroscopy demonstrated that ferric ions predominantly localize to endothelial-associated RBCs and RBC-derived structures rather than to the endothelium. With continuing time points, RBC-derived structures rapidly recruit platelets, resulting in large complexes that subsequently enlarge and coalesce, quickly covering the endothelial surface. Further studies demonstrated that neither von Willebrand factor nor platelet glycoprotein Ib-α receptor (GPIb-α) is required for RBCs to adhere to the endothelium, and that deficiency of GPIb-α greatly abrogated the recruitment of platelets to the endothelial-associated RBC material. These findings illuminate the mechanisms of FeCl(3)-mediated thrombosis and reveal a previously unrecognized ability of RBCs to participate in thrombosis by mediating platelet adhesion to the intact endothelial surface.

Maternal attitudes to newborn screening for fragile X syndrome.

Although fragile X syndrome (FXS) is the commonest cause of inherited intellectual disability the mean age of diagnosis in Australia is 5.5 years. Newborn screening for FXS can provide an early diagnosis, preventing the "diagnostic odyssey", allowing access to early interventions, and providing reproductive information for parents. Parents of affected children support newborn screening, but few clinical studies have evaluated community attitudes. A pilot study in 2009-2010 was performed in a tertiary hospital to explore feasibility and maternal attitudes. FXS testing of male and female newborns was offered to mothers in addition to routine newborn screening. Mothers were provided with information about FXS, inheritance pattern, carrier status, and associated adult-onset disorders. One thousand nine hundred seventy-one of 2,094 mothers (94%) consented to testing of 2,000 newborns. 86% completed the attitudinal survey and 10% provided written comments. Almost all parents (99%) elected to be informed of both premutation and full mutation status and there was little concern about identification of carrier status or associated adult-onset disorders. Most mothers (96%) were comfortable being approached in the postnatal period and supported testing because no extra blood test was required. Mothers considered an early diagnosis beneficial to help prepare for a child with additional needs (93%) and for reproductive planning (64%). Some were anxious about the potential test results (10%) and others felt their feelings towards their newborn may change if diagnosed with FXS (16%). High participation rates and maternal attitudes indicate a high level of maternal acceptance and voluntary support for newborn screening for FXS.

Large-scale evaluation of the immuno-mycologics lateral flow and enzyme-linked immunoassays for detection of cryptococcal antigen in serum and cerebrospinal fluid.

Cryptococcosis is a systemic infection caused by the pathogenic yeasts Cryptococcus neoformans and C. gattii. Detection of cryptococcal capsular antigen (CrAg) in serum and cerebrospinal fluid (CSF) plays an important diagnostic role. We prospectively compared the new Immuno-Mycologics Inc. (IMMY) lateral flow assay (LFA) and enzyme immunoassay (EIA) to our current CrAg test (Premier EIA; Meridian Bioscience Inc.). Discordant samples were retested with the latex-Cryptococcus antigen test (IMMY) and using serotype-specific monoclonal antibodies (MAbs). A total of 589 serum and 411 CSF specimens were tested in parallel. Qualitative agreement across assays was 97.7%. In all, 56 (41 serum and 15 CSF) samples were positive and 921 (527 serum and 394 CSF) samples were negative by all three assays. The 23 discrepant specimens were all Meridian EIA negative. Of 23 discordant specimens, 20 (87.0%) were positive by both the IMMY LFA and EIA, 2 were LFA positive only, and 1 was EIA positive only. Eleven discrepant specimens had adequate volume for latex agglutination (LA) testing; 8 were LA positive, and 3 were LA negative. LA-negative samples (2 CSF samples and 1 serum) had low IMMY LFA/EIA titers (≤1:10). Serotype-specific MAb analysis of the LA-positive samples suggested that these specimens contained CrAg epitopes similar to those of serotype C strains. In conclusion, the IMMY assays showed excellent overall concordance with the Meridian EIA. Assay performance differences were related to issues of analytic sensitivity and possible serotype bias. Incomplete access to patient-level data combined with low specimen volumes limited our ability to fully resolve discrepant results.

Effective interventions for cumulative trauma disorders of the upper extremity in computer users: practice models based on systematic review.

OBJECTIVE: A systematic review of over 4600 abstracts was performed to address the effectiveness of the current cumulative trauma disorder (CTD) interventions focused on the upper extremities of computer users. PARTICIPANTS: The researchers were the study participants. They included one Professor of Occupational Therapy and five Masters of Occupational Therapy Students from a Midwestern University. The Professor of Occupational Therapy has been practicing for 29 years. METHODS: The researchers employed stringent inclusion criteria for this review based on similar systematic review papers. Criteria for high quality qualitative research were incorporated to include studies other than randomized-controlled trials. This approach considered knowledge gained from specific interventions that were studied in greater detail with fewer clients. RESULTS: The results of this study identified 25 articles that met the inclusion criteria. Further review ranked the selected articles into high, medium, or low quality based on criteria adapted from other studies. The highest levels of evidence were found for education and training in ergonomics, forearm supports, ergonomic keyboards, ergonomic mice, and exercise/rest breaks. CONCLUSIONS: Two models of practice were created from this review to assist occupational therapists or other professionals with intervention strategies for computer users with CTDs.

Selection of endometrial carcinomas for DNA mismatch repair protein immunohistochemistry using patient age and tumor morphology enhances detection of mismatch repair abnormalities.

Women with hereditary nonpolyposis colorectal cancer (HNPCC) have a high risk for endometrial cancer (EC) and frequently present with a gynecologic cancer as their first or sentinel malignancy. Identification of these patients is important given their personal and family risk for synchronous and metachronous tumors. The revised Bethesda Guidelines provide screening criteria for HNPCC in colorectal cancers. However, there are currently no such screening recommendations for women with endometrial carcinoma. We applied some of the colorectal cancer screening criteria, including age and tumor morphology, to endometrial endometrioid carcinoma. The purpose of this study was to describe patient and tumor characteristics and to assess the ability of these criteria to enhance detection of mismatch repair (MMR) deficiency, and hence HNPCC in EC. Immunohistochemistry (IHC) for DNA mismatch repair (IHC-MMR) proteins was performed in a defined subset of patients with EC. This included women younger than 50 years of age and women >or=50 years whose tumors showed morphologic features suggestive of MMR deficiency (TM-MMR). The extent of IHC-MMR in the older patient group was compared with that in a comparison group of EC >or=50 years that was previously analyzed for microsatellite instability status. Seventy-one patients met the selection criteria for IHC testing; 32 (45%) showed abnormal results. The rate of IHC abnormality in the younger group was approximately 30% with a nearly equal distribution of MLH1/PMS2 and MSH2/MSH6 abnormalities. In the older age group, TM-MMR triggered IHC analysis in 31 of 34 cases. Of these, 18 cases showed loss of IHC-MMR (58% of cases), 7 with loss of MSH2/MSH6. In contrast, the rate of microsatellite instability in the comparison group was only 21%. The IHC abnormal group showed more frequent tumor infiltrating lymphocytes, dedifferentiated EC, more tumors centered in the lower uterine segment, and more frequent synchronous clear cell carcinomas of the ovary than tumors with a normal immunophenotype. Although many of the patients with loss of IHC-MMR showed personal and/or family history (13 of 32) of HNPCC-associated tumors, most did not. Tumor morphology (TM-MMR) along with IHC-MMR enhances the detection of EC patients at risk of HNPCC.