Blood-Based Multiomics-Guided Detection of a Precancerous Pancreatic Tumor.

Over a decade ago, longitudinal multiomics analysis was pioneered for early disease detection and individually tailored precision health interventions. However, high sample processing costs, expansive multiomics measurements along with complex data analysis have made this approach to precision/personalized medicine impractical. Here we describe in a case report, a more practical approach that uses fewer measurements, annual sampling, and faster decision making. We also show how this approach offers promise to detect an exceedingly rare and potentially fatal condition before it fully manifests. Specifically, we describe in the present case report how longitudinal multiomics monitoring (LMOM) helped detect a precancerous pancreatic tumor and led to a successful surgical intervention. The patient, enrolled in an annual blood-based LMOM since 2018, had dramatic changes in the June 2021 and 2022 annual metabolomics and proteomics results that prompted further clinical diagnostic testing for pancreatic cancer. Using abdominal magnetic resonance imaging, a 2.6 cm lesion in the tail of the patient's pancreas was detected. The tumor fluid from an aspiration biopsy had 10,000 times that of normal carcinoembryonic antigen levels. After the tumor was surgically resected, histopathological findings confirmed it was a precancerous pancreatic tumor. Postoperative omics testing indicated that most metabolite and protein levels returned to patient's 2018 levels. This case report illustrates the potentials of blood LMOM for precision/personalized medicine, and new ways of thinking medical innovation for a potentially life-saving early diagnosis of pancreatic cancer. Blood LMOM warrants future programmatic translational research with the goals of precision medicine, and individually tailored cancer diagnoses and treatments.

Adherence to Dietary Approaches to Stop Hypertension Eating Plan and Prevalence of Irritable Bowel Syndrome in Adults.

BACKGROUND/AIMS: Despite huge evidence on the link between adherence to dietary approaches to stop hypertension (DASH) eating pattern and several metabolic abnormalities, the association of this diet with irritable bowel syndrome (IBS) has not been investigated so far. We aim to examine the association between adherence to the DASH diet and prevalence of IBS symptoms and subtypes in adults. METHODS: This cross-sectional study was done among 3362 adult people in Isfahan, Iran. Usual dietary intakes were assessed using a validated 106-item dish-based semi-quantitative food frequency questionnaire. To investigate participants' adherence to DASH-style diet, we created DASH score based on 8 main foods and nutrients emphasized or minimized in the DASH diet. Participants were classified into 3 categories according to their DASH-style diet scores. A validated modified Persian version of the Rome III questionnaire was applied for assessment of IBS. RESULTS: Totally, 22.2% of study participants were affected by IBS. After adjustment for potential confounding factors, we found that participants in the highest tertile of DASH score had lower odds of IBS (OR, 0.65; 95% CI, 0.50-0.83) compared with those in the lowest tertile. The same findings were also reached for IBS with constipation (OR for the highest vs the lowest tertile of DASH-style diet = 0.56; 95% CI, 0.38-0.85). No significant association was seen between adherence to DASH-style diet and IBS with diarrhea (OR, 1.31; 95% CI, 0.83-2.06). CONCLUSIONS: We found a significant inverse association between adherence to DASH dietary pattern and odds of IBS and IBS with constipation. Further prospective studies are required to confirm these findings.

Application of metabolomics to the study of irritable bowel syndrome.

The pathophysiology of irritable bowel syndrome and the detection of biomarkers of specific mechanisms and/or predictors of therapeutic response remain elusive. This roadblock reflects, in large part, the complexity and heterogeneity of the disorder. Recently, there has been growing evidence of a dietary and/or microbiome interaction with the host that may trigger symptoms in a subset of patients. While a number of techniques are available to examine these potential interactions, "omic" approaches such as metabolomics are becoming more widely used. Metabolomics measures hundreds and potentially thousands of known and unknown small molecule chemicals (metabolites) to provide a unique look into mechanisms that underlie symptom generation and potential predictors of therapeutic response. In this issue of the journal, Lee et al use nuclear magnetic resonance (NMR) to demonstrate the value of this approach to study IBS. This review examines the use of metabolomics to better understand IBS, focusing on what has been learned to date, practical and technical considerations, its potential for future research and how the study by Lee et al have contributed to these concepts.

Healthy lifestyle score and irritable bowel syndrome: A cross-sectional study in adults.

BACKGROUND: Lifestyle modifications play an important role in the management of irritable bowel syndrome (IBS), but there is limited information on any associations of combined lifestyle-related factors with IBS in Middle Eastern populations. We, therefore, assessed the associations of a "lifestyle score," in analogy to lifestyle scores applied in studies of other disorders, with IBS in adults. METHODS: In a cross-sectional study on 3363 Iranian adults, a healthy lifestyle score (HLS) was constructed using information about dietary habits, dietary intake, physical activity, smoking status, and psychological distress, which was collected using validated questionnaires. A modified version of the Rome III questionnaire (in Persian) was used to diagnose IBS and its subtypes. KEY RESULTS: Individuals with the highest HLS had a 65% lower odds of having IBS compared with those in the lowest category (OR: 0.35; 95% CI: 0.26-0.48). Participants with healthy dietary habits, including regular meal pattern, slow/moderate eating rate, moderate intra-meal fluid consumption, moderate/long meal-to-sleep interval, and low/moderate consumption of fatty foods, had significantly lower odds of having IBS compared with those with unhealthy dietary habits (OR: 0.81; 95% CI: 0.69-0.96). Moreover, individuals with lower levels of psychological distress, compared with those with higher levels of distress, had significantly lower odds of IBS (OR: 0.49; 95% CI: 0.40-0.60). CONCLUSIONS AND INFERENCES: Our data suggest that having an overall "healthy lifestyle" is related to substantially reduced odds of IBS, suggesting that adhering to a healthy lifestyle pattern, including dietary habits, diet quality, physical activity, smoking, and psychological distress, can be considered as a key management strategy for IBS.

FODMAPs alter symptoms and the metabolome of patients with IBS: a randomised controlled trial.

OBJECTIVE: To gain mechanistic insights, we compared effects of low fermentable oligosaccharides, disaccharides and monosaccharides and polyols (FODMAP) and high FODMAP diets on symptoms, the metabolome and the microbiome of patients with IBS. DESIGN: We performed a controlled, single blind study of patients with IBS (Rome III criteria) randomised to a low (n=20) or high (n=20) FODMAP diet for 3 weeks. Symptoms were assessed using the IBS symptom severity scoring (IBS-SSS). The metabolome was evaluated using the lactulose breath test (LBT) and metabolic profiling in urine using mass spectrometry. Stool microbiota composition was analysed by 16S rRNA gene profiling. RESULTS: Thirty-seven patients (19 low FODMAP; 18 high FODMAP) completed the 3-week diet. The IBS-SSS was reduced in the low FODMAP diet group (p<0.001) but not the high FODMAP group. LBTs showed a minor decrease in H2 production in the low FODMAP compared with the high FODMAP group. Metabolic profiling of urine showed groups of patients with IBS differed significantly after the diet (p<0.01), with three metabolites (histamine, p-hydroxybenzoic acid, azelaic acid) being primarily responsible for discrimination between the two groups. Histamine, a measure of immune activation, was reduced eightfold in the low FODMAP group (p<0.05). Low FODMAP diet increased Actinobacteria richness and diversity, and high FODMAP diet decreased the relative abundance of bacteria involved in gas consumption. CONCLUSIONS: IBS symptoms are linked to FODMAP content and associated with alterations in the metabolome. In subsets of patients, FODMAPs modulate histamine levels and the microbiota, both of which could alter symptoms. TRIAL REGISTRATION NUMBER: NCT01829932.

Predictors of Early Failure After Fecal Microbiota Transplantation for the Therapy of Clostridium Difficile Infection: A Multicenter Study.

OBJECTIVES: Fecal microbiota transplant (FMT) is a highly efficacious treatment for recurrent or refractory Clostridium difficile infection (CDI); however, 10-20% of patients fail to achieve cure after a single FMT. The aim of this study was to identify risk factors associated with FMT failure and to develop and validate a prediction model for FMT failure. METHODS: Patient characteristics, CDI history, FMT characteristics, and outcomes data for patients treated between 2011 and 2015 at three academic tertiary referral centers were prospectively collected. Early FMT failure was defined as non-response or recurrence of diarrhea associated with positive stool C. difficile toxin or PCR within 1 month of FMT. Late FMT failure was defined as recurrence of diarrhea associated with positive stool C. difficile toxin or PCR between 1 and 3 months of the FMT. Patient data from two centers were used to determine independent predictors of FMT failure and to build a prediction model. A risk index was constructed based on coefficients of final predictors. The patient cohort from the third center was used to validate the prediction model. RESULTS: Of 328 patients in the developmental cohort, 73.5% (N=241) were females with a mean age of 61.4±19.3 years; 19.2% (N=63) had inflammatory bowel disease (IBD), and 23.5% (N=77) were immunocompromised. The indication for FMT was recurrent CDI in 87.2% (N=286) and severe or severe-complicated in 12.8% (N=42). FMT was performed as an inpatient in 16.7% (N=54). The stool source was patient-directed donors in 40% (N=130) of cases. The early FMT failure rate was 18.6%, and the late failure rate was 2.7%. In the multivariable analysis, predictors of early FMT failure included severe or severe-complicated CDI (odds ratio (OR) 5.95, 95% confidence interval (CI): 2.26-15.62), inpatient status during FMT (OR 3.78, 95% CI: 1.55-9.24), and previous CDI-related hospitalization (OR 1.43, 95% CI: 1.18-1.75); with each additional hospitalization, the odds of failure increased by 43%. Risk scores ranged from 0 to 13, with 0 indicating low risk, 1-2 indicating moderate risk, and ≥3 indicating high risk. In the developmental cohort, early FMT failure rates were 5.6% for low risk, 12.7% for moderate risk, and 41% for high-risk patients. Of 134 patients in the validation cohort, 57% (N=77) were females with a mean age of 66±18.1 years; 9.7% (N=13) had IBD, and 17.9% (N=24) were immunocompromised. The early FMT failure rate at 1 month was 19.4%, with an additional 3% failing by 3 months. In the validation cohort, FMT failure rates were 2.1% for low risk, 16.1% for moderate risk, and 35.7% for high risk patients. The area under the receiver operating characteristic curve (AUROC) for FMT failure was 0.81 in the developmental cohort and 0.84 in the validation cohort. CONCLUSIONS: Severe and severe-complicated indication, inpatient status during FMT, and the number of previous CDI-related hospitalizations are strongly associated with early failure of a single FMT for CDI. The novel prediction model has good discriminative power at identifying individuals who are at high risk of failure after FMT therapy and may assist the treating physician in subsequent management plans.

Prevalence of autoimmune thyroiditis in patients with polycystic ovary syndrome.

INTRODUCTION: Hypothyroidism is associated with pregnancy complications both for the mother and progeny and it should be considered in reproductive age. Thyroid autoimmunity is stated to be the main cause of hypothyroidism in iodine sufficient areas. Polycystic ovary syndrome (PCOS) is known as the most common endocrine disorder affecting women in reproductive age. Early diagnosis and treatment of hypothyroidism in PCOS may reduce the rate of infertility and pregnancy-related morbidity. In the present study we evaluated thyroid autoimmunity in PCOS patients. METHODS: Over a period of 12 months, 78 patients with PCOS were recruited to this case-control study. Three hundred and fifty age-matched women were studied as a control group. PCOS was defined according to the revised 2003 Rotterdam criteria. Thyroid size was estimated by inspection and palpation. Serum thyroid stimulating hormone (TSH), anti-thyroperoxidase antibody (anti-TPO Ab), and anti-thyroglobulin antibody (anti-Tg Ab) were measured. RESULTS: The mean ± SD of serum anti-TPO Ab in PCOS patients and subjects in the control group was 216 ± 428 and 131 ± 364 IU/mL, respectively (P = 0.04). Prevalence of goiter in PCOS patients was higher than that in control subjects (62.3 vs. 35.7%, P = 0.0001). Serum TSH and anti-Tg Ab in PCOS patients and control subjects did not differ significantly. CONCLUSION: In this case-control study, anti-thyroid antibodies and goiter prevalence were significantly higher in PCOS patients. These data suggest that thyroid exam and evaluation of thyroid function and autoimmunity should be considered in such patients.

Thiocyanate status does not play a role in the etiology of residual goiter in school children of Isfahan, Iran.

BACKGROUND: Despite long standing iodine supplementation in Iran the prevalence of goiter remains high in some areas. In the present study we investigated the possible role of thiocyanate as a goitrogen in the etiology of goiter in Isfahan, Iran. METHODS: A total of 2331 (6-13 year old) school children were selected by multistage random sampling. Thyroid size was estimated in each child by inspection and palpation. Urinary iodine concentration (UIC) and urinary thiocyanate (USCN) were measured. RESULTS: Overall, 32.9% of the 2331 students had goiter. The median UIC was 195.5 µg/L. The mean ± SD of USCN in goitrous and nongoitrous subjects was 0.42 ± 0.28 mg/dL and 0.41 ± 0.32 mg/dL, respectively (P=0.86). USCN level in goitrous and nongoitrous boys was 0.41 ± 0.32 mg/dL and 0.43 ± 0.37 mg/dL, respectively (P=0.67). USCN level in goitrous and nongoitrous girls was 0.43 ± 0.26 mg/dL and 0.40 ± 0.28 mg/dL, respectively (P=0.43). CONCLUSIONS: Thiocyanate overload does not play a role in high prevalence of goiter in the studied population. We suggest the role of other goitrogenic factors should be investigated in this region.

Selenium deficiency as a possible contributor of goiter in schoolchildren of Isfahan, Iran.

The prevalence of goiter still remains high in some areas of Iran in spite of iodine supplementation. In the present study, we investigated the role of selenium (Se) deficiency in the etiology of goiter in Isfahan. Two thousand three hundred thirty-one schoolchildren were selected by multistage random sampling. Thyroid size was estimated in each child by inspection and palpation. Urinary iodine concentration (UIC) and plasma Se were measured. Overall, 32.9% of the 2,331 children had goiter. The median UIC was 19.55 microg/dl. Plasma Se was measured in 96 goitrous and 72 nongoitrous children. The mean +/- SD of plasma Se in goitrous and nongoitrous children was 66.86 +/- 21.82 and 76.67 +/- 23.33 microg/l, respectively (P = 0.006). Goitrous girls had lower plasma Se level than nongoitrous girls (65.62 +/- 21.64 vs. 76.51 +/- 22.61 microg/dl, P = 0.02). Goitrous boys had lower plasma Se level than nongoitrous boys (68.45 +/- 22.21 vs. 76.91 +/- 24.76 microg/l, P = 0.14). The prevalence of Se deficiency was significantly higher in goitrous boys and girls than nongoitrous children. Se deficiency is among the contributors of goiter in Isfahan goitrous schoolchildren. However, the role of other micronutrient deficiencies or goitrogens should be investigated in this region.

Vitamin A status does not contribute to the residual goiter in schoolchildren of Isfahan, an iodine replenished area.

Two thousand three hundred and thirty-one schoolchildren were selected by multi-stage random sampling. The thyroid size was estimated by inspection and palpation. The urinary iodine concentration and serum retinol (SR) were measured in 454 and 468 schoolchildren, respectively. Overall, 32.9% of 2,331 children had goiter. The median urinary iodine concentration was 195.5 microg/l. The mean+/-standard deviation of SR in goitrous and non-goitrous children was 34.84+/-7.28 microg/dl and 33.73+/-7.87 microg/dl, respectively (P=0.14). There was no child with vitamin A deficiency (SR <20 microg/dl) in both the goitrous and non-goitrous groups. The prevalence of subjects with low vitamin A status (SR <30 microg/dl) in the goitrous and non-goitrous groups was 27.7% and 33.3%, respectively (P=0.21). In conclusion, the present study reveals that vitamin A deficiency and low vitamin A status are not among the contributing factors of goiter persistence in the studied area, and the role of other responsible factors should be investigated.

Unusual transmission route of Lymphogranuloma venereum; following sexual contact with a female donkey.

Here, we present a 20-year-old man who presented with painful inguinal and femoral masses. He gave a history of sexual contact with a mare 14 days before his recent illness. He was diagnosed with lymphogranuloma venereum based on the histopathological findings and a high titre of IgG (1:1400).

Endemic goiter in Semirom; there is no difference in vitamin A status between goitrous and nongoitrous children.

BACKGROUND: Despite long-standing iodine supplementation in Iran, the prevalence of goiter remains high in some areas. This suggests other nutritional deficiencies may be considered as responsible factors for goiter persistence. In the present study we investigated the possible role of vitamin A deficiency (VAD) and low vitamin A status in the etiology of endemic goiter in Semirom, Iran. MATERIALS AND METHODS: In this cross-sectional study, 1,828 students from 108 primary schools of urban and rural areas of Semirom were selected by multistage random cluster sampling. Thyroid size was estimated in each child by inspection and palpation. Urinary iodine concentration (UIC) and serum retinol (SR) were measured. RESULTS: Overall, 36.7% of schoolchildren had goiter. The median UIC was 18.5 microg/dL. The mean+/-SD of SR in goitrous and nongoitrous children was 38.84+/- 10.98 and 39.17+/-10.85 microg/dL respectively (p=0.82). There were two children with VAD (SR less than 20 microg/dL); one in the goitrous and one in the nongoitrous group. The prevalence of subjects with low vitamin A status (SR less than 30 microg/dL) in the goitrous and nongoitrous groups was 26.2 and 21.5% respectively (p=0.42). CONCLUSION: Goiter is still a public health problem in this region. Iodine deficiency, VAD or low vitamin A status is not among the contributors of goiter persistence in schoolchildren of Semirom. The role of other micronutrient deficiencies or goitrogens should be investigated.

An unusual presentation of brucellosis, involving multiple organ systems, with low agglutinating titers: a case report.

BACKGROUND: Brucellosis is a multi-system disease that may present with a broad spectrum of clinical manifestations. While hepatic involvement in brucellosis is not rare, it may rarely involve the kidney or display with cardiac manifestations. Central nervous system involvement in brucellosis sometimes can cause demyelinating syndromes. Here we present a case of brucella hepatitis, myocarditis, acute disseminated encephalomyelitis, and renal failure. CASE PRESENTATION: A 26-year-old man presented with fever, ataxia, and dysarthria. He was a shepherd and gave a history of low grade fever, chilly sensation, cold sweating, loss of appetite, arthralgia and 10 Kg weight loss during the previous 3 months. He had a body temperature of 39 degrees C at the time of admission. On laboratory tests he had elevated level of liver enzymes, blood urea nitrogen, Creatinine, Creatine phosphokinase (MB), and moderate proteinuria. He also had abnormal echocardiography and brain MRI. Enzyme-linked immunosorbent assay for IgG and IgM was negative. Standard tube agglutination test (STAT) and 2-mercaptoethanol (2-ME) titers were 1:80 and 1:40 respectively. Finally he was diagnosed with brucellosis by positive blood culture and the polymerase chain reaction for Brucella mellitensis. CONCLUSION: In endemic areas clinicians should consider brucellosis in any unusual presentation involving multiple organ systems, even if serology is inconclusive. In endemic areas low STAT and 2-ME titers should be considered as an indication of brucellosis and in these cases additional testing is recommended to rule out brucellosis.