Is patient age associated with risk of malignancy in a ≥4 cm cytologically benign thyroid nodule?

BackgroundCurrent data regarding the risk of malignancy in a large thyroid nodule with benign fine-needle aspiration biopsy(FNAB) is conflicting. We investigated the impact of patient age on the risk of malignancy in nodules≥4 cm with benign cytology.MethodsWe performed a single-institution retrospective review of patients who underwent surgery from 07/2008–08/2019 for a cytologically benign thyroid nodule ≥4 cm. The relationship between malignant histopathology and patient and ultrasound features was assessed with multivariable logistic regression.ResultsOf 474 nodules identified, 25(5.3%) were malignant on final pathology. In patients <55 years old, 21/273(7.7%) nodules were malignant, compared to 4/201(2.0%) in patients ≥55. Patient age ≥55 was independently associated with significantly lower risk of malignancy(OR:0.2,95%CI:0.1–0.7,p = 0.011). Increasing nodule size >4 cm and high-risk ultrasound features were not associated with risk of malignancy(OR:1.0,95%CI:0.7–1.4,p = 0.980, and OR:9.6,95%CI:0.9–107.8,p = 0.066, respectively).ConclusionsPatients <55 years old are 3.7-fold more likely to have a falsely benign FNA biopsy in a nodule≥4 cm.     

Association between age and disease specific mortality in medullary thyroid cancer

BackgroundThe aim of this study was to evaluate the association between age and disease specific mortality (DSM) among adults diagnosed with medullary thyroid cancer (MTC).MethodSurveillance, Epidemiology, and End Results (SEER-18) was used to analyze adult MTC patients stratified by age (18–64, 65–79, ≥80 years). Associations between patient demographics, tumor size, nodal status, metastatic disease, and extent of surgery on DSM was assessed with multivariable Cox regression.ResultsAmong 1457 patients with MTC, 1008 (69.2%) were younger adults, 371 (25.5%) older adults, and 78 (5.4%) were super-elderly. A significantly higher proportion of older adults and super-elderly had less than the recommended operation for MTC. On multivariable analysis, older adults and super-elderly were 2.9 and 6.7 times more likely to have an increased DSM (HR:2.91, 95% CI: 1.83–4.63; p < 0.001 and HR: 6.70, 95%CI: 3.69–12.20; p < 0.001). Extent of surgery or lymphadenectomy did not affect DSM.ConclusionsIncreased age is an independent predictor of DSM in patients with MTC.     

Kidney recipients with allograft failure,transition of kidney care (KRAFT): A survey of contemporary practices of transplant providers

Kidney allograft failure and return to dialysis carry a high risk of morbidity. A practice survey was developed by the AST Kidney Pancreas Community of Practice workgroup and distributed electronically to the AST members. There were 104 respondents who represented 92 kidney transplant centers. Most survey respondents were transplant nephrologists at academic centers. The most common approach to immunosuppression management was to withdraw the antimetabolite first (73%), while only 12% responded they would withdraw calcineurin inhibitor (CNI) first. More than 60% reported that the availability of a living donor is the most important factor in their decision to taper immunosuppression, followed by risk of infection, risk of sensitization, frailty, and side effects of medications. More than half of respondents reported that embolization was either not available or offered to less than 10% as an option for surgical intervention. Majority reported that ≤50% of failed allograft patients were re-listed before dialysis, and less than a quarter of transplant nephrologists performed frequent visits with their patients with failed kidney allograft after they return to dialysis. This survey demonstrates heterogeneity in the care of patients with a failing allograft and the need for more evidence to guide improvements in clinical practice related to transition of care.     

Binding of lipopeptide to CD14 induces physical proximity of CD14, TLR2 and TLR1

Lipoproteins or lipopeptides (LP) are bacterial cell wall components detected by the innate immune system. For LP, it has been shown that TLR2 is the essential receptor in cellular activation. However, molecular mechanisms of LP recognition are not yet clear. We used a FLAG-labeled derivative of the synthetic lipopeptide N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2R,S)-propyl]-(R)-cysteinyl-seryl-(lysyl)(3)-lysine (Pam(3)CSK(4)) to study the roles of CD14, TLR2 and TLR1 in binding and signaling of LP and their molecular interactions in human cells. The activity of Pam(3)CSK(4)-FLAG was TLR2 dependent, whereas the binding was enabled by CD14, as evaluated by flow cytometry and confocal microscopy. Using FRET and FRAP imaging techniques to study molecular associations, we could show that after Pam(3)CSK(4)-FLAG binding, CD14 and Pam(3)CSK(4)-FLAG associate with TLR2 and TLR1, and TLR2 is targeted to a low-mobility complex. Thus, LP binding to CD14 is the first step in the LP recognition, inducing physical proximity of CD14 and LP with TLR2/TLR1 and formation of the TLR2 signaling complex.     

Plant foods and colon cancer: an assessment of specific foods and their related nutrients (United States)

Plant foods have been associated inversely with colon cancer. Since amajor focus of this study was to identify components of plant foods whichmay account for their association with colon cancer, nutrients which arecommonly found in plant foods also were evaluated. A population-basedcase-control study was conducted in Northern California, Utah, and the TwinCities area of Minnesota (United States). Complete data were available frominterviewer-administered questionnaires on 1,993 cases and 2,410 controls.Higher intakes of vegetables (for highest relative to lowest quintile ofintake) were associated inversely with colon cancer risk: the odds ratio(OR) was 0.7 for both men (95 percent [CI] confidence interval = 0.5-0.9)and women (CI = 0.5-1.0). Associations were stronger among those withproximal tumors. Total fruit intake was not associated with colon cancerrisk although, among men, higher levels of whole grain intake wereassociated with a decreased risk (OR = 0.6, CI = 0.4-0.9 for older men);high intakes of refined grains were associated with an increased risk (OR =1.5, CI = 1.1-2.1). Dietary fiber intake was associated with a decreasedrisk of colon cancer: OR = 0.5 (CI = 0.3-0.9) for older men; OR = 0.7 (CI =0.4-1.2) for older women; OR = 0.6 (CI = 0.4-1.0) for men with proximaltumors; OR = 0.5 (CI = 0.3-0.9) for women with proximal tumors. Othernutrients, for which plant foods were the major contributor - such asvitamin B6, thiamin, and niacin (women only) - also were associatedinversely with colon cancer. Neither beta-carotene nor vitamin C wasprotective for colon cancer. Adjustment of plant foods for nutrients foundin plant foods or for supplement use did not appreciably alter the observedassociations between plant foods and colon cancer.     

A questionnaire to assess the generic and disease-specific health outcomes of patients with chronic hepatitis C

A 69-item questionnaire measuring generic functioning and well-being and disease-specific health outcomes was developed and tested using the pre-treatment data from patients with chronic hepatitis C (CHC) participating in two randomized trials of interferon -2b (n = 157). The questionnaire included all eight scales from the SF-36 and measures of nine other generic and disease-specific health concepts. Psychometric tests confirmed the assumptions underlying the construction and scoring of all generic and disease-specific scales. Cross-sectional tests of known groups validity showed that CHC patients scored worse on the generic scales than patients with other chronic conditions and worse than a healthy general population. The generic and disease-specific scale scores were lower in the presence of physical findings of CHC, as hypothesized, but only the physical functioning and bodily pain scales were linked to cirrhosis or extreme alanine aminotransferase (ALT) ratios. This instrument will be useful in studies of health outcome among patients with CHC, a condition whose health burden appears to have been underestimated in studies to date.     

Low Prenatal Weight Gain Among Adult WIC Participants Delivering Term Singleton Infants: Variation by Maternal and Program Participation Characteristics

Objective: To determine the association of maternal and prenatal WIC program participation characteristics with low prenatal weight gain among adult women delivering liveborn, singleton infants at term. Methods: WIC program data for 19,017 Black and White Alabama women delivering in 1994 were linked with birth certificate files to examine the association of anthropometric, demographic, reproductive, hematologic, behavioral and program participation characteristics with low prenatal weight gain. Results: One third (31.0%) had low prenatal weight gain as defined by the Institute of Medicine. The incidence of low weight gain was increased among women who had < 12 years of education, were single, Black, anemic, had low or normal pre-pregnancy body mass index (BMI), increased parity, interpregnancy intervals 24 months, used tobacco or alcohol, or entered prenatal care or WIC programs after the first trimester. After adjusting for selected maternal characteristics, the adjusted odds ratios (AOR) for low weight gain were increased with short interpregnancy intervals (AOR 1.21 to 2.20); tobacco use (AOR 1.16 to 1.40), anemia (AOR 1.20 to 1.25), and second trimester entry into prenatal care (AOR 1.14 to 1.20); the size of the AORs and 95% confidence intervals varied by BMI and racial subgroup. Conclusions: The results of this study suggest that WIC interventions targeting low prenatal weight gain be focused on risk factors present not only during pregnancy, but during the pre- and interconceptional periods as well. Interventions should target low BMI, tobacco use, and anemia, and include attention to nutrition screening and risk reduction among women in postpartum and family planning clinic settings.     

The effect of growth hormone on the growth failure of chronic renal failure

To investigate the effects of growth hormone (GH) on the reversal of growth failure in uremia, recombinant human GH (rhGH) was administered to rats with chronic renal failure (CRF). The dosage of rhGH was 3 IU/day (i.p.) for 13 days after the induction of CRF by 5/6 nephrectomy. Animals were classified into four groups: untreated nephrectomized rats (NX,n=40), GH-treated nephrectomized rats (NX+GH,n=18), sham-operated rats fed ad libitum (SHAMAL,n=27), and sham-operated rats pair-fed with 10 NX rats (SHAMPF,n=10). NX and NX+GH rats developed a similar and moderate degree of CRF, serum urea nitrogen being (mean±SEM) 49±3 and 54±4 mg/dl, respectively, compared with 16±4 and 19±0 mg/dl in SHAMAL and SHAMPF groups. Weight (56.0±3.3 g) and length (3.5±0.1 cm) gains of NX rats were lower than those of SHAMAL rats (94.2±4.0 g,P<-0.0001 and 4.1±0.2 cm,P<-0.01). Growth of the SHAMPF group and the matched NX rats was not significantly different. Weight (56.2±5.0 g) and length (3.4±0.2 cm) gains of NX+GH and NX rats were similar, the beneficial effect of GH therapy on growth being observed in only those animals with more severe degrees of uremia. This growth-promoting action resulted from greater food efficiency and not from stimulated food intake. The hypercholesterolemia seen in NX rats, 81±2 mg/dl versus 55±3 mg/dl in SHAMAL (P0.0001), was not increased in the NX+GH group, 87±3 mg/dl. There was a positive and significant correlation between serum cholesterol and serum urea nitrogen values in NX and NX+GH animals. This study suggests that growth impairment of mild CRF is mainly due to malnutrition and is refractory to GH administration. GH therapy improves the growth rate of animals with advanced CRF without aggravating their lipid abnormalities.     

MTHFR C677T and A1298C polymorphisms: diet, estrogen, and risk of colon cancer.

5,10-methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism, diverting metabolites toward methylation reactions or nucleotide synthesis. Using data from an incident case-control study (1608 cases and 1972 controls) we investigated two polymorphisms in the MTHFR gene, C677T and A1298C, and their associations with risk of colon cancer. All of the combined genotypes were evaluated separately, and the 1298AA/677CC (wild-type/wild-type) group was considered the reference group. Among both men and women, the 677TT/1298AA (variant/wild-type) genotype was associated with a small reduction in risk [men: odds ratio (OR), 0.7, 95% confidence interval (CI), 0.5-1.0; women: OR, 0.8, 95% CI, 0.5-1.2]. However, the 677CC/1298CC (wild-type/variant) genotype was associated with a statistically significant lower risk among women (OR, 0.6; 95% CI, 0.4-0.9) but not men. When the polymorphisms were considered individually, for A1298C a significant risk reduction associated with the homozygous variant CC genotype was seen among women only (OR, 0.6; 95% CI, 0.5-0.9), and nonstatistically significant reduced risks were observed for the variant 677 TT genotypes among both men and women. Stratification by nutrient intakes showed inverse associations with higher intakes of folate, vitamin B(2), B(6), B(12), and methionine among women with the MTHFR 677CC/1298AA genotypes, but not those with 677TT/1298AA. We observed opposite risk trends for both MTHFR variants, depending on whether women used hormone-replacement therapy or not (P for interaction = <.01). In summary, this study supports recent findings that the MTHFR A1298C polymorphism may be a predictor of colon cancer risk and have functional relevance. The possible interaction with hormone-replacement therapy warrants additional investigation.     

Aspirin, NSAIDs, and colorectal cancer: possible involvement in an insulin-related pathway.

INTRODUCTION: Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce risk of colorectal cancer. Although inhibition of cyclooxygenase (COX)-2 is generally thought to be the relevant mechanism, aspirin-like drugs apparently are involved in other pathways and mechanisms. We explore the associations between aspirin/NSAIDs, the insulin-related pathway, and the risk of colorectal cancer. METHODS: Genetic polymorphisms of five genes identified as being involved in an insulin-related pathway were genotyped using data collected in a case-control study of 1346 incident colon cancer cases and 1544 population-based controls and 952 incident rectal cancer cases and 1205 controls. Genotypes assessed were the 3' untranslated region poly(A) and the intron 8 BsmI polymorphisms of the VDR gene, a CA repeat polymorphism of the IGF1 gene, the A/C polymorphism at nucleotide -202 of the IGFBP3, the Gly972Arg polymorphism of the IRS1 gene, and the Gly1057Asp polymorphism of the IRS2 gene. RESULTS: Use of aspirin and NSAIDs was associated with a decreased risk of colorectal cancer, with slightly greater protection from NSAIDs than aspirin for rectal cancer. We observed a significant interaction between IRS1 genotype and aspirin/NSAIDs use and risk of colorectal cancer. Relative to the GR/RR IRS1 genotype, a protective effect from the GG IRS1 genotype was seen in those who did not use NSAIDs; use of NSAIDs was protective for all genotypes. These associations were especially strong for those diagnosed prior to age 65 (P interaction = 0.0006). We also observed a significant interaction between aspirin/NSAIDs use and the VDR gene. Having the SS or BB VDR genotypes reduced risk of colorectal cancer among non-aspirin/NSAID users; however, aspirin/NSAIDs reduced risk for all VDR genotypes. CONCLUSIONS: These data support the protective effect of aspirin and NSAIDs on colorectal cancer risk. In addition, the observed interactions for aspirin/NSAIDs and IRS1 and VDR genotypes suggest that mechanisms other than COX-2 inhibition may be contributing to the protective effect of aspirin and NSAIDs on colorectal cancer risk.