Effects of Intrarenal Reflux on Renal Growth in Children With Grades III-V Primary Vesicoureteral Reflux.

The phenomenon of intrarenal reflux (IRR) has been considered a crucial link between vesicoureteral reflux (VUR) and segmental scarring. We conducted a study on renal length in 104 children diagnosed with Grades III-V VUR, with or without IRR, using contrast-enhanced voiding urosonography (ceVUS). The patients were divided into two treatment groups: the conservative antibiotic prophylaxis (CAP) group and the operation group, which were further categorized into two subgroups: the IRR group and the non-IRR group. Our findings revealed an incidence rate of 35.96% (41/114) for IRR occurrence, with 43.42% (33/76) occurring in upper renal segments, 32.89% (25/76) in lower segments, and 23.68% (18/76) in middle segments. In the CAP group where the effects of IRR persisted, the renal growth observed was as follows: IRR group-0.19 ± 0.13 cm; non-IRR group-0.39 ± 0.23 cm; contralateral negative group-0.66 ± 0.35 cm; control group-0.46 ± 0 .25 cm respectively (P < .05). In the operation group, where the effects of IRR were eliminated, the renal growth for the IRR group, non-IRR group, contralateral negative group, and control group was 0.46 ± 0.22 cm, 0.54 ± 0.31 cm, 0.67 ± 0 .42 cm, and 0.36 ± 0.17 cm respectively (P < .005). In conclusion, the presence of IRR can impact renal growth in children diagnosed with Grades III-V primary VUR. Following surgical intervention, the IRR kidney does not exhibit catch-up growth; however, it demonstrates parallel growth alongside the unaffected kidney. Conversely, the non-IRR kidney experiences catch-up growth. Therefore, for children presenting with Grades III-V primary VUR combined with IRR, a more aggressive treatment approach such as surgery is recommended.

Process design and techno-economic analysis of activated carbon derived from anthracite coal.

Activated carbon (AC), renowned for its versatile applications in water treatment, air purification, and industrial processes, is a critical component in environmental remediation and resource recovery strategies. This study encompasses the process modeling of AC production using anthracite coal as a precursor, involving multiple activation stages at different operating conditions, coupled with a detailed techno-economic analysis aimed at assessing the operational feasibility and financial viability of the plant. The economic analysis explores the investigation of economic feasibility by performing a detailed cashflow and sensitivity analysis to identify key parameters influencing the plant's economic performance, including raw material and energy prices, operational and process parameters. Capital and operational costs are meticulously evaluated, encompassing raw material acquisition, labor, energy consumption, and equipment investment. Financial metrics like Net Present Value (NPV), Internal Rate of Return (IRR), and payout period (POP) are employed, and the results show that AC selling price, raw material cost and plant capacity are the most influential parameters determining the plant's feasibility. The minimum AC production cost of 1.28 $/kg is obtained, corresponding to coal flow rate of 14,550 kg/h. These findings provide valuable insights for stakeholders, policymakers, and investors seeking to engage in activated carbon production from anthracite.

A Comparative Kidney Transcriptome Analysis of Bicarbonate-Loaded insrr-Null Mice.

The maintenance of plasma pH is critical for life in all organisms. The kidney plays a critical role in acid-base regulation in vertebrates by controlling the plasma concentration of bicarbonate. The receptor tyrosine kinase IRR (insulin receptor-related receptor) is expressed in renal ß-intercalated cells and is involved in alkali sensing due to its ability to autophosphorylate under alkalization of extracellular medium (pH > 7.9). In mice with a knockout of the insrr gene, which encodes for IRR, urinary bicarbonate secretion in response to alkali loading is impaired. The specific regulatory mechanisms in the kidney that are under the control of IRR remain unknown. To address this issue, we analyzed and compared the kidney transcriptomes of wild-type and insrr knockout mice under basal or bicarbonate-loaded conditions. Transcriptomic analyses revealed a differential regulation of a number of genes in the kidney. Using TaqMan real-time PCR, we confirmed different expressions of the slc26a4, rps7, slc5a2, aqp6, plcd1, gapdh, rny3, kcnk5, slc6a6 and atp6v1g3 genes in IRR knockout mice. Also, we found that the expression of the kcnk5 gene is increased in wild-type mice after bicarbonate loading but not in knockout mice. Gene set enrichment analysis between the IRR knockout and wild-type samples identified that insrr knockout causes alterations in expression of genes related mostly to the ATP metabolic and electron transport chain processes.

Rare Case of Rickettsiosis Caused by Rickettsia monacensis, Portugal, 2021.

We report a case of rickettsiosis caused by Rickettsia monacensis in an immunocompetent 67-year-old man in Portugal who had eschar, erythematous rash, and an attached Ixodes ricinus tick. Seroconversion and eschar biopsy led to confirmed diagnosis by PCR. Physicians should be aware of this rare rickettsiosis, especially in geographic regions with the vector.

Changes in the Expression of the gapdh Gene in the Organs of insrr Knockout Mice.

The most important property of a living organism is the maintenance of optimal acid-base balance and the ionic composition of the internal environment. The kidneys are one of the main pH-regulating organs in the body. Receptor tyrosine kinase IRR (an insulin receptor-related receptor) is an alkaline pH-sensor. In mice (Mus Musculus) with a knockout of the insrr gene encoding the IRR receptor, bicarbonate secretion is impaired under the conditions of alkaline loading, which indicates the role of the receptor tyrosine kinase IRR in the regulation of acid-base balance in the body. In order to search for proteins functionally associated with the receptor tyrosine kinase IRR, we performed a large-scale sequencing of the mouse kidney transcriptome of wild type and insrr knockout mice kept under normal conditions and under alkaline conditions. As a result, we found a decrease in the gapdh gene expression in the kidneys of insrr knockout mice compared to wild type mice. RNA sequencing data were confirmed by TaqMan real-time PCR and Western blotting. Using the TaqMan real-time PCR method, we revealed a decrease in the level of gapdh expression not only in the kidneys, but also in the liver and brain of insrr knockout mice. Thus, the changes in the gapdh gene expression in the kidneys of insrr knockout mice may indicate a functional relationship between genes and a possible role of GAPDH in previously undescribed molecular mechanisms of regulation of acid-base balance in the body.

Bacterial iron detoxification at the molecular level.

Iron is an essential micronutrient, and, in the case of bacteria, its availability is commonly a growth-limiting factor. However, correct functioning of cells requires that the labile pool of chelatable "free" iron be tightly regulated. Correct metalation of proteins requiring iron as a cofactor demands that such a readily accessible source of iron exist, but overaccumulation results in an oxidative burden that, if unchecked, would lead to cell death. The toxicity of iron stems from its potential to catalyze formation of reactive oxygen species that, in addition to causing damage to biological molecules, can also lead to the formation of reactive nitrogen species. To avoid iron-mediated oxidative stress, bacteria utilize iron-dependent global regulators to sense the iron status of the cell and regulate the expression of proteins involved in the acquisition, storage, and efflux of iron accordingly. Here, we survey the current understanding of the structure and mechanism of the important members of each of these classes of protein. Diversity in the details of iron homeostasis mechanisms reflect the differing nutritional stresses resulting from the wide variety of ecological niches that bacteria inhabit. However, in this review, we seek to highlight the similarities of iron homeostasis between different bacteria, while acknowledging important variations. In this way, we hope to illustrate how bacteria have evolved common approaches to overcome the dual problems of the insolubility and potential toxicity of iron.

Familial Risk of Inflammatory Bowel Disease: A Population-Based Cohort Study in South Korea.

BACKGROUND & AIMS: Despite the rapid increase in inflammatory bowel disease (IBD), population-level familial risk estimates of IBDs still are lacking in Asian-Pacific countries. We aimed to quantify the familial risk of incident IBD among first-degree relatives (FDRs) of individuals with IBD according to age, sex, and familial relationship. METHODS: Using the South Korea National Health Insurance database (2002-2017), which has complete population coverage and confirmed accuracy of both FDR information and IBD diagnoses, we constructed a cohort of 21,940,795 study subjects comprising 12 million distinct families. We calculated incidence risk ratios of ulcerative colitis (UC) or Crohn's disease (CD) in individuals of affected FDRs compared with individuals without affected FDRs. RESULTS: Of 45,717 individuals with UC and 17,848 individuals with CD, 3.8% and 3.1% represented familial cases, respectively. Overall, there was a 10.2-fold (95% CI, 9.39-11.1) and a 22.1-fold (95% CI, 20.5-24.5) significantly higher adjusted risk of UC and CD among FDRs of individuals with vs without IBD. Familial risk was highest among twins, followed by nontwin siblings, and then offspring of affected parents. Familial risk generally was higher within generations (sibling-sibling) vs between generations (parent-offspring). Familial risk also increased with the increasing number of affected FDRs. CONCLUSIONS: According to this population-based analysis, there is a substantially increased risk of IBD among FDRs of affected individuals, with the highest risk among siblings and for CD. These findings might help with an earlier diagnosis and appropriate therapeutic intervention in FDRs of individuals with IBD. Dedicated studies are needed to evaluate the contributions of shared early-in-life environmental exposures and genetic factors.

Safety Evaluation of Initial CT-P6 Administration for 30 min during the Switch from Reference Trastuzumab in Maintenance Infusion: A Multicenter Observational Study.

CT-P6 is a biosimilar of trastuzumab and is recommended to be administered for 30-90 min in subsequent maintenance infusions to prevent infusion-related reactions (IRRs). We administered CT-P6 for 30 min as the first injection and as an alternative to reference trastuzumab in the maintenance infusion and evaluated the safety of the administration. A total of 140 patients with breast or gastric cancer, who received a switch from tri-weekly reference trastuzumab to CT-P6 for 30 min in maintenance infusions, were retrospectively evaluated. Premedication was administered prior to an infusion of CT-P6 and a cytotoxic agent. However, premedication was not provided when CT-P6 was co-administered with pertuzumab or administered alone. The primary endpoint was the incidence of IRRs. The secondary endpoint was the incidence of diarrhea and skin toxicity. Ninety-five percent of the patients had breast cancer, and 44.3% had advance-stage cancer. The treatment included CT-P6 alone (17.9%) or with cytotoxic agents (23.6%), antihormonal drugs (25.7%), and pertuzumab (62.9%). Median administration time of trastuzumab at the switch was 13 administrations (range 2-140). Premedication was administered to 20.7% patients. One patient (0.7%) experienced grade 3 IRR. The frequency of diarrhea in the reference trastuzumab group and the CT-P6 group was 7.1 and 6.4%, respectively, and that of skin toxicity was 6.4 and 5.0%, respectively, without differences. In conclusion, we first demonstrated that an initial CT-P6 administration for 30 min during the switch from reference trastuzumab in maintenance infusion is an acceptable administration method.

Evaluation of the Anticancer Potential of Crude, Irradiated Cerastes cerastes Snake Venom and Propolis Ethanolic Extract & Related Biological Alterations.

We aimed to evaluate the anticancer potential of crude venom (CV), γ irradiated Certastes cerastes venom (IRRV), and propolis ethanolic extract (PEE). IRRV showed a higher toxicity than CV, while CV-PEE showed higher toxicity than IRRV and CV against lung [A549] and prostate [PC3] cancer cells. Toxicity to [A549] and [PC3] cells was concentration and cell type dependent. In comparison to controls, apoptotic genes showed a significant upregulation of P53 and Casp-3 and a downregulation of Bcl-2. Also, induced elevated DNA accumulation in the [S] phase post PC3 cell treatment with IRRV and CV, as well as a significant DNA accumulation at G2/M phase after IRRV treatment of A549 cells. In contrast, PC3 cells showed a negligible cellular DNA accumulation after PEE treatment. Glutathione reductase [GR] was reduced in case of PC3 and A549 cell treated with IRRV, CV, and PEE compared with its values in untreated cell control. The Malondialdehyde [MDA] values in both cells recorded a significant elevation post IRRV treatment compared to the rest of the treatment regimen and untreated cell control. Similarly, IRRV and CV-PEE mix showed obviously higher reactive oxygen species [ROS] values than PC3 and A549 cell treatments with CV and PEE.

A prospective randomized study comparing jumbo biopsy forceps to cold snare for the resection of diminutive colorectal polyps.

BACKGROUND AND AIMS: The quality of colonoscopy is essential for successful colon cancer screening. Inadequate polypectomy technique can contribute to incomplete polypectomy. The primary outcome of this study was to compare the incomplete resection rate (IRR) for cold jumbo forceps polypectomy (JFP) and cold snare polypectomy (CSP). Secondary outcomes were to compare the rates of tissue retrieval and rates of procedure-related complications. METHODS: This prospective randomized parallel-group study assigned patients undergoing colonoscopy to jumbo biopsy forceps polypectomy (JFP) or cold snare polypectomy (CSP) for polyps ≤ 6 mm in size. After polyp removal was complete, the base of the polypectomy site was biopsied to evaluate for the presence of residual polyp tissue. RESULTS: The resection quality was evaluated in 151 patients with 261 polyps ≤ 6 mm. The IRR was 9.6% (25/261) for all polyps, 11.1% (16/144) for JFP, and 7.7% (9/117) for CSP (P = 0.41). Failure of tissue retrieval was noted in 0/144 (0%) of JFP and 5/117 (4.3%) of CSP (P = 0.02). There were no procedure-related complications in either group. CONCLUSION: Colon polyps are incompletely resected in a small but potentially significant percentage of cases. IRR are similar with the use of cold jumbo forceps and cold snare. Use of cold jumbo forceps may result in more successful tissue retrieval as compared to cold snare.

Insights into irr and rirA gene regulation on the virulence of Brucella melitensis M5-90.

Iron is a fundamental element required by most organisms, including Brucella. Several researchers have suggested that the iron response regulator (irr) and rhizobial iron regulator (rirA) genes regulate iron acquisition by Brucella abortus, influencing heme synthesis by and virulence of this pathogen. However, little is known about another Brucella species, Brucella melitensis. In this research, we successfully constructed two mutants: M5-90Δirr and M5-90ΔrirA. The adhesion, invasion, and intracellular survivability of these two mutants were evaluated in RAW264.7 cells infected with 1 × 106 CFU of M5-90Δirr, M5-90ΔrirA, or M5-90. We also tested the sensitivity of cells to hydrogen peroxide and their ability to grow. In addition, the virulence of these two mutants was evaluated in BALB/c mice. The results showed that the ability of these two mutants to invade and adhere inside the murine macrophages RAW264.7 was attenuated but their ability to replicate intracellularly was strengthened, enhancing the resistance to hydrogen peroxide. The M5-90Δirr mutant showed stronger growth ability than the parental strain under iron-limiting conditions. No differences were observed in the number of bacteria in spleen between M5-90 and M5-90Δirr at 7 or 15 days postinfection. However, the number of M5-90ΔrirA in spleen reduced significantly at 15 days postinfection. The splenic index of the M5-90Δirr group is evidently lower than that of M5-90. This is the first report that irr and rirA genes of B. melitensis are associated not only with virulence but also with growth ability. Together, our data suggest that M5-90Δirr is a promising Brucella vaccine candidate.

A Mathematical Model for the Effect of Low-Dose Radiation on the G2/M Transition.

We develop a mathematical model to study the immediate effect of low-dose radiation on the G2 checkpoint and the G2/M transition of the cell cycle via a radiation pathway (the ATM-Chk2 pathway) of an individual mammalian cell. The model consists of a system of nonlinear differential equations describing the dynamics of a network of regulatory proteins that play key roles in the G2/M transition, cell cycle oscillations, and the radiation pathway. We simulate the application of a single pulse of low-dose radiation at different intensities ([Formula: see text] 0-0.4 Gy) and times during the latter part of the G2-phase. We use bifurcation analysis to characterize the effect of radiation on the G2/M transition via the ATM-Chk2 pathway. We show that radiation between 0.1 and 0.3 Gy can delay the G2/M transition, and radiation higher than 0.3 Gy can fully activate the G2 checkpoint. Also, our results show that radiation can be low enough to neither delay the G2/M transition nor activate the G2 checkpoint ([Formula: see text] 0.1 Gy). Our model supports the idea that the cell response to radiation during G2-phase explains hyper-radiosensitivity and increased radioresistance (HRS/IRR) observed at low dose.

Interrater agreement between American and Chinese sleep centers according to the 2014 AASM standard.

OBJECTIVES: To determine inter-lab reliability in sleep stage scoring using the 2014 American Academy of Sleep Medicine (AASM) manual. To understand in-depth reasons for disagreement and provide suggestions for improvement. METHODS: This study consisted of 40 all-night polysomnographys (PSGs) from different samples. PSGs were segmented into 37,642 30-s epochs. Five doctors from China and two doctors from America scored the epochs following the 2014 AASM standard. Scoring disagreement between two centers was evaluated using Cohen's kappa (κ). After visual inspection of PSGs of deviating scorings, potential disagreement reasons were analyzed. RESULTS: Inter-lab reliability yielded a substantial degree (κ = 0.75 ± 0.01). Scoring for stage W (κ = 0.89) and R (κ = 0.87) achieved the highest agreement, while stage N1 (κ = 0.45) reflected the lowest. Considering the relative disagreement ratio, N2-N3 (22.09%), W-N1 (19.68%), and N1-N2 (18.75%) were the most frequent combinations of discrepancy. American and Chinese doctors showed certain characteristics in the scoring of discrepancy combination W-N1, N1-N2, and N2-N3. There are seven reasons for disagreement, namely "on-threshold characteristic" (29.21%), "context influence" (18.06%), "characteristic identification difficulty" (8.81%), "arousal-wake confusion" (7.57%), "derivation inconsistence" (2.15%), "on-borderline characteristic" (0.92%), and "misrecognition" (33.27%). CONCLUSIONS: This study demonstrated the sleep stage scoring agreement of the 2014 AASM manual and explored potential sources of labeling ambiguity. Improvement measures were suggested accordingly to help remove ambiguity for scorers and improve scoring reliability at the international level.

Ideal sedation for stroke thrombectomy: a prospective pilot single-center observational study.

OBJECTIVESeveral retrospective studies have supported the use of conscious sedation (CS) over general anesthesia (GA) as the preferred methods of sedation for stroke thrombectomy, but a recent randomized controlled trial showed no difference in outcomes after CS or GA. The purpose of the Ideal Sedation for Stroke Thrombectomy (ISST) study was to evaluate the difference in time and outcomes in the reperfusion of anterior circulation in ischemic stroke using GA and monitored anesthesia care (MAC).METHODSThe ISST study was a prospective, open-label registry. A total of 40 patients who underwent mechanical thrombectomy for anterior circulation ischemic stroke were enrolled. Informed consent was obtained from each patient before enrollment. The primary endpoint included the interval between the patient's arrival to the interventional radiology room and reperfusion time. Secondary endpoints were evaluated to estimate the effects on the outcome of patients between the 2 sedation methods.RESULTSOf the 40 patients, 32 received thrombectomy under MAC and 8 patients under GA. The male-to-female ratio was 18:14 in the MAC group and 4:4 in the GA group. The mean time from interventional radiology room arrival to reperfusion in the GA group was 2 times higher than that in the MAC group. Complete reperfusion (TICI grade 3) was achieved in more than 50% of patients in both groups. The mean modified Rankin Scale score at 3 months was < 2 in the MAC group and > 3 in the GA group (p = 0.021).CONCLUSIONSThe findings from the pilot study showed a significantly shorter time interval between IR arrival and reperfusion and better outcomes in patients undergoing reperfusion for ischemic stroke in the anterior circulation using MAC compared with GA.Clinical trial registration no.: NCT03036631 (clinicaltrials.gov).

Risk of chronic kidney disease in young adults with impaired glucose tolerance/impaired fasting glucose: a retrospective cohort study using electronic primary care records.

BACKGROUND: The risk of chronic kidney disease (CKD) is known to be elevated in patients with diabetes mellitus but the risk of young adults aged 18 to 40 years with impaired glucose tolerance/impaired fasting glucose (IGT/IFG) developing CKD is not well characterised. Furthermore, progression of IGT/IFG to diabetes and subsequent CKD development is not well understood. METHODS: A retrospective cohort study was undertaken using The Health Improvement Network (THIN) database, a large dataset of electronic patient records. THIN database is jointly managed by IMS Health Real World Evidence Solution ( http://www.epic-uk.org/index.html ) and In Practice System (InPs). Cases were aged 18 to 40, with a diagnosis of IGT/IFG and registered at a practice contributing to THIN between 2000 and 2015. The study population consisted of 40,092 patients, including 21,454 (53.5%) female and 18,638 (46.5%) male. The median follow-up was approximately 2 years. The outcome was a diagnosis of CKD determined from either clinical coding or laboratory results. For the primary analysis the unadjusted and adjusted relative risk of CKD in IGT/IFG was compared to age, sex and practice matched controls with normoglycaemia. For the secondary analysis we compared the incidence of CKD before to after a diagnosis of type 2 diabetes (T2DM) in the IGT/IFG study cohort. RESULTS: The Incidence Rate Ratio (IRR) for CKD for IGT/IFG compared to normoglycaemia was 4.0 [95% confidence interval (CI), 3.2 to 5.1, P < 0.001]. The adjusted IRR was 2.6 [95% CI, 2.0 to 3.4, P < 0.001]. The unadjusted IRR was 8.8 [95% CI, 7.7 to 10.0, P < 0.001] after IGT/IFG patients had developed T2DM and the adjusted IRR was 6.3 [95% CI, 5.5 to 7.2, P < 0.001]. CONCLUSION: Our results show that young IGT/IFG subjects are also at higher risk of developing CKD. This risk is modulated by the degree of baseline renal function and glucose tolerance, being higher in those developing T2DM.

A prospective association between dietary folate intake and type 2 diabetes risk among Korean adults aged 40 years or older: the Korean Multi-Rural Communities Cohort (MRCohort) Study.

It has not been well established whether dietary folate intake reduces the risk of diabetes development. We aimed to clarify the prospective association between dietary folate intake and type 2 diabetes (T2D) risk among 7333 Korean adults aged 40 years or older who were included in the Multi-Rural Communities Cohort. Dietary folate intake was estimated from all 106 food items listed on a FFQ, not including folate intake from supplements. Two different measurements of dietary folate intake were used: the baseline consumption and the average consumption from baseline until just before the end of follow-up. The association between folate intake and T2D risk was determined through a modified Poisson regression model with a robust error estimator controlling for potential confounders. For 29 745 person years, 319 cases of diabetes were ascertained. In multivariable analyses, dietary folate intake was inversely associated with risk of T2D for women, not for men. For women, the incidence rate ratio of diabetes in the third tertile compared with the first tertile was 0·57 (95 % CI 0·38-0·87, P for trend=0·0085) in the baseline consumption model and 0·64 (95 % CI 0·43-0·95, P for trend=0·0244) in the average consumption model. These inverse associations was found in both normal fasting blood glucose group and impaired fasting glucose group among women. Among non-users of multinutrients and vitamin supplements, the significant inverse association remained. Thus, higher dietary intake of folate is prospectively associated with lower risk of diabetes for women.

Longer Withdrawal Time Is Associated With a Reduced Incidence of Interval Cancer After Screening Colonoscopy.

BACKGROUND & AIMS: Withdrawal times and adenoma detection rates are widely used quality indicators for screening colonoscopy. More rapid withdrawal times have been associated with undetected adenomas, which can increase risk for interval colorectal cancer. METHODS: We analyzed records of 76,810 screening colonoscopies performed between 2004 and 2009, by 51 gastroenterologists practicing in Minneapolis and St Paul, MN. Colonoscopy records were linked electronically to the state cancer registry (Minnesota Cancer Surveillance System) to identify incident interval cancers that were diagnosed within 5.5 years after the screening examination. RESULTS: The physicians' mean ± SD withdrawal time was 8.6 ± 1.7 minutes and adenoma detection rates were 25% ± 9%. Longer mean withdrawal times were associated with higher adenoma detection rates (3.6% per minute; 95% confidence interval: 2.4% to 4.8%; P < .0001). We identified 78 cancers during 410,687 person-years of follow-up, for an annual rate of 0.19/1000 person-years. Physicians' mean annual withdrawal times were inversely associated with cancer incidence (P < .0001). Compared with withdrawal times ≥6 minutes, the adjusted incidence rate ratio for withdrawal times of <6 minutes was 2.3 (95% confidence interval: 1.5-3.4; P < .0001). CONCLUSIONS: Shorter mean annual withdrawal times during screening colonoscopies were independently associated with lower adenoma detection rates and increased risk of interval colorectal cancer.

Can an airway challenge test predict respiratory diseases? A population-based international study.

BACKGROUND: Evidence on the longitudinal association of airway responsiveness with respiratory diseases is scarce. The best indicator of responsiveness is still undetermined. OBJECTIVE: We investigated the association of airway responsiveness with the incidence of asthma, chronic obstructive pulmonary disease (COPD), and allergic rhinitis. METHODS: We studied 3851 subjects who underwent spirometry and methacholine challenge tests both at baseline (1991-1993), when they were 20 to 44 years old, and at follow-up (1999-2002) in the European Community Respiratory Health Survey. Airway responsiveness was defined based on the methacholine dose-response slope on both occasions. Incidence rate ratios for the association of airway responsiveness with disease occurrence were computed by using Poisson regression. RESULTS: With respect to reference (slope of the fourth quintile or greater), subjects with the greatest degree of airway responsiveness (slope less than the first quintile) showed the greatest risk of developing asthma, COPD, and allergic rhinitis (incidence rate ratios of 10.82, 5.53, and 4.84, respectively; all P < .01). A low slope predicted disease occurrence, even in subjects who did not reach a 20% decrease in FEV1 at the cumulative dose of 1 mg of methacholine (PD20 >1 mg). A decrease in slope over time was an independent predictor of disease risk. CONCLUSION: Airway responsiveness predicted new-onset asthma, COPD, and allergic rhinitis. Our study supports the use of a continuous noncensored indicator of airway responsiveness, such as the slope of the methacholine dose-response curve, in clinical practice and research because it showed clear advantages over PD20.

Prevention of interval colorectal cancers: what every clinician needs to know.

Colonoscopic screening and surveillance have been very effective tools in the fight against colorectal cancer (CRC). Colonoscopy is more than a cancer screening test; it also can prevent CRC by detecting and removing precancerous lesions. Despite this potential, there has been increasing concern about CRCs that occur after a previous colonoscopy and before the next screening/surveillance examination (interval CRCs). The etiology of interval CRC is thought to be caused mostly by missed or incompletely resected lesions on index colonoscopy with some contribution of rapidly progressive new lesions. If this is true, many interval cancers should be preventable by improving colonoscopy technique. There are a variety of strategies to decrease interval CRC rates including use of a split-dosed bowel preparation, optimizing withdrawal technique, ensuring complete polypectomy, and careful pathologic examination of the tissue removed. Furthermore, there should be an increased emphasis on how endoscopists are trained to cultivate high-quality technique throughout their careers. It is important to inform patients that even high-quality colonoscopy is not perfectly sensitive for the detection of advanced neoplasia. Improving colonoscopy quality can decrease interval CRC rates and further decrease CRC incidence and mortality.

Inflammatory bowel disease is associated with an increased risk of melanoma: a systematic review and meta-analysis.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) has been associated with an increased risk of nonmelanoma skin cancer, particularly among patients treated with thiopurines. It is unclear whether IBD affects risk for melanoma. We performed a systematic review and meta-analysis of cohort studies to determine the risk of melanoma in patients with IBD. METHODS: We conducted a systematic search of bibliographic databases through March 2013. Cohort studies reporting incident melanoma after IBD diagnosis and an estimate of incidence rate ratio or standardized incidence rate were included in the analysis. Pooled relative risk (RR) estimates with 95% confidence intervals (CIs) were calculated using the random-effects model. RESULTS: Our analysis included 12 studies, comprising a total of 172,837 patients with IBD; 179 cases of melanoma were reported from 1940 to 2009. The pooled crude incidence rate of melanoma in patients with IBD was 27.5 cases/100,000 person-years (95% CI, 19.9-37.0). Overall, IBD was associated with a 37% increase in risk of melanoma (12 studies: RR, 1.37; 95% CI, 1.10-1.70). The risk was increased among patients with Crohn's disease (7 studies: RR, 1.80; 95% CI, 1.17-2.75) and ulcerative colitis (7 studies: RR, 1.23; 95% CI, 1.01-1.50). The risk of melanoma was higher in studies performed before introduction of biologic therapies (before 1998) (8 studies: RR, 1.52; 95% CI, 1.02-2.25) but not in studies performed after 1998 (2 studies: RR, 1.08; 95% CI, 0.59-1.96). CONCLUSIONS: Based on a meta-analysis, IBD has been associated with an increased risk of melanoma, independent of the use of biologic therapy. Patients diagnosed with IBD should be counseled on their risk for melanoma.