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The Child Health and Development Studies is a > or =40-year follow-up of 20,754 pregnancies occurring between 1959 and 1967 in California. There were 84 cases of undescended testes at birth persisting to at least age 2 years among 7,574 liveborn sons whose mothers were interviewed in early pregnancy. Cases were matched to three controls on birth year and race. Compared with mothers of controls, mothers of cryptorchid boys consumed more caffeine during pregnancy (odds ratio = 1.4, 95% confidence interval: 1.1, 1.9 for an interquartile range equivalent to three cups of coffee per day) but were not more likely to smoke or drink alcohol when all behaviors were considered together. Other maternal and perinatal risk factors were not significantly associated with persistent cryptorchidism and did not confound the association with caffeine. [ABSTRACT FROM AUTHOR]

Infliximab is a tumour necrosis factor (TNF)-alpha antagonist that has revolutionised the treatment of Crohn's disease and rheumatoid arthritis. However, infliximab therapy can be complicated by a variety of adverse reactions. Acute infusion reactions occur during or shortly after infusion and typically consist of fever, chills, nausea, dyspnoea and headaches. Delayed reactions, characterised by myalgias, arthralgias, fever, rash, pruritus, facial, hand or lip oedema, dysphagia, urticaria, sore throat and headache may occur 3-12 days after infusion. Although the mechanisms of these reactions are not yet clearly defined, emerging evidence indicates that these reactions may be associated with the immune response against infliximab and the development of antibodies to infliximab.A number of studies have identified protective factors that may minimise adverse reactions, presumably related to the immune response against infliximab. Factors that may be protective by helping to establish immune tolerance for the foreign infliximab protein include concomitant administration of immunomodulators or corticosteroids, starting infliximab therapy with a 0, 2, 6-week induction regimen, maintenance dose administration with infusions every 8 weeks or less, and avoiding long periods between infusions.Infliximab therapy also may have other immunological consequences. There is evidence that infliximab may impede the appropriate immune response to a number of pathogens, prohibiting its use in patients with active infections. In addition, patients should be screened and appropriately treated for tuberculosis before initiating infliximab therapy. The development of autoantibodies, such as antinuclear antibody or anti-ds-DNA, has also been described with infliximab therapy, although the development of clinical lupus-like syndrome is rare. While there is a theoretical risk of increased rate of malignancies due to antagonism of TNFalpha, to date there is no clear evidence of such an effect. In addition, cardiac and neurological adverse events associated with infliximab therapy have been described. The mechanism for these adverse events is unclear.In summary, infliximab therapy can be an effective treatment for Crohn's disease; however, a number of immunological consequences and adverse events may complicate the infusion of this agent. Appropriate prophylaxis and therapy of these adverse reactions will allow infliximab to be used safely in the vast majority of patients. [ABSTRACT FROM AUTHOR]

Although religiosity is protective for mortality and morbidity, its relationship with depression is unclear. We used the 1994 Alameda County Study survey of 2,537 subjects aged 50-102 to analyze associations between two forms of religiosity and depression as well as the extent to which religiosity buffers relationships between stressors and depression. Non-organizational religiosity included prayer and importance of religious and spiritual beliefs; organizational religiosity included attendance at services and other activities. Non-organizational religiosity had no association with depression; organizational religiosity had a negative relationship that weakened slightly with the addition of health controls. Both forms of religiosity buffered associations with depression for non-family stressors, such as financial and health problems. However, non-organizational religiosity exacerbated associations with depression for child problems, and organizational religiosity exacerbated associations with depression for marital problems, abuse, and caregiving. Religiosity may help those experiencing non-family stressors, but may worsen matters for those facing family crises. [ABSTRACT FROM AUTHOR]

Background & Aims: Risankizumab is a selective interleukin-23 inhibitor approved for the treatment of Crohn's disease (CD). We report a large long-term real-world experience with risankizumab in CD., Methods: We performed a prospective monitoring of clinical outcomes in patients at a large tertiary center who started treatment with risankizumab. Patients with active luminal disease who had at least 12 weeks of follow-up were included in the effectiveness analysis. Harvey-Bradshaw Index, as well as C-reactive protein and fecal calprotectin, were used to monitor disease activity. Primary outcomes were clinical remission and steroid-free clinical remission rates at weeks 12, 26, and 52. Univariate analysis followed by a multivariate analysis using a logistic regression model was performed to identify predictors of steroid-free clinical remission at 1 year. All patients who started treatment with risankizumab for any indication were included in the safety analysis., Results: A total of 134 patients were included in the effectiveness analysis. Seventy (52%) were ustekinumab-experienced. Clinical remission rates were 69%, 64%, and 54% at weeks 12, 26, and 52, respectively. Steroid-free clinical remission rates at 12, 26, and 52 weeks were 58%, 58%, and 50%, respectively. Remission rates in ustekinumab-experienced patients were not statistically lower compared with naïve patients, and in a multivariate analysis, prior ustekinumab treatment was not associated with lower odds of achieving steroid-free clinical remission at 1 year. Adverse effects were assessed in 243 patients and were consistent with previous literature., Conclusions: This large real-world experience with risankizumab with long-term follow-up demonstrates effectiveness and safety in patients with CD; there was comparable effectiveness in ustekinumab-naïve and ustekinumab-experienced patients., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: The modified pouchitis disease activity index (mPDAI) based on clinical symptoms and endoscopic findings is used to diagnose pouchitis, but validated instruments to monitor pouchitis are still lacking. We recently established an endoscopic classification that described 7 endoscopic phenotypes with different outcomes. We assessed symptoms and compared mPDAIs among phenotypes in inflammatory bowel disease (IBD)., Methods: We retrospectively reviewed pouchoscopies and classified them into 7 main phenotypes: normal ( n  = 25), afferent limb (AL) involvement ( n  = 4), inlet involvement ( n  = 14), diffuse ( n  = 7), focal inflammation of the pouch body ( n  = 25), cuffitis ( n  = 18), and pouch-related fistulas ( n  = 10) with a single phenotype were included. Complete-case analysis was conducted., Results: One hundred and three IBD patients were included. The median mPDAI was 0 (IQR 0-1.0) in patients with a normal pouch. Among inflammatory phenotypes, the highest median mPDAI was 4.0 (IQR 2.25-4.75) in cuffitis, followed by 3.0 (IQR 2.5-4.0) in diffuse inflammation, 2.5 (IQR 1.25-4.0) in inlet involvement, 2.5 (IQR 2.0-3.5) in AL involvement, 2.0 (IQR 1.0-3.0) in focal inflammation, and 1.0 (IQR 0.25-2.0) in the fistula phenotype. Perianal symptoms were frequently observed in pouch-related fistulas (8/10, 80%) and cuffitis (13/15, 87%). Among patients with cuffitis, all had incomplete emptying (6/6, 100%)., Conclusions: We correlated the mPDAI with the endoscopic phenotypes and described the limited utility of symptoms in distinguishing between inflammatory phenotypes. Further studies are warranted to understand which symptoms should be monitored for each phenotype and whether mPDAI can be minimized after pouch normalization., Competing Interests: S.A., J.E.O., N.A.C., V.R., L.R.G., Y.Y., C.T., J.R., K.B.S., R.D.H., K.U., B.D.S., N.H.H., and A.S. have no relevant disclosures. R.D.C. is on the speaker’s bureau from AbbVie and Takeda. He is a consultant/advisor for AbbVie Laboratories, BM/celgene, Eli Lilly, Gilead Sciences, Janssen, Pfizer, Takeda, UCB Pharma. He has received clinical trial support/grants from Abbvie, BMS/Celgene, Boehringer Ingelheim, Crohn’s and Colitis Foundation of America, Genentech, Gilead Sciences, Hollister, Medimmune, Mesoblast Ltd., Osiris Therpeutics, Pfizer, Receptos, RedHill Biopharma, Sanofi-Aventis, Schwarz Pharma, Seres Therapeutics, Takeda Pharma, UCB Pharma. His wife is on the board of directors of Aerpio Therapeutics, Novus Therapeutics, Vital Therapeutics, Inc, and NantKwest. M.A.R. has served as a consultant for Pfizer. S.R.D. has served as a consultant for Pfizer and is on the speaker’s bureau for AbbVie. J.P. has received grant support from AbbVie and Takeda. He has served as a consultant for Veraste,. CVS Caremark and is on the advisory board for Takeda, Janssen and Pfizer. E.B.C. is the founder and chief medical officer of AVnovum Therapeutics. D.T.R. has received grant support from Takeda; and has served as a consultant for Abbvie, Altrubio, Amgen, AvaloTherapeutics, Bristol-Myers Squibb, Buhlmann Diagnostics Corp, Chronicles Health, ClostraBio, Connect BioPharma, Cytoki Pharma, Douglas Pharmaceuticals, EcoR1, Ferring Pharma, Image Analysis Group, Index Pharmaceuticals, Iterative Health, Janssen Pharmaceuticals, Lilly, Odyssey Therapeutics, Pfizer, Prometheus Biosciences, Reistone Biopharma, Samsung Neurologica, Sangamo Therapeutics, Shanghai Pharma Biotherapeutics USA, Takeda, Tissium S.A., and Trellus Health., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

The field of cyber risks is rapidly expanding, yet significant research remains to be conducted. Numerous taxonomy-based systems have been proposed in both the academic literature and industrial practice to classify cyber risk threats. However, the fragmentation of various approaches has resulted in a plethora of taxonomies, often incongruent with one another. In this study, we undertake a comprehensive review of these alternative taxonomies and offer a common framework for their classification based on their scope. Furthermore, we introduce desirable properties of a taxonomy, which enable comparisons of different taxonomies with the same scope. Finally, we discuss the managerial implications stemming from the utilization of each taxonomy class to support decision-making processes., (© 2024 The Author(s). Risk Analysis published by Wiley Periodicals LLC on behalf of Society for Risk Analysis.)

Background: Patients with inflammatory bowel disease (IBD) who undergo proctocolectomy with ileal pouch-anal anastomosis may develop pouchitis. We previously proposed a novel endoscopic classification of pouchitis describing 7 phenotypes with differing outcomes. This study assessed phenotype transitions over time., Methods: We classified pouch findings into 7 main phenotypes: (1) normal, (2) afferent limb (AL) involvement, (3) inlet (IL) involvement, (4) diffuse, (5) focal inflammation of the pouch body, (6) cuffitis, and (7) pouch-related fistulas noted more than 6 months after ileostomy takedown. Among 2 endoscopic phenotypes, the phenotype that was first identified was defined as the primary phenotype, and the phenotype observed later was defined as the subsequent phenotype., Results: We retrospectively reviewed 1359 pouchoscopies from 426 patients (90% preoperative diagnosis of ulcerative colitis). The frequency of primary phenotype was 31% for AL involvement, 42% for IL involvement, 28% for diffuse inflammation, 72% for focal inflammation, 45% for cuffitis, 18% for pouch-related fistulas, and 28% for normal pouch. The most common subsequent phenotype was focal inflammation (64.8%), followed by IL involvement (38.6%), cuffitis (37.8%), AL involvement (25.6%), diffuse inflammation (23.8%), normal pouch (22.8%), and pouch-related fistulas (11.9%). Subsequent diffuse inflammation, pouch-related fistulas, and AL or IL stenoses significantly increased the pouch excision risk. Patients who achieved subsequent normal pouch were less likely to have pouch excision than those who did not (8.1% vs 15.7%; P = .15)., Conclusions: Pouch phenotype and the risk of pouch loss can change over time. In patients with pouch inflammation, subsequent pouch normalization is feasible and associated with favorable outcome., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

L23 is a recognized cytokine involved in the pathogenesis of inflammatory bowel diseases (IBDs). 1 The first IL23-targeting agent that became available for clinical use in IBD was Ustekinumab, a monoclonal antibody that targets p40, a shared subunit of both IL23 and IL12. 2,3 Risankizumab (Skyrizi; Abbvie) is a humanized IgG1 monoclonal antibody which binds to the p19 subunit and therefore selectively inhibits IL23. 4 In June 2022, it was approved by the United States Food and Drug Administration for the treatment of moderately to severely active Crohn's disease (CD). Here, we describe the effectiveness and safety of risankizumab throughout the induction period in a real-world setting of a large tertiary center., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Pure shift NMR experiments greatly enhance spectral resolution by collapsing multiplet structures into singlets and, with water suppression, can be used for aqueous samples. Here, we combine ultra-clean pure-shift NMR (SAPPHIRE) with two different internally encoded water suppression schemes to achieve optimal performance for small molecule and macrocyclic peptide pharmaceuticals in water and acetonitrile-water mixtures.