Steroid Profiling and Circadian Cortisol Secretion in Patients with Mild Autonomous Cortisol Secretion: A Cross-Sectional Study.

CONTEXT: Mild autonomous cortisol secretion (MACS) is diagnosed based on post-dexamethasone cortisol>1.8 mcg/dL. Scarce evidence exists on steroid circadian secretion and steroid metabolome in MACS. OBJECTIVE: To characterize 24-hour (h) urine steroid metabolome in patients with MACS and determine circadian differences in urine steroid profiling and cortisol concentrations in patients with MACS versus referent subjects. DESIGN: Cross-sectional study, 2018-2023. SETTING: Referral center. PARTICIPANTS: Patients with MACS and age-, sex-, BMI-, and menopausal status-matched referent subjects. MEASUREMENTS: Urine was collected over 24h period as separate day- and night-time collections. High-resolution mass spectrometry assay was used to measure 25 steroids. A subgroup of patients and referent subjects were admitted for every 2h serum measurements of free and total cortisol. OUTCOMES: Steroids, sums, and ratios. RESULTS: Patients with MACS (n=72) had lower mcg/24h median androgens (2084 vs 3283, P<0.001), higher glucocorticoids (15754 vs 12936, P<0.001), and higher glucocorticoid/androgen ratio (8.7 vs 3.9, P<0.001), compared to referent subjects. Patients also had lower steroid day/night ratios compared to referent subjects, reflecting a higher relative nocturnal steroid production in MACS. In a subgroup of 12 patients with MACS and 10 referent subjects, the 24-hour area under the curves for total and free cortisol were similar. However, evening mean total (5.3 vs 4.0 mcg/dL, P=0.056) and free (0.2 vs 0.1 mcg/dL, P=0.035) cortisol was higher in patients vs referent subjects. CONCLUSION: Patients with MACS demonstrate an abnormal urine steroid metabolome, with a high glucocorticoid to androgen ratio, and a higher nocturnal steroid production.

New investigational drugs for steroid-refractory acute graft-versus-host disease: a review of the literature.

INTRODUCTION: Steroid-refractory acute graft-versus-host disease (SR-aGVHD) remains a formidable obstacle in the field of allogeneic hematopoietic cell transplantation (allo-HCT), significantly contributing to patient morbidity and mortality. The current therapeutic landscape for SR-aGVHD is limited, often yielding suboptimal results, thereby emphasizing the urgent need for innovative and effective treatments. AREAS COVERED: In light of the pivotal REACH2 trial, ruxolitinib phosphate, a Janus kinase inhibitor, has gained prominence as the standard treatment for SR-aGVHD. Nevertheless, a considerable number of patients either do not respond to or cannot tolerate this therapy. This review delves into emerging treatments for SR-aGVHD, including mesenchymal stromal cells (MSCs), fecal microbiota transplantation (FMT), CD3/CD7 blockade, neihulizumab, begelomab, tocilizumab, and vedolizumab. While some of these agents have shown encouraging results in early-phase trials, issues such as treatment-related toxicities and inconsistent responses in larger studies highlight the necessity for ongoing research. EXPERT OPINION: Current trials exploring new agents and combination therapies offer hope for fulfilling the unmet clinical needs in SR-aGVHD, potentially leading to more effective and precise treatment strategies.

Cancer to Cataracts: The Mechanistic Impact of Aldo-Keto Reductases in Chronic Diseases.

Aldo-keto reductases (AKRs) are a superfamily of promiscuous enzymes that have been chiseled by evolution to act as catalysts for numerous regulatory pathways in humans. However, they have not lost their promiscuity in the process, essentially making them a double-edged sword. The superfamily is involved in multiple metabolic pathways and are linked to chronic diseases such as cataracts, diabetes, and various cancers. Unlike other detoxifying enzymes such as cytochrome P450s (CYP450s), short-chain dehydrogenases (SDRs), and medium-chain dehydrogenases (MDRs), that participate in essential pathways, AKRs are more widely distributed and have members with interchangeable functions. Moreover, their promiscuity is ubiquitous across all species and participates in the resistance of pathogenic microbes. Moreover, the introduction of synthetic substrates, such as synthetic molecules and processed foods, results in unwanted "toxification" due to enzyme promiscuity, leading to chronic diseases.

The remarkable antitumor efficacy of corticosteroid treatment in patients with refractory thymomas.

BACKGROUND: Some case reports have found that corticosteroid treatments shrunk thymoma lesions remarkably after the failure of chemotherapy or surgery. However, few studies have comprehensibly evaluated the antitumor effects of corticosteroids in patients with invasive thymomas. METHODS: We reviewed the medical records of 13 consecutively enrolled patients with locally advanced or metastatic thymomas treated via corticosteroid monotherapies from January 2010 to March 2021 in our institute. A Cox's proportional hazard model and the Kaplan-Meier method were used to identify factors associated with survival. RESULTS: The median follow-up time was 26 months (range, 13-115 months). The median initial dose of corticosteroid was 0.90 mg/kg/day prednisolone equivalent (range, 0.4-1.1 mg/kg/day). Of the 13 cases, 7 (53.8%, 95% CI: 0.25-0.81) exhibited a partial response and 5 (38.5%, 95% CI: 0.14-0.68) stable disease. The median progression-free survival was 5.7 months [95% confidence interval (CI): 1.5-9.6 months]. The median overall survival was 25.3 months (95% CI: 7.1-not attained). The median duration of corticosteroid use was 3 months (range, 1-64 months). Patients with WHO subtype B thymomas exhibited a better overall response rate to corticosteroids than did patients with other disease subtypes (75%, 95% CI: 0.19-0.99). Adverse events of Grade 3 or more were not observed. CONCLUSIONS: Corticosteroids are clinically valuable for patients with thymomas.

A challenging diagnosis of spinal epidural lipomatosis: A case report and review of the literature.

INTRODUCTION: Spinal Epidural Lipomatosis (SEL) is a rare disorder of pathological overgrowth of the spinal epidural fat in the extradural space. The pathogenesis of SEL usually involves exogenous steroid use or endogenous steroids overproduction. However, idiopathic cases have been reported. Magnetic resonance imaging (MRI) is the gold standard for diagnosis. Both conservative and surgical approaches are employed in management of these patients. CASE PRESENTATION: A 17-year-old male presented to our hospital complaining of progressive lower limb weakness, loss of sensation with urinary incontinence which ended up with paraplegia. He underwent extensive investigations and received multiple inaccurate diagnoses. MRI of the thoracic spine showed spinal epidural lipomatosis with dorsal kyphosis. Hemi-laminectomy for spinal cord decompression and trans-pedicular fixation for correction of kyphosis were performed showing excellent outcomes. CLINICAL DISCUSSION: Diagnosing SEL can be challenging due to its symptom overlap with other neurological conditions. Thus, higher levels of clinical suspicions and utilization of numerous diagnostic modalities including MRI are required. Treatment is largely determined by the clinical presentation and the severity of symptoms. Given the severity of neurological symptoms in our case, surgical intervention was performed resulting in fully regained functionality of previously paralyzed muscles. CONCLUSION: This case highlights the rare presentation and the diagnostic challenges of spinal epidural lipomatosis SEL in a young patient who was misdiagnosed for 9 consecutive months before receiving the correct diagnosis, emphasizing the importance of considering SEL in the differential diagnosis for progressive neurological deficits and the importance of MRI, especially in atypical cases.

Risk of stricture after endoscopic submucosal dissection in the cervical esophagus and efficacy of local steroid injection for stricture prevention.

BACKGROUND AND AIMS: There is a high incidence of stricture after endoscopic submucosal dissection (ESD) for cervical esophageal cancer. We aimed to elucidate the risk factors for stricture and evaluate the efficacy of steroid injection for stricture prevention in the cervical esophagus. METHODS: We retrospectively analyzed 100 patients who underwent ESD for cervical esophageal cancer to: (1) identify the factors associated with stricture among patients who did not receive steroid injection; (2) compare the incidence of stricture between patients with and without steroid injection. RESULTS: Among 48 patients who did not receive steroid injection, there were significant differences in tumor size (P = .026), resection time (P = .028), and circumferential extent of the mucosal defect (P = .005) between patients with stricture (n = 5) and without stricture (n = 43). Compared with patients without steroid injection, patients with steroid injection had a significantly lower incidence of stricture when the post-ESD mucosal defect was < 3/4 and ≥ 1/2 (40% versus 8%, P = .039). As for the patients with a post-ESD mucosal defect of ≥ 3/4 (n = 13), local steroid injection was performed for all the patients, and 6 patients (46%) developed stricture. CONCLUSIONS: Patients who underwent ≥ 1/2 circumferential resection were at high risk of cervical esophageal stricture. Steroid injection had a stricture-prevention effect in patients with < 3/4 and ≥ 1/2 circumferential resection, but seemed to be insufficient in preventing stricture in patients with ≥ 3/4 circumferential resection.

Steroid metabolism and hormonal dynamics in normal and malignant ovaries.

The ovaries are key steroid hormone production sites in post-pubertal females. However, current research on steroidogenic enzymes, endogenous hormone concentrations and their effects on healthy ovarian function and malignant development is limited. Here, we discuss the importance of steroid enzymes in normal and malignant ovaries, alongside hormone concentrations, receptor expression and action. Key enzymes include STS, 3ß-HSD2, HSD17B1, ARK1C3, and aromatase, which influence ovarian steroidal action. Both androgen and oestrogen action, via their facilitating enzyme, drives ovarian follicle activation, development and maturation in healthy ovarian tissue. In ovarian cancer, some data suggest STS and oestrogen receptor α may be linked to aggressive forms, while various oestrogen-responsive factors may be involved in ovarian cancer metastasis. In contrast, androgen receptor expression and action vary across ovarian cancer subtypes. For future studies investigating steroidogenesis and steroidal activity in ovarian cancer, it is necessary to differentiate between disease subtypes for a comprehensive understanding.

Vesical Endometriosis in a male patient on treatment for papillary urothelial carcinoma.

Endometriosis denotes the abnormal growth of tissue resembling endometrium in ectopic sites and has largely been studied in women of reproductive age. It is an extremely rare phenomenon in men. We came across an exceptional clinical scenario of histologically proven bladder endometriosis in a 66-year-old man in relook bladder biopsy following completion of adjuvant intravesical Bacillus Calmette-Guerin induction course for G3pTa bladder cancer. We have pencilled down pathophysiology and commonly seen predisposing factors for "endometriosis in male patients" from available case reports and applied those findings to hypothesise the disease profile of our patient in this case report.

Glucocorticoid Receptors Orchestrate a Convergence of Host and Cellular Stress Signals in Triple Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks expression of the nuclear steroid receptors that bind estrogens (ER) and progestogens (PRs) and does not exhibit HER2 (Human epidermal growth factor 2) receptor overexpression. Even in the face of initially effective chemotherapies, TNBC patients often relapse. One primary cause for therapy-resistant tumor progression is the activation of cellular stress signaling pathways. The glucocorticoid receptor (GR), a corticosteroid-activated transcription factor most closely related to PR, is a mediator of both endocrine/host stress and local tumor microenvironment (TME)-derived and cellular stress responses. Interestingly, GR expression is associated with a good prognosis in ER+ breast cancer but predicts poor prognosis in TNBC. Classically, GR's transcriptional activity is regulated by circulating glucocorticoids. Additionally, GR is regulated by ligand-independent signaling events. Notably, the stress-activated protein kinase, p38 MAP kinase, phosphorylates GR at serine 134 (Ser134) in response to TME-derived growth factors and cytokines, including HGF and TGFß1. Phospho-Ser134-GR (p-Ser134-GR) associates with cytoplasmic and nuclear signaling molecules, including 14-3-3ζ, aryl hydrocarbon receptors (AhR), and hypoxia-inducible factors (HIFs). Phospho-GR/HIF-containing transcriptional complexes upregulate gene sets whose protein products include the components of inducible oncogenic signaling pathways (PTK6) that further promote cancer cell survival, chemoresistance, altered metabolism, and migratory/invasive behavior in TNBC. Recent studies have implicated liganded p-Ser134-GR (p-GR) in dexamethasone-mediated upregulation of genes related to TNBC cell motility and dysregulated metabolism. Herein, we review the tumor-promoting roles of GR and discuss how both ligand-dependent and ligand-independent/stress signaling-driven inputs to p-GR converge to orchestrate metastatic TNBC progression.

Real-World Outcomes of Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation in Japan: Retrospective Analysis of Transplant Registry Unified Management Program Registry: GVHD outcomes after allo-HSCT.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important therapeutic option for patients with hematological malignancies. However, the development of graft-versus-host disease (GVHD) after allo-HSCT remains a challenge. Although systemic steroid therapy is the established first-line therapy for acute GVHD (aGVHD) and chronic GVHD (cGVHD), many patients are unresponsive or resistant to corticosteroid therapy, and the response is insufficient. OBJECTIVE: To evaluate the clinical characteristics of patients who developed aGVHD and cGVHD after allo-HSCT. STUDY DESIGN: This noninterventional, retrospective study used large national registry data from the Transplant Registry Unified Management Program. The study included 29,690 patients with hematological diseases who underwent their first allo-HSCT between January 2010 and December 2019. The primary endpoints of this study were the cumulative incidence of aGVHD and cGVHD. The secondary endpoints were overall survival (OS) and non-relapse mortality (NRM) of patients with aGVHD and cGVHD and OS and NRM of patients who received second-line therapy for aGVHD. RESULTS: Of 29,690 patients who underwent allo-HSCT, 2,807, 6,167, 10,556, 774, and 9,339 patients received related bone marrow (RBM), related peripheral blood (RPB), unrelated bone marrow, unrelated peripheral blood (UPB), and unrelated cord blood, respectively. The cumulative incidence of aGVHD (grades II-IV) at 100 days was high after the related and unrelated mismatched transplantation. Furthermore, response rate for the first- and second-line therapy for aGVHD was low in the RBM/RPB-mismatched (59.6%/61.6%) and UPB-mismatched subgroup (45.5%), respectively. The 3-year NRM in patients with aGVHD was high in the RPB and UPB mismatched subgroups (37.9% and 31.2%, respectively). CONCLUSION: Developing a novel treatment for steroid-refractory aGVHD is necessary to improve transplant outcomes, particularly for patients undergoing HLA-mismatched transplantation.

EGFR-TKI-induced Factor V deficiency in a patient with advanced non-small cell lung cancer: The first case report.

Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is routinely prescribed as first-line therapy for advanced non-small cell lung cancer, regardless of the presence of the T790M resistance mutation. This study reports a rare case of Factor V inhibitor detection during osimertinib therapy in a patient with lung adenocarcinoma. These findings underscore the importance of vigilant monitoring for coagulation abnormalities during EGFR-TKI therapy.

Ruxolitinib plus basiliximab therapy for steroid-refractory acute graft-versus-host disease in unrelated cord blood transplantation: a large-scale study.

Steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is a major cause of mortality after allogeneic stem cell transplantation (allo-HSCT). We aimed to evaluate the effectiveness and safety of ruxolitinib plus basiliximab for treating SR-aGVHD after unrelated cord blood transplantation (UCBT). Among the 1154 patients with hematological malignancies who underwent UCBT between February 2014 and May 2022, 198 patients with grade II to IV SR-aGVHD were enrolled, 112 of whom were treated with basiliximab alone (basiliximab group) and 86 of whom received basiliximab plus ruxolitinib (combined therapy group). The combined therapy group demonstrated a significantly higher complete response rate (CRR) on day 28 (36.0%) than did the basiliximab group (12.5%, P < 0.001). SR-aGVHD patients were further stratified into standard-risk and high-risk groups using the refined Minnesota aGVHD risk score. For standard-risk patients, combined therapy significantly improved the CRR (51.1% versus 13.6%, P < 0.001) and 3-year overall survival (74.5% versus 52.4%, P = 0.033). However, high-risk patients did not exhibit the same benefits. Compared with basiliximab monotherapy, ruxolitinib plus basiliximab therapy was an effective therapy for patients with standard-risk SR-aGVHD following UCBT. The effectiveness of combined therapy in high-risk patients was not apparent, indicating the need for other treatments.

Linear Leucoderma Following Intralesional Steroid Injection.

Intralesional steroid injections avoid potential side effects associated with systemic administration, such as hypothalamus-pituitary-adrenal axis suppression, endocrine changes, allergic reactions, syncope, and blindness, but do not spare local side effects, such as pain, hemorrhage, ulceration, atrophy, hypopigmentation, calcification, secondary infection, granuloma formation, and allergic reaction. Linear leukoderma following intralesional steroid is a rare but known complication. Here, we report a case of a 23-year-old female presented with cutaneous linear depigmentation along the volar aspect of her left forearm developed three months following a single episode of injection triamcinolone acetonide for ganglion cyst.

MiR-223 inhibits proliferation and steroid hormone synthesis of ovarian granulosa cell via the AKT signaling pathway by targeting CRIM1 in chicken.

Within the poultry industry, hens' reproductive performance is of great economic significance. The development and growth of follicles is a key aspect of hen egg production, and ovarian follicle growth and development are closely associated with granulosa cells (GCs) proliferation and the synthesis of steroid hormones. It has been confirmed by numerous studies that microRNAs (miRNAs) play important roles in the steroid hormone synthesis and proliferation of GCs. In this study, we examined the main miRNAs influencing hens' ability to reproduce, identified the miR-223 that is mainly expressed in atretic follicles based on sequencing, and investigated its role in GCs. Then, we used miR-223 mimic and inhibitor to knockdown or overexpress miR-223 expression. The result showed that miR-223 significantly inhibits both the steroid hormone synthesis and the proliferation of GCs. Subsequently, the results of the dual luciferase reporter experiment and bioinformatics prediction demonstrated that cysteine rich transmembrane BMP regulator 1 (CRIM1) was a downstream target gene of miR-223, and overexpression of miR-223 prevented CRIM1 expression. The function of CRIM1 was further investigated, and we observed a significant reduction in the synthesis of steroid hormones and the proliferation of GCs after transfection with CRIM1 siRNA. The opposite function of miR-223 was observed for CRIM1 in our study. Additionally, we demonstrated the involvement of the miR-223/CRIM1 axis in GCs through modulation of the AKT signaling pathway. Our data demonstrate the pivotal role of the miR-223 in the proliferation and steroid hormone synthesis of chicken GCs, which helps to explain how non-coding RNA (ncRNA) affects chicken reproductive function.

Corticosteroid Injections within 2 weeks Following Knee Arthroscopy is Associated with Increased Infection Risk.

PURPOSE: We quantified the risk of 90-day postoperative infection following arthroscopy, stratified by specific time intervals of corticosteroid injection (CSI) postoperatively (0-2 weeks, 2-4 weeks, 4-6 weeks, and 6-8 weeks). METHODS: A national, all-payer database was queried. In the primary and secondary analyses, the main outcome was infection at 90-days. Infection was defined by documentation of a septic knee or surgical-site infection according to International Classification of Disease (ICD) Ninth Revision (9) and Tenth Revision (10) codes, and Current Procedure Terminology (CPT) codes. RESULTS: In the multivariable regression, the odds ratio (OR) of postoperative infection at 90-days was greater in the CSI injections within 0-<2 weeks (OR 3.31, 95% CI 1.85-5.92, P<0.001) and 2-<4 weeks (OR 2.72 95% CI 1.57-4.71, P=0.003) cohorts in comparison to the control group. When comparing CSI administered within 0-2 weeks to CSI administered within 2-4 weeks, there was a greater odds of postoperative infection (OR 2.50) at 90-days following arthroscopy. CONCLUSION: CSI given within 2 weeks following knee arthroscopy increases the risk of postoperative infection the greatest whereas CSI given with 4 weeks increases the risk but to a lesser degree.

Recurrent Reactive Infectious Mucocutaneous Eruption in an Adult Male Secondary to Mycoplasma Infection: A Case Report.

Mycoplasma pneumoniae commonly causes respiratory tract infections but can also involve the skin and mucosal surfaces. Reactive infectious mucocutaneous eruption (RIME) secondary to mycoplasma infection is uncommon in adults but is an important clinical entity. We present the case of a 26-year-old male who experienced recurrent episodes of erythematous and painful oral ulcers without any prodromal or respiratory symptoms. Serological testing confirmed a recent mycoplasma infection. The patient was successfully treated with oral steroids and supportive therapy. This case underscores the challenges of diagnosing RIME, particularly in the absence of typical respiratory symptoms. Moreover, oral steroid therapy with supportive treatment may suffice to manage RIME if the patient lacks an ongoing infection or other underlying pathologies.

Investigating risk factors and treatment options for severe, partially steroid responsive, and steroid-refractory checkpoint inhibitor pneumonitis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized cancer care with incredible reductions in mortality. One of the most devastating complications of treatment is ICI-related pneumonitis (ICI-p). Despite this, little is known regarding risk factors for severe pneumonitis and treatment effectiveness of various therapeutic options for steroid-refractory disease. To address this, we conducted a retrospective study on patients with cancer who developed ICI-p. METHODS: We examined consecutive patients who received ICIs and developed ICI-p. Risk factors of interest for severe disease and steroid-refractory ICI-p, including pre-treatment pulmonary function tests (PFTs) and chest imaging, were compared between patients with severe (grades 3-5) and mild (grades 1-2) pneumonitis. The clinical and treatment courses for patients with steroid-refractory ICI-p were recorded. RESULTS: A total of 132 patients developed ICI-p, with 60 patients having mild and 72 with severe disease. We found that lower forced vital capacity percent predicted (66.24 vs 85.05, P = .05), lower total lung capacity percent predicted (85.23 vs 99.71, P = .13), and specific radiographic patterns on pre-treatment chest imaging were predictors of severe disease. Initial corticosteroid dose of less than 1 milligram per kilogram prednisone equivalent (P = .14) was correlated with partially steroid-responsive or steroid-refractory ICI-p. Ten patients had steroid refractory ICI-p, and those who received IVIG alone as the immune suppressant beyond corticosteroids had improved survival (P = 05). CONCLUSIONS: We are the first to identify pre-treatment PFTs and chest imaging abnormalities as risk factors for severe ICI-p. We also found that lower corticosteroid doses were associated with partially steroid-responsive and steroid-refractory ICI-p. Larger, prospective studies are needed to validate our results.

Impact of trenbolone on selected organs.

Trenbolone is a synthetic analogue of testosterone, belonging to the nandrolone group. It has both a strong anabolic effect and a limited androgenic effect (i.e. an androgen and anabolic steroid - AAS). It is used illegally by professional or amateur athletes, who want to improve their athletic performance and appearance by increasing their muscle mass. Trenbolone, like other AASs, are harmful, with 90% of users experiencing injurious side effects. It acts systemically on the body, and as such, its side effects can manifest as symptoms from different systems. Nevertheless, its popularity is increasing. This paper reviews the current state of knowledge regarding the adverse effects of trenbolone on the nervous, reproductive, immune systems and breast, muscular and adipose tissues. However, various other adverse consequences of trenbolone utilization are observed, with severe acne and gynaecomastia affecting approximately one-third of all users, as well as excessive body hair, stretch marks, hypertension and cardiac arrhythmia. The drugs are also subject to contamination, with use frequently resulting in local inflammation at the injection site, muscle adhesions and fibrosis, nerve damage or, in extreme cases, necrosis of the injection site. Additionally, due to the lack of available knowledge on the subject, many of the effects of trenbolone use remain unknown. Moreover, the fact that multiple AASs may be used simultaneously presents a significant problem in their study. Therefore, further research is necessary to better understand the effects of AAS on the body, and to expand our currently incomplete knowledge of their functional pathways.

Clinical practice and outcome of patients with elderly-onset ulcerative colitis: Insights from a nationwide claims database study in Japan.

Background and Aim: The number of older patients with ulcerative colitis is increasing; however, limited data exist regarding the differences between elderly- and non-elderly-onset ulcerative colitis. We aimed to compare the clinical practice and course of elderly-onset ulcerative colitis with those of non-elderly-onset ulcerative colitis. Methods: We selected older patients with ulcerative colitis and divided them into the elderly- and non-elderly-onset ulcerative colitis groups according to their age at onset. We compared the cumulative systemic steroid-free, molecular targeting drug-free, and surgery-free rates between the two groups. We performed a multivariate analysis to identify the clinical factors related to systemic steroid administration, the use of molecular targeting drugs, surgery, and death. Results: We collected data of 2669 and 277 elderly and non-elderly-onset ulcerative colitis patients, respectively. The cumulative systemic steroid-free rate of elderly-onset ulcerative colitis was significantly lower than that of non-elderly-onset ulcerative colitis. However, no difference was observed in the cumulative molecular targeting drugs and surgery-free rates between the two groups. Elderly-onset ulcerative colitis significantly increased the risk of systemic steroid administration and death but not the use of molecular targeting drugs and surgery. Conclusion: The disease severity of ulcerative colitis and clinical practice may not differ between the elderly- and non-elderly-onset groups. However, elderly-onset ulcerative colitis was associated with increased mortality risk. Thus, we need to pay attention to the patients' condition and appropriate timing of surgery for patients with elderly-onset ulcerative colitis.

Diet, lifestyle factors, comorbidities, and hepatocellular carcinoma risk in a middle eastern country: a case-control study.

BACKGROUND: Hepatocellular Carcinoma (HCC) can be classified as one of the most common malignancies worldwide. There is scarcity of the published data on the risk factors for HCC in the Gulf Cooperation Council countries specifically Kuwait. Therefore, this case-control study sought to examine the risk factors associated with HCC in Kuwait. METHODS: Fifty-three histopathologically confirmed HCC cases were recruited from the Kuwait Cancer Control Center Registry. One hundred ninety-six controls (1:4 ratio) were selected from medical and/ or surgical outpatient's clinics at all six public hospitals of Kuwait. A structured questionnaire was used to collect the data both from cases and controls through face-to-face interviews. A multivariable logistic regression model was fitted to the case-control data. Adjusted odds ratios (ORadj) and their 95% confidence intervals (CI) were computed using the parameters' estimates of the final model and used for interpretation of the model. RESULTS: The HCC cases compared with the controls were 41.6 times more likely to have had the history of non-alcoholic fatty liver disease (NAFLD) (ORadj = 41.6; 95% CI: 8.9-193.5; p < 0.001). The cases compared with the controls were more likely to have reported the history of heavy alcohol drinking (ORadj = 14.2; 95% CI: 1.2-173.4; p = 0.038). Furthermore, compared with the controls, the HCC cases tended to frequently consume milk and/or milk substitutes (≥ 3 glass/ week) (ORadj = 7.2; 95% CI: 1.2-43.4). Conversely however, there was a significant protective effect if the participants reportedly have had regularly used olive oil in their routine diet as a source of fat (ORadj = 0.17; 95% CI: 0.04-0.80) or regularly used non-steroid anti-inflammatory drugs (NSAIDs) (ORadj = 0.20; 95% CI: 0.05-0.71). CONCLUSIONS: This study showed that heavy alcohol consumption, NAFLD history, and excessive consumption of milk/ milk substitutes were associated with a significantly increased HCC risk. Conversely however, regular use of olive oil in the diet as a source of fat or regular use of NSAIDs had a significantly protective effect against HCC risk. Adapting healthy dietary habits and preventing/ treating NAFLD may minimize the HCC risk. Future research with a larger sample size may contemplate validating the results of this study and unraveling additional risk factors contributing to HCC risk. The resultant data may help design and implement evidence-based educational programs for the prevention of HCC in this and other similar settings.