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Crohn's & Colitis 360 Apr 2024Crohn's disease (CD) is an immune-mediated inflammatory disorder of the gastrointestinal tract with perianal disease being one of the challenging possible...
BACKGROUND
Crohn's disease (CD) is an immune-mediated inflammatory disorder of the gastrointestinal tract with perianal disease being one of the challenging possible manifestations. Here, we report, an ad hoc analysis of the safety and effectiveness of 1-year use of ustekinumab (UST) for CD in patients with perianal manifestations using post-marketing surveillance (PMS) data in Japan.
METHODS
Among 341 patients enrolled in the PMS, 229 and 224 patients who had baseline Crohn's Disease Activity Index (CDAI) data used for evaluating perianal manifestations were included in the safety and efficacy analysis sets, respectively. Incidence of adverse drug reactions, clinical remission, the mean or its change in CDAI scores, and CDAI items were evaluated through week 52 in the presence or absence of perianal manifestations at baseline. The prevalence of perianal manifestations was also described.
RESULTS
Comparing patients with and without baseline perianal manifestations at week 52, there was no difference in ADR incidence (9.1% [ = 66] vs. 15.3% [ = 163]), no difference in clinical remission (68.3% vs. 59.9%; = 0.269), and decreased mean change of CDAI score (-82.9 [ = 60] vs. -68.8 [ = 137]). The proportion of patients with perianal manifestations decreased after UST treatment in both biologics-naïve patients (23.5% [ = 4/17]) and patients who had received biologics (35.0% [ = 14/40]) at week 52.
CONCLUSIONS
In Japanese clinical practice, UST is safe and effective in CD patients with and without perianal manifestations. The therapy might be also beneficial in those with manifestations regardless of prior use of other biologics.
PubMed: 38827168
DOI: 10.1093/crocol/otae035 -
Cureus May 2024A rare autosomal recessive condition called infantile systemic hyalinosis (ISH) is characterized by early-onset skin lesions that progress to the formation of numerous...
A rare autosomal recessive condition called infantile systemic hyalinosis (ISH) is characterized by early-onset skin lesions that progress to the formation of numerous contractures. The underlying disease is the progressive accumulation of hyaline substances in many tissues. We are presenting the case of a male infant who was referred for evaluation and management at the age of six months. The infant had a history of recurrent episodes of diarrhea and showed limited movement in all four limbs. Upon physical examination, hyperpigmented papulonodular lesions on bony prominences and perianal regions were found, coupled with contractures in the elbow and knee joints. Hyaline deposition in the mid-dermal region was confirmed by histopathological analysis of a skin biopsy sample. The baby also had acute otitis media, which needed to be treated with antibiotics. Parents were counseled regarding the disease's diagnosis, complications, prognosis, and inheritance pattern. This case highlights the clinical presentation, diagnostic process, and management strategies employed in the care of ISH, emphasizing the importance of early recognition and multidisciplinary management in mitigating its devastating effects.
PubMed: 38826988
DOI: 10.7759/cureus.59510 -
Stem Cells (Dayton, Ohio) Jun 2024Mesenchymal Stromal Cells (MSCs) are investigated as cellular therapeutics for Inflammatory Bowel Diseases and associated Perianal Fistula, although consistent efficacy...
Mesenchymal Stromal Cells (MSCs) are investigated as cellular therapeutics for Inflammatory Bowel Diseases and associated Perianal Fistula, although consistent efficacy remains a concern. Determining host factors that modulate MSCs' potency including their secretion of angiogenic & wound healing factors, immunosuppression and anti-inflammatory properties are important determinants of their functionality. We investigated the mechanisms that regulate the secretion of angiogenic & wound healing factors and immune suppression of human bone marrow MSCs. Secretory analysis of MSCs focusing on eighteen angiogenic & wound healing secretory molecules identified the most abundancy of Vascular Endothelial Growth Factor-A(VEGF-A). MSC viability and secretion of other angiogenic factors are not dependent on VEGF-A secretion which exclude the autocrine role of VEGF-A on MSC's fitness. However, combination of inflammatory cytokines IFNγand TNFαreduces MSC's VEGF-A secretion. To identify the effect of intestinal microvasculature on MSCs' potency, coculture analysis was performed between Human Large Intestine Microvascular Endothelial Cells(HLMVECs) and human bone marrow derived MSCs. HLMVECs do not attenuate MSCs' viability despite blocking their VEGF-A secretion. In addition, HLMVECs neither attenuate MSC's IFNγmediated upregulation of immunosuppressive enzyme Indoleamine 2,3-dioxygenase(IDO) nor abrogate suppression of T cell proliferation despite the attenuation of VEGF-A secretion. We found that HLMVECs express copious amounts of endothelial nitric oxide synthase (eNOS) and mechanistic analysis showed that pharmacological blocking reverses HLMVEC mediated attenuation of MSC's VEGF-A secretion. Together these results suggest that secretion of VEGF-A and immunosuppression are separable functions of MSCs which are regulated by distinct mechanisms in the host.
PubMed: 38826008
DOI: 10.1093/stmcls/sxae040 -
International Journal of Clinical... May 2024Concurrent chemoradiotherapy (CCRT) is the standard treatment for locoregional anal squamous cell carcinoma (ASCC) in western countries. However, there have been few...
BACKGROUND
Concurrent chemoradiotherapy (CCRT) is the standard treatment for locoregional anal squamous cell carcinoma (ASCC) in western countries. However, there have been few reports on the clinical outcomes of CCRT in Japan. This study aimed to evaluate the clinical outcomes of CCRT, prognostic factors, and the clinical impact of programmed cell death-ligand 1 (PD-L1) expression of ASCC in Japan.
METHODS
Patients with locoregional ASCC were enrolled between 2007 and 2017. All patients received CCRT consisting of ≥ 45 Gy of radiation, 5-fluorouracil, and mitomycin C. Disease-free survival (DFS), overall survival (OS), and adverse events (AEs) were estimated. Expression of p16 and PD-L1 were assessed by immunohistochemical staining (IHC).
RESULTS
This study included 36 patients, of whom 30 (83.3%) were female. Among the participants, 32 (88.9%) achieved complete clinical remission, while six (16.7%) experienced recurrence. The five-year DFS and five-year OS were 72.2% and 84.7%, respectively. Grades ≥ 3 serious AEs included neutropenia in 10 (27.7%) and perianal dermatitis in eight (22.2%). In a univariate analysis, male sex, lymph node metastasis, and large tumor size were significantly associated with worse outcome. In a multivariate analysis, tumor size was an independent factor associated with short DFS. Of the 30 patients whose biopsy specimens were available for IHC, 29 (96.7%) were positive for p16, and 13 (43.3%) were positive for PD-L1. However, PD-L1 expression did not show any clinical impact.
CONCLUSIONS
The comparative etiology, clinical outcomes, and prognostic factors of CCRT observed in Japanese patients with locoregional ASCC were consistent with western data.
PubMed: 38819609
DOI: 10.1007/s10147-024-02540-0 -
The Turkish Journal of Pediatrics May 2024Hyaline fibromatosis syndrome is a rare autosomal recessive disorder caused by ANTXR2 pathogenic variants. The disorder is characterized by the deposition of amorphous...
BACKGROUND
Hyaline fibromatosis syndrome is a rare autosomal recessive disorder caused by ANTXR2 pathogenic variants. The disorder is characterized by the deposition of amorphous hyaline material in connective tissues. The hallmarks of the disease are joint contractures, generalized skin stiffness, hyperpigmented papules over extensor surfaces of joints, fleshy perianal masses, severe diarrhea, and gingival hypertrophy. The severity of the disease varies and prognosis is poor. No specific treatment is yet available. Most patients with the severe form of the condition pass away before the second year of age. In this study, we describe the clinical and molecular findings of a cohort of seven hyaline fibromatosis syndrome patients who were diagnosed and followed up at a single tertiary reference center in Turkey.
METHODS
Genomic DNA was extracted by standard salting out method from peripheric blood samples of three patients. In one patient DNA extraction was performed on pathology slides since peripheric blood DNA was not available. All coding exons of the ANTXR2 were amplified and sequenced on ABI Prism 3500 Genetic Analyser.
RESULTS
Sanger sequencing was performed in 3 patients and homozygous c.945T>G p.(Cys315Trp), c.1073dup p.(Ala359CysfsTer13), and c.1074del p.(Ala359HisfsTer50) variants were identified in ANTXR2. All patients passed away before the age of five years.
CONCLUSIONS
HFS is a rare, progressive disorder with a broad phenotypic spectrum. HFS can be recognized easily with distinctive clinical features. Nevertheless, it has poor prognosis with increased mortality due to severe clinical decompensation.
Topics: Humans; Hyaline Fibromatosis Syndrome; Male; Female; Infant; Child, Preschool; Receptors, Peptide; Turkey; Child
PubMed: 38814306
DOI: 10.24953/turkjpediatr.2024.4511 -
Expert Opinion on Drug Safety May 2024Vaccine-associated paralytic poliomyelitis (VAPP) is a rare adverse event of oral poliovirus vaccines (OPV), particularly affecting immunodeficient individuals.
BACKGROUND
Vaccine-associated paralytic poliomyelitis (VAPP) is a rare adverse event of oral poliovirus vaccines (OPV), particularly affecting immunodeficient individuals.
RESEARCH DESIGN AND METHODS
This study aimed to (1) Assess the association between OPV and VAPP using Vaccine Adverse Event Reporting System (VAERS) database (2) Outline patient characteristics and risk factors associated with the occurrence of VAPP in OPV recipients through a systematic review of case reports and case series. A disproportionality analysis was conducted using the data from VAERS, encompassing adverse events reported from 1990 till February 2023. Additionally, we conducted a systematic review of case reports and case series using PubMed, Scopus, and Embase databases.
RESULTS
The VAERS data revealed 130 VAPP reports among 1,739,903 OPV linked adverse events, with year 2010 reporting the strongest association. The systematic review of 37 studies highlighted VAPP occurrence within 2 months to 4 years post-vaccination, typically with acute flaccid paralysis. Immunodeficiency and perianal abscess emerged as major risk factors. Out of the 37 included studies, 27 showed consistent causal association of VAPP with OPV using WHO-AEFI causality assessment tool.
CONCLUSION
The study emphasized the seriousness of VAPP and highlights its association with OPV, identifying immunodeficiency as a prominent contributor to VAPP manifestation.
PubMed: 38813942
DOI: 10.1080/14740338.2024.2359616 -
Journal of Paediatrics and Child Health May 2024
PubMed: 38812458
DOI: 10.1111/jpc.16570 -
World Journal of Psychiatry May 2024Psychological distress, especially depression, associated with perianal fistulizing Crohn's disease (PFCD) is widespread and refractory. However, there is a surprising...
BACKGROUND
Psychological distress, especially depression, associated with perianal fistulizing Crohn's disease (PFCD) is widespread and refractory. However, there is a surprising paucity of studies to date that have sought to identify the prevalence and risk factors of depression associated with PFCD.
AIM
To estimate the prevalence of depressive symptoms and investigate the depression-related risk factors in patients with PFCD.
METHODS
The study was conducted in the form of survey and clinical data collection questionnaire and specialized medical staff. Depressive symptoms, life quality, and fatigue severity of patients with PFCD were assessed by Patient Health Questionnaire-9, Inflammatory Bowel Disease Patient Quality of Life Questionnaire (IBDQ), and Inflammatory Bowel Disease (IBD) Fatigue Patient Self-assessment Scale. The basic demographic information, overall disease features, perianal clinical information, and laboratory inflammation indicators were also gathered. Multivariate regression analysis was ultimately used to ascertain the risk factors of depression associated with PFCD.
RESULTS
A total of 123 patients with PFCD were involved, and 56.91% were suffering from depression. According to multivariate logistic regression analysis, Perianal Disease Activity Index (PDAI) score [odds ratio (OR) = 0.69, 95% confidence interval (CI): 0.50 to 0.95], IBDQ score (OR = 0.93, 95%CI: 0.88 to 0.97), modified Van Assche index (OR = 1.24, 95%CI: 1.01 to 1.53), and IBD Fatigue score (OR = 1.72, 95%CI: 1.23 to 2.42) were independent risk factors of depression-related prevalence among patients with PFCD ( < 0.05). Multiple linear regression analysis revealed that the increasing perianal modified Van Assche index ( value = 0.166, 95%CI: 0.02 to 0.31) and decreasing IBDQ score ( value = -0.116, 95%CI: -0.14 to -0.09) were independently associated with the severity of depression ( < 0.05).
CONCLUSION
Depressive symptoms in PFCD patients have significantly high prevalence. PDAI score, modified Van Assche index, quality of life, and fatigue severity were the main independent risk factors.
PubMed: 38808090
DOI: 10.5498/wjp.v14.i5.715 -
Clinical Case Reports Jun 2024Inflammatory bowel disease is rare in infants and it includes perianal Crohn's disease, which is inflammation at or near the anus. An early diagnosis is essential to...
Inflammatory bowel disease is rare in infants and it includes perianal Crohn's disease, which is inflammation at or near the anus. An early diagnosis is essential to prevent the complications that may affect the development and growth of the child.
PubMed: 38803326
DOI: 10.1002/ccr3.8963 -
Acta Obstetricia Et Gynecologica... May 2024It is still unclear whether Crohn's disease (CD) might be associated with diminished ovarian reserve (OvR) and factors influencing anti-Mullerian hormone (AMH) levels in... (Review)
Review
INTRODUCTION
It is still unclear whether Crohn's disease (CD) might be associated with diminished ovarian reserve (OvR) and factors influencing anti-Mullerian hormone (AMH) levels in CD are poorly known.
MATERIAL AND METHODS
We conducted a comprehensive literature search of multiple electronic databases from inception to June 2022 to identify all studies reporting AMH levels or factors associated with diminished OvR in patients with CD.
RESULTS
Of the 48 studies identified in our search, eight (including 418 patients with CD) were finally included. The mean difference (95% confidence interval [CI]) in the AMH level between pooled CD patients and controls was -0.56 (-1.14 to 0.03) (p = 0.06). A history of CD-related surgery was not associated with a lower OvR (odds ratio, OR [95% CI] 1.34, [0.66-2.7]; p = 0.4). While disease activity and perianal disease seems associated with a low OvR, disease location (L2 vs. L1, OR [95% CI] = 95% CI [0.47-7.4]; p = 0.4) and L3 vs. L1 (OR [95% CI] = 1.44 [0.67-3.12]; p = 0.3), CD medication, and disease behavior were not.
CONCLUSIONS
Our systematic review and meta-analysis did not identify a significantly low OvR in patients with CD. Contrary to CD-related surgery risk factor, active disease was associated lower AMH levels.
PubMed: 38803058
DOI: 10.1111/aogs.14853