Summary Background Primary biliary cholangitis (PBC) is an autoimmune hepatobiliary disorder characterized by destruction of liver bile ducts leading to intrahepatic cholestasis. It causes intractable pruritus for which ultraviolet (UV)B phototherapy is an experimental treatment when alternative therapies fail. The pathophysiology of cholestatic itch and the mechanism of action of narrowband UVB in this condition remains poorly understood. Objectives To summarize the current literature and propose testable hypotheses for the mechanism of action of phototherapy in attenuating itch. Methods A focused PubMed search for articles relating to the pathogenesis of itch in cholestatic disease was performed. A total of 3855 articles were screened and 50 were found suitable for literature review. Evidence from this literature review was combined with author expertise in the area. Results Formulated hypotheses focus on the role of bile salts, autotaxin and specific receptors including G‐protein‐coupled bile acid receptor, Gpbar1 (also known as TGR5) and the nuclear transcription factor farnesoid X receptor. Conclusions Several testable mechanisms through which phototherapy may exert its effects are discussed in this review. The next steps are to carry out an objective assessment of the efficacy of phototherapy in cholestatic pruritus, gain further knowledge on the underlying pathways, and subsequently trial its use against current licensed therapies. Such studies could lead to increased mechanistic understanding, identification of novel therapeutic targets and the potential to refine phototherapy protocols, leading to improved control of itch and quality of life in patients with PBC. What's already known about this topic? Primary biliary cholangitis (PBC) is frequently associated with intractable pruritus for which current treatment options are often unsuccessful. Phototherapy is used as an experimental treatment for PBC‐associated pruritus when alternative better‐studied treatments fail. What does this study add? This study reviews the current literature on the pathophysiology and management of cholestatic pruritus, an area which remains poorly understood. We propose testable hypotheses of the mechanisms behind the attenuation of cholestatic pruritus with phototherapy.
Background The distinction between normal and pathological extra-axial cerebrospinal fluid (CSF) spaces is unclear, with the use of the term benign external hydrocephalus (BEH) not being well defined in clinical practice. This study aimed to establish a distribution of metrics of the subarachnoid space in a population of children diagnosed as normal, and investigate the clinical use of the term BEH. Methods A retrospective case-control study on magnetic resonance image scans was performed on 150 children diagnosed as normal and 10 children diagnosed with BEH. Measurements were taken in the axial plane for CSF width (CSFW), and interhemispheric width (IHW). Results Normal controls had a mean age of 11.1 ± 7.6 months (78 male, 72 female) and the BEH sample had a mean age of 10.6 ± 7.8 months (six male, four female). Mean CSFW was 7.96 ± 4.79 mm in the BEH sample compared to 4.58 ± 2.25 mm in the normal sample ( p < 0.05). Mean IHW was 6.30 ± 2.79 mm in the BEH sample compared to 3.89 ± 1.83 mm in the normal sample ( p < 0.05). However, a substantial overlap between the two distributions of CSFW was found, with 50% of BEH patients lying within a single standard deviation of the mean of normal individuals. Conclusion The absence of diagnostic criteria for BEH means reporting is variable. Patients being diagnosed with BEH who have no other clinical defects may represent the extreme of the normal population rather than a distinct clinical entity.
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Acute kidney injury (AKI) is a common medical problem with a multitude of aetiologies. Prompt diagnosis and management is key in the prevention of complications. Cutaneous signs can often give diagnostic clues of underlying systemic diseases causing AKI. This review summarises cutaneous findings of diseases causing AKI in adults. Knowledge of such cutaneous signs could lead to earlier diagnosis of underlying kidney disease and facilitate management strategies in a timely manner. Acute interstitial nephritis, polyarteritis nodosa, Kawasaki's disease, granulomatosis with polyangiitis (previously Wegener's granulomatosis), microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis (previously Churg-Strauss syndrome), Henoch-Schonlein purpura, cryoglobulinaemia, Sjogren's Syndrome, systemic sclerosis, nephrogenic systemic fibrosis, dermatomyositis, systemic lupus erythematosus, amyloidosis, and cholesterol embolisation syndrome were highlighted as diseases causing AKI with cutaneous manifestations.
Background: Acute pelvic discomfort in pregnant and postpartum people can be difficult to diagnose and treat. Ultrasound is still the most common imaging modality used to evaluate pregnant and postpartum women. Aim: To see how useful ultrasonography is in evaluating several causes of pain in pelvic during early pregnancy. Methodology: A descriptive study was conducted at University of Lahore Teaching Hospital. Data of 344 participants were designated done suitable sample method. SPSS version 25 was used for data analysis. Results: In this table, 344 patients with pelvic pain are reported; 108 (31.4%) patients had bleeding, 58(16.9%) had fibroids out of 344 patients, 60 (17.4%) had cyst and 19 (5.5%) patients had ectopic pregnancy, 236 patients were not count for bleeding status in which 223 (94.5%) patients had no ectopic pregnancy & 13 (5.5%) patients had ectopic pregnancy. 108 patients were count for bleeding status, in which 6 (5.6%) patients had ectopic pregnancy & 102 (94.4%) patients had not ectopic pregnancy, 236 patients were not count for bleeding status in which 235 (99.6%) patients had no fibroids & 1 (0.4%) patients had fibroids. Conclusion: Fibroids and cysts were the most common findings in female with pain in pelvic in early pregnancy. Key words:Pain inLower abdominal, early pregnancy, first trimester, fibroid, Gestational sac, crown lump length.
Methotrexate (MTX) is an effective treatment for atopic eczema (AE), but its mechanism of action remains undefined. Our previous work identified keratinocytes as a direct target of MTX by increasing epidermal differentiation. Evidence supports the concept of DNA damage-induced keratinocyte differentiation; however, this has not been characterized in the context of MTX. We tested the hypothesis that MTX may act therapeutically in AE by inducing DNA damage and activating downstream DNA damage response signalling pathways. Patients with AE starting MTX (initial dose 10 mg weekly) were recruited (n = 12). The FLG status was determined by DNA genotyping. Clinical data and skin biopsies from lesional and nonlesional skin were collected at week 0 (baseline), week 2 [visit 1 (V1)] and week 12 [visit 2 (V2)] following MTX initiation. γH2A.X, a marker of DNA damage, was quantified to explore the relationship between DNA damage secondary to MTX treatment and FLG status. γH2A.X and filaggrin protein epidermal immunostaining were quantified. The male-to-female ratio was 8 : 4 and median participant age was 45 years. Median Eczema Area and Severity Index (EASI) score improved from 23.5 (baseline, n = 12) to 14.6 at V1 (n = 12) and 9.0 at V2 (n = 8). Median Dermatology Life Quality Index reduced from 15 (baseline, n = 12) to 10.5 (V2, n = 8). Four patients were FLG heterozygotes and eight were FLG wild type. In combined analysis of all patients, epidermal γH2A.X increased in lesional skin at both time points [n = 6 (V1: P = 0.022; V2: P = 0.009)] and in nonlesional skin by V2 (n = 6; P = 0.021). γH2A.X increased in lesional skin at V2 in both FLG heterozygotes (P = 0.044) and wild types (P = 0.038). Epidermal filaggrin in lesional and nonlesional skin increased at V1 and V2 in all patients combined (n = 5; P = 0.029). Filaggrin increased in the nonlesional skin of FLG heterozygotes (P = 0.044) and in the lesional skin of FLG wild-type patients (P = 0.009) by V2. Transcriptomic (RNAseq) analysis was performed on skin biopsies (n = 11 patients; n = 42 samples). We explored the relationship of gene expression with severity (EASI) and FLG status. AKR1B10, IL22 and LGALS7 expression increased with disease severity. The AKR1B10 (regulates keratinocyte differentiation) and LGALS7 expression (expressed during barrier dysfunction) response with EASI was enhanced in FLG heterozygotes vs. wild-type patients. Canonical pathways were upregulated in lesional skin at V2 vs. baseline. Through epidermal immunostaining and transcriptomic gene analysis, we demonstrated evidence of DNA damage and filaggrin induction in patients with AE following MTX therapy, with associated improved disease outcomes.
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