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Italian Journal of Pediatrics Jun 2024Townes-Brocks syndrome (TBS) is a rare genetic disorder characterized by imperforate anus, dysplastic ears, thumb malformations, and other abnormalities. Previous...
BACKGROUND
Townes-Brocks syndrome (TBS) is a rare genetic disorder characterized by imperforate anus, dysplastic ears, thumb malformations, and other abnormalities. Previous studies have revealed that mutations in the SALL1 gene can disrupt normal development, resulting in the characteristic features of Townes-Brocks syndrome. Spalt-like transcription factors (SALLs) are highly conserved proteins that play important roles in various cellular processes, including embryonic development, cell differentiation, and cell survival. Over 400 different variants or mutations have been reported in the SALL1 gene in individuals with TBS. Most of these variants lead to the formation of premature termination codons (PTCs), also known as nonsense mutations. The majority of these PTCs occur in a specific region of the SALL1 gene called the "hotspot region", which is particularly susceptible to mutation.
METHODS
In this study, we conducted whole-exome sequencing on a three-generation Chinese family with anorectal malformations.
RESULTS
We identified a novel heterozygous mutation (chr16:51175376:c.757 C > T p.Gln253*) in the SALL1 gene. Molecular analysis revealed a heterozygous C to T transition at nucleotide position 757 in exon 2 of the SALL1 (NM_002968) gene. This mutation is predicted to result in the substitution of the Gln253 codon with a premature stop codon (p.Gln253*). The glutamine-rich domain forms a long alpha helix, enabling the mutant protein to interact with the wild-type SALL1 protein. This interaction may result in steric hindrance effects on the wild-type SALL1 protein.
CONCLUSIONS
Our findings have expanded the mutation database of the SALL1 gene, which is significant for genetic counseling and clinical surveillance in the affected family. Furthermore, our study enhances the understanding of Townes-Brocks syndrome and has the potential to improve its diagnosis and treatment.
Topics: Humans; Transcription Factors; Abnormalities, Multiple; Anus, Imperforate; Female; Male; Pedigree; China; Mutation; Rare Diseases; Anorectal Malformations; Asian People; East Asian People; Hearing Loss, Sensorineural; Thumb
PubMed: 38915054
DOI: 10.1186/s13052-024-01691-0 -
ACG Case Reports Journal Jun 2024Crohn's disease (CD) represents a subtype of inflammatory bowel disease and can affect any portion of the gastrointestinal tract, from the mouth to the anus, with the...
Crohn's disease (CD) represents a subtype of inflammatory bowel disease and can affect any portion of the gastrointestinal tract, from the mouth to the anus, with the capacity to affect extraintestinal organs. Salpingo-oophoritis is an uncommon manifestation of CD. There is only a limited number of documented case reports. We present the case of a patient with ileocolonic CD and secondary granulomatous salpingo-oophoritis. We emphasize the significance of clinical suspicion and an interdisciplinary approach as crucial factors in ensuring the effective management of the case.
PubMed: 38912374
DOI: 10.14309/crj.0000000000001388 -
Infection and Drug Resistance 2024Syphilis is a complex, systemic infectious disease caused by . Secondary syphilitic lesions typically manifest within 3 months following initial exposure to . The...
Syphilis is a complex, systemic infectious disease caused by . Secondary syphilitic lesions typically manifest within 3 months following initial exposure to . The predominant cutaneous manifestations of secondary syphilis are macula and papule. Certain individuals with syphilis may present with an atypical rash during the secondary stage owing to immunosuppression and other factors. Herein, we report a rare case of atypical recurrent secondary syphilis around the anus in a 65-year-old woman. Based on cerebrospinal fluid findings and skin biopsy results, the patient was ultimately diagnosed as neurosyphilis and recurrent secondary syphilis. Following intravenous antibiotic therapy, the patient's rash improved significantly. This case underscores the importance for physicians to remain vigilant regarding the possibility of syphilis when encountering cases exhibiting unusual clinical manifestations, as a definitive diagnosis necessitates a comprehensive evaluation.
PubMed: 38912217
DOI: 10.2147/IDR.S470153 -
Current Status and Role of Artificial Intelligence in Anorectal Diseases and Pelvic Floor Disorders.JSLS : Journal of the Society of... 2024Anorectal diseases and pelvic floor disorders are prevalent among the general population. Patients may present with overlapping symptoms, delaying diagnosis, and... (Review)
Review
BACKGROUND
Anorectal diseases and pelvic floor disorders are prevalent among the general population. Patients may present with overlapping symptoms, delaying diagnosis, and lowering quality of life. Treating physicians encounter numerous challenges attributed to the complex nature of pelvic anatomy, limitations of diagnostic techniques, and lack of available resources. This article is an overview of the current state of artificial intelligence (AI) in tackling the difficulties of managing benign anorectal disorders and pelvic floor disorders.
METHODS
A systematic literature review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the PubMed database to identify all potentially relevant studies published from January 2000 to August 2023. Search queries were built using the following terms: AI, machine learning, deep learning, benign anorectal disease, pelvic floor disorder, fecal incontinence, obstructive defecation, anal fistula, rectal prolapse, and anorectal manometry. Malignant anorectal articles and abstracts were excluded. Data from selected articles were analyzed.
RESULTS
139 articles were found, 15 of which met our inclusion and exclusion criteria. The most common AI module was convolutional neural network. researchers were able to develop AI modules to optimize imaging studies for pelvis, fistula, and abscess anatomy, facilitated anorectal manometry interpretation, and improved high-definition anoscope use. None of the modules were validated in an external cohort.
CONCLUSION
There is potential for AI to enhance the management of pelvic floor and benign anorectal diseases. Ongoing research necessitates the use of multidisciplinary approaches and collaboration between physicians and AI programmers to tackle pressing challenges.
Topics: Humans; Pelvic Floor Disorders; Artificial Intelligence; Rectal Diseases; Anus Diseases; Manometry; Fecal Incontinence
PubMed: 38910957
DOI: 10.4293/JSLS.2024.00007 -
Acta Oncologica (Stockholm, Sweden) Jun 2024MicroRNA (MiR) influences the growth of cancer by regulation of mRNA for 50-60% of all genes. We present as per our knowledge the first global analysis of microRNA...
BACKGROUND
MicroRNA (MiR) influences the growth of cancer by regulation of mRNA for 50-60% of all genes. We present as per our knowledge the first global analysis of microRNA expression in anal cancer patients and their prognostic impact.
METHODS
Twenty-nine patients with T1-4 N0-3 M0 anal cancer treated with curative intent from September 2003 to April 2011 were included in the study. RNA was extracted from fresh frozen tissue and sequenced using NGS. Differentially expressed microRNAs were identified using the R-package DEseq2 and the endpoints were time to progression (TTP) and cancer specific survival (CSS).
RESULTS
Five microRNAs were significantly associated with 5-year progression free survival (PFS): Low expression of two microRNAs was associated with higher PFS, miR-1246 (100% vs. 55.6%, p = 0.008), and miR-135b-5p (92.9% vs. 59.3%, p = 0.041). On the other hand, high expressions of three microRNAs were associated with higher PFS, miR-148a-3p (93.3% vs. 53.6%, p = 0.025), miR-99a-5p (92.9% vs. 57.1%, p = 0.016), and let-7c-3p (92.9% vs. 57.1%, p = 0.016). Corresponding findings were documented for CSS.
INTERPRETATION
Our study identified five microRNAs as prognostic markers in anal cancer. MiR-1246 and microRNA-135b-5p were oncoMiRs (miRs with oncogene effects), while miR-148a-3p, miR- 99a-5p, and let-7c-3p acted as tumour suppressors in anal cancer patients.
Topics: Humans; MicroRNAs; Male; Female; Biomarkers, Tumor; Prognosis; Anus Neoplasms; Middle Aged; Aged; Adult; Gene Expression Regulation, Neoplastic; Aged, 80 and over; Progression-Free Survival
PubMed: 38899393
DOI: 10.2340/1651-226X.2024.27976 -
Cell Reports Jun 2024p53 regulates multiple signaling pathways and maintains cell homeostasis under conditions of DNA damage and oxidative stress. Although USP7 has been shown to promote p53...
p53 regulates multiple signaling pathways and maintains cell homeostasis under conditions of DNA damage and oxidative stress. Although USP7 has been shown to promote p53 stability via deubiquitination, the USP7-p53 activation mechanism has remained unclear. Here, we propose that DNA damage induces reactive oxygen species (ROS) production and activates ATM-CHK2, and CHK2 then phosphorylates USP7 at S168 and T231. USP7 phosphorylation is essential for its deubiquitination activity toward p53. USP7 also deubiquitinates CHK2 at K119 and K131, increasing CHK2 stability and creating a positive feedback loop between CHK2 and USP7. Compared to peri-tumor tissues, thyroid cancer and colon cancer tissues show higher CHK2 and phosphorylated USP7 (S168, T231) levels, and these levels are positively correlated. Collectively, our results uncover a phosphorylation-deubiquitination positive feedback loop involving the CHK2-USP7 axis that supports the stabilization of p53 and the maintenance of cell homeostasis.
PubMed: 38879877
DOI: 10.1016/j.celrep.2024.114366 -
Clinical Gastroenterology and... Jun 2024Perianal fistulizing Crohn's disease (PFCD)-associated anorectal and fistula cancers are rare but often devastating diagnoses. However, given the low incidence and... (Review)
Review
BACKGROUND AND AIMS
Perianal fistulizing Crohn's disease (PFCD)-associated anorectal and fistula cancers are rare but often devastating diagnoses. However, given the low incidence and consequent lack of data and clinical trials in the field, there is little to no guidance on screening and management of these cancers. To inform clinical practice, we developed consensus guidelines on PFCD-associated anorectal and fistula cancers by multidisciplinary experts from the international TOpClass consortium.
METHODS
We conducted a systematic review by standard methodology, using the Newcastle-Ottawa Scale quality assessment tool. We subsequently developed consensus statements using a Delphi consensus approach.
RESULTS
Of 561 articles identified, 110 were eligible, and 76 articles were included. The overall quality of evidence was low. The TOpClass consortium reached consensus on six structured statements addressing screening, risk assessment, and management of PFCD-associated anorectal and fistula cancers. Patients with longstanding (>10 years) PFCD should be considered at small but increased risk of developing perianal cancer, including squamous cell carcinoma of the anus(SCCA) and anorectal carcinoma. Risk factors for SCCA, notably human papilloma virus (HPV), should be considered. New, refractory, or progressive perianal symptoms should prompt evaluation for fistula cancer. There was no consensus on timing or frequency of screening in patients with asymptomatic perianal fistula. Multiple modalities may be required for diagnosis, including an exam under anesthesia (EUA) with biopsy. Multidisciplinary team efforts were deemed central to the management of fistula cancers.
CONCLUSION
Inflammatory bowel disease (IBD) clinicians should be aware of the risk of PFCD-associated anorectal and fistula cancers in all patients with PFCD. The TOpClass consortium consensus statements outlined herein offer guidance in managing this challenging scenario.
PubMed: 38871152
DOI: 10.1016/j.cgh.2024.05.029 -
Urology Case Reports Jul 2024This case report presents a rare occurrence of isolated bladder exstrophy with a normal phallus in a one-day-old male newborn. The patient also presented with...
This case report presents a rare occurrence of isolated bladder exstrophy with a normal phallus in a one-day-old male newborn. The patient also presented with imperforated anus, congenital heart disease, and a left ectopic kidney. Surgical interventions included cut-back anoplasty, bilateral ureteral reimplantation, and primary bladder closure in a single operation, resulting in a successful outcome without complications. Three months of follow-up showed satisfactory results.
PubMed: 38868626
DOI: 10.1016/j.eucr.2024.102755 -
Ugeskrift For Laeger May 2024
Topics: Humans; Condylomata Acuminata; Male; Female; Anus Neoplasms
PubMed: 38847314
DOI: 10.61409/V72029 -
Endoscopy Dec 2024
Topics: Humans; Anus Neoplasms; Male; Endoscopic Mucosal Resection; Carcinoma, Squamous Cell
PubMed: 38838728
DOI: 10.1055/a-2321-9527