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American Family Physician Aug 2021With more than 200 types identified, human papillomavirus (HPV) commonly causes infections of the skin and mucosa. HPV infection is the most common sexually transmitted... (Review)
Review
With more than 200 types identified, human papillomavirus (HPV) commonly causes infections of the skin and mucosa. HPV infection is the most common sexually transmitted infection in the United States. Although most HPV infections are transient and subclinical, some lead to clinical manifestations ranging from benign papillomas or warts to intraepithelial lesions. In some patients, persistent infection with high-risk mucosal types, especially HPV-16 and HPV-18, causes anal, cervical, oropharyngeal, penile, vaginal, and vulvar cancers. Most HPV-related cancers are believed to be caused by sexual spread of the virus. A history of multiple sex partners; initiation of sexual activity at an early age; not using barrier protection; other sexually transmitted infections, including HIV; an immunocompromised state; alcohol use; and smoking have been identified as risk factors for persistent HPV infections. Screening for HPV infection is effective in identifying precancerous lesions and allows for interventions that can prevent the development of cancer. Use of condoms and dental dams may decrease spread of the virus. Vaccination is the primary method of prevention. The nonavalent HPV vaccine is effective in preventing the development of high-grade precancerous cervical lesions in noninfected patients. Vaccination is ideally administered at 11 or 12 years of age, irrespective of the patient's sex. In general, a two-dose series is recommended if administered before 15 years of age; however, individuals who are immunocompromised require three doses.
Topics: Humans; Incidence; Papillomaviridae; Papillomavirus Infections; Papillomavirus Vaccines; United States; Vaccination
PubMed: 34383440
DOI: No ID Found -
International Journal of Surgery... Sep 2019Despite a burgeoning literature during the last two decades regarding perioperative risk management of anal fistula, little is known about its risk factors that... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Despite a burgeoning literature during the last two decades regarding perioperative risk management of anal fistula, little is known about its risk factors that influence postoperative recurrence. We performed a meta-analysis to summarize and assess the credibility of evidence of potential risk factors for anal fistula recurrence (AFR) after surgery.
METHODS
Pubmed and EMBASE without language restriction were searched from inception to April 2018 that reported risk factors which predisposed recurrence after anal fistula surgery. We excluded studies that involved patients with anal fistula associated with Crohn's disease. MOOSE guidelines were followed when this meta-analysis was performed. We used random-effects models to pool relative risks (RRs) with 95% confidence intervals (CIs). Evidence from observational studies was graded into high-quality (Class I), moderate-quality (Class II/III) and low-quality (Class IV) based on Egger's P value, total sample size and between-study heterogeneity.
RESULTS
Of 3514 citations screened, 20 unique observational studies comprising 6168 patients were involved in data synthesis. High-quality evidence showed that AFR was associated with high transsphincteric fistula (RR, 4.77; 95% CI, 3.83 to 5.95), internal opening unidentified (RR, 8.54; 95% CI, 5.29 to 13.80), and horseshoe extensions (RR, 1.92; 95% CI, 1.43 to 2.59). Moderate-quality evidence suggested an association with prior anal surgery (RR, 1.52; 95% CI, 1.04 to 2.23), seton placement surgery (RR, 2.97; 95% CI, 1.10 to 8.06), and multiple fistula tract (RR, 4.77; 95% CI, 1.46 to 15.51). High-quality evidence demonstrated no significant association with gender or smoking; moderate-quality evidence also suggested no association with age, tertiary referral, alcohol use, diabetes mellitus, obesity, preoperative seton drainage, high internal opening, postoperative drainage, mucosal advancement flap surgery, supralevator extensions, location or type of anal fistula.
CONCLUSION
Several patient, surgery and fistula-related factors are significantly associated with postoperative AFR. These findings strengthen clinical awareness of early warning to identify patients with high-risk disease recurrence for AFR.
Topics: Adult; Female; Humans; Male; Postoperative Complications; Rectal Fistula; Recurrence; Risk Factors
PubMed: 31400504
DOI: 10.1016/j.ijsu.2019.08.003 -
Cureus Dec 2020Crohn's disease (CD) is a transmural inflammatory bowel disease (IBD) that can affect any part of the gastrointestinal (GI) tract. With the disease's progression,... (Review)
Review
Crohn's disease (CD) is a transmural inflammatory bowel disease (IBD) that can affect any part of the gastrointestinal (GI) tract. With the disease's progression, adhesions and transmural fissuring, intra-abdominal abscesses, and fistula tracts may develop. An anal fistula (or fistula-in-ano) is a chronic abnormal epithelial lined tract communicating the anorectal lumen (internal opening) to the perineal or buttock skin (external opening). The risk of fistula development varies from 14%-38%. It can cause significant morbidity, which adversely impacts the quality of life. It is mostly believed that an anal crypt gland infection causes anal abscesses, leading to fistula development. Crohn's disease's pathogenesis involves Th1 and Th17 hypersensitivity due to an unknown antigen within the intestinal mucosa. Evidence to support this review was gathered via the Pubmed database. Search terms used were combinations of "Perianal fistula," "seton," "immunotherapy." Studies were reviewed and cross-referenced for additional reports. Setons are surgical thread loops passed from the external to the internal opening of the fistula tract and exteriorized through the anorectal canal, facilitating abscess drainage and inciting a local inflammatory reaction, thus promoting the resolution of the fistula. Biologicals such as anti-tumor necrosis factor (TNF) antibody (infliximab, adalimumab, certolizumab), anti-IL-12/23 (ustekinumab), and anti-α₄β₇ integrin antibody (vedolizumab) have been approved for Crohn's disease targeting the Th1/Th17-mediated inflammation. Other therapeutic modalities are fistulotomy, cyanoacrylate glue, bioprosthetic plugs, mucosal advancement flap, ligation of inter-sphincteric fistula tract (LIFT), diverting stoma, proctectomy, video-assisted anal fistula treatment (VAAFT), and fistula laser closure (FiLaC). Our review found that chronic seton therapy should be the primary approach, especially if the patient has a perianal abscess. It has a low incidence of re-intervention, recurrent abscess formation, and side-branching of the fistulous tract, with preservation of the fistulous tract's patency and cost-effectiveness. The major disadvantage of seton therapy is the discomfort and time to achieve stability. Among the biologicals, infliximab is the only therapy which has a statistically significant effect on the healing rate of perianal Crohn's fistula compared to placebo, but the major disadvantage associated with anti-TNF as sole therapy is high re-intervention rate, prolong maintenance therapy, high recurrence rate, and severe side effects. We hypothesize that the two aspects should be addressed concurrently to increase the fistula healing or closure rate. First, the seton should be used as initial therapy to maintain tract patency to allow abscess drainage and minimize the intestinal flora colonization within the tract mucosa, thereby leukocytic infiltration and propagation of inflammation within the tract. The second aspect that has to be considered is that we should target the initial stimulation of the Th1/Th17 mediated hypersensitivity instead of a factor/cytokine involved in the inflammation mediation. Although the unknown antigen triggering such hypersensitivity is not clear, we could target the RAR-related orphan receptor γ (RORγ)-T (transcription factor involved in activation of Th17 cells) and the T-bet (transcription factor involved in activation of Th17 cells) within the GI mucosa by a novel target immune therapy.
PubMed: 33415035
DOI: 10.7759/cureus.11882 -
Gastroenterology Apr 2021Restorative proctocolectomy with ileal pouch-anal anastomosis is a surgical procedure in patients with ulcerative colitis refractory to medical therapies. Pouchitis, the... (Comparative Study)
Comparative Study
BACKGROUND & AIMS
Restorative proctocolectomy with ileal pouch-anal anastomosis is a surgical procedure in patients with ulcerative colitis refractory to medical therapies. Pouchitis, the most common complication, is inflammation of the pouch of unknown etiology. To define how the intestinal immune system is distinctly organized during pouchitis, we analyzed tissues from patients with and without pouchitis and from patients with ulcerative colitis using single-cell RNA sequencing (scRNA-seq).
METHODS
We examined pouch lamina propria CD45+ hematopoietic cells from intestinal tissues of ulcerative colitis patients with (n = 15) and without an ileal pouch-anal anastomosis (n = 11). Further in silico meta-analysis was performed to generate transcriptional interaction networks and identify biomarkers for patients with inflamed pouches.
RESULTS
In addition to tissue-specific signatures, we identified a population of IL1B/LYZ+ myeloid cells and FOXP3/BATF+ T cells that distinguish inflamed tissues, which we further validated in other scRNA-seq datasets from patients with inflammatory bowel disease (IBD). Cell-type-specific transcriptional markers obtained from scRNA-seq was used to infer representation from bulk RNA sequencing datasets, which further implicated myeloid cells expressing IL1B and S100A8/A9 calprotectin as interacting with stromal cells, and Bacteroidales and Clostridiales bacterial taxa. We found that nonresponsiveness to anti-integrin biologic therapies in patients with ulcerative colitis was associated with the signature of IL1B+/LYZ+ myeloid cells in a subset of patients.
CONCLUSIONS
Features of intestinal inflammation during pouchitis and ulcerative colitis are similar, which may have clinical implications for the management of pouchitis. scRNA-seq enables meta-analysis of multiple studies, which may facilitate the identification of biomarkers to personalize therapy for patients with IBD. The processed single cell count tables are provided in Gene Expression Omnibus; GSE162335. Raw sequence data are not public and are protected by controlled-access for patient privacy.
Topics: Adolescent; Adult; Case-Control Studies; Colitis, Ulcerative; Colon; Colonic Pouches; Female; Gene Expression Profiling; Humans; Male; Middle Aged; Myeloid Cells; Phenotype; Pouchitis; Proctocolectomy, Restorative; RNA-Seq; Single-Cell Analysis; T-Lymphocytes; Transcriptome; Treatment Outcome; Young Adult
PubMed: 33359089
DOI: 10.1053/j.gastro.2020.12.030 -
Frontiers in Allergy 2021Itch is a nociceptive sensation linked with reflexes and cognitive motor actions. We traditionally think of itch as a sensation of the skin related to allergy, an insect... (Review)
Review
Itch is a nociceptive sensation linked with reflexes and cognitive motor actions. We traditionally think of itch as a sensation of the skin related to allergy, an insect sting or interestingly, anxiety and frustration. Less understood and considered are the physiological processes involved in the itching sensation that occurs at mucosal and junctional dermal sites, which is extraordinary as from an evolutionary point of view these sites serve important guardian roles, rich in sensory nerves and inflammatory cells. Despite itch being an ancient reflex and evolutionarily conserved phenomenon, better clinical understanding of the nuances between sites of itch sensation may lead to improved clinical outcomes. This review invites readers to appreciate itch beyond the skin by highlighting several specific itch patterns-nasal, oral, auricular, vulvovaginal, anal, and perineal itch-the pathophysiological mechanisms that underlie them, the clinical patterns these may cause, and some unique treatments.
PubMed: 35386995
DOI: 10.3389/falgy.2021.700368 -
Cureus Apr 2021The present study discusses opioid-induced constipation (OIC) in advanced cancer patients, focusing on the OIC definition, pathophysiology, and treatment. OIC is any... (Review)
Review
The present study discusses opioid-induced constipation (OIC) in advanced cancer patients, focusing on the OIC definition, pathophysiology, and treatment. OIC is any change from baseline defecation patterns and bowel habits that developed after starting opioid therapy. The condition is characterized by bowel frequency reduction, worsening or development of straining, a sensation of incomplete defecation, or distress associated with bowel habits. OIC is common in advanced cancer patients, with a prevalence of approximately 51%-87% in patients taking opioids for pain management. Patients are likely to experience severe distress, work productivity reduction, poor quality of life, and increased healthcare utilization. OIC has a complex pathophysiology that involves propulsive and peristalsis impairment, intestinal mucosal secretion inhibition, intestinal fluid absorption enhancement, and anal sphincters function impairment. The Rome III criteria are used to assess and diagnose clinical OIC and can also be diagnosed through the Patient Assessment of Constipation (PAC) measures, including the symptom survey (PAC-SYM) and quality of life survey (PAC-QOL). Non-pharmacological treatment of OIC involves lifestyle habits and dietary adjustments, although these interventions might be insufficient to manage the condition. Pharmacological treatments involve the use of traditional laxatives and newer agents like peripherally acting mu-opioid receptor agonists (PAMORAs), including naldemedine, naloxegol, and methylnaltrexone. More novel treatments for OIC that target the pathophysiology are still needed and should be studied carefully for safety and efficacy.
PubMed: 33850679
DOI: 10.7759/cureus.14386 -
Science Advances Sep 2023Intestinal stem cell (ISC) is a promising therapeutic target for inflammatory bowel disease. Cholesterol availability is critical for ISC stemness. Low plasma...
Intestinal stem cell (ISC) is a promising therapeutic target for inflammatory bowel disease. Cholesterol availability is critical for ISC stemness. Low plasma cholesterol is a typical feature of Crohn's disease (CD); however, its impact on mucosal healing remains unclear. Here, we identified an essential role of sorting nexin 10 (SNX10) in maintaining the stemness of ISCs. SNX10 expression in intestinal tissues positively correlates with the severity of human CD and mouse colitis. Conditional SNX10 knockout in intestinal epithelial cells or ISCs promotes intestinal mucosal repair by maintaining the ISC population associated with increased intracellular cholesterol synthesis. Disassociation of ERLIN2 with SCAP by SNX10 deletion enhances the activation of SREBP2, resulting in increased cholesterol biosynthesis. DC-SX029, a small-molecule inhibitor of SNX10, was used to verify the druggable potential of SNX10 for the treatment of patients with CD. Our study provides a strategy for mucosal healing through SREBP2-mediated stemness restoration of ISCs.
Topics: Animals; Humans; Mice; Inflammatory Bowel Diseases; Intestinal Mucosa; Intestines; Sorting Nexins; Stem Cells
PubMed: 37647408
DOI: 10.1126/sciadv.adh5016 -
Clinics in Colon and Rectal Surgery Jan 2022Anorectal strictures are a notoriously difficult to treat phenotype of perianal Crohn's disease. Quality of life is diminished due to ongoing pain, incontinence,... (Review)
Review
Anorectal strictures are a notoriously difficult to treat phenotype of perianal Crohn's disease. Quality of life is diminished due to ongoing pain, incontinence, difficulty with stool evacuation, and recurrent medical and surgical treatments. Medical therapy is aimed at treating luminal disease and mucosal ulceration to prevent worsening of fibrosis. Clinical examination and endoscopic intervention can be used for serial dilations of strictures. Unfortunately, despite optimal medical therapy and endoscopic intervention with serial anal dilations, surgery with intestinal diversion or proctocolectomy may be required as part of the treatment algorithm in a significant proportion of patients.
PubMed: 35069029
DOI: 10.1055/s-0041-1740037 -
Viruses May 2023The main objectives were to describe the prevalence of HPV, its genotypes and HPV-associated dysplastic lesions in the oropharyngeal mucosa of PLHIV and related factors.
BACKGROUND
The main objectives were to describe the prevalence of HPV, its genotypes and HPV-associated dysplastic lesions in the oropharyngeal mucosa of PLHIV and related factors.
MATERIAL AND METHODS
This cross-sectional prospective study consecutively enrolled PLHIV attending our specialist outpatient units. At visit, HIV-related clinical and analytical variables were gathered, and oropharyngeal mucosa exudates were taken to detect HPV and other STIs by polymerase chain reaction. Samples were also taken from the anal canal of all participants and from the genital mucosa of the women for HPV detection/genotyping and cytological study.
RESULTS
The 300 participants had a mean age of 45.1 years; 78.7% were MSM and 21.3% women; 25.3% had a history of AIDS; 99.7% were taking ART; and 27.3% had received an HPV vaccine. HPV infection prevalence in the oropharynx was 13%, with genotype 16 being the most frequent (2.3%), and none had dysplasia. Simultaneous infection with (HR: 4.02 (95% CI: 1.06-15.24)) and a history of anal HSIL or SCCA (HR: 21.52 (95% CI: 1.59-291.6)) were risk factors for oropharyngeal HPV infection, whereas ART duration (8.8 vs. 7.4 years) was a protective factor (HR: 0.989 (95% CI: 0.98-0.99)).
CONCLUSIONS
The prevalence of HPV infection and dysplasia was low in the oropharyngeal mucosae. A higher exposure to ART was protective against oral HPV infection.
Topics: Male; Humans; Female; Middle Aged; Anal Canal; Papillomavirus Infections; HIV Infections; Homosexuality, Male; Cross-Sectional Studies; Prospective Studies; Papillomaviridae; Risk Factors; Mucous Membrane; Genotype; Hyperplasia; Oropharynx; Genitalia; Prevalence
PubMed: 37243256
DOI: 10.3390/v15051170