Ex-vivo rectal tissue infection with HIV-1 to assess time to protection following oral preexposure prophylaxis with tenofovir disoproxil/emtricitabine.

OBJECTIVES: We wished to assess time to protection from HIV-1 infection following oral tenofovir disoproxil and emtricitabine (TDF/FTC) as preexposure prophylaxis (PrEP), using ex-vivo rectal tissue infections and drug concentration measures in blood and rectal tissue. DESIGN/METHODS: Participants from the ANRS PREVENIR study (NCT03113123) were offered this sub-study after a 14-day wash-out. We used an ex-vivo model to evaluate rectal tissue HIV-1 susceptibility before and after PrEP, 2 h after two pills or 7 days of a daily pill of TDF/FTC. PrEP efficacy was expressed by the difference (after-before) of 14-day cumulative p24 antigen levels. TFV-DP and FTC-TP levels were measured in rectal tissue and PBMCs and correlated with HIV-1 infection. RESULTS: Twelve and 11 men were analyzed in the 2 h-double dose and 7 days-single dose groups, respectively. Cumulative p24 differences after-before PrEP were -144 pg/ml/mg (IQR[-259;-108]) for the 2 h-double dose group ( P  = 0.0005) and -179 pg/ml/mg (IQR [-253;-86]) for the 7 days-single dose group ( P  = 0.001), with no differences between groups ( P  = 0.93). Rectal TFV-DP was below quantification after a double dose, but FTC-TP levels were similar to levels at 7 days. There was a significant correlation between rectal FTC-TP levels and p24 changes after a double dose ( R  = -0.84; P  = 0.0001). CONCLUSION: Oral TDF/FTC provided similar protection against HIV-1 infection of rectal tissue 2 h after a double dose or 7 days of a daily dose. At 2 h, this protection seems driven by high FTC-TP concentrations in rectal tissue. This confirms the importance of combining TDF and FTC to achieve early protection.

Anal Monkeypox Disease: Description of 65 Cases.

BACKGROUND: Monkeypox is a zoonosis endemic in Africa caused by 3 orthopoxvirus clades. Knowledge of the disease is limited, but a worldwide outbreak involving a new route of transmission was declared in April 2022. OBJECTIVE: This study aimed to describe anal symptoms and outcomes in patients infected with Monkeypox virus presenting to an emergency proctology unit in Paris. DESIGN: This was an observational study. SETTING: We reported anal symptoms of all consecutive patients with monkeypox anal infection in a single proctology center between June 16, 2022, and July 26, 2022. Association with sexually transmitted infections and outcomes were also recorded. PATIENTS: Sixty-five men with a mean age of 39.6 (19.9-64.6) years with confirmed monkeypox anal infection were included in the study. MAIN OUTCOME MEASURES: Anal symptoms and their severity were clinically assessed. A favorable outcome consisted of a complete resolution of clinical manifestation. RESULTS: Sexual transmission was reported in 51 patients (78.4%), among whom 63 (97%) were men who have sex with men. Twenty-eight (43%) were living with HIV, and 24 (36.9%) were taking tenofovir/emtricitabine for HIV preexposure prophylaxis. Anal symptoms appeared first in 36 patients (55.4%) and skin rash or other general symptoms in 22 patients (33.8%). Incubation time was 6.9 (1-26) days. Symptoms included painful perianal (n = 42 patients; 64.6%), anal (n = 28, 43%), and rectal (n = 25; 38.4%) ulcerations and perianal vesicles (n = 24; 36.9%). Proctitis was observed in 49 patients (75.4%). It was mild in 20 (40.8%) and intense in 29 (59.2%), and severe proctitis mimicking high intersphincteric suppuration was found in 4 (8.2%). Fifteen patients (23.1%) had concurrent sexually transmitted infection and 3 were hospitalized. Complete symptom resolution occurred within 12 days. LIMITATIONS: We performed a single-center study during a short period of time. CONCLUSIONS: Proctological symptoms are frequent in the current outbreak of monkeypox disease, probably linked to the route of transmission. Rectal ulcerations mimicking high intersphincteric suppuration should be recognized to avoid unnecessary surgery. See Video Abstract . ENFERMEDAD ANAL DE LA VIRUELA DEL MONO DESCRIPCIN DE CASOS: ANTECEDENTES:La viruela del simio mono es una zoonosis endémica en África causada por tres clados de orthopoxvirus. El conocimiento de la enfermedad es limitado, pero en abril de 2022 se declaró un brote mundial que implica una nueva vía de transmisión.OBJETIVO:Describir los síntomas anales y los resultados en pacientes que sufren de infección por Monkeypox que asistieron a una unidad de proctología de emergencia en París.DISEÑO:Un estudio observacional.ESCENARIO:Informamos los síntomas anales de todos los pacientes consecutivos con infección anal por viruela del mono en un solo centro de proctología entre el 16/6/2022 y el 26/7/2022. También se registró la asociación con infecciones de transmisión sexual (ITS) y el resultado.PACIENTES:Sesenta y cinco hombres de 39,6 [19,9-64,6] años con infección anal confirmada.PRINCIPALES MEDIDAS DE RESULTADO:Los síntomas anales y su gravedad se evaluaron clínicamente. Un resultado favorable consistió en una resolución completa de la manifestación clínica.RESULTADOS:La transmisión sexual se informó en 51 (78,4%) pacientes, de los cuales 63 (97%) eran hombres que tuvieron sexo con hombres. Veintiocho (43%) vivían con el VIH y 24 (36,9%) tomaban Emtricitabina/Tenofovir para profilaxis previa por exposición al VIH. Los síntomas anales aparecieron primero en 36 (55,4%) pacientes y la erupción cutánea u otros síntomas generales en 22 (33,8%). El tiempo de incubación fue de 6,9 [1-26] días. Los síntomas incluyeron ulceraciones perianales dolorosas (n = 42 pacientes, 64,6%), anales (n = 28, 43%), rectales (n = 25, 38,4%) y vesículas perianales (n = 24, 36,9%). Se observó proctitis en 49 (75,4%) pacientes. Fue leve en 20 (40,8%) e intensa en 29 (59,2%) y proctitis severa simulando supuración interesfinteriana alta en 4 (8,2%). Quince (23,1%) pacientes presentaban ITS concurrentes y 3 fueron hospitalizados. La resolución completa de los síntomas ocurrió dentro de los 12 días.LIMITACIONES:Estudio de un solo centro y durante corto período de tiempo.CONCLUSIÓN:Los síntomas proctológicos son frecuentes en el brote actual de la enfermedad de la viruela del mono, probablemente relacionados con la vía de transmisión. Las ulceraciones rectales que simulan una supuración interesfinteriana alta deben reconocerse para evitar una cirugía innecesaria. (Traducción-Dr. Fidel Ruiz Healy ).

Frequency and risk factors of severe postoperative bleeding after proctological surgery: a retrospective case-control study.

PURPOSE: The aim of this study was to assess frequency and risk factors of severe bleeding after proctological surgery requiring hemostatic surgery observed after publication of the French guidelines for anticoagulant and platelet-inhibitor treatment. METHODS: All patients who underwent proctological surgery between January 2012 and March 2017 in a referral center were included. Delay, severity of bleeding, and need for blood transfusion were recorded. Patients with severe postoperative bleeding were matched to controls at a 2:1 ratio adjusted on the operator, and the type of surgery. RESULTS: Among the 8,890 operated patients, 65 (0.7%) needed a postoperative hemostatic procedure in an operating room. The risk of a hemostatic surgery was significantly increased after hemorrhoidal surgery compared with other procedures (1.9% vs. 0.5%, P<10-4) and was most frequent after Milligan-Morgan hemorrhoidectomy (2.5%). Mean bleeding time was 6.2 days and no bleeding occurred after day 15. Blood transfusion rate was 0.1%. Treatment with anticoagulants and platelet inhibitors were managed according to recommendations and did not increase the severity of bleeding. The risk of severe bleeding was significantly lower in active smokers vs. non-smokers in univariate (16.9% vs. 36.2%, P=0.007) and multivariate (odds ratio, 0.31; 95% confidence interval, 0.14-0.65) analysis whereas sex, age, and body mass were not significantly associated with bleeding. CONCLUSION: Severe postoperative bleeding occurs in 0.7% of patients, but varies with type of procedure and is not affected by anticoagulant or antiplatelet treatment. These treatments given in accordance with the new guidelines do not increase the severity of postoperative bleeding.

Increased Long-term Risk of Anal Fistula After Proctologic Surgery: A Case-Control Study.

PURPOSE: Anal fistula is a common condition in proctology, usually requiring surgical treatment. Few risk factors have been clearly identified based on solid evidence. Our research objective was to determine whether history of anal surgery was a risk factor for subsequent anal fistula. METHODS: We conducted a case-control study from January 1, 2012 through December 31, 2013 in our tertiary center, comprising 280 cases that underwent surgery for anal fistula and 123 control patients seeking a consultation for upper gastrointestinal symptoms. Patients with inflammatory bowel disease were excluded. For both cases and controls, the following variables were recorded: sex, any prior anal surgery, diabetes mellitus, infection with human immunodeficiency virus, and smoking status. For each variable, confidence interval and odds ratio (OR) were calculated. RESULTS: In univariate analysis, male sex (73.2% vs. 31.7%, P < 0.0001), active smoking (38.1% vs. 22%, P = 0.0015), and prior anal surgery (16.0% vs. 4.1%, P = 0.0008) were associated with higher risk of anal fistula. In multivariate analysis, only male sex (OR, 5.5; 95% confidence interval [CI], 5.42 to 9.10; P < 0.0001) and previous anal surgery (OR, 4.48; 95% CI, 1.79 to 13.7; P = 0.0008) remained independently associated with anal fistula occurrence. CONCLUSION: The epidemiology of anal fistula is poorly assessed despite the high frequency at which it is diagnosed. Our findings suggest that history of any kind of anal surgery is a risk factor for further onset of anal fistula. Surgeons and patients must be informed of this issue.

Single-dose pharmacokinetics and pharmacodynamics of oral tenofovir and emtricitabine in blood, saliva and rectal tissue: a sub-study of the ANRS IPERGAY trial.

OBJECTIVES: In the ANRS IPERGAY pre-exposure prophylaxis (PrEP) trial, a single dose of tenofovir disoproxil fumarate and emtricitabine was taken orally 2-24 h before sexual intercourse. A sub-study was conducted to assess the pharmacokinetics of tenofovir and emtricitabine in blood, saliva and rectal tissue following this initial oral intake. METHODS: Plasma, PBMC, saliva and rectal tissue sampling was performed over 24 h in 12 seronegative men before enrolment in the ANRS IPERGAY trial, following a single dose of 600 mg tenofovir disoproxil fumarate/400 mg emtricitabine. Ex vivo HIV infectibility of rectal biopsies was also assessed. RESULTS: The median plasma Tmax of tenofovir (median Cmax: 401 µg/L) and emtricitabine (median Cmax: 2868 µg/L) was obtained 1 h (range: 0.5-4) and 2 h (range: 1-4) after dosing, respectively. The median C24 of tenofovir and emtricitabine was 40 and 63 µg/L, respectively. The median PBMC tenofovir diphosphate and emtricitabine triphosphate levels were 12.2 and 16.7 fmol/106 cells and 2800 and 2000 fmol/106 cells at 2 and 24 h after dosing, respectively. Saliva/plasma AUC0-24 ratios were 2% and 17% for tenofovir and emtricitabine, respectively. Emtricitabine was detected in rectal tissue 30 min after dosing, whereas tenofovir was only detectable at 24 h. Ex vivo HIV infectibility assays of rectal biopsies showed partial protection after dosing (P < 0.07). DISCUSSION: A single high dose of oral tenofovir disoproxil fumarate/emtricitabine provides rapid and high blood levels of tenofovir and emtricitabine, with rapid diffusion of emtricitabine in saliva and rectal tissue.

Prevalence of anal cytologic abnormalities in a French referral population: a prospective study with special emphasis on HIV, HPV, and smoking.

PURPOSE: Studying anal cytology to detect intraepithelial neoplasia has been demonstrated to be useful in highly selected populations. This study was designed to determine the frequency of abnormal smears in a wide sample of patients consulting for anorectal symptoms. METHODS: An anal smear was proposed during each consultation during a three-month period. RESULTS: A total of 205 patients (112 females) were included. After the consultation, visible condylomas were detected in 12 (6 percent) of the cases. Two hundred three (99 percent) smears were able to be analyzed. No case of high-grade squamous intraepithelial lesion was found. Four cases of low-grade squamous intraepithelial lesion were found, all in HIV patients with a history of condylomatous lesions. Forty smears were interpreted as atypical squamous cells of undetermined significance and 159 were normal. The prevalence in this population of low-grade squamous intraepithelial lesion was 19 percent (4/21) in HIV seropositive males, and 15 percent (4/26) in the case of a past history of condyloma. The factors associated with an abnormal smear (low-grade squamous intraepithelial lesion or atypical squamous cells of undetermined significance) were a history of anal condylomatous lesions (odd ratio, 4.9; range, 2.1-11.5), HIV seropositivity (odd ratio, 4; range, 1.6-9.9), and smoking (odd ratio, 2.1; range, 1.1-11.5). CONCLUSIONS: This work confirms that the frequency of low-grade squamous intraepithelial lesion is raised in HIV-seropositive males and also where there is a history of condyloma, which corroborates the necessity for regular monitoring and screening of these patients at risk. This study also suggests that the use of tobacco is associated with anal cytologic abnormalities.

Proctalgia fugax: demographic and clinical characteristics. What every doctor should know from a prospective study of 54 patients.

PURPOSE: This prospective study was designed to describe a typical attack of proctalgia fugax. METHODS: Patients were recruited from May 2003 to June 2004. Whatever the reason for consultation, they were systematically asked: "Do you ever suffer intermittent and recurring anorectal pain lasting for at least three seconds?" If the answer was yes, they were interviewed with a questionnaire and had a proctologic examination. The criterion for proctalgia fugax was a positive answer with a negative examination. RESULTS: The study included 1,809 patients. Fifty-four of these patients (3 percent) had proctalgia fugax and 83 percent of them had never sought medical advice for this problem. The mean age was 51 (range, 18-87) years. Thirty-seven patients were females (69 percent). The onset of pain was sudden and without a trigger factor in 85 percent of cases. Attacks occurred in the daytime (33 percent) as well as at night (35 percent). The pain was described as cramping, spasm-like, or stabbing in 76 percent of cases. It did not radiate in 93 percent of cases. There were no concomitant symptoms in 81 percent of cases. Attacks stopped spontaneously in 67 percent of cases. The average duration was 15 minutes (range, 5 seconds to 90 minutes). The average annual number of attacks was 13 (range, 1-180). CONCLUSIONS: Proctalgia fugax affects twice as many females as males at approximately aged 50 years. Commonly the roughly once-monthly attack occurs as a sudden pain with no trigger factor, diurnally as often as nocturnally. The nonradiating cramp, spasm, or stabbing pain, without concomitant symptoms, is most severe on average after 15 minutes and declines spontaneously.

Formalin application in the treatment of chronic radiation-induced hemorrhagic proctitis--an effective but not risk-free procedure: a prospective study of 33 patients.

PURPOSE: This prospective study evaluated the efficacy and safety of local formalin application in chronic refractory radiation-induced hemorrhagic proctitis. METHODS: All patients were treated under anesthesia by direct application of 4 percent formalin to the affected rectal areas. RESULTS: The study included 33 patients (17 women) and was conducted between January 1994 and December 2001. There were 11 anal cancers (33 percent), 11 prostate cancers, 9 cervical or endometrial cancers, 1 bladder cancer, and 1 rectal cancer. The mean number of daily rectal bleeds was 2.7 (range, 0.5-15). Nineteen patients (58 percent) were blood transfusion dependent. Twenty-three patients had only one formalin application and 10 patients required a second application because of the persistent bleeding. The treatment was effective in 23 cases (70 percent): 13 patients had complete cessation of bleeding and 10 patients had only minor bleeding. Six anal or rectal strictures occurred: 4 patients had been treated for anal cancer (36 percent) and 2 patients had been treated for other cancers (9 percent). None of the strictures was malignant. Anal incontinence worsened in 5 patients of the 11 who had been treated for anal cancer (45 percent) and occurred in 4 of the 22 other patients (18 percent). CONCLUSION: Formalin application is an effective treatment for chronic radiation-induced hemorrhagic proctitis. However, local morbidity is not negligible. This result may be related to the high proportion of anal cancers in the series. In our opinion, therefore, formalin application should be reserved for severe hemorrhagic proctitis refractory to medical treatment and should be thoroughly discussed in cases of anorectal radiation-induced stricture, prior anal incontinence, or treated anal cancer.