Long-term Evaluation of Fistulotomy and Immediate Sphincteroplasty as a Treatment for Complex Anal Fistula.

BACKGROUND: Fistulotomy with immediate sphincteroplasty is a technique that can heal fistulas and decrease fecal incontinence more effectively than fistulotomy alone, in selected patients. OBJECTIVE: We aimed to perform a long-term evaluation of fecal incontinence after fistulotomy and immediate sphincteroplasty in patients with complex anal fistula. DESIGN: This prospective study included patients undergoing fistulotomy and immediate sphincteroplasty for complex anal fistula from January 2000 to December 2010. SETTINGS: The study was conducted by 2 colorectal surgeons in the coloproctology unit of the General Hospital of Elche. PATIENTS: We included patients aged ≥18 years with complex anal fistulas of cryptoglandular origin. MAIN OUTCOME MEASURES: Main outcomes were recurrence and continence after fistulotomy and immediate sphincteroplasty, according to fistula tract height and preoperative continence status. RESULTS: A total of 107 patients were included; 68.2% were men, with a mean age of 48 years and mean fistula duration of 12.8 months. The range and median follow-up period were 84 to 204 and 96 months. Thirty-seven fistulas were not primary. The overall healing rate was 84.1%. Primary fistulas healed by the end of follow-up in 58 (82.9%) of 70 patients; recurrent fistulas healed in 32 (86.5%) of 37; high tracts healed in 31 (83.8%) of 37, and nonhigh fistulas healed in 59 (84.3%) of 70. Male sex (OR = 0.66 (95% CI, 0.20-2.13); p > 0.05) and recurrent fistulas (OR = 0.43 (95% CI, 0.11-1.68); p > 0.05) could have a protective effect against postoperative fecal incontinence; however, more studies with larger sample sizes are necessary to confirm this result, whereas high fistulas showed a 4-fold increased risk of incontinence (range, 1.22-13.06; p < 0.01). One in 5 high-tracts patients experienced continence deterioration. LIMITATIONS: This was a prospective study, and randomized clinical trials with more patients and longer follow-up are needed to compare fistulotomy and immediate sphincteroplasty with other sphincter-preserving techniques. CONCLUSIONS: Fistulotomy and immediate sphincteroplasty are good options for treating complex anal fistulas, especially for recurrent fistulas, men, and patients with nonhigh tracts, with acceptable recurrence and incontinence rates. See Video Abstract at http://links.lww.com/DCR/B498. EVALUACIN A LARGO PLAZO DE LA FISTULOTOMA Y LA ESFINTEROPLASTIA INMEDIATA COMO TRATAMIENTO PARA LA FSTULA ANAL COMPLEJA: ANTECEDENTES:La fistulotomía y la esfinteroplastia inmediata es una técnica que puede curar las fístulas y disminuir la incontinencia fecal de manera más efectiva que la fistulotomía sola, en pacientes seleccionados.OBJETIVO:Nuestro objetivo fue realizar una evaluación a largo plazo de la incontinencia fecal después de la fistulotomía y la esfinteroplastia inmediata en pacientes con fístula anal compleja.DISEÑO:Este estudio prospectivo incluyó pacientes sometidos a fistulotomía y esfinteroplastia inmediata por fístula anal compleja, desde enero de 2000 hasta diciembre de 2010.ENTORNO CLINICO:El estudio fue realizado por dos cirujanos colorrectales de la Unidad de Coloproctología del Hospital General de Elche.PACIENTES:Se incluyeron pacientes ≥ 18 años con fístulas anales complejas de origen criptoglandular.PRINCIPALES MEDIDAS DE VALORACION:Los principales resultados fueron la recurrencia y la continencia después de la fistulotomía y la esfinteroplastia inmediata, de acuerdo con la altura del trayecto de la fístula y el estado de continencia preoperatoria.RESULTADOS:Se incluyeron un total de 107 pacientes; El 68,2% eran varones, con una edad media de 48 años y una duración media de la fístula de 12,8 meses. El rango y la mediana del período de seguimiento fue de 84-204 y 96 meses, respectivamente. Treinta y siete fístulas no fueron primarias. La tasa de curación general fue del 84,1%. Las fístulas primarias cicatrizaron al final del seguimiento en 58/70 (82,9%) pacientes; las fístulas recurrentes cicatrizaron en 32/37 (86,5%); los tractos altos cicatrizaron en 31/37 (83,8%) y las fístulas no altas cicatrizaron en 59/70 (84,3%). El sexo masculino (razón de posibilidades: 0,66 [0,20-2,13], p > 0,05) y las fístulas recurrentes (razón de posibilidades: 0,43 [0,11-1,68], p > 0,05) podrían tener un efecto protector contra la incontinencia fecal postoperatoria, sin embargo, más estudios con una muestra más grande son necesarios para confirmar este resultado. Fistulas altas mostraron un riesgo cuatro veces mayor de incontinencia ([1.22-13.06], p < 0.01). Uno de cada cinco pacientes con tractos altos experimentó un deterioro de la continencia.LIMITACIONES:Este fue un estudio prospectivo y se necesitan ensayos clínicos aleatorios con más pacientes y un seguimiento más prolongado para comparar la fistulotomía y la esfinteroplastia inmediata con otras técnicas de preservación del esfínter.CONCLUSIÓN:La fistulotomía y la esfinteroplastia inmediata son buenas opciones para el tratamiento de fístulas anales complejas, especialmente para fístulas recurrentes, varones y pacientes con tractos no altos, con tasas aceptables de recurrencia e incontinencia. Consulte Video Resumen en http://links.lww.com/DCR/B498.

Effect of home-based prehabilitation in an enhanced recovery after surgery program for patients undergoing colorectal cancer surgery during the COVID-19 pandemic.

BACKGROUND: Surgery remains the first curative treatment for colorectal cancer. Prehabilitation seems to attenuate the loss of lean mass in the early postoperative period. However, its long-term role has not been studied. Lockdown due to the COVID-19 pandemic has forced to carry out the prehabilitation program at home. This study aimed to assess the effect of home prehabilitation on body composition, complications, and hospital stay in patients undergoing oncological colorectal surgery. METHODS: A prospective and randomized clinical study was conducted in 20 patients operated of colorectal cancer during COVID-19 lockdown (13 March to 21 June 2020) in a single university clinical hospital. Patients were randomized into two study groups (10 per group): prehabilitation vs standard care. Changes in lean mass and fat mass at 45 and 90 days after surgery were measured using multifrequency bioelectrical impedance analysis. RESULTS: Prehabilitation managed to reduce hospital stay (4.8 vs 7.2 days, p = 0.052) and postoperative complications (20% vs 50%, p = 0.16). Forty-five days after surgery, the loss of lean mass decreased (1.7% vs 7.1%, p = 0.17). These differences in lean mass were attenuated at 90 days; however, the standard care group increased considerably their fat mass compared to the prehabilitation group (+ 8.72% vs - 8.16%). CONCLUSIONS: Home prehabilitation has proven its effectiveness, achieving an attenuation of lean mass loss in the early postoperative period and a lower gain in fat mass in the late postoperative period. In addition, it has managed to reduce hospital stays and postoperative complications. REGISTRATION NUMBER: This article is part of an ongoing, randomized, and controlled clinical trial approved by the ethics committee of our hospital and registered in ClinicalTrials.gov in August 2018 with registration number NCT03618329.

Photodynamic Therapy for the Treatment of Complex Anal Fistula.

BACKGROUND AND OBJECTIVES: To validate and analyze the results of intralesional photodynamic therapy in the treatment of complex anal fistula. STUDY DESIGN/MATERIALS AND METHODS: This prospective multicentric observational study enrolled patients treated for complex anal fistula who underwent intralesional photodynamic therapy (i-PDT). The included patients were treated from January 2016 to December 2018 with a minimum follow-up of 1 year to evaluate recurrence, continence and postoperative morbidity. Intralesional 5-aminolevulinic acid (ALA) gel (2%) was injected directly into the fistula. The internal and external orifices were closed. After an incubation period of 2 hours, the fistula was irradiated using an optical fiber connected to a red laser (Multidiode 630 PDT) operating at 1 W/cm for 3 minutes (180 J). RESULTS: In total, 49 patients were included (61.2% male). The mean age was 48 years, and the mean duration of fistula was 13 months. Of the fistulas included, 75.5% were medium transphincteric, and 24.5% were high transphincteric. The median fistula length was 4 ± 1,14 cm (range: 3-5). A total of 41 patients (83.7%) had a previous history of fistula surgery. Preoperatively, some degree of anal incontinence was found in 5 patients (10.2%). No center reported any other procedure-related complications intraoperatively. Phototoxicity was found in one patient. In the first 48 hours after the procedure, fever was reported in 2 patients (4%). At the end of follow-up, total healing was observed in 32/49 patients (65.3%). No patient reported new incontinence postoperatively. CONCLUSION: i-PDT could be considered a good choice in patients with complex anal fistulas to avoid surgery and its complications. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Clinical relevance of monitoring serum adalimumab levels in axial spondyloarthritis.

Our aim was to assess the relationship between serum adalimumab levels, anti-drug antibodies (ADA) and disease activity in patients with axial spondylarthritis (SpA). We have carried out a single-centre cross-sectional study. adalimumab and ADA levels were analysed with ELISA and correlated with SpA activity using BASDAI and ASDAS scores. Adalimumab cut-off value was calculated to discriminate inactive disease/low disease activity (BASDAI < 4; ASDAS < 2.1) from moderate/high disease activity (BASDAI ≥ 4; ASDAS ≥ 2.1), using a receiver operating characteristic (ROC) curve. Up to January 2016, 51 consecutive patients were included. The median (range) age was 46.6 (18-68) and 47.1% were women. ADA prevalence was 27.5%, with none detected in the 21.6% receiving concomitant disease-modifying antirheumatic drugs (DMARDs) (p = 0.021). Adalimumab level was normal (> 3 mg/l) in 36 patients (70.6%), all without ADA. Fifteen patients (29.4%) had subtherapeutic adalimumab levels (< 3 mg/l), with ADA in 14 (93%). Median adalimumab (mg/l) was significantly higher in patients with inactive disease/low disease activity: BASDAI < 4 vs ≥ 4: 9.5 vs 2.6 (p < 0.01); ASDAS-CRP < 2.1 vs ≥ 2.1: 9.3 vs 0.3 (p < 0.001); ASDAS-ESR < 2.1 vs ≥ 2.1: 9.9 vs 3.0 (p < 0.001), and this finding was consistent with the result of the multivariate model. Patients with inactive disease/low disease activity presented significantly lower ADA levels. The adalimumab level cut-offs and area under the curve (AUC) obtained in the ROC curves were: ASDAS-CRP (< 2.1) 4.6 mg/l (AUC 81.2%; 95% CI 67.5-94.9; p < 0.001); ASDAS-ESR (< 2.1) 7.7 mg/l (AUC 82.4%; 95% CI 69.3-95.5; p < 0.001); BASDAI (< 4) 6.4 mg/l (AUC 73.5%; 95% CI 58.6-88.3; p < 0.01). In conclusion, presence of ADA in axial SpA patients treated with adalimumab was associated with lower serum drug levels. ADA levels were lower and adalimumab levels were higher in patients with inactive disease/low disease activity based on BASDAI and ASDAS indices. Concomitant treatment with MTX reduces de likelihood of finding ADA. Serum adalimumab levels above 4.6 mg/l are recommended to avoid compromising efficacy.

Obesity decreases clinical efficacy and levels of adalimumab in patients with ankylosing spondylitis.

OBJECTIVES: Obesity can be a factor that affects response to anti-TNF drugs. However, studies on patients with ankylosing spondylitis (AS) are rare. We aimed to determine whether obesity affects serum levels of adalimumab (ADL), and immunogenicity and clinical efficacy of the drug in patients with AS. METHODS: A cross-sectional study on 57 patients with axial AS receiving ADL was conducted. They received DMARD per standard of care at their rheumatologist's discretion. Patients' body mass index (BMI) was obtained when ADL treatment began. Clinical response was evaluated using the Spanish versions of the BASDAI index and the ASDAS ESR index. Serum concentrations of free ADL (trough level) and anti-ADL antibodies were measured using Promonitor-ADL and Promonitor Anti-ADL ELISA kits (Progenika Grifols SA, Spain), just prior to the next subcutaneous injection of ADL. RESULTS: Patients with BMI >30 kg/ m2 (obese) as opposed to BMI <25 kg/ m2 (normal), presented lower blood ADL levels [5.0 (5.52) vs. 9.14 (4.3), p=0.032], increased ASDAS scores (2.58 [0.79] vs. 1.9 [0.83], p=0.03), and shorter ADL treatment time: 1.01 [0.84] vs. (1.85 [1.65]; p=0.08]), and increased BASDAI results (5.04 [2.5] vs. 3.5 [1.88]; p=0.06). Obese patients showed a lower probability of clinical response to ADL versus non-obese patients with regard to achieving BASDAI ≤4 (OR: 3.5, 95%CI: 0.84-17.19; p=0.05) or ASDAS ≤2.1 (OR: 4.64, 95%CI: 1.02-24.13; p=0.02). CONCLUSIONS: Of the AS patients receiving treatment with ADL, those that are obese had significantly lower serum ADL levels and decreased clinical response without an increase in immunogenicity.

Clinical relevance of monitoring serum levels of adalimumab in patients with rheumatoid arthritis in daily practice.

OBJECTIVES: The aim of this paper is to assess the usefulness of measuring serum levels of adalimumab (ADL) and anti-ADL antibodies in 57 patients with rheumatoid arthritis (RA) treated with ADL for at least 3 months in daily practice. METHODS: All patients received concomitant disease-modifying anti-rheumatic drug (DMARD). Receiver-operator characteristics (ROC) analysis was used to obtain the cut-off value of ADL for low disease activity (DAS28-ESR ≤3.2). RESULTS: Anti-ADL antibodies were detected in 4 (7%) patients with a mean (SD) DAS28 score of 4.6 (0.9). Patients with positive anti-ADL antibodies had significantly lower levels of ADL and higher DAS28 scores than those with negative antibodies. Patients with DAS28 ≤3.2 as compared with patients with DAS28 >3.2 showed significantly better SDAI score, higher serum concentrations of ADL and none of them showed anti-ADL antibodies. The cut-off of serum level of ADL for DAS28 <3.2 was 4.3 mg/L. According to serum levels of ADL, patients were grouped into group 1 (low level) <5.5 mg/L, group 2 (medium level) 5.5-11.3 mg/L and group 3 (high level) >11.3 mg/L. Patients in the medium group were closed to clinical remission (median DAS28 2.7) and patients in the high group were on clinical remission (DAS28 2.1). CONCLUSIONS: Serum levels of ADL should be maintained >4.3 mg/L. In patients with ADL levels >11.3 mg/L, a decrease of the dose of ADL or an increase in the interval between doses may be planned. The presence of anti-ADL antibodies was associated with a loss of clinical efficacy of ADL.

Practical application of acid dissociation in monitoring patients treated with adalimumab.

Patients treated with adalimumab (ADL) can induce anti-ADL antibodies (AAA) formation that is associated with low drug levels and clinical non-response. But, in the majority of the assays, the measurement of AAA is hampered by the presence of the drug itself. In support of immunogenicity assessment in clinical samples with subtherapeutic ADL levels, we proved acid pre-treatment for AAA detection with the Promonitor-enzyme-linked immunosorbent assay (ELISA). Were measured AAA after acidification in 32 serum samples with a subtherapeutic ADL trough level. ADL and AAA concentrations were measured by ELISA (Promonitor). The impact of drug concentration on AAA recovery (with or without acidification) was also evaluated by mixing known amounts of ADL (0.25, 0.5 and 1 mg/L) and AAA (100, 200, 300 and 400 AU/mL) from clinical samples in pooled serum. The drug significantly inhibited the detection of AAA in untreated samples. And progressively higher levels of ADL cause increasing inhibition of signal. Acid pre-treatment carried a significant increase in assay response, particularly at lower free ADL concentrations. AAA were detected in the 53 % of the samples after acid dissociation. In seven patients, the positive AAA after dissociation was detected in the first monitoring of ADL and five patients were positive 3 months later for AAA with the standard assay. Monitoring AAA using acid dissociation in patients with subtherapeutic circulating level of ADL could detect precocious problems of bioavailability, assess the immunogenicity of ADL and may be used to optimise dose regimens, thereby preventing prolonged use of inadequate therapy and guide change of treatment.

Diabetes mellitus as a cause of premature death in small areas of Spain by socioeconomic level from 2016 to 2020: A multiple-cause approach.

OBJECTIVE: This study aimed to assess premature mortality due to Diabetes in small areas of Spain between 2016 and 2020, and its relationship with socioeconomic level and the immediate cause of death. As a secondary objective, we evaluated the effect of the Covid 19 pandemic. METHODS: This was an ecological study of premature mortality due to Diabetes from 2016 to 2020, with a focus on small areas. All deaths in people under 75 years of age due to Diabetes as the underlying cause were included RESULTS: The final sample comprised 7382 premature deaths in 5967 census tracts. Women living in census tracts with an high level of deprivation(RR=2.40) were at a significantly higher risk. Mortality from Diabetes increased with deprivation, especially people aged 0-54(RR=2.40). People with an immediate cause of death related to a circulatory disease, living in census tracts with an high level of deprivation(RR=3.86) was associated with a significantly greater risk of death with underlying Diabetes. When a disease of the circulatory system was recorded as the immediate cause of death, being 65-74 years (RR=71.01) was associated with a significantly higher risk of premature mortality. CONCLUSIONS: Living in geographic areas with higher levels of socioeconomic deprivation is associated with a higher risk of premature death from Diabetes in Spain. This relationship has a greater impact on women, people under 54 years, and people at risk of death caused directly by diseases of the circulatory system. Premature mortality due to diabetes saw a modest increase in 2020.

Phytochemicals in date co-products and their antioxidant activity.

The date agro-industry needs to find appropriate techniques to give value to their co-products. This study analyzes twelve intermediate food products (IFPs) from date co-products, Medjool and Confitera cv. at several ripening stages, blanched and unblanched, for their content in bioactive compounds (phenols, tannins, flavonoids, carotenoids and anthocyanins) and the antioxidant activity (AA). IFPs from the more unripe stages had the highest AA and phytochemicals content, mainly phenols, up to 1.4 g GAE/100 g, with high proportions of tannins. Flavonoids were found in high amounts, up to 874 mg RE/100 g. Among the AA are significant the antiradical efficiency (4.62 mM TE/100 g) and chelating activity (252 µM EDTA/100 g). Blanching was beneficial for Confitera IFPs. A positive correlation was found between phenols, tannins and flavonoids and the AA; and their content could be used as indicator of the AA. Date IFPs have potential use as an antioxidant functional ingredient.

[Duration of treatment with etanercept and motives for discontinuation in a cohort of patients with rheumatic disease]. / Duración del tratamiento con etanercept y razones de discontinuación en una cohorte de pacientes con patología reumática.

OBJECTIVE: To evaluate the duration of etanercept (ETN) treatment and motives for discontinuation in our local cohort of patients with rheumatic pathology and compare them to the group with other biological treatments. PATIENTS AND METHODS: Prospective observational cohort study. Disease diagnosis, start and end date and motive for discontinuation were recorded. Survival estimation was explored using Kaplan-Meier analysis with remaining patients censored at 1-year, 2-years and 5-years follow-up. RESULTS: Ninety-two (45%) out of 205 patients started ETN treatment. Disease diagnoses recorded were: 48% rheumatoid arthritis, 33% ankylosing spondylitis, 11% psoriatic arthritis, 8% others (juvenile idiopathic arthritis, inflammatory bowel disease related spondylitis, SAPHO syndrome). 52% of patients are still on the drug. The motives for discontinuation were: inefficacy (65%), adverse events (33%) and lack of compliance (2%). Two patients discontinued ETN due to prolonged disease control. Adverse events were: infection (4 patients), post-injection skin reaction (3), uveitis (3), neoplasia (2) and others (3). Using a Kaplan-Meier analysis, at 1-year 64% (CI(95%) 54-74) of patients with ETN treatment had not experienced treatment failure, at 2-years, 59% (48-69) and at 5-years, 43% (30-52). With the rest of biologicals estimated survival was 61% (51-68), 47,5% (40-55) and 23% (10,5-32) respectively. Statistical analysis revealed significant differences (log-rank: P=.024; Breslow: P=.068; Tarone-Ware: P=.040). CONCLUSIONS: In our cohort of patients treated with ETN the estimated survival was better than patients treated with other biological drugs at 1-year, 2-years and 5-years.