Discontinuation of Anti-Tumour Necrosis Factor Therapy in Patients with Perianal Fistulizing Crohn's Disease: Individual Participant Data Meta-Analysis of 309 Patients from 12 Studies.

BACKGROUND: The risk of relapse after anti-tumour necrosis factor [TNF] therapy discontinuation in Crohn's disease patients with perianal fistulas [pCD] is unclear. We aimed to assess this risk. METHODS: A systematic literature search was conducted to identify cohort studies on the incidence of relapse following anti-TNF discontinuation in pCD patients. Individual participant data were requested from the original study cohorts. Inclusion criteria were age ≥16 years, pCD as a (co)indication for start of anti-TNF therapy, more than three doses, and remission of luminal and pCD at anti-TNF discontinuation. The primary outcome was the cumulative incidence of CD relapse using Kaplan-Meier estimates. Secondary outcomes included response to re-treatment and risk factors associated with relapse as assessed by Cox regression analysis. RESULTS: In total, 309 patients from 12 studies in ten countries were included. The median duration of anti-TNF treatment was 14 months [interquartile range 5.8-32.5]. Most patients were treated for pCD without active luminal disease [89%], received first-line anti-TNF therapy [87%], and continued immunomodulatory therapy following anti-TNF discontinuation [78%]. The overall cumulative incidence of relapse was 36% (95% confidence interval [CI] 25-48%) and 42% [95% CI 32-53%] at 1 and 2 years after anti-TNF discontinuation, respectively. Risk factors for relapse included smoking (hazard ratio [HR] 1.5 [1.0, 2.1]) and history of proctitis (HR 1.7 [1.1, 2.5]). The overall re-treatment response rate was 82%. CONCLUSIONS: This individual participant data meta-analysis, on predominantly patients with pCD without active luminal disease and first-line anti-TNF therapy, shows that over half of patients remain in remission 2 years after anti-TNF discontinuation. Therefore, anti-TNF discontinuation may be considered in this subgroup.

Bulletproof Temporal Bone: A Case of Self-Inflicted Ballistic Injury.

Temporal bone injuries due to gunshot wounds are uncommon but devastating, with a high risk of damage to critical neurovascular structures. The high resistance of the temporal bone, the densest bone in the human body, can sometimes avoid a fatal outcome. However, the complications are in many cases devastating and include hearing loss, facial paralysis, cerebrospinal fluid leakage, intracranial damage, and vascular injuries. Our goal was to report a case of ballistic injury to the temporal bone and describe the surgical approach taken for treatment. A 74-year-old man was transferred to the emergency room of our tertiary hospital, intubated and sedated, after an attempted suicide with a firearm. The CT scan showed the metal projectile lodged within the temporal bone on the right side, with the destruction of the ossicular chain and bony labyrinth. After stabilization, sedation was reversed, and the otolaryngology team was called. On examination, the entry wound was located in the cavum concha, with no active bleeding but presenting active otorrhea of cerebrospinal fluid. The patient had complete peripheral facial paralysis on the right side and spontaneous horizontal nystagmus toward the left side. Empirical antibiotic therapy was initiated. A subtotal petrosectomy was performed, with the removal of the foreign body, repair of the cerebrospinal fluid fistula, obliteration of the cavity with abdominal fat, and closure of the external auditory canal. He was discharged on the 11th-day post-surgery, maintaining complete facial paralysis and right-side anacusis, but was able to walk with assistance. In conclusion, penetrating trauma of the temporal bone is a potentially life-threatening situation, and patients that survive have a guarded prognosis, as it often leads to permanent sequelae even when managed promptly.

Laryngectomy: Phonation Alternatives and Their Impact on the Quality of Life.

Background The decision to consent to surgery is a life-changing moment. This study addresses the impact of total laryngectomy (TL) on phonation and its effect on the quality of life (QoL) of patients. The primary objective of this cohort study is to compare the alternatives in phonation rehabilitation, and the secondary objective is to identify concurrent predictors of vocal outcomes. Methodology To perform a comprehensive analysis, we reviewed data from patients who underwent TL with bilateral radical neck dissection in the Department of Otolaryngology, Head and Neck Surgery at Centro Hospitalar Universitário de Santo António between January 2010 and October 2022. Adult patients who consented to participate in the study and underwent subjective evaluation were included in this study. Data regarding clinical history was primarily collected. Statistical analysis was performed using SPSS version 26 (IBM Corp., Armonk, NY, USA). Different types of vocal rehabilitation formed the subgroups to be compared. An additional analysis was performed for baseline variables collected in the clinical records, and vocal outcomes were measured using the Self-Evaluation of Communication Experiences After Laryngectomy (SECEL) questionnaire. Furthermore, linear models taking SECEL scores as the outcome were developed. Results The first search identified a total of 124 patients operated during the study period. In total, 63 patients were alive at the time of the current follow-up, with 61 deaths (49%). Overall, 26 of the 63 alive patients completed the SECEL questionnaire. All patients were male. The mean age at diagnosis was 62.2 ± 10.6 years. The mean age at the time of subjective vocal assessment with the SECEL questionnaire was 66.3 ± 10.4 years. The mean time of follow-up after the initial diagnosis was 4 ± 3.8 years. A statistically significant difference was observed in esophageal speech (ES), which was inferior to other modalities (mean SECEL total score for ES: 46.6 ± 12.2 vs. mean SECEL total score for all other modalities: 33 ± 15.1; p = 0.03). The follow-up time correlated significantly with vocal function, as measured by the SECEL questionnaire (p = 0.013). Conclusions The SECEL questionnaire can be a valuable tool to evaluate QoL in laryngectomy patients, given its usefulness in assessing the psychological impact derived from vocal functionality in this group. ES appears inferior to other modalities regarding voice-related QoL.

Prediction of Relapse After Anti-Tumor Necrosis Factor Cessation in Crohn's Disease: Individual Participant Data Meta-analysis of 1317 Patients From 14 Studies.

BACKGROUND & AIMS: Tools for stratification of relapse risk of Crohn's disease (CD) after anti-tumor necrosis factor (TNF) therapy cessation are needed. We aimed to validate a previously developed prediction model from the diSconTinuation in CrOhn's disease patients in stable Remission on combined therapy with Immunosuppressants (STORI) trial, and to develop an updated model. METHODS: Cohort studies were selected that reported on anti-TNF cessation in 30 or more CD patients in remission. Individual participant data were requested for luminal CD patients and anti-TNF treatment duration of 6 months or longer. The discriminative ability (concordance-statistic [C-statistic]) and calibration (agreement between observed and predicted risks) were explored for the STORI model. Next, an updated prognostic model was constructed, with performance assessment by cross-validation. RESULTS: This individual participant data meta-analysis included 1317 patients from 14 studies in 11 countries. Relapses after anti-TNF cessation occurred in 632 of 1317 patients after a median of 13 months. The pooled 1-year relapse rate was 38%. The STORI prediction model showed poor discriminative ability (C-statistic, 0.51). The updated model reached a moderate discriminative ability (C-statistic, 0.59), and included clinical symptoms at cessation (hazard ratio [HR], 2.2; 95% CI, 1.2-4), younger age at diagnosis (HR, 1.5 for A1 (age at diagnosis ≤16 years) vs A2 (age at diagnosis 17 - 40 years); 95% CI, 1.11-1.89), no concomitant immunosuppressants (HR, 1.4; 95% CI, 1.18-172), smoking (HR, 1.4; 95% CI, 1.15-1.67), second line anti-TNF (HR, 1.3; 95% CI, 1.01-1.69), upper gastrointestinal tract involvement (HR, 1.3 for L4 vs non-L4; 95% CI, 0.96-1.79), adalimumab (HR, 1.22 vs infliximab; 95% CI, 0.99-1.50), age at cessation (HR, 1.2 per 10 years younger; 95% CI, 1-1.33), C-reactive protein (HR, 1.04 per doubling; 95% CI, 1.00-1.08), and longer disease duration (HR, 1.07 per 5 years; 95% CI, 0.98-1.17). In subanalysis, the discriminative ability of the model improved by adding fecal calprotectin (C-statistic, 0.63). CONCLUSIONS: This updated prediction model showed a reasonable discriminative ability, exceeding the performance of a previously published model. It might be useful to guide clinical decisions on anti-TNF therapy cessation in CD patients after further validation.