Royal Bournemouth Hospital

Background/Objectives: Anti-tumour necrosis factor (anti-TNF) medications were historically commonly prescribed as the first-line biologic treatment for chronic inflammatory pouch conditions. However, their use in these conditions is mainly based on retrospective studies of relatively small numbers of patients with short follow up periods. We aimed to describe the long-term outcomes of first-line anti-TNF therapy in a large, multi-centre, multi-national patient cohort with chronic inflammatory pouch conditions. Methods: This was an observational, retrospective, multi-centre, multi-national study. We included patients with chronic inflammatory pouch conditions initially treated with anti-TNF drugs infliximab (IFX) or adalimumab (ADA), who had a follow up of at least 1 year. The primary outcome was anti-TNF treatment persistence, defined as continuation of anti-TNF throughout the study period. The secondary outcome was pouch failure, defined by the need for a defunctioning ileostomy or pouch excision. Results: We recruited 98 patients with chronic inflammatory pouch conditions initially treated with anti-TNF medications—63 (64.3%) treated with IFX and 35 (35.7%) treated with ADA. Average follow up length was 94.2 months (±54.5). At the end of the study period only 22/98 (22.4%) patients were still on anti-TNF treatment. In those in whom the first-line anti-TNF was discontinued, the median time to discontinuation was 12.2 months (range 5.1–26.9 months). The most common cause for anti-TNF discontinuation was lack of efficacy despite adequate serum drug levels and absence of anti-drug antibody formation (30 patients, 30.6%). Loss of response due to anti-drug antibody formation was the cause for discontinuation in 18 patients (18.4%), while 12 patients (12.2%) stopped treatment because of adverse events or safety concerns. Out of the 76 patients discontinuing anti-TNF treatment, 34 (34.7% of the cohort) developed pouch failure, and 42 (42.8% of the cohort) are currently treated with a different medical therapy. Conclusions: First-line anti-TNF therapy for chronic pouch inflammatory conditions is associated with low long-term persistence rates. This is due to a combination of lack of efficacy and adverse events. A significant percentage of patients initially treated with anti-TNF therapy develop pouch failure.

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Abstract Background Prepouch ileitis (PPI) is inflammation of the ileum proximal to an ileoanal pouch, usually associated with pouchitis. The treatment of PPI as a specific entity is poorly studied, and long-term follow-up data are lacking. We aimed to describe the long term outcomes of biologic therapy in a large, multi-centre multi-national cohort of PPI patients. Methods This was an observational, retrospective, multi-centre, multi-national study. We included patients with an endoscopic diagnosis of PPI, treated with biologic medications, who had a follow up of at least 1 year. The primary outcome was first line biologic treatment persistence, defined as continuation of the biologic treatment throughout the study period. Secondary outcome was pouch failure, defined by the need for a defunctioning ileostomy or pouch excision. Results There were 55 patients in our cohort. Males comprised 58.2% of our cohort (32/55). Average patient age was 57, and average age at UC diagnosis was 25.1. Average follow up length was 113.2 months (range 20 - 236 months) Infliximab was first line treatment in 33 patients (60%), while 20 (36.3%) initially received Adalimumab and 2 (3.7%) received Vedolizumab treatment. Second line advanced medical treatments in our cohort included infliximab (2 patients), adalimumab (12 patients), vedolizumab (10 patients), ustekinumab (6 patients) and upadacitinib (1 patient). At the end of the study period only 9 out of 55 patients (16.4%) were still on first line biologic treatment. Persistence rates for infliximab (5/33, 15.1%) and adalimumab (3/20, 15%) were similar (p=0.99). Out of the 46 patients failing first line biologic treatment, 22 (40% of the cohort) developed pouch failure, and 24 (43.6% of the cohort) are currently treated with a different medical therapy. Conclusion First line biologic treatment for PPI is associated with low long term persistence rates. A significant percentage of PPI patients initially treated with biologics develop pouch failure.

Introduction: The introduction of targeted agents has radically changed the management of patients with chronic lymphocytic leukemia (CLL). Randomized controlled trials have shown the superiority of targeted agents over chemoimmunotherapy (CIT) in patients with relapsed/refractory (R/R) CLL. Following these trials, the treatment paradigm of CLL in daily practice shifted from CIT to targeted agents in any line of treatment. However, it is largely unknown if this has improved the overall survival (OS) of patients with R/R CLL in the real world. Methods: This is a retrospective, observational study that aimed to explore differences in the OS of patients with CLL in a real-world setting. Patients who received second-line treatment for CLL between 2010 and 2019 in five European countries (Czech Republic, Greece, Italy, Spain, and the United Kingdom) were eligible for the study. The patients were allocated to two different groups (CIT-era and BTKi-era groups) according to the actual use of BTKis in R/R settings in each country. The year when the use of BTKis surpassed 30% in any line was defined as the cutoff year for each country. Cases treated before the cutoff year were allocated to the CIT-era group, and cases treated after the cutoff year were allocated to the BTKi-era group. We compared the OS from the initial date of second line treatment between the two groups. The analysis was also done after adjusting for age at second line treatment through propensity score matching. Results: A total of 1877 patients (1384 in the CIT-era group and 493 in the BTKi-era group) from 38 centers were eligible for the study. The cutoff year was 2019, 2018, 2017, 2016, and 2014 for the Czech Republic, Greece, Italy, Spain, and the United Kingdom, respectively. In both groups, most patients were males [919 (66.4%) in the CIT-era and 337 (68.4%) in the BTKi-era group, p=0.461]. Patients in the CIT-era group were younger at both diagnosis [64 years (interquartile range (IQR)=57-71) vs 66 (IQR=59-74), p=0.001 for CIT-era and BTKi-era groups, respectively] and the start of second-line treatment [69 years (IQR=63-76) vs 73 (IQR=65, 79) p=0.001 for the CIT-era and BTKi-era groups, respectively]. The CIRS score was higher in the BTKi-era group [3 (IQR=1.25-6) vs 4 (IQR=2-6), p=0.053 for the CIT-era and BTKi-era groups, respectively]. Unfavorable disease biomarkers were similarly distributed among the two groups [del(11q): 215 (27.7%) vs. 80 (24.2%), p=0.26 | del(17p): 117 (14.7%) vs. 54 (15.7%), p=0.7 | TP53 mutations: 94 (19%) vs. 41 (17.3%), p=0.66 | unmutated immunoglobulin heavy variable (IGHV) gene status: 792 (78.8%) vs 276 (76.2%), p=0.35 for the CIT-era and BTKi-era groups, respectively]. The follow-up time from diagnosis (153 months [95% confidence intervals (CI):149-160) vs 106.6 (95% CI:98-115) for CIT-era and BTKi-era groups, respectively] and second-line treatment [81 months (95% CI:77-86) vs 30 (95% CI:27- 33) for CIT-era and BTKi-era groups, respectively] were longer for the CIT-era group. Patients in the BTKi-era group had statistically significantly better OS compared to the CIT-era group (Hazard ratio (HR): 0.74 95% CI: 0.61-0.91, p=0.003). This difference was even more pronounced when comparing OS using propensity score matching (HR: 0.71, 95% CI: 0.58-0.88, p=0.001). The median OS for the CIT-era group was 65 months (95% CI=57-71), while the median OS for the BTKi-era group was not reached (95% CI=not estimable, not estimable). Finally, we performed a univariable and multivariable analysis (MVA) to assess the risk factors for death in the entire population. TP53 aberrations and unmutated IGHV gene status remained the only statistically significant risk factors for death in the MVA (HR: 1.7, 95% CI: 1.03-3.13, p=0.039, HR: 2.48, 95% CI: 1.08-5.66, p=0.032, respectively). The only protective factor against death was treatment with BTKis in the R/R setting (HR: 0.5, 95% CI: 0.28-0.88, p=0.017). Conclusion: Our findings demonstrated that the availability of BTKis has improved the OS of patients with R/R CLL in the real-world setting.

BackgroundGeneral practitioners (GPs) often expedite indeterminate scrotal lumps for urological evaluation. While a scrotal examination by a urologist is crucial, ultrasound (US) has become a routine component of clinical assessment regardless of the clinical examination findings and the nature of the symptoms. This study aimed to evaluate the efficacy of clinical examination compared to scrotal ultrasound, even when the suspicion of cancer was low.MethodologyA retrospective review of all fast-track testicular referrals seen in the clinic between January 2018 and January 2021 was conducted. Data on clinical examination findings, ultrasound results, and final diagnoses were analyzed. Patients for whom ultrasound scans were available before clinical examination were excluded from the study to avoid confounding the results.ResultsA total of 398 male subjects were referred for urological assessment, and 123 cases were excluded based on specified exclusion criteria. Two hundred seventy-five patients were identified who underwent clinical examination by urologists and subsequent ultrasound scans. Among 30 (11%) potentially malignant cases, 18 (60%) were confirmed malignancies. Sixty-eight (24.7%) cases were deemed unlikely to be malignant, and an ultrasound scan confirmed 40 (58.8%) cases as normal and four (5.9%) cases of unexpected malignancy. Ultrasonography confirmed 19 of 27 hydroceles (70.4%), 64 of 89 epididymal cysts (71.9%), and 5 of 9 varicoceles (55.6%). Of 51 epididymo-orchitis cases, 14 (27.5%) were confirmed.ConclusionsUrological examinations demonstrated high reliability in most cases, with clinical diagnoses frequently corroborated by ultrasonographic findings. The results indicate that when there is no clinical indication for an ultrasound scan, it is more efficient to avoid unnecessary ultrasonography, as it can be time-consuming without providing additional diagnostic benefits. This underscores the value of thorough clinical assessment in guiding the need for further imaging.

The clinical relevance of cardiac troponin (cTn) elevation in takotsubo syndrome (TTS) remains uncertain. The present study sought to investigate the role of cardiac troponin (cTn) elevations in mortality prediction of patients with Takotsubo syndrome (TTS). Patients enrolled in the International Takotsubo (InterTAK) Registry from January 2011 to February 2020 with available data on peak cTn levels were included in the analysis. Peak cTn levels during the index hospitalization were used to define clinically relevant myocardial injury. The threshold at which clinically relevant myocardial injury drives mortality at 1 year was identified using restricted cubic spline analysis. Out of 2'938 patients, 222 (7.6%) patients died during 1-year follow-up. A more than 28.8-fold increase of cTn above the upper reference limit was identified as threshold for clinically relevant myocardial injury. The presence of clinically relevant myocardial injury was significantly associated with an increased risk of mortality at 5 years (adjusted HR 1.58, 95% CI 1.18-2.12, p =.002). Clinically relevant myocardial injury was related to an increased 5-year mortality risk in patients with apical TTS (adjusted HR 1.57, 95% CI 1.21-2.03, p =.001), in presence of physical stressors (adjusted HR 1.60, 95% CI 1.22-2.11, p =.001), and in absence of emotional stressors (adjusted HR 1.49, 95% CI, 1.17-1.89, p =.001). This study for the first time determined a troponin threshold for the identification of TTS patients at excess risk of mortality. These findings advance risk stratification in TTS and assist in identifying patients in need for close monitoring and follow-up.