Screen Failures and Causes in Inflammatory Bowel Disease Randomized Controlled Trials: A Study of 16 913 Screened Patients.

INTRODUCTION: While recruitment rates in inflammatory bowel disease (IBD) trials are continuously decreasing, the underlying reasons are likely multifactorial but remain poorly defined. Screen failure (SF) proportions and causes have not been extensively explored in IBD. AIM: We assessed SF proportions and underlying SF reasons in IBD phase 2 and 3 clinical trials. METHODS: We analyzed SF-related data from 17 randomized controlled phase 2 or 3 IBD trials. Twelve trials were in ulcerative colitis (UC) and 5 trials were in Crohn's disease (CD) operated by a single contract research organization, IQVIA. Differences between patient groups were tested for significance by Mann-Whitney and Fisher's tests when appropriate. RESULTS: We analyzed a total of 11 161 patients with UC and 5752 patients with CD. The mean SF proportion was 0.43 per trial in UC. The primary reason for SFs in UC was not meeting the overall (modified) Mayo score inclusion threshold and/or the endoscopic subscore of at least 2 (33.8% of all SF). In CD clinical trials, the mean SF proportion was at 0.53. The primary cause for SFs was not meeting the CDAI eligibility criteria (23.1% of all SFs). SF proportions were significantly higher in CD versus UC trials (P = .027). Clostridium difficile or any other intestinal infection and not meeting tuberculosis screening criteria were other major reasons for SFs both in UC and CD. CONCLUSION: High SF proportion in IBD clinical trials, particularly for CD studies, pose obstacles to patient recruitment. While underlying causes are diverse, arbitrarily defined clinical and/or endoscopic eligibility criteria remain the major limiting factors.

Analyzing data from 17 IBD clinical trials with over 16 000 screened patients, we found a screen failure (SF) proportion of 44% for UC and 51% for CD. The primary cause of SF was inadequate clinical and/or endoscopic activity scores.

Diffusion of activated ATM explains γH2AX and MDC1 spread beyond the DNA damage site.

During DNA repair, ATM-induced H2AX histone phosphorylation and MDC1 recruitment spread megabases beyond the damage site. While loop extrusion has been suggested to drive this spread, the underlying mechanism remains unclear. Herein, we provide two lines of evidence that loop extrusion is not the only driver of damage-induced γH2AX spread. First, cohesin loader NIPBL and cohesin subunit RAD21 accumulate considerably later than the phosphorylation of H2AX and MDC1 recruitment at micro-IR-induced damage. Second, auxin-induced RAD21 depletion does not affect γH2AX/MDC1 spread following micro-irradiation or DSB induction by zeocin. To determine if diffusion of activated ATM could account for the observed behavior, we measured the exchange rate and diffusion constants of ATM and MDC1 within damaged and unperturbed chromatin. Using these measurements, we introduced a quantitative model in which the freely diffusing activated ATM phosphorylates H2AX. This model faithfully describes the dynamics of ATM and subsequent γH2AX/MDC1 spread at complex DNA lesions.

An extensor digitorum brevis manus coexisting with the typical extensor indicis muscle: a rare dissection finding.

The forearm extensor muscle and hand extensor tendons are composed of several structures with unique anatomy identified with high morphological variability. During a routine dissection of a 74-year-old donated male cadaver, the right hand was isolated for educational purposes. After carefully dissecting the structures, an accessory muscle was identified. The accessory muscle corresponded to the extensor digitorum brevis manus (EDBM) inserted into the extensor indicis (EI) tendon, which was typically identified. According to the current literature, this occurrence corresponds to a rare variant, with 0.36-0.38% prevalence between the cadaveric studies. Knowledge of the hand extensor musculature is essential for orthopedics and plastic surgeons operating in the region to avoid iatrogenic injury.

A Rare Case of Sural Schwannoma With Involvement of the Medial Sural Cutaneous Nerve: A Case Report and Literature Review.

Schwannomas are benign tumors derived from Schwann cells, typically occurring in the head, neck, and upper extremities, but are less frequent in the lower extremities. They can arise sporadically or from genetic conditions such as neurofibromatosis type 2, associated with NF2 gene mutations. This report details the case of a 57-year-old female with a two-year history of a painless, slowly growing mass in the posterior aspect of the right proximal cruris. Physical examination revealed a 2 cm, elastic-hard, mobile, non-tender mass with a positive Tinel's sign. Ultrasound and magnetic resonance imaging suggested a benign nerve sheath tumor characterized by hypoechoic features. The performed surgery revealed that the tumor involved the medial sural cutaneous nerve. Histologic analysis confirmed the diagnosis of schwannoma, showing typical Antoni A and Antoni B regions. Postoperative recovery was uneventful, with no recurrence or neurological deficits at the two-month follow-up. This case demonstrates an unusual localization of a sural schwannoma and highlights the importance of precise physical examination and imaging to diagnose schwannomas accurately. Clinicians should consider schwannoma as a differential diagnosis in patients presenting with slow-growing palpable masses in the lower extremities.

Unraveling the Complex Molecular Interplay and Vascular Adaptive Changes in Hypertension-Induced Kidney Disease.

Angiogenesis, the natural mechanism by which fresh blood vessels develop from preexisting ones, is altered in arterial hypertension (AH), impacting renal function. Studies have shown that hypertension-induced renal damage involves changes in capillary density (CD), indicating alterations in vascularization. We aimed to elucidate the role of the apelin receptor (APLNR), neuronal nitric oxide synthase (nNOS), and vascular endothelial growth factor (VEGF) in hypertension-induced renal damage. We used two groups of spontaneously hypertensive rats aged 6 and 12 months, representing different stages of AH, and compared them to age-matched normotensive controls. The kidney tissue samples were prepared through a well-established protocol. All data analysis was conducted with a dedicated software program. APLNR was localized in tubular epithelial cells and the endothelial cells of the glomeruli, with higher expression in older SHRs. The localization of nNOS and VEGF was similar. The expression of APLNR and nNOS increased with AH progression, while VEGF levels decreased. CD was lower in young SHRs compared to controls and decreased significantly in older SHRs in comparison to age-matched controls. Our statistical analysis revealed significant differences in molecule expression between age groups and varying correlations between the expression of the three molecules and CD.

An accessory head of the extensor indicis: a rare case report.

PURPOSE: A deep knowledge of the variations of the posterior forearm musculature is crucial for assessing and diagnosing conditions in this region. Extensor indicis (EI) is one of the muscles in this region, which exhibits diverse anatomical variations. This report documents an extremely unusual form of the EI with an accessory head on the dorsum of the hand. METHODS: During routine dissection, an extremely rare presentation of the EI was found in the left forearm of a 94-year-old female cadaver. RESULTS: This unusual EI consisted of two muscle bellies. The traditional belly originated from the distal two-thirds of the ulna. The muscle became tendinous around the carpal area, distal to the extensor retinaculum. The tendon was subsequently joined by an accessory muscle belly originating from the distal radioulnar ligament. The EI tendon inserted onto the dorsal expansion of the index finger, ulnar to that of the extensor digitorum. The posterior interosseous nerve innervated the muscle. CONCLUSION: Herein, we report an extremely rare form of the EI. To our knowledge, EI with an accessory head has only been reported rarely over the past 200 years. Moreover, our report appears to be the first case with photographic details of this anatomical variation. Clinicians should be aware of this variation for proper diagnosis and treatment.

The superior thyroid artery origin pattern: a systematic review with meta-analysis.

PURPOSE: The current systematic review with meta-analysis aimed to investigate the pooled prevalence of the superior thyroid artery (STA) pattern of origin (distinct or fused-common origin with adjacent arteries in the form of a common trunk). The standard and uncommon variants were also studied, considering the STA's exact surface of origin and the relationship with the upper border of the thyroid cartilage (TC, reference point), considering the laterality effect. Thus, the STA topographical anatomy was considered. METHODS: An evidence-based systematic review with meta-analysis was performed according to the PRISMA 2020 guidelines. A literature search was conducted in four online databases using specific keywords, the pooled prevalence was calculated using statistical analysis in the R programming language, and multiple subgroup analyses were performed. RESULTS: The most common distinct origin of the STA was from the external carotid artery (ECA) (56.94% pooled prevalence, 95%CI: 50.89-62.89), and the rarest one was from the internal carotid artery (ICA) (< 0.01%, 95%CI: 0.00-0.00). Common trunks were also investigated, with the thyrolingual trunk emanating from the ECA estimated at 0.61% (95%CI: 0.21-1.14), representing the most common. Subgroup analysis based on the nationality, type of study, and sample size, as well as a comparison between left and right sides and males and females, were investigated. CONCLUSIONS: The most common STA origin was estimated as the ECA, the medial surface of origin, and above the TC upper border. Adequate knowledge of STA origin is paramount for surgeons, especially during thyroidectomy, not to cause iatrogenic injury to the external branch of the superior laryngeal nerve.

Please be very careful, when describing variant muscle.

This is Letter accompanies a Case Report, see article.

A Rare Case of Large Lateral Chest Wall Hibernoma.

Hibernomas, rare benign tumors originating from brown adipose tissue, pose diagnostic challenges due to their infrequent occurrence and slow growth. We present a case of a 38-year-old woman with a progressively enlarging mass in her right lateral chest wall, initially stable in size but growing during pregnancy and causing pain and functional impairment. Radiological evaluation, including x-ray and MRI, provided inconclusive results, necessitating a biopsy for a definitive diagnosis. Ultrasound-guided needle aspiration biopsy revealed typical histopathological features consistent with hibernoma. A subsequent total surgical excision with negative margins was performed. The patient achieved complete recovery without recurrence during two years of follow-up. This case underscores the importance of considering hibernoma in the differential diagnosis of adipose tissue tumors, particularly in atypical clinical presentations. Moreover, it highlights the challenges in diagnosing and managing hibernomas and emphasizes the role of MRI and biopsy in achieving accurate diagnosis and optimal treatment outcomes. Continued reporting of such cases is crucial for increasing awareness and improving the management of this rare tumor.