No abstract available

1. Sodium 2-mercaptoethanesulfonate (MESNA) is widely used as a uroprotective agent to prevent haemorrhagic cystitis (HC) associated with oxazaphosphorine chemotherapy; however, emerging evidence suggests broader cytoprotective potential beyond the urinary system.

2. This review systematically compiles and evaluates preclinical and clinical evidence on the multi-organ protective effects of MESNA, including its roles in mitigating nephrotoxicity, hepatotoxicity, cardiotoxicity, neurotoxicity, pulmonary injury, gastrointestinal damage, and reproductive toxicity.

3. The protective mechanisms of MESNA are primarily attributed to its thiol-mediated detoxification, antioxidant activity, and anti-inflammatory effects, including scavenging of reactive oxygen species (ROS), reduction of lipid peroxidation, modulation of cytokine responses, and maintenance of cellular redox balance.

4. In addition to its established clinical use in oncology, MESNA demonstrates potential applications in surgical procedures, ischemia-reperfusion injury, and combination therapies, although current clinical evidence supporting its systemic protective effects remains limited.

5. Despite its promising therapeutic profile, factors such as short plasma half-life, limited systemic bioavailability, and variability in clinical outcomes highlight the need for further mechanistic studies and well-designed clinical trials to establish its role as a multi-organ cytoprotective agent.

Paravalvular leak (PVL) refers to the retrograde flow of blood through a channel between an implanted valve prosthesis and native cardiac tissue, due to the absence of an appropriate seal. Most PVLs are haemodynamically non-significant; however, large leaks can present with symptoms of heart failure and/or haemolysis, with impact on quality of life. In many patients, re-operation is associated with high risk and alternative treatments using transcatheter closure techniques have been applied. We present the case of a septuagenarian male who underwent aortic PVL closure facilitated by use of a guide catheter extension and intravascular ultrasound. This report illustrates that these adjunctive techniques, more commonly used in coronary angioplasty procedures, can be used to enable complex PVL closure.

Background and objective: Uncertainty regarding the diagnostic accuracy of ultrasound for testicular torsion (TT) and a lack of high-level evidence to inform international guidelines have led to significant global variation in its use. The objective of this study was to assess the diagnostic accuracy of ultrasound for TT.

Methods: This systematic review was undertaken in accordance with the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy. A comprehensive electronic search strategy was applied up to January 4, 2024. Colour Doppler sonography (CDS) was the primary index test, with surgical scrotal exploration or clinical follow-up as the reference standard. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to assess the risk of bias and applicability. Meta-analyses were performed using bivariate models.

Key findings and limitations: Sixty-three studies met the inclusion criteria; 54 (85.7%) assessed CDS, and the others assessed spectral doppler sonography (n = 6), contrast enhanced ultrasound (n = 1), or an alternative combination of ultrasound technologies (n = 2). The summary sensitivity (95% confidence interval [CI]) and specificity (95% CI) of CDS for the diagnosis of TT were 95.3% (91.4-97.5) and 98.3% (96.2-99.3), respectively (42 studies, 4422 participants). Patient selection (related to the risk of bias and applicability concern) was identified as the domain of the greatest methodological concern on QUADAS-2 assessment.

Conclusions and clinical implications: CDS has high diagnostic accuracy for TT. The ideal patient pathway for suspected TT should integrate timely access to ultrasound alongside clinical assessment, with careful patient counselling.

Esculetin (ESC), a naturally occurring coumarin derivative identified in various medicinal plants, has garnered significant interest owing to its multifaceted pharmacological attributes. This narrative review synthesizes contemporary experimental data derived from in silico, in vitro, and in vivo investigations pertaining to ESC within cancer-associated frameworks and chemotherapy-induced organ toxicities. The extant literature indicates that ESC possesses antioxidant and anti-inflammatory properties and influences numerous signaling cascades pertinent to oxidative stress, inflammation, and oncogenic mechanisms. Within the scope of experimental investigations, ESC has been documented to amplify the anticancer efficacy of specific chemotherapeutic agents while concurrently mitigating chemotherapy-related toxicities in vital organs. The aforementioned protective effects are primarily ascribed to the preservation of redox equilibrium, attenuation of pro-inflammatory mediators, and the induction of cytoprotective pathways. Notwithstanding, clinical trials assessing ESC within these contexts are presently deficient, and discrepancies in experimental paradigms, dosing strategies, and bioavailability concerns related to formulation may impede direct translation to clinical practice. Collectively, this review elucidates ESC's structural and chemical attributes, principal pharmacological mechanisms, and its burgeoning preclinical significance in cancer models and the management of chemotherapy-induced toxicity. Subsequent research endeavors should emphasize the establishment of standardized experimental frameworks, pharmacokinetic validation, and clinical assessment to ascertain translational significance.

No abstract available

We present a rare case of allergic bronchopulmonary aspergillosis (ABPA) with endobronchial aspergilloma in a 70-year-old man who presented with acute total collapse of the left lung. Initial imaging raised concern for malignancy, but bronchoscopy revealed a fungal ball obstructing the left main bronchus. Serological markers confirmed ABPA. Treatment with bronchoscopy-guided clearance, oral corticosteroids, and voriconazole led to complete clinical and radiological recovery. This case highlights the importance of considering fungal aetiologies in atypical presentations of lung collapse

Objective:
We conducted a systematic review and meta-analysis to assess the effectiveness of Intensive Community Care and Services (ICCS) compared with treatment as usual (TAU), including inpatient care, and to synthesize common psychosocial interventions used within ICCS.

Method:
We searched 14 databases from Jan 1, 1999, to May 30, 2025, for quantitative studies of ICCS for adolescents predominantly (aged 12-18 years) with mental health problems. We used a random-effects meta-analysis of randomized controlled trials (RCTs) comparing ICCS versus TAU (and inpatient care only), on psychosocial functioning, mental health and cost-effectiveness outcomes. We used a narrative synthesis with an adapted Delphi approach to identify common psychosocial interventions and theoretical mechanisms. The protocol was registered in PROSPERO.

Results:
We included 48 publications on 35 unique ICCS evaluations (N=6917 adolescents; median age 14.5 years) involving admission avoidance/home treatment, assertive outreach and family preservation models. Meta-analysis of 11 unique RCTs (range: 297-1176 participants per outcome) showed that, compared with TAU, ICCS yielded statistically significant improvements in psychosocial functioning (Hedges' g= 0.15, 95% CI=0.04, 0.26; 9 RCTs), reductions in inpatient admission days (-0.48 -0.82, -0.15; 4 RCTs), total emotional and behavioral problems (-0.15, -0.30, -0.01; 5 RCTs), and externalizing symptoms (-0.18, -0.30,-0.06; 6 RCTs) post-treatment. The effect for psychosocial functioning increased and remained significant when comparing ICCS with inpatient care only (0.25, 0.04, 0.46; 5 RCTs). No significant differences were found for internalizing symptoms, family functioning, or total costs. The narrative synthesis showed that psychosocial interventions consistently included enhanced engagement strategies, cognitive behavioral therapy, family systems approaches, and dialectical behavior therapy skills.

Conclusion:
For adolescents with severe mental health problems, ICCS yielded small but significant improvements in psychosocial functioning, reductions in inpatient days and emotional and behavioral symptoms, while achieving comparable effects for other outcomes. Findings support the expansion of ICCS as a viable alternative to inpatient care. Future research should prioritize multisite RCTs and developing and evaluating standardized psychosocial intervention guidelines to enhance treatment fidelity and outcomes

Purpose of review:
Point-of-care ultrasound (POCUS) has transformed emergency medicine by providing a noninvasive, accessible, repeatable, efficient, and cost-effective imaging tool to the bedside. This article is a narrative review of the most impactful POCUS literature over the past 18 months, identifying and highlighting the most common emerging themes.

Recent findings:
We identified five main themes in the recent POCUS literature: ultrasound-guided regional anesthesia, POCUS in resuscitation, diagnostic POCUS, technology and artificial intelligence, and POCUS governance and administration.

Summary:
The recent body of literature strengthens the utility of POCUS in emergency medicine, demonstrating its efficacy, safety, and efficiency across multiple clinical scenarios. The literature continues to expand the scope of POCUS by covering new diagnostic applications and integrating emerging technologies, while continuing to build a robust governance framework. Future research should focus on patient-oriented outcomes, implications of POCUS protocolization and clinical application, and the impact of POCUS at hospital and healthcare systems levels.

No Abstract Available

Objectives: Self-compassion is a positive psychological factor linked to improved physical and psychological outcomes across different chronic illness populations. However, the extent to which self-compassion contributes to reduced distress across different conditions or as a function of participant factors is not clear. The current meta-analysis aimed to quantify the association between self-compassion and psychological distress in different chronic illness populations and evaluate the factors that moderate this association.

Methods: A systematic search of three electronic databases identified research reporting associations between self-compassion and psychological distress in chronic illness. A random effects meta-analysis was conducted to evaluate the association between self-compassion and psychological distress. Moderator analyses were conducted for sample characteristics and distress types. A bespoke tool evaluated study quality.

Results: Searches yielded 51 eligible studies with 57 effect sizes. Meta-analysis revealed that self-compassion was negatively associated with psychological distress (r = -.516; 95% CIs [-.55, -.48]; p = .000). Moderator analyses were significant for distress type and chronic illness group, with effects being largest for stress and neurological conditions. Effects did not vary by sex, age or illness duration.

Conclusions: Findings from this first comprehensive investigation of the link between self-compassion and distress in chronic illness highlight the protective role of self-compassion for chronic illness populations. These results lay the foundation for further research into understanding the processes that link self-compassion to lower psychological distress, and that examine the effectiveness of self-compassion interventions in chronic illness populations, to further advance knowledge and inform practice in this area.

Fractured and missing teeth within the aesthetic zone have always posed a clinical challenge for the dental team. Management and treatment requires the input from a number of dental specialists to guarantee a high quality result. A case report is presented to demonstrate an effective combined orthodontic/restorative approach that fully restored aesthetics and function. The report is of a 14-year-old girl who traumatized her maxillary central incisors, in a dentition that was already compromised as she had congenital absence of her maxillary left lateral incisor.

Using fixed orthodontic appliances, the fractured teeth were extruded to bring the fracture line above the level of the alveolar bone. This movement allowed an immediate aesthetic improvement, using stainless steel prefabricated posts and composite resin buildups, which also facilitated further orthodontic tooth movement. Teeth, that would otherwise have been extracted, were salvaged and, utilizing a multidisciplinary team approach, a reasonable long-term prognosis has resulted.

CPD/Clinical Relevance: This case report aims to demonstrate how a multidisciplinary team approach in Orthodontics can be utilized for management of severely handicapped dentitions that have sustained dental injury. It is not the aim of this case report to discuss the treatment of dental injuries but to demonstrate and provide an overview of the possible treatment modalities that can be effective in restoring function and aesthetics, with special consideration given to missing teeth and subgingival crown fractures within the aesthetic zone.

BACKGROUND: Cancer of unknown primary is the fourth most common cause of cancer death in the United Kingdom. National guidance in 2010 recommended the establishment of a dedicated unknown primary team to facilitate targeted investigation and symptom control. A service development project was undertaken to identify those affected by malignancy of unknown origin and institute a pathway for coordinating their care led by a palliative physician.
METHOD: In order to describe the patient population and illness trajectory and to assess the effect of the new pathway on the clinical outcomes we used a retrospective and prospective comparative case notes survey to identify the pre- and post-pathway population. This took place in secondary care. Inclusion criteria were patients with metastatic disease with no known primary; exclusion criteria were where the site of metastasis was so suggestive of a primary that it would be managed as per that disease process. 88 patients were included.
RESULTS: Mean age was 72.5 years. The mean survival time from presentation was 81.8 days. There was no difference pre or during pathway implementation in age, performance status or survival time. There was no reduction in the numbers referred for tumour directed therapy. There was a non-statistically significant reduction in the number who died in hospital during the pathway implementation.
CONCLUSIONS: This study suggests having a metastatic malignancy of unknown primary origin service led by a palliative physician does not reduce the number referred for tumour directed therapy. It also adds evidence of the poor prognosis and thus the need for early palliative care input.

Environments that support pre- and post-registration students' and staff learning are vital to ensure the delivery of high quality patient care by knowledgeable and competent healthcare practitioners. A project was undertaken at Chesterfield Royal Hospital NHS Foundation Trust to modernise and enhance preceptorship against a background of national and local drivers. This article describes the development, piloting and evaluation of a new role designed to support and enhance practice learning environments for newly qualified nurses, preceptors, pre-registration nursing students and mentors. The article identifies the factors that affect clinical learning environments and discusses some practical solutions to the challenges associated with learning in practice. Finally, the article offers some recommendations and implications for practice in relation to the pilot outcomes.

Purpose: To describe a hitherto unreported late ocular surface complication of retinal detachment surgery around a radial segment explant.

Methods: A single case report of a 72-year-old white man, with a previous history of right scleral buckling surgery for retinal detachment surgery 25 years ago, presented with right-sided ptosis of 6 months duration.

Results: Ocular surface examination showed a prominent right supero-nasal quadrant radial segment explant, around which there was bulky pink conjunctival mass, extending from the supero-medial fornix down to the medial canthal area and inferior medial fornix with similar changes seen on the upper medial tarsal conjunctiva. The clinical differential diagnosis was either inflammation from an exposed radial explant or lymphoma. Biopsies of the conjunctival mass showed perivascular and interstitial solid eosinophilic deposits of amyloid, with scattered giant cells; the amyloid was of AL type. There was no morphological or immunohistochemical evidence of lymphoma or a plasma cell neoplasm in the specimen.

Conclusion: This is the first report of localized conjunctival amyloid deposition, secondary to a retinal detachment radial explant. It is proposed that the localized amyloid deposit arose from the ocular surface irritative effects of the radial explant.

Esophageal varices are dilated submucosal esophageal veins that connect the portal and systemic circulations. Bleeding esophageal varices is a well-recognized complication of liver cirrhosis.It is known that in active variceal bleeding, treatment needs to be started promptly. Treatments comprise band ligation, sclerotherapy, removable stent placement, balloon tamponade, and transjugular intrahepatic portosystemic shunt (TIPS).We report a case in which hemodynamic stability can be maintained with the use of Purastat to control bleeding

Lifelong learning refers to the systematic acquisition, renewal, updating and completion of knowledge. It is synonymous with the term 'self-directed learning'. This is a new educational strategy meant to consolidate knowledge in a fashion that is reproducible for a lifetime with successful application to both known and unknown clinical exercises. The development of lifelong learning is based on the principles of andragogy (autonomy and independence in one's learning activities), reflection and learning from experience. This paper deals with the development of these theories culminating in the advent of self-directed learning. Evidence to support experiential, reflective and self-directed learning is provided, including the use of rating scales. An example from obstetrics is used to highlight the application of these principles. There are barriers to adopting a new educational paradigm, however, lifelong learning remains an excellent tool for continuous professional development.

Introduction Seroma formation is the most common complication after modified radical mastectomy (MRM). It leads to increased pain and discomfort, potentially prolonging morbidity and treatment. Various treatment modalities are being used to decrease the incidence of seroma formation. The objective of this study was to compare intravenous hydrocortisone injection versus placebo in patients undergoing MRM in terms of frequency of post-operative seroma formation. Methods This randomized, double-blinded, placebo-controlled study was conducted at Surgical Unit-I, Holy Family Hospital, Rawalpindi, Pakistan from January 2021 to December 2021. A total of 152 female patients were randomly assigned to each of the study and placebo groups. Group I patients received 100 mg of hydrocortisone intravenously while group II patients received one ml of 0.9% normal saline intravenously prior to induction of general anesthesia for MRM. The incidence of seroma formation after 10 days of MRM and total drain volume till their removal was measured in all patients. Results The mean age was 48.42±10.15 in Group I, while it was 47.67±10.75 in Group II. Mean drain output till removal was 99.14±31.01 ml in the hydrocortisone group and 177.57±63.37 ml in the placebo group. Forty-eight patients developed seroma (31.58%), of whom nine received intravenous hydrocortisone and 39 received normal saline (P=0.000). Conclusion Intravenous hydrocortisone is effective in terms of frequency of post-operative seroma formation as compared to placebo in patients undergoing MRM.

This article aims to outline the role and training of orthodontic auxiliaries in the UK, including the development of orthodontic therapists (OTs). The limitations and findings from a survey taken to understand the training and scope of orthodontic auxiliaries across Europe are provided and we reflect on the desirability and feasibility of standardized training for OTs, particularly in light of Brexit.

CPD/Clinical Relevance: Orthodontic auxiliaries are important members of the dental team. It is important that the training, role and scope of practice of all team members are understood to allow safe delegation and supervision.

This article describes the problem of disorientation in students as they become doctors. Disorientation arises because students have a poor or inaccurate understanding of what they are training to become. If they do not know what they are becoming it is hard for them to prioritise and contextualise their learning, to make sense of information about where they are now (assessment and feedback) or to determine the steps they need to take to develop (formative feedback and "feedforward"). It is also a barrier to the early development of professional identity. Using the analogy of a map, the paper describes the idea of a curriculum that is articulated as a developmental journey--a "roadmap curriculum". This is not incompatible with a competency-based curriculum, and certainly requires the same integration of knowledge, skills and attitudes. However, the semantic essence of a roadmap curriculum is fundamentally different; it must describe the pathway or pathways of development toward being a doctor in ways that are both authentic to qualified doctors and meaningful to learners. Examples from within and outside medicine are cited. Potential advantages and implications of this kind of curricular reform are discussed.