Metastatic prostate cancer men’s attitudes towards treatment of the local tumour and metastasis evaluative research (IP5-MATTER) : protocol for a prospective, multicentre discrete choice experiment study

Acknowledgements We would like to thank all the participants, study PIs, trial clinicians, research nurses, Imperial Clinical Trial Unit staff and other site staff who have been responsible for setting up, recruiting participants and collecting the data for the IP5-MATTER trial. We are also grateful for the ongoing support of the Trial Management Group and our IP5-MATTER patient representatives. Finally, we would like to thank our trial funder the Wellcome Trust and University College London Hospitals (UCLH) Charity. Funding MJC’s research is support by University College London Hospitals (UCLH) Charity and the Wellcome Trust. Mesfin Genie and Verity Watson are based at the Health Economics Research Unit (HERU), University of Aberdeen. HERU is funded by the Chief Scientists Office of the Scottish Government Health and Social Care Directorate. KTJ acknowledges research grant from the UK National Institute of Health Research Clinical Research Network Eastern and has received educational grants from Bayer UK, Janssen Oncology, Pfizer, Roche, and Takeda. HUA’s research is supported by core funding from the United Kingdom’s National Institute of Health Research (NIHR) Imperial Biomedical Research Centre.Peer reviewedPublisher PD

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p

COMPARATIVE EVALUATION OF EFFECTIVITY AND SAFETY OF TOPICAL AMOROLFINE AND CLOTRIMAZOLE IN THE TREATMENT OF TINEA CORPORIS

Background: Tinea corporis is a common superficial dermatophytosis seen in tropical countries. Newer molecules are constantly being introduced for its treatment. Topical clotrimazole is in vogue as the treatment for this condition for a long time. Amorolfine is a comparatively recently introduced drug for topical use in this condition. Aims: To assess the effectivity and safety of amorolfine 0.25% cream in patients with tinea corporis, in comparison to clotrimazole 1% cream. Materials and Methods: Patients presenting with symptoms of tinea corporis were mycologically confirmed for the presence of fungal hyphae. They were randomly divided into two groups: one group received amorolfine and the other received clotrimazole. Treatment duration was for 4 weeks and study duration was for 8 weeks. Evaluation was carried out using the standard clinical parameters on day 1, day 14, day 28 and a follow-up on day 56. Adverse effects were also recorded. Data entry was done in Excel datasheet and analyzed with Epiinfo 2002. Chi-square test and t-test were used according to the type of data. Results: The patients of the two groups were matched at baseline in respect to their demographic profile. Analysis of collected data showed significant improvement in both the groups, suggesting that both the drugs were effective agents in tinea corporis infection. Between-groups comparison of mycological cure rate and clinical improvement showed no significant difference. Conclusion: Amorolfine 0.25% cream is found to be safe and effective, like clotrimazole, when used topically in tinea corporis

Bilateral tubal pregnancy: A diagnostic dilemma

ABSTRACT Bilateral tubal ectopic pregnancy is very rare and usually occurs following ovulation stimulation. Moreover preoperative diagnosis is very difficult. We are presenting a case of bilateral tubal ectopic pregnancy occurring spontaneously. Hence careful follow-up with combination of color Doppler and serum beta HCG estimation of patients after laparoscopic or open surgery for ectopic pregnancies is needed to avoid such unusual event

In Vitro and In Vivo Bone Regeneration Assessment of Titanium-Doped Waste Eggshell-Derived Hydroxyapatite in the Animal Model

Inthis work, a titanium-doped hydroxyapatite (HAp) scaffold wasproduced from two different sources (natural eggshell and laboratory-gradereagents) to compare the efficacy of natural and synthetic resourcesof HAp materials on new bone regeneration. This comparative studyalso reports the effect of Ti doping on the physical, mechanical,and in vitro as well as in vivo biological properties of the HAp scaffold.Pellets were prepared in the conventional powder metallurgy route,compacted, and sintered at 900 & DEG;C, showing sufficient porosityfor bony ingrowth. The physical-mechanical characterizations wereperformed by density, porosity evaluation, XRD, FTIR, SEM analysis,and hardness measurement. In vitro interactions were evaluated bybactericidal assay, hemolysis, MTT assay, and interaction with simulatedbody fluid. All categories of pellets showed absolute nonhemolyticand nontoxic character. Furthermore, significant apatite formationwas observed on the Ti-doped HAp samples in the simulated body fluidimmersion study. The developed porous pellets were implanted to assessthe bone defect healing in the femoral condyle of healthy rabbits.A 2 month study after implantation showed no marked inflammatory reactionfor any samples. Radiological analysis, histological analysis, SEManalysis, and oxytetracycline labeling studies depicted better invasionof mature osseous tissue in the pores of doped eggshell-derived HApscaffolds as compared to the undoped HAp, and laboratory-made samples.Quantification using oxytetracycline labeling depicted 59.31 & PLUSMN;1.89% new bone formation for Ti-doped eggshell HAp as compared toTi-doped pure HAp (54.41 & PLUSMN; 1.93) and other undoped samples. Histologicalstudies showed the presence of abundant osteoblastic and osteoclasticcells in Ti-doped eggshell HAp in contrast to other samples. Radiologicaland SEM data also showed similar results. The results indicated thatTi-doped biosourced HAp samples have good biocompatibility, new bone-formingability, and could be used as a bone grafting material in orthopedicsurgery

Additional Treatments to the Local tumour for metastatic prostate cancer - Assessment of Novel Treatment Algorithms (IP2-ATLANTA): Protocol for a multicentre, phase II randomised controlled trial

Introduction Survival in men diagnosed with de novo synchronous metastatic prostate cancer has increased following the use of upfront systemic treatment, using chemotherapy and other novel androgen receptor targeted agents, in addition to standard androgen deprivation therapy (ADT). Local cytoreductive and metastasis-directed interventions are hypothesised to confer additional survival benefit. In this setting, IP2-ATLANTA will explore progression-free survival (PFS) outcomes with the addition of sequential multimodal local and metastasis-directed treatments compared with standard care alone. Methods A phase II, prospective, multicentre, three-arm randomised controlled trial incorporating an embedded feasibility pilot. All men with new histologically diagnosed, hormone-sensitive, metastatic prostate cancer, within 4 months of commencing ADT and of performance status 0 to 2 are eligible. Patients will be randomised to Control (standard of care (SOC)) OR Intervention 1 (minimally invasive ablative therapy to prostate±pelvic lymph node dissection (PLND)) OR Intervention 2 (cytoreductive radical prostatectomy±PLND OR prostate radiotherapy±pelvic lymph node radiotherapy (PLNRT)). Metastatic burden will be prespecified using the Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease (CHAARTED) definition. Men with low burden disease in intervention arms are eligible for metastasis-directed therapy, in the form of stereotactic ablative body radiotherapy (SABR) or surgery. Standard systemic therapy will be administered in all arms with ADT±upfront systemic chemotherapy or androgen receptor agents. Patients will be followed-up for a minimum of 2 years. Primary outcome: PFS. Secondary outcomes include predictive factors for PFS and overall survival; urinary, sexual and rectal side effects. Embedded feasibility sample size is 80, with 918 patients required in the main phase II component. Study recruitment commenced in April 2019, with planned follow-up completed by April 2024. Ethics and dissemination Approved by the Health Research Authority (HRA) Research Ethics Committee Wales-5 (19/WA0005). Study results will be submitted for publication in peer-reviewed journals