The number of patients desiring fertility-preserving treatment for endometrial cancer rather than standard surgical management continues to increase. We aimed to evaluate the efficacies of fertility-preserving treatments on the live birth rate, remission and relapse rates for women with stage 1a grade 1 endometrial carcinoma to support patient counselling. We performed a meta-analysis for our primary outcomes of overall remission and relapse rate, and for secondary analysis, we divided papers into treatment type: systemic progestins, intrauterine progestins or hysteroscopic resection and adjuvant hormonal treatment. Thirty-five observational studies met inclusion criteria, with a total of 624 patients. Overall, conservative treatment of endometrial cancer showed a remission rate of 77% (95% CI: 70–84%), a relapse rate of 20% (95% CI: 13–27%) and a live birth rate of 20% (95% CI: 15–25%) with more favourable outcomes for the hysteroscopic resection group. Hysteroscopic resection and adjuvant hormonal treatment had the most favourable fertility and oncological outcomes. Further high-quality prospective multi-centre trials are warranted to determine the optimal treatment regimen and dosage and risk stratification for these patients. The number of women diagnosed with womb cancer who want to preserve their fertility is increasing. Traditional treatment involves surgery to remove the womb and ovaries, rendering women infertile. Fertility-preserving treatments (e.g. hormone therapy, removing only affected areas) exist but their impact on remission, relapse and fertility is not certain. Our team discovered that for women who underwent fertility-preserving treatment: three in four had cancer remission, one in five had cancer relapse and one in five had a successful birth. More research is needed to work out the best fertility-preserving treatment and identify which women are more likely to have successful pregnancies. Overall, our research will help to counsel women diagnosed with womb cancer who want to preserve their fertility or are unsuitable for major surgery more effectively.
Underlying liver disease and the intrinsic chemoresistance have historically hampered the development of efficacious treatments in HCC. However, in the last few years, immunotherapy-based combinations have emerged as efficacious therapeutic strategy in this setting. This paper critically summarizes the recent therapeutic progress in the systemic treatment of HCC.This paper examines the preclinical rationale of the following combinations in HCC: dual checkpoint inhibitors, immune checkpoint inhibitors plus anti-angiogenic agents, and immune checkpoint inhibitors plus tyrosine kinase inhibitors. Results of recent clinical studies are presented, along with a brief overview of ongoing and future trials.The approval of atezolizumab plus bevacizumab and the positive results of the HIMALAYA trial have broadened the therapeutic scenario for advanced HCC, opening, at the same time, new challenges. First of all, predictive biomarkers to allocate patients to the best treatment are eagerly required; second, specific studies are urgently needed to define the use of new combinations in patients usually excluded from clinical trials, e.g. those with deranged liver function and HIV or transplant recipients. Finally, with new combinations being translated into earlier stages, profound changes are soon expected in the adjuvant and neoadjuvant setting.
Transthyretin amyloid cardiomyopathy (ATTR-CM) is increasingly diagnosed at an early stage of the disease natural history, defined as National Amyloidosis Centre (NAC) ATTR Stage I. The natural history of early-stage ATTR-CM remains poorly characterized.
Aims Tourette's Syndrome (TS) is a neurodevelopmental disorder, which often presents in childhood and is hallmarked by motor and vocal tics. Obsessive-Compulsive Disorder (OCD) is a chronic neuropsychiatric condition characterised by intrusive thoughts and time-consuming repetitive behaviours. Research suggests that 15-20% of adult patients with TS will also meet the diagnostic criteria for OCD. Both illnesses appear to have neurobiological similarities but a differing course and clinical response to pharmacological treatments. Despite this, research into optimal management of adults with co-occurring TS or other tic disorders and OCD remains sparse. Comorbidities, are known to be poor predictor of response to selective serotonin reuptake inhibitors (SSRI) monotherapy in OCD and are often associated with treatment-refractory OCD. Similarly SSRI monotherapy in patients with OCD and comorbid TS can sometimes worsen motor tics (1 in 2000) and fail to improve OCD symptoms. In this review, we aim to evaluate evidence on the management of patients with co-occurring TS and OCD and address an important knowledge gap in clinical practice. Method This review was conducted in accordance with PRISMA Guidelines. We performed a search using PubMed, Cochrane Library and PsychINFO using the following Boolean Input “Tourettic-OCD” OR “tic-related OCD” OR ((OCD OR “obsessive-compulsive” OR “obsessive compulsive”) AND (Tourette OR “Tourette's” OR Tourettes OR tic))”. The search was conducted until January 2020. We then screened the articles of systematic reviews to extract additional studies from their reference lists. Result 1888 studies were identified, of which 15 clinical trials were included in our systematic review. The presence of tics in patients with OCD are a major predictor for treatment-refractory OCD and a lack of improvement following monotherapy with SSRIs. Dual therapy with an SSRI and antipsychotics (particularly risperidone) are associated with improved outcomes in OCD patients with tics and TS patients with obsessive-compulsive symptoms. However, conjoint therapy with neuroleptics and SSRIs was only investigated when OCD burden was unsatisfactory following SSRI monotherapy. Conclusion There are clinical implications when a patient with OCD also has a chronic tic disorder. The findings indicate the need for further research, particularly in the form of a larger cohort in randomised controlled trials, to determine when it is best to initiate patients with OCD and comorbid tic disorders on a dual antipsychotic-SSRI management strategy. Further evidence should also be done to determine other characteristics that predict an improvement to conjoint SSRI/neuroleptic therapy for effective symptom reduction.
UNSTRUCTURED The COVID-19 pandemic has inspired us, as medical students, to reflect upon the communication training we have received in medical school and the obstacles we have faced in the clinic due to COVID-19. We hold the view that our communication training is inadequate; this view is driven by our limited exposure to patients, a situation that is currently being exacerbated by the pandemic. The medical curriculum must be inclusive of all groups and take into account the new challenges arising during the COVID-19 pandemic.
The laws governing cannabis are evolving worldwide and associated with changing patterns of use. The main psychoactive drug in cannabis is Δ9-tetrahydrocannabinol (THC), a partial agonist at the endocannabinoid CB1 receptor. Acutely, cannabis and THC produce a range of effects on several neurocognitive and pharmacological systems. These include effects on executive, emotional, reward and memory processing via direct interactions with the endocannabinoid system and indirect effects on the glutamatergic, GABAergic and dopaminergic systems. Cannabidiol, a non-intoxicating cannabinoid found in some forms of cannabis, may offset some of these acute effects. Heavy repeated cannabis use, particularly during adolescence, has been associated with adverse effects on these systems, which increase the risk of mental illnesses including addiction and psychosis. Here, we provide a comprehensive state of the art review on the acute and chronic neuropsychopharmacology of cannabis by synthesizing the available neuroimaging research in humans. We describe the effects of drug exposure during development, implications for understanding psychosis and cannabis use disorder, and methodological considerations. Greater understanding of the precise mechanisms underlying the effects of cannabis may also give rise to new treatment targets.
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