Can stratification biomarkers address the heterogeneity of autism spectrum disorder?

The search for biomarkers for autism spectrum disorder (henceforth autism) has received a lot of attention due to their potential clinical relevance. The clinical and aetiological heterogeneity of autism suggests the presence of subgroups. The lack of identification of a valid diagnostic biomarker for autism, and the inconsistencies seen in studies assessing differences between autism and typically developing control groups, may be partially explained by the vast heterogeneity observed in autism. The focus now is to better understand the clinical and biological heterogeneity and identify stratification biomarkers, which are measures that describe subgroups of individuals with shared biology. Using stratification approaches to assess treatment within pre-defined subgroups could clarify who may benefit from different treatments and therapies, and ultimately lead to more effective individualised treatment plans.

Management of post-acute COVID-19 patients in geriatric rehabilitation: EuGMS guidance

Purpose To describe a guidance on the management of post-acute COVID 19 patients in geriatric rehabilitation. Methods The guidance is based on guidelines for post-acute COVID-19 geriatric rehabilitation developed in the Netherlands, updated with recent insights from literature, related guidance from other countries and disciplines, and combined with experiences from experts in countries participating in the Geriatric Rehabilitation Special Interest Group of the European Geriatric Medicine Society. Results This guidance for post-acute COVID-19 rehabilitation is divided into a section addressing general recommendations for geriatric rehabilitation and a section addressing specific processes and procedures. The Sect. “General recommendations for geriatric rehabilitation” addresses: (1) general requirements for post-acute COVID-19 rehabilitation and (2) critical aspects for quality assurance during COVID-19 pandemic. The Sect. “Specific processes and procedures”, addresses the following topics: (1) patient selection; (2) admission; (3) treatment; (4) discharge; and (5) follow-up and monitoring. Conclusion Providing tailored geriatric rehabilitation treatment to post-acute COVID-19 patients is a challenge for which the guidance is designed to provide support. There is a strong need for additional evidence on COVID-19 geriatric rehabilitation including developing an understanding of risk profiles of older patients living with frailty to develop individualised treatment regimes. The present guidance will be regularly updated based on additional evidence from practice and research.

KRAS mutation: from undruggable to druggable in cancer

Cancer is the leading cause of death worldwide, and its treatment and outcomes have been dramatically revolutionised by targeted therapies. As the most frequently mutated oncogene, Kirsten rat sarcoma viral oncogene homologue (KRAS) has attracted substantial attention. The understanding of KRAS is constantly being updated by numerous studies on KRAS in the initiation and progression of cancer diseases. However, KRAS has been deemed a challenging therapeutic target, even “undruggable”, after drug-targeting efforts over the past four decades. Recently, there have been surprising advances in directly targeted drugs for KRAS, especially in KRAS (G12C) inhibitors, such as AMG510 (sotorasib) and MRTX849 (adagrasib), which have obtained encouraging results in clinical trials. Excitingly, AMG510 was the first drug-targeting KRAS (G12C) to be approved for clinical use this year. This review summarises the most recent understanding of fundamental aspects of KRAS, the relationship between the KRAS mutations and tumour immune evasion, and new progress in targeting KRAS, particularly KRAS (G12C). Moreover, the possible mechanisms of resistance to KRAS (G12C) inhibitors and possible combination therapies are summarised, with a view to providing the best regimen for individualised treatment with KRAS (G12C) inhibitors and achieving truly precise treatment.

Graves' disease: pathophysiological aspects and considerations about using the chemometric analysis in the study of the disease

Graves’ disease is an immune system disorder that results in the overproduction of thyroid hormones (hyperthyroidism). Thyroid disorders are a societal problem of great public concern because of their high prevalence. This problem can affect the well-being and quality of life of patients. The predisposing factors leading to this disease are not yet fully established and are likely to be interconnected in a complex way.  Chemometric analysis allows for the detection of specific relationships between the medical parameter measurements obtained from the patients in an observation group, and the identification of patterns of similarity between these patients. It is not commonly used in clinical trials; however, it can provide reliable information which may help in creating more successful, individualised treatment strategies for established groups (patterns) of patients. The aim of this review is to summarize the latest knowledge about the risk factors for Graves’ disease and considerations about using the chemometric analysis in the study of the disease.

The therapeutic and prognostic implications of immunobiology in colorectal cancer: a review

Colorectal cancer represents the second leading cause of cancer-related death worldwide. The therapeutic field of immuno-oncology has rapidly gained momentum, with strikingly promising results observed in clinical practice. Increasing emphasis has been placed on the role of the immune response in tumorigenesis, therapy and predicting prognosis. Enhanced understanding of the dynamic and complex tumour-immune microenvironment has enabled the development of molecularly directed, individualised treatment. Analysis of intra-tumoural lymphocyte infiltration and the dichotomisation of colorectal cancer into microsatellite stable and unstable disease has important therapeutic and prognostic implications, with potential to capitalise further on this data. This review discusses the latest evidence surrounding the tumour biology and immune landscape of colorectal cancer, novel immunotherapies and the interaction of the immune system with each apex of the tripartite of cancer management (oncotherapeutics, radiotherapy and surgery). By utilising the synergy of chemotherapeutic agents and immunotherapies, and identifying prognostic and predictive immunological biomarkers, we may enter an era of unprecedented disease control, survivorship and cure rates.

Central sleep apnea in patients with heart failure: whom to screen and how to treat? – A brief review

Central sleep apnoea (CSA) in patients with heart failure (HF) has gained considerable interest in the sleep field within the last decade. Early detection and polysomnography (PSG) patterns recently stated, as well as limited therapeutic approaches remain challenging, that of the positive airway pressure (PAP) therapies show positive effects on cardiovascular mortality in randomised controlled trials (RCTs). The era of personalised medicine promotes further analyses of phenotyping of HF patients for individualised treatment consecutively.

Developing a model to predict individualised treatment for gonorrhoea: a modelling study

ObjectiveTo develop a tool predicting individualised treatment for gonorrhoea, enabling treatment with previously recommended antibiotics, to reduce use of last-line treatment ceftriaxone.DesignA modelling study.SettingEngland and Wales.ParticipantsIndividuals accessing sentinel health services.InterventionDeveloping an Excel model which uses participants’ demographic, behavioural and clinical characteristics to predict susceptibility to legacy antibiotics. Model parameters were calculated using data for 2015–2017 from the Gonococcal Resistance to Antimicrobials Surveillance Programme.Main outcome measuresEstimated number of doses of ceftriaxone saved, and number of people delayed effective treatment, by model use in clinical practice. Model outputs are the predicted risk of resistance to ciprofloxacin, azithromycin, penicillin and cefixime, in groups of individuals with different combinations of characteristics (gender, sexual orientation, number of recent sexual partners, age, ethnicity), and a treatment recommendation.ResultsBetween 2015 and 2017, 8013 isolates were collected: 64% from men who have sex with men, 18% from heterosexual men and 18% from women. Across participant subgroups, stratified by all predictors, resistance prevalence was high for ciprofloxacin (range: 11%–51%) and penicillin (range: 6%–33%). Resistance prevalence for azithromycin and cefixime ranged from 0% to 13% and for ceftriaxone it was 0%. Simulating model use, 88% of individuals could be given cefixime and 10% azithromycin, saving 97% of ceftriaxone doses, with 1% of individuals delayed effective treatment.ConclusionsUsing demographic and behavioural characteristics, we could not reliably identify a participant subset in which ciprofloxacin or penicillin would be effective. Cefixime resistance was almost universally low; however, substituting ceftriaxone for near-uniform treatment with cefixime risks re-emergence of resistance to cefixime and ceftriaxone. Several subgroups had low azithromycin resistance, but widespread azithromycin monotherapy risks resistance at population level. However, this dataset had limitations; further exploration of individual characteristics to predict resistance to a wider range of legacy antibiotics may still be appropriate.