Pancreatic cancer in 2021: What you need to know to win.
Ontology highlight
ABSTRACT: Pancreatic cancer is one of the solid tumors with the worst prognosis. Five-year survival rate is less than 10%. Surgical resection is the only potentially curative treatment, but the tumor is often diagnosed at an advanced stage of the disease and surgery could be performed in a very limited number of patients. Moreover, surgery is still associated with high post-operative morbidity, while other therapies still offer very disappointing results. This article reviews every aspect of pancreatic cancer, focusing on the elements that can improve prognosis. It was written with the aim of describing everything you need to know in 2021 in order to face this difficult challenge.
Project description:PARP inhibitors (PARPi) have been demonstrated to exhibit profound anti-tumour activity in individuals whose cancers have a defect in the homologous recombination DNA repair pathway. Here, we describe the current consensus as to how PARPi work and how drug resistance to these agents emerges. We discuss the need to refine the current repertoire of clinical-grade companion biomarkers to be used with PARPi, so that patient stratification can be improved, the early emergence of drug resistance can be detected and dose-limiting toxicity can be predicted. We also highlight current thoughts about how PARPi resistance might be treated.
Project description:We review the current status of multidisciplinary care for patients with inflammatory breast cancer (IBC) and discuss what further research is needed to advance the care of patients with this disease.We performed a comprehensive review of the English-language literature on IBC through computerized literature searches.Significant advances in imaging, including digital mammography, high-resolution ultrasonography with Doppler capabilities, magnetic resonance imaging, and positron emission tomography-computed tomography, have improved the diagnosis and staging of IBC. There are currently no established molecular criteria for distinguishing IBC from noninflammatory breast cancer. Such criteria would be helpful for the diagnosis and development of novel targeted therapies. Combinations of neoadjuvant systemic chemotherapy, surgery, and radiation therapy have led to an improved prognosis; however, the overall 5-year survival rate for patients with IBC remains very low (?30%). Sentinel lymph node biopsy and skin-sparing mastectomy are not recommended for patients with IBC.Optimal management of IBC requires close coordination among medical, surgical, and radiation oncologists, as well as radiologists and pathologists. There is a need to identify molecular changes that define the pathogenesis of IBC to enable eradication of IBC with the use of IBC-specific targeted therapies.
Project description:BackgroundPneumonia is the single largest cause of death in under-five children worldwide. We conducted a systematic review to identify the knowledge gaps around childhood pneumonia in Bhutan.MethodsWe searched PubMed, ScienceDirect and Google scholar from conception to 3rd December 2018, World Health Organization, UNICEF, Bhutan's Ministry of Health and other local databases for relevant reports. We included any report describing pneumonia in Bhutanese children with regards to the burden of the disease, aetiology, related risk factors, clinical and prognostic characteristics, surveillance systems and national preventive strategies. Two review authors identified the records. We summarized the findings narratively.ResultsWe included 44 records. Although with notable decreasing trends, pneumonia is still accountable for a high burden and mortality rate in Bhutanese children. The national surveillance system focuses mainly on influenza identification but has recently introduced other viral aetiology to monitor. We found very scarce or no data with regard to the bacterial aetiology, related risk factors and clinico-radiological and prognostic characteristics.ConclusionThere is a dearth of data regarding the epidemiological, microbiological, clinical and radiological characteristics of pneumonia in children in Bhutan, leading to challenges while implementing evidence-based management and effective national preventive strategies.
Project description:The large GTPase dynamin is the first protein shown to catalyze membrane fission. Dynamin and its related proteins are essential to many cell functions, from endocytosis to organelle division and fusion, and it plays a critical role in many physiological functions such as synaptic transmission and muscle contraction. Research of the past three decades has focused on understanding how dynamin works. In this review, we present the basis for an emerging consensus on how dynamin functions. Three properties of dynamin are strongly supported by experimental data: first, dynamin oligomerizes into a helical polymer; second, dynamin oligomer constricts in the presence of GTP; and third, dynamin catalyzes membrane fission upon GTP hydrolysis. We present the two current models for fission, essentially diverging in how GTP energy is spent. We further discuss how future research might solve the remaining open questions presently under discussion.
Project description:Podcasts have become increasingly popular tools for medical education in recent years. Only requiring a computer or smart phone, podcasts are readily accessible to healthcare professionals, helping to disseminate medical information quickly and creating a wide community of listeners. With numerous medical podcasts available and limited spare time, it can be challenging for a healthcare professional to identify the most high-yield podcast. This perspectives piece describes the role of podcasts in medical education before sharing five in-depth recommendations from Yale School of Nursing and Yale School of Medicine students and faculty. These five podcasts are: The Curbsiders Internal Medicine Podcast, Flip the Script, The Clinical Problem Solvers, 2 Docs Talk, and Key Literature in Medical Education (KeyLIME) Podcast. Each podcast summary includes its average length, the episode frequency, the intended audience, a brief description, a representative episode, and quotes from interviews with the podcast hosts.
Project description:In patients with diabetes, where cardiovascular morbidity is highly prevalent, recent cardiovascular outcomes trials have identified therapies in the modern glucagon-like peptide 1 receptor agonist (GLP-1RA) and sodium-glucose cotransporter 2 inhibitor (SGLT2i) classes that significantly reduce cardiovascular events. A number of drugs in both classes have demonstrated reductions in the risk of the composite outcome of major adverse cardiovascular events (myocardial infarction, stroke, and cardiovascular death). In addition, SGLT2i drugs have a substantial impact on hospitalization for heart failure. Because GLP-1RA and SGLT2i are effective in reducing cardiovascular events, independent of their effects on blood glucose, cardiologists should be familiar with how to use them. This review outlines the evidence of cardiovascular benefit for current GLP-1RA and SGLT2i drugs, practical information for prescribing them, and putative mechanisms, so that these therapies can be incorporated along with antihypertensives, statins, and antiplatelet therapies into the routine care of patients.
Project description:Purpose of reviewSevere acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) emerged in December 2019, rapidly reaching global pandemic proportions. Coronavirus disease 2019 (COVID-19) has presented unique challenges to the rheumatology community. It is known that many individuals with rheumatic disease are at increased risk of severe disease from other infections, sparking a similar fear for COVID-19. In addition, medications routinely used in rheumatology practice are being trialled as treatments, with the potential for drug shortages for rheumatology patients.Recent findingsUnderlying comorbidities and active disease are associated with worse COVID-19 outcomes in patients with rheumatic disease. Tocilizumab and hydroxychloroquine have not proven to be effective treatments in the management of COVID-19. Telehealth has become an essential tool for the rheumatology community to monitor patients during the pandemic. In this article, we summarise the available COVID-19 evidence that is of relevance to the rheumatology community. We discuss the risk of contracting COVID-19 in individuals with rheumatic disease, along with presenting features and clinical outcomes. We provide an overview of the treatments for COVID-19 which have significance for rheumatology. We highlight published recommendations which can guide our management of rheumatic disease populations during this pandemic. Finally, we discuss the challenges in delivering effective care virtually and present methods and tools which could be adapted for use.
Project description:To assess a large national sample of bladder cancer pathology reports to determine if they contained the components necessary for clinical decision-making.We examined a random sample of 507 bladder cancer pathology reports from the national Department of Veterans Affairs Corporate Data Warehouse to assess whether each included information on the 4 report components explicitly recommended by the College of American Pathologists' protocol for the examination of such specimens: histology, grade, presence vs absence of muscularis propria in the specimen, and microscopic extent. We then assessed variation in the proportion of reports lacking at least 1 component across Department of Veterans Affairs facilities.One hundred eight of 507 reports (21%) lacked at least 1 of the 4 components, with microscopic extent and presence vs absence of muscularis propria in the specimen most commonly missing (each in 11% of reports). There was wide variation across facilities in the proportion of reports lacking at least 1 component, ranging from 0% to 80%.One-fifth of bladder cancer pathology reports lack information needed for clinical decision-making. The wide variation in incomplete report rates across facilities implies that some facilities already have implemented best practices assuring complete reporting whereas others have room for improvement. Future work to better understand barriers and facilitators of complete reporting may lead to interventions that improve bladder cancer care.
Project description:There is a fairly consistent, albeit non-universal body of research documenting cognitive declines after cancer and its treatments. While few of these studies have included subjects aged 65 years and older, it is logical to expect that older patients are at risk of cognitive decline. Here, we use breast cancer as an exemplar disease for inquiry into the intersection of aging and cognitive effects of cancer and its therapies. There are a striking number of common underlying potential biological risks and pathways for the development of cancer, cancer-related cognitive declines, and aging processes, including the development of a frail phenotype. Candidate shared pathways include changes in hormonal milieu, inflammation, oxidative stress, DNA damage and compromised DNA repair, genetic susceptibility, decreased brain blood flow or disruption of the blood-brain barrier, direct neurotoxicity, decreased telomere length, and cell senescence. There also are similar structure and functional changes seen in brain imaging studies of cancer patients and those seen with "normal" aging and Alzheimer's disease. Disentangling the role of these overlapping processes is difficult since they require aged animal models and large samples of older human subjects. From what we do know, frailty and its low cognitive reserve seem to be a clinically useful marker of risk for cognitive decline after cancer and its treatments. This and other results from this review suggest the value of geriatric assessments to identify older patients at the highest risk of cognitive decline. Further research is needed to understand the interactions between aging, genetic predisposition, lifestyle factors, and frailty phenotypes to best identify the subgroups of older patients at greatest risk for decline and to develop behavioral and pharmacological interventions targeting this group. We recommend that basic science and population trials be developed specifically for older hosts with intermediate endpoints of relevance to this group, including cognitive function and trajectories of frailty. Clinicians and their older patients can advance the field by active encouragement of and participation in research designed to improve the care and outcomes of the growing population of older cancer patients.
Project description:Introduction:Nonpuerperal uterine inversion (NPUI) is a rare clinical problem with diagnostic and surgical challenges. The objective of our study was to review the literature on NPUI and describe causative pathologies, diagnosis, and different surgical options available for treatment. Materials and Methods:A comprehensive literature review was carried out on MEDLINE and Google Scholar databases to look for NPUI using the term "non-puerperal uterine inversion," and further went through the cross-references of the published articles. Data are published case reports from 1911 to September 2018. Of the 153 published cases, 133 reports had adequate details of surgery for analysis. These reports were analyzed, concerning the clinical presentation, methods of diagnosis, and surgical treatment. Results:Mean age of the women was 46.3 years (standard deviation: 18, N?=?153). Leiomyoma remained the commonest (56.2%) aetiology. While malignancies contributed to 32.02% of cases, 9.2% were idiopathic. High degree of clinical suspicion and identification of unique features on ultrasonography and magnetic resonance imaging enable prompt diagnosis. In cases of uncertainty, laparoscopy or biopsy of the mass was used to confirm the diagnosis. Hysterectomy or repositioning and repair of the uterus are the only treatment options available. The surgical methods implemented were analyzed in three aspects: route of surgical access, method of repositioning, and final surgical procedure undertaken. The majority (48.8%) had only abdominal access, while 27.1% had both abdominal and vaginal access. Haultain procedure was the most useful procedure for reposition (18.0%) of the uterus. The majority (39.7%) required abdominal hysterectomy with or without debulking of the tumour abdominally, while 15.0% had uterine repair after repositioning. We reviewed the different surgical techniques and described and proposed a treatment algorithm. Conclusions:Fibroids were the commonest cause for NPUI. Malignancies accounted for one-third of cases. A combined abdominal and vaginal approach, followed by hysterectomy or repair after repositioning, seems to be better for nonmalignant cases.