HCC EV ECG score: An extracellular vesicle-based protein assay for detection of early-stage hepatocellular carcinoma.

BACKGROUND AND AIMS: The sensitivity of current surveillance methods for detecting early-stage hepatocellular carcinoma (HCC) is suboptimal. Extracellular vesicles (EVs) are promising circulating biomarkers for early cancer detection. In this study, we aim to develop an HCC EV-based surface protein assay for early detection of HCC. APPROACH AND RESULTS: Tissue microarray was used to evaluate four potential HCC-associated protein markers. An HCC EV surface protein assay, composed of covalent chemistry-mediated HCC EV purification and real-time immuno-polymerase chain reaction readouts, was developed and optimized for quantifying subpopulations of EVs. An HCC EV ECG score, calculated from the readouts of three HCC EV subpopulations ( E pCAM + CD63 + , C D147 + CD63 + , and G PC3 + CD63 + HCC EVs), was established for detecting early-stage HCC. A phase 2 biomarker study was conducted to evaluate the performance of ECG score in a training cohort ( n  = 106) and an independent validation cohort ( n  = 72).Overall, 99.7% of tissue microarray stained positive for at least one of the four HCC-associated protein markers (EpCAM, CD147, GPC3, and ASGPR1) that were subsequently validated in HCC EVs. In the training cohort, HCC EV ECG score demonstrated an area under the receiver operating curve (AUROC) of 0.95 (95% confidence interval [CI], 0.90-0.99) for distinguishing early-stage HCC from cirrhosis with a sensitivity of 91% and a specificity of 90%. The AUROCs of the HCC EV ECG score remained excellent in the validation cohort (0.93; 95% CI, 0.87-0.99) and in the subgroups by etiology (viral: 0.95; 95% CI, 0.90-1.00; nonviral: 0.94; 95% CI, 0.88-0.99). CONCLUSION: HCC EV ECG score demonstrated great potential for detecting early-stage HCC. It could augment current surveillance methods and improve patients' outcomes.

Polypharmacy in Hospice and Palliative Care.

In patients with limited life expectancy, or if the clinician would not be surprised if the patient were to die within a year, reconsidering the treatment targets and engaging in an open discussion with the patient on their goals of care would be appropriate. When a desire to deprescribe has been reached by both clinician and patient, a stepwise and guided approach to deprescribing with regular follow-ups is recommended. This article discusses common medications that can be deprescribed in the palliative/hospice patients and provides toolkits for future reference.

Cost-effective methylome sequencing of cell-free DNA for accurately detecting and locating cancer.

Early cancer detection by cell-free DNA faces multiple challenges: low fraction of tumor cell-free DNA, molecular heterogeneity of cancer, and sample sizes that are not sufficient to reflect diverse patient populations. Here, we develop a cancer detection approach to address these challenges. It consists of an assay, cfMethyl-Seq, for cost-effective sequencing of the cell-free DNA methylome (with > 12-fold enrichment over whole genome bisulfite sequencing in CpG islands), and a computational method to extract methylation information and diagnose patients. Applying our approach to 408 colon, liver, lung, and stomach cancer patients and controls, at 97.9% specificity we achieve 80.7% and 74.5% sensitivity in detecting all-stage and early-stage cancer, and 89.1% and 85.0% accuracy for locating tissue-of-origin of all-stage and early-stage cancer, respectively. Our approach cost-effectively retains methylome profiles of cancer abnormalities, allowing us to learn new features and expand to other cancer types as training cohorts grow.

The Wide and Unpredictable Scope of Synthetic Cannabinoids Toxicity.

Drug use and abuse continue to be a large public health concern worldwide. Over the past decade, novel or atypical drugs have emerged and become increasingly popular. In the recent past, compounds similar to tetrahydrocannabinoid (THC), the active ingredient of marijuana, have been synthetically produced and offered commercially as legal substances. Since the initial communications of their abuse in 2008, few case reports have been published illustrating the misuse of these substances with signs and symptoms of intoxication. Even though synthetic cannabinoids have been restricted, they are still readily available across USA and their use has been dramatically increasing, with a concomitant increment in reports to poison control centers and emergency department (ED) visits. We describe a case of acute hypoxemic/hypercapnic respiratory failure as a consequence of acute congestive heart failure (CHF) developed from myocardial stunning resulting from a non-ST-segment elevation myocardial infarction (MI) following the consumption of synthetic cannabinoids.

Triage of Patients Consulted for ICU Admission During Times of ICU-Bed Shortage.

BACKGROUND: The demand for specialized medical services such as critical care often exceeds availability, thus rationing of intensive care unit (ICU) beds commonly leads to difficult triage decisions. Many factors can play a role in the decision to admit a patient to the ICU, including severity of illness and the need for specific treatments limited to these units. Although triage decisions would be based solely on patient and institutional level factors, it is likely that intensivists make different decisions when there are fewer ICU beds available. The objective of this study is to evaluate the characteristics of patients referred for ICU admission during times of limited beds availability. METHODS: A single center, prospective, observational study was conducted among consecutive patients in whom an evaluation for ICU admission was requested during times of ICU overcrowding, which comprised the months of April and May 2014. RESULTS: A total of 95 patients were evaluated for possible ICU admission during the study period. Their mean APACHE-II score was 16.8 (median 16, range 3 - 36). Sixty-four patients (67.4%) were accepted to ICU, 18 patients (18.9%) were triaged to SDU, and 13 patients (13.7%) were admitted to hospital wards. ICU had no beds available 24 times (39.3%) during the study period, and in 39 opportunities (63.9%) only one bed was available. Twenty-four patients (25.3%) were evaluated when there were no available beds, and eight of those patients (33%) were admitted to ICU. A total of 17 patients (17.9%) died in the hospital, and 15 (23.4%) expired in ICU. CONCLUSION: ICU beds are a scarce resource for which demand periodically exceeds supply, raising concerns about mechanisms for resource allocation during times of limited beds availability. At our institution, triage decisions were not related to the number of available beds in ICU, age, or gender. A linear correlation was observed between severity of illness, expressed by APACHE-II scores, and the likelihood of being admitted to ICU. Alternative locations outside the ICU in which care for critically ill patients could be delivered should be considered during times of extreme ICU-bed shortage.

A general ploidy model for the evolution of helping in viscous populations.

There is growing interest in understanding how kin selection drives the evolution of social behaviours in viscous populations. A key result, that has inspired much work on this topic, is the exact cancellation of the genetic relatedness and kin competition effects of dispersal in the simplest models of population viscosity, such that a reduction in the rate of dispersal neither promotes nor inhibits the evolution of helping behaviour. This theoretical result has been demonstrated for populations characterised by haploid, diploid and haplodiploid modes of inheritance. Here we develop a model of general ploidy that recovers these three scenarios as special cases and allows examination of scenarios that have not been considered previously. Specifically, we: clarify the importance of the implicit assumption of monandry in previous models; show that the cancellation result obtains in some models of ploidy but not in others; and reveal that the cancellation result obtains for different reasons in different models of ploidy. The cancellation result therefore hinges upon a population's genetic system as well as its demography.

Telephone-administered cognitive behavior therapy for obsessive-compulsive disorder.

Exposure with response prevention and cognitive behavior therapy are widely recognized as effective treatments for obsessive-compulsive disorder. Unfortunately, many people with obsessive-compulsive disorder--particularly those living in rural areas--do not have access to therapists providing these treatments. Accordingly, we investigated the efficacy of telephone-administered cognitive behavior therapy for obsessive-compulsive disorder. Two open trials are reported, for a total of 33 people with obsessive-compulsive disorder (without major depression). The first trial consisted of 12 weeks on a waiting list followed by 12 weeks of treatment (delayed treatment). The second trial consisted of 12 weeks of immediate treatment. Obsessive-compulsive symptoms did not change during the waiting period. Symptoms declined from pre- to post-treatment, with gains maintained at 12-week follow-up. For the pooled sample our pre-to-post-treatment effect size was as large or larger than those obtained in other studies of reduced contact treatment, and similar to those of face-to-face exposure with response prevention. Our proportion of treatment dropouts tended to be lower than those of other reduced contact interventions. The results suggest that telephone-administered cognitive behavior therapy is effective and well-tolerated, at least for people with obsessive-compulsive disorder without major depression. It remains to be seen whether this treatment is safe and effective when comorbid major depression is present.

Efficacy of telephone-administered cognitive behaviour therapy for obsessive-compulsive spectrum disorders: case studies.

Cognitive behaviour therapy is effective for obsessive-compulsive disorder and for obsessive-compulsive spectrum disorders such as trichotillomania. Unfortunately, many people with these disorders, especially those living in rural areas, have limited access to treatment. Telephone-administered cognitive behaviour therapy may help address this problem. In a recent study of telephone treatment for obsessive-compulsive disorder, we found that such treatment was often effective (42% in remission at post-treatment, and 47% in remission at 12-week follow-up). This article presents 2 case reports of the same treatment, applied to obsessive-compulsive spectrum disorders (trichotillomania and compulsive skin picking). Treatment was associated with symptom reduction for both participants, although one subsequently relapsed. Possible reasons for relapse are discussed. The findings encourage further studies to identify the characteristics of people most likely to benefit from telephone treatment for spectrum disorders.