An immune dysfunction score for stratification of patients with acute infection based on whole-blood gene expression.

Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investigated the use of whole-blood transcriptomics for stratification of patients with severe infection by integrating data from 3149 samples from patients with sepsis due to community-acquired pneumonia or fecal peritonitis admitted to intensive care and healthy individuals into a gene expression reference map. We used this map to derive a quantitative sepsis response signature (SRSq) score reflective of immune dysfunction and predictive of clinical outcomes, which can be estimated using a 7- or 12-gene signature. Last, we built a machine learning framework, SepstratifieR, to deploy SRSq in adult and pediatric bacterial and viral sepsis, H1N1 influenza, and COVID-19, demonstrating clinically relevant stratification across diseases and revealing some of the physiological alterations linking immune dysregulation to mortality. Our method enables early identification of individuals with dysfunctional immune profiles, bringing us closer to precision medicine in infection.

Evaluation of an unscheduled care model delivered by advanced nurse practitioners in a primary-care setting.

BACKGROUND: Considering new models of delivery may help reduce increasing pressures on primary care. One potentially viable solution is utilising Advanced Practitioners to deliver unscheduled afternoon visits otherwise undertaken by a General Practitioner (GP). AIMS: Evaluate the feasibility of utilising an Advanced Nurse Practitioner (ANP) to deliver unscheduled home visits on behalf of GPs in a primary care setting. METHODS: Following a telephone request from patients, ANPs conducted unscheduled home visits on behalf of GPs over a six-month period. Service-level data collected included patient-facing time and outcome of visits. Practice staff and ANPs participated in mind-mapping sessions to explore perceptions of the service. RESULTS: There were 239 accepted referrals (total visiting time 106.55 hours). The most common outcomes for visits were 'medication and worsening statement given' (107 cases) and 'self-care advice' (47 cases). GPs were very satisfied with the service (average score 90%), reporting reductions in stress and capacity improvements. Given the low referral rejection rate, ANPs discussed the potential to increase the number of practices able to access this model, in addition to the possibility of utilising other practitioners (such as paramedics or physiotherapists) to deliver the same service. CONCLUSIONS: It appears delivering unscheduled care provision using an ANP is feasible and acceptable to GPs.

Lipoprotein-X disease in the setting of severe cholestatic hepatobiliary autoimmune disease.

Severe cholestatic disease and hyperlipidemia are both commonly encountered by medical professionals. This article reviews the current pathophysiological model of lipoprotein-X syndrome related to 3 cases from 2 academic medical centers in the United States.

Case report of male child with elevated lipoprotein (a) leading to acute ischemic stroke.

Acute ischemic stroke (AIS) in children is rare with almost 40% diagnosed as cryptogenic. One possible mechanism associated with AIS is an elevated Lipoprotein (a) [Lp(a)] level. Here, we discuss the case of an 11-year old boy who presented with multiple thrombotic strokes secondary to elevated Lp(a), which was identified as the only risk factor and immediately treated with lipoprotein apheresis (LA). Eighteen months post-AIS, he is still receiving LA treatments and has made remarkable progress in his recovery without another cerebrovascular event.

Old dog, new tricks: the attentional set-shifting test as a novel cognitive behavioral task after controlled cortical impact injury.

Cognitive impairment associated with prefrontal cortical dysfunction is a major component of disability in traumatic brain injury (TBI) survivors. Specifically, deficits of cognitive flexibility and attentional set-shifting are present across all levels of injury severity. Though alterations in spatial learning have been extensively described in experimental models of TBI, studies investigating more complex cognitive deficits are relatively scarce. Hence, the aim of this preclinical study was to expand on this important issue by evaluating the effect of three injury levels on executive function and behavioral flexibility performance as assessed using an attentional set-shifting test (AST). Isoflurane-anesthetized male rats received a controlled cortical impact (CCI) injury (2.6, 2.8, and 3.0 mm cortical depth at 4 m/sec) or sham injury, whereas an additional group had no surgical manipulation (naïve). Four weeks postsurgery, rats were tested on the AST, which involved a series of discriminative tasks of increasing difficulty, such as simple and compound discriminations, stimulus reversals, and intra- and extradimensional (ED) shifts. TBI produced accompanying impact depth-dependent increases in cortical lesion volumes, with the 3.0-mm cortical depth group displaying significantly larger injury volumes than the 2.6-mm group (p=0.05). Further, injury severity-induced deficits in ED set-shifting and stimulus reversals, as well as increases in total response error rates and total set loss errors, were observed. These novel findings demonstrate executive function and behavioral flexibility deficits in our animal model of CCI injury and provide the impetus to integrate the AST in the standard neurotrauma behavioral battery to further evaluate cognitive dysfunction after TBI. Ongoing experiments in our laboratory are assessing AST performance after pharmacological and rehabilitative therapies post-TBI, as well as elucidating possible mechanisms underlying the observed neuropsychological deficits.