Citations

Abstract Rationale Early diagnosis of sepsis continues to be a clinical challenge despite guideline-based early and serial assessments and integration of clinical and laboratory indices. Exhaled volatile organic compounds (VOC) have been shown to provide a rapid and non-invasive bedside diagnostic aid based on metabolism related to infection and the immune response. However, there is heterogeneous accuracy across different technological platforms. We hypothesized that a handheld electrochemical breath device could identify a VOC signature that would differentiate patients with sepsis from healthy controls. Methods We evaluated a handheld, non-invasive, bedside device that captures VOC signal in exhaled breath. We collected data from 20 patients with known sepsis secondary to pneumonia based on benchmark clinical and laboratory data, and 20 age- and sex-matched healthy controls in a pilot case-control design. The interactions between VOCs and the electrochemical sensor array within the device were measured over the course of one minute of breath collection from each subject. In this time, voltage was swept across the array periodically, with the capacitance of the sensor array changing with voltage and the VOC interactions. Several metrics were derived from the resulting capacitance-voltage curves, and ten were selected based on importance to be used as inputs into several unsupervised and supervised statistical learning methods. One of these methods was Principal Component Analysis (PCA), which is a dimensionality reduction technique that creates variables by linearly transforming the original inputs. These variables are known as components, and in this study, the majority of the original information was contained in the first two. These components were visualized in a 2-dimensional scatter plot, shown below (Figure 1). Results The generated PCA scatter plot showed distinct separation between sepsis and control subjects along the x-axis, or Principal Component 1 (Figure 1). Conclusion In this case-control pilot, a handheld electrochemical breath device showed biologically plausible separation between VOC signatures of patients with sepsis and healthy controls. More definitive diagnostic results would require a large cohort with sepsis mimics and head-to-head comparison with the standard of care (laboratory work-up and clinical scoring system) versus a hybrid approach of both. This abstract is funded by: milewski foundation

Summary Chimeric antigen receptor T cells directed against CD‐19 are highly effective therapies for various subtypes of B‐cell non‐Hodgkin lymphoma (NHL). We have studied the impact of patient‐specific lymphocyte growth kinetics after lymphoid depletion chemotherapy on both long‐term outcomes and toxicity in patients with diffuse large B‐cell non‐Hodgkin lymphoma (DLBCL). The growth of the lymphocyte populations early after chimeric antigen receptor T‐cell (CAR‐T) therapy is well described by an exponential function and the growth rate of the cells appears to be one of the most critical determinants of overall survival in these patients. The maximum lymphocyte peak and the area under curve for lymphocytes within the first 4 weeks after CAR‐T therapy had no impact on survival. Receiver operator characteristic analysis determined that a replication rate ≥0.3876/day is associated with superior rates of complete response and durable responses. This threshold is associated with higher grades of cytokine release syndrome and the need for tocilizumab. However, patients with this threshold have a median overall survival of 3.04 years compared to 1.035 years for patients with slower lymphocyte replication ( p = 0.0206). The major determinant of depth of response and durability of response to CAR‐T in NHL is the speed of lymphocyte expansion.

Introduction: Vertebral compression fractures (VCFs) pose a considerable healthcare burden and are linked to elevated morbidity and mortality. Despite available anti-osteoporotic treatments (AOTs), guideline adherence is lacking. This study aims to evaluate subsequent hip fracture incidence after index VCF and to elucidate AOT prescribing patterns in VCF patients, further assessing the impact of surgical interventions on these patterns. Materials and Methods: Patients with index VCFs between 2010 and 2021 were identified using the PearlDiver database. Diagnostic and procedural data were recorded using International Classification of Diseases (ICD-9, ICD-10) and Current Procedural Terminology (CPT) codes. Patients under age 50 and follow-up <one year following index VCF were excluded. Patients were categorized based on whether they received AOT within one year, preceding and after index VCF, and were subsequently propensity-matched 1:3 based on age, sex, and Elixhauser Comorbidity Index (ECI) score to compare hip fracture incidence following index VCF. Sub-analysis was performed for operatively managed VCFs (kyphoplasty/vertebroplasty). Statistical tests included Chi-squared for categorical outcomes, and Kruskal–Wallis for continuous measures. Results: Of 637,701 patients, 72.6% were female. The overall subsequent hip fracture incidence was 2.6% at one year and 12.9% for all-time follow-up. Propensity-matched analysis indicated higher subsequent hip fracture rates in patients initiated on AOT post-index VCF (one year: 3.8% vs. 3.5%, p = 0.0013; all-time: 14.3% vs. 13.0%, p < 0.0001). Conclusions: The study reveals an unexpected increase in subsequent hip fractures among patients initiated on AOT post-index VCF, likely due to selection bias. These findings highlight the need for refined osteoporosis-management strategies to improve guideline adherence, thereby mitigating patient morbidity and mortality.

Introduction: There has been a shift in prehospital systems of care to prioritize transporting acute ischemic stroke (AIS) patients with suspected emergent large vessel occlusion (ELVO) stroke to thrombectomy capable stroke centers (TSCs), as opposed to primary stroke centers (PSCs) which may be closer and offer intravenous thrombolysis faster. Large scale data on clinical outcomes in direct triage are lacking. Methods: We conducted a systematic review and meta-analysis using PRISMA guidelines with the Nested Knowledge AutoLit platform to search PubMed for relevant terms from 01/2015 to 05/2022. Our primary endpoint was proportion of patients with a good clinical outcome [modified Rankin Score (mRS) 0-2] at 90 days. Results: We identified 390 studies, 16 of which compared direct triage to various models and were included. Amongst these, Mobile Stroke Unit (MSU; n=1), Mothership only (n=1), Drip-and-Ship only (n=3), and Mothership + Drip-and-Ship (n=11) were compared to Direct Triage. Among the eleven that reported 90-day functional status outcomes, there were no discernible trends. Four studies that compared 90-day functional outcomes amongst patients who received EVT and compared Direct Triage to Drip-and-Ship + Mothership models were analyzed. Baseline age, sex, and presenting NIHSS were similar. Patients who underwent Direct Triage were more likely to have a good outcome (mRS 0-2) at 90-days (OR 1.35, 95% CI 1.03-1.76). Conclusions: Amongst patients who received EVT, patients who underwent Direct Triage were more likely to have better functional outcomes at 90 days. Direct Triage of AIS patients is a promising strategy to improve clinical outcomes in patients who undergo EVT. More research is needed in patients who do not receive EVT.

Abstract Background and Aims Following liver resection (LR) for HCC, the likelihood of survival is dynamic, in that multiple recurrences and/or metastases are possible, each having variable impacts on outcomes. We sought to evaluate the natural progression, pattern, and timing of various disease states after LR for HCC using multistate modeling and to create a practical calculator to provide prognostic information for patients and clinicians. Approach and Results Adult patients undergoing LR for HCC between January 2000 and December 2018 were retrospectively identified at a single center. Multistate analysis modeled post‐LR tumor progression by describing transitions between distinct disease states. In this model, the states included surgery, intrahepatic recurrence (first, second, third, fourth, fifth), distant metastasis with or without intrahepatic recurrence, and death. Of the 486 patients included, 169 (34.8%) remained recurrence‐free, 205 (42.2%) developed intrahepatic recurrence, 80 (16.5%) developed distant metastasis, and 32 (7%) died. For an average patient having undergone LR, there was a 33.1% chance of remaining disease‐free, a 31.0% chance of at least one intrahepatic recurrence, a 16.3% chance of distant metastasis, and a 19.8% chance of death within the first 60 months post‐LR. The transition probability from surgery to first intrahepatic recurrence, without a subsequent state transition, increased from 3% (3 months) to 17.4% (30 months) and 17.2% (60 months). Factors that could modify these probabilities included tumor size, satellite lesions, and microvascular invasion. The online multistate model calculator can be found on https://multistatehcc.shinyapps.io/home/. Conclusions In contrast to standard single time‐to‐event estimates, multistate modeling provides more realistic prognostication of outcomes after LR for HCC by taking into account many postoperative disease states and transitions between them. Our multistate modeling calculator can provide meaningful data to guide the management of patients undergoing postoperative surveillance and therapy.

Background/Objective: Alteplase may elevate international normalized ratio (INR) results, although the exact rate of elevation occurrence is not firmly established in the literature. The purpose of this study is to determine the occurrence rate of INR elevation following alteplase administration. We also aimed to determine what factors are independently associated with the development of elevated INR following alteplase administration for ischemic stroke. Methods: We conducted a multicenter, retrospective, cohort study of patients who received alteplase for acute ischemic stroke. Patients were screened for baseline INR measurement and a repeat value within 24 hours of alteplase administration. The primary outcome was the percent of patients who experienced ≥0.4-point increase in INR. Secondary outcomes included the rate of adverse bleeding events and identification of factors independently associated with elevated INR following alteplase administration. Results and Conclusions: Two hundred and sixty-one patients were included, with 44 (16.9%) patients having an INR increase of 0.4 or more. Patients with an INR increase ≥0.4 experienced a nonstatistically significant increase in bleeding episodes (8.8% vs 18.2%; P = .10). We identified African American race (odds ratio, 3.48, 95% confidence interval, 1.5-7.6; P = .002) as an independent predictor of INR increase ≥0.04. An INR elevation is common following receipt of alteplase for ischemic stroke. Those of African American race were at increased risk of INR elevation; however, more studies are needed to determine whether these patients are at a higher bleeding risk as a result of INR elevation.

In this paper, a previously developed medical software using orthogonal frontal and lateral X-rays is employed to reconstruct the rib cage and thoracic volume for scoliosis patients. The thoracic volumes of ten adult scoliosis patients with different treatments during their adolescence are followed up. This study provides an evidence that thoracic volume measurement can be used to infer the pulmonary function for spine deformity patients with moderate to severe scoliosis Cobb angle. Based on the calculation of the thoracic volumes in scoliosis patients, we correlate the parameters in the pulmonary function test to the measured thoracic volume through our software. The findings show the strong correlation between total lung capacity and the thoracic volume, and a significant correlation between the vital capacity/residual volume and the thoracic volume. An interpretation of the findings, limitation, and the future application are pointed out.

In clinical settings, doctors classify pulmonary disorders into two main categories, obstructive lung disease and restrictive lung disease. The former is characterized by the airway obstruction which is associated with several disorders like chronic bronchitis, asthma, bronchiectasis, and emphysema [1]. The latter is caused by different conditions where one of the triggers is tied to the spine deformity. In general, a pulmonary function test (PFT) [2] is used to evaluate and diagnose lung function, and physicians depend on the test results to identify the disease patterns of the patients (obstructive or restrictive lung disease). In the PFT, some parameters including total lung capacity (TLC), vital capacity (VC), and residual volume (RV) can infer the lung volume and lung capacity. Other parameters, such as forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1), are often employed to assess the pulmonary mechanics. Scoliosis is an abnormal lateral curvature of the spine which involves not only the curvature from side to side but also an axial rotation of the vertebrae. Restrictive lung disease often happens in scoliosis patients, especially with severe spine deformity. Spine deformity if left untreated may lead to progression of the spinal curve, respiratory complications, and the reduction of life expectancy due to the decrease in thoracic volume for lung expansion. However, the relationship between thoracic volume and pulmonary function is not broadly discussed, and anatomic abnormalities in spine deformity (ex: scoliosis, kyphosis, and osteoporosis) can affect thoracic volume. Adequate thoracic volume is needed to promote pulmonary function. Previous literature has shown that the deformity of the thoracic rib cage will have detrimental effects on the respiratory function in adolescent idiopathic scoliosis patients [3–4]. In this paper, we aim to correlate thoracic volume and the parameters in PFTs in adult scoliosis patients 25–35 years after receiving treatments during their adolescence, either with physical bracing or spinal fusion surgery.

Traumatic brain injury (TBI) is a global public health epidemic. In the US alone, more than 3 million people sustain a TBI annually. It is one of the most disabling injuries as it may cause motor and sensory deficits and lead to severe cognitive, emotional, and psychosocial impairment, crippling vital areas of higher functioning. Fueled by the recognition of TBI as the “signature injury” in our wounded soldiers in Iraq and Afghanistan, and its often devastating impact on athletes playing contact sports, interest in TBI and TBI research has increased dramatically. Unfortunately, despite increased awareness of its detrimental consequences, there has been little progress in developing effective TBI interventions. Recent evidence, however, strongly indicates that nutritional intervention may provide a unique opportunity to enhance the neuronal repair process after TBI. To date, two omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have the most promising laboratory evidence for their neuro-restorative capacities in TBI. Although both animal models and human studies of brain injuries suggest they may provide benefits, there has been no clinical trial evaluating the effects of n-3 fatty acids on resilience to, or treatment, of TBI. This article reviews the known functions of n-3 fatty acids in the brain and their specific role in the cellular and biochemical pathways underlying neurotraumatic injury. We also highlight recent studies on the therapeutic impact of enhanced omega 3 intake in vivo , and how this may be a particularly promising approach to improving functional outcome in patients with TBI.