Citations

Background: The goal of this study was to categorize patients with abnormal serum phosphate upon hospital admission into distinct clusters utilizing an unsupervised machine learning approach, and to assess the mortality risk associated with these clusters. Methods: We utilized the consensus clustering approach on demographic information, comorbidities, principal diagnoses, and laboratory data of hypophosphatemia (serum phosphate ≤ 2.4 mg/dL) and hyperphosphatemia cohorts (serum phosphate ≥ 4.6 mg/dL). The standardized mean difference was applied to determine each cluster’s key features. We assessed the association of the clusters with mortality. Results: In the hypophosphatemia cohort (n = 3113), the consensus cluster analysis identified two clusters. The key features of patients in Cluster 2, compared with Cluster 1, included: older age; a higher comorbidity burden, particularly hypertension; diabetes mellitus; coronary artery disease; lower eGFR; and more acute kidney injury (AKI) at admission. Cluster 2 had a comparable hospital mortality (3.7% vs. 2.9%; p = 0.17), but a higher one-year mortality (26.8% vs. 14.0%; p < 0.001), and five-year mortality (20.2% vs. 44.3%; p < 0.001), compared to Cluster 1. In the hyperphosphatemia cohort (n = 7252), the analysis identified two clusters. The key features of patients in Cluster 2, compared with Cluster 1, included: older age; more primary admission for kidney disease; more history of hypertension; more end-stage kidney disease; more AKI at admission; and higher admission potassium, magnesium, and phosphate. Cluster 2 had a higher hospital (8.9% vs. 2.4%; p < 0.001) one-year mortality (32.9% vs. 14.8%; p < 0.001), and five-year mortality (24.5% vs. 51.1%; p < 0.001), compared with Cluster 1. Conclusion: Our cluster analysis classified clinically distinct phenotypes with different mortality risks among hospitalized patients with serum phosphate derangements. Age, comorbidities, and kidney function were the key features that differentiated the phenotypes.

Background: Pediatric brain tumor survivors are at risk for poor social outcomes. It remains unknown whether cognitive sparing with proton radiotherapy (PRT) supports better social outcomes relative to photon radiotherapy (XRT). We hypothesized that survivors treated with PRT would outperform those treated with XRT on measures of cognitive and social outcomes. Further, we hypothesized that cognitive performance would predict survivor social outcomes. Procedure: Survivors who underwent PRT (n=38) or XRT (n=20) participated in a neurocognitive evaluation >1 year post-radiotherapy. Group differences in cognitive and social functioning were assessed using ANCOVA. Regression analyses examined predictors of peer relations and social skills. Results: Age at evaluation, radiation dose, tumor diameter, and sex did not differ between groups (all p>0.05). However, XRT participants were younger at diagnosis (XRT M=5.0 years, PRT M=7.6 years) and further out from radiotherapy (XRT M=8.7 years, PRT M=4.6 years). The XRT group performed worse than the PRT group on measures of processing speed (p=0.01) and verbal memory (p<0.01); however, social outcomes did not differ by radiation type. The proportion of survivors with impairment in peer relations and social skills exceeded expectation (2(1)=38.67, p<0.001; 2(1)=5.63, p<0.05), and verbal memory approached significance as a unique predictor of peer relations (t=-2.01, p=0.05). Total tumor RT dose significantly predicted social skills (t=-2.23, p<0.05). Conclusions: Regardless of radiation modality, survivors are at risk for social challenges, with one-quarter being socially excluded or undervalued. Deficits in verbal memory may place survivors at particular risk. Results support monitoring of cognitive and social functioning throughout survivorship.

Summary Background There are limited data on the influence of seasons on the outcomes of acute myocardial infarction-cardiac arrest (AMI-CA). Aim To evaluate the outcomes of AMI-CA by seasons in the United States Design Retrospective cohort study Methods Using the National Inpatient Sample from 2000 to 2017, adult (&gt;18 years) admissions with AMI-CA were identified. Seasons were defined by the month of admission as spring, summer, fall and winter. The outcomes of interest were prevalence of AMI-CA, in-hospital mortality, use of coronary angiography, percutaneous coronary intervention (PCI), hospital length of stay, hospitalization costs and discharge disposition. Results Of the 10 880 856 AMI admissions, 546 334 (5.0%) were complicated by CA, with a higher prevalence in fall and winter (5.1% each) compared to summer (5.0%) and spring (4.9%). Baseline characteristics of AMI-CA admissions admitted in various seasons were largely similar. Compared to AMI-CA admissions in spring, summer and fall, AMI-CA admissions in winter had slightly lower rates of coronary angiography (63.3–64.3% vs. 61.4%) and PCI (47.2–48.4% vs. 45.6%). Compared to those admitted in the spring, adjusted in-hospital mortality was higher for winter {46.8% vs. 44.2%; odds ratio (OR) 1.08 [95% confidence interval (CI) 1.06–1.10]; P &lt; 0.001}, lower for summer [43% vs. 44.2%; OR 0.97 (95% CI 0.95–0.98); P &lt; 0.001] and comparable for fall [44.4% vs. 44.2%; OR 1.01 (95% CI 0.99–1.03); P = 0.31] AMI-CA admissions. Length of hospital stay, total hospitalization charges and discharge dispositions for AMI-CA admissions were comparable across the seasons. Conclusions AMI-CA admissions in the winter were associated with lower rates of coronary angiography and PCI, and higher rates of in-hospital mortality compared to the other seasons.

AbstractObjectiveThis study was undertaken to determine whether the vertical parasagittal approach or the lateral peri‐insular/peri‐Sylvian approach to hemispheric surgery is the superior technique in achieving long‐term seizure freedom.MethodsWe conducted a post hoc subgroup analysis of the HOPS (Hemispheric Surgery Outcome Prediction Scale) study, an international, multicenter, retrospective cohort study that identified predictors of seizure freedom through logistic regression modeling. Only patients undergoing vertical parasagittal, lateral peri‐insular/peri‐Sylvian, or lateral trans‐Sylvian hemispherotomy were included in this post hoc analysis. Differences in seizure freedom rates were assessed using a time‐to‐event method and calculated using the Kaplan–Meier survival method.ResultsData for 672 participants across 23 centers were collected on the specific hemispherotomy approach. Of these, 72 (10.7%) underwent vertical parasagittal hemispherotomy and 600 (89.3%) underwent lateral peri‐insular/peri‐Sylvian or trans‐Sylvian hemispherotomy. Seizure freedom was obtained in 62.4% (95% confidence interval [CI] = 53.5%–70.2%) of the entire cohort at 10‐year follow‐up. Seizure freedom was 88.8% (95% CI = 78.9%–94.3%) at 1‐year follow‐up and persisted at 85.5% (95% CI = 74.7%–92.0%) across 5‐ and 10‐year follow‐up in the vertical subgroup. In contrast, seizure freedom decreased from 89.2% (95% CI = 86.3%–91.5%) at 1‐year to 72.1% (95% CI = 66.9%–76.7%) at 5‐year to 57.2% (95% CI = 46.6%–66.4%) at 10‐year follow‐up for the lateral subgroup. Log‐rank test found that vertical hemispherotomy was associated with durable seizure‐free progression compared to the lateral approach (p = .01). Patients undergoing the lateral hemispherotomy technique had a shorter time‐to‐seizure recurrence (hazard ratio = 2.56, 95% CI = 1.08–6.04, p = .03) and increased seizure recurrence odds (odds ratio = 3.67, 95% CI = 1.05–12.86, p = .04) compared to those undergoing the vertical hemispherotomy technique.SignificanceThis pilot study demonstrated more durable seizure freedom of the vertical technique compared to lateral hemispherotomy techniques. Further studies, such as prospective expertise‐based observational studies or a randomized clinical trial, are required to determine whether a vertical approach to hemispheric surgery provides superior long‐term seizure outcomes.

Background: Sleep apnea is one of the most common conditions around the world. This disorder can significantly impact cardiovascular morbidity and mortality. Atrial overdrive pacing (AOP) is a treatment modality that can potentially decrease respiratory events. There is currently a lack of evidence to confirm the benefits of AOP. We aimed to assess the impact of AOP in patients with obstructive sleep apnea (OSA), central sleep apnea (CSA), and mixed type. Methods: A literature search for studies that reported the impact on apnea–hypopnea index (AHI) by cardiac implantable electronic devices with different pacing modes was conducted using MEDLINE, Embase, and Cochrane Database from inception through July 2020. Pooled standard mean difference with 95%CI was calculated using a random-effects model. Results: Fifteen studies, including thirteen randomized studies and two observational studies containing 440 patients, were identified. The standard mean difference in apnea–hypopnea index of atrial overdrive pacing demonstrated less duration of apnea/hypopnea in patients with atrial overdrive pacing (AOP) (SMD −0.29, 95%CI: −0.48, −0.10, I2 = 57%). Additional analysis was performed to assess the effect of atrial overdrive pacing in patients with or without severe sleep apnea syndrome (mean AHI < 30 defined as non-severe). There was no statistically significant difference in standardized mean in AHI in both subgroups between AOP and control groups (SMD −0.25, severe sleep apnea syndrome SMD −0.03, I2 = 0.00%). Conclusions: AOP was associated with a statistically significant reduction in AHI, but the magnitude of reduction was small. AOP may potentially be used as an adjunctive treatment with other modalities in treating patients with sleep apnea.

Antimicrobial susceptibility testing (AST) is routinely used to establish predictive antibiotic resistance metrics to guide the treatment of bacterial pathogens. Recently, a novel phenotype termed “bicarbonate (NaHCO3)-responsiveness” was identified in a relatively high frequency of clinical MRSA strains, wherein isolates demonstrate in vitro “susceptibility” to standard β-lactams (oxacillin [OXA]; cefazolin [CFZ]) in the presence of NaHCO3, and in vivo susceptibility to these β-lactams in experimental endocarditis models. We investigated whether a targeted phenotypic-genotypic screening of MRSA could rule in or rule out NaHCO3 susceptibility upfront. We studied 30 well-characterized clinical MRSA bloodstream isolates, including 15 MIC-susceptible to CFZ and OXA in NaHCO3-supplemented Mueller–Hinton Broth (MHB); and 15 MIC-resistant to both β-lactams in this media. Using a two-tiered strategy, isolates were first screened by standard disk diffusion for susceptibility to a combination of amoxicillin-clavulanate [AMC]. Isolates then underwent genomic sequence typing: MLST (clonal complex [CC]); agr; SCCmec; and mecA promoter and coding region. The combination of AMC disk susceptibility testing plus mecA and spa genotyping was able to predict MRSA strains that were more or less likely to be NaHCO3-responsive in vitro, with a high degree of sensitivity and specificity. Validation of this screening algorithm was performed in six strains from the overall cohort using an ex vivo model of endocarditis. This ex vivo model recapitulated the in vitro predictions of NaHCO3-responsiveness vs. nonresponsiveness above in five of the six strains.

Background The presence of atrial fibrillation (AF) in patients with heart failure with preserved ejection fraction (HFpEF) dramatically increases higher morbidity and mortality. Recent studies have suggested that early rhythm control may alleviate the burden of poor outcomes. Currently, there remain limited data on whether rhythm or rate control has better efficacy. This study sought to compare both strategies in HFpEF patients with AF. Methods Databases were searched throughout 2020. Studies that reported cardiovascular outcomes amongst HFpEF patients with AF who received either rhythm or rate control were included. Estimates of the effects from the individual studies were extracted and combined using random-effects, a generic inverse variance method of DerSimonian and Laird. Results Five observational studies were included in the analysis, consisting of 16,953 patients, 13.8% of whom were receiving rhythm control. In comparison with rate control, rhythm control was associated with decreased overall mortality rates (pooled RR 0.85, 95% CI 0.75–0.95, with I2 = 0%, p value = 0.009). Conclusions In HFpEF patients with AF, rhythm control was associated with lower mortality, compared to rate control. Further studies are warranted to validate our observation.

Breast cancer is a heterogenous disease with variability in tumor cells and in the surrounding tumor microenvironment (TME). Understanding the molecular diversity in breast cancer is critical for improving prediction of therapeutic response and prognostication. High-plex spatial profiling of tumors enables characterization of heterogeneity in the breast TME, which can holistically illuminate the biology of tumor growth, dissemination and, ultimately, response to therapy. The GeoMx Digital Spatial Profiler (DSP) enables researchers to spatially resolve and quantify proteins and RNA transcripts from tissue sections. The platform is compatible with both formalin-fixed paraffin-embedded and frozen tissues. RNA profiling was developed at the whole transcriptome level for human and mouse samples and protein profiling of 100-plex for human samples. Tissue can be optically segmented for analysis of regions of interest or cell populations to study biology-directed tissue characterization. The GeoMx Breast Cancer Consortium (GBCC) is composed of breast cancer researchers who are developing innovative approaches for spatial profiling to accelerate biomarker discovery. Here, the GBCC presents best practices for GeoMx profiling to promote the collection of high-quality data, optimization of data analysis and integration of datasets to advance collaboration and meta-analyses. Although the capabilities of the platform are presented in the context of breast cancer research, they can be generalized to a variety of other tumor types that are characterized by high heterogeneity.

Background and Objectives: Contemporary data on the prevalence, management and outcomes of acute myocardial infarction (AMI) in relation to body mass index (BMI) are limited. Materials and Methods: Using the National Inpatient Sample from 2008 through 2017, we identified adult AMI hospitalizations and categorized them into underweight (BMI < 19.9 kg/m2), normal BMI and overweight/obese (BMI > 24.9 kg/m2) groups. We evaluated in-hospital mortality, utilization of cardiac procedures and resource utilization among these groups. Results: Among 6,089,979 admissions for AMI, 38,070 (0.6%) were underweight, 5,094,721 (83.7%) had normal BMI, and 957,188 (15.7%) were overweight or obese. Over the study period, an increase in the prevalence of AMI was observed in underweight and overweight/obese admissions. Underweight AMI admissions were, on average, older, with higher comorbidity, whereas overweight/obese admissions were younger and had lower comorbidity. In comparison to the normal BMI and overweight/obese categories, significantly lower use of coronary angiography (62.3% vs. 74.6% vs. 37.9%) and PCI (40.8% vs. 47.7% vs. 19.6%) was observed in underweight admissions (all p < 0.001). The underweight category was associated with significantly higher in-hospital mortality (10.0% vs. 5.5%; OR 1.23 (95% CI 1.18–1.27), p < 0.001), whereas being overweight/obese was associated with significantly lower in-hospital mortality compared to normal BMI admissions (3.1% vs. 5.5%; OR 0.73 (95% CI 0.72–0.74), p < 0.001). Underweight AMI admissions had longer lengths of in-hospital stay with frequent discharges to skilled nursing facilities, while overweight/obese admissions had higher hospitalization costs. Conclusions: In-hospital management and outcomes of AMI vary by BMI. Underweight status was associated with worse outcomes, whereas the obesity paradox was apparent, with better outcomes for overweight/obese admissions.

Background and Objectives: Despite the association between hyperchloremia and adverse outcomes, mortality risks among patients with hyperchloremia have not consistently been observed among all studies with different patient populations with hyperchloremia. The objective of this study was to characterize hyperchloremic patients at hospital admission into clusters using an unsupervised machine learning approach and to evaluate the mortality risk among these distinct clusters. Materials and Methods: We performed consensus cluster analysis based on demographic information, principal diagnoses, comorbidities, and laboratory data among 11,394 hospitalized adult patients with admission serum chloride of >108 mEq/L. We calculated the standardized mean difference of each variable to identify each cluster’s key features. We assessed the association of each hyperchloremia cluster with hospital and one-year mortality. Results: There were three distinct clusters of patients with admission hyperchloremia: 3237 (28%), 4059 (36%), and 4098 (36%) patients in clusters 1 through 3, respectively. Cluster 1 was characterized by higher serum chloride but lower serum sodium, bicarbonate, hemoglobin, and albumin. Cluster 2 was characterized by younger age, lower comorbidity score, lower serum chloride, and higher estimated glomerular filtration (eGFR), hemoglobin, and albumin. Cluster 3 was characterized by older age, higher comorbidity score, higher serum sodium, potassium, and lower eGFR. Compared with cluster 2, odds ratios for hospital mortality were 3.60 (95% CI 2.33–5.56) for cluster 1, and 4.83 (95% CI 3.21–7.28) for cluster 3, whereas hazard ratios for one-year mortality were 4.49 (95% CI 3.53–5.70) for cluster 1 and 6.96 (95% CI 5.56–8.72) for cluster 3. Conclusions: Our cluster analysis identified three clinically distinct phenotypes with differing mortality risks in hospitalized patients with admission hyperchloremia.