Nanoscale organization of cardiac calcium channels is dependent on thyroid hormone status.

Thyroid hormone dysfunction is frequently observed in patients with chronic illnesses including heart failure which increases risk of adverse events. This study examined effects of thyroid hormones (TH) on cardiac T-tubule (TT) integrity, Ca2+ sparks, and nanoscale organization of ion channels in excitation-contraction (EC)-coupling, including L-type calcium channel (Cav1.2), ryanodine receptor-type 2 (RyR2), and junctophilin-2 (Jph2). TH deficiency was established in adult female rats by propyl-thiouracil (PTU) ingestion for 8 weeks; followed by randomization to continued PTU without or with oral triiodo-L-thyronine (T3; 10 ug/kg/d) for two additional weeks (PTU+T3). Confocal microscopy of isolated cardiomyocytes (CM) showed significant misalignment of TTs, and increased Ca2+ sparks in thyroid-deficient CMs. Density-Based Spatial Clustering of Applications with Noise (DBSCAN) analysis of STochastic Optical Reconstruction Microscopy (STORM) images showed decreased (p<0.0001) RyR2 cluster number per cell area in PTU CMs compared to euthyroid (EU) control myocytes, and this was normalized by T3-treatment. Cav1.2 channels and Jph2 localized within 210 nm radius of the RyR2 clusters were significantly reduced in PTU myocytes, and these values were increased with T3 treatment. A significant percentage of the RyR2 clusters in the PTU myocytes had neither Cav1.2 or Jph2, suggesting fewer functional clusters in EC-coupling. Nearest neighbor distances between RyR2 clusters were greater (p<0.001) in PTU cells compared to EU and T3-treated CMs that corresponds to disarray of TTs at the sarcomere z-discs. These results support a regulatory role of T3 in the nanoscale organization of RyR2 clusters and co-localization of Cav1.2 and Jph2 in optimizing EC-coupling.

Comparing gastrointestinal stromal tumor outcomes between geriatric and non-geriatric patients: A population-based analysis.

BACKGROUND: Gastrointestinal Stromal Tumors (GISTs) are the most common mesenchymal tumors of the GI tract. SEER is an extensive cancer database which proves useful in analyzing population trends. This analysis investigated GIST outcomes between geriatric & non-geriatric patients. METHODS: SEER*STAT 8.4.0.1 was used to extract relevant GIST data from 2000 to 2019. Geriatric age was defined as ≥70 years. Variables included age, sex, surgery, cancer-specific death, and overall survival. Statistical tests included univariate analysis using KM survival estimate (95% confidence interval) to calculate 5-year survival (5YS). Log-Rank tests determined statistical significance. Multivariable Cox's PH regression estimated the geriatric hazard death ratio adjusted for sex, stage, and surgery. RESULTS: The number of patients included was 13,579, yielding overall 5YS of 68.6% (95% CI 67.7-69.5). Cancer-specific death was 39.11% in 2000 & 3.33% in 2019. Non-geriatric & geriatric patient data yielded 5YS of 77.4% (76.4%-78.3%) and 53.3% (51.7%-54.8%) respectively (p < 0.0001). For no surgery/surgery, younger patient data yielded 5YS of 48.7% (45.8%-51.4%) and 83.7% (82.7%-84.7%) respectively (p < 0.0001); geriatric data yielded 5YS of 29.3% (26.5%-32.1%) and 62.8% (60.8%-64.6%) respectively (p < 0.0001). Multivariable analysis yielded a geriatric hazard death of 2.56 (2.42-2.70) (p < 0.0001). CONCLUSIONS: Cancer-specific death decreased since 2000, indicating an improvement in survival & treatment methods. Observed lower survival rates overall in the geriatric group. Surgery appeared to enhance survival rates in both groups, suggesting that surgery is an important factor in GIST survival regardless of age. Large prospective studies will help define clinical management for geriatric patients.

Ultralow-Dose Dynamic Expiratory CT and Repeated Imaging Enhance Evaluation for Tracheomalacia.

OBJECTIVE: This study aims to determine if a novel imaging protocol (ultralow-dose dynamic expiratory computed tomography [CT] with repeated imaging) identifies tracheomalacia (TM) more reliably than traditional dynamic tracheal CT. METHODS: We performed a retrospective evaluation of 184 consecutive ultralow-dose dynamic CTs for TM during 2017. The protocol obtains images during 1 inspiration and 2 forced expirations. Tracheal narrowing during both expirations (airway narrowing [percentage] during first dynamic expiration CT [DE1], airway narrowing [percentage] during second dynamic expiration CT [DE2]) was reported as a percentage of inspiratory area. We identified maximum narrowing of each patient's sequence (maximum narrowing [percentage] on either dynamic expiration CT [DEmax] = greatest narrowing of DE1 or DE2) and compared DE1, DE2, and DEmax in individual studies and between patients. Outcomes included frequency of TM, tracheal narrowing, and severity. Reliability was assessed by comparing tracheal area narrowing and TM grade. RESULTS: There was significantly more airway narrowing using 2 expiratory image acquisitions. Average DEmax tracheal area was 12% narrower than DE1 alone and 21% worse than DE2 alone (both P < 0.001). Using DEmax, TM was diagnosed 35% more often than DE1 alone and 31% more often than DE2 alone ( P < 0.001). DEmax identified more severe distribution of TM compared with DE1 or DE2 alone ( P < 0.001). Reliability between DE1 and DE2 was good for tracheal narrowing and moderate for TM grade. The mean effective radiation dose was 2.41 millisievert (mSv) for routine inspiration CT and 0.07 mSv for each dynamic expiration CT (total effective radiation, 2.55 mSv). CONCLUSIONS: Dynamic expiration CT with 2 expiratory image acquisitions enhanced evaluation of TM, minimally increased radiation dose, and should be considered as a noninvasive screening option.

Discharge From the Postanesthesia Care Unit With Motor Blockade After Spinal Anesthesia Safely Optimizes Fast Track Recovery in Primary Total Hip and Knee Arthroplasty.

BACKGROUND: Post anesthesia care units (PACU) await return of motor function in lower extremities, prior to discharge for patients undergoing spinal anesthesia. The purpose of this study was to assess the impact of a newly utilized recovery protocol that facilitated early discharges of patients undergoing total hip and knee arthroplasties (THA/TKA) to the floor before full motor recovery from spinal anesthesia is achieved. METHODS: A total of 647 patients undergoing spinal anesthesia for primary THA (n = 190) and TKA (n = 457) were divided into 2 groups: (1) Early PACU discharge group: patients with partial or full motor blockade at discharge. (2) Control PACU discharge group: patients with full motor recovery at discharge. Readiness for discharge was assessed using a modified Aldrete Score system. The primary outcome was incidences of hypotension or rapid responses post-operatively. RESULTS: There was no significant difference in the incidence of hypotension between the two groups (1.4 versus 1.39%, P = 1.0) and zero rapid responses were noted. Early discharge shortened mean PACU LOS time from 86.50 minutes to 70.27 minutes (P < .01). There was no difference in the incidence of nausea (0.55 versus 0%; P = .51) ordizziness (2.22 versus 0.35%; P = .09). CONCLUSION: In this retrospective observational study, we found that early PACU discharge did not result in an increase in hemodynamic consequences on the surgical floor. Thus, discharge from PACU can be safely and more expeditiously performed without waiting for return of motor function in patients receiving spinal anesthesia for THA/TKA using a modified Aldrete Score recovery protocol.

Component resolved diagnostics in peanut sensitized children with and without a history of clinical reaction.

Background: Serum Peanut-specific-IgE (PN-sIgE) and peanut-component-resolved-diagnostics (CRD) are often ordered simultaneously in the evaluation for peanut allergy. Results often guide the plans for peanut oral challenge. However, the clinical utility of CRD at different total PN-sIgE levels is unclear. A commonly used predefined CRD Ara h2 cutoff value in the literature predicting probability of peanut challenge outcomes is 0.35kUA/L. Objective: To examine the utility of CRD in patients with and without a history of clinical reactivity to peanut (PN). Methods: This was a retrospective chart review of 196 children with PN-sIgE and CRD testing, of which, 98 patients had a clinical history of an IgE-mediated reaction when exposed to PN and 98 did not. The Fisher's exact test was used to assess the relationship between CRD and PN-sIgE at different cutoff levels, McNemar test and Gwet's approach (AC1 statistic) were used to examine agreement between CRD and PN-sIgE, and logistic regression was used to assess differences in the findings between patients with and without reaction history. Results: Ara h 1, 2, 3, or 9 (ARAH) levels ≤0.35 kUA/L were significantly associated with PN-sIgE levels <2 kUA/L rather than ≥2 kUA/L (p < 0.0001). When the ARAH threshold was increased to 1 kUA/L and 2 kUA/L, these thresholds were still significantly associated with PN-sIgE levels of <2, <5, and <14 kUA/L. These findings were not significantly different in patients with and without a history of clinical reactivity. Conclusion: ARAH values correlated with PN-sIgE. Regardless of clinical history, ARAH levels are unlikely to be below 0.35, 1, or 2 kUA/L if the PN-sIgE level is >2 kUA/L. Thus, if possible, practitioners should consider PN-sIgE rather than automatically ordering CRD with PN-sIgE every time. Laboratory procedures that allow automatically and reflexively adding CRD when the PN-sIgE level is ≤5 kUA/L can be helpful. However, further studies are needed in subjects with challenge-proven PN allergy.

A Novel Brain Injury Biomarker Correlates with Cyanosis in Infants with Congenital Heart Disease.

Cyanotic heart lesions are a complex subset of congenital heart disease (CHD) in which patients are desaturated until surgical repair or palliation. We hypothesized that a direct relationship would exist between degree of desaturation and presence of systemic inflammation and brain injury in unrepaired patients less than 1 year of age. The pre-operative desaturation with augmented systemic inflammation would predict a more complex post-operative course. Fifty patients with CHD were enrolled in this study and classified as cyanotic (O2 ≤ 90%) or acyanotic (O2 > 90%) based on SpO2. Serum inflammatory mediators measured included interleukins (IL)-6, IL-8, IL-12p70, IL-10, IL-1ß, tumor necrosis factor (TNF)-α, interferon (INF)-γ; macrophage inhibitory factor (MIF) and a novel brain biomarker, phosphorylated neurofilament heavy subunit (pNF-H). Twenty-two cyanotic and 28 acyanotic subjects were enrolled with SpO2 of 78 ± 18% and 98 ± 2% (p < 0.001), respectively, and mean age of 72 days (range 2-303) and 102 days (range 1-274), respectively. Cyanotic vs acyanotic subjects had elevated serum IL-6 (6.6 ± 7.6 vs 2.9 ± 2.9 pg/ml, p = 0.019) and pNF-H (222 ± 637 vs 57 ± 121 pg/ml, p = 0.046), and both biomarkers correlated with degree of desaturation (Spearman rank-order correlation ρ = - 0.30, p = 0.037 and ρ = - 0.29 p = 0.049, respectively). Post-operative inotrope scores at 24 h and duration of mechanical ventilation correlated inversely with pre-operative oxygen saturation (ρ = - 0.380, p = 0.014 and ρ = - 0.362, p = 0.020, respectively). The degree of pre-operative desaturation correlated with a more complicated post-operative course supporting the need for advanced peri-operative therapy in this population.

Maternal Body Mass Index and Amniotic Fluid Index in Late Gestation.

OBJECTIVES: To determine the effect, if any, of an increasing maternal body mass index (BMI) on sonographically diagnosed oligohydramnios in late gestation and how it subsequently affects obstetric and neonatal outcomes. METHODS: This retrospective cohort study evaluated all women with singleton gestations who had a sonographic examination at 40 to 42 weeks' gestational age at North Shore University Hospital from 2010 through 2013. Underweight women (prepregnancy BMI < 18.5 kg/m2 ) were excluded because of higher rates of oligohydramnios and fetal growth restriction. Patients were classified into 5 groups by late-pregnancy BMI. The primary variable of interest was the diagnosis of oligohydramnios (amniotic fluid index < 5 cm). Secondary variables of interest included the mode of delivery and indication for primary cesarean delivery. A multivariable logistic regression analysis was performed. RESULTS: Oligohydramnios was identified in 189 of 1671 patients (11.3%). There was no significant difference in the amniotic fluid index between BMI groups. The rate of primary cesarean delivery increased with each successive BMI group (P < .001) such that women in the class III obesity group had an approximately 3-fold higher rate of primary cesarean delivery than women in the normal BMI group and a 2-fold higher rate than women in the overweight BMI group. In the final multivariable logistic regression model, a high BMI, nulliparity, and excessive gestational weight gain were associated with primary cesarean delivery. However, oligohydramnios did not contribute significantly to the model. CONCLUSIONS: The maternal BMI is not associated with oligohydramnios in late gestation. An increasing maternal BMI significantly increases the risk of primary cesarean delivery.

Quantitative Ultrasound Analysis of Proximal and Distal Cervical Tissue Echogenicity in Premature Cervical Remodeling.

OBJECTIVES: To determine whether a novel, noninvasive quantitative ultrasound (US) technique can detect differences in proximal and distal cervical tissue echogenicity in women with and without a shortened cervical length (CL). METHODS: We conducted a retrospective case-control study of singleton pregnancies at 16 to 26 weeks' gestation in which a transvaginal US examination was performed to measure CL from 2013 to 2015. Initial CLs in cases and controls were less than 2.5 cm and 2.5 cm or greater, respectively. For each US image, a region of interest was selected in the proximal and distal cervical stroma, in both the anterior and posterior cervical lips. The Floyd-Steinberg dithering algorithm transformed grayscale pixels in each region of interest into a binary map. A histogram tabulated the number of black and white pixels, allowing determination of the percent echogenicity. The difference in the percent echogenicity was calculated by subtracting the distal cervical echogenicity (average of anterior and posterior lips) from the proximal cervical echogenicity (average of anterior and posterior lips). RESULTS: Ultrasound images from 177 women were analyzed. There was a difference in the percent echogenicity (P < .0001) when comparing women with a short cervix (mean ± SD, 9.8 ± 10.1; n = 102) to women with a normal CL (17.2 ± 9.5; n = 75). Differences were attributable to changes in proximal (P < .008) rather than distal cervical echogenicity. Regardless of CL, the proximal cervix was more echogenic than the distal cervix. CONCLUSIONS: A quantitative US analysis of cervical tissue can detect differences in echogenicity between the proximal and distal cervix in the second trimester. Proximal cervical echogenicity is lower with CL of less than 2.5 cm compared to a normal CL.

Ultrasonic Assessment of Cervical Heterogeneity for Prediction of Spontaneous Preterm Birth: A Feasibility Study.

BACKGROUND: In a normal pregnancy, cervical collagen fibers remain organized in predictable patterns throughout most of the gestation. Cervical remodeling reflects a rearrangement of collagen fibers in which they become increasingly disordered and contribute to the pathogenesis of spontaneous preterm birth. Quantitative ultrasound analysis of cervical tissue echotexture may have the capacity to identify microstructural changes before the onset of cervical shortening. OBJECTIVE: The primary objective of this study was to examine the utility of a novel quantitative sonographic marker, the cervical heterogeneity index (HI), which reflects the relative organization of cervical collagen fibers. Also, we aimed to determine an optimal HI cut-point to predict spontaneous preterm birth. STUDY DESIGN: This retrospective cohort study employed a novel image-processing technique on transvaginal ultrasound images of the cervix in gestations between 14 and 28 completed weeks. The transvaginal sonography images were analyzed in MATLAB (MathWorks, Natick, MA) using a custom image-processing technique that assessed the relative heterogeneity of the cervical tissue. RESULTS: A total of 151 subjects were included in the study. The mean HI in subjects who delivered preterm and at term was 8.28 ± 3.73 and 12.35 ± 5.80, respectively (p < 0.0001). Thus, decreased tissue heterogeneity was associated with preterm birth, and increased tissue heterogeneity was associated with delivery at term. In our study population, preterm birth was associated with a short cervix (<2.5 cm), history of preterm birth and lower HI, and our findings indicate that HI may improve prediction of preterm birth. CONCLUSION: Quantitative ultrasound measurement of the cervical HI is a promising, noninvasive tool for early prediction of spontaneous preterm birth.

Effect of Maternal Body Mass Index and Amniotic Fluid Index on the Accuracy of Sonographic Estimation of Fetal Weight in Late Gestation.

OBJECTIVE: The objective of this study was to determine the effect, if any, of maternal body mass index (BMI) and amniotic fluid index (AFI) on the accuracy of sonographic estimated fetal weight (EFW) at 40 to 42 weeks' gestation. METHODS: This was a retrospective cohort study of singleton gestations with ultrasound performed at 40 to 42 weeks from 2010 to 2013. In this study, patients with documented BMI and sonographic EFW and AFI, concurrently, within 7 days of delivery were included. Chronic medical conditions and fetal anomalies were excluded from this study. The primary variable of interest was the rate of substantial error in EFW, defined as absolute percentage error (APE) >10%. RESULTS: A total of 1,000 pregnancies were included. Overall, the APE was 6.0 ± 4.5% and the rate of substantial error was 17.4% (n = 174). There was no significant difference in APE or rate of substantial error between BMI groups. In the final multivariable logistic regression model, the rate of substantial error was increased in women with oligohydramnios (OR 1.79; 95% CI: 1.10-2.92). Furthermore, oligohydramnios was significantly more likely to overestimate EFW while polyhydramnios was more likely to underestimate EFW. Maternal BMI did not affect the accuracy of sonographic EFW. CONCLUSION: Sonographic EFW may be affected by extremes of AFI in the postdates period. Maternal BMI does not affect EFW accuracy at 40 to 42 weeks.

Nicotinic acetylcholine receptor-mediated protection of the rat heart exposed to ischemia reperfusion.

Reperfusion injury following acute myocardial infarction is associated with significant morbidity. Activation of neuronal or non-neuronal cholinergic pathways in the heart has been shown to reduce ischemic injury and this effect has been attributed primarily to muscarinic acetylcholine receptors. In contrast, the role of nicotinic receptors, specifically alpha-7 subtype (α7nAChR) in the myocardium remains unknown which offers an opportunity to potentially repurpose several agonists/modulators that are currently under development for neurologic indications. Treatment of ex vivo and in vivo rat models of cardiac ischemia/reperfusion (I/R) with a selective α7nAChR agonist (GTS21) showed significant increases in left ventricular developing pressure, and rates of pressure development without effects on heart rate. These positive functional effects were blocked by co-administration with methyllycaconatine (MLA), a selective antagonist of α7nAChRs. In vivo, delivery of GTS21 at the initiation of reperfusion, reduced infarct size by 42% (p<0.01) and decreased tissue reactive oxygen species (ROS) by 62% (p<0.01). Flow cytometry of MitoTracker Red stained mitochondria showed that mitochondrial membrane potential was normalized in mitochondria isolated from GTS21 treated compared to untreated I/R hearts. Intracellular ATP concentration in cultured cardiomyocytes exposed to hypoxia/reoxygenation was reduced (p<0.001), but significantly increased to normoxic levels with GTS21 treatment, and this was abrogated by MLA pretreatment. Activation of stress-activated kinases, JNK and p38MAPK, were significantly reduced by GTS21 in I/R. We conclude that targeting myocardial 17nAChRs in I/R may provide therapeutic benefit by improving cardiac contractile function through a mechanism that preserves mitochondrial membrane potential, maintains intracellular ATP and reduces ROS generation, thus limiting infarct size.

Clinical characteristics associated with days to discharge among patients admitted with a primary diagnosis of lower limb cellulitis.

BACKGROUND: Clinicians have limited ability to classify risk of prolonged hospitalization among patients with lower limb cellulitis. OBJECTIVE: We sought to identify characteristics associated with days to discharge and prolonged stay. METHODS: We conducted retrospective cohort analysis including patients admitted with a primary diagnosis of lower limb cellulitis at community and tertiary hospitals. RESULTS: There were 4224 admissions for lower limb cellulitis among 3692 patients. Mean age of the cohort was 64.4 years. Frequencies of tobacco smoking, obesity, and diabetes mellitus were 25.1%, 44.9%, and 19.3%, respectively. Patients having decreased likelihood of discharge included those with the following: 10-year age increments 0.90 (95% confidence interval [CI] 0.88-0.92), obesity 0.90 (95% CI 0.83-0.97), diabetes mellitus 0.90 (95% CI 0.82-0.98), tachycardia 0.76 (95% CI 0.67-0.85), hypotension 0.77 (95% CI 0.65-0.90), leukocytosis 0.86 (95% CI 0.79-0.93), neutrophilia 0.80 (95% CI 0.73-0.87), elevated serum creatinine 0.74 (95% CI 0.68-0.81), and low serum bicarbonate 0.84 (95% CI 0.75-0.95). LIMITATIONS: This analysis is retrospective and based on coded data. Unknown confounding variables may also influence prolonged stay. CONCLUSIONS: Patients with lower limb cellulitis and prolonged stay have a number of clinical characteristics which may be used to classify risk for prolonged stay.

Clinical Factors Associated with Readmission among Patients with Lower Limb Cellulitis.

BACKGROUND: There is substantial allocation of resources directed towards evaluation and management of lower limb cellulitis (LLC) in the acute care setting. Readmission for LLC is poorly understood, and there is little evidence with which to identify patients at risk for readmission. OBJECTIVE: To describe demographics, comorbidities, admission vital signs, and laboratory markers of infection among patients with LLC who are readmitted, and to investigate which among these factors is associated with readmission. METHODS: A cross-sectional retrospective cohort study was performed at tertiary and community hospitals within a regional health care system in order to summarize readmission characteristics. Univariate and multivariate models were created to estimate the likelihood of independent variables being associated with LLC readmission. RESULTS: The readmission rate was 11.2% with a median age of 68.6 years for the cohort. Increased age and subsidized insurance were associated with more frequent admissions. For every 10-year age increase, cellulitis subjects had a 14% increase in readmission odds (OR 1.14, CI 1.07-1.20). Patients with subsidized insurance had an almost twofold increased risk (OR 1.88, CI 1.42-2.50). Smoking, obesity, hypertension, diabetes mellitus, renal insufficiency, tachycardia, hypotension, leukocytosis, and neutrophilia were not more frequent in readmitted patients. CONCLUSIONS: Older age and subsidized insurance were associated with readmission whereas severity indicators for infection including abnormal vital signs and laboratory markers were not significantly associated. Factors other than severity of infection, such as socioeconomic factors, may influence clinical decisions related to readmission for LLC.

Adjuvant radiation therapy in uterine carcinosarcoma: A population-based analysis of patient demographic and clinical characteristics, patterns of care and outcomes.

OBJECTIVE: To examine clinical and demographic characteristics of a population-based cohort of patients with uterine carcinosarcoma (UCS), to assess access to treatment and survival patterns. METHODS: Surveillance, Epidemiology and End Results database was queried for patients diagnosed in 1999-2010 and treated with surgery with or without adjuvant radiation therapy (aRT). The Kaplan-Meier method was used to estimate survival functions, and Cox proportional hazards regression - to analyze the effect of covariates on survival. RESULTS: 2342 patients were eligible. African Americans presented with more advanced AJCC stages than other races (35.4% vs. 29.1%; p<0.01). African Americans vs. others, and women diagnosed in 1999-2004 vs. in 2005-2010, received aRT at a similar rate: 36.5% vs. 39.9% (p=NS), and 39.5% vs. 38.9% (p=NS), respectively. There was a trend towards higher aRT utilization among patients younger than 65 vs. older (41.4% vs. 37.5%; p<0.06). We observed better overall and cause-specific survival in the aRT group: 42 vs. 22 (p<0.0001) and 57 vs. 28months (p<0.0001), respectively. Black race, diagnosis in 1999-2004, advanced stage and age≥65years carried a higher risk of UCS death. CONCLUSIONS: We observed greater survival rate in the aRT group. African Americans were more likely to present with later stage disease and die of UCS than non-African Americans. Age and stage, but not race, influenced receipt of aRT. Patients treated more recently survived longer.

Outcomes following Kidney transplantation in IgA nephropathy: a UNOS/OPTN analysis.

This study updates assessment of post-transplant outcomes in IgAN patients in the modern era of immunosuppression. Using UNOS/OPTN data, patients ≥18 yr of age with first kidney transplant (1/1/1999 to 12/31/2008) were analyzed. Multivariable Cox regression models and propensity score-based matching techniques were used to estimate hazard ratios (HRs) for death-censored allograft survival (DCGS) and patient survival in IgAN compared to non-IgAN. Results of multivariable regression were stratified by donor type (living vs. deceased). A total of 107, 747 recipients were included (4589 with IgAN and 103 158 with non-IgAN). Adjusted HR for DCGS showed no significant difference between IgAN and non-IgAN. IgAN had higher patient survival compared to non-IgAN (HR 0.54, 95% CI 0.47-0.62, p < 0.0001 for deceased donors; HR 0.42, 95% CI 0.33-0.54, p < 0.0001 for living donors). Propensity score-matched analysis was similar, with no significant difference in DCGS between matched groups and higher patient survival in IgAN patients compared to non-IgAN group (HR 0.54, 95% CI 0.47, 0.63; p-value <0.0001). IgAN patients with first kidney transplant have superior patient survival and similar graft survival compared to non-IgAN recipients. Results can be used in prognostication and informed decision-making about kidney transplantation in patients with IgAN.

Elevated circulating levels of the pro-inflammatory cytokine macrophage migration inhibitory factor in individuals with acute spinal cord injury.

OBJECTIVE: To test the hypothesis that macrophage migration inhibitory factor (MIF) is elevated in the circulation of individuals with acute spinal cord injury (SCI) compared with uninjured individuals. DESIGN: Prospective, observational pilot study. SETTING: Academic medical center. PARTICIPANTS: Adults with acute traumatic SCI (n=18) and uninjured participants (n=18), comparable in age and sex distribution. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The primary outcome measure was the plasma MIF levels. Potential correlations were examined between MIF and clinical/demographic variables. The secondary outcome was to determine if other immune mediators were elevated in participants with acute SCI and if their levels correlated with the MIF. RESULTS: MIF was significantly elevated in subjects with acute SCI compared with control subjects at 0 to 3 (P<.0029), 4 to 7 (P<.0001), and 8 to 11 (P<.0015) days postinjury (DPI). At 0 to 3 DPI, levels of cytokines interleukin-6 (P<.00017), interleukin-9 (P<.0047), interleukin-16 (P<.007), interleukin-18 (P<.014), chemokines growth-related oncogene α/chemokine (C-X-C motif) ligand 1 (P<.0127) and macrophage inflammatory protein 1-ß/chemokine (C-C motif) ligand 4 (P<.0015), and growth factors hepatocyte growth factor (HGF) (P<.0001) and stem cell growth factor-ß (P<.0103) were also significantly elevated in subjects with acute SCI. With the exception of interleukin-9, all of these factors remained significantly elevated at 4 to 7 DPI; a subset (interleukin-16, HGF, stem cell growth factor-ß) remained elevated throughout the study. Within individuals, MIF levels correlated with HGF (P<.018) and interleukin-16 (P<.01). CONCLUSIONS: These data demonstrate that MIF is significantly elevated in subjects with acute SCI, supporting further investigation of MIF and other inflammatory mediators in acute SCI, where they may contribute to primary and secondary functional outcomes.

Does a palliative care consult decrease the cost of caring for hospitalized patients with dementia?

OBJECTIVE: Advanced dementia (AD) is a terminal disease. Palliative care is increasingly becoming of critical importance for patients afflicted with AD. The primary objective of this study was to compare pharmacy cost before and after a palliative care consultation (PCC) in patients with end-stage dementia. A secondary objective was to investigate the cost of particular types of medication before and after a PCC. METHOD: This was a retrospective study of 60 hospitalized patients with end-stage dementia at a large academic tertiary care hospital from January 1, 2010 to October 1, 2011, in order to investigate pharmacy costs before and after a PCC. In addition to demographics, we carried out a comparison of the average daily pharmacy cost and comparison of the proportion of subjects taking each medication type (cardiac, analgesics, antibiotics, antipsychotics and antiemetics) before and after a PCC. RESULTS: There was a significant decrease in overall average daily pharmacy cost from before to after a PCC ($31.16 ± 24.71 vs. $20.83 ± 19.56; p < 0.003). There was also a significant difference in the proportion of subjects taking analgesics before and after PCC (55 vs. 73.3%; p < 0.009), with a significant average daily analgesic cost rise from pre- to post-PCC: $1.36 ± 5.07 (median = $0.05) versus. $2.35 ± 5.35 (median = $0.71), respectively, p < 0.011; average daily antiemetics cost showed a moderate increase from pre- to post-PCC: $0.08 ± 0.37 (median = $0) versus $0.23 ± 0.75 (median = $0), respectively, p < 0.047. SIGNIFICANCE OF RESULTS: Our findings indicate that PCC is associated with overall decreased medication cost in hospitalized AD patients. Additionally, receiving a PCC was related to greater use of pain medications in hospitalized dementia patients. Our study corroborates the benefits of palliative care team intervention in managing elderly hospitalized dementia patients.

Does adjuvant radiotherapy benefit patients with diffuse-type gastric cancer? Results from the Surveillance, Epidemiology, and End Results database.

BACKGROUND: Diffuse-type gastric cancer is observed in approximately one-third of gastric cancers, yet the optimal treatment remains controversial. In the recently published Intergroup 0116 trial, a subgroup analysis demonstrated a lack of a long-term survival benefit for adjuvant chemoradiation therapy among patients with diffuse-type gastric cancer. METHODS: The Surveillance, Epidemiology, and End Results registry database was queried for patients who were newly diagnosed with diffuse-type gastric cancer between 2002 and 2005 and underwent surgical resection with or without adjuvant radiotherapy (RT). Overall survival (OS) was analyzed by the Kaplan-Meier method. Cox proportional hazards models were used to investigate the association between adjuvant RT and OS, with and without adjusting for other factors. In addition, propensity score methods were used to control for the possible effects of measured confounders. RESULTS: A total of 1889 cases of surgically resected diffuse-type gastric cancer were included in the analysis; of these cases, 782 patients received adjuvant RT and 1107 did not receive RT. The median survival time was 30 months in the group treated with adjuvant RT versus 18 months in the group that did not receive RT with matched propensity scores (P<.001). The Cox model confirmed the improvement in OS in patients who received adjuvant RT (hazard ratio, 0.75; 95% confidence interval, 0.65-0.82 [P<.001]). CONCLUSIONS: The current population-based observational study suggested a potential survival benefit for adjuvant RT among patients with diffuse-type gastric cancer. The standard treatment will likely remain controversial until evidence becomes available from phase 3 randomized trials exclusively for patients with diffuse-type gastric cancer.

Medical orders for life-sustaining treatment: is it time yet?

OBJECTIVE: As the aging population faces complex end-of-life issues, we studied the intervals between long-term care admission and advance directive completion, and between completion and death. We also sought to determine the interdisciplinary team's compliance with documented wishes. METHOD: A cross-sectional study of 182 long-term care residents in two facilities with and without completed medical orders for life-sustaining treatment (MOLST) in the New York Metropolitan area was conducted. Demographic variables included: gender, age, ethnicity, and diagnosis. Measures included: admission date, MOLST execution date, and date of death. Resident advance directive documentation was compared with clinical intervention at time of death, including intubation and mechanical ventilation. RESULTS: Of the residents studied, 68.7% were female, 91% were Caucasian and 91.8% were ≥ 65 years of age (mean age: 83). The median time from admission to MOLST signing was 48 days. Median time from admission to MOLST signing for Caucasians was 21 days; for non-Caucasians was 229 days. Fifty-two percent of MOLST were signed by children, and 24% by residents. Of those with signed forms, 25% signed on day of admission, 37% signed within 7 days, and 47% signed within 21 days. Only 3% of residents died the day their MOLST was signed, whereas 12% died within a week, and 22% died within 30 days. Finally, among the 68 subjects who signed a MOLST and died, 87% had their wishes met. SIGNIFICANCE OF RESULTS: In this era of growing time constraints and increased regulations, medical directors of long-term care facilities and those team members caring for residents urgently need a clear and simple approach to the goals of care for their residents. The MOLST is an ideal tool in caring for older adults at the end of life, providing concrete guidance, not only with regard to do not resuscitate (DNR) and do not intubate (DNI) orders, but also for practical approaches to daily care for the interdisciplinary team.