Acute Rise Research Articles

S2817 Glycopenic Hepatopathy in a Patient With Recurrent Diabetic Ketoacidosis: A Rare Complication of Poorly Controlled Type 1 Diabetes Mellitus

Introduction: Glycogenic hepatopathy (GH) is a rare condition predominately seen in patients with poorly controlled type 1 diabetes mellitus. This condition develops due to excessive accumulation of glycogen in the hepatocytes, leading to significant hepatomegaly and transient liver dysfunction with elevated liver enzymes. Case Description/Methods: A 24-year-old female with a history of poorly controlled type 1 diabetes mellitus complicated by multiple admissions for diabetic ketoacidosis (DKA) presented with acute onset abdominal pain, nausea and vomiting. Physical exam was significant for tender hepatomegaly. Admission laboratory results were significant for serum glucose 189 mg/dL, bicarbonate 5 mmol/L, anion gap 35 mmol/L, beta-hydroxybutyrate 6.5 mmol/L, and HbA1c 11.4%. Admission hepatic panel was significant for alanine aminotransferase 31 U/L, aspartate aminotransferase 56 U/L, alkaline phosphatase 138 U/L with normal bilirubin and prothrombin time. Patient was treated with insulin and intravenous fluids with resolution of her DKA. However, her clinical course was complicated by persistent abdominal pain with an acute rise in liver enzymes (alanine aminotransferase 216 U/L, aspartate aminotransferase 249 U/L, alkaline phosphatase 116 U/L with normal bilirubin and prothrombin time). Triglyceride level was elevated at 214mg/dL. Abdominal computed tomography was notable for hepatomegaly with liver size of 24 cm. Workup for hepatitis, HIV, COVID-19, autoimmune hepatitis, hemochromatosis, and Wilson's disease were negative. Patient underwent liver biopsy that demonstrated diffuse hepatocyte cytoplasmic clearing, consistent with GH. The patient was medically managed with strict glycemic control, diabetic diet and endocrinology input throughout admission. One week after hospital discharge, the patient remained asymptomatic and liver function tests returned to normal limits. Discussion: GH is a rare condition that should be considered in patients with poorly controlled diabetes mellitus who present with hepatomegaly and acute liver injury. While GH presents similarly to NAFLD, it can only be differentiated and definitely diagnosed by liver biopsy. This condition should not be overlooked as it is a favorable diagnosis with a good prognosis compared to other liver disease associated with diabetes mellitus. Further studies are needed to better understand the characteristics of this disease, and future development of non-invasive, rapid diagnostic testing could help avoid extensive and costly workups. (Figure Presented).

Cardiovascular prognosis in patients admitted to an emergency department with hypertensive emergencies and urgencies.

At present, few data are available on the prognosis of hypertensive emergencies and urgencies admitted to emergency departments. The aim of our study was to evaluate the incidence of total and cardiovascular events during follow-up in hypertensive patients admitted to the emergency departments of Brescia Hospital (Northern Italy) with hypertensive emergencies or urgencies from 1 January to 31 December 2015. Medical records of patients aged more than 18 years, admitted to the emergency department with SBP values at least 180 mmHg (SBP) and/or DBP values at least 120 mmHg (DBP) were collected and analysed (18% of patients were classified as 'hypertensive emergency' and 82% as 'hypertensive urgency'). Data in 895 patients (385 men and 510 women, mean age 70. 5 ± 15 years) were analysed; the mean duration of follow-up after admission to the emergency department was 12 ± 5 months. During the follow-up, 96 cardiovascular events (28 fatal) occurred (20 cardiac events, 30 cerebrovascular events, 26 hospital admission for heart failure, 20 cases of new onset kidney disease). In 40 patients (4.5%), a new episode of acute blood pressure rise with referral to the emergency department was recorded. Cardiovascular mortality and morbidity were greater in patients with a previous hypertensive emergency (14.5 vs. 4.5% in patients with hypertensive emergency and urgency, respectively, chi-square, P < 0.0001). Similar results were obtained when the occurrence of cerebrovascular or renal events were considered separately. Admission to the emergency department for hypertensive emergencies and urgencies identifies hypertensive patients at increased risk for fatal and nonfatal cardiovascular events. Our findings add some new finding suggesting that further research in this field should be improved aiming to define, prevent, treat and follow hypertensive urgencies and emergencies.

Possible influence of neurosteroids in the anxiolytic effects of alpha-casozepine

Alpha-casozepine (α CZP), a tryptic hydrolysate of milk casein is a decapeptide shown to promote sleep and produce anxiolytic or anticonvulsant activity. Intriguingly, studies indicate structural similarities to benzodiazepine (BZD)-like molecules (e.g., diazepam), resulting in positive modulation of γ-aminobutyric acid A type (GABAA) receptors. However, some unexplained anomalous behaviour of α-CZP includes 1) 1000 times less affinity for BZD site on GABAA receptor in vitro conditions, whereas in vivo it showed 10-fold increased affinity when compared to diazepam; 2) anxiolytic effects were observed only in stressed conditions and 3) unlike diazepam, it failed to exhibit dependence or habituation. Interestingly, neurosteroids like allopregnanolone or its analogues that are synthesized de novo have both genomic and non-genomic actions. The rapid nongenomic neuronal inhibition of these compounds is mediated by GABAA receptors through autocrine and paracrine actions. Studies have shown that changes in the levels of neurosteroids during acute (rise) and chronic stress (decreased), consequently, altering the senetivity of GABAA receptor subunits. Neurosteroids even at low concentration (nanomolar range) potentiate the response of GABA indirectly, while at higher concentrations they directly activate the receptor-channel complex. Interestingly, coadministration of neurosteroids and BZPs has shown not only to prevent the development of tolerance of BZP and augmented recovery from BZP withdrawal anxiety and hyperactivity in mice. The combination also produced synergetic anxiolytic effects. Taken together, the evidence suggests possible implications of neurosteroids in the actions of CZP via BZD receptors. The present hypothesis brings out the possible role of neurosteroids and the various factors that might participate in CZP-induce anxiolytic effects.

B-PO02-217 NOVEL SOLUTION TO THE MIGRATION OF A TRANSVENOUS ICD PULSE GENERATOR

Migration of a submammary transvenous ICD (TV-ICD) pulse generator is an uncommon event that can be exacerbated by the presence of a saline breast implant, and can impact defibrillation threshold (DFT). Device relocation may become necessary. To describe the successful relocation of a submammary TV-ICD to a mid-axillary pocket of a prior subcutaneous ICD (S-ICD), in a patient whose device migrated anterior to a saline breast implant resulting in an acute change in shock impedance. N/A A 38-year-old female with a history of bi-lateral saline breast implants (2000) and malignant mitral valve prolapse with PVC-induced ventricular fibrillation underwent a secondary-prevention S-ICD implant, which was eventually removed for inappropriate shocks. A single-chamber TV ICD was then implanted in a left-sided submammary position, underneath a saline breast implant. Four months after implant there was an acute rise in high-voltage (HV) impedance (> 110 ohms), corresponding to migration of the TV ICD generator anterior to the breast implant (Figure A and B). Patient declined re-location to the prior submammary position and a traditional pre-pectoral (infraclavicular) position (for aesthetic reasons). As such, the TV ICD pulse generator was repositioned to the mid-axillary position, previously used for the S-ICD implant (Figure C and D). DFT was successful (45 ohms) and HV impedance normalized and remained within normal range at follow-up (Figure E and F). Implantation of TV ICD pulse generator in the mid-axillary location can be considered for patients in whom submammary or infraclavicular positions are either not desired or not feasible.

Lean Six Sigma Methodology and the Future of Quality Improvement Education in Anesthesiology.

Lean Six Sigma Methodology and the Future of Quality Improvement Education in Anesthesiology.

MO990THE RELATIONSHIP BETWEEN T-CELL INFILTRATION IN BIOPSY PROVEN ACUTE T-CELL MEDIATED REJECTION WITH ALLOGRAFT FUNCTION

Abstract Background and Aims Todays increasing effort are made to detect non-invasive and reliable methods for prediction of organ rejection. In the current study, we evaluated the degree of CD3, CD20, Th17 and Tregs infiltration in kidney biopsy of the patients with acute cellular rejection and the possible relation with graft outcome. Method From 70 biopsy proven ATCMR according to Banff criteria in whom kidney biopsy were done based on acute creatinine rise, 50 patients were selected. 20 patients excluded because of insufficient specimen or clinical data. All of recruited patients experienced their first episode of ATCMR. 21 patients had deceased donors and 29 had living ones. Paraffin sections were deparaffinized then dehydrated using alcohols. The tissues were incubated with Antibodies in two stages. First, they were incubated with antihuman IL-17 monoclonal antibody and polyclonal antibody against FOXP3. The results analyzed with SPSS version 20. P value less than 0.05 was considered as significant. Results FOXP3 mean cell count in stable graft function group was 7.88 but in impaired graft group was 8.02, which was not statistically significant (P-value :0. 96). Th17 mean cell count in stable group was 5.0 but in impaired group was 10.1, which was not significant too (P-value: 0.24). FOXP3/Th17 ratio was higher in stable group (1.4 versus 1.12) but without any statistically important value (P-value: 0.22) .CD3 count was higher in impaired group (29.8 versus 27.7) and CD20 count was more in stable group (8.8 versus 7.8) without any significant values (P-value: 0.7 and 0.62) respectively. FOXP3 positive cell count was higher in failure to response group (9.95 vs. 6.63) but with non-significant P-value of 0.1. Th17 count was higher also in this group (11.3 vs. 8.3) but with non-significant value .The FOXP3/Th17 ratio was higher in appropriate response group (1.19 vs. 1.15) with P-value 0.8 .CD3 count was higher in response group and CD20 in failure group vice versa (31.2 vs. 27.3 and 7.96 vs. 8.06) also with nonsignificant values Conclusion We observed that allografts with higher Th17 at biopsy had lower levels of GFR in the next 12 months. One conclusion can be that assessing the Th17 infiltration is more effective than FOXP3 Tregs in predicting the prognosis of renal transplant .

Precipitation of Euglycemic DKA (euDKA) From the Initiation of SGLT2 Inhibitor (SGLT2i) and 0-Carb Diet Inpatient

Background: SGLT2i are increasingly prescribed for their cardiorenal benefits. Nationally renowned endocrinologists have begun to actively discuss the need for guidelines on safe use of SGLT2i inpatient, with the most common indication being treatment for advanced heart failure (HF). However, no consensus has been reached to date. While in the hospital, patients with HF who are taking SGLT2i are at an increased risk for developing euDKA due to volume depletion, critical illnesses, and restricted dietary intake. We present a case of euDKA inpatient in a man admitted for HF treated with empagliflozin (EMPA). Clinical Case: A 54-year-old man with HF and non-ischemic cardiomyopathy was admitted for decompensated HF. The patient was also newly diagnosed with T2D on admission when he presented with an elevated blood glucose (BG) of 395 mg/dL (n 62–125 mg/dL) and an elevated A1C of 13.6% (n 4–6%). Cardiologists initiated EMPA 25 mg PO daily on hospital day (HD) 2, in addition to MDI insulin. On HD3, a 0-carb diet was started for a planned FDG PET/CT scan to assess the etiology of cardiomyopathy. With an extremely limited food selection, the patient became largely fasting between HD3-6 while awaiting the PET scan, eating only eggs once a day. On HD6, patient developed chest pain and hypotension and was found to be in euDKA with AKI. Labs were notable for arterial pH 7.14 (n 7.35–7.45), CO2 12 meq/L (n 22–32 meq/L), anion gap (AG) 23 (n 4–12), BG 238 mg/dL (n 62–125 mg/dL), beta-hydroxybutyrate 7.29 mmol/L (n <0.30 mmol/L), and an acute rise in creatinine from 0.8 to 1.4 mg/dL (n 0.51–1.18 mg/dL). In addition to stopping the EMPA, the patient required treatment with IV insulin and fluids for 24 hours, with resolution of euDKA, hypovolemia, and AKI. Patient was safely discharged on HD14 on MDI insulin and metformin. Conclusion: While euDKA is increasingly recognized outpatient and perioperatively, it is under-recognized in the hospital setting. A study reported 94 patients at one center using SGLT2i inpatient experiencing no euDKA (1). However, hospitalized patients taking SGLT2i remain vulnerable to euDKA, especially with concurrent critical illnesses, volume depletion and restricted dietary intake. Zero-carb intake triggers energy production by ketosis, which greatly amplifies the risk of euDKA on SGLT2i. There are currently no guidelines for safe use of SGLT2i inpatient. When using SGLT2i inpatient, we advocate for clinicians to closely monitor patients’ symptoms and AG twice a day and consider holding SGLT2i with prolonged fasting of >24 hours to readily prevent, diagnose and treat euDKA. We recommend educating clinicians on the side effects associated with SGLT2i, developing EMR alerts, and involving endocrinologists with inpatient use of SGLT2i in high-risk patients.

Role of CORT Duration and Estradiol Dependence for Stress-level of CORT to Inhibit Pulsatile LH Secretion in Female Mice

Two common responses to stress include elevated circulating glucocorticoids and impaired luteinizing hormone (LH) secretion. We have shown that a chronic stress-level of corticosterone (CORT) can slow LH pulses in female mice and that this reduction required estradiol. In addition, the decrease in LH secretion was associated with a suppression in neuronal activation of arcuate kisspeptin (Kiss1) neurons, regarded as the LH pulse generator. Although the increment of the chronic CORT rise was physiological, the duration of the rise exceeded that of a normal CORT response to an acute stressor. Therefore, the goal of the current study was to investigate whether an acute, exogenous CORT rise is sufficient to inhibit LH pulses and arcuate Kiss1 expression, and whether estradiol is necessary for this inhibition. For this study, adult C57bl6 female mice were ovariectomized and implanted with either an implant filled with oil (OVX) or 100 ng estradiol (OVX+E), which approximates a diestrus level of estradiol. Blood samples to measure pulsatile LH were collected every 6 minutes for 90 minutes prior to and following the initiation of CORT or saline treatment. Animals were randomly assigned to receive one of 4 treatments: a single injection of CORT (0.6 mg/kg, i.p) or saline, or three successive injections separated by 30 minutes of CORT (3xCORT) or saline (3xSaline). This dose of CORT elicited a CORT elevation similar to the endogenous CORT rise induced by restraint stress. One injection of CORT elicited an elevation for 30 minutes; the three-injection paradigm elevated CORT for 90 minutes, the entirety of the post injection LH sampling period. Regardless of estradiol status, LH did not differ between the pre and post injection period in mice administered a single injection of CORT or saline. In contrast, in OVX+E mice, 3xCORT significantly slowed the frequency of LH pulses (pulses/90 min: 2.7±0.2 vs 1.4±0.3; pre vs post, p<0.05) compared to mice given 3xSaline (pulses/90 min: 2.9±0.4 vs 2.8±0.4; pre vs post, p>0.05). Interestingly, in OVX mice, there was no impairment of LH secretion in response to either 3xCORT (pulses/90 min: 4.9±0.4 vs 4.7±0.5; pre vs post, p>0.05) or 3xSaline. Knowing that glucocorticoid receptors are present in arcuate Kiss1 cells, we investigated the effect of CORT on Kiss1 expression. Brains were collected 3 hrs following the initiation of the 3xSaline or 3xCORT treatment, and the arcuate nucleus was micropunched for measurement of Kiss1. In OVX+E mice, Kiss1 expression in the arcuate nucleus was suppressed 47% by 3xCORT compared to 3xSaline treated mice (p<0.05). Collectively these data show that an acute CORT rise is sufficient to impair pulsatile LH secretion and Kiss1 expression, but the rise has to be sustained for more than 30 minutes and requires the presence of estradiol. Whether CORT is acting directly or indirectly on arcuate Kiss1 neurons to impair LH secretion remains to be determined.

Зрошення гіпертонічним розчином розірваної ехінококової кісти печінки: унікальний випадок успішного лікування тяжкої ятрогенної гіпернатріємії

У статтi повідомляється про унікальний випадок розриву ехінококової кісти, який вимагав зрошення гіпертонічним розчином, що є однією зі стандартних форм лікування цих пацієнтів. У пацієнта розвинулася гостра ятрогенна гіпернатріємія, яка досягла рівня 197 ммоль, що рідко описується в літературі. Різке підвищення рівня натрію в сироватці крові значно збільшує ризик розвитку синдрому осмотичної демієлінізації. Після корекції гіпернатріємії стан пацієнта покращився, неврологічного дефіциту не було. У літературі описується дуже мало випадків у дорослих, які пережили цей ступінь гіпернатріємії без ускладнень, навіть після успішного лікування, оскільки смертність сягає 70 %, у той час як рівень натрію у сироватці підвищується до 160 ммоль. Запобігання тяжкій гіпернатріємії є наріжним каменем у зниженні смертності. Частий контроль рівня натрію в сироватці крові є обов’язковим для запобігання неврологічним ускладненням.

CARDIOVASCULAR RISK AND OUTCOME IN PATIENTS WITH HYPERTENSIVE EMERGENCIES AND URGENCIES IN AN EMERGENCY DEPARTMENT. AN ITALIAN GREEK COLLABORATION

Objective: Background: at present, few data are available on the prognosis of hypertensive emergencies and urgencies admitted to Emergency Departments (ED). The aim of our study was to evaluate the incidence of total and cardiovascular events during follow-up in hypertensive patients admitted in 2 ED in Italy and Greece with hypertensive emergencies or urgencies. Design and method: Methods: medical records of patients aged &gt; 18 yrs, admitted to the ED with blood pressure values &gt; = 180 mmHg (SBP) and/or &gt; = 120 mmHg (DBP) were collected and analysed (24% of patients were classified as “hypertensive emergency” and 76 % as “hypertensive urgency”). Data in 1218 patients (556 men and 662 women, mean age 70 + 13 years) were analysed; the mean duration of follow-up after admission to the ED was 19.5 + 7 months years. Results: Results: During the follow-up cardiovascular events occurred in 148 patients (69 cardiac events, 43 cerebrovascular events). In 272 pts (22 %) a new episode of acute BP rise was recorded. A total of 87 deaths was recorded during follow-up (in 28 patients for cardiovascular causes). All cause and CV mortality were greater in patients with a previous hypertensive emergency (14.7 vs 4.7 %, chisquare p = 0.0001 and 5.8 vs 1.2% chisquare p &lt; 0.0001 for all-cause and for CV mortality, respectively). The incidence of non fatal cardiovascular events was 10,11 and 2,11 per 100 patient-years in patients with hypertensive emergency and urgency, respectively and similar results were obtained when we considered separately the occurrence of cerebrovascular events. Conclusions: Conclusions: admission to the ED for hypertensive emergencies identifies hypertensive patients at increased risk for fatal and non fatal cardiovascular events. Our results underline the need for an accurate follow-up in patients with hypertensive emergencies and urgencies.

Career Services in the Post‐COVID‐19 Era: A Paradigm for Career Counseling Unemployed Individuals

The 2019 novel coronavirus (COVID‐19) pandemic has caused unprecedented economic disruption and unemployment worldwide, threatening to become both a financial and a humanitarian crisis. Prolonged labor market recession and an acute rise of unemployment are expected. The main question for career counselors will be how to provide effective career counseling to unemployed people in the post‐COVID‐19 world, where they may face many other unemployment‐related problems. In this article, we suggest application of a holistic intervention model of career counseling for unemployed people that was designed to address the consequences of the acute financial recession in Greece.

Development of a large animal rabbit model for chronic periprosthetic joint infection.

AimsPeriprosthetic joint infections (PJIs) and osteomyelitis are clinical challenges that are difficult to eradicate. Well-characterized large animal models necessary for testing and validating new treatment strategies for these conditions are lacking. The purpose of this study was to develop a rabbit model of chronic PJI in the distal femur.MethodsFresh suspensions of Staphylococcus aureus (ATCC 25923) were prepared in phosphate-buffered saline (PBS) (1 × 109 colony-forming units (CFUs)/ml). Periprosthetic osteomyelitis in female New Zealand white rabbits was induced by intraosseous injection of planktonic bacterial suspension into a predrilled bone tunnel prior to implant screw placement, examined at five and 28 days (n = 5/group) after surgery, and compared to a control aseptic screw group. Radiographs were obtained weekly, and blood was collected to measure ESR, CRP, and white blood cell (WBC) counts. Bone samples and implanted screws were harvested on day 28, and processed for histological analysis and viability assay of bacteria, respectively.ResultsIntraosseous periprosthetic introduction of planktonic bacteria induced an acute rise in ESR and CRP that subsided by day 14, and resulted in radiologically evident periprosthetic osteolysis by day 28 accompanied by elevated WBC counts and histological evidence of bacteria in the bone tunnels after screw removal. The aseptic screw group induced no increase in ESR, and no lysis developed around the implants. Bacterial viability was confirmed by implant sonication fluid culture.ConclusionIntraosseous periprosthetic introduction of planktonic bacteria reliably induces survivable chronic PJI in rabbits.Cite this article: Bone Joint Res 2021;10(3):156–165.

An exploratory assessment of stretch-induced transmural myocardial fiber kinematics in right ventricular pressure overload

Right ventricular (RV) remodeling and longitudinal fiber reorientation in the setting of pulmonary hypertension (PH) affects ventricular structure and function, eventually leading to RV failure. Characterizing the kinematics of myocardial fibers helps better understanding the underlying mechanisms of fiber realignment in PH. In the current work, high-frequency ultrasound imaging and structurally-informed finite element (FE) models were employed for an exploratory evaluation of the stretch-induced kinematics of RV fibers. Image-based experimental evaluation of fiber kinematics in porcine myocardium revealed the capability of affine assumptions to effectively approximate myofiber realignment in the RV free wall. The developed imaging framework provides a noninvasive modality to quantify transmural RV myofiber kinematics in large animal models. FE modeling results demonstrated that chronic pressure overload, but not solely an acute rise in pressures, results in kinematic shift of RV fibers towards the longitudinal direction. Additionally, FE simulations suggest a potential protective role for concentric hypertrophy (increased wall thickness) against fiber reorientation, while eccentric hypertrophy (RV dilation) resulted in longitudinal fiber realignment. Our study improves the current understanding of the role of different remodeling events involved in transmural myofiber reorientation in PH. Future experimentations are warranted to test the model-generated hypotheses.

Inflation volume-balloon diameter and inflation pressure-balloon diameter characteristics of commonly used bronchial blocker balloons for single-lung ventilation in children.

Balloon-tipped bronchial blocker catheters are widely used in pediatric thoracic anesthesia to establish single-lung ventilation. In clinical practice, their balloons demonstrate sudden expansion when inflated with air. In addition, there are concerns related to the high inflation pressures required to expand the balloons. This in vitro study assessed inflation volume- and inflation pressure-balloon diameter characteristics of the Fogarty arterial embolectomy catheters and Arndt endobronchial blockers. Balloon diameters were photographically assessed during unrestricted volume- and pressure-guided inflation, using air up to the maximum allowed inflation volume as indicated by the manufacturers. Inflation pressures required to open the blocker balloons and inflation pressures needed to expand them to maximum indicated diameter were measured. Volume-guided inflation demonstrated a late acute rise in diameter in Fogarty blocker balloons, whereas in the Arndt endobronchial blocker balloons almost linear inflation volume-to-diameter characteristics were observed. Pressure-guided inflation on the other hand demonstrated low-volume, high-pressure characteristics in the Fogarty blocker balloons, with inflation pressures required to expand the balloons to maximum diameters ranging from (mean (SD)) 636 (75) to 947 (152) cmH2 O. The inflation pressures required to open the Fogarty blocker balloons were even >1000cmH2 O. Inflation pressures required to expand the 5 F, 7 F, and 9 F Arndt endobronchial blocker balloons to maximum indicated diameter were much lower, namely at 218 (15), 252 (28), and 163 (8) cmH2 O. Based on these study findings, the balloons of Fogarty arterial embolectomy catheters represent high-pressure devices and do not permit stepwise controlled bronchial blockage. The Arndt endobronchial blockers have some advantages over the Fogarty blocker devices, but also represent high-pressure equipment and must be used with caution and limited duration. Manufacturers are asked to design pediatric endobronchial blocker catheters with truly high-volume, low-pressure balloons in accordance to age-related pediatric airway dimensions.

Chronic elevation of cardiac troponin I predicts the extent of coronary disease in hemodialysis patients presenting with acute enzyme elevation

IntroductionElevation of cardiac troponin I (cTn-I) is associated with coronary artery disease (CAD) in asymptomatic patients with end-stage renal disease (ESRD) receiving hemodialysis. We aim to investigate the diagnostic value of chronically elevated cTn-I in ESRD patients presenting with an acute rise in serum cTn-I levels. MethodsWe performed a retrospective analysis of 364 patients. Using coronary angiography, we correlated baseline elevation of cTn-I with the severity of CAD when hemodialysis patients present with acute symptomatic elevation in serum cTn-I. ResultsIn hemodialysis patients presenting with a rise in serum cTn-I above baseline levels, 59% had severe CAD, and 17% had no angiographic evidence of CAD. Hemodialysis patients with severe CAD had significantly higher baseline cTn-I levels compared to patients with non-severe CAD or normal coronaries (p < 0.0001). Baseline elevation of cTn-I in the severe CAD group was correlated with the degree of CAD occlusion (r2 0.56, p < 0.0001), fitting a positive linear model. Furthermore, baseline cTn-I differentiates between patients with and without severe CAD with a test accuracy of 0.72 (95% CI, 0.69–0.75, p < 0.001). At a value of ≥0.2 ng/mL (cutoff for myocardial necrosis), the specificity of baseline cTn-I for underlying severe CAD was 0.95. ConclusionsElevated baseline cTn-I has good accuracy for anticipating more advanced angiographic CAD when hemodialysis patients present with a symptomatic rise in serum cTn-I above baseline levels. Baseline elevation of cTn-I can be used for cardiac disease risk management in hemodialysis patients presenting with symptoms suggestive of CAD.

Assigning Causality for Abnormal Tryptases: α-Gal and Other Causes of Anaphylaxis, Mastocytosis and More

The diagnosis of anaphylaxis can be clinically challenging but is supported by an acute rise in tryptase. Here we sought to establish the incidence of cases of tryptase-confirmed anaphylaxis attributable to alpha-gal, a major cause of allergic reactions in our area. We also describe other causes of tryptase-confirmed anaphylaxis and other explanations for elevated tryptase.

91 Utility of serial amniotic fluid analysis for intrapartum infection prediction of Triple-I: our first steps.

The NICHD introduced suspected triple-I (intrauterine inflammation or infection) in 2015 to provide specific diagnostic recommendations for chorioamnionitis. Their criteria yielded a sensitivity and specificity of 67.6% and 38.1% for adverse infectious outcomes, respectively, with positive and negative likelihood ratios for histologically-confirmed triple-I being 1.20 and 0.70. We aim to augment the utility of triple-I definitions by examining serially-sampled amniotic fluid (AF) in laboring patients with and without suspected triple-I/Isolated Maternal Fever (IMF). This prospective cohort study enrolled term, singleton pregnancies in labor at an academic-community hospital. Patients who required an intrauterine pressure catheter (IUPC) for standard indications had AF aspirated and analyzed for: glucose, cell count, and aerobic culture at several standardized times: at IUPC placement and every 4 hours until delivery. Cohort I & II designate patients with and without triple-I/IMF, respectively. 18 patients with IUPC enrolled; 5 with triple-I/IMF and 13 who remained afebrile. Baseline AF WBC in Cohort I was 85 (IQR 58 – 144) cells/mL which increased to 222 (IQR 144 – 452) just before first fever with significant increase to 6150 (IQR 1193 – 7180)[p < 0.002] by final aspiration before delivery. In contrast, baseline AF WBC in Cohort II was 43 (IQR 19 – 70) with a nonsignificant increase to 188 (IQR 79 – 365) before delivery (Figure 1). Cohort I had a 66-fold increase from baseline to final WBC count compared to a 25-fold increase in Cohort II. AF WBC before delivery were significantly different between cohorts (p < 0.034). Remaining results in Table 1. Our preliminary results suggest that serial intrapartum AF assessment is a possible reproducible technique. Notably, there is an acute rise observed in AF WBC preceding maternal fever, suggesting this may be an early indicator of developing infection and possibly aid clinicians in antibiotic decision-making. In future studies, we aim to correlate these changes in AF parameters with maternal/newborn clinical outcomes.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Changing Incidence and Survival of Primary Central Nervous System Lymphoma in Australia: A 33-Year National Population-Based Study.

Primary central nervous system lymphoma (PCNSL) is a rare brain cancer that remains challenging to study. Epidemiology of PCNSL in the Australian population, which is racially and ethnically diverse, has not been examined previously. Using ICD-O-3.1 Morphology and Topography Codes to identify cases, we analyzed complete datasets from the comprehensive Australian Cancer Database (1982-2014, adults aged ≥ 20 years) to establish incidence rates and trends of PCNSL, and to define survival outcomes of individuals diagnosed with PCNSL, including the predominant diffuse large B-cell lymphoma (DLBCL) type. Age-standardized incidence of PCNSL increased by an average annual 6.8% percent over the study period, with current incidence of 0.43 (95% confidence interval, 0.41-0.46) per 100,000 person-years, in comparison to 21.89 (21.41-22.38) per 100,000 person-years for non-CNS lymphoma. Increase in incidence was characterized by an acute rise between 1996 and 1999, was more pronounced with increasing age, and was driven by increasing incidence of DLBCL. Overall survival for persons diagnosed with PCNSL improved significantly across the study period, with 5-year survival probability increasing from 0.21 (95% confidence interval, 0.16-0.26) to 0.33 (0.30-0.36), and median survival increasing from 318 to 600 days, between 1982-1999 and 2000-2014. Increase in survival was significantly higher for persons with DLBCL versus non-DLBCL PCNSL, but substantially lower than that for persons with non-CNS lymphoma, who had a 5-year survival probability of 0.62 (0.62-0.62) and a median survival of 3388 days in 2000-2014. This study links increasing incidence of PCNSL in Australia to increasing incidence of DLCBL, including in younger adults, and highlights the improving, but low, survival outcome of this cancer.

Stressed erythrophagocytosis induces immunosuppression during sepsis through heme-mediated STAT1 dysregulation.

Macrophages are main effectors of heme metabolism, increasing transiently in the liver during heightened disposal of damaged or senescent RBCs (sRBCs). Macrophages are also essential in defense against microbial threats, but pathological states of heme excess may be immunosuppressive. Herein, we uncovered a mechanism whereby an acute rise in sRBC disposal by macrophages led to an immunosuppressive phenotype after intrapulmonary Klebsiella pneumoniae infection characterized by increased extrapulmonary bacterial proliferation and reduced survival from sepsis in mice. The impaired immunity to K. pneumoniae during heightened sRBC disposal was independent of iron acquisition by bacterial siderophores, in that K. pneumoniae mutants lacking siderophore function recapitulated the findings observed with the WT strain. Rather, sRBC disposal induced a liver transcriptomic profile notable for suppression of Stat1 and IFN-related responses during K. pneumoniae sepsis. Excess heme handling by macrophages recapitulated STAT1 suppression during infection that required synergistic NRF1 and NRF2 activation but was independent of heme oxygenase-1 induction. Whereas iron was dispensable, the porphyrin moiety of heme was sufficient to mediate suppression of STAT1-dependent responses in human and mouse macrophages and promoted liver dissemination of K. pneumoniae in vivo. Thus, cellular heme metabolism dysfunction negatively regulated the STAT1 pathway, with implications in severe infection.

Transscleral cyclophotocoagulation with MicroPulse® laser versus Ahmed valve implantation in patients with advanced primary open-angle glaucoma

To compare the efficacy of transscleral cyclophotocoagulation with MicroPulse® laser (Iridex, Silicon Valley, California, USA) with 3000mW to Ahmed valve implantation in eyes with advanced stage of primary open-angle glaucoma. In a prospective observational clinical study, 30 patients (30 eyes) with advanced open-angle glaucoma were randomized for either micropulse transscleral cyclophotocoagulation with 3000mW or Ahmed valve implantation. Fifteen eyes were treated with transscleral cyclophotocoagulation with MicroPulse® laser with 3000mW (group A) and 15 eyes with Ahmed valve implantation (group B). As inclusion criteria are included the diagnosis of advanced primary open-angle glaucoma, an intraocular pressure above 21mmHg, cup-to-disk ratio 0.9-1.0, failure to meet the target IOP with either maximal tolerated local medical therapy (2-4 antiglaucoma agents) or systemic therapy (acetazolamide). The follow-up time of the study was 12months. An absolute success was defined the achievement of IOP between 6 and 15mmHg and at least 30% reduction of the IOP from baseline under reduced or the same number of antiglaucoma agents after the surgical procedure without following glaucoma surgeries and as qualified success the achievement of IOP between 6 and 18mmHg and at least 20% reduction of the IOP from baseline regardless of the number of postoperative antiglaucoma agents. The efficacy was evaluated by estimating the absolute success rate and the qualified success rate using the Kaplan-Meier survival analysis. A reduction of the intraocular pressure > 30% was achieved in 33.3% of group A and in 73.3% of group B during the follow-up period of 12months. A statistically significant decrease in the number of eye drops was observed in both groups (p < 0.01). 53.3% of the eyes of group A underwent additional anti-glaucoma procedures to achieve target intraocular pressure. The number of the local medications that were administered 12months after the ocular surgery was 2 (± 1.3) in group A and 0.57 (± 0.9) in group B, compared to 3.2 (± 0.78) in group A and 3.33 (± 0.7) in group B administered prior to the surgery (p: 0.016). 8 eyes (53.33%) in group A were referred for additional treatment due to an acute postoperative rise in IOP (5 eyes: mTS-CPC, 1 eye: canaloplasty, 2 eyes: AGV implantation). No further anti-glaucoma procedures were necessary in group B. The Ahmed valve implantation achieves a more efficient decrease of the intraocular pressure as well as of the number of antiglaucoma agents than the transscleral cyclophotocoagulation with MicroPulse® diode laser 3000mW. Additionally, the Ahmed valve implantation showed better results in terms of absolute and qualified success rates in the treatment of advanced primary open-angle glaucoma.