Median Plasma Research Articles

Admission eGFR predicts in-hospital mortality independently of admission glycemia and C-peptide in patients with type 2 diabetes mellitus and COVID-19

Objective Type 2 diabetes mellitus (T2DM) and impaired kidney function are associated with a higher risk of poor outcomes of coronavirus disease 2019 (COVID-19). We conducted a retrospective study in hospitalized T2DM patients with COVID-19 to assess the association between in-hospital mortality and admission values of different hematological/biochemical parameters, including estimated glomerular filtration rate (eGFR), plasma glucose and C-peptide (the latter serving as a marker of beta-cell function). Methods The study included T2DM patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who were consecutively admitted to our Institution between 1 October 2020 and 1 April 2021. Results Patients (n = 74) were categorized into survivors (n = 55) and non-survivors (n = 19). Non-survivors exhibited significantly higher median white blood cell (WBC) count, D-dimer, neutrophil-to-lymphocyte ratio, high-sensitivity C-reactive protein (hsCRP), and procalcitonin levels, as well as significantly lower median serum 25-hydroxyvitamin D [25(OH)D] levels compared to survivors. Non-survivors exhibited significantly higher median admission plasma glucose (APG) values compared to survivors (210 vs. 166 mg/dL; p = .026). There was no statistically significant difference in median values of (random) plasma C-peptide between non-survivors and survivors (3.55 vs. 3.24 ng/mL; p = .906). A significantly higher percentage of patients with an eGFR < 60 mL/min/1.73 m2 was observed in the non-survivor group as compared to the survivor group (57.9% vs. 23.6%; p = .006). A multivariate analysis performed by a logistic regression model after adjusting for major confounders (age, sex, body mass index, major comorbidities) showed a significant inverse association between admission eGFR values and risk of in-hospital mortality (OR, 0.956; 95% CI, 0.931-0.983; p = .001). We also found a significant positive association between admission WBC count and risk of in-hospital mortality (OR, 1.210; 95% CI, 1.043–1.404; p = .011). Conclusions Admission eGFR and WBC count predict in-hospital COVID-19 mortality among T2DM patients, independently of traditional risk factors, APG and random plasma C-peptide. Hospitalized patients with COVID-19 and comorbid T2DM associated with impaired kidney function at admission should be considered at high risk for adverse outcomes and death.

Osmotic pump maintains plasma concentrations of meloxicam for 6 days after orthopedic surgery in pigeons (Columba livia).

To determine the plasma concentration of meloxicam delivered via an osmotic pump in pigeons undergoing orthopedic surgery and if an osmotic pump is a suitable alternative to repeated oral administration of this drug. 16 free-ranging pigeons presented for rehabilitation with a wing fracture. An osmotic pump filled with 0.2 mL of 40 mg/mL meloxicam injectable solution was implanted subcutaneously in the inguinal fold of 9 pigeons under anesthesia for orthopedic surgery. The pumps were removed 7 days postsurgery. Blood samples were collected before pump implantation (time 0) and 3, 24, 72, and 168 hours after pump implantation in 2 pigeons in a pilot study then at 12, 24, 72, and 144 hours in the 7 pigeons of the main study. The blood of 7 other pigeons receiving meloxicam at 2 mg/kg, PO, every 12 hours was also sampled between 2 to 6 hours after the last meloxicam administration. Plasma meloxicam concentrations were measured via high-performance liquid chromatography. The plasma concentration of meloxicam was maintained at significant levels from 12 hours to 6 days after osmotic pump implantation. Median and minimum plasma concentrations in implanted pigeons were maintained at the same or higher level than those measured in pigeons that received meloxicam at a dose known to be analgesic in this species. No adverse effects attributable to either osmotic pump implantation and removal or meloxicam delivery were observed in this study. Plasma concentrations levels of meloxicam in pigeons implanted with osmotic pumps were maintained at a similar concentration or higher than the suggested analgesic meloxicam plasma concentration in this species. Thus, osmotic pumps could represent a suitable alternative to the frequent capture and handling of birds for analgesic drug administration.

A Vegetarian Diet Significantly Changes Plasma Kynurenine Concentrations.

Tryptophan is an essential amino acid and a precursor of a number of physiologically important metabolites, including serotonin, melatonin, tryptamine, and kynurenines. We assessed tryptophan, kynurenines, and vitamin B2 and B6, as well as biomarkers of liver function and inflammation, in a group of 158 female omnivores and vegetarians aged 18-40 years. The majority of women were omnivores, and 22% were vegetarians. Vegetarians had 25% lower serum ALT, significantly higher pyridoxal concentrations, and significantly lower plasma concentrations of most kynurenines, varying from 8% lower concentrations of median plasma kynurenine to 42% lower concentrations of plasma xanthurenic acid, compared to omnivores. No significant differences were observed in vitamin B2 status or in inflammation markers, C-reactive protein and neopterin between the groups. Vegetarians had lower levels of several plasma kynurenines compared to omnivores. The reason for this is unknown; however, lower ALT concentrations, suggesting a better liver status, and a more favourable vitamin B6 status might be contributing factors.

Impact of lifestyle factors on dietary vitamin B6 intake and plasma pyridoxal 5'-phosphate level in UK adults: National Diet and Nutrition Survey Rolling Programme (NDNS) (2008-2017).

Reduction in dietary vitamin B6 intake is associated with an increased relative risk of diseases such as cancer, atherosclerosis and cognitive dysfunction. The current research has assessed vitamin B6 intakes and PLP concentrations as a marker of vitamin B6 status among the UK adult (≥ 19 years) population. This study was carried out using a cross-sectional analysis of the National Diet and Nutrition Survey Rolling Programme (NDNS) (2008-2017). The impacts of lifestyle factors, including type of diet, smoking, alcohol consumption, and commonly used medications grouped by therapeutic usage, were determined, and data were analysed using IBM SPSS®. Results are expressed as medians (25th-75th percentiles), with P values ≤ 0·05 considered statistically significant. Among UK adults, the median intakes of total population of dietary vitamin B6 met the reference nutrient intake and median plasma PLP concentrations were above the cut-off of vitamin B6 deficiency; however, we found an association between reduction in vitamin B6 intake and plasma PLP concentration and age group (P < 0·001). Smokers had significantly lower plasma PLP concentrations than non-smokers (P < 0·001). Moreover, regression analysis showed some commonly used medications were associated with plasma PLP levels reduction (P < 0·05). Taken together, we report on a tendency for dietary vitamin B6 intake and plasma PLP concentrations to decrease with age and lifestyle factors such as smoking and medication usage. This information could have important implications for smokers and in the elderly population using multiple medications (polypharmacy).

Adult-onset immunodeficiency induced by anti-interferon-γ autoantibodies: report of 13 cases

Objective: To investigate the clinical characteristics of a group of patients with adult-onset immunodeficiency (AOID) induced by anti-interferon-γ autoantibodies (AIGA). Methods: Thirteen cases of AOID in a northern China medical center (Peking Union Medical College Hospital) from October 2020 to April 2022 were included. Data comprising clinical manifestations, laboratory results, infection sites and pathogens were collected. Results: Among the 13 patients, 5 were male. The median age of disease onset was 47 (14 to 71) years. The median time from symptom onset to diagnosis was 4 years (1 to 8 years). Four patients were from northern China, and 9 from southern China. Common symptoms included lymphadenopathy (13/13), fever (12/13), respiratory tract symptoms (12/13), and weight loss (11/13). Laboratory tests showed increased levels of white blood cell count (9/13), neutrophil count and proportion (9/13), erythrocyte sedimentation rate (ESR) (12/13), and C reactive protein (CRP) (11/13). The median plasma titers of AIGA upon diagnosis were 5681(3194, 13246). Sites of infection included lungs (12/13), lymph nodes (9/13), bones and joints (9/13), skin and soft tissue (7/13), blood flow and bone marrow (4/13), and glands (3/13). Most patients had nontuberculous mycobacteria (NTM) (12/13) infection. Seven patients had more than one pathogen. Conclusions: AOID also affects patients visiting northern China hospitals. AIGA screening is recommended among patients with disseminated NTM infections or recurrent infections.

Plasma Copper Concentration Is Associated with Cardiovascular Mortality in Male Kidney Transplant Recipients.

Kidney transplant recipients (KTR) are at increased risk of cardiovascular mortality. We investigated whether, in KTR, post-transplantation copper status is associated with the risk of cardiovascular mortality and potential effect modification by sex. In this cohort study, plasma copper was measured using mass spectrometry in extensively-phenotyped KTR with a functioning allograft >1-year. Cox regression analyses with the inclusion of multiplicative interaction terms were performed. In 660 KTR (53 ± 13 years old, 56% male), the median baseline plasma copper was 15.42 (IQR 13.53-17.63) µmol/L. During a median follow-up of 5 years, 141 KTR died, 53 (38%) due to cardiovascular causes. Higher plasma copper was associated with an increased risk of cardiovascular mortality in the overall KTR population (HR 1.37; 95% CI, 1.07-1.77 per 1-SD, p = 0.01). Sex was a significant effect modifier of this association (Pinteraction = 0.01). Among male KTR, higher plasma copper concentration was independently associated with a two-fold higher risk of cardiovascular mortality (HR 2.09; 95% CI, 1.42-3.07 per 1-SD, p < 0.001). Among female KTR, this association was absent. This evidence offers a rationale for considering a sex-specific assessment of copper's role in cardiovascular risk evaluation. Further studies are warranted to elucidate whether copper-targeted interventions may decrease cardiovascular mortality in male KTR.

Ultra-long-acting in-situ forming implants with cabotegravir protect female macaques against rectal SHIV infection

Ultra-long-acting delivery platforms for HIV pre-exposure prophylaxis (PrEP) may increase adherence and maximize public health benefit. We report on an injectable, biodegradable, and removable in-situ forming implant (ISFI) that is administered subcutaneously and can release the integrase inhibitor cabotegravir (CAB) above protective benchmarks for more than 6 months. CAB ISFIs are well-tolerated in female mice and female macaques showing no signs of toxicity or chronic inflammation. In macaques, median plasma CAB concentrations exceed established PrEP protection benchmarks within 3 weeks and confer complete protection against repeated rectal SHIV challenges. Implant removal via a small incision in 2 macaques at week 12 results in a 7- to 48-fold decrease in plasma CAB levels within 72 hours. Modeling to translate CAB ISFI dosing suggests that a 3 mL injection would exceed protective benchmarks in humans for over 5 months post administration. Our results support the clinical advancement of CAB ISFIs for ultra-long-acting PrEP in humans.

Evaluation of plasma doravirine concentrations in patients with HIV-1 undergoing hemodialysis

The pharmacokinetics of doravirine (DOR) have not been clarified in patients undergoing hemodialysis (HD). In this study, we evaluated the pharmacokinetics of DOR in four HIV-1-infected patients undergoing HD who were administered DOR. The participants were patients undergoing HD for end-stage renal disease and were administered DOR. DOR was administered once daily (one tablet of 100 mg), every evening. On days of HD treatment, DOR was administered after the end of the procedure. After administration of DOR for at least 1 week, the plasma DOR concentration was measured. The median plasma trough DOR concentration was 766.9 ng/mL (range: 509–1085 ng/mL). The median DOR clearance by HD, DOR elimination rate, half-life (T1/2) of plasma DOR concentration during HD, and T1/2 during the non-HD period were 85.04 mL/min, 73.12%, 7.71 h, and 13.76 h, respectively. The T1/2 during the HD period was significantly shorter than the T1/2 during the non-HD period (p = 0.0030). In this study, elimination of DOR by HD was confirmed. Viral suppression was maintained in all patients undergoing HD, and none had adverse events or safety problems. As DOR is eliminated by HD, monitoring its plasma concentration is considered necessary for clinical use.

Clozapine: Dose, Sex, Ethnicity, Smoking Habit, Age, Body Weight, and Plasma Clozapine and N-Desmethylclozapine (Norclozapine) Concentrations in Clinical Practice.

Guidance on clozapine dosing in treatment refractory schizophrenia is based largely on data from young adult male White patients. This study aimed to audit the plasma clozapine and N-desmethylclozapine (norclozapine) concentrations attained in male and female patients of different ethnicity and smoking habit. The effect of dose, sex, ethnicity, age, body weight, and smoking habit on plasma clozapine and norclozapine concentrations were studied using data from a therapeutic drug monitoring service, 1993 to 2017. There were 371,610 samples (48,098 patients, 32,855 male). Ethnicity was recorded for 763 Afro-Caribbean, 536 Asian, and 7940 White patients. Males were prescribed significantly higher median doses than females but attained significantly lower median plasma clozapine and norclozapine concentrations. Asian and Afro-Caribbean males were prescribed significantly lower and higher median doses, respectively, than White males but attained significantly higher and lower median plasma clozapine and norclozapine concentrations, respectively. Data from 78,431 samples (23,516 patients) were analyzed using a linear mixed model. The predicted dose to attain a predose plasma clozapine concentration of 0.35 mg/L in a nonsmoking White male aged 40 years, with weight of 70 kg, and plasma clozapine-norclozapine ratio of 1.32 was 344 mg/d (95% confidence interval, 227-526 mg/d). The predicted dose was 33% higher and 20% lower in otherwise analogous Afro-Caribbean and Asian patients, respectively. In all cases, the predicted dose was increased by 36% in smokers and decreased by 22% in females. Research is needed to further investigate the complex relationships between dose, sex, ethnicity, plasma clozapine and norclozapine concentrations, and clinical outcome such as weight gain.

Maternal Midpregnancy Plasma trans 18:1 Fatty Acid Concentrations Are Positively Associated with Risk of Maternal Vascular Complications and Child Low Birth Weight

Background: Evidence is plentiful that trans fatty acids (TFAs) induce vascular inflammation with adverse metabolic consequences. However, it is not clear whether TFAs increase the risk of vascular pregnancy complications such as preeclampsia.Objective: We investigated associations between midpregnancy maternal plasma trans 18:1 fatty acid (t18:1) concentrations and pregnancy course and outcomes.Methods: Participants were 6695 pregnant women and newborns from the Generation R Study, Rotterdam, Netherlands (enrollment in 2001-2005). Maternal midpregnancy (mean ± SD gestational age: 20.7 ± 1.2 wk) t18:1 plasma concentrations were determined and related to gestational age and sex-adjusted birth weight SD scores, placental weight, and the risk of preeclampsia. In addition, we explored potential time trends by testing the association of maternal plasma t18:1 concentrations with birth weight in birth cohorts given the Dutch industry-initiative to lower food TFA contents during the inclusion period. Multiple logistic and linear regression analyses were performed, taking various socioeconomic and biological covariates into account.Results: A higher midpregnancy maternal plasma t18:1 concentration was associated with lower birth weight (SD score, adjusted β: -0.10; 95% CI: -0.15, -0.04; P < 0.001) and placental weight (kilograms, adjusted β: -10,65; 95% CI: -20.23, -1.07; P = 0.03) and with a higher risk of preeclampsia (adjusted OR: 1.65; 95% CI: 1.10, 2.49; P = 0.02). We observed a 31% decrease in the median plasma t18:1 concentration in our population over time, but the association between the plasma t18:1 concentration standardized per birth year and birth weight was comparable between birth-year cohorts (years 2001-2005).Conclusions: A higher maternal midpregnancy plasma t18:1 concentration was associated with lower birth weight and placental weight and with a higher risk of preeclampsia. Although the intake of TFAs in our population decreased during the inclusion period, the association with adverse pregnancy outcomes was unchanged even at lower maternal plasma t18:1 concentrations.

Distinguishing immune-mediated thrombotic thrombocytopenic purpura from septic disseminated intravascular coagulation using plasma levels of haptoglobin and factor XIII activity

BackgroundBoth immune-mediated thrombotic thrombocytopenic purpura (iTTP) and septic disseminated intravascular coagulation (DIC) are life-threatening disorders developed by platelet-consuming microvascular thrombi and necessitate immediate therapeutic interventions. Although severe deficiencies of plasma haptoglobin in iTTP and factor XIII (FXIII) activity in septic DIC have been reported, few studies have focused on the possibility of using these markers to distinguish between iTTP and septic DIC. ObjectivesWe investigated whether the plasma levels of haptoglobin and FXIII activity could be helpful for differential diagnosis. MethodsThirty-five patients with iTTP and 30 with septic DIC were enrolled in the study. Patient characteristics, coagulation, and fibrinolytic markers were collected from the clinical data. Plasma haptoglobin and FXIII activities were measured using chromogenic Enzyme-Linked Immuno Sorbent Assay and an automated instrument, respectively. ResultsThe median plasma haptoglobin level was 0.39 mg/dL and 54.20 mg/dL in the iTTP and septic DIC groups, respectively. The median plasma FXIII activities were 91.3% and 36.3% in the iTTP and septic DIC groups, respectively. In the receiver operating characteristic curve analysis, the cutoff level of plasma haptoglobin was 2.868 mg/dL and the area under the curve was 0.832. The cutoff level for plasma FXIII activity and the area under the curve were 76.0% and 0.931, respectively. The thrombotic thrombocytopenic purpura (TTP)/DIC index was defined by FXIII activity (percentage) and haptoglobin (milligrams per decilitre). Laboratory TTP was defined as an index ≥60 and laboratory DIC <60. The sensitivity and specificity of the TTP/DIC index were 94.3% and 86.7%, respectively. ConclusionThe TTP/DIC index, composed of plasma levels of haptoglobin and FXIII activity, is useful in differentiating iTTP from septic DIC.

POSTER ABSTRACTS

POSTER ABSTRACTS

Clinical development and evaluation of plasma angiogenesis factors from phase II study of FOLFIRI plus ramucirumab with recurrent colorectal cancer refractory to adjuvant chemotherapy with oxaliplatin/fluoropyrimidine (RAINCLOUD): RAINCLOUD-TR.

173 Background: Higher levels of vascular endothelial growth factor-D (VEGF-D) is a potential predictive biomarker for ramucirumab (Ram) efficacy on overall survival and progression-free survival (PFS) in Ram+FOLFIRI vs Placebo+FOLFIRI for bevacizumab (Bev) refractory metastatic colorectal cancer (mCRC). However, it is not clear whether VEGF-D acts as a predictive biomarker in pts who pretreated without Bev. RAINCLOUD showed the clinical benefit of FOLFIRI+ plus Ram for pts with recurrent CRC refractory to adjuvant chemotherapy (median PFS was 6.2 months (M); ESMO-GI 2022). RAINCLOUD-TR was designed as a prospective biomarker study estimating the association of biomarkers with Ram efficacy. Methods: Plasma sample collections were done at time points of pre-/ post-treatments in pts receiving FOLFIRI+Ram. Measurements of 17 factors (including VEGF-A, VEGF-D and PlGF) were performed by multiplex assay with Luminex technology. The high/ low groups were defined bases on the median plasma level at the baseline. Results: From September 2017 to September 2021, 81 plasma samples were collected from 48 pts and 32 pts in both pre/ and post treatment. Level of VEGF-A, VEGF-D, PlGF and TSP-2 were all significantly higher in post vs pre-treatment [Table]. The ORR analyses were as follows; VEGF-A, VEGF-D and PlGF in low vs high were 50.0%/33.3% (p=0.35, HR 1.97), 55.0% /33.3% (p=0.22, HR 2.39), and 60.0%/28.6% (p=0.35, HR 1.95). The PFS analyses were as follows; VEGF-A, VEGF-D, and PlGF in low vs high were 6.1M/6.0M (p=0.815, HR 0.92), 7.6M /5.6M (p=0.095, HR 0.56), and 8.0M/4.2M (p=0.014, HR 0.40). In other factors, low TSP-2 were better ORR (low vs high: 66.7%/20.0% (p=0.004, HR 7.54) and PFS 7.5M/4.3M (p=0.022, HR 0.45). Conclusions: In this exploratory study, PFS was numerically greater for pts with low vs high VEGF-D for Ram in pts with mCRC pretreated without Bev. VEGF-D may not be predictive biomarker, but TSP-2 may be a potential prognostic biomarker, further studies in larger cohorts are needed to confirm our results. Clinical trial information: UMIN000028678 . [Table: see text]

Association of Inflammatory Biomarkers With Survival Among Patients With Stage III Colon Cancer

The association of chronic inflammation with colorectal cancer recurrence and death is not well understood, and data from large well-designed prospective cohorts are limited. To assess the associations of inflammatory biomarkers with survival among patients with stage III colon cancer. This cohort study was derived from a National Cancer Institute-sponsored adjuvant chemotherapy trial Cancer and Leukemia Group B/Southwest Oncology Group 80702 (CALGB/SWOG 80702) conducted between June 22, 2010, and November 20, 2015, with follow-up ending on August 10, 2020. A total of 1494 patients with plasma samples available for inflammatory biomarker assays were included. Data were analyzed from July 29, 2021, to February 27, 2022. Plasma inflammatory biomarkers (interleukin 6 [IL-6], soluble tumor necrosis factor α receptor 2 [sTNF-αR2], and high-sensitivity C-reactive protein [hsCRP]; quintiles) that were assayed 3 to 8 weeks after surgery but before chemotherapy randomization. The primary outcome was disease-free survival, defined as time from randomization to colon cancer recurrence or death from any cause. Secondary outcomes were recurrence-free survival and overall survival. Hazard ratios for the associations of inflammatory biomarkers and survival were estimated via Cox proportional hazards regression. Of 1494 patients (median follow-up, 5.9 years [IQR, 4.7-6.1 years]), the median age was 61.3 years (IQR, 54.0-68.8 years), 828 (55.4%) were male, and 327 recurrences, 244 deaths, and 387 events for disease-free survival were observed. Plasma samples were collected at a median of 6.9 weeks (IQR, 5.6-8.1 weeks) after surgery. The median plasma concentration was 3.8 pg/mL (IQR, 2.3-6.2 pg/mL) for IL-6, 2.9 × 103 pg/mL (IQR, 2.3-3.6 × 103 pg/mL) for sTNF-αR2, and 2.6 mg/L (IQR, 1.2-5.6 mg/L) for hsCRP. Compared with patients in the lowest quintile of inflammation, patients in the highest quintile of inflammation had a significantly increased risk of recurrence or death (adjusted hazard ratios for IL-6: 1.52 [95% CI, 1.07-2.14]; P = .01 for trend; for sTNF-αR2: 1.77 [95% CI, 1.23-2.55]; P < .001 for trend; and for hsCRP: 1.65 [95% CI, 1.17-2.34]; P = .006 for trend). Additionally, a significant interaction was not observed between inflammatory biomarkers and celecoxib intervention for disease-free survival. Similar results were observed for recurrence-free survival and overall survival. This cohort study found that higher inflammation after diagnosis was significantly associated with worse survival outcomes among patients with stage III colon cancer. This finding warrants further investigation to evaluate whether anti-inflammatory interventions may improve colon cancer outcomes. ClinicalTrials.gov Identifier: NCT01150045.

Clinical study on the feasibility of new thrombus markers in predicting massive cerebral infarction.

This study investigated the diagnostic performance of the thrombin-antithrombin complex (TAT), plasmin-α2 plasmin inhibitor complex (PIC), tissue plasminogen activator-plasminogen activator inhibitor complex (t-PAIC), and thrombomodulin (TM) in the early identification of massive cerebral infarction. A total of 423 patients with cerebral infarction confirmed by imaging examination were divided into the massive cerebral infarction (MCI) group and the non-massive cerebral infarction (NMCI) group. TAT, PIC, t-PAIC, and TM were measured immediately after admission. The diagnostic performance was analyzed by the receiver characteristic operating curve (ROC). The median plasma concentrations of TAT, PIC, and t-PAIC in patients with MCI at early onset were 5.10 ng/ml, 1.11 μg/ml, and 8.80 ng/ml, respectively, which were higher than those in patients with NMCI (2.20 ng/ml, 0.59 μg/ml, and 7.35 ng/ml), and the difference was statistically significant (P < 0.001). TAT was shown to be an independent risk factor for the development of massive cerebral infarction by a multivariate logistic regression analysis (OR = 1.138). A ROC curve analysis showed that PIC had the best performance in identifying MCI at an early stage (AUC = 82.8%), with a sensitivity of 80.7% and a specificity of 76.2% when the PIC concentration was ≥0.8 μg/ml; TAT had the highest specificity in identifying MCI, with a specificity of 80.6% when the TAT concentration was ≥3.97 ng/ml. The detection of PIC, TAT, t-PAIC, and TM is a comprehensive assessment of vascular endothelial damage and activation of the coagulation and fibrinolytic systems and has diagnostic value for early identification of patients with MCI, which, together with its ease of detection, can be used as a plasma marker for early identification of large vessel occlusion.

Prevalence of Admission Hyponatremia in Patients With Diabetes Treated With and Without an SGLT2 inhibitor.

Hyponatremia often reflects a free water excess. Sodium/glucose cotransporter 2 (SGLT2) inhibitors increase free water excretion through glucose-induced osmotic diuresis. In 2 randomized double-blind, placebo-controlled trials in patients with the syndrome of inappropriate antidiuresis (SIAD), we showed that empagliflozin increased plasma sodium concentration more effectively than placebo. We hypothesized that long-term therapy with SGLT2 inhibitors might reduce the prevalence of hyponatremia on hospital admission. In this retrospective analysis, we extracted data from adult patients with type 2 diabetes (T2DM) hospitalized at the University Hospital Basel between 2015 and 2020. Patients with an SGLT2 inhibitor on admission were matched 1:1 according to age, gender, diagnosis of heart failure, and principal diagnosis to patients without an SGLT2 inhibitor on admission. The primary outcome was the prevalence of hyponatremia (plasma sodium concentration corrected for glycemia <135 mmol/L) on admission. We analyzed 821 patients with T2DM treated with and 821 patients with T2DM without an SGLT2 inhibitor on admission. Hyponatremia prevalence on admission was 9.9% in the treated group, and 8.9% in the matched control group (P = .554), in other words, the risk for hyponatremia did not differ (multivariable adjusted odds ratio 1.08, 95% CI 0.72-1.44, P = .666). There was no difference in the median (interquartile range) plasma sodium concentration between the groups (treated 140 mmol/L [138-142], controls 140 mmol/L [138-142]; P = .1017). Based on these retrospective findings, treatment with SGLT2 inhibitors does not prevent hyponatremia. However, prospective randomized data suggest their efficacy at a higher dosage in overt SIAD.

Cardiac magnetic resonance in giant cell myocarditis: a matched comparison with cardiac sarcoidosis.

Giant cell myocarditis (GCM) is an inflammatory cardiomyopathy akin to cardiac sarcoidosis (CS). We decided to study the findings of GCM on cardiac magnetic resonance (CMR) imaging and to compare GCM with CS. CMR studies of 18 GCM patients were analyzed and compared with 18 CS controls matched for age, sex, left ventricular (LV) ejection fraction and presenting cardiac manifestations. The analysts were blinded to clinical data. On admission, the duration of symptoms (median) was 0.2 months in GCM vs. 2.4 months in CS (P = 0.002), cardiac troponin T was elevated (>50 ng/L) in 16/17 patients with GCM and in 2/16 with CS (P < 0.001), their respective median plasma B-type natriuretic propeptides measuring 4488 ng/L and 1223 ng/L (P = 0.011). On CMR imaging, LV diastolic volume was smaller in GCM (177 ± 32 mL vs. 211 ± 58 mL, P = 0.014) without other volumetric or wall thickness measurements differing between the groups. Every GCM patient had multifocal late gadolinium enhancement (LGE) in a distribution indistinguishable from CS both longitudinally, circumferentially, and radially across the LV segments. LGE mass averaged 17.4 ± 6.3% of LV mass in GCM vs 25.0 ± 13.4% in CS (P = 0.037). Involvement of insertion points extending across the septum into the right ventricular wall, the "hook sign" of CS, was present in 53% of GCM and 50% of CS. In GCM, CMR findings are qualitatively indistinguishable from CS despite myocardial inflammation being clinically more acute and injurious. When matched for LV dysfunction and presenting features, LV size and LGE mass are smaller in GCM.

Clinical and serological association of plasma 25-hydroxyvitamin D (25(OH)D) levels in lupus and the short-term effects of oral vitamin D supplementation

Background and objectivesData on the association of vitamin D levels and clinical phenotype and disease activity in systemic lupus erythematosus (SLE) is controversial. Further, the optimal dose of oral vitamin D supplementation in SLE is not clear. Thus, the present study was designed to determine the association of plasma vitamin D levels with clinical phenotype, disease variables and serology in a large, cohort of SLE from South Asia and to evaluate the short-term effect of two different dosage regimens of oral vitamin D supplementation on disease flares and plasma vitamin D levels.MethodsThis is a two-phase study. Phase I was a cross-sectional analytical study of patients from north (26.85° N) and south India (11.94° N). Plasma 25-hydroxyvitamin-D(25(OH)D) was measured, and its association with demography, serology, disease activity, Galectin-9 and CXCL-10 was analysed. In phase II, patients with SLEDAI-2KG < 10 and on stable immunosuppression were randomised to receive either high dose (weekly 60,000 U*5, followed by 60,000 U monthly) or routine dose (30,000 U monthly) oral vitamin D. Outcomes were assessed at 6 monthsResultsPhase I included 702 patients with a mean age of 29.46 + 10.7 years. The median plasma vitamin D was 22.83 (13.8–31.8) ng/ml. Deficiency (< 20 ng/ml) was seen in 41.5% of patients. Patients from South India had higher vitamin D levels (27.06 ± 20.21 ng/dl) as compared to North India (17.15 ± 16.07 ng/ml) (p < 0.01). Univariate analyses demonstrated weak negative correlation of vitamin D with SLEDAI2K and positive correlation with age. Galactin-9 had modest correlation with SLEDAI2K but not with vitamin D levels. On multiple linear regression, centre of recruitment (β = 4.37) and age (β = 0.18) predicted (p < 0.05) plasma vitamin D levels.In the phase II, 91 randomised to 2 groups completed 6 months. Median change in plasma vitamin D levels was more in high dose (9.5 versus 2.6 ng/ml; p = 0.04). There were 14 SLE flares and six minor adverse events which were equal across both groups.ConclusionVitamin D deficiency is common in SLE. Geographical location of residence is the major determinant rather than the disease activity. The IFN regulated proteins reflect disease activity independent of vitamin D levels. High-dose oral vitamin D supplementation seems safe and more effective in improving vitamin D levels in SLE.Trial registrationThe second phase of this study was a registered randomised controlled trial CTRI/2019/06/019658 [registered on: 14/06/2019].

Pharmacokinetics of acetaminophen after a single Oral administration of 20 or 40 mg/kg to 7-9 Day-old foals.

Acetaminophen is utilized in human infants for pain management and fever. Neonatal foals might benefit from administration of acetaminophen but effective and safe dosage regimens for neonatal foals remains to be determined. The objective was to determine the plasma pharmacokinetics of acetaminophen following oral administration of a single dose of 20 mg/kg or 40 mg/kg to neonatal foals. A secondary objective was to evaluate any changes in hematology and biochemistry profiles. Randomized study. Eight clinically healthy 7-9-day old Quarter Horse foals (3 colts and 5 fillies) received a single oral dose of acetaminophen either 20 (n = 4) or 40 (n = 4) mg/kg. Hematology and biochemistry profiles were evaluated before and 7 days after drug administration. Blood samples were collected before and 8 times after acetaminophen administration for 48 h to quantify plasma acetaminophen concentrations. Plasma pharmacokinetic parameters were estimated using non- compartmental analysis. The median peak plasma concentrations (and range) occurred at 1.5 (0.5-2) hours, and 1.0 (1-2) hours for the 20 and 40 mg/kg doses. The maximum plasma concentration (and range) was 12 (7.9-17.4) μg/mL for the 20 mg/kg dose and 14 (11-18) μg/mL for 40 mg/kg dose. The median AUC0-∞ ranged from 46 to 100 and 79 to 160 h*-μg/mL for the 20 and 40 mg/kg dose, respectively. Hematology and biochemistry profiles remained within normal limits. Plasma disposition of acetaminophen after oral administration of 20 and 40 mg/kg to neonates is comparable to adult horses. However, safety and the optimal dosage regimen of acetaminophen for treating pain and or pyrexia in neonates in this age group remains to be determined.

PS-C24-8: PLASMA ANGIOTENSIN CONVERTING ENZYME 2 ACTIVITY IN HOSPITALISED PATIENTS WITH ACUTE HEART FAILURE CLASSIFIED BY LEFT VENTRICULAR EJECTION FRACTION

Objective: Angiotensin-converting enzyme 2 (ACE2) is present on endothelial cells with a role to degrade angiotensin II. In this study, we investigate plasma ACE2 levels in patients admitted with acute decompensated heart failure (ADHF) and determine if levels differ according to ejection fraction (EF). Design and Method: We prospectively recruited 9 controls and 117 ADHF inpatients, determined EF using echocardiography, measured plasma ACE2 activity using an in-house assay and NT-proBNP levels using a commercially available assay. Patients were classified according to 2021 European Guidelines as HF with reduced EF (HFrEF), mildly reduced EF (HFmrEF) or preserved EF (HFpEF). Results: In addition to NT-proBNP level, median plasma ACE2 activity was increased in ADHF patients (n = 117) compared to controls (1.33 [0.02, 4.02] vs 15.36 [9.02, 27.9] pmol/mL/min, p &lt; 0.0001). In ADHF, plasma ACE2 activity was negatively associated with EF (r = -0.43, p &lt; 0.0001). Overall, 58% of patients had HFrEF, 10% had HFmrEF and 32% had HFpEF. Patients with HFrEF had a higher median plasma ACE2 activity compared to those with HFpEF (18.3 [12.3, 30.0] vs 11.4 [4.8, 17.9] pmol/mL/min, p = 0.001) and higher NT-proBNP levels (p = 0.001). There was no difference in plasma ACE2 activity between patients with HFmrEF and HFpEF or HFmrEF and HFrEF. Conclusions: Plasma ACE2 activity is elevated in patients hospitalised with ADHF and is significantly higher in HFrEF compared to other types of HF. Further studies are needed to determine if measurement of plasma ACE2 can assist in better definition /classification of the patient phenotype to facilitate improved treatment.