Serial Measurements Research Articles

Impaired maternal central hemodynamics precede the onset of vascular disorders of pregnancy at high altitude.

Hypertensive disorders of pregnancy represent an escalating global health concern with increasing incidence in low- to middle-income countries and high-income countries alike. The current lack of methods to detect the subclinical stages of preeclampsia (PE) and fetal growth restriction (FGR), two common vascular disorders of pregnancy, limits treatment options to minimize acute- and long-term adverse outcomes for both mother and child. To determine whether impaired maternal cardiovascular or uteroplacental vascular function precedes the onset of PE and/or FGR (PE-FGR), we used non-invasive techniques to obtain serial measurements of maternal cardiac output (CO), stroke volume (SV), systemic vascular resistance (SVR), as well as uterine and fetal arterial resistance at gestational weeks 10-16, 20-24 and 30-34 for 79 maternal-infant pairs in La Paz-El Alto, Bolivia (3850 m), where the chronic hypoxia of high altitude increases the incidence of PE and FGR. Compared to controls (n=55), PE-FGR cases (n=24) had lower SV, higher SVR, and greater uterine artery resistance at 10-16 weeks. In addition, fetuses of women with lower SV and higher SVR at 10-16 weeks showed evidence of brain sparing at 30-34 weeks and had lower birth weights, respectively. While the trajectory of SV and SVR across pregnancy was similar between groups, PE-FGR cases had a comparatively blunted rise in CO from the first to the third visit. Impaired maternal central hemodynamics and increased uteroplacental resistance precede PE-FGR onset, highlighting the potential use of such measures for identifying high-risk pregnancies at high altitudes.

Evaluating the diagnostic and prognostic utility of serial KL-6 measurements in connective tissue disease patients at risk for interstitial lung disease: correlations with pulmonary function tests and high-resolution computed tomography

BackgroundInterstitial lung diseases associated with connective tissue diseases (CTD-ILD) necessitate reliable biomarkers for effective management. This study assesses the utility of serial Krebs von den Lungen-6 (KL-6) measurements in predicting disease activity and progression in CTD-ILD patients.MethodsIn a prospective cohort study at a tertiary care center, 50 patients with CTD at risk of or diagnosed with ILD were enrolled. KL-6 levels and pulmonary function tests (PFTs) were measured at baseline, 6, and 12 months, alongside high-resolution computed tomography (HRCT).ResultsInitial KL-6 levels were inversely correlated with PFTs, with mean values starting at 504.96 U/mL (SD ± 508.46), escalating to 739.42 U/mL (SD ± 612.75) at 6 months, and peaking at 1150.27 U/mL (SD ± 1106.70) by 12 months, reflecting disease progression. Higher KL-6 levels were consistently linked with declines in Forced Vital Capacity (FVC) (p = 0.019) and Diffusing Capacity for Carbon Monoxide (DLCO) (p < 0.001). Radiologically, increased KL-6 correlated with subpleural thickening (p = 0.003), septal thickening (p = 0.036), ground-glass opacities (p = 0.018), and other signs of advanced ILD. Sensitivity and specificity of KL-6 for detecting ILD were 86.7% and 71.4%, respectively, at a ≥ 400 U/mL threshold, improving at higher thresholds. Over the study period, patients with elevated KL-6 levels demonstrated more pronounced radiological and functional deterioration.ConclusionSerial KL-6 measurements effectively reflect disease activity and progression in CTD-ILD, with strong correlations to functional and radiological outcomes. These findings support the use of KL-6 as a valuable biomarker in the routine clinical management of these complex disorders. Our study demonstrates the significant predictive value of KL-6 for both the diagnosis and monitoring of CTD-ILD, suggesting its integration into clinical practice can enhance patient care and treatment strategies.

Predictive validity of interleukin 6 (IL-6) for the mortality in critically ill COVID-19 patients with the B.1.617.2 (Delta) variant in Vietnam: a single-centre, cross-sectional study

ObjectivesTo investigate the serum IL-6 levels and their rate of change in predicting the mortality of critically ill patients with COVID-19 in Vietnam.DesignA single-centre, cross-sectional study.SettingAn Intensive Care Centre for...

Intraperitoneal immunotherapy with denileukin diftitox (ONTAK) in recurrent refractory ovarian cancer

BackgroundDenileukin diftitox (ONTAK) is a diphtheria/IL-2R fusion protein able to deplete regulatory T cells in peripheral blood. Regulatory T cells in the local immune microenvironment have been shown to be associated with poor prognosis in ovarian cancer. This study examined whether denileukin diftitox (ONTAK) could be safely administered intraperitoneal in patients with advanced refractory ovarian cancer and assessed its effects on regulatory T cells and tumor associated cytokines in ascites and peripheral blood. Patients and methodsA phase I dose escalation study of intraperitoneal denileukin diftitox (ONTAK) enrolled 10 patients with advanced, refractory ovarian carcinoma at 3 doses (5 μg/kg, 15 μg/kg, and 25 μg/kg). Serial CA-125 measurements assessed clinical response. Regulatory T cells were quantified using RT-PCR and cytokine levels measured by Luminex. ResultsThe maximum tolerated dose was 15 μg/kg with a dose limiting toxicity observed in 1 out of 6 patients in the expansion group. The majority of adverse events were transient grades 1–2. One patient treated at the 25 μg/kg dose experienced cytokine storm with prolonged hospitalization. 3 patients had decreases in CA-125 after treatment but none met criteria for partial response. Treatment with denileukin diftitox (ONTAK) decreased regulatory T cells in peripheral blood and ascites. Treated patients did not show any significant changes in IL-8, TGF-β, sIL2Ra in ascites or peripheral blood. ConclusionsDenileukin diftitox (ONTAK) can be safely administered intraperitoneally to recurrent refractory ovarian cancer patients. Regulatory T cells were reduced in ascites and peripheral blood, but there were no significant changes in cytokine levels.Clinical Trial Registration:ClinicalTrials.gov # NCT00357448

“The Itsy-Bitsy Water Bead Went Down the Baby's Mouth. Will Drinking Gastrografin Help to Flush It Out?”

IntroductionForeign body ingestion is a common occurrence in the pediatric population. Superabsorbent polymers (i.e., water beads [WB]), such as Orbeez, are brightly colored spheres, can expand up to 100x their original size and are marketed as toys for kids. Ingested WB may lead to a bowel obstruction and typically require surgical removal. MethodsFully expanded WBs (N = 15) were placed into 1 of the 3 solutions: water (N = 5), gastrografin (N = 5), or 1:1 mixture of gg and water (N = 5), with serial diameter measurements obtained at 1, 4, 8, and 24 h. Additionally, fully expanded WBs were placed into succus containing post mortem porcine small bowel and mixed with gastrografin (N = 10) or nothing (N = 10), with diameters measured prior to placement and at 4 h. ResultsAt all time points, the mean WB diameter of the gastrografin arm was significantly smaller than the other two arms (P < 0.01). WBs submerged in gastrografin saw a 58% reduction in diameter at 4 h compared to 45% reduction in the 1:1 mixture and a 2% growth in water (P < 0.01). When placed into small bowel containing gastrografin, the mean WB diameter decreased by 47% at 4 h versus 37% in the control arm (P < 0.01). ConclusionsGastrografin significantly reduced the size of WB in both the in-vitro and ex-vivo post mortem animal study; and it may offer a nonsurgical option for the management of water bead ingestion. Studies assessing the clinical efficacy of a gastrografin nonoperative management strategy are needed.

Autoantibody-Based Clinicoradiopathologic Phenotyping of Idiopathic Inflammatory Myopathies: An Indian Cohort.

We aim to characterize the clinical, pathological, laboratory and imaging features of various antibody defined IIM subgroups in Indian population. 103 patients who satisfied 2017 ACR/ EULAR Classification criteria for IIM, and tested seropositive for myositis antibodies using Immunoblot technique were retrospectively identified. Patients were classified into following subgroups - Mi2B group, SRP group, Anti RNA Synthetase antibody group (Jo 1, PL 7, PL 12, OJ), multiple MSA, only MAA group (U1RNP, Ro 52, SS-A, SS-B, PM Scl 75, PM Scl 100). Clinical, laboratory, histopathology and imaging parameters were compared among different groups. Ro52 (n = 31; 22.46%) was the most common autoantibody seen in our cohort followed by Mi2B (n = 26; 18.84%) and SRP (n = 20; 14.49%). Skin manifestations (p = 0.053) and joint involvement (p = 0.023) were seen more frequently among Mi2B and MAA sub groups. Three out of 4 patients with persisting antibody positivity on serial measurements developed clinical relapse between 2 and 3 years after the initial episode. Remaining 2 patients showed declining titres of antibodies and developed no clinical relapses during follow up period of 5 and 6 years. Among histopathology features, perifascicular atrophy was found to be more prevalent among Mi2B (55.6%) and MAA subgroups (31.3%) (p value = 0.037). In thigh muscle MRI, Mi2B group showed a pattern of diffuse involvement of affected muscles without regional preference, with sparing of hamstring group. SRP group showed characteristic pattern of edema involving peripheral regions of Quadriceps femoris and central regions of Adductor group along with severe atrophy involving hamstring and adductor compartment muscles. ILD was seen in 27.5% of patients who underwent CT Chest. 3 patients were found to have underlying malignancy at the time of diagnosis of myositis (Mi2B = 2 and PM Scl = 1). Classification of IIM patients based on myositis antibodies yields subgroups with certain differences in clinical, laboratory, histopathological and imaging features.

Longitudinal change in cervical length measured after prophylactic cerclage in predicting spontaneous preterm birth.

To evaluate the value of serial post-cerclage cervical length measurements in predicting preterm birth. This was a retrospective study of women with a singleton pregnancy who underwent prophylactic transvaginal cerclage from 2017 to 2023. Prophylactic cerclage was performed in women with an obstetric history of cervical insufficiency. After cerclage, all participants underwent routine transvaginal cervical measurement every 2-4 weeks until 32-34 weeks of gestation. Trajectory patterns of changes in cervical length were identified through latent class trajectory modeling. The association of patterns with spontaneous preterm birth and pregnancy interval was analyzed by multivariable logistic regression analysis and Cox proportional hazards regression models. The specific characteristics of changes in cervical length associated with preterm birth were identified. We involved 225 women and acquired a total of 1248 measurements of cervical length. Two distinct trajectories of cervical length change along gestation were identified: Class 1 (persistent shortening of cervix, n = 52 [23.11%]) and class 2 (stable cervix, n = 173 [76.89%]). Women in class 1 were highly associated with spontaneous preterm birth, with a hazard ratio (95% confidence interval [CI]) of 2.00 (1.36, 2.96). The average shortening rate ≥0.24 cm per week and cervical length ≤1.1 cm was significantly associated with spontaneous preterm birth at different gestational age. Serial sonographic cervical length measurements after prophylactic cerclage are valuable in predicting preterm birth.

Evaluation of the safety and effect of lyophilized canine-specific albumin to increase serum albumin concentration and colloid osmotic pressure in healthy dogs.

To evaluate the safety of repeated administration of a lyophilized canine-specific albumin (CSA) product and to quantify its effect on serum albumin concentrations and colloid osmotic pressure (COP) in healthy dogs. Prospective study. University research facility. Six healthy, adult, purpose-bred Beagles. Dogs received 1g/kg of 16% CSA intravenously on days 1, 2, and 14 and were observed, with serial measurement of vital parameters during and for 2hours after each infusion, to monitor for adverse events or evidence of a hypersensitivity reaction. Serum albumin concentration and COP were measured at predetermined time points before and after each infusion. One dog experienced a single episode of vomiting approximately 1hour after completion of the second infusion. No other adverse reactions were observed during the 28-day study period. Serum albumin concentration was increased by a mean of 0.57g/dL (5.7g/L) (P=0.003) when measured 2hours after the first CSA infusion, and albumin concentration remained significantly higher than baseline at 24hours after infusion, with a mean difference of 0.42g/dL (4.2g/dL) (P<0.001). The second and third CSA infusions similarly increased serum albumin concentration at 2hours (P=0.001 and P=0.001, respectively) and 24hours (P=0.012 and P=0.007, respectively) after infusion. COP increased by a mean of 2.03mmHg at 2hours after the first infusion (P=0.013) and remained significantly higher than baseline at 24hours after infusion, with a mean difference of 1.52mmHg (P=0.002). The second CSA infusion similarly increased COP at 2hours (P<0.001) and 24hours (P=0.017) after infusion. The third CSA infusion increased COP at 2hours after infusion (P=0.004) but did not achieve statistical significance at 24hours after infusion (P=0.053). A 1-g/kg dose of lyophilized CSA was effective at increasing serum albumin concentration and COP. Repeated infusions of CSA appear safe in healthy dogs.

The Single-Dose Pharmacokinetics of a Compounded Levetiracetam Formulation and Bioequivalence to a Commercial Formulation in Healthy Dogs.

Levetiracetam (LEV) is an anti-epileptic drug used extra-label in dogs. Commercially available extended-release formulations (LEV-ER), administered twice daily, cannot be crushed or split, limiting their use in small dogs. A compounded LEV-ER formulation (PO-COMP) can purportedly be partitioned without loss of extended-release properties. The aims of this study were to establish the pharmacokinetic parameters of PO-COMP, divided at the tablet score, and determine the bioequivalence of partitioned PO-COMP to an intact commercially available Food and Drug Administration-approved human oral generic formulation of LEV-ER (PO-COMM). In a randomized crossover design, 12 healthy dogs received a single IV dose (30 mg/kg) of IV-COMM, a single oral dose (500 mg) of intact PO-COMM, or a single oral dose (500 mg) of partitioned PO-COMP and underwent serial measurement of plasma LEV concentrations over 24 h. PO-COMP was bioequivalent to PO-COMM using the 90% confidence interval method for maximum concentration (-3.2% difference [CI -7.4% to -1.1%]) and area under the curve (-14.4% difference [CI -17.8% to 10.8%]). PO-COMP may improve medication adherence and seizure control relative to immediate-release LEV, which requires three times daily dosing. Efficacy studies of PO-COMP are warranted.

Abstract 4117646: The Ultimate Test in Hemocompatibility: HeartMate3 Restart After Prolonged Pump Shut Down

Introduction: The HeartMate 3 (HM3) LVAD, was shown to have a higher survival free of hemocompatibility related adverse events (HRAE) compared to its predecessors (HM2, HVAD). Superior HM3 outcomes are attributed to wide blood flow pathways coupled with frictionless movement and intrinsic pulsatility, reducing shear stress and blood stasis. It is unknown if improved hemocompatibility can withstand pump restart after prolonged shutdown. We herein report a case of HM3 pump stoppage without subsequent HRAE. Case Presentation: A 41-year-old male underwent HVAD implant in 2019 for advanced non-ischemic cardiomyopathy. This was exchanged to HM3 for recurrent neurological events despite therapeutic anticoagulation. Ten months after exchange, he awakened one morning to find his LVAD had been off for an unknown period but had not heard any device alarms (85dB if on battery power, 165dB if on wall power). Since he felt well he changed to battery power resulting in immediate pump restart. Log file analysis showed pump stoppage 2 am – 10 am, without preceding low flow alarms or power elevations. Management and Outcomes: In the ER INR was 1.5 (2.8 one week prior) and systemic heparin was started. Evaluation included: 1) CT brain without acute infarcts 2) echocardiogram without intracardiac thrombus 3) CT Angiography with patency of the inflow cannula and outflow graft 4) stable serial LDH measurements. The controller was exchanged, and analysis noted normal function. 1-year later the patient is maintained on warfarin and aspirin 325mg without further HRAE. Given the patient’s neurologic history and pump stoppage event, we did not invoke ARIES trial guidance and thus continued aspirin. Conclusion: Pump stoppage occurs when there is complete battery depletion, disconnection of both power leads, or the percutaneous lead from system controller. Our case is unique in that the duration of pump shutdown was 8 hours and INR subtherapeutic, without HRAE in the background of neurologic events on HVAD support. It has been previously reported that complete outflow graft thrombosis can occur shortly after LVAD decommissioning. The HM3 User Manual recommends restarting the pump immediately if off for a few minutes and using clinical judgment for longer durations due to increased risk for thromboembolic events. Our case adds to the paucity of existing data on improved hemocompatibility of the HM3 during rare circumstances of the ultimate test in hemocompatibility: complete pump shut down.

Abstract 4124289: Changes in high-sensitivity cardiac troponin I and associated cardiovascular risk: Analyses From the FOURIER Trial

Background: Circulating high-sensitivity cardiac troponin I (hs-cTnI) is associated with the risk of future cardiovascular (CV) events in stable patients (pts). Data are scarce regarding changes of hs-cTnI in a stable setting. Aims: To study baseline and changes of hs-cTnI in pts with atherosclerotic CV disease (ASCVD), and the association with risk of major CV events. Methods: We measured hs-cTnI (Abbott ARCHITECT) at baseline (BL) and 24 weeks (wks) in 20,718 pts enrolled in a nested biomarker study of the FOURIER trial, which tested the PCSK9i evolocumab vs. placebo in pts with ASCVD on statin and LDL &gt; 70 or non-HDL &gt; 100 mg/dL. The primary endpoint was an adjudicated composite of CV death, MI, stroke, hosp. for unstable angina, or coronary revascularization. The HR (95% CI) across percent-change of hs-cTnI was investigated in pts with quantifiable hs-cTnI at BL and 24 wks (lower limit of quantification (LLOQ) 3.6ng/L) using restricted-cubic splines and Cox-PH models, adjusted for sex, age, LDL at BL, prior MI, randomized treatment, eGFR, DM, HTN, prior HF, and BMI. A Generalized Additive Model was used to predict event rates as a function of hs-cTnI BL and absolute change, flexibly evaluated with a non-linear interaction. All models were based on 3-year follow-up using landmark analysis from 24 wks. Results: Median age was 63 yrs (25 th , 75 th percentiles: 56, 69), 75.5% were male, 86.1% had CAD, 13.7% PAD, and 19.0% a prior stroke. Of these pts, 11,021 (46.8%) had hs-cTnI &gt; LLOQ at BL and 24 wks. The median hs-cTnI at 24 wks was 6.6ng/L (5 th , 25 th , 75 th , 95 th percentiles are: 3.7, 4.7, 11.9, 51.1 ng/L). The absolute event rate of the primary endpoint across hs-cTnI BL and depending on absolute hs-cTnI change to 24 wks is shown in Fig. A . Higher Hs-cTnI BL was associated with higher event rates (p &lt; 0.001). Additionally, absolute reductions and increases of hs-cTnI from BL to 24 wks resulted in reduced and increased event rates, respectively, across hs-cTnI BL . Additionally, relative decrease and increase of hs-cTnI from BL to 24 wks were associated with reduced and increased relative risk, respectively (p for overall effect &lt; 0.001, Fig. B ). Conclusion: Changes in hs-cTnI are associated with the risk of future CV events. Serial measurements of hs-cTnI may aid in reclassification of CV risk and the identification of pts whose CV risk changes with time.

BIOM-73. CYTOKINE DYNAMIC DURING RADIATION THERAPY PREDICTS SURVIVAL IN GLIOBLASTOMA

Abstract Radiation Therapy affects a wide range of circulating lymphocyte subpopulations that are integral to mounting a successful lymphocyte-mediated immune response. Lymphopenia is associated with inferior tumor control and could be addressed to improve outcomes in glioblastoma. RT is one significant and potentially actionable iatrogenic suppressor of immune response that may limit the success of therapy. We hypothesized that a comprehensive evaluation of serial cytokine measurements during concurrent radiation and chemotherapy in glioblastoma will provide information about systemic immune status during treatment. 16 patients were enrolled in a single-institution, observational, immune surveillance study between 2018 and 2019. Peripheral blood was collected prior to starting radiation, and then weekly for a total of 7 timepoints. Plasma was isolated from blood, and cytokine levels were measured with a Luminex 23-cytokine panel. Survival was defined at 2 years since diagnosis. Patients &amp;gt;2 years were called survivors and &amp;lt;2 years were called non-survivors. Cytokine levels were compared with a cohort of 4 healthy controls. All data are log2 transformed using formula log2(x+1). ANOVA was used to find cytokines that differ among 3 groups. Only for those cytokines with significant ANOVA results, pair-wise t-test was performed. We found a total of 12 cytokines that were increased in plasma in glioblastoma patients undergoing radiation compared to control. Top cytokines to show differences were IL-10, M-CSF, TGF-b3 and TIM-3 (p&amp;lt;0.05). The others to show a difference were IP-10, MCP-1, TGF-b2, IL-34, PD-L1, LAG-3, PD-1, and CTLA-4. These cytokines are known to be immunosuppressive, and our results demonstrate a soluble mechanism of immunosuppression in this patient population. This cytokine signature can predict early during treatment the overall survival in patients with glioblastoma.

Periodontitis Is Associated With Arterial Stiffness as Measured by Serial Cardio-Ankle Vascular Index (CAVI): A10-Year Cohort Study.

To investigate the effect of periodontitis on the long-term changes of the cardio-ankle vascular index (CAVI). A 10-year retrospective cohort study of 3842 Thai participants (range 25-76 years) with normal CAVI at the study initiation was undertaken. Full-mouth periodontal examination was performed by calibrated periodontists, and the extent and severity of periodontitis were determined at 5-year intervals. Serial CAVI measurements were used to examine the incidence of high CAVI (≥ 9.0) and changes in CAVI over time (ΔCAVI). Participants with a higher extent or severity of periodontitis were found to have a significantly higher mean ΔCAVI. The incidence of high CAVI was also observed to be higher in those with periodontitis compared to those without it. The adjusted risk ratios for developing high CAVI were 1.309 and 1.513 for localized and generalized periodontitis, respectively. Participants with severe periodontitis had a 37% higher likelihood of developing CAVI ≥ 9.0 compared to individuals with no/mild periodontitis. This risk was consistent with a significant change in ΔCAVI of 0.054-0.140. Periodontitis, both in terms of extent and severity, was found to have a significant dose-dependent effect on the risk of developing high CAVI over a 10-year period, suggesting a causal relationship between these two parameters.

Interleukin-6 receptor antibodies (tocilizumab) in acute myocardial infarction with intermediate to high risk of cardiogenic shock development (DOBERMANN-T): study protocol for a double-blinded, placebo-controlled, single-center, randomized clinical trial

BackgroundInflammation and neurohormonal activation play a significant role in the adverse outcome seen in acute myocardial infarction (AMI) and the development of cardiogenic shock (CS), which is associated with a mortality rate up to 50%. Treatment with anti-inflammatory drugs such as tocilizumab, an interleukin-6 receptor antagonist, has been shown to reduce troponin release and reduce the myocardial infarct size in AMI patients and it may therefore have cardioprotective properties.MethodsThis is a double-blind, placebo-controlled, single-center randomized clinical trial, including adult AMI patients without CS at hospital arrival, undergoing percutaneous coronary intervention (PCI) within 24 h from symptom onset, and at intermediate to high risk of developing CS (ORBI risk score ≥ 10). A total of 100 participants will be randomized to receive a single intravenous dose of tocilizumab (280 mg) or placebo (normal saline). The primary outcome is peak plasma pro-B-type natriuretic peptide (proBNP) within 48 h, assessed using serial measurements at intervals: before infusion, 12, 24, 36, and 48 h after infusion. Secondary endpoints include the following: (1) cardiac magnetic resonance imaging (CMR) during 24–48 h after admission and at follow-up after 3 months with assessment of left ventricular area at risk, final infarct size, and the derived salvage index and (2) biochemical markers of inflammation (C-reactive protein and leukocyte counts) and cardiac injury (troponin T and creatinine kinase MB).DiscussionModulation of interleukin-6-mediated inflammation in patients with AMI, treated with acute PCI, and at intermediate to high risk of in-hospital CS may lead to increased hemodynamic stability and reduced left ventricular infarct size, which will be assessed using blood biomarkers with proBNP as the primary outcome and inflammatory markers, troponin T, and CMR with myocardial salvage index as the secondary endpoints.Trial registrationRegistered with the Regional Ethics Committee (H-21045751), EudraCT (2021–002028-19), ClinicalTrials.gov (NCT05350592). Study registration date: 2022-03-08, Universal Trial Number U1111-1277–8523.

Impact of Serial Serum Free Light Chain Measurements on Response and Progression Assessments in Multiple Myeloma Patients with Measurable Disease

Impact of Serial Serum Free Light Chain Measurements on Response and Progression Assessments in Multiple Myeloma Patients with Measurable Disease

Variation between countries for routine transvaginal cervical length measurement and interventions to prevent preterm birth

ObjectiveTo assess the variation between countries for routine transvaginal ultrasound assessment of the cervical length and interventions offered to prevent preterm birth (PTB). Study DesignAn anonymous digital questionnaire was sent out between August and October 2023 to delegates of the European Spontaneous Preterm Birth Congress. Outcomes assessed included method, indications (i.e. singleton pregnancy in women with or without a history of PTB, or a multiple pregnancy), timing and frequency of routine cervical length measurement, interventions offered to pregnant women with a short cervix or a history of PTB, and advice on physical- and sexual activity. ResultsIn total, 247 visitors of the European Spontaneous Preterm Birth Congress were approached for this study and 103 (42 %) participants completed the questionnaire representing 15 countries. Most participants worked in a Public/University hospital (n = 54, 53 %) and worked as a specialist (registrar or consultant; n = 84, 82 %). In most countries, the cervix was measured via a straight-line method without the cervical isthmus, but variety existed also within countries. Routine cervical length measurement in women with no prior PTB or a multiple pregnancy is rarely performed in the first trimester. For women with a history of PTB, 39 (38 %) respondents from six countries reported to start serial cervical measurement in the first trimester and 99 (96 %) from 14 countries in the second trimester. Follow-up for women at risk for PTB mainly occurs fortnightly (n = 40, 39 %) or monthly (n = 14, 14 %). However, follow-up is often individualized according to patient’s history and/or cervical length. In women with a history of PTB or a short cervix progesterone is administered vaginally (n = 99, 96 %), however dosage vary between 100 mg and 400 mg daily. The timing and gestational age at which a (primary/secondary/tertiary) vaginal cerclage is offered widely differ between countries (e.g. up to 24–28 weeks of gestation for a secondary cerclage). Advice on restrictions regarding sexual activity in pregnancy is frequently prescribed for women with a short cervix (n = 38, 37 %). ConclusionSubstantial variation exist between and within countries regarding the indications and timing of cervical length measurement and interventions offered. There is a need for a more universal approach to manage patients at risk for PTB based on the existing evidence.

The Stress-Induced Hyperprolactinemia Might Not Be that Stress-Induced as Argued: Observational Case-Control Study

ObjectiveThe mechanism behind prolactin (PRL) elevation in stress-induced hyperprolactinemia (si-HP) in humans is unclear. This study aimed to investigate the effect of psychological stress and venous puncture (VP) pain on si-HP. MethodsThe study included 91 individuals (9 males, 82 females) referred for HP. Anxiety levels were assessed using the Anxiety Sensitivity Index-3 (ASI-3) and the State-Trait Anxiety Inventory (STAI-1 and STAI-2), and visual scales were used to evaluate trypanophobia, nosocomephobia, and scanxiety. Serial PRL measurements were performed with venous cannula (VC) at 0 minute (min), 30 min, and 60 min for the first 32 patients and with the VP method at the same intervals for the following 59 patients. si-HP was defined as PRL levels at 60 min (PRL 60min) decreasing to normal limits according to gender. ResultsThere were 23 HP (−), 25 HP (+), and 19 si-HP individuals, as well as 24 with macroprolactinaemia. The frequency of si-HP in the VC group (n = 7/32) was similar to that in the VP group (12/59, P = .9). The prolactin levels at 0 minute (PRL0min) and prolactin levels at 60 minutes (PRL60min) levels of the VC group were similar to those of the VP group. Trypanophobia, nosocomephobia, scanxiety, ASI-3, STAI-1, and STAI-2 scale scores were similar between the si-HP group and other groups. Trypanophobia, nosocomephobia, scanxiety, ASI-3, STAI-1, and STAI-2 scales scores were not correlated with PRL0min or PRL60min levels. ConclusionSi-HP is independent of states momentary or trait anxiety, and phobias trypanophobia, nosocomephobia and scanxiety. In this context, the relevance of the nomenclature of si-HP is controversial.

Early Mixed Donor Chimerism is a Strong Negative Prognostic Indicator in Allogeneic Stem Cell Transplant for AML and MDS

Allogeneic bone marrow transplantation remains the most potent curative therapy for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) due to the graft-versus-tumor effect provided by donor cells. Donor chimerism is utilized early after transplantation to evaluate engraftment and to monitor the persistence of donor hematopoiesis. Literature is conflicting regarding to the prognostic utility of early mixed donor chimerism, chimerism kinetic patterns as well as factors associated with it and we sought to clarify this uncertainty. In this single-centre retrospective analysis, 141 adults aged 18 years of age or older with AML (n = 104) and MDS (n = 37) who received their first transplant from HLA matched related, matched unrelated or mismatched related (haploidentical) donors between 2016 and 2022 and had at least day 30 chimerism measured were included. Approximately 30% received post-transplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis and 67% of subjects received reduced-intensity conditioning. Chimerism was measured using STR-PCR from unfractionated peripheral blood mononuclear cells (whole blood; WB) and CD3+ (T cell; TC) compartment at each time point. Complete donor chimerism was defined as ≥95% whereas <95% defined as mixed. Competing risk analysis was used to estimate cumulative incidence of relapse with kinetic calculations completed using an increment factor. Kaplan-Meier was used for overall survival (OS) and relapse-free survival (RFS). Cox proportional hazards regression was used to explore prognostic factors for OS and RFS. Both day 30 mixed WB and TC donor chimerism were individually associated with an increased risk of relapse and worse overall and relapse-free survival at days 30, 60 and 90 post-transplant. Day 30 mixed WB was more specific for relapse (86%), while mixed TC was more sensitive (67%). Complete day 30 chimerism had a negative predictive value of 63% and 70% and positive predictive value of 57% and 67% for WB and TC, respectively. Day 30 WB and TC donor chimerism of <88.92% and 89.29% had specificities of 79.17% and 82.19% although sensitivities only approximated 50%. Evaluating the kinetics of chimerism over the first 90 days provided additional information for prognosticating relapse than absolute chimerism values at individual time points in both WB day 30 to 90 [HR, 1.75 (95% CI, 1.04 to 2.94); P < .035] and TC day 60 to 90 [HR, 1.32 (95% CI, 1.03, 1.69); P < .29]. Twice as many patients with complete chimerism developed acute GVHD compared to those with mixed chimerism. Factors that were found to be associated with day 30 mixed TC chimerism were donor source, ATG GVHD prophylaxis, myeloablative conditioning and female sex, while only donor source was associated with mixed WB. Both TC and WB day 30 mixed chimerism were associated with an increased risk of relapse. Early mixed WB and TC chimerism is strongly associated with a worse overall and relapse-free survival. The serial measurement of chimerism early post-transplant for monitoring chimerism kinetics provides additional prognostic information beyond the absolute donor chimerism value at a single time point. Haploidentical stem cell transplants were associated with a lower likelihood of mixed chimerism than other donor sources.

Performance Assessment of Satellite-Based Precipitation Products in the 2023 Summer Extreme Precipitation Events over North China

In the summer of 2023, North China experienced a rare extreme precipitation storm due to Typhoons Doksuri and Khanun, leading to significant secondary disasters and highlighting the urgent need for accurate rainfall forecasting. Satellite-based quantitative precipitation estimation (QPE) products like Integrated Multi-Satellite Retrievals for GPM (IMERG) and Global Satellite Mapping of Precipitation (GSMaP) from the Global Precipitation Measurement (GPM) Mission have great potential for enhancing forecasts, necessitating a quantitative evaluation before deployment. This study uses a dense rain gauge as a benchmark to assess the accuracy and capability of the latest version 7B IMERG and version 8 GSMaP satellite-based QPE products for the 2023 summer extreme precipitation in North China. These satellite-based QPE products include four satellite-only products, namely IMERG early run (IMERG_ER) and IMERG late run (IMERG_LR), GSMaP near-real-time (GSMaP_NRT), and GSMaP microwave-infrared reanalyzed (GSMaP_MVK), along with two gauge-corrected products, namely IMERG final run (IMERG_FR) and GSMaP gauge adjusted (GSMaP_Gauge). The results show that (1) GSMaP_MVK, IMERG_LR, and IMERG_FR effectively capture the space distribution of the extreme rainfall, with relatively high correlation coefficients (CCs) of approximately 0.77, 0.75, and 0.79. The IMERG_ER, GSMaP_NRT, and GSMaP_Gauge products exhibit a less accurate spatial pattern capture (CCs about 0.66, 0.73, and 0.67, respectively). Each of the six QPE products tends to underestimate rainfall (RBs &lt; 0%). (2) The IMERG products surpass the corresponding GSMaP products in serial rainfall measurement. IMERG_LR demonstrates superior performance with the lowest root-mean-square error (RMSE) (about 0.38 mm), the highest CC (0.97), and less underestimation (RB about −6.37%). (3) The IMERG products at rainfall rates ≥ 30 mm/h, GSMaP_NRT and GSMaP_MVK products at rainfall rates ≥ 55 mm/h, and GSMaP_Gauge products at ≥ 40 mm/h showed marked limitations in event detection, with a near-zero probability of detection (POD) and a nearly 100% false alarm ratio (FAR). In this extreme precipitation event, caution is needed when using the IMERG and GSMaP products.

Long-term follow-up of single-chamber atrial pacing - system upgrade and wenckebach block point behavior: potential implications for leadless AAI pacing?

Abstract Introduction Until recently leadless pacemakers (PM) did not support atrial pacing. A novel dual chamber leadless PM system now provides treatment option for a wide range of indications. Single-chamber atrial stimulation (AAI) for the treatment of symptomatic sick sinus syndrome (SSS) is scarcely used due to concerns about the potential development of atrioventricular block (AVB) and development of paroxysmal atrial fibrillation (AF). Long-term follow-up data of AAI-PM is however scarce. Little is known about the role of serial Wenckebach block point (WBP) measurements in AAI-PM patients for risk stratification. Purpose To assess the incidence of dual chamber upgrade of patients treated with AAI-PM for SSS during long-term follow-up and to investigate the role of serial WBP measurements for risk stratification. Methods Prospectively enrolled patients undergoing implantation of an AAI-PM between October 2002 and December 2023. WBP was measured at implantation and serially during follow up. Results We included a total of 178 patients, of which 58% were female and the median age at implantation was 78 [IQR 71 – 83] years. The median follow-up duration was 6.5 [IQR 2.0 – 9.7] years. 24 patients (13.5%) received a system upgrade to DDD including 3 patients (1.7%) with a mode change to ventricular pacing only (VVI). Adjusted for years of follow-up the upgrade rate was 2.1% per year. Median time to system upgrade was 5.2 [IQR 1.6 – 8.7] years. Reasons for system upgrade were high-degree AVB (38%), low WBP (17%), atrial arrhythmias (33%), unclear syncope (8%) and infection (4%). Median WBP at implantation was 130 [120 – 140] bpm, showing a significant decline over time in the upgrade-group with 105 [95 – 130] bpm compared to the rest of the cohort with 130 [120-130] bpm (p = 0.009). A decline in WBP &amp;gt;20 bpm was found in 17.9% patients and a decline of 10-20 bpm in 33.7% of patients. New-onset atrial arrythmias were found in 36 patients (20%), 29% in the upgrade group and 19% in the rest of the cohort (p = 0.3). Neither age at implantation, sex, WBP at implantation, nor atrial arrhythmia prior to implantation were predictive for the need of a future system upgrade. Conclusion In this cohort of patients undergoing AAI-PM implantation for SSS, a system upgrade was required in 2% per year. The WBP remained stable in 48% of patients. Therefore, AAI-PM due to SSS emerges as a judicious and secure therapeutic modality, warranting increased consideration in the light of new treatment options for leadless pacing.