Clear Cutoff Research Articles

Psoas Muscle Index and Density as Prognostic Predictors in Patients Hospitalized with Acute Pancreatitis.

Background: Early prognostication of acute pancreatitis (AP) patients for those at high risk of complications during hospitalization can facilitate clinical decision-making. Sarcopenia has been proven to be a risk factor for poor prognosis in patients with AP. We aimed to evaluate the association between the muscle parameters measured in computed tomography (CT) and the clinical outcomes of hospitalized patients with AP. Methods: A total of 132 consecutive patients hospitalized between 1 January 2015 and 31 December 2021 for AP with a valid CT scan were analyzed. The first CT conducted during hospitalization was analyzed for psoas muscle area (PMA), index (PMI), and density (PMD) at the L3 vertebral level. The main adverse outcomes indicating a worse prognosis were the development of extrapancreatic complications, infections, ICU transfer, in-hospital mortality, and hospitalization length. Results: The lowest tertile of PMI, as a surrogate for sarcopenia, was significantly correlated with increased rates of extrapancreatic complications, infections, and longer hospitalizations. It was additionally correlated with a worse CT severity index. The results for PMA and PMD also showed worse outcomes, largely mirroring the results for PMI. Although in-hospital mortality was relatively low, none of the patients died in the highest tertile of PMI. A clear cutoff with sufficient predictive capability could not be found. Conclusions: A low psoas muscle index can serve as an additional potential predictive marker for more severe disease and worse outcomes in hospitalized acute pancreatitis patients. More studies are needed to determine its combination with existing prediction tools.

TeV Analysis of a Source-rich Region with the HAWC Observatory: Is HESS J1809-193 a Potential Hadronic PeVatron?

HESS J1809-193 is an unidentified TeV source, first detected by the High Energy Stereoscopic System (H.E.S.S.) collaboration. The emission originates in a source-rich region that includes several supernova remnants (SNRs) and pulsars including SNR G11.1+0.1, SNR G11.0-0.0, and the young radio pulsar PSR J1809-1917. Originally classified as a pulsar wind nebula candidate, recent studies show the peak of the TeV region overlapping with a system of molecular clouds. This resulted in the revision of the original leptonic scenario to look for alternate hadronic scenarios. Marked as a potential PeVatron candidate, this region has been studied extensively by H.E.S.S. due to its emission extending up to several tens of TeV. In this work, we use 2398 days of data from the High Altitude Water Cherenkov (HAWC) observatory to carry out a systematic source search of the HESS J1809-193 region. We were able to resolve emission detected as an extended component (modelled as a symmetric Gaussian with a 1σ radius of 0.°21) with no clear cutoff at high energies and emitting photons up to 210 TeV. We model the multiwavelength observations for the region around HESS J1809-193 using a time-dependent leptonic model and a lepto-hadronic model. Our model indicates that both scenarios could explain the observed data within the region of HESS J1809-193.

Clinical Significance of B-Type Natriuretic Peptide and N-Terminal Pro-B-Type Natriuretic Peptide in Pediatric Patients: Insights into Their Utility in the Presence or Absence of Pre-Existing Heart Conditions.

The clinical significance of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in pediatric patients remains an area of evolving understanding, particularly regarding their utility in the presence or absence of pre-existing heart conditions. While clear cutoff values and established roles in heart failure are understood in adult patients, pediatric norms vary with age, complicating interpretation. Notably, the emergence of multi-system inflammatory syndrome in children (MIS-C) has highlighted the importance of these markers not only in the detection of acute heart failure but also as a marker of disease severity and even as a differential diagnosis tool. This review summarizes current knowledge on the utility of BNP and NT-proBNP in pediatric patients. Their unique physiology, including circulation and compensation mechanisms, likely influence BNP and NT-proBNP release, potentially even in non-heart failure states. Factors such as dynamic volemic changes accompanying inflammatory diseases in children may contribute. Thus, understanding the nuanced roles of BNP and NT-proBNP in pediatric populations is crucial for the accurate diagnosis, management, and differentiation of cardiac and non-cardiac conditions.

The Value of Red Cell Distribution Width and Its Correlation with Other Parameters in Ovarian Cancer

Abstract Background: The red cell distribution width (RDW) is a measure of the range of variation in the red blood cell size. It reflects red blood cell volume heterogeneity and is a part of the whole blood cell count. The use of the RDW in the diagnosis of malignant tumors has recently attracted much attention. Related research has mainly focused on endometrial cancer, lung cancer, and liver cancer. Aim of the Study: This study investigated the correlation between the RDW and ovarian cancer by observing changes in the RDW in patients with different stages of ovarian cancer. Patients and Methods: A case–control study involving 50 females with ovarian cancer and 50 healthy females conducted at Baghdad Oncology Teaching Hospital, and Al-Imamian Al-Kadhimiyain Medical City from January 1, 2022, to December 30, 2022. Data collection included demographic data, complete blood count with the calculation of platelets to lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR), transferrin saturation, and cancer antigen 125 (CA-125). Adult females with histologically proven ovarian cancer were included in this research. Patients with conditions that affect red blood cells were excluded from the study. Results: The mean age was 52.6 ± 10.4 years old for the cases and 50.0 ± 11.4 years for the control group. Platelets count (PLT), absolute neutrophil count (ANC), PLR, NLR, RDW, and CA-125 were significantly higher in the women with ovarian cancer in comparison to the control group (P < 0.001). RDW values were found to be positively correlated with white blood cell, PLT, ANC, NLR, PLR, and CA-125 values (P < 0.001). RDW values were also positively associated with cancer stage; thus, higher values of RDW are to be expected with a higher stage of cancer (P < 0.001). The optimal cutoff point for RDW was found to be 14.6% with a sensitivity of 92%, specificity of 90%, and an area under the curve of 96%. Conclusion: The RDW is increased with ovarian cancer, and a clear cutoff point for the prediction of ovarian cancer has been observed. Furthermore, RDW was positively correlated with cancer stage and inflammatory markers including PLT, ANC, PLR, NLR, and a tumor marker CA-125.

High-quality 2D Ruddlesden-Popper perovskites single crystal and its intrinsic spectral properties

High-quality 2D Ruddlesden-Popper perovskite (RPP) single crystals with large size are highly desirable for fundamental research and different related applications, which also is critical to understand the reported divergent spectral properties of 2D RPP. In this study, we successfully prepared crack free (n-C12H25NH3)2(CH3NH3)Pb2I7 single crystal with a lateral size up to centimeter by regulating the interlayer interaction and aggregate behavior of this layered self-assembly lattice. The RPP crystals show step-like absorbance band with a clear cutoff at 588 nm. The optical band gap was determined as 2.1 eV, which was consistent with previous theoretical calculation results, and clarified its divergent spectral properties. Moreover, a narrow photoluminescence (PL) peak at 623 nm was observed near the band edge. Time-resolved PL measurements revealed a highly reproducible decaying pathway, comprising three distinct components with lifetime as τ1 ∼ 0.57, τ2 ∼ 2.33 ns and τ3 ∼ 11.40 ns respectively. This crystal has demonstrated remarkable long-term chemical stability under ambient conditions.

393 Cerebral Oximetry Using the USIC Protocol Is a Reliable Tool for Indicating Selective Intraluminal Shunting During Carotid Endarterectomy

INTRODUCTION: Indication to selective shunting during carotid endarterectomy (CEA) is based on monitoring during the procedure. Cerebral oximetry (CO) using near-infrared spectroscopy (NIRS) is one of the monitoring tools but no clear cut off value for an intraluminal shunt insertion has been established. METHODS: 125 patients underwent CEA under LA and were monitored clinically through the whole procedure. The patients also underwent bilateral NIRS monitoring during the surgery. During the monitoring period, we first clamped the external carotid artery (ECA), and after a 1 minute delay followed by clipping the internal carotid artery (ICA). The decrease in the cerebral oximetry values was analyzed separately after selective ICA clipping (ÚstÍ Selective Internal carotid artery Clamping “USIC” protocol). The decision to use a shunt was based solely on clinical symptomatology but the NIRS data were recorded and analyzed. All patients underwent DWI before and after CEA. RESULTS: One hundred and six patients (85%) underwent CEA without clinical deterioration while 19 patients (15%) clinically deteriorated during surgery. The mean drop in the cerebral oximetry after selective ICA clamping in clinically stable patients was 6% while in patients with clinical deterioration the NIRS decreased by 15% (p < 0.05). When we set the cut-off value for selective shunting as a 10% decrease of the ipsilateral cerebral oximetry after selective ICA clamping, the sensitivity of the technique was 100% and the specificity 83%. CONCLUSIONS: Our study showed that a 10% decrease in the ipsilateral brain tissue oximetry after selective cross-clamping the ICA provides a reliable cut-off for selective shunting during CEA. More, bilateral NIRS monitoring allows differentiation between systemic or local events leading to brain hypoxia.

A unique circulating microRNA pairs signature serves as a superior tool for early diagnosis of pan-cancer

Cancer remains a major burden globally and the critical role of early diagnosis is self-evident. Although various miRNA-based signatures have been developed in past decades, clinical utilization is limited due to a lack of precise cutoff value. Here, we innovatively developed a signature based on pairwise expression of miRNAs (miRPs) for pan-cancer diagnosis using machine learning approach. We analyzed miRNA spectrum of 15832 patients, who were divided into training, validation, test, and external test sets, with 13 different cancers from 10 cohorts. Five different machine-learning (ML) algorithms (XGBoost, SVM, RandomForest, LASSO, and Logistic) were adopted for signature construction. The best ML algorithm and the optimal number of miRPs included were identified using area under the curve (AUC) and youden index in validation set. The AUC of the best model was compared to previously published 25 signatures. Overall, Random Forest approach including 31 miRPs (31-miRP) was developed, proving highly efficient in cancer diagnosis across different datasets and cancer types (AUC range: 0.980–1.000). Regarding diagnosis of cancers at early stage, 31-miRP also exhibited high capacities, with AUC ranging from 0.961 to 0.998. Moreover, 31-miRP exhibited advantages in differentiating cancers from normal tissues (AUC range: 0.976–0.998) as well as differentiating cancers from corresponding benign lesions. Encouragingly, comparing to previously published 25 different signatures, 31-miRP also demonstrated clear advantages. In conclusion, 31-miRP acts as a powerful model for cancer diagnosis, characterized by high specificity and sensitivity as well as a clear cutoff value, thereby holding potential as a reliable tool for cancer diagnosis at early stage.

Timing of Surgery and Preoperative Predictors of Surgical Site Infections for Patients with Depressed Skull Fractures in a Sub-Saharan Tertiary Hospital: A Prospective Cohort Study.

Surgical site infections (SSIs) remain a major cause of life-threatening morbidity following surgery for depressed skull fractures (DSFs) among patients with traumatic brain injury (TBI). The timing of the surgery for DSF has been questioned as a risk of SSI without a clear cutoff. We aimed to compare the risk of SSI within 3 months between surgery done before versus after 48 h of injury and with its preoperative predictors. We conducted a prospective cohort study at Mulago Hospital, Uganda. Patients with mild-to-moderate TBI with DSF were followed up perioperatively from the operating time up to 3 months. The outcome variables were the incidence risk of SSI, types of SSI, microbial culture patterns of wound isolates, and hospital length of stay. We enrolled 127 patients with DSF, median age = 24 (interquartile range [IQR] = 17-31 years), 88.2% (112/127) male, and assault victims = 53.5%. The frontal bone involved 59%, while 50.4% had a dural tear. The incidence of SSI was 18.9%, mainly superficial incisional infection; Gram-negative microorganisms were the most common isolates (64.7%). The group of surgical intervention >48 h had an increased incidence of SSI (57.3% vs. 42.7%, p = 0.006), a longer median of postoperative hospital stay (8[IQR = 6-12] days versus 5 [IQR = 4-9], [p < 0.001]), and a higher rate of reoperation (71.4% vs. 28.6%, p = 0.05) in comparison with the group of ≤48 h. In multivariate analysis between the group of SSI and no SSI, surgical timing >48 h (95% confidence interval [CI], 1.25-6.22), pneumocranium on computed tomography [CT] scan (95% CI: 1.50-5.36), and involvement of air sinus (95% CI: 1.55-5.47) were associated with a >2.5-fold increase in the rate of SSI. The SSI group had a longer median hospital stay (p value <0.001). The SSI risk in DSF is high following a surgical intervention >48 h of injury, with predictors such as the frontal location of DSF, pneumocranium on a CT scan, and involvement of the air sinus. We recommend early surgical intervention within 48 h of injury.

Management of patellar instability in skeletally immature patients.

Surgical intervention is the treatment of choice for recurrent lateral patellar instability. Surgery should be considered for first time lateral patella dislocations with osteochondral fractures or underlying anatomical risk factors. Primary repair and nonanatomical imbrications/reconstructions have fallen out of favor due to abnormal biomechanics and high rates of recurrence. Anatomical reconstruction of the MPFL using a variety of auto and allograft tissues have yielded good outcomes and low redislocation rates. Physeal sparing MPFL reconstruction techniques under radiological control are safe and do not cause growth disturbance. Allografts may be indicated for hyperlax patients. Although no clear cutoff points exist, correction of valgus and excessive femoral anteversion should be considered when indicated. Osteochondral and chondral injuries are common and should be addressed during surgery for instability.

BASET scoring: A novel simple biometric score for screening and grading obstructive sleep apnea

BackgroundPolysomnography (PSG) is the gold-standard diagnostic tool for Obstructive Sleep Apnea (OSA). However, the availability of PSG is limited, and OSA is widely underdiagnosed; more than 80% of most developed nations undiagnosed. There is no diagnostic validated simple tool with clear cutoff point for predicting and roll out patient with OSA in primary care clinics significantly alters clinical outcomes. ObjectivesOur study aimed to assess the validity of BASET scoring as a new potential tool for screening and grading the severity of OSA patients. MethodsAfter institution review board approval and formal patient consent, 144 subjects for suspected OSA and their relatives were enrolled. All subjects were subjected to a full night PSG study after history taking, sleep questionnaires, and physical examination, including BASET score components: B= Body Mass Index (BMI), A= Abdominal circumference (AC), S = Snoring, E= Epworth Sleepiness Scale, and T= Tongue teeth imprint. ROC analysis that used to assess the optimal cutoff point of the BASET score and to compare its accuracy for predicting OSA with Berlin and STOP-Bang scores. ResultsThis study included 63 OSAS patients, 33 (52.38%) males and 30 (47.62%) females, and 81 controls; 22 (27.16%) males and 50 (72.84%) females. The Cronbach's alpha for the 5 BASET score components was 0.846, indicating the internal consistency reliability of the scale. Moreover, BASET score has a moderately strong positive significant correlation (r = 0.778, p<0.001) with AHI. By ROC analysis, the accuracy of the three measures was generally high, with BASET score predicting OSA most accurately (AUC=0.984, 95%CI: 0.956–0.999), followed by STOP-Bang (AUC=0.939, 95%CI: (0.887–0.972) and Berlin (AUC=0.901, 95%CI: 0.841–0.945). The AUC of BASET score was significantly higher compared to the Berlin score (difference= 0.0825, 95%CI: 0.039–0.125) and STOP-Bang score (difference= 0.0447, 95%CI: 0.011–0.078). On the other hand, there was no difference between the AUC of Berlin and STOP-Bang scores (difference=0.0378, 95%CI: 0.006 - 0.081 4). BASET score was significantly (p<0.001) associated with OSA grades, ConclusionBASET score is a convenient, reliable, and valid tool for diagnosing OSA. BASET score is more accurate for predicting OSA than Berlin and STOP-Bang scores, while there is no difference between Berlin and STOP-Bang scores. BASET score indicates OSA grades. Registration of clinical trials by numberNCT05511974. Name of the registryClinicalTrials.gov URL: https://clinicaltrials.gov/

Systematic review and meta-analysis of galactomannan antigen testing in serum and bronchoalveolar lavage for the diagnosis of chronic pulmonary aspergillosis: defining a cutoff.

A clear cutoff value of galactomannan (GM) has not been established for chronic pulmonary aspergillosis (CPA) and is frequently extrapolated from invasive pulmonary aspergillosis. We performed a systematic review and meta-analysis to evaluate the diagnostic performance of serum and bronchoalveolar lavage (BAL) GM, and to propose a cutoff. We extracted from the studies the cutoff of serum or/and BAL GM associated with true positives, false positives, true negatives, and false negatives. We performed a multi-cutoff model and a non-parametric random effect model. We estimated the optimal cutoff and the area under the curve (AUC) for GM in serum and BAL samples. Nine studies from 1999 to 2021 were included. Overall, the optimal cutoff of serum GM was 0.96 with a sensitivity of 0.29 (95%CI: 0.14-0.51); specificity of 0.88 (95%CI: 0.73-0.95); and AUC of 0.529 (with a CI: [0.415-0.682] [0.307-0.713]). The AUC for the non-parametric ROC model was 0.631. For BAL GM the cutoff was 0.67 with a sensitivity of 0.68 (95%CI: 0.51-0.82), specificity of 0.84 (95%CI: 0.70-0.92), and AUC of 0.814 (with a CI: [0.696-0.895] [0.733-0.881]). The AUC for the non-parametric model was 0.789. The diagnosis of CPA requires the assessment of a combination of mycological and serological factors, as no single serum and/or BAL GM antigen test is adequate. BAL GM performed better than serum, with better sensitivity and excellent accuracy.

DIAGNOSTIC VALUE OF MEDIAN NERVE CONDUCTION VELOCITY ACROSS WRIST AMONG PATIENTS WITH SUSPECTED CARPAL TUNNEL SYNDROME

Background: Carpal Tunnel Syndrome (CTS) is the most prevalent type of compressive neuropathy. At present, electrodiagnosis is considered the gold standard in diagnosing CTS. However, no clear cutoff point has been established regarding the diagnostic value of the median nerve conduction velocity, across the carpal tunnel area, among patients with CTS.&#x0D; Objectives: This study aimed to determine the cutoff point for patients’ median nerve conduction velocity (NCV), to diagnose CTS among suspected patients, which is determined using electrical stimulations conducted across the carpal tunnel area. The present study also aimed to determine the diagnostic value of the median nerve conduction velocity across the carpal tunnel area, compared with the standard method.&#x0D; Methods: This cross-sectional study was conducted among 56 participants (106 wrists) suspected of CTS. Motor and sensory NCV across the carpal tunnel was investigated to yield diagnostic value of CTS compared with the standard technique.&#x0D; Results: The optimal cutoff point in diagnosing CTS using the wrist to midpalm conduction velocity, was 40 m/s (with a sensitivity of 87.04% and specificity of 87.18%) for the sensory nerve conduction study, and 35 m/s (with a sensitivity of 88.06% and specificity of 89.74%) for the motor nerve conduction study.&#x0D; Conclusion: Our study determined that the optimal cutoff conduction velocities for CTS diagnosis, using the wrist-to-midpalm electrical stimulation method, was 40 m/s for the sensory nerve, and 35 m/s for the motor nerve.

Efficacy and pharmacokinetics of ozoralizumab, an anti-TNFα NANOBODY® compound, in patients with rheumatoid arthritis: 52-week results from the OHZORA and NATSUZORA trials

IntroductionOzoralizumab (OZR), a tumor necrosis factor alpha (TNFα) inhibitor, is a NANOBODY® compound that binds to TNFα and human serum albumin. The main objective of this study was to analyze the pharmacokinetics (PK) of the drug and its correlation with clinical efficacy in patients with rheumatoid arthritis (RA).MethodsEfficacy data were analyzed from the OHZORA trial, in which OZR 30 or 80 mg was administered to Japanese patients with RA at 4-week intervals for 52 weeks in combination with methotrexate (MTX; n = 381), and the NATSUZORA trial, in which OZR 30 or 80 mg was administered without concomitant MTX (n = 140). Effects of patient baseline characteristics and anti-drug antibodies (ADAs) on the PK and efficacy of OZR were investigated, and a post hoc analysis of PK effects on drug efficacy was performed.ResultsThe maximum plasma concentration (Cmax) was reached in 6 days in both the 30 and 80 mg groups, with an elimination half-life of 18 days. The Cmax and area under the plasma concentration–time curve increased in a dose-dependent manner, and the trough concentration reached steady state by week 16. The exposure of OZR correlated negatively with patient body weight and was not affected by other patient baseline characteristics. Effects of ADAs on the exposure and efficacy of OZR were limited in both trials. However, antibodies that neutralize the binding to TNFα had some effect on the exposure and efficacy of OZR in the NATSUZORA trial. The receiver operating characteristic analysis of the effect of trough concentration on the American College of Rheumatology 20% and 50% improvement rates was retrospectively performed, and a cutoff trough concentration of approximately 1 μg/mL at week 16 was obtained in both trials. The efficacy indicators in the subgroup with trough concentration ≥ 1 μg/mL were higher than those in the < 1 μg/mL subgroup at week 16, while no clear cutoff was obtained at week 52 in both trials.ConclusionsOZR showed a long half-life and favorable PK properties. A post hoc analysis suggested sustained efficacy independent of trough concentration by subcutaneous administration of OZR 30 mg at 4-week intervals for 52 weeks.Trial registrationJapicCTI, OHZORA trial: JapicCTI-184029, registration date July 9, 2018; NATSUZORA trial: JapicCTI-184031, registration date July 9, 2018.

HESS J1809−193: A halo of escaped electrons around a pulsar wind nebula?

Context. HESS J1809−193 is an unassociated very-high-energy γ-ray source located on the Galactic plane. While it has been connected to the nebula of the energetic pulsar PSR J1809−1917, supernova remnants and molecular clouds present in the vicinity also constitute possible associations. Recently, the detection of γ-ray emission up to energies of ∼100 TeV with the HAWC observatory has led to renewed interest in HESS J1809−193. Aims. We aim to understand the origin of the γ-ray emission of HESS J1809−193. Methods. We analysed 93.2 h of data taken on HESS J1809−193 above 0.27 TeV with the High Energy Stereoscopic System (H.E.S.S.), using a multi-component, three-dimensional likelihood analysis. In addition, we provide a new analysis of 12.5 yr of Fermi-LAT data above 1 GeV within the region of HESS J1809−193. The obtained results are interpreted in a time-dependent modelling framework. Results. For the first time, we were able to resolve the emission detected with H.E.S.S. into two components: an extended component (modelled as an elongated Gaussian with a 1-σ semi-major and semi-minor axis of ∼0.62° and ∼0.35°, respectively) that exhibits a spectral cutoff at ∼13 TeV, and a compact component (modelled as a symmetric Gaussian with a 1-σ radius of ∼0.1°) that is located close to PSR J1809−1917 and shows no clear spectral cutoff. The Fermi-LAT analysis also revealed extended γ-ray emission, on scales similar to that of the extended H.E.S.S. component. Conclusions. Our modelling indicates that based on its spectrum and spatial extent, the extended H.E.S.S. component is likely caused by inverse Compton emission from old electrons that form a halo around the pulsar wind nebula. The compact component could be connected to either the pulsar wind nebula or the supernova remnant and molecular clouds. Due to its comparatively steep spectrum, modelling the Fermi-LAT emission together with the H.E.S.S. components is not straightforward.

Abstract TP37: Door-in-door-out Time Is Not Related To Outcomes In Large Vessel Occlusion Stroke

Endovascular thrombectomy (EVT) a significantly improves outcomes in large vessel occlusion (LVO) stroke. Time to thrombectomy is a major determinant of neurologic outcomes. When patients with LVO arrive at a stroke center that does not perform thrombectomy they require urgent transfer to an endovascular-capable stroke center (ESC) for EVT. The goal of this study was to determine the association between door-in-door-out time (DIDO) and 90-day outcomes in a large multi-center registry. Methods: We conducted a retrospective review of patients from the Optimizing Prehospital Stroke Systems of Care-Reacting to Changing Paradigms (OPUS-REACH) registry initially evaluated at non-ESC and then transferred to ESC for EVT. We determined the association between DIDO times and 90-day outcomes as measured by the modified Rankin scale (mRS). Results: The mean DIDO time for patients with good outcomes was 17 minutes shorter than patients with poor outcomes (122 minutes v. 139 minutes). DIDO cutoff times of cohorts of ≤ 60 minutes, ≤ 90 minutes, or ≤ 120 were not associated with improved functional outcomes for those undergoing EVT (46.4% vs 32.3% p=0.12; 38.6% vs 30.6%, p=0.10; and 36.4% vs 28.9%, p=0.10, respectively). This trend for time cohorts held even for those with hyperacute strokes of &lt;4-hour onset. Lower baseline NIHSS (11.9 vs 18.2, p=&lt;0.001) was associated with improved outcomes. Conclusion: Although the DIDO time was shorter for patients with a good outcome, no clear time cutoff was associated with improved outcomes for LVOS. Factors associated with improved outcomes were a lower stroke severity score at presentation. This study underscores the need to streamline DIDO times but not to set an artificial benchmark not supported by evidence.

Low to Moderate Prenatal Alcohol Exposure and Neurodevelopmental Outcomes: A Narrative Review and Methodological Considerations.

Although abstinence is recommended in pregnancy, many pregnancies are exposed to alcohol. Observational studies of the effects of low to moderate prenatal alcohol exposure (PAE) and neurodevelopmental outcomes have yielded inconsistent results, with some studies finding an increased risk of adverse neurobehavioral and cognitive outcomes, and other studies finding no changes or reduced risk of the same outcomes. The purpose of this narrative review is to summarize these inconsistencies and apply a methodological framework to discuss how different parameters contribute to the findings. The authors also provide recommendations on how to advance future research in this area. The PubMed, Web of Science, and Embase databases were searched, along with reference lists of selected systematic reviews and meta-analyses. Search terms used were (infant or child or children or adolescent or offspring) AND (low or light or mild or moderate or low-to-moderate) AND (drinking or alcohol or drinks) AND (pregnancy or prenatal or fetal) AND (neurodevelopment or behavioral or psychological or cognitive or developmental) NOT (mice or rat or fish or animal) NOT (meta-analysis or review). Peer-reviewed original research studies were included if they analyzed associations between an exposure defined and characterized as low/light or moderate PAE with offspring neurodevelopmental outcomes. Animal studies, studies that did not provide clear cutoff points to classify PAE categories, studies lacking an abstinence control group, and studies that did not present a multivariable-adjusted measure of association were excluded. The searches identified 2,422 papers, with 36 papers meeting eligibility criteria. These studies were carried out across nine countries and included samples ranging from approximately 500 to 40,000 participants. Cognitive, academic, socioemotional, and behavioral outcomes were assessed from infancy through age 19. When the findings from the selected articles were summarized by geographic region, exposure definition, or neurodevelopmental outcome, no consistent observations or patterns emerged between low to moderate PAE and offspring outcomes. Although some studies found positive (i.e., beneficial) associations between low to moderate PAE and outcomes (primarily outcomes related to cognition) and others found negative (i.e., detrimental) associations (primarily for behavioral outcomes), most findings were null (i.e., showed no effect of PAE). The heterogeneity in study results is likely due to methodological issues, including residual confounding, effect measure modification, and exposure misclassification that make synthesis of studies difficult. Alternative study designs, including longitudinal trajectory analysis, sibling design, negative controls, and instrumental variable analyses, may reduce biases and are discussed. To date, the consequences of light to moderate levels of PAE on neurodevelopment remain unresolved; studies that advance methodological rigor will be important contributions to the field.

Investigation of the urinary sodium-to-potassium ratio target level based on the recommended dietary intake goals for the Japanese population: The INTERMAP Japan

Growing epidemiological evidence has shown an association of the urinary sodium (Na) to potassium (K) ratio (Na/K ratio) with blood pressure and cardiovascular diseases. However, no clear cutoff level has been defined. We investigated the cutoff level of the urinary Na/K ratio under different dietary guidelines for Japanese individuals, especially that endorsed by the 2020 revised Japanese Dietary Reference Intakes (DRIs). A population of 1145 Japanese men and women aged 40 to 59 years from the INTERMAP study was examined. Using high-quality standardized data, the averages of two 24 h urinary collections and four 24 h dietary recalls were used to calculate the 24 h urinary and dietary Na/K ratios, respectively. Associations between the urinary and dietary Na/K ratios were tested by sex- and age-adjusted partial correlation. The optimal urinary Na/K ratio cutoff level was determined by receiver operating characteristic (ROC) curves and sex-specific cross tables for recommended dietary K and salt. Overall, the average molar ratio of 24 h urinary Na/K was 4.3. We found moderate correlations (P < 0.001) of the 24 h urinary Na/K ratio with 24 h urinary Na and K excretion (r = 0.52, r = −0.49, respectively) and the dietary Na/K ratio (r = 0.53). ROC curves showed that a 24 h urinary Na/K ratio of approximately 2 predicted Na and K intake that meets the dietary goals of the Japanese DRIs. The range of urinary Na/K ratios meeting the dietary goals of the Japanese DRIs for both Na and K was 1.6‒2.2 for men and 1.7‒1.9 for women. Accomplishing a urinary Na/K ratio of 2 would be desirable to achieve the DRIs dietary goals for both Na and K simultaneously in middle-aged Japanese men and women accustomed to Japanese dietary habits. This observational study is registered at www.clinicaltrials.gov as NCT00005271.

Prognostic value of high-sensitivity cardiac troponin I early after coronary artery bypass graft surgery

BackgroundThe diagnosis of periprocedural myocardial infarction (PMI) after coronary artery bypass graft (CABG) is based on biochemical markers along with clinical and instrumental findings. However, there is not a clear cutoff value of high-sensitivity cardiac troponin (hs-cTn) to identify PMI. We hypothesized that isolated hs-cTn concentrations in the first 24 h following CABG could predict cardiac adverse events (in-hospital death and PMI) and/or left ventricular ejection fraction (LVEF) decrease.MethodsWe retrospectively enrolled all consecutive adult patients undergoing CABG, alone or in association with other cardiac surgery procedures, over 1 year. Hs-cTn I concentrations (Access, Beckman Coulter) were serially measured in the post-operative period and analyzed according to post-operative outcomes.Results300 patients were enrolled; 71.3% underwent CABG alone, 33.7% for acute coronary syndrome. Most patients showed hs-cTn I values superior to the limit required by the latest guidelines for the diagnosis of PMI. Five patients (1.7%) died, 8% developed a PMI, 10.6% showed a LVEF decrease ≥ 10%. Hs-cTn I concentrations did not significantly differ with respect to death and/or PMI whereas they were associated with LVEF decrease ≥ 10% (p value < 0.005 at any time interval), in particular hs-cTn I values at 9–12 h post-operatively. A hs-cTn I cutoff of 5556 ng/L, a value 281 (for males) and 479 (for females) times higher than the URL, at 9–12 h post-operatively was identified, representing the best balance between sensitivity (55%) and specificity (79%) in predicting LVEF decrease ≥ 10%.ConclusionsHs-cTn I at 9–12 h post-CABG may be useful to early identify patients at risk for LVEF decrease and to guide early investigation and management of possible post-operative complications.

Oxidatively Damaged Nucleic Acid: Linking Diabetes and Cancer.

Significance: Our current knowledge of the mechanism between diabetes and cancer is limited. Oxidatively damaged nucleic acid is considered a critical factor to explore the connections between these two diseases. Recent Advances: The link between diabetes mellitus and cancer has attracted increasing attention in recent years. Emerging evidence supports that oxidatively damaged nucleic acid caused by an imbalance between reactive oxygen species generation and elimination is a bridge connecting diabetes and cancer. 8-Oxo-7,8-dihydro-2'-deoxyguanosine and 8-oxo-7,8-dihydroguanosine assume important roles as biomarkers in assessing the relationship between oxidatively damaged nucleic acid and cancer. Critical Issues: The consequences of diabetes are extensive and may lead to the occurrence of cancer by influencing a combination of factors. At present, there is no direct evidence that diabetes causes cancer by affecting a single factor. Furthermore, the difficulty in controlling variables and differences in detection methods lead to poor reliability and repeatability of results, and there are no clear cutoff values for biomarkers to indicate cancer risk. Future Directions: A better understanding of connections as well as mechanisms between diabetes and cancer is still needed. Both diabetes and cancer are currently intractable diseases. Further exploration of the specific mechanism of oxidatively damaged nucleic acid in the connection between diabetes and cancer is urgently needed. In the future, it is necessary to further take oxidatively damaged nucleic acid as an entry point to provide new ideas for the diagnosis and treatment of diabetes and cancer. Experimental drugs targeting the repair process of oxidatively generated damage require an extensive preclinical evaluation and could ultimately provide new treatment strategies for these diseases. Antioxid. Redox Signal. 37, 1153-1167.

How Should Deceased Donor Organs Be Allocated? The Patient's Perspective Derived from Semi-Structured Interviews.

PurposeThe gap between the supply and demand for deceased donor organs is increasing worldwide, while patients on waiting lists for organ transplantation die. This situation requires ethical donor organ allocation rules. The patients’ perspective on donor organ allocation rules offers a highly relevant and unique perspective that may differ from the perspectives of physicians and the general public.Patients and MethodsSemi-structured telephone interviews were conducted with the regional group coordinators of the federal self-help organization for organ transplanted patients and their relatives in Germany in early 2021. Twelve interviews were conducted with patients and relatives of transplantation patients who received transplants for the affected organs including the lungs, heart, kidney, and liver. Transcripts were analyzed using the deductive framework method which was based on an earlier study. All criteria were reported following the COREQ statement.ResultsParticipants emphasized aspects of “medical urgency” and “effectiveness/benefit” of transplantation and associated trade-offs as well as the recipient’s responsibility for organ failure (“own fault”), the appreciation for the gifted graft and the patient’s capability of taking care of it (“appreciation/responsibility”). Patients acknowledged that urgent patients should be prioritized and they showed a clear preference toward allocation rules that strive to maximize both the life years and quality of life gained by transplantation.ConclusionThe patients’ perspective is unique in that patients agree on certain rules for allocation and share many preferences, but also have a hard time finding clear cutoff points when considering selecting a participant for allocation. Patient representatives should therefore be consulted in the debate on donor organ allocation rules.