Single Cutoff Research Articles

Triggering the Untriggered: The First Einstein Probe-detected Gamma-Ray Burst 240219A and Its Implications

The Einstein Probe (EP) achieved its first detection and localization of a bright X-ray flare, EP240219a, on 2024 February 19, during its commissioning phase. Subsequent targeted searches triggered by the EP240219a alert identified a faint, untriggered gamma-ray burst (GRB) in the archived data of Fermi Gamma-ray Burst Monitor (GBM), Swift Burst Alert Telescope (BAT), and Insight-HXMT/HE. The EP Wide-field X-ray Telescope (WXT) light curve reveals a long duration of approximately 160 s with a slow decay, whereas the Fermi/GBM light curve shows a total duration of approximately 70 s. The peak in the Fermi/GBM light curve occurs slightly later with respect to the peak seen in the EP/WXT light curve. Our spectral analysis shows that a single cutoff power-law (PL) model effectively describes the joint EP/WXT–Fermi/GBM spectra in general, indicating coherent broad emission typical of GRBs. The model yielded a photon index of ∼–1.70 ± 0.05 and a peak energy of ∼257 ± 134 keV. After detection of GRB 240219A, long-term observations identified several candidates in optical and radio wavelengths, none of which was confirmed as the afterglow counterpart during subsequent optical and near-infrared follow-ups. The analysis of GRB 240219A classifies it as an X-ray-rich GRB (XRR) with a high peak energy, presenting both challenges and opportunities for studying the physical origins of X-ray flashes, XRRs, and classical GRBs. Furthermore, linking the cutoff PL component to nonthermal synchrotron radiation suggests that the burst is driven by a Poynting flux-dominated outflow.

Reassessing Glycemic Control: A Novel Method for 90-Day Major Complication Stratification Based on Hemoglobin A1c and Same-Day Glucose Levels for Patients Undergoing Total Knee Arthroplasty

BackgroundGlucose levels obtained on the day of surgery may be predictive of complications following total knee arthroplasty (TKA). Established glucose thresholds for TKA are either nonspecific or have low predictive power. Therefore, the purpose of this study was to create data-driven hemoglobin A1c (HbA1c) and same-day glucose thresholds associated with varying risks of 90-day major and surgical site infection (SSI) complications following TKA. MethodsStratum-specific likelihood ratio analysis was conducted to determine data-driven HbA1c and glucose strata associated with varying risks of 90-day major and SSI complications. Each strata was then propensity score matched to the lowest strata based on age, sex, hypertension, heart failure, chronic obstructive pulmonary disorder, and obesity. The risk ratio (RR) for complications in each stratum with respect to the lowest matched stratum was analyzed. ResultsFour data-driven HbA1c (%) strata (4.5 to 5.9, 6.0 to 6.4, 6.5 to 7.9, and 8.0+) and two same-day glucose (mg/dL) strata (60 to 189 and 190+) were identified that predicted 90-day major complications. When compared to the propensity-matched lowest strata (4.5 to 5.9%), the risk of 90-day major complications sequentially increased as the HbA1c (%) strata increased: 6.0 to 6.4 (RR: 1.23; P = 0.024), 6.5 to 7.9 (RR: 1.38; P < 0.001), and 8.0+ (RR: 2.0; P < 0.001). When compared to the propensity-matched lowest strata (60 to 189 mg/dL), the 190+ mg/dL strata had a higher risk of 90-day major complications (RR: 1.18; P = 0.016). No HbA1c or same-day glucose strata had significantly different risks of 90-day SSI. ConclusionsThe multiple strata identified for HbA1c demonstrate that a single HbA1c cutoff as identified in prior literature may be missing a larger picture for risk stratification. The threshold identified for same-day glucose can be utilized in day-of-surgery glycemic control guidelines to further reduce the risk of 90-day major complications.

Flexible modeling of headache frequency fluctuations in migraine with hidden Markov models.

To explore hidden Markov models (HMMs) as an approach for defining clinically meaningful headache-frequency-based groups in migraine. Monthly headache frequency in patients with migraine is known to vary over time. This variation has not been completely characterized and is not well accounted for in the classification of individuals as having chronic or episodic migraine, a diagnosis with potentially significant impacts on the individual. This study investigated variation in reported headache frequency in a migraine population and proposed a model for classifying individuals by frequency while accounting for natural variation. The American Registry for Migraine Research (ARMR) was a longitudinal multisite study of United States adults with migraine. Study participants completed quarterly questionnaires and daily headache diaries. A series of HMMs were fit to monthly headache frequency data calculated from the diary data of ARMR. Changes in monthly headache frequency tended to be small, with 47% of transitions resulting in a change of 0 or 1 day. A substantial portion (24%) of months reflected daily headache with individuals ever reporting daily headache likely to consistently report daily headache. An HMM with four states with mean monthly headache frequency emissions of 3.52 (95% Prediction Interval [PI] 0-8), 10.10 (95% PI 4-17), 20.29 (95% PI 12-28), and constant 28 days/month had the best fit of the models tested. Of sequential month-to-month headache frequency transitions, 12% were across the 15-headache days chronic migraine cutoff. Under the HMM, 38.7% of those transitions involved a change in the HMM state, and the remaining 61.3% of the time, a change in chronic migraine classification was not accompanied by a change in the HMM state. A divide between the second and third states of this model aligns most strongly with the current episodic/chronic distinction, although there is a meaningful overlap between the states that supports the need for flexibility. An HMM has appealing properties for classifying individuals according to their headache frequency while accounting for natural variation in frequency. This empirically derived model may provide an informative classification approach that is more stable than the use of a single cutoff value.

Prognostic and Predictive Potential of CCL5 Expression in Muscle-Invasive Bladder Cancer Patients.

Bladder cancer (BC) is the 12th most commonly diagnosed cancer worldwide. Although there are several well-established molecular and immunological classifications, prognostic and predictive markers for tumor cells and immune cells are still needed. Using a tissue microarray, we analyzed the expression of the chemokine CC motif ligand 5 (CCL5) by immunohistochemistry (IHC) in 175 muscle-invasive BC samples. The application of a single cutoff for the staining status of tumor cells (TCs; positive vs. negative) and immune cells (ICs; positive vs. negative) revealed 75 patients (42.9%) and 123 patients (70.3%) with CCL5-positive TCs or ICs, respectively. IHC results were associated with prognostic and predictive data. Multivariate Cox regression analysis revealed that positive CCL5 staining in TCs was associated with significantly shorter disease-specific survival (DSS; RR = 1.51; p = 0.047), but CCL5-negative ICs were associated with significantly shorter overall survival (OS; RR = 1.66; p = 0.005), DSS (RR = 2.02; p = 0.001) and recurrence-free survival (RFS; RR = 1.94; p = 0.002). Adjuvant chemotherapy was favorable for patients with CCL5-negative ICs for OS (RR = 0.30; p = 0.006), DSS (RR = 0.36; p = 0.022) and RFS (RR = 0.41; p = 0.046) but not for patients with CCL5-positive ICs, except in the subgroup of N1 + N2 patients, where it was associated with better OS. We suggest that CCL5 expression can be a prognostic and predictive marker for muscle-invasive bladder cancer patients.

Outcomes from a new modified single needle laparoscopic percutaneous extraperitoneal closure and cut off for pediatric inguinal hernia

Inguinal hernia is a prevalent surgical condition in pediatric patients. Despite the efficacy of current treatment modalities, a certain recurrence rate still persists. Hence, our objective in this study is to introduce an innovative surgical technique designed to minimize surgical complications. We conducted a retrospective analysis on 809 pediatric cases that underwent laparoscopic repair with our innovative technique for inguinal hernia from June 2020 to June 2022. Demographic information, perioperative details, and postoperative follow-up outcomes were thoroughly assessed. All surgeries were conducted laparoscopically under general anesthesia. The procedure commenced by encircling the hernia sac with two sutures under laparoscopic guidance. Subsequently, the sac was exteriorized from the body using the two sutures, followed by ligation and excision of the hernia sac. The research findings demonstrate that the duration of unilateral and bilateral procedures was recorded as 15.9 ± 4.8 and 21.7 ± 3.9 min, respectively. Incision infection occurred in 7 patients (0.87%), and Male Complicated Inguinal Hernia (MCIH) was observed in 2 patients (0.23%). Notably, there were no occurrences of iatrogenic cryptorchidism, testicular atrophy, or recurrence (0%) during the follow-up period. In conclusion, our novel modification shows a notable reduction in postoperative recurrence rates and alleviates the impact of the procedure on the positioning of the testis or uterus. This modified technique is both safe and valuable, thus warranting broader adoption and promotion.

The Ki67 dilemma: investigating prognostic cut-offs and reproducibility for automated Ki67 scoring in breast cancer

PurposeQuantification of Ki67 in breast cancer is a well-established prognostic and predictive marker, but inter-laboratory variability has hampered its clinical usefulness. This study compares the prognostic value and reproducibility of Ki67 scoring using four automated, digital image analysis (DIA) methods and two manual methods.MethodsThe study cohort consisted of 367 patients diagnosed between 1990 and 2004, with hormone receptor positive, HER2 negative, lymph node negative breast cancer. Manual scoring of Ki67 was performed using predefined criteria. DIA Ki67 scoring was performed using QuPath and Visiopharm® platforms. Reproducibility was assessed by the intraclass correlation coefficient (ICC). ROC curve survival analysis identified optimal cutoff values in addition to recommendations by the International Ki67 Working Group and Norwegian Guidelines. Kaplan–Meier curves, log-rank test and Cox regression analysis assessed the association between Ki67 scoring and distant metastasis (DM) free survival.ResultsThe manual hotspot and global scoring methods showed good agreement when compared to their counterpart DIA methods (ICC > 0.780), and good to excellent agreement between different DIA hotspot scoring platforms (ICC 0.781–0.906). Different Ki67 cutoffs demonstrate significant DM-free survival (p < 0.05). DIA scoring had greater prognostic value for DM-free survival using a 14% cutoff (HR 3.054–4.077) than manual scoring (HR 2.012–2.056). The use of a single cutoff for all scoring methods affected the distribution of prediction outcomes (e.g. false positives and negatives).ConclusionThis study demonstrates that DIA scoring of Ki67 is superior to manual methods, but further study is required to standardize automated, DIA scoring and definition of a clinical cut-off.

Validation study of age-independent fibrosis score (Fibrosis-3 index) in patients with metabolic dysfunction-associated steatotic liver disease.

Because the accuracy of the Fibrosis-4 (FIB-4) index for predicting liver fibrosis changes with age, the need for different cut-offs in various age groups has frequently been discussed. We developed the age-independent score, the Fibrosis-3 (FIB-3) index, and have shown its usefulness in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to validate the diagnostic ability of the FIB-3 index to predict fibrosis progression using a large new patient cohort. The ability of the FIB-3 index to predict liver fibrosis was analyzed by comparing it with that of the FIB-4 index using data from 1398 patients with MASLD enrolled in the Asia-based clinical outcome NAFLD study. The areas under the receiver operating characteristic curves for predicting fibrosis stage F3 or higher were not different between the FIB-3 and FIB-4 indices in the entire cohort. Using the single ideal cut-offs of the indices (3.41 for FIB-3 index and 2.01 for FIB-4 index), the predictive accuracy of the FIB-3 index was not significantly different from that of the FIB-4 index among patients aged <60years; however, the accuracy of the FIB-3 index was significantly higher than that of the FIB-4 index in those aged ≥60years (0.645 and 0.529, respectively; p<0.0001). The high ability of the FIB-3 index with a single cut-off to predict liver fibrosis in patients with MASLD was confirmed. The FIB-3 index could serve as a useful tool for assessing liver fibrosis regardless of age.

Time to Reflect on Return to Sport Timing Following ACL Reconstruction.

The time of return to sport following anterior cruciate ligament (ACL) reconstruction is a commonly discussed topic within clinical settings and the sports medicine literature. Emerging science has demonstrated protective effects of delaying the time of sport clearance on athlete reinjury. Though a single time cutoff is unlikely to be applicable for all athletes, large inconsistencies in the time of return to sport clearanceare present in both the literature and withinprescribed clinical protocols. A multitude of patient factors, such as perceived function, objective function, confidence, post-operative goals, among others, are vital for how athletes are progressed and released for sport participation. This Current Opinion article is constructed to discussthe time to return to sport after ACL reconstruction-factors that may influence timing decisions, how time is assessed within the scientific literature-and to promote discussion on this common topic within the sports medicine and athletic communities. The aim of the article is not to establish defined clinical time cutoffs for this population.

Shift Volume Directly Impacts Neuroradiology Error Rate at a Large Academic Medical Center: The Case for Volume Limits.

Unlike in Europe and Japan, guidelines or recommendations from specialized radiological societies on workflow management and adaptive intervention to reduce error rates are currently lacking in the United States. This study of neuroradiologic reads at a large US academic medical center, which may hopefully contribute to this discussion, found a direct relationship between error rate and shift volume. CT and MR imaging reports from our institution's Neuroradiology Quality Assurance database (years 2014-2020) were searched for attending physician errors. Data were collected on shift volume specific error rates per 1000 interpreted studies and RADPEER scores. Optimal cutoff points for 2, 3 and 4 groups of shift volumes were computed along with subgroups' error rates. A total of 643 errors were found, 91.7% of which were clinically significant (RADPEER 2b, 3b). The overall error rate (errors/1000 examinations) was 2.36. The best single shift volume cutoff point generated 2 groups: ≤ 26 studies (error rate 1.59) and > 26 studies (2.58; OR: 1.63, P < .001). The best 2 shift volume cutoff points generated 3 shift volume groups: ≤ 19 (1.34), 20-28 (1.88; OR: 1.4, P = .1) and ≥ 29 (2.6; OR: 1.94, P < .001). The best 3 shift volume cutoff points generated 4 groups: ≤ 24 (1.59), 25-66 (2.44; OR: 1.54, P < .001), 67-90 (3.03; OR: 1.91, P < .001), and ≥ 91 (2.07; OR: 1.30, P = .25). The group with shift volume ≥ 91 had a limited sample size. Lower shift volumes yielded significantly lower error rates. The lowest error rates were observed with shift volumes that were limited to 19-26 studies. Error rates at shift volumes between 67-90 studies were 226% higher, compared with the error rate at shift volumes of ≤ 19 studies.

Refining Protein Envelopes with a Transition Region for Enhanced Direct Phasing in Protein Crystallography

In protein crystallography, the determination of an accurate protein envelope is of paramount importance for ab initio phasing of diffraction data. In our previous work, we introduced an approach to ascertain the protein envelope by seeking an optimal cutoff value on a weighted-average density map. In this paper, we present a significant advancement in our approach by focusing on identifying a transition region that demarcates the boundary between the protein and solvent regions, rather than relying solely on a single cutoff value. Within this transition region, we conducted a meticulous search for the protein envelope using a finer map and our proposed transition hybrid input–output (THIO) algorithm. Through this improvement, we achieved a refined protein envelope even when starting from random phases, enabling us to determine protein structures with irregular envelopes and successfully phase crystals with reduced solvent contents. To validate the efficacy of our method, we conducted tests using real diffraction data from five protein crystals, each containing solvent contents ranging from 60% to 65%. Solving these structures through conventional direct methods proved difficult due to the limited solvent content. The mean phase error obtained through our proposed method was about 30°. The reconstructed model matched with the structure in the protein data bank with a root mean square deviation (r.m.s.d.) of about 1 Å. These results serve as compelling evidence that the utilization of the proposed transition region in conjunction with the THIO algorithm contributes significantly to the construction of a reliable protein envelope. This, in turn, becomes indispensable for the direct phasing of protein crystals with lower solvent contents.

Determining Pneumocystis jirovecii Colonisation from Infection Using PCR-Based Diagnostics in HIV-Negative Individuals.

Pneumocystis jirovecii pneumonia is increasingly diagnosed with highly sensitive PCR diagnostics in immunocompromised, HIV-negative individuals. We assessed the performance of our in-house quantitative PCR with the aim to optimise interpretation. Retrospective audit of all positive P. jirovecii qPCRs on induced sputum or BAL fluid at a single centre from 2012 to 2023. Medical and laboratory records were analysed and people with HIV were excluded. Cases were categorised as colonisation, high-probability PCP or uncertain PCP infection against a clinical gold standard incorporating clinico-radiological data. Quantitative PCR assay targeting the 5s gene was utilised throughout the time period. Of the 82 positive qPCRs, 28 were categorised as high-probability PCP infection, 30 as uncertain PCP and 24 as colonisation. There was a significant difference in qPCR values stratified by clinical category but not respiratory sample type. Current assay performance with a cutoff of 2.5 × 105 copies/mL had a sensitivity of 50% (95% CI, 30.65-69.35%) and specificity of 83.33% (95% CI, 62.62-95.26%). Youden Index calculated at 6.5 × 104 copies/mL had a sensitivity of 75% (56.64-87.32%, 95% CI) and specificity of 66.67% (46.71-82.03%, 95% CI). High and low cutoffs were explored. Significant variables associated with infection were age > 70 years old, the presence of fever, hypoxia or ground glass changes. A single qPCR cutoff cannot reliably determine P. jirovecii infection from colonisation. Low and high cutoffs are useful, however, a large "possible infection" cohort will remain where interpretation of clinic-radiological factors remains essential. Standardisation of assays with prospective validation in specific immunocompromised groups will allow greater generalisability and allow large-scale prospective assay validation to be performed.

Hemodynamic Failure Staging With Blood Oxygenation Level-Dependent Cerebrovascular Reactivity and Acetazolamide-Challenged (15O-)H2O-Positron Emission Tomography Across Individual Cerebrovascular Territories.

Staging of hemodynamic failure (HF) in symptomatic patients with cerebrovascular steno-occlusive disease is required to assess the risk of ischemic stroke. Since the gold standard positron emission tomography-based perfusion reserve is unsuitable as a routine clinical imaging tool, blood oxygenation level-dependent cerebrovascular reactivity (BOLD-CVR) with CO2 is a promising surrogate imaging approach. We investigated the accuracy of standardized BOLD-CVR to classify the extent of HF. Patients with symptomatic unilateral cerebrovascular steno-occlusive disease, who underwent both an acetazolamide challenge (15O-)H2O-positron emission tomography and BOLD-CVR examination, were included. HF staging of vascular territories was assessed using qualitative inspection of the positron emission tomography perfusion reserve images. The optimum BOLD-CVR cutoff points between HF stages 0-1-2 were determined by comparing the quantitative BOLD-CVR data to the qualitative (15O-)H2O-positron emission tomography classification using the 3-dimensional accuracy index to the randomly assigned training and test data sets with the following determination of a single cutoff for clinical application. In the 2-case scenario, classifying data points as HF 0 or 1-2 and HF 0-1 or 2, BOLD-CVR showed an accuracy of >0.7 for all vascular territories for HF 1 and HF 2 cutoff points. In particular, the middle cerebral artery territory had an accuracy of 0.79 for HF 1 and 0.83 for HF 2, whereas the anterior cerebral artery had an accuracy of 0.78 for HF 1 and 0.82 for HF 2. Standardized and clinically accessible BOLD-CVR examinations harbor sufficient data to provide specific cerebrovascular reactivity cutoff points for HF staging across individual vascular territories in symptomatic patients with unilateral cerebrovascular steno-occlusive disease.

81 An Examination of a Multiple Cutoff Performance Validity Index

Objective:Recent consensus guidelines have advocated for the use of multivariate performance validity assessment on ability-based measures such those used in neuropsychological assessment. Further, previous research has demonstrated that aggregating performance validity indicators may produce superior classification accuracy. The present study builds upon this research by aggregating data from three of the most commonly used performance validity measures (Test of Memory Malingering [TOMM], Rey Fifteen Item Test with recognition trial [FIT plus recognition], and Reliable Digit Span [RDS]) to create a performance validity composite measure in a veteran mild traumatic brain injury (mTBI) population.Participants and Methods:Data of patients evaluated at a VA hospital who had completed the RDS, FIT plus recognition, and TOMM as part of their clinical neuropsychological evaluation were analyzed (n = 20). Two composite performance validity indexes were created: a Single Cutoff Performance Validity Index (SC-PVI), which measures the quantity of failures across performance validity measures (PVMs) by summing the total number of PVM failures, and a Multiple Cutoff Performance Validity Index (MC-PVI) which measures the number of failures as well as degree of failure(s) across measures of performance validity (e.g., a participant would attain a score of 3 if their PVM performance failed to reach a conservative cut point; they would obtain a score of 1 if they met conservative cut point, yet failed to reach a liberal cut point).Results:Only one participant (5%) attained a score of 0 on the SC-PVI (i.e., passing all PVTs using standard cutoffs) and MC-PVI (i.e., passing the most liberal cut points on all three PVMs). Conversely, eight participants (40%) attained a score of 3 on the SC-PVI (i.e., failed all three PVMs) and four participants (20%) attained a score of 9 (i.e., failed the most conservative cut points on all three PVMs). Results showed a significant (p &lt; .001) ordinal association between the two indices (G = .984); however, there was no significant agreement between SC-PVI and MC-PVI models (k = -.087; p = .127).Conclusions:Data revealed discordant findings between the three PVMs utilized. The majority of participants (75%) scored between 2-8 on the MC-PVI, meaning that they did not exceed all liberal cut points or fail all conservative cut points. These “grey area” scores suggest an indeterminate range of performance validity, which cannot be captured by a solitary cut point or neatly classified as pass or fail. The utility of multiple cutoff performance validity models (i.e., aggregating PVMs to consider the severity of failure and number of failures) is that they capture the nuance of these data when determining and discussing the credibility of a profile. Multiple cut point data also highlight how the choice of cutoff influences the outcome of performance validity research and clinical decision making. As such, future research on the classification accuracy of this MC-PVI is needed.

Risk factors for blood transfusion and postoperative anaemia following total knee arthroplasty.

Blood transfusion and postoperative anaemia are complications of total knee arthroplasty (TKA) that are associated with substantial healthcare costs, morbidity, and mortality. There are few data from large datasets on the risk factors for these complications. We retrospectively reviewed the records of TKA patients from a single tertiary care institution from February 2016 to December 2020. There were a total of 14,901 patients in this cohort with a mean age of 67.9 years (SD 9.2), and 5,575 patients (37.4%) were male. Outcomes included perioperative blood transfusion and postoperative anaemia, defined a priori as haemoglobin level < 10 g/dl measured on the first day postoperatively. In order to establish a preoperative haemoglobin cutoff, we investigated a preoperative haemoglobin level that would limit transfusion likelihood to ≤ 1% (13 g/dl) and postoperative anaemia likelihood to 4.1%. Risk factors were assessed through multivariable Poisson regression modelling with robust error variance. In multivariable analyses, each gram of tranexamic acid reduced transfusion likelihood by 39% (adjusted risk ratio (ARR) 0.61 (95% confidence interval (CI) 0.47 to 0.78)). Risk factors associated with an increased risk of transfusion included operating time (ARR 2.07 (95% CI 1.54 to 2.77)) and drain use (ARR 1.73 (95% CI 1.34 to 2.24)). In this study, we found that increased tranexamic acid dosing, decreased operating time, and decreased drain use may reduce transfusions following TKA. We also established a single preoperative haemoglobin cutoff of 13 g/dl that could help minimize transfusions and reduce postoperative complete blood counts.

Correlation between Perfusion-Weighted Magnetic Resonance Imaging (MRI) Features with Histopathological Grading of Glioma

Background: Gliomas are the most common primary neoplasm of the brain. It histopathologically grades I to IV. I and II are low grade while III, IV are high grade. Low-grade gliomas are usually subject to either strict follow-up or surgery. The treatment for high grade gliomas is typically surgery, followed by concomitant radiation therapy and chemotherapy. Conventional MRI has limitations for the grading of gliomas. In addition to conventional MRI techniques, a variety of new techniques such as perfusion-weighted MRI which noninvasively measures cerebral perfusion that can be used for better assessment of glioma. This will be helpful for therapeutic approach and counseling about prognosis of the patient. Methods: This cross sectional observational study was conducted in the Department of Neurosurgery, Bangabandhu Sheikh Mujib Medical University from IRB clearance to 18 months. The patients who fulfill the selection criteria were enrolled in this study. Written informed consent was taken from the patients and/or the legal guardian/ responsible family members after completely explaining to them the procedure and the purpose of the study. Patient’s data was collected in questionnaire/data collection sheet. The privacy of the patient was strictly maintained and the patient’s information will not be disclosed to any source. The study data will only be used for the purpose of this scientific study. This study was not causing any additional harm to the patients. All the patients were evaluated by a standard conventional contrast-enhanced study with perfusion-weighted image on Siemens 3 Tesla MRI. The histopathological grading of the tumor was done as per the WHO classification of 2007. Then correlation was done between PWI finding and WHO histopathological grading. Results: Measurement of relative cerebral blood volume in glioma patients was done in PW-MRI preoperatively. Out of the 35 tumors evaluated, 17 were found as low rCBV and 18 as high. Histopathological examination of glioma was done postoperatively. Among 35 tumors, 19 are low grade gliomas and 16 are high grade gliomas. For the correlation between relative cerebral blood volume in preoperative PW MRI and histopathological grading of glioma, Spearman’s Rank Correlation Coefficient Test was done. We found a significant positive coefficient value of r = 0.572 with a significant p-value of p = &lt;0.001. A single cutoff relative cerebral blood volume value of 1.7 for low versus high grade glioma was found to be 77.8% sensitive and 88.2% specific. Conclusion: The present study ascertains that histopathological grading of glioma is positively correlated with relative cerebral blood volume in PW MRI. Bang. J Neurosurgery 2022; 12(1): 12-19

Accuracy of spleen stiffness measurement for the diagnosis of clinically significant portal hypertension in patients with compensated advanced chronic liver disease: a systematic review and individual patient data meta-analysis

The diagnosis of clinically significant portal hypertension is crucial for prognosis and treatment guidance in patients with compensated advanced chronic liver disease (ACLD). Spleen stiffness measurement (SSM) might improve the non-invasive diagnosis of clinically significant portal hypertension, but previous studies have reported heterogeneous SSM cutoffs. We aimed to evaluate the accuracy of SSM and SSM-based algorithms in this setting. In this systematic review and individual patient data meta-analysis, we searched PubMed, Embase, Scopus, Web of Science, and the Cochrane Library from database inception to Dec 31, 2022, for articles, abstracts, and letters, with no restrictions on language. Cross-sectional studies reporting hepatic venous pressure gradient and SSM by different techniques (transient elastography; two-dimensional shear-wave elastography [2D-SWE]; point shear-wave elastography [p-SWE]) in adults (≥18 years) with compensated ACLD were eligible for inclusion. The main outcome was the diagnostic performance of two SSM-based algorithms, with the Baveno VII model as a reference, evaluating sensitivity and specificity, as well as summary negative predictive values (NPVs) and positive predictive values (PPVs). In the Baveno VII model, clinically significant portal hypertension was ruled out if patients had a liver stiffness measurement (LSM) of 15 kPa or less and a platelet count of 150 × 109 platelets per L or higher and ruled in if they had an LSM of greater than 25 kPa. The two SSM-based models combined these same cutoffs with additional criteria. In the Baveno VII-SSM single cutoff model, clinically significant portal hypertension was ruled out if at least two of the following were present: LSM of 15 kPa or less, platelet count of 150 × 109 platelets per L or higher, and SSM of 40 kPa or less; and ruled in if at least two were present: LSM of greater than 25 kPa, platelet count of less than 150 × 109 platelets per L, and SSM of greater than 40 kPa. The Baveno VII-SSM dual cutoff model used the same criteria, but with a cutoff of SSM of less than 21 kPa to rule out, and greater than 50 kPa to rule in, clinically significant portal hypertension. This study is registered with PROSPERO, CRD42019127164. Of the 44 records assessed for eligibility, 17 studies (with 1245 patients) were included in the meta-analysis. In the transient elastography cohort (n=600), the Baveno VII algorithm was validated for both ruling out (NPV 100%, 95% CI 64-100; sensitivity 100%, 95% CI 70-100) and ruling in (PPV 95%, 85-98; specificity 94%, 95% CI 87-97) clinically significant portal hypertension, but the proportion of patients with indeterminate results (grey zone) was 48% (95% CI 44-52); 57% (95% CI 52-62) of patients with clinically significant portal hypertension were included in the rule-in zone. The Baveno VII-SSM dual cutoff model had adequate NPV (98%, 95% CI 58-100; sensitivity 100%, 95% CI 91-100) and PPV (93%, 95% CI 84-97; specificity 89%, 95% CI 84-93), with 32% (95% CI 28-36) of patients in the grey zone; 76% (95% CI 72-80) of the patients with clinically significant portal hypertension were in the rule-in zone. The Baveno VII-SSM single cutoff model had a sensitivity of 93% (95% CI 85-97) and a NPV of 85% (95% CI 60-96) for ruling out, and a specificity of 86% (95% CI 80-91) and a PPV of 92% (95% CI 83-95) for ruling in, clinically significant portal hypertension. 88% (95% CI 84-91) of patients with clinically significant portal hypertension were included in the rule-in zone and 9% (95% CI 7-12) of patients were in the grey zone. In the 2D-SWE cohort (n=225), all three algorithms could safely rule in clinically significant portal hypertension with adequate PPV (≥90%), but NPV was inadequate for ruling out clinically significant portal hypertension. Insufficient data were available to evaluate the performance of SSM assessed by p-SWE. Heterogeneity was low (I2<25%) for most estimates. Algorithms combining Baveno VII criteria with SSM showed good performance and reduced the diagnostic grey zone for clinically significant portal hypertension compared with Baveno VII criteria alone. Future studies should evaluate whether SSM-based diagnosis allows for the identification of patients who would benefit from non-selective β-blocker treatment. None.

Nangibotide for precision immunomodulation in septic shock and COVID-19

Nangibotide for precision immunomodulation in septic shock and COVID-19

International Newborn Screening Practices for the Early Detection of Congenital Adrenal Hyperplasia

Introduction: Newborn screening (NBS) programmes vary internationally in their approach to screening. Guidelines for congenital adrenal hyperplasia (CAH) screening recommend the use of two-tier testing and gestational age cutoffs to minimise false-positive results. The aims of this study were to describe (1) the approaches; (2) protocols used; and (3) available outcomes for CAH screening internationally. Methods: All members of the International Society for Neonatal Screening were asked to describe their CAH NBS protocols, with an emphasis on the use of second-tier testing, 17-hydroxyprogesterone (17OHP) cutoffs, and gestational age and birth weight adjustments. If available, screening outcomes were requested. Results: Representatives from 23 screening programmes provided data. Most (n = 14; 61%) recommend sampling at 48–72 h of life. Fourteen (61%) use single-tier testing and 9 have a two-tier testing protocol. Gestational age cutoffs are used in 10 programmes, birth weight cutoffs in 3, and a combination of both in 9. One programme does not use either method of adjusting 17OHP cutoffs. Case definition of a positive test and the response to a positive test differed between programmes. Conclusions: We have demonstrated significant variation across all aspects of NBS for CAH, including timing, the use of single versus two-tier testing and cutoff interpretation. Collaboration between international screening programmes and implementation of new techniques to improve screen efficacy will facilitate ongoing expansion and quality improvement in CAH NBS.

A Genetic Algorithm Optimization Model for Stability of an Inclined Cutoff with Soil-Embedded Depth

A coupled artificial neural network model with a genetic algorithm optimization model is developed for a practical case of a single cutoff. The proposed cutoff is of a soil-embedded vertical part with an inclined extension. The model successfully found the optimum dimensions of the vertical and inclined parts, the optimum angle of inclination, and the optimum length of protection downstream of the cutoff for a factor of safety of 3 against piping. Two thousand one hundred cases are modeled first using Geo-studio software to find the required length of downstream protection against piping for different lengths of the vertical, inclined lengths of the cutoff, its angle of inclination, soil layer depth, and degree of anisotropy. Then the created data set was used to develop an Artificial Neural Network (ANN) model for finding the length of protection required. The ANN model showed high performance with a determination coefficient of (0.922). The genetic algorithm model needs a minimum number of randomly generated populations of 100000 and three crossover iterations to produce a stable optimum solution. Running the model for different practical cases showed that the optimum angle variation was low and fluctuated around 30o. This low angle variation was due to its lower effect on the downstream soil protection length compared to the other decision variables. At the same time, the other dimensions varied with input variables, such as the depth of the soil layer, the seepage driving head, and the degree of isotropy. For a degree of anisotropy (ratio of vertical to horizontal hydraulic gradient) less than 0.5, the results showed no need for protection against piping; hence it is recommended to use minimum dimensions for such a case. The coupled model can easily obtain the optimum dimensions for any given input. Importance analysis showed that the optimum length of the downstream protection was highly affected by the vertical and inclined length of the cutoff, while it was less affected by the angle of inclination. Correlation analysis supported the importance analysis.

A statistical approach for identifying primary substrates of ZSWIM8-mediated microRNA degradation in small-RNA sequencing data

BackgroundOne strategy for identifying targets of a regulatory factor is to perturb the factor and use high-throughput RNA sequencing to examine the consequences. However, distinguishing direct targets from secondary effects and experimental noise can be challenging when confounding signal is present in the background at varying levels.ResultsHere, we present a statistical modeling strategy to identify microRNAs that are primary substrates of target-directed miRNA degradation (TDMD) mediated by ZSWIM8. This method uses a bi-beta-uniform mixture (BBUM) model to separate primary from background signal components, leveraging the expectation that primary signal is restricted to upregulation and not downregulation upon loss of ZSWIM8. The BBUM model strategy retained the apparent sensitivity and specificity of the previous ad hoc approach but was more robust against outliers, achieved a more consistent stringency, and could be performed using a single cutoff of false discovery rate (FDR).ConclusionsWe developed the BBUM model, a robust statistical modeling strategy to account for background secondary signal in differential expression data. It performed well for identifying primary substrates of TDMD and should be useful for other applications in which the primary regulatory targets are only upregulated or only downregulated. The BBUM model, FDR-correction algorithm, and significance-testing methods are available as an R package at https://github.com/wyppeter/bbum.