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Purpose To investigate the efficacy and safety of bevacizumab plus carboplatin and paclitaxel in patients with advanced or recurrent non-small-cell lung cancer. Patients and Methods In a phase II trial, 99 patients were randomly assigned to bevacizumab 7.5 (n = 32) or 15 mg/kg (n = 35) plus carboplatin (area under the curve = 6) and paclitaxel (200 mg/m2) every 3 weeks or carboplatin and paclitaxel alone (n = 32). Primary efficacy end points were time to disease progression and best confirmed response rate. On disease progression, patients in the control arm had the option to receive single-agent bevacizumab 15 mg/kg every 3 weeks. Results Compared with the control arm, treatment with carboplatin and paclitaxel plus bevacizumab (15 mg/kg) resulted in a higher response rate (31.5% v 18.8%), longer median time to progression (7.4 v 4.2 months) and a modest increase in survival (17.7 v 14.9 months). Of the 19 control patients that crossed over to single-agent bevacizumab, five experienced stable disease, and 1-year survival was 47%. Bleeding was the most prominent adverse event and was manifested in two distinct clinical patterns; minor mucocutaneous hemorrhage and major hemoptysis. Major hemoptysis was associated with squamous cell histology, tumor necrosis and cavitation, and disease location close to major blood vessels. Conclusion Bevacizumab in combination with carboplatin and paclitaxel improved overall response and time to progression in patients with advanced or recurrent non-small-cell lung cancer. Patients with nonsquamous cell histology appear to be a subpopulation with improved outcome and acceptable safety risks.

Context Urodynamic study (UDS) provides the most objective assessment of bladder outlet obstruction (BOO) but is impractical to be recommended routinely in outpatient services. Intravesical prostatic protrusion (IPP) had been described to obstruct urinary flow by creating an anatomical ball-valve effect, but there remains a lack of pooled evidence that can objectively correlate with BOO in benign prostatic hyperplasia. Objective To update the current evidence on the predictive role of IPP in determining BOO and unsuccessful trial without catheter (TWOC). Evidence acquisition A comprehensive literature search was performed to identify studies that evaluated IPP in diagnosing UDS-determined BOO and TWOC. The search included the PubMed/MEDLINE, EMBASE, and Cochrane Library up to January 2021. An updated systemic review and meta-analysis was performed. Evidence synthesis A total of 18 studies with 4128 patients were examined. Eleven studies with 1478 patients examined the role of IPP in UDS-determined BOO. The pooled area under the curve (AUC) was 0.83 (95% confidence interval [CI]: 0.79–0.86), and at a cut-off of >10 mm, the sensitivity (Sn) and specificity (Sp) were 0.71 (95% CI: 0.61–0.78) and 0.77 (95% CI: 0.68–0.84), respectively. The probability-modifying plot revealed positive and negative likelihood ratios of 3.34 (95% CI: 2.56–4.36) and 0.35 (95% CI: 0.26–0.45), respectively. Seven studies with 2650 patients examined IPP in predicting unsuccessful TWOC, with a pooled AUC of 0.74 (95% CI: 0.70–0.84), with Sn of 0.51 (95% CI: 0.43–0.60) and Sp of 0.79 (95% CI: 0.73–0.84) at an IPP cut-off of >10 mm. Five studies compared prostate volume (PV) and IPP and revealed a lower AUC of PV at 0.71 (95% CI: 0.67–0.75), which was an inferior parameter in diagnosing BOO (p Conclusions This systemic review provided evidence that IPP is a reliable clinical parameter that correlates strongly with underlying BOO and unsuccessful TWOC. Patient summary In this review, we comprehensively reviewed all the literature to date on evaluating the clinical utility of intravesical prostatic protrusion (IPP). We have demonstrated that IPP correlates strongly with urodynamic study (UDS)-determined bladder outlet obstruction and failure of trial without catheter (TWOC). Outpatient IPP measurement is a quick, inexpensive, and reproducible clinical parameter that can determine the severity of benign prostatic hyperplasia. The clinical role of IPP in predicting failure of TWOC selects patients who are best treated with aggressive surgical approaches rather than conservative medical therapies. More importantly, IPP can facilitate the discriminatory use of invasive UDS, reserved for patients with a strong suspicion of concomitant detrusor abnormalities.

Increased pulse pressure (IPP) is associated with an estimated glomerular filtration ≤ 60/mL/min/1.73 mTo determine the usefulness of IPP as a diagnostic test for K/DOQI stage III-b CKD.Diagnostic test study that included adult patients without comorbidities, registered in the Health Workers Cohort. The CKD-EPI formula was used to calculate glomerular filtration. Pulse pressure was determined by subtracting diastolic from systolic blood pressure. Sensitivity, specificity, positive predictive value, negative predictive value and prevalence were calculated using standard formulas. A ROC curve was generated to determine the area under the curve.A total of 6,215 patients were included. An IPP ≥ 50 mmHg was observed to have a sensitivity of 74 %, specificity of 70 %, positive predictive value of 1 %, negative predictive value of 100 % and a prevalence of 1 %. The inflection point in the ROC curve to identify K/DOQI III-b CKD was 0.71.An IPP ≥ 50 mmHg is useful as a diagnostic test to identify people with K/DOQI stage III-b CKD.La presión de pulso ampliada (PPA) se asocia a un filtrado glomerular calculado ≤ 60/mL/minuto/1.73 mDeterminar la utilidad de la PPA como prueba diagnóstica de IRC estadio K/DOQI III-b.Estudio de prueba diagnóstica que incluyó a pacientes adultos sin comorbilidades, registrados en la Cohorte de Trabajadores de la Salud. Se utilizó la fórmula CKD-EPI para calcular la filtración glomerular. Se determinó la presión de pulso restando la presión arterial diastólica a la presión arterial sistólica. Se calculó sensibilidad, especificidad, valor predictivo positivo, valor predictivo negativo y prevalencia. Se elaboró una curva ROC para determinar el área bajo la curva.Se incluyeron 6215 pacientes. Se observó que una PPA ≥ 50 mm Hg tuvo sensibilidad de 74 %, especificidad de 70 %, valor predictivo positivo de 1 %, valor predictivo negativo de 100 % y prevalencia de 1 %. El punto de inflexión en la curva ROC para identificar IRC K/DOQI III-b fue de 0.71.La PPA ≥ 50 mm Hg es útil como prueba diagnóstica para identificar a personas con IRC estadio K/DOQI III-b.

OBJECTIVES To determine the accuracy of the 5-time stand-to-sit (5TSTS) test for the identification of older adults with reduced gait speed. DESIGN Cross-sectional study. SETTING AND PARTICIPANTS A total of 559 community-dwelling older adults were included in the study, divided into groups of women (n=465) and men (n=94). METHODS 5TSTS and gait speed were assessed. Multiple linear regression analysis with adjustment was performed in order to determine the association between 5TSTS and gait speed, followed by the receiver operating characteristic (ROC) curve for the identification of the usefulness of 5TSTS to discriminate older adults with reduced gait speed. Based on the ROC curve, we identified the area under the curve, the sensitivity, specificity, and cutoff points of the 5TSST. Statistical analyses were made using the SPSS software (version 25.0), and a significance level of 5% (P ≤ .05) was adopted. RESULTS The 5TSTS showed correlation with gait speed. Additionally, 5TSTS was able to discriminate reduced gait speed with moderate accuracy (P < .05; AUC between 0.7 and 0.8). For women, the cutoff scores for 5TSTS to identify gait speed

The primary aim of our study was to evaluate diagnostic accuracy of the tibial tubercle-trochlear groove (TT-TG) distance relative to associated quotients produced from trochlear width (TT-TG distance/TW) and trochlear dysplasia index (TT-TG distance/TDI) for detecting patellofemoral instability. Secondary aims included identifying thresholds for risk and comparing differences between cases and controls.Consecutive sampling of electronic medical records produced 48 (21 males, 27 females) patellofemoral instability cases (19 ± 7 years old) and 79 (61 males, 18 females) controls (23 ± 4 years old) who had a history of isolated meniscal lesion, as evaluated by magnetic resonance imaging. Standardized methods were employed with measurements executed in a blinded and randomized manner. A receiver operating characteristic curve assessed accuracy by area under the curve (AUC). The index of union (IU) was employed to identify a threshold for risk. Two-sample t-tests examined group differences. P.05 denoted statistical significance.The AUC values were .69 (.60, .79) for TT-TG distance, .81 (.73, .88) for TT-TG distance/TW, and .85 (.78, .91) for TT-TG distance/TDI. Thresholds were 14.7 mm for TT-TG distance, .36 for TT-TG distance/TW, and 1.88 for TT-TG distance/TDI. Cases demonstrated statistically significant (P.001) greater values for each measure compared with controls: TT-TG distance (15.8 ± 4.2 mm vs 12.9 ± 3.6 mm, [1.4, 4.3]); TT-TG distance/TW (.51 ± .24 vs .31 ± .09, [.13, .27]); TT-TG distance/TDI (3.07 ± 1.55 vs 1.7 ± .7, [.9, 1.84]).The TT-TG distance, TT-TG distance/TW, and TT-TG distance/TDI measures were 69%, 81%, and 85%, respectively, accurate for determining patellofemoral instability risk. Thresholds for risk were 14.7 mm for TT-TG distance, .36 for TT-TG distance/TW, and 1.88 for TT-TG distance/TDI. The thresholds reported in this study may help in advancing clinical decision-making.Level III, diagnostic retrospective comparative observatory trial.

Purpose To investigate the relationship between the lateral femoral condyle ratio (LFCR) among osseous morphologic characteristics of the knee and anterior cruciate ligament (ACL) injury in female patients. Methods Inclusion criteria were female patients (ACL group, n = 59) undergoing primary ACL reconstruction from 2012 to 2018. Control female patients (control group, n = 58) were matched by age, height, and body mass index to ACL group. They had no meniscal or ligament tear, and no trochlear dysplasia on magnetic resonance imaging. The LFCR, notch width index (NWI), and posterior tibial slope (PTS) were measured and compared between the ACL and control groups. For each risk factor, the receiver operating characteristic curve and the area under the curve and its 95% confidence interval (CI) was calculated to determine the cutoff for detecting increased risk of ACL injury. Results The LFCR was significantly larger in the knees in the ACL group than in the control group (P = .001). The NWI was significantly smaller and the PTS was significantly larger in the knees in the ACL group than in the control group (P = .000, P = .000, respectively). The NWI (odds ratio [OR] 1.41; P = .000) was the most significant factor, followed by the PTS (OR 1.29; P = .003) and the LFCR (OR 1.26; P = .001). The area under the curve (0.67, 95% CI 0.58-0.77) for the LFCR had a sensitivity of 66% and specificity of 66% to predict an ACL injury. The cutoff of 63.9 was associated with an increased risk for ACL injury (OR 3.71; 95% CI 1.73-7.95). Conclusions An increased LFCR was associated with female ACL injury. The LFCR, NWI, and PTS are predictive risk factors for an ACL injury. These findings need to be considered for clinician in identifying female patients at risk for an ACL injury. Level of Evidence III, retrospective comparative prognostic trial.

BACKGROUND: Early recognition of severe COVID-19 is essential for timely patient triage. AIMS: We aim to report clinical and laboratory findings and patient outcomes at a tertiary hospital in Melbourne, Australia. METHODS: This is a retrospective study of adult inpatients with COVID-19 admitted to Northern Health from March to September 2020. Data were extracted from electronic medical records. RESULTS: Key admission data was available for 182 patients (median age 67.0 years (interquartile range, 47.9-83.1; 51.1% female). 56 (30.8%) were from residential care. 117 (64.3%) patients were assigned Goals-of-Patient-Care (GOPC) A or B and 65 (35.7%) GOPC C or D. Comorbidities were present in 135 patients (74.2%). 63.2% of patients received antibiotics, 6.6% had antivirals, 45.6% received systemic glucocorticoid and 3.3% had tocilizumab. 56 (30.8%) developed clinical deterioration (24 requiring ventilation, 21 receiving critical care, 34 died). Overall, in-hospital clinical deterioration was significantly associated with older age (p

The prevalence of metabolic syndrome (MetS) is more common in patients with hypertension and is associated with an increased risk of target organ damage and/or cardiovascular disease (CVD). Omentin-1 is a beneficial adipokine considered to play a role in MetS and MetS-related states such as obesity, diabetes, and coronary artery disease. The aim of this study was to determine the relationship between circulating omentin-1 levels and MetS uncomplicated by diabetes or CVD (nascent MetS) in patients with hypertension. In this study, 110 patients (54 men, 49%; average age: 49.72±11.32 years) treated for hypertension but without overt diabetes and/or CVD were enrolled. 66 patients were stratified into MetS (+) (group 1) and 44 patients into MetS (−) (group 2) according to the American Heart Association/National Heart, Lung, and Blood Institute criteria. The triglyceride glucose (TyG) index was used to assess insulin resistance. Circulating omentin-1 levels in venous blood samples were measured by an ELISA kit. Circulating omentin-1 levels in patients with MetS were significantly lower than in patients without MetS (46.35 ng/mL (42.70–57.70 ng/mL) vs 130.95 ng/mL (62.83–236.48 ng/mL), p

Background Urine tissue inhibitor of metalloproteinases-2/insulin-like growth factor-binding protein 7 (TIMP-2/IGFBP7) (NephroCheck, Ortho Clinical Diagnostics, Raritan, NJ, USA) is a US Food and Drug Administration-approved biomarker for risk assessment of acute kidney injury (AKI) in critically ill adult patients in intensive care units; however, its clinical impact in the emergency department (ED) remains unproven. We evaluated the utility of NephroCheck for predicting AKI development and short-term mortality in the ED. Methods This was a prospective, observational, five-center international study. We consecutively enrolled ED patients admitted with ≥30% risk of AKI development (assessed by ED physician: ED score) or acute diseases. Serum creatinine was tested on ED arrival (T0), day 1, and day 2 (T48); urine for NephroCheck was collected at T0 and T48. We performed ROC curve and reclassification analyses. Results Among the 529 patients enrolled (213 females; median age, 65 years), AKI developed in 59 (11.2%) patients. The T0 NephroCheck value was higher in the AKI group than in the non-AKI group (median 0.77 vs. 0.29 (ng/m)2/1,000, P=0.001), and better predicted AKI development than the ED score (area under the curve [AUC], 0.64 vs. 0.53; P=0.04). In reclassification analyses, adding NephroCheck to the ED score improved the prediction of AKI development (P Conclusions NephroCheck can predict both AKI development and short-term mortality in at-risk ED patients. NephroCheck would be a useful biomarker for early ruling-in or ruling-out of AKI in the ED.

BACKGROUND: Survival after heart transplant has greatly improved, with median survival now over 12 years. Cardiac allograft vasculopathy (CAV), has become a major source of long-term morbidity and mortality. Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is used for CAV surveillance, but there is limited data on its prognostic utility. METHODS: We retrospectively identified patients undergoing SPECT MPI for CAV surveillance at a single, large-volume center. Images were assessed with semi-quantitative visual scoring (summed stress score [SSS] and summed rest score [SRS]) and quantitatively with total perfusion defect (TPD). RESULTS: We studied 503 patients (mean age 62.5, 69.3% male) at a median of 9.0 years post-transplant. During mean follow-up of 5.1 ± 2.5 years, 114 (22.6%) patients died. The diagnostic accuracy for significant CAV (ISHLT grade 2 or 3) was highest for SSS with an area under the curve (AUC) of 0.650 and stress TPD (AUC 0.648), with no significant difference between SSS and stress TPD (p=0.061). Stress TPD (adjusted hazard ratio 1.07, p=0.018) was independently associated with all-cause mortality, while SSS was not (p=0.064). The prognostic accuracy of quantitative assessment of perfusion tended to be higher compared to semi-quantitative assessment, with the highest accuracy for stress TPD (area under the receiver operating curve 0.584). CONCLUSIONS: While SPECT MPI identified a cohort of higher risk patients, with quantitative analysis of perfusion demonstrating higher prognostic accuracy. However, the overall prognostic accuracy was modest and alternative non-invasive modalities may be more suitable for CAV surveillance.

Despite the fact that acetylsalicylic acid (ASA) is the "gold" standard for the prevention of cardiovascular complications in patients with coronary heart disease (CAD), a number of patients still have risks of atherothrombosis. In the present study, the antithrombotic effect of ASA in patients with CAD was assessed in platelet-rich plasma (PRP) using integral tests of the hemostasis study: the T-TAS system (Total Thrombus-formation Analysis System) and the thrombin generation test (TGT). The study involved 34 patients with stable CAD (11 women, 23 men) and people (15 women, 18 men) in the control group. As a result of assessing the activity of thrombus formation using the T-TAS system, a significant decrease in the area under the curve (AUC10) was found in the group with CAD patients compared with the control (135.6 [88.0-222.3] and 260.5 [217.3-301.9], respectively, p.Nesmotria na to, chto atsetilsalitsilovaia kislota (ASK) iavliaetsia zolotym standartom profilaktiki serdechno-sosudistykh oslozhneniĭ (SSO) u bol'nykh ishemicheskoĭ bolezn'iu serdtsa (IBS), vse zhe u riada patsientov sokhraniaiutsia riski aterotromboza. V nastoiashchem issledovanii provedena otsenka antitromboticheskogo éffekta ASK u patsientov s IBS s pomoshch'iu integral'nykh testov issledovaniia gemostaza: sistemy T-TAS (total thrombus-formation analysis system) i testa generatsii trombina (TGT) v bogatoĭ trombotsitami plazme (PRP — platelet rich plasma). Obsledovano 34 patsienta so stabil'noĭ IBS (11 zhenshchin, 23 muzhchiny) i 33 cheloveka (15 zhenshchin, 18 muzhchin) gruppy kontrolia. V rezul'tate otsenki aktivnosti tromboobrazovaniia s pomoshch'iu sistemy T-TAS obnaruzheno znachimoe snizhenie ploshchadi pod krivoĭ (AUC10) v gruppe s IBS po sravneniiu s kontrol'noĭ (135,6 [88,0-222,3] i 260,5 [217,3-301,9], r.

BACKGROUND AND OBJECTIVES: The prognosis of patients undergoing kidney tumor resection or kidney donation is linked to many histologic criteria. These criteria notably include glomerular density, glomerular volume, vascular luminal stenosis, and severity of interstitial fibrosis/tubular atrophy. Automated measurements through a deep-learning approach could save time and provide more precise data. This work aimed to develop a free tool to automatically obtain kidney histologic prognostic features. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In total, 241 samples of healthy kidney tissue were split into three independent cohorts. The “Training” cohort (n=65) was used to train two convolutional neural networks: one to detect the cortex and a second to segment the kidney structures. The “Test” cohort (n=50) assessed their performance by comparing manually outlined regions of interest to predicted ones. The “Application” cohort (n=126) compared prognostic histologic data obtained manually or through the algorithm on the basis of the combination of the two convolutional neural networks. RESULTS: In the Test cohort, the networks isolated the cortex and segmented the elements of interest with good performances (>90% of the cortex, healthy tubules, glomeruli, and even globally sclerotic glomeruli were detected). In the Application cohort, the expected and predicted prognostic data were significantly correlated. The correlation coefficients r were 0.85 for glomerular volume, 0.51 for glomerular density, 0.75 for interstitial fibrosis, 0.71 for tubular atrophy, and 0.73 for vascular intimal thickness, respectively. The algorithm had a good ability to predict significant (>25%) tubular atrophy and interstitial fibrosis level (receiver operator characteristic curve with an area under the curve, 0.92 and 0.91, respectively) or a significant vascular luminal stenosis (>50%) (area under the curve, 0.85). CONCLUSION: This freely available tool enables the automated segmentation of kidney tissue to obtain prognostic histologic data in a fast, objective, reliable, and reproducible way.

Objective To establish and validate a predictive formula for calculating the possibility of developing delayed neurological sequelae (DNS) after acute carbon monoxide (CO) poisoning to facilitate better decision-making about treatment strategies. Methods This study retrospectively enrolled 605 consecutive patients who had been newly diagnosed with CO poisoning from the Central Hospital of Enshi Prefecture between January 1, 2015 and December 31, 2020. The cohort was randomly divided into two subgroups: the development cohort (n = 104) and validation cohort (n = 44). Univariate analysis and backward elimination of multivariate logistic regression were used to identify predictive factors, and a predictive formula was established. The performance was assessed using the area under the curve (AUC), the mean AUC of five-fold cross-validation, and calibration plots. Results The formula included four commonly available predictors: initial GCS score, duration of exposure, CK, and abnormal findings on MRI. We next created a formula to calculate the risk score for developing DNS: Risk score = −4.54 + 3.35 * (Abnormal findings on MRI = yes) - 0.51 * (Initial GCS score) + 0.65 * (Duration of exposure) + 0.01 * (CK). Then, the probability of developing DNS could be calculated: Probability of DNS = 1/(1 + e Risk score). The model revealed good discrimination with AUC, and mean AUC of fivefold cross-validation in two cohort, and the calibration plots showed good calibration. Conclusions This study established a prediction predictive formula for predicting developing of DNS, which could facilitate better decision-making about treatment strategies.

BackgroundThe visual system could be included in the diagnostic criteria for multiple sclerosis (MS) to demonstrate dissemination in space (DIS) and dissemination in time (DIT).ObjectiveTo investigate the diagnostic value of retinal asymmetry in MS.MethodsA prospective, longitudinal study in individuals with MS (n=151) and healthy controls (n=27). Optical coherence tomography (OCT) was performed at 0, 2 and 4 years. Macular ganglion cell and inner plexiform layer (mGCIPL) thickness was determined as well as measures for retinal asymmetry: the inter-eye percentage difference (IEPD) and inter-eye absolute difference (IEAD). Receiver operator characteristics curves were plotted and the area under the curve (AUC) was calculated for group comparisons of the mGCIPL, IEPD, IEAD and atrophy rates.ResultsThe diagnostic accuracy of both the IEPD and IEAD for differentiating bilateral and unilateral MS optic neuritis was high and stable over time (AUCs 0.88–0.93). The IEPD slightly outperformed the IEAD. Atrophy rates showed low discriminatory abilities for differentiating MS from controls (AUC 0.49–0.58).ConclusionThe inter-eye differences of the mGCIPL have value for demonstration of DIS but in individuals with longstanding MS not for DIT. This may be considered as a test to detect DIS in future diagnostic criteria. Validation in a large prospective study in people presenting with symptoms suggestive of MS is required.

研究グループは、TAVI施術者に対する基本チェックリストによるフレイルの評価が経カテーテル大動脈弁留置術(TAVI)後3年の総死亡の予測因子として有用であることを明らかにしました。本研究成果により、基本チェックリストがフレイルを簡便かつ客観的に評価し、適切な治療方針の決定に役立つと期待できます。フレイルの指標とTAVIとの関連性はこれまでに報告されていますが、それらの指標は検査を多く要するものや、簡便であっても客観性に欠けるものがあります。今回、本研究グループは、2016年1月から2020年12月に本学医学部附属病院でTAVIを施行した280例を対象とし、従来のフレイルの指標に加えて基本チェックリストによるフレイルの評価を行いました。その結果、基本チェックリストにより算出したフレイルの指標は、従来のフレイルの指標と比較し同等であり、生存時間分析でTAVI後3年の死亡の独立した因子であることが分かりました。また、基本チェックリストの総スコア(25点満点)で3群に分類して解析したところ、フレイル群(13～25点)でTAVI後3年の死亡が有意に高いことが分かりました。, Background: Frailty is a major risk factor for death and disability following transcatheter aortic valve implantation (TAVI). The Kihon checklist (KCL) is a simple self-reporting yes/no survey consisting of 25 questions and is used as a screening tool to identify frailty in the primary care setting. No clinical studies have focused on frailty calculated by the KCL in the TAVI cohort. We investigated the 3-year prognostic impact of frailty evaluated by the KCL in patients who underwent TAVI. ......

Identification of human miRNAs involved in coronavirus-host interplay is important due to the current COVID-19 pandemic. Therefore, this study aimed to measure the circulating plasma miR-155 expression level in COVID-19 patients and healthy controls to investigate its roles in the pathogenesis and severity of COVID-19 disease and to assess its usefulness as a clinical biomarker for the detection of COVID-19 disease and the severity of infection. A total of 150 COVID-19 patients and 50 controls were enrolled into our study. Beside the routine laboratory work and chest computed tomography (CT) scans of COVID-19 patients, plasma miR-155 expression level was measured using reverse transcription quantitative real-time PCR (RT-qPCR) technique. Our results demonstrated increased miR-155 expression level in COVID-19 patients compared to controls, in severe compared to moderate COVID-19 patients, and in non-survival compared to survival COVID-19 patients. miR-155 expression level also had significant correlation with clinicopathological characteristics of COVID-19 patients such as chest CT findings, CRP, ferritin, mortality, D-dimer, WBC count, and lymphocytes and neutrophils percentages. Also, our results showed that the area under the curve (AUC) for miR-155 was 0.986 with 90% sensitivity and 100% specificity when used as a biomarker for the detection of COVID-19 disease; while in detection of severity of COVID-19 disease, AUC for miR-155 was 0.75 with 76% sensitivity and specificity. From these results we can conclude that miR-155 has a crucial role in the pathogenesis and severity of COVID-19; also, it could be a good diagnostic clinical biomarker for the detection of COVID-19 disease and the severity of infection.

Although hypochloremia is strongly associated with adverse prognosis in acute heart failure (AHF), it is unknown whether incorporating hypochloremia into the preexisting risk model improves the model performance. We calculated the Get With The Guidelines-Heart Failure (GWTG-HF) risk score in 1,428 patients with AHF (derivation cohort) and developed 2 risk scores incorporating brain natriuretic peptide (BNP) into the GWTG-HF risk score (GWTG-BNP risk score) and incorporating both BNP and hypochloremia (GWTG-BNP-Cl risk score). Hypochloremia was defined as

OBJECTIVE The optic nerve sheath diameter (ONSD) excluding the dura mater (ONSDE; i.e., the subarachnoid diameter) and the ONSD including the dura mater (ONSDI) have been used differently in studies, but the predictive ability of these two different measurements of the ONSD as measured by invasive intracranial pressure (ICP) monitoring has never been compared. Additionally, studies on the prediction of ICP using central retinal artery (CRA) Doppler ultrasonography are scarce. The authors aimed to determine how the two different ONSD measurements, the ONSD/eyeball transverse diameter (ETD) ratio, and transorbital Doppler ultrasonography parameters are associated with ICP via external ventricular drainage (EVD). METHODS This prospective observational study included 50 patients with brain injury who underwent EVD between August 2019 and September 2020. The mean of three repeated measurements of the ONSDI and ONSDE was calculated to reduce artifact and off-axis measurements. ETD, an immutable value, was measured from the initial brain CT with a clear outline of the eyeball. Simultaneously, flow velocities in the CRA and posterior ciliary artery (PCA) were compared with the ICP. RESULTS The ONSDE, ONSDI, and ONSD/ETD ratio were significantly associated with ICP (p = 0.005, p < 0.001, and p < 0.001, respectively). The ONSD/ETD ratio showed the highest predictive power of increased ICP (area under the curve [AUC] 0.897). The ONSDI was correlated more with the ICP than was the ONSDE (AUC 0.855 vs 0.783). None of the Doppler ultrasonography parameters in the CRA and PCA were associated with ICP. CONCLUSIONS The ONSD/ETD ratio is a better predictor of increased ICP compared with the ONSDI or ONSDE in brain-injured patients with nonsevere ICP. The ONSDI may be more available for predicting the ICP than the ONSDE.

Background Alcohol withdrawal syndrome (AWS) is an uncommon occurrence in trauma victims. However, the syndrome can cause a prolonged hospital stay. Therefore, the purpose of this study is to develop and validate the risk factors of AWS so that interventions can be applied to high-risk patients. Methods All adult trauma patients with an injury severity score of ≥1 and greater than one hospital day were included in the study. The Trauma Quality Improvement Program (TQIP) database from 2013-2016 was accessed for the study. Patient demography, injury and comorbidities were compared between the patients who developed AWS and who did not develop AWS. The data were split into 2 datasets: training and testing. Eighty percent (80%) of the data was randomly selected for the training dataset to develop the risk factors. The remaining 20% of the data were used for validation of the risk factors using multivariable analysis. The receiving operating characteristics (ROC) curve and area under the curve (AUC) were generated for model fitness. All P values Results A total of 497,819 patients qualified for the study. Only 6,894 (1.38%) patients developed AWS during their hospitalization. The median age of the patients, who developed AWS, was 54 years. The patients were predominantly male (84% vs. 63.1%) and Caucasian (80.3% vs. 76.1%). The multivariable analysis showed an age range of 45 years to 74 years old, male gender, Caucasian race, a history of chronic alcoholic abuse, hypertension and cirrhosis increased the risk of AWS. The AUC of the model of 0.910, 95% CI; [0.901, 0.918] showed an excellent model for predicting the risk of the development of AWS. Conclusion Approximately 1.4% of the trauma victims developed AWS. Certain patient demographic and comorbidity characteristics, and head injury have a higher risk of developing of AWS.

Background Anal squamous cell carcinoma (ASCC) is the main subtype of anal cancer and has great heterogeneity in prognosis. We aimed to construct a nomogram for predicting their 1‐, 3‐, and 5‐year overall survival (OS) rates. Methods Patients with ASCC, enrolled between January 1, 2010 and December 31, 2017, were identified from the SEER database. They were divided into a training group and a validation group in a ratio of 7:3. Univariate and multivariate Cox analyses were used to identify the prognostic factors for OS. Then a prognostic nomogram was established and validated by Harrell consistency index (C‐index), area under the curve (AUC) of the receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Results We identified 761 patients in training group and 326 patients in validation group. Four prognostic factors including age, sex, AJCC stage, and radiotherapy were identified and integrated to construct a prognostic nomogram. The C‐index and AUC values proved the model's effectiveness and calibration plots manifested its excellent discrimination. Furthermore, in comparison to the AJCC stage, the C‐index, AUC, and DCA proved the nomogram to be of good predictive value. Finally, we constructed a risk stratification model for dividing patients into low‐risk, medium‐risk, and high‐risk groups, and there were obvious differences in OS. Conclusions A prognostic nomogram was firstly established for predicting the survival probability of ASCC patients and helping clinicians improve their risk management., First, from the SEER database, we identified the prognostic factors for anal squamous cell carcinoma (ASCC) patients and develop a nomogram to better predict the prognosis of ASCC patients. Secondly, through comparison, our predictive model is a further improvement of traditional AJCC staging system based on patient’s demographic and clinicopathological features not only in survival prediction, but also in clinical utility.

Objective To compare the potential healing prognosis of the different routine noninvasive techniques implemented in the International Working Group Diabetic Foot Guidelines with the novel use of hyperspectral imaging (HSI) in patients with diabetic foot ulcers (DFUs). Methods Twenty-one patients with active DFUs participated in this 1-year prospective study in a specialized diabetic foot unit between December 2018 and January 2020. HSI was performed at baseline to quantify tissue oxygenation and should be presented on an anatomical map by analyzing the following parameters: (1) oxygen saturation of the hemoglobin, (2) tissue hemoglobin index, (3) the near-infrared perfusion index, and (4) tissue water index. In addition, transcutaneous oxygen pressure (TcpO2), systolic toe and ankle pressures, ankle-brachial index, and toe-brachial index values were calculated for the ulcerated limb. The primary outcome measure was wound healing, defined as complete epithelization without any drainage confirmed for at least 10 days after closure was first documented at 24 weeks. Results During the follow-up period 14 patients (66.66 %) healed and 7 patients did not heal (33.3%) by 24 weeks. The TcpO2 optimal cut-off point as determined by a balance of sensitivity and specificity of 28.5 mm Hg that yielded a sensitivity of 91% and a specificity of 100%, and area under the curve of 0.989 (P = .005; 95% confidence interval [CI], 0.945-1.000). Followed by the oxygen saturation of the hemoglobin optimal cut-off point as determined by a balance of sensitivity and specificity of 48.5 mm Hg that yielded a sensitivity of 93% and a specificity of 0.71%, and area under the curve of 0.932 (P = .013; 95% CI, 0.787-1.000). The logistic regression analyses showed that TcpO2 was the only variable associated with wound healing at 24 weeks (P Conclusions The HSI was shown to be effective in the prognosis of DFU healing compared with other noninvasive test; only TcpO2 values resulted in better diagnosis potential in wound healing.

PURPOSE The correct estimation of accessory pathway (AP) localization from surface ECG is critical before the procedure. Our study aimed to detect the predictive value of the V1r + DIIq criterion for differentiating right- from left-sided paraseptal APs. METHODS We retrospectively included 58 patients with (Wolff-Parkinson-White) WPW syndrome and paraseptal APs who underwent successful catheter ablation (37 male, 21 female; mean age 34.4 ± 13.6 years). The V1r + DIIq criterion was calculated using the following formula: V1r + DIIq (mV) = initial r wave amplitude in V1 + q wave amplitude in DII. The combined criterion included V1r + DIIq

High‐dose methotrexate (HDMTX) pharmacokinetics (PKs), including the best estimated glomerular filtration rate (eGFR) equation that reflects methotrexate (MTX) clearance, requires investigation. This prospective, observational, single‐center study evaluated adult patients with lymphoma treated with HDMTX. Samples were collected at predefined time points up to 96 h postinfusion. MTX and 7‐hydroxy‐MTX PKs were estimated by standard noncompartmental analysis. Linear regression determined which serum creatinine‐ or cystatin C‐based eGFR equation best predicted MTX clearance. The 80 included patients had a median (interquartile range [IQR]) age of 68.6 years (IQR 59.2–75.6), 54 (67.5%) were men, and 74 (92.5%) were White. The median (IQR) dose of MTX was 7.6 (IQR 4.8–11.3) grams. Median clearance was similar across three dosing levels at 4.5–5.6 L/h and was consistent with linear PKs. Liver function, weight, age, sex, concomitant chemotherapy, and number of previous MTX doses did not impact clearance. MTX area under the curve (AUC) values varied over a fourfold range and appeared to increase in proportion to the dose. The eGFRcys (ml/min) equation most closely correlated with MTX clearance in both the entire cohort and after excluding outlier MTX clearance values (r = 0.31 and 0.51, respectively). HDMTX as a 4‐h infusion displays high interpatient pharmacokinetic variability. Population PK modeling to optimize MTX AUC attainment requires further evaluation. The cystatin C‐based eGFR equation most closely estimated MTX clearance and should be investigated for dosing and monitoring in adults requiring MTX as part of lymphoma management.

OBJECTIVE Postoperative urinary retention (POUR) is a common complication after spine surgery and is associated with prolongation of hospital stay, increased hospital cost, increased rate of urinary tract infection, bladder overdistention, and autonomic dysregulation. POUR incidence following spine surgery ranges between 5.6% and 38%; no reliable prediction tool to identify those at higher risk is available, and that constitutes an important gap in the literature. The objective of this study was to develop and validate a preoperative risk model to predict the occurrence of POUR following routine elective spine surgery. METHODS The authors conducted a retrospective chart review of consecutive adults who underwent lumbar spine surgery between June 1, 2017, and June 1, 2019. Patient characteristics, preexisting ICD-10 codes, preoperative pain and opioid use, preoperative alpha-1 blocker use, details of surgical planning, development of POUR, and management strategies were abstracted from electronic medical records. A binomial logistic model and a multilayer perceptron (MLP) were optimized using training and validation sets. The models’ performance was then evaluated on model-naïve patients (not a part of either cohort). The models were then stacked to take advantage of each model’s strengths and to avoid their weaknesses. Four additional models were developed from previously published models adjusted to include only relevant factors (i.e., factors known preoperatively and applied to the lumbar spine). RESULTS Overall, 891 patients were included in the cohort, with a mean of 59.6 ± 15.5 years of age, 52.7% male, BMI 30.4 ± 6.4, American Society of Anesthesiologists class 2.8 ± 0.6, and a mean of 5.6 ± 5.7 comorbidities. The rate of POUR was found to be 25.9%. The two models were comparable, with an area under the curve (AUC) of 0.737 for the regression model and 0.735 for the neural network. By combining the two models, an AUC of 0.753 was achieved. With a regression model probability cutoff of 0.24 and a neural network cutoff of 0.23, maximal sensitivity and specificity were achieved, with specificity 68.2%, sensitivity 72.9%, negative predictive value 88.2%, and positive predictive value 43.4%. Both models individually outperformed previously published models (AUC 0.516–0.645) when applied to the current data set. CONCLUSIONS This predictive model can be a powerful preoperative tool in predicting patients who will be likely to develop POUR. By using a combination of regression and neural network modeling, good sensitivity, specificity, and NPV are achieved.

Background Multiple Sclerosis (MS) is an immune-mediated demyelinating disease mainly affecting the Central Nervous System (CNS). 80% of MS patients present the Relapsing-Remitting form (RRMS). Pleiotrophin (PTN), a cytokine previously associated with other autoimmune and neurological diseases, could play a role in the pathophysiology of RRMS due to its neuro and immunomodulatory effect. However, PTN has never been explored in RRMS patients. Aim of the study To determine PTN serum levels in patients with RRMS, treated with Glatiramer acetate (GA) or Interferon-beta (IFN-β), as well as in non-treated patients and healthy controls as a first attempt to explore PTN in RRMS. Methods PTN serum levels were quantified by ELISA in 57 patients and 18 controls. Results We demonstrated that PTN serum levels are significantly higher in RRMS patients. In IFN-β treated patients alone, PTN correlated positively with time of disease evolution and time of IFN-β use and correlated negatively with the MS severity score (MSSS). When comparing groups according to weight status, we observed that PTN is statistically increased in overweight female patients and that weight does not affect male patients. The Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) curve analysis was higher for males compared to females. Conclusion PTN serum level is higher in RRMS patients and that is associated with sex, BMI and IFN-β treatment. Therefore, we propose that PTN could be playing a role in MS. Further studies must be performed to identify the exact role of PTN in this pathology.

Background We created an estimation model for hypothermic circulatory arrest time and analyzed the risk factors for major adverse outcomes in total arch replacement. Methods This study involved 272 patients who underwent total arch replacement. The estimation model for hypothermic circulatory arrest time was established using multiple linear regression analysis, and the predicted hypothermic circulatory arrest time from this model was analyzed to detect risk factors. Results Atrial fibrillation, rupture, malperfusion, saccular aneurysm, cardiopulmonary bypass time, and hypothermic circulatory arrest time were identified as independent risk factors associated with major adverse outcomes. The estimation model for hypothermic circulatory arrest time was established as follows: hypothermic circulatory arrest time = 99.3 – 0.19 × age + 0.65 × body mass index + 6.19 × previous cardiac operation + 11.7 × acute dissection + 8.9 × rupture + 0.19 × aortic angulation + 0.15 × length to the distal anastomosis site – 6.17 × total arch replacement surgeon case volume – 3.06 × surgery year. The predicted hypothermic circulatory arrest time calculated by this estimation model was evaluated using multivariate logistic analysis, which identified atrial fibrillation, rupture, malperfusion, saccular aneurysm, and predicted hypothermic circulatory arrest time as risk factors. Conclusions As with the actual hypothermic circulatory arrest time, the predicted hypothermic circulatory arrest time using our model detected significant factors associated with major adverse outcomes. These results indicated that this prediction model for hypothermic circulatory arrest time may be effective.

Objectives There is debate regarding the timing of procedural sedation and analgesia (PSA) in relation to fasting status. Point-of-care ultrasound (POCUS) provides the ability to measure gastric content and is being used as a surrogate for aspiration risk in anesthesia. We sought to evaluate the gastric content of pediatric emergency department (PED) patients undergoing PSA using POCUS. Methods We performed a prospective observational study using a convenience sample of pediatric patients undergoing PSA between July 1, 2018, and June 30, 2019. Following a brief history, gastric content was measured using POCUS in both supine and right lateral decubitus positions at 2-hour intervals until the time of PSA. Qualitative content and calculated volume were classified based on the Perlas Model of anesthesia "Risk" assessment. Results Ninety-three patients were enrolled with 61.3% male and mean age of 6.5 years. Gastric content was determined in 92 patients. There were 79.3% that had "high risk" content at the time of PSA, with a median fasting time of 6.25 hours and no serious adverse events. Fasting duration had a weak to moderate ability to predict "risk" category (area under the curve = 0.73), with no patient (n = 17) who underwent multiple evaluations awaiting PSA progressing from "high" to "low risk." Conclusions The majority of PED patients undergoing PSA at our institution had "high risk" gastric content with no clinically significant change occurring during serial evaluations. This calls into question the utility of delaying PSA based upon fasting status and lends support to a more comprehensive risk-benefit approach when planning pediatric PSA.

Objective To identify the association between readily available laboratory biomarkers and the development of severe sepsis in children presenting to the emergency department (ED) with systemic inflammatory response syndrome (SIRS). Methods In this retrospective cohort study, ED patient encounters from June 2018 to June 2019 that triggered an automated sepsis alert based on SIRS criteria were analyzed. Encounters were included if the patient had any of the following laboratory tests sent within 6 h of ED arrival: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), lactic acid, and procalcitonin. For each of the biomarkers, a receiver operating characteristic (ROC) curve was created for our primary outcome, severe sepsis within 24 h of ED disposition, and our secondary outcome, severe sepsis with a positive bacterial culture. For each ROC curve, we calculated the area under the curve (AUC) with 95% confidence intervals (95% CI) and created cutoff points to achieve 90% sensitivity and 90% sensitivity for the primary and secondary outcomes. Results During the study period, 4349/61,195 (7.1%) encounters triggered an automated sepsis alert. Of those, 1207/4349 (27.8%) had one of the candidate biomarkers sent within 6 h of ED arrival and were included in the study. A total of 100/1207 (8.3%) met criteria for severe sepsis within 24 h of arrival, and 41/100 severe sepsis cases (41%) were deemed culture-positive. Procalcitonin had the highest AUC for identifying severe sepsis [0.62 (95% CI 0.52–0.73)] while ESR and CRP had the highest AUC for culture-positive sepsis [0.68 (95% CI 0.47–0.89) and 0.67 (95% CI 0.53–0.81), respectively]. At 90% sensitivity for detecting severe sepsis, all of the biomarker threshold values fell within that laboratory test's normal range. At 90% specificity for severe sepsis, threshold values were as follows: procalcitonin 2.72 ng/mL, CRP 16.79 mg/dL, ESR 79.5 mm/h and lactic acid 3.6 mmol/L. Conclusion Our data indicate that CRP, ESR, lactic acid, and procalcitonin elevations were all specific, but not sensitive, in identifying children in the ED with SIRS who go on to develop severe sepsis.

Background Frailty is increasingly being recognized as a public health issue, straining healthcare resources and increasing costs to care for these patients. Frailty is the decline in physical and cognitive reserves leading to increased vulnerability to stressors such as surgery or disease states. The goal of this pilot diagnostic accuracy study was to identify whether point-of-care ultrasound measurements of the quadriceps and rectus femoris muscles can be used to discriminate between frail and not-frail patients and predict postoperative outcomes. This study hypothesized that ultrasound could discriminate between frail and not-frail patients before surgery. Methods Preoperative ultrasound measurements of the quadriceps and rectus femoris were obtained in patients with previous computed tomography scans. Using the computed tomography scans, psoas muscle area was measured in all patients for comparative purposes. Frailty was identified using the Fried phenotype assessment. Postoperative outcomes included unplanned intensive care unit admission, delirium, intensive care unit length of stay, hospital length of stay, unplanned skilled nursing facility admission, rehospitalization, falls within 30 days, and all-cause 30-day and 1-yr mortality. Results A total of 32 patients and 20 healthy volunteers were included. Frailty was identified in 18 of the 32 patients. Receiver operating characteristic curve analysis showed that quadriceps depth and psoas muscle area are able to identify frailty (area under the curve–receiver operating characteristic, 0.80 [95% CI, 0.64 to 0.97] and 0.88 [95% CI, 0.76 to 1.00], respectively), whereas the cross-sectional area of the rectus femoris is less promising (area under the curve–receiver operating characteristic, 0.70 [95% CI, 0.49 to 0.91]). Quadriceps depth was also associated with unplanned postoperative skilled nursing facility discharge disposition (area under the curve 0.81 [95% CI, 0.61 to 1.00]) and delirium (area under the curve 0.89 [95% CI, 0.77 to 1.00]). Conclusions Similar to computed tomography measurements of psoas muscle area, preoperative ultrasound measurements of quadriceps depth shows promise in discriminating between frail and not-frail patients before surgery. It was also associated with skilled nursing facility admission and postoperative delirium. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background Identifying sepsis patients with risk of in-hospital death early can improve the prognosis of patients. This study aimed to develop a model to predict in-hospital death of sepsis patients based on the Medical Information Mart for Intensive Care-Ⅲ (MIMIC-Ⅲ) database, and use clinical data to externally validate the model. Methods A total of 1,839 sepsis patients were used for model development, and 125 clinical cases were used for external validation. The discriminatory ability of the model was determined by calculating the area under the curve (AUC) with 95% confidence intervals (CI). Results The AUC of the random forest model and logistic regression model was 0.754 (95%CI, 0.732-0.776) and 0.703 (95%CI, 0.680-0.727), respectively, and the random forest model had higher AUC (Z = 3.070, P = .002). External validation showed that the AUC of the random forest model was 0.539 (95%CI, 0.440-0.628). Further validation was carried out according to gender and SOFA score. The AUC of the model in males and females was 0.648 and 0.412, respectively. In addition, the AUC of the model in the population with SOFA scores of 3-8, 9-12, and 13-15 were 0.705, 0.495, and 0.769, respectively. Conclusions The random forest model had a better predictive ability and a good applicability to external populations with SOFA score of 13-15.

Background One of the primary treatment for resectable advanced esophageal squamous cell cancer (ESCC) is neoadjuvant chemotherapy (NAC) followed by minimally invasive esophagectomy (MIE). Because the neutrophil-to-lymphocyte ratio (NLR) is a widely reported prognostic factor in several cancers, we investigated whether the preoperative NLR is a biomarker in ESCC patients treated with NAC and MIE. Methods In this study, we investigated 174 ESCC patients who underwent MIE from January 2010 to December 2015, including 121 patients who received NAC. The cutoff value of the NLR was analyzed using the receiver operating characteristic curve. Multivariate analyses were performed to clarify independent prognostic factors for overall survival (OS). Results The cutoff value of the NLR for OS in 121 patients who received NAC was 2.5 ng/ml, and the area under the curve was 0.63026 (p = 0.0127). The 5-year OS rate was 64% in those with an NLR 415 ml were independent poor prognostic factors. Conclusions NLR is a biomarker of prognosis in ESCC patients who undergo MIE after NAC.

The accuracy of ankle-brachial index (ABI) and toe-brachial index (TBI) in discriminating lower extremity peripheral artery disease (PAD) has not been evaluated in patients with chronic kidney disease (CKD). We measured ABI, TBI, and Doppler ultrasound in 100 predialysis patients with CKD without revascularization or amputation. Leg-specific ABI was calculated using higher systolic blood pressure (SBP) in posterior tibial or dorsalis pedis artery divided by higher brachial SBP; alternative ABI was calculated using lower SBP in posterior tibial or dorsalis pedis artery. PAD was defined as ≥50% stenosis detected by Doppler ultrasound. PAD risk classification score was calculated using cardiovascular disease risk factors. The area under the curve (AUC, 95% confidence interval [CI]) for discriminating ultrasound-diagnosed PAD was 0.78 (0.69 to 0.87) by ABI, 0.80 (0.71 to 0.89) by alternative ABI, and 0.74 (0.63 to 0.86) by TBI. Sensitivity and specificity were 25% and 97% for ABI ≤0.9, 41% and 95% for alternative ABI ≤0.9, and 45% and 93% for TBI ≤0.7, respectively. AUC (95% CI) of PAD risk classification score was 0.86 (0.78 to 0.94) with sensitivity and specificity of 95% and 60% for risk score ≥0.10, 76% and 76% for risk score ≥0.25, and 43% and 95% for risk score ≥0.55. Combining risk score with ABI, alternative ABI, and TBI increased AUC (95% CI) to 0.89 (0.82 to 0.96), 0.89 (0.80 to 0.98), and 0.87 (0.78 to 0.96), respectively. In conclusion, current ABI and TBI diagnostic criteria have high specificity but low sensitivity for classifying PAD in patients with CKD. PAD classification risk score based on cardiovascular disease risk factors improves the accuracy of PAD classification.

Purpose The purpose of this prospective study was to determine the capabilities of intravoxel incoherent motion (IVIM) MRI at 3 Tesla in discriminating between IgG4-related orbital disease (IgG4-ROD) and other causes of orbital inflammation. Materials and methods Main selection criteria for the patients enrolled in this prospective study were age over 18 years and histopathologicaly proven orbital inflammatory lesion. MRI examinations were performed prior to surgery and treatment in all patients with suspected orbital inflammation. Two neuroradiologists, blinded to clinical data, independently analyzed structural MRI examinations and IVIM sequences obtained with 15 b values ranging from 0 to 2000 s/mm². Apparent diffusion coefficient (ADC), “true” diffusion coefficient (D), perfusion fraction (f) and pseudodiffusion coefficient (D*) values were calculated from all orbital lesions. Diagnostic capabilities of IVIM parameters were assessed using receiver operating-characteristic (ROC) curves and area under the curve (AUC). Sensitivity, specificity, and accuracy of IVIM parameters were calculated for the best threshold values and reported with their corresponding 95% confidence intervals (CI). Results Thirty-five patients (21 women and 14 men; mean age, 49.2 ± 13.75 [SD] years; age range: 23–77 years) with 48 orbital lesions were enrolled in the study. Fifteen patients (15/35; 43%) had IgG4-ROD and 20 (20/35; 57%) had other causes of orbital inflammation. Median D value was significantly greater in patients with IgG4-ROD (1 × 10-3 mm2/s; interquartile range [IQR]: 0.9 × 10-3; 1.2 × 10-3) as compared to patients with non IgG4-ROD (0.80 × 10-3 mm2/s; IQR: 0.7 × 10-3; 1 × 10-3) (P = 0.04). There was no significant difference for ADC, f or D*. Area under the curve were of 0.54, 0.73, 0.63 and 0.56 for ADC, D, f and D*, respectively. Optimal threshold derived from ROC curves for D was 0.87 × 10-3 mm2/s, yielding 92% sensitivity (95% CI: 62–100%) and 71% specificity (95% CI: 44–90%) for the diagnosis of IgG4-ROD. No differences in standard morphological MRI criteria were found between IgG4-ROD and non IgG4-ROD. Conclusion Our study shows that IVIM MRI is a useful imaging technique to distinguish IgG4-ROD from other causes of orbital inflammation.

Immune cell-type composition changes with age, potentially weakening the response to infectious diseases. Profiling epigenetics marks of immune cells can help us understand the relationship with disease severity. We therefore leveraged a targeted DNA methylation method to study the differences in a cohort of pneumonia patients (both COVID-19 positive and negative) and unaffected individuals from peripheral blood. This approach allowed us to predict the pneumonia diagnosis with high accuracy (AUC = 0.92), and the PCR positivity to the SARS-CoV-2 viral genome with moderate, albeit lower, accuracy (AUC = 0.77). We were also able to predict the severity of pneumonia (PORT score) with an R2 = 0.69. By estimating immune cellular frequency from DNA methylation data, patients under the age of 65 positive to the SARS-CoV-2 genome (as revealed by PCR) showed an increase in T cells, and specifically in CD8+ cells, compared to the negative control group. Conversely, we observed a decreased frequency of neutrophils in the positive compared to the negative group. No significant difference was found in patients over the age of 65. The results suggest that this DNA methylation-based approach can be used as a cost-effective and clinically useful biomarker platform for predicting pneumonias and their severity. © 2022 Informa UK Limited, trading as Taylor & Francis Group.

OBJECTIVES In this study, we aimed to establish risk factors for primary spontaneous pneumomediastinum associated with Coronavirus disease 2019 (COVID-19) and reveal those which are significant. METHODS The study included 62 patients with primary spontaneous pneumomediastinum who presented to our hospital between 11 March 2020, the date of the first-reported COVID-19 case in our country, and 3 January 2021. Of these, 14 patients (22.6%) had COVID-19 and 48 patients (77.4%) did not have COVID-19. RESULTS Of the 62 patients included in the study, 41 (66.1%) were male and 21 (33.9%) were female. The mean age was 28.90 ± 16.86 (range, 16–84) years. The most common symptom at admission was chest pain (54.8%). The mean age of the patients with COVID-19 was 39.35 ± 23.04 years and that of the patients without COVID-19 was 25.85 ± 13.45 years (P < 0.001). In receiver-operating characteristic curve analysis, the area under the curve for age was 0.785 (95% confidence interval: 0.648–0.922) and the optimal cut-off value was 24 years for COVID-19-positive patients. The highest sensitivity and specificity values were 0.857 and 0.729. Twelve (85.79%) of the COVID-19-positive primary spontaneous pneumomediastinum patients were aged 24 years or older (P < 0.001). Five patients (8.1%) had positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test but no abnormal findings on computed tomography. CONCLUSIONS Having an age of more than 24 years was associated with a higher prevalence of pneumomediastinum in COVID-19 patients and emerged as an important risk factor. Multicentre studies with more cases are needed to determine whether pneumomediastinum is associated with additional other risk factors related to COVID-19., Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first detected in Turkey on 11 March 2020.

Introduction The present study was undertaken to investigate the prognostic value of the frontal QRS-T angle associated with adverse cardiac outcomes in patients with carbon monoxide (CO) poisoning in early stages in the emergency department. Materials and methods The data of 212 patients with CO poisoning who were admitted to the ED between January 2010 and May 2020 were retrospectively analyzed. The frontal QRS-T angle was obtained from the automatic reports of the EKG device. Results Compared to patients without myocardial damage, among patients with myocardial damage, statistically high creatinine, creatine kinase MB, cardiac troponin I, and frontal QRS-T angle values were found ( p < 0.001 for all parameters), while the saturation of arterial blood pH and arterial oxygen values were found to be lower ( p = 0.002 and p < 0.001, respectively). The frontal QRS-T angle values were correlated with creatine kinase, creatine kinase-MB, cardiac troponin I, and oxygen saturation (SpO2) in arterial blood (r = 0. 232, p = 0.001; r = 0. 253, p = < 0.001; r = 0. 389, p = < 0.001; r = −0. 198, p = 0.004, respectively). The optimum cut-off value of the frontal QRS-T angle was found to be 44.5 (area under the curve: 0.901, 95% confidence interval: 0.814–0.988, sensitivity: 87%, specificity: 84%). Conclusions The frontal QRS-T angle, a simple and inexpensive parameter that can be easily obtained from 12-lead surface electrocardiography, can be used as an early indicator in the detection of myocardial damage in patients with CO poisoning.

Patients with cerebral malaria with polymorphic Cytochrome P450 2C19 (CYP2C19) genotypes who receive concurrent treatment with quinine are at risk of inadequate or toxic therapeutic drug concentrations due to metabolic drug interactions. The study aimed to predict the potential dose regimens of quinine when coadministered with phenobarbital in adult patients with cerebral malaria and complications (e.g., lactic acidosis and acute renal failure) and concurrent with seizures and acute renal failure who carry wild‐type and polymorphic CYP2C19. The whole‐body physiologically based pharmacokinetic (PBPK) models for quinine, phenobarbital, and quinine–phenobarbital coadministration were constructed based on the previously published information using Simbiology®. Four published articles were used for model validation. A total of 100 virtual patients were simulated based on the 14‐day and 3‐day courses of treatment. using the drug–drug interaction approach. The predicted results were within 15% of the observed values. Standard phenobarbital dose, when administered with quinine, is suitable for all groups with single or continuous seizures regardless of CYP2C19 genotype, renal failure, and lactic acidosis. Dose adjustment based on area under the curve ratio provided inappropriate quinine concentrations. The recommended dose of quinine when coadministered with phenobarbital based on the PBPK model for all groups is a loading dose of 2000 mg intravenous (i.v.) infusion rate 250 mg/h followed by 1200 mg i.v. rate 150 mg/h. The developed PBPK models are credible for further simulations. Because the predicted quinine doses in all groups were similar regardless of the CYP2C19 genotype, genotyping may not be required.

OBJECTIVE To identify serum protein biomarkers that might distinguish patients with early inflammatory arthritis (IA) with psoriatic arthritis (PsA) from those with rheumatoid arthritis (RA) and may be used to support appropriate early intervention. METHODS The serum proteome of patients with PsA and patients with RA was interrogated using nano-liquid chromatography mass spectrometry (nano-LC-MS/MS) (n = 64 patients), an aptamer-based assay (SomaScan) targeting 1,129 proteins (n = 36 patients), and a multiplexed antibody assay (Luminex) for 48 proteins (n = 64 patients). Multiple reaction monitoring (MRM) assays were developed to evaluate the performance of putative markers using the discovery cohort (n = 60 patients) and subsequently an independent cohort of PsA and RA patients (n = 167). RESULTS Multivariate machine learning analysis of the protein discovery data from the 3 platforms revealed that it was possible to differentiate PsA patients from RA patients with an area under the curve (AUC) of 0.94 for nano-LC-MS/MS, 0.69 for bead-based immunoassay measurements, and 0.73 for aptamer-based analysis. Subsequently, in the separate verification and evaluation studies, random forest models revealed that a subset of proteins measured by MRM could differentiate PsA and RA patients with AUCs of 0.79 and 0.85, respectively. CONCLUSION We present a serum protein biomarker panel that can separate patients with early-onset IA with PsA from those with RA. With continued evaluation and refinement using additional and larger patient cohorts, including those with other arthropathies, we suggest that the panel identified here could contribute to improved clinical decision making.

Objective: Statin treatment reduces the risk of atherosclerotic cardiovascular disease but is associated with a modest increased risk of type 2 diabetes, especially in those with insulin resistance or prediabetes. Our objective was to determine the physiological mechanism for the increased type 2 diabetes risk. Approach and Results: We conducted an open-label clinical trial of atorvastatin 40 mg daily in adults without known atherosclerotic cardiovascular disease or type 2 diabetes at baseline. The co-primary outcomes were changes at 10 weeks versus baseline in insulin resistance as assessed by steady-state plasma glucose during the insulin suppression test and insulin secretion as assessed by insulin secretion rate area under the curve (ISR AUC ) during the graded-glucose infusion test. Secondary outcomes included glucose and insulin, both fasting and during oral glucose tolerance test. Of 75 participants who enrolled, 71 completed the study (median age 61 years, 37% women, 65% non-Hispanic White, median body mass index, 27.8 kg/m 2 ). Atorvastatin reduced LDL (low-density lipoprotein)-cholesterol (median decrease 53%, P P =0.01) and insulin secretion (ISR AUC ) by a median of 9% ( P AUC (median increase, 0.05%; P =0.03) and fasting insulin (median increase, 7%; P =0.01). Conclusions: In individuals without type 2 diabetes, high-intensity atorvastatin for 10 weeks increases insulin resistance and insulin secretion. Over time, the risk of new-onset diabetes with statin use may increase in individuals who become more insulin resistant but are unable to maintain compensatory increases in insulin secretion. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02437084. Graphic Abstract: A graphic abstract is available for this article.

Anal cancer has increasing incidence and is preceded by high‐grade anal intraepithelial neoplasia (HGAIN; AIN2–3). Previously, we identified and validated several methylation markers for accurate detection of anal cancer and HGAIN with cancer risk in HIV‐positive (HIV+) men who have sex with men (MSM). This study aimed to evaluate these markers in HIV‐negative risk groups. A cross‐sectional series of 176 tissue samples of anal cancer, AIN3, AIN2, AIN1 and control biopsies obtained in HIV‐negative women and men was tested for six methylation markers (ASCL1, LHX8, SST, WDR17, ZIC1 and ZNF582). Accuracy for detection of AIN3 and cancer (AIN3+) was determined by univariable and multivariable mixed‐effect ordinal logistic regression. Methylation levels of all markers increased with increasing severity of disease (P, Host cell DNA methylation plays a role in anal carcinogenesis in HIV‐negative (HIV‐neg) and HIV‐positive (HIV+) individuals, including men who have sex with men (MSM). Methylation levels are increased in high‐grade anal intraepithelial neoplasia at risk of progression towards anal cancer, making methylation markers promising prognostic biomarkers.

AIM: Anastomotic leakage (AL) in left-sided colorectal cancer is a serious complication, with an incidence rate of 6-18%. We developed a novel predictive model for AL in colorectal surgery with double-stapling technique (DST) anastomosis using auto-artificial intelligence (AI). PATIENTS AND METHODS: A total of 256 patients who underwent curative surgery for left-sided colorectal cancer between 2017 and 2021 were included. In addition to conventional clinicopathological factors, we included the type of circular stapler using DST, conventional double-row circular stapler (DCS) or EEA™ circular stapler with Tri-Staple™ technology, 28 mm Medium/Thick (Covidien, New Haven, CT, USA) which had triple-row circular stapler (TCS) as a covariate. Auto-AI software Prediction One (Sony Network Communications Inc.) was used to predict AL with 5-fold cross validation. Predictive accuracy was assessed using the area under the receiver operating characteristic curve. Prediction One also evaluated the 'importance of variables' (IOV) using a method based on permutation feature importance. RESULTS: The area under the curve of the AI model was 0.766. The type of circular stapler used was the most influential factor contributing to AL (IOV=0.551). CONCLUSION: This auto-AI predictive model demonstrated an improvement in accuracy compared to the conventional model. It was suggested that use of a TCS may contribute to a reduction in the AL rate.

Objectives The aim of the study was to assess the diagnostic performance and clinical utility of the neutrophil to lymphocyte ratio (NLR) in patients with suspected aortic dissection (AD) and investigate its role in predicting in-hospital mortality in AD. Methods NLR values were calculated and compared in 467 consecutive patients with initially suspected AD. A receiver operating characteristic (ROC) curve analysis with the area under the curve (AUC) was used to evaluate the discriminative accuracy and predictive capability of the NLR for AD. Clinical utility was determined by decision curve analysis (DCA). The association between NLR and in-hospital mortality was investigated by logistic regression analyses in patients diagnosed with AD. Results The NLR was significantly elevated in patients with AD, and the optimal cut-off point for the NLR to distinguish AD from other acute chest pain diseases was 5.67 [AUC (95% CI): 0.877 (0.844–0.905)]. We recommended an NLR of 2.43 as the appropriate cut-off point with 96.9% sensitivity and a negative likelihood ratio (LR) of 0.09 to satisfy clinical requirements for diagnosis. DCA showed that the use of NLR had a positive net benefit. The deceased patients with AD had a higher NLR than the discharged patients. Moreover, the NLR was an independent predictor of in-hospital mortality for AD [adjusted odds ratio (OR): 1.084 (1.029–1.142)], and patients with higher NLR values tended to have a higher risk of in-hospital mortality. The optimal cut-off point for the NLR to predict in-hospital mortality was 9.20 [AUC (95% CI): 0.695 (0.619–0.765)]. Conclusions As an easily available and inexpensive parameter, the NLR could serve as a valuable clinical biomarker for early differential diagnosis and prognosis assessment of AD.

BACKGROUND Patients' self-reports suggest that acute alcohol consumption may trigger a discrete atrial fibrillation (AF) event. OBJECTIVE To objectively ascertain whether alcohol consumption heightens risk for an AF episode. DESIGN A prospective, case-crossover analysis. SETTING Ambulatory persons in their natural environments. PARTICIPANTS Consenting patients with paroxysmal AF. MEASUREMENTS Participants were fitted with a continuous electrocardiogram (ECG) monitor and an ankle-worn transdermal ethanol sensor for 4 weeks. Real-time documentation of each alcoholic drink consumed was self-recorded using a button on the ECG recording device. Fingerstick blood tests for phosphatidylethanol (PEth) were used to corroborate ascertainments of drinking events. RESULTS Of 100 participants (mean age, 64 years [SD, 15]; 79% male; 85% White), 56 had at least 1 episode of AF. Results of PEth testing correlated with the number of real-time recorded drinks and with events detected by the transdermal alcohol sensor. An AF episode was associated with 2-fold higher odds of 1 alcoholic drink (odds ratio [OR], 2.02 [95% CI, 1.38 to 3.17]) and greater than 3-fold higher odds of at least 2 drinks (OR, 3.58 [CI, 1.63 to 7.89]) in the preceding 4 hours. Episodes of AF were also associated with higher odds of peak blood alcohol concentration (OR, 1.38 [CI, 1.04 to 1.83] per 0.1% increase in blood alcohol concentration) and the total area under the curve of alcohol exposure (OR, 1.14 [CI, 1.06 to 1.22] per 4.7% increase in alcohol exposure) inferred from the transdermal ethanol sensor in the preceding 12 hours. LIMITATION Confounding by other time-varying exposures that may accompany alcohol consumption cannot be excluded, and the findings from the current study of patients with AF consuming alcohol may not apply to the general population. CONCLUSION Individual AF episodes were associated with higher odds of recent alcohol consumption, providing objective evidence that a modifiable behavior may influence the probability that a discrete AF event will occur. PRIMARY FUNDING SOURCE National Institute on Alcohol Abuse and Alcoholism.

ObjectiveSalivary cortisol and cortisone are used as biomarkers of physiological stress. Careful sampling of saliva for profiling of awakening response and the diurnal slope can be challenging in free-living environments, and validated sampling protocols are lacking. Therefore, we investigated (1) the level of compliance to a three-day home-based salivary sampling protocol, and (2) the within subject day-to-day variability of cortisol and cortisone outcomes and the required measuring days to obtain high reproducibility.ResultsNineteen healthy adults (mean age: 42, 50% females) participated. Participants collected in total 434 salivary samples out of 456 scheduled (four samples per day over three consecutive days at two time points). We found high level of compliance to the proposed free-living salivary sampling protocol with 18 (95%) and 16 (84%) participants being compliant to numbers and timing of samples, respectively. The area under the curve for the morning salivary samples and peak-to-bed slope had moderate reproducibility for cortisol and cortisone (intraclass correlation coefficient: 0.51–0.68, and mean coefficient of variation: 14.7%-75.3%). Three-to-four measuring days were required for high reproducibility of the area under the curve for the morning salivary samples and peak-to-bed slope using this free-living salivary sampling protocol.Trial registration Clinical trial registered with www.clinicaltrials.gov (NCT03788525). ObjectiveSalivary cortisol and cortisone are used as biomarkers of physiological stress. Careful sampling of saliva for profiling of awakening response and the diurnal slope can be challenging in free-living environments, and validated sampling protocols are lacking. Therefore, we investigated (1) the level of compliance to a three-day home-based salivary sampling protocol, and (2) the within subject day-to-day variability of cortisol and cortisone outcomes and the required measuring days to obtain high reproducibility.ResultsNineteen healthy adults (mean age: 42, 50% females) participated. Participants collected in total 434 salivary samples out of 456 scheduled (four samples per day over three consecutive days at two time points). We found high level of compliance to the proposed free-living salivary sampling protocol with 18 (95%) and 16 (84%) participants being compliant to numbers and timing of samples, respectively. The area under the curve for the morning salivary samples and peak-to-bed slope had moderate reproducibility for cortisol and cortisone (intraclass correlation coefficient: 0.51–0.68, and mean coefficient of variation: 14.7%-75.3%). Three-to-four measuring days were required for high reproducibility of the area under the curve for the morning salivary samples and peak-to-bed slope using this free-living salivary sampling protocol.Trial registration Clinical trial registered with www.clinicaltrials.gov (NCT03788525).

Aims Heart failure (HF) and atrial fibrillation (AF) frequently coexist and are both associated with increased levels of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP). It is known that AF impairs the diagnostic accuracy of NT‐proBNP for HF. The aim of the present study was to compare the diagnostic and predictive accuracy of NT‐proBNP for HF and AF in stable outpatients with cardiovascular risk factors. Methods and results Data were obtained from the DIAST‐CHF trial, a prospective cohort study that recruited individuals with cardiovascular risk factors and followed them up for 12 years. Data were validated in three independent population‐based cohorts using the same inclusion/exclusion criteria: LIFE‐Adult (n = 2869), SHIP (n = 2013), and SHIP‐TREND (n = 2408). Serum levels of NT‐proBNP were taken once at baseline. The DIAST‐CHF study enrolled 1727 study participants (47.7% female, mean age 66.9 ± 8.1 years). At baseline, patients without AF or HF (n = 1375) had a median NT‐proBNP of 94 pg/mL (interquartile range 51;181). In patients with AF (n = 93), NT‐proBNP amounted to 667 (215;1130) pg/mL. It was significantly higher than in the first group (P 50% [n = 38; 603 (175;1070) pg/mL] and those without HF (P = 1.0). Receiver‐operating characteristic curves of NT‐proBNP showed a similar area under the curve (AUC) for the detection of AF at baseline (0.84, 95% CI [0.79–0.88]) and for HF with EF 50% was significantly lower (0.61 [0.56–0.65]) than for AF (P = 0.001). During follow‐up, AF was newly diagnosed in 157 (9.1%) and HF in 141 (9.6%) study participants. NT‐proBNP was a better predictor of incident AF during the first 2 years (AUC: 0.79 [0.75–0.83]) than of newly diagnosed HF (0.59 [0.55–0.63]; P 50% is very limited.

Introduction A high tumor mutational burden (TMB) (≥10 mut/Mb) has been associated with improved clinical benefit in non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI) and is a tumor agnostic indication for pembrolizumab across tumor types. We explored whether combining TMB with programmed cell death ligand 1 (PD-L1) and pretreatment neutrophil-lymphocyte ratio (NLR) was associated with improved outcomes in ICI-treated NSCLC. Methods We retrospectively analyzed patients treated with ICI with Foundation One genomic testing, including TMB. Optimal cutoff for prediction of response by TMB was determined by receiver operating characteristic analysis, and area under the curve (AUC) was calculated for all 3 biomarkers and combinations. Cox model was used to assess prognostic factors of overall survival (OS) and time to progression (TTP). Survival cutoffs calculated with Kaplan-Meier survival curves were TMB ≥10 mut/Mb, PD-L1 ≥50%, NLR Results Data from 88 patients treated were analyzed. The optimal TMB cutoff was 9.24 mut/Mb (AUC, 0.62), improving to 0.74 combining all 3 biomarkers. Adjusted Cox model showed that TMB ≥10 mut/Mb was an independent factor of OS (hazard ratio [HR], 0.31; 95% confidence interval; 0.14-0.69; P = .004) and TTP (HR, 0.46; 95% CI, 0.27-0.77; P = .003). The combination of high TMB with positive PD-L1 and low NLR was significantly associated with OS (P = .038) but not TTP. Conclusions TMB has modest predictive and prognostic power for clinical outcomes after ICI treatment. The combination of TMB, PD-L1, and NLR status improves this power.

Numerous studies have shown that cg05575921 methylation decreases in response to smoking. However, secondary to methodological issues, the magnitude and dose dependency of that response is as of yet unclear. This lack of certainty is a barrier to the use of DNA methylation clinically to assess and monitor smoking status. To better define this relationship, we conducted a joint analysis of methylation sensitive PCR digital (MSdPCR) assessments of cg05575921 methylation in whole blood and/or saliva DNA to smoking using samples from 421 smokers and 423 biochemically confirmed non-smokers from 4 previously published studies. We found that cg05575921 methylation manifested a curvilinear dose dependent decrease in response to increasing cigarette consumption. In whole blood DNA, the Receiver Operating Characteristic (ROC) Area Under the Curve (AUC) of cg05575921 methylation for predicting daily smoking status was 0.98. In saliva DNA, the gross AUC was 0.91 with correction for cellular heterogeneity improving the AUC to 0.94. Methylation status was significantly associated with the Fagerstrom Test for Nicotine Dependence score, but with significant sampling heterogeneity. We conclude that MSdPCR assessments of cg05575921 methylation are a potentially powerful, clinically implementable tool for the assessment and management of smoking.