Cohort Of Patients Research Articles

Real-world Effectiveness and Tolerability of Interferon-free Direct-acting Antiviral for 15,849 Patients with Chronic Hepatitis C: A Multinational Cohort Study.

As practice patterns and hepatitis C virus (HCV) genotypes (GT) vary geographically, a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal. This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs, focusing on GT3 and GT6. We analyzed the sustained virological response (SVR12) of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific, North America, and Europe between 07/01/2014-07/01/2021. The mean age was 62±13 years, with 49.6% male. The demographic breakdown was 91.1% Asian (52.9% Japanese, 25.7% Chinese/Taiwanese, 5.4% Korean, 3.3% Malaysian, and 2.9% Vietnamese), 6.4% White, 1.3% Hispanic/Latino, and 1% Black/African-American. Additionally, 34.8% had cirrhosis, 8.6% had hepatocellular carcinoma (HCC), and 24.9% were treatment-experienced (20.7% with interferon, 4.3% with direct-acting antivirals). The largest group was GT1 (10,246 [64.6%]), followed by GT2 (3,686 [23.2%]), GT3 (1,151 [7.2%]), GT6 (457 [2.8%]), GT4 (47 [0.3%]), GT5 (1 [0.006%]), and untyped GTs (261 [1.6%]). The overall SVR12 was 96.9%, with rates over 95% for GT1/2/3/6 but 91.5% for GT4. SVR12 for GT3 was 95.1% overall, 98.2% for GT3a, and 94.0% for GT3b. SVR12 was 98.3% overall for GT6, lower for patients with cirrhosis and treatment-experienced (TE) (93.8%) but ≥97.5% for treatment-naive patients regardless of cirrhosis status. On multivariable analysis, advanced age, prior treatment failure, cirrhosis, active HCC, and GT3/4 were independent predictors of lower SVR12, while being Asian was a significant predictor of achieving SVR12. In this diverse multinational real-world cohort of patients with various GTs, the overall cure rate was 96.9%, despite large numbers of patients with cirrhosis, HCC, TE, and GT3/6. SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent (>91%).

Analysis of risk factors for lymph node metastasis in 1096 patients with early gastric cancer and establishment of a predictive nomogram

Objective: To investigate the risk factors for lymph node metastasis in patients with early gastric cancer and establish a model for prediction of risk. Methods: The cohort of this retrospective observational study comprised 1096 patients who had undergone radical gastric cancer surgery combined with standard D1 lymphadenectomy and been diagnosed with early gastric cancer by postoperative pathology in Zhongshan Hospital affiliated with Fudan University from January 2016 to July 2022. The patients were allocated to groups with and without lymph node metastases. Clinicopathological characteristics were compared between the two groups and multi-factor logistic regression analysis used to identify independent risk factors for lymph node metastasis in patients with early gastric cancer. Indications for endoscopic resection in the Japanese Gastric Cancer Association (JGCA) guideline were also incorporated into construction of the model. The patient cohort was divided into training and validation sets in a 6:4 ratio. The identified independent risk factors were used to construct a predictive nomogram. Receiver operating characteristic curves were plotted separately and the difference between them in predictive efficacy was compared using the area under the curve (AUC). Results: A total of 1,096 patients with early gastric cancer were included, with 750 males and 346 females. Their average age was (61.4±10.9) years old, and the mean tumor diameter was (23.8±11.4) mm. Among them, 188 patients (17.2%) had positive lymph node metastasis, with 109 cases in N1 stage, 42 cases in N2 stage, and 37 cases in N3 stage. Additionally, 462 patients were in T1a stage, while 634 patients were in T1b stage. Univariate analysis showed that tumor diameter, location, Lauren classification, gross morphology, histological type, intravascular invasion, ulceration, differentiation type and tumor T stage were associated with lymph node metastasis after radical gastrectomy for early gastric cancer (all P<0.05). Multifactorial analysis showed that the presence of intravascular invasion (OR=14.822, 95%CI: 9.323-23.572, P<0.001), undifferentiated type (OR=3.095, 95%CI: 1.649-5.811, P<0.001), tumor T1b (OR=1.798, 95%CI: 1.053-3.079, P=0.032), and tumor diameter ≥2 cm (OR=1.229, 95%CI: 1.031-1.469, P=0.022) were independent risk factors for lymph node metastasis. The baseline data of the training set and validation set were consistent in terms of balance (all P>0.05). We used the above variables to establish a predictive nomogram for lymph node metastasis in patients with early gastric cancer. The AUC values obtained from the validation of the model in the training and validation sets were 0.880 (95%CI: 0.849-0.911) and 0.881 (95%CI: 0.841-0.921), respectively, and were significantly better than the predictive efficacy based on the JGCA guideline (AUC=0.777, 95%CI: 0.746-0.809, P<0.001). Conclusions: Patients with early gastric cancer and intravascular invasion, undifferentiated tumors, tumor T1b, and diameter ≥2 cm are at higher risk of postoperative lymph node metastasis than other patients. The predictive model developed in this study more accurately predicts lymph node metastasis in patients with early gastric cancer than previously proposed methods.

Structural and Molecular Imaging-based Characterization of Soft Tissue and Vascular Calcification in Hyperphosphatemic Familial Tumoral Calcinosis.

Hyperphosphatemic Familial Tumoral Calcinosis (HFTC) is a rare disorder caused by deficient FGF23 signaling and resultant ectopic calcification. In this study, we systematically characterized and quantified macro- and micro-calcification in an HFTC cohort using computed tomography (CT) and 18F-sodium fluoride positron emission tomography/CT (18F-NaF PET/CT). Fourier-transform infrared (FTIR) spectroscopy was performed on four phenotypically different calcifications from a patient with HFTC, showing the dominant component to be hydroxyapatite. Eleven patients with HFTC were studied with CT and/or 18F-NaF PET/CT. Qualitative review was done to describe the spectrum of imaging findings on both modalities. CT-based measures of volume (e.g., total calcific burden and lesion volume) and density (Hounsfield units) were quantified and compared to PET-based measures of metabolic activity (e.g., mean standardized uptake values). Microcalcification scores (mCSs) were calculated for the vasculature of six patients using 18F-NaF PET/CT and visualized on a standardized vascular atlas. Ectopic calcifications were present in 82% of patients, predominantly near joints and the distal extremities. Considerable heterogeneity was observed in total calcific burden per patient (823.0 ± 670.1cm3, n = 9) and lesion volume (282.5 ± 414.8cm3, n = 27). The largest lesions were found at the hips and shoulders. 18F-NaF PET offered the ability to differentiate active vs. quiescent calcifications. Calcifications were also noted in multiple anatomic locations, including brain parenchyma (50%). Vascular calcification was seen in the distal aorta, carotid, and coronaries in 50%, 70%, 73%, and 50%, respectively. 18F-NaF-avid, but CT-negative calcification was seen in a 17-year-old patient, implicating early onset vascular calcification. This first systematic assessment of calcifications in a cohort of patients with HFTC has identified the early onset, prevalence, and extent of macro- and micro-calcification. It supports 18F-NaF PET/CT as a clinical tool for distinguishing between active and inactive calcification, informing disease progression, and quantification of ectopic and vascular disease burden.

Beneficial therapeutic plasma exchange response in the treatment of severe relapses in patients with multiple sclerosis.

Therapeutic plasma exchange (PLEX) is effective as a second-line treatment of severe relapses of multiple sclerosis (MS) that failed to respond to standard steroid therapy. Our objective was to evaluate the effectiveness of PLEX in the severe MS relapses in a cohort of patients treated at Neurology Clinic, University Clinical Centre of Serbia, Belgrade, from 2007 until 2020. This retrospective study comprised 107 MS patients with 127 severe relapses treated with PLEX. Majority of our patients suffered from relapsing remitting MS (83.2%), 12.1% had secondary progressive MS and 4.7% had primary progressive MS. Mean age was 39.2 years (range, 19-79 years), female/male ratio 2.3:1. Pulse corticosteroid treatment was used before PLEX in 99.3% of patients. Median EDSS score at nadire during relapse was 6.0 (range 2.0-10.0). After PLEX, 73.8% relapses showed a marked clinical improvement, 7.1% showed mild improvement and in 19.0% there was no improvement. Median EDSS at discharge was 4.0 (6.0 at nadir of relapse vs. 4.0 at discharge; p<0.0001) and it was sustained at the same level, 6 month after PLEX. Multivariate regression analysis showed that higher EDSS at nadir during relapse (OR=0.63, 95% CI 0.41-0.96, p=0.039) and older age (OR=1.07, 95% CI 1.02- 1.12, p=0.010) were significantly associated with poor treatment response after 6- month follow-up. Adverse events occurred in 17.3 of procedures and they were completely resolved. Our study in a large cohort of MS patients confirmed that PLEX is effective.

Preventable predictive factors of post-colonoscopy colorectal cancer in inflammatory bowel disease.

Post-colonoscopy colorectal cancer (PCCRC) is a colorectal cancer (CRC) diagnosed after a colonoscopy in which no cancer is detected (index colonoscopy). Although the overall cumulative rates of PCCRC are low in both the general population and inflammatory bowel disease (IBD) patients, the overall incidence of PCCRC in IBD is greater than that documented in the general population. This study aimed to identify the index colonoscopy-related factors and patients' characteristics influencing IBD-associated PCCRC development. We carried out an observational, retrospective study in which IBD-associated PCCRCs were diagnosed between 2010 and 2023. The PCCRC group was compared to a control cohort of IBD patients without CRC matched 1:1 by several demographic and clinical features as well as characteristics of index colonoscopy to minimize selection bias. Among 61 CRCs identified, 37 (61%) were PCCRC. Twelve of 37 (32%) PCCRC were diagnosed within 12 months after the previous negative colonoscopy, 15 (41%) within 12-36 months, and 10 (27%) within 36-60 months. In the multivariate analysis, the inadequate bowel preparation of the index colonoscopy (OR: 5.9; 95% CI: 11.1- 31.4) and the presence of high-risk factors for CRC (OR: 24.03; 95% CI: 3.1-187.8) were independently associated with PCCRC. Conversely, prior exposure to immunosuppressors/biologics (OR: 0.17; 95% CI: 0.03-0.83) and random biopsies sampling at index colonoscopy (OR:0.19; 95% CI: 0.04-0.85) were inversely associated with PCCRC. More than 50% of CRCs in our population were PCCRC. PCCRCs were associated with previous inadequate cleansing and occurred more frequently in high-risk patients.

Early experience with mechanical hemodynamic support for catheter ablation of malignant ventricular tachycardia

Objective: To explore the role of mechanical hemodynamic support (MHS) in mapping and catheter ablation of patients with hemodynamically unstable ventricular tachycardia (VT), report single-center experience in a cohort of consecutive patients receiving VT ablation during MHS therapy, and provide evidence-based medical evidence for clinical practice. Methods: This was a retrospective cohort study. Patients with hemodynamically unstable VT who underwent catheter ablation with MHS at Beijing Anzhen Hospital, Capital Medical University between August 2021 and December 2023 were included. Patients were divided into rescue group and preventive group according to the purpose of treatment. Their demographic data, periprocedural details, and clinical outcomes were collected and analyzed. Results: A total of 15 patients with hemodynamically unstable VT were included (8 patients in the rescue group and 7 patients in the preventive group). The acute procedure was successful in all patients. One patient in the rescue group had surgical left ventricular assist device (LVAD) implantation, remaining 14 patients received extracorporeal membrane oxygenation (ECMO) for circulation support. ECMO decannulation was performed in 12 patients due to clinical and hemodynamic stability, of which 6 patients were decannulation immediately after surgery and the remaining patients were decannulation at 2.0 (2.5) d after surgery. Two patients in the rescue group died during the index admission due to refractory heart failure and cerebral hemorrhage. During a median follow-up of 30 d (1 d to 12 months), one patient with LVAD had one episode of ventricular fibrillation at 6 months after discharge, and no further episodes of ventricular fibrillation and/or VT occurred after treatment with antiarrhythmic drugs. No malignant ventricular arrhythmia occurred in the remaining 12 patients who were followed up. Conclusions: MHS contributes to the successful completion of mapping and catheter ablation in patients with hemodynamically unstable VT, providing desirable hemodynamic status for emergency and elective conditions.

A combination of left ventricular outflow tract velocity time integral and lung ultrasound to predict mortality in ST elevation myocardial infarction.

Development of ventricular failure and pulmonary edema is associated with a worse prognosis in ST-elevation myocardial infarction (STEMI). We aimed to evaluate the prognostic ability of a novel classification combining lung ultrasound (LUS) and left ventricular outflow tract (LVOT) velocity time integral (VTI) in patients with STEMI. LUS and LVOT-VTI were performed within 24h of admission in STEMI patients. A LUS combined with LVOT-VTI (LUV) classification was developed based on LUS with < or ≥ 3 positive zone scans, combined with LVOT-VTI > or ≤ 14. Patients were classified as A (< 3zones/ > 14cm VTI), B (≥ 3zones/ > 14cm VTI), C (< 3zones/ ≤ 14cm VTI) and D (≥ 3zones/ ≤ 14cm VTI). Primary outcome was occurrence of in-hospital mortality. Development of cardiogenic shock (CS) within 24h was also assessed. A total of 308 patients were included. Overall in-hospital mortality was 8.8%, while mortality for LUV A, B, C, and D was 0%, 3%, 12%, and 45%, respectively. The area under the curve (AUC) for predicting in-hospital mortality was 0.915. Moreover, after exclusion of patients admitted in Killip IV, at each increasing degree of LUV, a higher proportion of patients developed CS within 24h: LUV A = 0.0%, LUV B 5%, LUV C = 12.5% and LUV D = 30.8% (p < 0.0001). The AUC for predicting CS was 0.908 (p < 0.001). In a cohort of STEMI patients, LUV provided to be an excellent method for prediction of in-hospital mortality and development of CS. LUV classification is a fast, non-invasive and very user-friendly ultrasonographic evaluation method to stratify the risk of mortality and CS.

AI-powered prediction of HCC recurrence after surgical resection: Personalised intervention opportunities using patient-specific risk factors.

Hepatocellular carcinoma (HCC) recurrence following surgical resection remains a significant clinical challenge, necessitating reliable predictive models to guide personalised interventions. In this study, we sought to harness the power of artificial intelligence (AI) to develop a robust predictive model for HCC recurrence using comprehensive clinical datasets. Leveraging data from 958 patients across multiple centres in Australia and Hong Kong, we employed a multilayer perceptron (MLP) as the optimal classifier for model generation. Through rigorous internal cross-validation, including a cohort from the Chinese University of Hong Kong (CUHK), our AI model successfully identified specific pre-surgical risk factors associated with HCC recurrence. These factors encompassed hepatic synthetic function, liver disease aetiology, ethnicity and modifiable metabolic risk factors, collectively contributing to the predictive synergy of our model. Notably, our model exhibited high accuracy during cross-validation (.857 ± .023) and testing on the CUHK cohort (.835), with a notable degree of confidence in predicting HCC recurrence within accurately classified patient cohorts. To facilitate clinical application, we developed an online AI digital tool capable of real-time prediction of HCC recurrence risk, demonstrating acceptable accuracy at the individual patient level. Our findings underscore the potential of AI-driven predictive models in facilitating personalised risk stratification and targeted interventions to mitigate HCC recurrence by identifying modifiable risk factors unique to each patient. This model aims to aid clinicians in devising strategies to disrupt the underlying carcinogenic network driving recurrence.

Building Dual AI Models and Nomograms Using Noninvasive Parameters for Aiding Male Bladder Outlet Obstruction Diagnosis and Minimizing the Need for Invasive Video-Urodynamic Studies: Development and Validation Study.

Diagnosing underlying causes of nonneurogenic male lower urinary tract symptoms associated with bladder outlet obstruction (BOO) is challenging. Video-urodynamic studies (VUDS) and pressure-flow studies (PFS) are both invasive diagnostic methods for BOO. VUDS can more precisely differentiate etiologies of male BOO, such as benign prostatic obstruction, primary bladder neck obstruction, and dysfunctional voiding, potentially outperforming PFS. These examinations' invasive nature highlights the need for developing noninvasive predictive models to facilitate BOO diagnosis and reduce the necessity for invasive procedures. We conducted a retrospective study with a cohort of men with medication-refractory, nonneurogenic lower urinary tract symptoms suspected of BOO who underwent VUDS from 2001 to 2022. In total, 2 BOO predictive models were developed-1 based on the International Continence Society's definition (International Continence Society-defined bladder outlet obstruction; ICS-BOO) and the other on video-urodynamic studies-diagnosed bladder outlet obstruction (VBOO). The patient cohort was randomly split into training and test sets for analysis. A total of 6 machine learning algorithms, including logistic regression, were used for model development. During model development, we first performed development validation using repeated 5-fold cross-validation on the training set and then test validation to assess the model's performance on an independent test set. Both models were implemented as paper-based nomograms and integrated into a web-based artificial intelligence prediction tool to aid clinical decision-making. Among 307 patients, 26.7% (n=82) met the ICS-BOO criteria, while 82.1% (n=252) were diagnosed with VBOO. The ICS-BOO prediction model had a mean area under the receiver operating characteristic curve (AUC) of 0.74 (SD 0.09) and mean accuracy of 0.76 (SD 0.04) in development validation and AUC and accuracy of 0.86 and 0.77, respectively, in test validation. The VBOO prediction model yielded a mean AUC of 0.71 (SD 0.06) and mean accuracy of 0.77 (SD 0.06) internally, with AUC and accuracy of 0.72 and 0.76, respectively, externally. When both models' predictions are applied to the same patient, their combined insights can significantly enhance clinical decision-making and simplify the diagnostic pathway. By the dual-model prediction approach, if both models positively predict BOO, suggesting all cases actually resulted from medication-refractory primary bladder neck obstruction or benign prostatic obstruction, surgical intervention may be considered. Thus, VUDS might be unnecessary for 100 (32.6%) patients. Conversely, when ICS-BOO predictions are negative but VBOO predictions are positive, indicating varied etiology, VUDS rather than PFS is advised for precise diagnosis and guiding subsequent therapy, accurately identifying 51.1% (47/92) of patients for VUDS. The 2 machine learning models predicting ICS-BOO and VBOO, based on 6 noninvasive clinical parameters, demonstrate commendable discrimination performance. Using the dual-model prediction approach, when both models predict positively, VUDS may be avoided, assisting in male BOO diagnosis and reducing the need for such invasive procedures.

Preoperative ultra-hypofractionated radiotherapy for soft-tissue sarcomas: low rate of wound complications

Background: Normofractionated pre-operative radiotherapy (nRT) with 50 Gy applied in 25 fractions represents the most widely used radiotherapy (RT) regimen in combined local treatment of soft tissue sarcomas (STS). STS are characterized by a low α/β ratio of 4-5 Gy, which may translate into a higher sensitivity for hypofractionation. Increasing data from cohorts and phase II trials on ultra-hypofractionated RT (uhRT) regimens is available. We prospectively assessed our preoperative uhRT sarcoma patient cohort with a focus on short term wound complications (WC). Methods: This is a prospective registry analysis of a single center patient cohort, treated from 03.2020-10.2023 with uhRT (25 Gy in 5 fractions in 1 week). The same radiation oncologists (GS/CG) and surgeon (BF) performed the treatment (61/61 and 58/60), as well as the same reference pathologist (BB) confirmed all histopathological diagnoses. WC (according to CAN-NCIC-SR2 trial) and intermediate local control (LC) rates were assessed and compared with outcome data of a previously published cohort of 67 extremity/trunk sarcoma patients treated with nRT by the same authors (7% WC, 98% LC at 3 years). Results: After a mean/median follow-up (FU) of 19/19 months (range 0-46), LC at 1.5y was 94%. Surgery was performed at a mean/median of 20/16 days (range 4-60) after uhRT completion. WC were observed in 7/60 operated patients (12%), and in 5/51 (10%) extremity/trunk lesions. Early tolerance was excellent, limited to G0-1, even in 3 patients with prior RT to the same region. Clear resection margins were achieved in 55/60 patients (92%). Pathologic necrosis of ≥95% was reported in 5%, 75% achieved less than <50% necrosis. Conclusion: These results show low rates of WC and high LC for uhRT and are comparable to our previously published nRT data. This study supports the routine use of preoperative uhRT for STS.

Are community oncology practices with/without clinical research programs different? A comparison of patient and practice characteristics.

Expanding access to clinical trials in community settings is a potential approach to addressing disparities in accrual of historically underrepresented populations. However, little is known about the characteristics of practices that do not participate in research. We investigated differences in patient and practice characteristics of US community oncology practices with high vs low engagement in clinical research. We included patients from a real-world, nationwide electronic health record-derived, de-identified database who received active treatment for cancer at community oncology practices between 11/1/17 and 10/31/22. We assessed patient and practice characteristics and their associations with high vs low research engagement using descriptive analyses and logistic regression models. Seventy (39.3%) of 178 practices had high research engagement, treated 57.8% of the overall 568,540 patient cohort, and enrolled 3.25% of their patients on cancer treatment trials during the five-year observation period (v 0.27% enrollment among low engagement practices). Practices with low vs high research engagement treated higher proportions of the following patient groups: ages > =75 (24.2% v 21.8%), non-Latinx Black (12.6% v10.3%) or Latinx (11.6% v 6.1%), were within the lowest socioeconomic status quintile (21.9% v 16.5%), and were uninsured or had no documented insurance (22.2% v 13.6%). Patient groups historically underrepresented in oncology clinical trials are more likely to be treated at community practices with limited or no access to trials. These results suggest that investments to expand the clinical research footprint among practices with low research engagement could help address persistent inequities in trial representation.

Immunological biomarkers associated with survival in a cohort of Argentinian patients with Common Variable Immunodeficiency

BackgroundCommon Variable Immunodeficiency (CVID) is the most common symptomatic syndrome among inborn errors of immunity (IEI). Although several aspects of CVID immunopathology have been elucidated, predictive factors for mortality are incompletely defined. A genetic cause can only be identified in approximately 30% of patients. ObjectivesTo develop a mortality predictive score based on the immunophenotypes and genotypes of CVID patients. MethodsTwenty-one patients diagnosed with CVID in Cordoba, Argentina, were analyzed for clinical and laboratory data. Immunophenotyping was done by flow cytometry. CVID-associated mutations were identified by whole exome sequencing (WES). ResultsLive (15) and deceased (6) patients were compared. Univariate analysis showed significant differences in CD4+ T cells (p=0.002), Natural Killer (NK) cells (p=0.001) and memory switched B cells (p=0.001) between groups. Logistic regression analysis showed a negative correlation between CD4, NK and memory switched B cells counts and probability of survival over a 10-year period [CD4+ T cells: OR 1.01 (95% CI: 1.001-1,020); NK cells: OR 1.07 (95% CI:1.02-1.17) and memory switched B cells: OR 26.23 (95% CI: 2.06-2651.96). ROC curve analysis identified a survival cut off point for each parameter: CD4+ T cells 546 cell/ml AUC 0.87 (sensitivity 60%-specificity 100%), memory switched B cells 0.84 cells/ml AUC 0.92 (sensitivity 100%-specificity 85%), NK cells 45 cells/ml for AUC 0.92 (sensitivity 83%-specificity 100%), %). Genetic analysis on 14 patients from the cohort (9 females, 5 males) revealed mutations associated with IEI in 6 patients. ConclusionsA score to predict mortality is proposed based on CD4, NK and memory switched B cell number in patients with CVID.

Identifying Comprehensive Genomic Alterations and Potential Neoantigens for Cervical Cancer Immunotherapy in a Cohort of Chinese Squamous Cell Carcinoma of the Cervix

ObjectiveGenomic alterations and potential neoantigens for cervical cancer immunotherapy were identified in a cohort of Chinese patients with cervical squamous cell carcinoma (CSCC). MethodsWhole-exome sequencing was used to identify genomic alterations and potential neoantigens for CSCC immunotherapy. RNA Sequencing was performed to analyze neoantigen expression. ResultsSystematic bioinformatics analysis showed that C>T/G>A transitions/transversions were dominant in CSCCs. Missense mutations were the most frequent types of somatic mutation in the coding sequence regions. Mutational signature analysis detected signature 2, signature 6, and signature 7 in CSCC samples. PIK3CA, FBXW7, and BICRA were identified as potential driver genes, with BICRA as a newly reported gene. Genomic variation profiling identified 4,960 potential neoantigens, of which 114 were listed in two neoantigen-related databases. ConclusionThe present findings contribute to our understanding of the genomic characteristics of CSCC and provide a foundation for the development of new biotechnology methods for individualized immunotherapy in CSCC.

Machine Learning Predicts Unplanned Care Escalations for Post-Anesthesia Care Unit Patients during the Perioperative Period: A Single-Center Retrospective Study

Background: Despite low mortality for elective procedures in the United States and developed countries, some patients have unexpected care escalations (UCE) following post-anesthesia care unit (PACU) discharge. Studies indicate patient risk factors for UCE, but determining which factors are most important is unclear. Machine learning (ML) can predict clinical events. We hypothesized that ML could predict patient UCE after PACU discharge in surgical patients and identify specific risk factors. Methods: We conducted a single center, retrospective analysis of all patients undergoing non-cardiac surgery (elective and emergent). We collected data from pre-operative visits, intra-operative records, PACU admissions, and the rate of UCE. We trained a ML model with this data and tested the model on an independent data set to determine its efficacy. Finally, we evaluated the individual patient and clinical factors most likely to predict UCE risk. Results: Our study revealed that ML could predict UCE risk which was approximately 5% in both the training and testing groups. We were able to identify patient risk factors such as patient vital signs, emergent procedure, ASA Status, and non-surgical anesthesia time as significant variable. We plotted Shapley values for significant variables for each patient to help determine which of these variables had the greatest effect on UCE risk. Of note, the UCE risk factors identified frequently by ML were in alignment with anesthesiologist clinical practice and the current literature. Conclusions: We used ML to analyze data from a single-center, retrospective cohort of non-cardiac surgical patients, some of whom had an UCE. ML assigned risk prediction for patients to have UCE and determined perioperative factors associated with increased risk. We advocate to use ML to augment anesthesiologist clinical decision-making, help decide proper disposition from the PACU, and ensure the safest possible care of our patients.

Post-discharge complications and hospital readmissions are associated with nutritional risk and malnutrition status in a cohort of Canadian pediatric patients

BackgroundThis study constitutes a secondary analysis of a prospective cohort aiming to evaluate the potential correlation between nutritional risk and status at admission with the occurrence of post-discharge complications and hospital readmissions in children receiving care at high resource Centres.MethodsData was collected from 5 Canadian tertiary pediatric Centers between 2012 and 2016. Nutritional risk and status were evaluated at hospital admission with validated tools (STRONGkids and Subjective Global Nutrition Assessment [SGNA]) and anthropometric measurements. Thirty days after discharge, occurrence of post-discharge complications and hospital readmission were documented.ResultsA total of 360 participants were included in the study (median age, 6.1 years; median length of stay, 5 days). Following discharge, 24.1% experienced complications and 19.5% were readmitted to the hospital. The odds of experiencing complications were nearly tripled for participants with a high nutritional risk compared to a low risk (OR = 2.85; 95% CI [1.08–7.54]; P = 0.035) and those whose caregivers reported having a poor compared to a good appetite (OR = 2.96; 95% CI [1.59–5.50]; P < 0.001). According to SGNA, patients identified as malnourished had significantly higher odds of complications (OR, 1.92; 95% CI, 1.15–3.20; P = 0.013) and hospital readmission (OR, 1.95; 95% CI, 1.12–3.39; P = 0.017) than to those well-nourished.ConclusionsThis study showed that complications and readmission post-discharge are common, and these are more likely to occur in malnourished children compared to their well-nourished counterparts. Enhancing nutritional care during admission, at discharge and in the community may be an area for future outcome optimization.

Are Neonatal Birth Weights Reduced in Low-Risk Patients Diagnosed with COVID-19 during Pregnancy?

Studies have shown that the 2019 novel coronavirus disease (COVID-19) may be associated with an increased risk of adverse pregnancy outcomes including preeclampsia, preterm birth, and stillbirth. However, the relationship between COVID-19 and abnormal fetal growth (i.e., low neonatal birth weight) has not been elucidated. Because other viruses affect fetal growth, obstetrical providers began to recommend ultrasound studies during the third trimester to assess fetal growth in patients with COVID-19 during pregnancy. The aim of this study was to determine if neonatal birth weight was different between low-risk patients diagnosed with COVID-19 during pregnancy and low-risk patients without COVID-19 in pregnancy, to ascertain if third trimester growth ultrasound is warranted in this patient population. We performed a retrospective cohort study of low-risk pregnant patients (who had no other indications for sonographic fetal surveillance during the third trimester) with and without COVID-19 during pregnancy. Patient demographics, gestational dating, neonatal birth weights, and corresponding Alexander growth curve birth weight percentiles were collected. The primary outcome was small-for-gestational age (SGA) neonates, defined as birth weight < 10th percentile for gestational age at delivery (SGA10). Our cohort (N = 513) included 248 COVID-19-exposed patients and 265 patients who did not have COVID-19 during pregnancy. Gestational age at delivery and average neonatal birth weights were similar in COVID-19-exposed (38 weeks 5 days, 3,266 g) and unexposed patients (38 weeks 4 days, 3,224 g; p = 0.434, 0.358). Rates of SGA10 neonates were similar in the COVID-19-exposed (22/248, 8.9%) and -unexposed (23/265, 8.7%, p = 0.939) groups. Timing and severity of COVID-19 during pregnancy also were not associated with rates of SGA neonates. In a cohort of low-risk patients, rates of SGA neonates were similar in patients with and without COVID-19 during pregnancy. These findings suggest that ultrasound surveillance to detect fetal growth restriction in low-risk patients with COVID-19 during pregnancy is not warranted. · COVID-19 may be associated with fetal growth restriction.. · There are normal infant weights in patients with COVID-19 in pregnancy.. · Growth ultrasound is not needed in patients with COVID-19..

Correlation between matrix metalloproteinase-2, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinases-1 and white matter hyperintensities in patients with cerebral small vessel disease based on cranial magnetic resonance 3D imaging

ObjectiveThe objective of this study was to investigate the correlation between serum levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels and their ratios with the severity of white matter hyperintensities (WMHs) in patients with cerebral small vessel disease (CSVD). MethodsThis cross-sectional study was done on a prospective cohort of patients with CSVD. Qualitative and quantitative analyses of WMHs were performed using Fazekas grading and lesion prediction algorithm (LPA) methods. Biomarkers MMP-2, MMP-9, and TIMP-1 were measured to explore their correlation with the severity of WMHs. ResultsThe sample consisted of 144 patients with CSVD. There were 63 male and 81 female patients, with an average age of 67.604 ± 8.727 years. Among these, 58.33% presented with white matter hyperintensities at Fazekas grading level 1, with an average total template volume of WMHs of 4.305 mL. MMP-2 (P = 0.025), MMP-9 (P = 0.008), TIMP-1 (P = 0.026), and age (P = 0.007) were identified as independent correlates of WMHs based on Fazekas grading. Independent correlates of the total template volume of WMHs included MMP-2 (P = 0.023), TIMP-1 (P = 0.046), age (P = 0.047), systolic blood pressure (P = 0.047), and homocysteine (Hcy) (P = 0.014). In addition, age (P = 0.003; P < 0.001), interleukin-6 (IL-6) (P < 0.001; P = 0.044), Hcy (P < 0.001; P < 0.001), glycated hemoglobin (HbA1c) (P = 0.016; P = 0.043), and chronic kidney disease (P < 0.001; P < 0.001) were associated with both WMHs Fazekas grading and the total template volume of WMHs. ConclusionSerum levels of MMP-9, MMP-2, and TIMP-1 were independently associated with the Fazekas grading, while serum TIMP-1 and MMP-2 levels were independently related to the total template volume of WMHs. The association of TIMP-1 and MMP-2 with the severity of CSVD-related WMHs suggests their potential role as disease-related biomarkers. However, further research is required to uncover the specific mechanisms underlying these interactions.

Severe neutropenia unrelated to clozapine in patients receiving clozapine.

Clozapine is known to cause agranulocytosis. Mandatory monitoring schemes are aimed at reducing the risk of agranulocytosis and of the consequences of agranulocytosis. All cases of agranulocytosis occurring in people prescribed clozapine are assumed to be caused by clozapine. In a previous study, we examined a cohort of patients listed on our hospital database as having had clozapine-induced agranulocytosis and applied specific criteria to identify those with confirmed clozapine-related, life-threatening agranulocytosis. In this study, we examine the cases not meeting these specific criteria. In the original study, 9 of 23 cases met the criteria for clozapine-induced, life-threatening agranulocytosis. Of the 13 remaining cases for whom data were available, 5 were probably caused by clozapine but were not life-threatening. Three cases were the result of concomitant cancer chemotherapy. Three were anomalous results probably related to measurement error. For the remaining two cases, the cause was not identified. Not all cases of agranulocytosis occurring in people taking clozapine are caused by clozapine. The widely used threshold criterion-based diagnosis overestimates the risk of agranulocytosis. True clozapine-related agranulocytosis is best identified by pattern-based criteria: rapid fall in neutrophil counts over around 2 weeks to below 0.5 × 109/L for two consecutive days (unless clozapine is stopped very early or granulocyte colony stimulating factor is given) where other possible causes (benign ethnic neutropenia, cancer chemotherapy) can be ruled out.

Impact of inflammation on cognitive function in patients with highly inflammatory rheumatoid arthritis

ObjectiveTo evaluate cognitive function in patients with rheumatoid arthritis (RA) and inflammatory activity.Patients and methodsWe performed a cross-sectional study of a cohort of patients with RA initiating their first biological...

Diagnostic and prognostic performance of the LiverRisk score in tertiary care

Background & AimsThe LiverRisk score has been proposed as blood-based tool to estimate liver stiffness measurement (LSM), thereby stratifying the risk of compensated advanced chronic liver disease (cACLD, LSM≥10kPa) and liver-related events in subjects without known chronic liver disease (CLD). We aimed to evaluate its diagnostic/prognostic performance in tertiary care. MethodsSubjects referred to two hepatology outpatient clinics (cohort-I: n=5897; cohort-II: n=1558) were retrospectively included. Calibration/agreement of the LiverRisk score with LSM was assessed, and diagnostic accuracy for cACLD compared to FIB-4/APRI. The prediction of hepatic decompensation and utility of proposed cut-offs were evaluated. ResultsIn cohort-I/II, mean age was 48.3/51.8years, 44.2%/44.7% were female, predominant etiologies were viral hepatitis (51.8%)/ metabolic dysfunction-associated steatotic liver disease (63.7%), median LSM was 6.9 [5.1-10.9]/ 5.8 [4.5-8.8]kPa, and 1690 (28.7%)/ 322 (20.7%) had cACLD.Despite a moderate correlation (Pearson’s r: 0.325/0.422), the LiverRisk score systematically underestimated LSM (“bias”: 2.93/1.80points/kPa lower) and range of agreement was wide, especially at higher values.The diagnostic accuracy of the LiverRisk score for cACLD (AUROC: 0.757/0.790) was comparable to FIB-4 (0.769/0.813) and APRI (0.747/0.765). The proposed cut-off of 10 points yielded an accuracy of 74.2%/81.2%, high specificity (91.9/93.4%), but low negative predictive value (76.6/84.5%, Cohen’s κ=0.260/0.327).In cohort-I, 208 (3.5%) developed hepatic decompensation (median follow-up: 4.7 years). The LiverRisk score showed a reasonable accuracy for predicting hepatic decompensation within 1-5 years (AUROC: 0.778-0.832). However, it was inferior to LSM (0.847-0.901, p<0.001) and FIB-4 (0.898-0.913, p<0.001). Similar to the strata of other NIT, proposed LiverRisk groups had distinct risks of hepatic decompensation. ConclusionsThe LiverRisk score did not improve diagnosis of cACLD or prediction of hepatic decompensation in tertiary care setting. IMPACT AND IMPLICATIONThe LiverRisk score has been proposed as non-invasive tool to estimate liver stiffness measurement and thus, the risk of compensated advanced chronic liver disease and liver-related events. As automatic implementation into lab reports is being discussed, the question on its applicability outside of opportunistic screening in the general population arises.In two large cohorts of patients referred to hepatology outpatient clinics, the LiverRisk score did not accurately predict liver stiffness, did not improve cACLD identification, and had a lower predictive performance for hepatic decompensation as compared to FIB-4.While being a major step forward for screening patients without known liver disease in primary care, our findings indicate that the LiverRisk score does not improve patient management outside the primary care setting, i.e., in cohorts with a higher pre-test probability of cACLD.