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Ultrasound‐based surveillance has suboptimal sensitivity for early detection of hepatocellular carcinoma (HCC) in patients with cirrhosis. There are several emerging alternatives, including a novel multitarget HCC blood test (Mt‐HBT). We compared performance of mt‐HBT against ultrasound with or without alpha‐fetoprotein (AFP) for early HCC detection in patients with cirrhosis. Per the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) guidelines, two reviewers searched PubMed, Cochrane, Embase, and clinicaltrials.gov databases from January 1990 through December 2020 to identify studies reporting sensitivity and/or specificity of ultrasound and AFP for overall and early stage HCC detection in patients with cirrhosis. Mt‐HBT diagnostic performance was derived from a clinical validation study. A network meta‐analysis model was built for comparative assessment, and pooled estimates of sensitivity at a fixed specificity were estimated based on Bayesian binormal receiver operating characteristic models for each modality. Forty‐one studies (comprising 62,517 patients with cirrhosis) met inclusion criteria. Ultrasound‐alone sensitivity was 51.6% (95% credible interval [CrI], 43.3%–60.5%) for early stage HCC detection, which increased with the addition of AFP to 74.1% (95% CrI, 62.6%–82.4%); however, this was offset by decreased specificity (87.9% vs. 83.9%, respectively). With specificity fixed at 90%, mt‐HBT sensitivity for early stage HCC detection was higher than ultrasound alone (18.2%; 95% CrI, 0.2%–37.7%) and similar to ultrasound with AFP (−3.3%; 95% CrI, −22.3%–17.4%). Pairwise posterior probabilities suggested a preference for mt‐HBT over ultrasound alone in 97.4% of cases but only 36.3% of cases versus ultrasound with AFP. Conclusion: A blood‐based mt‐HBT has higher sensitivity than ultrasound alone for early stage HCC detection but similar sensitivity compared to ultrasound and AFP. Mt‐HBT could be a comparable alternative to existing methods for HCC surveillance in patients who are at risk. Based on a network meta‐analysis of existing literature, surveillance using ultrasound with AFP had a significantly higher sensitivity for early‐stage hepatocellular carcinoma (HCC) than ultrasound alone. A multi‐targeted HCC blood test (mt‐HBT) is a promising emerging surveillance strategy compared to ultrasound‐based surveillance.

Mechanistic pathways linking maternal polyunsaturated fatty acid (PUFA) status with gestational length are poorly delineated. This study examined whether inflammation and sleep quality serve as mediators, focusing on the antiinflammatory ω-3 docosahexaenoic acid (DHA; 22:6n3) and proinflammatory ω-6 arachidonic acid (AA; 20:4n6). Pregnant women (n = 135) provided a blood sample and completed the Pittsburgh Sleep Quality Index (PSQI) at 20-27 weeks gestation. Red blood cell (RBC) fatty acid levels were determined by gas chromatography and serum inflammatory markers [interleukin (IL)-6, IL-8, tumor necrosis factor-α, IL-1β, and C-reactive protein] by electrochemiluminescence using high sensitivity kits. Both higher serum IL-8 (95% CI = 0.10,3.84) and poor sleep (95% CI = 0.03,0.28) served as significant mediators linking lower DHA:AA ratios with shorter gestation. Further, a serial mediation model moving from the DHA:AA ratio → sleep → IL-8 → length of gestation was statistically significant (95% CI = 0.02, 0.79). These relationships remained after adjusting for depressive symptoms, age, BMI, income, race, and smoking. No interactions with race were observed in relation to length of gestation as a continuous variable. However, a significant interaction between race and the DHA:AA ratio in predicting preterm birth was observed (p = 0.049); among African Americans only, odds of preterm birth decreased as DHA:AA increased (p = 0.048). These data support a role for both inflammatory pathways and sleep quality in linking less optimal RBC PUFA status with shorter gestation in African American and European American women and suggest that African-Americans have greater risk for preterm birth in the context of a low DHA:AA ratio.

Despite the increasing availability of advanced endoscopic resections and its favorable safety profile, surgery for nonmalignant colorectal polyps has continually increased. We sought to evaluate readmission rates and outcomes of elective surgery for nonmalignant colorectal polyps on a national level in the United States. The Nationwide Readmissions Database (2010-2014 [International Classification of Diseases, Ninth Revision] and 2016-2018 [International Classification of Diseases, 10th Revision]) was used to identify all adult subjects (age ≥18 years) who underwent elective surgical resection of nonmalignant colorectal polyps. Multivariable analyses were performed for predictors of postoperative morbidity and 30-day readmission. Elective surgery for nonmalignant colorectal polyps was performed in 108,468 subjects from 2010 to 2014 and in 54,956 subjects from 2016 to 2018, most of whom were laparoscopic. Postoperative morbidity and 30-day readmission rates were 20.5% and 8.5% from 2010 to 2014, and 13.0% and 7.6% from 2016 to 2018, respectively. Index admission mortality rates were 0.3-0.4%; mortality rates were higher in those with postoperative morbidity. Multivariable analyses revealed that male sex, ≥3 comorbidities, insurance status, and open surgery predicted an increased risk of both postoperative morbidity and 30-day readmission. In addition, postoperative morbidity (2010-2014 [odds ratio 1.58; 95% confidence interval 1.44-1.74] and 2016-2018 [odds ratio 1.55; 95% confidence interval 1.37-1.75]) predicted early readmission. In this investigation of national practices, elective surgery for nonmalignant colorectal polyps remains common. There is considerable risk of adverse postoperative outcomes, which highlights the importance of increasing awareness of the range of endoscopic resections and referring subjects to expert endoscopy centers.

BackgroundChimeric antigen receptor T-cell (CAR-T) infusion is associated with early toxicity. Yet, whether early toxicity development holds ramifications for long-term outcomes is unknown.MethodsFrom a large cohort of consecutive adult patients treated with CAR-T therapies for relapsed or refractory lymphomas from 2016 to 2019, we assessed progression-free survival (PFS), by toxicity development (cytokine release syndrome (CRS), neurotoxicity, or cardiotoxicity]. We also assessed the relationship of toxicity development to objective disease response, and overall survival (OS). Multivariable regression was utilized to evaluate relationships between standard clinical and laboratory measures and disease outcomes. Differences in outcomes, by toxicity status, were also assessed via 30-day landmark analysis. Furthermore, we assessed the effects of early anti-CRS toxicity therapy use (at ≤grade 2 toxicity) on maximum toxicity grade observed, and long-term disease outcomes (PFS and OS).ResultsOverall, from 102 CAR-T-treated patients, 90 were identified as treated with single-agent therapy, of which 88.9% developed toxicity (80 CRS, 41 neurotoxicity, and 17 cardiotoxicity), including 28.9% with high-grade (≥3) events. The most common manifestations were hypotension at 96.6% and fever at 94.8%. Among patients with cardiac events, there was a non-significant trend toward a higher prevalence of concurrent or preceding high-grade (≥3) CRS. 50.0% required tocilizumab or corticosteroids. The median time to toxicity was 3 days; high grade CRS development was associated with cardiac and neurotoxicity. In multivariable regression, accounting for disease severity and traditional predictors of disease response, moderate (maximum grade 2) CRS development was associated with higher complete response at 1 year (HR: 2.34; p=0.07), and longer PFS (HR: 0.41; p=0.02, in landmark analysis), and OS (HR: 0.43; p=0.03). Among those with CRS, relative blood pressure (HR: 2.25; p=0.004), respectively, also associated with improved PFS. There was no difference in disease outcomes, or maximum toxicity grade (CRS, neurotoxicity, or cardiotoxicity) observed, based on the presence or absence of the use of early CRS-directed therapies.ConclusionsAmong adult lymphoma patients, moderate toxicity manifest as grade 2 CRS after CAR-T infusion may associate with favorable clinical outcomes. Further studies are needed to confirm these findings.

Hypoglycemia is associated with increased mortality, but the role of its etiology is unclear. This study aimed to examine the impact of hypoglycemia etiology on mortality risk among critically ill patients. This single-center, retrospective, cohort study evaluated adult patients admitted to the medical or surgical intensive care unit, who experienced medication-induced or spontaneous hypoglycemia (blood glucose <70 mg/dL) during intensive care unit admission. Patients who became hypoglycemic following receipt of glucose-lowering therapy within a predefined time period were categorized in the medication-induced group. Periods were determined for each agent based on expected pharmacokinetics in critically ill patients. Patients who became hypoglycemic with no identifiable cause were categorized in the spontaneous group. Primary analysis compared medication-induced and spontaneous hypoglycemia with a primary endpoint of all-cause hospital mortality. Secondary analyses stratified patients by diabetes, severity of hypoglycemia, and glycemic variability. A total of 642 patients were eligible for inclusion (305 medication-induced and 337 spontaneous). When adjusted for covariates, no difference in hospital mortality was observed based on hypoglycemia etiology (odds ratio, 1.22 [0.77-1.93]; P=.39). Regardless of etiology, hypoglycemic severity, frequency, and glycemic variability were significantly associated with higher odds of hospital mortality. Hypoglycemic etiology did not impact hospital mortality when patients were stratified by presence or absence of diabetes. Medication-induced hypoglycemia appears to be equally harmful as spontaneous hypoglycemia during critical illness. Future studies should aim to identify strategies to minimize hypoglycemia regardless of etiology, while also minimizing glycemic variability associated with hypoglycemia treatment.

To evaluate the diagnostic accuracy of fine-needle aspiration biopsy (FNAB) to preoperatively diagnose medullary thyroid cancer (MTC) among multiple international centers and evaluate how the cytological diagnosis alone could impact patient management. We performed a retrospective chart review of sporadic MTC (sMTC) patients from 12 institutions over the last 29 years. FNAB cytology results were compared to final pathologic diagnoses to calculate FNAB sensitivity. To evaluate the impact of cytology sensitivity for MTC according to current practice and to avoid confounding results by local treatment protocols, changes in treatment patterns over time, and the influence of ancillary findings (e.g., serum calcitonin), therapeutic interventions based on FNAB cytology alone were projected into 1 of 4 treatment categories: total thyroidectomy (TT) and central neck dissection (CND), TT without CND, diagnostic hemithyroidectomy, or observation. A total of 313 patients from 4 continents and 7 countries were included, 245 of whom underwent FNAB. FNAB cytology revealed MTC in 43.7% and possible MTC in an additional 2.4%. A total of 113 (46.1%) patients with surgical pathology revealing sMTC had FNAB findings that supported TT with CND, while 37 (15.1%) supported TT alone. In the remaining cases, diagnostic hemithyroidectomy and observation were projected in 32.7% and 6.1%, respectively. FNAB is an important diagnostic tool in the evaluation of thyroid nodules, but the low sensitivity of cytological evaluation alone in sMTC limits its ability to command an optimal preoperative evaluation and initial surgery in over half of affected patients.

Pazopanib (PAZ), a tyrosine kinase inhibitor used in the treatment of soft tissue sarcoma (STS), should not be administered with acid‐suppressive medications (ASMs) due to decreased drug solubility. Common practice for patients requiring ASM with PAZ is to separate administration by 12 hours; however, there is little real‐world evidence describing clinical outcomes using this strategy. The aim of this study was to determine whether concomitant ASM impacted efficacy and adverse event rates in patients with STS receiving PAZ. Medical records were retrospectively reviewed for patients with STS who received PAZ from June 2011 to July 2017. Patients were stratified into two groups, PAZ with or without ASM (PAZ + ASM or PAZ only). The primary objective was to determine whether progression‐free survival (PFS) differed between groups. Secondary objectives were to determine overall survival (OS) and occurrence of grade 3/4 toxicities. Ninety‐one patients were included in the study, 42 patients in the PAZ + ASM group and 49 in the PAZ only group. Median PFS was significantly shorter in the PAZ + ASM group than the PAZ only group (5.3 vs. 6.7 months). The PAZ + ASM group also had a 74% higher relative risk of progression or death than the PAZ only group, but there was no difference in OS. Regarding adverse events, the PAZ + ASM group trended toward lower levels of grade 3/4 hypertension (19% vs. 37%). These results suggest that ASM should be avoided in patients with STS receiving PAZ. Larger studies are needed to further elucidate the impact of ASM use with PAZ in clinical practice.

Background 18 F‐Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) positive (PET+) cytologically indeterminate thyroid nodules (ITNs) have variable cancer risk in the literature. The benign call rate (BCR) of Afirma Gene Classifier (Gene Expression Classifier, GEC, or Genome Sequence Classifier, GSC) in (PET +) ITNs is unknown. Methods This is a retrospective study at our institution of all patients with (PET+) ITNs (Bethesda III/IV) from 1 January 2010 to 21 May 2019 who underwent Afirma testing and/or surgery or repeat FNA with benign cytology. Results Forty‐five (PET+) ITNs were identified: 31 Afirma‐tested (GEC = 20, GSC = 11) and 14 either underwent surgery (n = 13) or repeat FNA (Benign cytology) (n = 1) without Afirma. The prevalence of cancer and noninvasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP) including only resected nodules and ITN with repeat benign FNA (n = 33) was 36.4% (12/33). Excluding all Afirma “suspicious” non‐resected ITNs and assuming all Afirma “benign” ITNs were truly benign, that prevalence was 28.6% (12/42). The BCR with GSC was 64% compared to 25% with GEC (p = 0.056). Combining GSC/GEC‐tested ITNs, the BCR was higher in ITNs demonstrating low/very low‐risk sonographic pattern by the American Thyroid Association (ATA) classification and ITNs scoring <4 by the American College of Radiology Thyroid Imaging, Reporting and Data System (ACR‐TI‐RADS) than ITNs with higher sonographic pattern/score (p = 0.025). Conclusions The prevalence of cancer/NIFTP in (PET+) ITNs was 28.6–36.4% depending on the method of calculation. The BCR of Afirma GSC was 64%. Combining Afirma GEC/GSC‐tested ITNs, BCR was higher in ITNs with a lower risk sonographic pattern. In this study, the prevalence of cancer and noninvasive follicular thyroid neoplasm with papillary‐like nuclear features in PET positive cytologically indeterminate thyroid nodules was 28.6–36.4% depending on the method of calculation. The benign call rate of Afirma GSC in these nodules was 64%. When combining Afirma GEC/GSC tested PET positive cytologically indeterminate thyroid nodules, the benign call rate was higher in nodules with a lower risk sonographic pattern.

Chronic pancreatitis (CP) is a progressive disease that leads to eventual loss of endocrine and exocrine function. Total pancreatectomy and islet autotransplantation (TPIAT) is a treatment option for patients with CP; however, predicting postoperative metabolic outcomes remains elusive. In this single-center retrospective study, we report pre-TPIAT characteristics, beta cell function indices, islet yield, and post-TPIAT glucose management data to further understand their relationship. Islet yield, glucose level, and insulin requirement for 72 hours postoperatively were collected for a total of 13 TPIAT recipients between 9-2013 and 9-2018. In addition, their glucose control and basal insulin requirements at 3, 6, and 12 months post-TPIAT were analyzed. All 13 subjects had normal baseline fasting glucose levels. Median islet yield was 4882 IEq/kg (interquartile range 3412 to 8987). Median postoperative total insulin requirement on day 3 was 0.43 units/kg. Pre-TPIAT baseline glucose, insulin, or c-peptide level did not have a significant correlation with the islet yield. Similarly, there was no correlation between islet yield and insulin requirement at 72-hour postoperatively. However, there was an inverse correlation between the absolute islet yield (IEq) and insulin requirement at 6 months and 12 months following post-TPIAT. Further analysis of the relationship between 72-hour post-op insulin requirement and insulin requirement at discharge, 3, 6, and 12 months showed a positive correlation. Despite the finding of inverse correlation of islet yield with long-term basal insulin requirement, this study was not able to detect a correlation between the preoperative parameters to postoperative short-term or long-term outcome as noted in other studies. The 72-hour postoperative insulin requirement is a helpful postoperative predictor of patients needing long-term insulin management following TPIAT. This observation may identify a high-risk group of patients in need of more intensive diabetes education and insulin treatment prior to hospital discharge.

In adults undergoing screening colonoscopy, a next-generation multitarget stool DNA test had higher sensitivity for colorectal cancer and advanced precancerous lesions than a fecal immunochemical test but lower specificity.