Machine Learning-based Development and Validation of a Scoring System for Screening High-Risk Esophageal Varices.

BACKGROUND & AIMS: Many patients with cirrhosis who undergo esophagogastroduodenoscopy (EGD) screening for esophageal varices (EVs) are found to have no or only small EVs. Endoscopic screening for EVs is therefore a potentially deferrable procedure that increases patient risk and healthcare cost. We developed and validated a scoring system, based on readily-available data, to reliably identify patients with EVs that need treatment. METHODS: We collected data from 238 patients with cirrhosis undergoing screening EGD from January 2016 through December 2017 at 3 separate hospitals in Los Angeles (training cohort). We abstracted data on patient sex, age, race/ethnicity, platelet counts, and levels of hemoglobin, serum sodium, aspartate aminotransferase, alanine aminotransferase, total bilirubin, international normalized ratio, albumin, urea nitrogen, and creatinine. We also included etiology of cirrhosis, presence of ascites, and presence of hepatic encephalopathy. We used a random forest algorithm to identify factors significantly associated with the presence of EVs and varices needing treatment (VNT) and calculated area under the receiver operating characteristic curve (AUROC). We called the resulting formula the EVendo score. We tested the accuracy of EVendo in a prospective study of 109 patients undergoing screening EGDs at the same medical centers from January 2018 through December 2018 (validation cohort). RESULTS: We developed an algorithm that identified patients with EVs and VNT based on international normalized ratio, level of aspartate aminotransferase, platelet counts, urea nitrogen, hemoglobin, and presence of ascites. The EVendo score identified patients with EVs in the training set with an AUROC of 0.84, patients with EVs in the validation set with and AUROC of 0.82, and EVs in patients with cirrhosis Child-Turcotte-Pugh class A (n = 235) with an AUROC of 0.81. The score identified patients with VNT in the training set with an AUROC of 0.74, VNT in the validation set with and AUROC of 0.75, and VNT in patients with cirrhosis Child-Turcotte-Pugh class A with and AUROC of 0.75. An EVendo score below 3.90 would have spared 30.5% patients from EGDs, missing only 2.8% of VNT. The same cutoff would have spared 40.0% of patients with Child-Turcotte-Pugh class A cirrhosis from EGDs, missing only 1.1% of VNT. CONCLUSIONS: We algorithmically developed a formula, called the EVendo score, that can be used to predict EVs and VNT based on readily available data in patients with cirrhosis. This score could help patients at low risk for VNT avoid unnecessary EGDs.

Three-dimensional carbon interdigitated electrode arrays for redox-amplification.

Three-dimensional (3D) carbon interdigitated electrode arrays (IDEAs) were fabricated using inexpensive, conventional, UV photolithography of SU-8 with modified exposure and post exposure bake settings followed by pyrolysis in an inert environment. The sensor performance was investigated as a function of both the IDEA digit width/gap ratio and digit height under flow and no flow conditions. We demonstrated a gradual increase in redox amplification with an increase in the IDEA digit width/gap ratio. The highest amplification of 37 was obtained for a width/gap ratio of 1.58 and for an electrode height of 1.1 µm. Redox amplification also increases significantly with an increase in the IDEA height, from a factor of 9 at a 0.22 µm digit height to a factor of 37 at a 1.1 µm height. The effect of potential sweep rates on redox amplification was also investigated. As the sweep rate was decreased from 50 mV/s to 5 mV/s, the collection efficiency increased from 0.92 to 0.97, whereas the amplification increased from 7 to 25. Under flow conditions, the amplification decreases substantially as the cycling of the redox species is impeded by convection, resulting in a drop in collection efficiency. The highest amplification of 37 dropped to 4 for the same electrode at a flow rate of 500 nL/s. Under flow, redox amplification increased with an increase in the IDEA height.

Aptamer-enabled efficient isolation of cancer cells from whole blood using a microfluidic device.

Circulating tumor cells (CTC) in the peripheral blood could provide important information for diagnosis of cancer metastasis and monitoring treatment progress. However, CTC are extremely rare in the bloodstream, making their detection and characterization technically challenging. We report here the development of an aptamer-mediated, micropillar-based microfluidic device that is able to efficiently isolate tumor cells from unprocessed whole blood. High-affinity aptamers were used as an alternative to antibodies for cancer cell isolation. The microscope-slide-sized device consists of >59,000 micropillars, which enhanced the probability of the interactions between aptamers and target cancer cells. The device geometry and the flow rate were investigated and optimized by studying their effects on the isolation of target leukemia cells from a cell mixture. The device yielded a capture efficiency of ~95% with purity of ~81% at the optimum flow rate of 600 nL/s. Further, we exploited the device for isolating colorectal tumor cells from unprocessed whole blood; as few as 10 tumor cells were captured from 1 mL of whole blood. We also addressed the question of low throughput of a typical microfluidic device by processing 1 mL of blood within 28 min. In addition, we found that ~93% of the captured cells were viable, making them suitable for subsequent molecular and cellular studies.

HIV Treatment with the Two-Drug Regimen Dolutegravir Plus Lamivudine in Real-world Clinical Practice: A Systematic Literature Review.

The two-drug regimen dolutegravir plus lamivudine demonstrated durable efficacy for up to 3 years in phase III studies and a high barrier to resistance in treatment-naive and virologically suppressed people with HIV (PWH). This systematic literature review summarizes real-world evidence evaluating effectiveness and safety of dolutegravir plus lamivudine. We searched Ovid MEDLINE®, Embase®, PubMed, Cochrane library, and relevant international conference proceedings from 2013 to 2020. Qualitative synthesis of virologic suppression at Week 48, treatment-emergent resistance, discontinuation rates, and comorbidities was undertaken, with no statistical analyses conducted. Linked publications and potential for duplication in reporting of outcomes for cohorts and populations were identified, and the publication reporting the highest number of PWH receiving dolutegravir plus lamivudine was included in the analysis. Thirty-four studies reporting on cohorts of PWH not suspected to be linked or to include duplicate data receiving dolutegravir plus lamivudine were identified (N = 5017). Of 3744 virologically suppressed PWH who switched to dolutegravir plus lamivudine, 603 (16%) reported history of virologic failure. Nineteen studies included effectiveness data (n = 3558), four of which included data from treatment-naive PWH (n = 69). In studies with > 100 PWH, high rates of virologic suppression (Week 48, 97-100%) were maintained with dolutegravir plus lamivudine, with low rates of virologic failure (0-3.3 per 100 person-years of follow-up); one instance of emergent integrase strand transfer inhibitor resistance was reported in a complex treatment-experienced individual. Rates of discontinuation due to adverse events were low and consistent with previously observed trial data. Dolutegravir plus lamivudine minimally impacted renal function and had minimal impact on or improved lipid profiles and bone mineral density. This systematic review demonstrates that effectiveness and safety of dolutegravir plus lamivudine in clinical practice support data from randomized controlled trials with regard to high rates of virologic response, low rates of discontinuation, and a high barrier to resistance.

Guidelines vs Actual Management of Skin and Soft Tissue Infections in the Emergency Department.

BACKGROUND: Infections of skin and soft tissue (SSTI) commonly cause visits to hospital emergency departments (EDs). The Infectious Diseases Society of America (IDSA) has published guidelines for the management of SSTI, but it is unclear how closely these guidelines are followed in practice. METHODS: We reviewed records of patients seen in the ED at a large tertiary care hospital to determine guidelines adherence in 4 important areas: the decision to hospitalize, choice of antibiotics, incision and drainage (I&D) of abscesses, and submission of specimens for culture. RESULTS: The decision to hospitalize did not comply with guidelines in 19.6% of cases. Nonrecommended antibiotics were begun in the ED in 71% of patients with nonpurulent infections and 68.4% of patients with purulent infections. Abscesses of mild severity were almost always treated with antibiotics, and I&D was often not done (both against recommendations). Blood cultures were done (against recommendations) in 29% of patients with mild-severity cellulitis. Abscess drainage was almost always sent for culture (recommendations neither favor nor oppose). Overall, treatment fully complied with guidelines in 20.1% of cases. CONCLUSIONS: Our results show a striking lack of concordance with IDSA guidelines in the ED management of SSTI. Social factors may account for discordant decisions regarding site of care. Use of trimethoprim/sulfamethoxazole (TMP/SMX) in cellulitis was the most common source of discordance; this practice is supported by some medical literature. Excess antibiotics were often used in cellulitis and after I&D of simple abscesses, opposing antibiotic stewardship. Ongoing education of ED doctors and continued review of published guidelines are needed.

Functional Capacity Evaluation Following Spinal Fusion Surgery.

STUDY DESIGN: Retrospective review of prospectively collected data. OBJECTIVE: The aim of the study was to characterize outcomes of functional capacity evaluations (FCEs) amongst patients undergoing spinal fusion surgery. SUMMARY OF BACKGROUND DATA: Injured workers often undergo an FCE upon reaching maximal medical improvement following surgery. To date, few studies have examined the results of FCEs following spinal fusion. METHODS: Patients undergoing an FCE following a minimally invasive transforaminal lumbar interbody fusion (TLIF) or anterior cervical discectomy and fusion (ACDF) were retrospectively identified. Based upon the FCE report, each patient's job-related preoperative physical requirement and postoperative work capability was categorized as light, medium, or heavy. Patients were characterized as being able to meet their preoperative job requirement if their FCE-determined capability was greater than or equal to their preoperative job requirement. Patient characteristics were tested for association with meeting preoperative job requirement using bivariate and multivariate regression. RESULTS: A total of 173 patients were identified: 71 (41.0%) and 102 (59.0%) underwent TLIF and ACDF, respectively. Of the 71 TLIF and 102 ACDF patients, 41 (58%) and 50 (49%) had light postoperative capabilities, 18 (25%) and 38 (37%) as medium, and 12 (17%) and 14 (14%) as heavy, respectively. Postoperatively, 26 (37%) of TLIF and 55 (54%) of ACDF patients were categorized as meeting their preoperative job requirement. Independent predictors of meeting preoperative job requirement following TLIF (P =0.002) and ACDF (P = 0.037) were lower preoperative job requirement, and younger age for ACDF (P < 0.001). CONCLUSION: Only one in five patients undergoing spinal fusion surgery for occupational injuries is able to perform heavy-duty work postoperatively. Similarly, approximately half of patients are able to perform medium-duty work. Moreover, a majority of patients are unable to return to their preoperative occupational responsibilities. These findings can be used to council patients regarding their likelihood of meeting postoperative work capacity. LEVEL OF EVIDENCE: 3.