Recombinant ADAMTS13 for Immune Thrombotic Thrombocytopenic Purpura.

In patients with immune thrombotic thrombocytopenic purpura (iTTP), autoantibodies against the metalloprotease ADAMTS13 lead to catastrophic microvascular thrombosis. However, the potential benefits of recombinant human ADAMTS13 (rADAMTS13) in patients with iTTP remain unknown. Here, we report the clinical use of rADAMTS13, which resulted in the rapid suppression of disease activity and complete recovery in a critically ill patient whose condition had proved to be refractory to all available treatments. We also show that rADAMTS13 causes immune complex formation, which saturates the autoantibody and may promote its clearance. Our data support the role of rADAMTS13 as a novel adjunctive therapy in patients with iTTP.

Cost analysis of care and blood transfusions in patients with Major Obstetric Haemorrhage in Ireland.

BACKGROUND AND OBJECTIVES: Obstetric haemorrhage is the leading cause of maternal morbidity and mortality worldwide. We aimed to estimate the economic cost of Major Obstetric Haemorrhage (MOH) and the cost of therapeutic blood components used in the management of MOH in Ireland. MATERIALS AND METHODS: We performed a nationwide cross-sectional study utilising top-down and bottom-up costing methods on women who experienced MOH during the years 2011-2013. Women with MOH were allocated to Diagnostic Related Groups (DRGs) based on the approach to MOH management (MOH group). The total number of blood components used for MOH treatment and the corresponding costs were recorded. A control group representative of a MOH-free maternity population was designed with predicted costs. All costs were expressed in Euro (€) using 2022 prices and the incremental cost of MOH to maternity costs was calculated. Cost contributions are expressed as percentages from the estimated total cost. RESULTS: A total of 447 MOH cases were suitable for sorting into DRGs. The estimated total cost of managing women who experienced MOH is approximately €3.2 million. The incremental cost of MOH is estimated as €1.87 million. The estimated total cost of blood components used in MOH management was €1.08 million and was based on an estimated total of 3997 products transfused. Red blood cell transfusions accounted for the highest contribution (20.22%) to MOH total cost estimates compared to other blood components. CONCLUSIONS: The total cost of caring for women with MOH in Ireland was approximately €3.2 million with blood component transfusions accounting for between one third and one half of the cost.

The Ideal Timing of Bilateral Total Knee Arthroplasty: Simultaneous Versus Staged.

Objectives: The ideal timing for patients undergoing bilateral total knee arthroplasty (TKA) remains unknown. The purpose of this study was to compare 90-day outcomes between unilateral, simultaneous bilateral, and staged bilateral TKA. Methods: The PearlDiver database was used to retrospectively identify 231,119 patients undergoing primary TKA during 2015-2020, of which 67,956 (29.4%) were bilateral. Bilateral TKA patients were divided into cohorts of simultaneous bilateral TKA and staged bilateral TKA at 1-14 days, 15-30 days, 31-90 days, and 91-365 days. Each bilateral TKA cohort underwent one-to-one matching with unilateral TKA patients based on age, gender, year, Elixhauser Comorbidity Index (ECI), and a history of obesity, diabetes, and tobacco use. Ninety-day outcomes were compared between matched groups via univariate and multivariate analysis. In staged bilateral TKA groups, outcomes were collected beginning after the second TKA. Results: Compared to unilateral TKA, simultaneous bilateral TKA was associated with higher rates of venous thromboembolism (VTE; odds ratio [OR] 1.28, 95% confidence interval [CI] 1.07-1.54, p=0.007), acute kidney injury (AKI; OR 1.47, CI 1.17-1.84, p=0.001), blood transfusion (OR 6.81, CI 5.43-8.65, p<0.001), and any complication (OR 1.63, CI 1.49-1.78, p<0.001). Staged bilateral TKA at any time interval studied was associated with a similar or decreased risk of individual complications, emergency department visits, readmissions, reoperations, and any complication relative to unilateral TKA. Conclusion: Simultaneous bilateral TKA is associated with an increased risk of adverse events compared to unilateral TKA. However, bilateral TKA staged at a short interval appears safe in appropriately selected patients.

Three Differing Methods of Treating Intraoperative Nondisplaced Calcar Fractures Demonstrate Similar Radiographic Stem Subsidence.

BACKGROUND: Several management strategies have been described to treat intraoperative calcar fractures during total hip arthroplasty (THA), including retaining the primary implant and utilizing cerclage cables (CCs) or switching the implant to one that bypasses the fracture and achieves diaphyseal fixation. However, the radiographic and clinical outcomes of these differing strategies have never been described and compared. METHODS: We retrospectively identified 50 patients who sustained an intraoperative calcar fracture out of 9,129 primary total hip arthroplasties (0.55%) performed by one of three surgeons between 2008 and 2022. Each of the three surgeons consistently employed a distinct strategy for the management of these fractures: retention of the primary metaphyseal-engaging implant and placement of CCs; exchange to a modular, tapered-fluted stem (MTF); or exchange to a fully-coated, diaphyseal-engaging stem (FC). Stem subsidence was then evaluated on standing anteroposterior pelvis radiographs at three months and one year postoperatively. Postoperative medical and surgical complication rates were evaluated. RESULTS: A total of fifteen patients were treated with CC, 15 with MTF, and 20 with FC. At three-month follow-up, mean stem subsidence was 0.43 ± 0.08 mm, 1.47 ± 0.36 mm, and 0.68 ± 0.39 mm for CC, MTF, and FC cohorts, respectively (P = .323). At one-year, mean stem subsidence was 0.70 ± 0.08 mm, 1.74 ± 0.69 mm, and 1.88 ± 0.90 mm for the CC, MTF, and FC cohorts, respectively (P = .485). Medical complications included 2 venous thromboembolic events (4%) within 90 days of surgery. There were 6 reoperations (12%); 3 (6%) for acute periprosthetic joint infection (all within the FC cohort); 2 (4%) for postoperative periprosthetic fractures (one fracture distal to the stem in the FC cohort and one fracture at the level of the stem in the MTF cohort), and 1 (2%) closed reduction for instability (within the CC cohort). CONCLUSIONS: The three described methods of managing intraoperative nondisplaced calcar fractures demonstrated little radiographic stem subsidence; however, the risk of reoperation was much higher than expected.

Estimating Glycemia From HbA1c and CGM: Analysis of Accuracy and Sources of Discrepancy.

OBJECTIVE: To examine the accuracy of different periods of continuous glucose monitoring (CGM), hemoglobin A1c (HbA1c), and their combination for estimating mean glycemia over 90 days (AG90). RESEARCH DESIGN AND METHODS: We retrospectively studied 985 CGM periods of 90 days with <10% missing data from 315 adults (86% of whom had type 1 diabetes) with paired HbA1c measurements. The impact of mean red blood cell age as a proxy for nonglycemic effects on HbA1c was estimated using published theoretical models and in comparison with empirical data. Given the lack of a gold standard measurement for AG90, we applied correction methods to generate a reference (eAG90) that we used to assess accuracy for HbA1c and CGM. RESULTS: Using 14 days of CGM at the end of the 90-day period resulted in a mean absolute error (95th percentile) of 14 (34) mg/dL when compared with eAG90. Nonglycemic effects on HbA1c led to a mean absolute error for average glucose calculated from HbA1c of 12 (29) mg/dL. Combining 14 days of CGM with HbA1c reduced the error to 10 (26) mg/dL. Mismatches between CGM and HbA1c >40 mg/dL occurred more than 5% of the time. CONCLUSIONS: The accuracy of estimates of eAG90 from limited periods of CGM can be improved by averaging with an HbA1c-based estimate or extending the monitoring period beyond ∼26 days. Large mismatches between eAG90 estimated from CGM and HbA1c are not unusual and may persist due to stable nonglycemic factors.

Hematologic setpoints are a stable and patient-specific deep phenotype.

The complete blood count is an important screening tool for healthy adults and is the most commonly ordered test at periodic physical exams. However, results are usually interpreted relative to one-size-fits-all reference intervals, undermining the goal of precision medicine to tailor medical care to the needs of individual patients based on their unique characteristics. Here we show that standard complete blood count indices in healthy adults have robust homeostatic setpoints that are patient-specific and stable, with the typical healthy adult's set of 9 blood count setpoints distinguishable from 98% of others, and with these differences persisting for decades. These setpoints reflect a deep physiologic phenotype, enabling improved detection of both acquired and genetic determinants of hematologic regulation, including discovery of multiple novel loci via GWAS analyses. Patient-specific reference intervals derived from setpoints enable more accurate personalized risk assessment, and the setpoints themselves are significantly correlated with mortality risk, providing new opportunities to enhance patient-specific screening and early intervention. This study shows complete blood count setpoints are sufficiently stable and patient-specific to help realize the promise of precision medicine for healthy adults.

Genetic reversal of the globin switch concurrently modulates both fetal and sickle hemoglobin and reduces red cell sickling.

We previously reported initial clinical results of post-transcriptional gene silencing of BCL11A expression (NCT03282656) reversing the fetal to adult hemoglobin switch. A goal of this approach is to increase fetal hemoglobin (HbF) expression while coordinately reducing sickle hemoglobin (HbS) expression. The resulting combinatorial effect should prove effective in inhibiting HbS polymerization at lower physiologic oxygen values thereby mitigating disease complications. Here we report results of exploratory single-cell analysis of patients in which BCL11A is targeted molecularly and compare results with cells of patients treated with hydroxyurea (HU), the current standard of care. We use single-cell assays to assess HbF, HbS, oxygen saturation, and hemoglobin polymer content in RBCs for nine gene therapy trial subjects (BCLshmiR, median HbF% = 27.9) and compare them to 10 HU-treated subjects demonstrating high and comparable levels of HbF (HU High Responders, median HbF% = 27.0). All BCL11A patients achieved the primary endpoint for NCT03282656, which was defined by an absolute neutrophil count greater than or equal to 0.5 × 109 cells/L for three consecutive days, achieved within 7 weeks following infusion. Flow cytometric assessment of single-RBC HbF and HbS shows fewer RBCs with high HbS% that would be most susceptible to sickling in BCLshmiR vs. HU High Responders: median 42% of RBCs with HbS%>70% in BCLshmiR vs. 61% in HU High Responders (p = 0.004). BCLshmiR subjects also demonstrate more RBCs resistant to HbS polymerization at lower physiologic oxygen tension: median 32% vs. 25% in HU High Responders (p = 0.006). Gene therapy-induced BCL11A down-regulation reverses the fetal-to-adult hemoglobin switch and induces RBCs with higher HbF%, lower HbS%, and greater resistance to deoxygenation-induced polymerization in clinical trial subjects compared with a cohort of highly responsive hydroxyurea-treated subjects.

Chloroplast magnesium transporters play essential but differential roles in maintaining magnesium homeostasis.

Magnesium (Mg2+) is essential for photosynthesis in the chloroplasts of land plants and algae. Being the central ion of chlorophyll, cofactor and activator of many photosynthetic enzymes including RuBisCO, magnesium-deficient plants may suffer from leaf chlorosis symptoms and retarded growth. Therefore, the chloroplast Mg2+ concentration is tightly controlled by magnesium transport proteins. Recently, three different transporters from two distinct families have been identified in the chloroplast inner envelope of the model plant Arabidopsis thaliana: MGT10, MGR8, and MGR9. Here, we assess the individual roles of these three proteins in maintaining chloroplast Mg2+ homeostasis and regulating photosynthesis, and if their role is conserved in the model green alga Chlamydomonas reinhardtii. Phylogenetic analysis and heterologous expression revealed that the CorC-like MGR8 and MGR9 transport Mg2+ by a different mechanism than the CorA-like MGT10. MGR8 and MGT10 genes are highest expressed in leaves, indicating a function in chloroplast Mg2+ transport. MGR9 is important for chloroplast function and plant adaptation in conditions of deficiency or excess of Mg2+. Transmission electron microscopy indicated that MGT10 plays a differential role in thylakoid stacking than MGR8 and MGR9. Furthermore, we report that MGR8, MGR9, and MGT10 are involved in building up the pH gradient across the thylakoid membrane and activating photoprotection in conditions of excess light, however the mechanism has not been resolved yet. While there are no chloroplast MGR-like transporters in Chlamydomonas, we show that MRS4 is a homolog of MGT10, that is required for photosynthesis and cell growth. Taken together, our findings reveal that the studied Mg2+ transporters play essential but differential roles in maintaining chloroplast Mg2+ homeostasis.

A targeted liquid chromatography mass spectrometry method for routine monitoring of cell culture media components for bioprocess development.

The analysis of cell culture media (CCM) components is critical for understanding cell growth kinetics and overall product quality during biomanufacturing. Given the diverse physical and chemical nature of CCM compounds present at a wide range of concentrations, there is an increasing demand for single-platform analytical assays with exceptional specificity and sensitivity. This study presents a targeted LC-MS/MS method for the identification and quantitation of 110 CCM analytes is presented, where target metabolites are monitored over an 20-min gradient. The analyte panel constitutes amino acids, vitamins, organic acids, nucleic acids, carbohydrates, and lipids. The method employs isotopically labeled standards to enable specific and accurate relative quantitation of CCM compounds based on physicochemical properties and retention time. Quantitation is performed on a triple quadrupole mass spectrometer operated in multiple reaction monitoring (MRM) mode. The method demonstrates strong linearity with an R2 of ≥0.99 with three orders of linear dynamic range and inter-day and intra-day precision with a%CV of <10% for spiked-in quality control samples. We also present three case studies to demonstrate method applicability in the bioprocessing space for developing vaccines and biologics.

Computer vision quantitation of erythrocyte shape abnormalities provides diagnostic, prognostic, and mechanistic insight.

Examination of red blood cell (RBC) morphology in peripheral blood smears can help diagnose hematologic diseases, even in resource-limited settings, but this analysis remains subjective and semiquantitative with low throughput. Prior attempts to develop automated tools have been hampered by their poor reproducibility and limited clinical validation. Here, we present a novel, open-source machine-learning approach (denoted as RBC-diff) to quantify abnormal RBCs in peripheral smear images and generate an RBC morphology differential. RBC-diff cell counts showed high accuracy for single-cell classification (mean AUC, 0.93) and quantitation across smears (mean R2, 0.76 compared with experts, interexperts R2, 0.75). RBC-diff counts were concordant with the clinical morphology grading for 300 000+ images and recovered the expected pathophysiologic signals in diverse clinical cohorts. Criteria using RBC-diff counts distinguished thrombotic thrombocytopenic purpura and hemolytic uremic syndrome from other thrombotic microangiopathies, providing greater specificity than clinical morphology grading (72% vs 41%; P < .001) while maintaining high sensitivity (94% to 100%). Elevated RBC-diff schistocyte counts were associated with increased 6-month all-cause mortality in a cohort of 58 950 inpatients (9.5% mortality for schist. >1%, vs 4.7% for schist; <0.5%; P < .001) after controlling for comorbidities, demographics, clinical morphology grading, and blood count indices. RBC-diff also enabled the estimation of single-cell volume-morphology distributions, providing insight into the influence of morphology on routine blood count measures. Our codebase and expert-annotated images are included here to spur further advancement. These results illustrate that computer vision can enable rapid and accurate quantitation of RBC morphology, which may provide value in both clinical and research contexts.

Invasive Gastrointestinal Endoscopy Following Total Joint Arthroplasty Increases the Risk for Periprosthetic Joint Infection.

BACKGROUND: The safety of postoperative colonoscopy and endoscopy following total joint arthroplasty (TJA) remains largely unknown. The objective of this study was to characterize the effect of gastrointestinal endoscopic procedures after TJA on the risk of postoperative periprosthetic joint infection (PJI). METHODS: Using a large national database, patients who underwent an endoscopic procedure (colonoscopy or esophagogastroduodenoscopy (EGD)) within 12 months after primary TJA were identified and matched in a 1:1 fashion based on procedure (primary total knee arthroplasty (TKA) versus total hip arthroplasty (THA)), age, sex, Charlson Comorbidity Index (CCI), and smoking status with patients who did not undergo endoscopy. A total of 142,055 patients who underwent endoscopy within 12 months following TJA (96,804 TKAs and 45,251 THAs) were identified and matched. The impact of timing of endoscopy relative to TJA on postoperative outcomes was assessed. Preoperative comorbidity profiles and 1-year complications were compared. Statistical analyses included Chi-squared tests and multivariate logistic regressions with outcomes considered significant at P < .05. RESULTS: Multivariate analyses revealed that endoscopy within 2 months following TKA and 1 month of THA was associated with a significantly increased odds of periprosthetic joint infection (odds ratio (OR): 1.29 [1.08-1.53]; P = .004; OR: 1.41 [1.01-1.90]; P = .033, respectively). Patients who underwent endoscopy greater than 2 months from the timing of their TKA and 1 month from THA were not at significantly greater risk of developing PJI. CONCLUSION: These data suggest that invasive endoscopic procedures should be delayed if possible by at least 2 months following TKA and 1 month following THA to minimize the risk of PJI.

Outpatient Total Knee Arthroplasty Shows Decreasing Complication Burden From 2010 to 2020.

BACKGROUND: The number of total knee arthroplasties (TKAs) performed on an outpatient basis continues to increase. The purpose of this study was to compare complication rates over the last decade to evaluate trends in the safety of outpatient TKA. METHODS: Patients who underwent TKA from 2010 to 2020 from a large administrative claims database were retrospectively identified and stratified based on the year of surgery. Propensity-score matching was performed to match patients who were discharged within 24 hours of surgery to inpatients based on age, sex, comorbidity index, and year of surgery. Linear regression analyses were used to compare trends from 2010 to 2020. The 90-day adverse events in the early cohort (2010-2012) were compared to those in the late cohort (2018-2020) using multivariable regression analyses. Of the 547,137 patients in the sample, 28,951 outpatients (5.3%) were propensity matched to inpatients. RESULTS: The incidence of outpatient TKA increased from 2010 to 2018 (1.9 versus 13.8%, P < .001). Despite a similar complication rate early (24.1 versus 22.6%, P = .164), outpatient TKA had fewer complications at the end of the study period (13.7 versus 16.7%, P < .001). Multivariate analyses demonstrated that the risk of any complication after outpatient TKA was lower than inpatient from 2018 to 2020 (odds ratio, 0.78; 95% confidence interval, 0.71-0.84). CONCLUSIONS: Complications in both cohorts declined dramatically suggesting improvements in quality of care over time, with the greatest decline in patients undergoing outpatient surgery. These results suggest that outpatient TKA today is not higher risk for the patient than inpatient TKA. LEVEL OF EVIDENCE: Level III.

Structural features stabilized by divalent cation coordination within hepatitis E virus ORF1 are critical for viral replication.

Hepatitis E virus (HEV) is an RNA virus responsible for over 20 million infections annually. HEV's open reading frame (ORF)1 polyprotein is essential for genome replication, though it is unknown how the different subdomains function within a structural context. Our data show that ORF1 operates as a multifunctional protein, which is not subject to proteolytic processing. Supporting this model, scanning mutagenesis performed on the putative papain-like cysteine protease (pPCP) domain revealed six cysteines essential for viral replication. Our data are consistent with their role in divalent metal ion coordination, which governs local and interdomain interactions that are critical for the overall structure of ORF1; furthermore, the 'pPCP' domain can only rescue viral genome replication in trans when expressed in the context of the full-length ORF1 protein but not as an individual subdomain. Taken together, our work provides a comprehensive model of the structure and function of HEV ORF1.

Microfluidic study of retention and elimination of abnormal red blood cells by human spleen with implications for sickle cell disease.

The spleen clears altered red blood cells (RBCs) from circulation, contributing to the balance between RBC formation (erythropoiesis) and removal. The splenic RBC retention and elimination occur predominantly in open circulation where RBCs flow through macrophages and inter-endothelial slits (IESs). The mechanisms underlying and interconnecting these processes significantly impact clinical outcomes. In sickle cell disease (SCD), blockage of intrasplenic sickled RBCs is observed in infants splenectomized due to acute splenic sequestration crisis (ASSC). This life-threatening RBC pooling and organ swelling event is plausibly triggered or enhanced by intra-tissular hypoxia. We present an oxygen-mediated spleen-on-a-chip platform for in vitro investigations of the homeostatic balance in the spleen. To demonstrate and validate the benefits of this general microfluidic platform, we focus on SCD and study the effects of hypoxia on splenic RBC retention and elimination. We observe that RBC retention by IESs and RBC-macrophage adhesion are faster in blood samples from SCD patients than those from healthy subjects. This difference is markedly exacerbated under hypoxia. Moreover, the sickled RBCs under hypoxia show distinctly different phagocytosis processes from those non-sickled RBCs under hypoxia or normoxia. We find that reoxygenation significantly alleviates RBC retention at IESs, and leads to rapid unsickling and fragmentation of the ingested sickled RBCs inside macrophages. These results provide unique mechanistic insights into how the spleen maintains its homeostatic balance between splenic RBC retention and elimination, and shed light on how disruptions in this balance could lead to anemia, splenomegaly, and ASSC in SCD and possible clinical manifestations in other hematologic diseases.

Development and validation of LC-MS/MS method for quantification of protease inhibitor Pepstatin A to monitor its robust clearance in vaccine downstream process.

Pepstatin A reversibly inhibits aspartic acid proteases and minimizes the impact of protease-induced degradation in recombinant protein manufacturing process. Pepstatin A is considered as a process-related impurity and must be characterized and controlled during manufacturing. Herein we describe the development and validation of an LC-MS/MS method for the quantitation of pepstatin A to monitor its robust clearance in vaccine purification process. Analyte extraction from process intermediates was carried out using 10% acetonitrile/water extraction method. Acetyl-pepstatin was used as internal standard (IS). Pepstatin A and IS were resolved on a C18 column using 10 mM ammonium acetate in water and methanol/acetonitrile mobile phase system. A triple quadrupole mass spectrometer operating in the positive electrospray ionization mode with multiple reaction monitoring was used to detect Pepstatin A and IS transitions of m/z 686.5 to 229.3 and 644.5 to 229.3, respectively. The method was validated for specificity, linearity, accuracy, repeatability (precision), intermediate precision, and assay robustness. The assay was linear over the range of calibration standards 0.5-100 ng/mL. The Lower-limit-of-quantification (LLOQ) of the method was 0.50 ng/mL.

The Effects of Daily Prednisone and Tocilizumab on Hemoglobin A1c During the Treatment of Giant Cell Arteritis.

OBJECTIVE: To study the longitudinal effects of both glucocorticoids and tocilizumab, an interleukin-6 receptor inhibitor, on hemoglobin A1c (HbA1c ) levels during glucocorticoid tapering. METHODS: We analyzed patients with complete data from the Giant Cell Arteritis Clinical Research Study (GiACTA) to investigate the impact of both glycemic and nonglycemic factors on changes in HbA1c levels over the 52-week trial. Giant cell arteritis (GCA) patients were randomized to receive either tocilizumab or placebo in addition to glucocorticoids. We used a multivariable mixed-effects model to evaluate associations of HbA1c level with daily glucocorticoid dose, randomization to receive tocilizumab, and red blood cell count in patients with and those without diabetes mellitus at baseline, over 52 weeks. RESULTS: In 209 patients, the median HbA1c level decreased by 0.50% (P < 0.01) in the group that received both tocilizumab and glucocorticoids (tocilizumab/glucocorticoid) and by 0.10% (P < 0.01) in the glucocorticoid-only group. Randomization to tocilizumab/glucocorticoid was associated with lower HbA1c (ß = -0.209% in those without diabetes, P < 0.01; ß = -0.290% in those with diabetes, P = 0.23). These changes had a sizable impact on glucose tolerance classification: 42.5% of patients in the tocilizumab/glucocorticoid group improved from prediabetes status to normal, compared to only 12.5% of patients treated with glucocorticoids alone. Daily glucocorticoid dose was associated with HbA1c level in patients with baseline diabetes (ß = 0.018%/mg, P < 0.01) and those without baseline diabetes (ß = 0.005%/mg, P < 0.01). CONCLUSION: Tocilizumab treatment was associated with a substantial reduction in HbA1c level, independent of glucocorticoid exposure, which may be achieved through a combination of glycemic and nonglycemic effects.

The Effect of Segmentation Threshold on Computational Fluid Dynamic Analysis of Nasal Airflow.

BACKGROUND: The objective analysis of nasal airflow stands to benefit greatly from the adoption of computational fluid dynamic (CFD) methodologies. In this emerging field, no standards currently exist in regard to the ideal modeling parameters of the nasal airway. Such standards will be necessary for this tool to become clinically relevant. METHODS: Human nasal airways were modeled from a healthy control, segmented, and analyzed with an in-house immersed boundary method. The segmentation Hounsfield unit (HU) threshold was varied to measure its effect in relation to airflow velocity magnitude and pressure change. FINDINGS: Surface area and volume have a linear relationship to HU threshold, whereas CFD variables had a more complex relationship. INTERPRETATION: The HU threshold should be included in nasal airflow CFD analysis. Future work is required to determine the optimal segmentation threshold.

Ten Traits of Great Physicians! And Tips to Help You Improve.

There are certain traits that differentiate great doctors from good doctors. This article will discuss some of these traits along with tips you can incorporate to go from good to great. By applying these tips, I hope you will enhance your ability to practice medicine and improve your patients' experience.