Comparison of the effects of normothermic machine perfusion and cold storage preservation on porcine intestinal allograft regenerative potential and viability.

Intestinal transplantation (IT) is the final treatment option for intestinal failure. Static cold storage (CS) is the standard preservation method used for intestinal allografts. However, CS and subsequent transplantation induce ischemia-reperfusion injury (IRI). Severe IRI impairs epithelial barrier function, including loss of intestinal stem cells (ISC), critical to epithelial regeneration. Normothermic machine perfusion (NMP) preservation of kidney and liver allografts minimizes CS-associated IRI; however, it has not been used clinically for IT. We hypothesized that intestine NMP would induce less epithelial injury and better protect the intestine's regenerative ability when compared with CS. Full-length porcine jejunum and ileum were procured, stored at 4 °C, or perfused at 34 °C for 6 hours (T6), and transplanted. Histology was assessed following procurement (T0), T6, and 1 hour after reperfusion. Real-time quantitative reverse transcription polymerase chain reaction, immunofluorescence, and crypt culture measured ISC viability and proliferative potential. A greater number of NMP-preserved intestine recipients survived posttransplant, which correlated with significantly decreased tissue injury following 1-hour reperfusion in NMP compared with CS samples. Additionally, ISC gene expression, spheroid area, and cellular proliferation were significantly increased in NMP-T6 compared with CS-T6 intestine. NMP appears to reduce IRI and improve graft regeneration with improved ISC viability and proliferation.

Exposure to Environmental Pesticides and the Risk of Autism Spectrum Disorders: A Population-Based Case-Control Study.

Background and Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by challenges in communication, social interactions, and repetitive behaviors. Although the factors that influence the development of this condition are unknown, certain chemical compounds such as pesticides have been proposed as possible contributors. Due to the lack of an established causal link between pesticide exposure and ASD, this study aimed to evaluate this potential association. Materials and Methods: A case-control study was carried out to ascertain the prevalence and risk associated with ASD in relation to pesticide exposure over a 21-year study period (2000-2021). Results: We included 2821 individuals diagnosed with ASD residing in areas of both high and low pesticide exposure in southern Spain. There was a rise in the ASD prevalence rate in regions with elevated pesticide use when compared to regions with low use [odds ratio (OR): 1.34, 95% confidence interval (CI), (1.24-1.44)]. Notably, men had the highest likelihood, with an OR: 1.42, 95% CI, (1.30-1.55). Furthermore, after performing multiple binary logistic regression adjusted for age, sex, and geographical area, males exhibited a higher likelihood compared to females [OR: 2.41, 95% CI, (2.21-2.62)]. Conclusions: Overall, this research suggests a connection between heightened environmental pesticide exposure due to increased agricultural use and autism.

BAFF promotes heightened BCR responsiveness and manifestations of chronic GVHD after allogeneic stem cell transplantation.

Patients with chronic graft-versus-host disease (cGVHD) have increased B cell-activating factor (BAFF) levels, but whether BAFF promotes disease after allogeneic bone marrow transplantation (allo-BMT) remains unknown. In a major histocompatibility complex-mismatched model with cGVHD-like manifestations, we first examined B-lymphopenic µMT allo-BMT recipients and found that increased BAFF levels in cGVHD mice were not merely a reflection of B-cell number. Mice that later developed cGVHD had significantly increased numbers of recipient fibroblastic reticular cells with higher BAFF transcript levels. Increased BAFF production by donor cells also likely contributed to cGVHD, because BAFF transcript in CD4+ T cells from diseased mice and patients was increased. cGVHD manifestations in mice were associated with high BAFF/B-cell ratios and persistence of B-cell receptor (BCR)-activated B cells in peripheral blood and lesional tissue. By employing BAFF transgenic (Tg) mice donor cells, we addressed whether high BAFF contributed to BCR activation in cGVHD. BAFF increased NOTCH2 expression on B cells, augmenting BCR responsiveness to surrogate antigen and NOTCH ligand. BAFF Tg B cells had significantly increased protein levels of the proximal BCR signaling molecule SYK, and high SYK protein was maintained by BAFF after in vitro BCR activation or when alloantigen was present in vivo. Using T cell-depleted (BM only) BAFF Tg donors, we found that BAFF promoted cGVHD manifestations, circulating GL7+ B cells, and alloantibody production. We demonstrate that pathologic production of BAFF promotes an altered B-cell compartment and augments BCR responsiveness. Our findings compel studies of therapeutic targeting of BAFF and BCR pathways in patients with cGVHD.

Tumor necrosis is an underappreciated histopathologic factor in the grading of chondrosarcoma.

BACKGROUND: Cartilaginous neoplasms can be challenging to grade; there is a need to create an evidence-based rubric for grading. The goal of this study was to identify histopathologic features of chondrosarcoma that were associated with 5-year survival and to compare these to traditional patient, tumor and treatment variables. METHODS: This was a retrospective review of all patients undergoing surgical resection of a primary chondrosarcoma with at least 2 years of follow up. All specimens were independently reviewed by two pathologists and histopathologic features scored. Univariate and multivariate analyses were performed utilizing Kaplan Meier and proportional hazards methods to identify variables associated with 5-year disease specific survival (DSS) and disease free survival (DFS). RESULTS: We identified 51 patients with an average follow up of 49 months eligible for inclusion. 30% of tumors were low grade, 45% were intermediate grade, and 25% were high grade. In a univariate analysis considering histopathologic factors, higher tumor mitotic rate (HR 8.9, p < 0.001), tumor dedifferentiation (HR 7.3, p < 0.001), increased tumor cellularity (HR 5.8, p = 0.001), increased tumor atypia (HR 5.8, p = 0.001), LVI (HR 4.7, p = 0.04) and higher tumor necrosis (HR 3.7, p = 0.02) were all associated with worse 5-year DSS. In a multivariate analysis controlling for potentially confounding variables, higher tumor necrosis was significantly associated with disease specific survival survival (HR 3.58, p = 0.035); none of the factors were associated with DFS. CONCLUSIONS: This study provides an evidence-based means for considering histopathologic markers and their association with prognosis in chondrosarcoma. Our findings suggest that necrosis and LVI warrant further study.

Comparing Survival Outcomes of Patients With LI-RADS-M Hepatocellular Carcinomas and Intrahepatic Cholangiocarcinomas.

BACKGROUND: There is a sparsity of data evaluating outcomes of patients with Liver Imaging Reporting and Data System (LI-RADS) (LR)-M lesions. PURPOSE: To compare overall survival (OS) and progression free survival (PFS) between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) meeting LR-M criteria and to evaluate factors associated with prognosis. STUDY TYPE: Retrospective. SUBJECTS: Patients at risk for HCC with at least one LR-M lesion with histologic diagnosis, from 8 academic centers, yielding 120 patients with 120 LR-M lesions (84 men [mean age 62 years] and 36 women [mean age 66 years]). FIELD STRENGTH/SEQUENCE: A 1.5 and 3.0 T/3D T1 -weighted gradient echo, T2 -weighted fast spin-echo. ASSESSMENT: The imaging categorization of each lesion as LR-M was made clinically by a single radiologist at each site and patient outcome measures were collected. STATISTICAL TESTS: OS, PFS, and potential independent predictors were evaluated by Kaplan-Meier method, log-rank test, and Cox proportional hazard model. A P value of <0.05 was considered significant. RESULTS: A total of 120 patients with 120 LR-M lesions were included; on histology 65 were HCC and 55 were iCCA. There was similar median OS for patients with LR-M HCC compared to patients with iCCA (738 days vs. 769 days, P = 0.576). There were no significant differences between patients with HCC and iCCA in terms of sex (47:18 vs. 37:18, P = 0.549), age (63.0 ± 8.4 vs. 63.4 ± 7.8, P = 0.847), etiology of liver disease (P = 0.202), presence of cirrhosis (100% vs. 100%, P = 1.000), tumor size (4.73 ± 3.28 vs. 4.75 ± 2.58, P = 0.980), method of lesion histologic diagnosis (P = 0.646), and proportion of patients who underwent locoregional therapy (60.0% vs. 38.2%, P = 0.100) or surgery (134.8 ± 165.5 vs. 142.5 ± 205.6, P = 0.913). Using multivariable analysis, nonsurgical compared to surgical management (HR, 4.58), larger tumor size (HR, 1.19), and higher MELD score (HR, 1.12) were independently associated with worse OS. DATA CONCLUSION: There was similar OS in patients with LR-M HCC and LR-M iCCA, suggesting that LR-M imaging features may more closely reflect patient outcomes than histology. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 5.

EWSR1::NR4A3 gene fusion in a cutaneous atypical myoepithelial neoplasm.

Myoepithelial neoplasms of the skin and soft tissue are rare and share histopathologic features with their salivary gland counterpart. We present a case of an atypical myoepithelial neoplasm from the back of a 72-year-old female. This lesion harbored an EWSR1::NR4A3 gene fusion, a genetic signature characteristically seen in extraskeletal myxoid chondrosarcoma. To our knowledge, this is a unique case of an atypical cutaneous myoepithelial neoplasm harboring EWSR1::NR4A3 fusion.

Progress towards the elimination of hepatitis B in children in Colombia: A novel two-phase study approach.

The World Health Organization (WHO) has established a target to eliminate mother-to-child-transmission (EMTCT) of hepatitis B virus (HBV), defined as a prevalence of hepatitis B surface antigen (HBsAg) of ≤0.1% among children, by 2030. Using nationally representative serosurveys to verify achievement of this target requires large sample sizes and significant resources. We assessed the feasibility of a potentially more efficient two-phase method to verify EMTCT of HBV in Colombia. In the first phase, we conducted a risk assessment to identify municipalities at the highest risk of ongoing HBV transmission. We ranked the 1122 municipalities of Colombia based on the reports of HBV infection in pregnant women per 1000 population. Municipalities with ≥0.3 reports per 1000 persons (equating to the top quartile) were further assessed based on health facility birth rates, coverage with three doses of hepatitis B vaccine (HepB3) and seroprevalence data. Hepatitis B risk was considered to be further increased for municipalities with HepB3 coverage or health facility birth rate <90%. In the second phase, we conducted a multistage household serosurvey of children aged 5-10 years in 36 municipalities with the highest assessed HBV risk. HBsAg was not detected in any of 3203 children tested, yielding a 90% upper confidence bound of <0.1% prevalence. Coverage with HepB3 and hepatitis B birth dose was high at 97.5% and 95.6%, respectively. These results support the conclusion that Colombia has likely achieved EMTCT of HBV.

LR-3 and LR-4 Lesions Are More Likely to Be Hepatocellular Carcinoma in Transplant Patients with LR-5 or LR-TR Lesions.

BACKGROUND: Liver Imaging Reporting and Data System (LI-RADS) classifies liver nodules from LR-1 to LR-5 based on risk for hepatocellular carcinoma (HCC). It is challenging to know the nature of the LR-3 and LR-4 lesions. AIMS: To test our hypothesis that in patients with a definite HCC (LR-5) or treated HCC (LR-TR), a coexisting LR-3 or LR-4 lesion is more likely to represent HCC compared to patients without LR-5 or LR-TR lesions. METHODS: We conducted a retrospective study including all adult patients who received liver transplantation in our institution from 1/1/2014 to 3/3/2020 who had any LR-3 or LR-4 lesion on pre-transplant MRI. RESULTS: Seventy-eight patients were included in the final cohort (115 LR-3 and LR-4 lesions total). When accompanied by LR-5 or LR-TR lesions, 41% (28/69) of LR-3 lesions were HCC compared to 12% (3/25) when not accompanied by LR-5 LR-TR lesions. When accompanied by LR-5 or LR-TR lesions, 83% (10/12) of LR-4 lesions were HCC, versus 33% (3/9) when not accompanied by LR-5 or LR-TR lesions. In a multivariable analysis of all lesions, the presence of a LR-5 or LR-TR lesion was significantly associated with LR-3 or LR-4 lesions representing HCC (OR 6.4, p = 0.01). CONCLUSION: LR-3 and LR-4 lesions are more likely to be HCC in patients with LR-5 or LR-TR lesions. The presence of coexisting definite HCC may be a useful diagnostic feature to improve risk stratification of lesions without typical imaging features of HCC. This may also affect decision-making prior to liver transplant when HCC burden must be accurately determined.

Neutrophils promote tumor resistance to radiation therapy.

Nearly two-thirds of cancer patients are treated with radiation therapy (RT), often with the intent to achieve complete and permanent tumor regression (local control). RT is the primary treatment modality used to achieve local control for many malignancies, including locally advanced cervical cancer, head and neck cancer, and lung cancer. The addition of concurrent platinum-based radiosensitizing chemotherapy improves local control and patient survival. Enhanced outcomes with concurrent chemoradiotherapy may result from increased direct killing of tumor cells and effects on nontumor cell populations. Many patients treated with concurrent chemoradiotherapy exhibit a decline in neutrophil count, but the effects of neutrophils on radiation therapy are controversial. To investigate the clinical significance of neutrophils in the response to RT, we examined patient outcomes and circulating neutrophil counts in cervical cancer patients treated with definitive chemoradiation. Although pretreatment neutrophil count did not correlate with outcome, lower absolute neutrophil count after starting concurrent chemoradiotherapy was associated with higher rates of local control, metastasis-free survival, and overall survival. To define the role of neutrophils in tumor response to RT, we used genetic and pharmacological approaches to deplete neutrophils in an autochthonous mouse model of soft tissue sarcoma. Neutrophil depletion prior to image-guided focal irradiation improved tumor response to RT. Our results indicate that neutrophils promote resistance to radiation therapy. The efficacy of chemoradiotherapy may depend on the impact of treatment on peripheral neutrophil count, which has the potential to serve as an inexpensive and widely available biomarker.

Effects of probiotics on cognitive and emotional functions in healthy older adults: Protocol for a double-blind randomized placebo-controlled crossover trial.

Aging is a process that includes changes in cognitive and emotional functions, as well as changes in the diversity and integrity of gut microbiota. Probiotic treatments have recently been studied as a potential new therapeutic approach to alleviate a wide range of problems in other populations; however, clinical studies in older adults remain insufficient and limited. Thus, the aim of this project is to evaluate the efficacy of a multispecies probiotic formulation as a therapeutic strategy for attenuating the emotional and cognitive decline associated with aging in adults over the age of 55. This is a double-blind randomized placebo-controlled crossover trial involving at least 32 older adults and comparing two conditions: (a) probiotic, providing a multispecies probiotic for 10 weeks (Lactobacillus rhamnosus and Bifidobacterium lactis); and (b) placebo, receiving a harmless substance (potato starch). Despite the increasing use of probiotics for the treatment of cognitive and emotional problems, no study has yet focused on this group, to the best of our knowledge. Therapeutic strategies of the kind outlined in this protocol will help to shed light on the current state of knowledge about this topic, as well as promote health programs tailored to this population, which would encourage active aging and healthy lifestyles. Not only do we expect improvements in the emotional dimension in terms of anxiety, stress, depression, and sleep quality, we also expect improvements in the cognitive dimension in terms of attention, memory, and decreased impulsivity.

Opioid system influences gut-brain axis: Dysbiosis and related alterations.

Opioid drugs are widely used to treat chronic pain, but their misuse can lead to tolerance, dependence, and addiction and have created a significant public health problem. In addition, food-derived opioid peptides, known as exorphins, like gluten exorphins have been shown to have harmful effects in certain pathologies like celiac disease, for example. Several studies support the involvement of the opioid system in the development of disorders such as autism spectrum syndrome. Moreover, bidirectional communication between the intestine and brain has been shown to be altered in various neurodegenerative diseases including Alzheimer´s and Parkinson´s. The presence of opioid receptors in both the digestive tract and the central nervous system (CNS) suggests that opioid drugs and exorphins may modulate the gut-brain axis. Morphine, for example, has shown a dysbiotic effect on the bacterial microbiota in addition to inducing an increase in intestinal permeability facilitating bacterial translocation. Furthermore, certain components of bacteria can modify the expression of opioid receptors at the central level increasing sensitivity to pain. Strategies based on use of probiotics have resulted in improvements in symptoms of autism and Parkinson´s disease. In this manuscript, we review the role of the opioid system in disorders and CNS pathologies and the involvement of the gut-brain axis.

LI-RADS Treatment Response Algorithm: Performance and Diagnostic Accuracy.

Background In 2017, the Liver Imaging Reporting and Data System (LI-RADS) included an algorithm for the assessment of hepatocellular carcinoma (HCC) treated with local-regional therapy. The aim of the algorithm was to enable standardized evaluation of treatment response to guide subsequent therapy. However, the performance of the algorithm has not yet been validated in the literature. Purpose To evaluate the performance of the LI-RADS 2017 Treatment Response algorithm for assessing the histopathologic viability of HCC treated with bland arterial embolization. Materials and Methods This retrospective study included patients who underwent bland arterial embolization for HCC between 2006 and 2016 and subsequent liver transplantation. Three radiologists independently assessed all treated lesions by using the CT/MRI LI-RADS 2017 Treatment Response algorithm. Radiology and posttransplant histopathology reports were then compared. Lesions were categorized on the basis of explant pathologic findings as either completely (100%) or incompletely (<100%) necrotic, and performance characteristics and predictive values for the LI-RADS Treatment Response (LR-TR) Viable and Nonviable categories were calculated for each reader. Interreader association was calculated by using the Fleiss κ. Results A total of 45 adults (mean age, 57.1 years ± 8.2; 13 women) with 63 total lesions were included. For predicting incomplete histopathologic tumor necrosis, the accuracy of the LR-TR Viable category for the three readers was 60%-65%, and the positive predictive value was 86%-96%. For predicting complete histopathologic tumor necrosis, the accuracy of the LR-TR Nonviable category was 67%-71%, and the negative predictive value was 81%-87%. By consensus, 17 (27%) of 63 lesions were categorized as LR-TR Equivocal, and 12 of these lesions were incompletely necrotic. Interreader association for the LR-TR category was moderate (κ = 0.55; 95% confidence interval: 0.47, 0.67). Conclusion The Liver Imaging Reporting and Data System 2017 Treatment Response algorithm had high predictive value and moderate interreader association for the histopathologic viability of hepatocellular carcinoma treated with bland arterial embolization when lesions were assessed as Viable or Nonviable. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Gervais in this issue.

Stress and the gut microbiota-brain axis.

Stress is a nonspecific response of the body to any demand imposed upon it, disrupting the body homoeostasis and manifested with symptoms such as anxiety, depression or even headache. These responses are quite frequent in the present competitive world. The aim of this review is to explore the effect of stress on gut microbiota. First, we summarize evidence of where the microbiota composition has changed as a response to a stressful situation, and thereby the effect of the stress response. Likewise, we review different interventions that can modulate microbiota and could modulate the stress according to the underlying mechanisms whereby the gut-brain axis influences stress. Finally, we review both preclinical and clinical studies that provide evidence of the effect of gut modulation on stress. In conclusion, the influence of stress on gut microbiota and gut microbiota on stress modulation is clear for different stressors, but although the preclinical evidence is so extensive, the clinical evidence is more limited. A better understanding of the mechanism underlying stress modulation through the microbiota may open new avenues for the design of therapeutics that could boost the pursued clinical benefits. These new designs should not only focus on stress but also on stress-related disorders such as anxiety and depression, in both healthy individuals and different populations.

Late Gastrointestinal Complications of Allogeneic Hematopoietic Stem Cell Transplantation in Adults.

Gastrointestinal (GI) complications including graft-versus-host disease (GVHD) are a major cause of morbidity and mortality in allogenic stem transplant recipients. Although several studies have previously looked into the acute GI complications, fewer smaller studies have reported late complications. In this large study we focus on the late (100 days post-transplant) GI complications in allogenic stem transplant recipients. In this single-center, retrospective study of all adult allogenic stem cell transplant recipients who had their transplant at Duke University over a 6-year period, 479 patients underwent allogenic stem cell transplant, of whom 392 recipients survived for at least 100 days post-transplant. Late GI symptoms were noted in 71 patients, prompting endoscopic evaluation. The primary endpoint of our study was the diagnosis of GI-GVHD based on endoscopic findings, whereas overall survival and nonrelapse mortality were the secondary endpoints. Of the 71 patients who underwent endoscopy, 45 (63%) had GI-GVHD. Of these 45 patients, 39 (87%) had late acute GVHD, 1 (2%) had chronic GVHD, and 5 patients (11%) had overlap disease. Of the patients who did not have GVHD, the symptoms were mostly related to infectious and inflammatory causes. Less common causes included drug toxicity, food intolerance, disease relapse, and motility issues. In a multivariate analysis the factors most indicative of GI-GVHD were histologic findings of apoptosis on the tissue specimen (odds ratio, 2.35; 95% confidence interval, 1.18 to 4.70; P = .015) and clinical findings of diarrhea (odds ratio, 5.43; 95% confidence interval, 1.25 to 23.54; P = .024). The median survival time from the first endoscopy was 8.5 months. The incidence of nonrelapse mortality at 6 months was 31% in patients with GI-GVHD and 19% in patients without GI-GVHD (P = .42). All patients with GI-GVHD were on steroid therapy, and 31% of them received total parenteral nutrition. In our population close to one-fifth of allogenic transplant recipients experienced late GI complications, warranting endoscopic evaluation. Most of these patients were found to have GI-GVHD that had a high incidence of nonrelapse mortality at 6 months and close to one-third of these patients needed total parenteral nutrition.

Gut-brain axis in the executive function of austism spectrum disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired communication and social interactions, and repetitive behavioural patterns. These patterns are believed to be dysfunctional symptoms in executive processing, which impact other cognitive functions such as attention or cognitive flexibility. In recent years, several studies have shown that certain intestinal bacteria may play a role in shaping cognitive networks encompassing emotional and social domains. A microbiota-gut-brain axis is known to exist, establishing several mechanisms by which microbiota may modulate brain development, function and behaviour, including immune, endocrine and neural pathways. As the aetiology of ASD is largely unknown, some studies have shown that intestinal bacteria may be involved in its pathogenesis. The aim of this review was to focus on the role of the gut-brain axis in ASD and, specifically, on its role in executive functions. First, we summarize the relationship between the gastrointestinal and cognitive symptoms of ASD patients. In addition, we highlight the evidence that supports and emphasizes the involvement of gut microbiota, and the putative underlying mechanisms in this population. Finally, we present evidence from preclinical and clinical studies on the modulation of microbiota and their effects on cognitive symptoms, specifically in relation to executive function. In conclusion, manipulation of microbiota could be a positive intervention to improve ASD symptoms. However, more research evaluating the role of microbiota in the cognitive symptoms ASD is needed.

Probiotics in digestive, emotional, and pain-related disorders.

In recent years, interest in the relationship between gut microbiota and disease states has grown considerably. Indeed, several strategies have been employed to modify the microbiome through the administration of different diets, by the administration of antibiotics or probiotics, or even by transplantation of feces. In the present manuscript, we focus specifically on the potential application of probiotics, which seem to be a safe strategy, in the management of digestive, pain, and emotional disorders. We present evidence from animal models and human studies, notwithstanding that translation to clinic still deserves further investigation. The microbiome influences gut functions as well as neurological activity by a variety of mechanisms, which are also discussed. The design and performance of larger trials is urgently needed to verify whether these new strategies might be useful not only for the treatment of disorders affecting the gastrointestinal tract but also in the management of emotional and pain disorders not directly related to the gut.

Brincidofovir (CMX001) Toxicity Associated With Epithelial Apoptosis and Crypt Drop Out in a Hematopoietic Cell Transplant Patient: Challenges in Distinguishing Drug Toxicity From GVHD.

Brincidofovir (CMX001) is an oral agent with activity against double-strand DNA viruses undergoing clinical trials in immunocompromised patients. We report a patient clinically diagnosed with brincidofovir-related gastrointestinal (GI) toxicity and his histologic findings. A 2-year-old boy with medulloblastoma undergoing autologous hematopoietic cell transplantation developed adenovirus viremia 9 days posttransplant. After initial treatment with intravenous cidofovir he was started on oral brincidofovir as part of a clinical trial. He developed hematochezia, anorexia, and emesis 11 weeks later. Sigmoid colon biopsy showed marked crypt drop out, moderate epithelial apoptosis, and lamina propria edema. The pathologic diagnosis was drug-related injury versus infection. Brincidofovir toxicity was diagnosed clinically and the drug was discontinued. His GI symptoms improved in 2 weeks with supportive care and octreotide. Brincidofovir causes GI toxicity and histologically demonstrates epithelial apoptosis and crypt injury, similar to graft versus host disease and mycophenolate mofetil toxicity.

Current Valuation of Pathology Service.

Health care reform has accelerated as the existing health care system undergoes continuing financial stress. Medicare's new value-based payment system, commonly referred to as MACRA, provides opportunities for physicians to participate in this new system in a variety of ways. However, many of the value-based adjustments are based on existing valuations of services through traditional mechanisms. To achieve appropriate valuation of pathologist's services in the new payment models, it is imperative that we continue to achieve proper valuation of services through the traditional mechanisms.