Should a Stoma Be Used After Intestinal Transplant.

As we all acknowledge benefits of ostomies, they can come with significant morbidity, quality of life issues, and major complications, especially during reversal procedures. In recent years, we have started to observe that similar graft and patient survival can be achieved without ostomies in certain cases. This observation and practice adopted in a few large-volume transplant centers opened a new discussion about the necessity of ostomies in intestinal transplantation. There is still more time and randomized studies will be needed to better understand and analyze the risk/benefits of "No-ostomy" approach in intestinal transplantation.

Endoscopic Surveillance of the Intestinal Allograft: Recommendations From the Intestinal Rehabilitation and Transplant Association Working Group.

Intestinal transplant (ITx) rejection lacks a reliable noninvasive biomarker and rejection surveillance relies on serial endoscopies and mucosal biopsies followed by histologic assessment. Endoscopic biopsies are also essential for identifying other ITx-related complications such as infectious, allergic, and inflammatory graft enteritis as well as post-transplant lymphoproliferative disease or graft versus host disease. In spite of its central role in ITx, published guidelines on endoscopy and biopsy are lacking and significant variability between centers in terms of timing and technical performance exists. Therefore, an international expert group convened and discussed several aspects related to the surveillance endoscopy after ITx with the aim to summarize and standardize its practice. This article summarizes these considerations on endoscopic ITx monitoring and highlights practices of surveillance and for-cause endoscopy, biopsy techniques, pathologic evaluation, potential risks and complications, outsourcing, and less-invasive monitoring techniques.

Changes in Cancer Screening Knowledge Among a Prospective Cohort of Spanish-Speaking Hispanic Community Outreach Event Participants in Florida and Puerto Rico.

The current study examined cancer prevention and early detection awareness (pre-workshop) and changes in knowledge (from pre- to post-workshop) among Hispanic/Latino (H/L) community members who participated in Spanish-language educational outreach events in Puerto Rico (PR) and Florida (FL). Spanish-language educational outreach events were comprised of an educational session lasting approximately 45-60 min and were delivered to groups in rural and urban community settings by a single trained community health educator (CHE). The research team assessed sociodemographic characteristics, personal and familial cancer health history, as well as awareness and knowledge (pre-test) of a range of cancer prevention and screening topics. Following the presentation, participants completed a post-test knowledge survey which also measured likelihood of engaging in cancer screening, cancer preventive behaviors, and cancer research as a result of information presented during the session. Change in the average knowledge score was evaluated using a paired samples t-test. Post-session likelihood of completing cancer screening and preventive behaviors and engaging in cancer research were examined using descriptive statistics and group/site comparisons. The percentage reporting awareness of screening procedures ranged from 33% (PSA test) to 79% (mammogram). H/L in PR reported higher percentage of stool blood test awareness when compared to H/L in FL (χ2(1)= 19.20, p<.001). The average knowledge score increased from 5.97 at pre-test to 7.09 at post-test (Cohen's d=0.69). The increase was significant across all participants (t(315)= 12.4, p<.001), as well as within the FL site (t(124)= 6.66, p<.001, d=0.59) and the PR site (t(190)=10.66, p<.001, d=0.77). Results from this study suggest that educational outreach events delivered to H/L community members by a CHE are valuable strategies to address challenges regarding cancer screening knowledge and engagement in multiple behaviors.

Expression of SmATPDases 1 and 2 in Schistosoma mansoni eggs favours IL-10 production in infected individuals.

A role of IL-10 is down-regulating T-cell responses to schistosome antigens. Since SmATPDases can be correlated to modulation of the immune response, we evaluated the expression of enzymes in S. mansoni eggs. Faecal samples were collected from 40 infected individuals to detect coding regions of the SmATPDases. The cytokines were measured in supernatants of PBMC. The analysis was performed by the global median determination and set up high producers (HP) of cytokines. Six individuals expressed SmATPDase1, six expressed SmATPDase2 and six expressed both enzymes. The group who expressed only SmATPDase1 showed a high frequency of IFN-γ, TNF IL-4 HP; individuals who expressed only SmATPDase2 showed a high frequency of IFN-γ, IL-6 and IL-4 HP; and individuals who expressed both enzymes showed a high frequency of IL-10 HP. The comparison of the IFN-γ/IL-10 ratio presented higher indices in the group who had SmATPDase 2 expression than those who had the expression of both enzymes. The positive correlation between infection intensity and IL-10 levels remained only in the positive SmATPDase group. The IL-10 is the only cytokine induced by the expression of both enzymes. Our data suggest that the expression of both enzymes seems to be a factor that modulates the host immune response by inducing high IL-10 production.

Liver Inclusion Appears to Be Protective Against Graft Loss-Due-to Chronic But Not Acute Rejection Following Intestinal Transplantation.

In intestinal transplantation, while other centers have shown that liver-including allografts have significantly more favorable graft survival and graft loss-due-to chronic rejection (CHR) rates, our center has consistently shown that modified multivisceral (MMV) and full multivisceral (MV) allografts have significantly more favorable acute cellular rejection (ACR) and severe ACR rates compared with isolated intestine (I) and liver-intestine (LI) allografts. In the attempt to resolve this apparent discrepancy, we performed stepwise Cox multivariable analyses of the hazard rates of developing graft loss-due-to acute rejection (AR) vs. CHR among 350 consecutive intestinal transplants at our center with long-term follow-up (median: 13.5 years post-transplant). Observed percentages developing graft loss-due-to AR and CHR were 14.3% (50/350) and 6.6% (23/350), respectively. Only one baseline variable was selected into the Cox model indicating a significantly lower hazard rate of developing graft loss-due-to AR: Transplant Type MMV or MV (p < 0.000001). Conversely, two baseline variables were selected into the Cox model indicating a significantly lower hazard rate of developing graft loss-due-to CHR: Received Donor Liver (LI or MV) (p = 0.002) and Received Induction (p = 0.007). In summary, while MMV/MV transplants (who receive extensive native lymphoid tissue removal) offered protection against graft loss-due-to AR, liver-containing grafts appeared to offer protection against graft loss-due-to CHR, supporting the results of other studies.

The First Collective Examination of Immunosuppressive Practices Among American Intestinal Transplant Centers.

Background: Unlike other solid organs, no standardized treatment algorithms exist for intestinal transplantation (ITx). We established a consortium of American ITx centers to evaluate current practices. Methods: All American centers performing ITx during the past 3 y were invited to participate. As a consortium, we generated questions to evaluate and collect data from each institution. The data were compiled and analyzed. Results: Ten centers participated, performing 211 ITx during the past 3 y (range, 3-46; mean 21.1). Induction regimens varied widely. Thymoglobulin was the most common, used in the plurality of patients (85/211; 40.3%), but there was no consensus regimen. Similarly, regimens for the treatment of acute cellular rejection, antibody-mediated rejection, and graft-versus-host disease varied significantly between centers. We also evaluated differences in maintenance immunosuppression protocols, desensitization regimens, mammalian target of rapamycin use, antimetabolite use, and posttransplantation surveillance practices. Maintenance tacrolimus levels, stoma presence, and scoping frequency were not associated with differences in rejection events. Definitive association between treatments and outcomes, including graft and patient survival, was not the intention of this initial collaboration and is prevented by the lack of patient-level data and the presence of confounders. However, we identified trends regarding rejection episodes after various induction strategies that require further investigation in our subsequent collaborations. Conclusions: This initial collaboration reveals the extreme heterogeneity of practices among American ITx centers. Future collaboration will explore patient-level data, stratified by age and transplant type (isolated intestine versus multivisceral), to explore the association between treatment regimens and outcomes.

Clinical characteristics and outcomes in CMV infection in intestinal transplant recipients: A single-center experience.

BACKGROUND: Cytomegalovirus (CMV) infection is one of the most common posttransplantation infections and has been associated with increased rejection and mortality. Data in intestinal transplants recipients are limited. METHODS: This is a single-center, retrospective cohort study of all intestinal transplants performed between January 1, 2009, and August 31, 2020. We included recipients of all ages who were at risk of CMV infection. To identify the risk factors, we conducted at first univariate and multivariate analysis. For the multivariate analysis, we developed a logistic regression model based on the result of univariate analysis. RESULTS: Ninety five patients with a median age of 32 (interquartile range [IQR] 4, 50) were included. CMV donor seropositive/recipient seronegative were 17 (17.9%). Overall, 22.1% of the recipients developed CMV infection at a median time of 155 (IQR 28-254) days from transplant, including 4 CMV syndrome and 6 CMV end-organ disease. Overall, 90.4%, (19/21) developed DNAemia while on prophylaxis. Median peak viral load and time to negativity was 16 000 (IQR 1034-43 892) IU/mL and 56 (IQR 49-109) days, respectively. (Val)ganciclovir and foscarnet were utilized in 17 (80.9%) and 1 (4.76%) recipients, respectively. Recurrences of CMV DNAemia and graft rejection were observed in three and six recipients, respectively. Younger age was identified as a risk factor (p = .032, odds ratio 0.97, 95% confidence interval 0.95-0.99) to develop CMV DNAemia. CONCLUSION: A significant proportion of intestinal transplant recipients developed CMV infection while on prophylaxis. Better methods such as CMV cell mediated immunity guided prophylaxis should be used to prevent infections in this population.

The importance of avoiding time-dependent bias when testing the prognostic value of an intervening event - Two acute cellular rejection examples in intestinal transplantation.

In testing the prognostic value of the occurrence of an intervening event (clinical event that occurs posttransplant), 3 proper statistical methodologies for testing its prognostic value exist (time-dependent covariate, landmark, and semi-Markov modeling methods). However, time-dependent bias has appeared in many clinical reports, whereby the intervening event is statistically treated as a baseline variable (as if it occurred at transplant). Using a single-center cohort of 445 intestinal transplant cases to test the prognostic value of first acute cellular rejection (ACR) and severe (grade of) ACR on the hazard rate of developing graft loss, we demonstrate how the inclusion of such time-dependent bias can lead to severe underestimation of the true hazard ratio (HR). The (statistically more powerful) time-dependent covariate method in Cox's multivariable model yielded significantly unfavorable effects of first ACR (P < .0001; HR = 2.492) and severe ACR (P < .0001; HR = 4.531). In contrast, when using the time-dependent biased approach, multivariable analysis yielded an incorrect conclusion for the prognostic value of first ACR (P = .31, HR = 0.877, 35.2% of 2.492) and a much smaller estimated effect of severe ACR (P = .0008; HR = 1.589; 35.1% of 4.531). In conclusion, this study demonstrates the importance of avoiding time-dependent bias when testing the prognostic value of an intervening event.

Pulmonary Infections in Intestinal Transplant Recipients With Preexisting Pulmonary Nodules.

BACKGROUND: Pulmonary nodules in asymptomatic patients could represent latent pulmonary infections. Intestinal transplant (ITx) recipients with preexisting lung nodules might be at higher risk for pulmonary infections. However, data is scarce. METHODS: This retrospective study included adult patients who underwent ITx from May 2016 to May 2020. Chest computed tomography scans performed within 12 months before ITx were obtained to evaluate for preexisting pulmonary nodules. Screening for endemic mycoses, Aspergillus, Cryptococcus, and latent tuberculosis infection performed within 12 months before ITx was obtained. We assessed for worsening pulmonary nodules, and fungal and mycobacterial infections during the first year post-transplant. Survival and graft loss at 1-year post-transplant was also assessed. RESULTS: Forty-four patients underwent ITx. Thirty-one had preexisting lung nodules. No invasive fungi were recorded in the pretransplant period and one individual had latent tuberculosis infection. In the post-transplant period, one individual developed probable invasive aspergillosis and had worsening nodular opacities, whereas one had disseminated histoplasmosis with stable lung nodules in chest computed tomography. No mycobacterial infections were documented. The cohort survival was 84% at 12 months after transplant. CONCLUSION: Preexisting pulmonary nodules were common in the cohort (71%), yet latent and active pulmonary infections were rare. Appearance of new or worsening pulmonary nodules does not appear to directly correlate with pulmonary infections in the post-transplant period. Routine chest computed tomography is not recommended in the pretransplant period, but follow-up is favored in patients with confirmed nodular opacities. Clinical monitoring is essential.

Behavioral beliefs about genetic counseling among high-risk Latina breast cancer survivors in Florida and Puerto Rico.

Compared with non-Hispanic White women, Latina women are less likely to receive genetic counseling (GC) and testing (GT) following BC diagnosis. This study used secondary data analysis to explore beliefs about GC among Latina BC survivors in and outside the US mainland. GC/GT-naïve, high-risk, Spanish-preferring Latina BC survivors (n = 52) in FL and PR completed the Behavioral Beliefs about GC scale. Participants reported high positive beliefs about GC (M = 4.19, SD = 0.92); the majority agreed that GC was beneficial to understand cancer risk (90%) and promote discussion (87%) in their family. Participants reported low-to-moderate scores for barriers (Ms = 1.53-3.40; SDs = 0.59-0.90). The most frequently endorsed barriers were desire for additional GC information (M = 3.44; SD = 0.90), and GC logistic concerns (M = 2.71; SD = 0.80). No statistically significant differences for barriers and benefits scales were identified by place of residence (all ps ≥ 0.12). These findings highlight the importance of delivering culturally sensitive GC information to high-risk Latina BC survivors.

Development of a Patient Activation Toolkit for Hepatitis C Virus Testing.

We evaluated the acceptability of a patient activation toolkit for hepatitis C virus (HCV) testing amidst universal adult guidelines. We developed a patient-facing toolkit that included a letter to the patient from their healthcare provider, HCV factsheet, and question prompt list, which contained questions for their provider about HCV infection and testing. We conducted qualitative interviews with patients ages 18-78 (n = 17), using a semi-structured interview guide based on learner verification. We assessed attraction, comprehension, cultural-linguistic acceptability, self-efficacy, and persuasiveness of toolkit materials using direct content analysis. Participants reported materials were attractive, offering suggestions to improve readability. They reported some understanding of materials but requested use of less medical jargon, particularly for the factsheet. Participants discussed cultural acceptability and suggested ways to improve language inclusiveness and comfort with content, given stigma surrounding HCV risk factors. Participants reported that including a letter, factsheet, and QPL improved the persuasiveness of materials, and they conveyed their motivation to be tested for HCV. Results indicate preliminary acceptability for use of the patient activation toolkit, which will be refined based on participants' recommendations. Overall, this patient activation toolkit holds promise for increasing HCV testing rates.

Provider discussion of genetic counseling among high-risk Spanish-preferring Latina breast cancer survivors.

Among high-risk breast cancer (BC) survivors, genetic counseling (GC) and genetic testing (GT) may inform cascade testing and risk management. Compared to non-Hispanic White BC survivors, Spanish-preferring Latina BC survivors are less likely to report discussing GC with a healthcare provider. However, few studies have examined Latinas' experiences with GC/GT, particularly outside of the mainland USA. This study aimed to compare frequency of provider discussion of GC between Spanish-preferring Latina BC survivors living in Florida (FL) and Puerto Rico (PR). We conducted secondary data analysis of baseline assessments from a randomized pilot of an educational intervention for Spanish-preferring Latina BC survivors. Participants (N = 52) were GC/GT-naive, but met clinical criteria for GC/GT referral. Participants self-reported sociodemographic, clinical, and cultural variables, including previous provider discussion of GC. Descriptive statistics characterized frequency of GC discussion. Logistic regression examined the relationships between sociodemographic, clinical, and cultural characteristics and GC discussion. Only 31% of participants reported previous GC discussion. More participants from PR reported having GC discussions (43% vs. 21% in the mainland USA). In multivariable analyses, greater likelihood of GC discussion was associated with PR (vs. mainland USA) residence (odds ratio [OR] = 6.00, p = .03), older age at baseline (OR = 1.19, p = .04), and younger age at BC diagnosis (OR = 0.80, p = .03). Few high-risk Spanish-preferring Latina BC survivors in the mainland USA and PR had discussed GC with their providers. These results highlight a gap in the implementation of evidence-based genetics guidelines. Provider-directed interventions may be needed to increase uptake of GC/GT among Latina BC survivors.

Some families have changes in the BRCA genes that increase their risk for developing breast cancer compared to those who do not have these gene changes. Through genetic testing, we can identify breast cancer survivors who have these gene changes so their families can take action to prevent future cancers. Breast cancer survivors who are diagnosed at a young age, or who have a strong family history of breast and ovarian cancer, are eligible for genetic counseling and BRCA testing. Yet, compared to women from other racial and ethnic groups, fewer Latina breast cancer survivors have genetic counseling and testing. This study explored frequency of healthcare providers' discussion about genetic counseling among Spanish-preferring Latina breast cancer survivors living in Florida and Puerto Rico. Although all participants were eligible, only 3 out of 10 indicated that a provider previously discussed genetic counseling with them. Participants who were living in Puerto Rico, older at study entry, or younger at the time of their breast cancer diagnosis were more likely to have discussed genetic counseling with a healthcare provider. Healthcare providers are important for identifying and referring high-risk Spanish-preferring Latinas for genetic counseling in and outside the mainland USA.

Insect chitosan as a natural antimicrobial against vegetative cells of Bacillus cereus in a cooked rice matrix.

This study investigates the antimicrobial activity of insect chitosan against vegetative cells of Bacillus cereus in a rice matrix. Sample culture solutions were prepared with different concentrations of insect chitosan (150, 180, 220 and 250 µg/mL) and tested at three temperatures (30 °C, 20 °C and 10 °C), which simulate different storage temperature scenarios of precooked rice. The results indicate that insect chitosan has antimicrobial activity that depends on temperature and chitosan concentration. For the assays with chitosan at 10 °C, all concentrations were bactericidal during the study time, reaching a maximum inactivation of 6 log cycles for 250 µg/mL. At 20 °C and at 30 °C a bacteriostatic activity was observed for concentrations of 150 µg/mL and 180 µg/mL. Results also showed that concentrations of 220 µg/mL and 250 µg/mL were bactericidal for all the temperatures tested during the storage time. When rice is cooked and not stored at an appropriate temperature, below 10 °C, the consumer's health is at risk. In these cases, insect chitosan could be a good additional control measure to control B. cereus growth and toxin formation in cooked rice.

Cutaneous amyloid is a biomarker in early ATTRv neuropathy and progresses across disease stages.

OBJECTIVE: To determine the sensitivity and specificity of cutaneous amyloid deposition in relation to patient-reported measures in the earliest disease stage of hereditary ATTR amyloidosis (ATTRv). METHODS: In a cross-sectional study, we analyzed 88 individuals with TTR mutations, 47 of whom were in the earliest disease stage and without clinically evident neuropathy, 12 healthy controls, and 13 disease controls with diabetes. All participants' neuropathy symptoms and signs were assessed using validated patient and clinician-reported measures and 3-mm skin punch biopsies were immunostained using protein gene product 9.5 and Congo Red. RESULTS: Amyloid can be detected in the earliest disease stages in up to 86% of patients with ATTRv amyloidosis. Amyloid was not detected in healthy individuals or individuals with diabetic peripheral neuropathy supporting a sensitivity of 86% and a specificity of 100%. The cutaneous deposition of amyloid correlates with neuropathy sensory symptoms, measured with the Neuropathy Total Symptom Score-6 (R = 0.46, p < 0.01); pain measured with the Brief Pain Symptom Inventory (R = 0.44, p < 0.05); autonomic symptoms, measured with the Boston Autonomic Symptom Questionnaire (R = 0.38, p < 0.05); and quality of life measured with the Norfolk Diabetic Neuropathy Quality of Life Questionnaire (R = 0.44, p < 0.05). Individuals with amyloid deposition were more likely to have sensory symptoms, pain, autonomic impairment, and reduced quality of life than ATTRv patients without amyloid deposition. INTERPRETATION: These findings have implications for understanding the earliest manifestations of the clinical phenotype of ATTRv-associated neuropathy, for the pathophysiological construct of disease staging, and for timing the introduction of disease-modifying therapy.

Genetic variants, gene expression, and soluble CD36 analysis in acute coronary syndrome: Differential protein concentration between ST-segment elevation myocardial infarction and unstable angina.

BACKGROUND: Atherosclerosis plays an important role in the pathophysiology of acute coronary syndrome (ACS). CD36 is a scavenger receptor involved in lipid metabolism. Some single-nucleotide variants in the non-coding region could indirectly alter the expression and the function of the protein. OBJECTIVE: The aim of this study was to investigate the gene and protein expression associated with CD36 variants (rs1194182;C > G; rs1049654;C > A, rs1334512;G > T, and rs3211892;G > A) in ACS patients from the western Mexican population. METHODS: We recruited 310 ACS patients and 308 subjects in the control group (CG). Genotyping was determined by TaqMan SNP genotyping assays. CD36 expression at the mRNA level was quantified by TaqMan gene expression assays. Soluble CD36 (sCD36) was measured by enzyme-linked immunosorbent assay. RESULTS: We show that rs1194182G > C variant provides a protective effect with a 1.7-fold lower susceptibility to develop ACS (p  = 0.03); however, this association was masked by diabetes and dyslipidemia. We observed a higher sCD36 concentration in patient with ST-segment elevation myocardial infarction (STEMI) compared with patients with unstable angina (UA) (p  = 0.038). Likewise, in diabetic patients versus non-diabetic (p < 0.001). We observed in patients an increase in CD36 mRNA expression (1.91 times higher) than in the CG (p  = 0.02). CONCLUSION: The rs1194182 seems to be associated with diabetes in a risky manner, in ACS patients and protective for dyslipidemia in both groups. The concentration of sCD36 seems to be associated with the clinical spectrum of the ACS patients and the presence of diabetes, since patients with STEMI present significantly elevated level compared with UA.

Developing the Florida Academic Cancer Center Alliance Health Disparities Common Measure: The Florida Health and Ancestry Survey.

PURPOSE: Our specific aim was to develop and assess the consensus-based validity of common measures for understanding health behaviors and ancestry in Florida's population subgroups and establish the feasibility of wide-scale implementation of the measures and biospecimen collection within three cancer centers' catchment areas. METHODS: Using the National Cancer Institute's Grid-Enabled Measures web-based platform and an iterative process, we developed the Florida Health and Ancestry Survey (FHAS). We then used three sampling approaches to implement the FHAS: community-engaged, panel respondent, and random digit dialing (RDD). We asked a subset of participants to provide a saliva sample for future validation of subjective ancestry report with DNA-derived ancestry markers. RESULTS: This process supported the FHAS content validity. As an indicator of feasibility, the goals for completed surveys by sampling approach were met for two of the three cancer centers, yielding a total of 1438 completed surveys. The RDD approach produced the most representative sample. The panel sampling approach produced inadequate representation of older individuals and males. The community-engaged approach along with social media recruitment produced extreme underrepresentation only for males. Two of the cancer centers mailed biospecimen kits, whereas one did not due to resource constraints. On average, the community engaged approach was more productive in obtaining returned biospecimen samples (80%) than the panel approach (48%). CONCLUSIONS: We successfully developed and implemented the FHAS as a common measure to show its feasibility for understanding cancer health disparities in Florida. We identified sampling approach successes and challenges to obtaining biospecimens for ancestry research.

Investigation of the predictive influence of personal and gubernatorial politics on COVID-19 related behaviors and beliefs.

Given the varied emotional and behavioral responses to the COVID-19 pandemic across the United States, further attention to the personal and societal influences on such responses is necessary. We investigated the predictive influence of personal political affiliation and the congruity of personal and governor political affiliation on COVID-19 emotional and behavioral responses, with specific attention to the influence of intolerance of uncertainty (IU) on emotional response. These factors were assessed in two studies of adults in the United States (N = 480, N = 272). We utilized a series of hierarchical linear and logistic regressions to assess predictors of 4 outcomes: (1) trust in governor's response to the pandemic, (2) COVID-19 related worry, and the (3) usage and (4) perceived efficacy of protective health behaviors (e.g., wearing a mask). Across these studies, we found that IU predicted increased COVID-19 related worry. Further, age and personal political affiliation, but not concordance with governor affiliation, predicted COVID-19 behavioral responses. These findings are discussed in relation to the potential importance of linking health messaging to personal characteristics.

Next-Generation DNA Sequencing-Based Gene Panel for Diagnosis and Genetic Risk Stratification in Onco-Hematology.

A suitable diagnostic classification of myeloid neoplasms and acute leukemias requires testing for a large number of molecular biomarkers. Next-generation sequencing is a technology able to integrate identification of the vast majority of them in a single test. This manuscript includes the design, analytical validation and clinical feasibility evaluation of a molecular diagnostic kit for onco-hematological diseases. It is based on sequencing of the coding regions of 76 genes (seeking single-nucleotide variants, small insertions or deletions and CNVs), as well as the search for fusions in 27 target genes. The kit has also been designed to detect large CNVs throughout the genome by including specific probes and employing a custom bioinformatics approach. The analytical and clinical feasibility validation of the Haematology OncoKitDx panel has been carried out from the sequencing of 170 patient samples from 6 hospitals (in addition to the use of commercial reference samples). The analytical validation showed sensitivity and specificity close to 100% for all the parameters evaluated, with a detection limit of 2% for SNVs and SVs, and 20% for CNVs. Clinically relevant mutations were detected in 94% of all patients. An analysis of the correlation between the genetic risk classification of AML (according to ELN 2017) established by the hospitals and that obtained by the Haematology OncoKitDx panel showed an almost perfect correlation (K = 0.94). Among the AML samples with a molecular diagnosis, established by the centers according to the WHO, the Haematology OncoKitDx analysis showed the same result in 97% of them. The panel was able to adequately differentiate between MPN subtypes and also detected alterations that modified the diagnosis (FIP1L1-PDGFRA). Likewise, the cytogenetic risk derived from the CNV plot generated by the NGS panel correlated substantially with the results of the conventional karyotype (K = 0.71) among MDS samples. In addition, the panel detected the main biomarkers of prognostic value among patients with ALL. This validated solution enables a reliable analysis of a large number of molecular biomarkers from a DNA sample in a single assay.

PharmOmics: A species- and tissue-specific drug signature database and gene-network-based drug repositioning tool.

Drug development has been hampered by a high failure rate in clinical trials due to our incomplete understanding of drug functions across organs and species. Therefore, elucidating species- and tissue-specific drug functions can provide insights into therapeutic efficacy, potential adverse effects, and interspecies differences necessary for effective translational medicine. Here, we present PharmOmics, a drug knowledgebase and analytical tool that is hosted on an interactive web server. Using tissue- and species-specific transcriptome data from human, mouse, and rat curated from different databases, we implemented a gene-network-based approach for drug repositioning. We demonstrate the potential of PharmOmics to retrieve known therapeutic drugs and identify drugs with tissue toxicity using in silico performance assessment. We further validated predicted drugs for nonalcoholic fatty liver disease in mice. By combining tissue- and species-specific in vivo drug signatures with gene networks, PharmOmics serves as a complementary tool to support drug characterization and network-based medicine.