Midline structures and cortical development in fetuses with late growth restriction according to Doppler status: prospective study.

OBJECTIVE: Fetuses with late growth restriction (FGR) have a higher risk of sub-optimal neurocognitive performance after birth. Previous studies have reported that impaired brain and cortical development can start in utero. The primary aim of this study was to report midline structures and cortical development in fetuses with late growth restriction according to its severity; the secondary aim was to elucidate whether the severity of FGR, as defined by the presence of abnormal Doppler findings, plays a role in affecting brain growth and maturation. METHODS: Prospective cross-sectional study including fetuses with late FGR undergoing neurosonography between 32 and 34 weeks of gestation. Midline structures (corpus callosum (CC) and cerebellar vermis (CV) length) and cortical development, including the depth of Sylvian (SF), parieto-occipital (POF) and calcarine (CF) were compared between FGR, small (SGA) and appropriate for gestational age (AGA) fetuses, defined upon the Delphi criteria. Sub-group analysis according to the severity of FGR (normal vs abnormal fetal Dopplers) was also performed. Univariate analysis was used to analyze the data. RESULTS: 52 FGR with normal, 60 with abnormal Dopplers, 64 SGA and 100 AGA fetuses were included in the analysis. SGA and FGR fetuses showed significant differences in absolute values of CC (median (interquartile range) control 43.47 (28.9-56.05), vs SGA 41.85 (27.82-51.79), vs FGR ND 38.54 (29.12-50.53), vs FGR AD 31.72 (23.8-40.19) K= 26.68; p<0.0001), CV (control 24.85 (17.55-29.21), SGA K=16.71; p=0.0008), SF (control 14.52 (10.65-16.76) vs SGA 12.71 (9.8-15.10) vs FGR ND 11.93 (9.12-13.43) VS FGR A 8.30 (6.72-10.33) K=75.82; p<0.0001), POF (control 8.56 (6.31-11.09) vs SGA 8.11 (5.58-10.43) vs FGR ND 7.81 (6.14-9.29) vs FGR AD 6.56 (4.22-7.99), K=45.06; p<0.0001) and CF ( control 9.27 (6.70-11.45) vs SGA 8.23 (5.67-10.65) vs FGR ND 7.68 (5.22-9.41) vs FGR AD 6.26 (4.48-7.19) K=46.14; p<0.0001) when compared to AGA controls with a progressive reduction across groups. When neurosonographic variables were corrected for fetal HC values, significant difference in the length of CC, SF, POF and CF but CV were observed only in FGR fetuses with abnormal Doppler when compared to AGA controls. CONCLUSIONS: Late onset small fetuses showed shorter CC length and a delayed cortical development when compared to control. After controlling for HC size these differences remain significant only in FGR fetuses with abnormal Dopplers. These findings support the existence of a link between brain development and impaired placental function. This article is protected by copyright. All rights reserved.

Immune Activation following Irbesartan Treatment in a Colorectal Cancer Patient: A Case Study.

Colorectal cancers are one of the most prevalent tumour types worldwide and, despite the emergence of targeted and biologic therapies, have among the highest mortality rates. The Personalized OncoGenomics (POG) program at BC Cancer performs whole genome and transcriptome analysis (WGTA) to identify specific alterations in an individual's cancer that may be most effectively targeted. Informed using WGTA, a patient with advanced mismatch repair-deficient colorectal cancer was treated with the antihypertensive drug irbesartan and experienced a profound and durable response. We describe the subsequent relapse of this patient and potential mechanisms of response using WGTA and multiplex immunohistochemistry (m-IHC) profiling of biopsies before and after treatment from the same metastatic site of the L3 spine. We did not observe marked differences in the genomic landscape before and after treatment. Analyses revealed an increase in immune signalling and infiltrating immune cells, particularly CD8+ T cells, in the relapsed tumour. These results indicate that the observed anti-tumour response to irbesartan may have been due to an activated immune response. Determining whether there may be other cancer contexts in which irbesartan may be similarly valuable will require additional studies.

A COVID-19 nosocomial cluster in a university hospital in southern Italy: a social network analysis.

Introduction: Healthcare workers on duty at the hospital are at high risk of COVID-19 infection. However, despite the introduction of risk-lowering practices in the hospital setting, there have been many cases of SARS-COV-2 infection among Health Care Workers. Fast and efficient contact tracing and Sars-CoV-2 PCR-based testing of the close contacts of Health Care Workers with confirmed infections are essential steps to limit nosocomial outbreaks. Methods: This cross-sectional study was conducted at Bari Policlinico General University-Hospital (Apulia, Italy) and describes the management of a cluster of SARS-COV-2 infections in three Operative Units. The contact tracing activities and the measures implemented to control the outbreak are described. Results: Among the 186 Health Care Workers active in the cluster setting, there were 9 (4.8%) confirmed cases, including the index case. Due to the outbreak, three Operative Units were closed to limit virus circulation. Health Care Workers with confirmed infections tested negative after a mean of 28.0±6.6 days (range: 13-37) and none required hospitalization. Conclusions: Protection of the health of Health Care Workers during the COVID-19 pandemic should be a public health priority. However, despite recent recommendations and the implementation of protective measures, SARS-COV-2 infections of Health Care Workers remain at a high rate, indicative of the continued high risk of cluster onset in the nosocomial setting.

A new paradigm of hospital care for SARS-COV-2 patients in the post-emergency phase in Italy.

Abstract: In Italy, at the beginning of the SARS-CoV-2 pandemic, the main organizational model of hospital care was represented by the physical or functional division of hospitals and wards into COVID and non-COVID areas, in order to separate SARS-CoV-2-infected patients from the others. Now that the emergency phase has reached its long-awaited end, it is necessary to develop a new hospital care paradigm that may deal with SARS-CoV-2-positive patients discriminating between those who are hospitalized because of COVID-19 and those who are diagnosed with SARS-CoV-2 infection immediately before or after the first access to healthcare facilities.

The Ideal Physical Therapist from the Perspective of Individuals With Limb Loss.

BACKGROUND: Effective rehabilitation after limb loss is necessary to maximize function and promote independence. Physical therapists (PT) are one of the primary drivers of the rehabilitation process. While general physical therapy knowledge and abilities have been shown to be important to the rehabilitation process, it is unclear what individuals with limb loss value in their PT's. OBJECTIVE: The purpose of this study was to understand the elements that define an ideal PT from the perspective of individuals with limb loss. METHODOLOGY: Mixed-method design consisting of a 20-item web-based survey and semi-structured interviews that were administered to individuals 18 years or older, who spoke English, and had a history of lower limb loss. FINDINGS: Individuals with limb loss describe an ideal PT as promoting a therapeutic alliance, having specialized knowledge, and collaborating with a prosthetist. Knowledge of the PT as it relates to limb loss was found to be both the greatest facilitator and barrier to the rehabilitation process. CONCLUSION: From the perspective of those with limb loss, an ideal PT promotes a strong therapeutic alliance through communication, has specialized knowledge when it comes to the limb loss rehabilitation process, and collaborates with the prosthetist to problem-solve throughout the rehabilitation process.

Whole-genome and transcriptome analysis enhances precision cancer treatment options.

BACKGROUND: Recent advances are enabling delivery of precision genomic medicine to cancer clinics. While the majority of approaches profile panels of selected genes or hotspot regions, comprehensive data provided by whole-genome and transcriptome sequencing and analysis (WGTA) present an opportunity to align a much larger proportion of patients to therapies. PATIENTS AND METHODS: Samples from 570 patients with advanced or metastatic cancer of diverse types enrolled in the Personalized OncoGenomics (POG) program underwent WGTA. DNA-based data, including mutations, copy number and mutation signatures, were combined with RNA-based data, including gene expression and fusions, to generate comprehensive WGTA profiles. A multidisciplinary molecular tumour board used WGTA profiles to identify and prioritize clinically actionable alterations and inform therapy. Patient responses to WGTA-informed therapies were collected. RESULTS: Clinically actionable targets were identified for 83% of patients, of which 37% of patients received WGTA-informed treatments. RNA expression data were particularly informative, contributing to 67% of WGTA-informed treatments; 25% of treatments were informed by RNA expression alone. Of a total 248 WGTA-informed treatments, 46% resulted in clinical benefit. RNA expression data were comparable to DNA-based mutation and copy number data in aligning to clinically beneficial treatments. Genome signatures also guided therapeutics including platinum, poly-ADP ribose polymerase inhibitors and immunotherapies. Patients accessed WGTA-informed treatments through clinical trials (19%), off-label use (35%) and as standard therapies (46%) including those which would not otherwise have been the next choice of therapy, demonstrating the utility of genomic information to direct use of chemotherapies as well as targeted therapies. CONCLUSIONS: Integrating RNA expression and genome data illuminated treatment options that resulted in 46% of treated patients experiencing positive clinical benefit, supporting the use of comprehensive WGTA profiling in clinical cancer care.

Spatial Distribution and Location of Natural Organic Matter on Sediment Particles by Scanning Electron Microscopic Analysis and the Development of a New Persistent Organic Pollutant-Sediment Kinetic Desorption Model.

Natural organic matter (NOM) has long been shown to be the dominant factor in determining equilibrium and kinetic processes during sorption and desorption phenomena in sediment and soil experiments. Although several models have been suggested for predicting these processes, few offer mechanistic interpretations because the spatial location of organic matter on sediment particles is unknown. This investigation manually examined sediment particles from multiple locations, containing varying concentrations of NOM, using scanning electron microscopy with energy dispersive X-ray spectroscopy to determine the types of particles present by categorizing them as individual particles, aggregates, and "other" (detritus, algae, etc.). These types of particles were subsequently analyzed for their elemental composition, specifically the spatial location of carbon. By creating a carbon map of each particle, this investigation has determined that organic matter tends to occur in 2 forms: large aggregates or dispersed across individual sediment particles. These findings were then used to propose a more mechanistically sound mathematical model for pollutant desorption phenomena, assigning the traditional labile kinetic release component to the dispersed NOM spread randomly across sediment particles and the nonlabile kinetic release component to diffusion from densely packed NOM aggregates. Environ Toxicol Chem 2021;40:323-332. © 2020 SETAC.

Antimicrobial efficacy of photodynamic therapy (PDT) in periodontitis and peri-implantitis: A systematic review.

To systematically review the literature regarding the antimicrobial effects of photodynamic therapy (PDT) on multi-bacterial species in periodontitis and peri-implantitis disease. The addressed focused question was: "Does PDT show antimicrobial efficacy against multi-bacterial species colonization in periodontal pockets and on the surface of dental implants?" Electronic databases including MEDLINE and EMBASE up to and including December 2018 were searched. Of the ninety studied analyzed, seven were included, four for the study of PDT in peri-implantitis disease and three for periodontal disease. All studies reported the multibacterial species outcomes after the application of antimicrobial PDT. All studies showed a significant reduction in the bacterial load, both in studies based on periodontal and peri-implantary disease, with an average reduction of the total amount of bacterial load of 99.3%. Moreover, the change in clinical parameters is equally important, with an average reduction of PPD of 1.01 mm (from 4.92 to 3.49 ± SD with a percentage reduction of 29%); of BoP of 50%; of RCAL of 1.19 mm (from 9.93 to 8.74, with an average percentage reduction of 12%); of PI of 0.3 (from 1 to 0.7 with a percentage reduction of 30%) and of GI of 1.2 (from 1.8 to 0.6 with a percentage reduction of 66.6%). This review demonstrated significant reduction in the bacterial load in periodontal pocket and dental implant surface with the use of PDT. The results of this review should be considered preliminary and further studies with standardized laser parameters are needed to obtain strong conclusions.

Photodynamic therapy (PDT) in non-surgical treatment of periodontitis.

Periodontitis represents a major problem for patients, since it is not possible to eliminate the bacteria that are responsible for this pathology with a pharmacological treatment. The present study included forty-four patients with periodontitis, who had undergone disinfection via photodynamic therapy (PDT) using a laser source having a 635 nm wavelength associated with a photoactivable substance (methylene blue). Clinical assessment of plaque index (PI), bleeding on probing (BOP), probing depth (PD), calculus index (CI), gingival recession (REC) and clinical attachment level (CAL) were recorded at base line, 1 month (4 weeks) after treatment and again 3 months (12 weeks) after treatment, while site radiography (RX) and microbiological test (MT) were recorded at base line and 3 months (12 weeks) after treatment. The outcomes show a good efficacy of the PDT in the elimination of the periodontal pathogenic microflora and in the improvement of the clinical parameters considered: from the base line to the final check after 12 weeks it has been observed a reduction in REC of about 16.9%, a reduction of CAL of about 17.85%, a reduction of the BoP of about 93.3%, a reduction of the PD of about 17%, a reduction of the CI of about 66.3%, a reduction of PI of about 44%, and microbiologically a reduction of the total amount of bacteria with proven parodontopathic properties (red complex bacteria) of about 58.74%. Within the limits of the present study, PDT can be reasonably considered as a good carrier that leads to significant improvements in the parameters (clinical and microbiological) considered.

Successful targeting of the NRG1 pathway indicates novel treatment strategy for metastatic cancer.

BACKGROUND: NRG1 fusion-positive lung cancers have emerged as potentially actionable events in lung cancer, but clinical support is currently limited and no evidence of efficacy of this approach in cancers beyond lung has been shown. PATIENTS AND METHODS: Here, we describe two patients with advanced cancers refractory to standard therapies. Patient 1 had lung adenocarcinoma and patient 2 cholangiocarcinoma. Whole-genome and transcriptome sequencing were carried out for these cases with select findings validated by fluorescence in situ hybridization. RESULTS: Both tumors were found to be positive for NRG1 gene fusions. In patient 1, an SDC4-NRG1 gene fusion was detected, similar gene fusions having been described in lung cancers previously. In patient 2, a novel ATP1B1-NRG1 gene fusion was detected. Cholangiocarcinoma is not a disease type in which NRG1 fusions had been described previously. Integrative genome analysis was used to assess the potential functional significance of the detected genomic events including the gene fusions, prioritizing therapeutic strategies targeting the HER-family of growth factor receptors. Both patients were treated with the pan HER-family kinase inhibitor afatinib and both displayed significant and durable response to treatment. Upon progression sites of disease were sequenced. The lack of obvious genomic events to describe the disease progression indicated that broad transcriptomic or epigenetic mechanisms could be attributed to the lack of prolonged response to afatinib. CONCLUSION: These observations lend further support to the use of pan HER-tyrosine kinase inhibitors for the treatment of NRG1 fusion-positive in both cancers of lung and hepatocellular origin and indicate more broadly that cancers found to be NRG1 fusion-positive may benefit from such a clinical approach regardless of their site of origin. CLINICAL TRIAL INFORMATION: Personalized Oncogenomics (POG) Program of British Columbia: Utilization of Genomic Analysis to Better Understand Tumour Heterogeneity and Evolution (NCT02155621).

Carcinoma ex pleomorphic adenoma: case report and options for systemic therapy.

The most common benign salivary tumour is a pleomorphic adenoma. Transformation to malignancy, carcinoma ex pleomorphic adenoma (cxpa), occurs in 6% of cases. Management focuses on surgical resection and radiotherapy; however, rare cases require systemic management. We present the case of a 60-year-old woman with a cxpa of the left parotid gland who required systemic therapy for locally recurrent disease. Treatment options were guided by the literature concerning malignant salivary gland tumour and by whole-genome and transcriptome sequencing of the tumour. The patient received multiple systemic agents during the course of her disease, with cyclophosphamide-doxorubicin-cisplatin providing the best control (partial response). Genomeand transcriptome-directed therapy, including sorafenib and vismodegib, were utilized with limited clinical benefit. Malignant transformation in cxpa is a complex process, and therapy directed at a single tumour pathway might not be sufficient to control disease.

Is the atrophic phenotype of tibiofemoral osteoarthritis associated with faster progression of disease? The MOST study.

OBJECTIVE: To assess the associations of atrophic tibiofemoral osteoarthritis (OA) with progression of radiographic joint space narrowing (JSN) and magnetic resonance imaging (MRI)-defined progression of cartilage damage. DESIGN: Participants of the Multicenter Osteoarthritis (MOST) Study with available radiographic and MRI assessments at baseline and 30 months were included. The atrophic OA phenotype was defined as Osteoarthritis Research Society International (OARSI) grades 1 or 2 for JSN and grade 0 for osteophytes. Based on MRI, atrophic OA was defined as tibiofemoral (TF) cartilage damage grades ≥3 in at least 2 of 10 subregions with absent or tiny osteophytes in all TF subregions. Progression of JSN and cartilage loss on MRI, was defined as (1) no, (2) slow, and (3) fast progression. Co-variance and logistic regression with generalized estimated equations were performed to assess the association of atrophic knee OA with any progression, compared to non-atrophic OA knees. RESULTS: A total of 476 knees from 432 participants were included. There were 50 (10.5%) knees with atrophic OA using the radiographic definition, and 16 (3.4%) knees with atrophic OA using MRI definition. Non-atrophic OA knees more commonly exhibited fast progression of JSN and cartilage damage. Logistic regression showed that the atrophic phenotype of knee OA was associated with a decreased likelihood of progression of JSN and cartilage loss. CONCLUSION: In this sample, the atrophic phenotype of knee OA was associated with a decreased likelihood of progression of JSN and cartilage loss compared to the non-atrophic knee OA phenotype.

The thrombopoietin/MPL axis is activated in the Gata1low mouse model of myelofibrosis and is associated with a defective RPS14 signature.

Myelofibrosis (MF) is characterized by hyperactivation of thrombopoietin (TPO) signaling, which induces a RPS14 deficiency that de-regulates GATA1 in megakaryocytes by hampering its mRNA translation. As mice carrying the hypomorphic Gata1low mutation, which reduces the levels of Gata1 mRNA in megakaryocytes, develop MF, we investigated whether the TPO axis is hyperactive in this model. Gata1low mice contained two times more Tpo mRNA in liver and TPO in plasma than wild-type littermates. Furthermore, Gata1low LSKs expressed levels of Mpl mRNA (five times greater than normal) and protein (two times lower than normal) similar to those expressed by LSKs from TPO-treated wild-type mice. Gata1low marrow and spleen contained more JAK2/STAT5 than wild-type tissues, an indication that these organs were reach of TPO-responsive cells. Moreover, treatment of Gata1low mice with the JAK inhibitor ruxolitinib reduced their splenomegaly. Also in Gata1low mice activation of the TPO/MPL axis was associated with a RSP14 deficiency and a discordant microarray ribosome signature (reduced RPS24, RPS26 and SBDS expression). Finally, electron microscopy revealed that Gata1low megakaryocytes contained poorly developed endoplasmic reticulum with rare polysomes. In summary, Gata1low mice are a bona fide model of MF, which recapitulates the hyperactivation of the TPO/MPL/JAK2 axis observed in megakaryocytes from myelofibrotic patients.

Out of hospital cardiac arrest survivors with inconclusive coronary angiogram: Impact of cardiovascular magnetic resonance on clinical management and decision-making.

BACKGROUND: Non-traumatic out of hospital cardiac arrest (OHCA) is the leading cause of death worldwide, mainly due to acute coronary syndromes. Urgent coronary angiography with view to revascularisation is recommended in patients with suspected acute coronary syndrome. Diagnosis and management of patients with inconclusive coronary angiogram (unobstructed coronaries or unidentified culprit lesion) is challenging. We sought to assess the role of Cardiovascular Magnetic Resonance (CMR) in the diagnosis and management of OHCA survivors with an inconclusive coronary angiogram. METHODS AND RESULTS: This is a retrospective multicentre CMR registry analysis of OHCA survivors with an inconclusive angiogram. Clinical, ECG and multi-modality imaging data were analysed. Clinical impact of CMR was defined as a change in diagnosis or management. Out of 174 OHCA survivors referred for CMR, 110 patients (63%, 84 male, median age 58) had an inconclusive angiogram. CMR identified a pathologic substrate in 76/110 patients (69%): ischemic heart disease was found in 45 (41%) and non-ischemic heart disease in 31 (28%). A structurally normal heart was found in 25 patients (23%) and non-specific findings in 9 (8%). As compared to trans-thoracic echocardiogram, CMR proved to be superior in identifying a pathologic substrate (69% vs 54%, p=0.018). The CMR study carried a clinical impact in 70% of patients, determining a change in diagnosis in 25%, in management in 29% and a change in both in 16%. CONCLUSIONS: CMR showed a promising role in the diagnostic work-up of OHCA survivors with inconclusive angiogram and its wider use should be considered.

Prediction and evaluation of resting energy expenditure in a large group of obese outpatients.

BACKGROUND/OBJECTIVES: The aim of this study was to compare resting energy expenditure (REE) measured (MREE) by indirect calorimetry (IC) and REE predicted (PREE) from established predictive equations in a large sample of obese Caucasian adults. SUBJECTS/METHODS: We evaluated 1851 obese patients (body mass index (BMI)>30 kg m-2) aged between 18a and 65 years. Data were obtained by comparing MREE with PREE, derived from different equations, within and between normal weight and obese groups. The mean differences between PREE and MREE as well as the accuracy prediction within ±10% level were investigated in the whole sample and in three subgroups, classified by BMI (Group 1=30-39.9 kg m-2; Group 2=40-49.9 kg m-2; Group 3>50 kg m-2). RESULTS: We observed that FAO, Henry and Muller3 (body composition (BC)) equations provided good mean PREE-MREE (bias -0.7, -0.3 and 0.9%; root mean standard error (RMSE) 273, 263 and 269 kcal per day, respectively); HB and Henry equations were more accurate individually (57 and 56.9%). Only the Muller1 (BC) equation gave the lowest PREE-MREE difference (bias -1.7%; RMSE 228 kcal per day) in females, while Johnstone and De Lorenzo equations were the most accurate (55.1 and 54.8%). When the sample was split into three subgroups according to BMI, no differences were found in males; however, the majority of the equations included in this study failed to estimate REE in severely obese females (BMI>40 kg m-2). Overall, prediction accuracy was low (~55%) for all predictive equations, regardless of BMI. CONCLUSIONS: Different established equations can be used for estimating REE at the population level in both sexes. However, the accuracy was very low for all predictive equations used, particularly among females and when BMI was high, limiting their use in clinical practice. Our findings suggest that the validation of new predictive equations would improve the accuracy of REE prediction, especially for severely obese subjects (BMI>40 kg m-2).

A time-and-motion approach to micro-costing of high-throughput genomic assays.

BACKGROUND: Genomic technologies are increasingly used to guide clinical decision-making in cancer control. Economic evidence about the cost-effectiveness of genomic technologies is limited, in part because of a lack of published comprehensive cost estimates. In the present micro-costing study, we used a time-and-motion approach to derive cost estimates for 3 genomic assays and processes-digital gene expression profiling (gep), fluorescence in situ hybridization (fish), and targeted capture sequencing, including bioinformatics analysis-in the context of lymphoma patient management. METHODS: The setting for the study was the Department of Lymphoid Cancer Research laboratory at the BC Cancer Agency in Vancouver, British Columbia. Mean per-case hands-on time and resource measurements were determined from a series of direct observations of each assay. Per-case cost estimates were calculated using a bottom-up costing approach, with labour, capital and equipment, supplies and reagents, and overhead costs included. RESULTS: The most labour-intensive assay was found to be fish at 258.2 minutes per case, followed by targeted capture sequencing (124.1 minutes per case) and digital gep (14.9 minutes per case). Based on a historical case throughput of 180 cases annually, the mean per-case cost (2014 Canadian dollars) was estimated to be $1,029.16 for targeted capture sequencing and bioinformatics analysis, $596.60 for fish, and $898.35 for digital gep with an 807-gene code set. CONCLUSIONS: With the growing emphasis on personalized approaches to cancer management, the need for economic evaluations of high-throughput genomic assays is increasing. Through economic modelling and budget-impact analyses, the cost estimates presented here can be used to inform priority-setting decisions about the implementation of such assays in clinical practice.

Hematological complications in anorexia nervosa.

BACKGROUND/OBJECTIVES: Anemia, leukopenia and, although less frequently, thrombocytopenia are possible hematological complications of anorexia nervosa considered strictly secondary to chronic malnutrition. This is a retrospective study on the prevalence of these disorders in a large cohort of 318 female patients with AN (20.4±5.6 years, body mass index (BMI) 15.9±1.6 kg/m2), recruited in the Outpatient Unit for Malnutrition secondary to Eating Disorders at the Department of Clinical Medicine and Surgery, Federico II University Hospital, since February 1991 to December 2012. SUBJECTS/METHODS: Patients were studied on an outpatient basis after obtaining medical history, clinical examination, routine hematobiochemical and endocrine tests, electrocardiography, psychiatric interview and bioelectrical impedance analysis and, in particular, phase angle determination. All patients with other comorbidities, in particular with mean corpuscular volume <80 fl, were excluded for suspected genetic alteration in the synthesis of hemoglobin. RESULTS: Hematologic data showed that 16.7% of patients had anemia, 7.9% neutropenia and 8.9% thrombocytopenia. These abnormalities were strictly related to the duration of illness (P=0.028), and to protein energy malnutrition, in particular, BMI and phase angle (P<0.001). CONCLUSIONS: Our study offers description of the incidence of hematologic defects in a selected and large sample of AN female patients, suggesting that its incidence is related to the degree and duration of protein energy malnutrition.

Response to angiotensin blockade with irbesartan in a patient with metastatic colorectal cancer.

BACKGROUND: A patient suffering from metastatic colorectal cancer, treatment-related toxicity and resistance to standard chemotherapy and radiation was assessed as part of a personalized oncogenomics initiative to derive potential alternative therapeutic strategies. PATIENTS AND METHODS: Whole-genome and transcriptome sequencing was used to interrogate a metastatic tumor refractory to standard treatments of a patient with mismatch repair-deficient metastatic colorectal cancer. RESULTS: Integrative genomic analysis indicated overexpression of the AP-1 transcriptional complex suggesting experimental therapeutic rationales, including blockade of the renin-angiotensin system. This led to the repurposing of the angiotensin II receptor antagonist, irbesartan, as an anticancer therapy, resulting in the patient experiencing a dramatic and durable response. CONCLUSIONS: This case highlights the utility of comprehensive integrative genomic profiling and bioinformatics analysis to provide hypothetical rationales for personalized treatment options.