Personalized Nutrition for Management of Micronutrient Deficiency—Literature Review in Non-bariatric Populations and Possible Utility in Bariatric Cohort

Abstract Background Bariatric surgery can effectively treat morbid obesity; however, micronutrient deficiencies are common despite recommendations for high-dose supplements. Genetic predisposition to deficiencies underscores necessary identification of high-risk candidates. Personalized nutrition (PN) can be a tool to manage these deficiencies. Methods Medline, PubMed, and Google Scholar were searched. Articles involving genetic testing, micronutrient metabolism, and bariatric surgery were included. Results Studies show associations between genetic variants and micronutrient metabolism. Research demonstrates genetic testing to be a predictor for outcomes among obesity and bariatric surgery populations. There is limited research in bariatric surgery and micronutrient genetic variants. Conclusion Genotype-based PN is becoming feasible to provide an effective treatment of micronutrient deficiencies associated with bariatric surgery. The role of genomic technology in micronutrient recommendations needs further investigation.

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The role of endoluminal interventions in the preparation of high-risk patients with super-obesity for bariatric surgery

General Surgery ◽

10.30978/gs-2021-1-18 ◽

2021 ◽

Author(s):

O. Y. Ioffe ◽

M. S. Kryvopustov ◽

O. P. Stetsenko ◽

T. V. Tarasiuk ◽

Y. P. Tsiura

Keyword(s):

Bariatric Surgery ◽

Body Mass Index ◽

Morbid Obesity ◽

High Risk ◽

Intragastric Balloon ◽

Conservative Therapy ◽

Control Group ◽

Obese Patients ◽

Super Obesity

Obesity causes increased morbidity, disability and mortality rates as well as affects the quality of life. Given the known risks to the patient’s health, the International Federation for the Surgery of Obesity and Metabolic Disorders pays special attention to the problem of morbid obesity (body mass index ≥ 40 kg/m2), with particular emphasis on super‑obesity (body mass index ≥ 50 kg/m2). Objective is to investigate the role of endoluminal interventions in the preparation of super obese patients with high risk of surgical and anaesthesia‑related complications for bariatric surgery. Materials and methods. From 2011 to 2018, 97 patients with morbid obesity and high risk of surgery and anaesthesia‑related complications (ASA PS III — IV) underwent a course of treatment at the clinical setting of the Department of General Surgery No2 of Bohomolets National Medical University. The treatment was carried out in 2 stages. In the main group (n = 60), the first stage of treatment included the intragastric balloon placement for a term of 6 months. The control group (n = 37) received a six‑month conservative therapy. In the second stage of treatment the patients of both groups underwent a surgical procedure for the morbid obesity management. Results. The outcomes of the first stage of treatment showed that the patients, who underwent the intragastric balloon placement, had statistically significantly (p < 0.001) higher mean the percentage of excess weight loss (% EWL) than the patients who received conservative therapy. In the main group, the average ASA PS score, which is identified as an anaesthetic and surgical risk indicator, decreased from 3.28 (95 % confidence interval (CI) 3.17 — 3.40) to 2.15 (95 % CI 2.06 — 2.24, p < 0.001), and in the control group — from 3.24 (95 % CI 3.10 — 3.39) to 3.14 (95 % CI 2.96 — 3.31, p > 0.05). Conclusions. The results of the study provide strong evidence that the intragastric balloon placement for a term of 6 months reduces surgical and anaesthetic risks, contributes to the improved function of the cardiovascular and respiratory systems as well as gives a boost to carbohydrate metabolism, and, therefore, can be suggested for the preparation of super obese patients with high risk of surgical and anaesthesia‑related complications for bariatric surgery.

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Early Consolidation with High Dose Therapy and Autologous Stem Cell Transplantation in HIV-Associated Non Hodgkin Lymphoma At High Risk (Aaipi 2–3). an Interim Report of a Multicenter Phase II Trial.

Blood ◽

10.1182/blood.v120.21.3124.3124 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3124-3124 ◽

Cited By ~ 1

Author(s):

Alessandro Re ◽

Mariagrazia Michieli ◽

Bernardino Allione ◽

Salvatore Casari ◽

Chiara Cattaneo ◽

...

Keyword(s):

High Risk ◽

High Dose ◽

Hepatic Toxicity ◽

First Line ◽

High Dose Therapy ◽

Anaplastic Lymphoma ◽

Cd34 Cells ◽

Grade Iii ◽

First Line Treatment

Abstract Abstract 3124 Background. Outcome of aggressive HIV-associated NHL (HIV-NHL) with adverse prognostic features is not satisfactory with standard therapy. High dose therapy (HDT) and autologous stem cell transplantation (ASCT) has been demonstrated safe and active in HIV-NHL in the salvage setting. Aims. To define the role of HDT and ASCT in the upfront treatment of HIV-NHL at high risk, in terms of efficacy and toxicity. We report the interim results of a multicenter study including HDT and ASCT as consolidation after first-line treatment of HIV-NHL at high-risk. Patients and methods. Inclusion criteria: untreated aggressive HIV-NHL (including DLBCL, plasmablastic, anaplastic lymphoma), aa-IPI 2–3, age 18–60, CD4+ count >50/mcl and availability of effective HAART. Burkitt and CNS lymphoma are excluded. Patients (pts) receive R-CHOP-21 (CHOP-21 or CHOP-14 for CD20 negative lymphoma) for 6 cycles and, if responsive, undergo stem cells mobilization and collection after Cyclophosphamide 4gr/ms + G-CSF followed by HDT with BEAM and ASCT. Involved-field radiotherapy on previous bulky or residual disease is recommended. Pts receive HAART during the entire treatment program. Overall survival (OS) at 2 years is the primary endpoint. Results. Since January 2007 to July 2012, 23 pts were registered and 20 entered the study. Median age was 47.5 years (range, 27–62). Fifteen pts (75%) had DLBCL, 4 (20%) plasmablastic and 1 (5%) anaplastic lymphoma. ECOG PS was >1 in 11 pts (55%); Ann-Arbor stage III/IV, 5(25%)/15(75%); B symptoms, 12 (60%); LDH > n.v., 18 (90%); aaIPI 2/3, 10 (50%)/10(50%). Fourteen pts (70%) had a prior history of HIV-positivity and 13 (65%) were on HAART at NHL diagnosis; thirteen (65%) had detectable HIV-viremia. Median CD4+ count was 283/mcl (58–571). Nine pts (45%) had HCV infection. Seventeen pts received (R)-CHOP-21 and 3 pts with plasmablastic histology received CHOP-14. One pt is still on treatment and 19/20 are evaluable for (R)-CHOP response. One had toxic death (due to hepatic failure), 2 had prolonged cytopenia (1 with severe hepatic toxicity) that lead to withdrawal of therapy and 16 completed (R)-CHOP therapy: 11 pts had complete remission (CR), 4 partial remission (PR) and 1 disease progression (PD) (ORR 79%,CR 58%, PR 21%, according to intention to treat). One pt is ongoing and 14 collected CD34+ cells after Cyclophosphamide + G-CSF (median CD34+ cells 7.35 × 10e6/Kg, range 2.65–10.0). Two pts had early disease progression after collection, 1 did not receive HDT because of cardiac ejection fraction < 50% at evaluation before BEAM and 1 is ongoing. So far, 10 pts received ASCT according to the protocol. Moreover, three pts received radiotherapy (2 on previous bulky and 1 on testicular disease). HDT-related toxicities included 2 grade II and 5 grade III GI and 1 grade III hepatic toxicity. Prior to engraftment 1 VZV infection, 1 Clostridium difficile colitis, 1 sigmoiditis and 5 episodes of FUO were registered. There were no transplant-related deaths. One case of CMV reactivation and no opportunistic infections were registered during observation. All transplanted pts are alive and relapse-free after a median of 43 ms (range, 4–58) after transplant (Figure 1). In the entire series, with a median f-up of 29.5 ms (range, 4–65), the 2-years PFS and OS of the entire series from study entry were 73% (+10.3%) and 76% (+10.6%), respectively (Figure 2). Conclusions. This is the first prospective trial addressing the role of HDT and ASCT in first line treatment of HIV-LNH. The procedure was well tolerated and the clinical results highly encouraging. Interim evaluation of OS in this very high risk series of pts is satisfactory and accrual is ongoing. Disclosures: No relevant conflicts of interest to declare.

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Early Consolidation with High Dose Therapy and Autologous Stem Cell Transplantation in HIV-Associated Non Hodgkin Lymphoma at High Risk (aa-IPI 2-3). Mature Results of a Multicenter Prospective Phase II Trial

Blood ◽

10.1182/blood.v124.21.2528.2528 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2528-2528 ◽

Cited By ~ 1

Author(s):

Alessandro Re ◽

Chiara Cattaneo ◽

Salvatore Casari ◽

Guido Gini ◽

Mariagrazia Michieli ◽

...

Keyword(s):

High Risk ◽

High Dose ◽

Hepatic Toxicity ◽

First Line ◽

High Dose Therapy ◽

Anaplastic Lymphoma ◽

Grade Ii ◽

Cmv Reactivation ◽

Entire Treatment

Abstract Background. Outcome of HIV-associated NHL (HIV-NHL) with adverse prognostic features is not satisfactory with standard therapy. High dose therapy (HDT) and autologous stem cell transplantation (ASCT) has proven safe and active in HIV-NHL in salvage setting. Aims. To define the role of HDT and ASCT in the upfront treatment of HIV-NHL at high risk, in terms of efficacy and toxicity. We report the mature results of a multicenter prospective study including HDT and ASCT as consolidation after first-line treatment of HIV-NHL at high-risk. Patients and methods. Inclusion criteria: untreated aggressive HIV-NHL (including DLBCL, plasmablastic, anaplastic lymphoma), aa-IPI 2-3, age 18-60, CD4+ count >50/mcl and availability of effective HAART.. Patients (pts) received R-CHOP (no Rituximab for CD20 negative lymphoma) for 6 cycles and, if responsive, underwent stem cells collection after Cyclophosphamide 4gr/ms + G-CSF followed by HDT with BEAM and ASCT. Involved-field radiotherapy on previous bulky or residual disease was recommended. Patients (pts) received HAART during the entire treatment program. Results: From January 2007 to July 2014, 29 pts were registered and 25 entered the study. Median age was 48 years (range, 27-62). Nineteen pts had DLBCL, 5 plasmablastic, 1 anaplastic lymphoma. ECOG PS was >1 in 14 pts (56%); Ann-Arbor stage III/IV, 7(28%)/18(72%); B symptoms, 16 (64%); LDH >n.v., 18 (88%); aaIPI 2/3, 13 (52%)/12 (48%). Eighteen pts (72%) had a prior history of HIV-positivity, and 17 (68%) were on HAART at NHL diagnosis. In 7 pts HIV and NHL diagnosis were concomitant. Fourteen pts (56%) had detectable HIV-viremia (range 40->500.000 cp/mL). Median CD4+ count was 255/mcl (51-571). Ten pts (40%) had HCV infection. Twenty-two pts received (R)-CHOP-21 and 3 pts with plasmablastic histology received CHOP-14. One pt is on treatment and 24/25 are evaluable for (R)-CHOP response. One pt died of hepatic failure and 1 due to cerebral hemorrhage, 2 had prolonged cytopenia (plus severe hepatic toxicity in 1) and 1 infectious complications that lead to withdrawal from the trial [however 1 achieved a complete remission (CR) and 2 died of progressive disease]; 19 pts completed (R)-CHOP according to the study: 14 had CR, 4 partial remission (PR) and 1 disease progression (PD). On an intention to treat basis: ORR 79.2%, CR 62.5%, PR 16.7%. Seventeen/18 pts collected stem cells (median CD34+ cells 7.4 x 10e6/Kg, range 2.6-10.1) and 1 failed mobilization. Two pts had early disease progression after collection, 1 did not receive HDT because of cardiac ejection fraction <50% at evaluation before BEAM and 14 actually received ASCT according to the protocol. Lymphoma stage IV and aa-IPI 3 were significantly associated with the risk of not receiving ASCT (p.02 and p.03 respectively, Fisher exact test). HDT-related toxicities included 5 grade II, 5 grade III and I grade IV gastrointestinal toxicity and 2 grade II and 1 grade III hepatic toxicity. Prior to engraftment, 1 VZV infection, 1 Clostridium difficile colitis, 1 sigmoiditis, 1 CMV reactivation and 9 FUO were registered. There were no transplant-related deaths. One case of CMV reactivation, 1 bacterial pneumonia and no opportunistic infections were registered during subsequent observation. After a median f-up of 50 ms (2-89), 5-years OS and PFS of the entire series were 74.6% (+8.9%) and 70.9% (+9.2%), respectively (Figure 1). All transplanted pts (100%) are alive and relapse-free after a median of 38.5 ms (1-82) after transplant (Figure 2). Conclusions: This is the first prospective trial addressing the role of HDT and ASCT in first line treatment of HIV-LNH. Almost 60% of pts were able to complete the entire treatment program and the ASCT was well tolerated. The OS in this series of pts at high risk is satisfactory and no relapse occurred in pts who received ASCT, after a prolonged follow-up. Further improvement could result from an increase in the rate of patients who receive ASCT. HDT with ASCT seems an effective way to consolidate first response and improve outcome in HIV-NHL at high risk . Fig 1 Survival from study entry (25 pts) Fig 1. Survival from study entry (25 pts) Fig 2 Survival after transplant (14 pts) Fig 2. Survival after transplant (14 pts) Disclosures No relevant conflicts of interest to declare.

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The role of autologous stem-cell transplantation in high-risk neuroblastoma consolidated by anti-GD2 immunotherapy: Results of 2 consecutive studies in a single referral institution.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.10539 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 10539-10539

Author(s):

Jaume Mora ◽

Alicia Castañeda ◽

Miguel Angel Flores ◽

Vicente Santa-María ◽

Moira Garraus ◽

...

Keyword(s):

Stem Cell ◽

High Risk ◽

High Dose Chemotherapy ◽

High Dose ◽

Cooperative Groups ◽

Gm Csf ◽

Stem Cell Rescue ◽

Single Center Study ◽

Study Population

10539 Background: Treatment of high-risk NB within the major international cooperative groups (COG and SIOP) comprise intensive induction, consolidation with high dose chemotherapy and autologous stem cell rescue (ASCR) followed by anti-GD2 immunotherapy and isotretinoin as maintenance therapy. In the COG studies dinutuximab and cytokines (GM-CSF and IL-2) were used to treat patients in complete remission (CR) after ASCR whereas SIOPEN studies used dinutuximab-beta plus/minus IL-2 and included patients with responsive (no progression 109 days after ASCR) but refractory (skeletal metaiodobenzylguanidine positivity with three or fewer areas of abnormal uptake). Methods: Since December 2014, HR-NB patients referred to HSJD were eligible for consolidation with anti-GD2/GM-CSF immunotherapy in 2 consecutive studies (dinutuximab for EudraCT 2013-004864-69 and naxitamab for 017-001829-40) and naxitamab/GM-CSF compassionate use (CU) with or without prior ASCR. Patients were enrolled in 1st CR or with primary refractory bone/bone marrow (B/BM) disease. We accrued a study population of two groups whose consolidative therapy, aside from ASCR, was similar: anti-GD2 (dinutuximab or naxitamab) antibodies + GM-CSF and local radiotherapy. This is a retrospective analysis of their event-free survival (EFS) and overall survival (OS) calculated from study entry. Results: From Dec 14 til Dec 19, 67 study patients were treated with the COG (dinutuximab + GM-CSF+ IL-2 + RA) regimen (n = 21) in the HSJD-HRNB-Ch14.18 study or with Naxitamab and GM-CSF in the Ymabs study 201 (n = 12) or CU (n = 34). 23 patients were treated with primary refractory disease in the B/BM, and 44 in 1st CR. The 67 study patients included 13 (19%) treated following single ASCR and 54 following induction chemotherapy and surgery. Median follow-up for all surviving patients is 16.2 months. Two-year rates for ASCR and non-ASCR patients were, respectively: EFS 64% vs. 54% (p = 0.28), and OS 66.7% vs. 84% (p = 0.8). For the 44 pts in 1st CR, 2-year rates for ASCR and non-ASCR patients were, respectively: EFS 65% vs. 58% (p = 0.48), and OS 71% vs. 85% (p = 0.63). Conclusions: In this retrospective, single center study, ASCR did not provide survival benefit when anti-GD2 + GM-CSF based immunotherapy was used for consolidation after dose-intensive conventional chemotherapy.

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Hypoadiponectinaemia and high risk of type 2 diabetes are associated with adiponectin-encoding (ACDC) gene promoter variants in morbid obesity: evidence for a role of ACDC in diabesity

Diabetologia ◽

10.1007/s00125-005-1729-z ◽

2005 ◽

Vol 48 (5) ◽

pp. 892-899 ◽

Cited By ~ 88

Author(s):

F. Vasseur ◽

N. Helbecque ◽

S. Lobbens ◽

V. Vasseur-Delannoy ◽

C. Dina ◽

...

Keyword(s):

Type 2 Diabetes ◽

Morbid Obesity ◽

High Risk ◽

Gene Promoter

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Prostate cancer susceptibility genes: lessons learned and challenges posed.

Endocrine Related Cancer ◽

10.1677/erc.0.0100225 ◽

2003 ◽

pp. 225-259 ◽

Cited By ~ 63

Author(s):

J Simard ◽

M Dumont ◽

D Labuda ◽

D Sinnett ◽

C Meloche ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Genetic Variants ◽

Cancer Susceptibility ◽

Susceptibility Genes ◽

Screening Methods ◽

Cancer Susceptibility Genes ◽

Prostate Cancer Susceptibility ◽

Common Genetic Variants

In most developed countries, prostate cancer is the most frequently diagnosed malignancy in men. The extent to which the marked racial/ethnic difference in its incidence rate is attributable to screening methods, environmental, hormonal and/or genetic factors remains unknown. A positive family history is among the strongest epidemiological risk factors for prostate cancer. It is now well recognized that the role of candidate genetic markers to this multifactorial malignancy is more difficult to identify than the identification of other cancer susceptibility genes. Indeed, despite the localization of several susceptibility loci, there has been limited success in identifying high-risk susceptibility genes analogous to BRCA1 or BRCA2 for breast and ovarian cancer. Nonetheless, three strong candidate susceptibility genes have been described, namely ELAC2 (chromosome 17p11/HPC2 region), 2'-5'-oligoadenylate-dependent ribonuclease L (RNASEL), a gene in the HPC1 region, and Macrophage Scavenger Receptor 1 (MSR1), a gene within a region of linkage on chromosome 8p. Additional studies using larger cohorts are needed to fully evaluate the role of these susceptibility genes in prostate cancer risk. It is also of interest to mention that a significant percentage of men with early-onset prostate cancer harbor germline mutation in the BRCA2 gene thus confirming its role as a high-risk prostate cancer susceptibility gene. Although initial segregation analyses supported the hypothesis that a number of rare highly penetrant loci contribute to the Mendelian inheritance of prostate cancer, current experimental evidence better supports the hypothesis that some of the familial risks may be due to inheritance of multiple moderate-risk genetic variants. In this regard, it is not surprising that analyses of genes encoding key proteins involved in androgen biosynthesis and action led to the observation of a significant association between a susceptibility to prostate cancer and common genetic variants in some of those genes.

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Intensive Fludarabine, High Dose Cytarabine and Idarubicin-Based Induction for Younger NPM1-Mutated AML Patient: Overcoming the Negative Prognosis of FLT3-ITD Mutation

Blood ◽

10.1182/blood-2020-142887 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 32-33

Author(s):

Paola Minetto ◽

Anna Candoni ◽

Fabio Guolo ◽

Marino Clavio ◽

Maria Elena Zannier ◽

...

Keyword(s):

High Risk ◽

Risk Stratification ◽

High Dose ◽

Prognostic Impact ◽

Allogeneic Bone ◽

Npm1 Mutation ◽

Mutational Status ◽

High Dose Cytarabine ◽

Allelic Burden

NPM1 and FLT3 mutational status assessment is recommended in acute myeloid leukemia (AML) at diagnosis by European Leukemia Net (ELN) risk stratification. The presence of NPM1 mutation (NPM1-mut) partially overcomes the negative prognostic impact of FLT3-ITD, which is also modulated by FLT3-ITD/wild-type allelic ratio. Targeted drugs are available for FLT3-mutated AML but no data are available so far on the efficacy of intensified front-line regimens in overcoming the negative prognostic role of FLT3-ITD mutation. We investigated the efficacy of an intensive fludarabine, high dose cytarabine (ARA-C) and Idarubicin (IDA) induction regimen (FLAI) as frontline treatment for fit, de novo AML patients according to NPM1 and FLT3-ITD mutational status. One-hundred and forty-nine consecutive AML patients, treated in 3 Hematology Italian centers from January 2008 to January 2018, were included in this analysis. Twenty nine patients had isolated FLT3-ITD, 59 concomitant FLT3-ITD and NPM1-mut and 61 isolated NPM1-mut. Median age was 51 yrs (range: 18-65). All patients received FLAI induction (fludarabine 30 mg/sqm and ARA-C 2g/sqm on days 1 to 5 plus IDA 10 mg/sqm on days 1-3-5). For patients achieving CR fludarabine was omitted on II induction and IDA dose was increased to 12 mg/sqm. Before ELN 2017 risk stratification was adopted, patients with isolated FLT3-ITD mutation were scheduled to receive allogeneic bone marrow transplantation (allo-BMT) in first CR regardless of allelic burden. For patients with AML with NPM1 mutation and concomitant FLT3-ITD indication to allo-BMT in 1st complete remission was mainly based on minimal residual disease (MRD) status. MRD was evaluated on marrow samples using multicolor flow-cytometry (MFC) or NPM1 expression levels. Negative MFC-MRD was defined by the presence of less than 25 clustered leukemic cells/105 total events (threshold of 0.025%, Minetto et. al, BJH 2019). NPM1-mut (NPM1-A, B and D) was measured using Muta Quant Kit Ipsogen from Qiagen. FLT3-ITD allelic burden was available in31/64 of FLT3-ITD patients. Overall, 60-days mortality was 4.7%. After first induction cycles, 129 patients achieved CR (86.6%). Thirty-five/129 (25.5%) CR patients underwent BMT in first CR. After a median follow up of 68 months, 3-year overall survival (OS) was 58.6% (median not reached). In univariate analysis OS duration was affected by NPM1, FLT3 mutational status and ELN risk score. However, NPM1-mutated patient was not negatively affected by the presence of FLT3-ITD, regardless of allelic burden. This observation was even more evident in patients younger than 55 yrs (3 yy OS 64% and 68% for NPM1-mutated with or w/o FLT3-ITD, respectively (p=n.s, Figure 1), regardless of FLT3-ITD allelic burden. ELN 2017 high risk patients displayed the worst prognosis (3-year OS 35.2%). Multivariate analysis showed that NPM1 mutation was the strongest predictor of survival. In order to assess the impact of allo-BMT in 1st CR we performed a Landmark Analysis including patients alive and in CR at day 90. Interestingly, performing allo-BMT in 1st CR did not impact OS in the whole cohort of patients and irrespectively of NPM1 and FLT3 mutational status. The only subgroup who benefit from allo-BMT in first CR was high risk ELN2017 (p<0.05). Despite the potential bias due to the retrospective nature of the analysis, our data indicate that intensive fludarabine-high dose cytarabine-based induction exerts a strong anti-leukemic efficacy in younger AML patients carrying NPM1 mutation irrespectively of FLT3 mutational status. Our data potentially question the role of BMT in first CR in this setting. Figure Disclosures Bocchia: CELGENE: Honoraria; Incyte: Honoraria.

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