Evaluation of scientific validity and appropriateness of artificial intelligence-assisted ChatGPT advices in dietary treatment of methylmalonic acidemia.

Background The prevalence of undernutrition ranges from 25% to 70% and severe undernutrition from 1% to 30% among individuals with active inflammatory bowel disease (IBD). The aetiology of malnutrition is multifactorial. There are not many studies that have assessed nutrition after therapy modification and dietary advice. Aim To study the prevalence of undernutrition in IBD and the change after nutritional advice. Methods In this single-centre prospective cohort study, 218 consecutive patients with IBD were screened. Patients with associated diseases that could lead to undernutrition were excluded (N=18). Nutritional assessment was done as per the European Society for Clinical Nutrition and Metabolism (ESPEN) definition: BMI <18.5 kg/m2 or unintentional weight loss >10% were defined as undernutrition and the Malnutrition Inflammation Risk Tool (MIRT) score was calculated. Obesity was defined as per the WHO Asian BMI classification: grade 1 (BMI 25-29.9 Kg/m2) and obesity grade 2 (BMI >30 Kg/m2)1. Patients were given nutritional advice and therapy was optimized as per disease activity. BMI and MIRT were calculated on subsequent visits to assess response to nutritional advice. Results Of 200 patients (median age 39 [IQR 28-53] years; 96 females), 105 had ulcerative colitis (UC), 93 Crohn’s disease (CD), and 2 IBD-unclassified. Fifty-four (27%) patients had undernutrition (28 UC, 25 CD, and 1 IBD-U). Sixty-one (30.5%) patients were obese. At follow up (median duration 24 months), of 37/54 patients with BMI <18.5 Kg/m2, BMI increased in 24 (64.8%) and decreased in 13 (35.1%); of 17 patients with >10% unintentional weight loss, 5 (29.4%) had increased weight on follow-up. MIRT score decreased in 24/54 patients (44.4%), remained same in 14 (25.9%), and increased in 16 patients (29.6%). Of the 24 patients with decrease in MIRT score, 7/24 (29.1%) received only dietary advice, 10 (41.6%) received dietary advice and optimization of IBD treatment, and 7 (29.1%) received only optimization of IBD treatment. Conclusion The prevalence of undernutrition and obesity in patients with IBD was 27% and 30.5%, respectively. After dietary advice and therapy optimization, nutrition improved in 53.7% while MIRT score decreased in 43.3% of patients.

BackgroundMutations in methylmalonyl-CoA mutase cause methylmalonic acidemia, a common organic aciduria. Current treatment regimens rely on dietary management and, in severely affected patients, liver or combined liver-kidney transplantation. For undetermined reasons, transplantation does not correct the biochemical phenotype.MethodsTo study the metabolic disturbances seen in this disorder, we have created a murine model with a null allele at the methylmalonyl-CoA mutase locus and correlated the results observed in the knock-out mice to patient data. To gain insight into the origin and magnitude of methylmalonic acid (MMA) production in humans with methylmalonyl-CoA mutase deficiency, we evaluated two methylmalonic acidemia patients who had received different variants of combined liver-kidney transplants, one with a complete liver replacement-kidney transplant and the other with an auxiliary liver graft-kidney transplant, and compared their metabolite production to four untransplanted patients with intact renal function.ResultsEnzymatic, Western and Northern analyses demonstrated that the targeted allele was null and correctable by lentiviral complementation. Metabolite studies defined the magnitude and tempo of plasma MMA concentrations in the mice. Before a fatal metabolic crisis developed in the first 24–48 hours, the methylmalonic acid content per gram wet-weight was massively elevated in the skeletal muscle as well as the kidneys, liver and brain. Near the end of life, extreme elevations in tissue MMA were present primarily in the liver. The transplant patients studied when well and on dietary therapy, displayed massive elevations of MMA in the plasma and urine, comparable to the levels seen in the untransplanted patients with similar enzymatic phenotypes and dietary regimens.ConclusionThe combined observations from the murine metabolite studies and patient investigations indicate that during homeostasis, a large portion of circulating MMA has an extra-heptorenal origin and likely derives from the skeletal muscle. Our studies suggest that modulating skeletal muscle metabolism may represent a strategy to increase metabolic capacity in methylmalonic acidemia as well as other organic acidurias. This mouse model will be useful for further investigations exploring disease mechanisms and therapeutic interventions in methylmalonic acidemia, a devastating disorder of intermediary metabolism.

Methylmalonic acidaemia (MMA) is a genetic disorder caused by defects in methylmalonyl-CoA mutase or in any of the different proteins involved in the synthesis of adenosylcobalamin. The aim of this work was to examine the biochemical and clinical phenotype of 32 MMA patients according to their genotype, and to study the mutant mRNA stability by real-time PCR analysis. Using cellular and biochemical methods, we classified our patient cohort as having the MMA forms mut (n = 19), cblA (n = 9) and cblB (n = 4). All the mut (0) and some of the cblB patients had the most severe clinical and biochemical manifestations, displaying non-inducible propionate incorporation in the presence of hydroxocobalamin (OHCbl) in vitro and high plasma odd-numbered long-chain fatty acid (OLCFA) concentrations under dietary therapy. In contrast, mut (-) and cblA patients exhibited a milder phenotype with propionate incorporation enhanced by OHCbl and normal OLCFA levels under dietary therapy. No missense mutations identified in the MUT gene, including mut (0) and mut (-) changes, affected mRNA stability. A new sequence variation (c.562G>C) in the MMAA gene was identified. Most of the cblA patients carried premature termination codons (PTC) in both alleles. Interestingly, the transcripts containing the PTC mutations were insensitive to nonsense-mediated decay (NMD).

Methylmalonic aciduria (MMA) and propionic aciduria (PA) are organic acidurias characterised by the accumulation of toxic metabolites and hyperammonaemia related to secondary N-acetylglutamate deficiency. Carglumic acid, a synthetic analogue of N-acetylglutamate, decreases ammonia levels by restoring the functioning of the urea cycle. However, there are limited data available on the long-term safety and effectiveness of carglumic acid. Here, we present an interim analysis of the ongoing, long-term, prospective, observational PROTECT study (NCT04176523), which is investigating the long-term use of carglumic acid in children and adults with MMA and PA. Individuals with MMA or PA from France, Germany, Italy, Norway, Spain, Sweden and the UK who have received at least 1 year of carglumic acid treatment as part of their usual care are eligible for inclusion. The primary objective is the number and duration of acute metabolic decompensation events with hyperammonaemia (ammonia level >159 µmol/L during a patient's first month of life or >60 µmol/L thereafter, with an increased lactate level [> 1.8 mmol/L] and/or acidosis [pH < 7.35]) before and after treatment with carglumic acid. Peak plasma ammonia levels during the last decompensation event before and the first decompensation event after carglumic acid initiation, and the annualised rate of decompensation events before and after treatment initiation are also being assessed. Secondary objectives include the duration of hospital stay associated with decompensation events. Data are being collected at approximately 12 months' and 18 months' follow-up. Of the patients currently enrolled in the PROTECT study, data from ten available patients with MMA (n = 4) and PA (n = 6) were analysed. The patients had received carglumic acid for 14-77 (mean 36) months. Carglumic acid reduced the median peak ammonia level of the total patient population from 250 µmol/L (range 97-2569) before treatment to 103 µmol/L (range 97-171) after treatment. The annualised rate of acute metabolic decompensations with hyperammonaemia was reduced by a median of - 41% (range - 100% to + 60%) after treatment with carglumic acid. Of the five patients who experienced a decompensation event before treatment and for whom a post-treatment rate could be calculated, the annualised decompensation event rate was lower after carglumic acid treatment in four patients. The mean duration of hospital inpatient stay during decompensation events was shorter after than before carglumic acid treatment initiation in four of five patients for whom length of stay could be calculated. In this group of patients with MMA and PA, treatment with carglumic acid for at least 1 year reduced peak plasma ammonia levels in the total patient population and reduced the frequency of metabolic decompensation events, as well as the duration of inpatient stay due to metabolic decompensations in a subset of patients. ClinicalTrials.gov, NCT04176523. Registered 25 November, 2019, retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04176523 .

Effective immunoglobulin therapy for brief tonic seizures in methylmalonic acidemia

A basic difference between dietary and drug therapy of hypercholesterolemia is that dietary therapy can be used as part of a population strategy, whereas the decision to use drugs is always made on an individual basis. In each case, the decision to treat must be based on the assumption that more good than harm is caused to the patient. This is a difficult situation for the physician. As long as there is no easy way of assessing the state and rate of progression of coronary lesions, the physician must treat the patient on statistical grounds only, i.e., rely on the results of studies showing that lowering serum cholesterol significantly decreases the risk of coronary events. Such evidence has recently been strengthened, which increases motivation for both physician and patients. The current general opinion is that drug therapy must be generally confined to those at high risk, i.e., patients with severe hypercholesterolemia. For individuals with moderately elevated serum cholesterol levels, dietary advice and correction of other risk factors should be adequate.

The management of the severe variants of methylmalonic and propionic acidaemia remains difficult. With conventional therapy of diet, carnitine and antibiotics, mortality is high and long-term complications are common. Liver transplantation appears to be an important alternative.

BackgroundMethylmalonic acidaemia (MMA) is a genetic metabolic disorder caused by congenital defects that may result in multisystem damage. However, MMA complicated with acute myeloid leukemia (AML) is very rare.Case presentationHere, we report a case of MMA with AML in a boy aged 7 years and 6 months. The boy was screened for MMA after birth and received long-term treatment with dietary control, vitamin B12, and L-carnitine. He was readmitted at the age of 7 years and 6 months with systemic bleeding spots and was diagnosed with AML by bone marrow cytology. When the diagnosis was clear, the patient received chemotherapy in addition to maintenance treatment for MMA. His blood routine, liver and kidney function, blood biochemistry, blood glucose, blood lipids, lactic acid and blood ammonia were monitored continuously. Bone marrow cytology one month after starting chemotherapy showed complete remission. Sorafenib was also added during chemotherapy and was discontinued 1 year after completion of chemotherapy. At the end of chemotherapy, he chose venetoclax for consolidation, and to date, the patient's condition is stable, with sustained CR and no relapse.ConclusionMMA combined with AML is rare. The prevention of infection, comprehensive assessment of nutritional status, continuous monitoring of related indicators and overall situation should be prioritized and comprehensive and individualized treatment approaches are paramount.

Credible evidence-based diet and nutrition advice is essential for patients with cancer. This study aimed to explore what advice patients with cancer obtained before a formal dietetic visit. A multicenter, observational study was conducted in seven hospital-based oncology services. Consecutive patients were recruited at first dietetic assessment. In addition to routine dietetic assessment, participants completed a four-item questionnaire describing diet and nutrition advice obtained since diagnosis. Seventy-seven patients participated. More than 80% had multiple nutrition-impact symptoms. In total, 53 (69%) obtained advice from professional and nonprofessional sources before dietetic visit. Family and friends were the most common sources of advice. More than one third got advice from (nondietetic) healthcare professionals. Most advice related to "foods to include" (61%) and "foods to avoid" (54%) in the diet. Many of the "foods to avoid" were important sources of micro- and macronutrients. Advice about dietary supplements (31%) and specific diets (28%) was common, rarely evidence-based, and frequently contradictory. Participants found it difficult to discern what advice was trustworthy and reliable. Despite this, most followed the advice. The majority of patients received diet and nutrition advice before first dietetic visit. Most of this came from nonprofessional sources. Any advice from nondietetic healthcare professionals was inconsistent or vague. This was mainly related to the avoidance and/or inclusion of particular foods and was often contradictory. Nevertheless, patients usually followed such advice fully. To help manage their frequent nutrition-impact symptoms and resolve the contradictory advice they had received, many expressed the need for earlier professional dietetic consultation.

Sirs, Methylmalonic aciduria (MMA) is an inborn error of metabolism, characterized by deficiency of the mitochondrial enzyme methylmalonyl-CoA mutase or by defects in the synthesis of 5-deoxyadenosylcobalamin, a cofactor of methylmalonyl-CoA mutase. Affected children suffer from lethargy, failure to thrive, and muscular hypotonia, and may have ketoacidotic, hypoglycemic, and hyperammonemic coma. Biochemically, the disease is characterized by accumulation of methylmalonate and, due to activation of alternative pathways of propionate oxidation, by accumulation of proprionate, 3-hydroxyproprionate, and 2-methylcitrate. Some of these organic acids have been suggested to act as endogenous toxins, inducing a synergistic inhibition of mitochondrial energy metabolism [1, 2]. Dietary and emergency therapy and thus outcome have substantially improved [3]. In brief, treatment is based on a restriction of natural protein and administration of precursor-free amino acid mixtures, as well as supplementation of carnitine. To avoid malnutrition and catabolism, affected patients require close monitoring during therapy. Secondary organ damage, however, remains insufficiently resolved, particularly if metabolic control is inadequate. Impairment of renal function is observed in a majority of patients [4]. It is characterized by tubulointerstitial nephritis with mononuclear cell infiltration, interstitial fibrosis, and tubular atrophy [5, 6, 7, 8]. Chronic renal failure (CRF) usually develops within the 1st or 2nd decade of life. However, adequate dietary control of protein metabolism is likely to slow the progression of renal disease, although this has not yet been investigated in prospective, observational studies. We report a 16-year-old male adolescent with vitamin B12-unresponsive MMA (mut ) and partially reversible end-stage renal disease, most likely due to improved metabolic control. In this patient, MMA was diagnosed shortly after birth, and a low-protein diet and carnitine supplementation was initiated. There were several episodes of metabolic decompensation due to inadequate metabolic control during infancy and childhood, resulting in neurological sequelae and CRF. Notably, a reduced glomerular filtration rate (GFR) was noted at 2.3 years of age. At 9 years of age, he developed spastic diplegia. CRF slowly progressed until puberty. At the age of 15 years, the patient was referred to our unit with a creatinine of 6.6 mg/dl and a GFR of 8 ml/min per 1.73 m (Fig. 1A). Transient hypercalcemia due to treatment of secondary hyperparathyroidism with 1, 25-dihydroxyvitamin D3 had resolved at the time of admission. Selective metabolic investigations revealed insufficient metabolic control, most likely due to inadequate adherence to the recommended dietary regimen. High-performance liquid chromatography analysis of plasma carnitine showed strongly elevated acylcarnitines, but free carnitine was within the normal range due to supplementation (Fig. 1B). Differentiation of acylcarnitines using tandem mass spectrometry of dried blood spots showed a predominant elevation of propionylcarnitine (Fig. 1B). Organic acid analysis of urine revealed a urinary excretion of methylmalonate, 2-methylcitrate, lactate, and pyruvate (Fig. 1C). ParathyC. P. Schmitt · O. Mehls · T. L. Weber Division of Pediatric Nephrology, Department of General Pediatrics, University Children’s Hospital, Heidelberg, Germany

The aim of the study was to compare the effects of high-intensity interval training (HIIT) and nutrition advice on cardiometabolic biomarkers, hormonal parameters, and cardiorespiratory fitness in adolescent girls with obesity. Adolescent girls with obesity (n = 44, aged 13-19 years) were randomized into a 12-week intervention as follows: (i) dietary advice and HIIT (n = 22), and (ii) dietary advice only (n = 22). The concentration of biomarkers of inflammation, biochemical and hormonal testing, oral glucose tolerance test, cardiorespiratory fitness, physical activity levels, and nutrition were assessed. After a 3-month intervention, the diet+HIIT group significantly increased insulin sensitivity index (-0.34 ± 1.52 vs. 1.05 ± 3.21; p = 0.001) and work load (0.6 ± 11.3 W vs. 14.6 ± 20.2 W; p = 0.024) and decreased glucose area under the curve (-0.29 ± 4.69 vs. -0.98 ± 4.06; p = 0.040), insulin area under the curve (-9.65 ± 117.9 vs. -98.7 ± 201.8; p = 0.003), and high-sensitivity C-reactive protein (hs-CRP) (0.12 ± 1.92 mg/L vs. -1.47 ± 3.67 mg/L; p = 0.039) in comparison with the diet group. Regarding within-group changes, both groups had significant improvements in body mass index (BMI), BMI-standard deviation score, body fat percentage, and systolic blood pressure. Positive impact on waist circumference, waist circumference/height ratio, diastolic blood pressure, hs-CRP, work load, maximal heart rate, and resting heart rate was observed only after the diet+HIIT intervention. No significant change was noted in peak oxygen uptake, lipid profile, and hormonal parameters between groups after intervention. Novelty HIIT and nutrition advice increased insulin sensitivity and decreased BMI, body fat, systolic blood pressure, and diastolic blood pressure. Nutrition advice decreased BMI, body fat, and systolic blood pressure in adolescent girls with obesity.

Artificial intelligence: Friend or foe?

Isolated methylmalonic acidemia (MMA), a group of autosomal recessive inborn errors of metabolism, is most commonly caused by complete (mut(0)) or partial (mut(-)) deficiency of the enzyme methylmalonyl-CoA mutase (MUT). The severe metabolic instability and increased mortality experienced by many affected individuals, especially those with mut(0) MMA, has led centers to use elective liver transplantation as a treatment for these patients. We have previously demonstrated the efficacy of systemic adeno-associated viral (AAV) gene delivery as a treatment for MMA in a murine model and therefore sought to survey AAV antibody titers against serotypes 2, 8, and 9 in a group of well-characterized MMA patients, accrued via a dedicated natural history study ( clinicaltrials.gov ID: NCT00078078). Plasma samples provided by 42 patients (8 mut(-) and 34 mut(0); 10 had received organ transplantation), who ranged in age between 2 and 31 years, were analyzed to examine AAV2 (n = 35), AAV8 (n = 41), and AAV9 (n = 42) antibody titers. In total, the seroprevalence of antibodies against AAV2, AAV8, or AAV9 was 20%, 22%, and 24%, respectively. We observed a lower-than-expected seropositivity rate (titers ≥1:20) in the pediatric MMA patients (2-18 years) for both AAV2 (p < 0.05) and AAV8 (p < 0.01) neutralizing antibodies (NAbs) compared with historical controls. Those with positive NAb titers were typically older than 18 years (p < 0.05 all serotypes) or had received solid organ transplantation (p < 0.01 AAV8, AAV9). The mut(0) patients who had not been transplanted (n = 24)-that is, the subset with the greatest need for improved treatments-represented the seronegative majority, with 21 out of 24 patients lacking Abs against all AAV capsids tested. The unexpected lack of NAbs against AAV in this patient population has encouraging implications for systemic gene delivery as a treatment for mut MMA.

AimThis study aims to evaluate the role of dentures and dietary advice on the nutritional status of complete edentulous patients using the mini nutritional assessment-short form (MNA®-SF).ObjectiveThe objective of this study is to assess patients’ nutrition using MNA®-SF before denture insertion and nutritional advice, to evaluate patients’ nutrition using MNA®-SF after denture insertion and nutritional advice at one month and three months, and to assess and compare pre- and post-insertion differences in nutrition using MNA®-SF.Material and MethodAn observational study was conducted among 50 completely edentulous patients using the MNA®-SF questionnaire. They were asked the questions at baseline and then after they were given complete dentures, after which they were recalled after one month and three months to assess the nutritional status using MNA®-SF. All the questions were in the native language, so it was easy to understand the question and respond to it.ResultIt was found that the patient’s nutritional status had significant changes, which shows that the dietary advice and complete denture affected the patient’s nutritional status.ConclusionsThis study helped assess the efficacy and application of MNA®-SF in completely edentulous patients. In this study, we provided nutritional guidance to patients in addition to complete denture prostheses to encourage them to have healthy eating habits.

Introduction: Cancer, in particular breast cancer, is one of the leading causes of death among women. Good nutritional status contributes to the efficacy of treatment and recovery, and nutritional interventions can minimize the adverse effects of cancer therapy.Aim: The aim of this study was to describe the potential role of dietary counseling in breast cancer patients. The impact of nutritional advice on the nutritional status of patients, the use of dietary supplements, and the knowledge of phytoestrogens were assessed.Materials and Methods: The study was conducted between April and July 2016 in the Lublin Oncology Center on a group of 173 female patients undergoing breast cancer treatment. The patients filled out a questionnaire containing 34 open-ended and closed-ended questions. The collected data were processed in Excel and Statistica 5.0 programs, and the results were regarded as significant at P < 0.05.Results: The mean age of the evaluated patients was 66.8 ± 11.3 years. The duration of disease was significantly correlated with the patients’ nutritional status expressed by the body mass index (P = 0.0368). The main sources of knowledge about nutrition in cancer care were nurses (29.71%), physicians (12.31%), and nutritionists (13.78%). Patients who received nutritional advice had significantly greater knowledge about phytoestrogens (P = 0.0001), and they were of the opinion that a diet rich in phytoestrogens was safe (P = 0.001). More than 85% of the polled subjects used dietary supplements during treatment, and 2/3 of them did so without professional advice. In this study, 73.07% of the respondents regularly monitored their body weight. Patients who did not receive dietary advice less frequently informed their physician about weight changes.Conclusions: The nutritional status of patients was correlated with access to nutrition and dietary advice during illness. The risk of malnutrition was minimized when patients received and understood educational materials. The patients who did not receive dietary advice more frequently overdosed on dietary supplements. Phytoestrogens were more widely used by patients who regularly attended a dietitian.