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1.
Am J Clin Nutr ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38936776

RESUMO

BACKGROUND: Computed Tomography (CT) has an underutilized potential for evaluating body composition in clinical settings. Often conducted with intravenous contrast (IVC), CT scans yield unused body composition data due to unclear effects on skeletal muscle area (SMA), skeletal muscle index (SMI), and muscle density (SMD). OBJECTIVE: This study investigates whether weight-adjusted IVC influences SMA, SMI, and SMD differently in female and male compared to non-contrast abdominal CT. Additionally, the study explores associations between contrast and non-contrast assessed SMA, SMI, SMD, and demographic factors. METHODS: A comparative observational retrospective study was conducted on Danish patients who underwent consecutive four-phased contrast-enhanced abdominal CT scans (non-contrast, arterial, venous, and late venous phases). Muscle measures were evaluated using validated semi-automated threshold-based software by three independent raters. RESULTS: The study included 72 patients (51 male, 21 female) with a mean age of 59 (55, 62) years. Weight-adjusted IVC increased SMA by up to 3.28 cm2 (CI: 2.58, 3.98) corresponding to 2.4% (1.8, 2.9) in late venous phase compared to non-contrast CT. Analysis between sexes showed no difference in the effects of IVC on SMA and SMI between female and male. However, females exhibited a higher increase in SMD during the venous by a mean of 1.7 HU 0.9; 2.5) and late venous phases with a mean HU of 1.80 (1.0; 2.6) compared to males. Multivariate regression analysis indicated an association between the differences in SMD and sex during venous (-1.38 , 95%CI: - 2.48, -0.48) and late venous phases (-1.23, 95% CI: -2.27, -0.19) CONCLUSION: Weight-adjusted IVC leads to increased SMA, SMI, and SMD. While SMA and SMI differences were consistent across the sexes, females exhibited a significantly higher SMD increase than male in the venous and late venous phases. Further investigations are necessary to determine the applicability of SMD as a muscle quality proxy in IVC CT scans.

2.
Clin Nutr ESPEN ; 62: 33-42, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38901947

RESUMO

BACKGROUND: Limited benefit of pulmonary exercise rehabilitation has been associated with fulfilment of energy and protein requirements. OBJECTIVES: The aim was to enhance dietary intake towards requirements and to maintain changes after a pulmonary rehabilitation program. METHODS: This single arm intervention study included multidisciplinary focus on nutrition and three sessions of individual dietary counselling during a 10-week pulmonary exercise rehabilitation in five municipalities centers. Data were collected at baseline (P0), at the end of intervention (P1) and for two municipalities at three months post intervention (P2). RESULTS: Of the 111 included participants, (mean age 70.8 (±9)) 99 (89%) completed the rehabilitation including the three individual dietary counselling's. A very large variation in body composition including body mass index and exercise abilities was found. Protein intake improved from 64 (±22 g) (P0) to 88 (±25 g) (P1) (p < 0.001) and energy intake from 1676 (±505 kcal) (P0) to 1941 (±553 kcal) (p < 0.001) (P1) and Muscle Mass Index increased from 10.6 (±3.2) (P0) to 10.9 (±3.2) (P1) (p = 0.007); number of 30 s chair stand test improved from 10.9 (±2.8) repetitions (P0) to 14.1 (±4.3) repetitions (P1) (p < 0.001), distance in six-minut walking test improved from 377.2 (±131.2 m) (P0) to 404.1 (±128.6 m) (P1) (p < 0.001). Two municipalities completed the three months follow-up. For those, dietary improvements remained stable, including protein intake. CONCLUSION: Including three sessions of dietary counselling in a multi-professional effort was associated with improved individualized dietary intake, as well as physical function. Benefits remained almost unchanged after three months. Improvements in function could not be fully explained by improved intakes.


Assuntos
Ingestão de Energia , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos de Coortes , Índice de Massa Corporal , Aconselhamento , Composição Corporal , Estado Nutricional , Proteínas Alimentares/administração & dosagem , Exercício Físico , Terapia por Exercício/métodos , Dieta , Necessidades Nutricionais
3.
Clin Nutr ; 43(8): 1685-1693, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38879915

RESUMO

BACKGROUND AND AIMS: The aging process is often accompanied by high risk of malnutrition and elevated levels of growth differentiation factor 15 (GDF15). GDF15 is an increasingly recognized biomarker for regulation of metabolism, but few studies have investigated the connection between GDF15 and malnutrition in older age and how it relates to other features of aging such as decreased appetite and physical function. Therefore, we investigated the associations between GDF15 levels and nutritional status, appetite, and physical function in acutely admitted older adults. METHODS: Plasma GDF15 levels were measured using immunoassays in 302 older adults (≥65 years) admitted to the emergency department (ED). Nutritional status was evaluated with the Mini Nutritional Assessment Short-Form (MNA®-SF), appetite was evaluated with the Simplified Nutritional Appetite Questionnaire (SNAQ), and physical function was evaluated with handgrip strength (HGS), 30-s chair stand test (30s-RSS), and gait speed (GS). Associations between GDF15 and each outcome was determined by logistic regression adjusted for age, sex, and C-reactive protein (CRP). RESULTS: Each doubling in plasma GDF15 level was associated with an adjusted odds ratio (OR) (95% confidence interval) of 1.59 (1.10-2.29, P = 0.01) for risk of malnutrition compared to normal nutrition and 1.19 (0.85-1.69, P = 0.3)) for malnutrition compared to risk of malnutrition. Each doubling in GDF15 was associated with an adjusted OR of 1.63 (1.21-2.23)) for having poor appetite, 1.46 (1.07-1.99) for having low HGS, 1.74 (1.23-2.51) for having low 30s-RSS, and 1.99 (1.39-2.94) for having low GS. CONCLUSION: Among older adults admitted to the ED, higher GDF15 levels were significantly associated with malnutrition, poor appetite, and low physical function independent of age, sex, and CRP.

4.
Nutrition ; 123: 112396, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38554461

RESUMO

OBJECTIVE: Parenteral nutrition represents a therapeutic option for patients with type 3 intestinal failure. If used exclusively, parenteral nutrition has to be complete to provide all essential nutrients. The aim was to assess the availability of parenteral nutrition in all parts of the world, to better comprehend the global situation, and to prepare an action plan to increase access to parenteral nutrition. METHODS: An international survey using an electronic questionnaire was conducted in August 2019 and repeated in May 2022. An electronic questionnaire was sent to 52 members or affiliates of the International Clinical Nutrition Section of the American Society for Parenteral and Enteral Nutrition. Questions addressed the availability of parenteral nutrition admixtures and their components, reimbursement, and prescribing pre- and post-COVID-19 pandemic. All participating countries were categorized by their economic status. RESULTS: Thirty-six country representatives responded, answering all questions. Parenteral nutrition was available in all countries (100%), but in four countries (11.1%) three-chamber bags were the only option, and in six countries a multibottle system was still used. Liver-sparing amino acids were available in 18 (50%), kidney-sparing in eight (22.2%), and electrolyte-free in 11 (30.5%) countries (30.5%). In most countries (n = 28; 79.4%), fat-soluble and water-soluble vitamins were available. Trace elements solutions were unavailable in four (11.1%) countries. Parenteral nutrition was reimbursed in most countries (n = 33; 91.6%). No significant problems due to the coronavirus pandemic were reported. CONCLUSIONS: Despite the apparent high availability of parenteral nutrition worldwide, there are some factors that may have a substantial effect on the quality of parenteral nutrition admixtures. These shortages create an environment of inequality.


Assuntos
COVID-19 , Nutrição Parenteral , Humanos , COVID-19/epidemiologia , Nutrição Parenteral/estatística & dados numéricos , Nutrição Parenteral/métodos , Inquéritos e Questionários , Saúde Global , SARS-CoV-2 , Pandemias , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Soluções de Nutrição Parenteral/provisão & distribuição
5.
Scand J Immunol ; 99(2): e13336, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38441196

RESUMO

Host-microbiome interplay from birth is essential for immune imprinting and tuning. Live gut microbes and microbial-derived metabolites regulate the development and modulation of the immune system, but whether microbial metabolites solely are sufficient to induce immune maturation remains unclear. Sterile faecal filtrates (FFT) were generated from murine gut contents. Newborn germ-free (GF) mice were treated twice daily with FFT (GF-FFT) or saline (GF-NaCl) from post-natal day 5 until 4 weeks of age. A third group of GF neonates were conventionalized by the transfer of caecal microbiota with live gut microbes. Host immune compartments were comprehensively immunophenotyped and systemically analysed in all available immune-related organs using flow cytometry. Oral FFT was associated with reduced survival among neonates (n = 7/19; 36.8% mortality), while saline treatment was well tolerated (n = 1/17, 5.9% mortality). Four-week-old FFT-treated pups were comparable in body weight to GF-NaCl, and the major B-cell, conventional T-cell and unconventional T-cell subsets were unchanged from saline-treated mice. Live bacteria administered during early life induced clear changes in proportions of B cells, T cells and T-cell subsets in all mucosal tissues and secondary lymphoid organs compared to GF-FFT, including restoration of intestinal natural killer T (NKT) cells with characteristics similar to conventional pups. Our findings show that oral administration of a FFT made of microbial metabolites, antigens and bacteriophages alone is insufficient to induce normal immune development elicited by the presence of live bacteria. Reduced survival during neonatal FFT treatment suggests a potential bioactive attribute of sterile faecal filtrates.


Assuntos
Linfócitos B , Cloreto de Sódio , Animais , Camundongos , Administração Oral , Bactérias , Fezes
6.
Adv Respir Med ; 92(2): 123-144, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38525774

RESUMO

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) with low skeletal muscle mass and severe airway obstruction have higher mortality risks. However, the relationship between dynamic/static lung function (LF) and thoracic skeletal muscle measurements (SMM) remains unclear. This study explored patient characteristics (weight, BMI, exacerbations, dynamic/static LF, sex differences in LF and SMM, and the link between LF and SMM changes. METHODS: A retrospective analysis of a 12-month prospective follow-up study patients with stable COPD undergoing standardized treatment, covering mild to severe stages, was conducted. The baseline and follow-up assessments included computed tomography and body plethysmography. RESULTS: This study included 35 patients (17 females and 18 males). This study revealed that females had more stable LF but tended to have greater declines in SMM areas and indices than males (-5.4% vs. -1.9%, respectively), despite the fact that females were younger and had higher LF and less exacerbation than males. A multivariate linear regression showed a negative association between the inspiratory capacity/total lung capacity ratio (IC/TLC) and muscle fat area. CONCLUSIONS: The findings suggest distinct LF and BC progression patterns between male and female patients with COPD. A low IC/TLC ratio may predict increased muscle fat. Further studies are necessary to understand these relationships better.


Assuntos
Pulmão , Doença Pulmonar Obstrutiva Crônica , Humanos , Masculino , Feminino , Pulmão/diagnóstico por imagem , Seguimentos , Estudos Retrospectivos , Projetos Piloto , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Músculo Esquelético , Tomografia Computadorizada por Raios X
7.
Int J Circumpolar Health ; 83(1): 2312663, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38314517

RESUMO

Understanding ethnic variations in body composition is crucial for assessing health risks. Universal models may not suit all ethnicities, and there is limited data on the Inuit population. This study aimed to compare body composition between Inuit and European adults using computed tomography (CT) scans and to investigate the influence of demographics on these measurements. A retrospective analysis was conducted on 50 adults (29 Inuit and 21 European) who underwent standard trauma CT scans. Measurements focused on skeletal muscle index (SMI), various fat indices, and densities at the third lumbar vertebra level, analyzed using the Wilcoxon-Mann-Whitney test and multiple linear regression. Inuit women showed larger fat tissue indices and lower muscle and fat densities than European women. Differences in men were less pronouncehd, with only Intramuscular fat density being lower among Inuit men. Regression indicated that SMI was higher among men, and skeletal muscle density decreased with Inuit ethnicity and age, while visceral fat index was positively associated with age. This study suggests ethnic differences in body composition measures particularly among women, and indicates the need for Inuit-specific body composition models. It higlights the importance of further research into Inuit-specific body composition measurements for better health risk assessment.


Assuntos
Composição Corporal , População Europeia , Inuíte , Músculo Esquelético , Tomografia Computadorizada por Raios X , Adulto , Feminino , Humanos , Masculino , Composição Corporal/fisiologia , Projetos Piloto , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Medição de Risco , Distribuição da Gordura Corporal , Músculo Esquelético/diagnóstico por imagem
9.
Clin Nutr ; 43(2): 395-412, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38169174

RESUMO

Both acute and chronic pancreatitis are frequent diseases of the pancreas, which, despite being of benign nature, are related to a significant risk of malnutrition and may require nutritional support. Acute necrotizing pancreatitis is encountered in 20 % of patients with acute pancreatitis, is associated with increased morbidity and mortality, and may require artificial nutrition by enteral or parenteral route, as well as additional endoscopic, radiological or surgical interventions. Chronic pancreatitis represents a chronic inflammation of the pancreatic gland with development of fibrosis. Abdominal pain leading to decreased oral intake, as well as exocrine and endocrine failure are frequent complications of the disease. All of the above represent risk factors related to malnutrition. Therefore, patients with chronic pancreatitis should be considered at risk, screened and supplemented accordingly. Moreover, osteoporosis and increased facture risk should be acknowledged in patients with chronic pancreatitis, and preventive measures should be considered.


Assuntos
Desnutrição , Pancreatite Crônica , Humanos , Doença Aguda , Nutrição Enteral/efeitos adversos , Pancreatite Crônica/complicações , Pancreatite Crônica/terapia , Desnutrição/etiologia
10.
Lab Anim ; 58(1): 34-43, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37669442

RESUMO

Serum corticosterone, serum buprenorphine, body weight change, consumption of food and water and behaviour-based pain assessment were measured in catheterised and non-catheterised male Wistar rats undergoing myocardial infarct (MI) surgery under general anaesthesia following buprenorphine dosing by subcutaneous (Bup-SC, 0.05 mg/kg) and oral (Bup-O, 0.4 mg/kg) routes. Buprenorphine was dosed subcutaneously at half an hour before and 8, 16 and 24 hours after surgery (Bup-SC), orally at one hour before surgery (Bup-O1) or at one hour before and 12 hours after surgery (Bup-O2) in catheterised rats and at one hour before and 24 hours after surgery (Bup-O24) in non-catheterised rats. Serum corticosterone, body weight changes and food and water consumption were not significantly different between treatments in catheterised rats. Bup-SC resulted in rapidly decreasing serum concentrations below the clinically effective concentrations (1 ng/mL) already at two hours after the first dose. Bup-O provided significantly higher and slowly decreasing serum concentrations, at or above clinically effective concentrations, for 24 hours (Bup-O1) and 42 hours (Bup-O2) after surgery. In non-catheterised rats, body weight development and food consumption were significantly higher in Bup-O24 rats compared to Bup-SC rats. The results indicate that a SC buprenorphine dose of 0.05 mg/kg every eight hours provides long periods of serum concentrations below clinically effective levels, and that a higher dose and/or more frequent dosage are required to provide stable serum concentrations at or above clinically effective levels. A single oral buprenorphine dose of 0.4 mg/kg provides clinically effective and stable serum concentrations for 24 hours in rats after MI surgery.


Assuntos
Buprenorfina , Ratos , Masculino , Animais , Analgésicos Opioides , Corticosterona , Ratos Wistar , Resultado do Tratamento , Peso Corporal
11.
Scand J Gastroenterol ; 59(2): 192-201, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37997753

RESUMO

OBJECTIVES: The early life microbiome has been linked to inflammatory diseases in adulthood and a role for the microbiome in bile duct inflammation is supported by both human and murine studies. We utilized the NOD.c3c4 mouse model that develops a spontaneous immune-driven biliary disease with a known contribution of the microbiome to evaluate the temporal effects of the early life microbiome. MATERIALS AND METHODS: Germ-free (GF) NOD.c3c4 mice were conventionalized into a specific pathogen free environment at birth (conventionally raised, CONV-R) or at weaning (germ-free raised, GF-R) and compared with age and gender-matched GF and conventional (CONV) NOD.c3c4 mice. At 9 weeks of age, liver pathology was assessed by conventional histology and flow cytometry immunophenotyping. RESULTS: Neonatal exposure to microbes (CONV-R) increased biliary inflammation to similar levels as regular conventional NOD.c3c4 mice, while delayed exposure to microbes (GF-R) restrained the biliary inflammation. Neutrophil infiltration was increased in all conventionalized mice compared to GF. An immunophenotype in the liver similar to CONV was restored in both CONV-R and GF-R compared to GF mice displaying a proportional increase of B cells and reduction of T cells in the liver. CONCLUSIONS: Microbial exposure during early life has a temporal impact on biliary tract inflammation in the NOD.c3c4 mouse model suggesting that age-sensitive interaction with commensal microbes have long-lasting effects on biliary immunity that can be of importance for human cholangiopathies.


Assuntos
Colangite , Camundongos , Humanos , Animais , Camundongos Endogâmicos NOD , Fígado/patologia , Inflamação/patologia , Modelos Animais de Doenças , Ductos Biliares/patologia
12.
Viruses ; 15(11)2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-38005828

RESUMO

Molnupiravir, a prodrug known for its broad antiviral activity, has demonstrated efficacy in animal models of COVID-19, prompting clinical trials, in which initial results indicated a significant effect against the disease. However, subsequent clinical studies did not confirm these findings, leading to the refusal of molnupiravir for permanent market authorization in many countries. This report critically assessed 22 studies published in 18 reports that investigated the efficacy of molnupiravir in animal models of COVID-19, with the purpose of determining how well the design of these models informed human studies. We found that the administered doses of molnupiravir in most studies involving animal COVID-19 models were disproportionately higher than the dose recommended for human use. Specifically, when adjusted for body surface area, over half of the doses of molnupiravir used in the animal studies exceeded twice the human dose. Direct comparison of reported drug exposure across species after oral administration of molnupiravir indicated that the antiviral efficacy of the dose recommended for human use was underestimated in some animal models and overestimated in others. Frequently, molnupiravir was given prophylactically or shortly after SARS-CoV-2 inoculation in these models, in contrast to clinical trials where such timing is not consistently achieved. Furthermore, the recommended five-day treatment duration for humans was exceeded in several animal studies. Collectively, we suggest that design elements in the animal studies under examination contributed to a preference favoring molnupiravir, and thus inflated expectations for its efficacy against COVID-19. Addressing these elements may offer strategies to enhance the clinical efficacy of molnupiravir for the treatment of COVID-19. Such strategies include dose increment, early treatment initiation, administration by inhalation, and use of the drug in antiviral combination therapy.


Assuntos
COVID-19 , Animais , Humanos , SARS-CoV-2 , Modelos Animais , Antivirais/uso terapêutico
13.
Clin Nutr ESPEN ; 57: 29-38, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37739671

RESUMO

BACKGROUND & AIMS: Malnutrition is a common problem among hospitalized patients due to increased nutrient requirements and reduced food intake or uptake of nutrients. The aim of this prospective cohort study was to investigate the association of nutritional risk status (at or not at risk by NRS-2002) as well as energy and protein intake, use of oral nutritional supplements (ONS) and snack meals in at risk patients during hospitalization and adverse outcomes (length of stay (LOS), readmissions and mortality) at three-months follow-up. METHODS: Data were collected at baseline and at three-months follow-up in patients hospitalized at 31 units at a Danish University Hospital. Diet records were performed at baseline by using the nurses' quartile nutrition recording methods. Data about disease and clinical outcomes were collected from electronic medical records at baseline and three-months follow-up. RESULTS: A total of 318 patients were included. Patients at nutritional risk (n = 149, 47%) had higher risk of longer LOS (≥20 days (OR = 4.24 [1.81;9.95] and ≥30 days OR = 2.50 [1.22;5.14])), having one readmission (OR = 1.86 [1.15;3.01]) and death (OR = 2.56 [1.27;5.20]) compared to patients not at nutritional risk (n = 169, 53%). A longer LOS was associated with patients who achieved ≥75% of energy and protein requirements, consumed snack meals incl. and excl. oral nutritional supplements. Readmissions in patients at nutritional risk during the three-months were not associated with food intake during the index hospitalization. Mortality was observed in 43 of the 318 (13.5%) hospitalized patients. A lower mortality was associated with increased energy and protein intake in patients at nutritional risk. CONCLUSIONS: The results of this study indicate a longer LOS, higher readmission rate and increased mortality in patients at nutritional risk compared to patients not at risk. Patients at nutritional risk had lower risk of three-month mortality and longer LOS during index hospitalization with increased energy and protein intake. Readmissions in patients at nutritional risk were not affected by food intake. The association of nutritional risk with poorer outcomes indicates that good nutritional care including constant attention to food-intake during hospitalization can be beneficial regarding mortality.


Assuntos
Hospitalização , Humanos , Tempo de Internação , Estudos Prospectivos , Registros de Dieta , Hospitais Universitários
14.
medRxiv ; 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37693601

RESUMO

Affective or mood disorders are a leading cause of disability worldwide. The serotonergic system has been heavily implicated in the complex etiology and serves as a therapeutic target. The serotonin transporter (SERT) is a major regulator of serotonin neurotransmission, yet the disease-relevance of impaired SERT function remains unknown. Here, we present the first identification and functional characterization of disruptive coding SERT variants found in patients with psychiatric diseases. In a unique cohort of 144 patients characterized by treatment-resistant chronic affective disorders with a lifetime history of electroconvulsive therapy, we identified two previously uncharacterized coding SERT variants: SERT-N217S and SERT-A500T. Both variants were significantly enriched in the patient cohort compared to GnomAD (SERT-N217S: OR = 151, P = 0.0001 and SERT-A500T: OR = 1348, P = 0.0022) and ethnicity-matched healthy controls (SERT-N217S: OR ≥ 17.7, P ≤ 0.013 and SERT-A500T: OR = ∞, P = 0.029). Functional investigations revealed that the mutations exert distinct perturbations to SERT function, but their overall effects converge on a partial loss-of-function molecular phenotype. Thus, the SERT-A500T variant compromises the catalytic activity, while SERT-N217S disrupts proper glycosylation of SERT with a resulting dominant-negative trafficking deficiency. Moreover, we demonstrate that the trafficking deficiency of SERT-N217S is amenable to pharmacochaperoning by noribogaine. Collectively, our findings describe the first disease-associated loss-of-function SERT variants and implicate serotonergic disturbances arising from SERT dysfunction as a risk factor for chronic affective disorders.

15.
Br J Dermatol ; 189(5): 511-519, 2023 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-37290787

RESUMO

BACKGROUND: Indolent systemic mastocytosis (ISM) is characterized by excessive mast cell (MC) accumulation and MC-driven signs and symptoms. Currently used therapies are not approved and have limited efficacy. Lirentelimab (AK002) is a monoclonal antibody against sialic acid-binding immunoglobulin-like lectin (Siglec)-8 that inhibits MC activation. OBJECTIVES: To determine the safety, tolerability and efficacy of lirentelimab in reducing the symptoms of ISM. METHODS: At a specialty centre for mastocytosis in Germany, we conducted a phase I first-in-human single-ascending and multidose clinical trial of lirentelimab in patients with ISM. Eligible adults had World Health Organization-confirmed ISM and an unsatisfactory response to available treatment. In part A, patients received a single dose of lirentelimab 0.0003, 0.001, 0.003, 0.01 or 0.03 mg kg-1; in part B, patients received one lirentelimab dose of 0.3 mg kg-1 or 1.0 mg kg-1; and in part C, patients received either 1.0 mg kg-1 lirentelimab every 4 weeks for 6 months or ascending doses of lirentelimab (one dose of 1 mg kg-1 followed by five doses of 3-10 mg kg-1 every 4 weeks). The primary endpoint was safety/tolerability. Secondary endpoints included changes from baseline in Mastocytosis Symptom Questionnaire (MSQ), Mastocytosis Activity Score (MAS) and Mastocytosis Quality of Life Questionnaire (MC-QoL) scores at 2 weeks after the final dose. RESULTS: In 25 patients with ISM (13 in parts A + B and 12 in part C; median age 51 years, 76% female, median 4.6 years from diagnosis), the most common treatment-related adverse events (AEs) were feeling hot (76%) and experiencing a headache (48%). No serious AEs occurred. Median MSQ and MAS symptom severity scores in part C improved (vs. baseline) across all symptoms [MSQ: skin (38-56%), gastrointestinal (49-60%), neurological (47-59%), musculoskeletal (26-27%); MAS: skin (53-59%), gastrointestinal (72-85%), neurological (20-57%), musculoskeletal (25%)]. Median MC-QoL scores improved across all domains: symptoms (39%), social life/functioning (42%), emotions (57%) and skin (44%). CONCLUSIONS: Lirentelimab was generally well tolerated and improved symptoms and quality of life in patients with ISM. The therapeutic potential of lirentelimab should be considered for ISM.


Assuntos
Anticorpos Monoclonais , Antineoplásicos , Mastocitose Sistêmica , Mastocitose , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Mastócitos , Mastocitose/diagnóstico , Mastocitose Sistêmica/tratamento farmacológico , Mastocitose Sistêmica/complicações , Qualidade de Vida
16.
Crit Rev Oncol Hematol ; 188: 104038, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37236410

RESUMO

Acute radiation-induced diarrhoea (RID) is a well-known side effect of external radiation therapy for pelvic cancer. Acute RID is an unresolved clinical problem in approximately 80% of patients. We investigated the effect of nutritional interventions on acute RID in patients with pelvic cancer treated with curative radiotherapy. A search was conducted using PubMed, Embase.com, CINAHL, and Cochrane Library, from 1 January 2005 until 10 October 2022. We included randomised controlled trials or prospective observational studies. Eleven of the 21 identified studies had low quality of evidence, mainly because of low patient numbers distributed among several cancer diagnoses, and non-systematic assessment of acute RID. Interventions included probiotics (n = 6), prebiotics (n = 6), glutamine (n = 4), and others (n = 5). Five studies, of which two provided high quality evidence, showed that probiotics improved acute RID. Future well-designed studies investigating the effects of probiotics on acute RID are warranted. PROSPERO ID: CRD42020209499).


Assuntos
Neoplasias Pélvicas , Probióticos , Humanos , Neoplasias Pélvicas/complicações , Neoplasias Pélvicas/radioterapia , Diarreia/etiologia , Diarreia/terapia , Probióticos/uso terapêutico , Estudos Observacionais como Assunto
17.
Clin Nutr ESPEN ; 55: 212-220, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37202049

RESUMO

BACKGROUND AND AIMS: To investigate the incidence and the severity of COVID-19 infection in patients enrolled in the database for home parenteral nutrition (HPN) for chronic intestinal failure (CIF) of the European Society for Clinical Nutrition and Metabolism (ESPEN). METHODS: Period of observation: March 1st, 2020 March 1st, 2021. INCLUSION CRITERIA: patients included in the database since 2015 and still receiving HPN on March 1st, 2020 as well as new patients included in the database during the period of observation. Data related to the previous 12 months and recorded on March 1st 2021: 1) occurrence of COVID-19 infection since the beginning of the pandemic (yes, no, unknown); 2) infection severity (asymptomatic; mild, no-hospitalization; moderate, hospitalization no-ICU; severe, hospitalization in ICU); 3) vaccinated against COVID-19 (yes, no, unknown); 4) patient outcome on March 1st 2021: still on HPN, weaned off HPN, deceased, lost to follow up. RESULTS: Sixty-eight centres from 23 countries included 4680 patients. Data on COVID-19 were available for 55.1% of patients. The cumulative incidence of infection was 9.6% in the total group and ranged from 0% to 21.9% in the cohorts of individual countries. Infection severity was reported as: asymptomatic 26.7%, mild 32.0%, moderate 36.0%, severe 5.3%. Vaccination status was unknown in 62.0% of patients, non-vaccinated 25.2%, vaccinated 12.8%. Patient outcome was reported as: still on HPN 78.6%, weaned off HPN 10.6%, deceased 9.7%, lost to follow up 1.1%. A higher incidence of infection (p = 0.04), greater severity of infection (p < 0.001) and a lower vaccination percentage (p = 0.01) were observed in deceased patients. In COVID-19 infected patients, deaths due to infection accounted for 42.8% of total deaths. CONCLUSIONS: In patients on HPN for CIF, the incidence of COVID-19 infection differed greatly among countries. Although the majority of cases were reported to be asymptomatic or have mild symptoms only, COVID-19 was reported to be fatal in a significant proportion of infected patients. Lack of vaccination was associated with a higher risk of death.


Assuntos
COVID-19 , Enteropatias , Insuficiência Intestinal , Nutrição Parenteral no Domicílio , Humanos , COVID-19/epidemiologia , Enteropatias/epidemiologia , Enteropatias/terapia , Nutrição Parenteral no Domicílio/efeitos adversos
18.
Eur Radiol Exp ; 7(1): 26, 2023 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-37246199

RESUMO

BACKGROUND: Computed tomography (CT) is increasingly used in the clinical workup, and existing scan contains unused body composition data, potentially useful in a clinical setting. However, there is no healthy reference for contrast-enhanced thoracic CT-derived muscle measures. Therefore, we aimed at investigating whether there is a correlation between each of the thoracic and third lumbar vertebra level (L3) skeletal muscle area (SMA), skeletal muscle index (SMI), and skeletal muscle density (SMD) at contrast-enhanced CT in patients without chronic disease. METHODS: A proof-of-concept retrospective observational study was based on Caucasian patients without chronic disease, who received CT for trauma between 2012 and 2014. Muscle measures were assessed using a semiautomated threshold-based software by two raters independently. Pearson's correlation between each thoracic level and third lumbar and intraclass correlation between two raters and test-retest with SMA as proxy parameters were used. RESULTS: Twenty-one patients (11 males, 10 females; median age 29 years) were included. The second thoracic vertebra (T2) had the highest median of cumulated SMA (males 314.7 cm2, females 118.5 cm2) and SMI (97.8 cm2/m2 and 70.4 cm2/m2, respectively). The strongest SMA correlation was observed between T5 and L3 (r = 0.970), the SMI between T11 and L3 (r = 0.938), and the SMD between the T10 and L3 (r = 0.890). CONCLUSIONS: This study suggests that any of the thoracic levels can be valid to assess skeletal muscle mass. However, the T5 may be most favourable for measuring SMA, the T11 for SMI, and T10 for SMD when using contrast-enhanced thoracic CT. RELEVANCE STATEMENT: In COPD patients, a CT-derived thoracic muscle mass assessment may help identify who would benefit from focused pulmonary rehabilitation: thoracic contrast-enhanced CT conducted as part of the standard clinical workup can be used for this evaluation. KEY POINTS: • Any thoracic level can be used to assess thoracic muscle mass. • Thoracic level 5 is strongly associated with the 3rd lumbar muscle area. • A strong correlation between the thoracic level 11 and the 3rd lumbar muscle index. • Thoracic level 10 is strongly associated with the 3rd lumbar muscle density.


Assuntos
Vértebras Lombares , Músculo Esquelético , Masculino , Feminino , Humanos , Adulto , Músculo Esquelético/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Doença Crônica , Estudos Retrospectivos
19.
Clin Nutr ESPEN ; 54: 194-205, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36963863

RESUMO

BACKGROUND: Acute mesenteric ischaemia (AMI) is a condition with high mortality. This survey assesses current attitudes and practices to manage AMI worldwide. METHODS: A questionnaire survey about the practices of diagnosing and managing AMI, endorsed by several specialist societies, was sent to different medical specialists and hospitals worldwide. Data from individual health care professionals and from medical teams were collected. RESULTS: We collected 493 individual forms from 71 countries and 94 team forms from 34 countries. Almost half of respondents were surgeons, and most of the responding teams (70%) were led by surgeons. Most of the respondents indicated that diagnosis of AMI is often delayed but rarely missed. Emergency revascularisation is often considered for patients with AMI but rarely in cases of transmural ischaemia (intestinal infarction). Responses from team hospitals with a dedicated special unit (14 team forms) indicated more aggressive revascularisation. Abdominopelvic CT-scan with intravenous contrast was suggested as the most useful diagnostic test, indicated by approximately 90% of respondents. Medical history and risk factors were thought to be more important in diagnosis of AMI without transmural ischaemia, whereas for intestinal infarction, plasma lactate concentrations and surgical exploration were considered more useful. In elderly patients, a palliative approach is often chosen over extensive bowel resection. There was a large variability in anticoagulant treatment, as well as in timing of surgery to restore bowel continuity. CONCLUSIONS: Delayed diagnosis of AMI is common despite wide availability of an adequate imaging modality, i.e. CT-scan. Large variability in treatment approaches exists, indicating the need for updated guidelines. Increased awareness and knowledge of AMI may improve current practice until more robust evidence becomes available. Adherence to the existing guidelines may help in improving differences in treatment and outcomes.


Assuntos
Isquemia Mesentérica , Humanos , Idoso , Isquemia Mesentérica/diagnóstico , Isquemia Mesentérica/cirurgia , Intestinos , Isquemia/diagnóstico , Isquemia/terapia , Fatores de Risco , Infarto
20.
Clin Nutr ESPEN ; 54: 398-405, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36963885

RESUMO

BACKGROUND & AIM: Nutrient intake in patients at nutritional risk was recorded with the aim of reaching at least 75% of estimated requirements for energy and protein. However, the cutoff at 75% has only been sparsely investigated. The aim of this study was to re-evaluate the 75% cutoff of estimated energy and protein requirements among patients at or not at nutritional risk in relation to 30-day mortality and readmissions. METHODS: A 30-day follow-up study was performed among hospitalized patients in 31 units at a Danish University Hospital. Data was collected using the nurses' quartile nutrition registration method and electronic patient journals. All patients were screened using the NRS-2002 and classified as either at nutritional risk (NRS-2002, score ≥3) or not at nutritional risk (NRS-2002, score <3). Energy and protein requirements were estimated using weighted Harris-Benedict equation and 1.3 g/kg/day, respectively. RESULTS: In total, 318 patients were included in this study. Patients at nutritional risk were older, lower BMI, male, more comorbidities and a longer primary length of stay compared to patients not at nutritional risk (p < 0.05). After 30-day follow-up, mortality was higher among patients at risk (9.5% vs. 2.0%, p < 0.05). Patients at nutritional risk showed increased risk of mortality if they did not achieve 75% of estimated requirements (energy: OR = 8.08 [1.78; 36.79]; protein: OR = 3.40 [0.74; 15:53]). Furthermore, predicted probability of mortality decreased with increased energy and protein intakes. No significant associations were found for readmissions achieving 75% of estimated energy or protein requirements. A cutoff of 76-81% for energy and 58-62% for protein was equivalent with accepting a 6-8% mortality rate. CONCLUSION: The results of this study indicate that an energy intake ≥75% of estimated requirement among patients at nutritional risk has a preventative effect regarding mortality within one month, but not for readmissions.


Assuntos
Desnutrição , Humanos , Masculino , Seguimentos , Desnutrição/etiologia , Hospitalização , Estado Nutricional , Pacientes Internados
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