Vitamin D,selenium,and antidiabetic drugs in the treatment of type 2 diabetes mellitus with Hashimoto's thyroiditis

BACKGROUND Diabetes and thyroiditis are closely related.They occur in combination and cause significant damage to the body.There is no clear treatment for type-2 diabetes mellitus(T2DM)with Hashimoto's thyroiditis(HT).While single symptomatic drug treatment of the two diseases is less effective,combined drug treatment may improve efficacy.AIM To investigate the effect of a combination of vitamin D,selenium,and hypoglycemic agents in T2DM with HT.METHODS This retrospective study included 150 patients with T2DM and HT treated at The Central Hospital of Shaoyang from March 2020 to February 2023.Fifty patients were assigned to the control group,test group A,and test group B according to different treatment methods.The control group received low-iodine diet guidance and hypoglycemic drug treatment.Test group A received the control treatment plus vitamin D treatment.Test group B received the group A treatment plus selenium.Blood levels of markers of thyroid function[free T3(FT3),thyroid stimulating hormone(TSH),free T4(FT4)],autoantibodies[thyroid peroxidase antibody(TPOAB)and thyroid globulin antibody(TGAB)],blood lipid index[low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),triacylglycerol(TG)],blood glucose index[fasting blood glucose(FBG),and hemoglobin A1c(HbA1c)]were measured pre-treatment and 3 and 6 months after treatment.The relationships between serum 25-hydroxyvitamin D3[25(OH)D3]level and each of these indices were analyzed.RESULTS The levels of 25(OH)D3,FT3,FT4,and LDL-C increased in the order of the control group,test group A,and test group B(all P<0.05).The TPOAB,TGAB,TC,TG,FBG,HbA1c,and TSH levels increased in the order of test groups B,A,and the control group(all P<0.05).All the above indices were compared after 3 and 6 months of treatment.Pre-treatment,there was no divergence in serum 25(OH)D3 level,thyroid function-related indexes,autoantibodies level,blood glucose,and blood lipid index between the control group,test groups A and B(all P>0.05).The 25(OH)D3 levels in test groups A and B were negatively correlated with FT4 and TGAB(all P<0.05).CONCLUSION The combination drug treatment for T2DM with HT significantly improved thyroid function,autoantibody,and blood glucose and lipid levels.

Vitamin D, selenium in type 2 diabetes and Hashimoto's thyroiditis: Is it effective?

The study by Feng et al,explores treatment approaches for these coexisting conditions.It emphasizes the potential advantages of selenium and vitamin D supplementation but also raises methodological and patient selection concerns.Findings indicate a complex interplay between interventions and disease markers,prompting the need for further research.Despite limitations,the study offers valuable insights into managing the intricate relationship between type 2 diabetes mellitus and Hashimoto's thyroiditis.The authors'contributions shed light on potential treatment avenues,although careful consideration of study design and patient characteristics is warranted for future investigations in this domain.

Effect of Hashimoto’s Thyroiditis on Efficacy of 131I Ablation Therapy in Intermediate- and High-Risk of Thyroid Papillary Carcinoma

Objective: The purpose of this study was to investigate the effect of Hashimoto’s thyroiditis on efficacy of 131I ablation in intermediate- and high-risk of thyroid papillary carcinoma patients. The findings will help to develop a personalized treatment plan for patients with thyroid papillary carcinoma complicated with Hashimoto’s thyroiditis. Material and Methods: From January 2016 to December 2020, patients who were diagnosed with intermediate- and high-risk PTC with lymph node metastasis were analyzed retrospectively, excluding patients with incomplete clinical data, distant metastasis, positive TGAb, TSH Results: A total of 525 patients (166 males and 359 females) were included in the study, including 368 patients in ER group (70.1%) and 157 patients in NER group (29.9%). Eleven factors including combining Hashimoto’s thyroiditis, pre-ablative Tg levels, sex, tumor diameter, extraglandular invasion, multifocal, bilateral lesions, central lymph node metastasis, lateral lymph node metastasis, lymph node metastasis rate, thyroglobulin were statistically different between ER group and NER group with significance at P Conclusion: Hashimoto’s thyroiditis, Ps-Tg level and lateral lymph node metastasis are potential predictors for short-term efficacy of 131I treatment in intermediate- and high-risk thyroid papillary carcinoma. Hashimoto’s thyroiditis, high Ps-Tg level and increased number of lateral lymph node metastasis reduce the efficacy of 131I therapy in patients with intermediate and high risk thyroid papillary carcinoma.

Gallbladder Carcinoma of the Thyroid Revealed by an Acute Festered Thyroiditis: A Literature Study about a Case

The cutaneous extension of gallbladder thyroid carcinoma is uncommon and is among the aggressive forms of the disease. We are reporting the case of a woman of 54 that shows acute festered thyroiditis worsened by a necrotic ulcer wound on the skin lasting 3 weeks amid a big neglected hetero-multinodular goitre, evolving since 20 years. The anatomopathological test showed a gallbladder thyroid carcinoma of the thyroid with severe inflammation. The treatment consisted of a complete thyroidectomy with recurrent bilateral dredging. There was a favourable evolution. Gallbladder carcinoma, in its aggressive aspect, may be linked to the occurrence of acute festered thyroiditis. Therefore, the prognosis of our patient was favourable.

Doctor Song Fuyin's Experience in Treating Hashimoto's Thyroiditis Based on Qi,Blood Essence and Spirit Syndrome Differentiation Stage Classification

The paper systematically summarizes the experience of Director Song Fuyin in treating Hashimoto's thyroiditis which is a typical emotional disease that causes obvious changes in organ morphology and endocrine and body fluid metabolism.It belongs to the category of psychosomatic diseases,and is the embodiment of a series of pathogenesis processes of qi disease,blood disease,essence disease and deformation in TCM theory.The whole course of the disease is dominated by the dialectical relationship of mutual influence,mutual control,mutual root and mutual use among the deity disease,qi disease,blood disease,essence and spiritual disease.Therefore,the treatment emphasizes the dialectical relationship based on qi,blood,essence and spirit.At the beginning,the treatment focuses on regulating qi and clearing heat and eliminating phlegm;at the middle stage,the treatment focuses on replenishing essence and promoting yang and eliminating wind and calming the deity;at the late stage,the treatment focuses on replenishing qi and eliminating phlegm and promoting collages.Flexible use of calming the spirits,regulating qi,dispersing essence,eliminating phlegm,promoting blood and other methods of stage classification treatment,can be targeted,improve the cure rate of the disease.This article aims to clarify the experience of Director Song Fuyin in treating Hashimoto's thyroiditis based on syndrome differentiation of qi,blood essence and spirit.

The Role of Vitamin D on Thyroid Antibodies in Patients with Chronic Autoimmune Thyroiditis

Vitamin D deficiency is a global problem,which has taken the form of a pandemic.Existing data indicate that vitamin D is not only a nutrient.It has also a hormone-specific activity.Vitamin D is characterized by anti-inflammatory and immunomodulatory properties.Chronic autoimmune thyroiditis is a disease of autoimmune genesis,in which lymphocytic infiltration gradually destroys thyroid tissue.There are some evidences about vitamin D deficiency and the development of chronic autoimmune thyroiditis.The article has reviewed the current literature about the impact and the benefits of vitamin D on thyroid antibodies levels.

Coexistence of papillary thyroid microcarcinoma and mucosa-associated lymphoid tissue lymphoma in a context of Hashimoto's thyroiditis

Papillary thyroid cancer(PTC)represents 80%-85%of thyroid cancer and its prevalence has been rising in the last decades.Primary thyroid lymphoma(PTL)accounts for 3%of extranodal lymphomas and about 5%of thyroid malignancies,having a prevalence of one or two cases per million people.Mucosa-Associated Lymphoid Tissue lymphoma represents approximately30%of PTL.Both entities have an indolent course and a very good prognosis.Diagnosis is made by ultrasound and fine needle aspiration(FNA)or surgery specimen pathology.They have also been associated with Hashimoto’s thyroiditis(HT),but pathogenesis and its links remains to be known.Treatment remains controversial and surgery is generally accepted in cases of disease limited to thyroid,as the present.Patients with thyroid nodules should be observed and followed.If there is an enlargement by ultrasound or clinical symptoms,FNA should be performed promptly.Patients with HT deserve additional surveillance,since this condition is associated with both PTC and PTL.In this case,the management with surgery and radioactive iodine ablation therapy was effective for both entities.Patients with thyroid nodules should be properly evaluated with ultrasound and thyroid function tests.If there is an enlargement of the neck,reported by symptoms or ultrasound,it requires further investigation.HT is associated to both PTC and PTL so if the enlargement of the nodules is on this context additional tests such as FNA should be performed.In this case,the patient was managed with surgery and radioactive iodine ablation therapy and it was effective for both entities.

Selenium Supplementation Alleviates Autoimmune Thyroiditis by Regulating Expression of Th1/Th2 Cytokines

Selenium （Se） is an essential trace element. Autoimmune thyroid diseases （AITD） are destructive inflammatory or anti-receptor autoimmune diseases characterized by reactivity to self-thyroid antigens. However, the effects of Se on the cytokines in AITD are still unclear. So we researched the role of Selenium （Se） and Thl/Th2 cytokine productions in the pathogenesis of autoimmune thyroid diseases （AITD）.

Ascher syndrome: a rare case of blepharochalasis combined with double lip and Hashimoto’s thyroiditis

Dear Editor,I am Dr. Yao Fu, from the Department of Ophthalmology,Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. I write to present a rare case of Ascher syndrome.Ascher syndrome was described first in 1920, presenting as a combination of blepharochalasis, double lip, and non-toxic goitre(1)It is considered to be a rare, sporadic.

Role of color Doppler in differentiation of Graves' disease and thyroiditis in thyrotoxicosis

AIM:To evaluate the role of thyroid blood flow assessment by color-flow Doppler ultrasonography in the differential diagnosis of thyrotoxicosis and compare it to technetium pertechnetate thyroid scanning. METHODS:Twenty-six patients with thyrotoxicosis were included in the study. Clinical history was taken and physical examination and thyroid function tests were performed for all patients. Thyroid autoantibodies were measured. The thyroid glands of all patients were evaluated by gray scale ultrasonography for size, shape and echotexture. Color-flow Doppler ultrasonography of the thyroid tissue was performed and spectral flow analysis of both inferior thyroid arteries was assessed. Technetium99 pertechnetate scanning of the thyroid gland was done for all patients. According to thyroid scintigraphy, the patients were divided into two groups:18 cases with Graves' disease and 8 cases with Hashimoto's thyroiditis. All patients had suppressed thyrotropin. The diagnosis of Graves' disease and Hashimoto's thyroiditis was supported by the clinical picture and follow up of patients. RESULTS:Peak systolic velocities of the inferior thyroid arteries were significantly higher in patients with Graves' disease than in patients with thyroiditis (P = 0.004 in the right inferior thyroid artery and P = 0.001 in left inferior thyroid artery). Color-flow Doppler ultrasonography parameters demonstrated a sensitivity of 88.9% and a specificity of 87.5% in the differential diagnosis of thyrotoxicosis. CONCLUSION:Color Doppler flow of the inferior thyroid artery can be used in the differential diagnosis of thyrotoxicosis, especially when there is a contraindication of thyroid scintigraphy by radioactive material in some patients.

Presence of thyroid-associated ophthalmopathy in Hashimoto's thyroiditis

·AIM: To determine the prevalence of ophthalmopathy in Hashimoto’s patients and to make a comparison in subgroups of patients·METHODS: The study involved 110 Hashimoto’s thyroiditis patients and 50 control subjects attending to the endocrinology department of the hospital. Subgroup classification of patients was made as euthyroid,subclinic and clinic in Hashimato’s thyroiditis. All patients were evaluated by a single experienced ophthalmologist for the prevalence and characteristics of eye signs.·RESULTS:Theoverallprevalencesofeyechanges were22.7%(25 patients) in patients and 4%(2 persons) in control subjects respectively(P =0.002). In patients the most common symptom was retrobulbar eye pain with or without any eye movement. Thirteen patients had significant upper eyelid retraction(11.8%). Six patients had eye muscle dysfunction as reduced eye movements in up gaze. In control patients one person had proptosis and another had lid retraction. The clinical activity score and classification of the ophthalmopathy did not show any significant differences among subgroups.·CONCLUSION:Theeyesignsweremostlymild(22.7%)and the most common eye sign was the presence of upper eyelid retraction(11.8%). Additionally six patients had eye muscle dysfunction as reduced eye movements in up gaze. Therefore we recommend to make a routine ophthalmic examination in Hashimoto’s thyroiditis patients in order not to omit the associated ophthalmopathy.

Subacute Thyroiditis as Seen Initially in ENT Department—— A Reportof30 Cases

To assess the pharyngeal presentations and the diagnostic value of thyroid SPECT and thyroid fine needle aspiratory biopsy (FNAB) in subacute thyroiditis (SAT) as seen initially in ENT department, 30 patients, during the course of SAT, were examined for pharyngeal symptoms and tested for serum T 3, T 4 level. The thyroid SPECT imaging or thyroid FNAB were performed. Our results showed that, of the 30 patients, 21 had sore throat of various degrees, and 9 had abnormal sensation of throat. Six were diagnosed as having SAT by only SPECT, in the remaining 24, the final diagnoses was established by SPECT combined with FNAB. Two of them were finally diagnosed as having SAT by trial treatment with oral prednisone. It is concluded that sore throat and abnormal sensation of pharynx are the important presentations of SAT, and thyroid SPECT imaging and thyroid FNAB are valuable in diagnosing SAT.

Immune Intervention Effects on the Induction of Experimental Autoimmune Thyroiditis

To explore im mune intervention effects of the combined use of cycloporin A (Cs A ) and 1,2 5 - dihydroxyvitam in D3[1,2 5 (OH ) 2 D3]at low doses on experimental autoim mune thyroiditis (EAT) ,porcine thyroglobulin (p TG) was injected into a CBA mouse at the dose of 10 0μg on day 0 and day14 to establish the model of EAT.The immune prevention group from day0 to day2 8, and treatm ent group from day10 to day38were daily adm inistered Cs A(10 mg/ kg) intragastri- cally and/ or1,2 5 (OH) 2 D3(0 .2 μg/ kg) ip.After im munized by p TG,the m ice were sacrificed on day2 8and day38to examine their thyroid gland pathologically,and to check the levels of serum porcine thyroglobulin antibodies (p TGAb) ,porcine thyromicrosom al antibodies (p TMAb) .The incidences of EAT in the immune prevention group and treatment group,with administration of low dose of Cs A and 1,2 5 (OH) 2 D3,were decreased respectively by 4 4 .4 4 % and 37.5 0 % .Those of severe disease in the two groups were decreased respectively by71.4 3% and6 0 .32 % .The levels of serum p TGAb and p TMAb in the imm une prevention group were lower than those of the positive control group.It was concluded thatcombined use of Cs A and1,2 5 (OH) 2 D3at low doses could effectively prevent EAT with a synergic effect.

Effect of IL-10 gene transmission on the PTg-stimulated splenocytes proliferation and Th1 cytokines production from experimental autoimminue thyroiditis rats

To investigate the effects of gene therapy with IL-10 on PTg-induced proliferation of splenocytes and Thl cytokine production from PTg-stimulated splenocytes. Methods： EAT rats were divided into four groups ：group A （PBS＋PLL） , group B （pORF＋PLL）, group C （pORFmIL10＋PLL）, and group D （pORFmIL10＋ MEM）. The substances mixed with lipofectamine were injected into the thyroid tissues of rats on the 18th dday after immunization. The rats were sacrificed at the 8th week. In vitro proliferative responses to ConA and different concentration of PTg were measured by culturing 4 ×105 splenocytes pulsed with 18.5KBq of [^3H] thymidine for the final 12h and then harvested for liquid scintillation counting. In vitro splenocytes were cultured with PTg （25 mg/L）. Thl cytokine IFN-γ,TNF-α and IL-2 were detected by ELISA. Results： The proliferative response to PTg was suppressed in group C, compared with that of group A and B （P 〈 0.05）. The levels of IFN-γ,TNF-αand IL-2 in the supernatant of PTg-stimulated splenocytes were 3548.25±779.47 pg/ml, 27.66±10.50 pg/ml and 3617.73±609.15 pg/ml, respectively, which were much lower in group C than those in group A and B（P 〈 0.01, P 〈 0.05, P 〈 0.001, respectively）. Conclusion： IL- 10 gene transmission in thyroid tissues could inhibit PTg specific proliferation of splenocytes from EAT rats and the secretion 6f Th1 cytokines from PTg-stimulated splenocytes.

ACUPUNCTURE TREATMENT OF SUBACUTE THYROIDITIS WITH HYPERTHYROIDISM AT THE LATE STAGE

Causes inducing subacute thyroiditis have been unclear, but clinically it is treated mostlywith cortical hormones. In the present paper, it was reported that one case of subacute thyroiditis withhyperthyodism at the late stage was cured with acupuncture at Renying (ST 9), Fengchi (GB 20),Jiaji ponts on the neck and other points. In the treatment, differentiation of symptoms and signs wascombined with differentiation of disease, selection of proximal acupoints was combined with selectionof distal acupoints. The patient was treated in accordance with his physique. Therefore, the therapeu-tic effects were obtained rapidly.

Treatment of Hashimoto's thyroiditis traditional Chinese and western medicine:A review

Hashimoto's Thyroiditis is a common Autoimmune disease,and clinical related research has made great progress.This article summarizes the clinical and experimental studies on Hashimoto's Thyroiditis in recent years,summarizes in five aspects from its western medicine pathogenesis(Genetics,Environment,Gender,Immunity,mi RNA),traditional Chinese medicine etiology and pathogenesis,western medicine treatment(Glucocorticoid therapy,Chemokine receptor antagonist therapy,Nutrition therapy),traditional Chinese medicine therapy(Treatment by type,Treatment by stages,Treatment by liver,Treatment by spleen and kidney,Treatment by gas,blood,phlegm and blood stasis,Prescription of experience,Characteristic theory of physician and Characteristic therapy of Traditional Chinese Medicine)and combine traditional Chinese and western medicine treatment,and puts forward the integrated treatment of traditional Chinese and western medicine is the general trend of future diagnosis and treatment of Hashimoto thyroiditis.

Intervention and immune regulation of Fuzheng Xiaoying Decoction on experimental autoimmune thyroiditis model rats

Objective:To investigate the effect of Fuzheng Xiaoying Decoction on experimental autoimmune thyroiditis(EAT)model rats and explore its possible mechanism of immune regulation.Methods:Among the 40 female SD rats,10 were randomly selected as the blank group,and the rest were immunized with pig thyroglobulin and Freund's adjuvant combined with high iodine feeding to make the EAT model.After the model was established,they were randomly divided into three groups:the model group,the selenium yeast tablet group and the Fuzheng Xiaoying Decoction group,which were continuously gavaged for 2 months.The anti thyroid autoantibodies,thyroid function,IL-38 and Th17/Treg distribution were measured.The pathological changes of thyroid tissue were observed by HE staining.Results:Compared with the blank group,the levels of TPOAb and TGAb in the model group were significantly higher(P<0.05).Lymphocyte infiltration was seen in the thyroid tissue of the model group,and also the thyroid follicles were partially destroyed,the shape was irregular,and the colloid distribution was uneven,indicating that the modeling was successful.Compared with the model group,the levels of TPOAb and TGAb in the selenium yeast tablet group and the Fuzheng Xiaoying Decoction group decreased significantly(P<0.05).And the Fuzheng Xiaoying Decoction group had more significant improvement in thyroid follicle destruction and lymphocyte infiltration than the selenium yeast tablet group(P<0.05).Compared with the blank group,the levels of T3,T4,FT3 and FT4 in the model group increased,the level of IL-38 decreased,the proportion of Th17 increased,and the ratio of Th17/Treg increased(P<0.05).Compared with the model group,T4 level decreased,IL-38 level increased in the selenium yeast tablet group and the Fuzheng Xiaoying Decoction group(P<0.05).But there was no statistically significant difference in the reduction of Th17 proportion and Th17/Treg ratio between the above two groups and the model group(P>0.05).There was no significant difference in Treg ratio among the groups.Conclusion:Fuzheng Xiaoying Decoction can significantly reduce the level of anti thyroid autoantibodies in EAT rats by regulating the immunity of EAT rats,and improve the follicular destruction and lymphocyte infiltration of thyroid tissue in rats.

Efficacy of Xiaojin Capsules Combined with Selenium Yeast Capsules on 120 Cases of Hashimoto's Thyroiditis with Abnormal Thyroid Function

[Objectives]To explore the efficacy of Xiaojin Capsules combined with Selenium Yeast Capsules in the treatment of Hashimoto's thyroiditis(HT)with abnormal thyroid function.[Methods]A total of 180 HT patients who were treated in the First Affiliated Hospital of Henan University and Henan Provincial People's Hospital from December 2020 to December 2021 were selected as the research subjects and randomly divided into the observation group(n=120)and the control group(n=60)in at a tratio of 2∶1 ratio according to their visiting time.The observation group was treated with Xiaojin Capsules(oral,5 capsules each time,twice a day for 12 weeks)and Selenium Yeast Capsules(oral,1 capsule each time,twice a day for 12 weeks).The control group was treated with only Selenium Yeast Capsules(oral,1 capsule each time,twice a day for 12 weeks).[Results]The difference in the levels of thyroid peroxidase antibody(TPO-Ab),thyroglobulin antibody(TGAb),serum free triiodothyronine(FT_(3)),serum free thyroxine(FT_(4)),and thyroid stimulating hormone(TSH)between the observation group and control group was statistically significant(P<0.05).The diameters of thyroid between the observation group and the control group before,during and after treatment were significantly different(P<0.05).The total effective rate of the observation group was 82.5%(99/120),which was significantly higher than 56.67%(34/60)in the control group,and the difference was statistically significant(P<0.05).The cure rate(22.50%)in the observation group was significantly higher than the control group(3.33%),and the difference was statistically significant(P<0.01).The ineffective rate of the observation group was 17.50%,which was significantly lower than that of the control group(40.00%),and the difference was statistically significant(P<0.01).The markedly effective rate of the observation group was 40.83%,which was significantly higher than that of the control group(31.67%),and the difference was statistically significant(P<0.05).The effective rate in the observation group was 191%,and the effective rate in the control group was 21.67%,and the difference was not statistically significant(P>0.05).[Conclusions]Xiaojin Capsules combined with Selenium Yeast Capsules in the treatment of HT can eliminate or alleviate the clinical symptoms and signs,significantly reduce the levels of TPO-Ab and TGAb in serum,restore thyroid function,improve thyroid shape and structure in the treatment of HT,and the clinical effect is satisfactory.

Interferon-induced progression of autoimmune thyroiditis with enlarged thyroid glands in gynecological patient: A case report and literature review

A case report presents a progression of autoimmune thyroiditis with an abnormal enlargement of the thyroid glands and increased thyreotropin hormone concentration-associated with interferon treatment in human papillomavirus infected patient with the autoimmune thyroiditis and a daily L-thyroxin hormone replacement therapy background. Observation was supplemented with a brief review of literature and discussion. On the basis of this observation and a brief review of literature authors suggested that the potential adverse effects of interferon therapy are overbalanced than its benefits for gynecological patients, therefore any interferon treatment should be recommended with strict indications as well as after screening of conditions and functions of thyroid glands and other interferon target organs to avoid interferon treatment side effects. Practitioners especially gynecologists should inform their patients about pleiotropic interferon effects and its high frequent and wide range side effects before to start such kind of treatment.

Evaluation of Serum Trace Elements and Vitamin Levels in Hashimoto’s Thyroiditis: Single Centre Experience from Turkey

Aim: To determine levels of serum trace elements and vitamins, and to find out possible correlations between these elements and vitamins with thyroid function tests and thyroid autoantibody levels in patients having Hashimoto’s thyroiditis (HT). Methods: The study included 51 premenauposal women with untreated HT, aged 18 to 56 years without any known chronic diseases or chronic medicine usage, and 27 healthy premenauposal women aged 19 to 42 years old. Trace elements (selenium, zinc, copper, iron levels) and vitamins [A, E, B12, 25-OH-D, 1,25(OH)2D and folic acid levels] were evaluated in patient and control groups. Results: Consequently, serum trace elements and vitamin B12 levels did not significantly differ in patients with HT and control group. Thyroid functioning tests and autoantibody levels did not show any correlation with the levels of trace elements, vitamin A, vitamin E and 25-OH vitamin D. A correlation was detected between vitamin B12 and Anti thyroid peroxidase levels. Conclusion: The negative correlation between vitamin B12 and Anti thyroid peroxidase levels may demonstrate the necessity to screen the patients with HT for atrophic gastritis. We believe that more comprehensive studies with larger sample sizes are needed in which patients are randomized according to their nutritional status.