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1.
JBMR Plus ; 8(3): ziad010, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38741607

RESUMEN

Hypoparathyroidism (HypoPT) is a rare disease, often inadequately controlled by conventional treatment. PARALLAX was a mandatory post-marketing trial assessing pharmacokinetics and pharmacodynamics of different dosing regimens of recombinant human parathyroid hormone 1-84 (rhPTH[1-84]) for treating HypoPT. The present study (NCT03364738) was a phase 4, 1-yr open-label extension of PARALLAX. Patients received only 2 doses of rhPTH(1-84) in PARALLAX and were considered treatment-naive at the start of the current study. rhPTH(1-84) was initiated at 50 µg once daily, with doses adjusted based on albumin-corrected serum calcium levels. Albumin-corrected serum calcium (primary outcome measure), health-related quality of life (HRQoL), adverse events, and healthcare resource utilization (HCRU) were assessed. The mean age of the 22 patients included was 50.0 yr; 81.8% were women, and 90.9% were White. By the end of treatment (EOT), 95.5% of patients had albumin-corrected serum calcium values in the protocol-defined range of 1.88 mmol/L to the upper limit of normal. Serum phosphorus was within the healthy range, and albumin-corrected serum calcium-phosphorus product was below the upper healthy limit throughout, while mean 24-h urine calcium excretion decreased from baseline to EOT. Mean supplemental doses of calcium and active vitamin D were reduced from baseline to EOT (2402-855 mg/d and 0.8-0.2 µg/d, respectively). Mean serum bone turnover markers, bone-specific alkaline phosphatase, osteocalcin, procollagen type I N-terminal propeptide, and type I collagen C-telopeptide increased 2-5 fold from baseline to EOT. The HCRU, disease-related symptoms and impact on HRQoL improved numerically between baseline and EOT. Nine patients (40.9%) experienced treatment-related adverse events; no deaths were reported. Treatment with rhPTH(1-84) once daily for 1 yr improved HRQoL, maintained eucalcemia in 95% of patients, normalized serum phosphorus, and decreased urine calcium excretion. The effects observed on urine calcium and the safety profile are consistent with previous findings. Clinical trial identifier: NCT03364738.

2.
Front Immunol ; 15: 1382424, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38601161

RESUMEN

During pregnancy, the maternal immune system must allow and support the growth of the developing placenta while maintaining the integrity of the mother's body. The trophoblast's unique HLA signature is a key factor in this physiological process. This study focuses on decidual γδT cell populations and examines their expression of receptors that bind to non-classical HLA molecules, HLA-E and HLA-G. We demonstrate that decidual γδT cell subsets, including Vδ1, Vδ2, and double-negative (DN) Vδ1-/Vδ2- cells express HLA-specific regulatory receptors, such as NKG2C, NKG2A, ILT2, and KIR2DL4, each with varying dominance. Furthermore, decidual γδT cells produce cytokines (G-CSF, FGF2) and cytotoxic mediators (Granulysin, IFN-γ), suggesting functions in placental growth and pathogen defense. However, these processes seem to be controlled by factors other than trophoblast-derived non-classical HLA molecules. These findings indicate that decidual γδT cells have the potential to actively contribute to the maintenance of healthy human pregnancy.


Asunto(s)
Antineoplásicos , Placenta , Embarazo , Humanos , Femenino , Decidua , Antígenos HLA-G/genética , Antígenos HLA-G/metabolismo , Trofoblastos/metabolismo , Citocinas/metabolismo
3.
Artículo en Inglés | MEDLINE | ID: mdl-38449442

RESUMEN

CONTEXT: Hypoparathyroidism is a rare disorder characterized by a deficiency in parathyroid hormone (PTH) resulting in hypocalcemia, hyperphosphatemia, and hypercalciuria. Eneboparatide is an investigational peptide agonist of the PTH1 receptor for the treatment of chronic hypoparathyroidism (HP). OBJECTIVE: To evaluate the efficacy, safety, and tolerability of eneboparatide in HP patients. DESIGN: Open-label, phase 2 study. PARTICIPANTS: Twenty-eight patients (21 women, 7 men), mean age (range): 58 years (28-72), with HP were enrolled into 2 consecutive cohorts (C1, n = 12, and C2, n = 16). INTERVENTION: Following an optimization period, daily subcutaneous injections of eneboparatide were administered for 3 months at 20 µg/day (C1) or 10 µg/day (C2) starting dose. Conventional therapy was progressively removed and eneboparatide could be titrated up to 60 µg (C1) or 80 µg (C2). MAIN OUTCOMES: Proportion of patients achieving independence from conventional therapy, albumin-adjusted serum calcium (ADsCa), 24-h urine calcium (uCa), serum bone turnover markers (s-CTX and P1NP), bone mineral density (BMD), and adverse events (AEs). RESULTS: After 3 months, ≥ 88% patients achieved independence from conventional therapy while mean ADsCa was maintained within target range (7.8-9 mg/dL). Eneboparatide induced a rapid and sustained reduction of mean 24-hour uCa, even among patients with hypercalciuria. Bone turnover markers slightly increased and BMD remained unchanged, consistent with progressive resumption of physiologic bone turnover. Eneboparatide was well tolerated with no serious AEs. CONCLUSION: Eneboparatide allowed independence from conventional therapy and maintenance of serum calcium within a target range, while normalizing uCa excretion and producing a balanced resumption of bone turnover.

5.
Int J Mol Sci ; 25(3)2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38338701

RESUMEN

The function of natural autoantibodies (nAAbs) in maintaining immunological tolerance has been comprehensively explained; however, their function in pregnant patients dealing with autoimmune diseases has not been thoroughly investigated. As Hashimoto's thyroiditis (HT) is the predominant organ-specific autoimmune condition of women of childbearing age, this study's objective was to evaluate IgM and IgG nAAbs targeting mitochondrial citrate synthase (CS) and heat shock proteins (Hsp60 and Hsp70) in women diagnosed with HT who were pregnant (HTP). Serum samples collected from HTP and healthy pregnant (HP) women in the first and third trimesters were tested using in-house-developed enzyme-linked immunosorbent assays (ELISAs). Our findings indicate the stability of nAAbs against CS and Hsps throughout the pregnancies of both healthy women and those with HT. However, during both trimesters, HTP patients displayed elevated levels of IgM isotype nAAbs against Hsp60 and Hsp70 compared to HP women, suggesting a regulatory role of IgM nAAbs during the pregnancies of patients with HT. Nonetheless, levels of IgG isotype nAAbs against Hsps were lower solely in the third trimester among HTP patients, resulting in a higher IgM/IgG ratio, which indicates their importance in alterations of the nAAb network during pregnancy in patients with HT.


Asunto(s)
Enfermedades Autoinmunes , Enfermedad de Hashimoto , Embarazo , Humanos , Femenino , Autoanticuerpos , Mujeres Embarazadas , Proteínas de Choque Térmico , Proteínas HSP70 de Choque Térmico , Inmunoglobulina G , Chaperonina 60 , Inmunoglobulina M
6.
Endocr Pract ; 30(1): 11-18, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37805100

RESUMEN

OBJECTIVE: To assess the effect of relacorilant, a selective glucocorticoid receptor modulator under investigation for the treatment of patients with endogenous hypercortisolism (Cushing syndrome [CS]), on the heart rate-corrected QT interval (QTc). METHODS: Three clinical studies of relacorilant were included: (1) a first-in-human, randomized, placebo-controlled, ascending-dose (up to 500 mg of relacorilant) study in healthy volunteers; (2) a phase 1 placebo- and positive-controlled thorough QTc (TQT) study of 400 and 800 mg of relacorilant in healthy volunteers; and (3) a phase 2, open-label study of up to 400 mg of relacorilant administered daily for up to 16 weeks in patients with CS. Electrocardiogram recordings were taken, and QTc change from baseline (ΔQTc) was calculated. The association of plasma relacorilant concentration with the effect on QTc in healthy volunteers was assessed using linear mixed-effects modeling. RESULTS: Across all studies, no notable changes in the electrocardiogram parameters were observed. At all time points and with all doses of relacorilant, including supratherapeutic doses, ΔQTc was small, generally negative, and, in the placebo-controlled studies, similar to placebo. In the TQT study, placebo-corrected ΔQTc with relacorilant was small and negative, whereas placebo-corrected ΔQTc with moxifloxacin positive control showed rapid QTc prolongation. These results constituted a negative TQT study. The model-estimated slopes of the concentration-QTc relationship were slightly negative, excluding an association of relacorilant with prolonged QTc. CONCLUSION: At all doses studied, relacorilant consistently demonstrated a lack of QTc prolongation in healthy volunteers and patients with CS, including in the TQT study. Ongoing phase 3 studies will help further establish the overall benefit-risk profile of relacorilant.


Asunto(s)
Síndrome de Cushing , Síndrome de QT Prolongado , Humanos , Estudios Cruzados , Síndrome de Cushing/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Electrocardiografía , Voluntarios Sanos , Síndrome de QT Prolongado/inducido químicamente , Síndrome de QT Prolongado/tratamiento farmacológico , Moxifloxacino , Receptores de Glucocorticoides , Ensayos Clínicos Controlados Aleatorios como Asunto , Ensayos Clínicos Fase I como Asunto , Ensayos Clínicos Fase II como Asunto
7.
Orv Hetil ; 164(39): 1550-1555, 2023 Oct 01.
Artículo en Húngaro | MEDLINE | ID: mdl-37778009

RESUMEN

Neuroblastoma, representing one-tenth of childhood malignancies, is a clinically and prognostically heterogeneous disease. Survival in cases with poor prognosis has recently been significantly improved by rapidly evolving multimodal therapy. Our 4-year-old patient presented with bitemporal swelling and the diagnostic workup confirmed stage IV neuroblastoma (bone marrow and multiple bone metastases). While the tumor responded well to the initial treatment, it relapsed during post-consolidation therapy. As part of the salvage therapy for this high-risk disease with poor prognosis, 131-I-meta-iodo-benzyl-guanidine treatment was performed for the first time in our country, in a case of pediatric neuroblastoma. Neuroendocrine tissue cells express a norepinephrine transporter capable of uptaking the catecholamine analog meta-iodo-benzyl-guanidine. This mechanism makes it an adequate molecule for the imaging (123-I-meta-iodo-benzyl-guanidine) and target therapy (131-I-meta-iodo-benzyl-guanidine) of neuroendocrine tumors, including neuroblastoma. Treatment with 131-I-meta-iodo-benzyl-guanidine requires specific personnel and infrastructural equipment, particularly in pediatric cases. Careful organization and cooperation between nuclear medicine specialists and collaborating clinicians (pediatric oncologists and adult internists if necessary) are essential. Meta-iodo-benzyl-guanidine therapy, already routinely used abroad, has been considered as part of salvage therapy for recurrent neuroblastoma until now, but ongoing clinical trials suggest that it may become part of the first-line treatment soon. As the indications broaden, it is necessary to make it available for more and more children in our country. Orv Hetil. 2023; 164(39): 1550-1555.


Asunto(s)
3-Yodobencilguanidina , Neuroblastoma , Adulto , Niño , Humanos , Preescolar , 3-Yodobencilguanidina/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/radioterapia , Guanidinas/uso terapéutico
8.
J Immunol Res ; 2023: 5221658, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37663050

RESUMEN

T helper type 1 (Th1) and inflammatory cytokines play essential roles in early pregnancy and also in the pathogenesis of Hashimoto's thyroiditis (HT). Changes in the serum level of autoantibodies to cytokines, which may be able to modulate their availability and actions have been described in several autoimmune disorders. Yet, no data are available on anti-cytokine autoantibodies either during early pregnancy or in patients with HT. The aim of the study was to measure autoantibodies to inflammatory-, Th1- and Th22-cytokines in serum samples in healthy pregnancy (HP) and in pregnant women with HT (HTP). As pathological autoantibodies are hallmarks of HT, in addition we also measured anti-B-cell activator factor (BAFF) autoantibodies. The measurement was carried out with a Luminex multiplex assay and the Luminex MAGPIX Instrument, age-matched healthy women (HC) and women with HT (HT) were used as controls. In the first trimester of HP, anti-TNFα, anti-IL-8, and anti-IFNγ autoantibodies were significantly decreased, while autoantibodies to BAFF were significantly elevated compared to the HC. However, these alterations were not present in the HTP. Moreover, the levels of autoantibodies to IL-22 and TNFα were significantly increased in HTP compared to the HP. All differences in the levels of the investigated autoantibodies could be detected in the first trimester of pregnancies except for anti-IL-22 autoantibodies. According to our results we can conclude that alterations in the levels of autoantibodies to inflammatory and Th1 cytokines are physiological in the first trimester of pregnancy and their disturbance can be associated with autoimmune conditions such as HT.


Asunto(s)
Enfermedades Autoinmunes , Enfermedad de Hashimoto , Embarazo , Humanos , Femenino , Citocinas , Autoanticuerpos , Mujeres Embarazadas
10.
J Clin Med ; 12(14)2023 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-37510916

RESUMEN

BACKGROUND: The adrenocortical system and copeptin as prognostic markers were intensively investigated in critical illness. The potential predictive power of apelin-13 as a biomarker is largely unknown. We aimed to investigate the prognostic role of apelin-13 in relation to free cortisol, aldosterone, CRH, and copeptin in critically ill patients. METHODS: In this prospective observational study, 124 critically ill patients (64 men, 60 women, median age: 70 (59-78) years) were consecutively enrolled at the time of admission. All routinely available clinical and laboratory parameters were evaluated and correlated to hormonal changes. RESULTS: Serum apelin-13 was 1161 (617-2967) pg/mL in non-survivors vs. 2477 (800-3531) pg/mL in survivors (p = 0.054). The concentrations of apelin-13 and CRH had strong positive correlations (r = 0.685, p < 0.001) and were significantly higher in surviving non-septic patients (Apelin-13 (pg/mL): 2286 (790-3330) vs. 818 (574-2732) p < 0.05; CRH (pg/mL) 201 (84-317) vs. 89 (74-233) p < 0.05). Apelin-13 and free cortisol were independent determinants of survival in the multivariate Cox regression analysis, while copeptin, CRH, or aldosterone were not. CONCLUSIONS: Beyond free cortisol, serum apelin-13 may also help refine prognostic predictions in the early phase of critical illness, especially in non-septic patients.

11.
Int J Mol Sci ; 24(10)2023 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-37240453

RESUMEN

Calcium (Ca2+) flux acts as a central signaling pathway in B cells, and its alterations are associated with autoimmune dysregulation and B-cell malignancies. We standardized a flow-cytometry-based method using various stimuli to investigate the Ca2+ flux characteristics of circulating human B lymphocytes from healthy individuals. We found that different activating agents trigger distinct Ca2+ flux responses and that B-cell subsets show specific developmental-stage dependent Ca2+ flux response patterns. Naive B cells responded with a more substantial Ca2+ flux to B cell receptor (BCR) stimulation than memory B cells. Non-switched memory cells responded to anti-IgD stimulation with a naive-like Ca2+ flux pattern, whereas their anti-IgM response was memory-like. Peripheral antibody-secreting cells retained their IgG responsivity but showed reduced Ca2+ responses upon activation, indicating their loss of dependence on Ca2+ signaling. Ca2+ flux is a relevant functional test for B cells, and its alterations could provide insight into pathological B-cell activation development.


Asunto(s)
Subgrupos de Linfocitos B , Linfocitos B , Humanos , Subgrupos de Linfocitos B/metabolismo , Células Productoras de Anticuerpos , Receptores de Antígenos de Linfocitos B/metabolismo , Diferenciación Celular
12.
J Clin Endocrinol Metab ; 108(5): e148-e159, 2023 04 13.
Artículo en Inglés | MEDLINE | ID: mdl-36353760

RESUMEN

CONTEXT: Paltusotine is a once-daily, oral, nonpeptide small-molecule somatostatin receptor type 2 (SST2) agonist in clinical development for treatment of acromegaly. OBJECTIVE: This work aimed to evaluate change in insulin-like growth factor I (IGF-I) levels in patients switched from octreotide long-acting release or lanreotide depot monotherapy to paltusotine. METHODS: A phase 2, open-label, prospective, multicenter, multinational, nonrandomized, single-arm exploratory study was conducted in which dosage uptitrations were performed in a double-blinded manner. At 26 global sites, patients with acromegaly switched to paltusotine from injected somatostatin receptor ligand (SRL)-based therapy. Patients received 13-week treatment with once-daily oral paltusotine (10-40 mg/d). The primary end point was change from baseline to week 13 in IGF-I for patients who switched from long-acting octreotide or lanreotide depot monotherapy to paltusotine (group 1). All patients underwent a 4-week paltusotine washout at end of treatment period (wk 13-17). IGF-I, growth hormone (GH), patient-reported outcome, and safety data were collected. RESULTS: Forty-seven patients enrolled. In group 1 (n = 25), IGF-I and GH showed no significant change between SRL baseline and end of paltusotine treatment at week 13 (median change in IGF-I = -0.03×upper limit of normal [ULN]; P = .6285; GH = -0.05 ng/mL; P = .6285). IGF-I and GH rose significantly in the 4 weeks after withdrawing paltusotine (median change in IGF-I = 0.55×ULN; P < .0001 [median increase 39%]; GH = 0.72 ng/mL; P < .0001 [109.1% increase]). No patients discontinued because of adverse events (AE); no treatment-related serious AEs were reported. CONCLUSION: These results suggest once-daily oral paltusotine was effective in maintaining IGF-I values in patients with acromegaly who switched from injected SRLs. Paltusotine was well tolerated with a safety profile consistent with other SRLs.


Asunto(s)
Acromegalia , Hormona de Crecimiento Humana , Humanos , Acromegalia/tratamiento farmacológico , Acromegalia/metabolismo , Octreótido/uso terapéutico , Factor I del Crecimiento Similar a la Insulina/metabolismo , Estudios Prospectivos , Péptidos Cíclicos/efectos adversos , Resultado del Tratamiento
13.
Front Immunol ; 13: 1039166, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36389812

RESUMEN

Anti-thyroid antibody (ATA) positivity affects 1 out of 9 women in childbearing age and presents a significant risk for infertility. Emerging evidence indicates that alterations in the B cell receptor induced calcium (Ca2+) signaling could be key in the development of autoimmunity. We aimed to investigate the Ca2+ flux response of B lymphocyte subsets to BCR stimulation in Hashimoto's thyroiditis and related infertility. We collected peripheral blood samples from ATA+, infertile, euthyroid patients (HIE), hypothyroid, ATA+ patients before (H1) and after levothyroxine treatment (H2), and age-matched healthy controls (HC). All B cell subsets of ATA+, infertile, euthyroid patients showed elevated basal Ca2+ level and hyper-responsivity to BCR ligation compared to the other groups, which could reflect altered systemic immune function. The Ca2+ flux of hypothyroid patients was similar to healthy controls. The levothyroxine-treated patients had decreased prevalence of CD25+ B cells and lower basal Ca2+ level compared to pre-treatment. Our results support the role of altered Ca2+ flux of B cells in the early phase of thyroid autoimmunity and infertility.


Asunto(s)
Enfermedad de Hashimoto , Hipotiroidismo , Infertilidad Femenina , Humanos , Femenino , Tiroxina , Autoanticuerpos
14.
Front Endocrinol (Lausanne) ; 13: 981891, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36187132

RESUMEN

Objective: This study aimed to investigate the complex interactions of thyroid hormone, apelin, and copeptin in the fluid-ion homeostasis of patients with severe transitory hypothyroidism. Methods: In this prospective observational study, 39 patients (ECOG: 0; 11 men, 28 women, mean age: 50.3 ± 14.9 years) were investigated during short-term severe hypothyroidism due to surgical removal of the thyroid gland and after adequate thyroid replacement therapy. In addition to the routinely available lab tests, copeptin and apelin levels were determined using ELISA. Results: In the hypothyroid state, apelin concentration was lower, while copeptin levels did not differ compared to the euthyroid condition. Apelin showed a positive correlation with copeptin (p = 0.003), sodium (p = 0.002), NT-proBNP (p < 0.001), and fT4 (p < 0.001) and a negative correlation with thyroid-stimulating hormone (TSH) (p < 0.001). In multivariate linear regression models, copeptin and TSH proved to be significant independent predictors of apelin levels, of which TSH had an explanatory power of 48.7%. Aside from apelin, copeptin only correlated with sodium (p = 0.046). Sodium levels were negatively associated with TSH (p = 0.004) and positively with ACTH (p = 0.002) and cortisol (p = 0.047), in addition to copeptin. None of the parameters were independent predictors of serum sodium levels in a multivariate regression model. Conclusions: In short-term severe hypothyroidism, serum apelin level is markedly decreased, which may predispose susceptible patients to hyponatremia, while the level of copeptin is unchanged. TSH and copeptin are independent predictors of apelin concentration, of which TSH is stronger.


Asunto(s)
Hidrocortisona , Hipotiroidismo , Hormona Adrenocorticotrópica , Adulto , Anciano , Apelina , Femenino , Glicopéptidos , Humanos , Masculino , Persona de Mediana Edad , Sodio , Hormonas Tiroideas , Tirotropina
15.
Orv Hetil ; 163(31): 1243-1249, 2022 Jul 31.
Artículo en Húngaro | MEDLINE | ID: mdl-35908216

RESUMEN

Paragangliomas are mostly benign tumors originating from the sympathetic or parasympathetic ganglions, but malignant forms are also known. They are in the region of the head and neck, in the glomus caroticum, intra-abdominally as well as in the thorax. The investigation of the 39-year-old male patient began due to extremely high blood pressure, night sweats and a 10 kg weight loss. Chest CT scan described a huge mass in the right hilum, bronchoscopic sampling was inconclusive. Tumor biopsy was performed through right thoracotomy, but complete resection was not possible due to tissue adhesions and cardiac involvement. Histological examination verified paraganglioma, which was also confirmed by laboratory tests. Accordingly, somatostatin analog therapy was initiated, followed by I-131-MIBG treatment with good clinical effect. Coronary angiography confirmed that the right coronary artery contributed with two marginal branches to the blood supply of the thoracic mass. The tumor was successfully removed and after the cardio-thoracic surgery, the patient's antihypertensive therapy was stopped. There was no sign of relapse during follow-ups. During the medical investigation of severe blood pressure elevations, the possibility of paraganglioma should be considered. In these cases, invasive procedures, if not preceded by proper medication, can be fatal. By taking advantage of the ever-expanding therapeutic options and the cooperation between institutions, even patients with a giant paraganglioma can become tumor-free.


Asunto(s)
Radioisótopos de Yodo , Paraganglioma , 3-Yodobencilguanidina , Adulto , Humanos , Radioisótopos de Yodo/uso terapéutico , Masculino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Paraganglioma/diagnóstico , Paraganglioma/cirugía
16.
Eur Thyroid J ; 11(5)2022 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-35900798

RESUMEN

Introduction: Dysthyroid optic neuropathy (DON) is a rare, severe form of thyroid eye disease, in which decreased visual acuity is accompanied by characteristic MRI findings. The treatment of DON has always been a challenge. Case presentation: In a patient in whom visual acuity deteriorated on the left eye, mannitol 20% 200 mL followed by furosemide 40 mg 6 h later, administered daily, were initiated on the day of admission. Visual function by ophthalmology methods, and orbital compartment volumes and water content by MRI were followed. Intravenous diuretics resulted in an immediate therapeutic response. Visual acuity improved from 20/50 to 20/25 after 2 days of treatment. MRI revealed decreasing water content of both the muscle and connective tissue compartments without any volume changes. Subsequently, corticosteroids and orbital irradiation were started. Orbital decompression surgery was not required. Discussion/conclusion: Edematous swelling of orbital tissues is an established contributor of local pressure increase in thyroid eye disease. Diuretics reduce orbital pressure and, if confirmed by others, may be useful additions to the standard of care in sight-threatening DON.

17.
Front Med (Lausanne) ; 8: 671951, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34950676

RESUMEN

Background: The prevalence of hyponatremia is highly variable among patients with lung cancer. However, its prevalence and prognostic significance in subgroups of patients with lung cancer have not yet been evaluated in a meta-analysis. Methods: We have registered our meta-analysis and review protocol to the PROSPERO International Prospective Register of Systematic Reviews, with the following registration number: CRD42020167013. A systematic search was done in the following sources: MEDLINE, Embase, CENTRAL, Web of Science, ClinicalTrials.gov, a WHO Global Health Library. Results: We identified a total of 8,962 potentially eligible studies, and we included 31 articles in our evaluation. The prevalence of hyponatremia in patients with lung cancer varied between 3 and 94.8% with an average of 25% without any significant differences between the following subgroups: histotype, gender, age, Eastern Cooperative Oncology Group (ECOG) state, and the extent of disease. The overall survival (OS) was significantly lower in hyponatremic compared to normonatremic patients at 10 months [RR.59 (95% CI.47-0.74), p < 0.001] and at 20 months [RR.44 (95% CI.33-0.59), p < 0.001], with worse survival rates in non-small cell lung cancer (NSCLC) [RR.27 (95% CI.12-0.44), p < 0.001] than in small cell lung cancer (SCLC) [RR.42 (95% CI.27-0.57), p < 0.001]. If hyponatremia was corrected, OS at 10 months was significantly higher than in the uncorrected hyponatremia group [RR 1.83 (95% CI 1.37-2.44), p < 0.001], but, at 20 months, no statistically significant difference could be found between these subgroups [RR 2.65 (95% CI.94-7.50), p = 0.067]. Conclusions: Patients with lung cancer diagnosed with hyponatremia, especially patients with NSCLC, seem to have significantly lower survival rates than normonatremic patients. If hyponatremia remains uncorrected, the mortality rates might be even higher.

18.
Cancers (Basel) ; 13(2)2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33467717

RESUMEN

Thyroglobulin (Tg) is the most important tumor marker in differentiated thyroid cancer (DTC). The aim of this study was to assess the diagnostic and prognostic roles of postoperative stimulated and postablative lowest, highest, and one-year non-stimulated Tg values obtained during the follow-up of patients with DTC. In this retrospective study, 222 radioiodine-treated, anti-thyroglobulin antibody (TgAb)-negative DTC patients having at least 9 months' follow-up time were included (172 papillary and 50 follicular cancers; median age: 48 (from 15 to 91) years; female-male ratio: 158/64; median (quartiles) follow-up time: 54 (22-97) months). The 2015 American Thyroid Association guidelines were applied as criteria of the therapeutic response. Postoperative stimulated Tg values had significantly lower diagnostic accuracy than any of the non-stimulated postablative Tg values. One-year non-stimulated Tg had excellent prognostic value for structural disease: a cut-off value of 0.85 ng/mL had an 88.1% diagnostic accuracy. If the Tg value did not decrease below 0.75 ng/mL at any time during follow-up, the risk of residual disease was 25 times higher. The highest non-stimulated Tg during follow-up was the best predictor of residual disease (e.g., a Tg value exceeding 7.7 ng/mL indicated a 30-fold increase in risk). Non-stimulated Tg values measured during follow-up have excellent diagnostic accuracy to predict structural disease in DTC patients. The risk classification of a patient can safely be modified based on even a single Tg measurement.

19.
Magy Onkol ; 64(2): 112-117, 2020 Jun 10.
Artículo en Húngaro | MEDLINE | ID: mdl-32520004

RESUMEN

The first classic theranostic agent, radioactive iodine was used in the treatment of differentitated thyroid cancer (DTC) and it has an important role in the good prognosis of DTC even nowadays. I-131 provides a specific, molecular targeted therapy through the active uptake of iodide by sodium iodide symporter. The development of other theranostics also aimed the personalized therapy with minimal side effects and optimal therapeutic efficacy. The incidence of DTC which basically has good prognosis is increasing rapidly worldwide. This required the modification of guidelines to avoid the overtreatment of the disease, in the direction of less radical therapy. Currently, new pathological classification and staging systems were reported. The present work summarizes the new recommendations in the management of DTC, focusing on the indications of radioiodine therapy and reviewing the proposal of the Hungarian consensus conference.


Asunto(s)
Adenocarcinoma , Nanomedicina Teranóstica , Neoplasias de la Tiroides , Humanos , Radioisótopos de Yodo , Neoplasias de la Tiroides/diagnóstico por imagen
20.
Inflamm Bowel Dis ; 26(3): 331-346, 2020 02 11.
Artículo en Inglés | MEDLINE | ID: mdl-31504524

RESUMEN

BACKGROUND: Transition of adolescents from pediatric to adult care is of great importance in the management of inflammatory bowel disease (IBD). Our aim was to review and summarize the currently applied interventions and outcomes related to transition practices in IBD. METHODS: A systematic review was performed in accordance with the PRISMA Statement. We searched PubMed, EMBASE, CENTRAL, and Web of Science databases up to February 15, 2019. Controlled studies evaluating adolescents and young adults with IBD participating in structured transition interventions or patient educational programs and single-arm (before-after) studies were included. Several individual, health care, and social outcomes were assessed. The PROSPERO registration number is CRD42019118520. RESULTS: A total of 23 articles were eligible for qualitative synthesis. Eleven studies compared an intervention to a control group, whilst 12 studies were uncontrolled before-after studies. The age of the participants varied from 11 to 25 years. The most common structured transition interventions were joint visits and patient education programs. IBD nurses were operating as nominated transition coordinators in the transition process. Quality of life, patient satisfaction, self-efficacy, disease-specific knowledge, adherence rate, and nonattendance rate at outpatient clinic were identified as main health care transition outcomes besides disease-related outcomes. Despite the various study designs and methodological limitations, outcomes improved with the application of structured transition interventions in eleven of the studies. CONCLUSION: These results facilitate the design of randomized controlled trials along better standards in transitional care in IBD.


Asunto(s)
Servicios de Salud del Adolescente , Enfermedades Inflamatorias del Intestino/terapia , Calidad de Vida , Transición a la Atención de Adultos/normas , Adolescente , Humanos , Educación del Paciente como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Autocuidado/normas
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