Abnormal Thyroid Research Articles

Clinicopathological features and prognosis of idiopathic membranous nephropathy with thyroid dysfunction.

Thyroid dysfunction is common in patients with kidney disease. However, the relationship between thyroid dysfunction and idiopathic membranous nephropathy (IMN) remains unclear. This retrospective study aimed to investigate the clinicopathological characteristics and prognosis of patients with IMN and thyroid dysfunction compared to patients with IMN and without thyroid dysfunction. A total of 1052 patients with IMN diagnosed by renal biopsy were enrolled in this study, including 736 (70%) with normal thyroid function and 316 (30%) with abnormal thyroid function. We analyzed the clinicopathological features and prognostic data between the two groups, using propensity score matching (PSM) to reduce the bias. Logistic regression analysis was performed to investigate the risk factors for IMN combined with thyroid dysfunction. Kaplan-Meier curves and Cox regression analysis were used to evaluate the association between thyroid dysfunction and IMN. Patients with IMN and thyroid dysfunction exhibited more severe clinical features. Female sex, lower albumin level, higher D-dimer level, severe proteinuria, and decreased estimated glomerular filtration rate were predictors of thyroid dysfunction in patients with IMN. After PSM, 282 pairs were successfully matched. Results from the Kaplan-Meier curves indicated that the thyroid dysfunction group had a lower complete remission rate (P = 0.044), higher relapse rate (P < 0.001), and lower renal survival rate (P = 0.004). The multivariate Cox regression analysis revealed that thyroid dysfunction was an independent risk factor for complete remission [hazard ratio (HR) = 0.810, P = 0.045], relapse (HR = 1.721, P = 0.001), and composite endpoint event (HR = 2.113, P = 0.014) in IMN. Thyroid dysfunction is relatively common in patients with IMN, and the clinical indicators are more severe in these patients. Thyroid dysfunction is an independent risk factor for poor prognosis in patients with IMN. More attention should be paid to thyroid function in patients with IMN.

Thyroid Abnormalities in Children with Sepsis

Introduction: Sepsis is the most common cause of mortality in infants and children. A hormonal disorder that often affected in sepsis is thyroid hormones which occur in the form of euthyroid sick syndrome (ESS) or nonthyroidal illness syndrome (NTIS). The aim of study was to evaluate thyroid hormones changes and the outcome in children with sepsis. Materials and Methods: Present study is hospital based observational cohort study.70 children with diagnosed sepsis were required in sample size. Serum free T3, free T4 and TSH was measured on day one and also on follow up (7th day). Result: on day one Serum FT3 level was low in 40 (57.2%) subjects and Serum FT4 level was low in 12 (17.2%) subjects. TSH was normal in most 66 (94.2%) of subjects. Mortality was more in children with low serum FT3 (22.5%) as compared to those with normal FT3 (3.4%). Mortality was also more in children with low serum FT4 level (41.6%) as compared to those with normal FT4 level (8.7%), (p=0.002). Mortality was more in children with low serum FT3 (29%) on follow up as compared to those with normal FT3 (2.5%) (p=0.001). Conclusion: Thyroid hormones dysfunctions are common in children with sepsis. Mortality is significantly associated with low levels of serum FT3 &amp; FT4. So Thyroid hormones dysfunctions could be an indicator of disease severity with possible need for hormone supplementation. Keywords: Thyroid hormones, Serum free T3, free T4, TSH, sepsis, children

TREATMENT TACTICS FOR GENITAL PROLAPSES IN WOMEN WITH ABNORMAL UTERINE BLEEDING AND THYROID GLAND PATHOLOGY

Introduction. Patients with genital prolapse have various extragenital pathologies, in particular thyroid pathology, which affects the regulation of the menstrual cycle both in the reproductive and perimenopausal periods of a woman's life. Abnormal uterine bleeding caused by hormonal disorders, functional and organic changes in the thyroid gland is reported as a common problem of perimenopausal age. The aim of this study is to optimize the treatment of genital prolapse in women with abnormal uterine bleeding and thyroid pathology. Materials and methods. 49 perimenopausal women with genital prolapse who had thyroid pathology were examined and treated. They were divided into the main group (29 women with abnormal uterine bleeding) and the comparison group of 20 patients with genital prolapse without abnormal uterine bleeding. 20 women without signs of gynaecological and extragenital pathology made up the control group. Results. The presence of significant deviations in the serum content of steroid hormones in women with thyroid dysfunction allows us to confirm the relationship between proliferative processes in the endometrium and the functioning of the thyroid system. The examination revealed a significant relationship between thyroid dysfunction and the cause of abnormal uterine bleeding. Depending on the treatment method, the women of the main group were divided into 2 subgroups: the first subgroup included 19 patients who underwent vaginal extirpation of the uterus and simultaneous correction of genital prolapse with additional sacrospinal fixation of the vaginal stump using a mesh implant fragment. 10 patients were included in the second subgroup, which underwent hysteroresectoscopy due to abnormal uterine bleeding, and surgical treatment of genital prolapse was performed after a certain period of time (after 0.5-3 years, on average after 21-24 months). In the comparison group, planned vaginal extirpation of the uterus was performed. Conclusion. The improvement of the treatment of genital prolapse in women with abnormal uterine bleeding and thyroid pathology consists in combining vaginal removal of the uterus followed by strengthening of the vaginal dome through the use of sacrospinal fixation and/or a mesh implant in order to prevent recurrences and improve the economic indicators of the medical institution and the quality of life of patients.

To Compare TSH, T3, T4 Levels in Patients with Menstrual Disturbances with Normal Healthy Fertile Females

Thyroid disorders may influence reproductive performance in a variety of ways ranging from abnormal sexual development to menstrual irregularities to infertility. A close interplay exists between thyroid hormone and normal steroid action and secretion, which are necessary for normal ovarian function and thus fertility. In the present study, a total of 100 patients were studied. Out of these 100 patients, 50 patients were with a history of menstrual disturbances and 50 patients of reproductive age group with normal menstrual cycle and with proven fertility were taken as control. It is concluded from the present study that abnormal thyroid profile is associated with menstrual disturbances.

Clinical practice-latest insights in optimizing the care of children with Down syndrome.

An essential part of the care of children with Down syndrome is secondary screening for comorbidity. It is well known that comorbidity frequently occurs in these children. A new update of the Dutch Down syndrome medical guideline was developed to create a sound evidence base for several of these conditions. We present the latest insights and recommendations from this Dutch medical guideline which are based on the most relevant literature currently available and developed with rigorous methodology. The main focus of this revision of the guideline was on obstructive sleep apnea and other airway problems and hematologic disorders, such as transient abnormal myelopoiesis, leukemia, and thyroid disorders. Conclusion:This is a short summaryof the latest insights and recommendations from the updated Dutch medical guideline for children with Down syndrome.

Serum Lipidomic Analysis Reveals Biomarkers and Metabolic Pathways of Thyroid Dysfunction.

Abnormal thyroid hormone secretion is the most important feature of hypothyroidism and plays an important role in lipid metabolism. However, their connection has not been clearly established. This study aimed to identify the serum biomarkers and metabolic pathways associated with hyperthyroidism and hypothyroidism. The study enrolled discovery and validation sets of 175 and 300 participants, respectively, to identify and validate the serum biomarkers of hyperthyroidism and hypothyroidism via ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry lipidomics through univariate and multivariate analyses. Eight and six biomarkers were identified for hyperthyroidism and hypothyroidism, respectively. Spearman correlation analysis was used to assess the correlation between the biomarkers and thyroid dysfunction indicators; subsequently, metabolic pathway and network analyses were performed for these biomarkers. Most biomarkers exhibited significant correlation with thyroid dysfunction indicators, mainly being enriched in the glycerophospholipid (GPL) metabolism. The diagnostic accuracies of the biomarkers and biomarker panels were assessed via receiver operating characteristic curve analysis. All the biomarkers demonstrated good diagnostic performance, and the hyperthyroidism and hypothyroidism biomarker panels reached an area under the curve value of 1.000. The results were validated using the validation set. Therefore, our findings revealed that thyroid dysfunction primarily affects the human metabolism via the GPL metabolism, thus providing a theoretical basis for the clinical prevention and control of thyroid dysfunction.

Thyroid dysfunction after immune checkpoint inhibitor treatment in a single-center Chinese cohort: a retrospective study.

Thyroid dysfunction is a common adverse event after immune checkpoint inhibitor (ICI) therapy. The clinical manifestations of thyroid immune-related adverse events (irAEs) are variable and the underlying mechanisms remain unclear. To identify the clinical and biochemical characteristics of Chinese patients with ICI-related thyroid dysfunction. We retrospectively reviewed patients with carcinoma who received ICI therapy and underwent evaluation of thyroid function during hospitalization at Peking Union Medical College Hospital between January 1, 2017 and December 31, 2020. Clinical and biochemical features were analyzed in patients who developed ICI-related thyroid dysfunction. Survival analyses were performed to determine the effect of thyroid autoantibodies on thyroid abnormalities and the impact of thyroid irAEs on clinical outcomes. The cohort included 270 patients with a median follow-up of 17.7 months; 120 (44%) of these patients developed thyroid dysfunction on immunotherapy. The most common thyroid irAE was overt hypothyroidism (with/without transient thyrotoxicosis), which occurred in 38% of patients (n = 45), followed by subclinical thyrotoxicosis (n = 42), subclinical hypothyroidism (n = 27), and isolated overt thyrotoxicosis (n = 6). The median time to first clinical presentation was 49 days (interquartile range 23, 93) for thyrotoxicosis and 98 days (interquartile range 51, 172) for hypothyroidism. In patients treated with PD-1 inhibitors, hypothyroidism was strongly associated with younger age (odds ratio [OR] 0.44, 95% confidence interval [CI] 0.29-0.67; P < 0.001), previous thyroid disease (OR 4.30, 95% CI 1.54-11.99; P = 0.005), and a higher baseline thyroid-stimulating hormone level (OR 2.76, 95% CI 1.80-4.23; P < 0.001). Thyrotoxicosis was only associated with the baseline thyroid-stimulating hormone (TSH) level (OR 0.59, 95% CI 0.37-0.94; P = 0.025). Thyroid dysfunction after initiation of ICI therapy was associated with better progression-free survival (hazard ratio [HR] 0.61, 95% CI 0.44-0.86; P = 0.005) and overall survival (hazard ratio 0.67, 95% CI 0.45-0.99; P = 0.046). Anti-thyroglobulin antibody positivity increased the risk of thyroid irAEs. The occurrence of thyroid irAEs with diverse phenotypes is common. Distinct clinical and biochemical characteristics suggest heterogeneity among different subgroups of thyroid dysfunction, which requires further research to explore the under mechanism.

A Causality between Thyroid Function and Bone Mineral Density in Childhood: Abnormal Thyrotropin May Be Another Pediatric Predictor of Bone Fragility.

Low bone mass can occur in children and adolescents with numerous chronic conditions; however, the influence of abnormal thyroid hormone and thyroid-stimulating hormone (TSH) levels on low bone mineral density (BMD) in children and adolescents remains controversial. Investigating the effects of excessive or deficient thyroid hormone and TSH levels on the risk of childhood bone fragility may provide a better understanding of the role of thyroid function on bone density in the pediatric population. The triiodothyronine (T3), thyroxine (T4), and TSH levels and BMD of 619 children diagnosed with various underlying conditions and whose treatment was completed were simultaneously assessed. The T3, free thyroxine (FT4), and TSH levels were subcategorized based on the age-matched reference range, and the lumbar spine BMD (LSBMD) data were compared. The mean LSBMD z-score was 0.49 ± 1.28, while T3, FT4, and TSH levels were 1.25 ± 0.29 ng/mL, 1.28 ± 0.19 ng/dL, and 2.76 ± 1.87 µU/mL, respectively. Both lumbar and femoral BMD z-scores were lower in children with abnormal TSH levels. TSH abnormality was the strongest risk factor for decreased LSBMD z-scores, and thus could be an early indicator of low BMD in children and adolescents with various underlying conditions.

Cardiovascular and Thyroid Late Effects in Pediatric Patients With Hodgkin Lymphoma Treated With ABVD Protocol.

Hodgkin lymphoma (HL) survivors are at risk of developing a range of therapy-related complications. The goal of this study is to investigate therapy-related late-effects in HL survivors. We performed a cross-sectional study on 208 HL survivors who were treated at the National Cancer Institute or at the Children Cancer Hospital Egypt with doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy. Age at diagnosis ranged from 2.5 to 17.5 with a median of 8.7 years. The cumulative incidence of cardiac toxicity at 5 and 9 years were 18.7%±2.7% and 43.3%±4.4%, respectively. Preexisting cardiac abnormalities, cumulative anthracycline dose, and end of treatment cardiac status are strong predictors of late cardiotoxicity. Hypertension was observed in ~31% of patients. Young age and obesity at the time of treatment are important risk factors for hypertension. Thyroid abnormalities developed with a 5-year cumulative incidence of 2%±1%, whereas at 9 years the cumulative incidence was 27.9%±4.5%. Thyroid dysfunction was observed in 21.2% and thyroid tumors in 1.6% of cases. Subclinical hypothyroidism was the most common thyroid abnormality. Cardiotoxicity, hypertension, and thyroid dysfunction are frequent late effects after doxorubicin, bleomycin, vinblastine, and dacarbazine regimen, especially if combined with radiation therapy.

Breast MALT Lymphoma: A Clinical, Histomorphologic, and Immunophenotypic Evaluation.

Introduction. Primary breast extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is rare and understudied. Embryonically, mammary glands are developed as specialized skin appendages. It is possible that overlapping features exist between breast MALT lymphoma and primary cutaneous marginal zone lymphoma. Methods. We studied 5 primary and 6 secondary breast MALT lymphomas diagnosed in our institution during a 20-year period. Clinical and pathologic features of these lymphomas were analyzed and compared. Results. Most primary and secondary breast MALT lymphomas had similar clinical presentations as unilateral breast lesions without axillary lymphadenopathy. However, primary lymphomas tended to be diagnosed in older patients (median: 77 years old) than secondary lymphomas (median: 60 years old). Thyroid abnormality was a common finding in both primary (3/5) and secondary (5/6) lymphomas. Hashimoto's thyroiditis was diagnosed in one primary lymphoma. No distinct histopathologic findings were found in primary lymphomas. Features for primary cutaneous marginal zone lymphoma, including overexpression of IgG and IgG4 and high IgG4/IgG ratio, were absent in all primary but present in one secondary lymphoma with cutaneous origin. This secondary lymphoma also had expansion of CD30-positive cells. Conclusion. Primary breast MALT lymphoma does not share the distinctive features of primary cutaneous marginal zone lymphoma that set it apart from other extranodal marginal zone lymphomas. Having increased IgG- and IgG4-positive cells with a high IgG/IgG4 ratio in breast MALT lymphoma may indicate cutaneous origin. CD30 overexpression may be a feature seen in marginal zone lymphoma of cutaneous origin, which needs further studies to prove.

Effect of Antiretroviral Therapy to Thyroid Function Status on New Stage 1 and 2 Human Immunodeficiency Virus Patient

Background: Thyroid hormone is very important in regulating energy metabolism in all tissues of the human body. Thyroid dysfunction plays an important role in osteoporosis, hyperlipidemia and cardiovascular disease, all of which are associated with Human Immunodeficiency Virus (HIV) infection or therapy for HIV. Medications used to treat HIV infection are also said to be important factors that can cause thyroid abnormalities. This study aim is to see the effect of giving Antiretroviral Therapy (ART) to the thyroid function of new HIV patients in stage 1 and 2.&#x0D; Method: This prospective cohort study was conducted at Medan city health center and Medan Haji Adam Malik Hospital in March-June 2019. HIV patients who met the inclusion criteria were tested for thyroid function (Ft4 and TSH) before and after 3 months on ART, BMI, routine blood, CD4 and quality of life using the SF-36 questionnaire. Data analysis used paired t test and Pearson correlation.&#x0D; Result: 34 patients with stage 1 and 2 HIV showed normal thyroid function ; the average FT4 level was 1.03 ± 0.14 ng / dl and the average TSH level was 1.44 ± 0.68 µIU / mL. After 3 months of antiretroviral therapy, the mean thyroid function changes were obtained from the study subjects, where the mean FT4 results were 0.87 ± 0.13 ng / dl and the average TSH results were 1.76 ± 0.91 µIU / mL and the results were statistically significant with p 0.006 (p &lt;0.05). There was a statistically significant relationship between TSH and CD4 levels with BMI after ART administration (p &lt;0.05), but no statistically significant relationship was found between FT4 and BMI (p = 0.957). No statistically significant relationship was found between CD4 levels in study subjects and changes in fT4 levels (p = 0.557, r = 0.104) and TSH (p = 0.267, r = 0.196). There was also no significant difference in the quality of life of study subjects as seen from the SF-36 questionnaire both from changes in thyroid function and from CD4 levels.&#x0D; Conclusion: Stage 1 and 2 HIV patients who are on ART for 3 months experienced thyroid dysfunction.

Evaluation of Interactions Between Thyroid Dysfunction in End-Stage Renal Disease Patients: A Cross-Sectional Study.

Thyroid hormones have a very crucial role in the regulation of metabolism, synthesis of proteins, development, and influencing functions of various other hormones in the human body. While both kidneys play an essential role in the metabolism of thyroid hormone by conversion of thyroxine (T4) to triiodothyronine (T3). In patients with chronic renal failure, frequent abnormal thyroid functions are observed. To evaluate thyroid function in patients of chronic renal failure and to find out their correlation with the severity of the disease. A total of 192 patients were selected for the study after applying inclusion and exclusion criteria. A thyroid function test was done in all enrolled subjects. Serum estimation of T3, T4, and thyroid stimulating hormone (TSH) was done by the chemiluminescent immunoassay (CLIA) method, urea was estimated by the diacetyl monoxide method (DAM, Method), and serum creatinine by Jaffe's method. The results were evaluated for age, sex, and estimated glomerular filtration rate (eGFR) of the patients in view of thyroid dysfunction. Of all 192 patients enrolled in the study, 124 (64.58%) were male and 68 (35.41%) were females. The observed male-to-female ratio was 1.93:1.18. The mean age of the study group (mean +/- standard deviation, SD) in males was 42+/-18 and in females 38+/-11 years (p value = 0.258). Significant reductions of serum T3, T4, and elevation of TSH were noted in both sexes. A reduced level of T3 was observed in 38.54% (42 males and 32 females) patients, reduced T4 in 34.37% (42 males and 22 females) patients, and subclinical hypothyroidism (SCH) in 16.7% (12 males and 20 females) patients. Biochemical overt hypothyroidism was noted in 7.29% (six males and eight females) of patients. Chronic renal failure is a condition of thyroid hypofunction. A higher prevalence of SCH and clinical hypothyroidism is reported here in chronic kidney disease (CKD) patients. The severity of thyroid hypofunction increases with a progressive reduction in eGFR. Hypothyroidism in CKD patients may be due to different onset mechanisms other than anti-thyroid antibodies.

Iodine in the Therapy of Graves' Disease: A Century After Henry S. Plummer.

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Association of thyroid function with abnormal lipid metabolism in young patients with first-episode and drug naïve major depressive disorder.

Abnormal lipid metabolism in patients with major depressive disorder (MDD) has received increasing attention. The coexistence of MDD and abnormal thyroid function has been intensively studied. Moreover, thyroid function is closely related to lipid metabolism. The aim of this study was to investigate the relationship between thyroid function and abnormal lipid metabolism in young patients with first-episode and drug naïve (FEDN) MDD. A total of 1,251 outpatients aged 18-44 years with FEDN MDD were enrolled. Demographic data were collected, and lipid and thyroid function levels were measured, including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free tetraiodothyronine (FT4), anti-thyroglobulin antibody (TG-Ab), and anti-thyroid peroxidase antibody (TPO-Ab). The Hamilton Rating Scale for Depression (HAMD), Hamilton Anxiety Rating Scale (HAMA), and Positive and Negative Syndrome Scale (PANSS) positive subscale were also assessed for each patient. Compared with young MDD patients without comorbid lipid metabolism abnormalities, patients with comorbid lipid metabolism abnormalities had higher body mass index (BMI) values, HAMD score, HAMA score, PANSS positive subscale score, TSH levels, TG-Ab levels, and TPO-Ab levels. Binary logistic regression analysis showed that TSH level, HAMD score and BMI were risk factors for abnormal lipid metabolism. TSH levels were an independent risk factor for abnormal lipid metabolism in young MDD patients. Stepwise multiple linear regression showed that both TC and LDL-C levels were positively correlated with TSH levels, HAMD and PANSS positive subscale scores, respectively. HDL-C levels were negatively correlated with TSH levels. TG levels were positively correlated with TSH and TG-Ab levels and HAMD score. Our results show that thyroid function parameters, especially TSH levels, are implicated in abnormal lipid metabolism in young patients with FEDN MDD.

High Free T3 Levels in the Second Trimester are Correlated with the Control of Gestational Diabetes Mellitus

Gestational Diabetes Mellitus (GDM) and abnormal thyroid function are two common endocrine disorders occurring during pregnancy. In this study, we evaluated the correlation between the levels of different thyroid hormones and blood glucose control in pregnant women with diet-controlled GDM. Mid-pregnancy serum samples were obtained from 439 participants with GDM controlled by diet for analyses of thyroid function. A 2-h 75-g oral glucose tolerance test was used to evaluate the effect of blood glucose controlled by diet. According to blood glucose levels before and 2h after a meal, mothers were grouped into GDM-A1 (≤5.3mmol/L, ≤6.7mmol/L, respectively) and GDM-A2 (&gt;5.3 mmol, &gt;6.7mmol/L, respectively) and these groups were compared to the associated thyroid levels using multivariate logistic regression analysis. Our results show that fT3 was positively associated with GDM-A2. The adjusted odds ratio (95% confidence interval) comparing the highest and lowest fT3 quartile was 3.12 (1.66, 15.87) at the second trimester. Neither TSH nor fT4 was significantly associated with GDM-A2. Higher FT3 levels during the second trimester of pregnancy are a risk for GDM-A2 incidence. This provides new ideas for the control of GDM.

Variation in the reference range limits of thyroid function tests and association with the prevalence of levothyroxine treatment.

Many individuals with marginally abnormal thyroid function test (TFT) results may be treated and it is unknown if the limits of the TSH and FT4 reference intervals reported alongside the laboratory results are associated with the prevalence of levothyroxine treatment. We obtained information regarding reported TFT reference intervals from UK National Health Service (NHS) laboratories and evaluated its relationship with the prevalence of levothyroxine treatment for corresponding health areas for 2014. The upper limit of serum TSH was significantly, linearly, independently and negatively associated with prevalent levothyroxine treatment: -0.54% (95% confidence intervals -0.68% to -0.40%). The lower limit of serum FT4 was significantly and independently associated with the prevalence of levothyroxine treatment in a non-linear (J-shaped) manner with an increase being noted from a FT4 level of ≈9.5 pmol/L onwards. We conclude that minor changes in the reference range limits for serum TSH and FT4 are associated with levothyroxine treatment.

The significance of ophthalmological features in diagnosis of thyroid-associated ophthalmopathy

BackgroundThyroid-associated ophthalmopathy (TAO) is an autoimmune disorder. It has discriminable appearance. This study was conducted to dig the clinical significance of demographic characteristics and ophthalmologic diagram features in TAO diagnosis and stage/severity evaluation.ResultsWe included 320 males and 633 females, with an average age of 41.75 ± 13.75. A majority of TAO patients had hyperthyroidism, and most of them were in the inactive stage and at the moderate level. The thyroid function type, stage and severity were closely associated with hypopsia, eyelid congestion, conjunctival congestion, corneal ulcer, ocular motility disorder, best corrected visual acuity, and extraocular muscle thickening. Using these features, we established different logistic regression models to predict thyroid function subtypes, abnormal thyroid function, stage, and severity, in which the AUC of the ROC curve and accuracies were satisfactory.ConclusionTogether, TAO subtype, stage and severity can be diagnosed by auxiliary references including demographic factors, symptoms from complains, and image features. These non-invasive indices can be applied in a timely manner in clinical estimating TAO status.

Interim results of a first-in-human phase 1 study of Q-1802, a CLDN18.2/PD-L1 bsABs, in patients with relapsed or refractory solid tumors.

382 Background: Q-1802 is a humanized bispecific antibody that targets both the tumor -specific antigen CLDN18.2 and the immune checkpoint PD-L1. Q-1802 monotherapy dose-escalation study has been completed in China and dose-expansion study has enrolled 17 advanced subjects with advanced Gastric adenocarcinoma, pancreatic cancer, biliary tract cancer. Methods: This is a FIH, phase 1a/1b, multicenter, open label, single arm, dose escalation and dose expansion study of Q-1802, administered intravenously to 20-30 adult patients with resistant/refractory advanced or metastatic solid tumors who had failed standard therapies (NCT04856150). It aimed to evaluate the safety, tolerability, PK/PD profiles and preliminary efficacy of Q-1802 monotherapy. In the dose escalation phase (phase 1a), an accelerated titration followed by a 3+3 design was used to assess the safety and tolerability of Q-1802 (dose range 0.1 mg/kg to 20 mg/kg); and determine the maximum tolerated dose (MTD). Q-1802 was administered in a dose limiting toxicity (DLT) observation period followed by a Q2w treatment schedule. In the dose expansion phase (Phase 1b), one to two dose groups will be selected to enroll 9-23 Pts, including 3 negative CLDN18.2 expression and 6 positive CLDN18.2 expression in each group. Q-1802 was administered Q2w on a 14-day treatment cycle. Results: As of September 20, 2022, a total of 29 patients (median age 57.0 y; most patients received ≥3 prior regimens) were enrolled (12 Pts in phase 1a with DLT evaluation and 17 Pts in Phase 1b). The most common tumor types were GI cancers. There were no DLTs up to 20 mg/kg of Q-1802, inclusive. Two dose groups:10mg/kg and 20mg/kg were extended in Phase 1b study. Treatment-emergent adverse events were mostly grade 1-2 .The most common treatment related adverse events were Gastrointestinal AEs (89.7%, 26/29), including nausea 18/29 (62.1%), vomiting 18/29 (62.1%), abdominal pain 8/29 (27.6%), Gastroesophageal reflux disease 7/29 (24.1%). Grade 3 treatment-related AEs occurred 7/29 ( 24.1%), and gastrointestinal disease including nausea, vomiting has a higher percentage of 10.3% (3/29). Only one case has a grade 4 AE, hyponatremia, with a long term use of diuretics history. No death reported due to study related treatment. irAEs happened in 7 subjects, including abnormal thyroid function, fatigue, rash, arthritis. Most of irAEs were grade1-2. Among the 9 GIsubjects in the dose-expansion phase with CLDN18.2 positive expression who had measurable lesions and had received at least one post treatment tumor assessments, 2ptsachieved partial response and 4 achieved stable disease as the best overall response per RECIST1.1. Conclusions: Interim data from the present phase 1 study, demonstrate that Q-1802 has excellent preliminary safety, tolerability and preliminary anti-tumor activity up to doses of 20 mg/kg. The dose extension is still ongoing. Clinical trial information: NCT04856150 .

Significance of FDG-PET standardized uptake values in predicting thyroid disease.

This study aimed to determine a standardized cut-off value for abnormal 18F-fluorodeoxyglucose (FDG) accumulation in the thyroid gland. Herein, 7013 FDG-PET/CT scans were included. An automatic thyroid segmentation method using two U-nets (2D- and 3D-U-net) was constructed; mean FDG standardized uptake value (SUV), CT value, and volume of the thyroid gland were obtained from each participant. The values were categorized by thyroid function into three groups based on serum thyroid-stimulating hormone levels. Thyroid function and mean SUV with increments of 1 were analyzed, and risk for thyroid dysfunction was calculated. Thyroid dysfunction detection ability was examined using a machine learning method (LightGBM, Microsoft) with age, sex, height, weight, CT value, volume, and mean SUV as explanatory variables. Mean SUV was significantly higher in females with hypothyroidism. Almost 98.9% of participants in the normal group had mean SUV < 2 and 93.8% participants with mean SUV < 2 had normal thyroid function. The hypothyroidism group had more cases with mean SUV ≥ 2. The relative risk of having abnormal thyroid function was 4.6 with mean SUV ≥ 2. The sensitivity and specificity for detecting thyroid dysfunction using LightGBM (Microsoft) were 14.5 and 99%, respectively. Mean SUV ≥ 2 was strongly associated with abnormal thyroid function in this large cohort, indicating that mean SUV with FDG-PET/CT can be used as a criterion for thyroid evaluation. Preliminarily, this study shows the potential utility of detecting thyroid dysfunction based on imaging findings.

Myasthenia gravis in current status: epidemiology, types, etiology, pathophysiology, symptoms, diagnostic tests, prevention, treatment, and complications - correspondence.

Myasthenia gravis in current status: epidemiology, types, etiology, pathophysiology, symptoms, diagnostic tests, prevention, treatment, and complications - correspondence.