The incidence of thyroid carcinoma has been increasing worldwide. This is interpreted as an increase in the incidental detection of papillary thyroid microcarcinomas (PTMCs). However, mortality has ...not changed, suggesting overdiagnosis and overtreatment. Prospective clinical trials of active surveillance for low-risk PTMC (T1aN0M0) have been conducted in two Japanese institutions since the 1990s. Based on the favorable outcomes of these trials, active surveillance has been gradually adopted worldwide. A task force on the management of PTMC in adults organized by the Japan Thyroid Association therefore conducted a systematic review and has produced the present position paper based on the scientific evidence concerning active surveillance. This paper indicates evidence for the increased incidence of PTMC, favorable surgical outcomes for low-risk PTMC, recommended criteria for diagnosis using fine needle aspiration cytology, and evaluation of lymph node metastasis (LNM), extrathyroidal extension (ETE) and distant metastasis. Active surveillance has also been reported with a low incidence of disease progression and no subsequent recurrence or adverse events on survival if conversion surgery was performed at a slightly advanced stage. Active surveillance is a safe and valid strategy for PTMC, because it might preserve physical quality of life and reduce 10-year medical costs. However, some points should be noted when performing active surveillance. Immediate surgery is needed for PTMC showing high-risk features, such as clinical LNM, ETE or distant metastasis. Active surveillance should be performed under an appropriate medical team and should be continued for life.
Background: This study examined the appropriateness of the current paradigm for differential diagnosis of painless thyroiditis and Graves' disease (GD) in patients with thyrotoxicosis. Methods: We ...retrospectively evaluated the clinical course of 343 consecutive patients with hyperthyroidism diagnosed by Tc-99m pertechnetate thyroid uptake (TcTU) testing at our hospital from January 2011 to December 2017. Results: Of the 263 patients with normal or high TcTU levels (≥1.0%), 255 (97%) had unequivocal GD and 5 had spontaneous remission GD or atypical GD. Of the 10 patients with low TcTU levels (<1.0% and ≥0.5%), 7 had GD, while others had subclinical GD, spontaneous remission GD with later relapse, and painless thyroiditis. Of those with very low TcTU levels (<0.5%), most had thyroiditis (painless thyroiditis, 33/67 49%; subacute thyroiditis, 29/67 43%), and some were positive for anti-TSH receptor antibodies. Conclusion: Given that atypical GD may confound the diagnosis of thyrotoxicosis, it is essential to follow the patient as a tentative diagnosis, whatever the diagnosis. This is the first report clearly demonstrating that so far there is no gold standard for the diagnosis of GD. It is therefore urgent to establish a consensus on the definition of GD so that the specificity and sensitivity of future diagnostic tests can be determined.
Abstract
Nonalcoholic fatty liver disease (NAFLD) is related to subclinical atherosclerosis. However, whether the severity of the disease (or which histopathological component) is associated with ...subclinical atherosclerosis remains controversial. This study aimed to investigate the association between the histopathological severity of NAFLD and carotid intima-media thickness (CIMT) in Japanese patients with liver biopsy-proven NAFLD. Maximum-CIMT (max-CIMT) was measured as an index of carotid atherosclerosis in 195 biopsy-proven NAFLD patients. A significant association was observed between the severity of fibrosis (but not steatosis, inflammation, and ballooning) and max-CIMT. Older age, male gender, hypertension, and advanced fibrosis were independently linked to max-CIMT ≥ 1.2 mm. The prevalence of max-CIMT ≥ 1.2 mm was significantly higher in the advanced fibrosis group than in the non-advanced fibrosis group (75.4% versus 44.0%;
p
< 0.01). Non-invasive liver fibrosis markers and scoring systems, including fibrosis-4 index, NAFLD fibrosis score, hyaluronic acid, and Wisteria floribunda agglutinin positive Mac-2-binding protein, demonstrated that the diagnostic performance for max-CIMT ≥ 1.2 mm was similar to that of biopsy-based fibrosis staging. In conclusion, advanced fibrosis is significantly and independently associated with high-risk CIMT. Non-invasive fibrosis markers and scoring systems could help estimate the risk of atherosclerosis progression in patients with NAFLD.
Background: The number of people diagnosed with dementia worldwide is set to increase significantly. Patients with dementia often have comorbidities, particularly diabetes, and patients with type 2 ...diabetes mellitus (T2DM) have a high risk of cognitive decline. This study investigated whether older people with T2DM have disease-specific cognitive deficits. Methods: The Montreal Cognitive Assessment is a well-known tool for examining mild cognitive impairment, and the modified Japanese version (MoCA-J) has been confirmed as effective. Using the MoCA-J, we assessed the cognitive function of Japanese adults aged ≥75 years with and without T2DM and analyzed the results. Results: Thirty-three patients with T2DM and 23 non-DM patients completed the examination, and MoCA-J total scores differed between these groups (T2DM mean, 21.4 ± 3.5; non-DM mean, 23.5 ± 3.6). Only 9% of patients with T2DM and 39% of those with non-DM had scores ≥26, which is the cutoff point for mild cognitive impairment, although all patients were capable of self-care. Additionally, delayed recall scores were significantly lower for the older patients with T2DM had for the non-DM group. Conclusions: Patients aged ≥75 years with T2DM might have worse cognition than those without T2DM; the inability to perform delayed recall in T2DM patients suggests a decline in cognitive function. Therefore, patients aged ≥75 years with T2DM should receive explanations of their care that are individualized in relation to their cognitive status.
Background: Combination therapy with an alpha-glucosidase inhibitor or glinide plus a dipeptidyl peptidase-4 inhibitor is thought to be effective for glycemic control because of its effects on ...postprandial hyperglycemia. However, no studies have directly compared these two combination therapies in relation to efficacy and safety. Methods: Eighteen patients with type 2 diabetes were studied. All had diabetes not adequately controlled with diet and exercise therapy, an HbA1c level of ≥7.5%, and were not receiving any medication for diabetes. The patients were randomized to either miglitol- or repaglinide-based combination therapy with alogliptin. Patients received miglitol or repaglinide monotherapy for 3 months (the miglitol and repaglinide groups, respectively), after which alogliptin was added to each group as combination therapy for 3 months. A meal tolerance test (MTT) was performed before the start of treatment and at the end of monotherapy and combination therapy. Results: During the study period, decreases in HbA1c and glycated albumin were significantly greater in the repaglinide group than in the miglitol group; however, there was no significant difference between treatment groups at the end of the study. At the end of monotherapy, insulin secretion relative to glucose elevation (ISG0-30: area under the curve of insulin from 0 to 30 min during MTT AUC0-30 of IRI/AUC0-30 of plasma glucose) was significantly higher only in the repaglinide group; ISG0-30 did not significantly increase in either group after the addition of alogliptin. Conclusions: The addition of alogliptin to repaglinide monotherapy did not cause glucose-independent inappropriate insulin secretion and did not appear to increase the incidence of hypoglycemia.
Background : Combination therapy with an alpha-glucosidase inhibitor or glinide plus a dipeptidyl peptidase-4 inhibitor is thought to be effective for glycemic control because of its effects on ...postprandial hyperglycemia. However, no studies have directly compared these two combination therapies in relation to efficacy and safety. Methods : Eighteen patients with type 2 diabetes were studied. All had diabetes not adequately controlled with diet and exercise therapy, an HbA1c level of >=7.5%, and were not receiving any medication for diabetes. The patients were randomized to either miglitol- or repaglinide-based combination therapy with alogliptin. Patients received miglitol or repaglinide monotherapy for 3 months (the miglitol and repaglinide groups, respectively), after which alogliptin was added to each group as combination therapy for 3 months. A meal tolerance test (MTT) was performed before the start of treatment and at the end of monotherapy and combination therapy. Results : During the study period, decreases in HbA1c and glycated albumin were significantly greater in the repaglinide group than in the miglitol group ; however, there was no significant difference between treatment groups at the end of the study. At the end of monotherapy, insulin secretion relative to glucose elevation (ISG0-30 : area under the curve of insulin from 0 to 30 min during MTT AUC0-30 of IRI / AUC0-30 of plasma glucose) was significantly higher only in the repaglinide group ; ISG0-30 did not significantly increase in either group after the addition of alogliptin. Conclusions : The addition of alogliptin to repaglinide monotherapy did not cause glucose-independent inappropriate insulin secretion and did not appear to increase the incidence of hypoglycemia.
Aim: Glucagon-like peptide-1 can reduce both postprandial plasma glucose (PG) and chylomicron (CM) levels in patients with type 2 diabetes. However, there have been no reports regarding the ...relationship between the postprandial metabolism of PG and CM.Methods: Patients with type 2 diabetes who were admitted for glycemic control were randomized to insulin alone (Ins; n=16) or insulin plus vildagliptin 100 mg (InsV; n=16) groups. The insulin dose was adjusted to maintain normal blood glucose levels. The daily profiles of serum TG, remnant lipoprotein cholesterol (RemL-C), and apolipoprotein B48 (ApoB48) were estimated by frequent blood collection on admission and before discharge, and the daily glucose fluctuation profile was also estimated using continuous glucose monitoring (CGM) before discharge.Results: The daily profiles of serum TG and RemL-C indicated a significant decrease before discharge compared with on admission; however, no significant changes in serum ApoB48 levels were observed in either group. At discharge, daily glucose fluctuation profile and the change in the serum ApoB48 level from fasting to the peak of the daily profile was significantly smaller in the InsV group than in the Ins group. The increment of serum ApoB48 level was significantly correlated with the mean amplitude of glycemic excursions calculated using CGM data only in the Ins group (R2= 0.5242,P＜0.001).Conclusions: Short-term glycemic control decreased serum TG and RemL-C levels, but not ApoB48 levels, and the postprandial metabolism of PG and CM might be regulated by the same mechanism except GLP-1 effect.
Although the presence of nonalcoholic fatty liver disease (NAFLD) is known to be related to subclinical atherosclerosis, the relationship between the severity of NAFLD and subclinical atherosclerosis ...is not clear. This study aimed to clarify the factors related to subclinical arteriosclerosis, including the histopathological severity of the disease and PNPLA3 gene polymorphisms, in NAFLD patients. We measured brachial-ankle pulse wave velocity (baPWV) as an index of arterial stiffness in 153 biopsy-proven NAFLD patients. The baPWV values were significantly higher in the advanced fibrosis group than in the less advanced group (median, 1679 cm/s vs 1489 cm/s; p = 5.49×10-4). Multiple logistic regression analysis revealed that older age (≥55 years) (p = 8.57×10-3; OR = 3.03), hypertension (p = 1.05×10-3; OR = 3.46), and advanced fibrosis (p = 9.22×10-3; OR = 2.94) were independently linked to baPWV ≥1600 cm/s. NAFLD patients were categorized into low-risk group (number of risk factors = 0), intermediate-risk group (= 1), and high-risk group (≥2) based on their risk factors, including older age, hypertension, and biopsy-confirmed advanced fibrosis. The prevalence of baPWV ≥1600 cm/s was 7.1% (3/42) in the low-risk group, 30.8% (12/39) in the intermediate-risk group, and 63.9% (46/72) in the high-risk group. Non-invasive liver fibrosis markers and scores, including the FIB-4 index, NAFLD fibrosis score, hyaluronic acid, Wisteria floribunda agglutinin positive Mac-2-binding protein, and type IV collagen 7s, were feasible substitutes for invasive liver biopsy. Older age, hypertension, and advanced fibrosis are independently related to arterial stiffness, and a combination of these three factors may predict risk of arteriosclerosis in NAFLD patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background:
Although sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) improve not only glycemic control but also liver inflammation and fatty changes in patients with non-alcoholic fatty liver ...disease (NAFLD) and type 2 diabetes mellitus (T2DM), its sustainability and effect on liver fibrosis have remained unclear. The current study aimed to clarify the effects of 48-week SGLT2-I therapy on liver inflammation, fatty changes, and fibrosis in NAFLD patients with T2DM.
Methods:
This study evaluated the effects of SGLT2-I on NAFLD, including liver fibrosis assessed via transient elastography, in 56 patients with NAFLD who received SGLT2-I for 48 weeks. Moreover, changes in each clinical parameter between patients receiving SGLT2-I (the SGLT2-I group) and those receiving other oral hypoglycemic agents (OHAs) (the non-SGLT2-I group) were compared, using 1:1 propensity score matching to adjust for baseline factors.
Results:
The SGLT2-I group exhibited a significant decrease in controlled attenuation parameter (312 dB/m at baseline to 280 dB/m at week 48) and liver stiffness measurement (9.1–6.7 kPa) (p < 0.001 for both). After propensity score matching (44 patients each in the SGLT2-I and non-SGLT2-I groups), no significant difference in HbA1c decrease was observed between the two groups. However, compared with the non-SGLT2-I group, the SGLT2-I group showed a significant decrease in body weight (p < 0.001), alanine aminotransferase (p = 0.02), uric acid (p < 0.001), and Fibrosis-4 (FIB-4) index (p = 0.01) at week 48. The improvement in FIB-4 index, defined as a ⩾10% decline from baseline at week 48, was 56.8% (25/44) in the SGLT2-I group and 20.5% (9/44) in the non-SGLT2-I group (p < 0.001).
Conclusion:
SGLT2-Is improved not only glycemic control but also liver fatty infiltration and fibrosis in patients with NAFLD and T2DM, suggesting their possible superiority to other OHAs concerning these effects.
Abstract
Background
Immune checkpoint inhibitors (ICIs) can induce immune-related adverse events (irAEs) including thyroid dysfunction. There are only a few reports on Graves’ disease induced by ...ICIs. We report a case of new-onset Graves’ disease after the initiation of nivolumab therapy in a patient receiving gastric cancer treatment.
Case presentation
The patient was a 66-year-old Japanese man, who was administered nivolumab (240 mg every 3 weeks) as a third-line therapy for stage IVb gastric cancer. His thyroid function was normal before the initiation of nivolumab therapy. However, he developed thyrotoxicosis before the third administration of nivolumab. Elevated, bilateral, and diffuse uptake of radioactive tracer was observed in the
99m
Tc-pertechnetate scintigraphy. Furthermore, the thyroid-stimulating hormone receptor antibody (TRAb) and thyroid-stimulating antibody (TSAb) test results, which were negative before the first administration of nivolumab, were positive after starting the therapy. The patient was diagnosed with Graves’ disease, and the treatment with methimazole and potassium iodide restored thyroid function.
Conclusions
This is the first complete report of a case of new-onset Graves’ disease after starting nivolumab therapy, confirmed by diffusely increased thyroid uptake in scintigraphy and the positive conversion of antibodies against thyroid-stimulating hormone receptor. It is important to perform thyroid scintigraphy and ultrasonography to accurately diagnose and treat ICI-induced thyrotoxicosis, because there are various cases in which Graves’ disease is developed with negative and positive TRAb titres.
PDF
