A systematic review and meta-analysis of immune checkpoint therapy in relapsed or refractory non-Hodgkin lymphoma; a friend or foe?

Over the last decades, a revolution has occurred in oncology with the development of immune checkpoint inhibitors (ICIs). Following tremendous successes in solid tumors, interest has risen to explore these inhibitors in hematologic malignancies; while Hodgkin's lymphoma (HL) has shown overwhelming achievements, available data on different types of non-Hodgkin's lymphoma (NHL) vary considerably. To the best of our knowledge, no meta-analysis has assessed the efficacy and safety of ICI therapy in relapsed or refractory NHL patients. Meta-analysis of the included studies (n = 29) indicated PD-1 may probably be the more attractive ICI target rather than PD-L1 and CTLA-4 in NHL patients. Also, there is a plausible correlation between NHL subtypes and response to ICI therapy. While MF, ENKTL, RT, and PMBCL showed promising responses to ICI monotherapy, neither FL nor DLBCL had satisfactory responses; further necessitating novel strategies such as the application of ICIs in combination with other treatment strategies. Notably, among different combinations, BTK inhibitors showed an obvious improvement as compared to ICI monotherapy in both FL and DLBCL, however, the best results were obtained when ICI was combined with anti-CD20 monoclonal antibodies. Finally, while most NHL patients who received ICI treatment have experienced mild AEs, larger trials with long-term follow-up are required to confirm the safety, as well as the efficacy, of ICI therapy in NHL patients.     

Patterns of treatment failure for PD-(L)1 refractory extensive-stage small cell lung cancer in continued PD-(L)1 treatment

BackgroundAlthough immunotherapy greatly extends overall survival (OS) of patients with extensive-stage small cell lung cancer (ES-SCLC), a number of patients develop immunotherapy resistance (IR). Patterns of failure in ES-SCLC are not clarified. Our study aims to explore the clinical pattern of IR and prognostic factors for these patients.MethodsThe study was conducted from 117 ES-SCLC patients with immunotherapy between 2018 and 2022. Chi-square tests and Fishers' exact tests was used to explore failure patterns in different populations. Survival analyses of different progression patterns and subsequent treatment regimens were conducted by Kaplan–Meier curves and log-rank test.Results86 (73.5%) patients experienced IR. The patients with smoking (never smoker vs. current or ex-smoker, 59.5 % vs. 81.3%, P = 0.010), liver metastasis (extrahepatic metastasis vs. intrahepatic metastasis, 73.6 % vs. 90.9%, P = 0.050), and distant metastasis status (no distant metastasis vs. distant metastasis, 39.1 % vs. 81.9%, P<0.001) were associated with IR rates. Liver progression had a lower incidence in 1st line immunotherapy (1st line vs. ≥2nd lines, 14.0 % vs. 41.7%, P = 0.004) and a higher incidence in multiple progression (multiple progression vs. Oligo-progression, 39.4 % vs. 17.0%, P = 0.021). Cranial (41.7 % vs. 16.1%, P = 0.012) and distant lymph node (16.7 % vs. 3.2%, P = 0.049) progression were the main failure model for acquired IR in comparison to primary IR. Patients with new lesion progression only (17.73 vs. 9.17 months, P = 0.013) and non-hepatic progression (14.23 vs. 11.67 months, P = 0.042) had a longer OS. Patients in cross-line immunotherapy after IR had a favourable prognosis (17.07 vs. 11.93 months, P = 0.007).ConclusionThe most common failure pattern of immunotherapy for ES-SCLC was lung and regional lymph node progression. Brain and liver progression were the most common extra thoracic failure sites for 1st line and 2nd and more lines immunotherapy, respectively. There was a higher probability of primary IR in 2 lines and above immunotherapy. Patients with new only progression site and cross-line rechallenge immunotherapy had a better prognosis.     

Clinical,Hormonal, and Genetic Characteristics of 5α-Reductase Type 2 Deficiency in 103 Chinese Patients

Objective5α-Reductase type 2 (5α-RD2) deficiency causes variable degrees of undervirilization in patients. The correlation between its genotype and phenotype is unclear.MethodsWe retrospectively evaluated 103 patients with 46,XY disorders of sex development who were diagnosed with 5α-RD2 deficiency.ResultsThe prevalence of female sex assignment (P = .008) and the incidences of cryptorchidism (P = .0003) and bifid scrotum (P = .0002) in the non-p.R227Q variant group were higher, but there were no significant differences in the incidences of hypospadias and isolated microphallus. The external masculinization score in the non-p.R227Q variant group was lower than that in the homozygous p.R227Q variant (P = .019) and compound heterozygous p.R227Q variant groups (P = .013). The level of anti-Mullerian hormone in the non-p.R227Q variant group was lower than that in the homozygous p.R227Q variant (P < .001) and compound heterozygous p.R227Q variant groups (P = .006). The testosterone-to-dihydrotestosterone ratio of the homozygous p.R227Q variant group was higher than that of the non-p.R227Q variant (P = .018) and compound heterozygous p.R227Q variant groups (P = .029). Twenty-three reportedly pathogenic variants and 11 novel steroid 5α-reductase 2 (SRD5A2) variants were identified.ConclusionCompared with patients without p.R227Q, patients with p.R227Q exhibited higher external masculinization scores and anti-Mullerian hormone expression, a lower prevalence of female sex assignment, and lower incidences of cryptorchidism and bifid scrotum. We identified 23 reportedly pathogenic SRD5A2 variants and 11 novel SRD5A2 variants that led to 5α-RD2 deficiency. We established a genotype-phenotype correlation, and patients with p.R227Q showed a relatively mild phenotype.     

Etiology-, Sex-, and Tumor Size-Based Differences in Adrenocorticotropin-Dependent Cushing Syndrome

ObjectiveTo examine demographic, clinical, and biochemical differences in patients with adrenocorticotropin (ACTH)-dependent Cushing syndrome (CS) based on etiology, sex, and tumor size.MethodsThis was a single-center study of 211 patients with ACTH-dependent CS followed for 35 years. Patients were stratified into 3 groups based on etiology: Cushing disease (CD)/transsphenoidal surgery, Cushing disease/total bilateral adrenalectomy (CD/TBA), and ectopic ACTH secretion (EAS). Patients were also stratified based on sex and tumor size (nonvisualized, microadenoma, and macroadenoma).ResultsCD was the commonest cause of ACTH-dependent CS (190; 90%). Most patients presented in the third decade (median age, 29 years). Clinical features, cortisol, and ACTH were significantly greater in the EAS group. The CD/TBA group had more nonvisualized tumors (22% vs 8%; P = .000) and smaller tumor size (4 vs 6 mm; P = .001) compared with the CD/transsphenoidal surgery group. There was female predominance in CD (2.06:1) and male predominance in EAS (2:1). Men had shorter duration of symptoms (2 years; P = .014), were younger (23 years; P = .001), had lower body mass index (25.1 kg/m²; P = .000), and had more severe disease (low bone mineral density, hypokalemia). Macroadenomas were frequent (46; 24.2%), and ACTH correlated with tumor size in CD (r = 0.226; P = .005).ConclusionOur cohort presented at an earlier age than the Western population with a distinct, but slightly lower, female predilection. Patients with CD undergoing TBA had frequent negative imaging. Men had a clinical profile suggesting aggressive disease. Microadenoma and macroadenoma were difficult to distinguish on a clinicobiochemical basis.     

Post-COVID-19 effect on biochemical parameters in children: Should we take heed?

The aim of this research is to analyze the potential impact of the COVID-19 infection on the serum biochemical concentration of children 6 months after recovery from the infection.The study included 72 children with a median age of 11 years. The case group consisted of 37 children who had contracted COVID-19 6 months prior to the analysis. They reported no other pre- or post-covid chronic or systemic diseases. The control group consisted of 35 children who had no prior record of COVID-19 infection.The analysis showed a substantial variation (P = 0.026) in the mean urea values (mmol/L) between the case group (4.513 ± 0.839) and the control group (5.425 ± 1.173). However, both groups' urea levels were within the normal range of their age group. No statistical differences were found analyzing the variations between the two groups in the levels of LDH, AST, ALT, BiliT, GGT, AlbBCG2, CRP, CK, AlKP, UA, Phos, Crea2, Gluc, Ca, Na, K, Cl, TP, TC, TG, and HDL (P > 0.05). The DMFT score was substantially greater (P < 0.002) in the infected team (5.38 ± 2.841) in comparison to the non-infected group (2.6 ± 2.257).The study indicates that COVID-19 infection does not leave biochemical alterations among children who did not have pre-existing conditions. The biochemical analysis suggests that children recover better than adults from COVID-19. Furthermore, it calls for investigating non-lethal COVID-19 infection as a tool to discover underlying conditions. The DMFT score shows a correlation between COVID-19 infection and caries. However, the nature of the correlation is yet to be investigated.     

Clinical Evaluation of BRCA1/2 Mutation in Mexican Ovarian Cancer Patients

Ovarian cancer (OC) is an important cause of gynecologic cancer-related deaths. In Mexico, around 4700 new cases of OC are diagnosed per year and it represents the second cause of gynecological cancer mortality with more than 2700 deaths. Germline mutations in BRCA1/2 genes are present in 13–18% of OC cases. Few studies have evaluated the presence of mutations in BRCA genes in a population of OC Mexican patients and their relationship with clinical response and survival rates.A total of 179 OC patients were studied by molecular testing for BRCA1/2 through next-generation sequencing and multiplex ligation-dependent probe amplification. Recurrence-free survival (RFS) was estimated by the Kaplan–Meier method. BRCA mutation was detected in 33% of patients. A percentage of 66.1% were BRCA1 mutated and 33.9% were BRCA2 mutated. BRCA1 mutation carriers had a worst RFS compared with BRCA2 mutation carriers (37.6 [29–46.2] vs 72.7 [38.4–107.2]; P = 0.030). The most common mutation for BRCA1 was ex9-12del (28.2%) (Mexican founder mutation). The Mexican founder mutation had a better RFS than other BRCA1 mutations (86.1 [37.2–135.1] vs 34.5 [20.7–48.2]; P = 0.033). The presence of BRCA2 mutations in the ovarian cancer cluster region (OCCR) had a significantly better RFS than mutations in breast cancer cluster regions (BCCR) and not-related risk region (NRR) (NR vs 72.8 [39–106.6] vs 25.8 [8.3–43.2]; P = 0.013). These results demonstrate that the prevalence of BRCA1/2 positive patients in OC Mexican patients are the highest reported. Patients with mutations in BRCA2 have a better prognosis than those mutated in BRCA1. The Mexican founder mutation has an important role in clinical outcomes. These results highlight the importance to test all the HGSP (high-grade serous papillary) OC patients with or without cancer family history (CFH) in Mexican population.     

Bone Mineral Density in Pituitary Stalk Interruption Syndrome: The Role of Insulin-Like Growth Factor-1 and Testosterone at Different Skeletal Sites

ObjectiveThis study aimed to determine the clinical indicators influencing bone mineral density (BMD) of the lumbar spine and femoral neck in patients with pituitary stalk interruption syndrome (PSIS) who underwent multiple hormone replacement therapy (MHRT).MethodsMale patients with PSIS (n = 51) who underwent MHRT for at least 1 year were enrolled in this study. Their BMD parameters were recorded and compared with age-, weight-, and height-matched control adults. In addition, we performed multiple linear regression analysis to correlate clinical parameters with BMD parameters at 2 different sites.ResultsFifty-one patients with PSIS had a mean age of 30.39 ± 5.50 years. After 36 months of treatment, patients with PSIS who underwent MHRT had slightly lower BMD than those in the control group. Multiple linear regression models revealed a positive association between the Z-score values for the lumbar spine with treatment duration (r = 0.453, P < .001), insulin-like growth factor-1 (IGF-1) standard deviation score (SDS) values (r = 0.248, P = .038), and total testosterone level (r = 0.260, P = .036) and a positive association between the Z-score values for the femoral neck with treatment duration (r = 0.425, P < .001) and IGF-1 SDS values (r = 0.338, P = .009).ConclusionCollectively, long-term MHRT improves bone density in patients with PSIS to the normal range. A combination of recombinant human growth hormone replacement is more beneficial to the BMD than non–recombinant human growth hormone treatment. Moreover, serum IGF-1 contributes to femoral and lumbar mineralization, whereas serum testosterone plays a role in lumbar mineralization.     

The Added and Interpretative Value of CGM-Derived Parameters in Type 1 Diabetes Depends on the Level of Glycemic Control

ObjectiveIn type 1 diabetes mellitus (T1DM) management, continuous glucose monitoring (CGM)-derived parameters can provide additional insights, with time in range (TIR) and other parameters reflecting glycemic control and variability being put forward. This study aimed to examine the added and interpretative value of the CGM-derived indices TIR and coefficient of variation (CV%) in T1DM patients stratified according to their level of glycemic control by means of HbA1C.MethodsT1DM patients with a minimum disease duration of 10 years and without known macrovascular disease were enrolled. Patients were equipped with a blinded CGM device for 7 days. TIR and time spent in hypoglycemia and hyperglycemia were determined, and CV% was used as a parameter for glycemic variability. Pearson (r) and Spearman correlations (r_s) and a regression analysis were used to examine associations.ResultsNinety-five patients (age: 45 ± 10 years; HbA1C level: 7.7% ± 0.8% [61 ± 7 mmol/mol]) were included (mean blood glucose [MBG]: 159 ± 31 mg/dL; TIR: 55.8% ± 14.9%; CV%: 43.5% ± 7.8%) and labeled as having good (HbA1C level ≤7% [≤53 mmol/mol]; n = 20), moderate (7%-8%; n = 44), or poor (>8% [>64 mmol/mol]; n = 31) glycemic control. HbA1C was significantly associated with MBG (r_s = 0.48, P < .001) and time spent in hyperglycemia (total: r_s = 0.52; level 2: r = 0.46; P < .001) but not with time spent in hypoglycemia and CV%, even after an analysis of the HbA1C subgroups. Similarly, TIR was negatively associated with HbA1C (r = −0.53; P < .001), MBG (r_s = −0.81; P < .001), and time spent in hyperglycemia (total: r_s = −0.90; level 2: r_s = −0.84; P < .001) but not with time in hypoglycemia. The subgroup analyses, however, showed that TIR was associated with shorter time spent in level-2 hypoglycemia in patients with good (r_s = −0.60; P = .007) and moderate (r_s = −0.25; P = .047) glycemic control. In contrast, CV% was strongly positively associated with time in hypoglycemia (total: r_s = 0.78; level 2: r_s = 0.76; P < .001) but not with TIR or time in hyperglycemia in the entire cohort, although the subgroup analyses showed that TIR was negatively associated with CV% in patients with good glycemic control (r = −0.81, P < .001) and positively associated in patients with poor glycemic control (r = +0.47; P < .01).ConclusionThe CGM-derived metrics TIR and CV% are related to clinically important situations, TIR being strongly dependent on hyperglycemia and CV% being reflective of hypoglycemic risk. However, the interpretation and applicability of TIR and CV% and their relationship depends on the level of glycemic control of the individual patient, with CV% generally adding less clinically relevant information in those with poor control. This illustrates the need for further research and evaluation of composite measures of glycemic control in T1DM.     

Evaluation of Body Composition in Patients With and Without Adrenal Tumors and Without Overt Hypersecretory Syndromes

ObjectiveTo compare body composition between patients with autonomous cortisol secretion (ACS), those with nonfunctioning adrenal incidentalomas (NFAIs), and control subjects without adrenal tumors.MethodsA cross-sectional study was performed, incluidng the following 3 groups: patients with ACS (cortisol post–dexamethasone suppression test [DST] >1.8 μg/dL), NFAIs (cortisol post-DST ≤ 1.8 μg/dL), and patients without adrenal tumors (control group). Patients of the 3 groups were matched according to age (±5 years), sex, and body mass index (±5 kg/m²). Body composition was evaluated by bioelectrical impedance and abdominal computed tomography (CT) and urinary steroid profile by gas chromatography mass spectrometry.ResultsThis study enrolled 25 patients with ACS, 24 with NFAIs, and 24 control subjects. Based on CT images, a weak positive correlation between the serum cortisol level post-DST and subcutaneous fat area (r = 0.3, P =.048) was found. As assessed by bioelectrical impedance, lean mass and bone mass were positively correlated with the excretion of total androgens (r = 0.56, P <.001; and r = 0.58, P <.001, respectively); visceral mass was positively correlated with the excretion of glucocorticoid metabolites and total glucocorticoids (r = 0.28, P =.031; and r = 0.42, P =.001, respectively). Based on CT imaging evaluation, a positive correlation was observed between lean mass and androgen metabolites (r = 0.30, P =.036) and between visceral fat area, total fat area, and visceral/total fat area ratio and the excretion of glucocorticoid metabolites (r = 0.34, P =.014; r = 0.29, P =.042; and r = 0.31, P =.170, respectively).ConclusionThe urinary steroid profile observed in adrenal tumors, comprising a low excretion of androgen metabolites and high excretion of glucocorticoid metabolites, is associated with a lower lean mass and bone mass and higher level of visceral mass in patients with adrenal tumors.     

Nordic Walking Improves Cardiometabolic Parameters,Fitness Performance,and Quality of Life in Older Adults With Type 2 Diabetes

ObjectiveTo assess the effect of Nordic walking (NW) on cardiometabolic health, physical performance, and well-being in sedentary older adults with type 2 diabetes (T2D).MethodsFifteen subjects with T2D (female, 5; male, 10; age, 65 ± 6.2 years [mean ± standard deviation]; body mass index, 27.3 ± 4.9 kg/m² [mean ± standard deviation]) were enrolled in a 6-month NW training program. The fasting glucose and glycosylated hemoglobin levels, lipid profile (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides), systolic blood pressure (SBP), and diastolic blood pressures were measured before and after the intervention. Participants’ quality of life (Short-Form Health Survey) and physical fitness (6-minute walking test) were also evaluated.ResultsCompared with baseline, NW significantly improved the fasting glucose level (103.5 ± 18.5 vs 168.7 ± 37.7 mg/dL, P = .01), SBP (121.8 ± 12.2 vs 133 ± 14.4 mm Hg, P = .02), physical fitness (759.88 ± 69 vs 615.5 ± 62.6 m, P < .001), and both mental health (54.5 ± 4.4 vs 45.7 ± 5.6, P < .01) and physical health (49.8 ± 4.7 vs 40.3 ± 5.9, P < .01). The levels of glycosylated hemoglobin (6.15% ± 0.8% vs 6.4% ± 1%, P = .46), total cholesterol (162.2 ± 31.2 vs 175.5 ± 28.8 mg/dL, P = .13), low-density lipoprotein cholesterol (95.2 ± 24.2 vs 106.3 ± 32.3 mg/dL, P = .43), and triglycerides (135.5 ± 60.8 vs 127.6 ± 57.4 mg/dL, P = 0.26) improved without reaching significance.ConclusionNW training improved the glycemic levels, SBP, physical fitness, and perception of quality of life in older adults with T2D. NW represents a suitable complementary strategy to improve the global health status in this population.     

Association Between a Low-Carbohydrate Diet,Glycemic Control,and Quality of Life in Australian Adults Living With Type 1 Diabetes: A Pilot Study

ObjectiveTo examine if there is an association between a low-carbohydrate diet (LCD), glycemic control, and quality of life (QoL) in Australian adults with type 1 diabetes.MethodsThis single-group, pre-post, mixed methods (quantitative and qualitative) study was conducted in an outpatient tertiary hospital. Eligible participants were those aged ≥18 years, with type 1 diabetes for ≥1 year, and using multiple daily insulin injections. Participants followed a 12-week individualized LCD (<100 g/d). Daily glucose levels were monitored using a continuous glucose monitor. Glycated hemoglobin (HbA1c) and QoL were measured preintervention and postintervention. A post-hoc exploratory regression analysis determined whether changes in carbohydrate intake was associated with changes in HbA1c and QoL. Qualitative data collected postintervention explored participants’ perceptions relating to a LCD, glycemic control, and QoL.ResultsParticipants (n = 22) completed the 12-week LCD intervention. An LCD provided a statistically, significant improvement in HbA1c 0.83% (95% CI 0.32%-1.33%), P = .003 but did not impact QoL: estimated change 1.14 units (95% CI: ?5.34 to 7.61); P = .72. The post-hoc exploratory regression analysis showed that participants with poorer baseline glycemic control were more likely to respond to an LCD resulting in significant reductions in HbA1c. Participant perceptions relating to the study variables were mixed.ConclusionsAn LCD (<100 g/d) is a potentially effective and safe strategy to improve glycemic control without negatively effecting QoL in Australian adults with type 1 diabetes.     

Neoadjuvant PD-1 blockade plus chemotherapy versus chemotherapy alone in locally advanced stage II-III gastric cancer: A single-centre retrospective study

BackgroundPD-1 blockade has been shown to have promising efficacy and acceptable safety profiles in advanced and metastatic gastric cancer; however, the efficacy and safety of neoadjuvant PD-1 blockade-based immunotherapy plus chemotherapy in locally advanced gastric cancer (LAGC) remain uncertain.MethodsWe performed a retrospective review of patients with LAGC who received neoadjuvant treatment followed by D2 radical resection at the Affiliated Hospital of Qingdao University from 2019 to 2021. The primary aim was to investigate the difference in pathological response rates between neoadjuvant PD-1 immunotherapy plus chemotherapy and neoadjuvant chemotherapy alone. Multivariable models for pathological complete response (pCR) were constructed to investigate the factors that facilitate pCR. Trial registration: QYFYWZLL27406.ResultsA total of 77 patients were included in the analysis, among whom 34 (44.2%) received neoadjuvant PD-1 blockade immunotherapy plus chemotherapy. A higher pCR rate was observed in the neoadjuvant PD-1 blockade immunotherapy plus chemotherapy group (8 of 34, 23.5% vs. 2 of 43, 4.7%, P=0.019). Multivariate logistic regression analysis of pCR revealed neoadjuvant PD-1 blockade plus chemotherapy regimen promoted pCR (OR 12.95, P=0.016). Regarding safety, 76.5% (26 of 34) of patients in the PD-1 blockade plus chemotherapy group and 76.7% (33 of 43) of patients in the chemotherapy group experienced treatment-related adverse events (TRAEs), and grade 3 or worse adverse events were 29.4% (10 of 34) and 34.9% (15 of 43), respectively.ConclusionNeoadjuvant PD-1 blockade plus chemotherapy induced a higher pCR rate than neoadjuvant chemotherapy, and the combined therapy was tolerable in LAGC patients.     

Effects of taurine supplementation on productive performance,nutrient digestibility and gene expression of nutrient transporters in quails reared under heat stress

This study was conducted to examine the effects of dietary taurine supplementation on productive performance, nutrient digestibility, antioxidant status, and the gene expression of ileal nutrient transporters in laying quails reared under heat stress (HS). One hundred and eighty laying Japanese quails (Coturnix coturnix japonica) were fed a basal diet or basal diet supplemented with either 2.5 or 5 g of taurine per kg of diet, and reared at either 22 ± 2 °C for 24 h/d (thermoneutral, TN) or 34 ± 2 °C for 8 h/d (HS) for 12 weeks. The quails reared under HS consumed less feed, produced less egg, and had lower dry matter, organic matter and crude protein apparent digestibilities compared with the quails reared under the TN condition (P = 0.001). However, increasing taurine concentrations in the diet improved feed intake and egg production (P = 0.001), but also the apparent digestibilities (P ≤ 0.027) in quails reared under HS. The greater doses (5 g/kg) of taurine resulted in more responses. The quails reared under HS had greater serum and liver MDA concentrations (P = 0.0001) which decreased with dietary taurine supplementations, particularly greater doses. The gene expressions of ileal PEPT1, EAAT3, CAT1, CAT2, SGLT1, SGLT5, GLUT2, and GLUT5 decreased under HS conditions (P = 0.001). However, supplementing taurine, in a dose-dependent fashion, to the diet of quails reared under HS resulted in increases in the gene expressions of the transporters (P < 0.05) except for CAT1. The results of the present work showed that taurine supplementation, particularly with greater doses (5 g/kg), to the diet of laying quails kept under HS acts as alleviating negative effects of HS, resulting in improvements in productive performance and nutrient digestion, and also upregulation of ileal nutrient transporters.     

Positive Thyroid Peroxidase Antibody and Thyroglobulin Antibody are Associated With Better Clinicopathologic Features of Papillary Thyroid Cancer

ObjectiveTo compare the thyroid autoantibody status of patients with papillary thyroid cancer (PTC) and benign nodular goiter as well as possible associations between thyroid autoantibodies and clinicopathologic features of PTC.MethodsA total of 3934 participants who underwent thyroidectomy were enrolled in this retrospective study. Patients were divided into PTC and benign nodule groups according to pathological diagnosis. Based on the preoperative serum antibody results, PTC patients were divided into thyroid peroxidase antibody (TPOAb)-positive, thyroglobulin antibody (TgAb)-positive, dual TPOAb- and TgAb-positive, or antibody-negative groups.ResultsOf the 3934 enrolled patients, 2926 (74.4%) were diagnosed with PTC. Multivariate regression analyses suggested that high thyroid-stimulating hormone levels (adjusted odds ratio [OR] = 1.732, 95% CI [1.485-2.021], P < .001), positive TgAb (adjusted OR = 1.768, 95% CI [1.436-2.178], P < .001), and positive TPOAb (adjusted OR = 1.452, 95% CI [1.148-1.836], P = .002) were independent risk factors for predicting malignancy of thyroid nodules. Multinomial multiple logistic regression analyses indicated that positive TPOAb alone was an independent predictor of less central lymph node metastasis in PTC patients (adjusted OR = 0.643, 95% CI [0.448-0.923], P = .017), whereas positive TgAb alone was significantly associated with less extrathyroidal extension (adjusted OR = 0.778, 95% CI [0.622-0.974], P = .028). PTC patients with dual-positive TPOAb and TgAb displayed a decreased incidence of extrathyroidal extension (adjusted OR = 0.767, 95% CI [0.623-0.944], P = .012) and central lymph node metastasis (adjusted OR = 0.784, 95% CI [0.624-0.986], P = .037).ConclusionAlthough preoperative positive TPOAb and TgAb are independent predictive markers for PTC, they are also associated with better clinicopathologic features of PTC.     

Mutation and Expression of Gene YY1 in Pancreatic Neuroendocrine Tumors and Its Clinical Significance

ObjectiveThe clinical significance of the YY1 gene mutation and expression in pancreatic neuroendocrine tumors (PNETs) remains unknown. Therefore, this study aimed to comprehensively analyze the somatic mutation of YY1 in the different subtypes of PNETs.MethodsA total of 143 PNETs were assessed by Sanger sequencing to identify the somatic mutation of YY1 gene in various subtypes of PNETs. YY1 protein expression was examined in 103 PNETs by immunohistochemical staining and western blot. Gene mutation and its protein expression were correlated with clinicopathologic features.ResultsA recurrent mutation (chr14:100743807C>G) in the YY1 gene was identified in 15 of 83 insulinomas (18%) and in only 1 of 60 noninsulinoma PNETs (1.7%) (P = .0045). The YY1 mutation was not found in MEN1-associated insulinomas. The YY1 mutation in insulinomas was correlated with older age and lower serum glucose levels (age, 57 vs 42.5 years, P = .006; blood glucose, 25.2 vs 33.6 mg/dL, P = .008). YY1 protein expression was found in 100 of 103 PNETs, although expression was weaker in metastases than in localized tumors (P = .036). The stronger expression of YY1 protein was associated with favorable disease-free survival of patients with PNETs (log-rank, P = .011; n = 70). Multivariable statistical analysis showed that YY1 protein expression could be an independent predictor of prognosis.ConclusionThe hotspot YY1 mutation mostly occurred in insulinomas and rarely in noninsulinoma PNETs. The stronger YY1 protein expression was correlated with the better prognosis of PNETs patients.     

Quality of Life in Patients With Asymptomatic Primary Hyperparathyroidism After Parathyroidectomy: A 3-Year Longitudinal Study

ObjectiveImpaired quality of life (QoL) is considered as a nonclassical manifestation of primary hyperparathyroidism (PHPT). This study aimed to detect and compare changes in the QoL of patients with asymptomatic PHPT who had successful curative parathyroidectomy (PTX) 3 months and 3 years after the procedure.MethodsPatients with diagnosed PHPT were eligible for the study. There were 2 groups: the PTX group, with patients who underwent PTX, and the non-PTX group, with patients who were treated conservatively. QoL was assessed using Pasieka’s Parathyroid Assessment of Symptoms Questionnaire (PAS-Q) at baseline, 3 months, and 3 years.ResultsThirty-eight patients were included in the study: 18 in the PTX group and 20 in the non-PTX group. In the PTX group, the mean PAS-Q total score before PTX was 518, which was reduced significantly at the 3-month (P = .003) and 3-year assessments (P = .001). However, in the non-PTX group, the mean PAS-Q total score was 326 at baseline and increased continuously for 3 years (P = .019). At the 3-year evaluation, the mean total score was significantly higher compared to that of the PTX group (P = .021). Finally, there was a positive correlation between total serum calcium and PAS-Q score in the non-PTX group (r = 0.524, P = .018).ConclusionQoL of patients with PHPT improved significantly compared to that in conservative surveillance as early as 3 months after successful, curative PTX, and remained improved for 3 years. This finding strengthens, even more, the hypothesis that PTX contributes to better QoL, suggesting that the derangement of QoL may be considered as an individual indication for surgery.     

Correlation Between Hemoglobin Glycation Index Measured by Continuous Glucose Monitoring With Complications in Type 1 Diabetes

ObjectiveHbA1C is the “gold standard” parameter to evaluate glycemic control in diabetes; however, its correlation with mean glucose is not always perfect. The objective of this study was to correlate continuous glucose monitoring (CGM)-derived hemoglobin glycation index (HGI) with microvascular complications.MethodsWe conducted a cross-sectional study including permanent users of CGM with type 1 diabetes mellitus or latent autoimmune diabetes of the adult. HGI was estimated, and presence of microvascular complications was compared in subgroups with high or low HGI. A logistic regression analysis to assess the contribution of high HGI to chronic kidney disease (CKD) was performed.ResultsIn total, 52 participants who were aged 39.7 ± 14.7 years, with 73.1% women and 15.5 years (IQR, 7.5-29 years) since diagnosis, were included; 32.7% recorded diabetic retinopathy, 25% CKD, and 19.2% neuropathy. The median HbA1C was 7.6% (60 mmol/mol) and glucose management indicator (GMI) 7.0% (53 mmol/mol). The average HGI was 0.55% ± 0.66%. The measured HbA1C was higher in the group with high HGI (8.1% [65 mmol/mol] vs 6.9% [52 mmol/mol]; P < .001), whereas GMI (7.0% [53 mmol/mol] vs 7.0% [53 mmol/mol]; P = .495) and mean glucose were similar in both groups (153 mg/dL vs 153 mg/dL; P = .564). In the high HGI group, higher occurrence of CKD (P = .016) and neuropathy were observed (P = .025). High HGI was associated with increased risk of CKD (odds ratio [OR]: 5.05; 95% CI: 1.02-24.8; P = .04) after adjusting for time since diagnosis (OR: 1.09; 95% CI: 1.02-1.16; P = .008).ConclusionHigh HGI measured by CGM may be a useful marker for increased risk of microvascular diabetic complications.     

The Effects of Chronic Lymphocytic Thyroiditis on Clinicopathologic Factors in Papillary Thyroid Cancer

ObjectiveThis study evaluated the impact of chronic lymphocytic thyroiditis (CLT) on clinicopathologic parameters, prognostic outcome, and initial treatment responses in patients with papillary thyroid cancer (PTC).MethodsA retrospective review was conducted of 1409 patients with PTC, comprising 443 patients with pathology-proven PTC with CLT and 447 patients with PTC without CLT.ResultsThe median follow-up time was 58 months (range, 8-380 months), and the median age at the time of diagnosis was 43 years. The age at diagnosis was significantly lower in patients with CLT than in those without CLT (42 years vs 45 years, respectively; P = .001). The preoperative thyroid-stimulating hormone level was found to be significantly higher in patients with CLT than in those without CLT (1.71 mIU/L vs 1.28 mIU/L, respectively; P < .001). Multifocality and capsular, lymphovascular, and perineural invasion were detected at a higher rate in the group with CLT than in the group without CLT (P = .015, P = .024, P = .004, and P = .039, respectively). No difference was found between the 2 groups in terms of tumor size, bilaterality, extrathyroidal invasion, lymph node metastasis, disease stage, or response to treatment (P > .05).ConclusionThe results of the present study demonstrated that the coexistence of PTC and CLT is very frequent. Patients with the coexistence of PTC and CLT were diagnosed at a younger age, and the thyroid-stimulating hormone level was higher in these patients. Contrary to previous studies, no positive effect of the CLT and PTC combination was detected on any clinicopathologic factor. In addition, lymphovascular and perineural invasions, which had negative effects on prognosis, were more common in the group with CLT.     

Impact of Pancreatic Neuroendocrine Tumor on Mortality in Patients With von Hippel-Lindau Disease

ObjectiveThe main causes for morbidity and mortality in von Hippel-Lindau (VHL) disease are central nervous system hemangioblastoma and clear cell renal cell carcinoma, but the effect of VHL-related pancreatic neuroendocrine tumors (PNET) on patient outcome is unclear. We assessed the impact of PNET diagnosis in patients with VHL on all-cause mortality (ACM) risk.MethodsWe used the Surveillance, Epidemiology, and End Results database. Of 16 344 patients, 170 had VHL based on clinical diagnostic criteria, and 510 patients had PNET (91 VHL-related and 419 sporadic).ResultsSurvival analysis demonstrated a lower ACM among patients with VHL-related PNET compared to patients with sporadic PNET (log-rank test, P = .011). Among patients with VHL, ACM risk was higher with vs without PNET (P = .029). The subgroup analysis revealed a higher ACM risk with metastatic PNET (sporadic P = .0031 and VHL-related P = .08) and a similar trend for PNET diameter ≥3 cm (P = .06 and P = 0.1 in sporadic and VHL-related PNET, respectively). In a multivariable analysis of patients with VHL, diagnosis with PNET by itself was associated with a trend of lower risk for ACM, while presence of metastatic PNET was independently associated with increased ACM risk.ConclusionDiagnosis with PNET is not associated with a higher ACM risk in VHL by itself. The independent association of advanced PNET stage with higher mortality risk emphasizes the importance of active surveillance for detecting high-risk PNET at an early stage to allow timely intervention.     

Associations of Urinary Polycyclic Aromatic Hydrocarbons With Bone Mineral Density at Specific Body Sites in U.S. Adults,National Health and Nutrition Examination Survey 2001 to 2004

ObjectiveWe aimed to analyze the association between certain types of urinary polycyclic aromatic hydrocarbons (PAHs) and bone mineral density (BMD) at specific sites of the body.MethodsA total of 2978 eligible participants from the National Health and Nutrition Examination Survey 2001 to 2004 were included in this study. Data of 8 urinary PAHs and BMDs of 3 skeleton sites and the total body were analyzed. Univariate and multivariate linear regression analyses were performed to explore the association between urinary PAHs and BMDs. Subgroup analyses stratified by sex and body mass index were also performed.ResultsAfter adjustment for all confounders, elevated 3-fluorene (β = 0.046; 95% confidence intervals [CIs], 0.007-0.084) and 2-fluorene (β = 0.054; 95% CI, 0.007-0.100) levels were associated with greater left arm BMD, whereas no statistical differences were observed in the relationship between other PAHs and BMDs (all P > .05). Higher 3-fluorene and 2-fluorene levels were still associated with increased left arm BMD in men (P < .05), whereas the higher 2-phenanthrene level was related to decreased left arm BMD (β = ?0.062; 95% CI, ?0.105 to ?0.019), right arm BMD (β = ?0.059; 95% CI, ?0.091 to ?0.027), and total BMD (β = ?0.065; 95% CI, ?0.119 to ?0.012) in women. Similar results were also found in different body mass index populations (all P < .05).ConclusionCertain urinary PAHs are associated with BMDs at specific body sites. Future studies are needed to illustrate the mechanisms behind the association to establish a causal relationship.