Should We Use Prolactin Adjustment in Bilateral Inferior Petrosal Sinus Sampling to Diagnose Cushing Disease? A Joint Meta-Analysis of Head-to-Head Diagnostic Tests Accuracy Studies

ObjectivePrevious studies have shown inconsistent results regarding the usefulness of prolactin adjustment in bilateral inferior petrosal sinus sampling (BIPSS) in the differential diagnosis of adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome (CS). This meta-analysis compared the diagnostic accuracy of prolactin adjustment versus no adjustment in BIPSS.MethodsThis study searched the PubMed, Embase, Web of Science, Cochrane library, and WanFang databases for published data as of March 2022 on the use of prolactin adjustment in BIPSS to differentially diagnose ACTH-dependent CS. A Bayesian joint bivariate model was used in the head-to-head comparison of the diagnostic accuracy.ResultsThis meta-analysis included a total of 10 studies with 300 patients. The combined sensitivity and specificity for BIPSS without prolactin adjustment were 94.47% (95% CI, 88.67%-98.44%) and 91.14% (95% CI, 57.17%-99.80%), respectively. The combined sensitivity and specificity after prolactin adjustment were 99.97% (95% CI, 99.03%-100.00%) and 80.69% (95% CI, 50.27%-97.82%), respectively. After the prolactin adjustment, the sensitivity of BIPSS to diagnose Cushing disease was improved with a statistically significant difference (difference in sensitivity, 5.39%; 95% CI, 1.37%-11.26%), whereas the decrease in specificity was without a statistically significant difference (difference in specificity, −9.20%; 95% CI, −42.02% to 26.61%).ConclusionThis meta-analysis indicated that prolactin adjustment in BIPSS might help to recognize Cushing disease among patient with ACTH-dependent CS. However, prolactin adjustment may not help identify ectopic ACTH syndrome in BIPSS.     

Transverse and Longitudinal Ultrasound Location of Thyroid Nodules and Risk of Thyroid Cancer

BackgroundThe high prevalence of thyroid nodules demands accurate assessment tools to avoid unnecessary biopsies. Prior studies demonstrated a correlation between the longitudinal location of thyroid nodules and the likelihood of malignancy. No study has evaluated the predictive value of transverse location on ultrasonography with malignancy.MethodsWe retrospectively reviewed the records of thyroid nodules that underwent fine-needle aspiration over 13 years, including demographics, risk factors, nodule sonographic features, location, and surgical pathology. Univariate and multivariable logistic regression models were used to evaluate the risk of malignancy.ResultsOf the 668 thyroid nodules, 604 were analyzed with a definitive diagnosis. Thirty-seven nodules were malignant, representing a prevalence of 6.1%. In the longitudinal plane, the upper pole nodules carried the highest incidence of malignancy (14.9%). In the transverse plane, the highest incidence of malignancy occurred in nodules located laterally (12.5%) and anterior-laterally (11.8%). Compared with the upper pole, the odds of malignancy were significantly lower for lower pole (odds ratio [OR] = 0.26, 95% confidence interval [CI]: 0.09-0.70) and midlobe nodules (OR = 0.31, 95% CI: 0.12-0.83). In the transverse plane, posteriorly situated nodules carried a significantly lower risk of malignancy (OR = 0.07, 95% CI: 0.01-0.69). Multiple logistic regression confirmed these associations after adjusting for age, sex, family history, radiation exposure, nodule size, and sonographic characteristics.ConclusionBoth the transverse and longitudinal planes were independent predictors of cancer in thyroid nodules. Lateral, anterior-lateral, and upper pole nodules carried the highest risk and posterior nodules had the lowest risk of malignancy.     

Diagnostic Accuracy of Copeptin in the Differential Diagnosis of Patients With Diabetes Insipidus: A Systematic Review and Meta-analysis

ObjectiveAccurate diagnosis of diabetes insipidus (DI) is of significant importance for correct management. We aimed to evaluate the diagnostic accuracy of copeptin level measurements in the differential diagnosis between DI and primary polydipsia (PP).MethodsA literature search of electronic databases from January 1, 2005, to July 13, 2022, was performed. Primary studies that evaluated the diagnostic accuracy of copeptin concentration in patients with DI and PP were considered eligible. Two reviewers independently screened relevant articles and extracted data. The Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to assess the quality of the included studies. The hierarchical summary receiver operating characteristic model and bivariate method were used.ResultsSeven studies including 422 patients with polydipsia-polyuria syndrome were included; of the 422 patients, 189 (44.79%) presented with arginine vasopressin deficiency (AVP-D, cranial DI) and 212 (50.24%) with PP. The summary estimates of the diagnostic performance of stimulated copeptin to differentiate between PP and AVP-D were 0.93 (95% CI, 0.89-0.97) for sensitivity and 0.96 (95% CI, 0.88-1.00) for specificity. Baseline copeptin level showed high performance in identifying AVP resistance (nephrogenic DI), with a pooled sensitivity of 1.00 (95% CI, 0.82-1.00) and specificity of 1.00 (95% CI, 0.98-1.00); however, it showed little value in the differentiation between PP and AVP-D.ConclusionCopeptin level measurement is a useful tool for the differential diagnosis of patients with DI and PP. Stimulation before copeptin measurement is necessary in the diagnosis of AVP-D.     

Sex-Specific Associations Between Diabetes Mellitus and Hearing Loss in the Middle-Aged and Elderly Individuals: A National Cohort Study of Chinese Adults

ObjectiveTo examine the association between diabetes and hearing loss and whether the association varied by sex.MethodsThis cohort study based on nationally representative data from the China Health and Retirement Longitudinal Study included 16 140 Chinese adults aged >45 years between 2011 and 2018. Diabetes was identified by blood glucose levels, HbA1c levels, and a self-reported diagnosis at baseline. The main outcome was self-reported incident hearing loss. Cox proportional hazards regression models were performed to estimate the risk of hearing loss.ResultsWe documented 2388 cases of hearing loss during a median 6.9 years of follow-up. The incidence rates were 29.64 (95% CI, 28.07-31.29) per 1000 person-years in women and 25.23 (95% CI, 23.77-26.78) per 1000 person-years in men. After adjustment, the hazard ratios of hearing loss associated with diabetes were 1.20 (95% CI, 1.01-1.42) for women and 0.97 (95% CI, 0.78-1.19) for men. Compared with poor control of the blood sugar levels, the odds ratio for hearing loss for women with good glycemic control was reduced from 5.08 (95% CI, 1.31-19.66) to 1.26 (95% CI, 0.69-2.28), and the corresponding odds ratio for men was 1.65 (95% CI, 0.61-4.44) to 0.50 (95% CI, 0.18-1.38).ConclusionIn conclusion, we identified a differential effect of sex on hearing loss risk with more pronounced effects for women. Our data suggest that good blood glucose level control is helpful to prevent hearing loss.     

Association of Thyroid Function During Pregnancy With the Risk of Pre-eclampsia and Gestational Diabetes Mellitus

ObjectiveTo estimate the association of maternal thyroid dysfunction with the risk of gestational hypertension and diabetes. Whether the association was affected by gestational age at diagnosis and thyroid autoimmunity was further explored.MethodsA cohort study of 41 647 participants was conducted. Thyroid function (ie, thyroid-stimulating hormone [TSH] and free thyroxine [FT4]) was measured by electrochemiluminescence immunoassay. Thyroid antibody positivity (eg, thyroperoxidase, thyroglobulin, and TSH receptor antibody) was indicated if the values of these antibodies exceeded the upper targets of the reference range. The relationship between maternal thyroid dysfunction and the risk of pre-eclampsia (PE) and gestational diabetes mellitus (GDM) was assessed by multivariate logistic regression.ResultsIsolated hypothyroxinemia (defined as 5th ≤ TSH ≤ 95th percentile, FT4 < 5th percentile) was associated with the risk of PE (odds ratio [OR], 1.32; 95% CI, 1.10-1.58). Overt hypothyroidism (TSH > 95th percentile; FT4 < 5th percentile) was related to the risk of severe PE (OR, 2.59; 95% CI, 1.05-6.37). Being positive for TSH receptor antibody was associated with a decreased risk of GDM (OR, 0.49; 95% CI, 0.35-0.70). A marginally significant association between overt hypothyroidism detected at the first trimester and the risk of GDM was found (OR, 1.60; 95% CI, 1.00-2.83). The association of thyroid dysfunction with the risk of PE and GDM was stronger among pregnant women who were negative for autoantibodies.ConclusionSome types of thyroid dysfunction during pregnancy were associated with the risk of PE and GDM. The associations varied by gestational age at diagnosis and by thyroid autoantibody status.     

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.     

Role of TMPRSS6 rs855791 (T > C) polymorphism in reproductive age women with iron deficiency anemia from Lahore,Pakistan

BackgroundIron deficiency anemia (IDA) is the highest nutritional deficiency worldwide. It is a multifactorial disease, with a higher morbidity rate. TMPRSS6 polymorphisms importantly rs855791 is found to play an essential role in iron homeostasis in the human body. The rs855791 (T > C) polymorphism is highly associated with iron levels, and multiple blood parameters, leading to IDA. The role of TMPRSS6 rs855791 polymorphism and the significance of complete blood count (CBC) parameters in the pathogenesis of IDA is not yet studied in the Pakistani population.MethodsWe enrolled 113 cases and 136 controls to conduct a case control study. Complete blood count (CBC) and iron parameters were analyzed for association studies. PCR-RFLP based genotyping was performed.ResultsThe TMPRSS6 rs855791 (T > C) polymorphism is significantly associated with IDA pathogenesis as observed in the codominant model and recessive models (P < 0.05, OR: 1.5 and 95% CI: 0.9, 2.6, P < 0.05, OR: 0.5 and 95% CI: 0.2, 0.9 respectively). Elderly women among cases (30–49 years) were found to be more susceptible to IDA (P < 0.05, AOR: 2.1 and 95% CI: 1.0, 4.2). The most significant parameters associated with IDA were red blood cell count (RBC) and hematocrit (Hct%) (P < 0.05, AOR: 16.5, 95% CI: 7.6, 35.9 and P < 0.05, AOR: 10.1, 95% CI: 2.5, 41.6, respectively).ConclusionTMPRSS6 polymorphism at rs855791 (T > C) is significantly associated with IDA susceptibility in reproductive age women in Pakistan. Age, RBC count and Hct% are found to play an important role in IDA pathogenesis in our study population.     

SARS-CoV-2 Seroprevalence in Individuals With Type 1 and Type 2 Diabetes Compared With Controls

ObjectiveData for the association between diabetes and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility are conflicting. We aimed to evaluate this association using an analytical cross-sectional study design.MethodsStudy participants were recruited from endocrine clinics of our hospital and belonged to 3 groups: group 1 (type 1 diabetes mellitus [T1DM]), group 2 (type 2 diabetes mellitus [T2DM]), and group 3 (controls). All participants submitted blood samples for SARS-CoV-2 S1/S2 immunoglobulin G antibody test (LIAISON; DiaSorin) and were interviewed for a history of documented infection.ResultsWe evaluated a total of 643 participants (T1DM, 149; T2DM, 160; control, 334; mean age, 37.9 ± 11.5 years). A total of 324 (50.4%) participants were seropositive for SARS-CoV-2. The seropositivity rate was significantly higher in the T1DM (55.7% vs 44.9%, P = .028) and T2DM (56.9% vs 44.9%, P = .013) groups than in the control group. The antibody levels in seropositive participants with T1DM and T2DM were not significantly different from those in seropositive controls. On multivariable analysis, low education status (odds ratio [OR], 1.41 [95% CI, 1.03-1.94]; P = .035), diabetes (OR, 1.68 [95% CI, 1.20-2.34]; P = .002), and overweight/obesity (OR, 1.52 [95% CI, 1.10-2.10]; P = .012) showed a significant association with SARS-CoV-2 seropositivity. The association between diabetes and SARS-CoV-2 seropositivity was found to further increase in participants with coexisting overweight/obesity (adjusted OR, 2.63 [95% CI, 1.54-4.47]; P < .001).ConclusionSARS-CoV-2 seropositivity, assessed before the onset of the national vaccination program, was significantly higher in participants with T1DM and T2DM than in controls. The antibody response did not differ between seropositive participants with and without diabetes. These findings point toward an increased SARS-CoV-2 susceptibility for patients with diabetes, in general, without any differential effect of the diabetes type.     

Effects of Thyroid Dysfunction and the Thyroid-Stimulating Hormone Levels on the Risk of Atrial Fibrillation: A Systematic Review and Dose-Response Meta-Analysis from Cohort Studies

ObjectiveTo explore the relationship between thyroid dysfunction, thyroid-stimulating hormone (TSH) levels, and risks of atrial fibrillation (AF) in studies and conduct a dose-response meta-analysis on the correlation between the TSH levels and risk of AF.MethodsThirteen studies from 5 databases with 649 293 subjects (mean age, 65.1 years) were included. The dose-response meta-analysis was conducted by comparing the risk ratios (RRs) and 95% confidence intervals (CIs) for incident AF associated with different levels of TSH (vs TSH level of 0 mU/L) across studies. Data were collected until October 25, 2021.ResultsSubclinical hyperthyroidism, subclinical hypothyroidism, and clinical hyperthyroidism were associated with an increased risk of AF (RR, 1.70; 95% CI, 1.11-2.62; RR, 1.23; 95% CI, 1.05-1.44; and RR, 2.35; 95% CI, 1.07-5.16, respectively), whereas clinical hypothyroidism was not associated with the significantly increased risk of AF (RR, 1.20; 95% CI, 0.72-1.99). A nonlinear relationship was observed in 2 models (crude model, P_nonlinear < .001; adjusted model, P_nonlinear = .0391) between the TSH levels and risks of AF.ConclusionsOur study indicated that subclinical hyperthyroidism, subclinical hypothyroidism, clinical hyperthyroidism were associated with the risk of AF, and the results for the TSH levels and risk of AF were mixed, which showed a U-shaped relationship.     

Meniscal lesion detection and characterization in adult knee MRI: A deep learning model approach with external validation

PurposeEvaluation of a deep learning approach for the detection of meniscal tears and their characterization (presence/absence of migrated meniscal fragment).MethodsA large annotated adult knee MRI database was built combining medical expertise of radiologists and data scientists’ tools. Coronal and sagittal proton density fat suppressed-weighted images of 11,353 knee MRI examinations (10,401 individual patients) paired with their standardized structured reports were retrospectively collected. After database curation, deep learning models were trained and validated on a subset of 8058 examinations. Algorithm performance was evaluated on a test set of 299 examinations reviewed by 5 musculoskeletal specialists and compared to general radiologists’ reports. External validation was performed using the publicly available MRNet database. Receiver Operating Characteristic (ROC) curves results and Area Under the Curve (AUC) values were obtained on internal and external databases.ResultsA combined architecture of meniscal localization and lesion classification 3D convolutional neural networks reached AUC values of 0.93 (95% CI 0.82, 0.95) for medial and 0.84 (95% CI 0.78, 0.89) for lateral meniscal tear detection, and 0.91 (95% CI 0.87, 0.94) for medial and 0.95 (95% CI 0.92, 0.97) for lateral meniscal tear migration detection. External validation of the combined medial and lateral meniscal tear detection models resulted in an AUC of 0.83 (95% CI 0.75, 0.90) without further training and 0.89 (95% CI 0.82, 0.95) with fine tuning.ConclusionOur deep learning algorithm demonstrated high performance in knee menisci lesion detection and characterization, validated on an external database.     

CARD9 gene rs4077515 polymorphism is associated with the susceptibility of Hashimoto’s thyroiditis and the development of thyroid cancer

AmisHashimoto’s thyroiditis (HT) is the most common type of autoimmune thyroiditis and is a risk factor for the occurrence of thyroid papillary carcinoma (PTC). The study aimed to explore the distribution of CARD9 rs4077515 polymorphism in HT and PTC patients, in order to evaluate its association with the occurrence and development of HT.Methods150 HT patients and 120 PTC cases were included. Genotypes of CARD9 rs40775155 polymorphism were sequenced and counted.ResultsA remarkable increase trend of rs4077515 AA genotype was found in HT cases in comparison with the control group, while GG genotype frequency exhibited a down trend. An excess of A allele was also detected in HT group. HT cases carrying AG and AA genotypes had high risk to receive hormonotherapy and needed a much larger dose. In comparison with HT cases, both AG and AA appeared more frequently in PTC patients, and are associated with the tumor size, LN metastasis and surgical margin. The AG (OR = 2.566, 95 % CI = 1.376–4.786) and AA (OR = 3.040, 95 % CI = 1.525–6.060) genotype carriers had a greater risk of developing PTC. The A allele of rs4077515 polymorphism was a risk allele for the onset of PTC among HT cases (OR = 1.775, 95 % CI = 1.260–2.502).ConclusionCARD9 rs4077515 polymorphism is likely to be a risk factor for HT in the Chinese Han population, it also contributes to the development of PTC for HT patients.     

Bone Fragility in Hereditary Connective Tissue Disorders: A Systematic Review and Meta-Analysis

ObjectiveTo investigate bone fragility in patients with hereditary connective tissue disorders (HCTD), including Ehlers-Danlos syndrome (EDS), Marfan’s syndrome (MFS) and Loeys-Dietz syndrome (LDS).MethodsFrom inception to June 2022, potentially eligible studies were identified in the Medline and EMBASE databases using search strategy that included terms for “HCTD”, “Fracture” and “Osteoporosis”. Eligible studies must consist of a group of patients with HCTD and report prevalence/incidence of fracture/osteoporosis in their participants, with or without comparison with healthy individuals. Point estimates with standard errors were obtained from each study and combined using the generic inverse variance method.ResultsAmong the 4206 articles identified, 19 studies were included. The pooled prevalence of fracture in EDS, MFS, and LDS were 44% (95% confidence interval [CI], 25% to 65%, I² 88%), 17% (95% CI, 11% to 26%, I² 68%), 69% (95% CI, 47% to 85%, I² 83%), respectively. The pooled prevalence of osteoporosis in EDS was 17% (95% CI, 8% to 34%, I² 96%). EDS was associated with fracture [pooled odds ratio {OR} 4.90 (95% CI, 1.49 – 16.08, I² 86%)], but not osteoporosis [pooled OR 1.34 (95% CI, 0.28 – 6.36, I² 87%). One study reported a 5% (95% CI, 3% to 8%) prevalence of osteoporosis in MFS, which was associated with fracture [incidence rate ratio 1.35 (95% CI, 1.18 – 1.55)] and osteoporosis [subhazard ratio 3.97 (95% CI, 2.53 – 6.25)].ConclusionEDS was associated with fracture, which could be independent of osteoporosis status. MFS had a milder degree of increased risk of fracture and osteoporosis. Despite no data from cohort studies, there was a significantly higher rate of fracture in LDS.     

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.     

Comparison of New Glucose-Lowering Drugs on the Risk of Pancreatitis in Type 2 Diabetes: A Network Meta-Analysis

ObjectiveTo explore whether new glucose-lowering drugs increase the risk of pancreatitis in individuals with type 2 diabetes. This present network meta-analysis aimed to investigate the risk of pancreatitis associated with the use of glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors in the treatment of type 2 diabetes mellitus.MethodsPubMed, Web of Science, Embase, and the Cochrane Library were searched. The literature was published from the date of their inception to July 21, 2021, including placebo-controlled or head-to-head trials of 2 new glucose-lowering drugs. The relative ratio (RR) and 95% confidence interval (CI) were used to assess the risk of GLP-1 agonists and DPP-4 inhibitors for pancreatitis or pancreatic cancer among patients with type 2 diabetes.ResultsSeventeen studies were identified, covered 102 257 participants. The pooled results showed a neutral relationship between GLP-1 agonists and pancreatitis (overall RR, 0.96; 95% CI, 0.31-3.00) or pancreatic cancer (overall RR, 1.10; 95% CI, 0.31-4.10) compared with placebo. Meanwhile, DPP-4 inhibitors were not associated with the increased risk of pancreatitis (overall RR, 1.60; 95% CI, 0.25-11.00) or pancreatic cancer (overall RR, 0.79; 95% CI, 0.26-2.40). Among them, lixisenatide and saxagliptin may be the safest drugs compared with other drugs according to the ranking of probability. Sensitivity and subgroup analysis confirmed the stability of the core results.ConclusionThe most obvious finding of this study is that GLP-1 agonists and DPP-4 inhibitors are safe with respect to the risk of pancreatitis and pancreatic cancer compared with placebo. This conclusion may provide useful evidence for correlated clinical researches.     

Thyroid Immune-Related Adverse Events in Patients with Cancer Treated with anti-PD1/anti-CTLA4 Immune Checkpoint Inhibitor Combination: Clinical Course and Outcomes

ObjectiveThyroid immune-related adverse events (irAEs) have been reported to have prognostic significance among patients with cancer treated with anti-programmed cell death-1 (PD1) and anti-programmed death-ligand 1 monotherapies. We evaluated the clinical course and predictors of thyroid irAEs in relation to outcomes of patients with advanced cancer treated with combination anti-PD1/anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4).MethodsWe conducted a regional study and identified patients with advanced cancer who received ≥1 cycle of combination anti-PD1/anti-CTLA4 between 2015 and 2019 in Hong Kong. Thyroid function tests (TFTs) were monitored every 3 weeks. Thyroid irAE was defined by ≥2 abnormal TFTs after initiation of combination anti-PD1/anti-CTLA4 in the absence of other causes.ResultsOne hundred and three patients were included (median age: 59 years; 71.8% men). About 45% had prior anti-PD1 exposure. Upon median follow-up of 6.8 months, 17 patients (16.5%) developed thyroid irAEs, where 6 initially presented with thyrotoxicosis (overt, n = 4; subclinical, n = 2) and 11 with hypothyroidism (overt, n = 2; subclinical, n = 9). Eventually, 10 patients (58.8%) required continuous thyroxine replacement. Systemic steroid was not required in all cases. Prior anti-PD1 exposure (odds ratio, 3.67; 95% CI, 1.19–11.4; P = .024) independently predicted thyroid irAEs. Multivariable Cox regression analysis revealed that occurrence of thyroid irAEs was independently associated with better overall survival (adjusted hazard ratio, 0.34; 95% CI, 0.17–0.71; P = .004).ConclusionThyroid irAEs are common in routine clinical practice among patients with advanced cancer treated with anti-PD1/anti-CTLA4 combination and might have potential prognostic significance. Regular TFT monitoring is advised for timely treatment of thyroid irAEs to prevent potential morbidities.     

The Added Value of Second-Look Ultrasound in Patients With Primary Hyperparathyroidism With Discordant or Negative Previous Imaging Findings

ObjectiveThe preoperative localization for patients with primary hyperparathyroidism with negative or discordant previous imaging results has always been a difficult problem to be solved in clinical practice. Second-look ultrasound (US) is a viable but underestimated method. This study aimed to assess the added value of second-look US and explore the attributing factors.MethodsAmong 711 surgically confirmed patients with primary hyperparathyroidism, 63 patients with negative or discordant first-time US and ^99mTc-MIBI imaging results were retrospectively studied. All 63 patients underwent second-look US, and the results were compared with intraoperative findings and histopathologic diagnosis. The diagnostic value of second-look US was calculated, and the reasons for changed second-look US results were analyzed.ResultsSixty-three parathyroid lesions were found in 63 patients. The sensitivity, positive predictive value, and accuracy of second-look US were 92.1%, 95.1%, and 88.1%, respectively. Comparing the results of first-time and second-look US, we found that 54.0% of the patients got benefits from second-look US because 34 patients with negative results in the first-time US revealed localization with second-look US. Second-look US was more likely to produce changes in results for lesions with a lower location (OR, 3.23; 95% CI, 1.11-9.43, P < .05) and larger length-to-thickness ratio (3.0 vs 2.4, P < .05).ConclusionSecond-look US is a promising method to determine preoperative localization in patients with negative or discordant results of previous imaging findings. Lesions with elongated shape and lower location are more expected to be detected in second-look US when missed at the first time.     

Long-Term Prognosis of Acute Myocardial Infarction Associated With Metabolic Health and Obesity Status

ObjectiveEmerging evidence supports the favorable cardiovascular health in nonobese subjects with healthy metabolism. However, little is known regarding the prognosis across the range of metabolic phenotypes once cardiovascular disease is established. We examined the prognosis of patients with acute myocardial infarction (AMI) stratified according to metabolic health and obesity status.MethodsThis is a retrospective study on consecutive patients with AMI admitted to a tertiary hospital between 2014 and 2021. Patients were allocated into the following 4 groups based on metabolic and obesity profile: (1) metabolically healthy obese (MHO), (2) metabolically healthy nonobese (MHNO), (3) metabolically unhealthy obese (MUO), and (4) metabolically unhealthy nonobese (MUNO). Metabolic health was defined in accordance to the Biobank Standardisation and Harmonisation for Research Excellence in the European Union Healthy Obese Project. The primary outcome was all-cause mortality. The Cox regression analysis examined the independent association between mortality and metabolic phenotypes, adjusting for age, sex, AMI type, chronic kidney disease, smoking status, and left ventricular ejection fraction.ResultsOf 9958 patients, the majority (68.5%) were MUNO, followed by MUO (25.1%), MHNO (5.6%), and MHO (0.8%). MHO had the lowest mortality (7.4%), followed by MHNO (9.7%), MUO (19.2%), and MUNO (22.6%) (P < .001). Compared with MHNO, MUO (hazard ratio [HR], 1.737; 95% confidence interval [CI], 1.282-2.355; P < .001) and MUNO (HR, 1.482; 95% CI, 1.108-1.981; P = .008) had a significantly higher mortality risk but not MHO (HR, 1.390; 95% CI, 0.594-3.251; P = .447), after adjusting for confounders. The Kaplan-Meier curves showed favorable survival in the metabolically healthy and obesity groups, with the highest overall survival in the MHO, followed by MHNO, MUO, and MUNO (P < .001).ConclusionMetabolically healthy and obese patients with AMI have favorable prognosis compared with metabolically unhealthy and nonobese patients. It is equally important to prioritize intensive metabolic risk factor management to weight reduction in the early phase after AMI.     

Association of Vitamin D Status With Hospital Morbidity and Mortality in Adult Hospitalized Patients With COVID-19

ObjectiveTo determine the association between vitamin D status and morbidity and mortality in adult hospitalized coronavirus disease 2019 (COVID-19) patientsMethodsWe performed a retrospective chart review study in COVID-19 patients aged ≥18 year hospitalized at Boston University Medical Center between March 1 and August 4, 2020. All studied patients tested positive for COVID-19 and had serum levels of 25-hydroxyvitamin D (25[OH]D) results measured within 1 year prior to the date of positive tests. Medical information was retrieved from the electronic medical record and was analyzed to determine the association between vitamin D status and hospital morbidity and mortality.ResultsAmong the 287 patients, 100 (36%) were vitamin D sufficient (25[OH]D >30 ng/mL) and 41 (14%) died during hospitalization. Multivariate analysis in patients aged ≥65 years revealed that vitamin D sufficiency (25[OH]D ≥30 ng/mL) was statistically significantly associated with decreased odds of death (adjusted OR 0.33, 95% CI, 0.12-0.94), acute respiratory distress syndrome (adjusted OR 0.22, 95% CI, 0.05-0.96), and severe sepsis/septic shock (adjusted OR 0.26, 95% CI, 0.08-0.88), after adjustment for potential confounders. Among patients with body mass index <30 kg/m², vitamin D sufficiency was statistically significantly associated with a decreased odds of death (adjusted OR 0.18, 95% CI, 0.04-0.84). No significant association was found in the subgroups of patients aged <65 years or with body mass index ≥30 kg/m².ConclusionWe revealed an independent association between vitamin D sufficiency defined by serum 25(OH)D ≥30 ng/mL and decreased risk of mortality from COVID-19 in elderly patients and patients without obesity.