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.     

Differences in Clinical Manifestations and Tumor Features Between Metastatic Pheochromocytoma/Paraganglioma Patients With and Without Germline SDHB Mutation

ObjectiveTo compare metastatic pheochromocytoma/paraganglioma (MPP) patients with germline SDHB mutations (SDHB MPP) and without SDHB mutations (non-SDHB MPP) in terms of baseline clinical manifestations, tumor characteristics, and outcomes.MethodsClinical data were retrospectively reviewed in 101 MPP patients, including 34 SDHB MPP patients and 61 non-SDHB MPP patients.ResultsSDHB MPP patients presented at a younger age at onset, diagnosis, or metastasis (25 ± 16 vs 36 ± 14, 28 ± 17 vs 38 ± 15, and 31 ± 17 vs 44 ± 14 years old, respectively, P < .01 for all) than non-SDHB patients. Compared with their non-SDHB counterparts, SDHB patients were more likely to have paragangliomas (83% vs 47%, P < .05), synchronous metastases (44% vs 23%, P < .05), bone metastases (80% vs 48%, P < .01), and a shorter progression-free survival (3 years vs 5 years, P < .01). The Ki-67 index was higher in SDHB tumors (P < .05). The 5- and 10-year survival rates were 79% and 74%, respectively, in all patients. Seventeen patients died from MPP, and the time from metastasis to death in patients who had received systemic therapy was significantly longer than in those who had not (3.1 ± 1.5 vs 1.4 ± 0.7 years, P < .01).ConclusionCompared with MPP patients without SDHB mutations, MPP patients with SDHB mutations were younger at onset, diagnosis, or metastasis; had a higher incidence of synchronous metastases, higher ratio of paraganglioma, and higher Ki-67 index; had a shorter postoperative progression-free survival; and were more likely to develop bone metastasis or sole liver metastasis. Our results suggest that patients with SDHB mutations should be identified early and monitored regularly to achieve optimal clinical outcomes.     

Efficacy of Pulsatile Gonadotropin-Releasing Hormone Therapy in Male Patients: Comparison between Pituitary Stalk Interruption Syndrome and Congenital Hypogonadotropic Hypogonadism

ObjectivePulsatile gonadotropin-releasing hormone (GnRH), widely used to induce spermatogenesis in congenital hypogonadotropic hypogonadism (CHH) patients, can restore the pituitary-testis axis function in men with pituitary stalk interruption syndrome (PSIS). This retrospective study aimed to compare the differences in the long-term efficacy of pulsatile GnRH therapy on PSIS and CHH.MethodsPatients with PSIS (n = 25) or CHH (n = 64) who received pulsatile GnRH therapy for ≥3 months were included in this retrospective study. The rate of successful spermatogenesis, the median time to achieve spermatogenesis, serum gonadotropins, total testosterone, and testicular size were compared.ResultsBaseline characteristics were comparable except for the lower basal testosterone, triptorelin-stimulated peak luteinizing hormone (LH), and follicle-stimulating hormone in patients with PSIS. With similar duration of treatment and a significantly higher GnRH dose (P < .001), small increments in LH (2.82 [1.4, 4.55] vs 5.89 [3.88, 8.02] IU/L; P < .001), total testosterone (0.38 [0, 1.34] vs 2.34 [1.34, 3.66] ng/mL; P < .001), and testicular volume (5.3 ± 4.5 vs 8.8 ± 4.8 mL, P < .05) were observed. However, spermatogenesis rate (52.0% vs 70.3%, P > .05), median time of sperm appearance (14 vs 11 months, P > .05), sperm concentration, and progressive motility were comparable. Basal testicular volume (hazard ratio, 1.13; 95% CI, 1.01-1.27) and peak LH levels (hazard ratio, 1.11; 95% CI, 1.0-1.23) were predictors for early sperm appearance.ConclusionsPulsatile GnRH therapy can improve gonad function and induce spermatogenesis in men with PSIS. However, its efficacy may be inferior to that in CHH.     

Long-Term Follow-up of Graves Orbitopathy After Treatment With Short- or Long-Term Methimazole or Radioactive Iodine

ObjectiveThe aim of this study was to compare long-term outcomes in terms of new onset or worsening of Graves orbitopathy (GO) in patients with Graves disease treated with different therapeutic modalities for hyperthyroidism.MethodsA total of 1163 patients with Graves disease were enrolled in this study; 263 patients were treated with radioiodine and 808 patients received methimazole (MMI) therapy for a median of 18 months, of whom 178 patients continued MMI for a total of 96 months (long-term methimazole [LT-MMI]). The thyroid hormonal status and GO were evaluated regularly for a median of 159 months since enrollment.ResultsThe rates of relapse, euthyroidism, and hypothyroidism at the end of follow-up were as follows: radioiodine treatment group: 16%, 22%, and 62%, respectively; short-term MMI group: 59%, 36%, and 5%, respectively; and LT-MMI group: 18%, 80%, and 2%, respectively. During the first 18 months of therapy, worsening of GO (11.5% vs 5.7%) and de novo development of GO (12.5% vs 9.8%) were significantly more frequent after radioiodine treatment (P <.004). Overall worsening and de novo development of GO from >18 to 234 months occurred in 26 (9.9%) patients in the radioiodine group and 8 (4.5%) patients in the LT-MMI group (P <.037). No case of worsening or new onset of GO was observed in patients treated with LT-MMI from >60 to 234 months of follow-up.ConclusionProgression and development of GO were associated more with radioiodine treatment than with MMI treatment; GO may appear de novo or worsen years after radioiodine treatment but not after LT-MMI therapy.     

COVID-19 May Increase the Risk of Insulin Resistance in Adult Patients Without Diabetes: A 6-Month Prospective Study

ObjectiveDuring the coronavirus disease 2019 (COVID-19) pandemic, exploring insulin resistance and beta-cell activity is important for understanding COVID-19‒associated new-onset diabetes. We assessed insulin sensitivity and fasting insulin secretion in patients with COVID-19 without diabetes on admission and at 3 and 6 months after discharge.MethodsThis 6-month prospective study assessed data from the records of 64 patients without diabetes diagnosed with COVID-19 at Wenzhou Central Hospital, China. Each patient was followed up at 3 and 6 months after discharge. Repeated measures analysis of variance was used to investigate differences in multiple measurements of the same variable at different times. Linear regression analysis was performed to analyze the contributor for changes in the triglyceride-glucose (TyG) index.ResultsFasting C-peptide levels in patients at baseline were lower than the normal range. Compared with the baseline results, patients had significantly elevated fasting C-peptide levels (0.35 ± 0.24 vs 2.36 ± 0.98 vs 2.52 ± 1.11 μg/L; P < .001), homeostasis model assessment for beta-cell function (0.42, interquartile range [IQR] 0.36-0.62 vs 2.54, IQR 1.95-3.42 vs 2.90, IQR 2.02-4.23; P < .001), and TyG indices (8.57 ± 0.47 vs 8.73 ± 0.60 vs 8.82 ± 0.62; P = .006) and decreased fasting glucose levels (5.84 ± 1.21 vs 4.95 ± 0.76 vs 5.40 ± 0.68 mmol/L; P = .003) at the 3- and 6-month follow-up. Male gender, age, interferon-alfa treatment during hospitalization, and changes in total cholesterol and high-density lipoprotein levels were significantly associated with changes in the TyG index.ConclusionOur study provided the first evidence that COVID-19 may increase the risk of insulin resistance in patients without diabetes.     

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.     

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.     

Comparative Study of Initial Post-Therapeutic 131I Single-Photon Emission Computed Tomography/Computed Tomography and Reoperation for the Detection of Residual Lymph Node Metastasis in Patients With Papillary Thyroid Cancer

ObjectiveTo assess the diagnostic performance of initial post-therapeutic ¹³¹I single-photon emission computed tomography/computed tomography (SPECT/CT) compared with that of reoperation in detecting residual lymph node metastasis (LNM).MethodsPatients with iodine-avid LNM detected on the initial post-therapeutic ¹³¹I SPECT/CT and who underwent reoperative dissection within 6 months were included. LNMs (numbers and locations) detected via both methods were compared. The American Thyroid Association dynamic risk stratification was performed for patients receiving second radioactive iodine therapy after reoperation.ResultsFifty-three patients with 95 iodine-avid LNMs detected by ¹³¹I SPECT/CT were enrolled. Fifty-one (96.2%) patients had 212 LNMs confirmed by reoperation (P = .004). The sensitivity and specificity of ¹³¹I SPECT/CT in detecting LNM were 44.8% (95/212) and 91.6% (87/95), respectively. The location frequency of residual LNMs found by ¹³¹I SPECT/CT was similar to that of reoperation (P = .057). Thirty-two patients received a second radioactive iodine treatment, and 6 (18.8%) patients still had residual iodine-avid LNM on SPECT/CT. Therapeutic response was evaluated by American Thyroid Association dynamic risk stratification in 16 patients. The number of patients with structural incomplete response, biochemical incomplete response, indeterminate response, and excellent response was 4 (23.5%), 4 (23.5%), 5 (29.4%), and 3 (17.6%), respectively.Conclusion¹³¹I SPECT/CT has high specificity but relatively low sensitivity in detecting all residual LNMs. Approximately 80% of patients were rendered structurally disease free after reoperation.     

Effect of Treatment of OSA With CPAP on Glycemic Control in Adults With Type 2 Diabetes: The Diabetes Sleep Treatment Trial (DSTT)

ObjectiveThe effect of obstructive sleep apnea (OSA) treatment with continuous positive airway pressure (CPAP) on glycemic measures in patients with type 2 diabetes (T2D) remains unclear. We aimed to determine whether CPAP treatment of OSA improves glycemic measures in patients with T2D.MethodsThis randomized controlled trial (N = 98) examined changes in glycemic measures following 12 weeks of active (n = 49) or sham (n = 49) CPAP and consideried participants’ adherence to CPAP therapy (percentage of days with ≥4 hours use and average hours/day of use).ResultsBaseline treatment groups were similar. Regarding the efficacy of active vs sham-CPAP over time, at 6 weeks, both groups had similar reductions in fructosamine (mean difference [MD], 95% confidence interval [CI]: CPAP ?13.10 [?25.49 to ?0.7] vs. sham ?7.26 [?20.2 to 5.69]; P = .519) but different in HbA1c (CPAP ?0.24 [?0.48 to ?0.003] vs sham 0.15 [?0.10 to 0.4]; P = .027). At 12 weeks, reductions in HbA1c values were similar by group (CPAP ?0.26 [?0.53 to 0.002] vs sham ?0.24 [?0.53 to 0.04]; P = .924). HbA1c reductions were associated with a greater percentage of cumulative days of CPAP usage ≥4 hours per day (b [SE] = 0.006 [0.002]; P = .013) and cumulative hours of CPAP use (b [SE] = 0.08 [0.08]; P = .012). CPAP use of ≥7 hours was associated with a significant reduction in HbA1c (b [SE] 0.54 [0.16]; P = .0012).ConclusionCPAP treatment of OSA did not result in sustained improved glycemic control compared to sham in the intent-to-treat analysis. CPAP adherence was associated with greater improvements in glycemic control.     

Development and Internal Validation of A Prediction Tool To Assist Clinicians Selecting Second-Line Therapy Following Metformin Monotherapy For Type 2 Diabetes

ObjectiveAdults with type 2 diabetes (T2D) face increased risk of many long-term adverse outcomes. While managing patients with T2D, clinicians are challenged to stay informed regarding all new therapies and must consider potential risks and benefits resultant to their use. Metformin (MET) is typically prescribed as first-line therapy, but a second line is often needed, given MET can be insufficient for maintaining long-term glycemic control. Our objective was to develop a predictive decision-making tool to help clinicians use an outcome-based approach to select second-line therapies for patients when MET monotherapy is insufficient for glycemic control.MethodsElectronic health records of 19 277 adults with T2D on MET monotherapy and ≥3 months of either GLP-1RA, DPP-4i, Insulin, SGLT-2i, SFU, or TZD therapy were reviewed at Cleveland Clinic from patient visits occurring between 2005 and 2019. Separate models were developed to predict likelihood of each main outcome measure (stroke, myocardial infarction, worsening hypertension, renal failure, and death). Discrimination and calibration were assessed with bootstrapping.ResultsThe median follow-up time for those without an event was 3.6 years (interquartile range 1.9, 6.3). Model discrimination ability was evaluated by concordance indices (goodness of fit metric with values ranging between 0 and 1: 1 indicates perfect discrimination ability; 0.5 reflects same discrimination ability as chance) demonstrating strong discrimination ability, with concordance index values for outcomes as follows: myocardial infarction (0.786), stroke (0.805), worsening hypertension (0.855), renal failure (0.808), and death (0.827).ConclusionA decision-making tool has been developed that may afford clinicians a more objective and individualized approach to choosing a second-line therapy to control glycemia for persons with T2D.     

Clinical Applicability of Patient- and Clinician-Reported Outcome Tools in the Management of Patients With Acromegaly

ObjectiveWe aimed to assess treatment outcomes and disease control status in patients with acromegaly using patient- and clinician-reported outcome tools and to analyze correlations among different components of both tools.MethodsThis cross-sectional study included 72 patients from a national referral center with a median follow-up of 8 (5-12) years. The baseline SAGIT score at diagnosis was determined retrospectively, whereas the follow-up SAGIT and acromegaly quality of life questionnaire (AcroQoL) results were assessed at the most recent visit and by additional telephone interviews.ResultsAll SAGIT subscores decreased significantly from baseline to follow-up (global score from 14 to 4 [P < .001]). The SAGIT scores at baseline did not discriminate the current disease control status. However, a higher baseline SAGIT score and subscore T were associated with uncontrolled disease after the first-line treatment. Diagnostic delay was correlated with baseline S, A, G, and global SAGIT scores. At the follow-up, the global SAGIT score discriminated between cured/controlled and uncontrolled groups (4 vs 6 [P = .007]). The AcroQoL score was 69.3, with the personal relations subscale being the least affected and the physical scale being the most affected. There was no difference in the AcroQoL score between patients classified as uncontrolled or cured/controlled. At baseline and follow-up, there were significant negative correlations between S and A subscores and AcroQoL score. A higher body mass index, the presence of swelling, joint symptoms, headaches, sleep apnea, and hypertension significantly impaired quality of life.ConclusionOur results emphasize the complementary nature of the patient- and clinician-reported outcome tools in acromegaly management. We identified modifiable signs, symptoms, and comorbidities as treatment targets that might help clinicians improve quality of life in this population.     

Predictors of Hypothyroidism Following Empirical Dose Radioiodine in Toxic Thyroid Nodules: Real-Life Experience

ObjectiveWe aimed to determine the factors predicting hypothyroidism after radioactive iodine (RAI) treatment in patients with toxic adenoma and toxic multinodular goiter.MethodsWe retrospectively collected the data of 237 patients with toxic multinodular goiter or toxic adenoma who had consecutively received RAI treatment between 2014 and 2020 at 2 medical centers. Patients who received the second RAI treatment and whose medical records could not be accessed were excluded from the study. Finally, 133 patients were included in the study. RAI was administered at an empirical dose of 15 or 20 mCi.ResultsThe median age of the 133 participants was 69 years (interquartile range, 62-75 years), and 64.7% of the participants were women. A total of 42.1% of the patients had toxic adenoma, whereas 57.9% of patients had toxic multinodular goiter. The median follow-up was 24 months (interquartile range, 11-38 months). During the follow-up, 61.7% of patients became euthyroid, 30.8% developed hypothyroidism, and 7.5% remained hyperthyroid. The median month of hypothyroidism onset was 4 months (interquartile range, 2-9 months). Regression analysis revealed 2 factors that could predict hypothyroidism: thyroid-stimulating hormone (odds ratio, 2.548; 95% CI, 1.042-6.231; P = .04) and thyroid volume (odds ratio, 0.930; 95% CI, 0.885-0.978; P = .005).ConclusionOverall, 30.8% of the cases developed hypothyroidism after the RAI treatment. Approximately 78% of hypothyroidism developed within the first 10 months. The risk of hypothyroidism was higher in patients with higher thyroid-stimulating hormone and smaller thyroid volume.     

Predictors of Prolonged Euthyroidism After Radioactive Iodine Treatment for Graves’ Disease: A Pilot Study

ObjectivePatients with Graves’ disease who remain hyperthyroid under the treatment of antithyroid drugs (ATD) or cannot tolerate ATD usually receive radioactive iodine (RAI) to control disease activity. This pilot study aimed to identify predictors of prolonged euthyroidism > 12 months after receiving RAI.MethodsDemographic, clinical, and laboratory data from 117 patients receiving RAI were retrospectively collected, including age, gender, body surface area, smoking status, free thyroxine, thyrotropin, thyrotropin binding inhibiting immunoglobulin, microsomal antibody, thyroglobulin antibody, medication history, and thyroid volume. Only 85 patients without missing values were included in statistical analysis. The calculated RAI dose was the estimated thyroid volume × 0.4. The difference and ratio between the actual and calculated RAI doses were examined. A stepwise logistic regression analysis was conducted to identify important predictors of prolonged euthyroidism > 12 months. The cut-off values for discretizing continuous covariates were estimated by fitting generalized additive models.ResultsAmong the 85 patients on RAI, 18 (21.2%) achieved prolonged euthyroidism > 12 months, 38 (44.7%) remained hyperthyroid with decreased ATD doses, but 29 (34.1%) suffered permanent hypothyroidism and needed long-term levothyroxine. Logistic regression analysis revealed that patients with age > 66 years, 33 < age ≤ 66 years, quitting smoking vs nonsmoking or current smoking, 600 < micorsomal antibody ≤ 1729 IU/mL, 47% < thyrotropin binding inhibiting immunoglobulin ≤ 81%, 7 < thyroglobulin antibody ≤ 162 IU/mL, 0.63 < ratio between actual and calculated RAI doses ≤ 1.96, or taking hydroxychloroquine would have a higher chance of reaching prolonged euthyroidism > 12 months after receiving RAI. Its area under the Receiver Operating Characteristic (ROC) curve was 0.932.ConclusionPatients with Graves’ disease who received an actual RAI dose close to the calculated RAI dose achieved prolonged euthyroidism > 12 months if they also took hydroxychloroquine during RAI treatment.     

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 Evaluation of Low- and High-Dose Steroid Treatments in Subacute Thyroiditis: A Retrospective Observational Study

ObjectiveThe optimal steroid regimen in the treatment of subacute thyroiditis (SAT) is controversial. This study aims to compare low- and high-dose steroid regimens in the treatment of SAT.MethodsA single-center, retrospective observational cohort study with up to 1 year of follow-up was conducted. A total of 44 patients in the 16-mg methylprednisolone (MPS) group and 47 patients in the 48-mg MPS group were enrolled. Clinical and laboratory findings from the time of diagnosis to 1-year of the follow-up were assessed. Treatment response, recurrence, and hypothyroidism (HPT) rates were evaluated.ResultsClinical symptoms, sedimentation rates, C-reactive protein, and thyroid hormone levels of the patients were similar in the 2 groups. Recovery was achieved in all patients at the end of the treatments; however, treatment duration needed to be extended for 6 (13.6%) and 1 (2.1%) of the patients in the 16-mg and 48-mg MPS groups, respectively. The 48-mg MPS group had a higher SAT recurrence rate than the 16-mg MPS group (P = .04). Logistic regression analysis suggested that a lower thyroid-stimulating hormone level at the end of the treatment was a predictor of recurrence (β = –0.544, P = .014, 95% CI: 0.376-0.895). While the transient HPT rate was 10 (21.3%) and 10 (22.7%) in the 48-mg and 16-mg MPS groups, respectively, a permanent HPT developed in 5 (10.6%) of patients in the 48-mg MPS and 3 (6.8%) in the 16-mg MPS group. The permanent and transient HPT rates were determined to be similar in the low- and high-dose groups (P > .05).ConclusionLow-dose steroid therapy may be sufficient to achieve a complete recovery and better outcomes in SAT.     

Genotype-Phenotype Relationship and Follow-up Analysis of a Chinese Cohort With Osteogenesis Imperfecta

ObjectiveTo evaluate the genotype-phenotype relationship and the effect of treatment on the clinical course of osteogenesis imperfecta (OI).MethodsWe established a Chinese hospitalized cohort with OI and followed them up for an average of 6 years. All patients were confirmed as having OI using whole-exome sequencing. We analyzed the genotype-phenotype relationship based on different types, pathogenic mechanisms, and gene inheritance patterns of OI. Additionally, we assessed whether there was a difference in treatment efficacy based on genotype.ResultsOne hundred sixteen mutations in 6 pathogenic genes (COL1A1, COL1A2, IFITM5, SERPINF1, FKBP10, and WNT1) were identified in 116 patients with type I, III, IV, V, VI, XI, or XV OI. Compared with patients with COL1A1 mutations, patients with COL1A2 mutations were younger at the time of the first fracture, whereas other phenotypes were similar. When 3 groups (helical, haploinsufficiency, and non-collagen I gene mutations) were compared, patients with helical mutations were the shortest and most prone to dentinogenesis imperfecta. Patients with haploinsufficiency mutations were the oldest at the time of the first fracture. Moreover, patients with non-collagen I gene mutations were least susceptible to blue sclerae and had the highest fracture frequency. Furthermore, there were some minor phenotypic differences among non-collagen I gene mutations. Interestingly, pamidronate achieved excellent results in the treatment of patients with OI, and the treatment effect appeared to be unrelated to their genotypes.ConclusionOur findings indicated a genotype-phenotype relationship and a similar effect of pamidronate treatment in patients with OI, which could provide a basis for guiding clinical treatment and predicting OI prognosis.     

Patient Understanding of Discharge Instructions for Home Diabetes Self-Management and Risk for Hospital Readmission and Emergency Department Visits

ObjectiveThe primary objective of this study was to examine the patient comprehension of diabetes self-management instructions provided at hospital discharge as an associated risk of readmission.MethodsNoncritically ill patients with diabetes completed patient comprehension questionnaires (PCQ) within 48 hours of discharge. PCQ scores were compared among patients with and without readmission or emergency department (ED) visits at 30 and 90 days. Glycemic measures 48 hours preceding discharge were investigated. Diabetes Early Readmission Risk Indicators (DERRIs) were calculated for each patient.ResultsOf 128 patients who completed the PCQ, scores were similar among those with 30-day (n = 31) and 90-day (n = 54) readmission compared with no readmission (n = 72) (79.9 ± 14.4 vs 80.4 ± 15.6 vs 82.3 ± 16.4, respectively) or ED visits. Clarification of discharge information was provided for 47 patients. PCQ scores of 100% were achieved in 14% of those with and 86% without readmission at 30 days (P = .108). Of predischarge glycemic measures, glycemic variability was negatively associated with PCQ scores (P = .035). DERRIs were significantly higher among patients readmitted at 90 days but not 30 days.ConclusionThese results demonstrate similar PCQ scores between patients with and those without readmission or ED visits despite the need for corrective information in many patients. Measures of glycemic variability were associated with PCQ scores but not readmission risk. This study validates DERRI as a predictor for readmission at 90 days.     

Comparison of Preoperative Alpha-blockade for Resection of Paraganglioma and Pheochromocytoma

ObjectivePhenoxybenzamine (nonselective, noncompetitive alpha-blocker) is the preferred drug for preoperative treatment of pheochromocytoma, but doxazosin (selective, competitive alpha-blocker) may be equally effective. We compared the efficacy of doxazosin vs phenoxybenzamine.MethodsWe conducted a prospective study of patients undergoing pheochromocytoma or paraganglioma resection by randomizing pretreatment with phenoxybenzamine or doxazosin at a single tertiary referral center. The high cost of phenoxybenzamine led to high crossover to doxazosin. Randomization was halted, and a consecutive historical cohort of phenoxybenzamine patients was included for a case-control study design. The efficacy of alpha-blockade was assessed with preinduction infusion of incremental doses of phenylephrine. The primary outcomes were mortality, cardiovascular complications, and intensive care unit admission. The secondary outcomes were hemodynamic instability index (proportion of operation outside of hemodynamic goals), adequacy of blockade by the phenylephrine titration test, and drug costs.ResultsTwenty-four patients were prospectively enrolled (doxazosin, n = 20; phenoxybenzamine, n = 4), and 15 historical patients treated with phenoxybenzamine were added (total phenoxybenzamine, n = 19). No major cardiovascular complications occurred in either group. The phenylephrine dose-response curves showed less blood pressure rise in the phenoxybenzamine than in the doxazosin group (linear regression coefficient = 0.008 vs 0.018, P = .01), suggesting better alpha-blockade in the phenoxybenzamine group. The median hemodynamic instability index was 14% vs 13% in the phenoxybenzamine and doxazosin groups, respectively (P = .56). The median highest daily cost of phenoxybenzamine was $442.20 compared to $5.06 for doxazosin.ConclusionPhenoxybenzamine may blunt intraoperative hypertension better than doxazosin, but this difference did not translate to fewer cardiovascular complications and is offset by a considerably increased cost.