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Acromegaly is characterized by hypersecretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), accompanied by a compromise in the perception of wellness. The Patient-Assessed Acromegaly Symptom Questionnaire (PASQ) is relevant to assessing signs and symptoms but is mainly used to evaluate the efficacy of a pharmacological intervention. To explore the perioperative variation in symptom severity, the divergence between subgroups stratified according to clinical outcomes or treatment modalities, and the interaction between symptom scores and clinical indices, we prospectively recruited 106 patients with acromegaly from 2016 to 2018. Oral glucose tolerance and GH tests were performed, and PASQ was administered before treatment and 6 months postoperatively. Patients were divided into active (n = 49) and remission (n = 57) groups according to postoperative GH and IGF-1 levels. PASQ scores and GH and IGF-1 levels decreased significantly postoperatively in both groups. A significantly higher preoperative headache score and greater extent of decrease in arthralgia were seen in the active and remission groups, respectively. No significant variation in PASQ scores was found between patients receiving surgery alone and those receiving preoperative somatostatin analogs. Preoperative fasting GH (GH0) levels were positively correlated with preoperative excessive perspiration. Further regression analyses validated the variation in GH0 as a noteworthy determinant of the extent of change in soft-tissue swelling, excessive perspiration, fatigue, and total PASQ scores. Patient-reported symptoms were substantially alleviated after surgery, independent of endocrine remission or use of preoperative somatostatin. A GH level decrease was a notable coefficient for PASQ scores.

Pituitary neuroendocrine tumor (PitNET) is one of the most common intracranial tumors. Due to its extensive tumor heterogeneity and the lack of high-quality tissues for biomarker discovery, the causative molecular mechanisms are far from being fully defined. Therefore, more studies are needed to improve the current clinicopathological classification system, and advanced treatment strategies such as targeted therapy and immunotherapy are yet to be explored. Here, we performed the largest integrative genomics, transcriptomics, proteomics, and phosphoproteomics analysis reported to date for a cohort of 200 PitNET patients. Genomics data indicate that GNAS copy number gain can serve as a reliable diagnostic marker for hyperproliferation of the PIT1 lineage. Proteomics-based classification of PitNETs identified 7 clusters, among which, tumors overexpressing epithelial-mesenchymal transition (EMT) markers clustered into a more invasive subgroup. Further analysis identified potential therapeutic targets, including CDK6, TWIST1, EGFR, and VEGFR2, for different clusters. Immune subtyping to explore the potential for application of immunotherapy in PitNET identified an association between alterations in the JAK1-STAT1-PDL1 axis and immune exhaustion, and between changes in the JAK3-STAT6-FOS/JUN axis and immune infiltration. These identified molecular markers and alternations in various clusters/subtypes were further confirmed in an independent cohort of 750 PitNET patients. This proteogenomic analysis across traditional histological boundaries improves our current understanding of PitNET pathophysiology and suggests novel therapeutic targets and strategies.

An increased risk of ocular hypertension was seen in Cushing's disease.Systemic steroid use is a significant risk factor for increased intraocular pressure (IOP). The incidence of ocular hypertension may rise to 30%-40% of the general population due to topical or systemic glucocorticoid usage. However, the incidence of ocular hypertension in endogenous hypercortisolemia, as well as the ophthalmological outcomes after endocrine remission due to surgical resection, remain unknown.The IOP, visual field, and peripapillary retinal nerve fiber layer thickness were documented in all patients with Cushing's disease (CD) admitted to a tertiary pituitary center for surgery from January to July 2019. Patients with acromegaly and patients with nonfunctioning pituitary adenoma (NFPA) during the same study period served as controls. We calculated the odds ratio (OR), identified the risk factors of developing ocular hypertension, and presented postoperative trends of the IOP.A total of 52 patients (38.4±12.4 y old) with CD were included. The IOP was higher in patients with CD (left 19.4±5.4 mm Hg and right 20.0±7.1 mm Hg) than in patients with acromegaly (left 17.5±2.3 mm Hg and right 18.6±7.0 mm Hg, P =0.033) and patients with NFPA (left 17.8±2.6 mm Hg and right 17.4±2.4 mm Hg, P =0.005). A total of 21 eyes (20.2%) in patients with CD were diagnosed with ocular hypertension compared with 4 eyes (4.7%) in the acromegaly group and 4 eyes (4.5%) in the NFPA group. The OR of developing ocular hypertension in patients with CD was 5.1 [95% confidence interval (CI), 1.3-25.1, P =0.029] and 6.6 (95% CI, 1.8-30.3, P =0.007) when compared with the 2 control groups. Among patients with CD, those with a higher urine-free cortisol were more likely to develop ocular hypertension (OR=19.4, 95% CI, 1.7-72.6). The IOP decreased at 1 month after surgery in patients with CD, and the change was sustained for 3 months after surgery.An increased risk of ocular hypertension was seen in CD and suggests that endogenous hypercortisolemia should be considered as part of the glaucoma assessment. This result warrants the discretion of both ophthalmologists and neuroendocrinologists.

Mortality in coronavirus disease 2019 (COVID-19) patients has been linked to the presence of a "cytokine storm" induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which involves elevated levels of circulating cytokines and immune-cell hyperactivation. Targeting cytokines during the management of COVID-19 patients has the potential to improve survival rates and reduce mortality. Although cytokine blockers and immune-host modulators are currently being tested in severely ill COVID-19 patients to cope with the overwhelming systemic inflammation, there is not too many successful cases, thus finding new cytokine blockers to attenuate the cytokine storm syndrome is meaningful. In this paper, we significantly attenuated the inflammatory responses induced by mouse hepatitis viruses A59 and SARS-CoV-2 through a soluble DR5-Fc (sDR5-Fc) chimeric protein that blocked the TNF-related apoptosis-inducing ligand-death receptor 5 (TRAIL-DR5) interaction. Our findings indicates that blocking the TRAIL-DR5 pathway through the sDR5-Fc chimeric protein is a promising strategy to treat COVID-19 severe patients requiring intensive care unit admission or with chronic metabolic diseases.

Objective: Gonadal and sexual disturbances are commonly encountered in patients with Cushing’s disease. Nevertheless, the prevalence of hypogonadism in male Cushing’s disease, the risk factors as well as the recovery time have been scarcely reported. Therefore, we aimed to explore the prevalence of hypogonadism at baseline and its determinants. In addition, the recovery time of hypogonadism and risk factors for unrecovered gonadal axis in male Cushing’s disease with biochemical remission were investigated.Methods: We reviewed medical records of males with Cushing’s disease managed between 2010 and 2020. Fifty-two male patients were enrolled according to the criteria. Each case attained biochemical remission after transsphenoidal surgery. Demographic details, clinical features, 24-hour UFC, hormonal profile [serum PRL, FSH, LH, TT, ACTH, cortisol, TT4/FT4, TT3/ FT3, TSH and IGF-1] were measured at baseline and during follow-up. The maximal tumor diameter on MRI was recorded at diagnosis.Results: Hypogonadotropic hypogonadism was observed in thirty-nine patients (75%) at diagnosis. Total testosterone was negatively correlated with ACTH and 24-hour UFC. Midnight serum ACTH level at diagnosis was significantly associated with hypogonadism after adjusting for confounding factors. Thirty-two (80%) patients achieved eugonadism within 12 months after the surgery, of which twenty-eight (87.5%) achieved eugonadism within 3 months. Seven patients were persistently hypogonadal during the follow-up (>1 year), mainly due to the hypopituitarism as a complication of the therapies such as surgery.Conclusion: Hypogonadotropic hypogonadism is frequent in male Cushing’s disease, but it is reversible in most cases within one-year follow-up after remission.

Objective Patients with Cushing’s disease (CD) experienced transient central adrenal insufficiency (CAI) after successful surgery. However, the reported recovery time of hypothalamic-pituitary-adrenal (HPA) axis varied and the risk factors which could affect recovery time of HPA axis had not been extensively studied. This study aimed to analyze the duration of CAI and explore the risk factors affecting HPA axis recovery in post-operative CD patients with biochemical remission. Design and methods Medical records of diagnosis with CD in Huashan Hospital were reviewed between 2014 and 2020. 140 patients with biochemical remission and regular follow-up after surgery were enrolled in this retrospective cohort study according to the criteria. Demographic details, clinical and biochemical information at baseline and each follow-up (within 2 years) were collected and analyzed. Results Overall, 103 patients (73.6%) recovered from transient CAI within 2 years follow-up and the median recovery time was 12 months [95% confidence intervals (CI): 10–14]. The age and midnight ACTH at baseline were significantly lower, while the TT3 and FT3 levels were significantly higher in patients with recovered HPA compared to patients with CAI at 2-year follow-up(p

Purpose: The incidence of venous thromboembolism (VTE) in Cushing’s disease (CD) is about ten times higher than that in general population, which tends to be underestimated due to the missed detection of asymptomatic VTE events. VTE can occur at any stage of CD, mainly during the postoperative period. We aim to investigate the incidence and prothrombotic risk factors of postoperative VTE in CD patients and to further develop an assessment model to identify those at high risk of postoperative VTE events. Methods: We performed a retrospective study in 82 CD patients by evaluating their clinical, hormonal, and coagulation parameters, as well as ultrasonography and pulmonary angio-CT when necessary. Results: Nineteen patients (23.2%) developed VTE events, of which 14 developed VTE after endoscopic transsphenoidal surgery (ETS). The group of CD patients with postoperative VTE were elder (pConclusion: Advanced perioperative assessment needs to be taken to screen those with high VTE risks in CD patients. Moreover, physical movement and antithrombotic prophylaxis seems to be warranted during perioperative period.

Epistaxis after endoscopic endonasal skull base surgeries does not typically occur as an accidental circumstance but often results from multiple factors. We aimed to assess the possible risk factors associated with postoperative epistaxis.Patients who underwent endoscopic endonasal skull base surgery at Huashan hospital from August 2018 to November 2019 were enrolled in the study. Postoperative epistaxis was defined as severe, persistent, or recurrent arterial nosebleed, which required therapeutic intervention. Patients were divided into the epistaxis and no epistaxis groups. The incidence, clinical characteristics, management, and intraoperative findings were recorded.A total of 762 patients were included in the study. 20 (2.6%) patients experienced postoperative epistaxis, which happened in a delayed fashion between 6 and 30 postoperative days. Multivariate logistic regression analysis showed that arterial hypertension (OR=3.394, 95%CI: 1.094-10.531, P = 0.034) and preoperative systolic blood pressure (SBP) (OR=1.035, 95%CI: 1.002-1.068) were identified as predictors for postoperative epistaxis. The bleeding sites were identified at the left posterior septal artery (PSA) in 10 (62.5%) cases, the right PSA in 4 (25%) cases, the left palatovaginal artery in 1 (6.25%) case, and the right inferior turbinate branch of the posterior lateral nasal artery in 1 (6.25%) case, respectively. Direct bipolar cauterization was used to stop the bleeding. After definitive treatment, no patients had recurrent epistaxis.Arterial hypertension and preoperative SBP were associated with postoperative epistaxis after endoscopic endonasal skull base surgery, and the left PSA contributed to the dominant site of bleeding during surgical re-exploration.

Background Factors associated with visual outcomes after transcranial surgery for large-to-giant pituitary adenomas have not been fully elucidated. Methods We recruited 37 patients with large-to-giant pituitary adenomas between January 2014 and December 2016 and assessed their tumor characteristics and surgical outcomes. Visual acuity and visual field were evaluated by visual impairment score before and 3–6 months after transcranial surgery. Multivariable logistic regression analysis was applied to show the factors associated with visual outcomes after surgery. Results The severity levels of visual impairment before surgery were mild, moderate, severe, and complete in 24.3% (9/37), 24.3% (9/37), 35.1% (13/37), and 16.2% (6/37), respectively. After surgery, the visual function was improved, stabilized, and worsened in 43.2% (16/37), 43.2% (16/37), and 13.5% (5/37) of patients, respectively. Multivariable logistic regression analysis showed that subarachnoid space invasion was the only independent prognostic factor adversely influencing the postoperative visual outcomes. Patients with subarachnoid space invasion had a higher possibility of visual deterioration (36.4% vs. 3.8%; P = 0.021) after transcranial surgery, compared with those without subarachnoid space invasion. Conclusions Visual compromise is still an unignorable complication during transcranial surgery for large-to-giant pituitary adenomas. Subarachnoid space invasion indicated by preoperative magnetic resonance imaging was an independent negative predictor for visual outcomes after surgery.

Background Nonfunctioning pituitary adenoma (NFPA) and growth hormone pituitary adenoma (GHPA) are major subtypes of pituitary adenomas (PAs). The primary treatment is surgical resection. However, radical excision remains challenging, and few effective medical therapies are available. It is urgent to find novel targets for the treatment. Bromodomain-containing protein 4 (BRD4) is an epigenetic regulator that leads to aberrant transcriptional activation of oncogenes. Herein, we investigated the pathological role of BRD4 and evaluated the effectiveness of BRD4 inhibitors in the treatment of NFPA and GHPA. Methods The expression of BRD4 was detected in NFPA, GHPA, and normal pituitary tissues. The efficacies of BRD4 inhibitors were evaluated in GH3 and MMQ cell lines, patient-derived tumor cells, and in vivo mouse xenograft models of PA. Standard western blots, real-time PCR, and flow cytometry experiments were performed to investigate the effect of BRD4 inhibitors on cell cycle progression, apoptosis, and the expression patterns of downstream genes. Results Immunohistochemistry studies demonstrated the overexpression of BRD4 in NFPA and GHPA. In vitro and in vivo studies showed that treatment with the BRD4 inhibitor ZBC-260 significantly inhibited the proliferation of PA cells. Further mechanistic studies revealed that ZBC-260 could downregulate the expression of c-Myc, B-cell lymphoma 2 (Bcl2), and related genes, which are vital factors in pituitary tumorigenesis. Conclusion In this study, we determined the overexpression of BRD4 in NFPA and GHPA and assessed the effects of BRD4 inhibitors on PA cells in vitro and in vivo. Our findings suggest that BRD4 is a promising therapeutic target for NFPA and GHPA.

Incineration is widely adopted in municipal solid waste management, which produces large amounts of municipal solid waste incineration (MSWI) fly ash. The harmless treatment of MSWI fly ash requires the appropriate disposal of heavy metals and dioxins that are enriched in fly ash. This review summarizes recently developed harmless disposal methods for MSWI fly ash including solidification/stabilization, thermal treatment, and separation/extraction. In addition, we discuss heavy metal and dioxin fixation, and the removal capacity of fly ash via solidification/stabilization (including cement solidification, chemical stabilization, hydrothermal processes, and mechano-chemical methods), thermal treatment (including sintering, fuel-burning, or electric melting/vitrification), and separation/extraction (including water-washing, chemical reagent leaching, biological leaching, electrodialysis separation, chemical reagent extraction, and nanomaterials extraction). The advantages and disadvantages of different harmless treatment methods are compared and future research prospects and suggestions are summarized. This review provides general guidelines for the harmless treatment of MSWI fly ash in the future.

Cl is one of the main pollutants emitted from domestic waste incineration systems. In this study, we focused on the process of Ca dechlorination in the furnace of a circulating fluidized-bed waste incineration system. We analyzed the stability of CaCl2 and Ca in the furnace, the dechlorination process, and distribution of Cl in the incineration system. The results show that the optimal Ca/Cl molar ratio for Ca dechlorination in the circulating fluidized-bed waste incinerator is 2:1; moreover, the dechlorination product CaCl2 was found to decompose at high temperatures (> 850 °C). At temperatures > 700 °C, we measured CaCl2 decomposition rates up to 80%. Ca was added in the furnace, mainly to provide a dechlorination Ca source for the decomposition of limestone into tail flue gas. The amount of Ca2+ in the flue decreased gradually, parallelly to the temperature of the flue gas. Stable CaCl2 was formed after HCl was captured, and relatively small solid particles appeared in the ash collecting bag.

Background The pathogenesis of Cushing’s disease (CD) is still not adequately understood despite the identification of somatic driver mutations in USP8, BRAF, and USP48. In this multiomics study, we combined RNA sequencing (RNA-seq) with Sanger sequencing to depict transcriptional dysregulation under different gene mutation backgrounds. Furthermore, we evaluated the potential of achaete-scute complex homolog 1 (ASCL1), a pioneer transcription factor, as a novel therapeutic target for treatment of CD and its possible downstream pathway. Methods RNA-seq was adopted to investigate the gene expression profile of CD, and Sanger sequencing was adopted to detect gene mutations. Bioinformatics analysis was used to depict transcriptional dysregulation under different gene mutation backgrounds. The function of ASCL1 in hormone secretion, cell proliferation, and apoptosis were studied in vitro. The effectiveness of an ASCL1 inhibitor was evaluated in primary CD cells, and the clinical relevance of ASCL1 was examined in 68 patients with CD. RNA-seq in AtT-20 cells on Ascl1 knockdown combined with published chromatin immunoprecipitation sequencing data and dual luciferase assays were used to explore downstream pathways. Results ASCL1 was exclusively overexpressed in USP8-mutant and wild-type tumors. Ascl1 promoted adrenocorticotrophin hormone overproduction and tumorigenesis and directly regulated Pomc in AtT-20 cells. An ASCL1 inhibitor presented promising efficacy in both AtT-20 and primary CD cells. ASCL1 overexpression was associated with a larger tumor volume and higher adrenocorticotrophin secretion in patients with CD. Conclusion Our findings help to clarify the pathogenesis of CD and suggest that ASCL1 is a potential therapeutic target the treatment of CD. Summary The pathogenesis of Cushing’s disease (CD) is still not adequately understood despite the identification of somatic driver mutations in USP8, BRAF, and USP48. Moreover, few effective medical therapies are currently available for the treatment of CD. Here, using a multiomics approach, we first report the aberrant overexpression of the transcription factor gene ASCL1 in USP8-mutant and wild-type tumors of CD. Ascl1 promoted adrenocorticotrophin hormone overproduction and tumorigenesis and directly regulated Pomc in mouse AtT-20 cells. Notably, an ASCL1 inhibitor presented promising efficacy in both AtT-20 and primary CD cells. Importantly, ASCL1 overexpression was associated with a larger tumor volume and higher adrenocorticotrophin secretion in patients with CD. Thus, our findings improve understanding of CD pathogenesis and suggest that ASCL1 is a potential therapeutic target the treatment of CD.

To compare the efficacy of collagen sponge graft versus autologous fat graft in repairing grade 1 intraoperative CSF leakage and identify potential risk factors for failure repairing.We retrospectively recruited patients with grade 1 intraoperative CSF leakage repaired either with a collagen sponge (Group A), with autologous fat graft (Group B), or with only bipolar coagulation and gel foam packing (Group C). Patients with previous radiotherapy, repaired with additional materials, received postoperative lumbar drainage or without sufficient follow-up data were excluded. The primary outcome was the incidence of postoperative CSF leakage. We used propensity score matching to adjust for confounding when comparing Group A and Group B.459 patients (277 female and 182 male) were recruited. Among them, 296 patients were in Group A, 146 patients were in Group B, and the other 17 patients were in Group C. After propensity score matching, 146 and 146 patients were included in group A and group B, respectively. No difference was observed for the primary outcome in the matched cohort (p = 0.654) with three patients in Group A (1.0% and 2.1% before and after matching, respectively) and two patients in Group B (1.4% and 1.4% before and after matching, respectively) developed postoperative CSF leakage, respectively. Patients repaired only with gel foam and/or bipolar coagulation (OR 770.5, p 0.001) and older age (OR 1.16, p 0.001) were associated with a higher likelihood of postoperative CSF leakage.Collagen sponge is as effective as an autologous fat graft for grade 1 intraoperative CSF leakage repair during transsphenoidal surgery. Repair with gel foam and/or bipolar coagulation and older age are associated with a higher likelihood of postoperative CSF leakage.

Summary Rosiglitazone, a synthetic peroxisome proliferator-activated receptor γ (PPARγ) ligand, has been reported to reduce growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in 10 patients with acromegaly. However, the mechanisms remain unknown. Here, we reveal that PPARγ directly enhances 15-hydroxyprostaglandin dehydrogenase (15-PGDH) expression, whose expression is decreased and negatively correlates with tumor size in acromegaly. Rosiglitazone decreases GH production and promotes apoptosis and autophagy in GH3 and primary somatotroph adenoma cells and suppresses hepatic GH receptor (GHR) expression and IGF-1 secretion in HepG2 cells. Activating the PGE2/cAMP/PKA pathway directly increases GHR expression. Rosiglitazone suppresses tumor growth and decreases GH and IGF-1 levels in mice inoculated subcutaneously with GH3 cells. The above effects are all dependent on 15-PGDH expression. Rosiglitazone as monotherapy effectively decreases GH and IGF-1 levels in all nineteen patients with active acromegaly. Evidence suggests that rosiglitazone may be an alternative pharmacological approach for acromegaly by targeting both pituitary adenomas and liver., Graphical abstract, Highlights • Rosiglitazone reduces GH secretion in GH3 cells via upregulating 15-PGDH expression • Rosiglitazone suppresses IGF-1 secretion in HepG2 cells relied on 15-PGDH expression • Rosiglitazone inhibits tumor growth in mice inoculated subcutaneously with GH3 cells • Rosiglitazone reduces GH and IGF-1 levels in all 19 patients with active acromegaly, Medicine; Human specimen; Cancer

OBJECTIVE Cushing disease is a potentially fatal endocrine disorder caused by adrenocorticotropin (ACTH)-secreting microadenomas in the pituitary gland. Accurate detection and localization of the adenomas is the key to clinical treatment. This study analysed the value of contrast-enhanced Sampling Perfection with Application-optimized Contrasts using different flip angle Evolutions (SPACE) sequence in magnetic resonance imaging (MRI) assessment of ACTH-secreting pituitary microadenomas. DESIGN AND PATIENTS We carried out a retrospective study in which 45 patients with ACTH-secreting pituitary microadenomas were enrolled. Dynamic contrast-enhanced (DCE) coronal T1-SE sequence was performed. A contrast-enhanced coronal SPACE sequence was added immediately after DCE MRI finished. Two independent observers assessed the tumour existence and location, then the results were compared with surgical findings. RESULTS Twenty-four lesions (53.3%) were detected by the DCE T1-SE sequence alone, while 35 lesions (80.0%) were detected with the addition of contrast-enhanced SPACE sequence. The sensitivity (58.5% vs. 85.3%; p

In this study, the evolution and distribution of fluorine during the incineration of fluorine-containing waste in a hazardous waste incinerator were investigated. The evolution characteristics of fluorine during the pyrolysis of the waste were investigated using thermogravimetric analyzer coupled with Fourier transform infrared spectroscopy (TG-FTIR) analysis. The distribution of fluorine in the incineration systems and its form in the incineration residues were studied under two operating conditions. The results showed that fluorine in the waste had strong volatility and hydrogen fluoride (HF) and silicon fluoride (SiF4) were detected as the first fluorine compounds to be released during pyrolysis. The release of HF could be divided into three temperature ranges: 123.5–757.5 °C, 757.5–959.6 °C, and >959.6 °C. The emission of HF between 123.5 °C and 757.5 °C involved loosely bonded organic fluorine and ionic inorganic fluorine, while the HF released between 757.5 °C and 959.6 °C was caused by the crack of fixed carbon and further dehydroxylation, and the HF released above 959.6 °C was due to the decomposition of inorganic minerals. The emission of SiF4 was mainly concentrated between 132.6 °C and 684.0 °C, and almost no SiF4 was emitted from the waste above 684.0 °C. Less than 20.73% of the fluorine was retained in the incineration residues and over 79.17% of fluorine was absorbed in the absorbent solution of a wet flue gas desulfurization (WFGD) system. The amount of fluorine discharged into the atmosphere was below 0.12%. The fluorine in the bottom slag and burn-out chamber ash mainly existed in residual form. The proportions of water-soluble, exchangeable, and acid-soluble fluorine in the boiler ash and bag filter ash were both over 80%.

Objective The aim of this study was to evaluate thyroid functions in Cushing’s syndrome (CS), the dynamic changes of thyroid hormones and antithyroid antibodies in Cushing’s disease (CD) pre- and postoperatively. Design and methods This is a retrospective study enrolling 118 patients with CS (102 CD, 10 adrenal CS and 6 ectopic adrenocorticotropic syndrome (EAS)). Thyroid functions (thyroid-stimulation hormone (TSH), T3, free T3 (FT3), T4 and free T4 (FT4)) were measured in all CS at the time of diagnosis and in all CD 3 months after transsphenoidal pituitary tumor resection. Postoperative hormone monitoring within 3 months was conducted in 9 CD patients completing remission. Twenty-eight remitted CD patients experienced hormone and antithyroid antibody evaluation preoperatively and on the 3rd, 6th and 12th month after surgery. Results TSH, T3 and FT3 were below the reference range in 31%, 69% and 44% of the 118 CS patients. Remitted CD patients (81/102) had significantly higher TSH (P = 0.000), T3 (P = 0.000) and FT3 (P = 0.000) than those in the non-remission group (21/102). After remission of CD, TSH, T3 and FT3 showed a significant increase, with a few cases above the reference range. By 12 months, most CD patients’ thyroid functions returned to normal. Thyroid hormones (including TSH, T3 and FT3) were negatively associated with serum cortisol levels both before and after surgery. No significant changes of antithyroid autoantibodies were observed. Conclusions TSH, T3 and FT3 are suppressed in endogenous hypercortisolemia. After remission of CD, TSH, T3 and FT3 increased significantly, even above the reference range, but returned to normal 1 year after surgery in most cases. Antithyroid antibodies did not change significantly after remission of CD.

The factors associated with initial and delayed remission after growth hormone (GH)-secreting pituitary adenoma excision have not been completely elucidated.We recruited 185 consecutive patients who had undergone resection of GH-secreting pituitary adenomas from January 2013 to December 2014 and assessed their tumor characteristics and surgical outcomes. The criteria for initial or delayed remission (using the 2010 consensus criteria) were normalized insulin-like growth factor 1 (IGF-1) levels, GH levels0.4 μg/L with an oral glucose tolerance test, and/or random GH levels1.0 μg/L at or after the postoperative 3-month (PO3M) follow-up, without adjuvant therapy.Remission was achieved in 92 of 162 patients (56.8%) after surgery alone and was associated with a lower Knosp grade of 0-2 and lower postoperative day 1 GH level on multivariate regression analysis. A baseline IGF-1 index (IGF-1 level/upper limit of normal) of2.835 predicted for initial remission at the PO3M follow-up (positive predictive value, 95.3%; negative predictive value, 36.6%; P0.001). The PO3M IGF-1 index was significantly lower in the delayed remission group than in the nonremission group. Furthermore, the former had had fewer invasive tumors (1.23 ± 0.21 vs. 1.77 ± 0.37 [9.52% vs. 76.47%]; P0.001). A PO3M IGF-1 index of1.485 predicted for delayed remission during subsequent follow-up (positive predictive value, 84.6%; negative predictive value, 92.3%; P0.001).A lower Knosp grade of 0-2 and lower postoperative day 1 GH level were independent predictors of surgical remission. The baseline IGF-1 and PO3M IGF-1 indexes might predict for initial and delayed remission, respectively.

To explore the value of magnetic resonance textural analysis (MRTA) in assessing consistency of pituitary macroadenoma (PMA) based on contrast enhanced (CE) three-dimensional sampling perfection with application-optimized contrasts by using different flip angle evolution (3D-SPACE) images.Fifty-three patients with PMAs that underwent CE 3D-SPACE scanning by 3.0 T MRI and endoscopic trans-sphenoidal surgery were included in the present study. Consistency levels of PMAs were evaluated intraoperatively by two neurosurgeons. Each resection specimen was stained with HE and anti-collagen IV. MRTA was conducted and texture features were calculated. An unpaired t-test was used to analyze the differences of texture features between soft and hard PMAs. ROC curves by individual and combined features were used to calculate the diagnostic accuracy of MRTA in predicting PMA consistency.First-order energy and second-order correlation negatively correlated with hard PMAs, while first-order entropy and second-order variance, sum variance, and sum entropy positively correlated with stiffness. All showed significant differences between soft and hard PMAs (P 0.05). Diagnostic accuracy of combined negative features could achieve an AUC of 0.819, sensitivity of 88.9%, specificity of 61.5%, PPV of 70.6%, NPV of 84.2% and positive features could achieve an AUC of 0.836, sensitivity of 85.2%, specificity of 69.2%, PPV of 74.2%, NPV of 81.8% (P 0.001).MRTA using CE 3D-SPACE images is helpful for assessing PMA consistency preoperatively and noninvasively.

In this study, distribution and leaching characteristics of heavy metals (As, Cd, Cr, Cu, Pb, Se, Zn, and Hg) along flue gas cleaning systems were investigated in a hazardous waste incinerator located in Zhejiang, China. The particle size distribution, heavy metal loading, and morphological and mineralogical characteristics of solid incineration residues were assessed before and after acetic acid extraction. Results showed that Hg, Cd, As, Pb, and Zn were transmitted into the fly ash mainly by evaporation, condensation, and adsorption, while Se and Cr were mainly by entrainment. High chlorine availability in the industry hazardous waste favored the evaporation of Cu, Pb and Zn. Due to the mass ratio of the bottom slag in the incineration residues being more than 52%, most of Cu, Cr, As, and Zn remained in the bottom slag. Scarcely any Hg and less than 9.6% of Cd were found in the bottom slag. Cd was mainly retained in the fly ash and the absorbent solution of the wet flue gas desulfurization (WFGD) system while most of Pb was found in the fly ash. WFGD system had a high Hg removal efficiency and more than 74.7% of Hg was retained in the absorbent solution of WFGD system. The distinction in the distribution and migration characteristics of heavy metals between two continuous operating conditions was mainly due to the different physicochemical properties of wastes. The studied heavy metals in the bottom slag, with the exception of Zn, showed low leachability, with a leaching ratio below 2%. Cd and Zn presented the highest leachability, and over 56.2% of Cd and more than 39.5% of Zn in the fly ash were transferred into the leachate. For the each studied heavy metal, the leaching ratio in the bag filter ash was the highest.

The present study investigated the factors associated with recurrence during long-term follow-up in acromegaly and compared the recurrence rate between patients in remission with 2010 vs 2000 consensus criteria. We retrospectively recruited 133 adult acromegalic patients who had undergone transsphenoidal surgery (TSS) from January 2013 to December 2014 and assessed their clinical characteristics, surgical outcomes and recurrence. Surgical remission was defined as normalised insulin-like growth factor 1 (IGF-1) with nadir growth hormone (GH) during an oral glucose tolerance test (OGTT) < 1 μg/ L no less than 3 months after TSS without adjuvant therapy. Recurrence was defined as persistently reelevated IGF-1 after surgical remission. Cox regression analysis and Kaplan-Meier survival analysis were performed to evaluate the factors associated with recurrence. Remission was achieved in 77 cases (57.9%) after TSS alone. Recurrence was seen in five cases (6.5%) at 12, 12, 12, 36 and 54 months, respectively, after surgery. Cox regression analysis showed that a nadir GH < 0.4 μg /L (vs 0.4-1.0 μg /L) at surgical remission (odds ratio [OR] = 0.106; 95% confidence interval [CI] = 0.017-0.645; P = 0.015) and Ki-67 index (OR = 2.636; 95% CI = 1.023-6.791; P = 0.045) were independent factors influencing recurrence. Kaplan-Meier survival analysis showed that the median recurrence-free survival was 36 months (95% CI = 20-52) for patients with nadir GH 0.4-1.0 μg /L at surgical remission. The median recurrence-free survival for patients with nadir GH < 0.4 μg /L at surgical remission was much longer (ie, required further follow-up to estimate). A failure of GH suppression under 0.4 μg /L during an OGTT in patients with normalised IGF-1 and a higher Ki-67 index are independent predictors of recurrence after surgical remission in GH-secreting pituitary adenomas. Compared to patients with nadir GH < 0.4 μg /L, those with nadir GH 0.4-1.0 μg /L appear to have a significantly higher risk of recurrence.