Reversibility of Impaired Large-Scale Functional Brain Networks in Cushing's Disease after Surgery Treatment: A Longitudinal Study.

INTRODUCTION: Chronic exposure to excessive endogenous cortisol leads to brain changes in Cushing's disease (CD). However, it remains unclear how CD affects large-scale functional networks (FNs) and whether these effects are reversible after treatment. This study aimed to investigate functional network changes of CD patients and their reversibility in a longitudinal cohort. METHODS: Active CD patients (N = 37) were treated by transsphenoidal pituitary surgery and reexamined 3 months later. FNs were computed from resting-state fMRI data of the CD patients and matched normal controls (NCs, N = 37). A pattern classifier was built on the FNs to distinguish active CD patients from controls and applied to FNs of the CD patients at the 3-month follow-up. Two subgroups of endocrine-remitted CD patients were identified according to their classification scores, referred to as image-based phenotypically (IBP) recovered and unrecovered CD patients, respectively. The informative FNs identified by the classification model were compared between NCs, active CD patients, and endocrine-remitted patients as well as between IBP recovered and unrecovered CD patients to explore their functional network reversibility. RESULTS: All 37 CD patients reached endocrine remission after treatment. The classification model identified three informative FNs, including cerebellar network (CerebN), fronto-parietal network (FPN), and default mode network. Among them, CerebN and FPN partially recovered toward normal at 3 months after treatment. Moreover, the informative FNs were correlated with 24-h urinary-free cortisol and emotion scales in CD patients. CONCLUSION: These findings suggest that CD patients have aberrant FNs that are partially reversible toward normal after treatment.

Machine learning revealed stemness features and a novel stemness-based classification with appealing implications in discriminating the prognosis, immunotherapy and temozolomide responses of 906 glioblastoma patients.

Glioblastoma (GBM) is the most malignant and lethal intracranial tumor, with extremely limited treatment options. Immunotherapy has been widely studied in GBM, but none can significantly prolong the overall survival (OS) of patients without selection. Considering that GBM cancer stem cells (CSCs) play a non-negligible role in tumorigenesis and chemoradiotherapy resistance, we proposed a novel stemness-based classification of GBM and screened out certain population more responsive to immunotherapy. The one-class logistic regression algorithm was used to calculate the stemness index (mRNAsi) of 518 GBM patients from The Cancer Genome Atlas (TCGA) database based on transcriptomics of GBM and pluripotent stem cells. Based on their stemness signature, GBM patients were divided into two subtypes via consensus clustering, and patients in Stemness Subtype I presented significantly better OS but poorer progression-free survival than Stemness Subtype II. Genomic variations revealed patients in Stemness Subtype I had higher somatic mutation loads and copy number alteration burdens. Additionally, two stemness subtypes had distinct tumor immune microenvironment patterns. Tumor Immune Dysfunction and Exclusion and subclass mapping analysis further demonstrated patients in Stemness Subtype I were more likely to respond to immunotherapy, especially anti-PD1 treatment. The pRRophetic algorithm also indicated patients in Stemness Subtype I were more resistant to temozolomide therapy. Finally, multiple machine learning algorithms were used to develop a 7-gene Stemness Subtype Predictor, which were further validated in two external independent GBM cohorts. This novel stemness-based classification could provide a promising prognostic predictor for GBM and may guide physicians in selecting potential responders for preferential use of immunotherapy.

A Europium Metal-Organic Framework and Its Polymer Composite Membrane as Switch-Off Fluorescence Sensors for Antibiotic Detection in Lake Water.

The detection of antibiotic residues is of great significance in monitoring their overuse in healthcare, livestock and poultry farming, and agricultural production. Herein, EuCl3 and 4,4'-dicarboxyl-diphenoxyethene (H2DPOE) ionothermally reacted in 1-methyl-3-butylimidazolium chloride to give a europium metal-organic framework (Eu-DPOE). Eu-DPOE shows different fluorescence quenching rates for sensing eight antibiotics under different excitation wavelengths. Eu-DPOE displays a fast response, high selectivity, and sensitivity in antibiotic detection by fluorescence quenching. Eu-DPOE can sensitively detect TCs (tetracyclines), NOR (norfloxacin), NFT (furazolidone), ODZ (ornidazole), SDZ (sulfadiazine), and CHL (chloramphenicol) with limits of detection below 0.5 µmol/L. It provides a convenient and rapid tool for sensing antibiotics in aqueous solution. The detection mechanism is a competition absorption between DPOE2- and antibiotics with the supports from powder X-ray diffraction (PXRD), UV-vis spectra, and fluorescence lifetime. With a composite membrane of poly(vinylidene fluoride) (PVDF) matrix loading Eu-DPOE (Eu-DPOE@PVDF), Eu-DPOE@PVDF exhibits a visual fluorescence response to NOR under a 254 nm UV lamp and NFT and CTC under 365 nm. Eu-DPOE@PVDF is applied in the quantitative detection of CTC, NOR, and NFT in lake water with recovery rates ranging from 88.37 to 113.8%. Totally, fluorescence-quenched Eu-DPOE@PVDF exhibits a fast response, high selectivity, and sensitivity in sensing CTC, NOR, and NFT.

Transcriptional regulation of host insulin signaling pathway genes controlling larval development by Microplitis manilae parasitization.

Idiobiont parasitoids using other insects as hosts sabotage the host growth and development to ensure their offspring survival. Numerous studies have discovered that insect development is subtly regulated by the conserved insulin signaling pathway. However, little is known about how wasp parasitization disrupts host development controlled by the insulin signaling pathway. Here we address this study to determine the effect of wasp parasitism on host Spodoptera frugiperda development using the idiobiont parasitoid Microplitis manilae as a model. Upon M. manilae parasitization, the body weight, body length, and food consumption of host insect were dramatically reduced compared to the unparasitized S. frugiperda. We next identified the core genes involved in host insulin signaling pathway and further analyzed the domain organizations of these genes. Phylogenetic reconstruction based on the insulin receptors clustered S. frugiperda together with other noctuidae insects. In the latter study, we profiled the expression patterns of host insulin signaling pathway genes in response to M. manilae parasitization at 2, 24, and 48 h, significant decreases in mRNA levels were recorded in S. frugiperda larvae upon 24 and 48 h parasitization. These current findings substantially add to our understanding of the physiological interaction between parasitoid and host insects, thus contributing to revealing the molecular mechanism of parasitic wasps regulating host development.

Skin manifestations and submacroscopical features of acromegaly: A case-control study using dermoscopy and high-frequency ultrasound.

BACKGROUND: Although the cutaneous involvement of acromegaly has been recognized, the submacroscopical skin changes and the extent of skin thickening of patients remain unclear. OBJECTIVES: This study aimed at investigating the clinical cutaneous manifestations, dermoscopic features, and skin thickness revealed by high-frequency ultrasound (HFUS) of acromegalic patients. METHODS: A case-control observational study was conducted. Patients with acromegaly and controls were prospectively included and received thorough cutaneous examinations to compare the macroscopical and dermoscopic features. The skin thickness measured by HFUS and its correlation with clinical data were also assessed. RESULTS: Thirty-seven and 26 patients from acromegalic and control group were included, respectively. Clinical skin manifestations were recorded in detail. Under dermoscopy, red structureless area (91.9% vs. 65.4%, p = 0.021), perifollicular orange halo (78.4% vs. 26.9%, p = 0.005), and follicular plug (70.3% vs. 3.9%, p = 0.001) in the facial area, and perifollicular pigmentation (91.9% vs. 23.1%), broom-head hairs (83.8% vs. 3.9%), honeycomb-like pigmentation (97.3% vs. 38.46%), widened dermatoglyphics (81.1% vs. 3.9%) at the extremities (p < 0.001) were more prevalent in acromegaly. The mean skin thickness was 4.10 ± 0.48 mm for acromegaly, and 3.55 ± 0.52 mm for controls (p < 0.001) but no correlation with disease duration, adenoma size, and hormone level was found in acromegaly. CONCLUSIONS: Submacroscopical skin changes under dermoscopy and skin thickness increase assessed by HFUS can provide clinicians with subtle evidences for early detection of acromegaly and objective parameters for accurate assessment of its skin involvement.

Cytokine release syndrome and relevant factors of CD19 targeted chimeric antigen receptor T cell therapy in relapsed/refractory B cell hematological malignancies.

OBJECTIVES AND METHODS: We reviewed the outcomes of 77 episodes of CD19 CAR-T therapy in 67 patients with B cell hematological malignancies from October 2016 to January 2020. Factors related to the grade of cytokine release syndrome (CRS) were explored by multivariate analysis, nonparametric test was conducted to explore the correlation between CRS and response. Kaplan-Meier curves were used to indicate survival profiles, and the correlation between CRS and survival was determined by the log-rank test. RESULTS: The rate of complete remission (CR) was 74.0% (57/77). CRS of any grade occurred in 68 of 77 episodes (grade 1: 32.5%, grade 2: 24.7%, grade 3: 22.1%, grade 4: 6.5%, grade 5: 2.6%). Patients with a history of transplantation had less severe CRS, and dose escalation-based infusion reduced the severity of CRS. Severe CRS was related to a higher CR rate but had no significant impact on event-free survival (EFS), relapse-free survival (RFS), or overall survival (OS). CONCLUSION: As a common adverse reaction of CAR-T therapy, the severity of CRS can be alleviated by dose escalation infusion, a history of transplantation was correlated with less severe CRS. Severe CRS was related to better response but was unrelated to long-term survival.

Early Retinal Microcirculation in Nonfunctioning Pituitary Adenomas Without Visual Field Defects Using Optical Coherence Tomography Angiography.

BACKGROUND: For patients with nonfunctioning pituitary adenoma (NFPA) without manifesting visual acuity impairment or visual field defect (VFD), more sensitive and objective assessment methods will allow earlier detection before irreversible damage to the visual system. This study aimed to evaluate retinal vessel densities (VDs) alterations in these patients using optical coherence tomography angiography and to determine its diagnostic abilities. METHODS: Between patients with NFPA without VFDs and age-matched, sex-matched healthy control individuals, comparisons of visual field metrics, retinal structural thickness, and microcirculation were conducted after adjusting for axial length (AL) and signal index of scans. Receiver operating characteristic (ROC) curves were further depicted to assess the diagnostic performance of significant parameters. To explore the impact of symptom duration, tumor size, and axial length on the significant parameters, multivariate regression analysis was conducted. RESULTS: This cross-sectional study reviewed 107 patients with NFPA. Twenty-seven eyes of patients with NFPA without VFDs and 27 eyes of healthy controls were enrolled. Compared with healthy controls, patients with NFPA without VFDs had similar foveal avascular zone areas and perimeters, macular ganglion cell complex (mGCC) and peripapillary retinal nerve fiber layer thicknesses, and macular VDs. Only the VD in the radial peripapillary capillary (RPC) segment of the inferior temporal (IT) sector was much lower in the patient group. The 2 largest area under the ROC curves were the focal loss volume (FLV) of the mGCC and the VD in the RPC of the IT sector, both of which were significantly related to symptom duration and tumor size. CONCLUSIONS: At the early stage of NFPA before VFD and retinal thickness thinning, fundus microcirculation impairments may occur initially in the microvascular density of the RPC segment of the IT sector. The FLV and the VD of RPC at the IT sector may provide a basis for the early diagnosis of NFPA without VFD in clinical practice.

Moving toward a standardized diagnostic statement of pituitary adenoma using an information extraction model: a real-world study based on electronic medical records.

PURPOSE: Diagnostic statements for pituitary adenomas (PAs) are complex and unstandardized. We aimed to determine the most commonly used elements contained in the statements and their combination patterns and variations in real-world clinical practice, with the ultimate goal of promoting standardized diagnostic recording and establishing an efficient element extraction process. METHODS: Patient medical records from 2012 to 2020 that included PA among the first three diagnoses were included. After manually labeling the elements in the diagnostic texts, we obtained element types and training sets, according to which an information extraction model was constructed based on the word segmentation model "Jieba" to extract information contained in the remaining diagnostic texts. RESULTS: A total of 576 different diagnostic statements from 4010 texts of 3770 medical records were enrolled in the analysis. The first ten diagnostic elements related to PA were histopathology, tumor location, endocrine status, tumor size, invasiveness, recurrence, diagnostic confirmation, Knosp grade, residual tumor, and refractoriness. The automated extraction model achieved F1-scores that reached 100% for all ten elements in the second round and 97.3-100.0% in the test set consisting of an additional 532 diagnostic texts. Tumor location, endocrine status, histopathology, and tumor size were the most commonly used elements, and diagnoses composed of the above elements were the most frequent. Endocrine status had the greatest expression variability, followed by Knosp grade. Among all the terms, the percentage of loss of tumor size was among the highest (21%). Among statements where the principal diagnoses were PAs, 18.6% did not have information on tumor size, while for those with other diagnoses, this percentage rose to 48% (P < 0.001). CONCLUSION: Standardization of the diagnostic statement for PAs is unsatisfactory in real-world clinical practice. This study could help standardize a structured pattern for PA diagnosis and establish a foundation for research-friendly, high-quality clinical information extraction.

The Impact of Hypertension Definition Based on Two-visit Strategy on Estimate of Hypertension Burden: Results From the China Health and Nutrition Survey 1989-2011.

BACKGROUND: The diagnosis of hypertension should be based on the mean of two or more properly measured BP readings on each of two visits for clinical practice, but a one-visit strategy was applied in most epidemiological surveys. The impact of hypertension definition based on two visits on estimates of hypertension burden is unknown. This study aims to assess the impact of hypertension diagnosis based on a two-visit strategy for estimating hypertension burden in China. METHODS: The one-visit and two-visit strategies were applied to investigate the incidence of hypertension in a cohort study based on the China Health and Nutrition Survey (CHNS) 1989-2011. Additionally the prevalence of hypertension was investigated in a cross-sectional study based on the CHNS 2006-2009/2011 and the hypertension burden in China was estimated with data from the 2012-2015 China hypertension survey. RESULTS: Overall, the age-adjusted incidence of hypertension based on the two-visit strategy (1.82%; 95% confidence interval [CI], 1.74-1.90%) was 62.1% lower than estimation based on the one-visit strategy (4.80%; 95% CI, 4.68-4.93%). Similar results were found in the prevalence of hypertension (one-visit: 18.13% [95% CI, 17.34-18.92%]; two-visit: 9.47% [95% CI, 8.87-10.07%]). When the two-visit strategy was applied to the 2012-2015 China hypertension survey, the hypertension burden was predicted to be overestimated by 25.5-47.8% (based on JNC 7) and 23.5-48.2% (based on the 2017 ACC/AHA). CONCLUSION: The hypertension burden would decrease from 244.5 million persons to 127.5-182.3 million persons in China if the two-visit strategy was applied.

Clinical profiles of silent corticotroph adenomas compared with silent gonadotroph adenomas after adopting the 2017 WHO pituitary classification system.

PURPOSE: Silent corticotroph adenomas (SCAs) can be redefined according to the 2017 World Health Organization pituitary classification system with the introduction of T­PIT, a transcription factor. We studied the clinical features of these redefined SCAs. METHODS: We compared 112 patients with SCAs and 198 patients with silent gonadotroph adenomas (SGAs) who underwent surgery from January 2019 to May 2020. RESULTS: The prevalence of SCAs increased from 21.3 to 30.2% under the new classification rules. T-PIT-positive, adrenocorticotropic hormone-negative SCAs and T-PIT-positive, adrenocorticotropic hormone-positive SCAs exhibited similar clinical features. SCAs exhibited significant female preponderance (90.2% vs. 29.8%, P < 0.0001); more frequent invasion (36.6% vs. 7.6%, P < 0.0001), especially multiple-site invasion (P < 0.0001); and marked cystic changes on imaging compared with SGAs (54.5% vs. 19.2%, P < 0.0001). SCAs had a softer tumor consistency (89.2% vs. 61.1%, P < 0.0001). Gross total resection was achieved in 66.1% of SCAs and 66.2% of SGAs (P > 0.9999). The overall recurrence/progression rates of SCAs and SGAs were 9.8% and 6.6% at 14.1 and 13.5 months of follow-up, respectively (P = 0.3765). The proportion of patients with more than two recurrences requiring multiple surgeries and radiation was similar between SCAs and SGAs (7.1% vs. 3.0%, P = 0.1514). However, multiple recurrences of SCAs affected younger patients than SGAs (39.0 vs. 53.5 years, P = 0.0433). CONCLUSIONS: The prevalence of SCAs increased with the introduction of T-PIT. SCAs and SGAs exhibited comparable size and recurrence/progression rates, but SCAs showed increased invasion and more marked cystic change. Aggressive SCAs tended to affect younger patients. Close long-term monitoring for SCA recurrence/progression is required.

Study on the effect of municipal solid landfills on groundwater by combining the models of variable leakage rate, leachate concentration, and contaminant solute transport.

The landfill with low economic cost and technical barrier has become a popular option for municipal solid waste treatment, but it is likely to seriously pollute groundwater by solute leaching. In this study, the pollutants concentration model, leakage rate model, and the solute transport model were coupled to investigate the effect of municipal solid waste landfill on groundwater quality. Major results obtained are, (1) the leakage rate of leachate differs significantly among the landfilling stage, covering stage and completely covered stage as the leachate depth varies with the infiltration rainfall. The contact condition between HDPE and CCL was found to be a key factor in determining the leakage rate of leachate. Ensuring good connection between HPDE and CCL is thus critical in protecting groundwater from being polluted by landfill. (2) The NH3-N as a proxy for organic pollutants was generated via the degradation process, and Cl- as a proxy for inorganic pollutants is a leachable fraction of mobilized substances. The concentration of Cl- is higher than that of NH3-N before 7600 days, then the concentration of NH3-N becomes roughly stable while that of Cl- continues to decrease. (3) The load of NH3-N as a proxy for organic pollutants declines linearly downwards before the completely covering stage. The load of Cl- as a proxy for inorganic pollutants increased during the first five years, and then declined. (4) In the case study, the path of maximum pollutants concentration is perpendicular to the groundwater contour, and the maximum pollutants concentration has two peaks, occurring on 7106 days and 11,554 days, respectively. The change laws of maximum pollutants concentration are similar for different connections between HPDE and CCL.

Dynamic changes of views on the brain changes of Cushing's syndrome using different computer-assisted tool.

Cushing's syndrome (CS) provides a unique model for assessing the neurotoxic effect of chronic hypercortisolism on human brains. With the ongoing development of different computer-assisted tools, four research stages emerged, each with its own pearls and pitfalls. This review summarizes current knowledge and describes the dynamic changes of views on the brain changes of CS, especially in the current era of the rapid development of artificial intelligence and big data. The adverse effects of GC on brain are proven to be on structural, functional and cellular levels at the same time.

Associations of fat and carbohydrate intake with becoming overweight and obese: an 11-year longitudinal cohort study.

The effects of macronutrient intake on obesity are controversial. This research aims to investigate the associations between macronutrient intake and new-onset overweight/obesity. The relationship between the consumption of carbohydrate and total fat and obesity was assessed by the multivariable Cox model in this 11-year cohort, which included 6612 adults (3291 men and 3321 women) who were free of overweight and obesity at baseline. The dietary intake was recorded using a 24-h recall method for three consecutive days. Moreover, substitution models were developed to distinguish the effects of macronutrient composition alteration from energy intake modification. During 7·5 person years (interquartile range 4·3, 10·8) of follow-up, 1807 participants became overweight or obese. After adjusting for risk factors, the hazard ratio (HR) of overweight/obesity in extreme quintiles of fat was 1·48 (quintile 5 v. quintile 1, 95 % CI 1·16, 1·89; Ptrend = 0·02) in women. Additionally, replacing 5 % of energy from carbohydrate with equivalent energy from fat was associated with an estimated 4·3 % (HR 1·043, 95 % CI 1·007, 1·081) increase in overweight/obesity in women. Moreover, dietary carbohydrate was inversely associated with overweight/obesity (quintile 5 v. quintile 1, HR 0·70, 95 % CI 0·55, 0·89; Ptrend = 0·02) in women. Total fat was related to a higher risk of overweight/obesity, whereas high carbohydrate intake was related to a lower risk of overweight/obesity in women, which was not observed in men.

Plain Water Intake and Association With the Risk of Overweight in the Chinese Adult Population: China Health and Nutrition Survey 2006-2011.

BACKGROUND: The prevalence of overweight is increasing dramatically worldwide. The aim of our study was to investigate the association of plain water intake (PWI) with the risk of new-onset overweight risk among Chinese adults. METHODS: A total of 3,200 adults aged 18-65 who were free of overweight at baseline were enrolled from China Health and Nutrition Survey (CHNS) cohort study in 2006-2011. The risk of new-onset overweight with different amounts of PWI per day was analyzed in this 5-year cohort. A multiple logistic regression model was used to assess the association of PWI and the risk of new-onset overweight and adjust for potential confounders. Moreover, dose-response models were developed to estimate the linear relationship. RESULTS: During 5 years of follow-up, 1,018 incident cases were identified. Our analysis indicated an inverse association of more than 4 cups of PWI per day and the risk of new-onset overweight among normal weight individuals. Compared with participants who drank 2 to 3 cups PWI, the adjusted odds ratios (OR) of overweight were 0.741 (95% confidence interval [CI], 0.599-0.916) in participants who drank 4 to 5 cups PWI, and 0.547 (95% CI, 0.435-0.687) in participants who drank more than 6 cups PWI. The dose-response analysis showed that every cup of PWI was associated with a 6.5% and 8.4% decrease in the risk of new-onset overweight among men and women, respectively. The interactions of PWI and covariates on the risk of overweight were not found. CONCLUSION: Drinking more than 4 cups (≈1 liter) per day of plain water is associated with decrease in the risk of new-onset overweight among normal-weight individuals.

Trends in age of smoking initiation among the Chinese population born between 1950 and 1997.

OBJECTIVES: Smoking prevalence has significantly increased among Chinese adolescences in the past decades. The aim of our study is to investigate the trends and changing patterns in age of smoking initiation among the Chinese population. STUDY DESIGN: Pooled data from the 2006-2015 China Health and Nutrition Survey was used for analysis. A total of 10,032 adults aged ≥18 years who were born between 1950 and 1997 were separated into five birth cohorts (1950-1959, 1960-1969, 1970-1979, 1980-1989 and 1990-1997). METHODS: Age-specific (10-24 years) smoking initiation rates were calculated by gender, educational level and urbanisation. The multiple logistic models were used for estimates of changes in smoking initiation age. RESULTS: The mean age of smoking initiation decreased substantially from 22.0 years (95% confidence interval [CI]: 21.2-22.7) to 17.5 years (95% CI: 16.2-19.1) over five generations. A large decrease was seen in the initiation age group of 15-24 years in the 1980s cohort (15-19 years: odds ratio [OR] = 0.57; 95% CI: 0.19-0.97; 20-24 years: OR = 0.45; 95% CI: 0.18-0.82); a significant decrease was also found in the 1990s cohort (15-19 years: OR = 0.47; 95% CI: 0.11-0.94; 20-24 years old: OR = 0.34; 95% CI: 0.14-0.85). The peak age of smoking initiation changed from 20 years old to 18 years old over the five generations. CONCLUSIONS: The age of smoking initiation has decreased rapidly in the Chinese population in the past decades. Chinese adolescents are becoming the main target group for the tobacco marketing industry, and national legislations are urgently required.

Prediction of Recurrence after Transsphenoidal Surgery for Cushing's Disease: The Use of Machine Learning Algorithms.

BACKGROUND: There are no reliable predictive models for recurrence after transsphenoidal surgery (TSS) for Cushing's disease (CD). OBJECTIVES: This study aimed to develop machine learning (ML)-based predictive models for CD recurrence after initial TSS and to evaluate their performance. METHOD: A total of 354 CD patients were included in this retrospective, supervised learning, data mining study. Predictive models for recurrence were developed according to 17 variables using 7 algorithms. Models were evaluated based on the area under the receiver operating characteristic curve (AUC). RESULTS: All patients were followed up for over 12 months (mean ± SD 43.80 ± 35.61). The recurrence rate was 13.0%. Age (p < 0.001), postoperative morning serum cortisol nadir (p = 0.002), and postoperative (p < 0.001) and preoperative (p = 0.04) morning adrenocorticotropin (ACTH) level were significantly related to recurrence. AUCs of the 7 models ranged from 0.608 to 0.781. The best performance (AUC = 0.781, 95% CI 0.706, 0.856) appeared when 8 variables were introduced to the random forest (RF) algorithm, which was much better than that of logistic regression (AUC = 0.684, p = 0.008) and that of using only postoperative morning serum cortisol (AUC = 0.635, p < 0.001). According to the feature selection algorithms, the top 3 predictors were age, postoperative serum cortisol, and postoperative ACTH. CONCLUSIONS: Using ML-based models for prediction of the recurrence after initial TSS for CD is feasible, and RF performs best. The performance of most of ML-based models was significantly better than that of some conventional models.

Coagulative necrotic pituitary adenoma apoplexy: A retrospective study of 21 cases from a large pituitary center in China.

PURPOSE: Coagulative necrotic pituitary apoplexy (CNPA) is a clinical entity with unique intraoperative and histopathological manifestations. We aimed to improve the knowledge of this rare disease through the largest case series published to date. METHODS: A retrospective review of 21 CNPA patients was performed from among 5095 patients who underwent surgery for pituitary adenomas at a single institution between January 2009 and June 2017. The demographic, clinical, endocrine, neuroimaging, intraoperative, and histopathological findings, management and prognosis were summarized. RESULTS: Headache was the most common symptom that was observed in 21 patients, followed by visual disturbances (17/21, 81.0%), nausea and vomiting (16/21, 76.2%), electrolyte disturbance (13/21, 61.9%), and oculomotor palsies (10/21, 47.6%). Hypopituitarism with at least one anterior pituitary deficiency, especially panhypopituitarism (10/21, 47.6%), was present in 81.0% of patients. Most patients (81.0%) showed typical MRI appearances. All 21 patients underwent transsphenoidal surgery (TSS), and 16 patients had total tumor resection demonstrated by postoperative MRI. Cottage cheese-like necrosis was observed in 16 patients (76.2%) intraoperatively. Histopathology showed large areas of pink, acellular, coagulative necrotic areas in the central zone, and a pseudocapsule in the border zone. After follow-up for 4.3 ± 2.3 years, only 28.6% of patients still suffered from corticotropic deficiency, and 9.5% of patients had gonadotropic deficiency. These patients were administered the appropriate corresponding hormones for life. CONCLUSIONS: CNPA can be correctly diagnosed preoperatively by typical clinical and MRI characteristics. Early surgery combined with hyperbaric oxygen therapy early postoperatively usually yields satisfactory endocrine and neuro-ophthalmic outcomes.

Pituitary adenomas in patients with multiple endocrine neoplasia type 1: a single-center experience in China.

PURPOSE: To explore the clinical characteristics of pituitary adenomas in patients with MEN1 and to summarize treatment strategies for MEN1 in a Chinese population. METHODS: We retrospectively analyzed 54 MEN1 patients with pituitary adenomas diagnosed at Peking Union Medical College Hospital from March 2003 to January 2017. Clinical data, laboratory testing results, treatments of involved glands and treatment responses were collected and analyzed. RESULTS: The mean age at pituitary adenoma diagnosis was 53.9 ± 17.8. The patients initially consulted the Endocrinology, General Surgery and Neurosurgery departments, in descending frequency. The nonfunctioning adenoma, prolactinoma, GH-secreting adenoma, cosecreting adenoma, and ACTH-secreting adenoma subtypes accounted for 48.1%, 27.8%, 9.3%, 9.3% and 5.6% of the cases, respectively. The remission rate for prolactinomas was 46.2% (6/13) treated with bromocriptine. And the remission rates were 87.5% (7/8) and 100% (3/3) for GH-secreting adenomas and ACTH-secreting adenomas respectively achieved by transsphenoidal surgery. Nineteen (35.2%) patients with asymptomatic nonfunctioning pituitary adenomas showed no progression after a 35-month follow-up with close observation. Regarding treatment priority, patients with thymic carcinoid tumors received first-line surgery, 54% of the patients with enteropancreatic tumors had these tumors treated first, and 26% of all patients had their pituitary adenomas treated first. In acromegalic patients, pituitary lesions tended to be treated first (75%, p = 0.002). PHPT and adrenocortical adenomas can be managed with elective surgery. CONCLUSIONS: The treatment of MEN1 requires cooperation between multidisciplinary teams. Individualized treatment according to the severity of glandular involvement is needed. GH-secreting and ACTH-secreting pituitary adenomas require active treatment, while nonfunctioning pituitary adenomas can be observed closely.

Metformin inhibits growth and prolactin secretion of pituitary prolactinoma cells and xenografts.

Metformin (MET) is a diabetes drug that activates AMP-activated protein kinase (AMPK), and is suggested to have anticancer efficacy. Here, we investigated the role of AMPK signalling in prolactinoma (PRLoma), with particular respect to MET and bromocriptine (BC) as a PRLoma treatment. We analysed AMPK phosphorylation, dopamine D2 receptor (D2R), and oestrogen receptor (ER) expression in both BC-sensitive and -resistant PRLoma samples; effects of the AMPK agonist MET (alone or with BC) on in vitro proliferation and apoptosis, xenograft growth and prolactin (PRL) secretion of BC-sensitive and -resistant cells, and ER expression in xenografts. Some BC-resistant PRLomas showed high D2R expression but extremely low AMPK activation. MET significantly inhibited proliferation of cultured PRLoma cells; MET + BC notably restrained their PRL secretion. MET + BC further decreased tumour growth and serum PRL levels in xenografts than BC treatment alone. ER was down-regulated after AMPK activation in both cultured cells and xenografts. Together, we propose that the AMPK signalling pathway down-regulates ERα and ERß, and suppresses PRLoma growth as well as PRL secretion. Combined MET + BC is a potential treatment for PRLomas.

Tumour lateralization in Cushing's disease by inferior petrosal sinus sampling with desmopressin.

BACKGROUND: Bilateral inferior petrosal sinus sampling (IPSS) with corticotropin-releasing hormone (CRH) is currently the gold standard in the diagnosis of Cushing's disease (CD) and has also been used in tumour lateralization. Our objective was to determine the diagnostic value and lateralization accuracy of IPSS with desmopressin. METHODS: We retrospectively analysed 91 patients with Cushing's syndrome who had either negative findings on pituitary dynamic enhanced magnetic resonance imaging (MRI) or nonsuppressed high-dose dexamethasone suppression tests (HDDST). Thin-slice thoracoabdominal computed tomography (CT) and octreotide receptor imaging of whole body were also negative to rule out ectopic adrenocorticotropin hormone (ACTH) syndrome. All patients went through IPSS with desmopressin. Afterwards, transsphenoidal pituitary surgery, light microscope pathology and immunohistological staining for ACTH were performed in all patients. RESULTS: Diagnosis of CD. Among the 91 patients included, 90 were confirmed with CD, of whom 89 had positive IPSS findings, therefore the sensitivity was 98.9%. The one patient who was negative for CD also had negative IPSS findings, therefore the specificity was 100%. Tumour lateralization. Among the 51 patients who were ultimately diagnosed with CD and whose lateralization by IPSS and surgery was either left or right, 37 had IPSS lateralization in concordance with surgery, therefore the concordance rate was 72.5%. Patients in the concordant group had a higher frequency of right lateralization by surgery. CONCLUSIONS: IPSS with desmopressin is a sensitive approach in the diagnosis of CD and has moderate accuracy in tumour lateralization, making it an alternative choice to IPSS with CRH.