Factors contributing to development and resolution of dysglycemia in patients with pheochromocytomas and catecholamine-secreting paragangliomas.

BACKGROUND: Pheochromocytomas and paragangliomas (PPGLs) are a group of rare neuroendocrine tumors. Dysglycemia has been observed in patients with PPGLs in some small case series. However, there is limited information available on the factors associated with development and resolution of dysglycemia in these patients. PATIENTS AND METHODS: The clinical data of consecutive patients admitted to our hospital with PPGLs between January 2018 and June 2020 were retrospectively analyzed. Clinical characteristics were compared between patients with and without dysglycemia. Logistic regression analysis was used to identify risk factors and receiver-operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of the variables. RESULTS: Among 163 patients, 58.9% had preoperative dysglycemia. Patients with dysglycemia were significantly older at diagnosis (p = 0.01) and were significantly more likely to have hypertension (p = 0.007). White blood cell counts (p = 0.016), 24-hour urinary epinephrine (24hU-E) levels (p < 0.001) and 24-hour urinary norepinethrine levels (p = 0.008) were significantly higher in patients with dysglycemia. Regression analysis showed that age (odds ratio [OR] 1.028, 95% confidence interval [CI] 1.001-1.055; p = 0.041), hypertension (OR 2.164, 95% CI 1.014-4.619; p = 0.046) and the 24hU-E concentration (OR 1.010, 95% CI, 1.001-1.019; p = 0.025) were positively associated with preoperative dysglycemia. Taking age, hypertension, and 24hU-E into account in the same model, the area under the ROC curve for prediction of preoperative dysglycemia was 0.703. The proportion of patients with dysglycemia decreased significantly after surgery (p < 0.001) and patients with preoperative dyssglycemia that resolved after surgery tended to have a larger preoperative tumor diameter (p = 0.018). CONCLUSION: Age, hypertension, and the 24hU-E concentration are risk factors for preoperative dysglycemia. Removal of PPGLs can improve dysglycemia in most patients, and postoperative remission of dysglycemia is associated with the preoperative tumor diameter. These results are important for risk assessment and for selecting optimal therapies in patients with dysglycemia in PPGLs.KEY MESSAGESThere have been insufficient data to identify factors associated with development and resolution of dysglycemia in patients with PPGLs.Our results show that approximately half of the patients with PPGLs develop dysglycemia; age, hypertension, and the 24hU-E concentration are risk factors for preoperative dysglycemia.Removal of the PPGLs improves dysglycemia in a majority of patients, and a large preoperative tumor diameter is associated with remission of dysglycemia after surgery.

Clinical differences between small and large pheochromocytomas and paragangliomas.

Background: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors, most of which are characterized by the release of catecholamine, and range in diameters from less than 1 cm to 10 cm or more. However, knowledge of the differences in clinical features between small and large PPGLs is insufficient. Methods: A retrospective analysis of patients with PPGLs treated at our institution between January 2018 and June 2020 was performed. The clinical characteristics of patients were investigated, and comparisons were made between patients with large and small PPGLs. The logistic regression analysis was used to confirm the risk factors, and the receiver operating characteristic curve was used to evaluate the diagnostic performance of the variables. Results: Totally 263 patients were included, including 110 patients in small tumor group and 153 patients in large tumor group. There were more male patients in the large tumor group (p=0.009). More patients had hypertension (p<0.001) and diabetes (p=0.002) in the large tumor group. The 24-h urinary epinephrine (24hU-E) (p < 0.001) and 24-h urinary norepinephrine (24hU-NE) (p=0.002) concentrations were higher in the large tumor group. In terms of tumor location, adrenal-PPGLs were more frequent in the large tumor group (p<0.001). Multivariate logistic regression analysis showed that male sex [odds ratio (OR): 2.871, 95% confidence interval (CI): 1.444-5.711, p=0.003], 24hU-E concentrations (OR: 1.025, 95% CI:1.004-1.047, p=0.020), 24hU-NE concentrations (OR: 1.002, 95%CI: 1.001-1.004, p=0.045), and adrenal-PPGLs (OR: 2.510, 95% CI:1.256-5.018, p=0.009) were positive risk factors for large tumors. Taking above variables into the same model, the area under the receiver operating characteristic curve of the model for predicting the large tumor was 0.772 (95% CI: 0.706-0.834). After the short-term follow-up, there was no significant difference in tumor recurrence between the two groups (p=0.681). Conclusions: Significant differences in numerous clinical characteristics exist between large and small PPGLs. The male patients were more likely to be with large tumors, and such tumors were more likely to reside on the adrenal glands. Catecholamine measurements also help predict tumor size of PPGLs. Clinical decision-making will benefit from this information.

The clinical characteristics of patients with normotension in pheochromocytomas and paragangliomas.

PURPOSE: The predominant symptom of pheochromocytomas and paragangliomas (PPGLs) is variable hypertension (HTN); however, not all patients with PPGLs develop HTN. Studies of the clinical characteristics of normotensive patients and which patients are more likely to develop HTN in PPGLs are rare. This study was performed to identify the clinical features to better understand this clinical entity. METHODS: All consecutive adult patients with PPGLs were retrospectively enrolled from January 2018 to June 2020. The clinical characteristics of the patients were investigated. Multivariate logistic regression analysis was used to identify risk factors and receiver operating characteristic curves were used to evaluate the diagnostic performance of the variables. RESULTS: There were 203 patients in the analysis, including 115 patients with normotension. Fewer patients with normotensive PPGLs had diabetes (p < 0.001) and clinical symptoms (p < 0.001). The 24-h urinary epinephrine (p = 0.002) and 24-h urinary norepinephrine (24hU-NE) concentrations (p < 0.001) were lower, and tumor diameter (p < 0.001) was smaller in patients with normotensive PPGLs. Multivariate logistic regression analysis showed that diabetes and 24hU-NE concentration were independent and negative risk factors for normotensive PPGLs. The area under the curve of 24hU-NE concentration and diabetes for predicting normotensive PPGLs was 0.788 and 0.634, respectively. Combining diabetes and 24hU-NE concentration into one model, the area under the curve of the model for predicting normotensive PPGLs was 0.817. CONCLUSIONS: Normal blood pressure could not exclude PPGLs. Identifying the clinical characteristics of normotensive and hypertensive patients in PPGLs is helpful for risk stratification and individualized assessment and treatment.

The Clinical Characteristics of Pheochromocytomas and Paragangliomas with Negative Catecholamines.

Pheochromocytomas and paragangliomas (PPGLs) associated with negative catecholamines are not uncommon. However, few studies have examined clinical features of patients with these tumors. In the absence of available data, it is difficult to identify characteristics of patients with potential PPGLs and normal serum and urine screens. Therefore, an analysis of patients with PPGLs was conducted retrospectively to compare the clinical features of patients with positive and negative catecholamines. This study included 214 patients, including 69 patients with negative catecholamines. Prevalence rates of diabetes (p < 0.001) and hypertension (p < 0.001) were lower and tumor diameter (p < 0.001) was smaller in the negative-catecholamine group compared with the positive-catecholamine group. Multivariable logistic regression analysis showed that extra-adrenal PPGLs were independently positively associated with negative catecholamines (p = 0.004); hypertension (p = 0.001) and tumor diameter (p = 0.016) were independently negatively associated with negative catecholamines. There was no significant difference in tumor recurrence between the two groups (mean follow-up, 20.54 ± 11.83 months) (p = 0.44). The results demonstrated that PPGL patients with negative catecholamines were more likely to have extra-adrenal tumors and less likely to have comorbidities, and these patients should also be closely monitored for tumor recurrence.

Use of dexmedetomidine in patients with sepsis: a systematic review and meta-analysis of randomized-controlled trials.

BACKGROUND: Dexmedetomidine is widely used in patients with sepsis. However, its effect on septic patients remains controversial. The objective of this study was to summarize all randomized controlled trials (RCTs) examining dexmedetomidine use in sepsis patients. METHODS: This systematic review and meta-analysis included RCTs comparing dexmedetomidine with other sedatives in adult sepsis patients. We generated pooled relative risks (RRs) and standardized mean differences and performed trial sequential analysis and a cumulative meta-analysis. The primary outcome was mortality, and the secondary outcomes were the length of the intensive care unit stay, duration of mechanical ventilation, number of ventilation-free days, incidence of total adverse event, incidence of delirium, and levels of interleukin 6, tumor necrosis factor alpha, and alanine aminotransferase. RESULTS: We included 19 RCTs that enrolled 1929 patients. Compared with other sedatives, dexmedetomidine decreased the all-cause mortality (RR 0.83; 95% confidence interval [CI] [0.69, 0.99]) and inflammatory response (interleukin 6 and tumor necrosis factor alpha levels at 24 h: standardized mean difference (SMD) - 2.15; 95% CI [- 3.25, - 1.05] and SMD - 1.07, 95% CI [- 1.92, - 0.22], respectively). Trial sequential analysis showed that it is not up to required information size. The overall risk adverse events was similar between dexmedetomidine and the other sedatives (RR 1.27, 95% CI [0.69, 2.36]), but dexmedetomidine increased the risk of arrhythmias (RR 1.43, 95% CI [0.59, 3.51]). Length of intensive care unit stay (SMD - 0.22; 95% CI [- 0.85, - 0.41]), duration of mechanical ventilation (SMD 0.12; 95% CI [- 1.10, 1.35]), incidence of delirium (RR 0.98; 95% CI [0.72, 1.33]), and levels of alanine aminotransferase and creatinine at 24 h were not significantly reduced. CONCLUSIONS: Dexmedetomidine in sepsis patients could significantly reduce mortality compared with benzodiazepines but not with propofol. In addition, dexmedetomidine can significantly decrease inflammatory response in patients with sepsis compared with other sedatives. Dexmedetomidine might lead to an increased incidence of arrhythmias, but its safety profile did not show significant differences in the incidence of total adverse events. Future RCTs are needed to determine the sepsis patient population that would benefit most from dexmedetomidine and its optimal dosing regimen.

Risk Factors for Cardiac Complications in Patients With Pheochromocytoma and Paraganglioma: A Retrospective Single-Center Study.

Background: Catecholamine excess arising from pheochromocytomas and paragangliomas (PPGLs) can cause a wide spectrum of cardiac manifestations. Although there are reviews of reported cases, these reviews lack detailed data, which makes it impossible to perform an accurate analysis. In this study, we conducted a comprehensive analysis of cardiovascular complications (CCs), including PPGL-related myocardial injury, cardiogenic shock, and arrhythmias requiring antiarrhythmic therapy, in a large cohort of patients with PPGL. Methods: We retrospectively analyzed the clinical data of consecutive patients with PPGL admitted between January 2018 and June 2020. The prevalence and the characteristics of patients with CCs were investigated. Moreover, comparisons were made between patients with and without CCs. Results: Compared with the non-CC group, the percentage of men was significantly lower (14/41 vs.92/175, 34.1% vs. 52.6%, p = 0.034) and the proportion of patients with paroxysmal hypertension was significantly higher (13/41 vs.29/173, 31.7% vs.16.8%, p = 0.03) in the CC group. More patients showed excessive sweating (19/41 vs 64/175, 46.3% vs. 24.0%, p = 0.004) and PPGL crisis (7/41 vs. 10/175, 17.1% vs.5.7%, p=0.035) in the CC group. In terms of laboratory findings, higher white blood cell [7.36 (6.49, 20.23) vs. 5.95 (5.1, 6.97)×109/L, p<0.001] and platelet [339.28 ± 108.54 vs. 250.66 ± 70.83(×109/L), p = 0.021] counts were more common in the CC group. There was also a higher prevalence of combination-producing PPGL in the CC group (13/24 vs.20/149, 54.2% vs.13.4%, p<0.001). However, the tumor size, invasive behavior on histology, and hemorrhage or necrosis on histology did not differ between the two groups. Platelet count [odds ratio (OR): 1.009; 95% confidence interval (CI) 1.001-1.016; p=0.023] and combination-secreting PPGL (OR: 5.009; 95% CI 1.365-18.38; p=0.015) are independent risk factors for CCs in patients with PPGL. Conclusions: In patients with PPGL, even in the absence of signs and symptoms of CCs, a work up of cardiology should be strongly considered. Importantly, if patients with PPGLs have higher platelet counts and the combination-secreting pattern, they are more likely to have CCs. Thus, a careful cardiac evaluation should be performed.

Clinical Characteristics and Mortality of Non-tuberculous Mycobacterial Infection in Immunocompromised vs. Immunocompetent Hosts.

Immunosuppression and host vulnerability play a key role in non-tuberculous mycobacteria (NTM) pathogenesis. The objective of this study was to compare the clinical characteristics and mortality of NTM infections in immunocompromised and immunocompetent patients. We used a retrospective dataset obtained from our large, tertiary, urban, teaching hospital which is the medical records of hospitalized patients with NTM infections between January 1, 2013 to December 31, 2020. The information including clinical manifestations, imaging, and NTM etiological data were obtained from the hospital's clinical data system. A total of 480 patients with NTM infections completed species identification. 118 hospitalized NTM patients who met ATS/IDSA NTM diagnostic criteria and had complete medical records were included in the study. The average age was 49.4 years, 57 (48.3%) were female, and 64 (54.2%) were immunosuppressed hosts. In our study, the most common species in order of frequency were: M. intracellulare, M. abscessus, M. avium, and M. kansasii among NTM patients. The most common comorbidity was history of previous tuberculosis (30.5%). Besides malignancy, the most common immunodeficiencies were adult-onset immunodeficiency induced by anti-interferon-gamma autoantibody, SLE, and vasculitis. The immunocompromised patients with NTM had more clinical symptoms, comorbidities and lower lymphocyte counts compared to immunocompetent patients. The mortality we observed in immunocompromised patients of NTM disease was significantly higher than that of immunocompetent patients (HR 3.537, 95% CI 1.526-8.362). Immunosuppressed NTM patients with lower B and CD4+ T lymphocyte counts may more frequently present with disseminated NTM infections, clinical exacerbations, and higher mortality than immunocompetent patients.

Diagnosis and Outcome of Cardiac Paragangliomas: A Retrospective Observational Cohort Study in China.

Background: Cardiac paragangliomas (CPGLs) are rare neuroendocrine tumors that are easily overlooked and difficult to diagnose. Detailed comprehensive data regarding CPGL diagnosis and outcome are lacking. Methods: We retrospectively analyzed a cohort of 27 CPGL patients. This cohort represents the largest such cohort reported to date. Results: The prevalence of trilogy symptoms (concurrent palpitations, hyperhidrosis, and headache) was frequent (9/27, 33.3%). Sensitivity of echocardiography and contrast-enhanced computed tomography for localization of CPGL were 81.8% and 87%, respectively. Octreotide scintigraphy showed 100% sensitivity for detecting GPCLs, while sensitivity of I131-metaiodoben-zylguanidine scintigraphy was only 32.9%. Multiple tumors were found in 29.6% of patients. Most CPGLs originated from the epicardium or root of the great vessels (92.9%) and were mostly supplied by the coronary arteries and their branches (95.7%). Twenty-four patients underwent surgical treatment. Although local invasion was present in 40.0% of patients, it did not affect long-term outcome. Mean follow-up was 6.9 ± 3.6 years. Biochemical remission was achieved in 85% of patients. The recurrence rate was 15%. Conclusions: Manifestations of CPGLs are non-specific and they can be difficult to detect on imaging examinations. Octreotide scintigraphy should be performed in patients with suspected paragangliomas to screen for multiple lesions. Surgical resection of CPGLs can achieve symptom relief and biochemical remission.

Hypereosinophilia with Concurrent Venous Thromboembolism: Clinical Features, Potential Risk Factors, and Short-term Outcomes in a Chinese Cohort.

Idiopathic hypereosinophilia (IHE) and hypereosinophilic syndrome (HES) are benign haematological disorders. Studies have suggested that venous thromboembolism (VTE) is a rare but sometimes fatal complication of hypereosinophilia; however, data are limited. We retrospectively analysed clinical features and short-term outcomes of 63 consecutive patients (82.5% men; mean age, 40.92 ± 10.89 years) with IHE or HES with concurrent VTE from January 1998 through December 2018. Risk factors for pulmonary embolism (PE) were explored by multivariate logistic analysis. DVT and/or PE was detected by imaging in all patients. Independent risk factors for PE were a body mass index of >24.1 kg/m2 (odds ratio [OR]: 5.62, 95% confidence interval [CI]: 1.21-26.13, P = 0.028), peak absolute eosinophil count of >6.3 × 109/L (OR: 5.55, 95% CI: 1.292-23.875, P = 0.021), and >13.9-month duration of hypereosinophilia (OR: 4.51, 95% CI: 1.123-18.09, P = 0.034). All patients were treated with corticosteroids and anticoagulants. The short-term hypereosinophilia remission rate was 100%; no recurrent VTE or major bleeding was observed. Hypereosinophilia is a potential risk factor for VTE. PE in patients with IHE/HES and DVT is associated with a higher body mass index, higher peak absolute eosinophil count, and longer duration of hypereosinophilia. Corticosteroids and anticoagulants provided effective short-term control of hypereosinophilia and VTE.

[The timing of infusion of hypertonic saline to exert protective effect on intestinal barrier function in the rabbit with intestinal ischemia/reperfusion injury].

OBJECTIVE: To study the timing of infusion of hypertonic saline solution (HTS) to exert its protective effect on intestinal barrier function in rabbits with intestinal ischemia/reperfusion (I/R) injury. METHODS: Seventy-two rabbits were randomly divided into four groups (each n=18): sham operation group, I/R group, HTS pretreatment group and HTS delayed treatment group. The intestinal I/R models were produced by blocking the superior mesenteric artery (SMA) for 1 hour followed by release of the SMA. 7.5% HTS (6 ml/kg) was infused in HTS pretreatment group 5 minutes before release of SMA, and HTS was infused in delayed treatment group 2 hours after reperfusion and finished in 5 minutes. Levels of D-lactic acid (D-Lac), lipopolysaccharide (LPS), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) were determined before ischemia and 2, 4, 6 hours after reperfusion. The levels of malonaldehyde (MDA), superoxide dismutase (SOD), myeloperoxidase (MPO) in intestinal tissues of 8 rabbits in each group were measured at 6 hours after reperfusion. Meanwhile the intestinal morphological changes were observed, and the Chin score, which reflected the degree of injury to intestinal mucosa was calculated. RESULTS: Compared with sham operation group, D-Lac, LPS, TNF-α and IL-10 in I/R group were significantly increased from 2 hours after reperfusion (D-Lac: 18.91 ± 3.46 mg/L vs. 3.92 ± 0.61 mg/L, LPS: 869 ± 85 EU/L vs. 422 ± 27 EU/L, TNF-α: 23.80 ± 4.22 µg/L vs. 3.65 ± 0.51µg/L, IL-10: 8.90 ± 2.75 µg/L vs. 2.53 ± 0.80 µg/L, all P<0.05); MDA, MPO and Chiu score were significantly increased (MDA: 398 ± 28 nmol/mg vs. 173 ± 20 nmol/mg, MPO: 465 ± 52 mU/mg vs. 183 ± 25 mU/mg, Chiu score: 4.36 ± 0.52 vs. 0.38 ± 0.22, all P<0.05), while SOD decreased significantly (35 ± 9 U/mg vs. 52 ± 8 U/mg, P<0.05). Compared with I/R group, the levels of D-Lac, LPS, TNF-α, MDA, MPO and Chiu score in HTS pretreatment group were lower (D-Lac: 11.45 ± 0.92 mg/L vs. 18.91 ± 3.46 mg/L, LPS: 455 ± 114 EU/L vs. 869 ± 85 EU/L, TNF-α: 10.32 ± 2.11 µg/L vs. 23.80 ± 4.22 µg/L, MDA: 221 ± 21 nmol/mg vs. 398 ± 28 nmol/mg, MPO: 271 ± 20 mU/mg vs. 465 ± 52 mU/mg, Chiu score: 1.69 ± 0.24 vs. 4.36 ± 0.52, all P<0.05), while IL-10 and SOD were significantly increased (IL-10: 14.54 ± 2.02 µg/L vs. 8.90 ± 2.75 µg/L, SOD: 90 ± 14 U/mg vs. 35 ± 9 U/mg, both P<0.05). The levels of the above indexes in HTS delayed treatment group were similar to I/R group, and the effect was lower than that in HTS pretreatment group. CONCLUSIONS: HTS had the protective effect on intestine suffering from I/R injury. But the protective effect was time dependent, and early treatment shows protective effect.

[Apoptosis of gastric mucosa and gastric barrier dysfunction in acute ischemic stroke].

OBJECTIVE: To evaluate the role of gastric mucosa apoptosis in the stress of ischemic stroke, and to discuss the relationship between gastric mucosa apoptosis and gastric barrier. METHODS: Ten dogs were artificially made ischemic stroke by operation (IS group), and another 10 shamly-operated dogs were served as control group. Sucrose permeability were measured after the operation. All dogs were sacrificed 24 hours after operation to measure the gastric mucosal apoptosis index, gastric gross classification, and histological score. RESULTS: The gastric mucosal apoptosis index in the IS group were significantly higher than in the control group (14.83 +/- 4.41 vs. 5.60 +/- 2.61, P < 0.05). The gastric mucosal apoptosis index were correlated with the sucrose permeability (r = 0. 89, P < 0.05) , gastric gross classification (r = 0. 87, P < 0.05), and histological score (r = 0.92, P < 0.05). CONCLUSIONS: Although ischemic stroke will not cause the obvious damage in the respiratory and circulatory system, it is responsible for the apoptosis of epithelial cell in the gastric mucosa and gastric barrier dysfunction. The apoptosis index is closely correlated with the damage of the function and morphology of the gastric barrier, indicating that the epithelial cell apoptosis acceleration in the gastric mucosa may result in the damage of gastric barrier function.