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1.
《Endocrine practice》2021,27(9):886-893
ObjectiveThyroid immune-related adverse events (irAEs) have been reported to have prognostic significance among patients with cancer treated with anti-programmed cell death-1 (PD1) and anti-programmed death-ligand 1 monotherapies. We evaluated the clinical course and predictors of thyroid irAEs in relation to outcomes of patients with advanced cancer treated with combination anti-PD1/anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4).MethodsWe conducted a regional study and identified patients with advanced cancer who received ≥1 cycle of combination anti-PD1/anti-CTLA4 between 2015 and 2019 in Hong Kong. Thyroid function tests (TFTs) were monitored every 3 weeks. Thyroid irAE was defined by ≥2 abnormal TFTs after initiation of combination anti-PD1/anti-CTLA4 in the absence of other causes.ResultsOne hundred and three patients were included (median age: 59 years; 71.8% men). About 45% had prior anti-PD1 exposure. Upon median follow-up of 6.8 months, 17 patients (16.5%) developed thyroid irAEs, where 6 initially presented with thyrotoxicosis (overt, n = 4; subclinical, n = 2) and 11 with hypothyroidism (overt, n = 2; subclinical, n = 9). Eventually, 10 patients (58.8%) required continuous thyroxine replacement. Systemic steroid was not required in all cases. Prior anti-PD1 exposure (odds ratio, 3.67; 95% CI, 1.19–11.4; P = .024) independently predicted thyroid irAEs. Multivariable Cox regression analysis revealed that occurrence of thyroid irAEs was independently associated with better overall survival (adjusted hazard ratio, 0.34; 95% CI, 0.17–0.71; P = .004).ConclusionThyroid irAEs are common in routine clinical practice among patients with advanced cancer treated with anti-PD1/anti-CTLA4 combination and might have potential prognostic significance. Regular TFT monitoring is advised for timely treatment of thyroid irAEs to prevent potential morbidities. 相似文献
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《Endocrine practice》2021,27(4):348-353
ObjectiveTo compare metastatic pheochromocytoma/paraganglioma (MPP) patients with germline SDHB mutations (SDHB MPP) and without SDHB mutations (non-SDHB MPP) in terms of baseline clinical manifestations, tumor characteristics, and outcomes.MethodsClinical data were retrospectively reviewed in 101 MPP patients, including 34 SDHB MPP patients and 61 non-SDHB MPP patients.ResultsSDHB MPP patients presented at a younger age at onset, diagnosis, or metastasis (25 ± 16 vs 36 ± 14, 28 ± 17 vs 38 ± 15, and 31 ± 17 vs 44 ± 14 years old, respectively, P < .01 for all) than non-SDHB patients. Compared with their non-SDHB counterparts, SDHB patients were more likely to have paragangliomas (83% vs 47%, P < .05), synchronous metastases (44% vs 23%, P < .05), bone metastases (80% vs 48%, P < .01), and a shorter progression-free survival (3 years vs 5 years, P < .01). The Ki-67 index was higher in SDHB tumors (P < .05). The 5- and 10-year survival rates were 79% and 74%, respectively, in all patients. Seventeen patients died from MPP, and the time from metastasis to death in patients who had received systemic therapy was significantly longer than in those who had not (3.1 ± 1.5 vs 1.4 ± 0.7 years, P < .01).ConclusionCompared with MPP patients without SDHB mutations, MPP patients with SDHB mutations were younger at onset, diagnosis, or metastasis; had a higher incidence of synchronous metastases, higher ratio of paraganglioma, and higher Ki-67 index; had a shorter postoperative progression-free survival; and were more likely to develop bone metastasis or sole liver metastasis. Our results suggest that patients with SDHB mutations should be identified early and monitored regularly to achieve optimal clinical outcomes. 相似文献
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《Endocrine practice》2021,27(9):874-880
ObjectiveThe clinical significance of the YY1 gene mutation and expression in pancreatic neuroendocrine tumors (PNETs) remains unknown. Therefore, this study aimed to comprehensively analyze the somatic mutation of YY1 in the different subtypes of PNETs.MethodsA total of 143 PNETs were assessed by Sanger sequencing to identify the somatic mutation of YY1 gene in various subtypes of PNETs. YY1 protein expression was examined in 103 PNETs by immunohistochemical staining and western blot. Gene mutation and its protein expression were correlated with clinicopathologic features.ResultsA recurrent mutation (chr14:100743807C>G) in the YY1 gene was identified in 15 of 83 insulinomas (18%) and in only 1 of 60 noninsulinoma PNETs (1.7%) (P = .0045). The YY1 mutation was not found in MEN1-associated insulinomas. The YY1 mutation in insulinomas was correlated with older age and lower serum glucose levels (age, 57 vs 42.5 years, P = .006; blood glucose, 25.2 vs 33.6 mg/dL, P = .008). YY1 protein expression was found in 100 of 103 PNETs, although expression was weaker in metastases than in localized tumors (P = .036). The stronger expression of YY1 protein was associated with favorable disease-free survival of patients with PNETs (log-rank, P = .011; n = 70). Multivariable statistical analysis showed that YY1 protein expression could be an independent predictor of prognosis.ConclusionThe hotspot YY1 mutation mostly occurred in insulinomas and rarely in noninsulinoma PNETs. The stronger YY1 protein expression was correlated with the better prognosis of PNETs patients. 相似文献
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《Molecular & cellular proteomics : MCP》2022,21(12):100435
Metastasis is the primary cause of death for most breast cancer (BC) patients who succumb to the disease. During the hematogenous dissemination, circulating tumor cells interact with different blood components. Thus, there are microenvironmental and systemic processes contributing to cancer regulation. We have recently published that red blood cells (RBCs) that accompany circulating tumor cells have prognostic value in metastatic BC patients. RBC alterations are related to several diseases. Although the principal known role is gas transport, it has been recently assigned additional functions as regulatory cells on circulation. Hence, to explore their potential contribution to tumor progression, we characterized the proteomic composition of RBCs from 53 BC patients from stages I to III and IV, compared with 33 cancer-free controls. In this work, we observed that RBCs from BC patients showed a different proteomic profile compared to cancer-free controls and between different tumor stages. The differential proteins were mainly related to extracellular components, proteasome, and metabolism. Embryonic hemoglobins, not expected in adults’ RBCs, were detected in BC patients. Besides, lysosome-associated membrane glycoprotein 2 emerge as a new RBCs marker with diagnostic and prognostic potential for metastatic BC patients. Seemingly, RBCs are acquiring modifications in their proteomic composition that probably represents the systemic cancer disease, conditioned by the tumor microenvironment. 相似文献
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《Endocrine practice》2021,27(7):736-742
ObjectiveThe KCNJ5 mutation is the most frequent mutation in aldosterone-producing adenoma (APA). We aimed to illustrate the relationship between KCNJ5 and prognosis after adrenalectomy as a guide for further treatment.MethodsOur study included 458 patients with APA. Tumor tissues were screened for somatic mutations in KCNJ5 hot-spot regions. We performed a retrospective analysis to identify correlations between KCNJ5 and clinical outcomes in 334 patients with adrenal venous sampling lateralization.ResultsSomatic KCNJ5 mutations were identified in 324 of 458 patients with APA (70.7%). Compared with the KCNJ5-wild type patients, patients with KCNJ5 mutations were younger, had a higher proportion of women, and had shorter durations of hypertension, lower body mass indexes (BMIs), and lower systolic blood pressure values (P < .05). During follow-up, among the 334 patients with APA with adrenal venous sampling lateralization, 320 (95.8%) presented complete biochemical success and 187 (56.0%) presented complete clinical success. One hundred eighty-seven patients with primary aldosteronism who achieved complete clinical success presented the following characteristics: age <40 years (78.7%), BMI <24 kg/m2 (71.0%), hypertension duration <5 years (78.4%), females (66.9%), and KCNJ5 mutation (65.5%). A multivariate logistic regression analysis identified BMI, hypertension duration, and KCNJ5 mutation as independent predictors of complete clinical success.ConclusionThe prevalence of KCNJ5 mutations was 70.7%. KCNJ5 mutation is a protective factor of complete clinical success, while BMI and hypertension duration were risk factors of incomplete clinical success. 相似文献
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Heli Gao Jia Dong Wuhu Zhang Huaxiang Xu Longyun Ye Hao Li Quanxing Ni Wenquan Wang Liang Liu 《Endocrine practice》2022,28(3):292-297
ObjectiveThe role of alternate sequential administration of sunitinib and capecitabine/temozolomide (CAPTEM) in metastatic pancreatic neuroendocrine tumors (PanNETs) remains unexplored. We thus aimed to analyze the efficacy and tolerability of this strategy in advanced grade 1/grade 2 PanNETs.MethodsIn total, data of 43 patients with metastatic PanNET were collected from a real-world database of a cancer center. Twenty-four patients were treated with sunitinib followed by CAPTEM (group 1), and 19 patients were treated with CAPTEM followed by sunitinib (group 2).ResultsTwenty-three patients were treated with first-line sunitinib or CAPTEM, and 20 patients were pretreated with somatostatin analog (SSA) or SSA in combination with transcatheter arterial chemoembolization. The objective response rate with first-line treatment was similar in both groups, whereas that with second-line treatment was higher in group 1 than in group 2, albeit with no significant differences (21.1% vs 5.3%, respectively; P = .205). Median progression-free survival (mPFS) for first-line and second-line treatments did not differ between the 2 groups (11 and 12 months vs 12 and 8 months, respectively). Following subgroup analyses, treatment with first-line sunitinib and sunitinib after pretreated SSA had a longer mPFS than that with second-line sunitinib after CAPTEM (11 months vs 8 months, respectively; P = .046), whereas treatment with first-line CAPTEM and CAPTEM after pretreated SSA had an mPFS similar to that of second-line CAPTEM after sunitinib treatment. CAPTEM and sunitinib had similar tolerability.ConclusionAlternating sunitinib and CAPTEM were well tolerated and associated with similar mPFS in grade 1/grade 2 PanNETs. However, larger prospective studies are required to investigate the efficacy of alternate sequential therapies for metastatic PanNET. 相似文献
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《Endocrine practice》2022,28(10):1100-1106
ObjectiveSince January 2020, the highly contagious novel coronavirus SARS-CoV-2 has caused a global pandemic. Severe COVID-19 leads to a massive release of proinflammatory mediators, leading to diffuse damage to the lung parenchyma, and the development of acute respiratory distress syndrome. Treatment with the highly potent glucocorticoid (GC) dexamethasone was found to be effective in reducing mortality in severely affected patients.MethodsTo review the effects of glucocorticoids in the context of COVID-19 we performed a literature search in the PubMed database using the terms COVID-19 and glucocorticoid treatment. We identified 1429 article publications related to COVID-19 and glucocorticoid published from 1.1.2020 to the present including 238 review articles and 36 Randomized Controlled Trials. From these studies, we retrieved 13 Randomized Controlled Trials and 86 review articles that were relevant to our review topics. We focused on the recent literature dealing with glucocorticoid metabolism in critically ill patients and investigating the effects of glucocorticoid therapy on the immune system in COVID-19 patients with severe lung injury.ResultsIn our review, we have discussed the regulation of the hypothalamic-pituitary-adrenal axis in patients with critical illness, selection of a specific GC for critical illness-related GC insufficiency, and recent studies that investigated hypothalamic-pituitary-adrenal dysfunction in patients with COVID-19. We have also addressed the specific activation of the immune system with chronic endogenous glucocorticoid excess, as seen in patients with Cushing syndrome, and, finally, we have discussed immune activation due to coronavirus infection and the possible mechanisms leading to improved outcomes in patients with COVID-19 treated with GCs.ConclusionFor clinical endocrinologists prescribing GCs for their patients, a precise understanding of both the molecular- and cellular-level mechanisms of endogenous and exogenous GCs is imperative, including timing of administration, dosage, duration of treatment, and specific formulations of GCs. 相似文献
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《Endocrine practice》2022,28(9):859-866
Objective5α-Reductase type 2 (5α-RD2) deficiency causes variable degrees of undervirilization in patients. The correlation between its genotype and phenotype is unclear.MethodsWe retrospectively evaluated 103 patients with 46,XY disorders of sex development who were diagnosed with 5α-RD2 deficiency.ResultsThe prevalence of female sex assignment (P = .008) and the incidences of cryptorchidism (P = .0003) and bifid scrotum (P = .0002) in the non-p.R227Q variant group were higher, but there were no significant differences in the incidences of hypospadias and isolated microphallus. The external masculinization score in the non-p.R227Q variant group was lower than that in the homozygous p.R227Q variant (P = .019) and compound heterozygous p.R227Q variant groups (P = .013). The level of anti-Mullerian hormone in the non-p.R227Q variant group was lower than that in the homozygous p.R227Q variant (P < .001) and compound heterozygous p.R227Q variant groups (P = .006). The testosterone-to-dihydrotestosterone ratio of the homozygous p.R227Q variant group was higher than that of the non-p.R227Q variant (P = .018) and compound heterozygous p.R227Q variant groups (P = .029). Twenty-three reportedly pathogenic variants and 11 novel steroid 5α-reductase 2 (SRD5A2) variants were identified.ConclusionCompared with patients without p.R227Q, patients with p.R227Q exhibited higher external masculinization scores and anti-Mullerian hormone expression, a lower prevalence of female sex assignment, and lower incidences of cryptorchidism and bifid scrotum. We identified 23 reportedly pathogenic SRD5A2 variants and 11 novel SRD5A2 variants that led to 5α-RD2 deficiency. We established a genotype-phenotype correlation, and patients with p.R227Q showed a relatively mild phenotype. 相似文献
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《Endocrine practice》2021,27(9):912-917
ObjectiveActive surveillance (AS) is a management alternative for patients with low-risk papillary thyroid microcarcinoma (PTMC). To decide the best candidates for AS, clinicians can use a framework to classify PTMC patients as ideal, appropriate, or inappropriate. This study aimed to explore the correlation between the framework categories and surgical pathology.MethodsThis multicenter retrospective study was conducted between 2014 and 2016. We included 1997 patients who underwent thyroid surgery for the first time due to suspected PTMC and were confirmed as PTMC by postoperative pathology. The consistency of modified preoperative risk stratification and the pathologic condition were evaluated using a consistency ratio and the Kappa coefficient. Stratified analysis was also performed to test consistency in different age groups.ResultsBased on the decision-making framework, 558 (27.9%) patients could receive AS while 810 (40.6%) patients did not require immediate surgery according to the actual postoperative pathology. The sensitivity, false-positive rate, specificity, false-negative rate, and consistency rate were 82.39%, 56.91%, 43.09%, 17.61%, and 66.45%, respectively. The Kappa value was 0.268. Stratified analysis showed that the sensitivity was 87.7% among patients aged 18 to 59 years. In the group aged ≥60 years, the specificity was up to 87.5%, but the sensitivity was low.ConclusionThe results of the modified risk-stratified clinical decision-making framework did not have a high consistency with the postoperative results. However, the framework showed a good effect in selecting patients for immediate surgery in the younger group and patients for AS in the older group. 相似文献
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Rashika Bansal Elaine Cochran Megan Startzell Rebecca J. Brown 《Endocrine practice》2022,28(6):610-614
ObjectiveSevere insulin resistance syndromes, such as lipodystrophy, lead to diabetes, which is challenging to control. This study explored the safety and efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in a series of 12 patients with severe insulin resistance due to partial lipodystrophy.MethodsA retrospective chart review of the safety (N = 22) and efficacy (N = 12) of SGLT2is in patients with partial lipodystrophy was conducted at our institution. The efficacy outcomes included hemoglobin A1C level, insulin dose, fasting plasma glucose level, C-peptide level, lipid profile, 24-hour urinary glucose excretion, estimated glomerular filtration rate, and blood pressure before and after 12 months of SGLT2i treatment.ResultsThe hemoglobin A1C level decreased after SGLT2i treatment (at baseline: 9.2% ± 2.0% [77.0 ± 21.9 mmol/mol]; after 12 months: 8.4% ± 1.8% [68.0 ± 19.7 mmol/mol]; P = .028). Significant reductions were also noted in systolic (P = .011) and diastolic blood pressure (P = .013). There was a trend toward a decreased C-peptide level (P = .071). The fasting plasma glucose level, lipid level, and estimated glomerular filtration rate remained unchanged. The adverse effects included extremity pain, hypoglycemia, diabetic ketoacidosis (in a patient who was nonadherent to insulin), pancreatitis (in a patient with prior pancreatitis), and fungal infections.ConclusionSGLT2is reduced the hemoglobin A1C level in patients with partial lipodystrophy, with a similar safety profile compared with that in patients with type 2 diabetes. After individual consideration of the risks and benefits of SGLT2is, these may be considered a part of the treatment armamentarium for these rare forms of diabetes, but larger trials are needed to confirm these findings. 相似文献
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《Endocrine practice》2023,29(2):97-103
ObjectiveTo assess the diagnostic performance of initial post-therapeutic 131I single-photon emission computed tomography/computed tomography (SPECT/CT) compared with that of reoperation in detecting residual lymph node metastasis (LNM).MethodsPatients with iodine-avid LNM detected on the initial post-therapeutic 131I SPECT/CT and who underwent reoperative dissection within 6 months were included. LNMs (numbers and locations) detected via both methods were compared. The American Thyroid Association dynamic risk stratification was performed for patients receiving second radioactive iodine therapy after reoperation.ResultsFifty-three patients with 95 iodine-avid LNMs detected by 131I SPECT/CT were enrolled. Fifty-one (96.2%) patients had 212 LNMs confirmed by reoperation (P = .004). The sensitivity and specificity of 131I SPECT/CT in detecting LNM were 44.8% (95/212) and 91.6% (87/95), respectively. The location frequency of residual LNMs found by 131I SPECT/CT was similar to that of reoperation (P = .057). Thirty-two patients received a second radioactive iodine treatment, and 6 (18.8%) patients still had residual iodine-avid LNM on SPECT/CT. Therapeutic response was evaluated by American Thyroid Association dynamic risk stratification in 16 patients. The number of patients with structural incomplete response, biochemical incomplete response, indeterminate response, and excellent response was 4 (23.5%), 4 (23.5%), 5 (29.4%), and 3 (17.6%), respectively.Conclusion131I SPECT/CT has high specificity but relatively low sensitivity in detecting all residual LNMs. Approximately 80% of patients were rendered structurally disease free after reoperation. 相似文献
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ObjectiveTo evaluate the relationship between markers of glycemic variability (GV), assessed by blinded continuous glucose monitoring (CGM), and cardiovascular autonomic neuropathy (CAN) in patients with type 1 diabetes (T1D).MethodsGV indices, such as SD and coefficient of variation were obtained by blinded CGM through an electrode inserted into the subcutaneous tissue for at least 3 consecutive days. CAN was assessed by cardiovascular reflex tests and HRV.ResultsFifteen T1D patients were included: 7 (46.7%) women, aged 47.1 ± 11.6 years, with a diabetes duration of 26 years (20 to 29.5 years). Five patients (25%) were excluded from our study. The majority of our patients presented glycated hemoglobin (60%), SD (86.3%), and coefficient of variation (60%) above the established goals. Patients with defined CAN had a longer diabetes duration, higher glycated hemoglobin levels, lower glomerular filtration rate, lower prevalence of indices related to hypoglycemic stress, and short-term GV indices compared with patients without CAN.ConclusionOur study showed an inverse association between GV and CAN. The most important risk factors associated with CAN were age, diabetes duration, and markers of chronic hyperglycemia. Furthermore, the difficulty in the interpretation of data extracted from the blinded CGM system, which also requires a minimum of 3 capillary blood glucose measurements for calibration, should be carefully analyzed to ensure the accuracy and usefulness of the blinded CGM system as a tool for diabetes management in developing countries. Further studies are necessary to establish the role of GV in the development of CAN in patients with T1D. 相似文献
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Daniel Erez Coral Shefler Eytan Roitman Sigal Levy Zamir Dovrish Martin Ellis Orit Twito 《Endocrine practice》2022,28(2):129-134
ObjectiveAnemia is a known complication of diabetes mellitus (DM); however, its prevalence and prognostic relevance in patients with DM and pre-DM with normal kidney function have not been well defined. This study assessed the prevalence of anemia in patients with DM and pre-DM and evaluated its association with clinical outcomes during a 4-year follow-up period.MethodsThis retrospective analysis included patients with DM and pre-DM referred to the Meir Medical Center Endocrine Institute in 2015. Patients with an estimated glomerular filtration rate (eGFR) of <60 mL/min or any other recognized cause of anemia were excluded. The risk of developing microvascular or macrovascular complications or of death during the 4-year follow-up period was determined.ResultsA total of 622 patients (408 with DM and 214 with pre-DM) were included. The mean age of the patients was 64 ± 10.6 years, and 70% were women. The baseline hemoglobin A1C level was 7.1% ± 1.7% (54 mmol/mol), and the eGFR was 86.1 ± 15.3 mL/min. At the time of inclusion, 77 patients (19%) with DM and 23 (11%) with pre-DM had anemia (hemoglobin level 11.9 ± 0.8 and 11.8 ± 0.8 g/dL, respectively), compared with normal hemoglobin levels of 13.8 ± 0.9 and 13.7± 0.9 g/dL, respectively, in the others. A multivariable analysis demonstrated an inverse correlation between baseline hemoglobin (as a continuous variable) and mortality (P = .035), microvascular complications (P = .003), and eGFR decline (P < .001) but not between baseline hemoglobin and macrovascular complications (P = .567).ConclusionThis study found a significant prevalence of anemia unrelated to renal failure, both in patients with DM and pre-DM. Anemia in these patients is associated with the development of microvascular complications, eGFR decline, and mortality. These results underscore the need for intensive lifestyle and pharmacologic interventions in these patients. 相似文献
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《Endocrine practice》2021,27(12):1175-1182
ObjectiveTo develop and validate an individualized risk prediction model for the need for central cervical lymph node dissection in patients with clinical N0 papillary thyroid carcinoma (PTC) diagnosed using ultrasound.MethodsUpon retrospective review, derivation and internal validation cohorts comprised 1585 consecutive patients with PTC treated from January 2017 to December 2019 at hospital A. The external validation cohort consisted of 406 consecutive patients treated at hospital B from January 2016 to June 2020. Independent risk factors for central cervical lymph node metastasis (CLNM) were determined through univariable and multivariable logistic regression analysis. An individualized risk prediction model was constructed and illustrated as a nomogram, which was internally and externally validated.ResultsThe following risk factors of CLNM were established: a solitary primary thyroid nodule’s diameter, shape, calcification, and capsular abutment-to-lesion perimeter ratio. The areas under the receiver operating characteristic curves of the risk prediction model for the internal and external validation cohorts were 0.921 and 0.923, respectively. The calibration curve showed good agreement between the nomogram-estimated probability of CLNM and the actual CLNM rates in the 3 cohorts. The decision curve analysis confirmed the clinical usefulness of the nomogram.ConclusionThis study developed and validated a model for predicting the risk of CLNM in individual patients with clinical N0 PTC, which should be an efficient tool for guiding clinical treatment. 相似文献
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《Endocrine practice》2021,27(8):813-818
ObjectiveFrequent, finger-prick capillary blood glucose measurement is standard care, used to drive insulin infusion rates for inpatients being resuscitated from diabetic ketoacidosis (DKA). Over recent years there has been a shift toward continuous interstitial glucose monitoring, allowing monitoring of glucose without repeated invasive testing. While continuous interstitial glucose monitoring has been safely and reliably utilized in the outpatient setting, it has yet to be studied in acutely unwell patients with DKA. The aim of this study, allowing for physiologically lower interstitial compared to capillary glucose, was to determine if interstitial flash glucose monitoring (FGM) would lead to insulin infusion rates that were similar to capillary blood glucose (CapBG) in DKA.MethodsIn this study, 10 patients with diabetes mellitus, assessed to be in DKA, were enrolled. At the same time as standard DKA management commencement, simultaneous FGM measurements were obtained. Duplicate paired glucose readings were then analyzed for agreement.ResultsActual (CapBG-driven) and predicted (FGM determined) insulin infusion rates were similar. Minor differences in predicted insulin infusion rates were noted in 2/10 patients at higher glucose concentrations, which may relate to the lag in change in glucose in the interstitial space.ConclusionBased on our results, a trial of clinical outcomes in patients with DKA treated with insulin infusion rates driven by CapBG versus subcutaneous FGM appears justified. The FGM method of testing may improve patient comfort, obviate fatigue, improve staff time and direct patient contact, and potentially facilitate rapid discharge. 相似文献