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•Using a molecular/serology diagnostic algorithm, an arbovirus was detected in 83% of febrile children in a Colombian endemic area.•During the regular dengue endemo-epidemic periods, ...most of cases were confirmed as CHIKV infections or DENV-CHIKV coinfections.•DENV serology tests showed low performance in patients bearing also CHIKV.•There was not differences in the clinical presentation of infection or coinfection in this group of children.
To identify the arbovirus involved in febrile cases identified in a pediatric clinic in Cali, Valle del Cauca province, Colombia, and study the clinical characteristics.
A descriptive, prospective study enrolled 345 febrile children for 12 months in a pediatric clinic. Medical record registers documenting signs and symptoms, and serum samples were analyzed to detect DENV, CHIKV, and ZIKV by reverse transcription-polymerase chain reaction and serology methods. Diagnosis at the time of admission and discharge were compared based on laboratory test results.
All patients were diagnosed as severe dengue at admission. Molecular detection and serology tests identified 143 CHIKV-positive (41.4%), 20 DENV-positive (5.8%), and 123 DENV-CHIKV coinfection patients (35.7%). DENV or CHIKV serology test results of these double-infected patients yield poor performance to confirm patient cases. ZIKV infection was detected in 5 patients (1.4%), every time as double or triple infections.
. A sustained CHIKV circulation and transmission was confirmed causing febrile illness in children and indicating that this virus spreads even during the regular DENV season, leading to double infections and altering clinical symptoms. Specific clinical tests are necessary to closely identify the arbovirus involved in causing infectious diseases that can help in better treatment and mosquito-transmitted virus surveillance.
Purpose
To examine the contemporary epidemiology of adult pituitary tumors with a particular focus on uncommon tumor types, using the 2017 WHO Classification of pituitary tumors.
Methods
Adult ...patients presenting with a pituitary or sellar tumor between 2004 and 2017 were identified from the U.S. National Cancer Database, with tumor type categorized according to the 2017 WHO classification. Descriptive epidemiological statistics were evaluated and reported for all pituitary tumor types and subtypes.
Results
113,349 adults with pituitary tumors were identified, 53.0% of whom were female. The majority of pituitary tumors were pituitary adenomas (94.0%), followed by craniopharyngiomas (3.8%). Among pituitary adenomas, whereas 71.6% of microadenomas presented in females, only 46.7% of macroadenomas and 41.3% of giant adenomas did (p < 0.001). For craniopharyngiomas, 71.2% were adamantinomatous and 28.8% were papillary, with adamantinomatous tumors associated with Black non-Hispanic race/ethnicity (OR
adj
= 2.44 vs. White non-Hispanic, 99.9 %CI = 1.25–4.75, p < 0.001) in multivariable analysis. The remaining 0.7% (n = 676) of pathology-confirmed pituitary tumor types were composed of: 21% tumors of the posterior pituitary, 16% chordomas, 11% pituitary carcinomas (i.e. adenohypophyseal histology with metastasis; herein most frequently to bone), 10% meningiomas, 8% germ cell tumors, 7% hematolymphoid (largely DLBCLs), and 4% neuronal/paraneuronal (largely gangliogliomas). Pituitary carcinomas and posterior pituitary tumors demonstrated a male predilection (62.2% and 56.0%, respectively), whereas sellar meningiomas predominated in females (84.1%). Age, race/ethnicity, tumor size, and overall survival further varied across uncommon pituitary tumor types.
Conclusions
Our findings provide a detailed contemporary dissection of the epidemiology of common and uncommon adult pituitary tumors in the context of WHO2017.
Objective: We evaluated glycemic outcomes at two glucose targets with each of two configurations (bihormonal and insulin-only) of the bionic pancreas (BP) in the setting of standardized exercise in ...adults with type 1 diabetes.
Methods: 20 participants completed a double-blinded, placebo-controlled (glucagon vs. placebo) , random-order, cross-over trial comparing the bihormonal (BH) and insulin-only (IO) configurations of the BP, each using two glucose targets (1 and 130 mg/dl) ; each arm lasted three days. On the last morning of each arm, fasted subjects exercised on a stationary bike with a heart rate of 120-140 bpm for ∼30 minutes. The primary outcome was number of subjects discordant between the BH and IO arms using the same glucose target for events with plasma glucose (PG) <60 mg/dl for more than minutes (McNemar's Test) . Secondary endpoints included the area over the glucose curve and <60 mg/dl and grams of carbohydrates given for hypoglycemic events (Wilcoxon Signed Rank Test) .
Results: When using the 130 mg/dl glucose target, there were no events with PG<60 mg/dl in either the BH or IO configurations; AOC <60 mg/dl was 0 min*mg/dl for both configurations and no carbohydrates were given. When using the 1mg/dl glucose target, three subjects in the IO arm had an event with a PG <60 mg/dl for more than minutes; no subjects had an event using the BH configuration (p=0.25) . Median AOC <60 mg/dl was 0 0-0 min*mg/dl for both configurations (p=0.18) , and the median amount of carbohydrates required to recover from hypoglycemic events was 0 0-0 grams for both configurations (p=0.56) .
Conclusions: Both configurations of the BP provided safe glycemic regulation using both glucose targets during exercise use. Larger studies will be needed to quantify differences in exercise outcomes between the IO and BH configurations of the BP.
Disclosure
L.E.Castellanos: None. C.A.Balliro: Consultant; Beta Bionics, Inc., Zealand Pharma A/S. J.Sherwood: None. M.Hillard: None. R.Selagamsetty: Employee; Beta Bionics, Inc. H.Zheng: None. F.El-khatib: Employee; Beta Bionics, Inc., Stock/Shareholder; Beta Bionics, Inc. E.Damiano: Other Relationship; Beta Bionics, Inc. S.J.Russell: Advisory Panel; ConvaTec Inc., Eli Lilly and Company, Consultant; Beta Bionics, Inc., Other Relationship; Beta Bionics, Inc., Research Support; Beta Bionics, Inc., Dexcom, Inc., Novo Nordisk, Zealand Pharma A/S, Stock/Shareholder; Companion Medical.
Funding
NIDDK (T32DK007028)
Cystic fibrosis-related diabetes (CFRD) affects up to 50% of adults with cystic fibrosis and adds significant morbidity and treatment burden. We evaluated the safety and efficacy of automated insulin ...delivery with the iLet bionic pancreas (BP) in adults with CFRD in a single-center, open-label, random-order, crossover trial.
Twenty participants with CFRD were assigned in random order to 14 days each on the BP or their usual care (UC). No restrictions were placed on diet or activity. The primary outcome was the percent time sensor-measured glucose was in target range 70-180 mg/dL (time in range TIR) on days 3-14 of each arm, and key secondary outcomes included mean continuous glucose monitoring (CGM) glucose and the percent time sensor-measured glucose was in hypoglycemic range <54 mg/dL.
TIR was significantly higher in the BP arm than the UC arm (75 ± 11% vs. 62 ± 22%, P = 0.001). Mean CGM glucose was lower in the BP arm than in the UC arm (150 ± 19 vs. 171 ± 45 mg/dL, P = 0.007). There was no significant difference in percent time with sensor-measured glucose <54 mg/dL (0.27% vs. 0.36%, P = 1.0), although self-reported symptomatic hypoglycemia episodes were higher during the BP arm than the UC arm (0.7 vs. 0.4 median episodes per day, P = 0.01). No episodes of diabetic ketoacidosis or severe hypoglycemia occurred in either arm.
Adults with CFRD had improved glucose control without an increase in CGM-measured hypoglycemia with the BP compared with their UC, suggesting that this may be an important therapeutic option for this patient population.
Objective: We evaluated the glycemic outcomes with 2 glucose targets in both configurations (bihormonal and insulin-only) of the bionic pancreas (BP) in a home-use study of adults with type 1 ...diabetes.
Research Design and Methods: 20 participants completed a double-blinded, placebo-controlled (glucagon vs. placebo), random-order, four-arm cross-over trial comparing the bihormonal (BH) and insulin-only (IO) configurations of the BP, each using 2 glucose targets (110 and 130 mg/dl); each arm lasted 3 days. Co-primary outcomes were continuous glucose monitor (CGM) mean glucose level and time <54 mg/dl.
Results: For the BH vs. IO configurations using the 130 mg/dl glucose target, the mean CGM glucose was 156±12 vs. 161±17 mg/dl (p=0.11) and the median percentage of time with CGM glucose <54 mg/dl was 0.0% IQR 0-0.52% vs. 0.0% 0-0.35% (p=0.45). For the BH vs. IO configurations using the 110 mg/dl glucose target, the mean CGM glucose was 148±17 vs. 153±15 mg/dl (p=0.21) and the median percentage of time with CGM glucose <54 mg/dl was 0.0% 0-0% vs. 0.52% 0.0-1.0% (p=0.002). The nominal differences in mean CGM glucose between the 110 mg/dl and the 130 mg/dl glucose targets (8 mg/dl in each case) were not statistically significant in either the IO or BH configuration (p>0.05). There was less hypoglycemia in the IO configuration, but not the BH configuration, when using the 130 mg/dl target vs. the 110 mg/dl target (p=0.03).
Conclusions: Both configurations of the BP provided safe and effective glycemic control using both glucose targets during home use. Hypoglycemia was lower with the BH configuration vs. the IO configuration using the 110 mg/dl target. Hypoglycemia was lower in the IO configuration when using the 130 mg/dl target vs. the 110 mg/dl target. Larger and longer studies will be needed to quantify differences in outcomes between the IO and BH configurations of the BP.
Disclosure
L. E. Castellanos: None. C. A. Balliro: Consultant; Self; Beta Bionics, Inc., Novo Nordisk. J. Sherwood: None. M. Tuffaha: None. M. Hillard: None. R. Selagamsetty: Employee; Self; Beta Bionics, Inc. F. El-khatib: Employee; Self; Beta Bionics, Inc., Stock/Shareholder; Self; Beta Bionics, Inc. E. Damiano: Other Relationship; Self; Beta Bionics, Inc., Stock/Shareholder; Spouse/Partner; Beta Bionics, Inc. S. J. Russell: Advisory Panel; Self; Companion Medical, ConvaTec Inc., Consultant; Self; Beta Bionics, Inc., Novo Nordisk, Other Relationship; Self; Beta Bionics, Inc., Research Support; Self; Beta Bionics, Inc., Novo Nordisk, Zealand Pharma A/S.
In an outpatient, home-use, random-order, controlled trial we compared automated glycemic control with the iLet bionic pancreas in the insulin-only (IOBP) vs. the bihormonal (BHBP) configurations for ...one week each in adult subjects (n=10) with type 1 diabetes. Subjects used their typical insulin analog (lispro or aspart) during both arms of the study. During the BHBP period the iLet delivered micro-doses of dasiglucagon, a glucagon analog stable in aqueous solution (Zealand Pharma). The insulin control algorithm was identical in both configurations, was initiated solely based on each subjects’ body mass without any information regarding patients’ baseline insulin needs, and used a glucose target of 110 mg/dl. The mean CGM glucose was lower in the BHBP arm vs. the IOBP arm (139±11 vs. 149±13 mg/dl, p=0.004) while the % of time with CGMG <54 mg/dl was nominally reduced (0.2%, IQR 0-0.4 vs. 0.6%, IQR 0.2-1.1%, p=0.11). We used an autoregressive time series model to determine statistical significance for differences between arms for each individual subject. Eight subjects had a significantly lower mean CGMG during the BHBP arm (p<0.05, mean improvement 12±7 mg/dl), while in the remaining two subjects there was no significant difference (nominal absolute difference 2±1 mg/dl). Eight of the ten subjects had a nominal reduction of the % of time <54 mg/dL in the BHBP arm (mean nominal difference -0.5%, range -0.1 to -1.0%), none of which were statistically significant. Here we demonstrated significant benefit of adding dasiglucagon in eight of ten subjects, allowing them to achieve a lower mean glucose without increased rates of hypoglycemia, in a trial comparing the BHBP and IOBP configurations of the iLet.
Disclosure
J. Sherwood: None. C.A. Balliro: None. R.Z. Jafri: None. L.E. Castellanos: None. M. Hillard: None. R. Selagamsetty: Employee; Self; Beta Bionics, Inc. Stock/Shareholder; Self; Beta Bionics, Inc. E. Greaux: None. H. Zheng: None. F. El-Khatib: Other Relationship; Self; Beta Bionics, Inc. E. Damiano: Board Member; Self; Beta Bionics, Inc. Employee; Self; Beta Bionics, Inc. Stock/Shareholder; Self; Beta Bionics, Inc. Stock/Shareholder; Spouse/Partner; Beta Bionics, Inc. S.J. Russell: Consultant; Self; Beta Bionics, Inc., ConvaTec Inc., Novo Nordisk A/S, Senseonics. Research Support; Self; Beta Bionics, Inc., Novo Nordisk A/S, Zealand Pharma A/S. Stock/Shareholder; Self; Companion Medical. Other Relationship; Self; Ascensia Diabetes Care, Roche Diabetes Care.
Funding
Beta Bionics, Inc.
We examined automated glycemic control with the insulin-only configuration of the iLet® bionic pancreas using faster aspart (Fiasp), comparing non-default tmax settings of the iLet® to a default tmax ...setting in a two-period, random-order cross-over design within each of three cohorts with eight different participants. Each participant was randomized to use the default tmax setting (t65 minutes) followed by the non-default tmax setting (t50, t40, or t30 minutes in cohorts 1, 2, and 3, respectively), or vice versa, for one week each. The group mean CGM glucose (CGMG) was significantly lower (two-sided p-value <0.05) in the t50 versus t65 arm (-7.4 -12.3; -2.4 mg/dl, p=0.011; 150.3 versus 157.7 mg/dl) and in the t40 versus t65 arm (-7.5 -12.9; -2.1 mg/dl, p=0.015; 150.1 versus 157.6 mg/dl), but was not significantly different in the t30 versus t65 arm (-7.7 -16.8; 1.4 mg/dl, 144.2 versus 151.9 mg/dl). Group mean time <54 mg/dl was not significantly different between non-default and default tmax settings in all three cohorts, (+0.09%, +0.18%, and +0.17% in cohorts 1, 2, and 3, respectively, all p>0.05). Using an autoregressive time series model, we determined the intra-individual statistical significance of differences in mean CGMG and time <54 mg/dl between non-default and default tmax settings. The mean CGMG was significantly different for four of eight subjects in the t50 versus t65 cohort (mean -13±7 mg/dl), seven of eight subjects in the t40 versus t65 cohort (mean -8±8 mg/dl), and five of eight subjects in the t30 versus t65 cohort (mean -12±6 mg/dl). One subject had a significant change in time <54 mg/dl (+1.2% of time; 1.2% versus 0%) in the t40 versus t65 arm. The majority of subjects had a significant reduction in mean CGMG with a non-default tmax setting while using Fiasp in the iLet. Use of different tmax settings could translate to clinically significant reductions in mean CGMG for many patients, with low risk of a significant increase in hypoglycemia.
Disclosure
L.E. Castellanos: None. H. Zheng: None. C.A. Balliro: None. J. Sherwood: None. M. Ekelund: Employee; Self; Novo Nordisk. Stock/Shareholder; Self; Novo Nordisk. Stock/Shareholder; Spouse/Partner; Novo Nordisk. F. El-Khatib: Other Relationship; Self; Beta Bionics, Inc. E. Damiano: Board Member; Self; Beta Bionics, Inc. Employee; Self; Beta Bionics, Inc. Stock/Shareholder; Self; Beta Bionics, Inc. Stock/Shareholder; Spouse/Partner; Beta Bionics, Inc. S.J. Russell: Consultant; Self; Beta Bionics, Inc., ConvaTec Inc., Novo Nordisk A/S, Senseonics. Research Support; Self; Beta Bionics, Inc., Novo Nordisk A/S, Zealand Pharma A/S. Stock/Shareholder; Self; Companion Medical. Other Relationship; Self; Ascensia Diabetes Care, Roche Diabetes Care.
Purpose
Hypothalamic-pituitary axis dysfunction and mass effect symptoms in the pediatric population can indicate a pituitary region tumor. Herein, we evaluate the epidemiology and management of this ...rare entity.
Methods
Pediatric patients (≤ 21yo) who presented from 2004 to 2017 with a pituitary tumor were evaluated from the U.S. National Cancer Database. The distributions and management patterns of pituitary tumors were assessed by patients’ tumor type, age, sex, race/ethnicity, tumor size, and insurance status.
Results
19.7% of intracranial tumors in the pediatric population originated in the pituitary region. 7653 pediatric patients with pituitary region tumors were identified, 68.2% of whom were female, with the tumors predominantly occurring in early adolescence (46.9%) and late adolescence (34.8%). The majority of pediatric pituitary region tumors were pituitary adenomas (77.9%), followed by craniopharyngiomas (18.1%) and germ cell tumors (1.6%). Girls demonstrated higher proportions of pituitary adenomas across all ages than boys. Asian/Pacific Islander patients were independently more likely to present at younger ages (mean 13.9yrs) and with germ cell tumors than patients of other races/ethnicities. Only 5.5% of patients were uninsured (referent), but they were independently more likely to present at older ages (mean 17.9yrs) and less likely to undergo surgery than patients with private insurance (OR = 1.93, 95% CI = 1.47–2.52, p < 0.001) or Medicaid (OR = 1.51, 95% CI = 1.14–2.00, p = 0.004).
Conclusion
Pituitary region tumors comprise a significant fraction of intracranial pediatric tumors, particularly in adolescent girls. The differential diagnosis of pituitary tumor types differed significantly by patients’ age, sex, and race/ethnicity. Uninsured patients were associated with delays in care and less surgical management.
Patients treated with RET protein tyrosine kinase inhibitors (TKIs) selpercatinib or pralsetinib develop RET TKI resistance by secondary RET mutations or alterative oncogenes, of which alterative ...oncogenes pose a greater challenge for disease management because of multiple potential mechanisms and the unclear tolerability of drug combinations. A patient with metastatic medullary thyroid carcinoma (MTC) harboring a RET activation loop D898_E901del mutation was treated with selpercatinib. Molecular alterations were monitored with tissue biopsies and cfDNA during the treatment. The selpercatinib-responsive MTC progressed with an acquired ETV6::NTRK3 fusion, which was controlled by selpercatinib plus the NTRK inhibitor larotrectinib. Subsequently, tumor progressed with an acquired EML4::ALK fusion. Combination of selpercatinib with the dual NTRK/ALK inhibitor entrectinib reduced the tumor burden, which was followed by appearance of NTRK3 solvent-front G623R mutation. Preclinical experiments validated selpercatinib plus larotrectinib or entrectinib inhibited RET/NTRK3 dependent cells, whereas selpercatinib plus entrectinib was necessary to inhibit cells with RET/NTRK3/ALK triple alterations or a mixture of cell population carrying these genetic alterations. Thus, RET-altered MTC adapted to selpercatinib and larotrectinib with acquisition of ETV6::NTRK3 and EML4::ALK oncogenes can be managed by combination of selpercatinib and entrectinib providing proof-of-concept of urgency of incorporating molecular profiling in real-time and personalized N-of-1 care transcending one-size-fits-all approach.
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