CTNI-54. A SINGLE ARM PHASE II STUDY OF THE DUAL MTORC1/MTORC2 INHIBITOR VISTUSERTIB PROVIDED FOR SPORADIC PATIENTS WITH GRADE II-III MENINGIOMAS THAT RECUR OR PROGRESS AFTER SURGERY AND RADIATION

Grade II/III meningiomas have increased rates of recurrence with no approved medical therapies. The historical progression-free survival at 6 months (PFS-6) is 25% with rates >35% declared of interest for drug development. NF2 gene inactivation occurs in about half of meningiomas. Based on our studies showing mTORC1 and mTORC2/SGK1 pathway activation in NF2-deficient meningiomas and the paradoxical activation of the mTORC2/AKT pathway, we hypothesized that mTORC1/mTORC2 inhibitors would be active in meningiomas. We studied the effect of vistusertib in patients with progressive/recurrent grade II/III meningiomas (NCT03071874). Vistusertib was administered orally at 125mg twice daily on two consecutive days each week. MRIs were obtained every 56 days. Tumor size was defined as the largest cross-sectional area. Progression was defined as ≥ 25% increase in the sum of products of all measurable lesions over smallest sum observed. The primary endpoint was PFS-6. Secondary endpoints included toxicity, radiographic response, and correlative studies including immunohistochemistry for mTORC1/2 pathway activation and genetic biomarkers. Twenty-eight patients (13 female, median age 58 years, median KPS 80%) were enrolled. Median tumor size was 4.4cm; 71% were grade II and 50% harbored pathogenic NF2 variants. Four patients discontinued treatment voluntarily and 1 each withdrew for intercurrent illness and non-compliance. PFS-6 is 47% (CI, 26%-65%) and OS-12 is 72% (95%CI, 48%-86%). PFS but not OS was shorter for patients with grade 3 meningiomas; there was no difference in PFS/OS between genetic groups. Adverse events at least possibly related to vistusertib with frequency >10% include nausea, fatigue, hypophosphatemia, diarrhea, anorexia, dry mouth, hypertriglyceridemia, hypertension, vomiting, increased ALT, constipation, and weight loss. Vistusertib treatment was associated with a PFS-6 rate exceeding the target of 35% for recurrent high-grade meningioma. Adverse events were tolerable in this patient population. These data support the continued development of mTORC1/2 inhibitors in this setting.

21q22.11q22.12 deletion syndrome with secondary hemophagocytic lymphohistiocytosis

Haemophagocyticy lymyphohistiocytosis in the new-born is uncommon. Incidence is reported between 1 in 50,000 to 1,50,000 admissions. Usually it is primary or familial HLH in the first year of life. Secondary causes are due to viral, bacterial and fungal infections. A dysmorphic small for gestational age male neonate presented with sepsis and neonatal cholestasis. He also had associated HLH. Exom sequencing showed a 21q22.11q22.12 deletion. This has not known to have any association with familial HLH. He was managed with IVIG and steroids. The neonate made a recovery but succumbed later to an intercurrent illness.

Chronic Illness in Pediatric Critical Care

Children and Youth with Special Healthcare Needs (CYSHCN), children with medical complexity (CMC), and children with chronic, critical illness (CCI) represent pediatric populations with varying degrees of medical dependance and vulnerability. These populations are heterogeneous in underlying conditions, congenital and acquired, as well as intensity of baseline medical needs. In times of intercurrent illness or perioperative management, these patients often require acute care services in the pediatric intensive care (PICU) setting. This review describes epidemiologic trends in chronic illness in the PICU setting, differentiates these populations from those without significant baseline medical requirements, reviews models of care designed to address the intersection of acute and chronic illness, and posits considerations for future roles of PICU providers to optimize the care and outcomes of these children and their families.

Sick day advice for people with diabetes

In this article Martha Stewart discusses how illness affects diabetes management and outlines the ‘sick-day advice’ that should be shared with people living with type 1 and type 2 diabetes Intercurrent illness can cause glucose levels to rise in people with diabetes mellitus. These illnesses include the common cold, diarrhoea and vomiting, urinary tract infections and COVID-19. If diabetes is not managed well during illness it can escalate and result in more serious conditions, such as diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS), which would require emergency hospital admission. This article discusses how illness affects diabetes management and outlines the ‘sick-day advice’ that should be shared with people living with type 1 and type 2 diabetes.

A Case Report of Idiopathic Ketotic Hypoglycemia Masquerading as Epilepsy

Idiopathic ketotic hypoglycemia (IKH) is characterized by recurrent neurohypoglycemic symptoms with ketosis. Hypoglycemic episodes typically occur during early mornings, especially either with illness and/or prolonged fasting. We reported a case of IKH which presented with recurrent episodes of seizures during early morning with intercurrent illness and which was labeled as epilepsy and started on antiepileptic medication. The purpose of this case report is to alert clinicians about this condition, which is not an uncommon entity, but rarely thought of. Therefore, in view of keeping the IKH in mind, which can be prevented with proper diet advice during illness, unnecessary long-term antiepileptic therapy can be avoided.

SUN-167 Treatment Considerations for a Healthy Pregnancy in Women with Classical Congenital Adrenal Hyperplasia (CAH)

Background: CAH is caused by an enzyme deficiency involved in cortisol synthesis leading to an increase in ACTH. Increased ACTH causes elevated levels of steroid hormone precursors & chronic stimulation of the adrenal glands resulting in hyperplasia. The most common form of CAH is due to 21OH deficiency (21OHD) with the classic, salt-wasting form causing glucocorticoid & mineralocorticoid deficiency & androgen excess. Poorly controlled CAH causes increased production of androgens & progesterone & decreased fertility. Fertility in woman with 21OHD can be challenging due to decreased sexual interest & anatomical abnormalities. Despite these challenges, the pregnancy rate is not significantly lower in women with well controlled 21OHD. However, as these patients are uncommon recommendations for pregnancy can be challenging for endocrinologists. Clinical Case: A 27-year old G0P0 female with classic, salt losing CAH presented to discuss pregnancy. Her medications were hydrocortisone 10mg qAM & 5mg qHS & fludrocortisone 0.1mg daily. She denied symptoms of dehydration, nausea, vomiting, dizziness, or fatigue. She was diagnosed with CAH while in-utero & started on steroid therapy after birth. She did not require any surgical genital reconstruction. Menarche occurred at age 11 and she had regular menses every 35-40 days, with no evidence of excessive androgen exposure including excess body hair, deepening of her voice, or cliteromegaly. On physical exam she was normotensive & had no evidence of virilization or cushingoid features. She exhibited minor darkening of the palmar creases. Her labs were significant for free testosterone of 9.1 pg/ml (0.2-5.0 pg/ml), total testosterone of 115 ng/dl (2-45 ng/dl), ACTH of 780 pg/ml (6-50 pg/ml), androstenedione of 636 ng/dl (41-262 ng/dl), & 17 OHP of 1560 ng/dl (15-290 ng/dl). Her hydrocortisone dose was increased to 20 mg qAM & 10 mg qHS & fludrocortisone 0.1mg daily was continued. Our objectives were to normalize the androgen level & suppress serum progesterone to less than 2 nmol/L. If the objectives were not reached she would be converted to prednisone BID. Conclusion: Endocrine providers are the primary resource for fertility recommendations for 21OHD patients & must understand the challenges in this very rare group of patients. Collaboration with the perinatologist is crucial for success. The goals of preconception endocrine assessment in a patient with classic CAH are to adjust hormone therapy to ensure optimal endocrine milieu for conception & risk assessment of having a child affected with 21OHD. The patient will need a higher dose of fludrocortisone during the later part of pregnancy. Counseling that stress doses of glucocorticoids for intercurrent illness and during labor and delivery are required for both the patient and the obstetrician.

Intravenous insulin therapy in diabetes mellitus with hyperglycemic crisis and intercurrent illness

BackgroundHyperglycemic crisis is one of the complications of diabetes mellitus, which is common in hospitalized diabetic patient with intercurrent illness, requiring immediate action to control blood glucose. As an effort to attain rapid, gradually and more definite blood glucose, insulin is given intravenously. This study aimed to explore the patterns of blood glucose in hyperglycemic crisis and intercurrent illness, precipitating conditions, insulin regimen and blood glucose (BG) level results.MethodsIt was a cross-sectional study conducted on type 2 diabetic patients. The inclusion criteria were as follows: hospitalized in the general/internal medicine ward with or without any complication or comorbidity receiving intravenous insulin therapy; have pre- and post-BG data after insulin intervention.ResultsIn 3 months of the study period, 22 patients fulfilled the inclusion criteria with 28 cases of intravenous insulin therapy, and 1 patient could get more than one intervention. The major condition toward a hyperglycemic crisis condition was infection. The patient’s BG before interventions was 243 mg/dL to more than 600 mg/dL. The dosage of insulin varied from 4 to 10 units per hour, intravenously with a frequency of 1–4 times. The dosage consideration was not only based on BG levels but also on the patient’s condition. The reduction in BG level varied greatly between 0.2 and 28.1 mg/dL per unit of insulin. The BG level of three patients did not decrease. On the other hand, one patient experienced mild hypoglycemia.ConclusionsInfection conditions were the most common factor for the hyperglycemia crisis. Moreover, intravenous insulin dosing was done individually, and there was a large variation in the results of the decrease in BG levels.

The influence of selected factors on the level of stress among patients qualified for the operation

Introduction. The surgery and its circumstances are difficult situation for patient and his/her relatives. Patient is afraid of operation, itss consequences, hospitalization regardless of the type of surgery and course of anaesthesia. Obtaining reliable information by patient from the staff helps to understand the desirability of procedure and principles for preoperative preparation. Aim. The assessment of the influence selected factors on the level of stress perceived by patients qualified for the anaesthesia before the operation. Material and methods. A survey performed amongst 100 adult patients (women and men), qualified for anaesthesia prior to surgery in Independent Public Clinical Hospital No. 4 in Lublin (SPSK-4). Research tools – an authorial questionnaire composed of 19 questions and the scale of perceived stress PSS-10. Discussion. Research has shown that level of stress before anaesthesia and surgery was significantly higher in group of women than men. Furthermore, respondents who work occupationally more frequently had high and very high level of stress compared to the surveyed with pension, retirement or unemployed. Age, place of living, education, marital status, material status, presence of intercurrent illness, type of operation/anaesthesia as well as number of procedures found no relationship regarding the level of perceived stress. Conclusion. 1. The level of stress before anaesthesia for surgery is high. 2. Gender and professional activity affect the level of experienced stress. 3. The patient’s mental preparation may have an influence on perioperative stress reduction.