Multiple Boluses Research Articles

Effects of Statistical Practices for Longitudinal Group Comparison of the Penetration-Aspiration Scale on Power and Effect Size Estimation: A Monte Carlo Simulation Study.

Multiple bolus trials are administered during clinical and research swallowing assessments to comprehensively capture an individual's swallowing function. Despite valuable information obtained from these boluses, it remains common practice to use a single bolus (e.g., the worst score) to describe the degree of dysfunction. Researchers also often collapse continuous or ordinal swallowing measures into categories, potentially exacerbating information loss. These practices may adversely affect statistical power to detect and estimate smaller, yet potentially meaningful, treatment effects. This study sought to examine the impact of aggregating and categorizing penetration-aspiration scale (PAS) scores on statistical power and effect size estimates. We used a Monte Carlo approach to simulate three hypothetical within-subject treatment studies in Parkinson's disease and head and neck cancer across a range of data characteristics (e.g., sample size, number of bolus trials, variability). Different statistical models (aggregated or multilevel) as well as various PAS reduction approaches (i.e., types of categorizations) were performed to examine their impact on power and the accuracy of effect size estimates. Across all scenarios, multilevel models demonstrated higher statistical power to detect group-level longitudinal change and more accurate estimates compared to aggregated (worst score) models. Categorizing PAS scores also reduced power and biased effect size estimates compared to an ordinal approach, though this depended on the type of categorization and baseline PAS distribution. Multilevel models should be considered as a more robust approach for the statistical analysis of multiple boluses administered in standardized swallowing protocols due to its high sensitivity and accuracy to compare group-level changes in swallowing function. Importantly, this finding appears to be consistent across patient populations with distinct pathophysiology (i.e., PD and HNC) and patterns of airway invasion. The decision to categorize a continuous or ordinal outcome should be grounded in the clinical or research question with recognition that scale reduction may negatively affect the quality of statistical inferences in certain scenarios.

Nitroglycerin to Ameliorate Coronary Artery Spasm During Focal Pulsed-Field Ablation for Atrial Fibrillation

BackgroundIn treating atrial fibrillation, pulsed-field ablation (PFA) has comparable efficacy to conventional thermal ablation, but with important safety advantages: no esophageal injury or pulmonary vein stenosis, and rare phrenic nerve injury. However, when PFA is delivered in proximity to coronary arteries using a pentaspline catheter, which generates a broad electrical field, severe vasospasm can be provoked. ObjectivesThe authors sought to study the vasospastic potential of a focal PFA catheter with a narrower electrical field and develop a preventive strategy with nitroglycerin. MethodsDuring atrial fibrillation ablation, a focal PFA catheter was used for cavotricuspid isthmus ablation. Angiography of the right coronary artery (some with fractional flow reserve measurement) was performed before, during, and after PFA. Beyond no nitroglycerin (n = 5), and a few testing strategies (n = 8), 2 primary nitroglycerin administration strategies were studied: 1) multiple boluses (3-2 mg every 2 min) into the right atrium (n = 10), and 2) a bolus (3 mg) into the right atrium with continuous peripheral intravenous infusion (1 mg/min; n = 10). ResultsWithout nitroglycerin, cavotricuspid isthmus ablation provoked moderate-severe vasospasm in 4 of 5 (80%) patients (fractional flow reserve 0.71 ± 0.08). With repetitive nitroglycerin boluses, severe spasm did not occur, and mild-moderate vasospasm occurred in only 2 of 10 (20%). Using the bolus + infusion strategy, severe and mild-moderate spasm occurred in 1 and 3 of 10 patients (aggregate 40%). No patient had ST-segment changes. ConclusionsAblation of the cavotricuspid isthmus using a focal PFA catheter routinely provokes right coronary vasospasm. Pretreatment with high doses of parenteral nitroglycerin prevents severe spasm.

Resolution of sustained ventricular tachycardia in a horse presenting with colic with magnesium sulfate

SummaryCase reports demonstrating a return to sinus rhythm from sustained ventricular tachycardia (VT) are limited. VT is uncommon in horses but can be life threatening and has been reported in horses with primary gastrointestinal disease. Treatment is recommended if there is poor perfusion, if heart rate exceeds 100 beats/min, if multiform/polymorphic complexes or torsades des pointes is present. Lidocaine or magnesium sulfate is the first‐line medication. In this case, a 19‐year‐old Warmblood gelding with a history of exploratory laparotomy presented with an irregularly irregular cardiac rhythm and heart rate of 80 beats/min. ECG demonstrated VT with a heart rate of 75 beats/min. As the horse was already receiving a lidocaine bolus, the VT was treated with multiple boluses of intravenous magnesium sulfate over a period of several hours. This converted the VT to normal sinus rhythm (NSR) with heart rate of 44 beats/min and the horse remained in NSR until discharge 8 days later.

Rare Cause of Arrhythmia and Seizures in a Late-Preterm Newborn

Rare Cause of Arrhythmia and Seizures in a Late-Preterm Newborn

Ecthyma gangrenosum as a presenting feature of X-linked agammaglobulinemia: A case study.

A previously healthy 5-year-old boy presented with symptoms of fever, vomiting, and diarrhea for three days. He had extensive erythematous skin lesions mainly over his bilateral lower limbs. His parents were nonconsanguineous, and his two younger sisters were healthy. On arrival, he was in septic shock, thus requiring multiple fluid boluses, triple inotropes, and ventilation. The skin lesions started as macules that enlarged into papules and vesicles. Over the next 24 h, they rapidly evolved into multiple hemorrhagic bullae (Fig. 1A), which ruptured to form a gangrenous ulcer with gray-black eschar surrounded by an erythematous halo (Fig. 1B).

A Term Neonate with Multiorgan Dysfunction, Severe Metabolic Acidosis, and Hyperkalemia.

A Term Neonate with Multiorgan Dysfunction, Severe Metabolic Acidosis, and Hyperkalemia.

Homeward.

Homeward.

An Unexpected Cause of Recurrent Fetal Decelerations

An Unexpected Cause of Recurrent Fetal Decelerations

474. Unique Treatment Challenges with Multisystem Inflammatory Syndrome in Children (MIS-C) compared to Kawasaki Disease Shock Syndrome

BackgroundKawasaki disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) associated with Coronavirus Disease 2019 present similarly with mucocutaneous symptoms and fever. Both syndromes can progress to shock. Successful treatments for MIS-C are largely based on proven KD management. As more patients with MIS-C are treated, protocols are adjusted. Infectious Diseases (ID) specialists are often early consultants in these cases. Understanding differences in how body systems are affected in MIS-C versus KD is essential for management.Figure 1. Cardiac changes among patients with Kawasaki Disease shock syndrome (KDSS) and Muti-system Inflammatory Syndrome (MIS-C) MethodsThis is a single hospital comparison of 25 cases of MIS-C with mucocutaneous presentation and symptoms of shock and 25 consecutive cases of KD Shock Syndrome (KDSS). Cases were compared for demographics, symptoms, cardiac abnormalities, medical treatments, and cardiac recovery. ResultsPatients with MIS-C develop symptoms of shock including sustained hypotension and tachycardia at 3 times the rate of patients with KD (45% vs 13%; p< 0.001). On echocardiogram, left ventricular myocardial dysfunction, assessed by ejection fraction, is more commonly noted in cases of MIS-C than KDSS (fig 1). About half of patients with MIS-C show left ventricular myocardial dysfunction initially with normalization by 6 months post-presentation in the majority (96%). ConclusionCardiac changes and shock events related to KD and MIS-C are thought to be caused by differing inflammatory mediators. By comparing these two syndromes, we can determine ways to manage each optimally. MIS-C often results in left ventricular myocardial dysfunction, which is rarer in KD cases. Fluid resuscitation with multiple fluid boluses followed by inotropes to treat hypotension in cases of in MIS-C puts increased strain on the already weakened myocardium. Early intravenous immunoglobulin (IVIG) administration, even in the presence of mild hypotension, can simultaneously provide the patient with additional fluid and decrease the underlying inflammatory process. This prompt treatment might reduce the need for pressor support while protecting the myocardium from further damage. As early consultants in MIS-C, ID providers should be educated regarding the unique cardiac challenges of MIS-C and avoid delay in IVIG treatment and cardiologist and intensivist consultation.Disclosures All Authors: No reported disclosures

Multi-system inflammatory syndrome presenting with refractory shock in an infant, temporally associated with SARS-CoV2 infection

Children with COVID-19 largely remain asymptomatic or mildly symptomatic with gastroenteritis or influenza like presentation. However, few of them go on to develop features of multi-system inflammatory syndrome secondary to dysregulated cytokine release, resulting even in death. We report a 45 days old infant who presented to us with fluid unresponsive shock following protracted vomiting few hours prior to arrival. Eight days prior, child was admitted in COVID Isolation centre with mild illness, after testing positive on rapid Antigen Test and discharged 3 days later. Child when brought was severely acidotic and hence electively intubated. Shock did not improve even following multiple boluses and inotropic support on mechanical ventilation. Encephalopathy, myocardial dysfunction and acute kidney injury, with elevated inflammatory markers post COVID-19 suggested multi-system inflammation syndrome in him. The infant deteriorated rapidly and succumbed even before targeted therapy could be initiated. MIS-C presenting with refractory shock is increasingly being reported in pediatric age group and these children rapidly deteriorate without early recognition and treatment. Clinicians need a heightened suspicion for cytokine storm related complications and institute early immune-modulative therapy, especially during the present COVID-19 pandemic.

Unmasking of Neurosarcoidosis

Abstract Introduction: Central diabetes insipidus is a rare complication of neurosarcoidosis. In patients with concomitant adrenal insufficiency (AI), the symptoms of Diabetes Insipidus (DI) can be masked. Case: A 55-year-old female with past medical history of sarcoidosis presented to the hospital with hematemesis, nausea and dizziness. She has a past medical history of cardiac sarcoidosis that was revealed on a PET scan done before 10 years for which she was being treated with methotrexate and prednisone. She was off prednisone for a year prior to hospitalization. She underwent an upper endoscopy that showed diffusely erythematous gastric mucosa in the antrum. She was also hypotensive on admission, and she received packed red blood transfusions after which her sodium increased from 145mmol/L to 165mmol/L (Normal: 135-145mmol/L) in 48 hours. Further workup revealed persistent hypernatremia and urine osmolality was 75mOsm/kg H2O. (Normal: 50-1200mOsm/kg H2O). She was also hypoglycemic and hypotensive requiring multiple fluid boluses throughout her hospitalization. This prompted us to perform a random cortisol that came back at 2.1ug/dl (Normal: 3-23ug/dl) and 1.8ug/dl on two occasions. Cortisol Stimulation test was subsequently ordered, but was done only at 30 minutes, and Cortisol increased from 1.8ug/dl to 6.3ug/dl. Free thyroxine was 0.5 ng/dl (Normal: 0.9-1.8 ng/dl) and her TSH was 7.58uIU/ml (Normal: 0.55-4.78uIU/ml). MRI of the brain revealed extensive areas of extra-axial supra-sellar/infundibular nodular homogeneous intense enhancement that is most consistent with neuro-sarcoid. She was started on prednisone 40 mg daily, Desmopressin 0.05 mg twice daily, and levothyroxine as well. Her sodium level normalized and was 137mmol/L at discharge. She followed up later with outpatient Endocrinology and reported around 90lbs weight gain and no more episodes of nausea or vomiting or epistaxis or lightheadedness. Conclusion: The involvement of the hypothalamic-pituitary axis in sarcoidosis is extremely rare and attributes to &amp;lt; 1% of patients with a sellar mass. Small case series have shown that hypogonadism is the most common endocrine abnormality followed by DI. Our patient had a long-standing history of sarcoidosis with her pituitary dysfunction unmasked only on admission for other causes. She did not manifest any symptoms of DI or AI. There have been case reports where the symptoms of DI are masked due to underlying glucocorticoid deficiency. There have been theories that glucocorticoid deficiency impairs renal water excretion by both ADH (Anti-diuretic hormone) dependent and ADH independent pathways. Another notable feature in our case is that our patient presented with primary hypothyroidism. In fact, sarcoidosis has been commonly implicated in auto-immune polyglandular syndromes type 3, which can present with auto-immune thyroiditis more so in females.

Observations of Breaking Internal Tides on the Australian North West Shelf Edge

A comprehensive observational data set was used to examine shoreward propagating semidiurnal internal tides as they shoal, break and run-up as turbulent boluses across the edge of the Australian North West Shelf (NWS), offshore Dampier, during late winter 2013. The measured waveforms and wavefields supported the grouping of events into two distinct categories: (1) pre-; and, (2) post- wave breaking. It was found that the transition from (1) to (2) was marked by the rise of nonlinear steepening (α) and reduction in dispersion (β), both coefficients that parameterize nonlinear wave effects on the Korteweg-de Vries (KdV) equation. We introduced a criterion for wave breaking from the dimensionless parameter (δ) that relates these two terms: wave breaking occurs when δ &amp;lt; 1. In the first group, dispersive effects were dominant to spread energy out of the semidiurnal wave to a dispersive wave packet of short-period internal solitary waves (ISWs). In the second, dispersion was considered small compared to the cumulative effect of nonlinear steepening. Here, the semidiurnal wave built sufficient energy at its rear face to generate wave breaking, which has been known to produce multiple turbulent boluses. Similar observations have not been described for this region during winter months and highlight that the nonlinear internal wave field is an important feature on the NWS throughout the year. Additionally, measurements obtained through autonomous ocean glider profiles revealed some of the post-breaking characteristics that included intensive vertical mixing and transport of dense water and suspended material onshore of the shelf break.

Hydromorphone population pharmacokinetics in pediatric surgical patients.

Hydromorphone is an opioid agonist used for pediatric analgesia. Due to lack of data, pediatric dosing (based on adult pharmacokinetic models) is not optimal. This study characterizes hydromorphone population pharmacokinetics in pediatric surgical patients. In this prospective observational study, 34 children (4-18years, bodyweight 23-89.6kg) received multiple intravenous hydromorphone boluses followed by postoperative hydromorphone patient-controlled analgesia. Arterial blood samples were collected before and at 3, 10, 30, and 90 (and few samples at 1350) minutes after the first dose. Hydromorphone concentrations were measured by validated LC-MS/MS assay. Nonlinear mixed-effects modeling was used for pharmacokinetic model development. The final population pharmacokinetic model was evaluated by visual predictive check and bootstrap analysis. Monte Carlo simulations based on the final pharmacokinetic model determined optimal patient-controlled analgesia parameters to achieve a target of 20ng/mL (as the median effective analgesic concentration), using minimum effective analgesic concentration of 4ng/mL as a proxy for patient-controlled analgesia dose demand, and not exceeding the defined safe upper threshold of 40ng/mL. Hydromorphone pharmacokinetic profiles were adequately described by a two-compartmental model with first-order elimination. Bodyweight was found to be a significant covariate for hydromorphone clearance. Allometrically scaledpharmacokinetic parameter estimates (per 70kg), systemic clearance (0.748L/min), volume of distribution (33L), peripheral clearance (1.57L/min), and peripheral volume of distribution (146L) were similar to reported adult parameter estimates. Sex, race, age, and type of surgery were not identified as significant covariates. To identify optimal patient-controlled analgesia dosing parameters, we simulated several initial loading doses, demand doses, and lockout intervals. Our simulations support an initial patient-controlled analgesia loading dose of 15µg/kg followed by a demand dose of 6µg/kg with lockout intervals of 20minutes. After intravenous hydromorphone, plasma pharmacokinetic profiles in children undergoing different surgeries were well described by a two-compartment population allometric pharmacokinetic model using bodyweight as the size descriptor. Model informed simulations identified patient-controlled analgesia parameters to inform initial settings, with adjustments as needed based on observed individual effects.

SAT-131 Asymptomatic Severe Hypoglycemia with Lactic Acidosis in a Case of Non-Hodgkin’s Lymphoma - an Unusual Phenomenon of Hyper-Warburgism

INTRODUCTIONHypoglycemia in malignancy is well known with several etiologies; impaired liver function, insulin receptor autoantibodies, production of insulin-like substance by malignant cells or large tumor burden. Another possible mechanism is the Warburg effect where metabolism shifts towards glycolytic pathways over oxidative phosphorylation even under aerobic conditions leading to excess lactate production. This leads to glucose consumption due to shunting of glucose away from normal cells to cancer cells. Very few cases of lactic acidosis and severe hypoglycemia in Non-Hodgkin’s Lymphoma have been described in the literature. We report such an unusual case here.CASE DISCUSSIONA 52-year-old, African-American male was admitted for severe malnutrition with 80 lb. weight loss, severe hypoglycemia and progressively increasing right chest wall mass. On arrival, he had no classic symptoms of hypoglycemia. Physical exam revealed persistent tachycardia, white patches on oral mucosa and posterior tongue, and an indurated mass on right chest wall with extensive swelling of right upper limb. Lab work was significant for blood glucose (BG) of 41 mg/dL (60–100), lactate 16 mmol/L (0.5 to 2), anion gap 26 mEq/L (3–10), albumin 2.3 g/dL (3.4 to 5.4) and normal renal and liver function tests. Fingerstick sugar readings were persistently in the 20s with no response to multiple boluses of dextrose and glucagon. He was started on dextrose 5% (D5) drip and intravenous solumedrol. Solumedrol was weaned off and D5 titrated down to investigate causes of hypoglycemia. BG dropped to 39 and corresponding labs showed insulin level of < 2 mcUnit/mL (2–20), C-peptide of 0.2 ng/mL (0.8–6.0) and ketone level of 0.2 mmol/L (<0.4). IGF-1 and IGF-2 were both low at 26 ng/mL (61–200) and 113 ng/mL (333–967) respectively. A CT torso with contrast showed bilateral pleural effusions, moderate pericardial effusions and a large ill-defined heterogeneous mass along anterior chest wall. He underwent ultrasound guided biopsy of the chest wall mass and diagnosed with diffuse large B-cell lymphoma. He also tested positive for HIV/AIDS and Hepatitis C. PET scan showed diffuse FDG (fluorodeoxyglucose) uptake consistent with advanced disease. He was started on chemotherapy and lactate and BG normalized soon after 1st cycle.CONCLUSIONIn our case; suppressed insulin, low C-peptide and IGF-2 levels indicate non-insulin mediated hypoglycemia due to rapid glucose utilization by cancer cells. Severe hypoglycemia with lack of neuroglycopenic symptoms suggests use of lactate (rather than glucose) as an alternative metabolic fuel for brain, thus preserving its function. Our patient presented with an exaggerated Warburg effect (hyper-Warburgism) as evident by extreme glucose consumption, severe lactic acidosis and large tumor burden on FDG/PET. Chemotherapy must be instituted timely to correct these abnormalities.

Severe bronchoconstriction as part of a suspected anaphylactic reaction in a dog following administration of gadobutrol

A four-year-and-three-month-old Jack Russell terrier presented for investigation of acute-onset paraplegia, with an MRI performed under general anaesthesia. Following administration of a gadobutrol contrast medium, apnoea, cyanosis, resistance to ventilation,...

Regarding a successful treatment with artificial pancreas for a patient who attempted suicide using a high‐dose insulin s.c. injection

Dear Editor, We read with great interest an article published in Acute Medicine and Surgery by Toshihiro Sakurai et al. entitled “Successful treatment with artificial pancreas for a patient who attempted suicide using a high-dose insulin s.c. injection”.1 This article states that artificial pancreas (AP) systems can control blood glucose (BG) concentrations without a risk of hypoglycemia. We would like to share our understanding of the differences between APs intended for hospitalized patients and wearable APs intended for diabetes outpatients. To aid our discussion, we would consider a case published by Shah et al. in which a wearable AP, the MiniMed 670G (Medtronic Diabetes, Northridge, CA, USA) failed to prevent a suicide caused by an intentional insulin overdose. This wearable, insulin-only AP system not only failed to prevent the patient’s suicide from multiple large insulin boluses, but it actively contributed to the suicide. This is because the system continued administering prescheduled basal insulin even after the patient had become extremely hypoglycemic.2 It is important to distinguish between hospital APs for inpatients and wearable APs for outpatients. A hospital AP, like the STG-55 used by Sakurai et al., can deliver glucose i.v. Another AP intended for hospital use is being developed by Admetsys. This system, like the STG-55, is intended to deliver both insulin and glucose i.v.3 Almost every marketed wearable AP system delivers only insulin to lower elevated BG concentrations and nothing to raise the BG concentration in the event of hypoglycemia. These systems respond to hypoglycemia by halting insulin delivery, but they do not administer any agent to actively raise the BG concentration. An investigational wearable AP for outpatients containing two hormones from Beta Bionics (Boston, MA, USA), currently in development, could deliver glucagon s.c. to raise the BG concentration in the case of hypoglycemia.4 However, this agent would still be less effective than i.v. glucose, which is available with a hospital AP. Sakurai et al.’s patient benefitted from a hospital AP because they could receive glucose i.v., which is the best method for raising BG levels after an intentional insulin overdose. In the case reported by Sakurai et al., we believe a wearable AP would not have saved the patient. Recently a glucagon-only closed-loop system was proposed by Mulla et al.5 to treat hypoglycemia in hospitals. This system might seem promising for treating a hypoglycemic patient like the case reported by Sakurai et al. However, this system has drawbacks. These include: (i) this system cannot lower elevated BG concentrations, so it is not a true AP, (ii) this system is experimental and not cleared. In conclusion, we recommend that if a hypoglycemic patient appears to have taken an intentional insulin overdose, then the patient should be immediately brought to a hospital where i.v. glucose is available either through a hospital AP system or through standard treatments and monitoring. A patient using a wearable AP system should not depend on this device to correct their hypoglycemia from an insulin overdose. Approval of the research protocol: N/A. Informed consent: N/A. Registry and registration no. of the study: N/A. Animal studies: N/A. Conflict of interest: David C. Klonoff is a consultant for Dexcom, Eoflow, Fractyl, Lifecare, Novo, Roche Diagnostics, and Thirdwayv. The other authors have no conflict of interest. We acknowledge Annamarie Sucher-Jones for her expert editorial assistance.

Accuracy of low-weight versus standard syringe infusion pump devices depending on altitude

BackgroundIntravenous drug infusions in critically ill patients require accurate syringe infusion pumps (SIPs). This is particularly important during transportation of critically ill patients by helicopter emergency medical services (HEMS), where altitude may influence device performance. Because weight is a real concern in HEMS, new low-weight devices are very appealing.The aim of this study was to compare infusion flow rates delivered by low-weight versus standard SIP devices, in the prehospital emergency medicine setting, at different altitudes.MethodsWe conducted a comparative bench study involving five SIP devices (two standard and three low-weight models) at 300, 1700 and 3000 m altitude. The primary endpoint was the flow rate delivered by SIPs for prespecified values. We used two methods to measure flow. The normative method consisted in measuring weight (method A) and the alternate method consisted in measuring instantaneous flow (method B).ResultsUsing method A, no significant differences were found in median flow rates and interquartile range depending on device and altitude for a prespecified 10-mL/h flow. However, method B showed that low-weight SIPs delivered multiple sequential boluses with substantial variations (1.2–15.8 mL/h) rather than a prespecified continuous 5-mL/h flow. At 1700 m altitude, the interquartile range of delivered flows increased only for low-weight devices (p for interaction< 0.001).ConclusionsDespite satisfactory normative tests, low-weight SIPs deliver discontinuous flow with potential clinical implications for critically ill patients receiving vasoactive drugs. This study also highlights a thus far unknown negative impact of altitude on SIP function. We believe that normative requirements for SIP approval should be revised accordingly.

Successful Use of Octreotide Therapy for Refractory Levofloxacin-Induced Hypoglycemia: A Case Report and Literature Review

Fluoroquinolones are commonly prescribed antimicrobials that have been implicated in alterations of glucose metabolism. We report a case of refractory fluoroquinolone-induced hypoglycemia in a patient with type-2 diabetes mellitus on glipizide that was successfully treated with octreotide. A patient was admitted with hypoglycemia after having been initiated on levofloxacin therapy. Despite treating the hypoglycemia supportively with multiple boluses of 25 g of dextrose, a continuous dextrose infusion, and glucagon, the patient experienced repeated episodes of rebound hypoglycemia. The persistent hypoglycemia was eventually reversed with the administration of subcutaneous octreotide. Clinicians should be cognizant of this adverse effect of fluoroquinolones, as well as predisposing risk factors, and consider octreotide as an adjunctive therapy for refractory hypoglycemia cases.

SAT-500 Osteoblastic Metastasis in Prostate Cancer: A Sink Trap for Calcium in a Patient with Concomitant Secondary Hyperparathyroidism and Metastatic Prostate Cancer

Introduction Hypocalcemia in chronic kidney disease with secondary hyperparathyroidism is usually mild and seldom requires aggressive and protracted replacement. We report a case of refractory hypocalcemia in a patient with chronic kidney disease with incidentally detected bone metastatic prostate cancer. Clinical case A 62-year-old male presented with acute worsening of his mild chronic kidney disease. A CT scan done to evaluate this worsening of kidney function revealed incidental metastatic prostate cancer. Tc-99m whole body bone scan showed extensive bony metastases. Serum uncorrected calcium was 1.57 (2.09 - 2.46) mmol/L, albumin was 32 (40 - 51) g/L. Serum phosphate was 3.16 (0.94 - 1.50) mmol/L and iPTH was 38.1 (0.9 - 6.2) pmol/L. He was treated with intravenous calcium gluconate and was discharged on oral calcium acetate. He was subsequently commenced on prednisolone, anti-androgen agents and gonadotropin releasing hormone (GnRH) agonist for the cancer. He was readmitted seven months later for acute urinary retention with worsening of bilateral hydroureteronephrosis. His serum uncorrected calcium was now 1.49 mmol/L, albumin was 35 g/L, phosphate was 1.25 mmol/L, iPTH was 32.1 pmol/L and ALP was 253 (39 - 99) U/L. His eGFR was 35ml/min. Despite being treated with multiple boluses of intravenous calcium gluconate daily and oral calcium carbonate 5 grams and calcitriol 0.5 micrograms respectively three times daily, his calcium level never normalized. Patient was eventually transferred to hospice care and demised. Conclusion Osteoblastic bone metastases commonly found in patients with prostate cancer is very uncommonly associated with hypocalcemia. The increased osteoblastic activity acts as a sink trap causing increased uptake and utilization of calcium leading to hypocalcemia. This patient had Stage 3 CKD which is usually not associated with severe hypocalcemia. However, normalization of calcium level was not achieved despite high doses of intravenous and oral calcium supplementation. The incidentally detected bone metastatic prostate cancer is believed to have been responsible for his refractory hypocalcemia. The rare possibility of such malignancies with osteoblastic metastasis should be considered in the differential of protracted and severe hypocalcemia.

A severe case of refractory esophageal stenosis induced by nivolumab and responding to personalized treatment.

113 Background: The prevalence of esophageal stenosis caused by ICI in the context of induced immune mucositis and esophagitis is extremely rare. Methods: NA. Results: Case presentation: We report the case of a patient with stage IV pulmonary adenocarcinoma treated for 6 months with nivolumab who developed bilateral conjunctivitis followed by oropharyngeal mucositis and esophagitis complicated by a severe esophageal stenosis. The laryngeal margin and hypopharyngeal mucosa appeared highly inflammatory. Esophagogastroduodenoscopy revealed mucositis with a scar-like stricture immediately below the upper esophageal sphincter with nonulcerative mucosa and an inflammatory aspect of the entire esophagus. No involvement of the stomach was observed. Oropharynx biopsies displayed marked lymphocytic T cell-infiltration with several foci of monocellular necrosis in the squamous epithelium. A blood sample revealed a discrete increase in the ESR with no eosinophilia or leukocytosis. Liver and kidney function panel tests were normal. A CT scan reported no evidence of disease recurrence. Despite multiple boluses of methylprednisolone and high doses of prednisone continued for several months, the patient experienced very rapid symptomatological reappearance during three steroid tapering attempts and aggravation of his esophageal stenosis to an aphagic stage, requiring a nasogastric tube. This long course of high-dose corticosteroid treatment was complicated with osteoporosis-induced fractures with several spontaneous compressions of thoracolumbar vertebrae requiring an enlarged T10 to L5 cementoplasty. Anti-IL-6 blockade therapy with tocilizumab resulted in excellent response, allowing the total resolution of the irAEs leading to successful steroid tapering. Conclusions: Herein, we describe the first case of a patient who developed autoimmune mucositis and esophagitis complicated by a severe refractory esophageal stenosis induced during treatment by nivolumab, which completely resolved after personalized treatment with tocilizumab, suggesting a role of IL-6 blockade in the management of severe steroid refractory irAEs.