Onset Hyperglycemia Research Articles

Prediction of pancreatic cancer in patients with new onset hyperglycemia: A modified ENDPAC model

Background/ObjectivesThe Enriching New-Onset Diabetes for Pancreatic Cancer (ENDPAC) model relies primarily on fasting glucose values. Health systems have increasingly shifted practice towards use of glycated hemoglobin (HbA1c) measurement. We modified the ENDPAC model using patients with new onset hyperglycemia. MethodsFour cohorts of patients 50–84 years of age with HbA1c results ≥6.2–6.5 % in 2011–2018 were identified. A combine cohort was formed. A widened eligibility criterion was applied to form additional four individual cohorts and one combined cohort. The primary outcome was the diagnosis of pancreatic cancer within 3 years after the first elevated HbA1c testing. The performance of the modified ENDPAC model was evaluated by AUC, sensitivity, positive predictive value, cases detected, and total number of patients screened. ResultsThe individual and combined cohorts consisted of 39,001–79,060 and 69,334–92,818 patients, respectively (mean age 63.5–65.0 years). The three-year PC incidence rates were 0.47%–0.54 %. The AUC measures were in the range of 0.75–0.77 for the individual cohorts and 0.75 for the combined cohorts. When the four individual cohorts were combined, more PC cases can be identified (149 by the combined vs. 113–116 by individual cohorts when risk score was 5+). Performance measures were compromised in nonwhites. Asian and Pacific islanders had lower sensitivity compared to other racial and ethnic groups (29 % vs. 50–60 %) when risk score was 5+. ConclusionsThe modified ENDPAC model targets a broader population and thus identifies more high-risk patients for cancer screening. The differential performance needs to be considered when the model is applied to non-white population.

THU289 Hemichorea-Hemiballismus Syndrome Secondary To Steroid Induced Hyperglycemia In A Nondiabetic

Abstract Disclosure: E. Krishnaraju: None. K.N. Patolia: None. U.A. Ogar: None. S. Karki: None. A.G. Olafimihan: None. Introduction: Hemichorea-Hemiballismus syndrome (HCHB) associated with nonketotic hyperglycemia is a rare cause of acute to subacute acquired chorea. The syndrome is usually characterized by unilateral choreiform movements, poorly controlled diabetes mellitus, and striatal abnormalities on an MRI of the brain. Clinical Case: This is a case of a 70-year-old man with a history of congestive heart failure, hypertension, remote ischemic stroke, asymptomatic Paget's disease of the bone, chronic kidney disease, and statin-induced necrotizing myositis. Five months before his presentation, the patient was initiated on prednisone for myositis. On presenting to the ED, he had near resolution of his limb weakness from myositis but complained of one month of right-sided continuous involuntary tremors involving the right upper limb, lower limb, and face that resolved during his sleep. There was no family history of neurologic disorders or any history to suggest medication or illicit drug-induced movement disorders. On examination, the patient had normal cognitive functions and vital signs. Neurologic examination was remarkable for quick interspersed moderate amplitude choreiform movements of the right hand, forearm, proximal arm muscles, and right leg. Laboratory results revealed hyperglycemia and a newly elevated Hemoglobin A1c of 8.5, which was normal the year before. Infectious, hematologic, thyroid disease, and Wilson's disease workups were negative. Cerebrospinal fluid (CSF) analysis was remarkable for elevated glucose and identical oligoclonal bands in the serum and CSF, possibly suggestive of a nonspecific chronic systemic inflammatory state. Autoantibodies for paraneoplastic syndromes and autoimmune diseases, including autoimmune encephalitis were negative. There was also no evidence of occult malignancy on CT imaging of the chest, abdomen, and pelvis. MRI/MRA was significant for new small foci of susceptibility artifact in the bilateral basal ganglia, left cerebellar hemisphere, and cerebellar vermis, likely from chronic microvascular changes. The constellation of hemichorea and new onset hyperglycemia in the setting of a largely nondiagnostic workup raises suspicion for HBHC syndrome. Previous studies have found classic T1-weighted MRI hyperintensities in the basal ganglia, but normal imaging does not rule out a diagnosis of diabetic striatopathy. The patient was eventually discharged with mild improvement of his chorea after starting insulin and risperidone. Unfortunately, he was lost to follow-up and unexpectedly died of an unclear cause soon after. Conclusion: Metabolic complications of diabetes can manifest in complex ways. Non-ketotic hyperglycemic HCHB due to diabetic striatopathy is a rarely reported entity that is commonly misdiagnosed. This case is a unique presentation in a non-diabetic patient with steroid-induced hyperglycemia. Presentation: Thursday, June 15, 2023

Post-COVID-19 mucormycosis: A prospective, observational study in patients undergoing surgical treatment.

Post the second wave of COVID-19 in India, our institute became a dedicated center for managing COVID-19-associated mucormycosis (CAM), but there was a paucity of data regarding perioperative considerations in these patients. The objectives of present study was to describe the preoperative clinical profile, the perioperative complications and outcome of CAM patients undergoing urgent surgical debridement. This prospective observational study was conducted on CAM patients presenting for surgical debridement from July to September 2021. During preoperative visits, evaluation of extent of disease, any side effects of ongoing medical management and post-COVID-19 systemic sequalae were done. The details of anaesthetic management of these patients including airway management, intraoperative haemodynamic complications and need for perioperative blood transfusion were noted. One hundred twenty patients underwent surgical debridement; functional endoscopic sinus surgery (FESS) was carried out in 63% of patients, FESS with orbital exenteration in 17.5%, and maxillectomy in 12.5%. Diabetes mellitus was found in 70.8% and post-COVID new onset hyperglycemia in 29.1% of patients. Moderate-to-severe decline in post-COVID functional status (PCFS) scale was observed in 73.2% of patients, but with optimization, only 5.8% required ICU management. The concern during airway management was primarily difficulty in mask ventilation (17.5%). Intraoperatively, hemodynamic adverse events responded to conventional treatment for hypotension, judicious use of fluids and blood transfusion. Perioperatively, 10.8% of patients required blood transfusion and 4.2% of patients did not survive. Non-surviving patients were older, with a more aggressive involvement of CAM, and had comorbidities and a greater decline in functional capacity. A majority of patients reported a moderate-to-severe decline in PCFS that required a preoperative multisystem optimization and a tailored anesthetic approach for a successful perioperative outcome.

Hyperglycemia in COVID-19 infection without diabetes mellitus: Association with inflammatory markers.

New onset hyperglycemia is common in patients with severe coronavirus disease 2019 (COVID-19) infection. Cytokine storm due to COVID-19 infection is an essential etiology for new-onset hyperglycemia, but factors like direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced pancreatic β-cell failure have also been postulated to play a role. We plan to investigate further the mechanisms underlying SARS-CoV-2 infection-induced hyperglycemia, particularly the rationale of the cytokine-induced hyperglycemia hypothesis, by evaluating the association between inflammatory markers and new onset hyperglycemia in non-diabetic patients with COVID-19 infection. We conducted a retrospective case-control study on adults without diabetes mellitus hospitalized for COVID-19 infection. The serum levels of glucose and inflammatory markers at presentation before initiation of corticosteroid were collected. Hyperglycemia was defined as glucose levels ≥ 140 mg/dL. C-Reactive protein (CRP) ≥ 100 mg/L, ferritin ≥ 530 ng/mL, lactate dehydrogenase (LDH) ≥ 590 U/L, and D-dimer ≥ 0.5 mg/L were considered elevated. We used the χ 2 test for categorical variables and the Mann-Whitney U test for continuous variables and calculated the logistic regression for hyperglycemia. Of the 520 patients screened, 248 met the inclusion criteria. Baseline demographics were equally distributed between patients with hyperglycemia and those who were normoglycemic. Serum inflammatory markers in patients with or without new-onset hyperglycemia were elevated as follows: CRP (58.1% vs 65.6%, P = 0.29), ferritin (48.4% vs 34.9%, P = 0.14), D-dimer (37.1% vs 37.1%, P = 0.76) and LDH (19.4% vs 11.8%, P = 0.02). Logistic regression analysis showed LDH odds ratio (OR) = 1.623 (P = 0.256). We observed significantly higher mortality (24.2% vs 9.1%, P = 0.001; OR = 2.528, P = 0.024) and length of stay (8.89 vs 6.69, P = 0.026) in patients with hyperglycemia. Our study showed no association between CRP, ferritin, LDH, D-dimer levels, and new-onset hyperglycemia in non-diabetic patients with COVID-19 infection. It also shows an increased mortality risk and length of stay in patients with hyperglycemia. With new-onset hyperglycemia being closely associated with poor prognostic indices, it becomes pivotal to understand the underlying pathophysiological mechanisms behind the SARS-CoV-2 infection-induced hyperglycemia. We conclude that the stress hyperglycemia hypothesis is not the only mechanism of SARS-CoV-2 infection-induced hyperglycemia but rather a multicausal pathogenesis leading to hyperglycemia that requires further research and understanding. This would help us improve not only the clinical outcomes of COVID-19 disease and inpatient hyperglycemia management but also understand the long-term effects of SARS-CoV-2 infection and further management.

Profiling of mucormycosis in district of central rural India during COVID-19 pandemic: a record-based study

Background: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with a wide range of opportunistic bacterial and fungal infections. Several cases of Mucormycosis in people with COVID-19 have been increasingly reported world-wide, in particular from India. The primary reason that appears to be facilitating Mucorales spores to germinate in people with COVID-19 is an ideal environment of low oxygen (hypoxia), high glucose (diabetes, new onset hyperglycemia, steroid-induced hyperglycemia). Methods: Secondary data was obtained from District health office Wardha. We took Mucormycosis related data for May 2021 to August 2021. A Secondary data analysis was done as an age wise distribution, Sex wise distribution, classification of Mucormycosis and case load in Wardha district. Results: Total cases (overall) was about 132. 91% cases are totally recovered. In overall cases, 106 males and 26 females were affected due to Mucormycosis. Out of 132 cases, 128 cases were of Rhino cerebral type of Mucormycosis. 48% cases of Mucormycosis were from 45 to 60 years old patients.127 cases of Mucormycosis were related with COVID history and only 5 cases of Mucormycosis were not related with COVID history. 53% cases were needed oxygen support prior onset of case. Conclusions: A multidisciplinary strategy should incorporate early diagnosis, antifungal therapy, any necessary surgical consultation and treatment, as well as reversal of the underlying illness. Identification of individuals at risk, strict glycaemic control and avoidance of unnecessary corticosteroid in non-severe COVID-19 cases (normal oxygen saturation on room air) can help in preventing this complication.

Abstract A028: The Early Detection Initiative trial version 2: A platform trial to test novel approaches to pancreatic cancer screening in patients with new onset hyperglycemia and diabetes

Abstract The Early Detection Initiative (EDI) is an innovative study designed to build a platform that will evaluate novel approaches to early detection of resectable pancreatic ductal adenocarcinoma (PDAC) in patients over age 50 with new onset hyperglycemia and diabetes (NOD). This randomized controlled trial (RCT) of algorithm-based screening for PDAC uses a modified Zelen’s design with post-randomization consent. Eligible subjects are identified through electronic medical record (EMR) surveillance and randomized 1:1 to the Observation or Intervention Arm. The Enriching New-onset Diabetes for Pancreatic Cancer (ENDPAC) score, an algorithm that further risk stratifies NOD based on age and changes in weight and glycemic parameters, is calculated in the Intervention Arm. Consenting subjects with ENDPAC >0 have Computerized Tomography (CT) scan imaging for PDAC detection; potential harm, including over-diagnosis, is also estimated. At the time of abstract submission >2000 individuals have been randomized and >50 subjects consented for CT imaging. EDI version 2 adds several innovations in response to challenges encountered and experience gained so far. Most significantly, EDI v2 has a platform design with a common control arm and allows for multiple intervention arms. This opens the door for evaluating future new biomarkers for PDAC early detection in a high–risk NOD population, including new blood-based biomarkers for the early detection of cancer that are now commercially available. EDI v2 focuses primarily on co-efficacy endpoints (PDAC stage shift in ENDPAC >0 group, and in all patients, excluding non-consented patients); effectiveness evaluation becomes a secondary objective. This addresses the challenges of low consent rate (~25%) due to lack of awareness of connection between NOD and PDAC and low acceptance for a novel research screening modality. The analyses of primary endpoints were adjusted to accommodate potential over-diagnosis due to screening and imbalance between ENDPAC >0 and ENDPAC ≤0 groups due to low consent rate and likely imperfect enrichment by ENDPAC, when evaluating all patients. Electronic eligibility checks and consent shorten the recruitment time, a critical factor for stage shift due to rapid progression of PDAC. A pre-randomization screening pilot study is planned to enhance the post-randomization consent rate. Intervention to Control randomization ratio is changed to 2:1, allowing more rapid recruitment and, when factoring the consent rate, doubling the sample size of the observation arm. Through these innovations, EDI v2 maintains the full advantage of Zelen’s design that made the trial feasible in sample size and cost. Simulation studies demonstrate that our approach correctly controls the type-1 error and the trial has adequate statistical power. The EDI trial represents an innovative and contemporary approach to developing and refining an early detection strategy for pancreatic cancer. Citation Format: Ying-Qi Zhao, Suresh T. Chari, Anirban Maitra, Lynn M. Matrisian, Eva E. Shrader, Bechien U. Wu, Avinash Kambadakone, Barbara Kenner, Jo Ann S. Rinaudo, Sudhir Srivastava, Ying Huang, Ziding Feng. The Early Detection Initiative trial version 2: A platform trial to test novel approaches to pancreatic cancer screening in patients with new onset hyperglycemia and diabetes [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A028.

LBMON139 A Case of Adipsic Diabetes Insipidus In Patient With Third Ventricular Tumor And Right Frontal Craniotomy.

Abstract Introduction Adipsic diabetes insipidus (ADI) is a rare hypothalamic disorder consisting of central diabetes insipidus (CDI) and loss of thirst. In hyperosmolar state, signals from osmosensors integrate in the central thirst center resulting in stimulatory signals between subfornical-oragan, organum-vasculosm of lamina terminalis and median preoptic nucleus increasing thirst and release of vasopressin. Disruption in this mechanism leads to adipsia. Case presentation 27 yr old male with history of prediabetes, 4.6cm third ventricular epidermoid cyst s/p endoscopic ventriculosmoy, hypogonadotropic hypogonadism, central hypothyroidism, and CDI underwent right frontal craniotomy for residual third ventricular cyst. Developed worsening DI, new onset hyperglycemia, and secondary adrenal insufficiency. Discharged with oral DDAVP 300mcg oral twice daily for CDI. 1 week later presented to ED with weakness. BP 132/112, HR 139, RR 38, SPO2 94%. Labs significant for corrected sodium of 172 (136-145mmol/L), glucose 699 (70-99mg/dl), calcium 11.8 (8.3-10.6 mg/dl). Discharged after 3 weeks with intranasal DDAVP 10mcg twice daily (BID). Again presented 1 week after for weakness. Vitals BP 105/64, HR 134, F 37.3 C, RR 31, SPO2 96%. Corrected sodium of 174 (136-145mmol/L) and glucose 708 (70-99mg/dl). Denied missing medication. Reported no increased water intake. Patient was diagnosed with adipsic DI based on subjective lack of thirst during period of significant hyperosmolar hypernatremia state. Overtime switched to 10mcg BID intranasal DDAVP and started on 4L fixed water intake. Had 5L urine output daily. Sodium levels ranged from 132-137. Discharged on intranasal DDAVP 10mcg AM/20mcg PM, 4L daily fixed water intake, and twice weekly sodium checks as outpatient. Goal sodium 135-140. DDAVP adjusted after sodium rose to 145. At recent clinic visit continued fixed 4L fluid intake with extra 500-1L intake for increased sweating/exercise, and sodium level 134. A1c 10% on insulin, and weight gain of 70lbs since surgery (8mon piror), BMI of 45. Started on GLP-1RA and sleep study. Learning points: Less than 100 cases of ADI reported worldwide and associated with increased morbidity/mortality1. This patient likely developed ADI due to disruption of central thirst center from epidermoid cyst and trans frontal craniotomy. We must be hypervigilant for ADI in patients with third ventricular tumors who undergo frontal craniotomy. Management is complex and requires patients are followed closely with weekly labs, either fixed water intake or fixed DDAVP dose and adjustment depending on labs. Important to screen these patients for obesity and sleep apnea given increased likelihood of hypothalamic dysfunction1. Reference: Cuesta, M., Hannon, M. J. & Thompson, C. J. Adipsic diabetes insipidus in adult patients. Pituitary 20, 372-380 (2017). https://doi.org/10.1007/s11102-016-0784-4 Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

IS COVID 19 PANDEMIC ADDING MORE OF DIABETIC POPULATION: A STUDY IN CENTRAL INDIA

Background– COVID 19 is associated with high prevalence of diabetes along with other comorbidities which also increase the severity and mortality risk in COVID 19 disease. Recently many studies have shown the association between COVID 19 and new onset diabetes. This study was done with objectives1.To nd out the incidence of new onset of hyperglycemia/diabetes in COVID 19 patients and 2.To develop screening policy for detection of new onset hyperglycemia in COVID-19 patients. Materials And Methods- This study is a hospital based observational cross sectional and prospective, cohort study conducted in the COVID ICU of Dedicated COVID Hospital, Bundelkhand Government Medical College, Sagar (M.P.) India, a teaching tertiary care centre. Out of 1562 COVID 19 positive patients admitted with moderate to severe pneumonia from JULY 2020 to JANUARY 2021, 487 patients were hyperglycemic at the time of admission. Patients were categorized into two subgroups: 1.Patients with previously conrmed diabetes or Prediabetes and 2.Hyperglycemia with no existing diabetes. Patients in this later subgroup were our follow up subjects for this study; their blood sugar level was monitored regularly during their stay in hospital & a correlation of COVID 19 and hyperglycemia was observed. In present study Incidence of newResults- onset hyperglycemia was 16.8%; 262 out of 1562. Of all 1562 patients admitted in hospital, 660 (44.7%) were found to be hyperglycemic. Among 660 patients, 436 (66.06%) patients were already known diabetic or pre-diabetic and 262 (16.8) were with newly onset hyperglycemia. 15 out of 262 (5.7%) patients were expired during their disease course, 157(60%) remained hyperglycemic while 90 (34.3) had attained normoglycemia without anti-diabetic drugs. COVID 19 disease is causative factor for new onset hyperglycemia /new onsetConclusion- diabetes.

Role of secondary sepsis in COVID-19 mortality: Observations on patients with preexisting diabetes mellitus and newly diagnosed hyperglycemia.

Diabetics who develop severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) are more likely to have severe disease, higher odds of intensive care requirement and mortality. Fifteen percent of patients have new onset hyperglycemia. We studied the comparative outcomes between prior DM, newly detected hyperglycemia and assessed role of secondary sepsis on mortality. RWe performed a r etrospective study of confirmed SARS-CoV-2 patients at a tertiary care hospital in Chennai, India. Patients were divided as 2 groups (Group 1: With preexisting diabetes mellitus, Group 2: With newly diagnosed hyperglycemia due to newly detected diabetes mellitus or non-diabetic hyperglycemia. Clinical and laboratory data was analysed. Two hundred and thirty eight patients had prior-diabetes mellitus (Group 1) and 40 had newly diagnosed hyperglycemia (Group 2). Thirty four of group 1 and 7 of group 2 patients required intensive care. Mean capillary blood glucose (MCBG) during hospital stay was 207 mg/dl (Group 1) and 192 mg/dl (Group 2). Twentysix patients (9.3%) had secondary sepsis of which sixteen died. Logistic regression identified secondary sepsis(p<0.0001), elevated D-dimer >6 fold (p= 0.0001), elderly p=0.0045), male (p=0.0006), NLR >5 (p=0.01),serum creatinine ≥2 mg/dl (p=0.0004), FiO2 requirement >0.6 in first 48 hours (p=0.001) as mortality predictors.Our study observed a 14.38 % prevalence of newly diagnosed DM or non-diabetic hyperglycemia. Secondary sepsis and >6 fold elevation in D-dimer were strong predictors of mortality. Steroid use possibly contributed to secondary sepsis. Early identification and aggressive management of secondary sepsis are necessary for diabetics.

Risk factors and outcomes of COVID associated mucormycosis in kidney transplant recipients.

Invasive mucormycosis (IM) is a life-threatening fungal infection occurring mostly in solid organ transplant (SOT) recipients, patients with hematological malignancies, and diabetes. A sudden spurt of mucormycosis has been reported in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic in India; however, there is little data about coronavirusdisease 2019 (COVID-19) associated mucormycosis (CAM) in kidney transplant recipients (KTRs). We describe the clinical presentations, risk factors, treatment and outcomes of 11 mucormycosis cases in KTRs post-COVID-19 infection from February 2020 to June 2021 at a single center in India. Mucormycosis was seen in 11/102 (10.7%) KTRs during the pandemic. Six patients had mild disease and rest five had moderate disease. Seven patients had pre-existing diabetes mellitus and four developed new onset hyperglycemia after receiving steroids for COVID-19 infection. All had poorly controlled sugars at the time of presentation. Most common presentation was rhino-orbital-cerebral mucormycosis (ROCM) in 10/11 (89%) patients and one has pulmonary mucormycosis. All patients received combination of amphotericin B and surgical debridement/excision of affected tissue followed by posaconazole prophylaxis. Nine patients recovered, however two patients succumbed to their illness after median of 14 (7-21) days from diagnosis. One patient developed acute T-cell-mediated rejection during the course of recovery. At last follow up, the mean serum creatinine was 2.05mg/dl as compared to 1.4mg/dl at presentation. IM is a common fungal infection in transplant recipients in India after COVID-19. Early diagnosis and prompt treatment with combination of surgical debridement and liposomal amphotericin B are key to better outcomes in CAM. Judicious use of steroids and control of hyperglycemia is key to avoid flaring up of the fungal infection.

Is COVID 19 Pandemic Adding More of Diabetic Population: A Study In Central India

ABSTRACT Background– COVID 19 is associated with high prevalence of diabetes along with other comorbidities which also increase the severity and mortality risk in COVID 19 disease. Recently many studies have shown the association between COVID 19 and new onset diabetes. This study was done with objectives1.To find out the incidence of new onset of hyperglycemia/diabetes in COVID 19 patients and 2.To develop screening policy for detection of new onset hyperglycemia in COVID-19 patients Materials and methods- This study is a hospital based observational cross sectional and prospective, cohort study conducted in the COVID ICU of Dedicated COVID Hospital, Bundelkhand Government Medical College, Sagar (M.P.) India, a teaching tertiary care centre. Out of 1562 COVID 19 positive patients admitted with moderate to severe pneumonia from JULY 2020 to JANUARY 2021, 487 patients were hyperglycemic at the time of admission. Patients were categorized into two subgroups: 1.Patients with previously confirmed diabetes or Prediabetes and 2.Hyperglycemia with no existing diabetes. Patients in this later subgroup were our follow up subjects for this study; their blood sugar level was monitored regularly during their stay in hospital &amp; a correlation of COVID 19 and hyperglycemia was observed. Results- In present study Incidence of new onset hyperglycemia was 16.8%; 262 out of 1562. Of all 1562 patients admitted in hospital, 660 (44.7%) were found to be hyperglycemic. Among 660 patients, 436 (66.06%) patients were already known diabetic or pre-diabetic and 262 (16.8) were with newly onset hyperglycemia. 15 out of 262 (5.7%) patients were expired during their disease course, 157(60%) remained hyperglycemic while 90 (34.3) had attained normoglycemia without anti-diabetic drugs. Conclusion- COVID 19 disease is causative factor for new onset hyperglycemia /new onset diabetes

Early Detection Initiative: A randomized controlled trial of algorithm-based screening in patients with new onset hyperglycemia and diabetes for early detection of pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is the only leading cause of cancer death without an early detection strategy. In retrospective studies, 0.5–1% of subjects >50 years of age who newly develop biochemically-defined diabetes have been diagnosed with PDAC within 3 years of meeting new onset hyperglycemia and diabetes (NOD) criteria. The Enriching New-onset Diabetes for Pancreatic Cancer (ENDPAC) algorithm further risk stratifies NOD subjects based on age and changes in weight and diabetes parameters. We present the methodology for the Early Detection Initiative (EDI), a randomized controlled trial of algorithm-based screening in patients with NOD for early detection of PDAC. We hypothesize that study interventions (risk stratification with ENDPAC and imaging with Computerized Tomography (CT) scan) in NOD will identify earlier stage PDAC. EDI uses a modified Zelen's design with post-randomization consent. Eligible subjects will be identified through passive surveillance of electronic medical records and eligible study participants randomized 1:1 to the Intervention or Observation arm. The sample size is 12,500 subjects. The ENDPAC score will be calculated only in those randomized to the Intervention arm, with 50% (n = 3125) expected to have a high ENDPAC score. Consenting subjects in the high ENDPAC group will undergo CT imaging for PDAC detection and an estimate of potential harm. The effectiveness and efficacy evaluation will compare proportions of late stage PDAC between Intervention and Observation arm per randomization assignment or per protocol, respectively, with a planned interim analysis. The study is designed to improve the detection of sporadic PDAC when surgical intervention is possible.

Case Report: Pheochromocytoma Presenting with Cushing’s Syndrome and Hyperglycemia

Introduction: Pheochromocytomas are catecholamine-producing neuroendocrine tumors that arise from the adrenal medulla. Pheochromocytomas typically present with uncontrollable or paroxysmal hypertension that can be accompanied by other common initial symptoms, including headache, diaphoresis, arrhythmia, and pallor. Given the morbidity and mortality associated with undiagnosed pheochromocytomas, and their potential for treatment, primary care physicians should consider this tumor type, and other endocrinological phenomena, when evaluating new onset hyperglycemia. Clinical Findings: Patient G was a 76-year-old female who presented in her primary care office with newly uncontrollable hyperglycemia. During initial evaluation, her clinical condition deteriorated rapidly. Her laboratory studies revealed markedly elevated cortisol, adrenocorticotropic hormone (ACTH), and urine metanephrines. Imaging revealed a 3-cm left adrenal mass. Evaluation of ACTH and cortisol levels became complicated by discovery of a lung mass. Clinical Course: Left adrenalectomy led to resolution of hyperglycemia, catecholamine excess, and Cushing’s Syndrome. Tissue pathology of the pheochromocytoma identified ACTH receptor positivity. Conclusions: Pheochromocytoma is a rare but possible cause of Cushing’s Syndrome. Patient G’s resolution of hypercortisolemia after successful resection of the pheochromocytoma indicate the tumor’s role in her hyperglycemia and Cushing’s Syndrome. Despite the well-known association of uncontrollable or paroxysmal hypertension with pheochromocytoma, presenting symptoms vary significantly among patients. The heterogeneity of this neoplasm’s presentation highlights the role primary care can play in building this rare diagnosis into the differential early in the disease course.

COVID 19 ASSOCIATED INVASIVE FUNGAL INFECTIONS IN CHURU REGION OF RAJASTHAN

Background: COVID 19 or severe acute respiratory syndrome (SARS-CoV-2) evolved as global pandemic since December 2019 when it was first reported in Wuhan, China. Coinfection in patients with COVID-19 has been reported in multiple studies, being bacterial in origin the most frequent; and fungal infection being reported only in severe cases.&#x0D; Methods: This study was conducted at the department of E.N.T. at PanditDeenDayalUpadhyay Medical College, Churu. Cases presented to E.N.T. OPD with clinical features of invasive rhino-orbital fungal infection for the period of two month from 1st June 2021 were included in the study. Patients were clinically evaluated, HRCT, MRI scans and with KOH mount and culture of involved tissue ere done. Patient’s COVID-19 status was ascertained. The clinicopathological association of occurrence of invasive fungal infections in post covid and non-covid patients along with other risk factors like diabetes mellitus, immune compromised state and long-term steroid use was done using statistical methods&#x0D; Results: We studied 21 patients who attended our OPD with features of invasive fungal infection. Most common presentation was swelling and pain in the cheek region and red eye and swelling around the eye, three patients presented with maxillary swelling with blackish discoloration of teeth. Radiological findings were suggestive of fungal etiology in all patients. KOH mount showed fungal hyphae in 20 cases. Total 20 cases were post COVID status. Old DM was there in 12 patients whereas 9 patients showed new onset hyperglycemia.&#x0D; Conclusions: COVID-19 is associated with a significant incidence of secondary infections, both bacterial and fungal probably due to immune dysregulation. The widespread use of steroids/monoclonal antibodies/broad-spectrum antibiotics as part of the management protocols against COVID-19 may lead to the exacerbation of preexisting fungal diseases or development of new infection. Treating Physicians should make themselves aware and prepare for the possibility of invasive secondary fungal infections in patients with COVID-19 infection especially in patients with preexisting risk factors and should enable early diagnosis and treatment with the subsequent reduction of mortality and morbidity.&#x0D; Keywords: Coronavirus, COVID-19, mucormycosis, invasive fungal infections

Current cancer therapies and their influence on glucose control.

This review focuses on the development of hyperglycemia arising from widely used cancer therapies spanning four drug classes. These groups of medications were selected due to their significant association with new onset hyperglycemia, or of potentially severe clinical consequences when present. These classes include glucocorticoids that are frequently used in addition to chemotherapy treatments, and the antimetabolite class of 5-fluorouracil-related drugs. Both of these classes have been in use in cancer therapy since the 1950s. Also considered are the phosphatidyl inositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR)-inhibitors that provide cancer response advantages by disrupting cell growth, proliferation and survival signaling pathways, and have been in clinical use as early as 2007. The final class to be reviewed are the monoclonal antibodies selected to function as immune checkpoint inhibitors (ICIs). These were first used in 2011 for advanced melanoma and are rapidly becoming widely utilized in many solid tumors. For each drug class, the literature has been reviewed to answer relevant questions about these medications related specifically to the characteristics of the hyperglycemia that develops with use. The incidence of new glucose elevations in euglycemic individuals, as well as glycemic changes in those with established diabetes has been considered, as has the expected onset of hyperglycemia from their first use. This comparison emphasizes that some classes exhibit very immediate impacts on glucose levels, whereas other classes can have lengthy delays of up to 1 year. A comparison of the spectrum of severity of hyperglycemic consequences stresses that the appearance of diabetic ketoacidosis is rare for all classes except for the ICIs. There are distinct differences in the reversibility of glucose elevations after treatment is stopped, as the mTOR inhibitors and ICI classes have persistent hyperglycemia long term. These four highlighted drug categories differ in their underlying mechanisms driving hyperglycemia, with clinical presentations ranging from potent yet transient insulin resistant states [type 2 diabetes mellitus (T2DM) -like] to rare permanent insulin-deficient causes of hyperglycemia. Knowledge of the relative incidence of new onset hyperglycemia and the underlying causes are critical to appreciate how and when to best screen and treat patients taking any of these cancer drug therapies.

Glycemic control metrics using flash glucose monitoring and hospital complications in patients with COVID-19

Background and aimsFew studies have reported on the use of continuous glucose monitoring (CGM) during the Covid-19 pandemic. We aimed to examine glycemic control metrics using flash glucose monitoring during insulin treatment and the clinical outcome in hospitalized patients with COVID-19. MethodsProspective, single-center cohort of adult patients diagnosed with type 2 diabetes or hyperglycemia and COVID-19 infection treated with basal bolus insulin regimen. Glycemic control was assessed with the use of intermittent Freestyle Libre flash glucose monitoring during the hospital stay. Outcome of interest were time in range [TIR], time above [TAR] and below [TBR] range, glycemic variability [coefficient of variation [% CV]), and differences in a composite of complications including ICU admission, acute respiratory distress syndrome (ARDS) and acute kidney injury. ResultsA total of 60 patients were included (44 known diabetes and 16 new onset hyperglycemia). In total 190,080 data points of CGM were available, of which 72.5% of values were within the target area [TIR (70–180 mg/dL)], 22% TAR (>180 mg/dL), and 3% were TBR (<70 mg/dL). During treatment, the coefficient of variation (% CV) was 30%. There were no association with TIR, but patients with TAR >180 mg/dl had higher rates of a composite of complications (22.5% vs 16%, p = 0.04). ConclusionsBasal bolus insulin regimen was safe and effective in achieving inpatient glycemic control in most patients with COVID-19. The association between TAR and complications indicates the need for improved inpatient glycemic control in hospitalized patients with COVID-19.

Acute uncontrolled hyperglycemia, a non-specific presentation and predictor of covid-19 severity- a report of three cases

Coronavirus disease 2019 (COVID-19) is a pandemic caused by the severe acute respiratory coronavirus 2 (SARS Cov-2) which currently has caused over 76 million cases with over 1.6 million people dead worldwide. COVID-19 can manifest with several non-specific clinical presentations, posing a diagnostic challenge. Several studies have shown an increased COVID-19 severity in patients with Diabetes mellitus. However, some patients with COVID-19 severity may present with new-onset Diabetes mellitus or worsening blood glucose control in a known diabetic. There are various mechanisms by which the SARS Cov-2 causes hyperglycemia in infected patients. This can lead to hyperglycemia as a presentation of COVID-19 in the absence of specific signs and symptoms. We present three cases: two of them initially presented with acute onset hyperglycemia and were diagnosed with Diabetes mellitus but shortly developed clinical manifestations that led to the suspicion of COVID-19 and a positive COVID-19 RT-PCR test. The third was a diabetic with previously good glycaemic control which suddenly worsened for no reason and shortly after, also developed clinical manifestations that led to the suspicion of COVID-19 which was later confirmed. We recommend that patients with acute hyperglycemia state and/or worsening blood glucose control in patients with previously well controlled Diabetes mellitus should be evaluated for COVID-19 in order to reduce morbidity and mortality as hyperglycemia confers an increased disease severity

COVID-19 Associated Rhino-orbito-cerebral Mucormycosis: Clinical Profile and Imaging Spectrum

Introduction: Rhino-orbito-cerebral mucormycosis is a fatal disease caused by saprophytic fungi seen almost exclusively in diabetic and immunocompromised patients. Aim: To describe various imaging findings of mucormycosis, and to emphasise the importance of imaging in its diagnosis and management. Materials and Methods: A retrospective, observational, single centre study was done including patients with clinical and microbiological evidence of rhino-orbito-cerebral mucormycosis, who had a history of Coronavirus Disease 2019 (COVID-19) infection and had undergone Computed Tomography (CT) and/ or Magnetic Resonance Imaging (MRI) scan of the head, orbit, and paranasal sinuses during the period of one month from 1st-31st May 2021. The clinical and imaging data of 67 such cases were interpreted and analysed by two radiologists. Results: The study included 67 patients out of which 44 were male and 23 were female, and the average age of patients was 49±13 years. During their treatment for COVID-19, 55 (82.08%) patients had a history of hospitalisation and administration of supplemental oxygen, all 67 (100%) patients had taken broad spectrum antibiotics, 56 (83.58%) patients had taken steroids, 20 (29.85%) patients previously had a history of diabetes with worsening of glycaemic control during COVID-19 infection, and 47 (70.15%) patients were diagnosed with new onset hyperglycaemia. On imaging i.e., on CT and/or MRI with or without contrast, the infection was found to primarily affect the sino-nasal region. There was unilateral or bilateral involvement of single or multiple paranasal sinuses in all 67 patients with involvement of nasal cavity in 42 patients. Maxillary sinus was the most common and consistently involved sinus seen in all 67 patients, followed by ethmoid sinus seen in 54 patients. Additionally, 56 patients had extra-sinus disease with spread along vessels, nerves, or via bone erosion. CT showed soft tissue thickening, oedema, and fat stranding with or without bone erosion as the predominant finding in involved areas, while MRI showed Short Tau Inversion Recovery (STIR) hyperintense soft tissue thickening and postcontrast enhancement as the main finding. Conclusion: There is a complex interplay of various COVID-19 infection and treatment related factors that are responsible for increased susceptibility to mucormycosis infection. Imaging plays an important role in aiding the diagnosis, determining the extent and spread of infection, guiding the extent of the surgical intervention, and determining the prognosis of these patients. The contrast enhanced MRI along with plain CT should be the preferred choice of imaging.

Characterization of hyperglycemia in patients receiving immune checkpoint inhibitors: Beyond autoimmune insulin-dependent diabetes

AimsImmune-mediated beta cell destruction is known to cause hyperglycemia in patients receiving immune checkpoint inhibitor (ICI) cancer therapy. However, it is uncommon, and little is known about the full spectrum of hyperglycemia in patients receiving ICIs. We aimed to characterize the prevalence and factors associated with hyperglycemia in patients treated with ICIs. MethodsWe retrospectively analyzed patients receiving ICIs at an NCI-designated Cancer Center. We assessed the proportion of patients with new onset hyperglycemia (random glucose >11.1 mmol/L) after starting ICIs and used logistic regression to determine hyperglycemia predictors in patients without known diabetes. ResultsOf 411 patients, 385 had post-ICI glucose data. 105 (27%) had hyperglycemia. Of this group, 29 (28%) had new onset hyperglycemia, 19 of whom had glucocorticoid-associated hyperglycemia. The remaining 10 had unexplained hyperglycemia and none had known autoimmune diabetes. Among patients without known diabetes, race/ethnicity, obesity, and pre-ICI hyperglycemia were significantly associated with hyperglycemia after starting ICIs. ConclusionsWe found that new hyperglycemia in patients receiving ICIs was most commonly related to glucocorticoids. A small patient subset had new unexplained hyperglycemia, suggesting ICIs might have a role in promoting hyperglycemia. Recognizing factors associated with hyperglycemia in this population is crucial for appropriate management.

Co-microencapsulation of human umbilical cord-derived mesenchymal stem and pancreatic islet-derived insulin producing cells in experimental type 1 diabetes.

Post-partum umbilical cord Wharton Jelly-derived adult mesenchymal stem cells (hUCMS) hold anti-inflammatory and immunosuppressive properties. Human pancreatic islet-derived progenitor cells (hIDC) may de-differentiate, and subsequently re-differentiate into insulin producing cells. The two cell types share common molecules that facilitate their synergistic interaction and possibly crosstalk, likely useful for the cell therapy of type 1 diabetes (T1D). Upon microencapsulation in sodium alginate (AG), hUCMS and hIDC were able to form cell co-aggregates that looked well integrated and viable. We then grafted microencapsulated hUCMS/hIDC co-aggregates into non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice, and observed an acquired ability of cells to produce and store hormones. Finally, we transplanted these biohybrid constructs into NOD mice with recent onset, spontaneous overt diabetes, observing a decline of blood glucose levels. In vitro, we have shown that hUCMS inhibited proliferation of allogeneic polymorphonuclear blood cells from patients with T1D, while promoting expansion of FoxP3+ Tregs. Reversal of hyperglycemia in diabetic NODs seems to suggest that hUCMS and hIDC, upon co-microencapsulation, anatomically and functionally synergized to accomplish two goals: maintain tracer insulin output by hIDC, while exploting the immunoregulatory properties of hUCMS. We have gathered preliminary evidence that the two adult stem cell types within AG microcapsules, may synergistically promote tracer insulin production, while "freezing" the autoimmune disease process, and help reversal of the recent onset hyperglycemia in a spontaneous, autoimmune rodent model of diabetes, the NOD mouse, with no need for pharmacologic immunosuppression.