Acute presentation of immunotherapy-related diabetes mellitus without ketoacidosis, low C-peptide or elevated HbA1c.

Summary: The rapid rise in the use of immune checkpoint inhibitors as systemic cancer therapy has seen the emergence of immunotherapy-induced diabetes, a severe irreversible immunotherapy-related adverse event. Affected patients typically present with diabetic ketoacidosis (DKA) and low C-peptide consistent with insulin deficiency secondary to autoimmune ß-cell destruction. We present the unusual case of a 61-year-old female with metastatic ampullary duodenal adenocarcinoma with primary tumour adjacent to the pancreatic head. She was commenced on immunotherapy after conventional systemic chemotherapy. Acute-onset hyperglycaemia was detected after 7 weeks on weekly blood glucose monitoring, with no glucocorticoid use or prior history of diabetes. On presentation, there was no evidence of DKA, and her glycated haemoglobin level was within the normal non-diabetic range at 5.3%, reflecting the acuity of her presentation. Initial serum C-peptide was preserved; however, it became undetectable a few weeks later, confirming insulin deficiency. We describe a case of atypical presentation of immunotherapy-induced diabetes, review the existing literature on this emerging clinical entity and discuss the differential diagnosis for new-onset diabetes mellitus in patients with metastatic cancer. Learning points: Regular proactive glycaemic monitoring in patients receiving immunotherapy, particularly antibodies against programmed death ligand 1 and PD1, can facilitate very early detection of immunotherapy-induced diabetes, prompting insulin commencement and avoiding life-threatening presentations of diabetic ketoacidosis. Glycated haemoglobin can be within the normal range in patients diagnosed acutely with immunotherapy-induced diabetes. Serum C-peptide can be preserved initially in patients diagnosed with immunotherapy-induced diabetes but is likely to become undetectable during their illness. New-onset diabetes in patients with metastatic cancer carries a broad differential diagnosis.

Case Report: Hypoglycemia Due to Metastatic Insulinoma in Insulin-Dependent Type 2 Diabetes Successfully Treated With 177 Lu-DOTATATE.

We describe a 96-year-old man with insulin-dependent type 2 diabetes mellitus who, despite insulin cessation, presented with recurrent hypoglycemia associated with confirmed inappropriate endogenous hyperinsulinemia. 68Ga-DOTATATE-PET/CT scans demonstrated increased uptake in the pancreatic tail with multiple large intensely active liver metastases. Liver biopsy confirmed the diagnosis of well-differentiated metastatic neuroendocrine tumor. He was unsuitable for surgical resection and long-acting somatostatin analog therapy was ineffective. Subsequent management with four cycles of Lutate [177-Lutetium-DOTA0-Tyr3-octreotate (177Lu-DOTATATE)] resulted in resolution of hypoglycemia and ongoing clinical, biochemical, and radiological response 6 years after. This case is unique due to not only the paradoxical entity of insulinoma in insulin-dependent diabetes but also the positive sustained outcome after 177Lu-DOTATATE, given that unresectable metastatic insulinoma carries a poor prognosis. We review published cases of metastatic insulinoma in patients with diabetes mellitus as well as the literature to-date investigating efficacy and safety of Lutate therapy in metastatic insulinoma.

Correction to: Fusion Imaging of X-ray and Transesophageal Echocardiography Improves the Procedure of Left Atrial Appendage Closure.

The article "Fusion Imaging of X-ray and Transesophageal Echocardiography Improves the Procedure of Left Atrial Appendage Closure."

Fusion Imaging of X-ray and Transesophageal Echocardiography Improves the Procedure of Left Atrial Appendage Closure.

BACKGROUND: Left atrial appendage closure (LAAC) is an alternative treatment strategy for patients with atrial fibrillation who are at risk for thromboembolic events and considered not suitable for oral anticoagulation (OAC). LAAC is mainly performed under the guidance of transesophageal echocardiography (TEE) and fluoroscopy. The study presented here should analyze whether fusion imaging (FI) of transesophageal echocardiography and X-ray performed during LAAC is feasible and can improve the results of the procedure. METHODS: The data presented here are from a retrospective single center study. Sample size was defined as 50 patients in which LAAC was performed without fusion imaging (control group) and 25 patients were the LAAC procedure was guided by fusion imaging (treatment group). Inclusion criteria were defined as age > 18 years and completion of an LAAC procedure defined as deployment of a WATCHMAN 2.5 LAA occluder. Study endpoints were procedure time, amount of used contrast medium, radiation dose, final position of the WATCHMAN in TEE (deviation from ideal positioning), and clinical endpoints, respectively. RESULTS: LAA closure was successfully performed in all patients. No case of device embolism was occurring, and none of the patients experienced a periprocedural stroke/TIA nor a systemic embolism, respectively. Mean procedure time was 15 min shorter in the group of patients where fusion imaging was applied (p < 0.001). Additionally, the use of fusion imaging was associated with a significant reduction of contrast medium (20.6 ml less than in control; p < 0.045). Regarding the final position of the WATCHMAN, no relevant differences were found between the groups. The use of fusion imaging significantly reduced procedure time and the amount of contrast medium in patients undergoing LAAC.

A nasty surprise: cardiogenic shock induced by extensive dissection of the left internal mammary artery graft occurring 3 months after coronary angiography-a case report.

BACKGROUND: Acute dissection of the left internal mammary artery (LIMA) graft in patients with previous cardiac bypass surgery is a rare but potentially life-threatening condition. CASE SUMMARY: A 58-year-old man with history of coronary artery disease and bypass surgery 15 years ago presented with acute coronary syndrome (non-ST-elevation myocardial infarction, NSTEMI). Angiography showed severe three-vessel disease with occlusion of a saphenous vein graft (SVG) to the first diagonal branch but patents grafts to left artery descendent (LIMA) and SVG to the right coronary artery. No coronary intervention was performed and the patient was treated medically (aspirin and ticagrelor) and discharged home after 6 days. Three months later, the patient again was admitted to the hospital with acute coronary syndrome (NSTEMI) and developing cardiogenic shock. Angiography now showed an extensive flow limiting dissection of his LIMA graft with the dissection starting at the ostium of the LIMA. After implantation of an Impella 2.5, percutaneous coronary intervention (PCI) of the graft was performed under guidance by optical coherence tomography (OCT) leading to implantation of a drug-eluting stent into the ostium of the LIMA and repeated balloon dilatations of the medial and distal parts of the graft. Antegrade flow was established and the patient's condition improved so that the Impella was removed in the cath lab. After an uneventful course, the patient was discharged home after 6 days. Elective repeat angiography after 8 weeks showed an excellent functional result without persisting signs of LIMA dissection or stenosis. DISCUSSION: Acute dissection of a LIMA graft is a rare event that may lead to a life-threatening condition. According to the literature, LIMA dissection happens during coronary interventions in approximately half of the cases but it also may evolve spontaneously. However, as seen from our case, there might be a substantial delay between LIMA angiography and the clinical onset of dissection. In the vast majority of cases, dissection of LIMA can be treated by PCI. The use of Impella as reported for the first time in this case may improve the safety of the procedure. In accordance to PCI of the native coronary arteries, it seems possible to leave non-flow limiting dissections in cases of extensive disease in order to avoid the late complications of complete stenting of the graft.

Annual intramuscular injection of a megadose of cholecalciferol for treatment of vitamin D deficiency: efficacy and safety data.

AIM: To evaluate the efficacy and safety of an annual intramuscular injection of cholecalciferol for vitamin D deficiency. DESIGN: Prospective open-label study. PARTICIPANTS: Five men and 45 women (mean age 66.3 years) with vitamin D deficiency who were given a single therapeutic intramuscular injection of 600 000 IU (15 mg) cholecalciferol (vitamin D(3)). OUTCOME MEASURES: Serum levels of calcium, creatinine, 25-hydroxyvitamin D(3) (25OHD(3)) and parathyroid hormone, as well as early morning 2-hour urine calcium/creatinine excretion index. Specimens were collected at baseline and after 4 and 12 months of therapy. Data are reported as mean +/- 1 SD. RESULTS: Vitamin D deficiency was severe (< 12.5 nmol/L) in one participant, moderate (12.5-24 nmol/L) in 14, and mild (25-49 nmol/L) in 35. Twenty-four participants (48%) had secondary hyperparathyroidism. Following intramuscular cholecalciferol injection, serum 25OHD(3) levels normalised in all participants and remained above 50 nmol/L throughout the study. Serum 25OHD(3) levels were significantly higher at 4 months (114 +/- 35 nmol/L), and 12 months (73 +/- 13 nmol/L) compared with baseline (32 +/- 8 nmol/L) (P < 0.001), increasing by an average of 128% over the 12 months. There was a corresponding decrease in serum parathyroid hormone levels at 4 months (6 +/- 3 pmol/L) and at 12 months (5.2 +/- 3 pmol/L), with a 30% decrease at 12 months from baseline (7.4 +/- 4 pmol/L) (P < 0.01). Primary hyperparathyroidism was unmasked in one participant at 4 months and mild hypercalcaemia (serum calcium, < 2.70 mmol/L) was noted in two participants (4%) at 12 months. Serum creatinine levels remained normal in all participants throughout the study, while increases in 2-hour urine calcium/creatinine excretion index were seen in 10 participants (20%) at 12 months, three of whom had had elevated values at baseline. CONCLUSIONS: Once-yearly intramuscular cholecalciferol injection (600 000 IU) is effective therapy for vitamin D deficiency. While this therapy appears to be safe, the potential for developing hypercalciuria needs to be examined in a large randomised controlled trial.

Decrease of carotid intima-media thickness in patients at risk to cerebral ischemia after supplementation with folic acid, Vitamins B6 and B12.

OBJECTIVE: Hyperhomocysteinemia is associated with atherosclerotic risk. Although vitamins can lower homocysteine (Hcy), information about effects on atherosclerosis is scarce. METHODS: We used carotid intima-media thickness (IMT) as an accepted marker of atherosclerotic changes. Fifty patients (60 +/- 8 years) with IMT> or =1 mm were included. In a double blind, randomized trial they received daily 2.5 mg folic acid, 25 mg Vitamin B6, and 0.5mg Vitamin B12 or placebo for 1 year. RESULTS: In the treatment group, Hcy decreased from 10.50 +/- 3.93 to 6.56 +/- 1.53 micromol/l (P < 0.0001), whereas it remained unchanged in the placebo group (10.76 +/- 2.36 versus 10.45+/-3.30 micromol/l). IMT decreased from 1.50 +/- 0.44 to 1.42 +/- 0.48 mm (P = 0.034) in the treatment group, whereas it increased from 1.47 +/- 0.57 to 1.54 +/- 0.71 mm in the placebo group. The mean individual changes of IMT between both groups differed significantly (-0.08 +/- 0.17 versus 0.07 +/- 0.25 mm, P = 0.019). Multiple regression analysis revealed that the observed effect on IMT depended only on medication. CONCLUSIONS: Vitamin supplementation significantly reduces IMT in patients at risk. This effect is independent of Hcy concentration.

Motor vehicle accidents during episodes of hypoglycaemia--case reports and lessons to be learnt.

BACKGROUND: Hypoglycaemia is a common adverse effect of insulin treatment in individuals with diabetes, potentially leading to cognitive impairment, altered levels of consciousness and delayed reactions. If this happens while driving a motor vehicle, a disastrous accident may ensue. OBJECTIVE: This article describes the clinical scenarios of five men with type 1 diabetes who were involved in motor vehicle accidents due to severe hypoglycaemia and discusses the potential risk factors for hypoglycaemia. DISCUSSION: Reference is made to the specific management guidelines set out by the Australian Driver Licensing Authorities for individuals with diabetes. Sometimes, important ethical decisions can be difficult when managing diabetic individuals who fail to comply with therapy or who suffer hypoglycaemia related events and continue to drive a motor vehicle.