Recreational Nitrous Oxide-Induced Subacute Combined Degeneration of the Spinal Cord.

There is rising use of recreational nitrous oxide (N2O) in the community because of its availability as "whippet" canisters. Nitrous oxide use is still legal and outside the purview of the Drug Enforcement Administration (DEA). It is not detected on a routine drug screen, and patient history is key to establishing the diagnosis. We highlight a case of subacute combined degeneration in a young patient secondary to recreational nitrous oxide use, which improved with vitamin B12 replacement. A 19-year-old male with a history of recreational nitrous oxide use presented with progressive bilateral lower extremity paresthesia and ataxia. Neurological examination revealed deficits in vibration and proprioception, motor weakness, and diminished reflexes in the bilateral lower extremities. The laboratory results were significant for pancytopenia, profound vitamin B12 deficiency (55 ng/mL), and elevated methylmalonic acid (2.14 umol/L). The urine drug screen was negative. MRI showed subacute degeneration of the spinal cord dorsal column at C2-C5. Treatment with intramuscular cyanocobalamin resulted in the normalization of pancytopenia and B12 levels (573 ng/mL). The patient had partial resolution of neurological symptoms following the initiation of parenteral vitamin B12 replacement. The mechanism of subacute combined degeneration in the setting of nitrous oxide toxicity appears to be mediated by functional B12 deficiency. Oxidation of cobalt ion of vitamin B12 by nitrous oxide renders it unavailable as a coenzyme, leading to the accumulation of by-products that enter lipid metabolism, resulting in abnormal myelin synthesis, which ultimately manifests as subacute combined degeneration. Vitamin B12 deficiency of unclear etiology should raise suspicion for nitrous oxide toxicity as early initiation of replacement therapy with vitamin B12 can improve neurological function.

Ectopic ACTH Production Caused by Metastatic Parotid Gland Acinic Cell Carcinoma.

OBJECTIVE: To present a case of adrenocorticotropic hormone (ACTH) hypersecretion caused by a metastatic acinic cell carcinoma (AcCC) of the parotid. Only 6 cases have been reported prior to October 2019. We believe that this condition is under-reported and hope that improved recognition will improve its reporting. METHODS: Diagnosis in this case was done using surgical pathology of the primary tumor, involving lymph nodes, and a metastatic lesion. Following an initial misdiagnosis, a final diagnosis of AcCC was made using immunohistochemical staining. ACTH hypersecretion was diagnosed by testing for random ACTH, cortisol, and 24-hour urine aldosterone and cortisol levels. RESULTS: A 57-year-old man presented with hypokalemia, lower-extremity edema, and left-side rib pain 7 months following excision of a 4-cm left-parotid tumor. Immunostaining positive for DOG-1, CK7, pan-cytokeratin (including CAM5.2), and SOX10 led to the diagnosis of AcCC. ACTH hypersecretion was diagnosed based on a random ACTH level of 307 pg/mL (normal morning value, 7.2-63 pg/mL), a cortisol level of 33 µg/dL (normal morning value, 4.3-19.8 µg/dL; normal PM value, 3.1-15.0 µg/dL), a 24-hour urine aldosterone level of <0.7 U (normal, 2.0-20 U), and a 24-hour urine cortisol level of 4564 U (normal, 3.5-45 U). The patient's ACTH hypersecretion and hypokalemia were treated with potassium replacement, amiloride, and ketoconazole. His metastatic recurrence was treated with radiotherapy, chemotherapy, and immunotherapy. The patient died after being diagnosed with sepsis secondary to multifocal postobstructive pneumonia 4 months after the diagnosis of his metastatic recurrence. CONCLUSION: Ectopic ACTH production caused by metastatic AcCC is a rare phenomenon but has been increasingly described over the last 15 years. We believe that this condition likely has a greater prevalence than what is reported and that improved recognition will lead to improved outcomes.

Clinical Outcomes of the Self-Expandable Evolut R Valve Versus the Balloon-Expandable SAPIEN 3 Valve in Transcatheter Aortic Valve Implantation: A Meta-Analysis and Systematic Review.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is now indicated in patients with symptomatic aortic stenosis and low, moderate, and high surgical risk. There are multiple types of valves available in TAVR. SAPIEN 3, and Evolut R are two of the most commonly used valves. METHODS: We conducted a systematic review and meta-analysis of all studies that compared SAPIEN 3 vs Evolut R in patients undergoing TAVR. The primary endpoint of this meta-analysis was 30-day mortality. Secondary outcomes included major of life-threatening bleeding, risk of stroke, need of permanent pacemaker implantation, and risk of moderate to severe paravalvular regurgitation (PVR). RESULTS: We included a total of 9 studies. One study was a randomized clinical trial, five were prospective observational studies and three were retrospective. 30-day mortality rate was similar between SAPIEN 3 and Evolut R (odds ratio (OR) 1.19; 95% confidence interval (CI) 0.72 to 1.93; p = 0.47). The risk of major or life-threatening bleeding (OR of 0.83, 95% CI 0.50 to 1.39; p = 0.48), and the risk of stroke (OR of 0.82, 95% CI 0.38 to 1.78; p = 0.62) were also similar between the two types of valves. Compared to SAPIEN 3, Evolut R was associated with statistically significant risk of permanent pacemaker implantation (OR of 1.40, 95% CI 1.15 to 1.70; p = 0.0007), and moderate to severe PVR (OR of 2.56, 95% CI 1.14 to 5.74; p = 0.02). CONCLUSIONS: At 30 day follow up, both Evolut R and SAPIEN 3 shared similar risks of 30-day mortality, major or life-threatening bleeding, and stroke; however greater odds of pacemaker placement implantation and moderate to severe PVR were associated with Evolut R.

Meta-analysis Examining the Usefulness of Angiotensin Receptor blockers for the Prevention of Aortic Root Dilation in Patients With the Marfan Syndrome.

The Marfan syndrome (MFS) patients are highly predisposed to thoracic aortic aneurysm and/or dissection, with virtually every patient having evidence of aortic disease at some point during their lifetime. We conducted a meta-analysis to investigate the efficacy of angiotensin receptor blockers (ARBs) in slowing down the progression of aortic dilatation in MFS patients. PUBMED, EMBASE, and COCHRANE databases were searched for relevant articles published from inception to February 1, 2020. We included randomized clinical trials evaluating the effect of ARBs on aortic root size in patients with MFS with a follow-up period of at least 2.5 years. Seven studies were included with a total of 1,510 patients. Our analysis demonstrated a significantly smaller change in aortic root and ascending aorta dilation in the ARBs treated group when compared with placebo (mean difference 0.68; 95% confidence interval [CI] -1.31 to -0.04; p = 0.04, I2 = 94%, and mean difference -0.13, 95% CI -0.17 to -0.09; p < 0.00001, I2 = 0%, respectively). ARBs as an add-on therapy to beta-blockers resulted in a significantly smaller change in aortic root dilation when compared with the arm without ARBs (mean difference -2.06, 95% CI -2.54 to -1.58; p < 0.00001, I2 = 91%). However, there was no statistically significant difference in the number of clinical events (aortic complications/surgery) observed in the ARBs arm when compared with placebo (Risk ratio of 1.01, 95% CI 0.74 to 1.38; p = 0.94, I2 = 0%). In conclusion, ARBs therapy is associated with a slower progression of aortic root dilation when compared with placebo and as an addition to beta-blocker therapy.

A unique allosteric insulin receptor monoclonal antibody that prevents hypoglycemia in the SUR-1-/- mouse model of KATP hyperinsulinism.

Loss-of-function mutations of the ß-cell ATP-sensitive potassium channels (KATP) cause the most common and severe form of congenital hyperinsulinism (KATPHI), a disorder of ß-cell function characterized by severe hypoglycemia. Children with KATPHI are typically unresponsive to medical therapy and require pancreatectomy for intractable hypoglycemia. We tested the hypothesis that inhibition of insulin receptor signaling may prevent hypoglycemia in KATPHI. To test this hypothesis, we examined the effect of an antibody allosteric inhibitor of the insulin receptor, XMetD, on fasting plasma glucose in a mouse model of KATPHI (SUR-1-/- mice). SUR-1-/- and wild-type mice received twice weekly intraperitoneal injections of either XMetD or control antibody for 8 wks. Treatment with XMetD significantly decreased insulin sensitivity, and increased hepatic glucose output and fasting plasma glucose. These findings support the potential use of insulin receptor antagonists as a therapeutic approach to control the hypoglycemia in congenital hyperinsulinism.

Postprandial Hypoglycemia in Children after Gastric Surgery: Clinical Characterization and Pathophysiology.

BACKGROUND/AIMS: Dumping syndrome is a common complication in children after fundoplication and other gastric surgeries and is characterized by postprandial hypoglycemia (PPH). Children with PPH have an exaggerated GLP-1 response to a meal with an exaggerated insulin surge and subsequent hypoglycemia. We evaluated the role of GLP-1 in the pathogenesis of PPH by examining the effects of GLP-1 receptor blockade on glucose and insulin response to a meal. METHODS: Six children with known PPH after surgery underwent a mixed meal tolerance test with/without the GLP-1 receptor antagonist exendin-(9-39) using an open-label crossover design. RESULTS: Average nadir plasma glucose concentration was ≥65 mg/dl in all treatment conditions; however, 3 out of the 6 subjects had a nadir plasma glucose <65 mg/dl during vehicle infusion, while only 1 out of the 6 had a nadir plasma glucose <65 mg/dl during infusion of exendin-(9-39). Exendin-(9-39) suppressed postmeal insulin concentrations when compared to vehicle, with a lower peak insulin concentration observed in the children who received 500 pmol/kg/min of exendin-(9-39) (131.3 ± 125.1 pmol/l) compared to children who received 300 pmol/kg/min (231.1 ± 153.4 pmol/l) or vehicle (259.7 ± 120.2 pmol/l). Gastric emptying was not different between groups. CONCLUSION: Our results suggest that the exaggerated insulin response to a meal is at least in part due to the effects of GLP-1 on the pancreatic ß-cell and suggest that GLP-1 receptor antagonists may represent a potential avenue of treatment for children with PPH.