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Abstract Background Syndrome of apparent mineralocorticoid excess (AME) is characterized by excessive MR stimulation despite low levels of aldosterone. 11Beta-hydroxysteroid dehydrogenase-2 (11βDSH-2) inactivates cortisol to cortisone, preventing cortisol-induced MR activation. Genetic defects in 11βDSH-2 cause AME through accumulation of cortisol in the distal nephron, leading to MR activation induced hypertension, hypokalemia and metabolic alkalosis. Acquired AME can occur due to the ingestion of glycyrrhizic acid, found in licorice root, which inhibits 11βDSH-2 and has additional effects on cortisol homeostasis through inhibition of 11βDSH-1. Case report We present a case of acquired AME with a hyperadrenergic symptoms induced by ingestion of Advanced Liver Support, a nutritional supplement produced by Advanced BioNutritionals(R), in a 65-year-old Caucasian female who presented with accelerated hypertension, hypokalemia, metabolic alkalosis and adrenergic symptoms. Cessation of the licorice-containing supplement resulted in complete resolution of the patient's hypertension, symptoms and abnormal lab values. To our knowledge this is the first reported case of AME from this supplement, and the first to describe accompanying hyperadrenergic symptoms. Conclusions Glycyrrhizic acid is increasingly being found in unregulated nutritional supplements and has the potential to induce a reversable syndrome of AME. Acquired AME should be suspected in individuals who present with hypertension along with hypokalemia, metabolic alkalosis and low plasma renin and serum aldosterone levels.

Abstract Background Immune checkpoint inhibitors and mitogen-activated protein kinase inhibitors have become the standard of care in patients with advanced melanoma bearing V600 mutations. However, little is known about their nephrotoxicity. To date, only two cases of anti-glomerular basement membrane glomerulonephritis after exposure to checkpoint inhibitors have been documented. Herein, we report the first case of a patient with metastatic melanoma who developed linear Immunoglobulin G 3+, Immunoglobulin A 2+, kappa 2+, lambda 1+ anti-glomerular basement membrane glomerulonephritis with negative serology following treatment with checkpoint inhibitors and subsequently mitogen-activated protein kinase inhibitors. Case presentation A 58-year-old Caucasian male was referred to our outpatient nephrology clinic with acute kidney injury and proteinuria. He had received three cycles of ipilimumab and nivolumab for recurrent melanoma positive for the BRAF V600E mutation with metastasis to the lungs. Immunotherapy had been discontinued in the setting of severe adverse effects including dermatitis, colitis, and hepatitis. Because of persistent bilateral lung metastases and left pleural metastases, the patient had been initiated on dabrafenib and trametinib until his presentation to our clinic 6 months later. On presentation, his blood pressure was 172/89 mm/Hg and had 2+ edema bilaterally. His creatinine level was 2.4 mg/dL from a previous normal baseline with a urinary protein-to-creatinine ratio of 2 g/g. His urinalysis showed dysmorphic erythrocytes and red blood cell casts. Serologic testing was negative for antineutrophilic cytoplasmic antibodies, proteinase 3 antigen, myeloperoxidase, and anti-glomerular basement membrane antibody. Complement levels were normal. A renal biopsy showed focal crescentic (2 of 15 glomeruli with cellular crescents), proliferative, and sclerosing glomerulonephritis with diffuse linear staining of glomerular capillary loops dominant for IgG (3+), IgA (2+), kappa (2+), and lambda (1+) minimal changes. He was initiated on oral cyclophosphamide and pulse intravenous methylprednisolone followed by oral prednisone for 6 months, which stabilized his renal function until reinitiation of immunotherapy. Conclusions Acute kidney injury is an increasingly reported adverse effect of both drug classes, mostly affecting the tubulointerstitial compartment and infrequently the glomerulus. Although the biologic effect of these drugs on immune cells is not entirely understood, it is possible that BRAF-induced podocyte injury in combination with direct T-cell-mediated glomerular injury facilitated by checkpoint inhibitors led to the unmasking of cryptic antigens, loss of self-tolerance, and autoimmunity. More importantly, we show that treatment with corticosteroids and cyclophosphamide was able to improve and stabilize our patient’s renal function until the reinitiation of immunotherapy.

Oxcarbazepine and carbamazepine cause hyponatremia by unknown mechanisms. We describe a patient with complete central diabetes insipidus and seizures who developed worsening hyponatremia when her dose of oxcarbazepine was increased. The patient maintained a normal serum sodium level and has had appropriately concentrated urine for 5 years on just oxcarbazepine, despite undetectable antidiuretic hormone (ADH) levels. This suggests that oxcarbazepine (or one of its metabolites) may stimulate collecting tubule V2 receptor-G protein complex independent of ADH, resulting in increased renal tubular water reabsorption. Oxcarbazepine may be useful as an alternative therapy for patients with central diabetes insipidus.

Calcitriol-mediated hypercalcemia has been reported in malignant lymphomas and granulomatous diseases but not in lung carcinoma. We describe a patient with squamous cell lung carcinoma with hypercalcemia and elevated calcitriol levels. A 60-year-old Caucasian male patient with stage IIIB squamous cell lung cancer developed hypercalcemia at 14.8 mg/dL two years after receiving chemotherapy and radiotherapy where labs showed a serum intact PTH: 7 pg/mL, PTHrP: 30 pmol/L, 1,25-hydroxyvitamin D (calcitriol): 76 pg/mL, and 25-hydroxyvitamin D levels:

Major Tropical Cyclone (TC) events cause extensive damage in coastal regions of the western North Atlantic Basin. The short instrumental record leaves significant gaps in understanding long‐term trends in TC recurrence and intensity, creating uncertainty about future storm trends. Analysis of an ∼520‐year core record from Harvey Lake, located >80 km from the Atlantic coast in southwestern New Brunswick, Canada was carried out using: (a) end‐member mixing analysis (EMMA) of lake sediment grain size data to identify storm‐linked sedimentological processes; and (2) ITRAX X‐ray fluorescence (XRF) derived element/ratios (Fe, Ti, Ca/Sr, Zr/Rb, K/Rb, and Br + Cl/Al) associated with precipitation, weathering, catchment runoff, and air masses. Three derived end members were correlated to heavy rainfall events (EM01), spring freshet (EM02), and TCs (EM03). CONISS analysis of the EMMA and XRF core data resulted in recognition of four unique climatic zones distinguished by distinct distributions of TC and rainfall/weathering/runoff/and air masses. Numerous, major (EM01) rainfall events and (EM03) TC events characterized the basal core record during the early Little Ice Age (LIAa; Zone 1) phase, terminating at ∼1645. A near cessation of heavy rainfall and TC events differentiated the subsequent colder LIAb (∼1645–1825; Zone 2) and subsequent Little Ice Age Transition (∼1825–1895; Zone 3). A resurgence of major rainfall and TC events occurred during recovery from the LIA starting in ∼1895 (Zone 4). EMMA provides a robust tool for recognition of TC and major rainfall events, and greatly expands the potential for paleo‐storm activity research well inland from coastal regions. Key Points: Grain size End‐Member Mixing Analysis (EMMA) permits recognition of major storm and heavy rainfall events in an ∼500 years lake core recordCONISS zonation of EMMA and ITRAX data from core delineated phases of the Little Ice Age (LIA) and transition to modern warm eraStorm records and major rain events characterized LIAa, then nearly ceased before increasing dramatically during the modern warm era [ABSTRACT FROM AUTHOR]

A sediment core from a lagoon in southeastern Cuba was the focus of a multi-proxy paleoenvironmental study to investigate lagoon response to sea-level change and climate change and also to infer changes in the frequency of past hurricane strikes. The proxy data examined included benthic foraminifera, fossil pollen, particle size analysis, and macrocharcoal influx values. The core was dated using 137Cs and accelerator mass spectrometry (AMS) radiocarbon methods. The results show that lagoon formation began approximately 4000 years ago and that the lagoon environment evolved through four phases: (1) from ~4000 to 2800 cal. yr BP, the lagoon was a shallow polyhaline to euryhaline system with limited mangrove coverage; (2) from ~2800 to 2000 cal. yr BP, there was a decrease in salinity which facilitated the expansion of red mangrove; (3) from ~2000 to 1000 cal. yr BP, sea-level rise resulted in an increase in water depth and possibly salinity; and (4) from ~1000 cal. yr BP to the present, water level continued to rise and the mangrove environment diversified. The shift to lower salinity conditions from ~2800 to 2000 cal. yr BP may have been climate driven as similar changes are seen at lagoons elsewhere in Cuba. The particle size data show several periods where sand-sized particles are more abundant; these periods are similar to data from Puerto Rico that document times of relatively frequent hurricanes. This paper shows that coastal lagoons are useful archives of paleoclimatic and paleoenvironmental information in the Caribbean region and that they should be the focus of additional research efforts. [ABSTRACT FROM AUTHOR]

Arcellinida (testate lobose amoebae) were examined in near-surface sediment samples from 30 lakes located within the Gold Terra Resource Corporation (GTRC) Yellowknife City Gold Project, Northwest Territories, Canada, to assess the applicability of using the group as a robust tool to assess Arsenic (As) contamination. Lake contamination by As is of concern in the Yellowknife area because it is derived from geogenic (bedrock) and anthropogenic sources (legacy pollution from former mining operations, particularly the Giant Mine [1948–2004]). Statistical multivariate analyses (cluster analysis, non-metric multidimensional scaling [NMDS], and redundancy analysis [RDA]) were performed on geochemical (inductively coupled plasma mass spectrometry [ICP-MS]) and organic (loss-on-ignition) data to identify geochemical and hydrogeological controls on the arcellinidan distribution in the lakes. Three distinct faunal assemblages were identified using Cluster analysis and NMDS: 1) Elevated Arsenic Assemblage (EAA; Approximately Unbiased (AU) p -value = 97 %; median As =272.4 mg/kg, range = 42–1353 mg/kg ; n = 9); 2) Centropyxid-Dominated Assemblage (CDA; AU p -value = 87 %; median As =169.7 mg/kg, range 60–233 mg/kg ; n = 9); and, 3) Difflugiid-Dominated Assemblage (DDA; AU p -value = 95 %; median As =61.3 mg/kg, range = 16–316 mg/kg ; n = 12). Six statistically significant controls on assemblage structure were identified using RDA. These were As, calcium, iron, strontium, water depth, and total organic carbon (Arcellinida variance explained = 36.2 %) — As is the most significant control (12.2 %; p-value < 0.002). Stress-tolerant centropyxids dominate in lakes characterized by elevated sedimentary As concentrations (64 % centropyxids in EAA; 40 % centropyxids in CDA), while stress-sensitive taxa thrived in samples associated with lower As concentrations (DDA). Our results corroborate the findings of previous Arcellinida studies in subarctic Canada and confirms the reliability of using Arcellinida as a reconnaissance tool for tracking As contamination in impacted lakes. [ABSTRACT FROM AUTHOR]