Metformin-Associated Lactic Acidosis-Is This on Your Radar?

BACKGROUND: Metformin is a biguanide hyperglycemic agent used to manage non-insulin-dependent diabetes mellitus. Adverse reactions include mainly mild gastrointestinal adverse effects, but severe complications, such as metformin-associated lactic acidosis (MALA) can occur. Metformin is excreted renally and, therefore, not recommended in patients with renal impairment. The reported incidence of MALA is 3 cases per 100,000 patient-years. CASE REPORT: A 79-year-old woman with a complex medical history, including end-stage renal disease on dialysis and type 2 diabetes, presented to the emergency department (ED) for altered mental status. Prior to arrival, she was found to be hypoglycemic. Her laboratory results were significant for creatinine of 6.56 mg/dL and an anion gap of 52 mmol/L. The venous blood gas revealed a venous pH of 6.857 [reference range (7.32-7.43)], pCO2 of 15.9 mm Hg (40.6-60 mm Hg), HCO3 of 2.7 mmol/L (21-30 mmol/L), lactate of 27 mmol/L (0.5-2 mmol/L), and ammonia of 233 µmol/L. The patient was dialyzed emergently in the ED; repeat laboratory test results showed blood urea nitrogen of 10 mg/dL, creatinine of 1.65 mg/dL, carbon dioxide of 26 mmol/L, and anion gap of 13 mmol/L. The repeat ammonia was 16 µmol/L. The patient's metabolic encephalopathy resolved, and she was discharged home on hospital day 3. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: MALA has a high mortality rate (36%). Laboratory markers have not been found to be a reliable predictor of mortality. Sodium bicarbonate is controversial, but a pH < 7.15 indicates consideration of its use. A pH < 7.1 and a lactate level > 20 mmol/L indicate the need for emergent hemodialysis. Prompt recognition and management in the ED with early hemodialysis can result in good patient outcomes, with a return to their baseline function despite severe laboratory findings.

Identification of the novel role of sterol regulatory element binding proteins (SREBPs) in mechanotransduction and intraocular pressure regulation.

Trabecular meshwork (TM) cells are contractile and mechanosensitive, and they aid in maintaining intraocular pressure (IOP) homeostasis. Lipids are attributed to modulating TM contractility, with poor mechanistic understanding. In this study using human TM cells, we identify the mechanosensing role of the transcription factors sterol regulatory element binding proteins (SREBPs) involved in lipogenesis. By constitutively activating SREBPs and pharmacologically inactivating SREBPs, we have mechanistically deciphered the attributes of SREBPs in regulating the contractile properties of TM. The pharmacological inhibition of SREBPs by fatostatin and molecular inactivation of SREBPs ex vivo and in vivo, respectively, results in significant IOP lowering. As a proof of concept, fatostatin significantly decreased the SREBPs responsive genes and enzymes involved in lipogenic pathways as well as the levels of the phospholipid, cholesterol, and triglyceride. Further, we show that fatostatin mitigated actin polymerization machinery and stabilization, and decreased ECM synthesis and secretion. We thus postulate that lowering lipogenesis in the TM outflow pathway can hold the key to lowering IOP by modifying the TM biomechanics.

Spontaneous Hyphema and Vitreous Hemorrhage Causing Secondary Glaucoma in a Patient on Apixaban.

BACKGROUND: Spontaneous hyphema is the rare occurrence of hemorrhage within the anterior chamber of the eye without a predisposing traumatic event. Hyphema can be associated with acute elevations in intraocular pressure in up to 30% of cases, which poses a significant risk for permanent vision loss if not quickly recognized and treated in the emergency department (ED). Anticoagulant and antiplatelet medications have been previously associated with cases of spontaneous hyphema; however, there are limited reports of hyphema with associated acute glaucoma in a patient taking a direct oral anticoagulant. Due to the limited data of reversal therapies for direct oral anticoagulants in intraocular hemorrhage, these patients pose a challenge in deciding whether to reverse anticoagulation in the ED. CASE REPORT: We present a case of a 79-year-old man on apixaban anticoagulation therapy who presented to the ED with spontaneous painful vision loss in the right eye with associated hyphema. Point-of-care ultrasound revealed an associated vitreous hemorrhage, and tonometry was significant for acute glaucoma. As a result, the decision was made to reverse the patient's anticoagulation with four-factor activated prothrombin complex concentrate. Why Should an Emergency Physician Be Aware of This? This case is an example of acute secondary glaucoma due to a hyphema and vitreous hemorrhage. There is limited evidence regarding anticoagulation reversal in this setting. A second site of bleeding was identified by utilization of point-of-care ultrasound, which led to the diagnosis of a vitreous hemorrhage. This allowed for shared decision-making between the emergency physician, ophthalmologist, and patient regarding the risks and potential benefits of the reversal of anticoagulation. Ultimately, the patient decided to have his anticoagulation reversed to try and preserve vision.

An implant-supported rehabilitation case using innovative provisional restoration design and conversion as diagnostic and treatment modalities.

This article reviews and details a maxillary anterior implant-supported rehabilitation case that required an interdisciplinary approach. An innovative technique is presented, in which a transitional acrylic and wrought wire removable partial denture was converted at chairside to a provisional fixed bridge on the day of Stage II implant surgery. This technique underscores and illustrates the importance of diagnosis, planning, and sequential, coordinated treatment in dental rehabilitation.