Metformin toxicity in the intensive care unit: A case series and review of the literature.

Metformin toxicity is a life-threatening condition with high morbidity and mortality. Toxicity predominantly occurs in the setting of acute renal dysfunction, as the drug is solely eliminated by the kidneys. While this risk is widely known to clinicians, diagnosing metformin toxicity is challenging because commercially available serum metformin levels require days to weeks to result. Therefore, the intensivist must rely on medical history, clinical presentation, and routine laboratory findings to make the preliminary diagnosis. Treatment of metformin toxicity includes supportive fluid hydration, vasopressors, and emergent hemodialysis (HD). We report three critically ill patients who had near-fatal severe metformin-induced lactic acidosis. Their metformin levels were markedly higher than the toxicity threshold reported by the Federal Drug Agency. These patients made a prompt and complete recovery after the initiation of HD. We also review the pathophysiology, clinical presentation, diagnosis, and treatment of metformin toxicity.

Fatal hemorrhagic bronchopneumonia caused by Bordetella bronchiseptica in an immunocompetent patient.

Introduction: Bordetella bronchiseptica is a rare cause of hemorrhagic bronchopneumonia. Important to the clinician is a clear understanding that the treatment of this rare organism differs greatly from the successful antibiotic treatment of the more common Bordetella species, pertussis and parapertussis. Case report: A 64-year-old female presented to the emergency department after experiencing one week of worsening hemoptysis. Upon admission, she was afebrile and all initial laboratory test results were normal. Bronchoalveolar hemorrhage suggested by radiographic imaging was confirmed by bronchoscopy. Bronchoalveolar lavage (BAL) cultures contained unspeciated Bordetella. Rapid worsening of the hemoptysis led to intubation and the decision to perform bronchial artery embolization. However, the intensity of the hemoptysis persisted. Septic shock ensued despite treatment with broad spectrum antibiotics including azithromycin, vancomycin, and cefepime. The microbiological speciation results finalized shortly after the patient's death. The identified organism was B. bronchiseptica. Conclusions: Although macrolide antibiotics are first line treatment for B. pertussis and parapertussis, macrolide antibiotics are generally not effective against B. bronchiseptica. Clinical suspicion of B. bronchiseptica infection should prompt consideration of alternative antibiotics known to be effective against this rare species, including carbapenems and fluoroquinolones. The use of these latter antibiotics may advisably be considered as an empirical treatment during the delay of microbiological speciation.

Extrinsic lipoid pneumonia due to chronic polyethylene glycol consumption: A case report.

Extrinsic lipoid pneumonia (ELP) results from the aspiration of lipid-containing substances. Tissue or cell histopathology after Oil-Red-O staining can confirm the diagnosis, which requires proper tissue handling and preparation during bronchoscopy. Here, we report a case of ELP in a quadriplegic patient with a long history of dysphagia and polyethylene glycol consumption. Computed tomography (CT) of the chest revealed multiple, progressively enlarging, fat-attenuated, nodular pulmonary lesions. Bronchoscopy with bronchoalveolar lavage (BAL) and a transbronchial forceps biopsy confirmed the diagnosis of lipoid pneumonia. We discuss the clinical, radiological, and pathological features of ELP and highlight the preparatory steps required for obtaining a successful diagnosis.

Refractory pancytopenia upon initiation of asciminib in tyrosine kinase inhibitor-resistant chronic myeloid leukemia.

Asciminib, a "Specifically Targeting the ABL Myristoyl Pocket" inhibitor, is a new drug in the treatment of tyrosine kinase inhibitor (TKI)-resistant chronic myeloid leukemia (CML). Hemocytopenias associated with asciminib are common adverse events documented by clinical trials. We report a case of precipitous-onset pancytopenia with the initiation of asciminib treatment in a patient with TKI-resistant CML. This case had a confounding array of laboratory findings that evidenced a drug-induced hemophagocytic component. We hope that our case stimulates further reporting of similar cases to enhance the understanding of the pathophysiology underlying asciminib-induced hemocytopenias.

Selective IgG2-deficiency in yellow nail syndrome.

IgG2-deficiency increases susceptibility to recurrent pulmonary infections and the risk for bronchiectasis. Isolated IgG2-deficiency has not been previously described in Yellow Nail Syndrome (YNS).

Prolidase deficiency: A novel PEPD missense variant in exon 2.

Prolidase deficiency is an autosomal recessive disease that causes impaired collagen degradation. Altered collagen homeostasis results in the intracellular accumulation of imidodipeptides, which contain proline and hydroxyproline. The many clinical manifestations of prolidase deficiency include dysmorphic facial features, skeletal deformities, hepatosplenomegaly, necrotizing skin ulcers, and recurrent infections. Current clinical knowledge of this genetic disease relies upon few case reports due to its extreme rarity. Diagnosis is dependent on the detection of a pathologic gene variant. Additional diagnostic confirmation may be provided by urine amino acid quantification or reduced in vitro prolidase activity. We present a case of prolidase deficiency caused by a novel variant manifested by skeletal malformations and lifelong multisystemic infections. Genetic testing revealed a homozygous missense variant in the PEPD gene at nucleotide position 200, whereby adenine was replaced by guanine (c.200A > G). The corresponding amino acid change replaced glutamine with arginine at codon 67 (p.Gln67Arg). After boiling the urine sample for hydrolysis, quantitative urine amino acids demonstrated a markedly elevated proline level, confirming the diagnosis. We also provide a discussion of the pathophysiology, clinical manifestations, diagnostic testing, and clinical management of this disease.

Long-term low-dose cabergoline usage: Another association with cardiac valvulopathy.

A 60-year-old patient, professor of physics, presented in 1999 with sudden-onset vitiligo associated with hyperprolactinemia and a prolactinoma. Fearful of potential surgical complications at the peak of his career, the patient declined surgery and opted for medical management with bromocriptine. The decreasing effectiveness of bromocriptine after 5 years required a switch to cabergoline. After a 15-year-course of cabergoline therapy with a cumulative dose of 572 mg, echocardiographic monitoring demonstrated aortic and mitral valve thickening and regurgitation. An additional 3 years of cabergoline treatment (cumulative dose: 649 mg) resulted in worsening valve thickening and regurgitation. It is well-recognized that such valvular changes may occur with high-dose cabergoline treatment. We report a case of mitral and aortic vavulopathy in a patient who was treated with long-term (18 years) low-dosage (.5-1 mg weekly) cabergoline. cabergoline, echocardiography, valvulopathy.

Acquired Portosystemic Shunts in Cirrhosis and Portal Vein Thrombosis: A Case Report.

Acquired portosystemic shunts (PSS) are abnormal blood vessels that develop between the portal vein and systemic circulation as a result of portal hypertension. Recurrent hyperammonemic encephalopathy in our 62-year-old patient with cirrhosis and chronic portal vein thrombosis led to the discovery of an extremely rare and functioning portosystemic shunt (PSS). The PSS connected the inferior mesenteric and left renal veins. Such shunts are considered pathological structures and may require surgical intervention. The large PSS reported herein likely provided decompression of the portal hypertension. The concurrence of portal vein thrombosis clearly precluded any consideration of surgery. Therapeutic management in each instance of these shunts requires a full understanding of their origination, location, and physiologic implications.

Gastrointestinal histopathology of acute colchicine toxicity after lower dose treatment of pericarditis: A case report.

Colchicine is an anti-inflammatory alkaloid drug with anti-microtubule activity. Colchicine toxicity is a serious and potentially fatal complication associated with hallmark histopathological features most conspicuous in proliferative tissues such as the gastrointestinal tract. These features have only been reported in patients treated with high doses. We report a patient who experienced acute colchicine toxicity with gastrointestinal histologic changes after treatment with the lowest dose of colchicine. Knowledge of drug-drug interactions and the organs involved in colchicine metabolism is imperative when using colchicine, even when administered at its lowest dose.

Differential Diagnosis of Multiple Systemic Aneurysms.

Atherosclerosis and systemic hypertension are the most common pathogeneses of solitary acquired arterial aneurysms. The rare occurrence of multiple synchronous or metachronous arterial aneurysms requires considering alternative underlying causes. We present the unusual case of a male patient who sequentially developed multiple co-existing arterial aneurysms between the ages of 51 and 59. The sites of involvement included high-pressure systemic arteries and low-pressure pulmonary arteries. We discuss the broad differential diagnosis that includes heritable and non-inheritable etiologies. A keen clinical awareness of this broader array of arterial aneurysms is essential for accurate early diagnosis and proper management.

Congenital Porto-Azygous Shunt (Abernethy Malformation Type II) in an Elderly Patient: A Too-Often-Forgotten Occult Abnormality.

Congenital extrahepatic portosystemic shunts (CEPS) cause portal blood to circumvent the liver and its metabolism, allowing normally detoxified ammonia to accumulate in the systemic circulation. Hyperammonemia in the elderly often manifests clinically as toxic encephalopathy. We present a case of recurrent altered mental status in a 70-year-old patient that eluded diagnosis over several years. Hyperammonemia was the sole abnormality detected upon a thorough liver function evaluation prompted by the patient's history of remote liver disease. Enhanced computed tomography revealed an extrahepatic porto-azygous shunt arising from a hypoplastic portal vein. This case illustrates that, albeit rare, CEPS may express themselves for the first time in the elderly, a patient population that is frequently afflicted by many more common causes of altered mental status. CEPS should be considered in the differential diagnosis of inexplicable hyperammonemia in this age group.

Anti-3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase (Anti-HMG CoA) Myopathy With Cardiac Involvement: Presentation, Diagnosis, and Management.

Immune-mediated necrotizing myopathy (IMNM) is categorized into three groups: anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) IMNM, anti-signal recognition particle (SRP) IMNM, and seronegative IMNM. Cardiac involvement has been reported in a significant segment of patients with IMNM of the anti-SRP type. Emerging evidence now suggests that cardiac involvement is also implicated in the anti-HMGCR subgroup. In this report, we present a case of anti-HMGCR IMNM with cardiac involvement demonstrated by elevated troponin levels, a low ejection fraction of 40%, and regional wall motion abnormalities in the inferior, inferolateral, anteroseptal, inferoseptal, and anterolateral myocardial walls, as visualized on echocardiography. These findings markedly improved after treatment with intravenous immunoglobulin (IVIG) and prednisone. This case and other recent reports highlight the need for a cardiac workup in patients diagnosed with anti-HMGCR IMNM.

Massive empyema due to Lactococcus garvieae.

Introduction: Lactococcus garvieae, a zoonotic pathogen, may rarely infect humans through the consumption of fish. Documented manifestations of L. garvieae infection in humans include infective endocarditis, prosthetic joint infections, liver abscesses, peritoneal dialysis-associated peritonitis, osteomyelitis, meningitis, infective spondylodiscitis, acalculous cholecystitis, and urinary tract infection. Case report: An 87-year-old female was hospitalized for coffee-ground emesis secondary to acute gastritis after eating cooked fish. One week after her discharge, she developed new-onset confusion and was returned to the hospital. Chest computed tomography revealed total consolidation of the left lung and a multiloculated left pleural effusion. The patient required intubation and direct admission to the intensive care unit. Pleural fluid and blood cultures grew L. garvieae, which was susceptible to ceftriaxone, penicillin, and vancomycin. Despite intensive antibiotic therapy and supportive care for thirteen days, the patient remained in irreversible shock, and the family opted for comfort care. Conclusions: Heretofore unreported, this case demonstrates that L. garvieae can cause bronchopneumonia and empyema.

Pathogenesis and therapy of arteriovenous malformations: A case report and narrative review.

Arteriovenous malformations (AVMs) are abnormal communications between arteries and veins that lack intervening capillary beds. They have been described in almost every organ in the body, emerging sporadically or as part of well-described syndromes. Hereditary hemorrhagic telangiectasia (HHT) is a rare, progressive, and lifelong disease characterized by AVMs and recurrent hemorrhaging. In the last 2 decades, significant advances have been made in understanding the pathogenesis of this condition. The accumulation of knowledge has led to a natural evolution of therapy, from open surgery to endovascular procedures, and now to a role for medications in certain AVMs. Here, we review a case of HHT and describe the most up-to-date clinical practice, including diagnosis of HHT, subtypes of HHT, and medical therapy.

Massive left ventricular thrombosis in pericardial decompression syndrome.

BACKGROUND: Pericardial decompression syndrome (PDS) is defined as paradoxical hemodynamic deterioration associated with left, right, or bi-ventricular dilation and systolic dysfunction following pericardiocentesis. It is uncommon yet under-recognized, underreported, and associated with significant morbidity and mortality. CASE REPORT: We report a unique case of PDS associated with left ventricular (LV) systolic dysfunction and massive apical thrombosis following surgical removal of 800 ml of pericardial fluid in a 72-year-old man with undiagnosed lung cancer. Treatment with anticoagulation and anti-remodeling medications resulted in complete resolution of the thrombus and recovery of LV function. CONCLUSIONS: PDS, although rare, can lead to significant morbidity and mortality. Left ventricular apical thrombosis could result from PDS in the setting of hypercoagulable state. Treatment of the underlying disease may lead to successful resolution of PDS and its complications.

Dyspnea With Unilateral Pulmonary Ground Glass Opacities and Cavitary Lesions.

CASE PRESENTATION: A 62-year-old man presented with a 3-month history of shortness of breath and a dry cough. He had a medical history of hypertension (without use of angiotensin-converting enzyme inhibitors), hyperlipidemia, depression, and 10-pack-years of cigarette smoking several decades ago. He was a limousine driver and denied any history of occupational high-risk exposures. The patient denied significant weight gain or weight loss, night sweats, fevers, hemoptysis, chest pain, or palpitations. He had a normal physical examination. Pulmonary function studies with a hemoglobin level of 12.9 gm/dL revealed normal spirometry, normal lung volumes, and moderately low diffusion capacity (56% of predicted). A 6-minute walk test showed mild desaturation (97% to 92% after 432 m). Stress echo revealed ejection fraction of 60% with no regional wall motion abnormalities, no evidence of impaired diastolic filling, estimated peak pulmonary artery pressure 35 to 40 mm Hg, and no valvular abnormalities with desaturation to 87% during the test. Extensive rheumatologic, infectious disease, and hypercoagulability workup were unremarkable. BAL was negative for malignancy, infection, or eosinophilic lung disease.