Search Results (118)

After the first release of synthalin B (dodecamethylenbiguanide) in 1928 and its later retraction in the 1940s in Germany, the retraction of phenformin (N-Phenethylbiguanide) and of Buformin in the USA (but not outside) because of the lethal complication of acidosis seemed to have put an end to the era of the biguanides as oral antidiabetics. The strongly hygroscopic metformin (1-1-dimethylbiguanide), first synthesized 1922 and resuscitated as an oral antidiabetic (type 2 of the elderly) compound first released in 1959 in France and in other European countries, was used in the first large multicenter prospective long-term trial in England in the UKPDS (1977–1997). It was then released in the USA after a short-term prospective trial in healthy overweight “young” type 2 diabetics (mean age 53 years) in 1995 for oral treatment of type 2 diabetes. It was, however, prescribed to mostly multimorbid older patients (above 60–65 years of age). Metformin is now the most used oral drug for type 2 diabetes worldwide. While intravenous administration of biguanides does not have any glucose-lowering effect, their oral administration leads to enormous increase in their intestinal concentration (up to 300-fold compared to that measured in the blood), to reduced absorption of glucose from the diet, to increased excretion of glucose through the stool, and to decrease in insulin serum level through increased hepatic uptake and decreased production. Intravenously injected F18-labeled glucose in metformin-treated type 2 diabetics accumulates in the small and even more in the large intestine. The densitometry picture observed in metformin-treated overweight diabetics is like that observed in patients after bowel-cleansing or chronically taking different types of laxatives, where the accumulated radioactivity can even reach values observed in colon cancer. The glucose-lowering mechanism of action of metformin is therefore not only due to inhibition of glucose uptake in the small intestine but also to “attraction” of glucose from the hepatocyte into the intestine, possibly through the insulin-mediated uptake in the hepatocyte and its secretion into the bile. Furthermore, these compounds have also a diuretic effect (loss of sodium and water in the urine) Acute gastrointestinal side effects accompanied by fluid loss often lead to the drugs’ dose reduction and strongly limit adherence to therapy. Main long-term consequences are “chronic” dehydration, deficiency of vitamin B12 and of iron, and, as observed for all the biguanides, to “chronic” increase in fasting and postprandial lactate plasma level as a laboratory marker of a clinical condition characterized by hypotension, oliguria, adynamia, and evident lactic acidosis. Metformin is not different from the other biguanides: synthalin B, buformin, and phenformin. The mechanism of action of the biguanides as antihyperglycemic substances and their side effects are comparable if not even stronger (abdominal pain, nausea, vomiting, diarrhea, fluid loss) to those of laxatives. Full article

Background/Objectives: Acetazolamide is widely used for acute mountain sickness (AMS) prophylaxis. Whilst generally safe, acute kidney injury (AKI) is a rare but serious adverse event. We present a case of anuric AKI following minimal exposure to acetazolamide, contributing to the limited literature on its nephrotoxicity at prophylactic doses. Methods: A 54-year-old previously healthy male ingested 250 mg/day of oral acetazolamide for two days. He developed acute anuria and lumbar pain. Diagnostic evaluation included laboratory tests, imaging, microbiological cultures, autoimmune panels, and diuretic response. No signs of infection, urinary tract obstruction, or systemic disease were found. Results: The patient met KDIGO 2012 criteria for stage 3 AKI, with peak serum creatinine of 10.6 mg/dL and metabolic acidosis. Imaging confirmed non-obstructive nephrolithiasis. Conservative treatment failed; intermittent hemodialysis was initiated. Renal function recovered rapidly, with the normalization of serum creatinine and urinary output by day 4. Conclusions: This case represents the lowest cumulative dose of acetazolamide reported to cause stage 3 AKI. The findings support a pathophysiological mechanism involving sulfonamide-induced crystalluria and intratubular obstruction. Physicians should consider acetazolamide in the differential diagnosis of AKI, even with short-term prophylactic use. Full article

Background/Objectives: Diabetic ketoacidosis (DKA) is an acute and severe complication of diabetes mellitus, marked by hyperglycemia, ketosis, and acidosis. It is associated with significant metabolic and inflammatory adjustments that can impact multiple biochemical pathways. This study aimed to determine the serum sphingolipid profile in DKA and investigate its relationship with neutral sphingomyelinase (N-SMase), pro-inflammatory cytokines, β-hydroxybutyrate (β-OHB), and lactate levels. Methods: Thirty-three participants were divided into three groups: control (BMI ≤ 30, no health issues), obese (BMI > 30), and DKA (BMI ≤ 30). Sphingomyelins (16:0–24:0 SMs) and ceramides (C16–C24 CERs) were measured using ultra-fast liquid chromatography combined with tandem mass spectrometry (LC-MS/MS). N-SMase, interleukin 1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) levels were assessed by enzyme-linked immunosorbent assay. Evaluations were done in the DKA group before and after standard clinical treatment for DKA (post-DKA group), which included intravenous insulin therapy, fluid resuscitation, and electrolyte replacement, as per established clinical guidelines. Results: β-OHB levels were significantly higher in the DKA group than in the control, obese, and post-DKA groups. Although β-OHB levels decreased in the post-DKA group, they remained elevated compared to the control and obese groups. Lactate levels were also higher in the DKA group, with a significant decrease in the post-DKA group. TNF-α and IL-1β were higher in the obese group compared to control and DKA groups, and TNF-α decreased significantly in the post-DKA group compared to DKA. N-SMase, 16:0–18:0 SMs, and C18-C24 CER levels were lower in the DKA and post-DKA groups compared to obese and control groups. Serum β-OHB and lactate levels were significantly correlated with S1P, total CER, total SM, and N-SMase values. Conclusions: The study reveals significant metabolic and inflammatory differences in DKA and post-DKA states, suggesting a relationship between sphingolipids, N-SMase, and these alterations, which could offer insights into DKA pathophysiology and therapeutic targets. Full article

Background and Clinical Significance: Diabetic ketoacidosis (DKA) is a serious and potentially life-threatening condition, often triggered by infections or undiagnosed diabetes. Spontaneous pneumomediastinum (SPM) and pneumothorax are rare but recognized complications of DKA, possibly due to alveolar rupture from increased respiratory effort or vomiting. Sometimes, acute pancreatitis (AP) may further complicate DKA, but the co-occurrence of these three conditions remains exceptionally rare. Case Presentation: We describe the case of a 60-year-old woman without a known history of diabetes who arrived at the emergency department with abdominal pain, fatigue, vomiting, and altered mental status. Initial laboratory findings showed metabolic acidosis, hyperglycemia, and elevated anion gap, consistent with DKA. Imaging revealed spontaneous pneumomediastinum and subsequently a left-sided pneumothorax, without evidence of trauma or esophageal rupture. Epigastric pain, along with elevated serum lipase and CT findings, also confirmed acute pancreatitis. Despite the complexity of her condition, the patient responded well to supportive treatment, including oxygen therapy, fluid resuscitation, insulin infusion, and antibiotics. She was discharged in good condition after 28 days, with a confirmed diagnosis of type 2 diabetes, without further complications. Conclusions: This case highlights an unusual combination of DKA complicated by spontaneous pneumomediastinum, pneumothorax and acute pancreatitis in a previously undiagnosed diabetic patient. Because prompt intervention can lead to favorable outcomes even in complex, multisystem cases, early recognition of atypical DKA complications is critical in order to avoid misdiagnosis. Full article

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a rare disease with variable clinical manifestations. MELAS is most often caused by the human mitochondrial DNA (mtDNA) m.3243A>G variant. We describe cardiac magnetic resonance (CMR) imaging findings and clinical features of 22 subjects with the m.3243A>G mutation and endeavored to discover the role of CMR in MELAS cardiomyopathy diagnostics. The clinical symptoms, ECG findings, and laboratory tests were retrospectively collected from the electronic medical record. Ten subjects (46%) had cardiac symptoms, and eighteen subjects (82%) had some clinical symptoms or signs of MELAS. Seventeen subjects (77%) showed cardiac findings compatible with MELAS. An ECG showed a short PR interval in six subjects (27%). Two patients had a first-degree atrioventricular block. Repolarization changes in the ECG were observed in thirteen subjects (59%), whereas left ventricular hypertrophy voltage criteria were only observed in one subject. Patients with ECG abnormalities had a strong link between proBNP value and cardiac tissue composition (T1 relaxation, p < 0.02) and showed decreased CMR-based strain (p < 0.025). The CMR findings are heterogeneous in subjects with m.3243A>G. Cardiac MELAS may include left ventricular hypertrophy, which mimics sarcomericcardiomyopathy but maypredispose individuals to severe heart failure episodes triggered by acute critical situations. CMR may be used to clarify ECG findings. This study indicates that the genetic testing of MELAS should be considered in new cases of HCM or sudden heart failure phenotypes of unknown etiology. Full article

Background: Acute mesenteric ischemia (AMI) is a potentially life-threatening condition that requires prompt diagnosis and treatment. The presence of air within the arterial lumen, particularly in the abdomen, is an uncommon finding with varied etiologies. This case report presents a unique instance of AMI with air in the superior mesenteric artery (SMA), highlighting the complexities in diagnosis and management. Case presentation: An 89-year-old male with a history of smoking, hypertension, dyslipidemia, and atrial fibrillation presented with chest pain and underwent coronary angiography for suspected anterior ST-elevation myocardial infarction (STEMI). Following successful thromboaspiration and admission to the coronary care unit, he developed severe abdominal pain. A contrast-enhanced computed tomography (CECT) scan revealed a thromboembolic occlusion in the SMA, along with air filling in the SMA and its branches. An endovascular thrombectomy was performed, but the patient died the next day due to complications related to AMI and metabolic acidosis. Conclusions: This case underscores the challenges in diagnosing and managing AMI, particularly when accompanied by unusual imaging findings such as air within the SMA. The presence of air in the arterial system raises questions about its origin and clinical significance in the context of AMI. Further research is needed to understand the mechanisms and implications of this rare phenomenon, which may have implications for refining diagnostic and therapeutic strategies for AMI. Full article

Background: Acute Stanford Type A aortic dissection (ATAAD) is a devastating disease requiring immediate surgery. A life-threatening complication hereby represents organ malperfusion. Lactate is a product of anaerobic glycolysis indicating organ malperfusion. The current study analyzes preoperative lactate acidosis as a surrogate marker for patients’ outcome after surgery for ATAAD over a 15-year period. Methods: In a single-center setting, 306 consecutive patients, who underwent surgery for ATAAD between 2000 and 2016, were analyzed retrospectively. Serum lactate measurements were taken before surgery. To define a simple cut-point of the predictor lactate, the maximally selected rank statistics method was used. Results: Median survival was 9.3 ± 0.5 and CI 95% [8.3–10.2] years. Mean lactate levels were 1.95 mmol/L ± 2.19 mmol/L (range: 0.15–19.27 mmol/L). Patients with a lactate level > 3.71 mmol/L had a higher 30-day mortality compared to patients with lactate levels ≤ 3.71 mmol/L (51.5% versus 18.7%). In a logistic regression model adjusted for clinical baseline characteristics at index procedure, lactate levels > 3.71 mmol/L reached the highest Odd for 30-day mortality of all tested risk factors (OR = 7.292; CI95% [3.029–17.555]; p < 0.0001). Analyzing the overall mortality, the early effect of lactate level > 3.71 mmol/L persists. The HRs for overall mortality, however, revealed substantially lower effects (HR = 2.772; (CI95% [1.689–4.550]; p < 0.0001). In patients who survived the first 30 days postoperatively, no clinical parameter other than age had a significant impact on survival, including lactate > 3.71 mmol/L (p = 0.494). Conclusions: In patients with ATAAD, preoperative lactate represents an easily obtainable surrogate marker for organ malperfusion. A preoperative lactate level > 3.71 mmol/L depicts the strongest marker for early mortality after surgery. Full article

All parts of Alocasia × amazonica (A. amazonica, Araceae) pose a toxicological risk due to oxalate production. Ingestion of the plant extract may cause multi-organ damage and fatal outcomes. Given the rarity of poisoning cases, its toxicological profile and systemic effects remain insufficiently characterized. This study aimed to investigate and report an appropriate approach to managing a patient intoxicated with A. amazonica (Araceae). A case of intentional self-poisoning with A. amazonica is presented. The patient, a 63-year-old woman, ingested approximately 200–300 mL of liquid prepared from the grated root of the plant. The initial clinical presentation involved localized injuries to the oral cavity and gastrointestinal tract, including severe pain, hoarseness, aphonia, dysphagia, mucosal erosions, and necrosis. Additional symptoms included hematinic vomiting, hemorrhagic diarrhea, and abdominal discomfort. These superficial and mucosal lesions resolved without the development of adhesions. Systemic effects comprised impaired consciousness indicative of encephalopathy, early metabolic acidosis, pulmonary edema with acute respiratory insufficiency, mild liver dysfunction, and hematuria. The therapeutic protocol for oral poisoning management was appropriate, leading to the patient’s discharge after 20 days of hospitalization. Full article

Piperacillin/tazobactam (PT), a widely utilized broad-spectrum antibiotic, has been associated with acute kidney injury (AKI). Although the precise mechanism remains uncertain, and most cases of PT-associated AKI are mild, this report describes a rare and severe complication of PT, which manifested as severe AKI with necrotizing glomerulonephritis requiring hemodialysis. A 42-year-old man was transferred to the nephrology clinic due to progressive deterioration of kidney function. Prior to the transfer, the patient had been diagnosed with appendicitis complicated by peritonitis and received intravenous PT for 8 days. Baseline kidney function was normal, but serum creatinine subsequently increased to 7.2 mg/dL. Hemodialysis was initiated to address metabolic acidosis and edema. Kidney biopsy revealed severe acute tubular injury and necrotizing glomerulonephritis. Steroid therapy was initiated based on the biopsy findings, and serum creatinine returned to normal levels after 4 weeks of treatment. This case demonstrates that severe AKI with necrotizing glomerulonephritis can occur after PT use. Prompt kidney biopsy and the timely initiation of immunosuppressive therapy are essential for a favorable outcome. Full article

Electrolyte imbalances are a frequently overlooked yet critical component of obesity-related metabolic dysfunction, contributing to an increased risk of cardiovascular disease, kidney impairment, and metabolic emergencies such as diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic state (HHS), and acute kidney injury (AKI). These disturbances arise from insulin resistance, chronic inflammation, hormonal dysregulation, and renal dysfunction, leading to sodium retention, potassium depletion, and deficiencies in calcium and magnesium homeostasis. Managing electrolyte imbalances is essential in obesity management, as imbalances exacerbate hypertension, metabolic acidosis, neuromuscular complications, and insulin resistance. This review explores the pathophysiology of electrolyte disturbances in obesity and their impact on fluid balance, acid–base status, and metabolic health. Effective management strategies include individualized electrolyte monitoring, dietary sodium restriction, potassium supplementation, vitamin D and magnesium correction, and pharmacologic interventions targeting renin–angiotensin–aldosterone system (RAAS) activity and insulin resistance. Additionally, lifestyle interventions, including dietary modification, weight loss strategies, and hydration optimization, play a key role in preventing metabolic complications. Future research should investigate the long-term impact of electrolyte imbalances in obesity, the role of emerging therapies, and how lifestyle interventions can optimize electrolyte homeostasis and metabolic outcomes. A personalized, multidisciplinary approach integrating endocrinology, nephrology, and clinical nutrition is essential to improving the prevention and management of electrolyte imbalances in obese individuals. Full article

Background and Clinical Significance: Acute esophageal necrosis (AEN), or black esophagus, is an extraordinary rare source of acute upper gastrointestinal bleeding. Its pathogenesis is still poorly understood, whereas etiology seems to be multifactorial, mainly involving esophageal ischemia, increased acid reflux, and reduced mucosal defenses. Although alcohol abuse has been reported to be a common trigger factor, only one case of AEN due to severe alcoholic lactic acidosis has been described up to date. Case Presentation: Herein, we describe a case of a non-cirrhotic 61-year-old lady with a history of chronic alcohol abuse, who was admitted to the Emergency Room due to upper gastrointestinal (GI) bleeding. AEN caused by severe alcoholic lactic acidosis was promptly diagnosed by subsequent investigations, including blood test, urinalysis, computed tomography, and upper GI endoscopy. The treatment involved a multidisciplinary, aggressive medical approach, which included one hemodialysis session. Conclusions: This is the second documented case of AEN secondary to alcoholic lactic acidosis, successfully treated with a previously unreported aggressive multidisciplinary approach, involving one hemodialysis session. It highlights the value of a multidisciplinary approach in managing such complex and rare conditions. Full article

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency (HMGCS2D) is a rare metabolic disorder that impairs the body’s ability to produce ketone bodies and regulate energy metabolism. Diagnosing HMGCS2D is challenging because patients typically remain asymptomatic unless they experience fasting or illness. Due to the absence of reliable biochemical markers, genetic testing has become the definitive method for diagnosing HMGCS2D. This study included 19 patients from 14 unrelated families diagnosed with HMGCS2D in our department between October 2018 and October 2024. The clinical presentations, biochemical findings, molecular characteristics, and management strategies were systematically summarized and analyzed. Of the 19 cases studied, 16 were symptomatic, and 3 were asymptomatic. The onset of the first acute episode occurred between 10 days and 28 months of age. Triggers for the initial crisis in the symptomatic cases included poor feeding (93.8%), vomiting (56.3%), diarrhea (25.0%), and fever (18.8%). Clinical manifestations during the first episode were lethargy/coma (81.3%), rapid breathing (68.8%), hepatomegaly (56.3%), shock (37.5%), and seizures (18.8%). The biochemical abnormalities observed included elevated plasma transaminases (100%), metabolic acidosis (75%), hypoglycemia (56.3%), and elevated plasma ammonia levels (31.3%). Additionally, low free carnitine levels were found in seven cases, elevated C2 levels were found in one case, dicarboxylic aciduria was found in two cases, and ketonuria was found in two cases. Abnormal brain MRI findings were detected in three patients. Genetic analysis revealed seven HMGCS2 gene variants across the 19 cases. Notably, a novel variant, c.407A>T (p.D136V), was identified and has not been reported in any existing databases. Two common variants, c.559+1G>A and c.1090T>A (p.F364I), were present in 11 out of 19 cases (57.9%) and 10 out of 19 cases (55.5%), respectively. The implementation of a high glucose infusion and proactive management strategies—such as preventing prolonged fasting and providing enteral carbohydrate/glucose infusion during illness—effectively reduced the rate of acute relapses following accurate diagnosis. Currently, all 19 patients are alive, with ages ranging from 5 months to 14 years, and exhibit normal physical development. To the best of our knowledge, this study represents the first reported cases of HMGCS2D in Vietnamese patients. Our findings contribute to a broader understanding of the clinical phenotype and expand the known spectrum of HMGCS2 gene variants, enhancing current knowledge of this rare metabolic disorder. Full article

G protein-coupled receptors (GPRs), including pro-inflammatory GPR4 and ovarian cancer GPR1 (OGR1/GPR68), are involved in the pH sensing of the extracellular space and have been implicated in inflammatory bowel disease (IBD). Previous data show that a loss of GPR4 or OGR1 independently is associated with reduced intestinal inflammation in mouse models of experimental colitis. In the present manuscript, we investigated the impact of the simultaneous loss of GPR4 and OGR1 in animal models of IBD. To study the effects of combined loss of Gpr4 Ogr1 in IBD we used the well-established acute dextran sodium sulfate (DSS) and spontaneous Il10^−/− murine colitis models. Disease severity was assessed using multiple clinical scores (e.g., body weight loss, disease activity score, murine endoscopic index of colitis severity (MEICS) and histological analyses). Real-time quantitative polymerase chain reaction (qPCR), Western blot, and flow cytometry were used to investigate changes in pro-inflammatory cytokines expression and immune cells infiltration. We found that a combined loss of GPR4 and OGR1 significantly reduces colon inflammation in IBD relative to single deficiencies as evidenced by reduced body weight loss, disease score, CD4/CD8 ratio, and Il1β, Il6, and Tnf in the colon. Similarly, in the II10 deficiency model, the inflammation was significantly ameliorated upon the simultaneous deletion of GPR4 and OGR1, evidenced by a reduction in the MEICS score, colon length, Tnf and Il1β measurements, and a decrease in the number of macrophages in the colon, as compared to single deletions. Importantly, hydroxyproline levels were decreased close to baseline in Il10^−/− × Gpr4^−/− × Ogr1^−/− mice. Our findings demonstrate that the simultaneous loss of GRP4 and OGR1 functions exerts an additive effect on multiple parameters associated with colonic inflammation. These results further reinforce the hypothesis that chronic inflammatory acidosis is a driver of fibrosis and is dependent on GPR4 and OGR1 signaling. The inhibition of both GPR4 and OGR1 by pH-sensing receptor modulators may constitute as a potential therapeutic option for IBD, as both pH-sensing receptors appear to sustain inflammation by acting on complementary pro-inflammatory pathways. Full article

Diabetic ketoacidosis is the most common acute complication in children and adolescents with type 1 diabetes, and contributes significantly to morbidity, mortality, and healthcare burden. This review aims to explore the multifaceted aspects of severe diabetic ketoacidosis in pediatric age, including its epidemiology, pathogenesis, risk factors, complications and emphasizing advances in prevention strategies. Incidence rates vary due to influences from geographic, socioeconomic, cultural and demographic factors. Pathogenesis is linked to insulin deficiency and an excess of counter-regulatory hormones, which disrupt glucose, protein, and lipid metabolism, causing hyperglycemia, ketosis, acidosis, dehydration, and electrolyte imbalances. According to the International Society for Pediatric and Adolescent Diabetes guidelines, severe diabetic ketoacidosis is characterized by a pH < 7.1 or bicarbonate < 5 mmol/L. This condition can lead to a wide range of life-threatening complications, including cerebral edema that represents the leading cause of death. Several prevention strategies, including awareness campaigns, early diagnosis of diabetes, regular monitoring and management, effective insulin therapy, education, access to healthcare and technological assistance, may contribute to reduce the risk of severe diabetic ketoacidosis episodes in children and adolescents. Full article

Sodium bicarbonate has been used in the treatment of different pathologies, such as hyperkalemia, cardiac arrest, tricyclic antidepressant toxicity, aspirin toxicity, acute acidosis, lactic acidosis, diabetic ketoacidosis, rhabdomyolysis, and adrenergic receptors’ resistance to catecholamine in patients with shock. An ongoing debate about bicarbonate’s efficacy and potential harm has been raised for decades because of the lack of evidence supporting its potential efficacy. Despite the guidelines’ restrictions, sodium bicarbonate has been overused in clinical practice. The overuse of sodium bicarbonate could be because of the desire to correct the arterial blood gas parameters rapidly instead of achieving homeostasis by treating the cause of the metabolic acidosis. Moreover, it is believed that sodium bicarbonate may reverse acidosis-induced myocardial depression, hemodynamic instability, ventricular arrhythmias, impaired cellular energy production, resistance to catecholamines, altered metabolism, enzyme suppression, immune dysfunction, and ineffective oxygen delivery. On the other hand, it is crucial to pay attention to the potential harm that could be caused by excessive sodium bicarbonate administration. Sodium bicarbonate may cause paradoxical respiratory acidosis, intracellular acidosis, hypokalemia, hypocalcemia, alkalosis, impaired oxygen delivery, cerebrospinal fluid acidosis, and neurologic dysfunction. In this review, we discuss the pathophysiology of sodium bicarbonate-induced adverse effects and potential benefits. We also review the most recent clinical trials, observational studies, and guidelines discussing the use of sodium bicarbonate in different pathologies. Full article