Acute 2,4-dichlorophenoxyacetic acid herbicide poisoning in rural India: clinical spectrum, multiorgan toxicity, and outcomes in an eight-patient observational study.

Acute recumbency associated with necrotizing pancreatitis in a donkey.

Propionic acidemia in Mexico: Clinical and genotypic spectrum.

The kidney plays the major role in the maintenance of acid-base balance by reabsorbing the daily filtered load of bicarbonate and generating sufficient base to neutralize the acid produced by metabolism of ingested foodstuffs. Therefore, damage to the kidney caused by chronic kidney disease can be associated with a decrease in kidney ammonium excretion causing net acid excretion to fall below net acid production resulting in a positive acid balance. The acid retention can lead to eubicarbonatemic metabolic acidosis (tissue retention of acid without a change in systemic acid-base balance) or metabolic acidosis with or without acidemia. The acidosis can be associated with muscle wasting, bone disease, hypoalbuminemia, tissue inflammation, progression of chronic kidney disease (CKD), and increased mortality. Administration of base in the form of sodium bicarbonate, or sodium citrate may improve acid base balance and improve cellular function. However, recent large-scale trials have questioned its efficacy in slowing CKD progression, adding complexity to treatment decisions. Evidence that serum bicarbonate concentration >25 mEq/L might be associated with increased cardiovascular disease adds complexity to treatment decisions. Further study is warranted to determine whether sustained correction of CKD-related metabolic acidosis, with meaningful bicarbonate separation between study arms, improves hard clinical outcomes and to identify which patient subgroups derive net benefit.

Exchange proteins directly activated by cAMP (Epac1 and Epac2) are abundantly expressed in the glomerulus and epithelial cells of the renal tubule. Epac activity is rather benign at baseline, but it can be greatly potentiated in response to stress or during disease states. However, the significance of the Epac signaling cascade for kidney function is largely enigmatic. This review analyzes recently published evidence on the reno-protective actions of Epac1 and Epac2 isoforms in the pathology of glomerulonephritis and upon dietary acidification. Paralog-specific beneficial actions of Epac have been reported recently in the glomerulus and the collecting duct system. Activation of Epac1 promotes glycolysis and increases lactate production, thereby augmenting podocyte survival in an experimental model of glomerulonephritis. Dietary acidification greatly enhances renal Epac2, but not Epac1, expression to stimulate urinary acid excretion. Epac2 deficiency produces a distal renal tubule acidosis (RTA)-like phenotype associated with the inability to acidify urine due to impaired H + secretion by A-type intercalated cells. Activation of Epac1 and Epac2 isoforms is instrumental for defensive and adaptive responses in the pathophysiology of glomerulonephritis and metabolic acidosis. Further characterization and subsequent implementation of pharmacology-based treatments targeting individual Epac isoforms might be of considerable clinical importance.

Nocardia infection is a rare but severe complication in kidney transplant (KT) recipients, with high morbidity and mortality. Data on antibiotic tolerability in this population are scarce. We conducted a retrospective, multicentric study across six Spanish transplant units to analyze clinical characteristics, treatment strategies, and antibiotic tolerability in KT patients diagnosed with Nocardia infection. Twenty-six cases of Nocardia infection were identified, predominantly in elderly male patients with significant comorbidities and a high immunosuppressive burden. Pulmonary involvement was the most common presentation, although extrapulmonary manifestations also occurred. Only 36% of infections occurred within the first posttransplant year. Most patients received initial combination therapy, followed by prolonged treatment-primarily with trimethoprim-sulfamethoxazole (TMP-SMX) or linezolid. However, antibiotic tolerability was poor: TMP-SMX was discontinued in 80% of cases due to adverse effects, mainly hyperkalemia, metabolic acidosis, and acute kidney injury. Linezolid was withdrawn in 90% of patients because of myelotoxicity. Tedizolid, used in 38.4% of cases, showed better tolerability, with only 20% of treatment discontinuation and no relapses reported during follow-up. Overall, mortality during treatment reached 30.8%, mainly due to infectious causes. This is the largest series of Nocardia infection in KT recipients in Spain and the first to specifically evaluate antibiotic tolerability. TMP-SMX and linezolid were poorly tolerated, reinforcing the need for alternative strategies. Tedizolid showed a favorable safety profile and may be considered a promising first-line option in high-risk patients. Further prospective studies are needed to confirm these findings and support guideline development.

The term asphyxia refers to the condition in which there is impaired gas exchange in an individual, causing progressive hypoxia, hypercapnia and acidosis. During the perinatal period, this fetal condition is most often a consequence of impaired placental blood flow, which, in some children, can progress to hypoxic-ischemic brain injury. However, caution should be taken when considering the diagnosis of “asphyxia” in a newborn (NB), as: (1) it lacks a specific biochemical definition; and (2) it is often unjustifiably associated with impaired neurological activity, resulting in costly litigation. In fact, the manifestation of neonatal encephalopathy at birth may be due to asphyxia; however, it may be secondary to other causes, such as congenital metabolic defect, genetic anomalies or intracranial hemorrhage. Before an acute intrapartum hypoxic-ischemic event can be associated with a subsequent diagnosis of cerebral palsy, the Task Force on Neonatal Encephalopathy and Cerebral Palsy of the American Congress of Obstetricians and Gynecologists (ACOG) defines four essential criteria (ACOG, 2005): (1) evidence of metabolic acidosis in umbilical cord arterial blood obtained at the time of birth. parturition (pH < 7 and base deficit ≥ 12 mmol/L); (2) early onset of moderate or severe neonatal encephalopathy in children born at 34 or more weeks of gestation; (3) cerebral palsy of the dyskinetic or spastic quadriplegic type; and (4) exclusion of other identifiable etiologies, such as trauma, coagulation abnormalities, infectious diseases, or genetic abnormalities.

Serotonin syndrome is a potentially life-threatening condition caused by excessive concentrations of synaptic 5-hydroxytryptamine. At present, due to the absence of gold-standard laboratory diagnostic test and the variability of its clinical manifestations, it could be confused with other clinical conditions, leading to delayed diagnosis that may compromise patient prognosis and survival. This case report depicted a 59-year-old Chinese man who may developed serotonin syndrome during gastrointestinal endoscopy anesthesia with fentanyl injection while taking Angelica multiple times, resulting in the failure of gastrointestinal endoscopy. Related clinical symptoms were specifically manifested as generalized muscle clonus, sweating, fever, elevated blood pressure, tachycardia, and metabolic acidosis. The patient improved after symptomatic treatment. This case reveals that the combined use of Angelica sinensis and fentanyl injection may cause serotonin syndrome during surgery, which could threaten the patient's life and thus affect the operation. This case report highlights the importance of recognizing serotonin syndrome, identifying its clinical manifestations, and implementing timely clinical management strategies. It also emphasizes the potential risk of adverse reactions associated with traditional Chinese medicine, particularly avoiding combined use before and after anesthesia.

Metformin-associated lactic acidosis (MALA) is a rare but fatal complication of metformin therapy, typically precipitated by acute kidney injury (AKI), dehydration, or sepsis. Natural disasters disrupt healthcare access and increase gastrointestinal illness, data on MALA within the disaster settings are limited. We report 12 patients presenting with severe MALA during a major flooding event in Hat Yai, Southern Thailand, in late 2025. Disrupted infrastructure led to poor oral intake, dehydration, and delayed presentation, with many patients continuing metformin despite acute illness. At presentation, patients exhibited high-anion gap metabolic acidosis (pH range 6.78-7.31, peak lactate 24mmol/L) and advanced AKI. All patients required emergent renal replacement therapy (RRT), utilizing intermittent hemodialysis, slow low-efficiency dialysis, or continuous RRT depending on hemodynamic stability and clinical context. Timely RRT facilitated rapid biochemical correction and renal recovery. All the cohort survived to hospital discharge. This case series highlights flood-related healthcare disruption as an under-recognized precipitating factor for MALA. Severe MALA may occur despite therapeutic metformin dosing when acute illness, dehydration, and AKI coexist. Early recognition, prompt discontinuation of metformin, and timely initiation of RRT are critical for favorable outcomes. These findings underscore the importance of disaster-specific preventive strategies, including proactive dissemination of "sick-day rules," early nephrology involvement, and ensuring timely access to medical care for high-risk patients during natural disasters.

ObjectiveTo evaluate the association between admission blood gas parameters, particularly pH and base excess (BE), and serial amplitude-integrated electroencephalography (aEEG) background patterns, and to determine whether these early metabolic markers are associated with MRI-defined brain injury severity in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH).MethodsThis retrospective study included 80 neonates (gestational age ≥35 weeks) with moderate-to-severe HIE treated with TH. Admission pH and BE values were recorded. Serial aEEG monitoring was performed at 6, 24, 48, and 72 h of life, and background patterns were classified according to Hellström-Westas criteria. aEEG recordings were independently interpreted by two reviewers blinded to the clinical and MRI data. Brain MRI was performed in 74 neonates at a median postnatal age of 5 days and was evaluated by a blinded pediatric neuroradiologist.ResultsAdmission BE was significantly associated with aEEG background patterns at all evaluated time points (6 h: p = 0.001; 24 h: p = 0.003; 48 h: p = 0.034; 72 h: p = 0.005). Infants with more severely depressed aEEG patterns had more negative admission BE values. In contrast, neither admission pH nor BE was significantly associated with MRI-defined brain injury severity. Overall mortality was 7.5%.ConclusionAdmission metabolic derangement, particularly BE, is associated with early electrocortical depression on serial aEEG but not with MRI-defined structural brain injury severity in neonates with HIE treated with TH. These findings support a dissociation between early metabolic acidosis and established structural brain injury and underscore the importance of multimodal prognostic assessment in early clinical decision-making.

Acetazolamide attenuates lactate accumulation during high-altitude ascent in the Himalayas: a randomized pilot field study.

Delayed Recovery From Anesthesia Revealing Unrecognized Metabolic Acidosis and Hypokalemia in a Patient With Urinary Diversion

Introduction Daboia siamensis envenoming is a major cause of hematotoxicity and acute kidney injury in Southeast Asia. In Thailand, D. siamensis is a clinically important snake, yet detailed national data on its bites are limited. Hence, we aimed to determine the clinical characteristics, management, and outcomes of D. siamensis bites in Thailand, identify factors associated with acute kidney injury and hemodialysis, and analyze antivenom administration with reference to acute kidney injury and hemodialysis. Methods We conducted a 10-year retrospective cross-sectional study using data from the Ramathibodi Poison Center Toxic Exposure Surveillance System (2014–2023). All diagnosed D. siamensis bites were reviewed. Definite cases were defined when the snake species was identified via a live specimen, carcass, or photograph. Results A total of 185 patients were included, with 101 definite cases. Most (82.7%) were male, and the mean (±SD) age was 43.0 ± 16.6 years. Overall clinical manifestations included local effects (20.5%), coagulopathy (89.2%), acute kidney injury (50.3%), thrombocytopenia (31.4%), and rhabdomyolysis (28.1%). Antivenom was administered in 89.2% of cases. The median (IQR) length of hospital stay was 5 (3–7) days. The mortality rate was 3.8%. Tachycardia at presentation, initial proteinuria, and rhabdomyolysis were found to prognosticate the development of acute kidney injury. Metabolic acidosis at presentation and rhabdomyolysis were predictors of the requirement for hemodialysis. In addition, receiving antivenom within two hours may reduce the need for hemodialysis (odds ratio 0.153, 95% CI 0.035–0.674). Discussion Discrepancies between our findings and those of others on D. siamensis bites may have resulted from geographic variation in the venom composition and/or differences in the study period and population. Although antivenom treatment did not reverse renal injury, it may have prevented progression. Conclusions Systemic hematotoxicity and nephrotoxicity generally developed after a D. siamensis bite. Several clinical characteristics are potential markers of acute kidney injury and hemodialysis requirement after a D. siamensis bite, and early administration of antivenom may reduce the need for hemodialysis.

Critically ill children with low blood glucose concentrations in low-income settings suffer a high risk of mortality independent of other signs of disease severity and despite administration of the currently recommended treatment of hypoglycemia. This study explores other pathways that may relate to the high mortality risk, namely electrolyte derangements, metabolic acidosis, and hyperketonemia. Children ages 1 month to 5 years old presenting with one or more WHO emergency signs were recruited upon arrival to the Pediatric Accident and Emergency Department at Queen Elizabeth Central Hospital in Malawi between November 2022 and June 2024. A total of 12 hypoglycemic (blood glucose <2.5 mmol/L), 36 low glycemic (blood glucose 2.5-4.9 mmol/L), and 201 normoglycemic (blood glucose 5.0-10.0 mmol/L) children were enrolled. Low glycemic children had increased odds of acidosis (adjusted odds ratio [aOR] = 5.84, 95% CI: 1.17-29.2 for moderate acidosis; aOR = 27.1, 95% CI: 6.08-120.9 for severe acidosis). Among children with acidosis, there were increased odds of hypokalemia (aOR = 24.5, 95% CI: 2.91-205.88), hyponatremia (aOR = 2.58, 95% CI: 1.33-4.99 for moderate acidosis; aOR = 3.62, 95% CI: 1.71-7.68 for severe acidosis), and hypernatremia (aOR = 9.42, 95% CI: 2.50-35.5 for severe acidosis). There were no increased odds of potassium or sodium derangements in those with low glucose concentrations. Low blood glucose concentrations were associated with metabolic acidosis, which in turn, was associated with hypokalemia and hyponatremia/hypernatremia. However, there was no direct association between low blood glucose and electrolyte derangements.

The role of extracellular acidity in regulating parathyroid hormone (PTH) secretion in cultured mouse parathyroid glands (PTGs) has not studied to date, largely due to the technical difficulty of isolating mouse PTGs. We hypothesized that acidic extracellular pH directly stimulates PTH secretion through activation of a proton-sensing receptor, specifically ovarian cancer G protein-coupled receptor 1 (OGR1, also known as GPR68). To test this, we developed a method to reliably identify and isolate PTGs from male mice by administering 5-aminolevulinic acid (5-ALA), which induced selective fluorescence in these glands. Using this model, we demonstrate that acidic extracellular pH significantly stimulates PTH secretion in cultured mouse PTGs. Mechanistically, we identify OGR1 as the primary proton sensor mediating this response, as PTGs from OGR1 knockout mice failed to increase PTH secretion under acidic conditions, with no evidence of compensatory upregulation of other proton-sensing receptors. In addition, we found that low extracellular Ca2+ not only stimulates PTH secretion but also promotes extracellular acidification. Notably, low Ca2+ and acidic pH act synergistically to enhance PTH secretion in wild-type PTGs, an effect markedly attenuated in OGR1-deficient glands. Together, these findings establish a direct, OGR1-dependent mechanism by which extracellular acidity regulates PTH secretion and reveal an interaction between calcium and pH signaling in this process. This work provides a robust ex vivo model for studying PTG physiology and offers new insight into how metabolic acidosis may contribute to secondary hyperparathyroidism in chronic kidney disease, highlighting OGR1 signaling as a potential therapeutic target.

Do we adequately monitor for severe anion gap metabolic acidosis during sodium thiosulfate therapy for calciphylaxis?

INTRODUCTION: Acute massive blood loss is a critical condition associated with the loss of a significant volume of circulating blood, leading to hemorrhagic shock and multiorgan failure. In the setting of prehospital stage and scarce resources carrying out early and adequate intensive care may be impossible or significantly delayed. In these cases reduced oxygen delivery to tissues leads to severe ischemia, and cellular resistance to hypoxic damage becomes one of the key factors determining poor outcomes. Thus, in recent years special attention was given to cytoprotective properties of noble gases. OBJECTIVE: To study the effect of using respiratory mixtures with elevated concentrations of noble gases (argon and krypton) on survival in acute massive blood loss. MATERIALS AND METHODS: A prospective randomized controlled study was conducted on 16 pigs (35–50 kg). Experimental animals were randomized into 2 groups: a control group (n = 8) (30 % oxygen-air mixture) and an experimental group (n = 8) (“Argon-Krypton” mixture: 60 % argon, 30 % oxygen, and 10 % krypton). Acute massive blood loss up to 50 % of the total blood volume was simulated without infusion therapy. Animal survival over 2 hours was assessed, and hemodynamics, acid-base balance, arterial blood gas composition, and hematological parameters were monitored. RESULTS: In the experimental group, 1 animal died, compared to 3 animals in the control group (p &lt; 0.001). Following blood loss simulation the experimental group showed higher rates of mean arterial pressure 57 (53; 66) vs. 39 (20; 51) mm Hg, in the control group (p = 0.041), partial pressure of oxygen 132 (90; 146) vs. 84 (76; 94) mm Hg (p = 0.028) and arterial blood oxygen saturation 99 (97; 99) vs. 96 (94; 97) % (p = 0.015). Acid-base status remained stable in the experimental group, whereas progressive metabolic acidosis was observed in the control group; statistically significant intergroup differences were found within 2 hours of monitoring (p = 0.005). СONCLUSIONS: The use of a gas mixture containing argon and krypton in acute massive blood loss is associated with increased survival in large laboratory animals (pigs), promotes systemic hemodynamics stabilization and reduces the severity of metabolic acidosis.

Acute hyperkalaemia is a potentially life-threatening electrolyte disturbance frequently encountered in emergency departments. Timely recognition and appropriate treatment are critical to prevent serious complications such as cardiac arrhythmias and death. This narrative review summarises current evidence-based and guideline-based recommendations for the emergency management of hyperkalaemia, with a focus on practical challenges and frequently encountered clinical uncertainties. A selective literature search was conducted using PubMed, EMBASE and major international guidelines, emphasising clinical studies performed in emergency departments or acute care settings.Key treatment principles include therapy with intravenous calcium salts, primarily indicated in patients with ECG changes or serum potassium levels ≥6.5 mmol/L. Insulin-glucose therapy remains a cornerstone of transcellular potassium shifting but carries a considerable risk of subsequent hypoglycaemia, particularly in non-diabetic patients with low baseline glucose levels. Inhaled beta-agonists such as salbutamol provide an effective and synergistic potassium-lowering effect and are recommended in combination with insulin. The use of sodium bicarbonate remains uncertain and its indication appears limited to patients with severe comorbid conditions and metabolic acidosis. Diuretics may support potassium elimination in patients with volume overload, although prospective evidence in ED populations is lacking. Sodium polystyrene sulfonate is no longer recommended due to questionable efficacy and risk of gastrointestinal adverse events. Newer potassium binders, including sodium zirconium cyclosilicate and patiromer, show promise in recent studies but require further validation in acute care settings. Haemodialysis remains the definitive option in refractory cases or patients with end-stage renal disease.

Dose-dependent effects of methylene blue on hemodynamics, cytokines, oxidative stress, and organ dysfunction in a rat model of CLP-induced sepsis: An experimental study.

Hydroxychloroquine (HCQ)-induced renal phospholipidosis typically manifests as glomerular "zebra bodies", "myeloid bodies", and "curvilinear bodies" and is generally considered a benign histological mimic of Fabry disease. We report a case of HCQ-induced renal phospholipidosis with proximal tubulopathy presenting as slowly progressive kidney dysfunction and Fanconi syndrome, challenging the notion that renal phospholipidosis is clinically silent. A 36-year-old woman with systemic lupus erythematosus (SLE) treated with HCQ for 18 months presented with slowly progressive kidney dysfunction. Urinalysis showed minimal proteinuria and no active sediment suggestive of a lupus nephritis flare; however, urinary markers of tubular injury were markedly elevated. She exhibited normoglycemic glycosuria, pan-aminoaciduria, hypophosphatemia, hypouricemia, and metabolic acidosis, consistent with mild but distinct Fanconi syndrome. Her estimated glomerular filtration rate (eGFR) slope rapidly declined at - 11.2 mL/min/1.73m²/year during HCQ treatment. Kidney biopsy revealed glomerular z"zebra bodies", "myeloid bodies", and "curvilinear bodies" characteristic of HCQ-induced renal phospholipidosis, as well as lysosomes filled with electron-dense granules within glomeruli. Notably, lysosomes filled with electron-dense granules were also abundant in proximal tubular epithelial cells, resembling the "lysosomal accumulation of light chains" seen in light chain proximal tubulopathy (LCPT) without crystal formation and "lysosomes containing dark electron-dense aggregates" of chronic interstitial nephritis in agricultural communities (CINAC). Extensive clinical, biochemical, genetic, and histological evaluations excluded Fabry disease. Immunofluorescence demonstrated globotriaosylceramide (Gb3) minor and patchy positivity accumulation in both glomeruli and proximal tubules, suggesting that lysosomal metabolic dysfunction occurred similarly in glomerular cells and tubular epithelial cells. Based on these findings, a diagnosis of proximal tubulopathy secondary to HCQ-induced renal phospholipidosis was made. HCQ discontinuation resulted in the resolution of Fanconi syndrome and improvement of the eGFR slope to + 0.9 mL/min/1.73m²/year. This case indicates that HCQ-induced renal phospholipidosis is not merely a silent histological finding but can manifest as clinically significant proximal tubulopathy. The pathophysiology likely involves active tubular secretion of HCQ causing rapid lysosomal and transporter dysfunction analogous to LCPT without crystal formation and CINAC. While standard monitoring for lupus nephritis focuses on glomerular markers, monitoring tubular function markers in HCQ-treated patients may enable early detection of this potentially underdiagnosed complication.