RESUMO
Key Clinical Message: In managing Sjogren's syndrome, a thorough patient history, proper lab tests, and imaging are crucial. Clinicians should prioritize checking electrolyte levels in cases of muscle weakness, as early detection of hypokalemia can prevent severe complications. Proactive monitoring can avert renal tubular acidosis and improve patient outcomes. Abstract: Distal renal tubular acidosis (dRTA) occurs in approximately one-third of patients with Sjogren's syndrome, a systemic autoimmune disorder characterized by lymphocytic infiltration of exocrine glands, leading to dryness of mucous membranes. Hypokalemic paralysis, a well-documented but rare complication of dRTA, typically manifests as symmetric proximal muscle weakness of the extremities. We present the case of a 38-year-old woman with a history of Sjogren's syndrome diagnosed 3 years prior, who ceased her medication without medical supervision. She presented with quadriplegia, initially beginning unilaterally. This particular presentation is seldom documented in the literature. Laboratory investigations revealed hypokalemia and normal anion gap metabolic acidosis, consistent with dRTA-induced hypokalemic paralysis. Intravenous potassium chloride was administered, resulting in complete recovery of muscle strength. Hypokalemic paralysis associated with dRTA is typically reversible; however, delays in diagnosis and treatment can lead to life-threatening complications such as respiratory failure and arrhythmias. Therefore, clinicians should maintain a high index of suspicion for this condition in patients presenting with muscle weakness. Prompt and precise history takingand screening, and initiating appropriate management to prevent adverse outcomes.
RESUMO
Key Clinical Message: Metformin-associated lactic acidosis is a rare but serious complication in patients with type 2 diabetes, especially those with multiple health conditions. Prompt recognition and treatment, including potential renal replacement therapy, are crucial for managing severe acidosis and improving patient outcomes. Abstract: Metformin (MTF) is commonly prescribed as a first-line treatment for diabetes, effectively preventing microvascular and macrovascular complications. However, metformin-associated lactic acidosis is a rare yet severe complication, associated with a mortality rate of up to 50%. We encountered a case involving a 73-year-old woman with type 2 diabetes, mental illness, and hypothyroidism, who developed life-threatening lactic acidosis while on metformin therapy. Upon presenting to the emergency department with complaints of weakness, nausea, and decreased urination for 5 days, she also reported abdominal pain and shortness of breath. Hypotension was noted with a blood pressure of 80/50 mmHg. Initial laboratory results revealed severe acidosis, prompting discontinuation of MTF. Despite resuscitation efforts and vasopressor therapy, severe acidemia persisted, leading to the initiation of renal replacement therapy. Following treatment with continuous renal replacement therapy, her acidemia resolved, and she was discharged from the hospital on the sixth day without complications, with normal kidney function.
RESUMO
The tumor microenvironment is increasingly acknowledged as a critical contributor to cancer progression, mediating genetic and epigenetic alterations. Beyond diverse cellular interactions from the microenvironment, physicochemical factors such as tumor acidosis also significantly affect cancer dynamics. Recent research has highlighted that tumor acidosis facilitates invasion, immune escape, metastasis, and resistance to therapies. Thus, noninvasive measurement of tumor acidity and the development of targeted interventions represent promising strategies in oncology. Techniques like contrast-enhanced ultrasound (CEUS) can effectively assess blood perfusion, while ultrasound-stimulated microbubble cavitation (USMC) has proven to enhance tumor blood perfusion. We therefore aimed to determine whether CEUS assesses tumor acidity and whether USMC treatment can modulate tumor acidity. Firstly, we tracked CEUS perfusion parameters in MCF7 tumor models and compared them with in vivo tumor pH recorded by pH microsensors. We found that the peak intensity and area under curve of tumor contrast-enhanced ultrasound correlated well with tumor pH. We further conducted USMC treatment on MCF7 tumor-bearing mice, tracked changes of tumor blood perfusion and tumor pH in different perfusion regions before and after the USMC treatment to assess its impact on tumor acidity and optimize therapeutic ultrasound pressure. We discovered that USMC with 1.0 Mpa significantly improved tumor blood perfusion and tumor pH. Furthermore, tumor vascular pathology and PGI2 assays indicated that improved tumor perfusion was mainly due to vasodilation rather than angiogenesis. More importantly, analysis of glycolysis-related metabolites and enzymes demonstrated USMC treatment can reduce tumor acidity by reducing tumor glycolysis. These findings support that CEUS may serve as a potential biomarker to assess tumor acidity and USMC is a promising therapeutic modality for reducing tumor acidosis.
RESUMO
Many current cancer immunotherapies function by redirecting immune system components to recognize cancer biomarkers and initiate a cytotoxic attack. The lack of a universal tumor biomarker limits the therapeutic potential of these approaches. However, one feature characteristic of nearly all solid tumors is extracellular acidity. This inherent acidity provides the basis for targeted drug delivery via the pH-low insertion peptide (pHLIP), which selectively accumulates in tumors in vivo due to a pH-dependent membrane insertion propensity. Previously, we established that we could selectively decorate cancer cells with antigen-pHLIP conjugates to facilitate antibody recruitment and subsequent killing by engineered effector cells via antibody-depended cellular cytotoxicity (ADCC). Here, we present a novel strategy for opsonizing antibodies on target cell surfaces using click chemistry. We utilize pHLIP to facilitate selective tetrazine - trans-cyclooctene ligation of human IgGs to the cancer cell surface and induce ADCC. We demonstrate that our approach activates the primary ADCC signaling pathway via CD16a (FcγRIIIa) receptors on effector cells and induces the killing of cancer cell targets by engineered NK cells.
RESUMO
Relative uteroplacental insufficiency of labor (RUPI-L) is a clinical condition that refers to alterations in the fetal oxygen "demand-supply" equation caused by the onset of regular uterine activity. The term RUPI-L indicates a condition of "relative" uteroplacental insufficiency which is relative to a specific stressful circumstance, such as the onset of regular uterine activity. RUPI-L may be more prevalent in fetuses in which the ratio between the fetal oxygen supply and demand is already slightly reduced, such as in cases of subclinical placental insufficiency, post-term pregnancies, gestational diabetes, and other similar conditions. Prior to the onset of regular uterine activity, fetuses with a RUPI-L may present with normal features on the cardiotocography. However, with the onset of uterine contractions, these fetuses start to manifest abnormal fetal heart rate patterns which reflect the attempt to maintain adequate perfusion to essential central organs during episodes of transient reduction in oxygenation. If labor is allowed to continue without an appropriate intervention, progressively more frequent, and stronger uterine contractions may result in a rapid deterioration of the fetal oxygenation leading to hypoxia and acidosis. In this Commentary, we introduce the term relative uteroplacental insufficiency of labor and highlight the pathophysiology, as well as the common features observed in the fetal heart rate tracing and clinical implications.
RESUMO
Currently, risk stratification calculators for acute pancreatitis (AP) can at best predict acute pancreatitis mortality at 12 hours from the presentation. Given the severe morbidity associated with AP, the identification of additional prognostic indicators, which may afford earlier prediction in length of stay (LOS) and mortality, is desired. Metabolic acidosis can be a prognostic marker for the severity of AP, and venous bicarbonate can reliably and accurately be substituted for arterial base deficit to detect metabolic acidosis. Since serum bicarbonate, anion gap (AG), and corrected AG (CAG) are routinely obtained upon presentation to the emergency department and often daily in the hospital, we conducted a retrospective analysis of 443 patients, evaluating if venous bicarbonate could predict the severity of pancreatitis as well as mortality, admission to the ICU, ICU LOS, and hospital LOS. The inclusion of venous bicarbonate, AG, and CAG in the first 12 hours only slightly improved the predictive capabilities of the Bedside Index for Severity in Acute Pancreatitis (BISAP) score for these secondary outcomes. None of our incorporations of acidemia improved severity predictions more than the BISAP alone. Adding CAG to BISAP scoring had the largest effect on predicting ICU admission and hospital LOS (area under the curve (AUC): 1.12 (confidence interval (CI) 95%: 1.06-1.19), p <.001 and AUC 1.02 (CI 95% 1.01-1.04), p <.001; respectively). ICU LOS was not impacted by the addition of AG, CAG, or venous bicarbonate. In-hospital death (n=12) was too small to be determined.
RESUMO
Antineoplastic agents are often associated with a wide range of side effects, caused by either direct toxicity or indirect through their metabolism. Ifosfamide is a cytotoxic, antineoplastic medication that is known to cause a direct tubular injury with an associated normal anion gap metabolic acidosis due to type 1 or type 2 renal tubular acidosis (RTA). The manifestations and approach to its diagnosis have been well established. However, we present a case in which a patient presented with acute symptomatic hypokalemia in the setting of ongoing ifosfamide use for metastatic osteosarcoma but without the typical laboratory findings. The clinical- and laboratory-driven diagnosis of suspected type 3 renal tubular acidosis involving proximal and distal segments is suggested by this case report.
RESUMO
BACKGROUND: Subacute ruminal acidosis (SARA) causes an increase in endotoxin, which can induce immune and inflammatory responses in the ruminal epithelium of dairy cows. In non-ruminants, epigallocatechin-3-gallate (EGCG), a major bioactive ingredient of green tea, is well-known to alleviate inflammation. Whether EGCG confers protection against SARA-induced inflammation and the underlying mechanisms are unknown. RESULTS: In vivo, eight ruminally cannulated Holstein cows in mid-lactation were randomly assigned to either a low-concentrate (40%) diet (CON) or a high-concentrate (60%) diet (HC) for 3 weeks to induce SARA (n = 4). Cows with SARA had greater serum concentrations of tumor necrosis factor (TNF)-α and interleukin-6, and epithelium had histological signs of damage. In vitro, immortalized bovine ruminal epithelial cells (BREC) were treated with lipopolysaccharide (LPS) to imitate the inflammatory damage caused by SARA. Our data revealed that BREC treated with 10 µg/mL LPS for 6 h successfully induce a robust inflammatory response as indicated by increased phosphorylation of IκBα and nuclear factor kappa-B (NF-κB) p65. Pre-treatment of BREC with 50 µmol/L EGCG for 6 h before LPS challenge promoted the degradation of NLR family pyrin domain containing 3 (NLRP3) inflammasome through activation of autophagy, which further repressed activation of NF-κB pathway targeting Toll-like receptor 4 (TLR4). Analyses also revealed that the ECGG upregulated tight junction (TJ) protein expression upon incubation with LPS. CONCLUSIONS: Subacute ruminal acidosis causes ruminal epithelium injury and systemic inflammation in dairy cows. However, the anti-inflammatory effects of EGCG help preserve the integrity of the epithelial barrier through activating autophagy when BREC are exposed to LPS. Thus, EGCG could potentially serve as an effective therapeutic agent for SARA-associated inflammation.
RESUMO
Comorbidities in the elderly not only make them more susceptible to kidney disease, but also increase the risk of drug interactions due to polypharmacy. Such patients require regular kidney function tests when treated with renally excreted drugs. We conducted a retrospective study of post-mortem cases over a five- year period. Of 3040 toxicologically investigated cases, 3.8% had a history of renal failure. Thirteen deaths were directly attributable to inadequate drug dosing, 46% of which were related to lactic acidosis due to metformin accumulation. Appropriate dose adjustment could prevent fatal drug toxicity in patients with renal insufficiency.
Assuntos
Insuficiência Renal , Humanos , Estudos Retrospectivos , Idoso , Alemanha , Feminino , Masculino , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Metformina/efeitos adversos , Metformina/administração & dosagem , Metformina/uso terapêuticoRESUMO
BACKGROUND/AIM: The most commonly prescribed anti-seizures medications (ASMs) for the treatment of epilepsy are currently topiramate, zonisamide, lacosamide, carbamazepine and levetiracetam. The objective of this study was to examine the correlation between preoperative, intraoperative, and postoperative metabolic acidosis and the use of ASMs prior to craniotomy operations. MATERIALS AND METHODS: This retrospective cross-sectional study evaluated patients who underwent intracranial surgery with craniotomy under general anaesthesia between May 2020 and April 2023 and used ASMs. The patients were classified into four groups based on the pharmacological mechanisms of action of the ASMs administered before intracranial surgery (Group-I, zonisamide or topiramate; Group-II, lacosamide; Group-III, carbamazepine; Group-IV, levetiracetam). Metabolic acidosis severity was defined based on base excess (BE) levels: mild (-3 to -5), moderate (-5 to -10), and severe (below - 10). The study investigated the correlation between ASMs and the severity of metabolic acidosis in preoperative, intraoperative, and postoperative blood gas measurements. RESULTS: Out of 35 patients, 24 patients underwent intracranial surgery and 11 patients underwent epilepsy surgery. There were statistically significant differences in the severity of metabolic acidosis between preoperative (p < 0.001), intraoperative (p < 0.001) and postoperative (p = 0.01) groups. The preoperative mean BE of group-I was - 4.7, which was statistically lower than that of group-III (p = 0.01) and group-IV (p < 0.001). Intraoperatively and postoperatively, group-I had a mean BE of -7.5 and - 3.2, respectively, which was statistically lower than that of groups II (p = 0.007; p = 0.04), III (p = 0.002; p = 0.03), and IV (p < 0.001; p = 0.009). There was no statistically significant difference in BE between groups II, III and IV at all three time points. Group I had the lowest BE at all three time points. Intraoperative bicarbonate was administered to all patients in group I, whereas no intraoperative bicarbonate was required in the other groups. In group I, 50% of patients required postoperative intensive care. CONCLUSION: The use of ASMs in patients undergoing surgery is important in terms of mortality and morbidity. Topirimat and zonisamide are ASMs that can cause preoperative, intraoperative and postoperative metabolic acidosis. Patients receiving topirimat or zonisamide are particularly susceptible to metabolic acidosis. Special care should be taken in the management of anaesthesia in patients receiving these drugs, and monitoring of the perioperative metabolic status is essential.
Assuntos
Acidose , Anticonvulsivantes , Craniotomia , Topiramato , Zonisamida , Humanos , Craniotomia/efeitos adversos , Topiramato/administração & dosagem , Acidose/induzido quimicamente , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Estudos Retrospectivos , Feminino , Masculino , Estudos Transversais , Pessoa de Meia-Idade , Adulto , Complicações Pós-Operatórias/epidemiologia , Idoso , Epilepsia/cirurgia , Epilepsia/tratamento farmacológicoRESUMO
INTRODUCTION: Holocarboxylase synthetase deficiency (HLCS deficiency, OMIM #253270) is an exceedingly rare metabolic disorder resulting in multiple carboxylase deficiencies owing to impaired biotin cycle. Clinical manifestations include severe metabolic acidosis, hyperammonemia, tachypnea, skin rash, alopecia, feeding problems, hypotonia, developmental delay, seizures, and, in severe cases, death. METHODS AND RESULTS: An 8-day-old female neonate presented with severe lactic acidosis, necessitating sedation and mechanical ventilation. Despite receiving supportive care, no evident clinical improvement was observed, accompanied by the onset of generalized ichthyosis. Genetic analysis of actionable metabolic disorders revealed compound heterozygous variants of HLCS (NM_000411.8), specifically c.[710T>C (p.Leu237Pro)]; [1544G>A (p.Ser515Asn)], prompting the initiation of biotin mega-dose therapy (10 mg/day). Remarkably, dramatic clinical improvement in lactic acidosis was observed the day after initiating biotin administration, leading to the discontinuation of mechanical ventilation within 6 days. The patient remained in stable condition during follow-up, exhibiting normal growth and development along with consistently stable laboratory findings up to 18 months of age. CONCLUSION: Our case highlights the significance of early genetic testing in neonates with unexplained metabolic disorders to enable timely diagnosis and therapy initiation. Biotin therapy has demonstrated remarkable efficacy in improving the clinical condition of patients with HLCS deficiency, leading to favorable outcomes.
Assuntos
Biotina , Deficiência de Holocarboxilase Sintetase , Humanos , Feminino , Recém-Nascido , Biotina/uso terapêutico , Biotina/administração & dosagem , Deficiência de Holocarboxilase Sintetase/genética , Deficiência de Holocarboxilase Sintetase/tratamento farmacológico , Acidose Láctica/genética , Acidose Láctica/tratamento farmacológico , Complexo Vitamínico B/uso terapêutico , Complexo Vitamínico B/administração & dosagemRESUMO
During high-intensity (HI) exercise, metabolic acidosis significantly impairs exercise performance. Increasing the body's buffering capacity through training and exogenous intake of alkalizing supplements may improve high-intensity performance. Manipulating water and diet intake may influence the acid-base balance. The aim of this study was to determine the effects of mineral water rich in bicarbonate ions (STY) or placebo water (PLA) on circulating biomarkers and anaerobic performance and to verify whether alkalizing (ALK) or acidizing (ACI) diet would modulate these effects. Twenty-four athletes, assigned either to ALK (n = 12) or ACI (n = 12) diet for four weeks, completed a 1-min rowing Wingate Test in a double-blind and randomized trial after one week of daily hydration (1.5 to 2L/d) with either STY or PLA. Blood samples were taken before and after each test, and urine samples were collected each week. Chronic consumption of bicarbonate-rich water significantly impacted resting urinary pH irrespective of alkalizing or acidizing dietary intake. STY induced a significant increase in blood pH, lactate, and HCO3 - ion concentration post-exercise compared to PLA. Similar changes were observed when STY was associated with the ALK diet. In contrast, STY combined with the ACI diet only significantly affected urine pH and peak blood lactate compared to PLA (p < 0.05). No effect of bicarbonate-rich water was reported on anaerobic performance (p > 0.05). Our results suggest that consumption of bicarbonate-rich water alters acid-base balance during a warm-up and after HI exercise, could potentiate beneficial effects of an alkalizing diet on the acid-base balance after HI exercise, and reduces the acid load induced by an acidifying diet.
RESUMO
BACKGROUND: By controlling hypercapnia, respiratory acidosis, and associated consequences, extracorporeal CO2 removal (ECCO2R) has the potential to facilitate ultra-protective lung ventilation (UPLV) strategies and to decrease injury from mechanical ventilation. We convened a meeting of European intensivists and nephrologists and used a modified Delphi process to provide updated insights into the role of ECCO2R in acute respiratory distress syndrome (ARDS) and to identify recommendations for a future randomized controlled trial. RESULTS: The group agreed that lung protective ventilation and UPLV should have distinct definitions, with UPLV primarily defined by a tidal volume (VT) of 4-6 mL/kg predicted body weight with a driving pressure (ΔP) ≤ 14-15 cmH2O. Fourteen (93%) participants agreed that ECCO2R would be needed in the majority of patients to implement UPLV. Furthermore, 10 participants (majority, 63%) would select patients with PaO2:FiO2 > 100 mmHg (> 13.3 kPa) and 14 (consensus, 88%) would select patients with a ventilatory ratio of > 2.5-3. A minimum CO2 removal rate of 80 mL/min delivered by continuous renal support machines was suggested (11/14 participants, 79%) for this objective, using a short, double-lumen catheter inserted into the right internal jugular vein as the preferred vascular access. Of the participants, 14/15 (93%, consensus) stated that a new randomized trial of ECCO2R is needed in patients with ARDS. A ΔP of ≥ 14-15 cmH2O was suggested by 12/14 participants (86%) as the primary inclusion criterion. CONCLUSIONS: ECCO2R may facilitate UPLV with lower volume and pressures provided by the ventilator, while controlling respiratory acidosis. Since recent European Society of Intensive Care Medicine guidelines on ARDS recommended against the use of ECCO2R for the treatment of ARDS outside of randomized controlled trials, new trials of ECCO2R are urgently needed, with a ΔP of ≥ 14-15 cmH2O suggested as the primary inclusion criterion.
RESUMO
OBJECTIVE: To investigate the risk factors of renal tubular acidosis (RTA) in patients with primary Sjögren's syndrome (pSS) and create a personalized nomogram for predicting pSS-RTA patients. METHOD: Data from 99 pSS patients who underwent inpatient treatment at our hospital from January 2012 to January 2024 were retrospectively collected and analyzed. Bootstrap resampling technique, single-factor, and multi-factor logistic regression analyses were used to explore the risk factors for pSS-RTA. A nomogram was developed based on the results of the multivariate logistic model. The model was evaluated through receiver operating characteristic curve, C-index, calibration curve, and decision curve analysis. In addition, we graded the severity of pSS-RTA patients and used univariate analysis to assess the relationship between pSS-RTA severity and risk factors. RESULTS: A multivariate logistic regression analysis revealed that concurrent thyroid disease, long symptom duration, subjective dry mouth, and positive RF were independent risk factors for pSS-RTA patients. Based on them, a personalized nomogram predictive model was established. With a p-value of 0.657 from the Hosmer-Lemeshow test, the model demonstrated a good fit. The AUC values in the training and validation groups were 0.912 and 0.896, indicating a strong discriminative power of the nomogram. The calibration curves for the training and validation groups closely followed the diagonal line with a slope of 1, confirming the model's reliable predictive ability. Furthermore, the decision curve analysis showed that the nomogram model had a net benefit in predicting pSS-RTA, emphasizing its clinical value.This study did not find an association between the severity of pSS-RTA and risk factors. DISCUSSION: We developed a nomogram to predict RTA occurrence in pSS patients, and it is believed to provide a foundation for early identification and intervention for high-risk pSS patients.
Assuntos
Acidose Tubular Renal , Nomogramas , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/epidemiologia , Feminino , Acidose Tubular Renal/diagnóstico , Acidose Tubular Renal/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estudos Retrospectivos , Adulto , IdosoRESUMO
This case report describes a 65-year-old male who presented to the emergency department with significant lactic acidosis after self-poisoning by ingesting bispyribac sodium, a commonly known herbicide. This case highlights the rarity of poisoning with freely available herbicides in the literature, which may be elusive in clinical history and life-threatening in presentation. The patient had attempted to commit suicide with ingestion of an unidentified herbicide and was brought to the emergency department post two hours after the incident. He complained of abdominal pain. The hemodynamics of the patient were within normal limits. However, his initial lactate levels were elevated along with a high anion gap metabolic acidosis. The patient was provided symptomatic care and close monitoring. The ingested substance was later found to be bispyribac sodium. The patient symptomatically improved over time, with lactate levels attaining normal ranges, and was discharged after observation of 24 hours. Human ingestion of bispyribac sodium is mostly asymptomatic and non-fatal. The management in this case mainly consisted of symptomatic care. The initial presentation of herbicide poisoning in an emergency department setting as lactic acidosis and the subsequent evaluation to rule out other possible causes of lactic acidosis in the patient was challenging for the treating physician. The possibility of herbicide-mediated cellular damage and subsequent lactic acidosis is thought to be the reason for this rare presentation.
RESUMO
BACKGROUND: Pyroglutamic acidosis is a rare cause of high anion gap metabolic acidosis. Most cases of paracetamol related pyroglutamic acidosis are described in malnourished women and patients with kidney/liver failure, alcohol use or severe sepsis. In this report, we describe how pyroglutamic acidosis could be related to the use of chronic therapeutic paracetamol with only malnutrition as an associated risk factor. CASE PRESENTATION: We report a case of a 67-year-old male patient developing a pyroglutamic acidosis. The patient was initially admitted to hospital for infectious osteoarthritis and developed a metabolic acidosis during his hospital stay. Analgesics included daily therapeutic doses of paracetamol. What makes our case unusual is that our malnourished male patient did not have renal or hepatic failure. The diagnosis of paracetamol related pyroglutamic acidosis was made after ruling out the main causes of metabolic acidosis. It was further confirmed by urine organic acids measurement showing a markedly elevated level of pyroglutamic aciduria. Paracetamol was discontinued allowing a prompt correction of the anion gap. CONCLUSION: This case is a representative of pyroglutamic acidosis related to chronic therapeutic paracetamol with only malnutrition as an associated risk factor. Physicians should be aware of such unusual cause of metabolic acidosis, which may be more common than expected in hospitalized patients. A high clinical suspicion is needed when urine organic acids analysis is not available.
Assuntos
Acetaminofen , Acidose , Analgésicos não Narcóticos , Desnutrição , Humanos , Acetaminofen/efeitos adversos , Idoso , Masculino , Acidose/induzido quimicamente , Desnutrição/complicações , Analgésicos não Narcóticos/efeitos adversos , Ácido Pirrolidonocarboxílico , Equilíbrio Ácido-BaseRESUMO
Diabetic ketoacidosis (DKA) is one of the hyperglycemic emergencies seen in patients with poorly controlled diabetes mellitus. One of the potential cardiovascular complications of this hyperglycemic crisis, not that well documented in the literature, is takotsubo cardiomyopathy (TCM) also known as stress-induced cardiomyopathy or "broken heart syndrome". It is a reversible condition where the heart muscle becomes suddenly weakened and stunned, which is mostly known to develop in patients who have suffered a stressful life event or are undergoing an acute illness. We present an interesting case of a 45-year-old female with a history of poorly controlled diabetes mellitus who presented with significant hyperglycemia and laboratory results concerning DKA. The patient was also complaining of new-onset chest pain on arrival. Further workup revealed elevated troponin, severely reduced ejection fraction, and echocardiographic findings concerning TCM. The coexistence of DKA and TCM is rare but clinically significant. This case emphasizes the value of clinical vigilance in patients with this hyperglycemic crisis and encourages us to always consider stress-induced cardiomyopathy as a potential complication. Further research is needed to better elucidate the exact mechanisms linking DKA and stress-induced cardiomyopathy. This will help improve outcomes and prevent recurrence in this vulnerable patient population.
RESUMO
Marine fishes excrete excess H+ using basolateral Na+/K+-ATPase (NKA) and apical Na+/H+-exchanger 3 (NHE3) in gill ionocytes. However, the mechanisms that regulate H+ excretion during exposure to environmentally relevant hypercapnia (ERH) remain poorly understood. Here, we explored transcriptomic, proteomic, and cellular responses in gills of juvenile splitnose rockfish (Sebastes diploproa) exposed to three days of ERH conditions (pH ~7.5; ~1,600 µatm pCO2). Blood pH was fully regulated at ~7.75 despite a lack of significant changes in gill (1) mRNAs coding for proteins involved in blood acid-base regulation, (2) total NKA and NHE3 protein abundance, and (3) ionocyte density. However, ERH-exposed rockfish demonstrated increased NKA and NHE3 abundance on the ionocyte plasma membrane coupled with wider apical membranes and greater extension of apical microvilli. The observed gill ionocyte remodeling is consistent with enhanced H+ excretion that maintains blood pH homeostasis during exposure to ERH and does not necessitate changes at the expression or translation levels. These mechanisms of phenotypic plasticity may allow fishes to regulate blood pH during environmentally relevant acid-base challenges, and thus have important implications for both understanding how organisms respond to climate change and for selecting appropriate metrics to evaluate its impact on marine ecosystems.
RESUMO
Artificial neural networks (ANNs) are versatile tools capable of learning without prior knowledge. This study aims to evaluate whether ANN can calculate minute volume during spontaneous breathing after being trained using data from an animal model of metabolic acidosis. Data was collected from ten anesthetized, spontaneously breathing pigs divided randomly into two groups, one without dead space and the other with dead space at the beginning of the experiment. Each group underwent two equal sequences of pH lowering with pre-defined targets by continuous infusion of lactic acid. The inputs to ANNs were pH, ΔPaCO2 (variation of the arterial partial pressure of CO2), PaO2, and blood temperature which were sampled from the animal model. The output was the delta minute volume (ΔVM), (the change of minute volume as compared to the minute volume the animal had at the beginning of the experiment). The ANN performance was analyzed using mean squared error (MSE), linear regression, and the Bland-Altman (B-A) method. The animal experiment provided the necessary data to train the ANN. The best architecture of ANN had 17 intermediate neurons; the best performance of the finally trained ANN had a linear regression with R2 of 0.99, an MSE of 0.001 [L/min], a B-A analysis with bias ± standard deviation of 0.006 ± 0.039 [L/min]. ANNs can accurately estimate ΔVM using the same information that arrives at the respiratory centers. This performance makes them a promising component for the future development of closed-loop artificial ventilators.