Acid-base Disorders Research Articles

The Association between Dietary Acid Load and Non-Communicable Diseases: A Cohort Study in Shahrekord

Background and aim: It has recently been suggested that acid-base imbalances may play a role in some types of cardiovascular diseases and metabolic disorders. The aim of this study is to investigate the association between dietary acid load and common non-communicable diseases (NCDs). Methods: In this cross-sectional study, 1800 participants were enrolled in a cohort study in Shahrekord. Data were collected using a Food Frequency Questionnaire (FFQ). The potential renal acid load (PRAL) was calculated using the intestinal absorption of five nutrients including protein, potassium, phosphorus, magnesium, and calcium. The association of dietary acid load with NCDs was investigated in two models. Then, the raw model was adjusted by including calorie intake and age; after adjusting the effect of the two variables, the association between dietary acid load and the studied NCDs was not statistically significant. Results: The mean age of the participants was 51.49±9.27 years, and 941 (52.27%) of them were female. Mean±SD acid load score was -6.88±23.23. The results showed that there was a significant association between dietary acid load and age (P=0.005), weight (P=0.0001), waist circumference (P=0.016), hip circumference (P=0.0001), waist-to-hip ratio (P=0.01), body mass index (P=0.004), and triglyceride (P=0.012). In the raw model, a significant association was observed between dietary acid load and hypertension (OR=0.57, 0.39-0.8). Conclusion: In this study, no significant association was observed between dietary acid load and NCDs, but the variable was associated with weight and body mass index as the most important risk factors for NCDs.

Metabolic acidosis as a predictor of outcome in critically ill children – A single-center prospective observational study

Background: Acid-base disorders are common in critically ill patients and contribute significantly to mortality and morbidity. Metabolic acidosis (MA) can be measured by pH, base deficit, serum bicarbonate, and anion gap. A study was conducted to determine the incidence and type of MA among children admitted to the pediatric intensive care unit (PICU) and to assess its roles as a predictor of outcomes in them. Subjects and Methods: Over 1 year, 100 children between 1 month and 12 years of age who presented to the PICU with an MA or developed it within 24 h of admission were prospectively enrolled. Clinicodemographic data, pediatric sequential organ failure assessment score at admission, clinical outcome, and serial measurements of anion gap, serum lactate, and bicarbonate level were recorded. Results: The incidence of MA was 60.2% with a majority (52%) being high anion gap metabolic acidosis (HAGMA). The predominant condition (39%) leading to MA was catecholamine-resistant shock with organ dysfunction. Peak lactate value and bicarbonate nadir had a significant positive correlation with the duration of mechanical ventilation and inotropic support, but only peak lactate value was significantly associated with mortality. A peak lactate value of 2.19 mmol/L yielded the highest sensitivity and specificity for predicting mortality. There was no association was found between peak anion gap and morbidity or mortality. Conclusions: MA was observed in 60% of children in PICU, with HAGMA being the most common type. Peak lactate value and bicarbonate nadir were correlated with high morbidity, but only peak lactate value was significantly associated with mortality.

POLYCYSTIC OVARY SYNDROME (PCOS) AND ITS TREATMENT AS CAUSE OF SECONDARY ALDOSTERONISM: A DOG CHASING ITS TAIL

Objective: Polycystic Ovary Syndrome (PCOS) is a complex endocrine-metabolic disorder affecting about 7% of childbearing women. PCOS is characterized by anovulation, hyperandrogenism, insulin resistance and it is associated with an increased cardiovascular risk. PCOS patients may exhibit high blood pressure and signs of hydro-saline retention. Therefore, clinicians would be interested in performing hormonal screening for secondary hypertension. Design and method: We perform the aldosterone/direct renin concentration ratio as a screening test for primary aldosteronism (PA). The test was proceed after serum potassium correction and previous a wash-out period of interfering medications. The recumbent saline suppression test was performed with infusion of 2L NaCl 0.9% in 4 hours under standardized salt intake (9gr/24h). Aldosterone and direct renin were determined by chemiluminescent immunoassay technology (DiaSorin®). Results: A 33yrs old woman attended our renal outpatient clinic because of recurrent episodes of generalized swelling, diuresis contraction and fluid retention. The patient, known for PCOS, was treated with combined oral contraceptives and loop diuretics. She had no history of hypertension, but she repeatedly displayed very high aldosterone values. Clinical examination was unremarkable, in-office and home blood pressure values were normal. Laboratory data showed normal renal function and the absence of acid-base disorders; serum potassium was at lower limit of normal. A CT-scan showed normal adrenal glands. We performed a recumbent saline suppression test, previous a wash-out period of oral contraceptives (> 6 weeks) and loop diuretics (> 2 weeks). The results listed below are consistent with a baseline hyperaldosteronism with normal aldosterone adrenal response to volume expansion, excluding PA. Several years before, the same results were presented, without suspension of the oral contraceptives. Conclusions: In patients with PCOS the increased adrenal production of aldosterone is usually secondary and independent from the renin-aldosterone axis (direct stimulation of adrenal zona glomerulosa via testosterone). Other iatrogenic factors may affect the renin-aldosterone values, such us the use of oral contraceptives and diuretics. Therefore, a confirmatory test performed under standardized conditions is often required, in order to exclude primary versus secondary forms of hyperaldosteronism.

Hypercalcemia Etiologies in Pediatric Patients: An Informative Narrative Review

Background: Hypercalcemia, although less prevalent, is a critical diagnosis in pediatric patients, consisting of numerous etiologies that differ significantly from those in adults. In children, congenital causes are more prevalent. The differential diagnosis of hypercalcemia encompasses a broad spectrum of etiologies; however, up to 90% of all cases are diagnosed with either primary hyperparathyroidism or malignancy. Primary hyperparathyroidism predominates in ambulatory patients, while malignancy is more common among critically ill hospitalized patients. Objectives: This review addresses several important issues related to calcium metabolism and hypercalcemia: a) Overview of Calcium Metabolism b) Factors affecting serum total and ionized calcium concentration c) Clinical manifestations and importance of Hypercalcemia in pediatric patients d) Overview of the causes of Hypercalcemia in pediatric patients e) Overview of Hypercalcemia management Methods: A literature search was conducted for articles published from 2000 to 2024 using PubMed, Scopus, Web of Science, Cochrane, and Embase databases. The keywords used were: CALCIUM, Calcium metabolism disorders, hypercalcemia, Parathyroid hormone, Vitamin D, and acid-base imbalance. Results: This study provides a review of calcium metabolism and factors affecting total and ionized calcium concentrations, along with a definition of hypercalcemia, classification of its severity, its clinical manifestations, and a comprehensive overview of hypercalcemia etiologies categorized into parathyroid hormone (PTH)-related and unrelated causes. An overview of its management is also included. Conclusions: Hypercalcemia is an important disorder in both pediatric and adult patients. Before initiating a workup for hypercalcemia, it is crucial to understand the physiology of calcium and the factors affecting its serum concentrations. The etiologies of hypercalcemia in pediatric patients have a wide spectrum of differential diagnoses; primary hyperparathyroidism and malignancies account for 80-90% of all hypercalcemia cases found in clinical practice. Genetic and syndromic causes are usually more prevalent in pediatrics due to the nature of these conditions. Managing hypercalcemia requires two simultaneous approaches: first, measures aimed at lowering serum calcium concentrations and second, a workup for the underlying cause.

Orostachys malacophylla (pall.) fisch extracts alleviate intestinal inflammation in Drosophila

Ethnopharmacological relevanceOrostachys malacophylla (Pall.) Fisch (O. malacophylla) is a succulent herbaceous plant that is the Orostachys genus of Crassulaceae family. O. malacophylla has been widely used as a traditional Chinese medicine with antioxidant, anti-inflammatory, anti-febrile, antidote, anti-Toxoplasma gondii properties. However, the biological function of alleviating intestinal inflammation and key bioactive compounds were still unknown. Aim of the studyWe used a Drosophila model to study the protective effects and bioactive compounds of O. malacophylla water extract (OMWE) and butanol extract (OMBE) on intestinal inflammation. Materials and methodsDrosophila intestinal inflammation was induced by oral invasion of dextran sodium sulfate (DSS) or Erwinia carotovora carotovora 15 (Ecc15). We revealed the protective effects of two extracts by determining intestinal reactive oxygen species (ROS) and antimicrobial peptide (AMP) levels and intestinal integrity, and using network pharmacology analysis to identify bioactive compounds. ResultsWe demonstrated that both OMWE and OMBE could ameliorate the detrimental effects of DSS, including a decreased survival rate, elevated ROS levels, increased cell death, excessive proliferation of ISCs, acid-base imbalance, and disruption of intestinal integrity. Moreover, the overabundance of lipid droplets (LDs) and AMPs by Ecc15 infection is mitigated by these extracts, thereby enhancing the flies' resistance to adverse stimuli. In addition, we used widely targeted metabolomics and network pharmacology analysis to identify bioactive compounds associated with IBD healing that are present in OMWE and OMBE. ConclusionsIn summary, our research indicates that OMWE and OMBE significantly mitigate intestinal inflammation and have the potential to be effective therapeutic agents for IBD in humans.

Effects of low protein diets on acid-base balance, electrolyte balance, intestinal structure, and amino acid transport in piglets.

Reducing the dietary crude protein (CP) could effectively reduce pressure on protein ingredient supplies. However, few data have been reported about the extent to which CP can be reduced and whether limiting the use of soybean meal leads to electrolyte imbalance. In this experiment, using the low protein (LP) diet [2% lower than NRC (2012)], seventy-two piglets (35 days old) were randomly divided into 2 groups with 6 replicates of 6 piglets each: CON group (CP = 18.5%) and LP group (CP = 16.5%), to investigate the effect of the LP diet on electrolyte balance, acid-base balance, intestinal structure and amino acid transport in piglets. The results revealed that the LP diet decreased the average daily gain and dietary CP digestibility, and damaged the villi structure of the small intestine. Compared with the CON diet, the potassium content decreased and the chlorine content increased in the LP diet, and similar trends were shown in piglet serum. The arterial pH, pCO2, HCO3 -, and base excess of piglets in the LP group were lower than those in the CON group, while pO2 was higher than those in the CON group. Interestingly, the LP diet significantly increased the lysine content in piglet serum and significantly decreased the levels of arginine, leucine, and glutamic acid. Furthermore, the LP diet significantly affected the expression of some amino acid transport vectors (B0AT1, EAAC1, and y+LAT1). In summary, these findings suggested that the LP diet leads to acid-base imbalance, amino acid transport disorder and amino acids imbalance in piglets, and the dietary electrolyte may be a key factor in the impact of the LP diet on piglet growth performance and intestinal health.

Acute sodium bicarbonate administration improves ventilatory efficiency in experimental respiratory acidosis: clinical implications.

Administering sodium bicarbonate (NaHCO3) to patients with respiratory acidosis breathing spontaneously is contraindicated because it increases carbon dioxide load and depresses pulmonary ventilation. Nonetheless, several studies have reported salutary effects of NaHCO3 in patients with respiratory acidosis but the underlying mechanism remains uncertain. Considering that such reports have been ignored, we examined the ventilatory response of unanesthetized dogs with respiratory acidosis to hypertonic NaHCO3 infusion (1 N, 5 mmol/kg) and compared it with that of animals with normal acid-base status or one of the remaining acid-base disorders. Ventilatory response to NaHCO3 infusion was evaluated by examining the ensuing change in PaCO2 and the linear regression of the PaCO2 vs. pH relationship. Strikingly, PaCO2 failed to increase and the ΔPaCO2 vs. ΔpH slope was negative in respiratory acidosis, whereas PaCO2 increased consistently and the ΔPaCO2 vs. ΔpH slope was positive in the remaining study groups. These results cannot be explained by differences in buffering-induced decomposition of infused bicarbonate or baseline levels of blood pH, PaCO2, and pulmonary ventilation. We propose that NaHCO3 infusion improved the ventilatory efficiency of animals with respiratory acidosis, i.e., it decreased their ratio of total pulmonary ventilation to carbon dioxide excretion (VE/VCO2). Such exclusive effect of NaHCO3 infusion in animals with respiratory acidosis might emanate from baseline increased VD/VT (dead space/tidal volume) caused by bronchoconstriction and likely reduced pulmonary blood flow, defects that are reversed by alkali infusion. Our observations might explain the beneficial effects of NaHCO3 reported in patients with acute respiratory acidosis.

Blood gases, acid-base, and metabolic alterations in calves with bronchopneumonia diagnosed via clinical signs and thoracic ultrasonography: A cross-sectional study.

Bronchopneumonia (BP) in calves potentially causes systemic changes. To describe metabolic, arterial blood gas, and acid-base disorders in calves with BP diagnosed by thoracic ultrasound (TUS), Wisconsin score (WISC), and combinations of WISC and TUS. Two hundred thirty-one dairy preweaned dairy calves from 13 dairy farms. Cross-sectional study. Each calf sequentially underwent arterial blood gas evaluation, WISC score, venous sampling, and TUS. Calves were grouped based on a single diagnostic method and combination of WISC and 2 TUS cutoffs (≥1 cm; ≥3 cm) as healthy, upper respiratory tract infection, subclinical BP, and clinical BP. Oxygenation and acid-base variables were unaffected. Glucose concentration in TUS-affected calves was significantly lower (P < .001) than in healthy calves (median ≥TUS1cm = 5.2 mmol/L 25%-75% interquartile range [IQR] 4.5-6.1, <TUS1cm = 5.9 mmol/L IQR 5.5-6.6; ≥TUS3cm = 5.1 mmol/L IQR 4.4-6.2, <TUS3cm = 5.8 mmol/L IQR 5.3-6.4). Paraoxonase-1 was significantly lower (P < .001) in TUS-affected calves (≥TUS1cm = 64.1 U/mL IQR 40.8-78, <TUS1cm = 77.3 U/mL IQR 61.9-96.5; ≥TUS3cm = 59.2 U/mL IQR 37.7-72.4, <TUS3cm = 72.9 U/mL IQR 53.4-95.5). None of the variables highlighted clear distinctions in WISC-detected clinical and subclinical BP calves based on the combination of WISC and TUS. Clinical signs indicate minor systemic disorders compared to TUS. The abnormalities detected by ultrasonographic examination were moderate and did not deviate from normal reference ranges.

Research progress of astragaloside IV in treating acute kidney injury.

Acute kidney injury (AKI) is one of the most common clinical critical illnesses, with decreased glomerular filtration rate, retention of nitrogen products, water and electrolyte disorders, and acid-base imbalance as the main clinical manifestations. Presently, there is no effective treatment for acute kidney injury, but the main treatment is to cure the primary disease, remove risk factors, maintain acid-base and water-electrolyte balance, and undergo kidney replacement. However, the mortality rate is still high. Investigations and studies showed that the mortality rate of patients with acute kidney injury in the ICU is 5-80% [1]. In recent years, Chinese medicine has been widely used in acute kidney injury treatment due to its complete dialectical system and rich experience. Astragalus is a commonly used medicine in traditional Chinese medicine to treat acute kidney injury. Astragaloside IV is the main active component of traditional Chinese medicine, Astragalus membranaceus. This article summarizes the relevant studies on treating acute kidney injury with astragaloside IV.

Basic principles of infusion therapy

Infusion therapy (IT) is an essential tool for influencing homeostasis and an integral part of the complex treatment of urgent conditions and chronic diseases accompanied by fluid and electrolyte balance disorders. To this day the features of infusion therapy remain one of the most controversial and poorly studied topics, despite the centuries-old use of this method of treatment. Rational use of IT requires a clear understanding of the pathophysiological changes occurring in the patient’s body during acute and chronic pathology. Its main tasks are the elimination of volemic disorders, replenishment of circulating blood volume, restoration of microcirculation, as well as detoxification and elimination of hemocoagulation disorders. IT acquires particular importance as parenteral nutrition, with limited or excluded possibility of the enteral route of absorption of water, nutrients, and drugs. In the work, the authors focused on clinical and laboratory diagnostics and possible options for correcting acid-base, energy, fluid, and electrolyte disorders. The sequence of actions when prescribing IT is presented in detail; the criteria for calculating the volume of therapy and the initial selection of colloids or crystalloids for a specific clinical situation are considered.

Diagnostic threshold and performance of anion gap in screening for high anion gap metabolic acidosis.

The anion gap (AG) is commonly used to screen for acid-base disorders. It was proposed that the cut-off for high anion gap metabolic acidosis (HAGMA) may be lower with current laboratory techniques, although modern laboratory equipment are still calibrated to familiar reference ranges established with earlier techniques. The appropriate cut-off for HAGMA is unclear. This study aimed to assess the performance of AG as a screening test for HAGMA and to determine the optimal diagnostic threshold of AG for HAGMA. This was a retrospective analysis of a large, anonymised dataset extracted by computerised protocol from 2017 to 2019. All inpatients with blood samples taken for organic acids (lactate, ketone or salicylate) paired with a metabolic panel were included. The target condition was HAGMA secondary to elevated blood lactate, ketone and/or salicylate. Sensitivity for HAGMA was explored at various AG cut-off levels. Of 16,475 patients, 2,621 had organic acidosis. Median age was 65 years, and median estimated glomerular filtration rate was 70 mL/min/1.73 m2. With organic acidosis, the median AG was 23 (interquartile range [IQR] 20-29) mEq/L, while without organic acidosis, the median AG was 16 (IQR 14-19) mEq/L. The area under the curve-receiver operating characteristic of AG for HAGMA was 0.873. Desired sensitivity for HAGMA was set at ≥95%, and this was found with an AG threshold of ≥15 mEq/L (sensitivity 98.1%, specificity 34.0%). The recommended AG threshold value is ≥15 mEq/L with a high sensitivity for HAGMA. The AG should always be interpreted with the clinical context, and it should be repeated as the clinical picture evolves.

Kidney involvement in Wilson's disease: a review of the literature.

Wilson's disease (WD) is a rare inherited disease due to the mutation of the ATP7B gene, resulting in impaired hepatic copper excretion and its pathological accumulation in various organs such as the liver, the nervous system, or the kidneys. Whereas liver failure and neuropsychiatric disorders are the most common features, less is known about the renal complications. We conducted a review of the literature to define the characteristics and pathophysiology of kidney involvement during WD. This review shed light on strong evidence for direct copper toxicity to renal tubular cells. Excessive tubular copper accumulation might present with various degrees of tubular dysfunction, ranging from mild hydroelectrolytic and acid-base disorders to complete Fanconi syndrome. Proximal and distal renal tubular acidosis also favors development of nephrolithiasis, nephrocalcinosis, and bone metabolism abnormalities. Indirect complications might involve renal hypoperfusion as occurs in hepatorenal or cardiorenal syndrome, but also tubular casts' formation during acute hemolysis, rhabdomyolysis, or bile cast nephropathy. Acute kidney failure is not uncommon in severe WD patients, and independently increases mortality. Finally, specific and long-term therapy by D-penicillamin, one of the most efficient drugs in WD, can cause glomerular injuries, such as membranous nephropathy, minimal-change disease, and, rarely, severe glomerulonephritis. Altogether, our study supports the need for interdisciplinary evaluation of WD patients involving nephrologists, with regular monitoring of tubular and glomerular functions, to provide adequate prevention of renal and bone involvement.

Association of prehospital lactate levels with base excess in various emergencies - a retrospective study.

Blood gas analysis, including parameters like lactate and base excess (BE), is crucial in emergency medicine but less commonly utilized prehospital. This study aims to elucidate the relationship between lactate and BE in various emergencies in a prehospital setting and their prognostic implications. We conducted a retrospective analysis of prehospital emergency patients in Graz, Austria, from October 2015 to November 2020. Our primary aim was to assess the association between BE and lactate. This was assessed using Spearman's rank correlation and fitting a multiple linear regression model with lactate as the outcome, BE as the primary covariate of interest and age, sex, and medical emergency type as confounders. In our analysis population (n=312), lactate and BE levels were inversely correlated (Spearman's ρ, -0.75; p<0.001). From the adjusted multiple linear regression model (n=302), we estimated that a 1 mEq/L increase in BE levels was associated with an average change of -0.35 (95 % CI: -0.39, -0.30; p<0.001) mmol/L in lactate levels. Lactate levels were moderately useful for predicting mortality with notable variations across different emergency types. Our study highlights a significant inverse association between lactate levels and BE in the prehospital setting, underscoring their importance in early assessment and prognosis in emergency care. Additionally, the findings from our secondary aims emphasize the value of lactate in diagnosing acid-base disorders and predicting patient outcomes. Recognizing the nuances in lactate physiology is essential for effective prehospital care in various emergency scenarios.

Rodenticide poisoning leading to cerebral hemorrhage: A case report.

Anticoagulant rodenticides (ARs) are a substantial fraction of murine types. AR poisoning causes bleeding from the skin, mucous membranes, and multiple organs. However, reports of AR-induced cerebral hemorrhage are scarce. A 40-year-old male presented with dizziness, headache, and limb weakness for 5 days and with coagulopathy. Two days prior to the onset of these symptoms, the patient was exposed to dead mice. Rodenticide intoxication-induced cerebral hemorrhage. Vitamin K1 infusion, administration of dehydrating agents to reduce intracranial pressure, and correction of acid-base and electrolyte imbalances. After 9 days of treatment, the patient's symptoms were relieved, and reexamination revealed that coagulation parameters returned to normal levels. The patient was eventually discharged for observation with oral vitamin K1. Rodenticide poisoning can lead to intracerebral hemorrhage, and treatment with vitamin K1 infusion is effective. Rodenticide poisoning-induced cerebral hemorrhage is rarely reported. Because its symptoms are nonspecific, it is easy to miss the diagnosis or misdiagnose. When patients present with direct and indirect symptoms such as dizziness, headache, and limb weakness, rodenticide poisoning should be considered. Coagulation function and head computed tomography or magnetic resonance imaging examination should be performed at the earliest to confirm the diagnosis and provide timely treatment.

Alactic base excess (ABE): a novel internal milieu parameter-its concept and clinical importance.

Inspired by the Stewart-Figge acid-base approach, Gattinoni et al. recently introduced a new internal milieu parameter known as alactic base excess (ABE). The authors defined ABE as the sum of lactate and standard base excess. In the context of sepsis, ABE has been proposed as a valuable marker to discern between metabolic acidosis resulting from the accumulation of lactate and the retention of fixed acids, which can occur in cases of renal failure. Multiple studies have demonstrated that a negative ABE value (<-3mmol/L) represents an early marker of renal dysfunction, and significantly correlates with higher mortality rates in septic patients. In conclusion, ABE is a simple and useful parameter that can be used to better interpret a patient's acid-base status, assess renal function, and general prognosis in sepsis. By incorporating ABE into clinical practice, healthcare professionals can enhance their understanding of the complex acid-base imbalances in their patients and tailor more individualized, effective treatment plans.

Offspring of women with hyperemesis gravidarum are more likely to have cardiovascular abnormalities

BackgroundHyperemesis gravidarum (HG) is a severe form of pregnancy-related nausea and vomiting affecting 0.3–2.3% of pregnancies, which can lead to fluid, electrolyte, and acid–base imbalances, nutritional deficiencies, and weight loss, and is usually severe enough to require hospitalization. Abnormally elevated urinary ketones are commonly seen in patients with HG, and ketone bodies are free to pass through the placenta, and maternal hyperketonemia, with or without acidosis, is associated with an increased rate of stillbirth, an increased incidence of congenital anomalies, and impaired neurophysiologic development of the infant. This study investigates the obstetric outcomes of patients with HG and whether HG increases the incidence of cardiovascular disease in the offspring.MethodsThis study included 1020 pregnant women who were hospitalized in our hospital for HG and ultimately delivered in our hospital as well as pregnant women without HG in early gestation and delivered in our hospital from January 2019-January 2020, and we collected and followed up the clinical information of the pregnant women and their offspring.ResultsPregnant women with HG were more likely to have severe urinary ketones, the rate of early miscarriage and mid-term miscarriage was significantly higher in women with HG compared to pregnant women without HG. Fetal and neonatal head and abdominal circumferences were smaller in HG group than in control group.Neonatal birth weight and length were also lower in the HG group and cardiovascular anomalies were more likely to occur in the offspring of women with HG when all births were followed up for 3 years.ConclusionsHG may cause poor obstetric outcomes and was associated with the development of cardiovascular disease in the offspring of women with HG.

Analysing arterial blood gas results using the RoMe technique.

Arterial blood gas (ABG) analysis is a fundamental skill in healthcare practice, particularly when caring for acutely unwell or deteriorating patients. It can be useful in the assessment of patients' acid-base balance and gas exchange, thereby informing appropriate care and management. However, many nurses find interpreting ABG results challenging. This article outlines a simplified approach to ABG analysis using three main values - pH, partial pressure of carbon dioxide and bicarbonate - and applying the RoMe ('Respiratory opposite, Metabolic equal') technique. It also provides brief descriptions of selected acid-base imbalances and explains how to identify whether these are uncompensated, partially compensated or fully compensated.

Phenotyping Down syndrome: discovery and predictive modelling with electronic medical records.

Individuals with Down syndrome (DS) have a heightened risk for various co-occurring health conditions, including congenital heart disease (CHD). In this two-part study, electronic medical records (EMRs) were leveraged to examine co-occurring health conditions among individuals with DS (Study 1) and to investigate health conditions linked to surgical intervention among DS cases with CHD (Study 2). De-identified EMRs were acquired from Vanderbilt University Medical Center and facilitated creating a cohort of N=2282 DS cases (55% females), along with comparison groups for each study. In Study 1, DS cases were one-by-two sex and age matched with samples of case-controls and of individuals with other intellectual and developmental difficulties (IDDs). The phenome-disease association study (PheDAS) strategy was employed to reveal co-occurring health conditions in DS versus comparison groups, which were then ranked for how often they are discussed in relation to DS using the PubMed database and Novelty Finding Index. In Study 2, a subset of DS individuals with CHD [N=1098 (48%)] were identified to create longitudinal data for N=204 cases with surgical intervention (19%) versus 204 case-controls. Data were included in predictive models and assessed which model-based health conditions, when more prevalent, would increase the likelihood of surgical intervention. In Study 1, relative to case-controls and those with other IDDs, co-occurring health conditions among individuals with DS were confirmed to include heart failure, pulmonary heart disease, atrioventricular block, heart transplant/surgery and primary pulmonary hypertension (circulatory); hypothyroidism (endocrine/metabolic); and speech and language disorder and Alzheimer's disease (neurological/mental). Findings also revealed more versus less prevalent co-occurring health conditions in individuals with DS when comparing with those with other IDDs. Findings with high Novelty Finding Index were abnormal electrocardiogram, non-rheumatic aortic valve disorders and heart failure (circulatory); acid-base balance disorder (endocrine/metabolism); and abnormal blood chemistry (symptoms). In Study 2, the predictive models revealed that among individuals with DS and CHD, presence of health conditions such as congestive heart failure (circulatory), valvular heart disease and cardiac shunt (congenital), and pleural effusion and pulmonary collapse (respiratory) were associated with increased likelihood of surgical intervention. Research efforts using EMRs and rigorous statistical methods could shed light on the complexity in health profile among individuals with DS and other IDDs and motivate precision-care development.

Approach to acid-base disorders in primary care.

Approach to acid-base disorders in primary care.

Assessment of the prevalence of meningitis in clinically suspected cases of early and late onset neonatal sepsis

Background: Meningitis is more common in the neonatal period than any other time in life and is an important cause of morbidity and mortality globally. In India, rate of neonatal sepsis is reported 0.5 per 1000 live births. The major burden of neonatal sepsis and meningitis occurs in the developing world. According to WHO estimates there are approximately 5 million neonatal deaths in a year. The objective of the study is to assess the prevalence of meningitis in neonates with clinical suspicion of sepsis. Methods: The study was conducted among suspected cases of neonatal septicemia in neonatal intensive care unit (NICU), department of pediatrics, VPIMS, Lucknow. It is a prospective observational study. A total of 180 neonates were included in the study. Results: Out of 180 neonates, CSF examination of 131 (72.78%) neonates was normal, of 37 (20.56%) was suggestive of meningitis. Prevalence of meningitis in neonatal sepsis was 20.0%. It was 18.0% in early neonatal sepsis and 32.6% in late neonatal sepsis cases. Conclusions: The findings of present study suggested that there is a high risk of meningitis among neonatal sepsis cases. Cases with risk factors like twin birth, anemia, low TLC, low platelet count, acid-base imbalance and X-ray findings suggestive of pneumonitis should be kept in a high-risk category.