Unveiling the heightened susceptibility: Exploring early hypophosphatemia in critically ill trauma patients.

BACKGROUND: Phosphorus is a vital mineral crucial for various physiological functions. Critically ill trauma patients frequently experience hypophosphatemia during the immediate post-traumatic phase, potentially impacting outcomes. This study aims to investigate the incidence of early hypophosphatemia in critically major trauma patients. METHODS: In this prospective observational study, trauma patients admitted to the intensive care unit (ICU) within one day were enrolled. These patients were categorized into Hypo-P groups and Non-hypo groups based on the development of new-onset hypophosphatemia within 72 h after feeding. The primary outcome assessed was the incidence of new-onset hypophosphatemia. The secondary outcomes included ICU and hospital stay, ventilation duration, and mortality. RESULTS: 76.1% of patients developed a new onset of hypophosphatemia within 72 h after feeding. The Hypo-P group had significantly longer ICU stays (8.1 days ± 5.5 vs. 4.4 days ± 3.1; p = 0.0251) and trends towards extended hospital stay, ventilation duration, and higher mortality. Additionally, they demonstrated significantly higher urine fractional excretion of phosphate (FEPO4) on the first ICU day (29.2% ± 14.23 vs. 19.5% ± 8.39; p = 0.0242). CONCLUSION: Critically ill trauma patients exhibited a significantly higher incidence of early hypophosphatemia than typical ICU rates, indicating their heightened vulnerability. The significantly high urine FEPO4 underscores the crucial role of renal loss in disrupting phosphate metabolism in this early acute phase after trauma. A significant correlation was observed between hypophosphatemia and longer ICU stays. Monitoring and managing phosphate levels may influence outcomes, warranting further investigation.

Variable phenotypes and outcomes associated with the MMACHC c.482G > A mutation: follow-up in a large CblC disease cohort.

BACKGROUND: The aim of this study was to characterize the variable phenotypes and outcomes associated with the methylmalonic aciduria and homocystinuria type C protein gene (MMACHC) c.482G > A mutation in 195 Chinese cases with CblC disease. METHODS: We carried out a national, retrospective multicenter study of 195 Chinese patients with CblC disease attributable to the MMACHC c.482G > A variant either in a homozygous or compound heterozygous state. The control group consisted of 200 patients diagnosed with CblC disease who did not possess the c.482G > A mutation. Clinical features, including disease onset, symptoms, biochemical metabolites, gene mutation, and follow-up outcomes were reviewed and analyzed in detail. The median follow-up period spanned 3 years and 8 months, with a range of 1 year and 2 months to 12 years and 10 months. RESULTS: Among 195 patients carrying the c.482G > A variant, 125 (64.1%) cases were diagnosed by newborn screening (NBS), 60 (30.8%) cases were detected due to disease onset, and 10 (5.1%) cases were identified from sibling diagnoses. One hundred and seventeen (93.6%) individuals who were diagnosed by NBS, and nine patients who came from sibling diagnoses remained asymptomatic in this study. From 69 symptomatic patients of the c.482G > A group, more patients presented with later onset, and the top six common clinical symptoms at disease onset were developmental delay (59.4%), lower limb weakness and poor exercise tolerance (50.7%), cognitive decline (37.7%), gait instability and abnormal posture (36.2%), seizures (26.1%), and psychiatric and behavioral disturbances (24.6%). In the 159 symptomatic patients lacking c.482G > A variants, the most frequently observed clinical manifestations at disease onset included developmental delay (81.8%), lethargy and feeding difficulty (62.9%), lower limb weakness and poor exercise tolerance (54.7%), prolonged neonatal jaundice (51.6%), vomiting (47.2%), and seizures (32.7%). Before treatment, the levels of blood propionylcarnitine, propionylcarnitine/acetylcarnitine ratio, and homocysteine in the c.482G > A group were significantly lower (P < 0.05) than those in the non-c.482G > A group, while the concentration of urinary methylmalonic acid was slightly lower (P > 0.05). The degree of decline in the above metabolites after treatment in different groups significantly differed in both plasma total homocysteine values and urinary methylmalonic acid levels (P < 0.05). In patients carrying the c.482G > A variant compared with the non-c.428G > A group, there were markedly lower rates of mortality (0.5% vs. 2.0%) and developmental delay (20.5% vs. 65.5%). When compared with individuals diagnosed due to disease onset, those identified through NBS in either group exhibited a reduced proportion of disease onset (6.7% vs. 100% in the c.482G > A group, 54.4% vs. 100% in the non-c.482G > A group), lower mortality (0.0% vs. 1.7% in the c.482G > A group, 0.0% vs. 3.6% in the non-c.482G > A group), and had a higher percentage of patients exhibiting normal psychomotor and language development (99.3% vs. 33.3% in the c.482G > A group, 58.9% vs. 10.9% in the non-c.482G > A group). CONCLUSIONS: The c.482G > A variant in MMACHC is associated with late-onset and milder phenotypes of CblC disease. Patients with this mutation tend to have a relatively better response to hydroxocobalamin, better metabolic control, and more favorable neurological outcomes. NBS and other appropriate pre-symptomatic treatments seem to be helpful in early diagnosis, resulting in favorable clinical outcomes. Video Abstract (MP4 136794 kb).

Effects of empiric antibiotic treatment based on hospital cumulative antibiograms in patients with bacteraemic sepsis: a retrospective cohort study.

OBJECTIVES: To assess the effects of empiric antibiotics with different degrees of appropriateness based on hospital cumulative antibiograms in patients with bacteraemic sepsis presenting to the emergency department (ED). METHODS: This retrospective cohort study included adult patients with sepsis and positive blood culture reports in the ED from February 2016 to December 2018. Based on isolated pathogens and empiric antibiotics which the patients received, these patients were divided into two groups using a cut-off of 70% for overall antimicrobial susceptibility (OAS) on hospital cumulative antibiograms 6 months prior to ED admission. Multivariate regression and sensitivity analyses were performed. RESULTS: In this study, 1055 patients were included. We used multivariate regression models which were adjusted for age, sex, co-morbidities, site of infection, organ dysfunction, and septic shock. Empiric antibiotics with OAS of ≥70% were associated with reduced in-hospital deaths (adjusted odds ratio, 0.46; 95% CI, 0.28-0.77) and 30-day mortality (adjusted odds ratio, 0.53; 95% CI, 0.33-0.86). They were more likely to result in a shortened length of intensive care unit stay by 1.60 days (95% CI, -3.00 to -0.20). CONCLUSIONS: Treatment with empiric antibiotics with OAS of ≥70% based on hospital cumulative antibiograms is associated with lower mortality and shorter length of intensive care unit stay in patients with bacteraemic sepsis in the ED.

Successful management of delirium with dexmedetomidine in a patient with haloperidol-induced neuroleptic malignant syndrome: A case report.

BACKGROUND: We report a case of lorazepam-induced agitated delirium treated with haloperidol, which in turn triggered the onset of neuroleptic malignant syndrome (NMS). The latter condition, a medical emergency, was effectively treated with medical treatment and dexmedetomidine, a versatile and highly selective short-acting alpha-2 adrenergic agonist with sedative-hypnotic and anxiolytic effects. CASE SUMMARY: A 65-year-old man with a history of bipolar disorder presented to the emergency department with severe abdominal discomfort after binge eating. During his hospital stay, he received intravenous lorazepam for insomnia. On the next day, he became delirious and was thus treated with seven doses (5 mg each) of haloperidol over a 48 h period. Signs of NMS (hyperthermia, rigidity, myoclonus of upper limbs, impaired consciousness, tachypnea, and dark urine) became apparent and haloperidol was immediately suspended and brisk diuresis was initiated. On intensive care unit admission, he was confused, disoriented, and markedly agitated. Dexmedetomidine infusion was started with the goal of achieving a Richmond Agitation-Sedation Scale score of -1 or 0. NMS was resolved gradually and the patient stabilized, permitting discontinuation of dexmedetomidine after 3 d. CONCLUSION: Dexmedetomidine may be clinically helpful for the management of NMS, most likely because of its sympatholytic activity.

Effect of Extracorporeal Membrane Oxygenation on the New Vancomycin Dosing Regimen in Critically Ill Patients Receiving Continuous Venovenous Hemofiltration.

BACKGROUND: The optimal dosing regimen of vancomycin for critically ill patients receiving continuous venovenous hemofiltration (CVVH) remains controversial, not to mention those with concurrent use of extracorporeal membrane oxygenation (ECMO). We aimed to determine if a new dosing regimen can achieve the target vancomycin trough concentration (Ctrough) of 10-20 mcg/mL in patients receiving CVVH with or without ECMO. METHODS: We conducted a retrospective study by enrolling patients who received vancomycin while undergoing CVVH. The vancomycin dosing regimen was 15-20 mg/kg as the loading dose and 7.5 mg/kg every 12 hours as the maintenance doses. Serum concentration was determined after at least 4 doses of vancomycin were given. RESULTS: A total of 38 patients were enrolled, of which 21 were also on ECMO. The ultrafiltration rate of CVVH was 30.6 ± 5.5 mL·kg·h with the Ctrough of 14.7 ± 3.5 mcg/mL. Ctrough was within the target range in 82% of patients. All CVVH-only patients achieved the target concentration, whereas only 76.2% of those with concurrent ECMO did (P = 0.031). CONCLUSIONS: All patients receiving CVVH achieved the target Ctrough with this new dosing regimen, but those with concurrent ECMO did not. Ctrough must be more closely monitored in patients using ECMO simultaneously.

Diagnosis and therapeutic monitoring of inborn errors of metabolism in 100,077 newborns from Jining city in China.

BACKGROUND: Mandatory newborn screening for metabolic disorders has not been implemented in most parts of China. Newborn mortality and morbidity could be markedly reduced by early diagnosis and treatment of inborn errors of metabolism (IEM). Methods of screening for IEM by tandem mass spectrometry (MS/MS) have been developed, and their advantages include rapid testing, high sensitivity, high specificity, high throughput, and low sample volume (a single dried blood spot). METHODS: Dried blood spots of 100,077 newborns obtained from Jining city in 2014-2015 were screened by MS/MS. The screening results were further confirmed by clinical symptoms and biochemical analysis in combination with the detection of neonatal deficiency in organic acid, amino acid, or fatty acid metabolism and DNA analysis. RESULTS: The percentages of males and females among the 100,077 infants were 54.1% and 45.9%, respectively. Cut-off values were established by utilizing the percentile method. The screening results showed that 98,764 newborns were healthy, and 56 out of the 1313 newborns with suspected IEM were ultimately diagnosed with IEM. Among these 56 newborns, 19 (1:5267) had amino acid metabolism disorders, 26 (1:3849) had organic acid metabolism disorders, and 11 (1:9098) had fatty acid oxidation disorders. In addition, 54 patients with IEM were found to carry mutations, and the other 2 patients had argininemia. CONCLUSIONS: Fifty-six cases of metabolic disorders in Jining were confirmed via newborn screening (NBS) by MS/MS. Early diagnosis and treatment are crucial for the survival and well-being of affected children. A nationwide NBS program using MS/MS is recommended, especially in poor areas of China.