A 3-day-old male presented to a peripheral remote hospital in New South Wales, Australia, with tachypnea. He was found to have hypercalcemia, with ionized calcium >2.5 mmol/L (>10 mg/dL) (0.97-1.5 mmol/L or 1.14-1.3 mg/dL) and serum calcium of 3.85 mmol/L (15.43 mg/dL) (2.2-2.8 mmol/L or 8.5-10.5 mg/dL). Peak serum calcium was 5.4 mmol/L (21.64 mg/dL). He was transferred to a tertiary pediatric intensive care unit. Medical management (including hyperhydration, diuretics, corticosteroids, bisphosphonates, cinacalcet, and calcitonin) failed to maintain normocalcemia; therefore, total parathyroidectomy was performed on day 16 of life. Hungry bones syndrome developed postoperatively, requiring high doses of calcium, calcitriol, and phosphate supplementation. Genetic testing identified compound heterozygosity for 2 likely pathogenic variants in the calcium-sensing receptor gene. He is now 3 years old and is growing and developing without any concerns. This case highlights the importance of aggressive initial management in addressing severe hypercalcemia through perioperative management principles as well as the prolonged nature of hungry bones syndrome.

This case report highlights the effective use of intermittent hemodialysis (IHD) in warming a 71-year-old female patient with severe hypothermia who presented with a rectal temperature of 25 °C and signs of hemodynamic instability. The patient, found unconscious after prolonged exposure to cold exacerbated by alcohol consumption, initially showed some improvement in core temperature through active external rewarming methods. However, soon, her temperature plateaued at 27 °C. Patient was deemed unsuitable for extracorporeal membrane oxygenation (ECMO) or cardiopulmonary bypass (CPB) due to her age, and urgent IHD was initiated. This approach resulted in a stable increase in core temperature at approximately 2.0 °C/hr, along with normalization of lactic acidosis, creatinine phosphokinase, and correction of electrolyte imbalances, culminating in her full recovery and discharge after seven days in the hospital.After reviewing this case alongside similar ones from before, this case report highlights the efficacy and safety of IHD as an efficient, readily available, and less invasive method for rewarming moderate to severe hypothermic patients who are hemodynamically unstable patients but do not have cardiac arrest or renal dysfunction. IHD is especially useful when less invasive cooling devices (Artic Sun/ CoolGard) are not available or more invasive extracorporeal life support options (ECMO/ CPB) are either not indicated or unavailable. IHD can also help improve concurrent electrolyte imbalances and/or toxin buildup. The report further emphasizes the necessity of monitoring for potential complications, such as post-dialysis hypophosphatemia and rebound hyperkalemia, following successful rewarming.

UNASSIGNED: Chlamydia abortus causes abortions in ruminants; it can also cause miscarriages and stillbirths in pregnant women. However, it rarely causes pneumonia in humans. Here, we report a case of severe community-acquired pneumonia caused by C. abortus.
UNASSIGNED: On admission to our hospital, a 74-year-old woman reported that she had had a fever, cough, phlegm in her throat, and shortness of breath for 10 days. In the local hospital, she was initially diagnosed with community-acquired pneumonia and treated with piperacillin-tazobactam for 4 days. However, her condition worsened, and she was therefore transferred to our hospital. On arrival at our emergency department, she was diagnosed with severe community-acquired pneumonia and treated with a high-flow nasal cannula and meropenem; she was then transferred to the Department of Respiratory Medicine. There, her condition continued to worsen despite continued treatment with the high-flow nasal cannula and omadacycline. After 24 h and emergency tracheal intubation, the patient was sent to the intensive care unit (ICU) for further treatment. The doctors in the ICU again adjusted the treatment, this time to meropenem along with mechanical ventilation; they also instituted methylprednisolone, ulinastatin, nadroparin calcium, and human immunoglobulin. In addition, bronchoalveolar lavage fluid was sent for metagenomic next-generation sequencing (mNGS). Subsequent mNGS suggested the presence of C. abortus, sequence number 5072; we therefore discontinued the meropenem and implemented a combination of doxycycline and moxifloxacin. After 8 days of treatment in the ICU, the patient\'s condition improved; she was then extubated and, 3 days later, transferred back to the respiratory medicine department. The respiratory physician continued to administer doxycycline and moxifloxacin for 4 days, after which the patient was discharged with medication. A month later, a repeat computed tomography (CT) scan of the chest suggested that the lesions in both lungs had been largely absorbed.
UNASSIGNED: C. abortus can occasionally cause pneumonia in humans and, rarely, severe, life-threatening pneumonia. mNGS is uniquely suited for the early detection of this unusual infection. The combination of doxycycline and quinolones has been shown to be effective in severe pneumonia caused by C. abortus.

Drug-induced thrombocytopenia is a rare but significant adverse effect of certain medications, with the potential for severe bleeding, thrombosis, and death. This report discusses a rare case of severe thrombocytopenia induced by ceftaroline in a 69-year-old male with a history of atrial fibrillation on rivaroxaban and allergies to amoxicillin and sulfa drugs. Following the initiation of ceftaroline for left lower extremity purulent cellulitis, his platelet count dropped from 204,000 to 4,000 x 10³/μL within a day. Given the low platelet levels, anticoagulation therapy, and bleeding risk, immediate interventions and prompt recognition prevented major complications, highlighting the importance of recognizing drug-induced thrombocytopenia in clinical practice.

Malaria transmission and endemicity in Africa remains hugely disproportionate compared to the rest of the world. The complex life cycle of P. falciparum (Pf) between the vertebrate human host and the anopheline vector results in differential expression of genes within and between hosts. An in-depth understanding of Pf interaction with various human genes through regulatory elements will pave way for identification of newer tools in the arsenal for malaria control. Therefore, the regulatory elements (REs) involved in the over- or under-expression of various host immune genes hold the key to elucidating alternative control measures that can be applied for disease surveillance, prompt diagnosis and treatment. We carried out an RNAseq analysis to identify differentially expressed genes and network elucidation of non-coding RNAs and target genes associated with immune response in individuals with different clinical outcomes. Raw RNAseq datasets, retrieved for analyses include individuals with severe (Gambia-20), symptomatic (Burkina Faso-15), asymptomatic (Mali-16) malaria as well as uninfected controls (Tanzania-20; Mali-36). Of the total 107 datasets retrieved, we identified 5534 differentially expressed genes (DEGs) among disease and control groups. A peculiar pattern of DEGs was observed, with individuals presenting with severe/symptomatic malaria having the highest and most diverse upregulated genes, while a reverse phenomenon was recorded among asymptomatic and uninfected individuals. In addition, we identified 141 differentially expressed micro RNA (miRNA), of which 78 and 63 were upregulated and downregulated respectively. Interactome analysis revealed a moderate interaction between DEGs and miRNAs. Of all identified miRNA, five were unique (hsa-mir-32, hsa-mir-25, hsa-mir-221, hsa-mir-29 and hsa-mir-148) because of their connectivity to several genes, including hsa-mir-221 connected to 16 genes. Six-hundred and eight differentially expressed long non coding RNA (lncRNA) were also identified, including SLC7A11, LINC01524 among the upregulated ones. Our study provides important insight into host immune genes undergoing differential expression under different malaria conditions. It also identified unique miRNAs and lncRNAs that modify and/or regulate the expression of various immune genes. These regulatory elements we surmise, have the potential to serve a diagnostic purpose in discriminating between individuals with severe/symptomatic malaria and those with asymptomatic infection or uninfected, following further clinical validation from field isolates.

BACKGROUND: There is an urgent need for therapeutic strategies for inpatients with severe or critical COVID-19. The evaluation of the clinical benefits of nirmatrelvir and ritonavir (Nmr/r) for these patients beyond five days of symptom onset is insufficient.
METHODS: A new propensity score-matched cohort was constructed by using multicenter data from 6695 adult inpatients with COVID-19 from December 2022 to February 2023 in China after the epidemic control measures were lifted across the country. The severity of disease of the inpatients was based on the tenth trial edition of the Guidelines on the Diagnosis and Treatment of COVID-19 in China. The symptom onset of 1870 enrolled severe or critical inpatients was beyond five days, and they received either Nmr/r plus standard treatment or only standard care. The ratio of patients whose SOFA score improved more than 2 points, crucial respiratory endpoints, changes in inflammatory markers, safety on the seventh day following the initiation of Nmr/r treatment, and length of hospital stay were evaluated.
RESULTS: In the Nmr/r group, on Day 7, the number of patients with an improvement in SOFA score ≥ 2 was much greater than that in the standard treatment group (P = 0.024) without a significant decrease in glomerular filtration rate (P = 0.815). Additionally, the rate of new intubation was lower (P = 0.004) and the no intubation days were higher (P = 0.003) in the first 7 days in the Nmr/r group. Other clinical benefits were limited.
CONCLUSIONS: Our study may provide new insight that inpatients with severe or critical COVID-19 beyond five days of symptom onset benefit from Nmr/r. Future studies, particularly randomized controlled trials, are necessary to verify the above findings.

UNASSIGNED: The purpose of this study is to establishment and validation of an early predictive model for severe acute pancreatitis (SAP).
UNASSIGNED: From January 2015 to August 2022, 2986 AP patients admitted to Changsha Central Hospital were enrolled in this study. They were randomly divided into a modeling group (n = 2112) and a validation group (n = 874). In the modeling group, identify risk factors through logistic regression models and draw column charts. Use internal validation method to verify the accuracy of column chart prediction. Apply calibration curves to evaluate the consistency between nomograms and ideal observations. Draw a DCA curve to evaluate the net benefits of the prediction model.
UNASSIGNED: Nine variables including respiratory rate, heart rate, WBC, PDW, PT, SCR, AMY, CK, and TG are the risk factors for SAP. The column chart risk prediction model which was constructed based on these 9 independent factors has high prediction accuracy (modeling group AUC = 0.788, validation group AUC = 7.789). The calibration curve analysis shows that the prediction probabilities of the modeling and validation groups are consistent with the observation probabilities. By drawing a DCA curve, it shows that the model has a wide threshold range (0.01-0.88).
UNASSIGNED: The study developed an intuitive nomogram containing readily available laboratory parameters to predict the incidence rate of SAP.

Secondary hyperparathyroidism (SHPT) can progress to severe SHPT (sSHPT), which affects the survival rate and quality of life of patients. This retrospective cohort study investigated risk factors for sSHPT and the association between SHPT and mortality (all-cause and infection-related) among 771 clinically stable patients (421 male patients; mean age, 51.2 years; median dialysis vintage, 28.3 months) who underwent >3 months of regular peritoneal dialysis (PD) between January 2013 and March 2021. The sSHPT and non-sSHPT groups comprised 75 (9.7%) (median progression, 35 months) and 696 patients, respectively. sSHPT was defined as a serum intact parathyroid hormone (PTH) level >800 pg/mL observed three times after active vitamin D pulse therapy. The influence of sSHPT on the prognosis of and risk factors for sSHPT progression were evaluated using logistic and Cox regression analyses. After adjusting for confounding factors, higher (each 100-pg/mL increase) baseline PTH levels (95% confidence interval (CI) 1.206-1.649, p < .001), longer (each 1-year increase) dialysis vintages (95% CI 1.013-1.060, p = .002), higher concomitant diabetes rates (95% CI 1.375-10.374, p = .010), and lower (each 1-absolute unit decrease) Kt/V values (95% CI 0.859-0.984, p = .015) were independent risk factors for progression to sSHPT in patients on PD. During follow-up, 211 deaths occurred (sSHPT group, n = 35; non-sSHPT group, n = 176). The sSHPT group had significantly higher infection-related mortality rates than the non-sSHPT group (12.0% vs. 4.3%; p < .05), and sSHPT was associated with increased infection-related mortality. In conclusion, patients with sSHPT are at higher risk for death and infection-related mortality than patients without sSHPT.

UNASSIGNED: The global healthcare burden of COVID-19 pandemic has been unprecedented with a high mortality. Metabolomics, a powerful technique, has been increasingly utilized to study the host response to infections and to understand the progression of multi-system disorders such as COVID-19. Analysis of the host metabolites in response to SARS-CoV-2 infection can provide a snapshot of the endogenous metabolic landscape of the host and its role in shaping the interaction with SARS-CoV-2. Disease severity and consequently the clinical outcomes may be associated with a metabolic imbalance related to amino acids, lipids, and energy-generating pathways. Hence, the host metabolome can help predict potential clinical risks and outcomes.
UNASSIGNED: In this prospective study, using a targeted metabolomics approach, we studied the metabolic signature in 154 COVID-19 patients (males=138, age range 48-69 yrs) and related it to disease severity and mortality. Blood plasma concentrations of metabolites were quantified through LC-MS using MxP Quant 500 kit, which has a coverage of 630 metabolites from 26 biochemical classes including distinct classes of lipids and small organic molecules. We then employed Kaplan-Meier survival analysis to investigate the correlation between various metabolic markers, disease severity and patient outcomes.
UNASSIGNED: A comparison of survival outcomes between individuals with high levels of various metabolites (amino acids, tryptophan, kynurenine, serotonin, creatine, SDMA, ADMA, 1-MH and carnitine palmitoyltransferase 1 and 2 enzymes) and those with low levels revealed statistically significant differences in survival outcomes. We further used four key metabolic markers (tryptophan, kynurenine, asymmetric dimethylarginine, and 1-Methylhistidine) to develop a COVID-19 mortality risk model through the application of multiple machine-learning methods.
UNASSIGNED: Metabolomics analysis revealed distinct metabolic signatures among different severity groups, reflecting discernible alterations in amino acid levels and perturbations in tryptophan metabolism. Notably, critical patients exhibited higher levels of short chain acylcarnitines, concomitant with higher concentrations of SDMA, ADMA, and 1-MH in severe cases and non-survivors. Conversely, levels of 3-methylhistidine were lower in this context.

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