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.

OBJECTIVE: To estimate the highest power output at which predominant energy contribution is derived from the aerobic system (aerobic limit power: ALP) and to compare ALP with the upper boundary of the severe intensity exercise domain.
METHODS: Fifteen male individuals participated in this study. The upper boundary was estimated using i) linear relationship between time to achieve V ˙ O2max and time to task failure (PUPPERBOUND), ii) hyperbolic relationships between time to achieve V ˙ O2max vs. power output, and time to task failure vs. power output (PUPPERBOUND´), and iii) precalculated V ˙ O2max demand (IHIGH). ALP was estimated by aerobic, lactic, and phospholytic energy contributions using V ˙ O2 response, blood [lactate] response, and fast component of recovery V ˙ O2 kinetics, respectively.
RESULTS: ALP was determined as the highest power output providing predominant aerobic contribution; however, anaerobic pathways became the predominant energy source when ALP was exceeded by 5% (ALP + 5%) (from 46 to 52%; p = 0.003; ES:0.69). The V ˙ O2 during exercise at ALP was not statistically different from V ˙ O2max (p > 0.05), but V ˙ O2max could not be attained at ALP + 5% (p < 0.01; ES:0.63). ALP was similar to PUPPERBOUND and PUPPERBOUND´ (383 vs. 379 and 384 W; p > 0.05). There was a close agreement between ALP and PUPPERBOUND (r: 0.99; Bias: - 3 W; SEE: 6 W; TE: 8 W; LoA: - 17 to 10 W) and PUPPERBOUND´ (r: 0.98; Bias: 1 W; SEE: 8 W; TE: 8 W; LoA: - 15 to 17 W). ALP, PUPPERBOUND, and PUPPERBOUND´ were greater than IHIGH (339 ± 53 W; p < 0.001).
CONCLUSIONS: ALP may provide a new perspective to intensity domain framework.

UNASSIGNED: To illustrate the challenges encountered when gathering rapidly synthesized evidence in response to the coronavirus disease 2019 (COVID-19) pandemic.
UNASSIGNED: In this article, we describe the challenges encountered when we performed a systematic literature review (SLR) of randomized controlled trials (RCTs) on the efficacy and safety of treatments for severe COVID-19. The methods of the SLR are described in full, to show the context of our objectives. Then we use the results of the SLR to demonstrate the problems of producing synthesized evidence in this setting.
UNASSIGNED: Various challenges were identified during this SLR. These were primarily a result of heterogeneity in the study methodology of eligible studies. Definitions of the patient populations and outcome measurements were highly variable and the majority of studies demonstrated a high risk of bias, preventing quantitative synthesis of the collated evidence.
UNASSIGNED: Consolidating evidence from RCTs evaluating COVID-19 interventions was problematic. Guidance is needed for scenarios with high rapid output in primary research.

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.

OBJECTIVE: To identify clinical and radiological factors associated with a higher risk of developing a severe pituitary apoplexy (PA).
METHODS: Multicenter retrospective study of patients presenting with clinical PA in three Spanish tertiary hospitals of Madrid between 2008 and 2022. We classified PA as severe when presenting with an altered level of consciousness (Glasgow Coma Scale (GCS) < 15) or visual involvement.
RESULTS: A total of 71 PA cases were identified, of whom 80.28% (n = 57) were classified as severe PA. The median age was 60 (18 to 85 years old) and 67.6% (n = 48) were male. Most patients had macroadenomas, except for one patient with a microadenoma of 9 mm. Headache was the most common presenting symptom (90.1%) and anticoagulation was the most frequent predisposing risk factor, but it was not associated with a higher risk for severe PA (odds ratio [OR] 1.13 [0.21-5.90]). Severe cases were associated with male gender (OR 5.53 [1.59-19.27]), tumor size >20 mm (OR 17.67 [4.07-76.64]), and Knosp grade ≥2 (OR 9.6 [2.38-38.73]). In the multivariant analysis, the only variables associated with a higher risk for severe PA were tumor size and Knosp grade. Surgery was more common in severe PA than in non-severe (91.2% vs. 64.3%, P = 0.009).
CONCLUSIONS: A tumor size >20 mm and cavernous sinus invasion are risk factors for developing a severe PA. These risk factors can stratify patients at a higher risk of a worse clinical picture, and subsequently, more need of decompressive surgery.