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BACKGROUND This study describes the use of closed reduction percutaneous intramedullary fixation with Kirschner wires in 4 children with displaced metaphyseal-diaphyseal junction (MDJ) fractures of the distal humerus. MATERIAL AND METHODS Between August 2016 and August 2019, 4 patients (3 boys and 1 girl), whose mean age was 4 years 5 months (range 3 years 6 months to 5 years 4 months), with displaced MDJ fractures of the distal humerus were treated using closed reduction percutaneous intramedullary fixation with Kirschner wires. Three of the fractures were oblique and 1 was transverse. The operation time and the frequency of intraoperative fluoroscopy were recorded. All children were followed up for greater than 18 months, taking anteroposterior and lateral radiographs of the elbow joint to evaluate the outcomes. At the last follow-up, the Flynn elbow joint function score was used to evaluate clinical outcomes, and complications were recorded. RESULTS The mean operation time was 37.5 min (range 35-40 min) and the frequency of intraoperative fluoroscopy was 11.7 times (range 8-15 times). All of the fractures were confirmed to be healed based on radiographic results at 4 weeks after surgery. At the last follow-up, 4 children had normal elbow joint motion without elbow deformity. The Flynn score showed their outcomes were excellent. CONCLUSIONS Closed reduction percutaneous intramedullary fixation using Kirschner wires was an effective treatment for displaced MDJ fractures of the distal humerus in the 4 children described and was shown to be easy to perform with a short operation time.BACKGROUND Adrenal gland cysts are rare and often occur without any symptoms. Even with advanced imaging modalities, it is still difficult to differentiate a benign adrenal neoplasm from a malignant one. Therefore, it is difficult to arrive at a definitive diagnosis and provide treatment. CASE REPORT We describe a patient with asymptomatic adrenal incidentaloma. The patient was lost to follow-up until 7 years later. On resuming follow-up, an enlarged suprarenal tumor was noted on ultrasound imaging. Magnetic resonance imaging revealed a 6×4 cm tumor mass, and the peripheral part expressed progressive enhancement on dynamic contrast-enhanced images. Laboratory data showed slight hypokalemia, and a complete endocrine assessment was performed, which showed no abnormality. Because malignancy of the adrenal gland remained suspected, a laparoscopic adenectomy was performed. The pathological result showed an adrenal endothelial (vascular) cyst with the formation of thrombi and calcification, without any evidence of malignancy. CONCLUSIONS Adrenal cystic lesions can change with time. Routine imaging studies during follow-up are recommended, and endocrine evaluations should be performed as an initial adrenal tumor work-up. Surgery is the treatment of choice when the cyst is >6 cm in size, malignancy is suspected, or abnormal endocrine activity is present.Imagination and idealism are particularly important creative epistemic virtues for the medical sciences if we hope to improve the health of the world's ageing population. To date, imagination and idealism within the medical sciences have been dominated by a paradigm of disease control, a paradigm which has realised significant, but also limited, success. Disease control proved particularly successful in mitigating the early-life mortality risks from infectious diseases, but it has proved less successful when applied to the chronic diseases of late life (like cancer). The time is ripe for the emergence and prominence of a supplementary medical research paradigm, the paradigm of 'healthy ageing' which prioritises the goal of rate (of ageing) control rather than disease control. This is the difference between extending the human healthspan versus extending survival by managing (or trying to eliminate) the multi-morbidities, frailty and disability currently prevalent in late life. The idealism of the disease control paradigm is myopic because it ignores the health constraints imposed by the inborn ageing process itself, a biological reality which is already inflicting significant economic and disease burdens on the world's ageing populations. Unless the medical sciences retard the rate of biological ageing, these problems will continue to be amplified as larger numbers of persons survive into late life.

Prostaglandin E

(PGE

) increases pulmonary vascular permeability by activation of the PGE

receptor 3 (EP

), which may explain adverse pulmonary effects of the EP

/EP

receptor agonist sulprostone in patients. In addition, PGE

contributes to pulmonary oedema in response to platelet-activating factor (PAF). PAF increases endothelial permeability by recruiting the cation channel transient receptor potential canonical 6 (TRPC6) to endothelial caveolae

acid sphingomyelinase (ASMase). Yet, the roles of PGE

and EP

in this pathway are unknown. We hypothesised that EP

receptor activation may increase pulmonary vascular permeability by activation of TRPC6, and thus, synergise with ASMase-mediated TRPC6 recruitment in PAF-induced lung oedema.

In isolated lungs, we measured increases in endothelial calcium (ΔCa

) or lung weight (Δweight), and endothelial caveolar TRPC6 abundance as well as phosphorylation.

PAF-induced ΔCa

and Δweight were attenuated in EP

-deficient mice. Sulprostone replicat coincides with ASMase-dependent caveolar recruitment of TRPC6, resulting in rapid endothelial Ca2+ influx and barrier failure.

Circulating biomarkers for lung damage are lacking. Lung epithelium-specific DNA methylation patterns can potentially report the presence of lung-derived cell-free DNA (cfDNA) in blood, as an indication of lung cell death.

We sorted human lung alveolar and bronchial epithelial cells from surgical specimens, and obtained their methylomes using whole-genome bisulfite sequencing. We developed a PCR sequencing assay determining the methylation status of 17 loci with lung-specific methylation patterns, and used it to assess lung-derived cfDNA in the plasma of healthy volunteers and patients with lung disease.

Loci that are uniquely unmethylated in alveolar or bronchial epithelial cells are enriched for enhancers controlling lung-specific genes. Methylation markers extracted from these methylomes revealed that normal lung cell turnover probably releases cfDNA into the air spaces, rather than to blood. People with advanced lung cancer show a massive elevation of lung cfDNA concentration in blood. Among individuals undergoing bronchoscopy, lung-derived cfDNA is observed in the plasma of those later diagnosed with lung cancer, and to a lesser extent in those diagnosed with other lung diseases. Lung cfDNA is also elevated in patients with acute exacerbation of COPD compared with patients with stable disease, and is associated with future exacerbation and mortality in these patients.

Universal cfDNA methylation markers of normal lung epithelium allow for mutation-independent, sensitive and specific detection of lung-derived cfDNA, reporting on ongoing lung injury. Such markers can find broad utility in the study of normal and pathologic human lung dynamics.

Universal cfDNA methylation markers of normal lung epithelium allow for mutation-independent, sensitive and specific detection of lung-derived cfDNA, reporting on ongoing lung injury. Such markers can find broad utility in the study of normal and pathologic human lung dynamics.

To evaluate whether plasma biomarkers of amyloid (Aβ42/Aβ40), tau (p-tau181 and p-tau231), and neuroaxonal injury (neurofilament light chain [NfL]) detect brain amyloidosis consistently across racial groups.

Individuals enrolled in studies of memory and aging who self-identified as African American (AA) were matched 11 to self-identified non-Hispanic White (NHW) individuals by age,

ε4 carrier status, and cognitive status. Each participant underwent blood and CSF collection, and amyloid PET was performed in 103 participants (68%). Plasma Aβ42/Aβ40 was measured by a high-performance immunoprecipitation-mass spectrometry assay. Plasma p-tau181, p-tau231, and NfL were measured by Simoa immunoassays. CSF Aβ42/Aβ40 and amyloid PET status were used as primary and secondary reference standards of brain amyloidosis, respectively.

There were 76 matched pairs of AA and NHW participants (n = 152 total). For both AA and NHW groups, the median age was 68.4 years, 42% were

ε4 carriers, and 91% were cognitively n AA and NHW groups, but models based on plasma p-tau181, p-tau231, and NfL may perform inconsistently and could result in disproportionate misdiagnosis of AA individuals.

Models predicting brain amyloidosis using a high-performance plasma Aβ42/Aβ40 assay may provide an accurate and consistent measure of brain amyloidosis across AA and NHW groups, but models based on plasma p-tau181, p-tau231, and NfL may perform inconsistently and could result in disproportionate misdiagnosis of AA individuals.

To assess the accuracy of baseline CT perfusion (CTP) ischemic core estimates.

From SELECT (Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke), a prospective multicenter cohort study of imaging selection, patients undergoing endovascular thrombectomy who achieved complete reperfusion (modified Thrombolysis In Cerebral Ischemia score 3) and had follow-up diffusion-weighted imaging (DWI) available were evaluated. Follow-up DWI lesions were coregistered to baseline CTP. The difference between baseline CTP core (relative cerebral blood flow [rCBF] <30%) volume and follow-up infarct volume was classified as overestimation (core ≥10 mL larger than infarct), adequate, or underestimation (core ≥25 mL smaller than infarct) and spatial overlap was evaluated.

Of 101 included patients, median time from last known well (LKW) to imaging acquisition was 138 (82-244) minutes. The median baseline ischemic core estimate was 9 (0-31.9) mL and median follow-up infarct volume was 18.4 (5.3-tion, and occurred primarily in white matter. Use of a more conservative (rCBF <20%) threshold for estimating ischemic core in patients presenting within 90 minutes eliminated all significant overestimation cases.

ClinicalTrials.gov NCT03876457.

ClinicalTrials.gov NCT03876457.A 61-year-old woman was admitted to the hospital for management of a painful vaso-occlusive crisis. She had a history of sickle cell beta-thalassaemia and end-stage renal disease managed with intermittent haemodialysis. Cpd 20m concentration While hospitalised, she became lethargic and unresponsive and developed acute chest syndrome. Initial MR scan of brain, cerebrospinal fluid examination and continuous electroencephalogram were unremarkable, but subsequent MR scan of brain identified a right transverse venous sinus thrombosis and extensive supratentorial and infratentorial microhaemorrhages consistent with fat emboli. We; therefore, discuss a case of non-traumatic fat embolism syndrome, a rare complication of sickle cell disease.Idiopathic intracranial hypertension (IIH) is more common in women of reproductive age who have obesity, yet there is little information on its management specifically in pregnancy. Women with IIH should plan their pregnancy including discussing contraception before pregnancy, recognising that hormonal contraceptives are not contraindicated. Potentially teratogenic medications including acetazolamide and topiramate are not recommended during pregnancy or in those with immediate plans to conceive; prescribing acetazolamide in pregnancy must only follow discussion with the patient and their obstetrician. Ideally, patients should aim to achieve disease remission or control before pregnancy, through optimising their weight. Although weight gain is expected in pregnancy, excessive weight gain may exacerbate IIH and increase maternal and fetal complications; evidence-based recommendations for non-IIH pregnancies may help in guiding optimal gestational weight gain. The vast majority of women with IIH can have a normal vaginal delivery, with spinal or epidural anaesthesia if needed, provided the papilloedema is stable or the IIH is in remission.

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