Abstract
Background
Postoperative pneumocephalus is associated with a higher risk of recurrence of chronic subdural hematoma (cSDH). However, there is no verified simple way to measure the ...pneumocephalus volume at the bedside for daily clinical use. The ABC/2 method was shown to be a simple and reliable technique to estimate volumes of intracranial lesions, such as intracranial hematomas. This study aims to evaluate the accuracy of the ABC/2 formula in estimating volumes of pneumocephalus, as compared to the gold standard with computer-assisted volumetric analysis.
Methods
A total of 141 postoperative computed tomographic (CT) brain scans of cSDH patients with burr-hole drainage were analysed. Pneumocephalus volume was measured independently by both the ABC/2 formula and the computer-assisted volumetric measurement. For the computer-assisted measurement, the volume of the air was semiautomatically segmented and calculated by computer software. Linear regression was used to determine the correlation between the ABC/2 method and computer-assisted measurement.
Results
The postoperative pneumocephalus volume after bilateral burr-hole drainage was significantly larger than that of unilateral burr-hole drainage (29.34 ml versus 12.21 ml,
p
< 0.001). The estimated volumes by the formula ABC/2 significantly correlated to the volumes as measured by the computer-assisted volumetric technique, with
r
= 0.992 (
p
< 0.001). The Pearson correlation coefficient is very close to 1, which signifies a very strong positive correlation, and it is statistically significant.
Conclusions
An excellent correlation is observed between the ABC/2 method and the computer-assisted measurement. This study verified that the ABC/2 method is an accurate and simple “bedside” technique to estimate pneumocephalus volume.
Objective Patients with type 2 diabetes mellitus (T2DM) and peripheral arterial disease are classified as having very high cardiovascular risks. We therefore sought to determine whether assessments ...of the ankle brachial index (ABI) and brachial ankle pulse wave velocity (baPWV) together exhibited a superior association with the outcomes of T2DM. Methods A retrospective analysis of patients receiving ABI and baPWV during the period 2005-2007 was performed. Patients A total of 452 subjects were enrolled and followed-up for a mean 5.8 years after being grouped according to the ABI (<0.9 vs. ≥0.9) and baPWV (<1,700 cm/s vs. ≥1,700 cm/s). Results The outcomes were all-cause mortality and composite events (all-cause mortality, hospitalization for coronary artery disease, stroke, re-vascularization, amputation and diabetic foot). Inter-group differences in the smoking rate, duration of diabetes, systolic and pulse blood pressure, anti-platelet drugs, estimated glomerular filtration rate, and urine albumin excretion were significant. During the follow-up period, 17 (3.7%) individuals died and composite events were recorded in 64 cases (14.1%). A low ABI plus high baPWV was found be associated with poor outcomes compared with a normal ABI plus low baPWV (p<0.001). Meanwhile, a low ABI plus high baPWV was associated with an increased risk of all-cause mortality hazard ratio (HR) 17.01, 95% confidence interval (CI) 1.57-183.73, p=0.019 and composite events (HR 8.53, 95% CI 3.31-21.99, p<0.001). Conclusion In this study, the outcomes of patients with a low ABI plus high baPWV were the worst, while the subjects with a low ABI plus low baPWV or normal ABI exhibited similar outcomes. Therefore, the ABI plus baPWV exhibits a better association with the outcomes of T2DM.
The Ω-loop at the active site of β-lactamases exerts significant impact on the kinetics and substrate profile of these enzymes by forming part of the substrate binding site and posing as steric ...hindrance toward bulky substrates. Mutating certain residues on the Ω-loop has been a general strategy for molecular evolution of β-lactamases to expand their hydrolytic activity toward extended-spectrum antibiotics through a mechanism believed to involve enhanced structural flexibility of the Ω-loop. Yet no structural information is available that demonstrates such flexibility or its relation to substrate profile and enzyme kinetics. Here we report an engineered β-lactamase that contains an environment-sensitive fluorophore conjugated near its active site to probe the structural dynamics of the Ω-loop and to detect the binding of diverse substrates. Our results show that this engineered β-lactamase has improved binding kinetics and positive fluorescence signal toward oxyimino-cephalosporins, but shows little such effect to non-oxyimino-cephalosporins. Structural studies reveal that the Ω-loop adopts a less stabilized structure, and readily undergoes conformational change to accommodate the binding of bulky oxyimino-cephalosporins while no such change is observed for non-oxyimino-cephalosporins. Mutational studies further confirm that this substrate-induced structural change is directly responsible for the positive fluorescence signal specific to oxyimino-cephalosporins. Our data provide mechanistic evidence to support the long-standing model that the evolutionary strategy of mutating the Ω-loop leads to increased structural flexibility of this region, which in turn facilitates the binding of extended spectrum β-lactam antibiotics. The oxyimino-cephalosporin-specific fluorescence profile of our engineered β-lactamase also demonstrates the possibility of designing substrate-selective biosensing systems.
Precipitating hydrophobic injectable liquid (PHIL; MicroVention, Aliso Viejo, CA, USA) and Squid (Balt, Irvine, CA, USA) are 2 newer liquid embolic agents used in endovascular embolization of ...cerebral arteriovenous malformation (AVM). This study aims to investigate and compare the effectiveness and safety profile of the 2 newer liquid embolic agents in the embolization of cerebral AVM. This is a retrospective study on all patients diagnosed with cerebral AVM undergoing endovascular embolization with liquid embolic agents PHIL and Squid admitted to the Division of Neurosurgery, Department of Surgery in Prince of Wales Hospital from January 2014 to June 2021. Twenty-three patients with cerebral AVM were treated with 34 sessions of endovascular embolization with either PHIL or Squid (17 sessions each) liquid embolic agents with a male to female ratio of 2.3:1 (male 16; female 7) and mean age of 44.6 (range, 12 to 67). The mean total nidus obliteration rate per session was 57% (range, 5% to 100%). Twenty-one patients (91.3%) received further embolization, stereotactic radiosurgery, or surgical excision after initial endovascular embolization. There were 2 morbidities (1 neurological and 1 non-neurological, 6%) and no mortalities (0%). All patients had static or improvement in modified Rankin Scale at 3 to 6 months at discharge. PHIL and Squid are effective and safe liquid embolic agents for endovascular embolization of cerebral AVM, achieving satisfactory nidal obliteration rates and patient functional outcomes.
Protein Tyrosine Phosphatase, Receptor Type G (PTPRG) was identified as a candidate tumor suppressor gene in nasopharyngeal carcinoma (NPC). PTPRG induces significant in vivo tumor suppression in ...NPC. We identified EGFR as a PTPRG potential interacting partner and examined this interaction. Dephosphorylation of EGFR at EGFR-Y1068 and -Y1086 sites inactivated the PI3K/Akt signaling cascade and subsequent down-regulation of downstream pro-angiogenic and -invasive proteins (VEGF, IL6, and IL8) and suppressed tumor cell proliferation, angiogenesis, and invasion. The effect of Akt inhibition in NPC cells was further validated by Akt knockdown experiments in the PTPRG-down-regulated NPC cell lines. Our results suggested that inhibition of Akt in NPC cells induces tumor suppression at both the in vitro and in vivo levels, and also importantly, in vivo metastasis. In conclusion, we confirmed the vital role of PTPRG in inhibiting Akt signaling with the resultant suppression of in vivo tumorigenesis and metastasis.
This randomised trial showed that en bloc resection of the bladder tumour (ERBT) led to a significant reduction in the 1-yr recurrence rate in patients with non–muscle-invasive bladder cancer. With ...superiority in treatment efficacy, our study provided the best evidence to support ERBT as the first-line surgical treatment for patients with bladder tumours of ≤3 cm. The multicentre setting also showed that ERBT is generalisable with a comparable safety profile to standard resection.
Conventionally, standard resection (SR) is performed by resecting the bladder tumour in a piecemeal manner. En bloc resection of the bladder tumour (ERBT) has been proposed as an alternative technique in treating non–muscle-invasive bladder cancer (NMIBC). The objective of this study is to investigate whether ERBT could improve the 1-yr recurrence rate of NMIBC, as compared with SR.
A multicentre, randomised, phase 3 trial was conducted in Hong Kong. Adults with bladder tumour(s) of ≤ 3cm were enrolled from April 2017 to December 2020, and followed up until 1 yr after surgery. Patients were randomly assigned to receive either ERBT or SR in a 1:1 ratio. The primary outcome was 1-yr recurrence rate. A modified intention-to-treat analysis on patients with histologically confirmed NMIBC was performed. The main secondary outcomes included detrusor muscle sampling rate, operative time, hospital stay, 30-d complications, any residual or upstaging of disease upon second-look transurethral resection, and 1-yr progression rate.
A total of 350 patients underwent randomisation, and 276 patients were histologically confirmed to have NMIBC. At 1 yr, 31 patients in the ERBT group and 46 in the SR group developed recurrence; the Kaplan-Meier estimate of 1- yr recurrence rates were 29% (95% confidence interval, 18–37) in the ERBT group and 38% (95% confidence interval, 28–46) in the SR group (p = 0.007). Upon a subgroup analysis, patients with 1–3 cm tumour, single tumour, Ta disease, or intermediate-risk NMIBC had a significant benefit from ERBT. None of the patients in the ERBT group and three patients in the SR group developed progression to muscle-invasive bladder cancer; the Kaplan-Meier estimates of 1-yr progression rates were 0% in the ERBT group and 2.6% (95% confidence interval, 0–5.5) in the SR group (p = 0.065). The median operative time was 28 min (interquartile range, 20–45) in the ERBT group and 22 min (interquartile range, 15–30) in the SR group (p < 0.001). All other secondary outcomes were similar in the two groups.
In patients with NMIBC of ≤ 3cm, ERBT resulted in a significant reduction in the 1-yr recurrence rate when compared with SR. The study results support ERBT as the first-line surgical treatment for patients with bladder tumours of≤ 3cm.
Little is known about the efficacy of proton pump inhibitors compared with H(2) receptor antagonists in preventing adverse upper gastrointestinal complications in patients with acute coronary ...syndrome (ACS) or ST elevation myocardial infarction (STEMI) receiving aspirin, clopidogrel, and enoxaparin or thrombolytics. The objective of this study was to compare the efficacies of esomeprazole and famotidine in preventing gastrointestinal complications.
A double-blind, randomized, controlled trial was performed in patients receiving a combination of aspirin, clopidogrel, and either enoxaparin or thrombolytics. Patients received either esomeprazole (20 mg nocte) or famotidine (40 mg nocte) orally for 4-52 weeks, depending on the duration of dual antiplatelet therapy. The primary end point was upper gastrointestinal bleeding (GIB), perforation, or obstruction from ulcer/erosion (http://www.clinicaltrials.gov NCT00683111).
In all, 311 patients were recruited, with 163 and 148 patients in the esomeprazole and famotidine groups, respectively. Mean (s.d.) follow-up was 19.2 (17.6) and 17.6 (18.0) weeks, respectively. One (0.6%) patient in the esomeprazole group and 9 (6.1%) in the famotidine group reached the primary end point (log-rank test, P=0.0052, hazard ratio=0.095, 95% confidence interval: 0.005-0.504); all had upper GIB.
In patients with ACS or STEMI, esomeprazole is superior to famotidine in preventing upper gastrointestinal complications related to aspirin, clopidogrel, and enoxaparin or thrombolytics.
Besides prominent respiratory involvement, gastrointestinal manifestations are commonly reported in Coronavirus Disease 2019 (COVID-19) patients. We compared infection of ex vivo human intestinal ...tissues by SARS-CoV-2 and SARS-CoV with respect to their replication kinetics and immune activation profile.
Human intestinal tissues were obtained from patients while undergoing surgical operations at Queen Mary Hospital, Hong Kong. Upon surgical removal, the tissues were immediately processed and infected with SARS-CoV-2 or SARS-CoV. Replication kinetics were determined with immunohistochemistry, qRT-PCR, and plaque assays. Immune activation in the infected intestinal tissues was assessed by detecting the gene expression of interferons and representative pro-inflammatory cytokines and chemokines.
SARS-CoV-2 could infect and productively replicate in the ex vivo human intestinal tissues with release of infectious virus particles, but not in ex vivo human liver and kidney tissues. Importantly, SARS-CoV-2 replicated less efficiently than SARS-CoV, induced less cytopathology in the human intestinal epithelium, and induced a more robust innate immune response including the activation of both type I and type III interferons, than SARS-CoV in human intestinal tissues.
Using the ex vivo human intestinal tissues as a physiologically relevant model, our data indicated that SARS-CoV-2 could productively replicate in the human gut and suggested that the gastrointestinal tract might serve as an alternative route of virus dissemination. SARS-CoV-2 replicated less efficiently and induced less cytopathology than SARS-CoV in keeping with the clinical observations reported for COVID-19 and SARS, which might be the result of a more robust immune activation by SARS-CoV-2 than SARS-CoV in the human intestine.
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