Delivery of proteins/peptides to the gastrointestinal (GI) tract via peroral/oral route involves tremendous challenges due to unfavorable environmental conditions like harsh pH, presence of ...proteolytic enzymes and absorption barriers. Detailed research is being conducted at the academic and industrial levels to diminish these troubles and various products are under clinical trials. Several approaches have been established to optimize oral delivery of proteins and peptides and can be broadly categorized into chemical and physical strategies. Chemical strategies include site specific mutagenesis, proteinylation, glycosylation, PEGylation and prodrug approaches, whereas physical strategies comprise formulation based approaches including application of absorption enhancers and metabolism modifiers along with delivering them via colloidal carrier systems such as nanoparticles, liposomes, microparticles, and micro- and nano-emulsions. This review stands to accomplish the diverse aspects of oral delivery of proteins/peptides and summarizes the key concepts involved in targeting the biodrugs to specific sites of the GI tract such as the intestine and colon. Furthermore some light has also been shed on the current industrial practices followed in developing oral formulations of such bioactives.
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Among patients with acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, less than 40% regain functional independence when treated with intravenous tissue ...plasminogen activator (t-PA) alone. Thrombectomy with the use of a stent retriever, in addition to intravenous t-PA, increases reperfusion rates and may improve long-term functional outcome.
We randomly assigned eligible patients with stroke who were receiving or had received intravenous t-PA to continue with t-PA alone (control group) or to undergo endovascular thrombectomy with the use of a stent retriever within 6 hours after symptom onset (intervention group). Patients had confirmed occlusions in the proximal anterior intracranial circulation and an absence of large ischemic-core lesions. The primary outcome was the severity of global disability at 90 days, as assessed by means of the modified Rankin scale (with scores ranging from 0 no symptoms to 6 death).
The study was stopped early because of efficacy. At 39 centers, 196 patients underwent randomization (98 patients in each group). In the intervention group, the median time from qualifying imaging to groin puncture was 57 minutes, and the rate of substantial reperfusion at the end of the procedure was 88%. Thrombectomy with the stent retriever plus intravenous t-PA reduced disability at 90 days over the entire range of scores on the modified Rankin scale (P<0.001). The rate of functional independence (modified Rankin scale score, 0 to 2) was higher in the intervention group than in the control group (60% vs. 35%, P<0.001). There were no significant between-group differences in 90-day mortality (9% vs. 12%, P=0.50) or symptomatic intracranial hemorrhage (0% vs. 3%, P=0.12).
In patients receiving intravenous t-PA for acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, thrombectomy with a stent retriever within 6 hours after onset improved functional outcomes at 90 days. (Funded by Covidien; SWIFT PRIME ClinicalTrials.gov number, NCT01657461.).
Objective
Within the context of a prospective randomized trial (SWIFT PRIME), we assessed whether early imaging of stroke patients, primarily with computed tomography (CT) perfusion, can estimate the ...size of the irreversibly injured ischemic core and the volume of critically hypoperfused tissue. We also evaluated the accuracy of ischemic core and hypoperfusion volumes for predicting infarct volume in patients with the target mismatch profile.
Methods
Baseline ischemic core and hypoperfusion volumes were assessed prior to randomized treatment with intravenous (IV) tissue plasminogen activator (tPA) alone versus IV tPA + endovascular therapy (Solitaire stent‐retriever) using RAPID automated postprocessing software. Reperfusion was assessed with angiographic Thrombolysis in Cerebral Infarction scores at the end of the procedure (endovascular group) and Tmax > 6‐second volumes at 27 hours (both groups). Infarct volume was assessed at 27 hours on noncontrast CT or magnetic resonance imaging (MRI).
Results
A total of 151 patients with baseline imaging with CT perfusion (79%) or multimodal MRI (21%) were included. The median baseline ischemic core volume was 6ml (interquartile range = 0–16). Ischemic core volumes correlated with 27‐hour infarct volumes in patients who achieved reperfusion (r = 0.58, p < 0.0001). In patients who did not reperfuse (<10% reperfusion), baseline Tmax > 6‐second lesion volumes correlated with 27‐hour infarct volume (r = 0.78, p = 0.005). In target mismatch patients, the union of baseline core and early follow‐up Tmax > 6‐second volume (ie, predicted infarct volume) correlated with the 27‐hour infarct volume (r = 0.73, p < 0.0001); the median absolute difference between the observed and predicted volume was 13ml.
Interpretation
Ischemic core and hypoperfusion volumes, obtained primarily from CT perfusion scans, predict 27‐hour infarct volume in acute stroke patients who were treated with reperfusion therapies. ANN NEUROL 2016;79:76–89
Lignin is an abundant renewable natural biopolymer. Moreover, a significant development in lignin pretreatment and processing technologies has opened a new window to explore lignin and lignin-based ...bionanomaterials. In the last decade, lignin has been widely explored in different applications such as drug and gene delivery, tissue engineering, food science, water purification, biofuels, environmental, pharmaceuticals, nutraceutical, catalysis, and other interesting low-value-added energy applications. The complex nature and antioxidant, antimicrobial, and biocompatibility of lignin attracted its use in various biomedical applications because of ease of functionalization, availability of diverse functional sites, tunable physicochemical and mechanical properties. In addition to it, its diverse properties such as reactivity towards oxygen radical, metal chelation, renewable nature, biodegradability, favorable interaction with cells, nature to mimic the extracellular environment, and ease of nanoparticles preparation make it a very interesting material for biomedical use. Tremendous progress has been made in drug delivery and tissue engineering in recent years. However, still, it remains challenging to identify an ideal and compatible nanomaterial for biomedical applications. In this review, recent progress of lignin towards biomedical applications especially in drug delivery and in tissue engineering along with challenges, future possibilities have been comprehensively reviewed.
Clinical trials have demonstrated improved 90-day outcomes for patients with acute ischemic stroke treated with stent retriever thrombectomy plus tissue-type plasminogen activator (SST+tPA) compared ...with tPA. Previous studies suggested that this strategy may be cost-effective, but models were derived from pooled data and older assumptions.
In this prospective economic substudy conducted alongside the SWIFT-PRIME trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke), in-trial costs were measured for patients using detailed medical resource utilization and hospital billing data. Utility weights were assessed at 30 and 90 days using the EuroQol-5 dimension questionnaire. Post-trial costs and life-expectancy were estimated for each surviving patient using a model based on trial data and inputs derived from a contemporary cohort of ischemic stroke survivors.
Index hospitalization costs were $17 183 per patient higher for SST+tPA than for tPA ($45 761 versus $28 578; P<0.001), driven by initial procedure costs. Between discharge and 90 days, costs were $4904 per patient lower for SST+tPA than for tPA ($11 270 versus $16 174; P=0.014); total 90-day costs remained higher with SST+tPA ($57 031 versus $44 752; P<0.001). Higher utility values for SST+tPA led to higher in-trial quality-adjusted life years (0.131 versus 0.105; P=0.005). In lifetime projections, SST+tPA was associated with substantial gains in quality-adjusted life years (6.79 versus 5.05), cost savings of $23 203 per patient and was economically dominant when compared with tPA in 90% of bootstrap replicates.
Among patients with acute ischemic stroke enrolled in the SWIFT-PRIME trial, SST increased initial treatment costs, but was projected to improve quality-adjusted life-expectancy and reduce healthcare costs over a lifetime horizon compared with tPA.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657461.
Acute ischemic stroke due to tandem occlusions of the extracranial internal carotid artery and intracranial arteries has a poor natural history. We aimed to evaluate our single-center experience with ...endovascular treatment of this unique stroke population.
Consecutive patients with tandem occlusions of the internal carotid artery origin and an intracranial artery (ie, internal carotid artery terminus, M1 middle cerebral artery, or M2 middle cerebral artery) were studied retrospectively. Treatment consisted of proximal revascularization with angioplasty and stenting followed by intracranial intervention. Endpoints were recanalization of both extracranial and intracranial vessels (Thrombolysis In Myocardial Ischemia ≥2), parenchymal hematoma, and good clinical outcome (modified Rankin Scale ≤2) at 3 months.
We identified 77 patients with tandem occlusions. Recanalization occurred in 58 cases (75.3%) and parenchymal hematoma occurred in 8 cases (10.4%). Distal embolization occurred in 3 cases (3.9%). In 18 of 77 patients (23.4%), distal (ie, intracranial) recanalization was observed after proximal recanalization, obviating the need for distal intervention. Good clinical outcomes were achieved in 32 patients (41.6%). In multivariate analysis, Thrombolysis In Myocardial Ischemia ≥2 recanalization, baseline National Institutes of Health Stroke Scale score, baseline Alberta Stroke Programme Early CT score, and age were significantly associated with good outcome.
Endovascular therapy of tandem occlusions using extracranial internal carotid artery revascularization as the first step is technically feasible, has a high recanalization rate, and results in an acceptable rate of good clinical outcome. Future randomized, prospective studies should clarify the role of this approach.
Objectives We examined outcomes of patients resuscitated from cardiac arrest owing to ST-segment elevation myocardial infarction (STEMI) and predictors of survival and neurologic recovery. Background ...Immediately after resuscitation from cardiac arrest owing to STEMI, many patients show signs of neurologic impairment, and benefits of percutaneous coronary intervention and subsequent prognosis are not well defined. Methods Between January 1, 2002, and December 31, 2006, we retrospectively identified consecutive patients resuscitated from cardiac arrest, regardless of time to return of spontaneous circulation (ROSC) and neurologic status, and reviewed the outcomes of those who had STEMI. Mortality and neurologic recovery at discharge and long-term mortality were assessed by individual chart review for those who underwent emergent angiography. Results Our study population consisted of 98 patients; 64% survived to discharge, and 92% had a full neurologic recovery. Predictors of survival were shorter time to ROSC, younger age, neurologic status post-resuscitation (alert or minimally responsive), and male sex. Predictors of neurologic recovery included shorter time to ROSC, neurologic status post-resuscitation (alert or minimally responsive), and younger age. Ninety-six percent of patients who were alert post-resuscitation survived. Ninety-three percent of patients who were minimally responsive post-resuscitation survived. Fifty-nine patients were unresponsive post-resuscitation, with 44% survival, of whom 88% had full neurologic recovery. In the unresponsive group, unwitnessed arrest, prolonged ROSC, and older age were associated with increased risk of death, and older age and prolonged ROSC predicted poor neurologic recovery. Conclusions When resuscitated patients with STEMI are being evaluated in the emergency department, serious consideration should be given to emergent angiography and revascularization, regardless of neurologic status.
The scope of RNAi based therapeutics is unquestionable. However, if we dissect the current trend of clinical trials for afore mentioned drug class, some stark trends appear: 1) naked siRNA only ...exerts influence in topical mode whilst systemic delivery requires a carrier and 2) even after two decades of extensive efforts, not even a single siRNA containing product is commercially available. It was therefore felt that a perspective simplifying the unique intricacies of working with a merger of siRNA and liposomes from a pharmaceutical viewpoint could draw the attention of a wider array of interested researchers. We begin from the beginning and attempt to conduit the gap between theoretical logic and experimental/actual constraints. This, in turn could stimulate the next generation of investigators, gearing them to tackle the conundrum, which is siRNA delivery.
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Telemedicine is a form of healthcare delivery that employs communication technology to provide medical care to patients remotely. The use of telemedicine has seen a significant increase in recent ...years, presenting challenges such as patient privacy, data security, the need for reliable communication technology, and the potential for misdiagnosis without a physical examination. Digital Watermarking can assist in addressing such issues by incorporating a unique identifier into an image that can be used to authenticate its validity. To tackle these issues, this study proposes a robust digital watermarking approach tailored to brain medical images, combining hashing, the Elliptic Curve Digital Signature Algorithm (ECDSA), and the Integer Wavelet Transform-Discrete Cosine Transform (IWT-DCT). This method utilizes the Secure Hash Algorithm (SHA-256) to first segment the brain's Region of Interest (RoI). Subsequently, the hashed RoI, along with an ECDSA signature, is embedded into the high-frequency sub-bands of the medical image using IWT-DCT. The embedding process strategically alters the coefficients of the high-frequency sub-bands to accommodate the signature while minimizing perceptual distortion. The technique leverages the robustness of transformed-domain image watermarking techniques against various attacks and combines it with SHA-256 for integrity and ECDSA for authentication purposes. The results demonstrate that the suggested approach is robust to a variety of image processing techniques, including noise addition, filtering, and compression while maintaining high levels of imperceptibility. Key metrics such as the Peak Signal-to-Noise Ratio (PSNR), Mean Squared Error (MSE), and Structural Similarity Index (SSIM) were used to evaluate performance. The suggested strategy exhibited a substantial improvement over existing methods. The PSNR increased to 68.67, indicating higher image quality, while the MSE reduced to 0.96, demonstrating closer pixel values to the original image. Moreover, the SSIM reached 0.98, denoting a nearly perfect resemblance between the watermarked and original images. The suggested approach also demonstrated quick embedding and extraction speeds, as well as tamper detection capabilities.
•Segmenting the RoI in brain medical images.•The approach leverages the SHA-256 hashing algorithm. This hash acts as a digital fingerprint.•To validate medical images, the proposed method creates an ECDSA digital signature.•During the watermarking technique, the hashed RoI and ECDSA signatures are inserted.•The method has a high level of imperceptibility.
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