QbD-Based Fabrication of Biomimetic Hydroxyapatite Embedded Gelatin Nanoparticles for Localized Drug Delivery against Deteriorated Arthritic Joint Architecture.

Biomaterials such as nanohydroxyapatite and gelatin are widely explored to improve damaged joint architecture associated with rheumatoid arthritis (RA). Besides joint damage, RA is associated with inflammation of joints and cartilage, which potentiates the need for both bone nucleation and therapeutic intervention. For such purpose, a modified nanoprecipitation method is used herein to fabricate tofacitinib (Tofa)-loaded nanohydroxyapatite (nHA) embedded gelatin (GLT) nanoparticles (NPs) (Tofa-nHA-GLT NPs). The quality by design (QbD) approach is chosen to assess the key parameters that determine the efficiency of the NPs, and are further optimized via Box-Behnken design of experiment. The particle size, polydispersity, zeta potential, and encapsulation efficiency (EE) of the prepared NPs are found to be 269 nm, 0.18, -20.5 mV, and 90.7%, respectively. Furthermore, the NPs have improved stability, skin permeability, and a sustained drug release pattern at pH 6.5 (arthritic joint pH). Moreover, rhodamine-B loaded nHA-GLT NPs demonstrates considerably higher cellular uptake by the murine-derived macrophages than free rhodamine-B solution. In vitro, cell-based experiments confirm the good cell biocompatibility with insignificant toxicity. Thus, QbD-based approach has successfully led to the development of Tofa-nHA-GLT NPs with the potential to target inflamed arthritic joint.

Predictive Value of CT Brain Perfusion Studies in Acute Ischemic Infarct Taking MRI Stroke Protocol As Gold Standard.

Background Acute ischemic stroke is the leading cause of serious chronic disability worldwide. Imaging plays a key role in early diagnosis and intervention, thus reducing mortality and morbidity related to ischemic stroke. Computed tomography (CT) perfusion study is a valuable imaging tool for the assessment of acute infarction. The objective of this study was to determine the predictive value of CT perfusion in diagnosing acute ischemic infarction taking Magnetic Resonance Imaging (MRI) stroke protocol (including Diffusion Weighted Imaging (DWI)) as a gold standard. Methods The cross-sectional validation study was conducted at a teaching hospital in Islamabad from June 2019 to December 2019. The study comprised a total of 125 patients of either gender with suspected acute ischemic stroke. The patients were scanned for CT perfusion and MRI stroke protocol on the same day. Scans were reported separately for the detection of acute ischemic infarction by the same consultant radiologist. The predictive value of CT perfusion was calculated accordingly. Results Of the 125 patients, 58% were male and 42% were female. The age of selected patients ranged between 38 to 70 years with a mean age of 56.12 ± 9.69 years. Acute ischemic infarction was detected in 86 (69%) patients by CT perfusion study and in 120 (96%) patients by MRI stroke protocol. The positive predicted value of CT perfusion for the detection of acute infarction was calculated as 98.83 and the negative predicted value was 10.25. Conclusion CT perfusion study provides adequate sensitivity and specificity with good predictive value in the detection of acute ischemic infarct in stroke patients. This widely available and time-effective modality aids in the triage of patients for immediate endovascular intervention leading to maximal neurological benefit and improving outcomes.

High-Resolution CT Chest Findings in Suspected COVID-19 Pneumonia Patients With Negative Real-Time Polymerase Chain Reaction Assay.

Objective The study was conducted with the objective of describing High-resolution computed tomography (HRCT) chest findings of clinically suspected COVID-19 patients having a negative real-time polymerase chain reaction (RT-PCR) assay as well as prevalence and distribution of the HRCT chest manifestations consistent with the diagnosis of COVID-19 pneumonia. Methods This descriptive cross-sectional study was conducted prospectively on a total of 48 patients with high clinical suspicion for COVID-19 and a negative RT-PCR assay that was presented to the Diagnostic Radiology Department of Capital Hospital, Islamabad from July 2020 to December 2020. These patients were included via non-probability consecutive sampling, had a positive history of contact with a known COVID-19 patient and/or any two of the following signs and symptoms; fever, cough, malaise, body aches, arthralgia, new-onset loss of taste and smell, and dyspnea or oxygen saturation less than 85%. A detailed history was sought after informed consent and all these patients underwent non-contrast HRCT chest scans that were reported by an experienced consultant radiologist. The scans showing positive features for COVID-19 pneumonia were assessed for the nature and distribution of the disease. Results Amongst 48 suspects with negative RT-PCR assay, 38 (79.2%) showed ground-glass opacities, a hallmark feature of COVID-19 pneumonia. A total of 22 (57.89%) of these 38 patients had ground-glass opacities with a crazy-paving pattern, nine (23.68%) mixed ground-glass opacities with consolidation, and seven (18.42%) had pure ground-glass opacities. Among these 79.2% suspects, ground-glass opacities were multifocal in 37 (97.37%), bilateral in 35 (92.10%), peripheral in 36 (94.74%), and dorsally located in 32 (81.6%) cases. Subpleural atelectatic bands were seen in 18 (47.36%) of these, bronchovascular markings were prominent in 15 (39.47%), and reverse halo sign was positive in nine (23.68%) cases. Out of the rest of the cases, three were diagnosed as interstitial lung disease, two as chronic lung disease, and one as active pulmonary tuberculosis. Conclusion The majority of clinically suspected cases for COVID-19 showed hallmark findings on non-contrast HRCT chest scans in keeping with coronavirus disease regardless of a negative RT-PCR assay.