Comparison Between Mono VS Dual VS Triple Antiplatelet Therapy In Patients With Ischemic Heart Disease Undergoing PCI, A Network Meta-Analysis.

AIMS: We aim to research the efficacy and safety of single(SAPT), dual(DAPT), and triple(TAPT) antiplatelets approaches across IHD patients undergoing PCI. METHODS AND RESULTS: A network meta-analysis was conducted until April 1st, 2024, using the netmeta package in R studio 4.3.3. Primary outcomes were cardiac death, myocardial infarction(MI), stent thrombosis, stroke, and major bleeding(BARC 3-5). From 25 studies, a total of 65115 patients were included. For cardiac death, TAPT had no different risk than DAPT compared to SAPT [RR = 0.74; 95%CI (0.40 to 1.35); p-value = 0.33], [RR = 1.01, 95%CI (0.84 to 1.19); p-value = 0.87] respectively. For MI, TAPT had no different risk than DAPT compared to SAPT [RR = 0.77; 95%CI (0.51 to 1.16); p-value = 0.2047], [RR = 0.81, 95%CI (0.64 to 1.03); p-value = 0.0850] respectively. For stent thrombosis, DAPT had no different risk than TAPT compared to SAPT [RR = 0.74; 95%CI (0.45 to 1.21); p-value = 0.2284], [RR = 0.84, 95%CI (0.27 to 2.59); p-value = 0.7630] respectively. For stroke, DAPT had no different risk than TAPT in comparison to SAPT [RR = 0.91; 95%CI (0.75 to 1.10); p-value = 0.3209], and [RR = 0.87, 95%CI (0.43 to 1.76); p-value=0.6937], respectively. For Major bleeding(BARC 3-5), DAPT and TAPT increased major bleeding compared to SAPT, with only DAPT showing statistical significance. [RR = 1.43; 95%CI (1.09 to 1.88); p-value = 0.0107], and [RR = 2.78, 95%CI (0.90 to 4.78); p-value = 0.0852], respectively. CONCLUSION: DAPT and TAPT increased the risk of bleeding events compared to SAPT. However, we found no significant differences between these regimens for the other primary outcomes.

Perils of reduced dose apixaban in atrial fibrillation/flutter - A case report with a brief literature review.

Patients with atrial fibrillation/atrial flutter (AF) are notoriously predisposed to thromboembolic events secondary to the development of thrombi within the left atrium of the heart. AF accompanied by a fairly decent CHA2DS2-VASc score is a known indication for full anticoagulation, frequently with direct oral anticoagulants (DOACs), such as apixaban. Following extensive studies weighing the benefits of anticoagulation versus risks of major bleeding, patients meeting two or more of the dose-reduction criteria (age ≥80 years, weight ≤60 kg, and/or creatinine ≥ 1.5 mg/dL) require appropriate step-down to a reduced dose of apixaban. However, with rising concern for bleeding complications, many physicians are found to have been reducing the dose of apixaban despite the patient not completely meeting the defined criteria. Our study particularly emphasizes the risk of significantly increased thromboembolic complications in the setting of sub-therapeutic anticoagulation, in patients with both appropriately and inappropriately reduced doses of apixaban.

The variable domain from dynamin-related protein 1 promotes liquid-liquid phase separation that enhances its interaction with cardiolipin-containing membranes.

Dynamins are an essential superfamily of mechanoenzymes that remodel membranes and often contain a "variable domain" important for regulation. For the mitochondrial fission dynamin, dynamin-related protein 1, a regulatory role for the variable domain (VD) is demonstrated by gain- and loss-of-function mutations, yet the basis for this is unclear. Here, the isolated VD is shown to be intrinsically disordered and undergo a cooperative transition in the stabilizing osmolyte trimethylamine N-oxide. However, the osmolyte-induced state is not folded and surprisingly appears as a condensed state. Other co-solutes including known molecular crowder Ficoll PM 70, also induce a condensed state. Fluorescence recovery after photobleaching experiments reveal this state to be liquid-like indicating the VD undergoes a liquid-liquid phase separation under crowding conditions. These crowding conditions also enhance binding to cardiolipin, a mitochondrial lipid, which appears to promote phase separation. Since dynamin-related protein 1 is found assembled into discrete punctate structures on the mitochondrial surface, the inference from the present work is that these structures might arise from a condensed state involving the VD that may enable rapid tuning of mechanoenzyme assembly necessary for fission.

Glue embolization to the lung vasculature following histoacryl injection sclerotherapy: A neglected etiology of pulmonary embolism.

Pulmonary embolism is a significant complication of N-butyl-2-cyanoacrylate, commonly known as histoacryl, used to sclerose bleeding gastroesophageal varices. We present a 50-year-old female with seronegative chronic liver disease who was managed with endoscopic histoacryl injection sclerotherapy for bleeding gastric fundal varices. Following treatment, the patient developed sudden respiratory distress due to multiple pulmonary glue emboli, requiring inpatient supportive care along with close monitoring for a week. The patient slowly recovered with conservative management. On subsequent outpatient follow-up, the patient showed no signs of any long-term consequences. Our aim is to alert physicians regarding the uncommon occurrence of acute respiratory distress secondary to pulmonary embolism following histoacryl injection sclerotherapy, as well as to describe its clinical and radiological manifestations.

The variable domain from the mitochondrial fission mechanoenzyme Drp1 promotes liquid-liquid phase separation.

Dynamins are an essential superfamily of mechanoenzymes that remodel membranes and often contain a "variable domain" (VD) important for regulation. For the mitochondrial fission dynamin, Drp1, a regulatory role for the VD is demonstrated by mutations that can elongate, or fragment, mitochondria. How the VD encodes inhibitory and stimulatory activity is unclear. Here, isolated VD is shown to be intrinsically disordered (ID) yet undergoes a cooperative transition in the stabilizing osmolyte TMAO. However, the TMAO stabilized state is not folded and surprisingly appears as a condensed state. Other co-solutes including known molecular crowder Ficoll PM 70, also induce a condensed state. Fluorescence recovery after photobleaching experiments reveal this state to be liquid-like indicating the VD undergoes a liquid-liquid phase separation under crowding conditions. These crowding conditions also enhance binding to cardiolipin, a mitochondrial lipid, raising the possibility that phase separation may enable rapid tuning of Drp1 assembly necessary for fission.

Public Knowledge About COVID-19 Booster Vaccines in Pakistan: A Study Conducted in a Tertiary Care Hospital in Karachi.

The coronavirus disease 2019 (COVID-19) pandemic has deteriorated the healthcare system and economy worldwide. Globally, by making the primary vaccination against the coronavirus necessary, the surge in cases waned, but as the effects of this vaccination decreased after some time, to prevent another pandemic, vaccination was still necessary. As a result, receiving a COVID-19 booster shot can boost immunity against the coronavirus. This study aimed to assess knowledge of COVID-19 booster vaccines in Pakistan among the general public and understand the factors affecting the vaccination process in the state. In this cross-sectional study, non-probability convenience sampling was done. Its physical data collection was conducted in September 2022 in a tertiary care hospital in Karachi, Pakistan. Data were collected from 384 individuals who visited the hospital with consent before filling out the questionnaire. The mean age of respondents was 35.81 (standard deviation (SD) = ±13.006), and 98.7% of individuals were primarily vaccinated for COVID-19, but out of these, only 60.1% received the booster jab. The most commonly reported side effects of primary doses of COVID-19 and its booster were pain at the injection site, fatigue, and fever, but these effects did not appear to have as much of an impact on the vaccination process as education did. The results are evident that out of primarily vaccinated individuals against COVID-19, 40.16% are reluctant to receive its booster. Therefore, it is essential to create awareness among the masses about vaccination and its importance.

Endovascular coil embolization of ruptured and unruptured intracranial aneurysms: review of a 15 year single center experience in Pakistan.

OBJECTIVE: To assess the outcome of endovascular treatment of intracranial aneurysm over 15 years. METHODS: The retrospective study was conducted at the at Radiology Department of Aga Khan University Hospital, Karachi, and comprised medical records from April 2003 to April 2018 of patients who received endovascular treatment for intracranial aneurysm. Multiple variables reviewed included demographics, clinical presentation, aneurysm morphology, technique used, technique outcome and clinical outcome. Data was analysed using SPSS 22. RESULTS: Of the 242 patients, 111(45.8%) were males and 131(54.1%) were female. The overall mean age was 46.3+/-13.543 years (range: 9-78years). Aneurysm size was <5mm in 95(40.4%) patients, 5-10mm in 98(41.7%) and >10mm in 42(17.9%) patients. Aneurysms were located in the anterior communicating artery in 93(38.4%) patients, internal carotid artery 48(19.8%) patients and posterior communicating artery 26(10.7%) patients. Patients with higher initial Hess and Hunt grade were more likely to have higher modified Rankin scale score after treatment (p=0.001). Overall, 222(91.7%) patients were treated successfully. Complications were noted in 37(15.2%) patients and 10(4.0%) patients died. CONCLUSIONS: No correlation was found between Hess and Hunt grades and aneurysm severity based on aneurysm size, neck and ruptured/unruptured cases.

The Gene Expression Deconvolution Interactive Tool (GEDIT): accurate cell type quantification from gene expression data.

BACKGROUND: The cell type composition of heterogeneous tissue samples can be a critical variable in both clinical and laboratory settings. However, current experimental methods of cell type quantification (e.g., cell flow cytometry) are costly, time consuming and have potential to introduce bias. Computational approaches that use expression data to infer cell type abundance offer an alternative solution. While these methods have gained popularity, most fail to produce accurate predictions for the full range of platforms currently used by researchers or for the wide variety of tissue types often studied. RESULTS: We present the Gene Expression Deconvolution Interactive Tool (GEDIT), a flexible tool that utilizes gene expression data to accurately predict cell type abundances. Using both simulated and experimental data, we extensively evaluate the performance of GEDIT and demonstrate that it returns robust results under a wide variety of conditions. These conditions include multiple platforms (microarray and RNA-seq), tissue types (blood and stromal), and species (human and mouse). Finally, we provide reference data from 8 sources spanning a broad range of stromal and hematopoietic types in both human and mouse. GEDIT also accepts user-submitted reference data, thus allowing the estimation of any cell type or subtype, provided that reference data are available. CONCLUSIONS: GEDIT is a powerful method for evaluating the cell type composition of tissue samples and provides excellent accuracy and versatility compared to similar tools. The reference database provided here also allows users to obtain estimates for a wide variety of tissue samples without having to provide their own data.

Acute Kidney Injury after Congenital Heart Disease Surgery: A Single-Center Experience in a Low- to Middle-Income Country.

Background Acute kidney injury (AKI) is a commonly recognized clinical problem after congenital heart disease (CHD) surgery. Increased perioperative morbidity, development of chronic kidney disease, and increased mortality are the major concerns. We investigated frequency, risk factors, and outcomes of AKI after CHD surgery at our hospital. Methods This study was a retrospective analytic review conducted from January 2013 to October 2016 on patients aged between 1 month and 45 years who underwent cardiopulmonary bypass (CPB) for CHD surgery. The modified Kidney Disease Improving Global Outcomes criteria based on serum creatinine value was adopted to diagnose AKI. We assessed AKI frequency and its staging, and outcomes as AKI resolution, length of stay, and mortality. Stages II and III (plasma creatinine level two or more times the baseline) were labeled as severe AKI. Univariate and multivariate logistic regression analyses were conducted, and results were reported as mean with standard deviation and as frequencies with percentage. Odds ratios (ORs) with 95% confidence intervals (CIs) were reported for factors associated with the development of AKI. Results Of the 840 patients who underwent CHD surgery, 237 (28%) developed AKI. AKI stages II1 and III were seen in 101 (42%) and 103 (43%) patients, respectively. Prolonged CPB time > 120 minutes (adjusted OR [AOR]: 1.87; 95% CI: 1.22-2.88; p = 0.004) and hemoglobin > 16 gm/dL (AOR: 1.80; 95% CI: 1.16-2.78; p = 0.008) were associated with the development of AKI on multivariate analysis. AKI resolved spontaneously in 222 (94%) patients, and 10 (4%) patients who developed AKI died. Conclusions Most patients with AKI showed spontaneous resolution. Prolonged CPB time and increased hemoglobin were found to be significant risk factors. Our study found spontaneous resolution of AKI in most cases. However, preplanning and careful monitoring in patients with expected prolonged CPB time and increased baseline hemoglobin can prevent and identify AKI at an early stage.

Angiography and Therapeutic Embolisation of Bleeding Aberrant Iliac Artery Branches.

A 78-year female presented with the complain of per rectal fresh bleeding for 4 days. She was known to have diabetes and hypertension, 3 weeks back. She had an episode of left middle cerebral artery (MCA) stroke. After stroke, she suffered from upper limb weakness and aphasia. At the time of presentation, her vitals showed blood pressure of 118/52 mmHg, O2 saturation of 98%, temperature: 37°C, respiratory rate (RR) of 20/min, and heart rate (HR) of 90 bpm. After achieving hemodynamic stability, she was transferred to radiology department. Her presenting complain of active rectal bleeding was managed by interventional radiologist using angiographic embolisation. In this patient, it was found pooling of blood in a retrograde fashion in the sigmoid colon. Bleeding was initially believed to be coming from sigmoid arteries seen on images of CT scan and colonoscopy. However, arteriography showed that source of bleeding was from middle and inferior rectal arteries that originated from left internal iliac artery. The intervention radiology (IR) team had to put in extensive effort to locate and perform therapeutic embolisation.

Neuroimaging Findings in Tuberculosis: A Single-Center Experience in 559 Cases.

BACKGROUND AND PURPOSE: There is a paucity of literature related to the neuroimaging of CNS tuberculosis (TB) and largely covers pediatric CNS TB. The objective of this study was to determine the frequency of different forms of CNS TB and its associated complications and to study longitudinal disease course using computed tomography (CT) and MRI. METHODS: Retrospective chart and imaging review of patients diagnosed with CNS TB in a tertiary care hospital in Pakistan over a 10-year period. A total of 452 initial brain MRI and 209 CT scans were reviewed by an expert radiologist specialized in neuroimaging. This was followed by review of 53 MRI/52 CT and 7 MRI/14 CT first and second follow-up scans, respectively. RESULTS: Note that 559 patients, 296 males and 263 females were included in the study. On the initial CT scans, tuberculomas were found in 25 (12%), infarction in 54 (25%), basal meningeal enhancement in 29 (14%), and hydrocephalus in 84 (40%). On initial MRI, tuberculomas were found in 182 (40%), infarction in 120 (27%), basal meningeal enhancement in 184 (41%), and hydrocephalus in 116 (26%). On review of follow-up CT scans, 13 (25%) showed new or worsening hydrocephalus, 8 (15%) showed new infarcts, 1 exhibited new tuberculoma, and 5 showed worsening cerebral edema. On review of follow-up MRI scans, new or worsening hydrocephalus was seen in 3 (6%), new infarcts in 3 (6%), new tuberculoma in 10 (19%), worsening cerebral edema in 7 (13%), and TB myelitis in 4 (8%) patients. CONCLUSIONS: Tuberculoma, hydrocephalus, and cerebral infarcts are the most prominent findings in CNS tuberculosis. Our study showed development of new lesions on subsequent neuroimaging suggesting a dynamic and progressive nature of the disease process in some individuals.

Susceptibility profile of methicillin-resistant Staphylococcus aureus to linezolid in clinical isolates.

OBJECTIVE: To determine the resistance and sensitivity pattern of methicillin-resistant Staphylococcus aureus (MRSA) isolates to linezolid (LZD) along with its prevalence in a tertiary care hospital of Karachi, Pakistan. MATERIALS AND METHODS: A cross-sectional study was carried out. This study lasted for about 1 year. Prevalence and sensitivity of LZD, vancomycin, and oxacillin was tested against isolates of MRSA. RESULTS: Out of total 369 specimens 165 were found to be MRSA making the prevalence in our study 44.7%. All of the isolates which were tested positive for MRSA were susceptible to LZD and no resistance was noted when compared with previous studies performed in Europe and USA. CONCLUSION: Stringent implementation of infection control measures along with screening for resistance in patients on prolonged LZD therapy or who previously went under LZD therapy should be performed, coupled with judicious usage of the aforementioned antibiotic should be undertaken, as sufficient data is not available at this point for the clinical spectrum of LZD resistant S. aureus, antimicrobial resistance.