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Anti N-methyl-D-aspartate (NMDA) receptor encephalitis is new entity discovered over a decade. It is a type of autoimmune encephalitis characterized by a sequential onset of neuropsychiatric symptoms especially in the young population. Early diagnosis and treatment lead to better outcome and may prevent permanent neurological deficit or even death. Most patients respond well to first-line treatment and the resection of tumors associated with the disease. Here we present a case, which based on radiological findings, was diagnosed as cerebral venous sinus thrombosis (CVST), and was started on anticoagulation. Failure to respond to treatment and development of new movement abnormalities warranted for further investigations and he was found to have anti-NMDA receptor antibody positive in cerebrospinal fluid. Due to overlapping symptoms of CVST and encephalitis, high incidence of cerebral venous sinus thrombosis in this part of the world, and radiological findings, was initially thought to have CVST which was also confirmed on brain imaging. Lack of consent by the parents for a lumbar puncture delayed the definitive diagnosis. Patient developed movement disorder suggestive of autoimmune encephalitis, and this time after extensive counselling, when the cerebrospinal fluid was send for work up, it showed a positive anti-NMDA receptor antibody. He was promptly started on plasmapheresis after which patient had dramatic improvement both in movement abnormalities and neuropsychiatric symptoms.

Multisystem involvement has not been uncommon in SARS-CoV-2 infection. There has been reports of devastating neurological complication both during the infection and after the virus clears out. Here we present a rare case of sino-orbital mucormycosis, diagnosis of which was confirmed only on histopathology. Our patient presented with headache, 18 days after her recovery from SARS-CoV-2 infection and was extensively worked up for the cause. Initially she was treated as a severe sinusitis but failure to response to antibiotics treatment warranted for further investigations and imaging. Our patient had to undergo right eye enucleation plus debridement under general anesthesia under the care of ENT, Ophthalmology, Neurosurgery and Neurology. She is currently on anti-fungal treatment as advised by infectious disease department.

Background Significance of total ischemic time (TIT) in the context of ST-segment elevation myocardial infarction (STEMI) is still controversial. Therefore, in this study, we have evaluate the association of TIT with immediate outcomes in STEMI patients in whom recommended door to balloon (DTB) time of less than 90 min was achieved. Results A total of 5730 patients were included in this study, out of which 80.9% were male and median age was 55 [61–48] years. The median DTB was observed to be 60 [75–45] min and onset of chest pain to emergency room (ER) arrival time was 180 [300–120] min. Prolonged TIT was associated with poor pre-procedure thrombolysis in myocardial infarction (TIMI) flow grade (p = 0.022), number of diseased vessels (p = 0.002), use of intra-aortic balloon pump (p = 0.003), and in-hospital mortality (p = 0.002). Mortality rate was 4.5%, 5.7%, and 7.8% for the patients with TIT of ≤ 120 min, 121 to 240 min, and > 240 min, respectively. Thirty days’ risk of mortality on TIMI score was 4.97 ± 7.09%, 5.01 ± 6.99%, and 7.12 ± 8.64% for the patients with TIT of ≤ 120 min, 121 to 240 min, and > 240 min, respectively. Conclusions Prolonged total ischemic was associated with higher in-hospital mortality. Therefore, TIT can also be considered in the matrix of focus, along with DTB time and other clinical determinants to improve the survival from STEMI.

Breast cancer brain metastases (BCBMs) are one of the most difficult malignancies to treat due to the intracranial location and multifocal growth. Chemotherapy and molecular targeted therapy are extremely ineffective for BCBMs due to the inept brain accumulation because of the formidable blood‒brain barrier (BBB). Accumulation studies prove that low density lipoprotein receptor-related protein 1 (LRP1) is promising target for BBB transcytosis. However, as the primary clearance receptor for amyloid beta and tissue plasminogen activator, LRP1 at abluminal side of BBB can clear LRP1-targeting therapeutics. Matrix metalloproteinase-1 (MMP1) is highly enriched in metastatic niche to promote growth of BCBMs. Herein, it is reported that nanoparticles (NPs-K-s-A) tethered with MMP1-sensitive fusion peptide containing HER2-targeting K and LRP1-targeting angiopep-2 (A), can surmount the BBB and escape LRP1-mediated clearance in metastatic niche. NPs-K-s-A revealed infinitely superior brain accumulation to angiopep-2-decorated NPs-A in BCBMs bearing mice, while comparable brain accumulation in normal mice. The delivered doxorubicin and lapatinib synergistically inhibit BCBMs growth and prolongs survival of mice bearing BCBMs. Due to the efficient BBB penetration, special and remarkable clearance escape, and facilitated therapeutic outcome, the fusion peptide-based drug delivery strategy may serve as a potential approach for clinical management of BCBMs., Graphical abstract Brain-targeting drug delivery efficiency is boosted for therapy of brain metastases by fusion-peptide-decorated nanoparticles, via luminal LRP1-mediated BBB crossing and escaping from abluminal LRP1-mediated clearance through MMP1-triggered peptide cleavage.Image 1

The pandemic of severe acute respiratory virus (SARS-CoV-2) is characterized by respiratory symptoms with serious consequences, mainly associated with pneumonia and extreme ARDS. There is a lack of data about specific neurological manifestations of covid-19 infections literature. Epidemiological trials in fewer than 30% of a population reported symptoms of headache and delirium (Helms et al., 2020). Covid-19’s neurotropism is still debatable, uncertain and in the present case study patient with Covid-19 is identified. He suffered with extreme respiratory complications during hospitalization and eventually died.

Background: This study was conducted with the aim of providing a quantitative appraisal of clinical outcomes of trans-radial access for primary percutaneous coronary interventions (PCI) in patients with ST-segment evaluation myocardial infarction (STEMI). Methods: In this study, we compared two propensity-matched cohorts of patients who underwent primary PCI via trans-radial (TRA) and trans-femoral access (TFA) in a 1:1 ratio. The profile of two cohorts was matched for gender, age, and body mass index, diabetes, hypertension, family history, and smoking. The outcomes of primary PCI were compared for the two cohorts which included all-cause in-hospital mortality, heart failure, re-infarction, cardiogenic shock, bleeding, transfusion, cerebrovascular accident, and dialysis. Results: This analysis was performed on a total of 2316 patients with 1158 patients each in the TRA and TFA group. We observed significantly lower rates of mortality, 0.8% (9) vs. 3.5% (41); p

BACKGROUND Even though percutaneous coronary intervention (PCI) improved the survival of patients with acute myocardial infarction, still multivessel coronary artery disease remains an important factor burdening prognosis and it is being associated with a worse prognosis compared to single-vessel disease (SVD). AIM To compare the clinical profile and outcomes after the primary PCI in young patients with SVD vs multivessel disease (MVD). METHODS The retrospective cohort of patients were divided into two groups: SVD and MVD group. The study population consisted of both male and female young (≤ 45 years) patients presented with ST-elevation myocardial infarction (STEMI) at the National Institute of Cardiovascular Disease, Karachi, Pakistan and undergone primary PCI from 1st July 2017 to 31st March 2018. Pre and post-procedure management of the patients was as per the guidelines and institutional protocols. RESULTS A total of 571 patients with STEMI, ≤ 45 years were stratified into two groups by the number of vessels involved, 342 (59.9%) with SVD and 229 (40.1%) with MVD. The average age of these patients was 39.04 ± 4.86 years. A lower prevalence of hypertension and diabetes was observed in SVD as compare to MVD group (25.1% vs 38%, P < 0.01; 11.7% vs 27.5%, P < 0.001) respectively. While, smoking was more prevalent among the SVD group as compare to MVD group (36.3% vs 28.4%, P = 0.05). The high-C Lesion was observed in a significantly higher number of younger patients with MVD as compared to SVD group (48.8% vs 39.2%, P = 0.021). Post-procedure thrombolysis in myocardial infarction flow grade was found to be not associated with the number of diseased vessels with a P value of 0.426 and thrombolysis in myocardial infarction flow grade III was observed in 98% vs 96.5% of the patients is SVD vs MVD group. CONCLUSION The MVD comprised of around 40% of the young patients presented with STEMI. Also, this study shows that diabetes and hypertension have a certain role in the pathogenesis of multivessel diseases, therefore, preventive measures for diabetes and hypertension can be effective strategies in reducing the burden of premature STEMI.

Pakistan has been experiencing a continuous rise in the incidence of Crimean Congo Haemorrhagic Fever (CCHF). Sporadic cases of CCHF are reported from rural areas of Punjab, Azad Jammu Kashmir and Khyber Pakhtunkhwa and neighbouring Afghanistan where cattle herding is common. The objective of this paper was to describe the epidemiology of CCHF. A descriptive study was carried out in the CCHF isolation ward in Islamabad in a tertiary care hospital from February to November 2018. Using a standardised case definition, all patients admitted in the isolation ward with clinical evidence of CCHF were included in the study. After taking the informed consent, data were collected on demographic factors, history of animal contact, tick-bite history, co-morbidity, laboratory results and treatment outcome. Data were analysed as per time, place and person. During the study period, 40 suspected CCHF patients were admitted in the isolation ward, 32 (80%) males were affected. Mean age of the cases was 33.5 years (range 13–70 years). Most affected 17 (42.5%) age group was 20–29 years. Animal contact history was found in Thirty-seven (92.5%) of cases and 28 (70%) with tick bites. Most of the cases, 26 (65%), were reported from July to August. Forty patients in this study were tested by Real Time Polymerase Chain Reaction (PCR), 20 (50%) were positive, out of which 6(30%) expired. Majority of the positive patients were animal handlers by occupation (37.5%). Proper personal protective equipment was available. The reference laboratory facility was not available for immediate investigations was sent to National Institute of Health for confirmation. The overall results show the important risk factors for CCHF a history of tick bites, high-risk occupations and having contact with livestock. Public health measures should focus on preventing tick bites, increasing awareness of CCHF signs and symptoms, timely investigation, and treatment to reduce mortality. Our analyses recommend the government to set up isolation units in all major hospitals, and proper surveillance system.

IntroductionBreast cancer is one of the major and frequent tumors in the public health sector globally. The rising global prevalence of breast cancer has aroused attention in a viral etiology. Other than genetic and hormonal roles, viruses like Epstein - Barr virus (EBV) also participate in the development and advancement of breast cancer.AimThis study was conducted to detect the frequency of EBV genotypes in breast cancer patients and compare it with histopathological breast cancer changes.MethodsFormalin-fixed paraffin-embedded samples of breast cancer (N=60) ages ranged from 22-70 years were collected. EBV DNA was isolated, amplified, typed through PCR, and correlated with histopathological outcomes of breast cancer using SPSS software version 26.ResultsOur findings suggest that among breast cancer factors, Invasive ductal carcinoma (IDC) was the most common pathological pattern found among patients (90%), observed statistically significant (p= 0.01275). In regards to clinical staging, 8 (13.3 %) patients diagnosed with stage I, 39 (65 %) with stage II, and 13 (21.6 %) with stage III reported statistically significant association (p=0.0003). EBV DNA was detected in 68.3% (41/60) breast cancer patients, reported a statistically significant difference between the prevalence of EBV in breast cancer patients and normal samples (p= 0.001). Of 41 EBV-positive samples, 40 were EBV-1, while only 1 had EBV-2 infection (p < 0.001). No influence on cancer histology was observed. Regarding the association of breast cancer with EBV, histological type (P =0.209), tumor stage (P = 0.48), tumor grade (0.356), tumor sizes (p= 0.976), age (p= 0.1055), tumor laterality (p= 0.533) and ER/PR status (p=0.773) showed no significant association.ConclusionEBV-1 is prevalent in breast cancer patients and associated with IDC in the study area. For conclusive evidence, more studies are required based on a large sample size and by using more sensitive techniques.

The neurological manifestations of SARS-CoV-2 are wide-ranging from simple headache to severe demyelinating brain disease. This is a review of collected case reports of patients with SARS-CoV-2 with neurological manifestations presenting to the Pakistan Institute of Medical Sciences (PIMS). Neurological manifestations associated with SARS-CoV-2 such as encephalitis, acute cerebrovascular disease, encephalitis with chorea, post-COVID myositis and Guillain-Barre Syndrome (GBS) are of great concern but are often overlooked in the presence of life-threatening abnormal vital signs in severely ill SARS-CoV-2 patients. There is a need to diagnose these manifestations at the earliest opportunity to limit long-term consequences and complications. Much research is needed to explore the role of SARS-CoV-2 in causing these neurological manifestations by isolating it either from the cerebrospinal fluid (CSF) or the brain tissue of the deceased on autopsy. We also recommend exploring the risk factors that lead to the development of these neurological manifestations.

SARS-CoV-2 infections are transmitted through droplets or through direct contact with secretions from an infected person. The transmission of the virus through tears and other body secretions remains controversial. PCR detection of Covid-19 in the samples/swabs taken from nasopharynx, CSF fluid, and tears, clarifies that the virus may be transmitted through the modes other than aerosol droplets or direct contact. In order to control and prevent this infectious disease, cutting-off the route of transmission will be one of the most important steps. SARS-CoV-2 RNA has been detected in tears and conjunctival samples of patients. The ocular tropism of Covid-19 is still uncertain but contentious.

Genetic polymorphisms in the MTNR1B gene is associated with type 2 diabetes mellitus (T2DM); however, there is no evidence about its impact on the therapeutic efficacy of nateglinide. This prospective case–control study was designed to investigate the effect of MTNR1B rs10830963 gene variant on the therapeutic efficacy of nateglinide in treating T2DM. We genotyped untreated T2DM patients (N = 200) and healthy controls (N = 200) using the method of the high resolution of melting curve (HRM). Newly diagnosed T2DM patients (n = 60) with CYP2C9*1 and SLCO1B1 521TT genotypes were enrolled and given oral nateglinide (360 mg/d) for 8 weeks. The outcome was measured by collecting the venous blood samples before and at the 8th week of the treatment. The risk G allelic frequency of MTNR1B rs10830963 was higher in T2DM patients than the healthy subjects (P P MTNR1B rs10830963 polymorphism was associated with the therapeutic efficacy of nateglinide in T2DM patients. Also, the CC homozygotes had a better effect than G allele carriers.Trial registration Chinese Clinical Trial Register ChiCTR13003536, date of registration: May 14, 2013.

Background Covid-19 pandemic has been manifested mainly as respiratory and constitutional symptoms. Though, it may demonstrate the involvement of other systems i.e. cardiovascular system (CVS), central nervous system (CNS) or gastrointestinal system (GI). Discussion Systemic manifestation of Covid-19 requires further research. Recent surveys revealed a few alarming facts about Covid-19, that, when it hits the brain, can cause some serious complications like; psychosis, stroke and dementia. Case Presentation Here, the case is about two patients, having PCR confirmed Covid-19 and radiographic evidence of stroke, who eventually died during hospital stay. Data collection was done after informed consent and in retrospective manner.

Breast cancer brain metastases (BCBM) represent a major cause of morbidity and mortality among patients with breast cancer. Systemic drug therapy, which is usually effective against peripheral breast cancers, is often ineffective on BCBM due to its poor penetration through the blood-brain tumor barrier (BTB). In this study, prostate-specific membrane antigen (PSMA) with internalization function was found to be specifically up-regulated on BCBM-associated BTB while barely detectable in normal blood-brain barrier (BBB). Here, a nanotechnology approach is reported that can overcome the BTB through ACUPA (A) and cyclic TT1 (cT) co-functionalized nanoparticles (A-NPs-cT). A-NPs-cT selectively target PSMA on BTB for specific BTB crossing and specially bind with p32 for BCBM targeting. We disclosed the effectual synergism of doxorubicin (DOX) and lapatinib (LAP) for BCBM combined therapy. A-NPs-cT exhibited boosted uptake than integrin-targeting RGD-modified NPs in BTB endothelial cells and displayed about 4.57-fold stronger penetration through the BCBM-associated BTB as compared to the normal BBB. In vivo studies showed specific BTB crossing, and remission of BCBM and prolonged survival with DOX and LAP combinatorial regimen. A-NPs-cT based DOX and LAP innovative combined therapy envisioned improved therapeutic intervention for clinical management of BCBM, for which surgery is generally inapplicable and insufficient.

Objective: To determine the frequency of peri-pocedural myocardial infarction in patients with stable coronary artery disease undergoing elective percutaneous coronary angioplasty. Methodology: This was a descriptive study conducted in the cardiac cath lab of the National Institute of Cardiovascular Diseases Karachi, Pakistan. Patients with stable obstructive coronary artery disease undergoing elective coronary angioplasty were included in this study. PMI was defined as a rise in troponin I above five times the upper limit of the normal range (the third universal definition of MI). Collected data were entered and analyzed using SPSS 19. Results: Among the total of 107 patients male predominance, 82.2% (88), was observed and mean ± SD age of the patients was 52.02 ± 9.10 years with a majority, 92(86.0%), of patients between 41 to 80 years of age. Peri-procedural myocardial infarction (PMI) was found in 16(15.0%) of the patients and PMI was observed to be independent of baseline risk profile and angiographic characteristics of the patients. While, based on criteria of troponin I above three times the upper limit of the normal range, PMI was observed in 22(20.6%) of the patients. Conclusion: High incidence of the post-procedural rise of troponin in our study population is alarming. Further studies are required to identify the cause and hence identifying measures to prevent PMI. Universal single definition is required worldwide in order to get uniform results. Keywords: Post PCI Myocardial Infarction, Coronary angioplasty, Third universal definition

It is common sense that look of the skin generally reflects good health and human robustness. This is why cosmetic industries are concerned with the elegance of the finish product, the main obligation to be purchased the appearance of the formulation itself, and cosmetic application, for which the product is fabricated. Because of their nanosize and pearl-like nature, cosmetic lipid nanocarriers play an important role in the cosmetic industry. The features discussed in this chapter for cosmetic lipid nanocarriers include stability of the integrated substances, loading capacity, controlled/triggered release, occlusivity, film formation, and penetration through the skin. The technology for fabrication; issues concern production, including large and small scale production; regulatory aspects; status of the excipients and proof physical and chemical stability are described.

'Background:' Influenza is a common respiratory disease in Pakistan. However, the absence of a robust surveillance system makes it difficult to estimate the burden of disease. 'Purpose:' We conducted this study to identify key strengths and weaknesses of the laboratory-based influenza surveillance system in Pakistan and to make recommendations for improvement. 'Methods:' We conducted an evaluative descriptive study of the national laboratory-based influenza surveillance system from April to July 2017. We conducted this assessment using the updated guidelines for evaluating public health surveillance systems issued by CDC in 2011. 'Findings: 'The system was found to be simple and easy to operate, but with little flexibility to integrate with other pathogens and diseases. Data quality was good, given that 80% of observed forms were completed. Timeliness was good, as it takes only 24-48 hours from sample collection to report a submission to the central level. Acceptability was good, since both private and public sector hospitals and labs are involved. Sensitivity was 62% and positive predictive value (PPV) was 37.2%. The representativeness of lab based influenza surveillance system was poor, since it is a sentinel surveillance system with specific, strategically placed reporting sites. 'Conclusions:' The system meets its objectives. Sustainability and stability of the system needs to be improved by allocation of public funds. Coverage of the system should be expanded to improve representativeness. Regular capacity building with staff at reporting sites will ensure continued quality of reporting.

Door to balloon (DTB) time is a well established determinant of in-hospital outcome and long-term morbidity and mortality in the ST Elevation Myocardial Infarction (STEMI), however, significance of total ischemic time (TIT) is debatable. Therefore, aim of this study was to evaluate the association

OBJECTIVE Radial route of access is increasingly being used for coronary angiograms and intervention. However, radiation exposure of operators was not known in our set up with either transfemoral or transradial procedures. The objective of the study was to compare related peripheral arterial route radiation exposure of operators by assessing fluoroscopy time. The secondary objective was to determine the relationship of operator experience with fluoroscopy time. METHODS This observational study was conducted in a tertiary care center - Cardiovascular Institute of Karachi (Pakistan) during the period of July 1(st) 2009 to September 30(th) 2009. We studied 1016 consecutive adult patients referred for coronary angiography (CA) or percutaneous coronary intervention (PCI). Patients who underwent right heart catheterization or for valvuloplasty were excluded from the study. Out of these 1016 patients, 928 were diagnostic CAs (734 via femoral route [f-CA] and 194 via radial route [r-CA]) and 88 were PCI (64 via femoral route [f-PCI] and 24 via radial route [r-PCI]). Fluoroscopy time was recorded as a surrogate of radiation exposure. Statistical analysis was performed using unpaired t, Mann-Whitney U, Chi-square and ANOVA tests. RESULTS Mean fluoroscopy time was found to be significantly higher in patients who underwent r-CA (6.3±3.8 vs 4.0±2.9 min; p