Chylothorax is a rare postoperative complication of congenital heart surgery. It has high morbidity with increased hospital stay and cost of treatment. Damage to the thoracic duct, disruption of ...accessory lymphatic vessels, and increased venous pressure exceeding that in the thoracic duct have been proposed as the possible causes of chylothorax after surgery for congenital heart disease. Prompt diagnose with early initiation of treatment will reduce the duration of drainage. Staged treatment is the general principle in managing this serious complication. Loss of chyle leads to volume, nutritional and electrolyte depletion, immunological deficiencies and hematological complications. Identifying the underlying cause and addressing it is crucial to definitive management.
This study aims to assess the clinical presentation and the outcomes of a surgical correction of an anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). A retrospective ...review was carried out on the charts of six patients admitted for ALCAPA surgery at Aga Khan University Hospital, Karachi from March 2017 to May 2018.Dyspnoea, palpitation, poor feeding, fatiguability, pallor and a murmur of mitral regurgitation were the main presenting features. The pre-operative median left ventricular ejection fraction (LVEF) was 64%. Coronary reimplantation was performed in all the patients with a mitral valve repair being done in only one patient. The mea n LV EF was 66 .3%,p ost- ope rativel y. Mitra l regurgitation (MR) improved in patients post-operatively with trace in 2 patients and mild MR in one. Surgical correction by coronary re-implantation yields favourable outcomes in ALCAPA and significantly reduces the morbidity and mortality rates associated with the disease.
Insulin Receptor Substrate (IRS), an intracellular molecule devoid of an intrinsic kinase activity, is activated upon binding to IR which thereby works as a scaffold, organizing all signaling ...complexes and initiating the signaling process downstream. The level of IRS proteins and their stability in the cell is mostly maintained through the phosphorylation status of their tyrosine and serine residues. IRS is positively regulated by phosphorylation of its Tyr residues whereas a Ser residue phosphorylation attenuates it, although there exist some exceptions as well. Other post-translational modifications like O-linked glycosylation, N-linked glycosylation and acetylation also play a prominent role in IRS regulation. Since the discovery of the Warburg effect, people have been curious to find out all possible signaling networks and molecules that could lead to cancer and no doubt, the insulin signaling pathway is identified as one such pathway, which is highly deregulated in cancers. Eminent studies reveal that IRS is a pertinent regulator of cancer and is highly overexpressed in the five most commonly occurring cancers namely- Prostate, Ovarian, Breast, Colon and Lung cancers. IRS1 and IRS2 family members are actively involved in the progression, invasion and metastasis of these cancers. Recently, less studied IRS4 has also emerged as a contributor in ovarian, breast, colorectal and lung cancer, but no such studies related to IRS4 are found in Prostate cancer. The involvement of other IRS family members in cancer is still undiscovered and so paves the way for further exploration. This review is a time-lapse study of IRSs in the context of cancer done over the past two decades and it highlights all the major discoveries made till date, in these cancers from the perspective of IRS.
•IRS is the central molecule responsible for relaying the extracellular stimuli induced effects via its varied signaling network.•Activation and deactivation of IRS is regulated by the phosphorylation at its Tyrosine and Serine residues respectively.•IRS has a multifaceted involvement in progression and development of cancers.
Hospital associated infections or healthcare associated infections (HAIs) are a major threat to healthcare and medical management, mostly because of their recalcitrant nature. The primary cause of ...these HAIs is bacterial associations, especially the interspecies interactions. In interspecies interactions, more than one species co-exists in a common platform of extracellular polymeric substances (EPS), establishing a strong interspecies crosstalk and thereby lead to the formation of mixed species biofilms. In this process, the internal microenvironment and the surrounding EPS matrix of the biofilms ensure the protection of the microorganisms and allow them to survive under antagonistic conditions. The communications between the biofilm members as well as the interactions between the bacterial cells and the matrix polymers, also aid in the rigidity of the biofilm structure and allow the microorganisms to evade both the host immune response and a wide range of anti-microbials. Therefore, to design a treatment protocol for HAIs is difficult and it has become a growing point of concern. This review therefore first aims to discuss the role of microenvironment, molecular structure, cell-cell communication, and metabolism of mixed species biofilms in manifestation of HAIs. In addition, we discuss the electrochemical properties of mixed-species biofilms and their mechanism in developing drug resistance. Then we focus on the most dreaded bacterial HAI including oral and gut multi-species infections, catheter-associated urinary tract infections, surgical site infections, and ventilator-associated pneumonia. Further, we highlight the challenges to eradication of the mixed species biofilms and the current and prospective future strategies for the treatment of mixed species-associated HAI. Together, the review presents a comprehensive understanding of mixed species biofilm-mediated infections in clinical scenario, and summarizes the current challenge and prospect of therapeutic strategies against HAI.
•Mixed species biofilms are the principle causative agents of hospital associated infections.•The hospital associated infections being recalcitrant nature are extremely difficult to treat.•The microenvironment and inter species crosstalk in mixed species biofilm are the relevant mechanisms by which the biofilms acquire resistance.•The inception of nanotechnological advances is being currently investigated for effective treatment of these infections.
MUMPS MYOCARDITIS: A FORGOTTEN DISEASE? Hussain, Sheraz; Zahid, Mohammad Faizan; Rahman, Arshalooz Jamila ...
Journal of Ayub Medical College, Abbottabad,
2016 Jan-Mar, Letnik:
28, Številka:
1
Journal Article
Mumps is an acute viral illness that follows a self-limiting course but up to 10% of cases have a complicated course with the involvement of other organ systems. Myocarditis is reported as a ...complication but the incidence has greatly fallen ever since the development of the mumps vaccine. A child presented to our department with parotid swelling and fever. Persistent tachycardia with irregular pulse led to further cardiac work up which showed decreased ejection fraction and raised serum cardiac enzymes, indicating myocardial damage. With ionotropic agents and supportive care, there was complete normalization of ejection fraction and serum cardiac enzyme levels. He was discharged within a week of admission. This case highlights the importance of suspecting myocarditis in the setting of mumps, a diagnosis that precludes early suspicion in mumps patients suffering from cardiac symptoms not explained by other potential aetiologies. Early suspicion and timely supportive care are essential to ensure favourable outcomes.
Caveolin-1 (Cav-1) is a structural protein of caveolae that functions as a molecular organizer for different cellular functions including endocytosis and cellular signaling. Cancer cells take ...advantage of the physical position of Cav-1, as it can communicate with extracellular matrix, help to organize growth factor receptors, redistribute cholesterol and glycosphingolipids, and finally transduce signals within the cells for oncogenesis. Recent studies emphasize the exceeding involvement of Cav-1 with different lipid bodies and in altering the metabolism, especially lipid metabolism. However, the association of Cav-1 with different lipid bodies like lipid rafts, lipid droplets, cholesterols, sphingolipids, and fatty acids is remarkably dynamic. The lipid-Cav-1 alliance plays a dual role in carcinogenesis. Both cancer progression and regression are modified and affected by the type of lipid molecule's association with Cav-1. Accordingly, this Cav-1-lipid cooperation exemplifies a cancer-type-specific treatment strategy for a better prognosis of the disease. In this review, we first present Cav-1 as an oncogenic molecule and its communication via lipid raft. We discussed the involvement of Cav-1 with lipid droplets, Cholesterol, sphingolipids, gangliosides, and ceramides. Further, we describe the Cav-1-mediated altered Fatty acid metabolism in cancer and the strategic therapeutic approaches toward Cav-1 targeting.
Coronary artery involvement is the most dreaded long-term complication of Kawasaki disease. Our aim was to look at the pattern of cardiovascular involvement in Pakistani children admitted with ...Kawasaki disease.
This study included children admitted with Kawasaki disease at the Aga Khan University Hospital Karachi over a period of 14 years from January 1997 to December 2010. Information gathered included patient demographics, clinical features, investigations, echocardiographic findings, treatment and follow-up. Those with coronary artery involvement on initial echocardiogram remained on long-term follow-up with clinical examination and echocardiogram.
A total of 56 patients were admitted. (Mean age at diagnosis 33 ± 30 months, age range 2 months to 9 years). 18% of patients had incomplete features. Twenty-five percent (14/56) patients presented after 10 days of fever. Cardiac examination was normal except for tachycardia. Abnormal coronary arteries were seen in 23 patients (41%) - left main coronary artery in 23 (41%), left anterior descending and right main coronary artery in 20 (36%), circumflex branch in 17 (30%). Risk factors for cardiac involvement were male sex, fever >10 days duration at the time of initial presentation and neutrophil percentage >75% in the initial white blood cell counts. Fifty four of 56 cases received intravenous immunoglobulin (IVIG), Seventy-five percent of the patients received IVIG within 10 days of illness. Mean duration of follow-up was 2.5 years. Eight percent of the patients still continue to have abnormal coronaries. There was no mortality.
A higher incidence of coronary artery involvement was found in our study. Presentation after 10 days of illness increases the risk of coronary artery involvement. High index of suspicion among the general pediatricians about the disease can possibly be helpful for early referral and treatment.
Objectives To identify anthracycline-induced acute (within 1 month) and early-onset chronic progressive (within 1 year) cardiotoxicity in children younger than 16 years of age with childhood ...malignancies at a tertiary care centre of Pakistan. Design Prospective cohort study. Setting Aga Khan University, Karachi, Pakistan. Participants 110 children (aged 1 month–16 years). Intervention Anthracycline (doxorubicin and/or daunorubicin). Outcome measurements All children who received anthracycline as chemotherapy and three echocardiographic evaluations (baseline, 1 month and 1 year) between July 2010 and June 2012 were prospectively analysed for cardiac dysfunction. Statistical analysis including systolic and diastolic functions at baseline, 1 month and 1 year was carried out by repeated measures analysis of variance. Results Mean age was 74±44 months and 75 (68.2%) were males. Acute lymphoblastic leukaemia was seen in 70 (64%) patients. Doxorubicin alone was used in 59 (54%) and combination therapy was used in 35 (32%). A cumulative dose of anthracycline <300 mg/m2 was used in 95 (86%). Fifteen (14%) children developed cardiac dysfunction within a month and 28 (25%) children within a year. Of these 10/15 (66.6%) and 12/28 (43%) had isolated diastolic dysfunction, respectively, while 5/15 (33.3%) and 16/28 (57%) had combined systolic and diastolic dysfunction. Seven (6.4%) patients expired due to severe cardiac dysfunction. Eight of 59 (13.5%) children showed dose-related cardiotoxicity (p=<0.001). Cardiotoxicity was also high when the combination of doxorubicin and daunorubicin was used (p=0.004). Conclusions Incidence of anthracycline-induced cardiotoxicity is high. Long-term follow-up is essential to diagnose its late manifestations.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is seldom recognized clinically in infancy or under the age of 10. We report a case of a 9-year-old girl with ARVC, who presented with signs and ...symptoms of heart failure and palpitations. Holter monitoring showed frequent premature ventricular beats and echocardiogram revealed dilated and dysfunctional right ventricle with normal tricuspid valve and no evidence of intracardiac shunt. Cardiac magnetic resonance showed classical features of ARVC with both ventricular involvements. After optimization of medical treatment the patient was referred for ICD implantation.
Agitation is one of the most challenging neuropsychiatric symptoms to treat in Alzheimer's disease and has significant implications for patient and caregiver. A major source of difficulty in ...identifying safe and effective treatments for agitation is the lack of validated biomarkers. As such, patients may not be appropriately targeted, and biological response to pharmacotherapy cannot be adequately monitored.
This systematic review aimed to summarize evidence on the association between biomarkers and agitation/aggression in patients with Alzheimer's disease, utilizing the National Institute on Aging–Alzheimer's Association Research Framework and the Biomarkers, EndpointS, and other Tools Resource of the Food and Drug Association-National Institutes of Health Biomarker Working Group.
This review identified six classes of biomarkers (neuropathological, neurotransmitter, neuroimaging, apolipoprotein E (APOE) genotype, inflammatory, and clusterin) associated with agitation/aggression, which were mostly diagnostic in nature.
Future studies should investigate the predictive, prognostic, and monitoring capacity of biomarkers to provide insight into the longitudinal course of agitation/aggression, as well as predict and monitor biological response to a pharmacological intervention.
•Six classes of biomarkers from 57 studies were identified.•All biomarker classes (neuropathological, neurotransmitter, neuroimaging, apolipoprotein E (APOE) genotype, inflammatory, and clusterin) were associated with agitation, however, within each class there were either few studies or contradictory findings.•Most studies were diagnostic in nature and were associated with a high quality of evidence.
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