Presacral tumors: A systematic review of literature.

Presacral/Retrorectal tumors (RRT) are rare lesions that comprise a multitude of histological types. Data on surgical management are limited to case reports and small case series. The aim of the study was to provide a comprehensive review of the epidemiology, pathological subtypes, surgical approaches, and clinical outcomes. A PubMed search using terms "retrorectal tumor" and "presacral tumor" was used to identify articles reporting RRT of non-urological, non-gynecologic, and non-metastatic origin. Articles included were between 2015 and 2023. A total of 68 studies were included, comprising 570 patients. About 68.2% of patients were female, and the mean overall age of both sexes was 48.6 years. Based on histopathology, 466 patients (81.8%) had benign lesions, and 104 (18.2%) were malignant. In terms of surgical approach, 191 (33.5%) were treated anteriorly, 240 (42.1%) through a posterior approach, and 66 (11.6%) combined. The mean length of stay was 7.6 days. Patients treated using the posterior approach had a shorter length of stay (5.7 days) compared to the anterior and combined approaches. RRT are rare tumors of congenital nature with prevalence among the female sex. R0 resection is crucial in its management, and minimal access surgery appears to be a safer option in appropriate case selection.

Caveolin-1 and lipids: Association and their dualism in oncogenic regulation.

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.

The strategic involvement of IRS in cancer progression.

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.

Prenatally diagnosed large intrapericardial rhabdomyoma without haemodynamic compromise.

Cardiac rhabdomyoma is the most common primary cardiac tumour and is considered to be a hamartoma of developing embryonic cardiac myocytes. It is commonly seen in tuberous sclerosis. The size and location of the tumour is the surrogate determinant of the risk of haemodynamic compromise. Pericardial rhabdomyoma is very rare and tends to follow the inherent natural history of spontaneous regression. We present cases of two foetuses diagnosed with large pericardial rhabdomyoma and no haemodynamic consequences.

Post-Operative Chylothorax in Children Undergoing Congenital Heart Surgery.

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.

Glutathione Peroxidase Activity Is Altered in Vascular Cognitive Impairment-No Dementia and Is a Potential Marker for Verbal Memory Performance.

BACKGROUND: Coronary artery disease (CAD) increases risk for vascular cognitive impairment-no dementia (VCIND), a precursor to dementia, potentially through persistent oxidative stress. OBJECTIVE: This study assessed peripheral glutathione peroxidase activity (GPX), which is protective against oxidative stress, in VCIND versus cognitively normal CAD controls (CN). GPX activity was also evaluated as a biomarker of cognition, particularly verbal memory. METHODS: 120 CAD patients with VCIND (1SD below norms on executive function or verbal memory (VM)) or without (CN) participated in exercise rehabilitation for 24 weeks. Neurocognitive and cardiopulmonary fitness (VO2peak) assessments and plasma were collected at baseline and 24-weeks. RESULTS: GPX was higher in VCIND compared to CN (F1,119 = 3.996, p = 0.048). Higher GPX was associated with poorer baseline VM (ß= -0.182, p = 0.048), and longitudinally with VM decline controlling for sex, body mass index, VO2peak, and education (b[SE] = -0.02[0.01], p = 0.004). Only CN participants showed improved VM performance with increased fitness (b[SE] = 1.30[0.15], p < 0.005). CONCLUSION: GPX was elevated in VCIND consistent with a compensatory response to persistent oxidative stress. Increased GPX predicted poorer cognitive outcomes (verbal memory) in VCIND patients despite improved fitness.

Short And Midterm Outcome Of Fallot's Tetralogy Repair In Infancy: A Single Center Experience In A Developing Country.

BACKGROUND: Primary repair of ToF between 3-12 months is the preferred mode of treatment worldwide, with low surgical mortality. This study reviews our experience of ToF repair in infancy and its short and midterm outcomes in a single centre from a developing country. METHODS: Data of all patients with Tetralogy of Fallot repair during infancy from January 2007 to Feb 2018 was reviewed. Preoperative, operative, and postoperative data was analysed. Outcome of the infants was assessed through discharge/death, low cardiac output syndrome (LCOS), prolonged intubation, duration of cardiac intensive care unit (CICU) and hospital stay. RESULTS: Forty-four patients who underwent TOF repair in infancy during this period were included. The mean age and weight were 9.39±2.32 and 7.20±1.30 respectively, 77.3% (34 patients) were male, 68.18% (30 patients) had saturation >75%. Mean intubation period was 4.05±6.58 days, 12 (27.3%) patients developed LCOS, mean cardiopulmonary bypass (CPB) time, aortic cross clamp (ACC) time and ionotropic score were 133.52±62.4, 98.66±58.62 and 33.27±71.13 respectively. Mean CICU and hospital stay was 6.60±7.18 and 12.05±7.74 respectively. Five (11.3%) patients expired in postoperative period. Baseline saturation ≤75% is independent risk factor for LCOS and prolong intubation period. In the last six years our mortality decreased to 8% from 15.7% during the previous six years, while our mean intubation duration, CPB time, ACC, hospital stay and CICU stay have all shown improvement. CONCLUSIONS: TOF repair during infancy is safe procedure in expert hands with acceptable morbidity and mortality. Baseline saturation ≤75% is independent risk factor for LCOS and prolonged intubation period. Last six years have shown considerable improvement in our surgical morbidity and mortality due to improvement in surgical expertise.

Current Agents in Development for Treating Behavioral and Psychological Symptoms Associated with Dementia.

Behavioral and psychological symptoms associated with dementia are highly prevalent and are associated with an increased risk of institutionalization and mortality. Current pharmacological treatments for these symptoms include cholinesterase inhibitors, antipsychotics, and selective serotonin reuptake inhibitors. When used for treating behavioral and psychological symptoms associated with dementia, they are associated with limited efficacy and/or serious adverse events. As such, there has been extensive research into novel agents with varying mechanisms of action targeting behavioral and psychological symptoms associated with dementia. In this article, we present the results of a comprehensive literature search and review that evaluates current agents that have completed or are currently in clinical trials for treating behavioral and psychological symptoms associated with dementia as a primary outcome. We highlight novel agents from miscellaneous drug classes, such as dextromethorphan/quinidine, bupropion/dextromethorphan, lumateperone, deudextromethorphan/quinidine, methylphenidate and scyllo-inositol, and drugs from various therapeutic classes (including atypical antipsychotics, selective serotonin reuptake inhibitors, and cannabinoids) that have demonstrated promising results and were generally well tolerated. Future research with large appropriately powered studies using validated outcome measures for behavioral and psychological symptoms associated with dementia should be conducted to further establish the clinical utility of these agents.

Biomarkers of agitation and aggression in Alzheimer's disease: A systematic review.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Arrhythmogenic right ventricular cardiomyopathy with biventricular involvement and heart failure in a 9-year old girl.

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.

MUMPS MYOCARDITIS: A FORGOTTEN DISEASE?

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.

Anthracycline-induced cardiotoxicity: prospective cohort study from Pakistan.

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/m(2) 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.

Cardiac involvement in Kawasaki disease in Pakistani children.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Isolated non-compaction of left ventricular myocardium.

Isolated non-compaction of the left ventricle is a distinct form of cardiomyopathy. It may be idiopathic or secondary to an identifiable disease. The condition usually presents with symptoms of cardiac failure. The present report is of a child with this disease who was diagnosed at birth and was relatively stable at 5 years of age.

Blalock-Taussig shunt: experience from the developing world.

BACKGROUND: Palliative procedures have a role in congenital cardiac malformations that do not permit a complete early repair, and in centres where facilities for complete early repair do not exist. The lack of data on modified Blalock-Taussig shunt from developing countries prompted this analysis. METHODS: We report a retrospective study of 70 Blalock-Taussig shunt procedures in 63 patients over an 8-year period. Most of the procedures (54.0%) were done on children less than 4 months of age. Thirty-nine (58%) patients had Tetralogy of Fallot; the remaining patients had a wide spectrum of lesions. RESULTS: In the first year of the review period, the classical Blalock-Taussig shunt was done in six patients (9.5%) and the modified Blalock-Taussig shunt was used thereafter. In 49 patients who were followed up long term, clinical congestive cardiac failure developed in three (6%) and shunt failure was reported in 10 (14%). Of the 16 (33%) total deaths, six had serious comorbid conditions preoperatively. CONCLUSIONS: The Blalock-Taussig shunt is a relatively safe palliative procedure, requiring fewer resources and less expertise than corrective surgery, making it a suitable option in developing countries.