Outcomes and Long-Term Survival of Adolescent and Young Adult Patients Admitted to the Intensive Care Unit Following Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Experience of 152 Patients.

BACKGROUND AND OBJECTIVES: Prognostic factors reliably predicting outcomes for critically ill adolescent and young adult (AYA) patients undergoing allogeneic hematopoietic cell transplantation (allo-HSCT) are lacking. We assessed transplant and intensive care unit (ICU)-related factors impacting patient outcomes. PATIENTS AND METHODS: AYA patients who underwent allo-HSCT and required ICU admission at a Tertiary care Centre, during the period of 2003-2013, were included in this retrospective review. This was a non-interventional study. Only outcomes after the first allo-HSCT and index ICU admissions were analyzed. Disease-, transplant-, and ICU-related variables were analyzed to identify risk factors predictive of survival. RESULTS: Overall, 152 patients were included (males, 60.5%); median age at transplantation was 24 years (interquartile range [IQR] 18-32.5); median age at admission to the ICU was 25.8 years (IQR 19-34). Eighty-four percent underwent transplantation for a hematological malignancy; 129 (85%) received myeloablative conditioning. Seventy-one percent of ICU admissions occurred within the first year after allo-HSCT. ICU admission was primarily due to respiratory failure (47.3%) and sepsis (43.4%). One hundred and three patients (68%) died within 28 days of ICU admission. The 1- and 5-year overall survival rates were 19% and 17%, respectively. Main causes for ICU-related death were refractory septic shock with multiorgan failure (n = 49, 32%) and acute respiratory distress syndrome (ARDS) (n = 39, 26%). Univariate analysis showed that ICU mortality was associated with an Acute Physiology and Chronic Health Evaluation (APACHE) II score >20, a sequential organ failure assessment (SOFA score) > 12, a high lactate level, anemia, thrombocytopenia, leukopenia, hyperbilirubinemia, a high international normalized ratio (INR) and acute graft-versus-host disease (GVHD). Multivariate analysis identified thrombocytopenia, high INR, and acute GVHD as independent predictors of mortality. CONCLUSIONS: In AYA allo-HSCT patients admitted to the ICU, mortality remains high. Higher SOFA and APACHE scores, the need for organ support, thrombocytopenia, coagulopathy, and acute GVHD predict poor outcomes.

Impact of Hyperuricemia and Urate-Lowering Agents on Cardiovascular Diseases.

The association between hyperuricemia and cardiovascular diseases has been studied for many years. Research has shown a link between high uric acid levels and increased risk of including coronary artery disease hypertension and other cardiovascular conditions. Urate-lowering therapy, particularly with xanthine oxidase inhibitors like allopurinol, has shown promising results in reducing blood pressure in individuals with hyperuricemia and hypertension. Clinical trials and studies have demonstrated significant reductions in both systolic and diastolic blood pressure with urate-lowering treatment. Urate-lowering treatment has shown a favorable effect on reducing systolic blood pressure and major adverse cardiovascular events in patients with previous cardiovascular disease. In terms of cardiovascular safety, clinical trials have indicated that xanthine oxidase inhibitors such as febuxostat are non-inferior to allopurinol and do not increase the risk of death or serious adverse events. Overall, these findings highlight the importance of managing hyperuricemia and utilizing urate-lowering therapy to mitigate the adverse cardiovascular effects associated with elevated uric acid levels.

Crochetage, the Forgotten Electrocardiographic Sign.

Acquired complete heart block is a rare but severe arrhythmia caused by various factors such as infections, medications, and autoimmune conditions. Atrial septal defect (ASD) is a common congenital heart defect, with larger ASDs possibly causing symptoms such as fatigue, shortness of breath, and frequent respiratory infections. In some cases, high-grade atrioventricular block with ASD can occur; however, the exact incidence is not well established. We report a rare case of a 15-year-old male presenting with acute dizziness. Initial electrocardiogram (EKG) showed a complete heart block with a Crochetage sign. Patent foramen ovale (PFO) was confirmed by transthoracic and transesophageal echocardiograms. Closure of PFO and permanent pacemaker resulted in complete resolutions of symptoms and disappearance of Crochetage sign.

Role of genetic polymorphisms in clopidogrel response variability: a systematic review.

INTRODUCTION: Clopidogrel is a P2Y12 inhibitor that has become a mainstay treatment following percutaneous intervention with drug-eluting stent placement to decrease restenosis and its potential complications, including sudden cardiac death and ischaemic strokes in patients with significant vascular disease. AREAS COVERED: As a prodrug, the metabolism and efficacy of clopidogrel are contingent on the presence of wild-type CYP450 (CYP2C19) alleles. Genetic polymorphisms and variants are well known to impair its ability to prevent major adverse cardiovascular events in these patients, with inadequate response rates as high as 30% in previous publications. Patterns of allelic frequencies are expected to exhibit similarities between individuals of the same ancestry, ethnic group or geographic region. Accordingly, we seek to further elucidate worldwide prevalence rates for genetic polymorphisms in the CYP2C19-dependent metabolism of clopidogrel and review the potential of personalised CYP2C19 genotyping in clinical practice to mitigate this high treatment resistance and its associated burden on patients. EXPERTS' COMMENTARY: Our findings support the consideration of genotyping before initiation of therapy to guide adequate dosage or substitutions of other P2Y12 inhibitors to promote personalised, precision medicine and to prevent adverse events when these therapies may inevitably fail in patients with variants of the CYP450 (CYP2C19) system.

Effect of dietary supplementation of betaine and organic minerals on growth performance, serum biochemical parameters, nutrients digestibility, and growth-related genes in broilers under heat stress.

Global warming and climate changes have a detrimental impact on poultry production, causing substantial economic losses. This study investigated the effects of incorporating dietary betaine (BT) and organic minerals (OMs) on broilers' performance as well as their potential to mitigate the negative impacts of heat stress (HS). Six hundred 1-day-old Ross 308 chicks were randomly allocated to 12 experimental treatments with 5 replicates of 10 birds each (5 male + 5 female). The birds were provided with diets containing BT (0 and 2,000 ppm) and OMs (0, 250, and 500 ppm), either individually or in combination, under both thermoneutral and HS-inducing temperatures. The HS conditions involved exposing the birds to cyclic periods of elevated temperature (35°C ± 2°C) for 6 h daily, from 10:00 am to 4:00 pm, starting from d 10 and continuing until d 35. The exposure to HS deteriorated birds' growth performance; however, dietary BT and OMs inclusion improved the growth performance parameters bringing them close to normal levels. Carcass traits were not affected by dietary supplementation of BT, OMs, HS, or their interaction. Interestingly, while HS led to increased (P < 0.05) levels of total cholesterol, LDL-cholesterol, and hepatic malondialdehyde (MDA), these adverse effects were mitigated (P < 0.05) by the addition of BT and OMs. Moreover, dietary BT supplementation led to elevated serum total protein and globulin concentrations. Cyclic HS did not alter Mn, Zn, and Cu contents in the pectoral muscle. However, the incorporation of OMs at both levels increased concentrations of these minerals. Notably, the combination of 500 ppm OMs and 2,000 ppm BT improved Mn, Zn, Cu, and Fe digestibility, which has been compromised under HS conditions. Cyclic HS upregulated gene expression of interleukin-1ß, heat shock protein 70, and Toll-like receptor-4 while downregulated the expression of claudin-1, uncoupling protein, growth hormone receptor, superoxide dismutase 1, glutathione peroxidase 1 and insulin-like growth factor 1. The aforementioned gene expressions were reversed by the combination of higher dietary levels of BT and OMs. In conclusion, the dietary supplementation of 500 ppm OMs along with 2,000 ppm BT yielded significant improvements in growth performance and mineral digestibility among broiler chickens, regardless of thermal conditions. Moreover, this combination effectively restored the expression of growth-related genes even under heat-stress conditions.

COVID-19-Induced Cardiac Tamponade: A Case Study and a Literature Review.

COVID-19 presentation is heterogeneous. As a viral illness, it could cause pericardial effusion leading to cardiac tamponade. We present a patient coursing with this viral illness that was found to have cardiac tamponade. We report a case of a 79-year-old female who presented with shortness of breath and dry cough for one week and resulted positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Her initial chest X-ray showed a bottle-shaped heart. Computed chest tomography showed pericardial effusion, and an echocardiogram confirmed moderated pericardial effusion with signs of tamponade. He improved with conservative therapy with colchicine, ibuprofen, cefepime, dexamethasone, dolutegravir, and apixaban for pulmonary emboli. An early approach in cardiac tamponade induced by COVID-19 is crucial to promptly address an aggressive directed therapy, avoiding potential complications or unnecessary procedures.

Rice husk coated with copper oxide nanoparticles for 17α-ethinylestradiol removal from an aqueous solution: adsorption mechanisms and kinetics.

The 17 α-ethinylestradiol (EE2) adsorption from aqueous solution was examined using a novel adsorbent made from rice husk powder coated with CuO nanoparticles (CRH). Advanced analyses of FTIR, XRD, SEM, and EDSwere used to identify the classification parameters of a CRH-like surface morphology, configuration, and functional groups. The rice husk was coated with CuO nanoparticles, allowing it to create large surface area materials with significantly improved textural qualities with regard to functional use and adsorption performance, according to a detailed characterization of the synthesized materials. The adsorption process was applied successfully with elimination effectiveness of 100% which can be kept up to 61.3%. The parameters of adsorption were affecting the adsorption process significantly. Thermodynamic data stated that the process of adsorption was endothermic, spontaneous, chemisorption and the molecules of EE2 show affinity with the CRH. It was discovered that the adsorption process controlled by a pseudo-second-order kinetic model demonstrates that the chemisorption process was controlling EE2 removal. The Sips model is regarded as optimal for representing this practice, exhibiting a significantly high determination coefficient of 0.948. This coefficient implies that the adsorption mechanism indicates the occurrence of both heterogeneous and homogeneous adsorption. According to the findings, biomass can serve as a cheap, operative sorbent to remove estrogen from liquified solutions.

Novel Therapies for Celiac Disease: A Clinical Review Article.

Celiac disease is emerging as an autoimmune disorder with increasing prevalence and incidence. The mean age of presentation is also increasing with the passage of time. The delay in diagnosis is partly attributable to the asymptomatic state in which most patients present. The diagnosis of the disease is primarily based on biopsy, but serology can also be included for possible screening purposes. Although the primary management strategy is to eliminate gluten from the diet of such patients; however, compliance with the diet and follow-up to detect healing might be difficult to maintain. Therefore, there is a need to investigate further management therapies that can be easily administered and monitored. The aim of the review is to discuss the epidemiology, clinical presentation, and novel therapies being investigated for celiac disease.

Small Bowel Enteritis and Myocardial Depression Complicating Organophosphorus Poison in a Patient With Sleeve Gastrectomy and Intestinal Bypass Surgeries: An Atypical Presentation.

Organophosphate (OP) is a pesticide that has been used in agriculture and domestic pest control since the mid-1900s. Acute OP toxicity is caused by inhibiting the acetylcholinesterase (AChE) enzyme, resulting in a cholinergic surge. It is treated with atropine and pralidoxime. Our case is a patient with a past history of sleeve gastrectomy and intestinal bypass surgery presented after oral OP intake. He initially had small bowel enteritis, followed by lactic acidosis, acute renal injury, and distributive shock. The serum troponin had peaked 50-folds. The echocardiography showed myocardial depression and global hypokinesia with no significant wall motion abnormalities. In contrast to classic bradycardia with OP poisoning, our patient developed persistent sinus tachycardia on the second day. He had a concomitant alcohol withdrawal syndrome, which was managed with intravenous (IV) hydration and benzodiazepines. He had a dramatic improvement on the third day with near resolution of creatinine and lactic acid. The outpatient cardiac follow-up showed partial resolution of the left ventricular ejection fraction (EF) to 48%. In this literature, we discuss the complications and long-term effects of bariatric surgeries, particularly on gastric emptying and medication absorption. We also discuss OP mechanism of action, clinical presentation, therapeutic lines, and atypical presentations in the prior literatures.

COVID-19 therapy and vaccination: a clinical narrative review.

The SARS-CoV-2 pandemic is the most globally impacting health issue our world has faced over the last century. As of January 7, 2022, around 300 million cases have been reported worldwide, with over 5 million deaths. The SARS-CoV-2 infection causes a hyperactive host immune response leading to an excessive inflammatory reaction with the release of many cytokines - cytokine storm - commonly noticed in acute respiratory distress syndrome, sepsis and fulminant multiorgan failure. Since the beginning of the pandemic, the scientific medical community has worked on therapeutic procedures that interfere with the exaggerated immune response. Thromboembolic complications are widespread in patients who are critically ill with COVID-19. Anticoagulant therapy was initially considered a cornerstone in hospitalized patients and even in the early post-discharge period; however, later trials have aborted the clinical benefits except for suspicion of or confirmed thrombosis. Immunomodulatory therapies are still crucial in moderate to severe COVID-19. Immunomodulator therapies include various medications from steroids to hydroxychloroquine, tocilizumab and Anakinra. Anti-inflammatory agents, vitamin supplements and antimicrobial therapy had initial encouraging evidence, but there are limited data to review. Convalescent plasma, immunoglobulins, eculizumab, neutralizing IgG1 monoclonal antibodies and remdesivir have positively impacted inpatient mortality and hospital length of stay. Eventually, wide population vaccination was proven to be the best tool to overcome the SARS-CoV-2 pandemic and help humanity return to regular life. Many vaccines and various strategies have been used since December 2020. This review discusses how the SARS-CoV-2 pandemic has progressed and surged, and summarizes the safety and efficacy of the most used therapies and vaccines in the light of recent evidence.

Pre-workout Induced Demand Ischemia.

Pre-workout supplement use has increased in recent years. Multiple side effects and off-labeled substances have been reported. We report a case of a 35-year-old patient who recently started a pre-workout and was found to have sinus tachycardia, elevated troponin, and subclinical hyperthyroidism. The echocardiogram showed normal ejection fraction and no wall motion abnormality. Beta-blockade therapy with propranolol was offered, but she refused, and her symptoms and troponin levels improved after proper hydration within 36 hours. A cautious and accurate assessment of young, fitness-enthusiastic patients experiencing unusual chest pain is essential to identify a reversible cardiac injury and possible off-label substances in over-the-counter supplements.

Role of Fecal Microbiota Transplantation in Managing Clostridium Difficile Infection and Inflammatory Bowel Disease: A Narrative Review.

Fecal microbiota transplantation (FMT) has been emerging as an alternate treatment modality in the management of patients with dysbiosis by restoring abnormal gut microbiota composition through the transplantation of normal fecal microbiota from healthy donors. This technique has lately gained a lot of attention in the treatment of recurrent or refractory Clostridium difficile infection (CDI) owing to its high success rates combined with its favorable safety profile. FMT has also been attracting the interest of clinicians as a new treatment option for inflammatory bowel diseases (IBD). Here, we reviewed most of the recent advancements in the use of FMT for CDI as well as its use in the treatment of IBD.

Bovine Aortic Arch, A High-Risk Variant.

The bovine aortic arch is a vascular variant related to an increased incidence of vascular and neurological complications. It should be ruled out in patients with vague neurological symptoms without a clear etiology. Our case is of a 72-year-old female patient who presented with a syncopal episode; the workup incidentally showed the aortic arch bovine variant with evidence of ischemic white matter disease more than expected for age. After reviewing the related literature, we suggest that this aortic variant is likely an independent risk factor for multiple vascular complications. A close follow-up is essential, and screening should be considered for symptomatic family members.

Anomalous Origin of the Right Coronary Artery: An Uncommon Presentation.

The anomalous origin of the coronary artery is a relatively uncommon condition with a variant incidence depending on the modality of the imaging techniques such as transesophageal echocardiography (TEE), computed tomography angiography (CTA), magnetic resonance angiography (MRA), or invasive coronary angiography (ICA). The importance of diagnosing ectopic coronary artery origin comes from its possible relation to sudden cardiac death (SCD) cases in young populations. The anomalous origin of the coronary artery could cause myocardial ischemia and fibrosis; this would, in turn, increase the chances of fatal ventricular arrhythmias. In this report, we present a 40-year-old male, incidentally found to have persistent tachycardia and a gradually decreasing left ventricular ejection fraction (LVEF). He denied any symptoms or changes in his baseline, unlimited, functional capacity. However, his records were remarkable for persistent tachycardia over more than six months, raising concerns about tachyarrhythmia-induced cardiomyopathy related to his anatomical variations. We also discussed the guideline-directed therapeutic option for the abnormal origin of the coronary artery as per current guidelines.

Thapsigargin: key to new host-directed coronavirus antivirals?

Despite the great success of vaccines that protect against RNA virus infections, and the development and clinical use of a limited number of RNA virus-specific drugs, there is still an urgent need for new classes of antiviral drugs against circulating or emerging RNA viruses. To date, it has proved difficult to efficiently suppress RNA virus replication by targeting host cell functions, and there are no approved drugs of this type. This opinion article discusses the recent discovery of a pronounced and sustained antiviral activity of the plant-derived natural compound thapsigargin against enveloped RNA viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Middle East respiratory syndrome coronavirus (MERS-CoV), and influenza A virus. Based on its mechanisms of action, thapsigargin represents a new prototype of compounds with multimodal host-directed antiviral activity.

Impact of COVID-19 on the Gastrointestinal Tract: A Clinical Review.

Coronavirus disease 2019 (COVID-19) has spread rapidly throughout the world, causing a pandemic that has resulted in more than 5 million deaths globally. The gastrointestinal (GI) tract is known to have high expression of angiotensin-converting enzyme 2 (ACE2) receptors in the human body, making it prone to direct damage from the cellular invasion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Numerous GI symptoms have been reported among patients with COVID-19. This systemic review details the mechanism and effects of COVID-19 on the GI tract along with the hepatobiliary and pancreatic systems.

National Diagnostic Reference Levels for Nuclear Medicine in Kuwait.

The diagnostic reference level (DRL) is a patient-exposure optimization tool used to evaluate and provide guidance for radiation doses in medical imaging. In the past few decades, there has been a global increase in the number of diagnostic imaging procedures, including nuclear medicine procedures, and consequently in patient radiation exposure. This increase has encouraged international and national health-care organizations to take action and keep up with such changes to meet the expectation of increasing use of ionizing radiation in medicine. Methods: DRLs in Kuwait were established by investigating the administered activity of radiopharmaceuticals and CT radiation doses in hybrid imaging systems. The DRLs were determined on the basis of the 75th percentile of radiopharmaceutical administered activity distribution as recommended by the International Commission on Radiological Protection. Results: The DRLs determined in Kuwait agree well with other published DRLs in Europe, Japan, Korea, Australia, and the United States. Conclusion: This study presents the establishment process and the results of the first national DRLs for nuclear medicine procedures in Kuwait as a way to optimize radiation exposure.

Multi-level inhibition of coronavirus replication by chemical ER stress.

Coronaviruses (CoVs) are important human pathogens for which no specific treatment is available. Here, we provide evidence that pharmacological reprogramming of ER stress pathways can be exploited to suppress CoV replication. The ER stress inducer thapsigargin efficiently inhibits coronavirus (HCoV-229E, MERS-CoV, SARS-CoV-2) replication in different cell types including primary differentiated human bronchial epithelial cells, (partially) reverses the virus-induced translational shut-down, improves viability of infected cells and counteracts the CoV-mediated downregulation of IRE1α and the ER chaperone BiP. Proteome-wide analyses revealed specific pathways, protein networks and components that likely mediate the thapsigargin-induced antiviral state, including essential (HERPUD1) or novel (UBA6 and ZNF622) factors of ER quality control, and ER-associated protein degradation complexes. Additionally, thapsigargin blocks the CoV-induced selective autophagic flux involving p62/SQSTM1. The data show that thapsigargin hits several central mechanisms required for CoV replication, suggesting that this compound (or derivatives thereof) may be developed into broad-spectrum anti-CoV drugs.

How HIV-1 Integrase Associates with Human Mitochondrial Lysyl-tRNA Synthetase.

Replication of human immunodeficiency virus type 1 (HIV-1) requires the packaging of tRNALys,3 from the host cell into the new viral particles. The GagPol viral polyprotein precursor associates with mitochondrial lysyl-tRNA synthetase (mLysRS) in a complex with tRNALys, an essential step to initiate reverse transcription in the virions. The C-terminal integrase moiety of GagPol is essential for its association with mLysRS. We show that integrases from HIV-1 and HIV-2 bind mLysRS with the same efficiency. In this work, we have undertaken to probe the three-dimensional (3D) architecture of the complex of integrase with mLysRS. We first established that the C-terminal domain (CTD) of integrase is the major interacting domain with mLysRS. Using the pBpa-photo crosslinking approach, inter-protein cross-links were observed involving amino acid residues located at the surface of the catalytic domain of mLysRS and of the CTD of integrase. In parallel, using molecular docking simulation, a single structural model of complex was found to outscore other alternative conformations. Consistent with crosslinking experiments, this structural model was further probed experimentally. Five compensatory mutations in the two partners were successfully designed which supports the validity of the model. The complex highlights that binding of integrase could stabilize the tRNALys:mLysRS interaction.