Steroid-responsive anemia with bony dysplasias: What lurks behind!

Ghosal hematodiaphyseal dysplasia (GHDD) is an autosomal recessive disorder characterized by diaphyseal dysplasia of long bones, bone marrow fibrosis, and steroid-responsive anemia. Patients with this disease have a mutation in the thromboxane-AS1 (TBXAS1) gene located on chromosome 7q33.34. They present with short stature, varying grades of myelofibrosis, and, hence cytopenias. Patients with the above presentation were evaluated through clinical presentation, X-ray of long bones, bone marrow examinations, and confirmed by genetic testing. In this article, we present two cases: The first case is a 3-year-old boy who presented with progressive pallor and ecchymotic patches for a year. On investigation, he had bicytopenia and bone marrow fibrosis. His anemia was steroid responsive and was finally diagnosed as GHDD. The second case is a 20-month-old girl who presented with blood in stools, developmental delay, anemia, and increased intensity of long bones on X-ray. Since other investigations were normal, suspicion of GHDD was raised, and a genetic workup was conducted which suggested mutation in TBXAS1 gene, confirming the diagnosis of GHDD. Children with refractory anemia and cortical thickening on skeletogram should always be evaluated for dysplasias. Timely treatment with steroids reduces transfusion requirements and halts bone damage, thus leading to better growth and improved quality of life.

Nonclinical Safety Signals in PharmaPendium Improve the Predictability of Human Drug-Induced Liver Injury.

Drug-induced liver injury (DILI) is a leading cause of candidate attrition during drug development in the pharmaceutical industry. This study evaluated liver toxicity signals for 249 approved drugs (114 of "most-DILI concern" and 135 of "no-DILI concern") using PharmaPendium and assessed the association between nonclinical and clinical injuries using contingency table analysis. All animal liver findings were combined into eight toxicity categories based on nature and severity. Together, these analyses revealed that cholestasis [odds ratio (OR): 5.02; 95% confidence interval (CI) 1.04-24.03] or liver aminotransferase increases (OR: 1.86; 95% CI 1.09-3.09) in rats and steatosis (OR-1.9; 95% CI 1.03-3.49) or liver aminotransferase increases (OR-2.57; 95% CI 1.4-4.7) in dogs were significant predictors of human liver injury. The predictive value further improved when the liver injury categories were combined into less severe (steatosis, cholestasis, liver aminotransferase increase, hyperbilirubinemia, or jaundice) and more-severe (liver necrosis, acute liver failure, or hepatotoxicity) injuries. In particular, less-severe liver injuries in the following pairs of species predicted human hepatotoxicity {[dog and mouse] (OR: 2.70; 95% CI 1.25-5.84), [dog and rat] (OR-2.61; 95% CI 1.48-4.59), [monkey and mouse] (OR-4.22; 95% CI 1.33-13.32), and [monkey and rat] (OR-2.45; 95% CI 1.15-5.21)} were predictive of human hepatotoxicity. Meanwhile, severe liver injuries in both [dog and rat] (OR-1.9; 95% CI 1.04-3.49) were significant predictors of human liver toxicity. Therefore, we concluded that the occurrence of DILI in humans is highly likely if liver injuries are observed in one rodent and one nonrodent species and that liver aminotransferase increases in dogs and rats can predict DILI in humans. Together, these findings indicate that the liver safety signals observed in animal toxicity studies indicate potential DILI risk in humans and could therefore be used to prioritize small molecules with less potential to cause DILI in humans.

Inadvertent Placement of Thoracic Epidural Catheter in Pleural Cavity: A Case Report and Review of Published Literature.

Thoracic epidural placement is considered the gold standard for pain management for abdominal or thoracic surgery. It provides analgesia superior to that provided by opioids with a decreased risk of pulmonary complications. Insertion of a thoracic epidural catheter requires the knowledge and expertise of an anesthetist; epidural catheter insertion may be challenging especially when sited in the higher thoracic region, in patients with unusual neuraxial anatomy, patients unable to position adequately for insertion or morbidly obese patients. Postoperatively the anesthetic team is required to look after the patient and assess for any complications such as hypotension. Even though the incidence of complications may be low; however, some of these could have detrimental consequences for the patients such as epidural abscess, hematoma formation, and temporary or permanent neurological damage. In this case report, we will discuss a patient who underwent a three-stage esophagectomy for esophageal squamous cell carcinoma under general anesthesia with epidural analgesia. The epidural catheter (Portex® Epidural Minipack System with NRFit® connector, ICUmedical, USA) was found in the intrapleural space during video-assisted thoracoscopy for the thoracic part of esophagectomy. To facilitate surgical access, the catheter was removed immediately, and the patient was given patient-controlled analgesia with morphine for postoperative pain control.

Adverse Childhood Experiences in Autistic Children and Their Caregivers: Examining Intergenerational Continuity.

Although there is an urgent need to develop trauma-informed services for autistic youth, little research has evaluated adverse childhood experiences (ACEs) in autistic youth from an intergenerational perspective. 242 caregivers of autistic (n = 117) and non-autistic (n = 125) youth reported on ACEs that they experienced in their own childhoods and ACEs experienced by their children, as well as measures of depression, stress, and child autistic traits and behavioral concerns. Autistic youth and their caregivers both experienced significantly higher rates of ACEs than the non-autistic dyads. Intergenerational continuity, the association between caregiver and child ACEs, was significantly stronger for autistic youth. ACEs showed differential patterns of associations with parent depressive symptoms and child autistic traits across groups.

A Mental Health Survey of Medical Professionals Working During the COVID-19 Pandemic at Shaukat Khanum Cancer Hospital, Lahore.

Introduction The last months of 2019 saw the emergence of a novel coronavirus, SARS-COV-2, capable of causing widespread disease in humans. The rapid spread of this new disease culminated in one of the biggest pandemics in known history. The far-reaching social, economical, and health effects of this pandemic are still unfolding on a global scale. Given the interconnectedness of social, environmental, and biological factors in manifesting psychiatric illnesses, it is fair to assume that the profound effects of this pandemic would likely increase the strain on mental healthcare systems.  The objective of this study was to assess the mental health burden amongst healthcare workers at Shaukat Khanum Memorial Cancer Hospital and Research Center (SKMCH & RC) at the start of the COVID-19 pandemic and to identify any differences in the mental health scores of anxiety, depression, and sleep disturbance for professionals directly involved in the care of COVID-19 patients as compared to those who were not. Material and methods This was an observational cross-sectional clinical study that used self-reported questionnaires after approval from the hospital's ethical board. The sample size was calculated based on a study published previously by Huang using a 23.04% incidence of anxiety in medical staff. Depression was quantified using the Patient Health Questionnaire-9 score (PHQ-9), anxiety by the Beck Anxiety Inventory, and sleep quality using the Pittsburgh Sleep Quality Index checklist (PSQI). A total of 221 healthcare workers who completed the questionnaires were included in the study and the results were analyzed using SPSS Statistics v. 23 (IBM Corp., Armonk, NY). Levene's test was used to assess the equality of variances, and an independent sample t-test and chi-square test were applied for the comparison of means. A one-way ANOVA test was used to compare means across more than two groups. Results Of the 221 healthcare workers recruited in the study, 57% were males, and 43% were females. Among the sample, 43% of participants were doctors, 27.1% were nurses, and others were technicians and medical assistants. It was observed that 50% of males and 36% of female healthcare workers experienced moderate to severe depression at the onset of the pandemic. Furthermore, 35% of males and 25% of females suffered from moderate to severe anxiety, and more than 80% of our study population reported poor quality of sleep. Conclusion The present study reported a high prevalence of anxiety levels, depressive symptoms, and poor sleep quality among the healthcare professionals working in SKMCH & RC Lahore during the COVID-19 pandemic irrespective of direct contact with COVID-19 patients in a healthcare setting.

Assessment of Informed Consent and the Impact of Simulation on Anesthesia Trainees.

Introduction Over the years, the process of obtaining informed consent has evolved and now places an emphasis on the concept that patients should play a major role in medical decision making. Failure to adequately involve patients in making decisions regarding their health can lead to medicolegal consequences. Therefore, taking informed consent is a fundamental component of anaesthesia training. Simulation, for training, is an excellent tool that is being utilised widely in the training of medical professionals. The use of simulated training for teaching the process of informed consent is an innovative initiative that can provide improved results. Material and methods After approval from the institutional review board, a prospective clinical study was conducted at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, from August 2019 to September 2020. Sixteen anaesthesia trainees were randomly selected for the study. The study was divided into pre-interventional, interventional and post interventional phases. For data collection, a predesigned checklist was used. Data collected was analysed using SPSS version 23 (IBM Inc., Armonk, New York). The McNemar test was deployed to assess the difference between the baseline assessment and post-simulated training assessment; p-value < 0.05 was taken to be significant. Results Of the 16 participants, the majority were males (n= 13). A positive impact was observed in terms of improvement of the outcome of the following study components i.e., description of benefits of the procedure (p=0.01), disclosure of associated minor risks (p=0.005), disclosure of major risks (p=0.01), discussion of alternatives (p=0.001), teach back (p=0.001), documentation of patients' verbal agreement (p=0.01), and communication skills involving utilising the process of connecting, introduction, communication, permission, response, and exit (p = 0.01). Conclusion Simulated training had a positive impact in improving outcomes in the following study components: description of benefits of the procedure, disclosure of associated risks, discussion of alternatives, teach back, documentation of patients' verbal agreement, and utilisation of the process of connecting, introduction, communication, permission, responding, and exiting.