Mindfulness in the emergency department (MED): An asynchronous learning course to practise mindfulness and resilience in the emergency room of low resource setting

Owing to the fast-paced, stressful, and frequent crucial rapid decisions that trigger cognitive exhaustion, emergency physicians are especially vulnerable to burnout. Mindfulness practices have been defined in the literature and it focuses on the well-being and resilience. Mindfulness is characterised as the ability to use tools and expertise to mentally respond to environmental problems to fulfil psychological needs. To overcome burnout, a self-directed learning course was developed for emergency physicians that will include learning goals on mindfulness, peer group discussions and tasks, role playing and practising meditation exercises. It would concentrate on the foundations of mindfulness and resilience, learning and incorporating mindfulness, understanding the coping mechanisms and establishing a pathway to minimise anxiety and depression

The utility of early warning score in adults presenting with sepsis in the emergency department of a low resource setting

Background: Sepsis is a condition with high mortality and morbidity. Delay in early recognition and prompt management results in higher mortality. There are many clinical scores to identify early sepsis; however, Early Warning Score (EWS) has clinical/physiological parameters that are easy to apply in the ED for timely diagnosis and management. In the present study, we collected information regarding the utilization of EWS in timely identifying the sick patients at triage of a tertiary care center.Methods: This study was a descriptive cross-sectional investigation conducted in the ED of Aga Khan University Hospital in Karachi, the largest metropolitan city in Pakistan. A total of 240 participants were selected by non-probability convenient sampling after fulfilling the inclusion criteria. Data collected included EWS criteria, demography, length of hospital stay, patient disposition (ward, intensive care or high dependency area), and differentials like sepsis, severe sepsis or septic shock.Results: A total of 240 patients were enrolled, out of which 139 (57.9%) patients were male, and 101 (42.1%) were female with a mean age of 52.7 ± 15.3 years (range: 18 to 80 years). In this study, the length of stay (LOS) was 2.2 ± 1.1 (range: one to six days), and there was an EWS of 8.2 ± 2.6 (4-15). There were 143 patients in the elderly age group \u3e 50 years (59.6%); however, most elderly presented with sepsis among both age groups. The least affected age group was aged 16 to 30 years, with 23 (9.6%) cases. An EWS \u3e7 is best to detect cases with sepsis or severe sepsis with a sensitivity of 98.5% (95% CI: 92.13 to 99.92) and specificity of 89.57% (95% CI: 82.64 to 93.93). Similarly, the EWS for severe sepsis or septic shock was \u3e9 with a sensitivity of 86.76% (95% CI: 76.72 to 92.88) and specificity of 88.24% (95% CI: 78.47 to 93.92).Conclusions: This study revealed that the sensitivity and specificity of EWS for the detection of sepsis, severe sepsis and septic shock was found to be high; hence, it could be a valuable and readily useable system for early diagnosis and proper management of sepsis, severe sepsis, and septic shock

Management of penetrating brain injury

Penetrating brain injury (PBI), though less prevalent than closed head trauma, carries a worse prognosis. The publication of Guidelines for the Management of Penetrating Brain Injury in 2001, attempted to standardize the management of PBI. This paper provides a precise and updated account of the medical and surgical management of these unique injuries which still present a significant challenge to practicing neurosurgeons worldwide. The management algorithms presented in this document are based on Guidelines for the Management of Penetrating Brain Injury and the recommendations are from literature published after 2001. Optimum management of PBI requires adequate comprehension of mechanism and pathophysiology of injury. Based on current evidence, we recommend computed tomography scanning as the neuroradiologic modality of choice for PBI Patients. Cerebral angiography is recommended in Patients with PBI, where there is a high suspicion of vascular injury. It is still debatable whether craniectomy or craniotomy is the best approach in PBI Patients. The recent trend is toward a less aggressive debridement of deep-seated bone and missile fragments and a more aggressive antibiotic prophylaxis in an effort to improve outcomes. Cerebrospinal fluid (CSF) leaks are common in PBI Patients and surgical correction is recommended for those which do not close spontaneously or are refractory to CSF diversion through a ventricular or lumbar drain. The risk of post-traumatic epilepsy after PBI is high, and therefore, the use of prophylactic anticonvulsants is recommended. Advanced age, suicide attempts, associated coagulopathy, Glasgow coma scale score of 3 with bilaterally fixed and dilated pupils, and high initial intracranial pressure have been correlated with worse outcomes in PBI Patients

Role of Pneumococcal NanA Neuraminidase Activity in Peripheral Blood

The most frequent form of hemolytic-uremic syndrome (HUS) is associated with infections caused by Shiga-like toxin-producing Enterohaemorrhagic Escherichia coli (STEC). In rarer cases HUS can be triggered by Streptococcus pneumoniae. While production of Shiga-like toxins explains STEC-HUS, the mechanisms of pneumococcal HUS are less well known. S. pneumoniae produces neuraminidases with activity against cell surface sialic acids that are critical for factor H-mediated complement regulation on cells and platelets. The aim of this study was to find out whether S. pneumoniae neuraminidase NanA could trigger complement activation and hemolysis in whole blood. We studied clinical S. pneumoniae isolates and two laboratory strains, a wild-type strain expressing NanA, and a NanA deletion mutant for their ability to remove sialic acids from various human cells and platelets. Red blood cell lysis and activation of complement was measured ex vivo by incubating whole blood with bacterial culture supernatants. We show here that NanA expressing S. pneumoniae strains and isolates are able to remove sialic acids from cells, and platelets. Removal of sialic acids by NanA increased complement activity in whole blood, while absence of NanA blocked complement triggering and hemolytic activity indicating that removal of sialic acids by NanA could potentially trigger pHUS.Peer reviewe

Streptococcus pneumoniae pneumolysin and neuraminidase A convert high-density lipoproteins into pro-atherogenic particles

High-density lipoproteins (HDLs) are a group of different subpopulations of sialylated particles that have an essential role in the reverse cholesterol transport (RCT) pathway. Importantly, changes in the protein and lipid composition of HDLsmay lead to the formation of particles with reduced atheroprotective properties. Here, we show that Streptococcus pneumoniae pneumolysin (PLY) and neuraminidase A (NanA) impair HDL function by causing chemical and structural modifications of HDLs. The proteomic, lipidomic, cellular, and biochemical analysis revealed that PLY and NanA induce significant changes in sialic acid, protein, and lipid compositions of HDL. The modified HDL particles have reduced cholesterol acceptor potential from activated macrophages, elevated levels of malondialdehyde adducts, and show significantly increased complement activating capacity. These results suggest that accumulation of these modified HDL particles in the arterial intima may present a trigger for complement activation, inflammatory response, and thereby promote atherogenic disease progression.Peer reviewe

The Karachi intracranial stenosis study (KISS) Protocol: an urban multicenter case-control investigation reporting the clinical, radiologic and biochemical associations of intracranial stenosis in Pakistan.

Background: Intracranial stenosis is the most common cause of stroke among Asians. It has a poor prognosis with a high rate of recurrence. No effective medical or surgical treatment modality has been developed for the treatment of stroke due to intracranial stenosis. We aim to identify risk factors and biomarkers for intracranial stenosis and to develop techniques such as use of transcranial doppler to help diagnose intracranial stenosis in a cost-effective manner. Methods/Design: The Karachi Intracranial Stenosis Study (KISS) is a prospective, observational, case-control study to describe the clinical features and determine the risk factors of patients with stroke due to intracranial stenosis and compare them to those with stroke due to other etiologies as well as to unaffected individuals. We plan to recruit 200 patients with stroke due to intracranial stenosis and two control groups each of 150 matched individuals. The first set of controls will include patients with ischemic stroke that is due to other atherosclerotic mechanisms specifically lacunar and cardioembolic strokes. The second group will consist of stroke free individuals. Standardized interviews will be conducted to determine demographic, medical, social, and behavioral variables along with baseline medications. Mandatory procedures for inclusion in the study are clinical confirmation of stroke by a healthcare professional within 72 hours of onset, 12 lead electrocardiogram, and neuroimaging. In addition, lipid profile, serum glucose, creatinine and HbA1C will be measured in all participants. Ancillary tests will include carotid ultrasound, transcranial doppler and magnetic resonance or computed tomography angiogram to rule out concurrent carotid disease. Echocardiogram and other additional investigations will be performed at these centers at the discretion of the regional physicians. Discussion: The results of this study will help inform locally relevant clinical guidelines and effective public health and individual interventions

Expression of eukaryotic and archaeal protein conducting channels

Cotransin is a cyclodepsipeptide inhibitor of protein translocation and has been demonstrated to inhibit cotranslational translocation of a variety of proteins by targeting the mammalian ER translocation channel Sec61 (Besemer, Harant et al. 2005, Garrison, Kunkel et al. 2005). Genetic screens in cancer cells found out the mutations near the luminal plug domain of Sec61 confer resistance to cotransin inhibition and thus outline the proposed binding site for cotransin (MacKinnon, Paavilainen et al. 2014). However molecular details of cotransin interactions remain unknown. Purpose of my first project was to express the human Sec61 translocation channel in correct stoichiometric ratios. To our knowledge, heterotrimeric expression of Sec61 has not been achieved previously. Baculovirus system was chosen express the Sec61 heterotrimeric complex. To vary expression levels of Sec61α and Sec61γ relative to Sec61β, separate baculovirus constructs were prepared. Proper co-transfection ratios between these viruses to express Sec61subunits in correct stoichiometric ratios were calculated during my pro gradu and insect cell expression was then scaled up using the determined virus ratios. Results from Sec61 expression have returned sufficient quantities of the translocation channel for biochemical analyses. Final expression seems to contain high lipid/protein ratio, which may have been caused due to insect cells not-fully adapted to the media. The expression should be repeated in well-adapted healthy insect cells and then accessed for protein quality. For its isolation for crystallization studies, co-immunoprecipitation may be a preferred way to pull down the Sec61 complex. Detergent based solubilization may be alternatively used to isolate Sec61. The second part of my pro gradu work included expression of SecYEβ translocation channel from Pyrococcus furiosus, along with its various humanized mutants, whose DNA constructs had been provided by Dr. Ville Paavilainen. A major goal of this work was to express the mutants which bind to cotransin. Via photo-crosslinking and click chemistry analyses, a mutant binding to cotransin was identified and scaled-up. Our photo-crosslinking studies were able to demonstrate that the wild-type SecYEβ does not bind to cotransin in vitro. Results from photo-crosslinking assays during this project also demonstrated that other known translocation inhibitors Mycolactone and Apratoxin A can bind to mammalian Sec61 channel. These results are consistent with unpublished work from Paavilainen lab (Paatero et al)

Unusual trajectory of a bullet from the shoulder to the brain: an emergency department perspective on finding a missing bullet

Terminal ballistics continues to struggle with bullet trajectory reconstruction and interpretation. This is a case of a young man presented with a very unusual trajectory of a bullet from the left shoulder to the brain parenchyma. The single wound and altered mentation prompted a CT head and neck scan, which revealed a retained bullet in the brain parenchyma, traversing from the left shoulder, across the neck and into the brain without causing significant damage to vital organs. We managed the patient conservatively. Emergency physicians dealing with gunshot injuries should thoroughly search for the bullet in cases where only a single wound is present and the bullet is missing, and they should have a basic understanding of the ballistics to understand the mechanism and injury pattern sustained by the bullet. This atypical ballistic trajectory scenario emphasises the need to exercise vigilance in accurately predicting the trajectory when the ballistic route is unknown

Chlorine gas hazardous material incident in Karachi, Pakistan: A clinical experience from an emergency department of a tertiary care hospital

Objective: To determine the clinical characteristics, management and outcomes of patients presenting with chlorine gas exposure in an emergency setting. Methods: The single-centre, retrospective cross-sectional study was conducted at the emergency department of Aga Khan University Hospital, Karachi, and comprised data of all patients who presented on March 06, 2020, due to acute chlorine gas exposure after a specific industrial accident. Demographic and clinical data was recorded from the medical record files. The association between risk factors and complications was explored. Data was analysed using SPSS 20. Results: There were 51 male patients with a mean age of 33.10±8.37 years. The most commonly affected organ system was respiratory 49(96%), with 43(84.3) having shortness of breath. Eye irritation was found in 44(86.3%) cases and the central nervous system was involved in 14(27.4%). Most of the patients were admitted from the emergency department 36(70%). Regarding treatment, 1(1.9%) patient each required invasive and non-invasive mechanical ventilation. Complications included toxic pneumonitis 3(5.9%) and pneumomediastinum 1(1.7%). No correlation was found between smoking and complications (p\u3e0.05). Conclusions: Most patients showed complete resolution of symptoms after receiving supportive treatment, while complications were rare and there was no mortalit

Predictors of abnormal electroencephalogram and neuroimaging in children presenting to the emergency department with new-onset afebrile seizures

Background: Electroencephalogram and neuroimaging in pediatric patients with new-onset afebrile seizures are performed to detect any underlying pathological severe condition that may require emergent neuro-intervention and guide prognosis. This study aims to determine the predictors of abnormal EEG and neuroimaging in children presenting to the emergency department with new-onset afebrile seizures. Methods: This single-center cross-sectional study was conducted at a tertiary care hospital in Karachi, Pakistan, from July 01, 2019, to June 30, 2021. All patients aged one month to 18 years who presented with new-onset afebrile seizures were included. Demographic and clinical data were recorded, including age, gender, seizure type, duration of seizure, associated signs and symptoms, and disposition. Multivariable regression analysis was applied to determine the predictors of abnormal EEG and CT scan or MRI findings. Results: Out of 201 participants, most patients were in the infantile age group (41.3%), with an equal gender distribution. The most common type of seizure was generalized onset 152 (75.6%). EEG was performed on a total of 126 patients (62.7%) and out of these patients, 67 patients (53.1%) had abnormal findings. In a multivariable analysis, the age group of 5 to 10 years and seizure duration of more than 5 min were significantly associated with higher odds of abnormal EEG findings. In contrast, only the focal onset of seizure was significantly associated with higher odds of abnormal neuroimaging findings. Conclusion: The study emphasizes the need for a protocol regarding the performance of EEG and neuroimaging in children presenting to the ED with new-onset afebrile seizures that would aid emergency physicians in the direction of appropriate management, thus ensuring a better quality of patient care and outcome