Physiological Sequelae Research Articles

Psychological Sequelae of Covid 19 Calamity on Medical Personnel in Pakistan

Aim: To gauge the physiological sequelae of covid-19 pandemic on medical personnel in Pakistan. Place & duration: An online cross sectional study was conducted from May, 2020 to August, 2020 in Lahore. Methodology: 17 score PTSD check list civilian version was used to assess the symptoms of post-traumatic stress disorder in medical personnel. Results: Mean post-traumatic stress score (PTSS) was 39±15 with a range of 18-89. 66% (n=240) of the participants experienced moderate to extreme stress level. Chi Square test was used to determine an association between higher stress level and age, gender and staff category. Higher stress scores were associated with females (p<0.01). Conclusion: Rewarding the health personnel with gratitude, acknowledgement, financial compensations and provision of personal protective equipments (PPEs) can halt the psychological sequelae and is a promise to win this battle. Keywords: SARS coV2, Covid 19, PTSD, Health personnel

Detection and diagnosis of large airway collapse: a systematic review.

Large airway collapse (LAC) is a frequently encountered clinical problem, caused by tracheobronchomalacia +/− excessive dynamic airway collapse, yet there are currently no universally accepted diagnostic criteria. We systematically reviewed studies reporting a diagnostic approach to LAC in healthy adults and patients, to compare diagnostic modalities and criteria used. Electronic databases were searched for relevant studies between 1989 and 2019. Studies that reported a diagnostic approach using computed tomography (CT), magnetic resonance imaging or flexible fibreoptic bronchoscopy were included. Random effects meta-analyses were performed to estimate the prevalence of LAC in healthy subjects and in patients with chronic obstructive airway diseases. We included 41 studies, describing 10 071 subjects (47% female) with a mean±sd age of 59±9 years. Most studies (n=35) reported CT findings, and only three studies reported bronchoscopic findings. The most reported diagnostic criterion was a ≥50% reduction in tracheal or main bronchi calibre at end-expiration on dynamic expiratory CT. Meta-analyses of relevant studies found that 17% (95% CI: 0–61%) of healthy subjects and 27% (95% CI: 11–46%) of patients with chronic airways disease were classified as having LAC, using this threshold. The most reported approach to diagnose LAC utilises CT diagnostics, and at a threshold used by most clinicians (i.e., ≥50%) may classify a considerable proportion of healthy individuals as being abnormal and having LAC in a quarter of patients with chronic airways disease. Future work should focus on establishing more precise diagnostic criteria for LAC, relating this to relevant physiological and disease sequelae.

Invivo glucose imaging in multiple model organisms with an engineered single-wavelength sensor.

Glucose is arguably the most important molecule in metabolism, and its dysregulation underlies diabetes. We describe a family of single-wavelength genetically encoded glucose sensors with a high signal-to-noise ratio, fast kinetics, and affinities varying over four orders of magnitude (1μM to 10mM). The sensors allow mechanistic characterization of glucose transporters expressed in cultured cells with high spatial and temporal resolution. Imaging of neuron/glia co-cultures revealed ∼3-fold faster glucose changes in astrocytes. In larval Drosophila central nervous system explants, intracellular neuronal glucose fluxes suggested a rostro-caudal transport pathway in the ventral nerve cord neuropil. In zebrafish, expected glucose-related physiological sequelae of insulin and epinephrine treatments were directly visualized. Additionally, spontaneous muscle twitches induced glucose uptake in muscle, and sensory and pharmacological perturbations produced large changes in the brain. These sensors will enable rapid, high-resolution imaging of glucose influx, efflux, and metabolism in behaving animals.

Respiratory Sequelae Following SARS, MERS, and COVID-19: A Systematic Review and Meta-Analysis of Pulmonary Function Tests and CT Features

Background: SARS-CoV-2 (COVID-19) follows SARS-CoV (severe acute respiratory syndrome; SARS) and MERS-CoV (middle east respiratory syndrome; MERS) epidemics in the 21st century. Over 150 million COVID-19 cases are confirmed worldwide, with biomedical research focused principally on treatment and transmission prevention strategies, including vaccination. However, it is increasingly apparent residual respiratory symptoms persist in some COVID-19 survivors. Methods: This systematic review (PROPSERO ID: CRD42020202643) aims to define respiratory physiological and thoracic radiological sequelae following SARS, MERS and COVID-19 infection (more than 28 days after initial infection and hospital discharge). 27,817 studies from searches were assessed against eligibility criteria determined a priori by two independent reviewers. Meta-analysis of pulmonary function test parameters (DerSimonian and Laird random effects model) and meta-analysis of occurrence (proportions) of radiological features (Freeman-Tukey transformation random effects model) during follow-up using STATA v16 was performed. Findings: Pulmonary function studies show that TLco recovery is incomplete at 10-12 months after SARS (84.46% predicted [79.50 – 89.42], I2 89.57%) and MERS infections (75.51% [56.96 – 94.06], I2 72.90%), and 3-4 months after COVID-19 infections (75.44% [57.63 – 93.26], I2 98.27%). FEV1, FVC and TLC parameters plateau at 5-6 months post SARS infection. Following infection with COVID-19 (at 3-4 months) and SARS (at 18 months), ground-glass opacities were present in 38% (6-77, I2 95.64%) and 21% (14-29) of patients, reticulation in 30% (0 – 81) and 17% (11-25) of patients and interstitial thickening in 27% (15 – 39) and 25% (17 - 34) of patients respectively. Occurrences of other CT features include traction dilatation, parenchymal banding and honeycombing. Interpretation: Patients experience persistent respiratory sequelae following infection with SARS and MERS respectively. Current evidence from the COVID-19 pandemic demonstrates similar persistent respiratory sequelae at 3-4 months. Further research is required to determine the pathology, natural history and management of respiratory sequelae after COVID-19. Funding Statement: There was no funding source for this study. Declaration of Interests: We declare no competing interests in relation to this study.

Abstract No. 163 Feasibility of pancreatic particle embolization: a proof of safety study in a porcine model

Although particle embolization is a common treatment of hypervascular neuroendocrine metastases of the liver, this treatment is not considered an option for the originating pancreatic neuroendocrine tumor(s) due to theoretical concern for pancreatitis. The purpose of this study was to explore the safety of pancreatic embolization in a porcine model. Approval for this study was obtained from the Institutional Animal Care and Use Committee. A total of 6 domestic swine weighing between 90 and 110 pounds were obtained. A single nonsurvival animal underwent infusion of methylene blue dye into the dorsal pancreatic artery using a microcatheter followed by particle embolization to stasis using 100-300 μm Embosphere particles to confirm technical feasibility. Immediate laparotomy confirmed blue staining of pancreatic parenchyma without evidence of non-target embolization. Five survival animals underwent baseline serum lipase level assay, and particle embolization of the dorsal pancreatic artery was performed under general anesthesia. Animals were observed postoperatively for one week with monitoring of behavior, activity, food intake, and observation for signs of pancreatitis. After one week, repeat serum lipase was obtained, the animals were euthanized, and their pancreata excised for gross pathologic analysis. Technical success with embolization was achieved in all study animals. In the five survival animals that were monitored after embolization, behavior, activity levels and food intake returned to baseline by postoperative day #1. All animals survived to 7 days without signs or symptoms of significant pain, systemic infection or decline. There was no significant change in serum lipase levels comparing pre-procedure to day 7, with average serum lipase levels of 56.8 U/L and 40.2 U/L, respectively. At necropsy, regions of lobular expansion and discoloration were identified in all pancreata that are compatible with inflammation. These findings suggest that particle embolization of the dorsal pancreatic artery in swine is technically feasible and results in adequate ischemia to cause inflammation of target pancreatic tissues, but without biochemical signs of pancreatitis, systemic sequelae, or mortality after one week of observation. Based on this early data, further evaluation of particle embolization of the pancreas in animal models may be justified to further clarify safety and physiologic sequelae.

Physical inactivity and health inequality during coronavirus: a novel opportunity or total lockdown?

Government-restricted movement during the coronavirus pandemic in various countries around the world has led to rapid and fundamental changes in our health behaviour. As well as being at a higher...

Evidence Limitations in Determining Sexually Dimorphic Outcomes in Pediatric Post-Traumatic Hypopituitarism and the Path Forward.

Neuroendocrine dysfunction can occur as a consequence of traumatic brain injury (TBI), and disruptions to the hypothalamic-pituitary axis can be especially consequential to children. The purpose of our review is to summarize current literature relevant to studying sex differences in pediatric post-traumatic hypopituitarism (PTHP). Our understanding of incidence, time course, and impact is constrained by studies which are primarily small, are disadvantaged by significant methodological challenges, and have investigated limited temporal windows. Because hormonal changes underpin the basis of growth and development, the timing of injury and PTHP testing with respect to pubertal stage gains particular importance. Reciprocal relationships among neuroendocrine function, TBI, adverse childhood events, and physiological, psychological and cognitive sequelae are underconsidered influencers of sexually dimorphic outcomes. In light of the tremendous heterogeneity in this body of literature, we conclude with the common path upon which we must collectively arrive in order to make progress in understanding PTHP.

Traumatic Brain Injury: Effect of Litigation Status on Executive Functioning—A Pilot Study

AbstractTraumatic brain injury (TBI) is associated with a wide range of physiological, behavioral, emotional, and cognitive sequelae. Litigation status is one of the many factors that has an impact on recovery. The aim of this study was to compare executive functions, postconcussion, and depressive symptoms in TBI patients with and without litigation. A sample of 30 patients with TBI, 15 patients with litigation (medicolegal case [MLC]), and 15 without litigation (non-MLC) was assessed. The tools used were sociodemographic and clinical proforma, executive function tests, Rivermead Post-Concussion Symptom Questionnaire, and Beck Depression Inventory. Assessment revealed that more than 50% of patients showed deficits in category fluency, set shifting, and concept formation. The MLC group showed significant impairment on verbal working memory in comparison to the non-MLC group. The performance of both groups was comparable on tests of semantic fluency, visuospatial working memory, concept formation, set shifting, planning, and response inhibition. The MLC group showed more verbal working memory deficits in the absence of significant postconcussion and depressive symptoms on self-report measures.

Maternal activity restriction to reduce preterm birth: Time to put this fallacy to bed.

Activity restriction has traditionally been recommended to pregnant women, especially high-risk patients, to reduce preterm birth. However, there is no scientific evidence that bed-rest reduces preterm birth and, in many studies, women on bed-rest had higher rates of delivering preterm. Bed-rest in pregnancy is associated with significant physiological and psychosocial sequelae and reduced neonatal birth weight and be cannot be endorsed, even in women with a short cervix. The practice of prescribing bed-rest in pregnancy is outdated and should be abandoned.

Sexual function and dysfunction among women with anorexia nervosa: A systematic scoping review

Research suggests that a variety of biological and psychosocial factors are associated with the sexual health of women diagnosed with anorexia nervosa (AN). This systematic scoping review, conducted in accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines, synthesizes the current literature concerning sexual function and dysfunction in women with AN. We searched PubMed, EMBASE, and PsychInfo for literature published until April 2020. All study designs were eligible for inclusion, providing they focused on sexual function and dysfunction in women with AN. Studies that only included outcomes related to gender identity or sexual orientation were excluded. N = 28 studies met criteria for inclusion in the review. All studies were conducted in Western countries and the majority employed either a cohort or cross-sectional design. Although measures of sexual function and dysfunction varied markedly across studies, most studies adopted a biopsychosocial framework. Libido may be linked to body mass index (BMI), while other aspects of sexual functioning and behavior might not be specifically associated with weight status. Limited data are available on evidence-based interventions. Sexual dysfunction in women with AN is common. Although some of the variance is explained by low BMI, associated physiological sequelae and other psychosocial factors are also involved. Sexual dysfunction is a relevant clinical problem and clinicians should sensitively incorporate questions related to sexual function into their eating disorder assessments. Future research, using more robust designs and validated outcome measures, is needed to better understand causal pathways between the biological and psychosocial correlates of AN and sexual dysfunction. Identifying predictors of sexual function and dysfunction in more diverse groups of people with AN will support the development of evidence-based therapies.

Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) for Use in Temporizing Intra-Abdominal and Pelvic Hemorrhage: Physiologic Sequelae and Considerations.

REBOA has been used for several years by acute care surgeons for temporization of intra-abdominal, pelvic, and junctional hemorrhage. The physiology and consequences of aortic occlusion in these patients are largely unstudied.

Epidemiological and Clinico-radiological Evaluation of Head Injury in Pediatric Population.

ABSTRACTBackground:Head injury in infancy and childhood has been documented as the single most common cause of death. In India, children aged <15 years constitute 35% of the total population and contribute to 20–30% of all head injuries. In this study, we attempted to analyze the epidemiological factors, management, and outcome of traumatic brain injury (TBI). The objective of this study were to find the causes of head injury in children and its pattern of distribution in this population and to analyze the efforts required to prevent the injury and management focusing on limiting the progression of primary brain injury and minimizing secondary brain insult.Results:A total of 2714 patients with head injury were admitted at our hospital during the study period and, out of them, 508 (18.17%) were pediatric patients with age less than 18 years. Of the 508 patients, only 497 patients were included in this study. In the present study, 357 (71.83%) were males and 140 (28.16%) were females. In total, 351 cases were managed conservatively whereas surgical intervention was conducted in 146 cases (P < 0.001). In this study, the most common mode of injury was a road traffic accident (RTA) (46.88%; n=233), followed by fall from height (34.8%; n=173) (P < 0.001). It was also seen that epidural hematoma and fracture hematoma were the most common computed tomography findings in pediatric patients with head injury followed by parenchymal contusion or contusion with or without fracture followed by diffuse axonal injury. A total of 344 cases out of 497 cases were discharged with Glasgow outcome score (GOS)-5 whereas nine cases remained in a persistent vegetative state (GOS-2).Conclusion:Early intervention aimed at the primary lesion in TBI in children generally carries a good outcome, and limits as much as possible the ongoing biomechanical, physiological, and pathological sequelae post-TBI. In teenagers, the importance of proper self-care along with adequate safety gears while doing any TBI-prone activity should be emphasized.

Vascular Changes in the Retina and Choroid of Patients With EPAS1 Gain-of-Function Mutation Syndrome

Patients with the EPAS1 gain-of-function mutation syndrome (or Pacak-Zhuang syndrome) present with multiple paragangliomas or pheochromocytomas, duodenal somatostatinoma, polycythemia, headaches, and sometimes diminished visual acuity at an early age. The characteristic phenotype and known genetic cause of the syndrome provide an opportunity to study the role of hypoxia-inducible factor 2α (HIF-2α) in oxygen sensing, development in regions of physiologic hypoxia, and other pathological processes. To describe the ocular lesions in EPAS1 gain-of-function mutation syndrome and to establish whether early-onset diminished visual acuity is developmental or associated with long-term physiologic sequelae of the syndrome. This clinical case series with a transgenic murine model study was conducted from July 2013 to June 2019. Participants were 3 patients referred by their primary care physicians to the National Institutes of Health for evaluation of recurrent and metastatic paragangliomas or pheochromocytomas accompanied by polycythemia. The syndrome and somatic mosaicism in patients were confirmed by the identification of gain-of-function mutations in the EPAS1 gene in resected tumors and other tissues. Ocular findings in patients with EPAS1 gain-of-function mutation syndrome. A total of 3 patients (mean [SD] age, 29 [6.2] years) with confirmed ocular abnormalities were included in the study. Increased contrast accumulation at the posterior aspect of the globe was seen bilaterally on magnetic resonance imaging scans in all patients. Ophthalmoscopy images demonstrated fibrosis overlying the optic disc, tortuous and dilated retinal vessels, and retinal pigment epithelium changes. Optic disc edema and retinal exudates were also seen. Fluorescein angiography images showed leakage of dye from postcapillary venules surrounding the optic disc and highlighted aberrant retinal vascular patterns. Enhanced-depth imaging optical coherence tomography images showed substantial thickening of the choroid and dilation of choroidal vessels. The ocular features of the syndrome were confirmed with a transgenic model of mice with gain-of-function Epas1A529V mutation. In this case series, HIF-2α and hypoxia signaling was found to have a role in vessel development within the choroid and retina, indicating that the marked permanent choroidal thickening and tortuous and dilated veins seen in the choroid and retina in patients with EPAS1 gain-of-function mutation syndrome were suggestive of the persistence of venous elements within the developing mesenchyme. These findings may explain other eye and vascular abnormalities whose pathogenesis remains unclear.

Challenges in Clinical Management of Radiation-Induced Illnesses During Exploration Spaceflight.

INTRODUCTION: Analysis of historical solar particle events (SPEs) provides context for some understanding of acute radiation exposure risk to astronauts who will travel outside of low-Earth orbit. Predicted levels of radiation exposures to exploration crewmembers could produce some health impacts, including nausea, emesis, and fatigue, though more severe clinical manifestations are unlikely. Using current models of anticipated physiological sequelae, we evaluated the clinical challenges of managing radiation-related clinical concerns during exploration spaceflight.METHODS: A literature review was conducted to identify terrestrial management standards for radiation-induced illnesses, focusing on prodromal symptom treatment. Terrestrial management was compared to current spaceflight medical capabilities to identify gaps and highlight challenges involved in expanding capabilities for future exploration spaceflight.RESULTS: Current spaceflight medical resources, such as those found on the International Space Station, may be sufficient to manage some aspects of radiation-induced illness, although effective treatment of all potential manifestations would require substantial expansion of capabilities. Terrestrial adjunctive therapies or more experimental treatments are unavailable in current spaceflight medical capabilities but may have a role in future management of acute radiation exposure.DISCUSSION: Expanded medical capabilities for managing radiation-induced illnesses could be included onboard future exploration vehicles. However, this would require substantial research, time, and funding to reach flight readiness, and vehicle limitations may restrict such capabilities for exploration missions. The benefits of including expanded capabilities should be weighed against the likelihood of significant radiation exposure and extensive mission design constraints.Blue RS, Chancellor JC, Suresh R, Carnell LS, Reyes DP, Nowadly CD, Antonsen EL. Challenges in clinical management of radiation-induced illnesses during exploration spaceflight. Aerosp Med Hum Perform. 2019; 90(11):966-977.

A systematic review on the use of the emotion thermometer in individuals diagnosed with cancer.

Physiological and psychological sequelae are frequent after a cancer diagnosis and also on the long term. Screening could help detect psychological distress early and thus enable timely provision of adequate treatment. The emotion thermometer (ET) is a validated screening tool including five dimensions (distress, anxiety, depression, anger, and need-for-help). Reviewing the literature, we aimed to describe (a) the validity and (b) the application of the ET. Six databases were systematically searched for studies using the ET in individuals diagnosed with cancer. Included studies were critically appraised for methodological quality. ET validity and application were narratively synthesized. We identified 580 records eligible for title-abstract screening. Seventeen studies based on 13 different populations were included. Validation studies (5 of 17) concluded that the ET is sensitive to distress detection, delivering prompt and accurate results with no negative impact on clinic visit time. Furthermore, its use is accepted in patients and clinicians. The remaining 12 exploratory studies applied the ET for screening purposes (3 of 12), as outcome measure (6 of 12), or as predictor variable measure (3 of 12). Most studies were conducted in Europe (11 of 17), and 7 of the 12 exploratory studies used the recommended cutoff (greater than or equal to 4). Study populations were mostly female (9 of 13) with a mean age greater than 50 years (12 of 13) at study. Publications on distress screening with the ET are scarce, especially among young populations. However, research and studies' recommendations support the ET's utility as a valid and feasible tool for distress screening including anxiety and depression and suggest its implementation as part of a structured program for early screening in cancer care.

Congenital Oral Masses: An Anatomic Approach to Diagnosis.

Although congenital oral masses are rare, they are readily detectable during fetal US screening. Most congenital oral masses are benign, but some may cause mechanical airway obstruction, resulting in poor outcomes at delivery. The radiologist's ability to describe these abnormalities and their physiologic sequelae accurately can have a substantial effect on perinatal treatment. Furthermore, despite being rare, congenital oral lesions encountered at screening and at follow up fetal MRI provide the opportunity to make a specific diagnosis by following a simple anatomic approach. This article describes an anatomic algorithm as the framework for accurate diagnosis of congenital oral lesions. The imaging appearance of the most common congenital oral cavity neoplasms is outlined, including vascular anomalies, epulides, choristomas, congenital lingual thyroid anomalies, lingual hamartomas, and epignathi, and other conditions that mimic these at US. Also reviewed are perinatal management of masses that affect the fetal airway and the imaging features key to optimizing delivery outcomes. Online supplemental material is available for this article. ©RSNA, 2019.

Human Brain Region-Specific Alternative Splicing of TRPC3, the Type 3 Canonical Transient Receptor Potential Non-Selective Cation Channel.

Canonical transient receptor potential (TRPC) non-selective cation channels are broadly expressed by neurons, glia and the microvasculature of the brain. In neurons and astrocytes, these ion channels are coupled to group I metabotropic glutamate receptors via Gαq-phospholipase C signal transduction. In the mouse cerebellar Purkinje neurons, TRPC channels assembled as tetramers of TRPC3 subunits exclusively mediate this glutamatergic signalling mechanism and regulation of alternative splicing results in dominance of a high Ca2+ conducting TRPC3c isoform. This regional control of TRPC3 transcript type likely has physiological and pathophysiological sequelae. The current study provides a quantitative comparison of the TRPC3c splice variant and the TRPC3b full-length isoform expression across seven regions of the human brain. This shows that the cerebellum has the highest expression level of both isoforms and that regulation of alternative splicing results in a higher propensity of the TRPC3c isoform in the cerebellum relative to the TRPC3b isoform (in a 1:3 ratio). This compares with the other regions (motor cortex, hippocampus, midbrain subregions, pons and medulla) where the prevalence of TRPC3c relative to TRPC3b is typically less than half as abundant. The finding here of a bias in the high-conductance TRPC3c isoform in the cerebellum is consistent with the enhanced vulnerability of the cerebellum to ischaemic injury.

Adult Survivorship: Considerations Following CAR T-Cell Therapy.

Significant improvement in overall survival observed in patients on clinical trials and U.S. Food and Drug Administration approval of two chimeric antigen receptor (CAR) T-cell therapies have resulted in an increasing population of survivors who have undergone this therapy. Although adult survivors may experience similar physiologic and psychosocial sequelae to traditional cancer therapies, unique late effects and considerations are related to CAR T-cell therapy. This article reviews survivorship considerations, with particular attention paid to the physical, psychosocial, and financial effects for adults who have undergone CAR T-cell therapy. A review of the physiologic and psychosocial sequelae resulting from CAR T-cell therapy is presented, with a focus on late effects and financial toxicities of treatment. Physiologic concerns include B-cell aplasia and resulting hypogammaglobulinemia, as well as prolonged cytopenias and associated risk for infection. To date, adult CAR T-cell therapy survivorship data are limited. However, data from clinical trials suggest expected late effects from treatment. As this survivor population grows, research can identify physiologic and psychosocial needs unique to adult survivors and evaluate evidence-based interventions.

Pediatric Survivorship: Considerations Following CAR T-Cell Therapy.

This article presents an overview of pediatric relapsed and refractory acute lymphoblastic leukemia (ALL) and chimeric antigen receptor (CAR) T-cell therapy in pediatric patients. Acute and chronic post-CAR T-cell effects and considerations are discussed, along with survivorship considerations. A case study illustrates the identification and management of physiologic and psychosocial sequelae. B-cell aplasia, hypogammaglobulinemia, infections, and cumulative effects of CAR T-cell therapy and other treatments are a concern in the pediatric population. Unique to pediatric and young adult survivors of childbearing potential are implications for post-treatment fertility. Financial toxicities and psychosocial needs require a family-centered approach to interventions that address the impact of CAR T-cell therapy not only on the patient, but also on caregivers and siblings.

Sexuality and Menopause: Unique Issues in Gynecologic Cancer.

To provide current evidence on treatment- and disease-related sexual health concerns of women with gynecologic cancers. Literature from 2006-2017 from MEDLINE, and PubMed databases. There are both physiologic and psychosocial sexual health sequelae among women treated for gynecologic cancer, including induced menopause. The management of symptoms requires communication between provider and patient because the effects can be long lasting and directly affect the patient's quality of life. Assessment of and communication about potential sexual health changes should begin at the time of diagnosis of gynecologic malignancies and continue through survivorship.