Chronic pain through COVID.

Objectives: To identify good practice in the community management of chronic pain, and to understand the perspective of a group of healthcare service users towards the management of chronic pain using technology during the COVID-19 pandemic. Methods: Forty-five people, recruited via social media and Pain Association Scotland, participated in three focus groups hosted over Zoom. Focus groups were conducted using semi-structured questions to guide the conversation. Data were analysed using Ritchie / Spencer's Framework Analysis. Results: The participants shared observations of their experiences of remotely supported chronic pain services and insights into the potential for future chronic pain care provision. Experiences were in the majority positive with some describing their rapid engagement with technology during the COVID pandemic. Conclusion: Results suggest there is strong potential for telehealth to complement and support existing provision of pain management services.

Cricopharyngeal achalasia associated with laryngomalacia as a cause of failure to thrive.

OBJECTIVE: To describe a case of concurrent cricopharyngeal achalasia with laryngomalacia as a cause of failure to thrive, and to review the literature and management options of cricopharyngeal achalasia in the paediatric population. METHODS: A chart review was performed on a four-month-old male, referred for failure to thrive, and diagnosed with cricopharyngeal achalasia and laryngomalacia. A PubMed and Embase search for 'cricopharyngeal achalasia' and 'laryngomalacia' was conducted. A review of reported paediatric cricopharyngeal achalasia patients, with emphasis on management options, was undertaken. RESULTS: A flexible laryngoscopic examination confirmed the laryngomalacia diagnosis, and videofluoroscopic evaluation of swallowing demonstrated cricopharyngeal achalasia via a cricopharyngeal bar. Supraglottoplasty was performed, with botulinum toxin injection into the cricopharyngeus muscle, with resultant improvement in oral intake and resolution of failure to thrive. The literature review revealed no reported case of the combined pathologies as a cause of failure to thrive. CONCLUSION: Functional endoscopic evaluation of swallowing and videofluoroscopic evaluation of swallowing are complimentary in the evaluation of paediatric patients with failure to thrive and suspected oropharyngeal dysphagia. Both supraglottoplasty and botulinum toxin injection are effective for definitive management in cases of combined pathology, and can be safely performed in a single surgical setting.

Fis1 deficiency selects for compensatory mutations responsible for cell death and growth control defects.

Genetic mutations affecting mitochondrial fission and fusion proteins cause human neurological disorders, but are assumed to be well tolerated in yeast. The conserved mitochondrial fission protein Dnm1/Drp1 is required for normal mitochondrial division, but also promotes cell death in mammals and yeast. Fis1, an outer mitochondrial membrane-anchored receptor for Dnm1/Drp1, also can promote cell death in mammals, but appears to have prosurvival activity in yeast. Here we report that deletion of the FIS1 gene in yeast consistently results in acquisition of a secondary mutation that confers sensitivity to cell death. In several independently derived FIS1 knockouts, tiling arrays and genomic sequencing identified the secondary mutation as a premature termination in the same stress-response gene, WHI2. The WHI2 mutation rescues the mitochondrial respiratory defect (petite formation) caused by FIS1 deficiency, but also causes a failure to suppress cell growth during amino-acid deprivation. Thus, loss of Fis1 drives the selection for specific compensatory mutations that confer defective growth control and cell death regulation, characteristic of human tumor cells. The important long-term survival function of Fis1 that is compensated by WHI2 mutation appears to be independent of fission factor Dnm1/Drp1 and its adaptor Mdv1, but may be mediated through a second adaptor Caf4, as WHI2 is also mutated in a CAF4 knockout.

Histological outcome of delayed orchidectomy after primary chemotherapy for metastatic germ cell tumour of the testis.

AIMS: To identify the incidence of viable local tumour in the testis of patients undergoing delayed orchidectomy after initial presentation with advanced germ cell tumour (GCT) treated by primary chemotherapy. PATIENTS AND METHODS: Thirty-three patients presenting with advanced metastatic GCT were reviewed. The median age at presentation was 34 years. All received chemotherapy without previous orchidectomy. The decision to initiate chemotherapy without orchidectomy was based on a heavy tumour load and the patient's condition at initial presentation. A histological diagnosis was available from a biopsy of metastases in 23 patients; treatment in the remaining 10 patients was initiated after diagnosis based on a combination of elevated serum tumour markers, testicular findings and the presence of a retroperitoneal mass. RESULTS: Seminomatous GCT (SGCT) was diagnosed in 13 patients, non-seminomatous GCT (NSGCT) in 17 patients and mixed GCT (MGCT) in the remaining three patients. Bleomycin/etoposide/cisplatin-based chemotherapy was the principle regimen. After initial chemotherapy, all patients with pure SGCT had only scar tissue in the orchidectomy specimen, with no residual tumour. Nine of 17 patients (52.9%) with NSGCT had viable tumour remaining in the orchidectomy specimen. All three cases of MGCT had persistent viable invasive seminoma. Twenty-seven patients (81.8%) were recurrence free and alive after a median of 49 months of follow-up. CONCLUSIONS: Thirty-six per cent of patients had residual tumour locally in the testis after primary chemotherapy for metastatic GCT of the testis. However, in the cases with pure seminomatous disease, there was no residual tumour present. It may not be necessary to undertake delayed orchidectomy in these patients.

Endovascular stent grafts for acute blunt aortic injury.

BACKGROUND: Endovascular stent grafting (EVSG) has emerged as a new treatment for aortic disease and has recently been applied to the treatment of acute blunt aortic injury (BAI). The purpose of this study was to determine the outcome of EVSG for patients with BAI at two tertiary (Level I) trauma centers. METHODS: A retrospective review of patients treated between January 1, 1999, and February 1, 2003, at two centers, Calgary Health Region (Calgary, Alberta) and Harborview Medical Center (Seattle, WA), with EVSG for acute BAI is reported. Variables assessed included age, sex, Injury Severity Score, total length of stay (LOS), intensive care unit LOS, operative technique, complications, technical success, mortality, and follow-up data. RESULTS: Twenty-eight patients treated with EVSG for BAI were identified during this period. Twelve patients were excluded because injuries occurred more than 30 days before grafting (n = 7) or under a different protocol (n = 4), or the procedure was performed in a different center (n = 1). Sixteen patients with acute BAI were reviewed. The mean Injury Severity Score was 36.9 (SD, 17.0), with a median intensive care unit LOS of 7.5 days (interquartile range, 1-17 days) and total LOS of 24.5 days (interquartile range, 7-41 days). Mean follow-up was 10.7 months (range, 3-30 months). Technical success was achieved in all patients, no graft-related complications have been detected during follow-up, and no patient developed postoperative paraplegia. One postoperative mortality occurred secondary to severe comorbid injury. A single patient with a preoperative traumatic carotid dissection demonstrated a postoperative stroke, and one patient required thoracentesis for a pleural effusion. CONCLUSION: Repair of BAI with EVSG can be performed safely in patients with BAI. Mortality, morbidity, and especially paraplegia are reduced. Further long-term studies are required to support the routine use of EVSG technology for BAI.

Bilateral choanal atresia associated with nasal dermoid cyst and sinus: a case report and review of the literature.

The relationship of choanal atresia to various systemic malformations is well acknowledged by the CHARGE acronym: colobomas, heart defects, atresia choanae, retarded growth and development, genito-urinary defects, and ear defects. In the past, we have reported the finding of an isolated skull base malformation associated with choanal atresia. We report here a unique case of choanal atresia associated with a patent foramen cecum and intracranial extension of a dermoid sinus. The embryogenesis of this condition is accounted for by the mesodermal flow theory of choanal atresia formation, and implies a need for thorough imaging of the anterior skull base in cases of bilateral atresia.

A practical approach to exposure assessment programs in the private sector: a partial validation study of a qualitative chemical exposure assessment model.

Utilizing a computer-based exposure assessment program, a United States-based chemical company was able to predict which chemicals and tasks presented the greatest probability of exposure in the workplace. The data generated by the model also enabled the company to prioritize these tasks for quantitative exposure monitoring. The assessment program addressed potential chemical exposure to workers in a cost-effective way. This assessment program reduced a facility's cost of complying with the Occupational Safety and Health Administration (OSHA) standard by about 90 percent. Overall, the program reduced the company's cost by about $700,000 when compared to traditional methods used for achieving compliance with these regulations. In addition, by utilizing a computer-based approach, a facility did streamline its chemical exposure assessment process. A comparative evaluation study was conducted in conjunction with a graduate research project. The purpose of the study was to compare the company's qualitative exposure assessment model with several other exposure assessment models. The project compared hazard rankings calculated from three exposure assessment models with actual exposure data for three work scenarios. Overall, the models appeared to be predictive of measured exposures. Therefore, they can be useful tools to help make decisions on which exposures have the highest potential to cause occupational illness to employees and therefore require additional monitoring and follow-up.

Protein microarrays for highly parallel detection and quantitation of specific proteins and antibodies in complex solutions.

BACKGROUND: We have developed and tested a method for printing protein microarrays and using these microarrays in a comparative fluorescence assay to measure the abundance of many specific proteins in complex solutions. A robotic device was used to print hundreds of specific antibody or antigen solutions in an array on the surface of derivatized microscope slides. Two complex protein samples, one serving as a standard for comparative quantitation, the other representing an experimental sample in which the protein quantities were to be measured, were labeled by covalent attachment of spectrally resolvable fluorescent dyes. RESULTS: Specific antibody-antigen interactions localized specific components of the complex mixtures to defined cognate spots in the array, where the relative intensity of the fluorescent signal representing the experimental sample and the reference standard provided a measure of each protein's abundance in the experimental sample. To test the specificity, sensitivity and accuracy of this assay, we analyzed the performance of 115 antibody/antigen pairs. 50% of the arrayed antigens and 20% of the arrayed antibodies provided specific and accurate measurements of their cognate ligands at or below concentrations of 0.34 microg/ml and 1.6 microg/ml, respectively. Some of the antibody/antigen pairs allowed detection of the cognate ligands at absolute concentrations below 1 ng/ml, and partial concentrations of 1 part in 106, sensitivities sufficient for measurement of many clinically important proteins in patient blood samples. CONCLUSIONS: These results suggest that protein microarrays can provide a practical means to characterize patterns of variation in hundreds of thousands of different proteins in clinical or research applications.

The development of functional response units: the role of demarcating stimuli.

An experiment with rats examined the roles of demarcating stimuli and differential reinforcement probability on the development of functional response units. It examined the development of units in a probabilistic, free-operant situation in which the presence of demarcating stimuli was manipulated. In all conditions, behavior became organized into two-response sequences framed by changes in local reinforcement probability. A tone demarcating the beginning and end of contingent response sequences facilitated the development of functional response units, as in chunking, but the same units developed slowly in the absence of the tone. Complex functional response units developed even though reinforcement contigencies remained constant. These findings demonstrate that models of operant learning must include a mechanism for changing the response unit as a function of reinforcement history. Markov models may seem to be a natural technique for modeling response sequences because of their ability to predict individual responses as a function of reinforcement history; however, no class of Markov chain can incorporate changing response units in their predictions.

Telomere maintenance by recombination in human cells.

Telomeres of eukaryotic chromosomes contain many tandem repeats of a G-rich sequence (for example, TTAGGG in vertebrates). In most normal human cells, telomeres shorten with each cell division, and it is proposed that this limits the number of times these cells can replicate. Telomeres may be maintained in germline cells, and in many immortalized cells and cancers, by the telomerase holoenzyme (first discovered in the ciliate Tetrahymena), which uses an RNA subunit as template for synthesis of telomeric DNA by the reverse transcriptase catalytic subunit. Some immortalized human cell lines and some tumours maintain their telomeres in the absence of any detectable telomerase activity by a mechanism referred to as alternative lengthening of telomeres (ALT). Here we show that DNA sequences are copied from telomere to telomere in an immortalized human ALT cell line, indicating that ALT occurs by means of homologous recombination and copy switching.

Intermediate-term results of the free tracheal autograft for long segment congenital tracheal stenosis.

BACKGROUND/PURPOSE: Since 1996 a new procedure--the free tracheal autograft--has been used to repair long segment congenital tracheal stenosis (LSCTS). The purpose of this report is to examine the intermediate-term results of that technique. METHODS: Between January 1996 and July 1999, 10 infants underwent repair of LSCTS using a free tracheal autograft. Age ranged from 10 days to 23 months (mean age, 6.6 months). Six infants had a pulmonary artery (PA) sling; 5 had intracardiac anomalies. On cardiopulmonary bypass (CPB) the trachea was incised anteriorly through the area of stenosis. The midportion of the stenotic trachea was excised, and an end-to-end anastomosis was made posteriorly. The excised tracheal segment was trimmed and sutured in place anteriorly as a free autograft. In 5 patients the autograft was not long enough, and the upper portion of the tracheal opening was patched with pericardium. RESULTS: There was 1 death 26 days postoperatively in a child that had simultaneous repair of tetralogy of Fallot and required extracorporeal membrane oxygenation postoperatively for cardiac failure. The other 9 children are alive and well at 2 to 44 months postoperatively (mean follow-up, 24 months). One child had autograft dehiscence and required replacement of the autograft with an aortic homograft. Two children have tracheostomies at 6 and 36 months postoperatively. All children have had serial postoperative bronchoscopic examinations. Most recent bronchoscopies have shown widely patent tracheal lumina in all survivors. CONCLUSION: Intermediate-term follow-up of children with a free tracheal autograft continues to support our use of this technique as our procedure of choice for infants with LSCTS.

Asymmetric leaves1 mediates leaf patterning and stem cell function in Arabidopsis.

Meristem function in plants requires both the maintenance of stem cells and the specification of founder cells from which lateral organs arise. Lateral organs are patterned along proximodistal, dorsoventral and mediolateral axes. Here we show that the Arabidopsis mutant asymmetric leaves1 (as1) disrupts this process. AS1 encodes a myb domain protein, closely related to PHANTASTICA in Antirrhinum and ROUGH SHEATH2 in maize, both of which negatively regulate knotted-class homeobox genes. AS1 negatively regulates the homeobox genes KNAT1 and KNAT2 and is, in turn, negatively regulated by the meristematic homeobox gene SHOOT MERISTEMLESS. This genetic pathway defines a mechanism for differentiating between stem cells and organ founder cells within the shoot apical meristem and demonstrates that genes expressed in organ primordia interact with meristematic genes to regulate shoot morphogenesis.

Variability of neuropsychological deficits associated with carbon monoxide poisoning: four case reports.

Carbon monoxide (CO) poisoning is associated with variable neuropsychological deficits, depending on levels of CO exposure and individual differences. Studies to date have reported variable findings, as their subjects have been exposed to different levels of CO from different poisoning sources. Four unique case studies are presented, all of whom experienced the same level of CO poisoning (17-29%) in the same accident. Two of the individuals were brothers with an identical genetic disorder (i.e. syndactylism) and the other two were brother/sister. The results indicated: (1) variable neuropsychological deficits despite similar levels of CO poisoning; (2) consistent estimated decline in intelligence; (3) similar memory decline for the two brothers, but not for the brother and sister; and (4) consistent late-onset emotional-behavioural difficulties. The results also suggested that the neuropsychological and emotional-behavioural deficits had an impact on the individual's ability to work.

Pulmonary artery sling: results with median sternotomy, cardiopulmonary bypass, and reimplantation.

BACKGROUND: The classic surgical approach to pulmonary artery (PA) sling has been through a left thoracotomy with division of the left PA and reimplantation into the main PA anterior to the trachea. Another approach is anterior left PA translocation with distal tracheal resection. Since 1985, we have repaired PA sling with a median sternotomy approach, cardiopulmonary bypass, and division and reimplantation of the left PA into the main PA with simultaneous repair of associated tracheal stenosis. The purpose of this review is to determine the outcome of that strategy. METHODS: From 1985 to 1998, 16 infants had surgical treatment of PA sling, 14 had left PA division and reimplantation into the MPA, 2 patients had repair using the translocation technique. Mean age at repair was 6.9 months, median age was 4 months. All infants, except 1 with an absent right lung, were operated on at the time of diagnosis. All had rigid bronchoscopy, which revealed associated complete tracheal rings in 12 patients. Seven patients had tracheal repair with pericardial tracheoplasty, 4 had repair using a tracheal autograft technique, and 2 had a distal tracheal resection (one for tracheomalacia). Of the 2 patients having the translocation technique, 1 had a severely hypoplastic right lung and the other had complete absence of the right lung. RESULTS: There has been no operative mortality. Hospital stay ranged from 5 to 188 days (mean 36 +/- 42 days). There was 1 late death 7 months postoperatively from respiratory complications of pericardial tracheoplasty. All left pulmonary arteries are patent and blood flow to the left lung by nuclear scan (n = 10) ranges from 24% to 46% (mean 35% +/- 9%). CONCLUSION: The strategy of median sternotomy, cardiopulmonary bypass, and left PA division and reimplantation into the main PA with simultaneous tracheal repair has resulted in a low operative mortality and excellent patency of the left pulmonary artery. Results with repair of the commonly associated complete tracheal rings has recently improved with the use of the free tracheal autograft technique.

Right aortic arch, right ligamentum, absent left pulmonary artery: a rare vascular ring.

A 5-month-old infant presented with respiratory failure secondary to severe right bronchial compression. Diagnostic imaging revealed a right aortic arch and absent left pulmonary artery. Surgical relief was obtained via median sternotomy by dividing a right ligamentum and pexing the enlarged right pulmonary artery to the ascending aorta.

The use of balloon-expandable metallic stents in the treatment of pediatric tracheomalacia and bronchomalacia.

OBJECTIVE: To evaluate the use of balloon-expandable metallic stents in the treatment of children with tracheomalacia and bronchomalacia in whom conventional therapy has failed. DESIGN: Retrospective case series. SETTING: Tertiary pediatric otolaryngology and cardiothoracic surgery referral center. PATIENTS: Six patients were identified as having undergone bronchoscopic placement of metallic balloon-expandable stents between 1994 and 1997. The age at stent placement, prior surgical interventions, and indications for and sites of stent placement were noted. Also, the complications related to stent placement and the current airway status of the patients were reviewed. INTERVENTIONS: Twelve balloon-expandable metallic angioplasty stents (Palmaz; Johnson & Johnson Interventional Systems Co, Warren, NJ) were placed bronchoscopically in 6 patients. Six stents were placed in the lower trachea, and 6 were placed in the main bronchi. The stents were balloon expanded under fluoroscopic guidance. MAIN OUTCOME MEASURE: Discontinuation of mechanical ventilation. RESULTS: The age at stent placement ranged from 1.5 to 38 months (mean age at placement, 10 months). The indications for stent placement were (1) tracheomalacia or bronchomalacia, (2) pericardial patch or slide tracheoplasty failure, and (3) bronchomalacia caused by tetralogy of Fallot and large pulmonary arteries. The primary complication of stent placement was postoperative granulation tissue formation. One patient required the removal of 2 tracheal stents because of granulation tissue formation. There were 2 deaths in the series, 1 possibly related to stent placement. Four of the 6 patients were weaned from mechanical ventilation, and 3 experienced prolonged relief of airway obstruction. CONCLUSIONS: Metallic balloon-expandable stents are effective in relieving lower tracheomalacia and bronchomalacia in select patients. Only patients in whom conventional therapy has failed should be considered for stent placement.

A bronchoscopic, computer-assisted examination of the changes in dimension of the infant tracheal lumen with changes in head position: implications for emergency airway management.

BACKGROUND: Resuscitation guidelines caution against extreme extension or flexion of an infant's head because tracheal obstruction may occur. No data support this recommendation. The authors therefore examined the dimensions of the tracheal lumen in neutral, extended, and flexed head positions in infants undergoing general endotracheal anesthesia for elective surgery. METHODS: Eighteen healthy full-term infants were studied. A flexible fiberoptic bronchoscope was passed through a previously inserted endotracheal tube and positioned above the cricoid cartilage. Video recordings were taken in each of three head positions. Recordings were analyzed by an investigator blinded to head position. A computer-digitized technique was used to measure anterior-posterior and lateral dimensions and cross-sectional area. Data were analyzed using paired t tests and sign tests. RESULTS: No significant differences in mean tracheal dimensions with changes in head position were found. No infant had complete tracheal obstruction. Infants were equally as likely to have a small increase as they were to have a small decrease in tracheal dimension with changes in head position. CONCLUSIONS: Despite the belief that infants and neonates have obstruction at the level of the trachea with extreme positions of the head, the authors were unable to demonstrate this phenomenon.

Repair of congenital tracheal stenosis with a free tracheal autograft.

OBJECTIVES: Evaluate the results of a technique for repair of congenital tracheal stenosis by use of a free tracheal autograft. METHODS: Between January 1996 and July 1997, six infants with congenital tracheal stenosis resulting from complete tracheal rings underwent repair with a free tracheal autograft. Mean age at the time of repair was 4.9 months; mean weight was 5.4 kg. The approach was through a median sternotomy with cardiopulmonary bypass for respiratory support. The trachea was incised anteriorly through the area of stenosis, the midportion of the stenotic trachea was excised, and an end-to-end anastomosis was carried out posteriorly. The excised tracheal segment (1.3 to 2.2 cm long) was used as a free autograft to patch the lower trachea anteriorly. In four infants the autograft was augmented in the upper trachea with pericardium; in two patients with a shorter length of stenosis, the autograft completed the repair. Simultaneous pulmonary artery sling repair (4), ligation and division of patent ductus arteriosus (3), cricoid split (2), atrial and ventricular septal defect repair (1), and complete atrioventricular canal repair (1) were performed at the time of tracheal repair. RESULTS: The infants were extubated and discharged at a mean of 13 and 23 days postoperatively, respectively. One infant had recurrent tracheal stenosis related to the pericardial patch and required a tracheal stent and tracheostomy 4 months postoperatively. Our mean follow-up is 11 months. Bronchoscopic findings currently show widely patent tracheal lumina in all infants. CONCLUSIONS: The technique of free tracheal autograft with and without pericardial augmentation was successful in opening the airway of six infants with congenital tracheal stenosis and is currently our procedure of choice for children with this diagnosis.

Human stanniocalcin (STC): genomic structure, chromosomal localization, and the presence of CAG trinucleotide repeats.

Stanniocalcin (STC) is a glycoprotein hormone that is secreted by the corpuscle of Stannius, an endocrine gland of bony fish. It prevents hypercalcemia via mechanisms including inhibition of calcium uptake across the gills. Mammalian homologues have recently been reported but their function is unknown. Here we report the genomic organization and the transcription start site of the human STC gene and the existence of a polymorphic CAG trinucleotide repeat complex within the 5' untranslated region (UTR) of the mRNA and a smaller [CAG]6 repeat in the 3' UTR. As CAG repeats are associated with various human diseases, we used dual-color fluorescence in situ hybridization to localize the STC gene near markers D8S131 and D8S339 on chromosome 8p11.2-p21. STC should be considered a candidate gene for hereditary diseases mapped to this region.