Familial congenital laryngotracheal stenosis: A systematic review.

BACKGROUND: Congenital laryngotracheal stenosis (CLS) is a rare cause of stridor among newborns. Evidence has shown that several family members can be affected by CLS. Knowledge of the pathophysiology of familial congenital laryngotracheal stenosis (FCLS) will enable more effective therapeutic strategies. OBJECTIVE: To determine the clinical course and outcome of familial congenital laryngotracheal stenosis (FCLS). METHODS: A literature search was conducted over a period of one month (September 2023) by searching several databases to identify studies published from inception to 31st August 2023. RESULTS: Of 256 papers identified, five articles met the inclusion criteria. A total of 17 patients with slight female predominance (59 %) were identified. Familial congenital tracheal stenosis was reported in female twins (100 %). A variety of clinical presentations were listed. An endoscopic airway study was performed on all patients. 64.8 % of the included children were managed surgically. Genetic studies performed on 41 % of children could not locate genetic abnormalities. CONCLUSION: Consanguinity, twin births, and female gender could be predisposing factors for FCLS, although the quality of evidence is low due to the rarity of the condition.

Scalable and Consolidated Microbial Platform for Rare Earth Element Leaching and Recovery from Waste Sources.

Chemical methods for the extraction and refinement of technologically critical rare earth elements (REEs) are energy-intensive, hazardous, and environmentally destructive. Current biobased extraction systems rely on extremophilic organisms and generate many of the same detrimental effects as chemical methodologies. The mesophilic methylotrophic bacterium Methylobacterium extorquens AM1 was previously shown to grow using electronic waste by naturally acquiring REEs to power methanol metabolism. Here we show that growth using electronic waste as a sole REE source is scalable up to 10 L with consistent metal yields without the use of harsh acids or high temperatures. The addition of organic acids increases REE leaching in a nonspecific manner. REE-specific bioleaching can be engineered through the overproduction of REE-binding ligands (called lanthanophores) and pyrroloquinoline quinone. REE bioaccumulation increases with the leachate concentration and is highly specific. REEs are stored intracellularly in polyphosphate granules, and genetic engineering to eliminate exopolyphosphatase activity increases metal accumulation, confirming the link between phosphate metabolism and biological REE use. Finally, we report the innate ability of M. extorquens to grow using other complex REE sources, including pulverized smartphones, demonstrating the flexibility and potential for use as a recovery platform for these critical metals.

The incidence of juvenile onset recurrent respiratory papillomatosis at Starship Children's Hospital before and after a national HPV vaccination programme: a retrospective review.

AIM: To review and compare the incidence of juvenile onset recurrent respiratory papillomatosis (JRRP) at Starship Children's Hospital (SSH) before and after the introduction of a national HPV vaccination programme. METHODS: Patients treated for JRRP at SSH were identified retrospectively using ICD-10 code D14.1 over a 14-year period. The incidence of JRRP in the 10-year period prior to the introduction of HPV vaccination (1 September 1998 to 31 August 2008) was compared with the incidence after its introduction. A second comparison was made between the pre-vaccination incidence with the incidence over the most recent 6 years when the vaccination became more widely available. All New Zealand hospital ORL departments that referred children with JRRP to SSH exclusively were included. RESULTS: SSH manages about half of the New Zealand paediatric population with JRRP. The incidence of JRRP before the introduction of the HPV vaccination programme was 0.21 per 100,000 per year in children 14 years of age and younger. This remained stable between 2008 and 2022 (0.23 vs 0.21 per 100,000 per year). The mean incidence in the later post-vaccination period was 0.15 per 100,000 per year based on small numbers. CONCLUSION: The mean incidence of JRRP before and after the introduction of HPV has remained unchanged in children treated at SSH. More recently, a reduction in incidence has been noted, although this is based on small numbers. The low HPV vaccination rate (≤70%) may explain why a significant reduction in the incidence of JRRP seen overseas has not been observed in New Zealand. Ongoing surveillance and a national study would provide more insight into the true incidence and evolving trends.

Biosynthesis of Isonitrile- and Alkyne-Containing Natural Products.

Natural products are a diverse class of biologically produced compounds that participate in fundamental biological processes such as cell signaling, nutrient acquisition, and interference competition. Unique triple-bond functionalities like isonitriles and alkynes often drive bioactivity and may serve as indicators of novel chemical logic and enzymatic machinery. Yet, the biosynthetic underpinnings of these groups remain only partially understood, constraining the opportunity to rationally engineer biomolecules with these functionalities for applications in pharmaceuticals, bioorthogonal chemistry, and other value-added chemical processes. Here, we focus our review on characterized biosynthetic pathways for isonitrile and alkyne functionalities, their bioorthogonal transformations, and prospects for engineering their biosynthetic machinery for biotechnological applications.

Launching a saliva-based SARS-CoV-2 surveillance testing program on a university campus.

Regular surveillance testing of asymptomatic individuals for SARS-CoV-2 has been center to SARS-CoV-2 outbreak prevention on college and university campuses. Here we describe the voluntary saliva testing program instituted at the University of California, Berkeley during an early period of the SARS-CoV-2 pandemic in 2020. The program was administered as a research study ahead of clinical implementation, enabling us to launch surveillance testing while continuing to optimize the assay. Results of both the testing protocol itself and the study participants' experience show how the program succeeded in providing routine, robust testing capable of contributing to outbreak prevention within a campus community and offer strategies for encouraging participation and a sense of civic responsibility.

Small molecule natural products in human nasal/oral microbiota.

Small molecule natural products are a chemically diverse class of biomolecules that fulfill myriad biological functions, including autoregulation, communication with microbial neighbors and the host, interference competition, nutrient acquisition, and resistance to oxidative stress. Human commensal bacteria are increasingly recognized as a potential source of new natural products, which may provide insight into the molecular ecology of many different human body sites as well as novel scaffolds for therapeutic development. Here, we review the scientific literature on natural products derived from residents of the human nasal/oral cavity, discuss their discovery, biosynthesis, and ecological roles, and identify key questions in the study of these compounds.

Review of icatibant use in the Winnipeg Regional Health Authority.

BACKGROUND: This is a retrospective review of the Winnipeg Regional Health Authority's (WRHA) angioedema patients who were dispensed icatibant in hospital. Icatibant is a bradykinin B2 receptor antagonist indicated for Hereditary Angioedema (HAE) types I and II and is used off-label for HAE with normal C1INH (HAE-nC1INH) and ACE-inhibitor induced angioedema (ACEIIAE). The WRHA's use of icatibant is regulated by the Allergist on call. We characterized icatibant's use and the timeline from patient presentation, compared the real-world experience with the FAST-3 trial and hypothesized the factors which may affect response to icatibant. METHODS: Background data were collected on patients. Angioedema attack-related data included administered medications, performed investigations and the timeline to endpoints such as onset of symptom relief. Data was analyzed in R with the package "survival." Time-to-event data was analyzed using the Peto-Peto Prentice method or Mann-Whitney U-test. Data was also compared with published clinical trial data using the Sign Test. Fisher's Exact Test was used to produce descriptive statistics. RESULTS: Overall, 21 patients accounted for 23 angioedema attacks treated with icatibant. Approximately half the patients had a diagnosis of HAE-nC1IHN and half of ACEIIAE. Of those presenting with angioedema, 65% were first treated with conventional medication. Patients without a prior angioedema diagnosis were evaluated only 40-50% of the time for C4 levels or C1INH function or level. The median time from patients' arrival to the emergency department until the Allergy consultant's response was 1.77 h. Patients with HAE-nC1IHN had median times to onset of symptom relief and final clinical outcome (1.13 h, p = 0.34; 3.50 h, p = 0.11) similar to those reported in FAST-3 for HAE I/II. Patients with ACEIIAE had longer median times to onset of symptom relief (4.86 h, p = 0.01) than predicted. CONCLUSIONS: HAE-nC1INH may be an appropriate indication for treatment with icatibant. Conversely, the results of this study do not support the use of icatibant for the treatment of ACEIIAE, concordant with a growing body of literature. Patients should be stratified into groups of more- or less-likely icatibant-responders through history and laboratory investigations in order to prevent potential delays.

Investigation of secondary metabolism in the industrial butanol hyper-producer Clostridium saccharoperbutylacetonicum N1-4.

Clostridium saccharoperbutylacetonicum N1-4 (Csa) is a historically significant anaerobic bacterium which can perform saccharolytic fermentations to produce acetone, butanol, and ethanol (ABE). Recent genomic analyses have highlighted this organism's potential to produce polyketide and nonribosomal peptide secondary metabolites, but little is known regarding the identity and function of these metabolites. This study provides a detailed bioinformatic analysis of seven biosynthetic gene clusters (BGCs) present in the Csa genome that are predicted to produce polyketides/nonribosomal peptides. An RNA-seq-based untargeted transcriptomic approach revealed that five of seven BGCs were expressed during ABE fermentation. Additional characterization of a highly expressed nonribosomal peptide synthetase gene led to the discovery of its associated metabolite and its biosynthetic pathway. Transcriptomic analysis suggested an association of this nonribosomal peptide synthetase gene with butanol tolerance, which was supported by butanol challenge assays.

Penicillin Skin Testing, Challenge, and Desensitization in Pregnancy: A Systematic Review.

OBJECTIVE: This study sought to evaluate available evidence of the safety of penicillin skin testing (PST), challenge, and desensitization in pregnancy, with efforts to improve perinatal care for patients with a penicillin allergy history and mitigate the negative sequelae of unverified penicillin allergy labels. METHODS: A systematic review of studies was conducted using Cochrane Library, Medline, EMBASE, and International Pharmaceutical Abstracts. Included were peer-reviewed studies without date restrictions, published in English or French, relating to PST, challenge, or desensitization in pregnancy. Editorials, opinion pieces, and letters were excluded. Review authors independently screened citations and full-text articles, extracted data, and conducted quality assessment. Given the heterogeneity of study designs, a narrative synthesis was conducted. RESULTS: The search identified 1195 references, of which 18 studies met inclusion criteria. In total there were 231 patients with varying histories of penicillin allergy, the majority requiring treatment for syphilis or group B streptococcal (GBS) disease during pregnancy. Of the 203 participants who underwent PST, 83.7% had negative test results. Allergy-related reactions were rare in PST (1.5%) and challenge (0%), and although these reactions were more common in desensitization (19.7%), most were benign. Among the 231 cases, only one adverse pregnancy outcome was reported (0.4%). CONCLUSION: This review demonstrates that the known prevalence of true penicillin allergy extends to pregnant women. PST and desensitization can be safely applied during pregnancy and are tools that should be used more frequently. Further data on the safety of challenge during pregnancy are recommended.

Review of the Manitoba cohort of patients with hereditary angioedema with normal C1 inhibitor.

BACKGROUND: Hereditary angioedema with normal C1 inhibitor (HAE-nC1 INH) is a rare, underappreciated condition characterized by recurrent subcutaneous angioedema. The underlying pathophysiology and diagnostic criteria continues to evolve. There is a significant overlap between HAE-nC1 INH and idiopathic nonhistaminergic angioedema, ultimately this may be found to be the same condition. Characterization of cohorts suspected to have either of these conditions is warranted to help refine diagnosis, pathophysiology, and treatment response. METHODS: A retrospective chart review of 418 patients diagnosed with angioedema was conducted. The following inclusion criteria was used: lack of response to antihistamines, steroids, and epinephrine; normal C4, C1 inhibitor (C1 INH) level and function; lack of urticaria or pruritus; occurrence without offending drugs; and positive family history. Enzyme immunoassays for C1 INH function were performed at the Mayo Clinic. Charts meeting these criteria were reviewed for frequency and type of episodes as well as use and response to therapies. RESULTS: 6 patients met the above criteria. 3 of these completed genetic testing, none were found to have factor XII abnormalities. None had angiopoietin 1 or plasminogen gene sequencing. 5 of 6 patients were successfully treated with C1 INH or tranexamic acid for acute treatment of attacks (4 with C1 INH and 1 with tranexamic acid). 4 patients have used Icatibant with good response (typically under 40 min for near full recovery); of these, 3 required Icatibant as acute treatment after other therapies (C1 inhibitor and tranexamic acid) were ineffective. There were 9 patients who otherwise met criteria, but due to a lack of family history were classified as having idiopathic non-histaminergic angioedema. CONCLUSIONS: This retrospective chart review found 6 HAE-nC1 INH patients in Manitoba. 1 responded to tranexamic acid and not C1 INH, 4 typically responded to C1 INH, and 1 responded exclusively to Icatibant. All patients-4 total-who used Icatibant responded; of these 4 patients, 3 required Icatibant after other therapies had failed.

Natural products from anaerobes.

Natural product discovery in the microbial world has historically been biased toward aerobes. Recent in silico analysis demonstrates that genomes of anaerobes encode unexpected biosynthetic potential for natural products, however, chemical data on natural products from the anaerobic world are extremely limited. Here, we review the current body of work on natural products isolated from strictly anaerobic microbes, including recent genome mining efforts to discover polyketides and non-ribosomal peptides from anaerobes. These known natural products of anaerobes have demonstrated interesting molecular scaffolds, biosynthetic logic, and/or biological activities, making anaerobes a promising reservoir for future natural product discovery.

The bacterial species associated with aspirated foreign bodies in children.

OBJECTIVE: Inhaled foreign bodies in children are common and may be complicated by secondary airway tract infection. The inhaled foreign body may act as carrier of infectious material and the aim of this study was to explore the bacterial species associated with aspirated foreign bodies in a cohort of children. METHODS: Retrospective case series of 34 patients who underwent rigid laryngobronchoscopy because of foreign body aspiration. Each patient had a sample taken from tracheobronchial secretions during the procedure. RESULTS: The average patient age was 31.2 months and the average hospital stay was 2.5 days. Of the foreign bodies 24 (71%) were organic in nature and 10 (29%) were non-organic. Twenty eight (82.3%) patients had mixed oropharyngeal flora organisms growth. Fifteen (44%) samples were positive for organisms other than oropharyngeal flora with the most common cultured organisms being: Streptococcus pneumonia (4/12%), Haemophilus influenza (4/12%), Moraxella catarrhalis (4/12%). Four samples (12%) grew a fungus; Candida albicans was cultured in 3 patients and Aspergillus glaucus was identified in one sample. Of the non-oropharyngeal organisms 7(47%) demonstrated antibiotic resistance with four having resistance to amoxycillin, two resistant to penicillin and one resistant to cotrimoxazole. CONCLUSION: Some children who present with aspirated foreign body may be complicated with secondary airway infection. Antibacterial treatment might be considered in some of these cases. The regimen of antibiotics should aim to cover oropharyngeal flora, S. pneumonia, H. influenza and Moraxella catarrhalis.

Bacterial endosymbionts influence host sexuality and reveal reproductive genes of early divergent fungi.

Many heritable mutualisms, in which beneficial symbionts are transmitted vertically between host generations, originate as antagonisms with parasite dispersal constrained by the host. Only after the parasite gains control over its transmission is the symbiosis expected to transition from antagonism to mutualism. Here, we explore this prediction in the mutualism between the fungus Rhizopus microsporus (Rm, Mucoromycotina) and a beta-proteobacterium Burkholderia, which controls host asexual reproduction. We show that reproductive addiction of Rm to endobacteria extends to mating, and is mediated by the symbiont gaining transcriptional control of the fungal ras2 gene, which encodes a GTPase central to fungal reproductive development. We also discover candidate G-protein-coupled receptors for the perception of trisporic acids, mating pheromones unique to Mucoromycotina. Our results demonstrate that regulating host asexual proliferation and modifying its sexual reproduction are sufficient for the symbiont's control of its own transmission, needed for antagonism-to-mutualism transition in heritable symbioses. These properties establish the Rm-Burkholderia symbiosis as a powerful system for identifying reproductive genes in Mucoromycotina.

Retrotracheal Extraskeletal Ewing's Sarcoma: Case Report and Discussion on Airway Management.

Extraskeletal Ewing's sarcoma is a rare tumor, and the management of airway compromise in case of cervical Ewing's sarcoma has not been established. This report describes the case of a patient with retrotracheal Ewing's sarcoma and discusses a successful approach to airway management. A 12-year-old male presented with a 2-week history of sore throat and sleep-disordered breathing and 48 hours of stridor. Imaging confirmed a retrotracheal soft tissue mass with airway compromise. A planned and controlled approach to his airway management resulted in a secure airway prior to definitive treatment.

Long-standing inhaled foreign bodies in children: Characteristics and outcome.

OBJECTIVE: Aspirated foreign bodies in children present a potentially life-threatening condition and can be challenging to diagnose. This study aims to elucidate the characteristics and outcome of children with long-standing aspirated foreign bodies. METHODS: Retrospective case series of all cases of confirmed long-standing aspirated foreign bodies (LSAFB) between January 2003 to December 2015 in a single paediatric tertiary-level institution, defined as more than two weeks from choking episode or beginning of symptoms. RESULTS: Clinical files and operative records on 227 patients were screened and 35 children were confirmed to have been treated for LSAFB as per definition above. Median time to presentation was 4 weeks (mean 8.8 weeks). Eighty-six percent presented with cough and 51% with dyspnoea. Abnormal chest X-ray findings were found in 28 out 31 patients (90%). Organic foreign bodies (22) were more common than inorganic (14). Intraoperative granulation tissue was demonstrated in 89% of patients and in 46% of patients this was regarded as significant (defined as obstructing more than 50% of the involved airway lumen). Mean length of stay was 2.5 days. Nine patients (26%) had 11 respiratory complications; there were no mortalities. CONCLUSIONS: Paediatric LSAFB poses an uncommon diagnostic dilemma as there is often no witnessed history of aspiration event; and signs, symptoms and chest X-Ray findings are often non-specific. Laryngobronchoscopy is made more difficult by the presence of granulation tissue and the sequelae of prolonged non-treatment is a higher rate of chronic respiratory disease.

A novel combination of an IgE mediated adult onset food allergy and a suspected mast cell activation syndrome presenting as anaphylaxis.

BACKGROUND: Adult onset food allergy is a rare, but increasingly recognized phenomenon. Mast cell activation syndromes present an ongoing diagnostic and classification challenge. The combination of the two has been rarely described in the literature. CASE PRESENTATION: We present a case of a new onset, IgE mediated food allergy in combination with a mast cell activation syndrome in an elderly patient not known to have a history of atopy. He presented to a hospital with a first presentation of anaphylaxis manifesting profound hypotension following consumption of a stew consisting of fish and shellfish. He had a persistently elevated serum tryptase and demonstrated evidence of high titre serum specific IgE to shellfish. He responded well to histaminergic blockade. CONCLUSIONS: Given that mast cell activation syndromes pose an increased risk for recurrent, severe anaphylaxis and that secondary causes of mast cell activation syndromes are more prevalent with aging, this case highlights the importance of considering this entity when evaluating an elderly patient with a first presentation of anaphylaxis.

The starship children's hospital tonsillectomy: A further 10 years of experience.

OBJECTIVES/HYPOTHESIS: Tonsillectomy as a day-stay procedure remains controversial, although it is an established procedure in New Zealand. We reviewed our last 10 years' experience. METHODS: A prospective audit was used to determine unplanned conversion from day-stay to overnight hospital admission rates and the incidence of postoperative complications. RESULTS: There were 5,400 tonsillectomies performed over the 10-year study period (January 2004-January 2015); 71% as outpatients. The unplanned conversion rate to overnight stay was 0.4%. The median age of day-stay patients was 6.5 years (range 13 months-15 years) compared with those admitted for overnight stay (5 years; range 8 months-15 years). The primary postoperative bleed rate was 0.5% (confidence interval [CI] 0.3%-0.7%), and the combined primary and secondary posttonsillectomy bleed rate was 4.3% (CI 3.8%-5.0%). The rate of patients returning with postoperative complications within 1 month of surgery was 6.3% (CI 5.6%-7.0%). CONCLUSION: Day-stay tonsillectomy in the pediatric population is safe when performed using the described guidelines in a facility with appropriate resources. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:E416-E420, 2016.

What is behind the ear drum? The microbiology of otitis media and the nasopharyngeal flora in children in the era of pneumococcal vaccination.

AIM: This study aims to describe the microbiology of middle ear fluid (MEF) in a cohort of children vaccinated with Streptococcus pneumoniae conjugate vaccine (PCV7) having ventilation tube insertion. Nasopharyngeal (NP) carriage of otopathogens in these children is compared with children without history of otitis media. METHODS: Between May and November 2011, MEF and NP samples from 325 children aged <3 years were collected in three major centres in New Zealand at the time of ventilation tube insertion. An age-matched non-otitis-prone comparison group of 137 children had NP samples taken. A questionnaire was completed by both groups. RESULTS: Immunisation coverage with at least one dose of PCV7 was 97%. Haemophilus influenzae was cultured in 19.4% of MEF and was polymerase chain reaction (PCR) positive in 43.4%. S. pneumoniae and Moraxella catarrhalis were cultured in <10% of MEF samples but were PCR positive for 23.1% and 38.7%, respectively. H. influenzae was the most common organism isolated from NP samples (60%) in the grommet group, while M. catarrhalis (56%) was the most common in the non-otitis prone group. S. pneumoniae was more commonly found in the nasopharynx of children with ear disease (41% vs. 29%). 19F was the most prominent S. pneumoniae serotype in NP samples of both groups, but no serotype dominated in MEF. Ninety-five per cent of H. influenzae isolates were confirmed to be non-typeable H. influenzae. CONCLUSION: In this cohort of children with established ear disease requiring surgical intervention, non-typeable H. influenzae is the dominant pathogen in both the nasopharynx and MEF.