The Safety of the Laryngeal Mask Airway in Adenotonsillectomy: A Systematic Review and Meta-Analysis.

BACKGROUND: Adenotonsillectomy is one of the most common surgical procedures worldwide. The current standard for securing the airway in patients undergoing adenotonsillectomy is endotracheal tube (ETT) intubation. Several studies have investigated the use of the laryngeal mask airway (LMA) in this procedure. We conducted a systematic review and meta-analysis to compare the safety and efficacy of the LMA versus ETT in adenotonsillectomy. METHOD: Databases were searched from inception to 2022 for randomized controlled trials and comparative studies. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The primary outcome is the rate of perioperative respiratory adverse events (PRAEs). Secondary outcomes included the rate of conversion to ETT, desaturations, nausea/vomiting, and surgical time. A subgroup analysis, risk of bias, publication bias, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessments were also performed. RESULTS: Twelve studies were included in the analysis (4176 patients). The mean overall conversion to ETT was 8.36% [95% confidence interval (CI) = 8.17, 8.54], and for the pediatric group 8.27% (95% CI = 8.08, 8.47). The mean rate of conversion to ETT secondary to complications was 2.89% (95% CI = 2.76, 3.03) while the rest was from poor surgical access. Overall, there was no significant difference in PRAEs [odds ratio (OR) 1.16, 95% CI = 0.60, 2.22], desaturations (OR 0.79, 95% CI = 0.38, 1.64), or minor complications (OR 0.89, 95% CI = 0.50, 1.55). The use of LMA yielded significantly shorter operative time (mean difference -4.38 minutes, 95% CI = -8.28, -0.49) and emergence time (mean difference -4.15 minutes, 95% CI = -5.63, -2.67). CONCLUSION: For adenotonsillectomy surgery, LMA is a safe alternative to ETT and requires less operative time. Careful patient selection and judgment of the surgeon and anesthesiologist are necessary, especially given the 8% conversion to ETT rate.

Alternative Therapies for Ankyloglossia-Associated Breastfeeding Challenges: A Systematic Review.

Background: Ankyloglossia (AG) diagnoses are increasingly common, and management is not standardized. Nonsurgical alternative therapies are frequently recommended in conjunction with or instead of frenotomy, with uncertain evidence. Objective: To evaluate the efficacy of nonsurgical alternative therapies (chiropractic care, myofunctional therapy, and osteopathy) in improving breastfeeding for infants diagnosed with AG. Methods: PubMed, Embase, CINAHL, Scopus, Web of Science, Clinicaltrials.gov, and Google Scholar were searched (September-October 2023). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. A librarian-designed search included the terms "Ankyloglossia," "Non-surgical," "myofunctional therapy," "chiropractic," "osteopathy," and related therapies, with no date restrictions. English language studies of infants <24 months with AG and alternative therapy were included. Risk-of-bias evaluation used Newcastle-Ottawa Scale (NOS). Results: Of 1,304 identified articles, four studies (2016-2022) met inclusion criteria (two cross-sectional, one case report, and one case series). All studies reported frenotomy in combination with alternative therapy yielded favorable outcomes for maternal pain, weight gain, feeding duration, and maintenance of latch. The risk of bias was moderate for two studies, low for the case series, and not calculated for the case report, which has an inherent high risk of bias. All studies lacked control or comparator groups preventing definitive conclusions about the role of alternative therapies in AG. Conclusion: Although some studies suggest the potential benefits of combining alternative therapies with surgery for AG-related breastfeeding issues, the lack of control groups renders the evidence inconclusive. Nonsurgical approaches alone currently lack sufficient evidence. As these alternative therapies gain popularity, rigorous research is crucial to determine their cost-effectiveness and role in managing AG.

Detection of TTR Amyloid in the Conjunctiva Using a Novel Fluorescent Ocular Tracer.

Background: Transthyretin amyloidosis (ATTR) is a significant cause of cardiomyopathy and other morbidities in the elderly and Black Americans. ATTR can be treated with new disease-modifying therapies, but large shortfalls exist in its diagnosis. The objective of this study was to test whether TTR amyloid can be detected and imaged in the conjunctiva using a novel small-molecule fluorescent ocular tracer, with the implication that ATTR might be diagnosable by a simple eye examination. Methods: Three approaches were used in this study. First, AMDX-9101 was incubated with in vitro aggregated TTR protein, and changes in its excitation and emission spectra were quantified. Second, a cadaver eye from a patient with familial amyloid polyneuropathy type II TTR mutation and a vitrectomy sample from an hATTR patient were incubated with AMDX-9101 and counterstained with Congo Red and antibodies to TTR to determine whether AMDX-9101 labels disease-related TTR amyloid deposits in human conjunctiva and eye. Last, imaging of in vitro aggregated TTR amyloid labeled with AMDX-9101 was tested in a porcine ex vivo model, using a widely available clinical ophthalmic imaging device. Results: AMDX-9101 hyper-fluoresced in the presence of TTR amyloid in vitro, labeled TTR amyloid deposits in postmortem human conjunctiva and other ocular tissues and could be detected under the conjunctiva of a porcine eye using commercially available ophthalmic imaging equipment. Conclusions: AMDX-9101 enabled detection of TTR amyloid in the conjunctiva, and the fluorescent binding signal can be visualized using commercially available ophthalmic imaging equipment. Translational Relevance: AMDX-9101 detection of TTR amyloid may provide a potential new and noninvasive test for ATTR that could lead to earlier ATTR diagnosis, as well as facilitate development of new therapeutics.

Comprehensive multi-omic profiling of somatic mutations in malformations of cortical development.

Malformations of cortical development (MCD) are neurological conditions involving focal disruptions of cortical architecture and cellular organization that arise during embryogenesis, largely from somatic mosaic mutations, and cause intractable epilepsy. Identifying the genetic causes of MCD has been a challenge, as mutations remain at low allelic fractions in brain tissue resected to treat condition-related epilepsy. Here we report a genetic landscape from 283 brain resections, identifying 69 mutated genes through intensive profiling of somatic mutations, combining whole-exome and targeted-amplicon sequencing with functional validation including in utero electroporation of mice and single-nucleus RNA sequencing. Genotype-phenotype correlation analysis elucidated specific MCD gene sets associated with distinct pathophysiological and clinical phenotypes. The unique single-cell level spatiotemporal expression patterns of mutated genes in control and patient brains indicate critical roles in excitatory neurogenic pools during brain development and in promoting neuronal hyperexcitability after birth.

Treatment of Essential Vocal Tremor: A Scoping Review of Evidence-Based Therapeutic Modalities.

OBJECTIVES/HYPOTHESIS: Essential vocal tremor (EVT) is an uncommon but challenging condition to manage. Several medical and interventional treatment options have been reported but efficacy remains unclear. We performed a scoping review of high-quality clinical trials to identify effective evidence-based treatments for EVT. STUDY DESIGN: Scoping review. METHODS: Relevant studies were identified using the databases MedLine, Cochrane Central Register of Controlled Trials, and Embase. Subjective and objective outcomes for each modality were analyzed and the effect sizes were quantified using Hedges' g measure to allow comparison between studies. RESULTS: We identified 421 studies eligible for screening with 11 included in the final analysis. Evidence supporting effective EVT treatments was found for bilateral versus unilateral deep brain stimulation (DBS) (Hedges' g 0.65, 95% CI = 0.10-1.20) and octanoic acid (Hedges' g 1.15, 95% CI = 0.40-1.90). Evidence to support the use of methazolamide was not sufficient (Hedges' g 0.51, 95% CI = -0.64 to 1.66). Botulinum toxin (BT) injections were equivalent when comparing unilateral versus bilateral (Hedges' g -0.18, 95% CI = -1.06 to 0.70); BT did not display any advantage over propranolol (Hedges' g -0.47, 95% CI = -1.73 to 0.78) or injection augmentation (Hedges' g 0.068, 95% CI = -0.98 to 1.12). CONCLUSIONS: Our review finds very little high-quality evidence supporting any treatment for EVT. Octanoic acid reduced fluctuations in EVT but did not affect the perception of the tremor. In refractory cases, bilateral DBS was superior to unilateral DBS in improving subjective voice outcomes. Unilateral and bilateral BT injections were equivalent, and BT injection was not more effective than injection augmentation. Further direct comparison in well-designed prospective studies may help clarify optimal treatment for EVT patients.

Durability of Complete Response to Intralesional Interleukin-2 for In-Transit Melanoma.

BACKGROUND: Intralesional injection of interleukin-2 (IL-2) for in-transit melanoma (ITM) is associated with a high rate of complete response. However, there is a paucity of data on treatment durability and long-term outcomes. OBJECTIVES: To provide long-term data on patients with a complete response to IL-2 therapy for ITM. METHODS: Consecutive patients with ITM, treated with intralesional IL-2 therapy, at the Tom Baker Cancer Center were identified from April 2009 to August 2019. All patients received at least 4 cycles (every 2 weeks) of IL-2 (5 MIU/mL). Complete response was defined as sustained (ie, 3 months) clinical complete remission of all known in-transit disease. RESULTS: Sixty-five patients were treated with curative intent for in-transit disease with intralesional IL-2. Complete clinical response was identified in 44.6% (29/65). In this subset of patients, the median number of lesions per patient was 9 (range 1-40). The median total dose of IL-2 was 0.8 mL (IQR 0.4-1.5) per lesion. One patient received isolated limb infusion and 13.8% (4/29) received systemic immunotherapy as part of their initial management. At a median follow-up of 27 months (IQR 16-59), 34.5% (10/29) developed recurrent disease. Of these patients, 50.0% (5/10) presented with synchronous in-transit and distant metastases. The median time to recurrence was 10.5 months (IQR 5.8-16.3). CONCLUSION: With long-term follow-up, 65.5% of complete responders have a durable response to intralesional IL-2 therapy. In this cohort of patients, local in-transit recurrence is most likely to occur within 12 months and is often associated with concomitant distant disease.

Causes of infant mortality in Jordan.

OBJECTIVE: Jordan lacks accurate information on mortality and related indicators. Reporting of infant deaths is defective. Infant mortality rate based on registered deaths was 6/1000 live births, while estimates of this rate based on indirect methods varied between 29-70/1000 live births. Causes of death in general are grossly misrepresented in death certificates. The objective of this paper is to explore, in-depth, causes of infant mortality and related indicators. METHODS: An assessment of causes of death by verbal autopsy was carried out at the Department of Family and Community Medicine, University of Jordan, Amman, Jordan. This was applied between November 1995 through to October 1996, to a random sample of 200,000 persons living in 100 clusters representing the population and all geographic areas of Jordan. The verbal autopsy instrument was based on algorithms and filter questions to determine the underlying cause of death. In this sample there were 6028 infants among them 129 deaths were identified. Infant deaths were analyzed according to rates and causes of death were classified according to International Classification of Diseases (10th revision). RESULTS: Age-specific death rate was 21.4/1000 infants and gender specific death rates were 22.6/1000 male infants for males and 20.1/1000 female infants for females. The 3 leading causes of infant death were conditions originating in the perinatal period, congenital malformations and diseases of the respiratory system. The leading cause of death in the neonatal period was conditions originating in the perinatal period, while in the post-neonatal period, it was congenital malformations. Prematurity was the leading contributory cause of infant death. CONCLUSION: This study showed that causes of infant mortality in Jordan tend to be similar to those prevailing in developed countries.