Citations

Background Septoplasty is used to correct nasal obstruction from nasal septum deviation. However, the long‐term efficacy of septoplasty is unclear, and no literature reviews have examined long‐term outcomes of septoplasty with or without turbinate modification. This systematic review aimed to evaluate the long‐term efficacy of septoplasty with or without turbinate modification in improving nasal obstruction. Data Sources PubMed, EMBASE, Cochrane CENTRAL. Methods A systematic review of the literature was conducted using the aforementioned databases. Studies reporting outcomes 12+ months after functional septoplasty with or without turbinate surgery for nasal obstruction were included. Septorhinoplasties, concurrent sinus surgery, pediatric studies, and studies where septoplasty was performed for indications other than nasal obstruction were excluded. Results After screening, 35 studies with 4,432 patients were included. Mean weighted post‐operative follow‐up time was 29.1 months (range 12–120 months). All studies reported significant improvement in subjective and objective outcomes at long‐term follow‐up compared to baseline. When comparing short‐term (<12 months) to long‐term (≥12 months) outcomes, four studies noticed that subjective outcomes worsened slightly over time, but no study found a significant change in objective outcomes over time. In addition, 23 studies reported patient satisfaction and/or improvement rates, with 75.4% (2,348/3,113) of patients expressing satisfaction/improvement at an average of 27.0 months after surgery. Conclusions Overall, septoplasty with or without turbinate modification shows significant improvement in obstructive symptoms at long‐term follow‐up per both objective and subjective measures. Whether outcomes may worsen slightly over time remains indeterminate based on mixed results in the literature. Level of Evidence N/A Laryngoscope , 134:2525–2537, 2024

Abstract Aims In long QT syndrome (LQTS), primary prevention improves outcome; thus, early identification is key. The most common LQTS phenotype is a foetal heart rate (FHR) &lt; 3rd percentile for gestational age (GA) but the effects of cohort, genotype, variant, and maternal β-blocker therapy on FHR are unknown. We assessed the influence of these factors on FHR in pregnancies with familial LQTS and developed a FHR/GA threshold for LQTS. Methods and results In an international cohort of pregnancies in which one parent had LQTS, LQTS genotype, familial variant, and maternal β-blocker effects on FHR were assessed. We developed a testing algorithm for LQTS using FHR and GA as continuous predictors. Data included 1966 FHRs at 7–42 weeks’ GA from 267 pregnancies/164 LQTS families [220 LQTS type 1 (LQT1), 35 LQTS type 2 (LQT2), and 12 LQTS type 3 (LQT3)]. The FHRs were significantly lower in LQT1 and LQT2 but not LQT3 or LQTS negative. The LQT1 variants with non-nonsense and severe function loss (current density or β-adrenergic response) had lower FHR. Maternal β-blockers potentiated bradycardia in LQT1 and LQT2 but did not affect FHR in LQTS negative. A FHR/GA threshold predicted LQT1 and LQT2 with 74.9% accuracy, 71% sensitivity, and 81% specificity. Conclusion Genotype, LQT1 variant, and maternal β-blocker therapy affect FHR. A predictive threshold of FHR/GA significantly improves the accuracy, sensitivity, and specificity for LQT1 and LQT2, above the infant’s a priori 50% probability. We speculate this model may be useful in screening for LQTS in perinatal subjects without a known LQTS family history.

INTRODUCTION: There is a paucity of data on the real-world effectiveness of therapies in patients with Crohn's disease of the pouch. METHODS: This was a prospective multicenter study evaluating the primary outcome of remission at 12 months of therapy for Crohn's disease of the pouch. RESULTS: One hundred thirty-four patients were enrolled. Among the 77 patients with symptoms at baseline, 35 (46.7%) achieved remission at 12 months. Of them, 12 (34.3%) changed therapy. There was no significant association between therapy patterns and remission status. DISCUSSION: Approximately 50% with symptoms at enrollment achieved clinical remission at 12 months, most of whom did so without a change in therapy.

Lung diseases rank third in terms of mortality and represent a significant economic burden globally. Scientists have been conducting research to better understand respiratory diseases and find treatments for them. An ideal in vitro model must mimic the in vivo organ structure, physiology, and pathology. Organoids are self-organizing, three-dimensional (3D) structures originating from adult stem cells, embryonic lung bud progenitors, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs). These 3D organoid cultures may provide a platform for exploring tissue development, the regulatory mechanisms related to the repair of lung epithelia, pathophysiological and immunomodulatory responses to different respiratory conditions, and screening compounds for new drugs. To create 3D lung organoids in vitro, both co-culture and feeder-free methods have been used. However, there exists substantial heterogeneity in the organoid culture methods, including the sources of AT2 cells, media composition, and feeder cell origins. This article highlights the currently available methods for growing AT2 organoids and prospective improvements to improve the available culture techniques/conditions. Further, we discuss various applications, particularly those aimed at modeling human distal lung diseases and cell therapy.

Abstract PURPOSE/OBJECTIVE We seek to establish the feasibility of using spine stereotactic radiosurgery (SSRS) allowing for spinal cord dose constraint relaxation as the primary management of metastatic epidural spinal cord compression (MESCC) in inoperable patients monitoring for radiation myelopathy (RM) and radiographic local control (LC). MATERIAL/METHODS Patients with radiation naïve MESCC were enrolled on this prospective Phase 1 trial. Single fraction SSRS was delivered to a dose of 18 or 24 Gy. Spinal cord constraint relaxation was performed in sequential cohorts from an initial allowable Dmax cohort of 10 Gy up to 16 Gy only if tumor progression occurred without RM. RESULTS Thirty two patients enrolled on the trial of which 4, 12, 8 and 8 were in the 10 Gy, 12 Gy, 14 Gy and 16 Gy cord Dmax cohorts, respectively. At baseline, there were 10 sites with MESCC Grade 1B, 10 sites with Grade 1C, 9 sites with Grade 2, 2 sites with Grade 1A, and 1 site with Grade 3 disease. Of the 28 evaluable patients, the median overall survival was 32.3 months (range 5.8-122.6 mo). The 1-year and 5-year LC was 84.5% and 79.5%. The 2-year LC did not statistically differ between the 14-16 Gy cord Dmax combined cohorts and the 10-12 Gy cord Dmax combined cohorts (92.9% vs. 62.9%, p = 0.15). With a median clinical follow-up of 22.7 months (range 3-122.3 mo), there were no cases of RM including in the 13 patients who survived at least 3 years. In the cohort receiving a cord Dmax of 16 Gy, there were no cases of RM with a median follow-up of 18.6 mo (range 9.0-97.1 mo). CONCLUSION With long-term follow-up, these data demonstrate that SSRS is a safe and effective tool in patients with MESCC. Cord constraint relaxation may be considered in inoperable patients with MESCC.

Abstract BACKGROUND Glioblastoma (GBM) is an aggressive central nervous system (CNS) malignancy with poor prognosis. TTFields are electric fields that exert physical forces to disrupt cellular processes critical for cancer cell viability. TTFields therapy is approved for recurrent and newly diagnosed GBM, and pleural mesothelioma. We report long-term safety data from pediatric, adult and elderly patients with CNS malignancies receiving TTFields, from a global post-marketing surveillance (PMS) dataset. METHODS Unsolicited PMS data were collected from patients receiving TTFields (October 2011–October 2022). AEs were categorized using MedDRA version 25.1, and data stratified by age group (&lt; 18, 18–65, and &gt; 65 years). RESULTS Overall, 25,898 patients from the US, Europe, Israel, and Japan were included. Of these, 93 (0.4%) were &lt; 18 years (pediatric), 17,817 (69%) were 18–65 years (adult), and 7,808 (30%) were &gt; 65 years (elderly). Two-thirds (66%) of all patients were male. Demographic characteristics were therefore consistent with a typical GBM population. Of pediatric patients, 62% experienced ≥ 1 AE, with 53% related to TTFields. This was comparable in adults (72% and 56%, respectively), and elderly patients (75% and 57%, respectively). The most common TTFields-related AEs were skin reaction (pediatric: 39%; adult: 42%; elderly: 45%), heat (warmth) sensation (pediatric: 14%; adult: 12%; elderly: 12%), and electric (tingling) sensation (pediatric: 10%; adult: 15%; elderly: 10%). All-cause serious AEs occurred in 14%, 21% and 25% of pediatric, adult and elderly patients, respectively. No systemic toxicities were reported, regardless of age. CONCLUSIONS These long-term, real-world PMS data demonstrate that TTFields has a tolerable safety profile in pediatric, adult and elderly patients with CNS malignancies, with no new safety signals in any age group. Most AEs were localized skin reactions which are manageable. These data provide supportive evidence of the safety and broad applicability of TTFields, regardless of patient age.

AbstractContextEarly inflammatory thyroid eye disease (TED) can lead to symptomatic chronic disease, including disabling proptosis. Teprotumumab, an insulin-like growth factor-1 receptor (IGF-1R) inhibitor, previously demonstrated efficacy in acute, high-inflammation TED trials.ObjectiveWe present data from the first placebo-controlled trial with teprotumumab in chronic/low disease activity TED.MethodsThis randomized double-masked, placebo-controlled trial, conducted at 11 US centers, enrolled adult participants with TED duration of 2 to 10 years, Clinical Activity Score (CAS) ≤ 1 or no additional inflammation or progression in proptosis/diplopia for ≥1 year, proptosis ≥3 mm from before TED and/or from normal, euthyroid/mildly hypo/hyperthyroid, no prior teprotumumab, and no steroids within 3 weeks of baseline. Patients received (2:1) intravenous teprotumumab or placebo once every 3 weeks (total 8 infusions). The primary endpoint was proptosis (mm) improvement at Week 24. Adverse events (AEs) were assessed.ResultsA total of 62 (42 teprotumumab and 20 placebo) patients were randomized. At Week 24, least squares mean (SE) proptosis improvement was greater with teprotumumab (−2.41 [0.228]) than with placebo (−0.92 [0.323]), difference −1.48 (95% CI −2.28, −0.69; P = .0004). Proportions of patients with AEs were similar between groups. Hyperglycemia was reported in 6 (15%) vs 2 (10%) and hearing impairment in 9 (22%) vs 2 (10%) with teprotumumab and placebo, respectively. AEs led to discontinuation in 1 teprotumumab (left ear conductive hearing loss with congenital anomaly) and 1 placebo patient (infusion-related). There were no deaths.ConclusionTeprotumumab significantly improved proptosis vs placebo in longstanding/low inflammation TED, demonstrating efficacy regardless of disease duration/activity. The safety profile was comparable to that previously reported.

Abstract Background Myeloid cells comprise up to 50% of the total tumor mass in glioblastoma (GBM) and have been implicated in promoting tumor progression and immunosuppression. Modulating the response of myeloid cells to the tumor has emerged as a promising new approach for cancer treatment. In this regard, we focus on the Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), which has recently emerged as a novel immune modulator in peripheral tumors. Methods We studied the TREM2 expression profile in various patient tumor samples and conducted single-cell transcriptomic analysis in both GBM patients and the GL261 mouse glioma model. We utilized multiple mouse glioma models and employed state-of-the-art techniques such as invivo 2-photon imaging, spectrum flow cytometry, and in vitro co-culture assays to study TREM2 function in myeloid cell-mediated phagocytosis of tumor cells, antigen presentation, and response of CD4+ T cells within the tumor hemispheres. Results Our research revealed significantly elevated levels of TREM2 expression in brain tumors compared to other types of tumors in patients. TREM2 was predominantly localized in tumor-associated myeloid cells and was highly expressed in nearly all microglia, as well as various subtypes of macrophages. Surprisingly, in preclinical glioma models, TREM2 deficiency did not confer a beneficial effect; instead, it accelerated glioma progression. Through detailed investigations, we determined that TREM2 deficiency impaired the ability of tumor-myeloid cells to phagocytose tumor cells and led to reduced expression of MHCII. This deficiency further significantly decreased the presence of CD4+ T cells within the tumor hemispheres. Conclusions Our study unveiled a previously unrecognized protective role of tumor-myeloid TREM2. Specifically, we found that TREM2 enhances the phagocytosis of tumor cells and promotes an immune response by facilitating MHCII-associated CD4+ T-cell responses against gliomas.

Objective A follow-up of women 50 years or older with concomitant positive high-risk human papillomavirus (HPV) genotypes other than 16 and 18 (hrHPVO) and negative Pap test (NILMPap) was conducted to better understand the implications of hrHPVO positivity on potential risk of developing significant high-grade lesions. Material and Methods A retrospective review of 2014 cytology data of patients with co-testing (Pap test and HPV DNA) identified 85 women 50 years or older with NILMPap and hrHPVO+. Results Most patients (63) had repeat co-testing on next follow-up. Of these, 41 patients with persistent hrHPVO+ status, 3 developed cervical intraepithelial neoplasia 2 (CIN2), and 1 CIN3. Nineteen patients were followed with biopsies. Of these, 7 biopsies were abnormal, 5 of which showed low-grade (CIN1) and 2 high-grade (CIN3) histology; none progressed on further follow-up. Three patients were followed with Pap test only, all had NILMPap, and none progressed on further follow-up. In summary, of the 85 patients, 26 developed abnormal histology during follow-up, 6 of whom had high-grade histology (CIN2 and CIN3, 3 each). The 5-year risk of CIN1+ in this cohort was 43.8% and for CIN2+ was 12.3%. The risk of abnormal histology did not differ significantly by prior history of Pap tests, histology, and/or HPV results. Conclusions A persistent positivity for hrHPVO indicated higher likelihood to develop a lesion, and this risk was not reduced for patients 50 and older compared with the published screening population risk.