Advances in the Use of Hypoglossal Nerve Stimulator in Adolescents With Down Syndrome and Persistent Obstructive Sleep Apnea-A Systematic Review.

INTRODUCTION: The Hypoglossal Nerve Stimulator (HNS) is a novel therapy that has been extensively studied in adults and more recently, it has been incorporated in children with Down Syndrome (DS) with persistent obstructive sleep apnea after adenotonsillectomy and trial of continuous positive airway pressure treatment. This systematic review article aims to examine the existing literature on HNS use in children to explore the benefits, efficacy, and parental experiences. METHODS: MEDLINE, Web of Science and EMBASE were searched to include all studies published up to March 2nd, 2023, on the topic of HNS use in pediatric population under 21 years old. RESULTS: A total of 179 studies were initially identified from which 10 articles were consistent with the inclusion criteria. Nine articles addressed outcomes after implantation of the HNS device in children with DS and 1 article explored the parental experiences. Findings were similar across studies where after implantation of HNS, there was marked improvement in polysomnographic outcomes and quality of life scores with high level of compliance. CONCLUSIONS: HNS holds promise as an effective treatment option for pediatric patients with DS and persistent OSA after AT and CPAP trials. It significantly improves sleep-disordered breathing, quality of life, and neurocognitive measures, leading to substantial and sustained benefits for these children. While the findings are encouraging, further research is needed to explore the potential of HNS in other pediatric populations without DS and to raise awareness among healthcare providers about this treatment option. Overall, HNS may offer significant long-term benefits for the overall well-being and health of pediatric patients with DS and persistent OSA.

Landscape of Biomarkers in Non-small Cell Lung Cancer Using Comprehensive Genomic Profiling and PD-L1 Immunohistochemistry.

Comprehensive genomic profiling (CGP) and immunohistochemistry (IHC) are important biomarker tools used for patients with non-small cell lung cancer (NSCLC) given the expanding number of standard-of-care therapies that require companion diagnostic testing. We examined 9450 NSCLC real-world patient samples that underwent both CGP and programmed death-ligand 1 (PD-L1) IHC to understand the biomarker landscape in this patient cohort. By assessing National Comprehensive Cancer Network (NCCN)-recommended biomarkers including genomic alterations, tumor mutational burden (≥10 mutations/Mb cut-off), and PD-L1 expression (Tumor Proportion Score (TPS) ≥ 50% cut-off), we show that CGP + PD-L1 IHC yielded potentially actionable results for 70.5% of the 9,450 patients with NSCLC. Among the remaining 29.5% (2,789/9,450) of patients, 86.7% (2,419/2,789) were potentially eligible for another biomarker-associated therapy and/or clinical trial based on their genomic profile. In addition, in the PD-L1TPS≥50% disease subset, BRAF mutations, MET mutations, MET amplifications, and KRAS mutations were significantly enriched; and in the PD-L1TPS<50%, EGFR mutations, ERBB2 mutations, STK11 mutations, and KEAP1 mutations were enriched. These findings highlight the improved clinical utility of combining CGP with IHC to expand the biomarker-guided therapeutic options available for patients with NSCLC, relative to single biomarker testing alone.

Evaluation of Acupuncture's Efficacy Within Otolaryngology.

OBJECTIVES: Acupuncture is a form of Traditional Chinese Medicine that has minimal side effects, is cost-effective, can be easily administered, and may serve as a useful non-pharmaceutical therapy for certain conditions. However, studies and clinical practice guidelines are inconsistent in conclusions and recommendations about acupuncture. This qualitative review addresses the evidence available for acupuncture use in otolaryngology. METHODS: A literature review was completed using EMBASE, PubMed, and The Cochrane Collection for conditions within otolaryngology that have used and studied the comparative effects of acupuncture. Thirty studies ultimately fit the inclusion criteria and were used for this qualitative review. RESULTS: Studies included in this review contained a variety of conditions within otolaryngology, including allergic rhinitis, chronic rhinitis, tinnitus, sudden sensorineural hearing loss, post-viral olfactory dysfunction, dysphonia, and tonsillectomies. CONCLUSION: Given its safety profile, cost, and perceived benefit, recommendations and guidelines supporting acupuncture as an alternative or adjunctive therapy are surfacing for certain conditions such as allergic rhinitis. However, stronger conclusions with specific recommendations are limited by varied methodology between majority of the studies. Additional high-quality randomized control studies with low risk of bias are required to continue to assess the effects of acupuncture in the field of otolaryngology before stronger recommendations can be made on other conditions.

Phase II open label, multi-center clinical trial of modulation of intermediate endpoint biomarkers by 1α-hydroxyvitamin D2 in patients with clinically localized prostate cancer and high grade pin.

BACKGROUND: Prostate cancer is the most common malignancy and second leading cause of cancer related deaths in American men supporting the study of prostate cancer chemoprevention. Major risk factors for this disease have been associated with low serum levels of vitamin D. Here, we evaluate the biologic activity of a less calcemic vitamin D analog 1α-hydroxyvitamin D2 [1α-OH-D2] (Bone Care International, Inc.) in patients with prostate cancer and high grade prostatic intraepithelial neoplasia (HG PIN). METHODS: Patients with clinically organ-confined prostate cancer and HG PIN were randomized to 1α-OH-D2 versus placebo for 28 days prior to radical prostatectomy. Intermediate endpoint biomarkers included serum vitamin D metabolites, TGFß 1/2, free/total PSA, IGF-1, IGFBP-3, bFGF, and VEGF. Tissue endpoints included histology, MIB-1 and TUNEL staining, microvessel density and factor VIII staining, androgen receptor and PSA, vitamin D receptor expression and nuclear morphometry. RESULTS: The 1α-OH-D2 vitamin D analog was well tolerated and could be safely administered with good compliance and no evidence of hypercalcemia over 28 days. While serum vitamin D metabolite levels only slightly increased, evidence of biologic activity was observed with significant reductions in serum PTH levels. TGF-ß2 was the only biomarker significantly altered by vitamin D supplementation. Whether reduced TGF-ß2 levels in our study is an early indicator of response to vitamin D remains unclear. CONCLUSIONS: While further investigation of vitamin D may be warranted based on preclinical studies, results of the present trial do not appear to justify evaluation of 1α-OH-D2 in larger clinical prostate cancer prevention studies.

Cross your heart: Some historical comments about fibrinous pericarditis.

This article briefly describes the origin of one of the more common (food-related) pathologic terms--"bread and butter pericarditis." The eminent French physician, Laennec, the inventor of the stethoscope amongst several other important medical contributions, can be credited for having coined the term that is still in common usage amongst pathologists.

Aberration in the expression of the retinoid receptor, RXRalpha, in prostate cancer.

There is ample evidence for a role for retinoids in the development and maturation of prostatic epithelium. In recent experiments with conditional disruption of a specific retinoid receptor, namely, RXRalpha in the prostatic epithelium of the mouse, we observed that a major component of retinoid action in the prostate is indeed mediated by RXRalpha. The results clearly indicated that the inactivation of RXRalpha in the prostate epithelium leads to the development of preneoplastic lesions (Huang et al. Cancer Res 62: 4812-9, 2002). To determine the relation of this finding to human prostate cancer, we examined the expression of RXRalpha protein in human prostate cancer cell lines by western blotting and prostate cancer specimens by immunohistochemistry. Relative to the "normal" prostate epithelial cells, there was approximately two- to nine-fold decrease in the full-length 54 kD RXRalpha protein in each of the seven different prostate cancer cell lines tested. Similarly, while RXRalpha immunostaining was uniformly strong in the nuclei of most of the benign prostatic epithelial cells of the thirteen adenocarcinoma specimens tested, a highly heterogeneous pattern of expression was detected in the malignant epithelium, with some areas with low or no staining, others with mostly cytoplasmic staining, and some with both nuclear and cytoplasmic immunoreactivity. To evaluate the effect of RXRalpha modulation on the biologic properties of prostate cancer cell lines, we used a lentivirus expression system to overexpress RXRalpha in CWR22R prostate cancer cells that basally expressed a marginal level of the receptor. The sorted RXRalpha-transduced cells were compared to the corresponding vector control cells for proliferative and apoptotic properties. A correlation of reduction of cell growth or increased susceptibility to apoptosis with increases in the level of RXRalpha nuclear receptor was demonstrated. These effects were further enhanced when the cell culture medium was supplemented with a retinoid receptor panagonist, 9-cis retinoic acid. Together, these data support the notion that, like in mouse prostate, loss or reduction of RXRalpha activity might be a critical factor in prostate tumorigenesis in humans.