Trends in obstructive sleep apnea disease severity over nearly two decades: update on the VA San Diego experience.

Study Objectives: The Sleep Program at the VA San Diego Healthcare System (VASDHS) started a patient database over twenty years ago for its home sleep apnea testing (HSAT) program. An analysis of ten years of diagnostic HSAT data was reported on over 12 500 patients in 2014. Over this time period, severe obstructive sleep apnea (OSA) decreased in frequency. In contrast, mild OSA increased in frequency and was the most frequently reported severity in our analysis. In more recent times, the 2021 continuous positive airway pressure (CPAP) crisis created difficulties in dispersing CPAP therapies to individuals including Veterans with OSA, prompting our group to reexamine the HSAT database. Methods: A retrospective review was performed of the local clinical database of HSAT diagnostic testing of 8,928 sleep studies from 2018 to 2022. Results: The overall mean apnea-hypopnea index (AHI) decreased from 40.4/hour (2004) to 24.3/hour (2022) (p < .001). The two time periods were examined separately. For 2004-2013, it was found that the mean AHI in 2004 was not significantly different from the mean AHI in 2005, 2006, or 2007 but was significantly different from the mean AHI in each year from 2008 (mean AHI = 30.7/h) to 2013 (mean AHI = 26.1/hour). For 2019-2022, the mean AHI did not significantly differ between the 4 years. Conclusions: These findings have implications for OSA therapies. Additionally, the high prevalence of mild sleep apnea, which is typically associated with lesser adherence to PAP therapy, further highlights the importance of non-PAP alternatives to improve treatment effectiveness.

Beyond CPAP: modifying upper airway output for the treatment of OSA.

Obstructive Sleep Apnea (OSA) is exceedingly common but often under-treated. Continuous positive airway pressure (CPAP) has long been considered the gold standard of OSA therapy. Limitations to CPAP therapy include adherence and availability. The 2021 global CPAP shortage highlighted the need to tailor patient treatments beyond CPAP alone. Common CPAP alternative approaches include positional therapy, mandibular advancement devices, and upper airway surgery. Upper airway training consists of a variety of therapies, including exercise regimens, external neuromuscular electrical stimulation, and woodwind instruments. More invasive approaches include hypoglossal nerve stimulation devices. This review will focus on the approaches for modifying upper airway muscle behavior as a therapeutic modality in OSA.

Improving the process of ordering outside genomic testing for lung cancer FNA and small biopsy specimens - A multidisciplinary quality improvement project.

Objectives: Lung cancer is an important cause of mortality in the United States. Targeted mutation analysis has the potential to alter mortality in those with non-small-cell lung cancer. As such, the importance of timely tissue turnaround time (TAT) is substantial. We evaluated TAT at Mayo Clinic Arizona and found it to be delayed relative to national standards. Material and Methods: We conducted a series of plan, do, study, and act (PDSA) cycles at a single institution to identify areas for improvement with our lung cancer genomic testing. We assembled a multidisciplinary team and held serial meetings to discuss data from each PDSA cycle. Results: Using PDSA cycles and multidisciplinary discussions, we were able to identify a number of process limitations slowing TAT. We were then able to generate enhanced and timely communication between providers and pathology, educate and enforce the order/requisition workflow, and establish pathology accessioning with lung cancer specimens top priority. Conclusion: We were able to generate and implement a standard operating procedure for genomic testing of lung cancer specimens at our institution, thereby reducing tissue TAT.

Obstructive sleep apnea: personalizing CPAP alternative therapies to individual physiology.

INTRODUCTION: The recent continuous positive airway pressure (CPAP) crisis has highlighted the need for alternative obstructive sleep apnea (OSA) therapies. This article serves to review OSA pathophysiology and how sleep apnea mechanisms may be utilized to individualize alternative treatment options. AREAS COVERED: The research highlighted below focuses on 1) mechanisms of OSA pathogenesis and 2) CPAP alternative therapies based on mechanism of disease. We reviewed PubMed from inception to July 2022 for relevant articles pertaining to OSA pathogenesis, sleep apnea surgery, as well as sleep apnea alternative therapies. EXPERT OPINION: Although the field of individualized OSA treatment is still in its infancy, much has been learned about OSA traits and how they may be targeted based on a patient's physiology and preferences. While CPAP remains the gold-standard for OSA management, several novel alternatives are emerging. CPAP is a universal treatment approach for all severities of OSA. We believe that a personalized approach to OSA treatment beyond CPAP lies ahead. Additional research is needed with respect to implementation and combination of therapies longitudinally, but we are enthusiastic about the future of OSA treatment based on the data presented here.

Pulmonary Complications in Hematopoietic Stem Cell Transplant Recipients-A Clinician Primer.

Hematopoietic stem cell transplants (HSCT) are becoming more widespread as a result of optimization of conditioning regimens and prevention of short-term complications with prophylactic antibiotics and antifungals. However, pulmonary complications post-HSCT remain a leading cause of morbidity and mortality and are a challenge to clinicians in both diagnosis and treatment. This comprehensive review provides a primer for non-pulmonary healthcare providers, synthesizing the current evidence behind common infectious and non-infectious post-transplant pulmonary complications based on time (peri-engraftment, early post-transplantation, and late post-transplantation). Utilizing the combination of timing of presentation, clinical symptoms, histopathology, and radiographic findings should increase rates of early diagnosis, treatment, and prognostication of these severe illness states.

Unicentric castleman disease complicated by paraneoplastic bronchiolitis obliterans and pemphigus.

Bronchiolitis obliterans (BO) and paraneoplastic pemphigus are rare and ominous complications of Castleman disease. Collectively, these processes have been reported as part of paraneoplastic autoimmune multiorgan syndrome (PAMS), and they can occur in the setting of various hematologic malignant tumors, carcinoid tumors, and melanoma. Irrespective of the underlying malignancy driving PAMS, the clinical outcomes are uniformly poor, and there are no standard treatment regimens, given the clinical rarity of the syndrome. We describe 2 patients with unicentric Castleman disease complicated by paraneoplastic pemphigus and bronchiolitis obliterans. In addition to primary surgical resection for Castleman disease, we also used therapy from a treatment protocol used for bronchiolitis obliterans resulting from hematopoietic stem cell transplant (HSCT). We were able to treat the patients using intravenous immunoglobulin; rituximab; fluticasone, azithromycin, and montelukast (FAM); and rosuvastatin therapy. One patient demonstrated a favorable response, while the other demonstrated minimal response to this therapy.

Pneumocytic adenomyoepithelioma: A case providing support for the benignity of this extremely rare pulmonary neoplasm.

Pneumocytic adenomyoepithelioma is an extremely rare and poorly understood pulmonary neoplasm, so experience with this tumor is limited. Since the initial case series where the lesion was first proposed as a distinctive entity, only one additional report has been described. We present a case of pneumocytic adenomyoepithelioma with clinical and radiologic data that provide the first long-term evidence of the benignity of this extremely rare pulmonary neoplasm. We also review the available literature surrounding pneumocytic adenomyoepitheliomas. Our case provides important new data on the behavior of this lesion, as imaging studies showed essentially stable or very slowly progressive disease over the course of approximately 9 years. Collectively, this rare and poorly described lesion appears to behave in an indolent or benign fashion, a notion that our case further supports.

Monster Lung Cavity in a Heart Transplant Recipient.

Invasive mucormycosis infections occur in less than 1% of recipients of orthotopic heart transplants. Given the angioinvasive nature of these infections, the mortality rate is high. Little literature exists regarding the presentation and management of these infections. We present a case of a patient who developed an infection after orthotopic heart transplant, describe the successful multidisciplinary management surrounding his care, and review the available literature regarding mucormycosis infections in heart transplant recipients.

VV-ECMO-Assisted High-Risk Endobronchial Stenting as Rescue for Asphyxiating Mediastinal Mass.

The use of venovenous extracorporeal membrane oxygenation (VV-ECMO) has traditionally been limited to a narrow set of clinical circumstances, such as acute hypoxic respiratory failure, submassive pulmonary embolism, and cardiopulmonary collapse. Within the pediatric population, there have been cases of VV-ECMO in the context of extrinsic airway compression by a mediastinal mass, typically in the setting of either a lymphoma or germ cell tumors. However, the use of VV-ECMO for adults with extrinsic airway compression is comparatively limited. More specifically, VV-ECMO has been used as a bridge for tracheal reconstruction in both children and adults. Although, it has not been used in adults in the context of palliative endobronchial stent placement. We present a case of a 49-year-old woman with refractory multiple myeloma and extramedullary plasmacytoma presenting with acute hypoxic respiratory failure from extrinsic airway compression by a mediastinal plasmacytoma. We were able to use VV-ECMO to assist with endobronchial stent placement, followed by radiation therapy, and ultimately hospital discharge. In this article, we also review the literature surrounding VV-ECMO for extrinsic airway compression.

Intrathoracic ganglioneuroma presenting as an endobronchial mass.

Peripheral nerve sheath tumors (PNST) are exceedingly rare, especially outside of the posterior mediastinum. These tumors represent less than 1% of pulmonary tumors. Very few pulmonary PNSTs are ganglioneuromas. We present a case of a ganglioneuroma presenting as an endobronchial mass. CASE PRESENTATION: An 80 year old male was seen in pulmonary clinic for routine cancer screening. He had a 60-pack year smoking history. CT evaluation noted a 1cm right lower lobe endobronchial lesion. This lesion was present since 2012 and had slightly increased in size since that time from 8mm (Figure 1). The lesion was further assessed using virtual bronchoscopy (Figure 2). Bronchoscopy revealed an obstructing lesion, which was completely excised with the snare (Figure 3). Pathology revealed well-circumscribed tumor consisting of nests and trabeculae of round/polygonal cells with granular eosinophilic and basophilic cytoplasm. The tumor was chromogranin, synaptophysin, S-100, pancytokeratin, SOX10, and TTF-1 positive, consistent with a ganglioneuroma. DISCUSSION: Aside from a solitary article regarding 75 patient samples (which included only one ganglioneuroma) only a small number of intrathoracic PNSTs have been reported. Only a single case report of an endobronchial ganglioneuroma has been reported. Each of these lesions were benign, and detected on routine imaging evaluations. CONCLUSIONS: An intrapulmonary endobronchial location for a PNST is an exceedingly rare presentation of an already uncommon pathology.

Characterization of a novel radiation-induced sarcoma cell line.

BACKGROUND: Radiation-induced sarcoma (RIS) is a potential complication of cancer treatment. No widely available cell line models exist to facilitate studies of RIS. METHODS: We derived a spontaneously immortalized primary human cell line, UACC-SARC1, from a RIS. RESULTS: Short tandem repeat (STR) profiling of UACC-SARC1 was virtually identical to its parental tumor. Immunohistochemistry (IHC) analysis of the tumor and immunocytochemistry (ICC) analysis of UACC-SARC1 revealed shared expression of vimentin, osteonectin, CD68, Ki67 and PTEN but tumor-restricted expression of the histiocyte markers α1-antitrypsin and α1-antichymotrypsin. Karyotyping of the tumor demonstrated aneuploidy. Comparative genomic hybridization (CGH) provided direct genetic comparison between the tumor and UACC-SARC1. Sequencing of 740 mutation hotspots revealed no mutations in UACC-SARC1 nor in the tumor. NOD/SCID gamma mouse xenografts demonstrated tumor formation and metastasis. Clonogenicity assays demonstrated that 90% of single cells produced viable colonies. NOD/SCID gamma mice produced useful patient-derived xenografts for orthotopic or metastatic models. CONCLUSION: Our novel RIS strain constitutes a useful tool for pre-clinical studies of this rare, aggressive disease. UACC-SARC1 is an aneuploid cell line with complex genomics lacking common oncogenes or tumor suppressor genes as drivers of its biology. The UACC-SARC1 cell line will enable further studies of the drivers of RIS.

Aminolevulinic acid (ALA): photodynamic detection and potential therapeutic applications.

Aminolevulinic acid (ALA) is a heme precursor that may have potential applications for photodynamic detection and photodynamic therapy-based treatment of solid tumors in a variety of malignancies. ALA may have a role in other applications in surgical oncology based on its ability to discriminate neoplastic tissue from adjacent normal tissue. In this review, we provide a comprehensive summary of the published studies of ALA in noncutaneous solid malignancies.

In Vitro Assessment of the Inflammatory Breast Cancer Cell Line SUM 149: Discovery of 2 Single Nucleotide Polymorphisms in the RNase L Gene.

BACKGROUND: Inflammatory breast cancer (IBC) is a rare, highly aggressive form of breast cancer. The mechanism of IBC carcinogenesis remains unknown. We sought to evaluate potential genetic risk factors for IBC and whether or not the IBC cell lines SUM149 and SUM190 demonstrated evidence of viral infection. METHODS: We performed single nucleotide polymorphism (SNP) genotyping for 2 variants of the ribonuclease (RNase) L gene that have been correlated with the risk of prostate cancer due to a possible viral etiology. We evaluated dose-response to treatment with interferon-alpha (IFN-α); and assayed for evidence of the putative human mammary tumor virus (HMTV, which has been implicated in IBC) in SUM149 cells. A bioinformatic analysis was performed to evaluate expression of RNase L in IBC and non-IBC. RESULTS: 2 of 2 IBC cell lines were homozygous for RNase L common missense variants 462 and 541; whereas 2 of 10 non-IBC cell lines were homozygous positive for the 462 variant (p= 0.09) and 0 of 10 non-IBC cell lines were homozygous positive for the 541 variant (p = 0.015). Our real-time polymerase chain reaction (RT-PCR) and Southern blot analysis for sequences of HMTV revealed no evidence of the putative viral genome. CONCLUSION: We discovered 2 SNPs in the RNase L gene that were homozygously present in IBC cell lines. The 462 variant was absent in non-IBC lines. Our discovery of these SNPs present in IBC cell lines suggests a possible biomarker for risk of IBC. We found no evidence of HMTV in SUM149 cells. A query of a panel of human IBC and non-IBC samples showed no difference in RNase L expression. Further studies of the RNase L 462 and 541 variants in IBC tissues are warranted to validate our in vitro findings.