An Infrequently Encountered Cause of Hemoptysis.

Mitral stenosis (MS) is not a common entity in modern-day medicine, especially in developed countries, as the most common etiology is still rheumatic fever. MS can present mainly with a wide range of cardiac symptoms. However, infrequently, MS can cause extra-cardiac symptoms as well. We present a case report of a patient with severe bioprosthetic mitral valve stenosis with intermittent hemoptysis and cardiogenic shock. We aim to report this case to remind clinicians about this uncommon but significant cause of hemoptysis. This case report also emphasizes the importance of utilizing a team approach while treating patients with severe MS, especially if they have serious complications that could be life-threatening. We also aim to add to the current literature by reporting this case.

Association of hypoglossal nerve stimulator response with machine learning identified negative effort dependence patterns.

BACKGROUND: Hypoglossal nerve stimulator (HGNS) is a therapeutic option for moderate to severe obstructive sleep apnea (OSA). Improved patient selection criteria are needed to target those most likely to benefit. We hypothesized that the pattern of negative effort dependence (NED) on inspiratory flow limited waveforms recorded during sleep, which has been correlated with the site of upper airway collapse, would contribute to the prediction of HGNS outcome. We developed a machine learning (ML) algorithm to identify NED patterns in pre-treatment sleep studies. We hypothesized that the predominant NED pattern would differ between HGNS responders and non-responders. METHODS: An ML algorithm to identify NED patterns on the inspiratory portion of the nasal pressure waveform was derived from 5 development set polysomnograms. The algorithm was applied to pre-treatment sleep studies of subjects who underwent HGNS implantation to determine the percentage of each NED pattern. HGNS response was defined by STAR trial criteria for success (apnea-hypopnea index (AHI) reduced by > 50% and < 20/h) as well as by a change in AHI and oxygenation metrics. The predominant NED pattern in HGNS responders and non-responders was determined. Other variables including demographics and oxygenation metrics were also assessed between responders and non-responders. RESULTS: Of 45 subjects, 4 were excluded due to technically inadequate polysomnograms. In the remaining 41 subjects, ML accurately distinguished three NED patterns (minimal, non-discontinuous, and discontinuous). The percentage of NED minimal breaths was significantly greater in responders compared with non-responders (p = 0.01) when the response was defined based on STAR trial criteria, change in AHI, and oxygenation metrics. CONCLUSION: ML can accurately identify NED patterns in pre-treatment sleep studies. There was a statistically significant difference in the predominant NED pattern between HGNS responders and non-responders with a greater NED minimal pattern in responders. Prospective studies incorporating NED patterns into predictive modeling of factors determining HGNS outcomes are needed.

Randomized Open Investigation Determining Steroid Dose in Severe COVID-19: The ROIDS-Dose Clinical Trial.

Introduction Treatment with dexamethasone reduces mortality in patients with coronavirus disease 2019 (COVID-19) pneumonia requiring supplemental oxygen, but the optimal dose has not been determined. Objective To determine whether weight-based dexamethasone of 0.2 mg/kg is superior to 6 mg daily in reducing 28-day mortality in patients with COVID-19 and hypoxemia. Materials and methods A multicenter, open-label, randomized clinical trial was conducted between March 2021 and December 2021 at seven hospitals within Northwell Health. A total of 142 patients with confirmed COVID-19 and hypoxemia were included. Participants were randomized in a 1:1 ratio to dexamethasone 0.2 mg/kg intravenously daily (n = 70) or 6 mg daily (n = 72) for up to 10 days. Results There was no statistically significant difference in the primary outcome of 28-day all-cause mortality with deaths in 12 of 70 patients (17.14%) in the intervention group and 15 of 72 patients (20.83%) in the control group (p = 0.58). There were no statistically significant differences among the secondary outcomes. Conclusion In patients with COVID-19 and hypoxemia, the use of weight-based dexamethasone dosing was not superior to dexamethasone 6 mg in reducing all-cause mortality at 28 days. Clinical trial registration This study was registered under ClinicalTrials.gov (identifier: NCT04834375).

Effective use of monoclonal antibodies for treatment of persistent COVID-19 infection in a patient on rituximab.

As we are over a year into the COVID-19 pandemic, we have made many forward strides in therapeutics. These treatments, such as monoclonal antibodies, have help mitigate the detrimental and often fatal consequences of COVID-19. The current indication for the use of monoclonal antibodies is mild to moderate COVID-19 infection within 10 days of symptom onset in those who are at high risk of progression to severe disease. However, their role in patients with prolonged symptoms is not clear. We present a unique case of monoclonal antibodies use after 54 days of symptom onset in an immunosuppressed patient with persistent COVID-19 infection despite standard treatment. This case illustrates the potential use of monoclonal antibodies outside of the current recommended therapeutic window in immunosuppressed patients, who may have difficulty with viral clearance.

Insomnia: Pharmacologic Treatment.

Insomnia afflicts many geriatric patients worldwide and results in both clinical and economic consequences. Prescribing hypnotics to the elderly is particularly challenging due to multitudes of adverse effects and drug interactions. Although benzodiazepines and "Z" drugs such as zolpidem have been popular in the past, they carry a high risk of adverse effects in the elderly, such as devastating falls and injuries as well as potentially an increase in mortality. Newer classes of hypnotics such as dual orexin receptor antagonists are much better tolerated and can be explored as a potential treatment for insomnia in the elderly.

Space invader: pleural penetration of a hypoglossal nerve stimulator sensor lead.

The mainstay of treatment for obstructive sleep apnea is positive airway pressure therapy, which may be difficult for some patients to tolerate leading to compromised adherence and requiring alternative therapies. Hypoglossal nerve stimulation has become an option for those who meet implantation criteria. Implantation of the device is an ambulatory surgical procedure and is generally well-tolerated, though rare adverse events have been reported. We report an unusual complication of hypoglossal nerve stimulation in a patient who had initial success with this therapy. After 3 years of treatment, the sensor lead penetrated into the pleural space. Components of the hypoglossal nerve stimulation were explanted, and a new sensor lead and generator were reimplanted. The new device was activated, and therapy was successfully resumed. This case demonstrates that there is a potential for a delayed complication of sensor lead penetration into the pleural space, which has only rarely been reported. CITATION: Lou B, Hahn S, Korotun M, Quintero L, Shikowitz M, Greenberg H. Space invader: pleural penetration of a hypoglossal nerve stimulator sensor lead. J Clin Sleep Med. 2021;17(11):2329-2332.

Advances in Treatment of Sleep-Disordered Breathing.

BACKGROUND: Sleep-disordered breathing, composed of obstructive sleep apnea (OSA) and central sleep apnea (CSA), affects millions of people worldwide carrying with it significant morbidity and mortality. Diagnosis is made by polysomnography, and severity of sleep apnea is determined by the apnea-hypopnea index (AHI). Positive airway pressure (PAP) therapy has been the gold standard in treating both OSA and CSA. PAP therapy can greatly reduce AHI burden as well as morbidity and mortality and improve quality of life. AREAS OF UNCERTAINTY: However, patients report difficulties adhering to PAP therapy because of discomfort with mask interface, sensation of excessive pressure, and claustrophobia. Although other options exist to treat sleep apnea, such as mandibular advancement oral appliance devices, positional therapy, and surgery, these additional therapeutic modalities as current options have limitations. Emerging technology is now available to overcome hindrances to standard therapy. DATA SOURCES: A literature search was performed from the following databases: PubMed, Cochrane Library (Cochrane Database of Systematic Reviews), and Cochrane Central Register of Controlled Trials, and FDA device database (clinicaltrial.gov). THERAPEUTIC ADVANCES: Other modalities of treating sleep-disordered breathing now include the hypoglossal nerve stimulator, which stimulates the hypoglossal nerve during sleep to alleviate airflow obstruction by contracting the genioglossus muscle thus treating OSA. Similarly, the phrenic nerve stimulator restores a more stable breathing pattern during sleep by stimulating the phrenic nerve to activate the diaphragm during CSA. Both nerve stimulators have been shown to reduce AHI severity and improve quality of life for patients suffering from sleep-disordered breathing. CONCLUSIONS: PAP therapy, although the gold standard, has limitations in the treatment of sleep apnea. New modalities such as hypoglossal nerve stimulator and phrenic nerve stimulator may help to overcome difficulties with adherence and offer new options for treatment of both obstructive and central sleep apnea.

Acute Respiratory Failure Associated With Vaping.

The use of e-cigarettes to deliver aerosolized nicotine has gained popularity in recent years. Numerous reports have cited the development of acute pulmonary disease linked to vaping nicotine as well as marijuana-based products. As cultural attitudes evolve and policies shift toward the legalization of marijuana, its use has become more prevalent. Given the increased prevalence of marijuana consumption and e-cigarette usage, better insight into its potential to cause lung toxicity is warranted. The clinical, radiographic, and histopathologic characteristics of lung injury associated with vaping, particularly with marijuana-based products, have yet to be well described in the literature. We present eight patients, most of whom were admitted recently to our institution with acute respiratory failure following vaping. The majority of patients were young, with a median age of 31.5 years (range, 24-62 years) and with no known underlying lung disease. This case series highlights common clinical findings as well as the varied radiographic and histopathologic features of acute respiratory failure associated with vaping predominantly marijuana-based products. As more cases of vaping-associated pulmonary injury unfold, data will be available to further characterize this emerging disease entity. Improved understanding of disease pathogenesis and its clinical course will help clinicians determine optimal management and follow-up strategies for this patient population.

Ultrasound Billing for Intensivists.

Point-of-care ultrasonography is a key skill for the critical care clinician and is gaining widespread acceptance by clinicians in all areas of medicine. In addition to mastery of image acquisition, image interpretation, and clinical application, intensivists need to be adept with billing for their scanning activity. This article summarizes the requirements for documentation and image storage that must be met to obtain reimbursement for point-of-care ultrasonography services.

Acquiring Metastatic Competence by Oral Squamous Cell Carcinoma Cells Is Associated with Differential Expression of α-Tubulin Isoforms.

We performed comparative global proteomics analyses of patient-matched primary (686Tu) and metastatic (686Ln) OSCC cells. The metastatic OSCC 686Ln cells showed greater in vitro migratory/invasive potential and distinct cell shape from their parental primary 686Tu cells. Ettan DIGE analysis revealed 1316 proteins spots in both cell lines with >85% to be quantitatively similar (<2 folds) between the two cell lines. However, two protein spots among four serial spots were highly dominant in 686Ln cells. Mass spectrometry sequencing demonstrated all four spots to be α-tubulin isotypes. Further analysis showed no significant quantitative difference in the α-tubulin between the two cell lines either at mRNA or protein levels. Thus, two distinct isoforms of α-tubulin, probably due to posttranslational modification, were associated with metastatic 686Ln cells. Immunofluorescence demonstrated remarkable differences in the cytosolic α-tubulin distribution patterns between the two cells. In 686Tu cells, α-tubulin proteins formed a normal network composed of filaments. In contrast, α-tubulin in 686Ln cells exhibited only partial cytoskeletal distribution with the majority of the protein diffusely distributed within the cytosol. Since α-tubulin is critical for cell shape and mobility, our finding suggests a role of α-tubulin isoforms in acquisition of metastatic phenotype and represents potential target for therapeutic intervention.

Ataxia telangiectasia-mutated damage-signaling kinase- and proteasome-dependent destruction of Mre11-Rad50-Nbs1 subunits in Simian virus 40-infected primate cells.

Although the mechanism of simian virus 40 (SV40) DNA replication has been extensively investigated with cell extracts, viral DNA replication in productively infected cells utilizes additional viral and host functions whose interplay remains poorly understood. We show here that in SV40-infected primate cells, the activated ataxia telangiectasia-mutated (ATM) damage-signaling kinase, gamma-H2AX, and Mre11-Rad50-Nbs1 (MRN) assemble with T antigen and other viral DNA replication proteins in large nuclear foci. During infection, steady-state levels of MRN subunits decline, although the corresponding mRNA levels remain unchanged. A proteasome inhibitor stabilizes the MRN complex, suggesting that MRN may undergo proteasome-dependent degradation. Analysis of mutant T antigens with disrupted binding to the ubiquitin ligase CUL7 revealed that MRN subunits are stable in cells infected with mutant virus or transfected with mutant viral DNA, implicating CUL7 association with T antigen in MRN proteolysis. The mutant genomes produce fewer virus progeny than the wild type, suggesting that T antigen-CUL7-directed proteolysis facilitates virus propagation. Use of a specific ATM kinase inhibitor showed that ATM kinase signaling is a prerequisite for proteasome-dependent degradation of MRN subunits as well as for the localization of T antigen and damage-signaling proteins to viral replication foci and optimal viral DNA replication. Taken together, the results indicate that SV40 infection manipulates host DNA damage-signaling to reprogram the cell for viral replication, perhaps through mechanisms related to host recovery from DNA damage.