Serial Thoracic Transforaminal Epidural Steroid Injections for Post-herpetic Neuralgia: A Case Report.

The chronic neuropathic pain of post-herpetic neuralgia (PHN) often persists for months or years after the acute herpes zoster (shingles) episode, may be severe and intractable, and can severely impact the overall quality of life. Antivirals, analgesics, and nerve blocks can effectively shorten the course of shingles and may help to prevent PHN. Although vaccination effectively prevents shingles and PHN, current therapies may be ineffective, and pain management can be challenging when PHN occurs. A 78-year-old female with severe PHN pain in the right thoracolumbar spine, right flank, and right lower abdomen showed poor responses to treatment with amitriptyline, gabapentin, and oxycodone/acetaminophen. However, a series of three thoracic transforaminal epidural steroid injections (TFESIs) effectively treated the PHN and achieved near-complete pain resolution. TFESI can be considered an early and first-choice treatment for PHN, but several courses may be required to achieve adequate and prolonged symptom control.

Airway Hygiene in COVID-19 Pneumonia: Treatment Responses of 3 Critically Ill Cruise Ship Employees.

BACKGROUND COVID-19, the disease entity caused by the novel severe acute respiratory coronavirus 2 (SARS-CoV-2), continues to pose a major therapeutic challenge for clinicians. At present, an effective treatment regimen and vaccination has not been established. Many patients develop severe symptoms requiring endotracheal intubation and a prolonged stay in the Intensive Care Unit (ICU). In early postmortem examinations of COVID-19 patients, profuse viscous secretions were observed throughout the respiratory tract. Thus, oxygen supplementation without aggressive pulmonary hygiene management may be suboptimal. In the present case series, pulmonary hygiene management encompassed mucolytics, bronchodilators, and tracheal suctioning. We report 3 severe cases of COVID-19 pneumonia in cruise ship employees who were admitted to the ICU and responded to supportive mechanical ventilation and pulmonary hygiene management. CASE REPORT Three cruise ship employees with COVID-19 underwent endotracheal intubation and were admitted to the ICU for acute hypoxemic respiratory failure. Initial chest X-rays suggested multifocal pneumonia with superimposed acute respiratory distress syndrome (ARDS). A regimen of hydroxychloroquine, azithromycin, and dexamethasone was initiated on admission in all cases. Additionally, medications used for pulmonary hygiene were administered through a metered-dose inhaler (MDI) in line with the ventilator circuit. Endotracheal suctioning was performed prior to medication administration. The duration from endotracheal intubation to extubation ranged from 9 to 24 days. All 3 patients reached 30-day survival. CONCLUSIONS The cases reported highlight the importance of the use of airway hygiene with mucolytics, bronchodilators, and tracheal suctioning for patients with COVID-19 pneumonia requiring ventilatory support.

Treatment of Severe COVID-19 with Tocilizumab Mitigates Cytokine Storm and Averts Mechanical Ventilation During Acute Respiratory Distress: A Case Report and Literature Review.

COVID-19, caused by the novel severe acute respiratory coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China, in 2019 and has resulted in the current pandemic. The disease continues to pose a major therapeutic challenge. Patient mortality is ultimately caused by acute respiratory distress syndrome (ARDS). Cytokine release syndrome (or "cytokine storm") is likely to be a contributing factor to ARDS in many patients. Because interleukin 6 (IL-6) is known to play a key role in inflammation, IL-6 receptor inhibitors such as tocilizumab may potentially treat COVID-19 by attenuating cytokine release. We present the case of a 48-year-old male with severe COVID-19, on the verge of meeting intubation requirements, who needed progressive oxygen support for respiratory distress. The patient was treated with a non-weight-based dosage of tocilizumab to prevent the onset of a cytokine storm. We chose to administer an IL-6 inhibitor because of the gradually increasing levels of acute phase reactants identified on serial blood draws, as well as his declining respiratory status. The treatment was well-tolerated in conjunction with standard drug therapies for COVID-19 (hydroxychloroquine, azithromycin, and zinc). The patient subsequently experienced marked improvements in his respiratory symptoms and overall clinical status over the following days. We believe that tocilizumab played a substantial role in his ability to avert clinical decline, particularly the need for mechanical ventilation. Ultimately, the patient was downgraded from the ICU and discharged within days. We highlight the potential of IL-6 inhibitors to prevent the progression of respiratory disease to a point requiring ventilator support. This case underscores the potential importance of early serial measurements of IL-6 and cytokine storm-associated acute phase reactants, such as ferritin, D-dimer, and C-reactive protein, in guiding clinical decision-making in the management of patients with suspected COVID-19. Conclusion: The early, proactive identification of serum acute phase reactants should be implemented in the treatment of COVID-19 in order to screen for a primary contributor to mortality-the cytokine storm. This screening, when followed by aggressive early treatment for cytokine storm, may have optimal therapeutic benefits and obviate the need for mechanical ventilation, thereby decreasing mortality. Additionally, we review current evidence regarding cytokine release syndrome in COVID-19 and the use of IL-6 receptor inhibition as a therapeutic strategy, and examine other reported cases in the literature describing IL-6 antagonist treatment for patients with COVID-19.

Effects of Intratympanic Dexamethasone on High-Dose Radiation Ototoxicity In Vivo.

BACKGROUND: Stereotactic radiosurgery for lateral skull base tumors can cause hearing loss when the cochleae are exposed to high doses of single-fraction radiation. Currently, there are no known nondosimetric preventative treatments for radiation-induced ototoxicity. HYPOTHESIS: Intratympanic (IT) dexamethasone (DXM), a synthetic steroid, protects against radiation-induced auditory hair cell (HC) and hearing losses in rats in vivo. METHODS: Seven rats received radiation (12 Gy) to both cochleae. In irradiated rats and six nonirradiated rats, IT DXM was randomized to one ear, while tympanic puncture without DXM was performed on the contralateral ear. Baseline and 4-week postradiation auditory-evoked potential tests were performed. The cochleae were processed for HC viability. RESULTS: Cochleae exposed to radiation demonstrated more outer HC (OHC) loss in all turns than nonirradiated ears (p <0.05). OHCs were more susceptible to radiation injury than inner HCs in the middle and basal turns (p <0.05). In irradiated cochleae, there was a nonsignificant trend for less OHC loss with IT DXM in the basal turn when compared with placebo. IT DXM did not improve radiation-induced hearing threshold shifts; however, a high rate of tympanic membrane perforations occurred with irradiated ears which may contribute to this finding. CONCLUSION: Radiation induced loss of OHCs in all turns of the cochlea. IT DXM reduced OHC loss in the basal turn of irradiated ears; however, this finding did not achieve statistical significance. Although IT DXM did not affect radiation-induced hearing threshold shifts in adult rats in vivo, this may be due to a high rate of tympanic membrane perforations.

Dexamethasone Protects Against Apoptotic Cell Death of Cisplatin-exposed Auditory Hair Cells In Vitro.

HYPOTHESIS: Dexamethasone (DXM) protects against cisplatin-induced auditory hair cell (HC) loss in rat organ of Corti (OC) explants in vitro by reducing levels of oxidative stress and NADPH-Oxidase-3 (NOX-3). BACKGROUND: Intratympanic DXM has demonstrated protective effects against cisplatin-induced hearing loss in a few animal studies and one clinical trial. However, levels of protection with intratympanic DXM vary significantly between studies, which may not be a result of the intrinsic properties of DXM but rather reflect the diffusion of DXM into the cochlea. The molecular mechanisms and degree of DXM protection against cisplatin ototoxicity are currently unknown. METHODS: OC explants from 3-day-old rats were cultured with no treatment or various concentrations of cisplatin (2, 5, or 10 µM) and DXM (75, 150, or 300 µg/mL) in vitro. HC viability and TUNEL assay were performed after 72 hours in vitro and levels of oxidative stress and NOX-3 were evaluated with confocal microscopy after 48 hours in vitro. Analysis of variance with Tukey's post hoc testing was performed. RESULTS: Cisplatin initiated dose-dependent losses of outer HCs (OHCs) in the basal turns of exposed explants (p < 0.001). DXM protected against cisplatin (2 µM)-induced OHC loss in a dose-dependent manner with complete protection at 300 µg/mL of DXM (p < 0.001). DXM (150 µg/mL) significantly reduced levels of oxidative stress, NOX-3, and apoptosis in the basal turn of explants exposed to cisplatin (2 µM). CONCLUSIONS: DXM protects against cisplatin-induced loss of OHCs in the basal turn of rat OC explants as demonstrated by reductions in oxidative stress and NOX-3 production and decreased levels of apoptotic cell death.

Dexamethasone Protects Against Radiation-induced Loss of Auditory Hair Cells In Vitro.

HYPOTHESIS: Dexamethasone (DXM) protects against radiation-induced loss of auditory hair cells (HCs) in rat organ of Corti (OC) explants by reducing levels of oxidative stress and apoptosis. BACKGROUND: Radiation-induced sensorineural hearing loss (HL) is progressive, dose-dependent, and irreversible. Currently, there are no preventative therapeutic modalities for radiation-induced HL. DXM is a synthetic steroid that can potentially target many of the pathways involved in radiation-induced ototoxicity. METHODS: Whole OC explants were dissected from 3-day-old rat cochleae exposed to specific dosages of single-fraction radiation (0, 2, 5, 10, or 20 Gy), were either untreated or treated with DXM (75, 150, 300 µg/mL), and then cultured for 48 or 96 hours. Confocal microscopy for oxidative stress (CellRox, 48 h) and apoptosis (TUNEL assay, 96 h) and fluorescent microscopy for viable HC counts (fluorescein isothiocyanate-phalloidin, 96 h) were performed. Analysis of variance and Tukey post hoc testing were used for statistical analysis. RESULTS: Radiation exposure initiated dose-dependent losses of inner and outer HCs, predominantly in the basal turns of the OC explants. DXM protected against radiation-induced HC losses in a dose-dependent manner. DXM significantly reduced levels of oxidative stress and apoptosis in radiation-injured OC explants (p < 0.001). CONCLUSIONS: Radiation-initiated HC losses were dose-dependent in OC explants. DXM treatment protected explant HCs against radiation-initiated losses by decreasing the levels of oxidative stress and apoptosis. DXM may potentially be a therapeutic modality for preventing radiation-induced HL; further in vivo studies are necessary.

Short interfering RNA against Bax attenuates TNFα-induced ototoxicity in rat organ of Corti explants.

OBJECTIVE: Evaluate the effectiveness of short interfering RNA against Bax (Bax siRNA) as a treatment for tumor necrosis factor α (TNFα)-induced auditory hair cell (HC) loss in rat organ of Corti (OC) explants. STUDY DESIGN: Basic science. SETTING: Basic science laboratory, University of Miami Ear Institute. METHODS: Organ of Corti explants dissected from 3-day-old rats were cultured in control media, TNFα, and TNFα + Bax siRNA at 0, 48, and 72 hours in vitro. Real-time polymerase chain reaction, enzyme-linked immunosorbent assay, HC viability studies, immunofluorescence, and confocal microscopy were performed. Analysis of variance with post hoc testing was used with P < .05 considered significant. RESULTS: The TNFα-damaged explants demonstrated significant decreases in viable HCs in the basal turn with corresponding increased levels of Bax gene and protein expression, compared with control explant levels. The levels of viable HCs and Bax gene and protein expression in TNFα + Bax siRNA-treated explants approached levels measured in control explants. Immunolocalization studies showed increased Bax protein expression in basal turn HCs in TNFα-treated explants, whereas control explants and TNFα + Bax siRNA-treated explants had low levels of Bax expression. CONCLUSION: TNFα initiates the programmed cell death of auditory HCs in OC explants through upregulation of proapoptotic Bax gene and protein expression. Bax siRNA blocks TNFα-induced apoptosis of HCs by decreasing the TNFα-induced levels of Bax mRNA and protein expression in treated explants. Bax siRNA is an effective treatment for TNFα-induced ototoxicity in OC explants in vitro and has great potential to be a therapeutic agent against trauma/inflammation-induced hearing loss.

Mannitol protects hair cells against tumor necrosis factor α-induced loss.

HYPOTHESIS: Mannitol has otoprotective effects against tumor necrosis factor (TNF) α-induced auditory hair cell (HC) loss. BACKGROUND: Mannitol has been demonstrated to possess cytoprotective effects in several organ systems. Its protective effect on postischemic hearing loss has also been shown. Mannitol's otoprotective mechanism and site of action are at present unknown. MATERIALS AND METHODS: Organ of Corti (OC) explants were dissected from 3 day-old rat pups. The safety (nonototoxicity) of mannitol was assessed at 4 different concentrations (1-100 mM). Three experimental arms were designed including: a control group, TNFα group, and TNFα + mannitol group. Cell viability was determined by counts of fluorescein isothiocyanate (FITC) phalloidin stained HC. Immunofluorescence assay of phospho-c-Jun and the proapoptotic mediators, cleaved caspase-3, apoptosis inducing factor (AIF), and endonuclease G (Endo G) were performed. RESULTS: Analysis of HC density confirmed the safety of mannitol at concentration ranges of 1 to 100 mM. The ototoxic effect of TNFα was demonstrated (p < 0.05). The otoprotective effect of 100 mM mannitol in TNFα-challenged OC explants was also demonstrated (p < 0.001). Mannitol treatment reduced the high levels of phospho-c-Jun observed in the TNFα-challenged group. AIF cluster formation and EndoG translocation into the nuclei of HCs were also reduced by mannitol treatment. CONCLUSION: Mannitol significantly reduces the ototoxic effects of TNFα against auditory HC's potentially by inhibiting c-Jun N terminal kinase (JNK) activation pathway and AIF, EndoG nuclear translocation. This local otoprotective effect may have therapeutic implications in inner ear surgery, for example, cochlear implants, protection of residual hearing, as well as implications for postischemic inner ear insults.