Comparison of side effects of different steroids used in intratympanic injections.

OBJECTIVES: This study aimed to compare the side effects of different steroids used in the intratympanic injections (IT). METHODS: One hundred and sixty patients diagnosed with sudden sensorineural hearing loss and undergoing IT were assigned to four groups based on the type or concentration of steroids administered (Group DM5: 5 mg/ml Dexamethasone sodium phosphate; Group DM10: 10 mg/ml Dexamethasone sodium phosphate; Group MP: 40 mg/ml Methylprednisolone sodium succinate; Group BM: 4 mg/ml Betamethasone sodium phosphate). Each group comprised 40 patients, and all participants received IT six times. The study assessed and compared the degrees and duration of pain, dizziness, and tympanic membrane damage following IT. Patients were asked to report the pain they felt using the numeric rating scale (NRS). RESULTS: NRS scores for pain after IT showed significant differences among the four groups (p < 0.001). The average NRS scores for pain in each group were as follows: Group DM5: 1.53 ± 1.04; Group DM10: 1.45 ± 1.30; Group MP: 4.33 ± 2.22; Group BM: 6.03 ± 1.46. The durations of pain after IT also exhibited significant differences among the four groups (p < 0.001), with the longest duration observed in Group MP at 31.93 ± 15.20 min. CONCLUSION: Different types of steroids could lead to varying degrees of pain when used in IT. Betamethasone could cause the most severe pain, and methylprednisolone could result in the longest duration of pain.

Sudden irreversible hearing loss post COVID-19.

Sudden onset sensorineural hearing loss (SSNHL) is frequently seen by otolaryngologists. The exact pathophysiology of the disease is still unknown, with the most likely causative factor being following a viral infection. Immediate steroids are the best treatment to improve prognosis. Despite a plethora of papers in the literature describing SSNHL, there are only a few reported cases of hearing loss following COVID-19, none of which have been reported in the UK. This paper presents the first UK case of SSNHL following COVID-19. Physical examination and imaging excluded any other cause of hearing loss. A literature review showed that four other cases have been previously described. Hearing loss can be a significant cause of morbidity and can easily be missed in the intensive care setting. Being aware and screening for SSNHL following COVID-19 enables an early course of steroids, which offers the best chance of recovering hearing.

Compatible stability of methylprednisolone sodium succinate and tropisetron in 0.9% sodium chloride injection.

Background: A combination of methylprednisolone sodium succinate and tropisetron hydrochloride is commonly used to treat the nausea and vomiting associated with antineoplastic therapy. The objective of this study was to investigate the stability of tropisetron hydrochloride and methylprednisolone sodium succinate in 0.9% sodium chloride injection for up to 48 hours. Methods: Commercial solutions of methylprednisolone sodium succinate and tropisetron hydrochloride were obtained and further diluted with 0.9% sodium chloride injection to final concentrations of either 0.4 or 0.8 mg/mL (methylprednisolone sodium succinate) and 0.05 mg/mL (tropisetron). The admixtures were assessed for periods of up to 48 hours after storage at 4°C with protection from light and at 25°C without protection from light. Physical compatibility was determined visually, and the chemical compatibility was measured with high-performance liquid chromatography (HPLC) and by measurement of pH values. Results: HPLC analysis demonstrated that methylprednisolone sodium succinate and tropisetron hydrochloride in the various solutions were maintained at 97% of the initial concentrations or higher during the testing period. There were no changes observed by physical precipitation or pH in any of the prepared solutions. Conclusions: Tropisetron hydrochloride injection and methylprednisolone sodium succinate injection in 0.9% sodium chloride injection are stable for up to 48 hours at 4°C and 25°C.

PEGylated Liposomal Methyl Prednisolone Succinate does not Induce Infusion Reactions in Patients: A Correlation Between in Vitro Immunological and in Vivo Clinical Studies.

PEGylated nanomedicines are known to induce infusion reactions (IRs) that in some cases can be life-threatening. Herein, we report a case study in which a patient with rare mediastinal and intracardiac IgG4-related sclerosing disease received 8 treatments of intravenously administered PEGylated liposomal methylprednisolone-succinate (NSSL-MPS). Due to the ethical requirements to reduce IRs, the patient received a cocktail of premedication including low dose of steroids, acetaminophen and H2 blockers before each infusion. The treatment was well-tolerated in that IRs, complement activation, anti-PEG antibodies and accelerated blood clearance of the PEGylated drug were not detected. Prior to the clinical study, an in vitro panel of assays utilizing blood of healthy donors was used to determine the potential of a PEGylated drug to activate complement system, elicit pro-inflammatory cytokines, damage erythrocytes and affect various components of the blood coagulation system. The overall findings of the in vitro panel were negative and correlated with the results observed in the clinical phase.

Hyperbaric oxygen therapy in treatment of sudden sensorineural hearing loss: finding for the maximal therapeutic benefit of different applied pressures.

We compared the efficacy of hyperbaric oxygen (HBO2) therapy used in the treatment of sudden sensorineural hearing loss (SSNHL) as a supplementary therapy to the first-line medical treatment according to the different applied pressures used in HBO2 treatment while maintaining the same number of sessions, periodicity and exposure times. We evaluated data from 115 patients suffering from SSNHL within seven days of hearing loss: 35 patients received the standard treatment protocol (control group), and 80 individuals were treated with additional application of HBO2 therapy pressured to 2.0 ATA (H2.0; n=49) or 2.5 ATA (H2.5; n=31), respectively. Treatment success was assessed using pre- and post-treatment audiograms. We found significant differences in both HBO2 groups compared to the control group. In low frequencies the most significant differences can be seen in both H2.0 and H2.5. In spoken speech frequencies only the H2.0 group was statistically significant. In high frequencies the therapeutic benefits were the lowest. Furthermore, we found a notable difference in the therapeutic effect of HBO2 therapy according to the different applied pressure. At low frequencies, the use of 2.5 ATA pressure was more efficient. However, in the higher frequency ranges, the better hearing gains were obtained at the 2.0 ATA pressure. Our results support the possibility of optimizing treatments individually, depending on the type and frequency range of hearing impairment (shape of the audiogram) in favor of using the 2.0 ATA. This is important in terms of an individual approach to each patient as well as to minimize the burden of a patient in order to obtain the maximum therapeutic effect.

Acute direct traumatic optic neuropathy treated with steroids, minocycline and hyperbaric oxygen: a case report.

We describe the emergency management of a man who experienced acute vision loss diagnosed as direct traumatic optic neuropathy (TON) in his right eye (no light perception) after falling from a height. TON is caused by a high-impact mechanism of injury. Clinical findings include acute vision loss, which is typically immediate, afferent pupillary defect, decreased color vision, and visual field defects. Treatment is controversial because of the lack of strong evidence supporting intervention over observation. In this case report, our treatment strategy comprised immediate hyperbaric oxygen (HBO2) and daily high doses of a steroid. On the second day, minocycline was added to the treatment regimen for its neuroprotective effects. The patient was discharged after receiving six HBO2 treatments and six days of intravenous solumedrol transitioned to oral prednisone. After the third HBO2 treatment, his vision improved to 20/100; after the fourth treatment, it was 20/40 and plateaued. At the time of discharge, it was 20/40. At two-month follow-up, his corrected visual acuity was 20/60+2 in the affected eye. Immediate HBO2 for ischemic and mechanical injury to the optic nerve following trauma is a therapeutic option.

LDL-apheresis-induced remission of focal segmental glomerulosclerosis recurrence in pediatric renal transplant recipients.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) in pediatric patients is typically difficult to treat and will progress to end-stage renal disease (ESRD) in about 10% of cases. Following kidney transplantation, FSGS can recur in up to 56% of renal allografts-with a near 100% recurrence in subsequent transplants. METHODS: Four different pediatric centers across the USA and the UK employed a protocol using LDL-apheresis (LDL-A) and pulse solumedrol to treat recurrent FSGS after transplantation in seven patients. All the patients included in this series demonstrated immediate, or early, recurrence of FSGS, which clinically presented as nephrotic-range proteinuria within hours to days after implantation of the kidney. RESULTS: All patients experienced reductions in urinary protein to creatinine ratios resulting in partial or complete remission. All patients demonstrated improvements in their estimated GFRs at their most recent follow-up since LDL-A discontinuation. CONCLUSIONS: This case series describes the successful treatment, across four different pediatric centers, of seven pediatric patients with recurrent post-transplant FSGS using the Liposorber® LA-15 in combination with pulse solumedrol.

Recurrent Episodes of Diffuse Alveolar Hemorrhage in Systemic Sclerosis 30 Days Apart.

Diffuse alveolar hemorrhage (DAH) is a life-threatening clinicopathologic condition caused by accumulation of intra-alveolar red blood cells (RBCs) after disruption of the alveolar-capillary basement membrane that is often seen as a complication of various diseases, but is rare in systemic sclerosis. A 46-year-old female with systemic sclerosis presented to the emergency department complaining of right-sided chest pain. Initially, her electrocardiogram and chest X-ray (CXR) were unremarkable; however, she progressively decompensated into acute respiratory failure resulting in intubation. Repeat CXR and computed tomography scan showed diffuse bilateral alveolar infiltrates and pleural effusions. Video bronchoscopy with bronchoalveolar lavage showed numerous RBCs, neutrophils, macrophages, and respiratory epithelial cells consistent with acute DAH. She was started on intravenous pulse-dosing Solu-Medrol 1 g daily for 5 days. One month later, the patient returned with intractable nausea and vomiting. Again, she went into acute respiratory distress with a PaO2 of 59 while on a 10-L non-rebreather mask. CXR revealed development of alveolar infiltrates in the right lung. A bronchoscopy with bronchoalveolar lavage again showed numerous RBCs and neutrophils along with staining positive for hemosiderin-laden macrophages. Systemic sclerosis with alveolar hemorrhage is a rare occurrence; however, most cases are single episodes of hemorrhage, whereas we present a case with 2 confirmed episodes within 30 days. Its life-threatening nature makes a systemic approach and aggressive treatment crucial to decreasing morbidity and mortality-making it a diagnosis that should not be overlooked, especially in patients with nonspecific symptoms.

Therapeutic Effect of a Novel Nano-Drug Delivery System on Membranous Glomerulonephritis Rat Model Induced by Cationic Bovine Serum.

In order to explore a novel high efficacy drug delivery system for membranous glomerulonephritis (MGN), a complex chronic inflammation, methylprednisolone bovine serum albumin nanoparticles (ME BSA NPs) were designed. The nanoparticles were prepared by desolvation-chemical crosslinking method and its physicochemical characterizations were conducted. The experimental MGN rat models induced by cationic bovine serum albumin were established by a modified Border's method and applied in the pharmacodynamics study of ME BSA NPs. The results showed that the particle size, particle dispersion index, and entrapment efficiency of ME BSA NPs were 131.1 ± 3.4 nm, 0.159 ± 0.036, and 71.51 ± 1.74%, respectively. In addition, the image of transmission electron microscopy showed that the ME BSA NPs were the relatively uniform spherical particles. In the in vivo pharmacodynamics study, compared with saline group and SOLU-MEDROL® group, that the ME BSA NPs group was significantly reduced the levels of 24 h urinary protein (P < 0.01) and serum creatinine (P < 0.05). Consequently, these outcomes indicated that the nanoparticles we studied were a promising drug delivery system for the MGN disease, and it may be also useful for other complex chronic inflammations.

Nebulization of Cyclic Arginine-Glycine-(D)-Aspartic Acid-Peptide Grafted and Drug Encapsulated Liposomes for Inhibition of Acute Lung Injury.

PURPOSE: Acute lung injury (ALI) is a fatal syndrome in critically ill patients. It is characterized by lung edema and inflammation. Numerous pro-inflammatory mediators are released into alveoli. Among them, interleukin-1beta (IL-1ß) causes an increase in solute permeability across the alveolar-capillary barrier leading to edema. It activates key effector cells (alveolar epithelial and endothelial cells) releasing inflammatory chemokines and cytokines. The purpose of the study was to demonstrate that nebulized liposomes inhibit ALI in vivo. METHODS: In vivo ALI model was simulated through intra-tracheal instillation of IL-1ß solution (100 µg/mL in PBS, pH 7.2, 200 µL) in male Sprague-Dawley rats. Various formulations were tested in ALI induced rats. These formulations include plain liposomes (PL), methylprednisolone sodium succinate solution (MPS solution), cRGD-peptide grafted liposomes (LcRGD) and methylprednisolone sodium succinate encapsulated and cRGD-peptide grafted liposomes (MPS-LcRGD). Formulations were nebulized in vivo in rats using micro-pump nebulizer. RESULTS: Liposome formulations exhibited higher levels of drug concentration in lungs. The physicochemical parameters demonstrated that the liposome formulations were stable. On the basis of aerodynamic droplet-size, nebulized formulations were estimated to deposit in different regions of respiratory tract, especially alveolar region, Among the formulations, MPS-LcRGD caused significant reduction of edema, neutrophil infiltration and inflammation biochemical marker levels. CONCLUSION: From the results, it can be inferred that nebulization of targeted liposomes had facilitated spatial and temporal modulation of drug delivery resulting in alleviation of ALI.

Effect of Treating Acute Optic Neuritis With Bioequivalent Oral vs Intravenous Corticosteroids: A Randomized Clinical Trial.

Importance: Intravenous (IV) administration of corticosteroids is the standard of care in the treatment of acute optic neuritis. However, it is uncertain whether a bioequivalent dose of corticosteroid administered orally, which may be more cost-efficient and convenient for patients, is as effective as IV administration in the treatment of acute optic neuritis. Objective: To determine whether recovery of vision following treatment of acute optic neuritis with a high-dose IV corticosteroid is superior to that with a bioequivalent dose of an oral corticosteroid. Design, Setting, and Participants: This single-blind (participants unblinded) randomized clinical trial with 6-month follow-up was conducted at a single tertiary care center in London, Ontario, Canada. Participants were enrolled from March 2012 to May 2015, with the last participant's final visit occurring November 2015. Patients 18 to 64 years of age presenting within 14 days of acute optic neuritis onset, without any recovery at time of randomization and without history of optic neuritis in the same eye, were screened. Inclusion criteria included best-corrected visual acuity (BCVA) of 20/40 or worse and corticosteroids deemed required by treating physician. In total, 89 participants were screened; 64 were eligible, but 9 declined to participate. Thus, 55 participants were enrolled and randomized. Primary analysis was unadjusted and according to the intention-to-treat principle. Interventions: Participants were randomized 1:1 to the IV methylprednisolone sodium succinate (1000-mg) or oral prednisone (1250-mg) group. Main Outcomes and Measures: Primary outcome was recovery of the latency of the P100 component of the visual evoked potential at 6 months. Secondary outcomes were the P100 latency at 1 month and BCVA as assessed with Early Treatment Diabetic Retinopathy Study letter scores on the alphabet chart and scores on low-contrast letters at 1 and 6 months. Results: Of 55 randomized participants, the final analyzed cohort comprised 23 participants in the IV and 22 in the oral treatment groups. The mean (SD) age of the cohort was 34.6 (9.5) years, and there were 28 women (62.2%). At 6 months' recovery, P100 latency in the IV group improved by 62.9 milliseconds (from a mean [SD] of 181.9 [53.6] to 119.0 [16.5] milliseconds), and the oral group improved by 66.7 milliseconds (from a mean [SD] of 200.5 [67.2] to 133.8 [31.5] milliseconds), with no significant difference between groups (P = .07). Similarly, no significant group difference was found in the mean P100 latency recovery at 1 month. For BCVA, recovery between the groups did not reach statistical significance at 1 month or 6 months. In addition, improvements in low-contrast (1.25% and 2.5%) BCVA were not significantly different between treatment groups at 1 or 6 months' recovery. Conclusions and Relevance: This study finds that bioequivalent doses of oral corticosteroids may be used as an alternative to IV corticosteroids to treat acute optic neuritis. Trial Registration: clinicaltrials.gov Identifier: NCT01524250.

Lessons learned from administration of high-dose methylprednisolone sodium succinate for acute pediatric spinal cord injuries.

OBJECTIVE Methylprednisolone sodium succinate (MPSS) has been studied as a pharmacological adjunct that may be given to patients with acute spinal cord injury (ASCI) to improve neurological recovery. MPSS treatment became the standard of care in adults despite a lack of evidence supporting clinical benefit. More recently, new guidelines from neurological surgeon groups recommended no longer using MPSS for ASCI, due to questionable clinical benefit and known complications. However, little information exists in the pediatric population regarding MPSS use in the setting of ASCI. The aim of this paper was to describe steroid use and side effects in patients with ASCI at the authors' Level 1 pediatric trauma center in order to inform other hospitals that may still use this therapy. METHODS A retrospective chart review was conducted to determine adherence in ordering and delivery according to the guideline of the authors' institution and to determine types and frequency of complications. Inclusion criteria included age < 17 years, blunt trauma, physician concern for ASCI, and admission for ≥ 24 hours or treatment with high-dose intravenous MPSS. Exclusion criteria included penetrating trauma, no documentation of ASCI, and incomplete medical records. Charts were reviewed for a predetermined list of complications. RESULTS A total of 602 patient charts were reviewed; 354 patients were included in the study. MPSS was administered in 59 cases. In 34 (57.5%) the order was placed correctly. In 13 (38.2%) of these 34 cases, MPSS was administered according to the recommended timeline protocol. Overall, only 13 (22%) of 59 patients received the therapy according to protocol with regard to accurate ordering and administration. Among the patients with ASCI, 20 (55.6%) of the 36 who received steroids had complications, which was a significantly higher rate than in those who did not receive steroids (8 [24.2%] of 33, p = 0.008). Among the patients without ASCI, 10 (43.5%) of the 23 who received steroids also experienced significantly more complications than patients who did not receive steroids (50 [19.1%] of 262, p = 0.006). CONCLUSIONS High-dose MPSS for ASCI was not delivered to pediatric patients according to protocol with a high degree of reliability. Patients receiving steroids for pediatric ASCI were significantly more likely to experience complications than patients not receiving steroids. The findings presented, including complications of steroid use, support removal of high-dose MPSS as a treatment option for pediatric ASCI.

[A particular type of cicatricial Pemphigoid with unique IgA deposit]. / Forme particulière de Pemphigoide cicatricielle à dépôt unique d'IgA.

Cicatricial Pemphigoid is a subepithelial bullous dermatosis which essentially involves the mucous membranes with cicatricial evolution We report the case of a 66-year old patient hospitalized with erosive gingivitis associated with dysphagia, dyspnea and blurred vision. Dermatologic examination showed erosive lesions involving the palate and the pharynx. Ophthalmologic examination showed symblepharons, ectropion and bilateral cataract. Gingival biopsy revealed a necrotic detachment of the buccal epithelium. Direct immunofluorescence showed linear IgA deposit at the dermo-epidermal junction. Indirect immunofluorescence test was negative. The diagnosis of cicatricial pemphigoid was confirmed. Esophagogastroduodenoscopy objectified double stenosis of the esophagus. Nasopharyngeal and bronchial endoscopy showed ulceration of the epiglottis, hypopharynx, pharynx and bronchial tree. The patient was treated with Solumedrol bolus corresponding to 0.5mg/kg/day prednisone associated with 100mg/day disulone. The patient showed a favorable early clinical outcome complicated because of the aggravation of dysphagia and esophageal stenosis after 2 months. Our case study is singular due to the occurrence of a cicatricial pemphigoid in a male patient with a serious clinical picture due to lesions extending to conjunctival, oral, nasal, esophageal and bronchial mucous membranes associated with direct immunofluorescence only showing IgA deposit.

Are neutrophil/lymphocyte and platelet/lymphocyte ratios related with formation of sudden hearing loss and its prognosis?

OBJECTIVES: The aim of our study was to see whether the neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio (PLR) are the markers of idiopathic sudden hearing loss to be used in prognosis or not. MATERIALS AND METHODS: This study is a retrospective, case-control clinical trial. Forty-five patients diagnosed with idiopathic sudden hearing loss and treated with the same treatment protocol between March 2014 and December 2015 and 47 healthy volunteers coming to the hospital for a routine health check and accepting audiological and laboratory tests were included in our study. NLR and PLR values were calculated in consequence of complete blood count results obtained from the study and control groups. In addition, the study group was classified as treatment responsive and treatment unresponsive groups as a result of audiological examination performed after three months according to the Siegel criteria. NLR and PLR ratios between the groups were statistically evaluated. RESULTS: Average NLR and PLR values were significantly higher in the study group compared to the control group (P<0.001). Average NLR ratio of the group, which was treated with the same protocol but did not respond to treatment was found to be significantly higher compared to the group which responded to the treatment (P<0.001). There was no significant change in average PLR ratio. CONCLUSION: Although NLR and PLR are two important markers that can be detected from peripheral blood samples of patients developing idiopathic sudden hearing loss and can be calculated easily, increased NLR values were also found to be related to poor prognosis.

Nicolau Syndrome.

A 23 year-old man was admitted to the hospital with chief complaints of pain, edema and spasm of the left lower limb, as well as mottling of dorsal and plantar aspects of the foot.  One week before the current admission, he was treated with oral co-amoxiclave and intramuscular penicillin 6.3.3. Immediately after the third injection, he experienced burning and yellowish discoloration at the site of the injection wich then progressed to his leg and foot. Pain, significant edema, spasm and mottling occurred within 30 minutes of the injection. The patient was referred to the hospital after 36 hours from the beginning of the symptoms. Color Doppler sonography revealed no impairment in the lower extremity flow and the common femoral artery, superficial femoral, popliteal, dorsalis pedis and posterior tibialis arteries were normal. Superficial probe sonography detected mild effusion in the left ankle without collection.

Localized delivery of methylprednisolone sodium succinate with polymeric nanoparticles in experimental injured spinal cord model.

With important social and economic consequences, spinal cord injuries (SCIs) still exist among major health problems. Although many therapeutic agents and methods investigated for the treatment of acute SCI, only high dose methylprednisolone (MP) is being used currently in practice. Due to the serious side effects, high dose systemic MP administration after SCI is a critical issue that is mostly considered controversial. In our study, it is aimed to develop a nanoparticle-gel combined drug delivery system for localization of MP on trauma site and eliminating dose-dependent side effects by lowering the administered dose. For this purpose, methyl prednisolone sodium succinate (MPSS) loaded polycaprolactone based nanoparticles were developed and embedded in an implantable fibrin gel. The effects of MPSS delivery system are evaluated on an acute SCI rat model, by quantification the levels of three inflammatory cytokines (interleukin-1ß, interleukin-6 and caspase-3) and assessment of the damage on ultrastructural level by transmission electron microscopy. Developed NP-gel system showed very similar results with systemic high dose of MPSS. It is believed that developed system may be used as a tool for the safe and effective localized delivery of several other therapeutic molecules on injured spinal cord cases.

Koebnerization of Hailey-Hailey disease into a cutaneous drug eruption of acute generalized exanthematous pustulosis associated with systemic symptoms.

We describe a 65-year-old Caucasian female with well-controlled Hailey-Hailey disease (HHD) who developed acute generalized exanthematous pustulosis (AGEP) with severe systemic symptoms. Despite sparing of the patient's intertriginous skin, histopathologic evidence of HHD was observed in all biopsies, suggestive of a unique koebernization phenomenon of HHD to areas of cutaneous drug eruption. While internal organ involvement is less commonly reported in AGEP, there are an increasing number of patients with signs and symptoms suggestive of an AGEP/drug reaction with eosinophilia and systemic symptoms (DRESS) spectrum of cutaneous drug disorders. Early diagnosis of patients with AGEP and systemic symptoms is critical so that these patients may receive prompt and aggressive systemic therapy to decrease the risk of end organ damage and improve overall morbidity and mortality.