Comparison of the Use of Peripheral Nerve Stimulator and Quincke Needle for Lumbar Transforaminal Epidural Steroid Injections.

AIM: To compare the procedural features of transforaminal epidural steroid injection (TFESI) performed using two different needles (Stimuplex® and Quincke) in terms of procedure time, exposed radiation dose and adverse effects and complications, thus providing preliminary data to aid needle selection for TFESI. MATERIAL AND METHODS: Patients who received fluoroscopy-guided single-level lumbosacral TFESI between September 2020 and September 2021 were retrospectively included in this study. The patients were divided into two groups with respect to the needle type used for the procedure ? those treated with a Quincke needle were classified as Group Q and those treated with a Stimuplex® needle comprised Group S. Subsequently, the two groups were compared in terms of their demographic data, procedure time, radiation dose, amount of contrast use, first-hour numeric rating scale (NRS), intravascular flow and complication rates. RESULTS: The number of patients recruited for Groups Q and S was 65 and 61, respectively. No significant difference was observed between the groups regarding their demographic data, preprocedural NRS scores, procedure time, exposed radiation dose and the amount of contrast dye used. Notably, the first-hour NRS scores were found to be significantly lower in Group S (p=0.040) after the procedure. Moreover, the intravascular contrast spread was significantly different between the two groups (p < 0.05) ? it was encountered during four procedures in Group Q, but was altogether absent in Group S. CONCLUSION: The Stimuplex® needle may decrease the possibility of inadvertent intravascular leakages during TFESI and may also improve immediate pain scores after the procedure.

The clinical efficacy of single-hole punch excision combined with intralesional steroid injection for nodular keloid treatment: a self-controlled trial.

There are many methods to treat keloid, including various excision operations, laser, injection and radiotherapy. However, few studies have explored the effectiveness of single-hole punch excision in keloid treatment. This study aimed to investigate the efficacy and safety of lateral punch excision combined with intralesional steroid injection for keloid treatment through self-control trial. In this self-controlled trial, 50 patients meet the diagnosis of nodular keloid, and try to choose left-right symmetrical control, one skin lesion in the control group (50 skin lesionsin total) and the other in the observation group (50 skin lesions in total).The keloids in the treatment group were initially treated with punch excision combined with intralesional steroid injection, followed by injection treatment alone. Keloids in the control group received intralesional steroid injection alone. The Vancouver Scar Scale (VSS) of the keloid before and after the punch excision was evaluated; the keloid scores at different time points and the number of injection treatments required in both groups were compared, and adverse reactions were observed. The effective rate of the observation group was 86.0%, which was significantly higher than that of the control group (66.0%), and the recurrence rate of 22% was lower than that of the control group (χ2 = 4.141,63417), all of which were statistically significant (all P < 0.05). At the end of treatment, the VSS and total injection times in the observation group were significantly lower than those in the control group (t = 5.900,3.361), with statistical significance (P < 0.01). The combination of single-hole punch excision and intralesional steroid injection is an effective method to treat multiple nodular keloids, shortening the treatment course of tralesional steroid injection without obvious adverse reactions.

Longitudinal evaluation of adverse events due to steroid use in primary immune thrombocytopenia: A population-based study.

This study aimed to investigate the association between the steroid use patterns and the risk of AEs in patients with primary immune thrombocytopenia (ITP). A total of 2691 newly diagnosed adults with ITP between 2011 and 2018 were identified from the National Health Insurance Research Database in Taiwan, and the date of first steroid use was defined as the index date. Post-index steroid use was calculated on a 90-day basis as a time-dependent variable and categorized by the average prednisolone-equivalent daily dose (<10 mg vs. ≥10 mg) and intensity (medication possession ratio <80% vs. ≥80%). Patients were followed up for 1 year from the index date for acute AE events, while chronic AEs were assessed until death, or end of 2019. Compared to patients with low-dose+low-intensity steroid use, those with high-dose+high-intensity steroid use were associated with a higher risk of acute AE (adjusted incident rate ratio [aIRR]: 1.57, 95% confidence interval [CI]: 1.38-1.78, p < 0.01) and chronic AE (aIRR: 1.26, 95% CI: 1.08-1.47, p < 0.01). Metabolic/endocrine and ophthalmologic disorders demonstrated the strongest correlation with a high dose and intensity. The joint effect of steroid dose and intensity was observed in patients with ITP, and the findings suggest that steroids should be used carefully.

Vascular complications and outcomes following transcatheter aortic valve replacement in patients on chronic steroid therapy: a meta-analysis.

BACKGROUND: Chronic steroid (CS) therapy was reportedly linked to increased vascular complications following percutaneous coronary intervention. However, its association with vascular complications after transcatheter aortic valve replacement (TAVR) remained uncertain, with conflicting results being reported. OBJECTIVE: The authors aimed to compare the rate of vascular complications and outcomes between patients with and without CS use after TAVR. METHODS: The authors conducted a comprehensive literature search in PubMed, Embase, and Cochrane databases from their inception until 18th April 2022 for relevant studies. Endpoints were described according to Valve Academic Research Consortium-2 definitions. Effect sizes were pooled using DerSimonian and Laird random-effects model as risk ratio (RR) with 95% CI. RESULTS: Five studies with 6136 patients undergoing TAVR were included in the analysis. The included studies were published between 2015 and 2022. The mean ages of patients in both study groups were similar, with the CS group averaging 80 years and the nonsteroid group averaging 82 years. Notably, a higher proportion of patients in the CS group were female (56%) compared to the nonsteroid group (54%). CS use was associated with a significantly higher risk of major vascular complications (12.5 vs. 6.7%, RR 2.32, 95% CI: 1.73-3.11, P <0.001), major bleeding (16.8 vs. 13.1%, RR 1.61, 95% CI: 1.27-2.05, P <0.001), and aortic annulus rupture (2.3 vs. 0.6%, RR 4.66, 95% CI: 1.67-13.01, P <0.001). There was no significant difference in terms of minor vascular complications (RR 1.43, 95% CI: 1.00-2.04, P =0.05), in-hospital mortality (2.3 vs. 1.4%, RR 1.86, 95% CI: 0.74-4.70, P =0.19), and 30-day mortality (2.9 vs. 3.1%, RR 1.14, 95% CI: 0.53-2.46, P =0.74) between both groups. CONCLUSION: Our study showed that CS therapy is associated with increased major vascular complications, major bleeding, and annulus rupture following TAVR. Further large multicenter studies or randomized controlled trials are warranted to validate these findings.

Type 1 Autoimmune Pancreatitis in Europe: Clinical Profile and Response to Treatment.

BACKGROUND & AIMS: Autoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas with distinct pathophysiology and manifestations. Our aims were to characterize type 1 AIP in a large pan-European cohort and study the effectiveness of current treatment regimens. METHODS: We retrospectively analyzed adults diagnosed since 2005 with type 1 or not-otherwise-specified AIP in 42 European university hospitals. Type 1 AIP was uniformly diagnosed using specific diagnostic criteria. Patients with type 2 AIP and those who had undergone pancreatic surgery were excluded. The primary end point was complete remission, defined as the absence of clinical symptoms and resolution of the index radiologic pancreatic abnormalities attributed to AIP. RESULTS: We included 735 individuals with AIP (69% male; median age, 57 years; 85% White). Steroid treatment was started in 634 patients, of whom 9 (1%) were lost to follow-up. The remaining 625 had a 79% (496/625) complete, 18% (111/625) partial, and 97% (607/625) cumulative remission rate, whereas 3% (18/625) did not achieve remission. No treatment was given in 95 patients, who had a 61% complete (58/95), 19% partial (18/95), and 80% cumulative (76/95) spontaneous remission rate. Higher (≥0.4 mg/kg/day) corticosteroid doses were no more effective than lower (<0.4 mg/kg/day) doses (odds ratio, 0.428; 95% confidence interval, 0.054-3.387) and neither was a starting dose duration >2 weeks (odds ratio, 0.908; 95% confidence interval, 0.818-1.009). Elevated IgG4 levels were independently associated with a decreased chance of complete remission (odds ratio, 0.639; 95% confidence interval, 0.427-0.955). Relapse occurred in 30% of patients. Relapses within 6 months of remission induction were independent of the steroid-tapering duration, induction treatment duration, and total cumulative dose. CONCLUSIONS: Patients with type 1 AIP and elevated IgG4 level may need closer monitoring. For remission induction, a starting dose of 0.4 mg/kg/day for 2 weeks followed by a short taper period seems effective. This study provides no evidence to support more aggressive regimens.

Contrast flow in CT-guided lumbar interlaminar epidural steroid injections: does needle position effect the laterality of contrast flow?

PURPOSE: To evaluate the effect of needle position on the laterality of contrast flow in CT-guided lumbar interlaminar epidural steroid injections. MATERIALS AND METHODS: A retrospective review of consecutive CT-guided interlaminar lumbar epidural steroid injections was performed. The terminal needle tip position (midline or lateral) and the laterality of epidural contrast were evaluated by two readers. Contrast flow pattern was classified as ipsilateral to needle trajectory, bilateral, or contralateral. Bilateral flow was further divided into asymmetric, symmetrical, or asymmetric to the contralateral side. Inter-reader agreement was calculated with the kappa statistic. The relationship of needle position to contrast laterality was calculated with the chi statistic. Pain scores were compared for bilateral and unilateral flows with a two-tailed T test for independent means. RESULTS: A total of 250 injections were included in 204 patients, with an age range of 24 to 93 years. The most commonly injected level (145/250) was L4-L5. Agreement between the two readers was almost perfect and substantial (kappa 0.751-0.880). The majority of injections (154/250) demonstrated contrast flow ipsilateral to the needle trajectory, 90/250 demonstrated bilateral flow, and 6/250 had contralateral flow. Of the 90 cases with bilateral flow, 80% were performed with a midline terminal needle position (p < 0.001). There was no difference in immediate post-procedure pain scores between patients with ipsilateral or bilateral contrast flow. CONCLUSION: For interlaminar epidural steroid injections, a midline terminal needle tip position has a greater probability of producing bilateral contrast flow compared to a lateral terminal needle tip position.

Effects of the preoperative use and dosage of steroids on postoperative complications of gastric cancer surgery.

PURPOSE: To investigate the effects of preoperative steroid administration, including dosage, on complications after gastrectomy for gastric cancer. METHODS: We reviewed patients who underwent gastrectomy for gastric and esophagogastric junctional adenocarcinoma between 2013 and 2019 at the Department of Gastrointestinal Surgery, The University of Tokyo. RESULTS: Among the total 764 patients eligible for inclusion in the study, 17 were on steroid medication preoperatively (SD group) and 747 were not (ND group). The hemoglobin, serum albumin levels, and respiratory functions were significantly lower in the SD group than in the ND group. The incidence of postoperative complications classified as Clavien-Dindo (C-D) ≥ 2 was significantly greater in the SD group than in the ND group (64.7% vs. 25.6%, p < 0.001). Intra-abdominal infection (35.2% vs. 9.6%, p < 0.001) and anastomotic leakage (11.8% vs. 2.1%, p < 0.001) occurred more frequently in the SD group than in the ND group. On multiple logistic regression analysis for C-D ≥ 3 postoperative complications, the odds ratio for oral steroid use ≥ 5 mg per day as prednisolone had the highest value, of 13.0 (95% confidence interval 2.46-76.2, p < 0.01). CONCLUSION: Preoperative oral steroid use was identified as an independent risk factor for postoperative complications after gastrectomy for gastric cancer. Furthermore, the complication rate appears to increase as the oral steroid dosage is increased.

Factors Associated with Treatment Success After Interlaminar Epidural Steroid Injection for Cervical Radicular Pain.

AIM: To investigate the demographic, clinical and radiological findings associated with treatment success after interlaminar epidural steroid injection (ILESI) in radicular pain induced by cervical disc herniation. MATERIAL AND METHODS: In this retrospective study, the data of patients who received cervical ILESI between January 2017 and June 2021 were screened. Of 223 patients, 92 with unilateral radicular neck pain due to cervical disc herniation were included. Demographic data, symptom duration, and numerical rating scale scores at baseline, at three weeks, three months, and six months after treatment were collected from the medical records of the patients. Disc herniation level, cervical axis, disc height, presence and degree of spinal canal and neural foraminal stenosis, vertebral endplate signal change, and definitive presence of uncovertebral and facet osteoarthritis were evaluated using cervical spine magnetic resonance imaging. Treatment success was determined as ?50% reduction in pain scores at six months compared to baseline. RESULTS: Data of 92 patients (27 men, 65 women) were included. The mean age was 50.82 ± 10.22 years, and the median symptom duration was 12 (4.25 to 20) months. At six months after ILESI, treatment was successful in 58 (58.7%) patients and unsuccessful in 34 (41.3%) patients. Multivariable logistic regression analysis was performed to identify the factors associated with treatment success at six months post-injection. In the final model, neural foraminal stenosis (non-severe vs. severe) and spinal canal stenosis (non-severe vs. severe) were significantly associated with the treatment success (OR=3.02, 95% CI=1.40?10.95, p=0.009; OR=5.31, 95% CI=1.77?15.85, p=0.003). CONCLUSION: Treatment success of cervical ILESI at six months is favorable. However, the presence of severe neural foraminal and spinal canal stenosis is associated with a reduced likelihood of treatment success.

Timosaponin AIII Suppresses RAP1 Signaling Pathway to Enhance the Inhibitory Effect of Paclitaxel on Nasopharyngeal Carcinoma.

Although PTX has been identified as an effective drug for nasopharyngeal carcinoma (NPC) therapy, it has serious side effects in the human body. Previous studies have shown that timosaponin AIII (TSAIII) can inhibit the malignant progression of NPC cells. This study investigated the active mechanism of the combination of TSAIII and paclitaxel (PTX) on NPC. Cellular viability, apoptosis, apoptotic factors, and RAP1 signaling regulators were detected in the PNC cells (CNE-1 and HNE-2) and the subcutaneous CNE-1 transplanted nude mice treated with PTX or/and TSAIII. The results showed that TSAIII notably strengthened the inhibitory effect of PTX on the proliferation of NPC cells CNE-1 and HNE-2; upregulated the expression of Bax B-cell lymphoma 2 (Bcl-2)/Bcl-xL-associated death promoter (Bad), and Ras-associated protein1 (RAP1) GTPase activating protein (Rap1GAP); inhibited the level of Bcl-2, RAP1, and Ras guanine nucleotide releasing protein (RasGRP2); and significantly enhanced the promoting effect of PTX on apoptosis in the CNE-1 and HNE-2 cells. Besides, TSAIII strengthened the inhibitory effect of PTX on xenograft tumor in nude mice without adverse reactions. In conclusion, the combination administration of TSAIII and PTX had a significantly therapeutic effect on NPC and avoided the PTX's side effects, which may have acted as a new direction for the study of therapeutic approaches for NPC clinically.

Tratamiento con inmunoglobulina intravenosa y esteroides sistémicos en pacientes con necrólisis epidérmica tóxica: Experiencia en un hospital en Ciudad de México / Use of Intravenous Immunoglobulins and Systemic Corticosteroids in Patients with Toxic Epidermal Necrolysis: Experience of a Hospital in Mexico City

La necrólisis epidérmica tóxica es la reacción secundaria a medicamentos más grave dentro del espectro de las reacciones mucocutáneas. El tratamiento multidisciplinario es clave para disminuir la mortalidad de los pacientes, además de la suspensión del fármaco causal. Existen pocos estudios de tratamientos farmacológicos en pacientes con necrólisis epidérmica tóxica en Latinoamérica que combinen el uso de esteroides sistémicos e inmunoglobulina intravenosa (IgIV). Describimos 6 casos de pacientes con necrólisis epidérmica tóxica tratados con esteroides sistémicos e IgIV en un hospital de referencia dermatológica en Ciudad de México. Ningún paciente falleció ni presentó complicaciones a corto y mediano plazo de seguimiento. En la mayoría de los casos se empleó una dosis de IgIV de 1g/kg por 3-5 días y 1g de metilprednisolona por 3-5 días. El tiempo de ingreso hospitalario fue de 14,8 días. La combinación de esteroides sistémicos e IgIv parece ser una opción segura en pacientes con necrólisis epidérmica tóxica (AU)

Toxic epidermal necrolysis is the most serious mucocutaneous adverse drug reaction. Multidisciplinary treatment and withdrawal of the causative drug are key to reducing mortality. Few studies have analyzed the use of systemic corticosteroids and intravenous immunoglobulins (IVIG) in patients with toxic epidermal necrolysis in Latin America. We describe our experience with 6 cases treated at a dermatology referral hospital in Mexico City. None of the patients died or developed complications in the short or medium term. The most widely used regimen was a combination of IVIG 1 g/kg for 3 to 5 days and methylprednisolone 1 g for 3 to 5 days. Mean hospital stay was 14.8 days. The combined use of systemic corticosteroids and IVIG seems to be a safe treatment option for patients with toxic epidermal necrolysis (AU)

[Translated article] Use of Intravenous Immunoglobulins and Systemic Corticosteroids in Patients With Toxic Epidermal Necrolysis: Experience of a Hospital in Mexico City / Tratamiento con inmunoglobulina intravenosa y esteroides sistémicos en pacientes con necrólisis epidérmica tóxica: experiencia en un hospital en Ciudad de México

Toxic epidermal necrolysis is the most serious mucocutaneous adverse drug reaction. Multidisciplinary treatment and withdrawal of the causative drug are key to reducing mortality. Few studies have analyzed the use of systemic corticosteroids and intravenous immunoglobulins (IVIG) in patients with toxic epidermal necrolysis in Latin America. We describe our experience with 6 cases treated at a dermatology referral hospital in Mexico City. None of the patients died or developed complications in the short or medium term. The most widely used regimen was a combination of IVIG 1g/kg for 3–5 days and methylprednisolone 1g for 3–5 days. Mean hospital stay was 14.8 days. The combined use of systemic corticosteroids and IVIG seems to be a safe treatment option for patients with toxic epidermal necrolysis (AU)

La necrólisis epidérmica tóxica es la reacción secundaria a medicamentos más grave dentro del espectro de las reacciones mucocutáneas. El tratamiento multidisciplinario es clave para disminuir la mortalidad de los pacientes, además de la suspensión del fármaco causal. Existen pocos estudios de tratamientos farmacológicos en pacientes con necrólisis epidérmica tóxica en Latinoamérica que combinen el uso de esteroides sistémicos e inmunoglobulina intravenosa (IgIV). Describimos 6 casos de pacientes con necrólisis epidérmica tóxica tratados con esteroides sistémicos e IgIV en un hospital de referencia dermatológica en Ciudad de México. Ningún paciente falleció ni presentó complicaciones a corto y mediano plazo de seguimiento. En la mayoría de los casos se empleó una dosis de IgIV de 1g/kg por 3-5 días y 1g de metilprednisolona por 3-5 días. El tiempo de ingreso hospitalario fue de 14,8 días. La combinación de esteroides sistémicos e IgIv parece ser una opción segura en pacientes con necrólisis epidérmica tóxica (AU)

The Spontaneous Course of Human Herpesvirus 6 DNA-Associated Myocarditis and the Effect of Immunosuppressive Intervention.

INTRODUCTION: This study investigated the spontaneous clinical course of patients with endomyocardial biopsy (EMB)-proven lymphocytic myocarditis and cardiac human herpesvirus 6 (HHV6) DNA presence, and the effectiveness of steroid-based intervention in HHV6-positive patients. RESULTS: 756 heart failure (HF) patients underwent an EMB procedure to determine the underlying cause of unexplained HF. Low levels of HHV6 DNA, detectable by nested PCR only, were found in 10.4% of the cases (n = 79) of which 62% (n = 49) showed myocardial inflammation. The spontaneous course of patients with EMB-proven HHV6 DNA-associated lymphocytic myocarditis (n = 26) showed significant improvements in the left ventricular ejection fraction (LVEF) and clinical symptoms, respectively, in 15/26 (60%) patients, 3-12 months after disease onset. EMB mRNA expression of components of the NLRP3 inflammasome pathway and protein analysis of cardiac remodeling markers, analyzed by real-time PCR and MALDI mass spectrometry, respectively, did not differ between HHV6-positive and -negative patients. In another cohort of patients with ongoing symptoms related to lymphocytic myocarditis associated with cardiac levels of HHV6-DNA copy numbers <500 copies/µg cardiac DNA, quantified by real-time PCR, the efficacy and safety of steroid-based immunosuppression for six months was investigated. Steroid-based immunosuppression improved the LVEF (≥5%) in 8/10 patients and reduced cardiac inflammation in 7/10 patients, without an increase in cardiac HHV6 DNA levels in follow-up EMBs. CONCLUSION: Low HHV6 DNA levels are frequently detected in the myocardium, independent of inflammation. In patients with lymphocytic myocarditis with low levels of HHV6 DNA, the spontaneous clinical improvement is nearby 60%. In selected symptomatic patients with cardiac HHV6 DNA copy numbers less than 500 copies/µg cardiac DNA and without signs of an active systemic HHV6 infection, steroid-based therapy was found to be effective and safe. This finding needs to be further confirmed in large, randomized trials.

Early, biomarker-guided steroid dosing in COVID-19 Pneumonia: a pilot randomized controlled trial.

ClinicalTrials.gov identifier (NCT number): NCT03852537 , Registered February 25, 2019.

EDP-305 in patients with NASH: A phase II double-blind placebo-controlled dose-ranging study.

BACKGROUND & AIMS: EDP-305 is an oral farnesoid X receptor (FXR) agonist under development for the treatment of non-alcoholic steatohepatitis (NASH). Herein, we aimed to assess the efficacy, safety and tolerability of EDP-305 in patients with fibrotic NASH. METHODS: In this double-blind phase II study, patients with fibrotic NASH (without cirrhosis), diagnosed by historical biopsy or phenotypically, were randomized to EDP-305 1 mg, EDP-305 2.5 mg, or placebo, for 12 weeks. The primary endpoint was mean change in alanine aminotransferase (ALT) from baseline to Week 12, and the key secondary endpoint was mean change in liver fat content from baseline to Week 12. RESULTS: Between January 2018 and July 2019, 134 patients were randomized and 132 were evaluated. At Week 12, the least squares mean reductions from baseline in ALT for patients receiving 2.5 mg EDP-305 and 1 mg EDP-305 were -27.9 U/L (95% CI 0.03 to 24.9; p = 0.049) and -21.7 U/L (-5.8 to 18.3: p = 0.304), respectively, compared to -15.4 U/L for those receiving placebo. Absolute liver fat reduction was -7.1% (2.0-7.5; p = 0.0009) with 2.5 mg EDP-305, -3.3% with EDP-305 1 mg, and -2.4% with placebo. The most common (≥5%) adverse events were pruritus, nausea, vomiting, diarrhea, headache, and dizziness. Pruritus occurred in 50.9%, 9.1%, and 4.2% of patients in the 2.5 mg, 1 mg, and placebo groups, respectively, and led to study drug discontinuation in 20.8% of patients in the 2.5 mg group and 1.8% in the 1 mg group. CONCLUSIONS: EDP-305 reduced ALT levels and liver fat content, providing support for a longer-term trial assessing histological endpoints in patients with NASH. CLINICALTRIALS. GOV NUMBER: NCT03421431 LAY SUMMARY: Non-alcoholic fatty liver disease is a chronic hepatic disease that can progress to non-alcoholic steatohepatitis (NASH), which is associated with an increased risk of cirrhosis and liver cancer. Results from this phase II study support continued development of EDP-305, an oral farnesoid X receptor agonist, for the treatment of patients with NASH.

Single- and Multiple-Dose Pharmacokinetics and Safety of Vilaprisan in Healthy Postmenopausal Japanese Women: A Randomized Clinical Trial.

BACKGROUND AND OBJECTIVES: As the prevalence of some gynecological conditions depends on patient characteristics such as race/ethnicity, it is important to study therapies for these conditions in diverse populations. The study described in this article was conducted to investigate the safety, tolerability, and pharmacokinetics of vilaprisan, a selective progesterone receptor modulator, in Japanese women in Japan. It supplements two comparable studies that were conducted in healthy postmenopausal European and Chinese women, respectively. METHODS: In this exploratory randomized, placebo-controlled, double-blind, ascending-dose study, five groups of healthy postmenopausal Japanese women received vilaprisan as immediate-release tablets (1, 5, or 15 mg as a single dose or 1 or 5 mg/day for 28 days) or placebo tablets (single dosing: 8 subjects/dose step, thereof 2 subjects randomized to placebo; multiple dosing: 12 subjects/dose step, thereof 4 subjects randomized to placebo). Blood samples for pharmacokinetic profiles were collected over 14-19 days. Safety assessments were based on adverse event data, vital signs, electrocardiograms, clinical laboratory tests, and transvaginal ultrasound examinations. RESULTS: 48 participants were randomized, treated, and analyzed. Vilaprisan was rapidly absorbed, reaching maximum plasma concentrations (Cmax) between 1 and 3 h post dose. Post maximum, plasma concentrations rapidly declined, indicating pronounced distribution into tissues. The exposure of vilaprisan increased roughly dose-proportionally: The geometric mean (geometric coefficients of variation) areas under the concentration time curves from time zero to infinity (AUC∞) after single administration of 1, 5, or 15 mg vilaprisan were 67 µg·h/l (34%), 249 µg·h/l (15%), and 788 µg·h/l (37%), respectively. The AUC in the dosing interval after multiple administrations (AUC24,md) of 1 mg/day was 76 µg·h/l (59%), and the AUC24,md after 5 mg/day was 311 µg·h/l (20%). Geometric mean Cmax values also increased roughly dose-proportionally: They amounted to 6 µg/l (22%), 16 µg/l (33%), and 52 µg/l (27%) after single administration and to 8 µg/l (28%) and 31 µg/l (22%) after multiple administrations of the above doses. Mild adverse events were observed, similar to those observed in other clinical studies of vilaprisan. CONCLUSIONS: Overall, vilaprisan was safe and well tolerated. The exposure in Japanese women was similar to that observed in European and Chinese women in separate studies. TRIAL REGISTRATION: 15 Nov 2011 (no registration number assigned).

Complications and prognosis associated with intra-tympanic steroid injection to treat sudden sensorineural hearing impairment.

PURPOSE: The purpose of this study was to measure the incidence of complications in sudden sensorineural hearing loss (SSNHL) patients treated with intra-tympanic steroid injection (ITSI) and compare hearing recovery rates. MATERIALS AND METHODS: 123 patients with unilateral SSNHL receiving ITSIs were included in this study. Post-ITSI complications were documented including otalgia, dysgeusia, vertigo (duration>1 h), and persistent eardrum perforation. The pain intensity was evaluated with visual analog scale (VAS). Hearing was measured before ITSI and at 1 month after the final ITSI. We compared our patients' hearing threshold between presence and absence of different complications. RESULTS: 47.2% patients experienced post-injection otalgia with the average VAS score 3.2 (range 2-6). Five (4.1%) and six (4.9%) patients exhibited vertigo and persistent eardrum perforations, respectively. The patients were divided into three groups based on the absence of complications and the presence of vertigo and eardrum perforation. The hearing threshold improvements did not differ significantly among the three groups (p = 0.366). Although the difference was not significant (p = 0.664), the proportion of patients experiencing post-ITSI vertigo who were on contemporaneous oral steroids was lower than the proportion of non-vertigo patients on such steroids. CONCLUSION: The incidences of otalgia, vertigo, and persistent eardrum perforation in SSNHL patients treated with ITSI were 47.2%, 4.1% and 4.9%, respectively. We found no association between concurrent oral steroid use and the incidence of post-ITSI eardrum perforation or vertigo. Although statistical significance was lacking, patients who did not take contemporaneous oral steroids may have a higher rate of prolonged post-ITSI vertigo.