Neuroinfectious Emergencies.

OBJECTIVE: This article describes nervous system infections and complications that lead to neurologic emergencies. LATEST DEVELOPMENTS: New research on the use of dexamethasone in viral and fungal infections is reviewed. The use of advanced MRI techniques to evaluate nervous system infections is discussed. ESSENTIAL POINTS: Neurologic infections become emergencies when they lead to a rapid decline in a patient's function. Emergent complications may result from neurologic infections that, if not identified promptly, can lead to permanent deficits or death. These complications include cerebral edema and herniation, spinal cord compression, hydrocephalus, vasculopathy resulting in ischemic stroke, venous thrombosis, intracerebral hemorrhage, status epilepticus, and neuromuscular respiratory weakness.

Multiple use of preservative-free single dose unit dexamethasone 0.1% eye drops is safe within 24 hours.

BACKGROUND: Unpreserved single-dose unit (SDU) eye drops are commonly used to avoid benzalkonium chloride-related toxicity. Although intended for single use, many patients report off-label repeated use of SDUs over a prolonged period. We investigated whether repeated use of dexamethasone 0.1% SDUs in the same patient increases the bacterial contamination rate. METHODS: We prospectively enrolled patients scheduled for inpatient corneal and glaucoma surgery receiving dexamethasone 0.1% SDU four times per day from the same vial. To assess contamination rates, one drop from the vial was cultured immediately after opening the SDU (t0), 10 hours later after four drop applications (t10) and 24 hours after opening without further drop applications (t24). Conjunctival swabs were taken before and after drop application. Contamination rate was assessed with a standard clinical culturing protocol without introducing a positive control. RESULTS: 110 eyes of 109 patients were evaluated. Drops collected immediately after opening the SDU (t0) were contaminated in 9/110 cultures (8.1%). At t10, 13/110 cultures were contaminated (11.8%; p=0.267) and 11/110 at t24 (10.0%; t24 vs t0; p=1.00). In 5 of 21 cases of contaminated drops at t10 and/or t24, the same isolates were cultured from the initial conjunctival swab and the SDU. In three cases, the same bacterial species was found in consecutive samples. CONCLUSION: The contamination rate of the SDU did not increase after multiple use within 24 hours. Contamination from fingertip flora was more likely than from ocular surface flora. Reuse of dexamethasone 0.1% SDU in the same patient within 24 hours appears to be safe.

Efficacy of the efficacy between dexamethasone versus triamcinolone acetonide after cataract surgery: A systematic review and meta-analysis.

PURPOSE: To evaluate the clinical effects between dexamethasone and triamcinolone acetonide (TA) after phacoemulsification and intraocular lens implantation among cataract patients. METHODS: Pubmed, Embase, and the Cochrane Library were searched for studies published up to August 2020. The primary outcome was intraocular pressure. The secondary outcomes were the logarithm of the minimum angle of resolution (logMAR), anterior chamber cell, and anterior chamber flare. The pooled effect sizes were expressed as weighted mean differences (WMDs) or standardized mean differences (SMDs) of 95% confidence intervals (95% CIs). Cochrane Collaboration risk of bias tool and Newcastle-Ottawa scale criteria were used for the quality assessment of included studies. RESULTS: Seven relevant studies met the inclusion criteria. For the primary outcome, there was no significant difference between TA injection and dexamethasone in comparing intraocular pressure (IOP) (SMD = 0.22, 95% confidence interval [CI] [-0.29, 0.73], P = .408; I²â€…= 86.9%) in the first day after treatment and last day of assessment. For the secondary outcomes, the logMAR (WMD = 0.01, 95% CI [-0.06, 0.08]) and the anterior chamber flare (SMD = 0.08, 95% CI [-0.01, 0.18], P = .087; I²â€…= 0%) showed no differences. However, the amount of anterior chamber cells (SMD = -0.21, 95% CI [-0.42, -0.01], P = .044; I²â€…= 0%) in the TA injection on the first day postoperative was higher than for dexamethasone. After treatment, there was no difference between the 2 groups. CONCLUSIONS: This study supports that there were no differences in IOP, logMAR, and anterior chamber flare between TA injection and dexamethasone among cataract patients. TA injection treatment on the first day showed higher amounts of anterior chamber cells than with dexamethasone.

Early Experience with a Novel Treatment for Menière's Disease: A Long Acting Dexamethasone Formulation for Precise Delivery to the Round Window Membrane.

OBJECTIVE: To investigate the safety and feasibility of precise delivery of a long-acting gel formulation containing 6% dexamethasone (SPT-2101) to the round window membrane for the treatment of Menière's disease. STUDY DESIGN: Prospective, unblinded, cohort study. SETTING: Tertiary care neurotology clinic. PATIENTS: Adults 18 to 85 years with a diagnosis of unilateral definite Menière's disease per Barany society criteria. INTERVENTIONS: A single injection of a long-acting gel formulation under direct visualization into the round window niche. MAIN OUTCOME MEASURES: Procedure success rate, adverse events, and vertigo control. Vertigo control was measured with definitive vertigo days (DVDs), defined as any day with a vertigo attack lasting 20 minutes or longer. RESULTS: Ten subjects with unilateral Menière's disease were enrolled. Precise placement of SPT-2101 at the round window was achieved in all subjects with in-office microendoscopy. Adverse events included one tympanic membrane perforation, which healed spontaneously after the study, and two instances of otitis media, which resolved with antibiotics. The average number of DVDs was 7.6 during the baseline month, decreasing to 3.3 by month 1, 3.7 by month 2, and 1.9 by month 3. Seventy percent of subjects had zero DVDs during the third month after treatment. CONCLUSIONS: SPT-2101 delivery to the round window is safe and feasible, and controlled trials are warranted to formally assess efficacy.

Does the use of antenatal corticosteroids reduce respiratory morbidity in babies born in late preterm period?

BACKGROUND: The aim of this study is to determine the effectiveness of antenatal corticosteroid in reducing respiratory morbidity in babies born in the late preterm period. METHODS: Two hundred and eighty-six pregnant women at risk of having a late preterm delivery were studied. One hundred and forty-three (143) served as the cases and were given 2 doses of 12 mg intramuscular dexamethasone 12 h apart, while 143 served as the controls and were given a similar quantity of placebo. The women were followed up prospectively and data were collected on the pregnant women and their newborns on a standardized form. The neonates were assessed for acute respiratory distress syndrome and transient tachypnea of the newborn based on clinical signs, symptoms, and chest x-ray results (when indicated). The primary outcome was the occurrence of neonatal respiratory morbidity. RESULTS: The primary outcome occurred in 5 out of 130 infants (3.8%) in the dexamethasone group and 31 out of 122 (25.4%) in the placebo group (P value = 0.000003). Birth asphyxia, neonatal intensive care admission and need for active resuscitation at birth also occurred significantly less frequently in the dexamethasone group (P value 0.004, 0.009, 0.014 respectively). There were no significant group differences in the incidence of neonatal sepsis, neonatal jaundice, hypoglycemia and feeding difficulties. CONCLUSIONS: Administration of dexamethasone to women at risk for late preterm delivery significantly reduced the rate of neonatal respiratory complications, neonatal intensive care unit admission, and need for active resuscitation at birth. TRIAL REGISTRATION: PACTR ( www.pactr.org ) Registration Number: PACTR202304579281358. The study was retrospectively registered on April 19, 2023.

[The 505th case: refractory ascites and monoclonal immunoglobulin].

A 52-year-old woman was admitted with a primary complaint of abdominal distension and increased abdominal circumference for more than half a year. There was no evidence of infection or solid tumor on abdominocentesis or laparoscopic surgery. Concurrently, smoldering multiple myeloma was diagnosed. Due to refractory ascites and portal hypertension, a transjugular intrahepatic portosystemic shunt was performed, but the efficacy was not satisfactory. As the anemia progressed, she was finally diagnosed with active multiple myeloma after monoclonal plasma cells were detected in the ascites by flow cytometry. Treated with a triplet regimen that included bortezomib, cyclophosphamide, and dexamethasone (BCD), she achieved a very good partial response and ascites regressed.

Evaluation of the effects of pregabalin and dexamethasone coadministration on preemptive multimodal analgesia and anxiety in third molar surgeries: a triple-blind randomized clinical trial.

OBJECTIVE: To evaluate the efficacy of pregabalin and dexamethasone coadministration in preemptive analgesia and anxiety control in lower third molar surgery. MATERIALS AND METHODS: A triple-blind, split-mouth clinical trial conducted with patients divided into two groups: control group, receiving placebo and dexamethasone, and test group, receiving pregabalin and dexamethasone preoperatively. The evaluated variables were pain, measured by the Visual Analog Scale (VAS), anxiety assessed through the State-Trait Anxiety Inventory (STAI) questionnaires, hemodynamic parameters [Blood Pressure (BP), Heart Rate (HR), Oxygen Saturation (SpO2)], and sedation assessed by the Ramsay scale. RESULTS: A total of 31 patients were included. The test group exhibited a significant reduction in pain at 2,4,6,8,12,16,24, and 48 h after surgery and in the consumption of rescue analgesics. Anxiety, evaluated by STAI and VAS, showed a significant decrease in the test group (p < 0.001). Additionally, there was a significant decrease in BP at most of the assessed time points (p < 0.05) and a significant reduction in HR at two different time intervals (p = 0.003 and p = 0.009), indicating a positive effect in the test group. There was no significant difference in SpO2 between the groups. Sedation assessment revealed a significant difference at all time points favoring the test group (p < 0.05). There were no significant postoperative adverse effects. CONCLUSIONS: Pregabalin coadministered with dexamethasone demonstrated significant efficacy in controlling postoperative pain and anxiety, as well as a sedative effect. CLINICAL RELEVANCE: The coadministration of pregabalin with dexamethasone may presents potential advantages in both pain modulation and psychological well-being of individuals undergoing third molar surgeries. TRIAL REGISTRATION: Brazilian Clinical Trials Registry (REBEC), No. RBR-378h6t6.

Intrathecal Dexamethasone and Dexmedetomidine as Adjuncts to Bupivacaine in Elective Cesarean Section: A Case Series.

The purpose of this study was to investigate whether the combination of intrathecal dexamethasone and dexmedetomidine in combination with bupivacaine in spinal anesthesia is effective for reducing nausea, vomiting, shivering, and pain. A retrospective review of records was used to examine the outcomes of patients undergoing cesarean delivery under spinal anesthesia with dexamethasone, dexmedetomidine, and bupivacaine. The records of 11 consecutive patients who underwent cesarean delivery under spinal anesthesia with intrathecal dexamethasone and dexmedetomidine in combination with bupivacaine were evaluated. Data collected included patient demographics, medications and fluids administered, presence of nausea, vomiting, shivering, intraoperative breakthrough pain, and postoperative pain. There were no reported complications related to the administration of intrathecal dexamethasone and dexmedetomidine in combination with bupivacaine in this case series of patients. No patients required treatment for intraoperative vomiting, shivering, or breakthrough pain. One patient required opioid pain medication postoperatively. This case series demonstrates that the administration of intrathecal dexamethasone and dexmedetomidine in combination with bupivacaine for patients undergoing elective cesarean section appears to be safe and offers some advantages as to traditional methods of intrathecal delivery for this surgical procedure.

Intraoperative intravenous versus periarticular injection of glucocorticoids in improving clinical outcomes after total knee arthroplasty: A prospective, randomized and controlled study.

BACKGROUND: Glucocorticoids have been widely used in perioperative period for postoperative pain relief after total knee arthroplasty (TKA). However, the optimal administration protocols of glucocorticoids remain controversial. This study aims to compare the efficacy of glucocorticoids between intravenous and periarticular injection on clinical outcomes. METHODS: A total of 114 patients were randomly assigned to intravenous (IV) group (n = 57) and periarticular injection (PI) group (n = 57). The IV group received 10 mg dexamethasone intravenously and the PI group received periarticular injection of 10 mg dexamethasone during the procedure. The clinical outcomes were assessed using visual analogue scale (VAS), knee society score (KSS), range of motion (ROM), knee swelling, inflammation markers and complications after TKA. RESULTS: The VAS score during walking at 2nd day postoperatively was lower in the PI group compared with the IV group (2.08 ± 1.45 vs 2.73 ± 1.69, p = .039), and there was no significant difference at the other time points of VAS score in two groups. The inflammation markers, knee swelling, knee ROM and KSS score were not statistically different. Vomiting and other complications occurrence were not significantly different between the two groups. CONCLUSIONS: Intraoperative periarticular injection of glucocorticoids has similar analgesic effect compared to intravenous in the postoperative period following TKA and may be even more effective on the second postoperative day. In addition, periarticular injection of glucocorticoids does not impose an excess risk or complication on patients.

Corticosteroid monotherapy versus combined cytarabine continuous rate infusion and corticosteroid therapy in dogs with meningoencephalitis of unknown origin: A blinded, randomized, controlled trial.

BACKGROUND: Treatment options available for meningoencephalitis of unknown origin (MUO) in dogs are suboptimal, and currently, no single treatment protocol appears to be superior. OBJECTIVES: Compare neurological deterioration rates at 7 days between dogs with MUO treated with corticosteroids alone or combined with cytosine arabinoside (CA) continuous rate infusion (CRI) and compare clinical deterioration and survival at 30 and 100 days. ANIMALS: Sixty-nine dogs with magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) features or both compatible with MUO. METHODS: Parallel, blinded, randomized controlled trial. Simple randomization into 2 treatment groups: 4 mg/kg/day prednisolone (or dexamethasone equivalent) for 2 days or 200 mg/m2 CA CRI over 8 hours plus 2 mg/kg/day prednisolone. Blinding of the treatment protocol was carried out using reversible redaction of clinical records, and treatment failure was defined as deterioration of neurological assessment or death. Using intention-to-treat analysis, proportions failing treatment at 7, 30, and 100 days were compared using Fisher's exact test. All-cause mortality at 100 days was compared using Kaplan-Meier survival curves. RESULTS: Thirty-five dogs were allocated to corticosteroid only, and 34 dogs were allocated to combined CA CRI and corticosteroid. Proportions failing treatment at 7, 30, and 100 days were 7/35 (20%), 9/35 (26%), and 15/35 (43%) in the corticosteroid-only group and 8/34 (24%), 11/34 (32%), and 23/34 (68%) in the corticosteroid and CA CRI group. All-cause mortality at 100 days was not significantly different between groups (P = .62). Clinically relevant treatment-related adverse effects were not observed. CONCLUSIONS AND CLINICAL IMPORTANCE: We found no difference in outcome between corticosteroid monotherapy and combined cytarabine CRI and corticosteroid therapy at 7, 30, and 100 days after diagnosis in dogs with MUO.

Effects of preoperative inhaled budesonide combined with intravenous dexamethasone on postoperative sore throat in patients who underwent thyroidectomy: A randomized controlled trial.

BACKGROUND: This randomized controlled trial aimed to evaluate the efficacy of preoperative inhaled budesonide combined with intravenous dexamethasone on postoperative sore throat (POST) after general anesthesia in patients who underwent thyroidectomy. METHODS: Patients who underwent elective thyroidectomy were randomly divided into the intravenous dexamethasone group (group A) and budesonide inhalation combined with intravenous dexamethasone group (group B). All patients underwent general anesthesia. The incidence and severity of POST, hoarseness, and cough at 1, 6, 12, and 24 hours after surgery were evaluated and compared between the 2 groups. RESULTS: There were 48 and 49 patients in groups A and B, respectively. The incidence of POST was significantly lower at 6, 12, and 24 hours in group B than that in group A (P < .05). In addition, group B had a significantly lower incidence of coughing at 24 hours (P = .047). Compared with group A, the severity of POST was significantly lower at 6 (P = .027), 12 (P = .004), and 24 (P = .005) hours at rest, and at 6 (P = .002), 12 (P = .038), and 24 (P = .015) hours during swallowing in group B. The incidence and severity of hoarseness were comparable at each time-point between the 2 groups (P > .05). CONCLUSION: Preoperative inhaled budesonide combined with intravenous dexamethasone reduced the incidence and severity of POST at 6, 12, and 24 hours after extubation compared with intravenous dexamethasone alone in patients who underwent thyroidectomy. Additionally, this combination decreased the incidence of postoperative coughing at 24 hours.

The efficacy and tolerability of bortezomib, thalidomide, and dexamethasone induction therapy with a thalidomide dose step-up strategy in patients with newly diagnosed multiple myeloma: A prospective observational study.

BACKGROUND: Thalidomide-containing regimens cause adverse events (AEs) that may require a reduction in treatment intensity or even treatment discontinuation in patients with multiple myeloma. As thalidomide toxicity is dose-dependent, identifying the most appropriate dose for each patient is essential. AIMS: This study aimed to investigate the effects of a thalidomide dose step-up strategy on treatment response and progression-free survival (PFS). METHODS AND RESULTS: This prospective observational study included 93 patients with newly diagnosed multiple myeloma (NDMM) who received bortezomib, thalidomide, and dexamethasone (VTD). The present study assessed the incidence of thalidomide dose reduction and discontinuation, the overall dose intensity, and their effects on therapeutic efficacy. Furthermore, this study used Cox proportional hazard models to analyze the factors contributing to thalidomide intolerability. The results showed the overall response rates in all patients and the evaluable patients were 78.5% and 98.7%, respectively. The median PFS in the study cohort was not reached. The most common thalidomide-related AEs were constipation (32.3%) and skin rash (23.7%), resulting in dose reduction and discontinuation rates of 22.6% and 21.5%, respectively. The responders had a significantly higher average thalidomide dose intensity than the nonresponders (88.6% vs. 42.9%, p < .001). CONCLUSION: The thalidomide dose step-up approach is a viable option for patients with NDMM receiving VTD induction therapy with satisfactory efficacy and tolerability. However, thalidomide intolerance may lead to dose reduction or discontinuation due to unpredictable AEs, leading to lower dose intensity and potentially inferior treatment outcomes. In addition to a dose step-up strategy, optimal supportive care is critical for patients with multiple myeloma receiving VTD induction therapy.

Effect of Corticosteroid on Immunogenicity of SARS-CoV-2 Vaccines in Patients With Solid Cancer.

PURPOSE: Corticosteroids are known to diminish immune response ability, which is generally used in routine premedication for chemotherapy. The intersecting of timeframe between the corticosteroid's duration of action and peak COVID-19 vaccine efficacy could impair vaccine immunogenicity. Thus, inquiring about corticosteroids affecting the efficacy of vaccines to promote effective immunity in this population is needed. METHODS: This was a prospective longitudinal observational cohort study that enrolled patients with solid cancer classified into dexamethasone- and nondexamethasone-receiving groups. All participants were immunized with two doses of ChAdOx1 nCoV-19 or CoronaVac vaccines. This study's purpose was to compare corticosteroid's effect on immunogenicity responses to the SARS-CoV-2 S protein in patients with cancer after two doses of COVID-19 vaccine in the dexamethasone and nondexamethasone group. Secondary outcomes included the postimmunization anti-spike (S) immunoglobin G (IgG) seroconversion rate, the association of corticosteroid dosage, time duration, and immunogenicity level. RESULTS: Among the 161 enrolled patients with solid cancer, 71 and 90 were in the dexamethasone and nondexamethasone groups, respectively. The median anti-S IgG titer after COVID-19 vaccination in the dexamethasone group was lower than that in the nondexamethasone group with a statistically significant difference (47.22 v 141.09 U/mL, P = .035). The anti-S IgG seroconversion rate was also significantly lower in the dexamethasone group than in the nondexamethasone group (93.83% v 80.95%, P = .023). The lowest median anti-SARS-CoV-2 IgG titer level at 7.89 AU/mL was observed in patients with the highest dose of steroid group (≥37 mg of dexamethasone cumulative dose throughout the course of chemotherapy [per course]) and patients who were injected with COVID-19 vaccines on the same day of receiving dexamethasone, 25.41 AU/mL. CONCLUSION: Patients with solid cancer vaccinated against COVID-19 disease while receiving dexamethasone had lower immunogenicity responses than those who got vaccines without dexamethasone. The direct association between the immunogenicity level and steroid dosage, as well as length of duration from vaccination to dexamethasone, was observed.

Elotuzumab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: Extended follow-up of a multicenter, retrospective real-world experience with 321 cases outside of controlled clinical trials.

The ELOQUENT-3 trial demonstrated the superiority of the combination of elotuzumab, pomalidomide, and dexamethasone (EloPd) in terms of efficacy and safety, compared to Pd in relapsed/refractory multiple myeloma (RRMM), who had received at least two prior therapies, including lenalidomide and a proteasome inhibitor. The present study is an 18-month follow-up update of a previously published Italian real-life RRMM cohort of patients treated with EloPd. This revised analysis entered 319 RRMM patients accrued in 41 Italian centers. After a median follow-up of 17.7 months, 213 patients (66.4%) experienced disease progression or died. Median progression-free survival (PFS) and overall survival (OS) were 7.5 and 19.2 months, respectively. The updated multivariate analysis showed a significant reduction of PFS benefit magnitude both in advanced International Staging System (ISS) (II and III) stages and previous exposure to daratumumab cases. Instead, advanced ISS (II and III) stages and more than 2 previous lines of therapy maintained an independent prognostic impact on OS. Major adverse events included grade three-fourths neutropenia (24.9%), anemia (13.4%), lymphocytopenia (15.5%), and thrombocytopenia (10.7%), while infection rates and pneumonia were 19.3% and 8.7%, respectively. A slight increase in the incidence of neutropenia and lymphocytopenia was registered with longer follow-up. In conclusion, our real-world study still confirms that EloPd is a safe and possible therapeutic choice for RRMM. Nevertheless, novel strategies are desirable for those patients exposed to daratumumab.

A prospective randomized controlled clinical trial investigating the efficacy of low-dose olanzapine in preventing nausea and vomiting associated with oxaliplatin-based and irinotecan-based chemotherapy.

OBJECTIVE: The aim of this study is to assess the clinical efficacy of a 5 mg dosage of olanzapine in preventing chemotherapy-induced nausea and vomiting (CINV) associated with moderately emetogenic chemotherapy (MEC) among female patients diagnosed with gastrointestinal tract tumors. METHODS: Patients undergoing the oxaliplatin/irinotecan chemotherapy regimen were enrolled in this prospective controlled study. The olanzapine group received a 5 mg dosage of olanzapine along with palonosetron and dexamethasone, while the control group received a standard two-combination regimen consisting of dexamethasone and palonosetron. The primary endpoints included the total protection (TP) rates for the entire age group and the subgroup aged 60 years and above. Secondary endpoints encompassed the total protection rates during the acute and delayed phases within the two age brackets, as well as the total control (TC) rates and complete remission (CR) rates across all three phases (total, acute, and delayed). Additionally, the study involved the assessment of quality of life and the collection of adverse events associated with the interventions. RESULTS: 1) Regarding the primary endpoint, the total phase TP rates within both the entire age group and the age group exceeding 60 years demonstrated superiority in the olanzapine group when compared to the control group (66.7% vs 37.25%, P = 0.003; 68.8% vs 44.4%, P = 0.044). 2) In terms of secondary endpoints, the olanzapine group exhibited superior acute phase TP rates in both age brackets when compared to the control group (P < 0.05). The olanzapine group also demonstrated higher delayed-phase TP rates, TC rates across all three phases, and CR rates within the two age brackets, although the differences were not statistically significant (P > 0.05). Furthermore, the quality of life in the olanzapine group surpassed that of the control group for both age brackets (P < 0.05), characterized by enhanced appetite and a higher incidence of drowsiness in the patients treated with olanzapine when compared to those in the control group (P < 0.05). CONCLUSION: Olanzapine can enhance CINV induced by MEC regimen in female patients across all age groups, including the elderly, and therefore improve the quality of life for these patients. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/index.html , identifier: ChiCTR20000368269, 25/08/2020.

Impact of active pharmaceutical ingredient variables and oleaginous base on the in vitro drug release from ophthalmic ointments: An investigation using dexamethasone as a model drug.

The present study systematically investigates the impact of active pharmaceutical ingredient (API) variables and oleaginous base characteristics on the in vitro release (IVR) performance of ophthalmic ointments, utilizing dexamethasone as a model drug. The interplay between selected attributes (i.e., particle size distribution, crystallinity, and polymorphic form for API, and rheological factors for compendial-grade white petrolatum) and IVR performance was investigated. APIs from different vendors exhibited variations in crystallinity and polymorphism. Ointments containing amorphous dexamethasone presented higher release amounts/rates compared to crystalline counterparts, emphasizing the role of physical state in release kinetics. Variations in particle size of this lipophilic API (5.4 - 21.2 µm) did not appear to impact IVR performance significantly. In contrast, white petrolatum's rheological attributes, which varied substantially within USP-grade petrolatum, were found to critically affect the drug release rate and extent of the ointment. The study's comprehensive analysis establishes a coherent connection between the quality attributes of both API and petrolatum and IVR, delineating their intricate interdependent effects on ophthalmic ointment performance. These findings provide reference to formulation design, quality control, and regulatory considerations within the pharmaceutical industry, fostering a robust foundational understanding of commonly overlooked quality attributes in ophthalmic ointments.

Target trial emulation of carfilzomib safety among patients with relapsed/refractory multiple myeloma using a nationwide observational data in Korea.

PURPOSE: Carfilzomib, commonly used for relapsed/refractory multiple myeloma (RRMM), has been associated with various adverse events in randomized controlled trials (RCTs). However, real-world safety data for a more diverse population are needed, as carfilzomib received expedited approval. This study aimed to evaluate carfilzomib's safety in Korea by comparing new users of KRd (carfilzomib, lenalidomide, and dexamethasone) to Rd (lenalidomide and dexamethasone) using a nationwide administrative claims database. METHODS: The retrospective cohort study utilized target trial emulation, focusing on adverse events in various organ systems similar to the ASPIRE trial. RESULTS: This study included 4,580 RRMM patients between 2007 and 2020, and the KRd group showed significantly higher risks of hematologic adverse events (anemia, neutropenia, thrombocytopenia) and some non-hematologic adverse events (cough, hypokalemia, constipation, hypertension, heart failure) compared to the Rd group. Among non-hematologic adverse events, cardiovascular events (heart failure [HR 2.04; 95% CI 1.24-3.35], hypertension [HR 1.58; 95% CI 1.15-2.17]) had the highest risk in the KRd group. CONCLUSION: The safety profile of carfilzomib in Korean patients was similar to previous RCTs. Therefore, caution should be exercised when using carfilzomib in Asian individuals with RRMM due to the increased risk of cardiovascular adverse events.

Ibrutinib combined with immunochemotherapy with or without autologous stem-cell transplantation versus immunochemotherapy and autologous stem-cell transplantation in previously untreated patients with mantle cell lymphoma (TRIANGLE): a three-arm, randomised, open-label, phase 3 superiority trial of the European Mantle Cell Lymphoma Network.

BACKGROUND: Adding ibrutinib to standard immunochemotherapy might improve outcomes and challenge autologous stem-cell transplantation (ASCT) in younger (aged 65 years or younger) mantle cell lymphoma patients. This trial aimed to investigate whether the addition of ibrutinib results in a superior clinical outcome compared with the pre-trial immunochemotherapy standard with ASCT or an ibrutinib-containing treatment without ASCT. We also investigated whether standard treatment with ASCT is superior to a treatment adding ibrutinib but without ASCT. METHODS: The open-label, randomised, three-arm, parallel-group, superiority TRIANGLE trial was performed in 165 secondary or tertiary clinical centres in 13 European countries and Israel. Patients with previously untreated, stage II-IV mantle cell lymphoma, aged 18-65 years and suitable for ASCT were randomly assigned 1:1:1 to control group A or experimental groups A+I or I, stratified by study group and mantle cell lymphoma international prognostic index risk groups. Treatment in group A consisted of six alternating cycles of R-CHOP (intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous cyclophosphamide 750 mg/m2 on day 1, intravenous doxorubicin 50 mg/m2 on day 1, intravenous vincristine 1·4 mg/m2 on day 1, and oral prednisone 100 mg on days 1-5) and R-DHAP (or R-DHAOx, intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous or oral dexamethasone 40 mg on days 1-4, intravenous cytarabine 2 × 2 g/m2 for 3 h every 12 h on day 2, and intravenous cisplatin 100 mg/m2 over 24 h on day 1 or alternatively intravenous oxaliplatin 130 mg/m2 on day 1) followed by ASCT. In group A+I, ibrutinib (560 mg orally each day) was added on days 1-19 of R-CHOP cycles and as fixed-duration maintenance (560 mg orally each day for 2 years) after ASCT. In group I, ibrutinib was given the same way as in group A+I, but ASCT was omitted. Three pairwise one-sided log-rank tests for the primary outcome of failure-free survival were statistically monitored. The primary analysis was done by intention-to-treat. Adverse events were evaluated by treatment period among patients who started the respective treatment. This ongoing trial is registered with ClinicalTrials.gov, NCT02858258. FINDINGS: Between July 29, 2016 and Dec 28, 2020, 870 patients (662 men, 208 women) were randomly assigned to group A (n=288), group A+I (n=292), and group I (n=290). After 31 months median follow-up, group A+I was superior to group A with 3-year failure-free survival of 88% (95% CI 84-92) versus 72% (67-79; hazard ratio 0·52 [one-sided 98·3% CI 0-0·86]; one-sided p=0·0008). Superiority of group A over group I was not shown with 3-year failure-free survival 72% (67-79) versus 86% (82-91; hazard ratio 1·77 [one-sided 98·3% CI 0-3·76]; one-sided p=0·9979). The comparison of group A+I versus group I is ongoing. There were no relevant differences in grade 3-5 adverse events during induction or ASCT between patients treated with R-CHOP/R-DHAP or ibrutinib combined with R-CHOP/R-DHAP. During maintenance or follow-up, substantially more grade 3-5 haematological adverse events and infections were reported after ASCT plus ibrutinib (group A+I; haematological: 114 [50%] of 231 patients; infections: 58 [25%] of 231; fatal infections: two [1%] of 231) compared with ibrutinib only (group I; haematological: 74 [28%] of 269; infections: 52 [19%] of 269; fatal infections: two [1%] of 269) or after ASCT (group A; haematological: 51 [21%] of 238; infections: 32 [13%] of 238; fatal infections: three [1%] of 238). INTERPRETATION: Adding ibrutinib to first-line treatment resulted in superior efficacy in younger mantle cell lymphoma patients with increased toxicity when given after ASCT. Adding ibrutinib during induction and as maintenance should be part of first-line treatment of younger mantle cell lymphoma patients. Whether ASCT adds to an ibrutinib-containing regimen is not yet determined. FUNDING: Janssen and Leukemia & Lymphoma Society.

Wearable dual-drug controlled release patch for psoriasis treatment.

Wearable drug delivery systems (DDS) have made significant advancements in the field of precision medicine, offering precise regulation of drug dosage, location, and timing. The performance qualities that wearable DDS has always strived for are simplicity, efficiency, and intelligence. This paper proposes a wearable dual-drug synergistic release patch. The patch is powered by a built-in magnesium battery and utilizes a hydrogel containing viologen-based hyperbranched polyamidoamine as both a cathode material and an integrated drug reservoir. This design allows for the simultaneous release of both dexamethasone and tannic acid, overcoming the limitations of monotherapy and ensuring effective synergy for on-demand therapy. In a mouse model with praziquimod-induced psoriasis, the patch demonstrated therapeutic efficacy at a low voltage. The inflammatory skin returned to normal after 5 days with the on-demand release of dual drugs. This work provides a promising treatment option considering its straightforward construction and the therapeutic advantages of dual-drug synergy.