Possible therapeutics for Pseudomyxoma peritonei: a rare, lethal, and the least investigated disease

Pseudomyxoma peritonei (PMP) refers to a growth disorder characterized by glycoprotein neoplasm in the peritoneum, where mucin oversecretion occurs. The tumors of the appendix region are well associated with PMP; however, ovarian, colon, stomach, pancreas, and urachus tumors have also been linked to PMP. Other mucinous tumors in the pelvis, paracolic gutters, greater omentum, retrohepatic space, and Treitz ligament can be the reason for PMP. Despite being rare and having a slow growth rate, PMP can be lethal without treatment. It is treated with neoadjuvant chemotherapy with the option of cytoreductive surgery and intraperitoneal chemotherapy. In the current study, we hypothesize that there may be novel gentle ways to inhibit or eliminate the mucin. Dr. David Morris has used mucolytics - such as bromelain and N-acetyl cysteine to solubilize mucin. In the present review, we aimed to study the regulation of mucin expression by promoter methylation, and drugs that can inhibit mucin, such as boldine, amiloride, naltrexone, dexamethasone, and retinoid acid receptors antagonist. This review also explored some possible pathways, such as inhibition of Na + , Ca2+ channels and induction of DNA methyltransferase along with inhibition of ten-eleven translocation enzymes, which can be good targets to control mucin. Mucins are strong adhesive molecules that play great roles in clinging to cells or cell to cell. Besides, they have been greatly involved in metastasis and also act as disease markers for cancers. Diagnostic markers may have exclusive roles in disease initiation and progression. Therefore, the present review explores various drugs to control and target mucin in various diseases, specifically cancers. (AU)

Umbrales auditivos en pacientes con enfermedad de Méniere manejados con corticoides transtimpánicos / Hearing thresholds in Ménière's disease patients managed with transtympanic dexametasone

Introducción: Pese a que el uso de corticoides transtimpánicos en pacientes con enfermedad de Méniere es habitual en muchos centros, la evidencia respecto de su efecto sobre los umbrales auditivos es aún controversial. Objetivo: Estudiar los umbrales auditivos de pacientes con enfermedad de Méniere que recibieron corticoides transtimpánicos en el Servicio de Otorrinolaringología del Hospital Clínico de la Universidad de Chile. Material y Método: Estudio retrospectivo de pacientes con enfermedad de Méniere que consultaron entre los años 2015 y 2021. Se estudiaron los umbrales auditivos, antes y después de 3 inyecciones de dexametasona transtimpánica. Resultados: Se obtuvieron datos completos de 27 pacientes. Al comparar el promedio tonal puro antes y después del tratamiento, no se observaron diferencias significativas. A nivel individual, la variación de cambio de los umbrales auditivos con dexametasona se correlaciona en forma significativa con los umbrales auditivos previos a las inyecciones y con el tiempo transcurrido desde la última inyección, pero no con la edad. Conclusión: La terapia con dexametasona transtimpánica en pacientes con enfermedad de Méniere no altera los umbrales auditivos. Sin embargo, se requieren más estudios, para comprobar, si existe un efecto transitorio en los umbrales auditivos de los primeros días posterior al procedimiento.

Introduction: Although transtympanic corticosteroids are proposed in Méniere's disease patients refractory to standard medical therapy, the evidence regarding the effect of transtympanic corticosteroids on hearing thresholds is still controversial. Aim: To study the hearing thresholds of patients with Méniere's disease who were administrated with transtympanic corticosteroids at the Otorhinolaryngology Service of the University of Chile's Clinical Hospital. Material and Method: Retrospective study of Méniere's disease patients who consulted between 2015 and 2021. Demographic variables and hearing thresholds were studied before and after three transtympanic injections of dexamethasone. Results: A total of 27 patients were studied. There were non-significant differences in pure-tone hearing threshold averages before and after the injections. Individual variation in hearing thresholds correlates significantly with the pre-injection hearing thresholds and the period since the last injection, but not with age. Conclusion: Transtympanic dexamethasone therapy in patients with Meniere's disease does not alter hearing thresholds. However, more studies are needed to verify whether there is a transitory effect on hearing thresholds in the first days after the procedure.

Comparison of pingyangmycin fibrin glue composite and pingyangmycin dexamethasone composite in the treatment of pharyngolaryngeal venous malformation / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze and compare the efficacy and safety of pingyangmycin fibrin glue composite (PFG) and pingyangmycin dexamethasone composite (PD) in the treatment of pharyngolaryngeal venous malformation (VM). Methods: The clinical data of 98 patients with pharyngolaryngeal VM who underwent sclerotherapy with pingyangmycin composite in the First Affiliated Hospital of Sun Yat-sen University from June 2013 to November 2022 were retrospectively analyzed. According to their treatment, patients were divided into PFG group (n=34) and PD group (n=64), among those patients there were 54 males and 44 females, aged 1-77(37.06±18.86)years. The lesion size, total treatment times and adverse events were recorded before and after treatment. And the efficacy was divided into three grades: recovery, effective and invalid. According to the length of VM, all patients were divided into three subgroups, to compare the differences in efficacy and treatment times between each two groups.And finally the adverse events and their treatments were analyzed. SPSS 25.0 software was used for statistical analysis. Results: The efficacy of PFG group was 94.11%(32/34), the recovery rate was 85.29%(29/34).And the efficacy of PD group was 93.75%(60/64), the recovery rate was 64.06%(41/64). No serious adverse eventst occurred in subgroup comparison, there was no statistical difference between the two groups in efficacy and the times of treatments when the length was≤3 cm (Zefficacy=1.04, ttreatment times=2.18, P>0.05); when the length was 3-5 cm, there was no significant efficacy difference between the two groups(Zefficacy=1.17, P>0.05), but the treatment times of PFG were less (ttreatment times=4.87, P<0.01); when the length≥5 cm, efficacy of PFG was significantly better than PD (Zefficacy=2.94, P<0.01), and had fewer treatments times (ttreatment times=2.16, P<0.01). There were no serious adverse events in either group during treatment and follow-up. Conclusion: Both PFG and PD are safe and effective composite sclerotherapy agent for the treatment of laryngeal VM, but PFG has a higher cure rate and fewer treatment times for massive lesions.

Observation of the Curative Effect of the Dexamethasone Vitreous Cavity Implant for the Treatment of Irvine-Gass Syndrome / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the clinical efficacy of dexamethasone vitreous cavity implants (Ozurdex) for the treatment of macular edema (Irvine-Gass Syndrome) after cataract surgery.@*METHOD@#Eight patients (eight eyes) with Irvine-Gass syndrome were enrolled for vitreous injections with Ozurdex. The patients included six men (six eyes) and two women (two eyes) with a mean age of 67.12 ± 11.92 years. Changes in the patients best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure were compared before and after treatment.@*RESULT@#The mean visual acuity BCVA of the patients was 0.81 ± 0.26 before implantation, which improved to 0.20 ± 0.12, 0.13 ± 0.09, and 0.15 ± 0.13 at 2 weeks, 1 month, and 3 months after implantation, respectively ( P < 0.001). The patient's mean CMT before implantation was 703.00 ± 148.88 μm, and it reduced to 258.87 ± 37.40 μm, 236.25 ± 28.74 μm, and 278.00 ± 76.82 μm at 2 weeks, 1 month, and 3 months after implantation, respectively ( P < 0.001).@*CONCLUSION@#The dexamethasone vitreous cavity implant (Ozurdex) is a safe and effective treatment, which can effectively improve patient's visual acuity and reduce macular edema associated with cataract surgery.

Bendamustine combined with pomalidomide and dexamethasone in relapsed multiple myeloma with extramedullary disease: a multicenter study / 中华血液学杂志

Objective: To evaluate the efficacy and safety of bendamustine combined with pomalidomide and dexamethasone (BPD regimen) in the treatment of relapsed multiple myeloma (MM) with extramedullary disease. Methods: This open, single-arm, multicenter prospective cohort study included 30 relapsed MM patients with extramedullary disease diagnosed in seven hospitals including Qingdao Municipal Hospital. The patients were treated with BPD regimen from February 2021 to November 2022. This study analyzed the efficacy and adverse reactions of the BPD regimen. Results: The median age of the 30 patients was 62 (47-72) years, of which 18 (60% ) had first-time recurrence. The overall response rate (ORR) of the 18 patients with first-time recurrence was 100%, of which three (16.7% ) achieved complete remission, 10 (55.5% ) achieved very good partial remission (VGPR), and five (27.8% ) achieved partial remission (PR). The ORR of 12 patients with recurrence after second-line or above treatment was 50%, including zero patients with ≥VGPR and six patients (50% ) with PR. Three cases (25% ) had stable disease, and three cases (25% ) had disease progression. The one-year progression free survival rate of all patients was 65.2% (95% CI 37.2% -83.1% ), and the 1-year overall survival rate was 90.0% (95% CI 76.2% -95.4% ). The common grade 3-4 hematology adverse reactions included two cases (6.7% ) of neutropenia and one case (3.3% ) of thrombocytopenia. The overall adverse reactions are controllable. Conclusions: The BPD regimen has good efficacy and tolerance in relapsed MM patients with extramedullary disease.

The Efficacy and Safety of Daratumumab-Based Regimen in Treatment of Multiple Myeloma Patients with Renal Impairment / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and safety of daratumumab in treatment of multiple myeloma (MM) patients with renal impairment (RI).@*METHODS@#The clinical data of 15 MM patients with RI who received daratumumab-based regimen from January 2021 to March 2022 in three centers were retrospectively analyzed. Patients were treated with daratumumab or daratumumab combined with dexamethasone or daratumumab combined with bortezomib and dexamethasone and the curative effect and survival were analyzed.@*RESULTS@#The median age of 15 patients was 64 (ranged 54-82) years old. Six patients were IgG-MM, 2 were IgA-MM,1 was IgD-MM and 6 were light chain MM. Median estinated glomerular filtration rate (eGFR) was 22.48 ml/(min·1.73 M2). Overall response rate of 11 patients with MM was 91% (≥MR), including 1 case of stringent complete response (sCR), 2 cases of very good partial response (VGPR), 3 cases of partial response (PR) and 4 cases of minor response (MR). The rate of renal response was 60%(9/15), including 4 cases of complete response (CR), 1 case of PR and 4 cases of MR. A median time of optimal renal response was 21 (ranged 7-56) days. With a median follow-up of 3 months, the median progression-free survival and overall survival of all patients were not reached. After treatment with daratumumab-based regimen, grade 1-2 neutropenia was the most common hematological adverse reaction. Non-hematological adverse reactions were mainly infusion-related adverse reactions and infections.@*CONCLUSION@#Daratumumab-based regimens have good short-term efficacy and safety in the treatment of multiple myeloma patients with renal impairment.

Efficacy and safety of VRD regimen of autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma / 中华内科杂志

Objective: To explore the stem cell collection rate and efficacy and safety of patients aged 70 and below with newly diagnosed multiple myeloma (MM) treated with the VRD (bortezomib, lenalidomide and dexamethasone) regimen followed by autologous stem cell transplantation (ASCT). Methods: Retrospective case series study. The clinical data of 123 patients with newly diagnosed MM from August 1, 2018, to June 30, 2020, at the First Affiliated Hospital of Soochow University and Suzhou Hopes Hematology Hospital, who were eligible for VRD regimen sequential ASCT, were collected. The clinical characteristics, efficacy after induction therapy, mobilization regimen of autologous stem cells, autologous stem cell collection rate, and side effects and efficacy of ASCT were retrospectively analyzed. Results: Of the 123 patients, 67 were males. The median patient age was 56 (range: 31-70) years. Patients with IgG, IgA, IgD, and light-chain types accounted for 47.2% (58/123), 23.6% (29/123), 3.2% (4/123), and 26.0% (32/123) of patients, respectively. In addition, 25.2% (31/123) of patients had renal insufficiency (creatinine clearance rate<40 ml/min). Patients with Revised-International Staging System (R-ISS) Ⅲ accounted for 18.2% (22/121) of patients. After induction therapy, the rates of partial response and above, very-good partial response (VGPR) and above, and complete response (CR)+stringent CR were 82.1% (101/123), 75.6% (93/123), and 45.5% (56/123), respectively. Overall, 90.3% (84/93) of patients were mobilized with cyclophosphamide+granulocyte colony-stimulating factor (G-CSF) and 8 patients with G-CSF or G-CSF+plerixafor due to creatinine clearance rate<30 ml/min and one of them was mobilized with DECP (cisplatin, etoposide, cyclophosphamide and dexamethasone)+G-CSF for progressive disease. The rate of autologous stem cell collection (CD34+cells≥2×106/kg) after four courses of VRD regimen was 89.1% (82/92), and the rate of collection (CD34+cells≥5×106/kg) was 56.5% (52/92). Seventy-seven patients treated with the VRD regimen sequential ASCT. All patients had grade 4 neutropenia and thrombocytopenia. Among the nonhematologic adverse events during ASCT, the highest incidence was observed for gastrointestinal reactions (76.6%, 59/77), followed by oral mucositis (46.8%, 36/77), elevated aminotransferases (44.2%, 34/77), fever (37.7%, 29/77), infection (16.9%, 13/77) and heart-related adverse events (11.7%, 9/77). Among the adverse events, grade 3 adverse events included nausea (6.5%, 5/77), oral mucositis (5.2%, 4/77), vomiting (3.9%, 3/77), infection (2.6%, 2/77), elevated blood pressure after infusion (2.6%, 2/77), elevated alanine transaminase (1.3%, 1/77), and perianal mucositis (1.3%, 1/77); there were no grade 4 or above nonhematologic adverse events. The proportion of patients who achieved VGPR and above after VRD sequential ASCT was 100% (75/75), and the proportion of patients who were minimal residual disease-negative (<10-4 level) was 82.7% (62/75). Conclusion: In patients aged 70 and below with newly diagnosed MM treated with VRD induction therapy, the collection rate of autologous stem cells was good, and good efficacy and tolerability were noted after follow-up ASCT.

Impact of extending prevention of postoperative nausea and vomiting for cancer surgical patients in the PACU: a before and after retrospective study

Abstract Backgrounds Procedures for Postoperative Nausea and Vomiting (PONV) prevention are mostly based on identification of the risk factors before administering antiemetic drugs. The purpose of this study was to evaluate the impact of the extended use of antiemetic on the PONV in the Postanesthetic Care Unit (PACU). Methods Two separate 4-year periods (2007-2010, P1, and (2015-2018, P2) were evaluated. During P1, the protocol consisted of dexamethasone and droperidol for patients with a locally adapted high PONV score, followed by ondansetron for rescue in the PACU. For Period 2, dexamethasone (8 mg) and ondansetron (4 mg) were administered in patients under general or regional anesthesia, or sedation longer than 30 minutes, while droperidol (1.25 mg) in rescue was injected in cases of PONV in the PACU. An Anesthesia Information Management System was used to evaluate the intensity score of PONV (1 to 5), putative compliance, sedation, and perioperative opioid consumption upon arrival in the PACU. Results A total of 27,602 patients were assessed in P1 and 36,100 in P2. The administration of dexamethasone and ondansetron increased several fold (p < 0.0001). The high PONV scores were more improved in P2 than in P1, with scores (3+4+5) for P1 vs. P2, p < 0.0001. Overall, 99.7% of the patients in P2 were asymptomatic at discharge. Morphine consumption decreased from 6.9±1.5 mg in P1 to 3.5 ± 1.5 mg in P2 (p < 0.0001). Discussion The extension of pharmacological prevention of PONV was associated with a decrease in the intensity of severe PONV. However, uncertainty regarding confounding factors should not be ignored. IRB nº 92012/33465

Predictors of efficacy of corticosteroid switching from abiraterone plus prednisone to dexamethasone in patients with metastatic castration-resistant prostate cancer / 亚洲男科学杂志(英文版)

Corticosteroid switching can reverse abiraterone resistance in some patients with metastatic castration-resistant prostate cancer (mCRPC). Here, we investigated the potential biomarkers for predicting the efficacy of corticosteroid switching during treatment with abiraterone acetate (AA). We retrospectively analyzed 101 mCRPC patients receiving corticosteroid switching from West China Hospital and Sun Yat-Sen University Cancer Center between January 2016 and December 2018. All cases received AA plus prednisone as first-line therapy during mCRPC. Primary end points were biochemical progression-free survival (bPFS) and overall survival (OS). The risk groups were defined based on multivariate analysis. A total of 42 (41.6%) and 25 (24.8%) patients achieved 30% and 50% decline in prostate-specific antigen (PSA), respectively, after corticosteroid switching. The median bPFS and median OS on AA plus dexamethasone were 4.9 (95% confidence interval [CI]: 3.7-6.0) months and 18.8 (95% CI: 16.2-30.2) months, respectively. Aldo-keto reductase family 1 member C3 (AKR1C3) expression (hazard ratio [HR]: 2.15, 95% Cl: 1.22-3.80, P = 0.008) and baseline serum alkaline phosphatase (ALP; HR: 4.95, 95% Cl: 2.40-10.19, P < 0.001) were independent predictors of efficacy before corticosteroid switching in the multivariate analysis of bPFS. Only baseline serum ALP >160 IU l-1 (HR: 3.41, 95% Cl: 1.57-7.38, P = 0.002) together with PSA level at switch ≥50 ng ml-1 (HR: 2.59, 95% Cl: 1.22-5.47, P = 0.013) independently predicted poorer OS. Based on the predictive factors in multivariate analysis, we developed two risk stratification tools to select candidates for corticosteroid switching. Detection of serum ALP level, PSA level, and tissue AKR1C3 expression in mCRPC patients could help make clinical decisions for corticosteroid switching.

Effect of fire needling on imiquimod induced psoriasis-like lesion and STAT3 pathway in mice / 中国针灸

OBJECTIVE@#To observe the effect of fire needling on psoriasis-like lesion and the signal transducer and activator of transcription 3 (STAT3) pathway in mice and compare the therapeutic effect between different interventions of fire needling therapy (surrounding technique of fire needling, fire needling at "Dazhui" [GV 14] and "Zusanli" [ST 36]).@*METHODS@#Thirty male BALB/c mice were randomized into a blank group, a model group, a dexamthasone group, a surrounding technique group and an acupoint group, 6 mice in each one. Except the blank group, the mice in the rest groups were established as psoriasis-like lesion model by topical application with imiquimod cream, once daily, consecutively for 8 days. From day 4 to day 8, in the dexamthasone group, gastric infusion with 0.2 mL dexamthasone was administered, once daily. On day 4, 6 and 8, in the surrounding technique group, fire needling was exerted around the skin lesion; and fire needling was applied to "Dazhui" (GV 14) and "Zusanli" (ST 36) in the acupoint group, once a day. The changes in skin lesion on the dorsal parts of mice were observed in each group to score the psoriasis area and severity index (PASI). Using HE staining, the dermal morphological changes and epidermal thickness were observed in the mice of each group. The positive expression of proliferating cell-associated antigen Ki-67 was determined by immunofluorescence. Immunohistochemistry method was used to determine the expressions of , and T cells of skin tissue in each group. Using real-time PCR, the expressions of interleukin (IL)-17, IL-22, tumor necrosis factor α(TNF-α) mRNA were determined. Western blot method was adopted to determine the protein expressions of STAT3 and p-STAT3 in skin tissue in each group.@*RESULTS@#Compared with the blank group, the scores of each item and the total scores of PASI, as well as the epidermal thickness were all increased in the mice of the model group (P<0.01). Except for the erythema scores of the dexamethasone group and the surrounding technique group, the scores of each item and the total scores of PASI, as well as the epidermal thickness were all decreased in each intervention group as compared with the model group (P<0.01). The infiltration scores and the total scores in the dexamethasone group and the acupoint group were lower than those in the surrounding technique group respectively (P<0.01, P<0.05). In comparison with the blank group, Ki-67 positive cell numbers and the numbers of , and T cells in skin tissue were increased in the mice of the model group (P<0.01). Ki-67 positive cell numbers and the numbers of , and T cells were reduced in each intervention group as compared with the model group (P<0.01), and the numbers of and T cells in the acupoint group were less than the surrounding technique group (P<0.01). Compared with the blank group, the mRNA expressions of IL-17, IL-22 and TNF-α and the ratio of p-STAT3 to STAT3 were all increased in the model group (P<0.01). The mRNA expressions of IL-17, IL-22 and TNF-α and the ratio of p-STAT3 to STAT3 were all decreased in each intervention group as compared with the model group (P<0.01, P<0.05). The mRNA expressions of IL-17, IL-22 and TNF-α in the acupoint group, as well as mRNA expression of IL-17 in the surrounding technique group were all lower than the dexamethasone group (P<0.01), while, the mRNA expression of IL-22 in the acupoint group was lower than the surrounding technique group (P<0.01).@*CONCLUSION@#Fire needling therapy improves skin lesion severity in imiquimod induced psoriasis-like lesion of the mice, which is probably related to the inhibition of STAT3 pathway activation and the decrease of Th17 inflammatory factors expression. The systemic regulation of fire needling at "Dazhui" (GV 14) and "Zusanli" (ST 36) is superior to the local treatment.

Effect of dexamethasone combined with oxybuprocaine hydrochloride gel on prevention of postoperative sore throat after nasal endoscopy / 北京大学学报(医学版)

OBJECTIVE@#To explore the effectiveness and feasibility of dexamethasone combined with oxybuprocaine hydrochloride gel on the prevention of postoperative sore throat after nasal endoscopy.@*METHODS@#In the study, 60 patients with American Society of Anesthesiologist (ASA) physical statuses Ⅰ to Ⅱ, aged 18 to 72 years, scheduled for elective nasal endoscope surgery under general anesthesia requiring endotracheal intubation were randomly divided into dexamethasone combined with oxybuprocaine hydrochloride gel group (G group, n=30) and control group (C group, n=30). The patients in the G group received dexamethasone 0.1 mg/kg before induction and the oxybuprocaine gel was applied to the endotracheal catheter cuff and the front end within 15 cm. The patients in the C group received the same dose of saline and the saline was applied to the endotracheal catheter cuff and the front end within 15 cm. Then, all the patients in the two groups received the same induction and anesthesia maintainance. The operation time, anesthesia time, emergence time, extubation time and departure time were recorded. The intraoperative infusion volume, blood loss volume, propofol, remifentanil, rocuronium dosage were also recorded. The adverse reactions such as intraoperative hypotension, bradycardia and postoperative agitation were recorded. The postoperative sore throat score was recorded at the end of operation and 4 h, 8 h, 12 h, and 24 h after operation.@*RESULTS@#Compared with the C group, the emergence time [(8.4±3.9) min vs. (10.8±4.7) min], extubation time [(8.8±3.7) min vs. (11.9±4.8) min], and departure time [(20.0±5.3) min vs. (23.0±5.8) min] were significantly shorter, and the propofol dosage [(11.8±1.8) mg/kg vs. (15.9±4.6) mg/kg], remifentanil dosage [(10.9±4.7) μg/kg vs. (14.1±3.6) μg/kg] were significantly less in the G group, and there was no difference of rocuronium dosage in the two groups. Compared with the C group the incidence of intraoperative hypotension [10%(3/30) vs. 30%(9/30)], bradycardia [16.7%(5/30) vs. 20%(6/30)] and postoperative agitation [6.7%(2/30) vs. 23.3%(7/30)] were significantly lower in the C group. The postoperative sore throat score at the end of operation, 4 h, 8 h, 12 h and 24 h after operation in the G group were significantly lower than in the C group respectively [0 (0, 1) vs. 1 (1, 2), 0 (0, 0) vs. 1 (1, 2), 0 (0, 0) vs. 1 (1, 2), 0 (0, 0) vs. 1 (0.75, 1), 0 (0, 0) vs. 1 (0, 1)].@*CONCLUSION@#Dexamethasone combined with oxybuprocaine hydrochloride gel was effective and feasible on the prevention of postoperative sore throat after nasal endoscopy.

Design and evaluation of ocular hydrogel containing combination of ofloxacin and dexamethasone for the treatment of conjunctivitis

Abstract Conjunctivitis is an inflammation of the conjunctiva, which covers the white part of the eyeball. It can be caused by allergies, bacterial or viral infection. In situ hydrogels are three-dimensional hydrophilic cross-linked network of polymers. In situ hydrogel provided better therapeutic index when compared to conventional treatment. The present work describes the formulation and evaluation of ofloxacin and dexamethasone based on the concept of pH triggered in situ gelation. Carbopol 934p was used as the gelling agent in combination with HPMC, as a viscosity-enhancing agent, benzalkonium chloride as preservative, sodium chloride as tonicity adjusting agent. The prepared formulations were liquid at the low pH and underwent rapid transition into viscous gel at the pH of the tear fluid. Formulations were evaluated for various rheological, in vitro and in vivo release characteristics. Infrared spectroscopy studies showed that there were no interactions between the drug and polymers. Viscosity of the prepared hydrogels lies in the optimum range and drug was released up to 85 % as the end of 13 h. The prepared in situ hydrogel was sterile, non-irritant to the eye. The present study indicated that it is possible to develop safe and physiologically effective in situ hydrogel which is patient compliant.

Dexamethasone for treating SARS-CoV-2 infection: a systematic review and meta-analysis

ABSTRACT BACKGROUND: Considering the disruptions imposed by lockdowns and social distancing recommendations, coupled with overwhelmed healthcare systems, researchers worldwide have been exploring drug repositioning strategies for treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). OBJECTIVE: To compile results from randomized clinical trials on the effect of dexamethasone, compared with standard treatment for management of SARS-CoV-2. DESIGN AND SETTING: We conducted a systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in a Brazilian public university. METHODS: We sought to compile data from 6724 hospitalized patients with confirmed or suspected SARS-CoV-2 infection. RESULTS: Treatment with dexamethasone significantly reduced mortality within 28 days (risk ratio, RR: 0.89; 95% confidence interval, CI: 0.82-0.97). Dexamethasone use was linked with being discharged alive within 28 days (odds ratio, OR: 1.20; 95% CI: 1.07-1.33). CONCLUSIONS: This study suggests that dexamethasone may significantly improve the outcome among hospitalized patients with SARS-CoV-2 infection and associated severe respiratory complications. ­Further studies need to consider both dose-dependent administration and outcomes in early and later stages of the disease. PROSPERO platform: CRD42021229825.

Cyclophosphamide-glucocorticoids versus lenalidomide-dexamethasone as treatment for multiple myeloma at first relapse after autologous stem cell transplantation - a retrospective analysis

ABSTRACT There have been significant improvements in therapeutic options for relapsed multiple myeloma (MM) over the past two decades, with many novel agents including proteasome inhibitors, immunomodulatory agents, and more recently monoclonal antibodies demonstrating efficacy in this setting. However, there is a paucity of real-world data comparing outcomes seen in patients treated with novel agents as opposed to older agents. We report a historical single center cohort of patients diagnosed with myeloma between the years 1991-2012 in order to explore possible differences in outcomes. A total of 139 patients who underwent stem cell transplantation were included in our study. In our study, 88 patients were treated with cyclophosphamide and steroids alone at relapse whereas 51 patients were treated with Len-Dex. In the multivariate analysis, TTNT was shorter for patients who received Cyclo compared to Len-Dex (HR = 1.74; 95% CI, 1.01-2.99; p = 0.04); however, we could not detect an overall survival benefit (HR = 1.20; 95% CI 0.63-2.29; p = 0.57). Adverse event rates were similar in the two groups. In this retrospective single center analysis, Len-Dex was associated with longer TTNT compared with Cyclo at first relapse following autoSCT in MM; however its effect on overall survival in this setting was less clear.

The effectiveness of dexamethasone on the prognosis of dialysis patients with severe COVID-19

SUMMARY OBJECTIVE: This study aimed to investigate the effectiveness of dexamethasone in dialysis patients with COVID-19 and whether it predicts mortality. METHODS: This is a comparative cross-sectional study of 113 consecutive patients with COVID-19 with severe pneumonia signs. The patients were divided into two groups according to the use of dexamethasone treatment: group 1 (n=45) included patients who were treated with dexamethasone and group 2 (n=68) who did not receive dexamethasone. RESULTS: The mean age of both groups was 67.0±10.6 and 67.2±13.0 years, respectively (p=0.947). With respect to demographic and laboratory findings, there were no significant differences between the two groups (p>0.05). The hospitalization time of patients in group 1 was longer than that in group 2 (11 [7-17] days vs. 8 [5.3-14] days, p=0.093]. The 28-day survival rate was 54.2% in the group receiving dexamethasone treatment and 79.5% in the group not receiving dexamethasone treatment (p=0.440). CONCLUSION: Dexamethasone did not reduce mortality rates and the requirement for intensive care unit in dialysis patients with COVID-19. Larger prospective randomized clinical trials are required to associate personalized medicine with the corticosteroid treatment to select suitable patients who are more likely to show a benefit.

Encefalite herpética associada a mieloma múltiplo: desafio diagnóstico / Herpetic encephalitis associated with multiple myeloma: a diagnostic challenge

O mieloma múltiplo é a segunda neoplasia onco-hematológica mais comum, correspondendo a 1% das neoplasias malignas. Trata-se de uma condição subdiagnosticada, assim como a encefalite herpética. Entretanto, é comum a relação do mieloma com infecções, em decorrência do acometimento da imunidade humoral. A encefalite viral herpética tem como principal agente o vírus do herpes simples 1. O caso foi descrito baseado em um raciocínio clínico, visando contribuir para uma melhor caracterização do quadro clínico e do diagnóstico de duas entidades clínicas que possuem baixa suspeição diagnóstica e elevada morbimortalidade. Durante o curso da investigação, foram propostas variadas etiologias como responsáveis pelo rebaixamento do nível de consciência, levando a uma pesquisa de um espectro mais amplo de hipóteses diagnósticas, as quais precederam a confirmação do diagnóstico final. O quadro clínico atípico descrito apresentou obstáculos à suspeição diagnóstica correta, pois a ausência dos sinais e sintomas característicos de ambas as doenças levaram à pesquisa de um arsenal mais amplo de diagnósticos diferenciais. Assim, o atraso no diagnóstico e o início tardio do tratamento foram fatores que contribuíram para o prognóstico reservado do paciente. A associação dessas doenças é pouco descrita na literatura, de modo que mais estudos acerca do assunto se fazem necessários. (AU)

Multiple myeloma is the second most common onco-hematologic neoplasm, accounting for 1% of malignant neoplasms. As herpetic encephalitis, it is an underdiagnosed condition. However, the relation of myeloma with infections is common, due to the involvement of humoral immunity. Herpetic encephalitis has as its main etiological agent the herpes simplex virus 1. The case was described based on a clinical reasoning, aiming to contribute to a better characterization of the clinical picture and diagnosis of two entities that have low rates of diagnostic suspicion and high rates of morbidity and mortality. During the course of investigation, several etiologies were proposed as responsible for the decreased level of consciousness, leading to a search for a broader range of diagnostic hypotheses, which preceded confirmation of the final diagnosis. The atypical clinical picture described presented obstacles to the correct diagnostic suspicion, as the absence of symptoms and signs characteristic of both diseases led to the search for a broader arsenal of differential diagnoses. Thus, delayed diagnosis and late treatment were factors that contributed to the patient's reserved prognosis. The association of these diseases is poorly described in the literature, so further studies on that subject are required. (AU)

Short-Term Efficacy and Safety Profile of Generic Bortezomib in the Treatment of Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the short-term efficacy and safety of generic bortezomib in the treatment of Chinese patients with multiple myeloma (MM).@*METHODS@#Clinical data of 62 MM patients (median age of 62 years) who had accepted at least 2 cycles of chemotherapy based on generic bortezomib in our center from December 2017 to July 2019 were retrospectively analyzed, including 47 newly diagnosed patients and 15 with disease recurrence or progression.@*RESULTS@#Anemia, renal dysfunction, hypoproteinemia and high level of β @*CONCLUSION@#The disease severity can be rapidly alleviated after generic bortezomib-based chemotherapy, and a favorable short-term efficacy and survival have been observed with a generally acceptable toxicity profile. However, the long-term outcomes will be examined through further follow-up.

Clinical Analysis of 25 Non-Transplanted Multiple Myeloma Patients Treated with Bortezomib Maintenance / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy, survival and adverse effects of non-transplanted multiple myeloma (MM) patients treated with bortezomib maintenance.@*METHODS@#A total of 25 newly diagnosed/relapsed non-transplanted MM patients treated in West District of Beijing Chaoyang Hospital from June 2004 to November 2015 were analyzed retrospectively. All patients received PD regimen (bortezomib and dexamethasone), including bortezomib at a dose of 1.3 mg/m@*RESULTS@#Till November 1, 2017, 5 patients achieved stringent complete response (sCR), 8 patients achieved complete response (CR), 7 patients achieved very good partial response (VGPR), 4 patients achieved partial reponse (PR), while 1 patient achieved stable disease (SD). After maintenance therapy, 21 patients maintained the efficacy above PR, of which 1 patient was improved from CR to sCR; 4 patients adjusted chemotherapy after disease progressed. Median maintenance therapy was 9 cycles (range from 6 to 31), and the median maintenance time was 27 months (range from 18 to 97). Median follow-up time was 73 months (range from 25 to 171). Median progress-free survival (PFS) time was 30 months (range from 9 to 105) and overall survival (OS) time was 57 months (range from 27 to 160). Till November 1, 2019, 3-year survival rate was 84% (21/25), and 5-year survival rate was 72% (13/18). The most common adverse events were transient leukopenia, thrombocytopenia and peripheral neuropathy, which the patients could tolerate after the prevention and treatment.@*CONCLUSION@#Bortezomib-based maintenance therapy for non-transplanted MM patients can be an option in consideration of its safety and efficacy.