Qualitative Histologic Assessment vs. Geomorphometric Analysis of Nerve Fiber Shape after the Intraneural Application of Liposomal Bupivacaine / Evaluación Histológica Cualitativa Versus Análisis Geomorfométrico de la Forma de la Fibra Nerviosa Después de la Aplicación Intraneural de Bupivacaína Liposomal

SUMMARY: The preserved form of all components of the nerve fiber is a prerequisite for the proper conduction of the nerve impulse. various factors can change the shape of nerve fibers. In everyday practice, qualitative histological analysis is the gold standard for detecting changes in shape. Geometric morphometry is an innovative method that objectively enables the assessment of changes in nerve fibers' shape after local anesthetics action. A total of sixty sciatic nerves were used as material, which was intraneural injected with saline solution in the control group (n=30), and a solution of 1.33 % liposomal bupivacaine (n=30) in the test group. After the animals were sacrificed, nerve samples were taken and histological preparations were made. The preparations were first described and examined using a qualitative histological method, after which digital images were made. The images were entered into the MorphoJ program and processed using the method of geometric morphometry. Qualitative histological examination revealed no differences in nerve fibers after intraneurally applied physiological solution and liposomal bupivacaine. Using the method of geometric morphometry, a statistically significant change in the shape of axons was found after intraneurally applied saline solution and liposomal bupivacaine (p=0.0059). No significant differences in histological changes were found after the qualitative histological analysis of nerve fiber cross-section preparations. A statistically significant change in the shape of nerve fiber axons was observed after geometric morphometric analysis of digital images after intraneural application of saline and liposomal bupivacaine.

La forma conservada de todos los componentes de la fibra nerviosa es un requisito previo para la conducción correcta del impulso nervioso. Varios factores pueden cambiar la forma de las fibras nerviosas. En la práctica diaria, el análisis histológico cualitativo es el estándar de oro para detectar cambios de forma. La morfometría geométrica es un método innovador que permite evaluar objetivamente los cambios en la forma de las fibras nerviosas después de la acción de los anestésicos locales. Se utilizó como material un total de sesenta nervios ciáticos, que se inyectaron intraneuralmente con solución salina en el grupo control (n=30), y una solución de bupivacaína liposomal al 1,33 % (n=30) en el grupo de prueba. Después de sacrificados los animales, se tomaron muestras de nervios y se realizaron preparaciones histológicas. Primero se describieron y examinaron las preparaciones utilizando un método histológico cualitativo, después de lo cual se tomaron imágenes digitales. Las imágenes fueron ingresadas al programa MorphoJ y procesadas mediante el método de morfometría geométrica. El examen histológico cualitativo no reveló diferencias en las fibras nerviosas después de la aplicación intraneural de solución fisiológica y bupivacaína liposomal. Usando el método de morfometría geométrica, se encontró un cambio estadísticamente significativo en la forma de los axones después de la aplicación intraneural de solución salina y bupivacaína liposomal (p = 0,0059). No se encontraron diferencias significativas en los cambios histológicos después del análisis histológico cualitativo de las preparaciones de secciones transversales de fibras nerviosas. Se observó un cambio estadísticamente significativo en la forma de los axones de las fibras nerviosas después del análisis de morfometría geométrica de imágenes digitales después de la aplicación intraneural de solución salina y bupivacaína liposomal.

Evaluation of liposomal amphotericin B for the treatment of fungal keratitis in a tertiary eye care hospital

Purpose: To evaluate the efficacy of liposomal amphotericin B (L?AMB) for the treatment of fungal keratitis. Methods: Patients with fungal keratitis confirmed by potassium hydroxide (KOH) smear and/ or confocal microscopy were administered topical L?AMB and randomized into three groups treated with three different formulations. The medication was administered two hourly till clinical improvement was achieved, followed by six hourly till complete resolution. The outcome measures were time to clinical improvement, resolution of epithelial defect, stromal infiltrate, hypopyon, extent and density of corneal opacity, neovascularization, and best corrected visual acuity (BCVA) at 3 months. Results: Mean age of the patients was 46.6 ± 14.8 years, and trauma with vegetative matter was the most common predisposing factor. Aspergillus flavus (36%) was the most common fungus cultured, followed by Fusarium (23%). Mean time to clinical improvement, time to resolution of epithelial defect, mean time to resolution of infiltrate, and time to resolution of hypopyon were 3.45 ± 1.38, 25.35 ± 8.46, 37.97 ± 9.94, and 13.33 ± 4.90 days, respectively, and they were comparable among the three groups. There was a significant difference between treatment failure and success cases in terms of days of presentation (P < 0.01), size of the epithelial defect (P?value 0.04), and infiltrate size at presentation (P?value 0.04). At 3 months follow?up, no statistically significant difference was noted in BCVA and mean scar size among groups. Conclusion: L?AMB in a gel form is an effective antifungal agent that promotes the healing of fungal ulcers with notably least vascularization and better tolerance.

Analysis of incidence and influencing factors of interstitial pneumonia in diffuse large B-cell lymphoma after treatment of R-CHOP-like regimens / 白血病·淋巴瘤

Objective:To investigate the incidence of interstitial pneumonia (IP) and its risk factors in newly-diagnosed diffuse large B-cell lymphoma (DLBCL) after treatment of R-CHOP regimen (rituximab combined with cyclophosphamide + doxorubicin + vincristine + prednisone) and R-CDOP regimen (rituximab combined with cyclophosphamide + vincristine + liposomal doxorubicin + prednisone).Methods:The clinical data of 54 newly-diagnosed DLBCL patients who were admitted to the Central Hospital Affiliated to Shandong First Medical University from January 2015 to August 2020 were retrospectively analyzed, of which 25 cases were treated with R-CDOP regimen, and 29 cases were treated with R-CHOP regimen. The incidence of IP was compared in patients stratified according to different clinically factors, and the risk factors of IP were analyzed by multivariate logistic regression.Results:The patients with R-CDOP regimen [compared with R-CHOP regimen: 32.0% (8/25) vs. 3.4% (1/29)], normal lactate dehydrogenase level before treatment [compared with high level: 29.0% (9/31) vs. 0 (0/23)], eosinophilic count>0.1×10 9/L [compared with ≤0.1×10 9/L: 28.0% (7/25) vs. 6.9% (2/29)] and Ki-67 positive index<80% [compared with ≥80%: 23.1% (9/39) vs. 0 (0/15)] had a higher incidence of IP (all P<0.05), there were no statistical differences in the incidence of IP among patients stratified with age, gender, smoking history, underlying disease, stage, international prognostic index score, Eastern Cooperative Oncology Group score, type, B symptoms, β 2-microglobulin, and lymphocyte count (all P>0.05). Multivariate logistic regression analysis showed that the application of R-CDOP regimen was the independent risk factor for the incidence of IP (compared with R-CHOP regimen: OR = 2.898, 95% CI 1.358-6.176, P = 0.008). Conclusions:The application of chemotherapy with R-CDOP regimen in DLBCL patients increases the incidence risk of IP, which needs to be closely monitored and prevented during treatment.

Adverse Drug Reactions to Antifungals Used in the Management of COVID-19 Associated Rhino-Orbito-Cerebral Mucormycosis

Objectives: To determine the incidence and frequency of adverse drug reactions (ADRs) to find out factors, if any contributing to the same, while also exploring the use of amphotericin B deoxycholate as a cheaper and safe alternative to liposomal amphotericin B. Materials and Methods: It was a cross-sectional observational study, with a study population of 50 conducted over three months after ethics approval. All adult patients admitted to a tertiary care center, in a metropolitan city of Maharashtra, diagnosed with Rhino-orbito-cerebral mucormycosis, with a history of previous COVID-19 infection and receiving antifungals for the treatment of the same were included in the study. Central Drugs Standard Control Organization (CDSCO) ADR reporting forms were used to collect data. Results: Electrolyte disturbances mainly hypokalemia were the most frequently encountered ADR with both Amphotericin formulations (39/50; 20.31%) followed by pain at the injection site (33/50; 17.19%). Nephrotoxicity occurred slightly more frequently with Amphotericin B Deoxycholate (19/29; 65%), compared to Liposomal Amphotericin B (11/19; 57%), while Posaconazole was mainly associated with gastrointestinal (GI) disturbances and hepatotoxicity. Conclusion: Amphotericin B Deoxycholate was associated most with ADRs, hypokalemia, and pain at the injection site being the most frequent. However, concerning nephrotoxicity, both Amphotericin formulations showed only a modest difference. Posaconazole was associated with the least number of ADRs and had a favorable safety profile.

Liposomal amphotericin B is more effective in polymorphic lesions of post kala-azar dermal leishmaniasis

Background: Post kala-azar dermal leishmaniasis (PKDL) is thought to be the reservoir of infection for visceral leishmaniasis in South Asia. The development of strategies for the diagnosis and treatment of PKDL are important for the implementation of the visceral leishmaniasis elimination program. Aims: Liposomal amphotericin B (L-AMB) has been an overwhelming success in the treatment of visceral leishmaniasis. However, the empirical three-week regimen of L-AMB proposed for PKDL was shown to be inadequate, especially in the macular variant. This study aimed to delineate response of the different variants of PKDL to L-AMB. Methods: Skin biopsies were collected from PKDL cases at disease presentation and upon completion of treatment with L-AMB. Parasite DNA was detected by Internal Transcribed Spacer-1 PCR (ITS-1 PCR) and quantified by amplification of parasite kDNA. CD68 + macrophages were estimated in tissue sections by immunohistochemistry. Results: Treatment with L-AMB decreased the parasite load by 97% in polymorphic cases but only by 45% in macular cases. The median parasite load (89965 vs 5445 parasites/μg of genomic DNA) as well as infiltration by CD68+ cells before treatment was much greater in the polymorphic cases. Limitations: Although monitoring of the parasite load for 12 months post-treatment would have been ideal, this was not possible owing to logistical issues as well as the invasive nature of biopsy collection procedure. Conclusion: A dramatic decrease in the parasite burden was noted in patients with polymorphic lesions. Although patients with macular disease also had a decrease in parasite burden, this was not as marked as in the polymorphic cases. There was also a significantly greater infiltration of CD68 + macrophages in polymorphic PKDL before therapy

Comparison of liposomal Doxorubicin and Epirubicin in the treatment of diffuse large B-cell lymphoma / 中华老年医学杂志

Objective:To compare the efficacy and safety of pegylated liposomal Doxorubicin(PLD)and Epirubicin(EPI)as first-line chemotherapy for diffuse large B-cell lymphoma(DLBCL).Methods:Clinical data of DLBCL patients treated at Zhejiang Cancer Hospital from March 2013 to April 2018 were retrospectively collected.A total of 411 patients who had received first-line chemotherapy were included.Based on age, sex, Ann Arbor staging and other parameters and using the PSM method for 1∶1 matching, 151 patients were assigned into each of the PLD group and the EPI group.Efficacy and adverse events were compared between the PLD group and the EPI group.All patients were followed up for 3 years after treatment to monitor survival.Results:The complete response(CR)rate in the PLD group was 81.5%, and the CR rate in the EPI group was 72.2%.The objective response rate(ORR)of the PLD group was 98%, and the ORR of the EPI group was 96.7%.There was no significant difference in CR rate( χ2=0.478, P=0.489)or ORR between the two groups( χ2=0.007, P=0.934). In the PLD group, myelosuppression occurred in 25 cases(16.6%)and cardiotoxicity-related events in 21 cases(13.9%); in the EPI group, there were 24 cases(15.9%)of myelosuppression and the same number of cases of cardiotoxicity-related events, and there were no significant differences in myelosuppression( χ2=0.018, P=0.895)or cardiotoxicity( χ2=0.174, P=0.677)between the two groups.During the 3-year follow-up, the progression free survival(PFS)rates of the PLD group and the EPI group were 79.1% and 69.6%, respectively, with a statistically significant difference between the two groups( χ2=3.930, P=0.047). Both the PLD group and the EPI group had a 3-year OS rate of 85.2%, with no statistically significant difference between the two groups( χ2=0.402, P=0.538). Conclusions:The 3-year progression-free survival of DLBCL patients with PLD as first-line chemotherapy is significantly better than with EPI, and the 3-year overall survival, short-term efficacy and myelosuppression are comparable to those with EPI.

Efficacy of conformal intensity-modulated radiotherapy with paclitaxel liposome versus cisplatin in the treatment of locally advanced cervical cancer / 中国基层医药

Objective:To investigate the efficacy of conformal intensity-modulated radiotherapy combined with paclitaxel liposome versus cisplatin in the treatment of locally advanced cervical cancer. Methods:Sixty patients with cervical cancer who received treatment in Rushan People's Hospital from February 2014 to September 2016 were included in this study. They were randomly assigned to undergo either conformal intensity-modulated radiotherapy combined with cisplatin (control group, n = 30) or conformal intensity-modulated radiotherapy combined with paclitaxel liposome (observation group, n = 30) for five cycles. Clinical efficacy and incidence of adverse reactions were compared between the two groups. Results:Total response rate in the observation group was slightly, but not significantly, higher than that in the control group [93.3% (28/30) vs. 90.0% (27/30), P > 0.05]. The incidences of myelosuppression and gastrointestinal reactions in the observation group were 26.7% (8/30) and 53.3% (16/30), respectively, which were significantly lower than those in the control group [46.7% (14/30), 76.7% (23/30), χ2 = 5.16, 7.17, both P < 0.05]. After radiotherapy and chemotherapy, the score of quality of life in the observation group was significantly higher than that in the control group ( t = 3.19, 4.12, 3.22, 4.53, 3.63, 3.08, 3.78, all P < 0.05). Conclusion:Conformal intensity-modulated radiotherapy combined with paclitaxel liposome for treatment of locally advanced cervical cancer can effectively reduce myelosuppression and gastrointestinal reactions and improve quality of life. Conformal intensity-modulated radiotherapy combined with paclitaxel liposome has certain clinical significance in the treatment of locally advanced cervical cancer.

Liposomal amphotericin B was successfully used to treat a case of kala-azar with prominent renal damage / 中华地方病学杂志

Objective:To analyze the diagnosis and treatment process of a kala-azar case with prominent renal damage treated with liposomal amphotericin B (L-AmB), and to provide theoretical basis for clinical diagnosis and treatment.Methods:A retrospective analysis method was used to analyze the clinical data, diagnosis and treatment process and laboratory test results of a case of kala-azar with prominent renal damage who presented to the Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University on June 30, 2020.Results:A 56-year-old female patient presented with fever (the highest body temperature was 38.2 ℃) and chills. The results of clinical laboratory tests showed that hemoglobin(55 g/L), red blood cell (2.68 × 10 12/L), white blood cell (1.06 × 10 9/L) and platelet count (8.00 × 10 9/L) were decreased, renal function showed abnormal blood urea nitrogen and creatinine, spleen enlargement, etc., and the diagnosis of kala-azar combined with kidney insufficiency was confirmed by blood and bone marrow Leishmania spp. examination. With the assistance of continuous renal replacement therapy (CRRT), after a small dose of L-AmB was initially and slowly increased and maintained at a low dose, the patient's body temperature was normal, the blood routine showed that the three-lineage cells gradually increased, and the renal function showed blood urea nitrogen and creatinine decreased gradually the spleen was retracted; no recurrence was found at follow-up after 6 months, and renal function returned to normal. Conclusions:L-AmB is safe and effective in the treatment of kala-azar with renal damage as the prominent manifestation. The patient is not only cured by etiology, but is also recovered renal function.

First line anlotinib plus liposomal doxorubicin for locally advanced or metastatic soft tissue sarcoma: A prospective, single-arm trial

Objective: To examine the efficacy and safety of anlotinib as firstline therapy to treat locally advanced or metastatic soft-tissue sarcoma. Methods: This is a single-arm trial. Treatment-naive patients (≥14 years) with locally advanced or metastatic soft tissue sarcoma were eligible. Each treatment cycle lasted for 3 weeks, and included liposomal doxorubicin (40-50 mg/m2) on day 1 and anlotinib (12 mg) on days 8-21. Starting from the 9th cycle, treatment consisted of only anlotinib. Treatment continued until disease progression or intolerable toxicities. The primary efficacy end point was progression-free survival (PFS). Results: Eight patients were enrolled between July 25, 2019 and January 8, 2020. The median number of treatment cycles was 5.5. Within 5.9 months median follow-up, PFS events occurred in 4 (4/8, 50%) patients. The median PFS was 11.3 months and the 6-month PFS rate was 56%. No patients attained complete response and 2 patients (fibrosarcoma, 1 patient and undifferentiated pleomorphic sarcoma, 1 patient) achieved partial response. Three patients (fibrosarcoma, 2 patients and synovial sarcoma, 1 patient) had stable disease. The objective response rate was 25% (2/8) for the study population, and the disease control rate was 75% (6/8). No new safety concerns emerged. Conclusions: Anlotinib plus liposomal doxorubicin demonstrated antitumor activities in previously untreated locally advanced or metastatic soft tissue sarcomas. Due to the small sample size, further investigations with a larger population should be undertaken to confirm the study findings.

Pharmaceutical strategies to extend pulmonary exposure of inhaled medicines

Pulmonary administration route has been extensively exploited for the treatment of local lung diseases such as asthma, chronic obstructive pulmonary diseases and respiratory infections, and systemic diseases such as diabetes. Most inhaled medicines could be cleared rapidly from the lungs and their therapeutic effects are transit. The inhaled medicines with extended pulmonary exposure may not only improve the patient compliance by reducing the frequency of drug administration, but also enhance the clinical benefits to the patients with improved therapeutic outcomes. This article systematically reviews the physical and chemical strategies to extend the pulmonary exposure of the inhaled medicines. It starts with an introduction of various physiological and pathophysiological barriers for designing inhaled medicines with extended lung exposure, which is followed by recent advances in various strategies to overcome these barriers. Finally, the applications of the inhaled medicines with extended lung exposure for the treatment of various diseases and the safety concerns associated to various strategies to extend the pulmonary exposure of the inhaled medicines are summarized.

Estimating direct costs of the treatment for mucosal leishmaniasis in Brazil

Abstract INTRODUCTION: The objective of this study was to estimate the direct medical costs of the treatment for mucosal leishmaniasis (ML) using three therapeutic approaches in the Brazilian context. METHODS: We performed this economic assessment from the perspective of the Brazilian public healthcare system. The following therapeutic approaches were evaluated: meglumine antimoniate, liposomal amphotericin B, and miltefosine. Direct medical costs were estimated considering four treatment components: a) drug, b) combined medical products, c) procedures, and d) complementary tests. RESULTS: Treatment with meglumine antimoniate had the lowest average cost per patient (US$ 167.66), followed by miltefosine (US$ 259.92) in the outpatient treatment regimen. The average cost of treatment with liposomal amphotericin B was US$ 715.35 both in inpatient regimen. In all estimates, the drugs accounted for more than 60% of the total cost for each treatment approach. CONCLUSIONS: These results demonstrate the marked differences in costs between the therapeutic alternatives for ML. In addition to efficacy rates and costs related to adverse events, our data have the potential to support a complete cost-effectiveness study in the future. Complete analyses comparing costs and benefits for interventions will assist health managers in choosing drugs for ML treatment in Brazil as well as in establishing effective public health policies.

Mucormicosis rinocerebral: Una revisión bibliográfica a propósito de un caso clínico / Rhinocerebral mucormycosis: A literature review and report of clinical case

RESUMEN La mucormicosis es una infección fúngica oportunista, poco común causada por hongos del orden de los mucorales. Ocurre a una tasa anual de 1.7 casos por cada millón de personas y presenta una tasa de mortalidad alta que oscila desde el 30 hasta el 90% de acuerdo con el estado sistémico del paciente. Los escenarios más complejos se observan en pacientes inmunosuprimidos, mientras que, en pacientes competentes, la invasión fúngica es bien controlada por el sistema inmune del huésped. La infección comienza luego de la ex-posición, inhalación e invasión de esporas dentro de la cavidad oral y nasal desde donde se puede diseminar a otras partes del cuerpo, permitiendo diferentes presentaciones clínicas en pacientes susceptibles. Actualmente, los registros internacionales de mortalidad de mucormicosis en niños con neoplasias van desde 41.3 a 66.6, por lo que el objetivo de este estudio es presentar un caso raro de mu-cormicosis rinocerebral en un paciente masculino de 4 años quien además presentó como enfermedad base una leucemia linfoblástica aguda B común, tratado con anfotericina B liposomal y debridación quirúrgica de las zonas afectadas. Finalmente, se realizó una revisión sistemática de la literatura disponible con el afán de determinar y describir los signos, síntomas, diagnóstico, tratamiento disponible y pronóstico de esta enfermedad.

ABSTRACT Mucormycosis is an uncommon opportunistic fungal infection caused by fungi of the mucoral order. Occurs at an annual rate of 1.7 cas-es per million people. It has a high mortality rate ranging from 30 to 90% according to the patient's systemic status. The most complex scenarios are observed in immunosuppressed patients, whereas, in competent patients, the fungal invasion is well controlled by the host's immune system. The infection begins after exposure, inhalation and invasion of spores into the oral and nasal cavity from where it can spread to other parts of the body, allowing different clinical presentations in susceptible patients. Currently, international records of mortality of mucormycosis in children with neoplasms range from 41.3 to 66.6. The objective of this study is to present a rare case of rhi-nocerebral mucormycosis in a 4-year-old male patient who also presented as a base disease a leukemia acute B-lymphoblastic disease. Our patient was treated with liposomal amphotericin B and surgical debridement of affected areas. In addition, a systematic review of the available literature was carried out with the aim of determining and describing the signs, symptoms, diagnosis, available treatment and prognosis of this disease.

Phenylethyl Resorcinol Loaded in Liposomal Cream Formulation for Cosmeceutical Application

Phenylethyl Resorcinol (PR)is a cosmeceutical skin lightening agent and the purpose of this study was to enhance its stability by using liposomal cream formulation which increases local efficacy and safety.Liposome formulation was prepared by modified ethanol injection method, and it contained soy phosphatidyl choline (SPC), cholesterol (CHO), Tween 80 (TW80) and deoxycholic acid (DA) mixed with 2% PR. The physicochemical properties, skin permeation as well as cellular study were evaluated in order to obtain the optimized formulation. The optimized liposome formulation composed of SPC:TW80:DA (84:16:2.5)and exhibited vesicle size, polydispersity index (PDI) and zeta potential of 286.4±8.04 nm, 0.317±0.03 and -39.20±3.85 mV, respectively. Entrapment efficiency (EE) of liposome formulation was 93.55±0.05%. The vesicle was spherical in shape and showed good physicochemical stability for 4 months. The skin permeation study demonstrated that liposome with a negative charge could result in a high PR skin deposition value of 1732.76±216.24 μg/cm2after 24 h. Cellular study showed that liposome formulation could inhibit melanin content in B16 melanoma cells and enhance cell viability in HaCaT keratinocyte cells. The optimized PR liposome was incorporated in cream and investigated physicochemical properties, stability and skin permeation.Liposomal PR cream showed a good stability and a superior result than PR cream in skin permeation parameters, as well as in tyrosinase inhibition

Maintenance of pegylated liposomal doxorubicin/carboplatin in patients with advanced ovarian cancer: randomized study of an Asian Gynecologic Oncology Group / 부인종양

The Efficacy and Safety Profile of First-line R-CDOPlike Regimen in Diffuse Large B-cell Lymphoma with Cardiovascular Diseases Or High Risk Factors / 中国药学杂志

OBJECTIVE: To evaluate the efficacy and safety profile of first-line R-CDOP(rituximab, cyclophosphamide, pegylated liposomal doxorubicin, vincristine, and prednisone) like regimen in diffuse large B-cell lymphoma (DLBCL) with cardiovascular diseases or risk factors. METHODS: DLBCL Patients who were diagnosed with at least one cardiovascular disease/risk factor and received first-line R-CDOPlike chemotherapy in our institute between January 2010 and November 2016 were collected. Cardiovascular diseases/risk factors were referred as:coronary heart disease, hypertension, age ≥60, hyperlipidemia, diabetes mellitus, obesity, history of smoking, and hypothyroidism/hyperthyroidism. Chemotherapy in our institute were retrospectively reviewed. RESULTS: A total of 94 DLBCL patients were recruited. All enrolled patients had history of a cardiovascular disease or presented a high-risk group of developing cardiovascular diseases:coronary heart disease 10 cases, hypertension 33 cases, hyperlipidemia 44 cases, diabetes mellitus 23 cases, obesity 15 cases, history of smoking 25 cases, hypothyroidism/hyperthyroidism 3 cases. A total of 74 patients had more than one cardiovascular disease or risk factors. A total of 34 patients were germinal center B-cell subtype(GCB) and 60 were non-germinal center B-cell subtype(non-GCB). First-line R-CDOP like chemotherapy was given at a median cycle of 4.5 (range, 2-8). Overall response rate(ORR) and complete response rate (CRR) were 92.6%(87/94) and 70.2%(66/94) for the whole group. 5-Year progression-free survival (PFS) and overall survival(OS) rates were 71.3% and 76.9% for overall. For GCB subtype and non-GCB subtype, 5-year PFS rates were 84.6% and 63.9% respectively(P<0.05), and 5-year OS rates were 80.6% and 74.6%, respectively(P=0.407). Grade III/ neutropenia and thrombocytopenia were documented in 53.2%(50/94) and 3.2% (3/94) of patients. 19 (20.2%) patients developed grade /Ⅱ cardiotoxicity. There was no grade III/ cardiac event causing chemotherapy delay or break off. No further cardiotoxicity occurred neither during follow-up. CONCLUSION: PLD-containing first-line R-CDOP like regimen is demonstrated as a highly effective and much tolerable alternative for DLBCL patients with cardiovascular diseases/risk factors.

Chinese expert consensus on management of adverse events of pegylated liposomal doxorubicin (2020 edition) / 中华肿瘤杂志

As a new type of anthracyclines, pegylated liposomal doxorubicin (PLD) is widely used in the treatment of a variety of malignant tumors, including soft tissue sarcoma, ovarian cancer, breast cancer, multiple myeloma, and so on. Compared with traditional anthracyclines, PLD can significantly decrease the incidences of adverse events such as cardiac toxicity and alopecia. However, the use of PLD will be accompanied with toxic side effects such as hand-foot syndrome, oral mucositis, and infusion reaction. This consensus will mainly focus on the mechanism, prevention and treatment of adverse events of PLD, in order to improve the therapeutic efficacy of PLD and life quality of patients.

Preparation and preliminary evaluation of ribavirin liposome-powder inhaler / 药学实践杂志

Objective In order to solve the obvious adverse reactions of ribavirin, to develop ribavirin liposome inhalation powder and to evaluate its quality characteristics. Methods The ribavirin liposomes were prepared by the thin film dispersion method, and then lyophilized to prepare ribavirin liposome powder. The appearance, fluidity, bulk density, encapsulation efficiency, particle size of the complex solution, PDI, potential and hydrophilicity were examined. Results Ribavirin liposome powder has good morphology, particle size, potential, fluidity and hydrophilicity, which can meet the basic requirements of powder medicine for drug administration. Conclusion The technique of preparing ribavirin liposome powder aerosol preparation by this method is feasible, and it provides the basic technology for future in vivo and in vitro studies.

Phase I study on pegylated liposomal doxorubicin in combination with docetaxel for patients with platinum-resistant or partially platinum-sensitive epithelial ovarian cancer: The Kansai Clinical Oncology Group study

Context: In platinum-resistant ovarian cancer, single-agent chemotherapy is recommended for the reduction of adverse events. However, in clinical practice, some patients can tolerate drug-specific adverse events. Aims: We assessed the safety of pegylated liposomal doxorubicin (PEG-LD) and docetaxel regimen in the first cycle of ovarian cancer. Settings and Design: We performed a phase I study to evaluate the combination therapy of PEG-LD and docetaxel. Materials and Methods: We recruited five patients with recurrent ovarian cancer within 12 months of first-line platinum-based chemotherapy. All patients had measurable disease severity. PEG-LD and docetaxel were intravenously administered on day 1 and every 21 days using three dose levels: 25 mg/m2 PEG-LD and 50 mg/m2 docetaxel; 30 mg/m2 PEG-LD and 50 mg/m2 docetaxel; and 30 mg/m2 PEG-LD and 60 mg/m2 docetaxel. Statistical Analysis Used: We defined the maximum tolerated dose of the combination therapy based on the modified Fibonacci method. Results: Five patients were enrolled in this study. The median treatment-free interval was 5.5 months. Two dose-limiting toxicities (Grade 4 neutropenia) were observed in two patients. One complete response, one partial response, one stable disease, and two progressive disease cases were observed. The overall response rate was 2/5, and the disease control rate was 3/5. The median overall survival was 7.4 months. Conclusions: We determined that 25 mg/m2 of PEG-LD and 50 mg/m2 of docetaxel were safe and effective doses. This preliminary efficacy and safety data should be further investigated in a Phase II trial.

Assessment of Treatment Outcome in Post-Kala-Azar Dermal Leishmaniasis (PKDL) Patients– A Record-Based Observational study in a Speciality Public Hospital, Kolkata

In the absence of effective vector control measures and vaccines against leishmaniasis, effective chemotherapy remains the mainstay of treatment. Identification of post-kala-azar dermal leishmaniasis (PKDL) is important due to the long and toxic treatment and the fact that PKDL patients may serve as a reservoir for visceral leishmaniasis (VL). This retrospective study was done to assess the outcome of pharmacotherapy in post-kala-azar dermal leishmaniasis (PKDL) patients in a specialty public hospital in Kolkata. Methods: The hospital records of all consecutive PKDL patients admitted at Calcutta School of Tropical Medicine (CSTM), Kolkata during the last five years - 2010-2014, were reviewed and the relevant information inputs as documented studied to realize the noted objectives. Clinical presentation on admission including presence of co-infections (particularly HIV), trends and patterns of treatment regimens and rationale thereof, if available; treatment (anti-leishmaniasis) outcomes in reference to efficacy, safety and tolerability, fatality like serious complications and mortality and adverse drug reactions (for anti-leishmaninal drugs primarily), if any was noted. Results: PKDL cases presented with insidious onset skin lesions of different types without much systemic illness. 2 out of 19 cases presented with fever and 2 other cases had mild anemia. PKDL cases presented with 4 types of skin lesions. Multiple macular or hyppigmented macular lesions were commonest, 8 out of 19 cases (42.10%). In PKDL cases treatment outcome was difficult to say unless parasitologically declared negative, though clinically regression of the lesions were visible in all cases. Tolerability was least with AmB followed by SSG and best with miltefosine. Conclusion: So, it can be concluded from this study that in this institute PKDL were treated with conventional and liposomal AmB as well as with SSG, miltefosine and combination therapy. Among the regimens short course L-AmB was found to be the most efficacious and tolerable in respect to ADRs and hospital stay.

Comparison of safety and toxicity of liposomal versus conventional Doxorubicin: an updated review

Cancer persists to be a major cause of hospitalization and death every year. With the passage of time, new formulations of anticancer drugs are being introduced to the market and are drawing the concern of healthcare professionals in terms of the superiority, toxicology, and cost-effectiveness of the new formulations in comparison to the conventional formulation of the same drugs. Doxorubicin, a highly potent chemotherapeutic agent, it comes with three formulations (pegylated liposomal, nonpegylated liposomal and non-liposomal conventional formulations). English-language literature of the three formulations of Doxorubicin has been reviewed to inform the healthcare professionals regarding the differences between these formulations. Liposomal Doxorubicin promotes better toxicology profile than non-liposomal conventional Doxorubicin with an increased cost. Due to very limited studies, the cost-effectiveness of liposomal Doxorubicin is not well defined. Apart from that, this review highlights the inter patient variability in regard to the clearance and volume of distribution following the administration of liposomal Doxorubicin. In conclusion, further studies regarding the superiority of liposomal formulation of Doxorubicin , efficacy and dose standardization of liposomal Doxorubicin should be sought in the near future in a more better way.