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AIDS ◽  
2021 ◽  
Vol 35 (Supplement 2) ◽  
pp. S153-S163
Emmanuelle Papot ◽  
Richard Kaplan ◽  
Marco Vitoria ◽  
Mark N. Polizzotto

2021 ◽  
Vol 12 ◽  
Zengfu Zhang ◽  
Jialin Zhou ◽  
Vivek Verma ◽  
Xu Liu ◽  
Meng Wu ◽  

Radiation-induced lung injury (RILI) is a form of radiation damage to normal lung tissue caused by radiotherapy (RT) for thoracic cancers, which is most commonly comprised of radiation pneumonitis (RP) and radiation pulmonary fibrosis (RPF). Moreover, with the widespread utilization of immunotherapies such as immune checkpoint inhibitors as first- and second-line treatments for various cancers, the incidence of immunotherapy-related lung injury (IRLI), a severe immune-related adverse event (irAE), has rapidly increased. To date, we know relatively little about the underlying mechanisms and signaling pathways of these complications. A better understanding of the signaling pathways may facilitate the prevention of lung injury and exploration of potential therapeutic targets. Therefore, this review provides an overview of the signaling pathways of RILI and IRLI and focuses on their crosstalk in diverse signaling pathways as well as on possible mechanisms of adverse events resulting from combined radiotherapy and immunotherapy. Furthermore, this review proposes potential therapeutic targets and avenues of further research based on signaling pathways. Many new studies on pyroptosis have renewed appreciation for the value and importance of pyroptosis in lung injury. Therefore, the authors posit that pyroptosis may be the common downstream pathway of RILI and IRLI; discussion is also conducted regarding further perspectives on pyroptosis as a crucial signaling pathway in lung injury treatment.

2021 ◽  
Vol 42 (2) ◽  
pp. 131-137
Isaris Chaokhamin ◽  
Worapat Attawettayanon ◽  
Virote Chalieopanyarwong ◽  
Monthira Tanthanuch ◽  

Objective: Many treatment options of metastatic castration-resistant prostate cancer (mCRPC) after docetaxel chemotherapy have proved efficacious in clinical trials but, to date, knowledge regarding oncological outcomes is limited. Materials and Methods: We assessed the oncological outcome of 4 drugs (abi- raterone acetate, cabazetaxel, enzalutamide and ketoconazole) in a normal clinical setting in a university-based hospital. Our cohort consisted of 69 patients with post-docetaxel mCRPC. The primary endpoint was overall survival (OS). The secondary endpoint was predicted factor associated overall survival with all sec- ond-line mCRPC treatment outcomes according to the Cox proportional hazards regression model. Results: This cohort consisted of 69 patients with progressive mCRPC after docetaxel chemotherapy. Median overall survival following treatment with abiraterone acetate and ketoconazole was 25.92 and 9.59 months respectively (p < 0.05). Overall survival rates at 1-year following abiraterone acetate, cabazetaxel, enzalutamide and ketoconazole therapy were 76.3%, 83.3%, 100% and 41.9%, respectively. Multivariable analysis found that abiraterone acetate, cabazitaxel and enzalutamide significantly improved survival in comparison to ketoconazole (p < 0.001). Conclusion: Analysis of overall survival following second-line treatment of mCRPC post docetaxel in our study statistically significantly confirmed that abiraterone acetate, cabazitaxel and enzalutamide improve overall survival in comparison to ketoconazole. The study also found that enzalutamide treatment resulted in better outcomes in comparison to the other drugs.

Pathogens ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1568
Stella Zawedde-Muyanja ◽  
Anja Reuter ◽  
Marco A. Tovar ◽  
Hamidah Hussain ◽  
Aime Loando Mboyo ◽  

In this review, we discuss considerations and successful models for providing decentralized diagnosis, treatment, and prevention services for children and adolescents. Key approaches to building decentralized capacity for childhood TB diagnosis in primary care facilities include provider training and increased access to child-focused diagnostic tools and techniques. Treatment of TB disease should be managed close to where patients live; pediatric formulations of both first- and second-line drugs should be widely available; and any hospitalization should be for as brief a period as medically indicated. TB preventive treatment for child and adolescent contacts must be greatly expanded, which will require home visits to identify contacts, building capacity to rule out TB, and adoption of shorter preventive regimens. Decentralization of TB services should involve the private sector, with collaborations outside the TB program in order to reach children and adolescents where they first enter the health care system. The impact of decentralization will be maximized if programs are family-centered and designed around responding to the needs of children and adolescents affected by TB, as well as their families.

Sabrina Schlüter ◽  
Norbert Bornfeld ◽  
Elbrus Valiyev ◽  
Dirk Flühs ◽  
Martin Stuschke ◽  

Purpose: To report the efficacy of combined intravitreal chemotherapy (IVC) and ruthenium-106 brachytherapy in retinoblastoma, either as first line or second line treatment following systemic chemoreduction or intraarterial chemotherapy. Methods: Retrospective data collection of 18 eyes from 18 patients treated with IVC and brachytherapy from August 2014 to December 2019. Results: The method described was our first line therapy in 6 patients, whereas it was used as second line treatment after chemoreduction in the remaining 12 patients. The eyes showed the following classification at initial presentation: 2 group B eyes, 3 group C eyes and 13 group D eyes. The mean follow-up was 19.5 months (range 2 – 53 months). Mean patient age at brachytherapy was 34.0 months (range 15 – 83 months). Median prescribed dose at the tumour base and apex was 574.5 ± 306.7Gy and 88.5 ± 12.2Gy, respectively. The ocular retention rate was 66.7%. Six eyes had to be enucleated due to uncontrollable subretinal and recurrent vitreous seeding, tumour relapse, recurrence of a solid tumour elsewhere in the eye and persistent vitreous bleeding with loss of tumour control. The mean number of intravitreal injections of Melphalan was 5.0. Two patients received a simultaneous injection of Topotecan for insufficient therapeutic response. With regard to radiogenic complications, we could observe temporary retinal and vitreous bleeding (27.8%), serous retinal detachment (44.4%) and radiogenic maculopathy and retinopathy (11.1%). None of the children showed metastatic disease during follow up. Conclusion: Ruthenium-106 plaque therapy in combination with intravitreal chemotherapy is an effective local therapy with good tumour control rates even in advanced eyes. Overall, the analysed therapeutic approach shows an acceptable side effect profile, especially when considering that EBRT and systemic polychemotherapy, or at least the number of cycles needed, with their increased incidence of adverse events can thus be avoided.

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2044
Zitong Shao ◽  
Waiting Tai ◽  
Yingshan Qiu ◽  
Rico C. H. Man ◽  
Qiuying Liao ◽  

Multi-drug-resistant tuberculosis (MDR-TB) is a huge public health problem. The treatment regimen of MDR-TB requires prolonged chemotherapy with multiple drugs including second-line anti-TB agents associated with severe adverse effects. Capreomycin, a polypeptide antibiotic, is the first choice of second-line anti-TB drugs in MDR-TB therapy. It requires repeated intramuscular or intravenous administration five times per week. Pulmonary drug delivery is non-invasive with the advantages of local targeting and reduced risk of systemic toxicity. In this study, inhaled dry powder formulation of capreomycin targeting the lung was developed using spray drying technique. Among the 16 formulations designed, the one containing 25% capreomycin (w/w) and spray-dried at an inlet temperature of 90 °C showed the best overall performance with the mass median aerodynamic diameter (MMAD) of 3.38 μm and a fine particle fraction (FPF) of around 65%. In the pharmacokinetic study in mice, drug concentration in the lungs was approximately 8-fold higher than the minimum inhibitory concentration (MIC) (1.25 to 2.5 µg/mL) for at least 24 h following intratracheal administration (20 mg/kg). Compared to intravenous injection, inhaled capreomycin showed significantly higher area under the curve, slower clearance and longer mean residence time in both the lungs and plasma.

2021 ◽  
Vol 0 (0) ◽  
Marta Opalińska ◽  
Anna Sowa-Staszczak ◽  
Ibraheem Al Maraih ◽  
Aleksandra Gilis-Januszewska ◽  
Alicja Hubalewska-Dydejczyk

Abstract Objectives Severe hypoglycemia in a course of inoperable insulinoma may be life-threating and often it is not well controlled, even by high doses of diazoxide requiring second line treatment. Among available methods PRRT is characterized by relatively low toxicity and is connected with favorable antitumor effect. The aim of the study was an evaluation of the PRRT effectiveness in control of hypoglycemia in patients with primary inoperable insulinoma. Methods Three patients (female with metastatic insulinoma, male with primary inoperable pancreatic tumor, female with MEN1 syndrome and hepatic metastases) were treated with PRRT due to severe hypoglycemia poorly controlled by diazoxide in course of primary inoperable insulinoma. Results Patient 1 baseline fasting glucose concentration increased from 2.4 mmol/L [3.30–5.60] to 5.9 mmol/L after PRRT. In patient 2 fasting glucose level 2.30 mmol/L increased after PRRT to 7.0 mmol/L, while baseline insulin level initially 31.15 uU/mL [2.6–24.9] decreased to 15.4 uU/mL. In patients 3, baseline fasting glucose level 2.5 mmol/L increased after PRRT to 7.9 mmol/L, and insulin decreased from 57.9 uU/mL to 6.3 uU/mL. In imaging there was partial response (PR) in patient 1 and 2 and stabilization of the tumor size in patient 3. In patient 2 reduction of tumor infiltration let for curative surgery performed 4 months after PPRT. Conclusions PRRT may be effective as a first or second line treatment in management of hypoglycemia for patients with hormonally active inoperable insulinoma.

2021 ◽  
pp. annrheumdis-2021-221163
Alejandro Balsa ◽  
Maria Jesus García de Yébenes ◽  
Loreto Carmona

Non-adherence challenges efficacy and costs of healthcare. Knowledge of the underlying factors is essential to design effective intervention strategies.ObjectivesTo estimate the prevalence of treatment adherence in rheumatoid arthritis (RA) and to evaluate its predictors.MethodsA 6-month prospective cohort study of patients with RA selected by systematic stratified sampling (33% on first disease-modifying rheumatic drug (DMARD), 33% on second-line DMARD and 33% on biologics). The outcome measure was treatment adherence, defined by a score greater than 80% both in the Compliance Questionnaire in Rheumatology and the Reported Adherence to Medication scale, and was estimated with 95% CIs. Predictive factors included sociodemographic, psychological, clinical, drug-related, patient–doctor relationship related and logistic. Their effect on 6-month adherence was examined by multilevel logistic models adjusted for baseline covariates.Results180 patients were recruited (77% women, mean age 60.8). The prevalence of adherence was 59.1% (95% CI 48.1% to 71.8%). Patients on biologics showed higher adherence and perceived a higher medication need than the others; patients on second-line DMARDs had experienced more adverse events than the others. The variables explaining adherence in the final multivariate model were the type of treatment prescribed (second-line DMARDs OR=5.22, and biologics OR=3.76), agreement on treatment (OR=4.57), having received information on treatment adaptation (OR=1.42) and the physician perception of patient trust (OR=1.58). These effects were independent of disease activity.ConclusionTreatment adherence in RA is far from complete. Psychological, communicational and logistic factors influence treatment adherence in RA to a greater extent than sociodemographic or clinical factors.

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5994
Constanze Elfgen ◽  
Vesna Bjelic-Radisic

A metastatic state of breast cancer (MBC) affects hundreds of thousands of women worldwide. In hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) MBC, cyclin-dependent kinase (CDK)4/6 inhibitors can improve the progression-free survival (PFS), as well as the overall survival (OS), in selected patients and have been established as first- and second-line therapies. However, as MBC remains uncurable, resistance to CDK4/6 inhibitors occurs and requires alternative treatment approaches. Data on targeted therapy continue to mature, and the number of publications has been constantly rising. This review provides a summary and update on the clinical relevance, patient selection, ongoing trials of CDK4/6 inhibitors, and further targeted therapy options. It focuses on clinical aspects and practicability, as well as adverse events and patient-reported outcomes.

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5974
Aliki Ntzifa ◽  
Dora Londra ◽  
Theodoros Rampias ◽  
Athanasios Kotsakis ◽  
Vassilis Georgoulias ◽  

Osimertinib has been an effective second-line treatment in EGFR mutant NSCLC patients; however, resistance inevitably occurs. DNA methylation has been previously implicated in NSCLC progression and often in therapy resistance, however its distinct role in osimertinib resistance is not elucidated as yet. In the present study, we directly compared DNA methylation of nine selected genes (RASSF1A, RASSF10, APC, WIF-1, BRMS1, SLFN11, RARβ, SHISA3, and FOXA1) in plasma-cfDNA and paired CTCs of NSCLC patients who were longitudinally monitored during osimertinib treatment. Peripheral blood (PB) from 42 NSCLC patients was obtained at two time points: (a) baseline: before treatment with osimertinib and (b) at progression of disease (PD). DNA methylation of the selected genes was detected in plasma-cfDNA (n = 80) and in paired CTCs (n = 74). Direct comparison of DNA methylation of six genes between plasma-cfDNA and paired CTC samples (n = 70) revealed a low concordance, indicating that CTCs and cfDNA give complementary information. DNA methylation analysis of plasma-cfDNA and CTCs indicated that when at least one of these genes was methylated there was a statistically significant increase at PD compared to baseline (p = 0.031). For the first time, DNA methylation analysis in plasma-cfDNA and paired CTCs of NSCLC patients during osimertinib therapy indicated that DNA methylation of these genes could be a possible resistance mechanism.

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