Clofarabine with topotecan, vinorelbine, and thiotepa reinduction regimen for children and young adults with relapsed AML

Effective reinduction regimens are needed for children with relapsed and refractory acute myeloid leukemia (AML) as outcomes remain poor. Therapeutic options are limited in this heavily pre-treated patient population, many of whom have reached lifetime recommended doses of anthracycline chemotherapy. The development of effective non-anthracycline based salvage regimens is crucial to these patients who are at significant risk of life-threatening cardiotoxicity. We previously reported results of a phase 2 trial of a clofarabine-based regimen with topotecan, vinorelbine, and thiotepa (TVTC) in patients with relapsed acute leukemias. Here we report on an expanded bicenter cohort of 33 patients, <25 years of age, with relapsed/refractory (R/R) AML treated with up to 2 cycles of the TVTC reinduction regimen from 2007 to 2018. The overall response rate (ORR), defined as complete remission (CR) or CR with partial recovery of platelet count (CRp), was 71.4% (95%CI: 41.9 to 91.6%) for those patients in first relapse (n=14) and 47.4% ( 95%CI: 24.4 to 71.1%) for patients in 2nd or greater relapse or refractory disease. Responses were seen across multiple high risk cytogenetic and molecular subtypes, with 84% of responders successfully bridged to allogeneic stem cell transplantation. The 5-year OS for patients in first relapse was 46.2% (95%CI: 19.1 to 73.3%) and 50.0% (95%CI: 26.9 to 73.1%) for patients who responded to TVTC. For pediatric and young adult patients with R/R AML, TVTC reinduction compares favorably with currently used salvage regimens and warrants further exploration.

Infectious risk in multiple sclerosis patients treated with disease-modifying therapies: A three-year observational cohort study

Background The disease-modifying therapies (DMTs) largely used in multiple sclerosis (MS) may result in higher infectious risk. Objective We aimed to investigate the infectious risk in DMT-treated MS patients. Methods MS patients were evaluated for infectious risk before starting, switching or during DMT. Results In this three-year observational cohort study 174 MS patients were enrolled. Among them, 18 patients were anti-HBc + and 19 patients were QuantiFERON®-TB Gold In-Tube (QFT) + . No patients with anti-HBc + showed a detectable HBV-DNA and all started DMT. Among QTB + patients, 17 latent TB infections (LTBIs) and 2 active TB infections (TBIs) were identified. After one month of LTBI prophylaxis or TB treatment, respectively, all patients started DMTs. Overall, 149 started DMTs. During DMTs, one ocrelizumab-treated patient with anti-HBc + developed HBV reactivation and six patients (3 on natalizumab, 2 on ocrelizumab and 1 on IFN-β) showed reactivation of HSV-1, with detectable plasma DNA. Finally, 1 cladribine-treated patient experienced VZV reactivation. All the reactivations of latent infections have been successfully treated. Conclusion Screening of infectious diseases in DMT candidate MS patients helps to mitigate the infectious risk. During DMTs, a regular assessment of infectious risk allows to avoid discontinuing MS therapy and guarantees a higher degree of safety.

Role of orthoptics and scoring system for orbital floor blowout fracture: surgical or conservative treatment

AIM: To assess the role of orthoptics in referring patients with orbital floor blowout fracture (OFBF) for conservative or surgical treatment and based on the results, to propose a scoring system for such decision making. METHODS: A retrospective analysis of 69 patients with OFBF was performed (35 treated conservatively, 34 surgically). The role of orthoptics in referring to surgery or conservative treatment was retrospectively evaluated, the factors with the highest significance for decision making were identified, and a scoring system proposed using Logistic regression. RESULTS: According to defined criteria, the treatment was unsuccessful in 2 (6%) surgically treated and only in one (3%) conservatively treated patient. The proposed scoring system includes the defect size and several values resulting from the orthoptic examination, the elevation of the eyebulb measured on Lancaster screen being the most significant. CONCLUSION: The study demonstrates the benefits of orthoptic examination when making decisions on conservative or surgical treatment and for diagnosing ocular motility disorder (with or without binocular diplopia) in OFBF patients. The proposed scoring system could, following verification in a prospective study, become a valuable adjunctive tool.

Correlation of ACE2 with RAS components after Losartan treatment in light of COVID-19

Angiotensin-converting enzyme 2 (ACE2) is an important factor in coronavirus disease (COVID-19) interactions. Losartan (LOS) belongs to the angiotensin receptor blocker (ARB) family. Additionally, the protective role of ACE2 restored by LOS has been suggested and clinically examined in the treatment of COVID-19 patients. Furthermore, clinical trials with LOS have been conducted. However, the mechanism through which LOS enhances ACE2 expression remains unclear. In addition, the response of ACE2 to LOS differs among patients. Our LOS-treated patient data revealed a correlated mechanism of ACE2 with components of the renin-angiotensinogen system. We observed a significant positive regulation of MAS1 and ACE2 expression. In the context of LOS treatment of COVID-19, ACE2 expression could depend on LOS regulated MAS1. Thus, MAS1 expression could predict the COVID-19 treatment response of LOS.

Informed consent in psychotherapy: a survey on attitudes among psychotherapists in Switzerland

Background The legal and ethical guidelines of psychological professional associations stipulate that informed consent by patients is an essential prerequisite for psychotherapy. Despite this awareness of the importance of informed consent, there is little empirical evidence on what psychotherapists’ attitudes towards informed consent are and how informed consent is implemented in psychotherapeutic practice. Methods 155 psychotherapists in Switzerland completed an online survey assessing their attitudes regarding informed consent. Results Among the surveyed psychotherapists, there was a high consensus on important information that should be communicated to patients in the context of informed consent. Almost all psychotherapists rated confidentiality and its exemptions (95%) and self-determined decision-making (97%) as important. The importance to disclose information regarding fees and the empirical effectiveness of the provided treatment, were both seen as important by more than 80% of participants. The disclosure of personal information about the therapist was rated as important by 60%. Other aspects, which are not direct components of informed consent but rather overarching goals, were also evaluated rather homogeneously: self-determined decision making of the patient was rated as important by almost all of the surveyed psychotherapists (97%). The following components were also judged as important by a majority of the participants: promotion of hope (80%) and discussion of treatment goals (93%). Most psychotherapists described the implementation of informed consent as an ongoing process, rather than a one-time event during the first session of therapy. Therapists’ age, postgraduate training, treated patient group, and setting influenced attitudes towards informed consent. Conclusions The present study shows that informed consent is perceived by psychotherapists as both a challenge and a resource. The implementation of informed consent in psychotherapy requires further research from a clinical and ethical perspective.

Tooth Loss During Supportive Periodontal Care in a Strict Non-surgically Treated Cohort – a Retrospective Data Analysis

Background: This retrospective study aimed to evaluate tooth loss (TL) within a strict non-surgically treated patient cohort after supportive periodontal care (SPC) of 2.5-10.7 years.Methods: Data for non-surgically treated patients were checked for: complete periodontal examination data at baseline (T0), after active periodontal therapy (T1), and after ≥2.5 years of SPC (T2); Smoking, diabetes mellitus, age (at least 18 years), plaque and gingival indices, bleeding on probing (BOP), percentage of residual pockets, SPC adherence, and number of SPCs were assessed as risk factors for TL.Results: 132 patients were included (76 female, mean age 56.7±10.3 years), mean T1–T2: 4.5±1.6 years. 26.5% of all patients lost 118 teeth (0.5 teeth/patient, 0.12 teeth/patient/year). Plaque and bleeding parameters: mean plaque control record (PCR): 59.77±28.07%, mean papilla bleeding index (PBI): 47.46±34.12%, mean BOP: 33.46±21.52%. SPC duration (p=0.013) and T2 BOP (p=0.048) were identified as patient-related risk factors for TL.Conclusion: The strictly non-surgical approach within the reported cohort was characterized by elevated BOP, PBI, and PCR scores, possibly highlighting the lack of surgical intervention and regular SPC as negative effect. An apparently low TL rate could be observed. Duration of SPC and BOP (T2) were identified as risk factors for TL.