Successful treatment of acute promyelocytic leukemia in pregnancy with single-agent all-trans retinoic acid.

PURPOSE: The diagnosis of acute promyelocytic leukemia (APL) in pregnancy is an uncommon, life-threatening emergency. Choice of treatment and management of complications are challenging. METHODS: We report the case of a patient with diagnosis of APL at gestational age (GA) 24 + 4. We describe the interdisciplinary management during pregnancy and delivery and provide a 2-year follow-up. Existing reports on APL in pregnancy are summarized. RESULTS: Single-agent induction therapy with all-trans retinoic acid (ATRA) was started and resulted in normalization of blood cell counts after 32 days. Vaginal delivery of a healthy baby occurred at GA 34 + 4. Consolidation therapy consisted of four courses of ATRA and arsenic trioxide (ATO). Less than 100 cases of APL in pregnancy are published. Misdiagnosis as HELLP syndrome with fatal outcome may occur. Combination therapies (ATRA-plus anthracyclines) were used in the majority of reports. CONCLUSIONS: Diagnosis and treatment of APL during pregnancy continues to be a challenge requiring interdisciplinary team work. Single-agent ATRA therapy may evolve as a safe and less-toxic treatment modality.

Diagnostic criteria of chronic conjunctivitis: atopic keratoconjunctivitis and vernal keratoconjunctivitis.

PURPOSE OF REVIEW: Chronic ocular allergies, vernal (VKC) and atopic keratoconjunctivitis (AKC) are relatively rare conditions that require definite diagnostic criteria to the most appropriate therapeutical approach. RECENT FINDINGS: The diagnosis of both VKC and AKC is generally based on clinical history, signs and symptoms, and the results of allergic tests, which allow to identify the different diseases phenotypes. However, other subtypes of the two diseases and/or overlaps may occur making the diagnosis non always so clear, such as VKC and AKC overlaps or adult-like VKC disease. Each of these phenotypes may be sustained by different mechanisms which are still not well defined but not only related to a type 2 inflammation. The further challenges will be to correlate clinical or molecular biomarkers to a single subtype or disease severity. SUMMARY: Definite criteria of chronic allergies will further guide to more specific therapeutical approaches.

Role of Renin-Angiotensin System Blockers on BCG Response in Nonmuscle Invasive, High Risk Bladder Cancer.

INTRODUCTION: The gold standard treatment for high-risk NMIBC is BCG immunotherapy. Some studies suggested an immomodulatory effects for commonly used drugs (ie, ACE-I and ARBs). We aimed to determine whether these drugs impact the prognosis of patients with high-risk NMIBC treated with BCG. MATERIALS AND METHODS: Retrospective analysis on 208 patients from a single academic center with primary high-risk NMIBC treated with transurethral resection followed by 6 weekly instillations of BCG and up to 12 monthly maintenance instillations. ARBs or ACE-I use at the time of treatment initiation was recorded. Inverse probability of treatment weighting (IPTW) was used to adjust for clinical and pathological covariates. IPTW-adjusted Kaplan-Meier curves and weighted Cox proportional hazards regression were used to compare 2-yr failure-free (2-yr FFS), failure-free (FFS), overall recurrence-free (RFS) and progression-free survival (PFS). RESULTS: A total of 68 patients were on ACE-I, and 38 on ARBs and treatment respectively. At a median follow-up of 26 months, ACE-I treatment had no significant impact on cancer-related outcomes. Conversely, patients treated with ARBs experienced significant improvements in 2-yr FFS (HR 0.3; 0.1-0.9, P = .004), FFS (HR 0.4, 0.1-0.9, P = .005), and PFS (HR 0.001; < 0.001-0.001, P < .001). No significant impact was found for ARB use in RFS (HR 0.6; P = .09). Sensitivity analyses confirmed these results. CONCLUSIONS: our findings support a potential role of the angiotensin-renin system in bladder cancer development. We identified ARBs as potential beneficial drugs that seems to act in synergy with BCG-immunotherapy.

Possible Strategies to Optimize a Biomarker Discovery Approach to Correlate with Neurological Outcome in Patients with Spinal Cord Injury: A Pilot Study.

The lack of reliable diagnostic and prognostic markers for spinal cord injured (SCI) patients is a severe obstacle in development and testing of new therapies, and it also impairs appropriate rehabilitation care. The sparse available data on the biochemical composition of cerebrospinal fluid (CSF) during the acute and/or chronic phase of the lesion provide, up until now, inconsistent results. In this pilot study, we then explored the possibility of combining a multi-parametric and bioinformatic analysis of CSF for its biological properties tested on different cells types, suitable for investigating inflammation and re-myelination. The patient enrollment was based on stringent inclusion criteria; that is, cervical and thoracic SCI trauma, CSF collection within 24 h of trauma, type of surgical approach for spine stabilization, and absence of steroid therapy before CSF collection. Eleven SCI patients and four healthy controls were included, and in three patients, CSF was also collected at 3 months after lesion. We identified 19 proteins among the 60 investigated cytokines, chemokines, growth factors, and structural biomarkers, which are transiently regulated 24 h after SCI. A bioinformatic analysis indicated that interleukin (IL)-6 and IL-10 are in the core of the interconnected net of activated proteins. Cell-based experiments indicate that CSF from SCI patients stimulates astroglia derivation from neural precursor cells, and an inverse correlation between IL-8 CSF level and oligodendrocyte precursor cells generated from neural stem cells was also observed. Results from this pilot study suggest that using a combined bioanalytic and biological approach to analyze SCI CSF at different times after injury could be a useful approach for identifying reliable diagnostic and prognostic markers in SCI.

Predicting return to work after acute myocardial infarction: Socio-occupational factors overcome clinical conditions.

OBJECTIVES: Return to work after acute myocardial infarction (AMI), a leading cause of death globally, is a multidimensional process influenced by clinical, psychological, social and occupational factors, the single impact of which, however, is still not well defined. The objective of this study was to investigate these 4 factors on return to work (RTW) within 365 days after AMI in a homogeneous cohort of patients who had undergone an urgent coronary angioplasty. PARTICIPANTS: We studied 102 patients, in employment at the time of AMI (88.24% of men), admitted to the Department of Cardiology of the University-Hospital of Ferrara between March 2015 to December 2016. Demographical and clinical characteristics were obtained from the cardiological records. After completing an interview on social and occupational variables and the Hospital Anxiety and Depression (HADS) questionnaire, patients underwent exercise capacity measurement and spirometry. RESULTS: Of the 102 patients, only 12 (12.76%) held a university degree, 68.63% were employees and 31.37% self-employed. The median number of sick-leave days was 44 (IQR 33-88). At day 30, 78.5% of all subjects had not returned to work, at day 60, 40.8% and at day 365 only 7.3% had not resumed working. At univariate analyses, educational degree (p = 0.026), self-employment status (p = 0.0005), white collar professional category (p = 0.020) and HADS depression score were significant for earlier return to work. The multivariate analysis confirms that having a university degree, being self-employed and presenting a lower value of HADS depression score increase the probability of a quicker return to work. CONCLUSIONS: These findings suggest that the strongest predictors of returning to work within 1 year after discharge for an acute myocardial infarction are related more to socio-occupational than to clinical parameters.

Variable RBE in proton therapy: comparison of different model predictions and their influence on clinical-like scenarios.

BACKGROUND: In proton radiation therapy a constant relative biological effectiveness (RBE) of 1.1 is usually assumed. However, biological experiments have evidenced RBE dependencies on dose level, proton linear energy transfer (LET) and tissue type. This work compares the predictions of three of the main radio-biological models proposed in the literature by Carabe-Fernandez, Wedenberg, Scholz and coworkers. METHODS: Using the chosen models, a spread-out Bragg peak (SOBP) as well as two exemplary clinical cases (single field and two fields) for cranial proton irradiation, all delivered with state-of-the-art pencil-beam scanning, have been analyzed in terms of absorbed dose, dose-averaged LET (LET D ), RBE-weighted dose (D RBE) and biological range shift distributions. RESULTS: In the systematic comparison of RBE predictions by the three models we could show different levels of agreement depending on (α/ß) x and LET values. The SOBP study emphasizes the variation of LET D and RBE not only as a function of depth but also of lateral distance from the central beam axis. Application to clinical-like scenario shows consistent discrepancies from the values obtained for a constant RBE of 1.1, when using a variable RBE scheme for proton irradiation in tissues with low (α/ß) x , regardless of the model. Biological range shifts of 0.6- 2.4 mm (for high (α/ß) x ) and 3.0 - 5.4 mm (for low (α/ß) x ) were found from the fall-off analysis of individual profiles of RBE-weighted fraction dose along the beam penetration depth. CONCLUSIONS: Although more experimental evidence is needed to validate the accuracy of the investigated models and their input parameters, their consistent trend suggests that their main RBE dependencies (dose, LET and (α/ß) x ) should be included in treatment planning systems. In particular, our results suggest that simpler models based on the linear-quadratic formalism and LETD might already be sufficient to reproduce important RBE dependencies for re-evaluation of plans optimized with the current RBE = 1.1 approximation. This approach would be a first step forward to consider RBE variations in proton therapy, thus enabling a more robust choice of biological dose delivery. The latter could in turn impact clinical outcome, especially in terms of reduced toxicities for tumors adjacent to organs at risk.