Assessing the Efficacy of Mitoxantrone and Doxorubicin as Frontline Anthracyclines During Induction Therapy of Newly Diagnosed Acute Promyelocytic Leukemia.

BACKGROUND: Therapeutic advances in acute promyelocytic leukemia (APL) have transformed it into today's most curable form of leukemia. However, recommended agents, including arsenic trioxide, idarubicin, or daunorubicin, are not easily available in low-middle-income countries, where outcomes remain suboptimal. We aimed to assess the efficacy and safety of more accessible anthracyclines. METHODS: We conducted a retrospective cohort study including sixty-one patients diagnosed with APL over a 15-year period. Patients received low-dose all-trans retinoic acid (ATRA, 25 mg/m2) with mitoxantrone or doxorubicin as an induction to remission therapy. Groups were compared using the χ2 and Student's t-tests. Kaplan-Meier analysis was used for survival analyses. RESULTS: Thirty (49.18%) patients received mitoxantrone, and 31 (50.82%) received doxorubicin. The median follow-up was 24.6 months (1-146). Twenty-eight (93.3%) patients achieved complete remission (CR) in the mitoxantrone group and 28 (87.1%) in the doxorubicin group (p=0.103), and the median time to CR was 40 and 31 days, respectively. Mitoxantrone had a 6.7% early mortality rate and a 16.7% relapse rate compared with doxorubicin (3.2% and 32.3%, respectively). No differences were found in survival (p = 0.795), hospitalization days (p = 0.261), or adverse events (p = 0.554). CONCLUSIONS: Using mitoxantrone or doxorubicin as induction therapy in newly diagnosed APL is a safe and adequate alternative with comparable outcomes to first-line agents in scenarios where the latter might not be readily available, such as in low-middle-income countries.

Infection-related mortality after HLA-identical and haploidentical hematopoietic cell transplantation using reduced-intensity conditioning in an outpatient setting.

BACKGROUND: Despite the improvements in supportive care for allogeneic-hematopoietic cell transplantation (allo-HCT) recipients, infectious complications and infection-related mortality (IRM) continue to be a major issue for transplantation centers. METHODS: We herein report the infectious complications and IRM of 107 and 89 patients that underwent haploidentical (haplo-HCT) or HLA-identical HCT at a tertiary referral center during 2013-2020. Patients in the haplo-HCT group received post-transplant cyclophosphamide (PT-Cy), and all received reduced-intensity conditioning regimens. RESULTS: More haplo-HCT recipients presented severe infections in the pre-engraftment period (22.4% vs. 6.7%, p = 0.003). Viral (14.9% vs. 4.5%, p = 0.016) and fungal (12.1% vs. 1.1%, p = 0.003) etiologies were more common in this period in this group. The 100-day and 2-year cumulative incidence of IRM was 15% and 21% for the haplo-HCT and 5.6% and 17% for the HLA-identical group; no significant differences were observed between the groups. Fungal pathogens mainly contributed to IRM (33.3%). Infections were the most common cause of mortality (40/81, 49.4%). There were significant differences in donor/recipient CMV serostatus between transplant groups (0.002). CONCLUSIONS: No differences in IRM were observed based on allo-HCT type, with more haplo-HCT patients suffering from severe infections in the pre-engraftment period. Studies to assess future prevention, diagnostic, and treatment strategies to reduce IRM are warranted.

Hematopoietic stem cell transplantation for uncommon immune-mediated neurological disorders: A literature review.

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP), stiff-person syndrome (SPS), neuromyelitis optica spectrum disorders (NMOSD) and severe refractory myasthenia gravis (MG) are immune-mediated neurological diseases that severely affect patients' functionality and quality of life, with a considerable percentage undergoing relapse or not responding to conventional treatment options. Autologous hematopoietic stem cell transplantation (auto-HSCT) has emerged as a potential second-line treatment alternative. METHODS: We performed a literature review in PubMed/Medline, EMBASE, Web of Science and Cochrane Library from inception to September 2021 of reported cases and studies of CIDP, SPS, NMOSD and MG that underwent HSCT as a treatment option. RESULTS: A total of 173 patients who underwent HSCT were found, including 32 patients described in case reports and 60 in a phase 2 clinical trial with CIDP, 29 patients with SPS, 42 patients with NMOSD and 10 patients with refractory MG. Complete remission was documented in 68/92 patients with CIDP, 13/29 with SPS and 10/10 with MG. From the NMOSD cases, 24/42 were relapse-free at last follow-up, with 13/33 having negative anti-AQ4 antibodies after HSCT. From all the included studies, only 8/173 patients received an allogeneic HSCT, 4/8 after a failed auto-HSCT. All showed clinical improvement and disease remission. CONCLUSION: HSCT has the potential to induce long-term remission in patients with CIDP, NMOSD, SPS or MG with adequate safety and tolerability. Collaboration between centers is needed to implement larger, homogeneous prospective studies, focusing on immunological correlates of favorable long-term response.

Autologous ATG-free hematopoietic stem cell transplantation for refractory autoimmune rheumatic diseases: a Latin American cohort.

Autologous hematopoietic stem cell transplantation (HSCT) has been recognized as treatment alternative for patients with severe, refractory autoimmune rheumatic diseases (ARDs). Usually, anti-thymocyte globulin (ATG)-containing conditioning regimens are employed; however, ATG is unavailable in some developing nations. We report our 15-year clinical experience autografting patients with ARDs with an ATG-free conditioning regimen and a brief assessment of patient-reported outcomes post-HSCT. All patients had active disease and were resistant to multiple lines of treatment. Event-free survival (EFS) was assessed using the Kaplan-Meier method. Eight patients underwent autologous HSCT. Diagnoses included juvenile idiopathic arthritis (n = 3), systemic lupus erythematosus (n = 2), systemic sclerosis (n = 2), and rheumatoid arthritis (n = 1). Median time from diagnosis to HSCT was 3 years (0.75-19). Hematological recovery was documented in all recipients, and 4 patients (50%) completed the procedure in a completely ambulatory setting. Five (62.5%) patients achieved complete response and 3 (37.5%) partial response. The median EFS was 7 months (95% CI, 4.97-9.02), and the 1-year EFS rate was 21.9% (95% CI, 18.25-25.76). Transplant-related mortality was 0%, and 1 recipient died 8 years post-HSCT due to chronic kidney disease. Six (75%) patients presented steroid dosage reduction post-HSCT, and 2 (25%) perceived improvement in functionality despite having relapsed. HSCT is a viable treatment alternative for selected patients with severe therapy-resistant ARDs, as an improvement in disease management and quality of life was documented. The need remains to elucidate the characteristics of the optimal HSCT candidate, as well as the adequate conditioning regimen when ATG is not available. Key Points • Despite advances in the treatment of autoimmune rheumatic diseases, some patients remain refractory. In this context, autologous hematopoietic stem cell transplantation (HSCT) rises as a viable alternative. • Of 8 HSCT recipients with autoimmune rheumatic diseases, 5 (62.5%) patients achieved complete response and 3 (37.5%) partial response, with a 1-year event-free survival of 21.9%. • Transplant-related mortality was 0%, with 4 (50%) patients autografted in a completely outpatient setting. • Even when relapse presented, patients reported an improvement in functionality and quality of life; also, a better response to DMARDs and a reduction in steroid dependency post-HSCT were documented.

Adherence to treatment in Parkinson's disease: A multicenter exploratory study with patients from six Latin American countries.

BACKGROUND: Adherence to treatment in Parkinson's disease (PD) is compromised due to the need for multiple therapies, comorbidities related to aging, and the complexity of therapeutic schemes. In the present study, we aimed to explore adherence to treatment in groups of PD patients from six Latin-American (LA) countries and identify its associated demographic and clinical parameters. METHODS: A multicenter, cross-sectional, exploratory study was conducted from September 2016 to March 2017. Treatment adherence was assessed using the simplified medication adherence questionnaire (SMAQ), applied to patients and caregivers. Sociodemographic and clinical variables (MDS-UPDRS Part III-IV, MMSE, Beck Depression Inventory-II (BDI-II)) were recorded. RESULTS: Eight hundred patients from six LA countries were evaluated. Nonadherence was reported in 58.25% of the population, according to patients. The most frequent issues were forgetfulness and correct timing of doses. A high level of agreement in adherence prevalence and most SMAQ items were observed between patients and their caregivers. The nonadherent population had a significantly higher proportion of unemployment, free access to medication, troublesome dyskinesias and off-periods, lesser years of education, and worse motor, cognitive, and mood scores. In multiple logistic and linear regression analyses, MDS-UPDRS Part III, BDI-II, gender, free access to medication, treatment with dopamine agonists alone, years of education, excessive concerns about adverse effects, and beliefs about being well-treated remained significant contributors to adherence measures. CONCLUSION: Educational strategies, greater involvement of PD patients in decision-making, and consideration of their beliefs and values might be of great need to improve medication adherence in this PD population.

Insights on chronic immune thrombocytopenia pathogenesis: A bench to bedside update.

Immune thrombocytopenia (ITP) is a heterogeneous disease with an unpredictable course. Chronicity can develop in up to two-thirds of adults and 20-25% of children, representing a significant burden on patients' quality of life. Despite acceptable responses to treatment, precise etiology and pathophysiology phenomena driving evolution to chronicity remain undefined. We analyzed reported risk factors for chronic ITP and associated them with proposed underlying mechanisms in its pathogenesis, including bone marrow (BM) microenvironment disturbances, clinical features, and immunological markers. Their understanding has diagnostic implications, such as screening for the presence of specific antibodies or BM examination employing molecular tools, which could help predict prognosis and recognize main pathogenic pathways in each patient. Identifying these underlying mechanisms could guide the use of personalized therapies such as all-trans retinoic acid, mTor inhibitors, FcRn inhibitors, oseltamivir, and others. Further research should lead to tailored treatments and chronic course prevention, improving patients' quality of life.

Microalbuminuria as a potential biomarker for Parkinson's disease severity: A hypothesis.

Parkinson's disease (PD) is the second most common neurodegenerative condition characterized by motor and non-motor symptoms causing a great burden in patients' quality of life. PD has been associated with various metabolic factors such as diabetes, hypertension, and more recently chronic kidney disease where proteinuria has been associated with an increased risk. The presence of small amounts of albumin in urine, microalbuminuria, is a common biomarker for endothelial damage and a predictive factor for not only cardiovascular but also neurological dysfunction. Multiple studies have assessed potential biomarkers for PD progression with great heterogeneity, we hypothesize the use of microalbuminuria as a potential marker that correlates with PD severity and might represent a feasible and simple method of evaluating PD patients in clinical practice. Evidence supporting the present hypothesis comes from oxidative stress, insulin resistance, and endothelial dysfunction. Oxidative stress is a key element in PD pathogenesis; studies have shown lower antioxidant capacity as PD progresses. On the other side, insulin signaling plays an important role in neuronal growth and survival, with its resistance being associated with PD. Microalbuminuria has been associated with both processes; increased levels of oxidative stress markers and decreased insulin sensitivity, hence its screening in PD might reflect these common pathological mechanisms. Moreover, the low vitamin D levels observed in PD patients, which are correlated with endothelial dysfunction and disease severity, might contribute to microalbuminuria induction. More evidence on this vascular approach comes from white matter lesions (WML), observed in brain imaging, which have been significantly associated with motor and non-motor function in PD patients and are independently associated with microalbuminuria. In this manner, an oxidant and insulin resistant environment, along with low vitamin D levels in PD patients, which are associated with microalbuminuria, might contribute altogether to WML. As the latter are correlated with motor and non-motor function, microalbuminuria might thus give insight on PD status. Prospective cohort studies with an adequate sample size, follow-up, and a thorough battery of clinical tests for PD are needed to confirm this hypothesis.

Linking chronic kidney disease and Parkinson's disease: a literature review.

Chronic kidney disease (CKD) has been typically implicated in cardiovascular risk, considering the function the kidney has related to blood pressure, vitamin D, red blood cell metabolism, and electrolyte and acid-base regulation. However, neurological consequences are also attributed to this disease. Among these, recent large epidemiological studies have demonstrated an increased risk for Parkinson's disease (PD) in patients with CKD. Multiple studies have evaluated individually the association of blood pressure, vitamin D, and red blood cell dysmetabolism with PD, however, no study has reviewed the potential mechanisms related to these components in context of CKD and PD. In this review, we explored the association of CKD and PD and linked the components of the former to propose potential pathways explaining a future increased risk for PD, where renin-angiotensin system, oxidative stress, and inflammation have a main role. Potential preventive and therapeutic interventions based on these associations are also explored. More preclinical studies are needed to confirm the potential link of CKD conditions and future PD risk, whereas more interventional studies targeting this association are warranted to confirm their potential benefit in PD.

Occipital condyle screw fixation viability according to age and gender anatomy: A computed tomography-based analysis.

OBJECTIVE: To assess the Occipital condyle morphology in an all-age population of Northeastern Mexico, and determine age and gender related changes for surgical viability. METHODS: A total of 175 consecutive HRCT scans were included and divided into 5 age groups. The condylar length, width, height, sagittal angle, anterior, posterior and medial intercondylar distances, and intercondylar angle of the OC were measured. RESULTS: Mean condylar length, width, and height in total population were 20.58 mm, 9.42 mm, and 9.02 mm, respectively. Differences were observed in most morphometric parameters when comparing age groups. Significant intergender differences in total population were observed in most parameters, when individualizing each age group the height remained significant in all. The group with the least height measurement was aged 5-9 years, this however, could allow the OC screw (≥6.5 mm) placement. CONCLUSION: Differences in most morphometric parameters of OC were observed between age groups and gender, particularly patients with 5-9 years. However, all groups presented a minimum height that allows the placement of a standard screw. A preoperative imaging study is always recommended due to the variability and complexity of the region.

Comparison of the effect of whole-body vibration therapy versus conventional therapy on functional balance of patients with Parkinson's disease: adding a mixed group.

OBJECTIVE: Assess the effect of Whole-Body Vibration (WBV) therapy in functional balance status of Parkinson's disease (PD) patients and compare this to conventional and combined therapy. INTRODUCTION: PD patients experience a decreased mobility, inactivity, and loss of independence as consequence of disturbances in gait, posture, and balance. Rehabilitation therapy is a non-pharmacological way of improving functionality. One of the most studied modalities is WBV, with multiple studies showing improvement in motor function. However, results in this manner are inconsistent. METHODS: Forty-five patients were enrolled in a non-randomized controlled trial and divided into three groups. Group 1 received conventional therapy (thermotherapy, stretching, strengthening, coordination and balance). Group 2 received WBV therapy, and group 3 patients underwent a combined therapy protocol. A total of 20 sessions (3 per week) were conducted, assessing Berg Balance Scale (BBS) before initial and after final session. RESULTS: The 3 intervention groups showed significant improvement in BBS scores after concluding the 20-session trial compared to initial assessment. When comparing mean change in BBS score from initial to final assessment, the combined therapy group had a greater increase compared to conventional therapy, but no significant differences were observed comparing to WBV group. Mean change in BBS score showed no significant difference between conventional therapy and WBV therapy group. CONCLUSIONS: WBV therapy is a useful tool as co-adjuvant in conventional therapy. The combination of both therapies is a significant therapeutic alternative for the improvement of functional balance status in PD patients compared to conventional therapy alone.

Does glitazone treatment have a role on the prevention of Parkinson's disease in adult diabetic population? A systematic review.

Lately, focus on the relation between Parkinson's disease (PD) and Diabetes has risen greatly, as neuroprotective properties have been attributed to insulin use. Several studies have assessed the effect of glitazones, an insulin-sensitizing agent, in diabetic population on PD future risk. However, reports on the effect of their use have been heterogeneous. We aimed to synthesize the available scientific evidence which assesses the effect of glitazone use in type 2 diabetes patients on PD incidence. A systematic review was performed on multiple electronic databases. Considered for inclusion were studies that assessed the incidence of PD in type 2 diabetes glitazone users. Two reviewers worked independently and in duplicate to assess all studies, extract information and assess the methodological quality in each included study. Four high quality retrospective cohorts fulfilled inclusion criteria. Comparison groups varied across studies. In each study, incidence of PD was lower in glitazone-exposed patients compared to their respective comparison group. Pooled analysis showed lesser risk of PD in ever versus never glitazone users (RR 0.75 [95% C.I. 0.67-0.85; p < .0001; I2 = 0]). Our pooled analysis showed lesser risk of PD in glitazone versus non glitazone users, however, we advise to take results with caution since results are non-adjusted to possible confounding variables, furthermore, different glitazone-exposure time, follow up and comparison groups are aspects that also need to be pointed out. More clinical research focused on glitazone use and its relation with PD is needed, as this could result in new potential treatment modalities.