Hydroxyurea for lifelong transfusion-dependent ß-thalassemia: A meta-analysis.

OBJECTIVE: Chronic blood transfusion remains the most feasible therapeutic option for lifelong transfusion-dependent ß-thalassemia (lifelong TDßT). However, it is associated with serious risks and complications. Hydroxyurea (HU), an oral chemotherapeutic drug, is expected to increase hemoglobin levels, thereby minimizing the burden of blood transfusion and its complications. Growing literature over the last twenty years suggests promising results of the use HU in lifelong TDßT; however, its role and safety remain unanswered questions. The objective of this study was to evaluate the clinical efficacy and safety of HU in patients with lifelong TDßT. METHODS: MEDLINE, EMBASE, Cochrane databases, and major preceding conferences for studies that assessed HU in lifelong TDßT patients were searched. The effect size was estimated as a proportion (responder/sample size). RESULTS: Eleven observational studies, collectively involving 859 patients, fulfilled eligibility criteria. HU was associated with a significant decrease in transfusion need with complete and overall (≥50%) response rates of 26% [95% confidence interval (CI), 13-41%] and 60% (95% CI, 41-78%), respectively. No serious adverse effects were reported. All of the studies had several limitations, such as lack of a comparison group. CONCLUSION: HU appears to be effective, well tolerated; however, large randomized clinical trials should be done to confirm such findings.

Herpesvirus Entry Mediator as an Immune Checkpoint Target and a Potential Prognostic Biomarker in Myeloid and Lymphoid Leukemia.

Herpesvirus entry mediator (HVEM) is a molecular switch that can modulate immune responses against cancer. The significance of HVEM as an immune checkpoint target and a potential prognostic biomarker in malignancies is still controversial. This study aims to determine whether HVEM is an immune checkpoint target with inhibitory effects on anti-tumor CD4+ T cell responses in vitro and whether HVEM gene expression is dysregulated in patients with acute lymphocytic leukemia (ALL). HVEM gene expression in tumor cell lines and peripheral blood mononuclear cells (PBMCs) from ALL patients and healthy controls was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Tumor cells were left untreated (control) or were treated with an HVEM blocker before co-culturing with CD4+ T cells in vitro in a carboxyfluorescein succinimidyl ester (CFSE)-dependent proliferation assay. HVEM expression was upregulated in the chronic myelogenous leukemia cell line (K562) (FC = 376.3, p = 0.086) compared with normal embryonic kidney cells (Hek293). CD4+ T cell proliferation was significantly increased in the HVEM blocker-treated K562 cells (p = 0.0033). Significant HVEM differences were detected in ALL PBMCs compared with the controls, and these were associated with newly diagnosed ALL (p = 0.0011) and relapsed/refractory (p = 0.0051) B cell ALL (p = 0.0039) patients. A significant differentiation between malignant ALL and the controls was observed in a receiver operating characteristic (ROC) curve analysis with AUC = 0.78 ± 0.092 (p = 0.014). These results indicate that HVEM is an inhibitory molecule that may serve as a target for immunotherapy and a potential ALL biomarker.

A Neonate with Acquired Factor VII Deficiency Successfully Managed with Immunomodulatory Therapy.

Acquired factor VII deficiency secondary to circulating inhibitors is rare in children but is a potentially life-threatening condition. Such a disease is challenging to diagnose and often difficult to manage. Here, we report on a newborn that presented with a catastrophic intracranial hemorrhage who failed to respond to conventional supportive measures including multiple doses of fresh frozen plasma and factor VII replacement; however, he had a complete correction of prothrombin time 8 h after immunomodulatory therapies in the form of steroid and intravenous immunoglobulin. Such measures helped stabilize his bleeding and allowed urgent neurosurgical intervention.

Chemotherapy readiness in pediatric oncology: Assessing an automated method to measure urine specific gravity.

As part of the evaluation for chemotherapy readiness, urine specific gravity is measured to assess the patient's overall hydration status. Depending on the accuracy of the methods used, patients may be adversely affected by having their chemotherapy delayed or prematurely started. To evaluate the diagnostic accuracy of a new automated urine dipstick readout device (Clinitek), we tested 196 consecutive urine samples for urine specific gravity and compared them with the practical gold standard, a urine refractometer. We found a high correlation between both tools among clean urine samples, but a poor correlation among the pathological urine samples.

Postgraduate Medical Training and COVID-19 Pandemic: Should We Stop, Freeze, or Continue?

While many countries in the world are going through a state of lockdown to limit the spread of coronavirus disease 2019 (COVID-19), such a state may affect postgraduate medical training (PGMT) adversely in different aspects. These include a decreased number of clinical cases related to the specialty, staff shortage, cancelation of educational conferences, and difficulties conducting formal in-training and licensing examinations. Trainees, program directors, licensing bodies, and other stakeholders are in a difficult situation regarding what to do next. Such a situation raises several critical questions related to the training that we tried to address here.

Minimising chemotherapy while optimising immune therapy for paediatric nodular lymphocyte-predominant Hodgkin's lymphoma.

Nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL) is a rare but distinct subtype of Hodgkin's lymphoma (HL) that carries a better prognosis than classical Hodgkin's lymphoma. Historically, both subtypes of Hodgkin's lymphomas (classical HL and NLPHL) have been grouped together and treated as classical Hodgkin's lymphoma. Recent studies have questioned this approach and have called for an alternative method due to expected severe long-term adverse events. We report two cases of NLPHL that were successfully treated with reduced chemotherapy cycles, as well as rituximab, in the form of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone).

Incidence trends of childhood acute lymphoblastic leukemia in Saudi Arabia: Increasing incidence or competing risks?

INTRODUCTION: The incidence of childhood acute lymphoblastic leukemia (cALL) varies between countries likely as a result of competing risks including infections, access-to-care, socioeconomic influences, and/or ethnicity. However, little is known about disease burden in high-income Arab countries offering free-of-charge healthcare. The hypothesis was that, due to population characteristics (young age, high fertility and parental consanguinity rate), the incidence of cALL in Saudi Arabia is equal or higher than that observed in high-income Western countries. METHODS: Saudi databases were used to calculate the incidence of cALL from 2001 to 2014. Incidence trends over time of children with ALL, 14-years of age or younger, were analyzed and compared with those reported in USA. RESULTS: The age-adjusted incidence over the years was lower in Saudi Arabia compared to USA. However, the incidence trend of cALL in Saudi Arabia was increasing at a rate higher than that observed in USA (p < 0.001). The overall incidence of cALL in Saudi Arabia increased from 1.58/100,000 in 2001 to 2.35/100,000 population in 2014. The median annual increase was 4.58 %. The incidence in males increased from 1.88 to 2.71/100,000, and from 1.21 to 1.86/100,000 population in females. CONCLUSIONS: The reported incidence of cALL in Saudi Arabia is rapidly increasing. The increasing trend may reflect evolving socioeconomic structure, improved access-to-cancer care, and improved diagnosis/ reporting capacity. This highlights the need for better understanding of cALL causes and the need for the formation of separate national pediatric cancer registries in different countries to monitor childhood cancer incidence trends.

Hydroxyurea for hemoglobin E/ß-thalassemia: a systematic review and meta-analysis.

Hemoglobin E-beta thalassemia (Hb E/ß-thalassemia) is a distinct, yet common, type of ß-thalassemia, in which the patient co-inherits a ß-thalassemia allele from one parent, and a structural variant, Hb E, from the other parent. This co-inheritance leads to remarkable clinical heterogeneity, varying degrees of chronic anemia, and a wide spectrum of complications due to ineffective erythropoiesis and iron overload. Hydroxyurea (HU), an oral chemotherapeutic drug, is expected to decrease disease severity. To assess the clinical efficacy and safety of HU in Hb E/ß-thalassemia patients. We searched MEDLINE, EMBASE, Cochrane databases, and major preceding conferences for studies that assessed HU in Hb E/ß-thalassemias patients. The effect size was estimated as a proportion (responder/sample size). Qualities of eligible studies were assessed using NIH tools. A total of five [one randomized clinical trial (RCT) and four observational] studies involving 106 patients were included. HU was associated with a significant RR of 46% with no statistical heterogeneity. No serious adverse effects were reported. Patients with Hb E/ß-thalassemia may benefit from a trial of HU, though large RCTs assessing efficacy should be conducted to confirm the findings of this meta-analysis and to assess long-term toxicity and response sustainability.

Hydroxyurea for nontransfusion-dependent ß-thalassemia: A systematic review and meta-analysis.

OBJECTIVE/BACKGROUND: Nontransfusion-dependent ß-thalassemia (NTDßT) syndromes consist of ß-thalassemia intermedia and moderate hemoglobin E/ß thalassemias. They are characterized by varying degrees of chronic anemia and a wide spectrum of complications due to ineffective erythropoiesis and iron overload from chronic transfusions. Hydroxyurea (HU), an oral chemotherapeutic drug, is anticipated to decrease disease severity. METHODS: We performed a meta-analysis to evaluate the clinical efficacy and safety of HU in NTDßT patients of any age. MEDLINE, EMBASE, Cochrane databases, and major conference proceedings for studies that assessed HU in NTDßT patients were searched. Qualities of eligible studies were assessed by National Institutes of Health tools. RESULTS: Seventeen studies, collectively involving 709 patients, fulfilled the eligibility criteria. HU was associated with a significant decrease in transfusion need in severe NTDßT with complete and overall (≥50%) response rates of 42% and 79%, respectively. For mild NTDßT, HU was effective in raising hemoglobin by 1g/L in 64% of patients. CONCLUSION: HU appears to be effective, well tolerated, and associated with mild and transient adverse events. NTDßT patients may benefit from a trial of HU, although large randomized clinical trials assessing its efficacy should be conducted to confirm the findings of this meta-analysis and to assess its long-term toxicity and response sustainability.

Management of Adolescent Low-Risk Classical Hodgkin Lymphoma: Which Chemotherapy Backbone Gives the Best Chance of Omitting Radiotherapy Safely.

Even though more than 90% of adolescents with low-risk classical Hodgkin lymphoma (LRcHL) will be cured with first-line therapy, many will suffer serious late toxic effects from radiotherapy (RT). The goals for care have shifted toward minimizing late toxic effects without compromising the outstanding cure rates by adapting a risk and response-based therapy. Recent published and ongoing randomized clinical trials, using functional imaging, may allow for better identification of those patients for whom RT may be safely omitted while maintaining excellent cure rates. To evaluate the best chemotherapy regimens with a reasonable toxicity profile and that are expected to have a high chance of omitting RT based on a response-directed therapy while maintaining high cure rates, a mini review was conducted of the recent clinical trials in pediatric and adult LRcHL. The UK RAPID trial chemotherapy backbone (3 × ABVD) followed by a response-based positron emission tomography scan offers up to a 75% chance of safely omitting RT without compromising the cure rate, which remained well above 90%.

Ten tips for receiving feedback effectively in clinical practice.

BACKGROUND: Despite being recognized as a fundamental part of the educational process and emphasized for several decades in medical education, the influence of the feedback process is still suboptimal. This may not be surprising, because the focus is primarily centered on only one half of the process - the teachers. The learners are the targets of the feedback process and improvement needs to be shifted. Learners need to be empowered with the skills needed to receive and utilize feedback and compensate for less than ideal feedback delivery due to the busy clinical environment. METHODS: Based on the available feedback literature and clinical experience regarding feedback, the author developed 10 tips to empower learners with the necessary skills to seek, receive, and handle feedback effectively, regardless of how it is delivered. Although, most of the tips are directed at the individual clinical trainee, this model can be utilized by clinical educators involved in learner development and serve as a framework for educational workshops or curriculum. RESULTS: Ten practical tips are identified that specifically address the learner's role in the feedback process. These tips not only help the learner to ask, receive, and handle the feedback, but will also ease the process for the teachers. Collectively, these tips help to overcome most, if not all, of the barriers to feedback and bridge the gaps in busy clinical practices. CONCLUSIONS: Feedback is a crucial element in the educational process and it is shown that we are still behind in the optimal use of it; thus, learners need to be taught how to better receive and utilize feedback. The focus in medical education needs to balance the two sides of the feedback process. It is time now to invest on the learner's development of skills that can be utilized in a busy day-to-day clinical practice.