IgA nephropathy in children: before and after the start of COVID-19.

BACKGROUND: We describe the clinical course of children with IgA nephropathy (IgAN), diagnosed before and after the emergence of COVID-19. We hypothesized that COVID-19 vaccination and/or infection resulted in more children with IgAN to present clinically. METHODS: We conducted a retrospective cohort study of children with IgAN diagnosed on kidney biopsy from 2014-2020 (Period 1) and 2021-2022 (Period 2). Baseline characteristics, clinical presentation, investigations and treatments were compared between patients diagnosed in Period 1 and Period 2, as well as between patients with and without chronic changes on kidney biopsy. Continuous variables were compared using the Wilcoxon rank sum test. Categorical variables were compared using χ2 or Fisher exact tests. RESULTS: Nineteen children with IgAN were diagnosed by kidney biopsy, with 10 during Period 1 and 9 patients during Period 2 (an average of 1-2 patients/year and 4-5 patients/year in Periods 1 and 2, respectively). The most common indication for kidney biopsy is proteinuria with urine protein/creatinine ratio 1.4 (interquartile range [IQR] 1.2-9.0) vs. 0.8 (IQR 0.6-1.5) g/g (p = 0.064) at time of kidney biopsy for patients in Period 1 and 2, respectively. Clinical course was similar in both periods. No patient required acute or chronic kidney replacement therapy. CONCLUSIONS: The rate of diagnosing children with IgAN was higher since the emergence of COVID-19, suggesting that COVID-19 may trigger an immune response responsible for IgAN, similar to other mucosal infections.

Adenine phosphoribosyl transferase (APRT) deficiency and a novel sequence variant in APRT with phenotypic diversity and a literature review.

Adenine phosphoribosyl transferase (APRT) deficiency is an autosomal recessive disorder and a rare cause of urolithiasis due to mutations in APRT (OMIM #102600). APRT deficiency results in increased urinary excretion of 2,8-dihydroxyadenine (DHA) which can cause urolithiasis and kidney failure. However, with prompt diagnosis, patients with APRT deficiency can be treated with xanthine oxidoreductase inhibitors which decrease urinary DHA excretion and improve outcomes. We report a pair of siblings, an 11-year-old brother and his 14-year-old sister with compound heterozygous variants c.270del (p.Lys91Serfs*46) and c.484_486del (p.Leu162del) in APRT with variable clinical presentation of APRT deficiency. The brother presented at 17 months of age with urolithiasis and severe acute kidney injury. His elder sister remained well and asymptomatic with normal kidney function and did not develop renal calculi. Brownish disk or sphere-like crystals with both concentric and radial markings were reported on urine microscopy in the sister on screening. The sister's diagnosis was confirmed with further laboratory evidence of absent red cell lysate APRT activity with corresponding elevated levels of urinary DHA. In conclusion, we identified a novel mutation in the APRT gene in a pair of siblings with greater phenotypic severity in the male.

Multicenter study on the genetics of glomerular diseases among southeast and south Asians: Deciphering Diversities - Renal Asian Genetics Network (DRAGoN).

Multinational studies have reported monogenic etiologies in 25%-30% of children with steroid-resistant nephrotic syndrome. Such large studies are lacking in Asia. We established Deciphering Diversities: Renal Asian Genetics Network (DRAGoN) and aimed to describe the genetic and clinical spectrums in Asians. We prospectively studied a cohort of 183 probands with suspected genetic glomerulopathies from South and Southeast Asia, of whom 17% had positive family history. Using multi-gene panel sequencing, we detected pathogenic variants in 26 (14%) probands, of whom one-third had COL4A4 or COL4A5 variants (n = 9, 5%). Of those with COL4A5 defects, only 25% had features suggestive of Alport syndrome. Besides traditional predictors for genetic disease (positive family history and extrarenal malformations), we identified novel predictors, namely older age (6.2 vs. 2.4 years; p = 0.001), hematuria (OR 5.6; 95% CI 2.1-14.8; p < 0.001), and proteinuria in the absence of nephrotic syndrome (OR 4.6; 95% CI 1.8-11.8; p = 0.001) at first manifestation. Among patients who first presented with proteinuria without nephrotic syndrome, the genetic diagnostic rates were >60% when a second risk factor (positive family history or extrarenal manifestation) co-existed. The genetic spectrum of glomerulopathies appears different in Asia. Collagen IV genes may be included in sequencing panels even when suggestive clinical features are absent.

Evaluation of a multidisciplinary care model to improve quality of life in rheumatoid arthritis: a randomised controlled trial.

BACKGROUND AND PURPOSE: Health-Related Quality of Life (HR-QOL) is an important patient-reported domain in patients with rheumatoid arthritis (RA). The uptake of multidisciplinary team (MDT) care in RA is generally low, due to initial high demand for resources. We hypothesised that whilst pharmacological treatments are effective in controlling disease activity, a multipronged intervention in an MDT may have a positive impact on HR-QOL. METHODS: This was a single-centre randomized parallel group, single-blind controlled trial of MDT vs. usual care in an established RA clinic. Data were collected through face-to-face questionnaires, medical records review, and joint counts by a blinded assessor at 0, 3 and 6 months. Adult RA patients were randomly assigned in a single visit to a 6-member MDT (rheumatologist, nurse, social worker, physiotherapist, occupational therapist, and podiatrist) or usual care. MDT providers prescribed medications and counselled patients on managing flares, medication adherence, coping, joint protection, exercise, footwear. The primary outcome was minimal clinically important difference (MCID) in HR-QOL (increase in European QOL-5-Dimension-3-Level, EQ-5D-3L by 0.1) at six months. RESULTS: 140 patients (86.3% female, 53.4% Chinese, median (IQR) age 56.6 (46.7, 62.4) years); 70 were randomized to each arm. Median (IQR) disease duration was 5.5 (2.4, 11.0) years and disease activity in 28 joints (DAS28) was 2.87 (2.08, 3.66). 123 patients completed the study. Twenty-six (40.6%) MDT vs. 23 (34.3%) usual care patients achieved an MCID in EQ-5D-3L, OR 1.3 (0.6, 2.7). In multivariable logistic regression, baseline EQ-5D-3L was the only predictor of achieving MCID. There was more disease modifying anti-rheumatic drug escalation in MDT (34.4% vs. 19.4%). Patients with high disease activity were more likely to achieve MCID in the MDT arm. CONCLUSIONS: A single visit by stable patients with low disease activity to an MDT failed to achieve MCID in the EQ-5D-3L; however, did achieve small but significant improvements in the EQ-5D-3L, DAS28, pain, coping and self-efficacy. To be sustainable, MDT care should be targeted at patients with high disease activity or those with a new diagnosis of RA. TRIAL REGISTRATION: The study is registered on ClinicalTrials.gov, identifier: NCT03099668.

Systematic Review and Meta-Analysis for Sexual Dysfunction in Women With Hypertension.

INTRODUCTION: Sexual dysfunction in hypertensive women is an often-neglected subject despite a reported prevalence of 42.1%. Although few reviews exist, a definitive relationship between hypertension and sexual dysfunction in women has not been clearly established. AIM: To review the existing literature to definitively examine sexual dysfunction in women with hypertension, in both treated and untreated subjects. METHODS: We performed a systematic search for published literature of 3 electronic databases (Scopus, EBSCOhost Medline Complete, and Cochrane Library) in August 2018. The search terms with relevant truncation and Boolean were developed according to a population exposure-comparator-outcome model combining pilot searches. The quality of included studies was assessed with the McMaster Critical Review Form for Quantitative Studies. Initial search, limited to the English language, included a total of 2,198 studies. 31 studies (18,260 subjects) met our inclusion criteria and were included in the review. Sexual dysfunction in these studies was measured using different tools. We extracted information of study setting, country, number of subjects, participants' age and blood pressure, comparators, and outcome. We ran a meta-analysis on the presence of sexual dysfunction as an outcome from the following comparisons: (i) hypertensive vs normotensive (ii) treated vs untreated hypertension, and (iii) exposure vs absence of specific class of anti-hypertensive drug. MAIN OUTCOME MEASURES: Women with sexual dysfunction and hypertension were included. RESULTS: We found significant sexual dysfunction in women with hypertension compared with the normotensive group (pooled odds ratio [OR] = 2.789, 95% CI = 1.452-5.357, P = .002). However, there was no statistical difference of sexual dysfunction in women with treated or untreated hypertension (OR = 1.229, 95% CI = 0.675-2.236, P = .5). Treatment with alpha-/beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, and diuretics resulted in no statistical difference in sexual dysfunction in hypertensive women. CLINICAL IMPLICATIONS: Because sexual dysfunction is prevalent in women with hypertension, it is imperative to address the underlying medical condition to manage this important clinical problem. STRENGTH & LIMITATIONS: Many studies had to be excluded from the meta-analysis, due to unavailability and incompleteness of data. Nevertheless, results of the review are useful to derive recommendations for alerting physicians of the need to routinely assess the sexual functioning of women with hypertension. CONCLUSION: We conclude that women with hypertension are at increased risk for sexual dysfunction, and our findings imply that evaluation for sexual dysfunction needs to be part of the clinical management guidelines for women with hypertension. Choy CL, Sidi H, Koon CS, et al. Systematic Review and Meta-Analysis for Sexual Dysfunction in Women With Hypertension. J Sex Med 2019;16:1029-1048.

Tropical countries may be willing to pay more to protect their forests.

Inadequate funding from developed countries has hampered international efforts to conserve biodiversity in tropical forests. We present two complementary research approaches that reveal a significant increase in public demand for conservation within tropical developing countries as those countries reach upper-middle-income (UMI) status. We highlight UMI tropical countries because they contain nearly four-fifths of tropical primary forests, which are rich in biodiversity and stored carbon. The first approach is a set of statistical analyses of various cross-country conservation indicators, which suggests that protective government policies have lagged behind the increase in public demand in these countries. The second approach is a case study from Malaysia, which reveals in a more integrated fashion the linkages from rising household income to increased household willingness to pay for conservation, nongovernmental organization activity, and delayed government action. Our findings suggest that domestic funding in UMI tropical countries can play a larger role in (i) closing the funding gap for tropical forest conservation, and (ii) paying for supplementary conservation actions linked to international payments for reduced greenhouse gas emissions from deforestation and forest degradation in tropical countries.

Reed-Sternberg cell-derived lymphotoxin-α activates endothelial cells to enhance T-cell recruitment in classical Hodgkin lymphoma.

It is known that cells within the inflammatory background in classical Hodgkin lymphoma (cHL) provide signals essential for the continual survival of the neoplastic Hodgkin and Reed-Sternberg (HRS) cells. However, the mechanisms underlying the recruitment of this inflammatory infiltrate into the involved lymph nodes are less well understood. In this study, we show in vitro that HRS cells secrete lymphotoxin-α (LTα) which acts on endothelial cells to upregulate the expression of adhesion molecules that are important for T cell recruitment. LTα also enhances the expression of hyaluronan which preferentially contributes to the recruitment of CD4(+) CD45RA(+) naïve T cells under in vitro defined flow conditions. Enhanced expression of LTα in HRS cells and tissue stroma; and hyaluronan on endothelial cells are readily detected in involved lymph nodes from cHL patients. Our study also shows that although NF-κB and AP-1 are involved, the cyclooxygenase (COX) pathway is the dominant regulator of LTα production in HRS cells. Using pharmacological inhibitors, our data suggest that activity of COX1, but not of COX2, directly regulates the expression of nuclear c-Fos in HRS cells. Our findings suggest that HRS cell-derived LTα is an important mediator that contributes to T cell recruitment into lesional lymph nodes in cHL.

Neurovirulence and immunogenicity of attenuated recombinant vesicular stomatitis viruses in nonhuman primates.

UNLABELLED: In previous work, a prototypic recombinant vesicular stomatitis virus Indiana serotype (rVSIV) vector expressing simian immunodeficiency virus (SIV) gag and human immunodeficiency virus type 1 (HIV-1) env antigens protected nonhuman primates (NHPs) from disease following challenge with an HIV-1/SIV recombinant (SHIV). However, when tested in a stringent NHP neurovirulence (NV) model, this vector was not adequately attenuated for clinical evaluation. For the work described here, the prototypic rVSIV vector was attenuated by combining specific G protein truncations with either N gene translocations or mutations (M33A and M51A) that ablate expression of subgenic M polypeptides, by incorporation of temperature-sensitive mutations in the N and L genes, and by deletion of the VSIV G gene to generate a replicon that is dependent on trans expression of G protein for in vitro propagation. When evaluated in a series of NHP NV studies, these attenuated rVSIV variants caused no clinical disease and demonstrated a very significant reduction in neuropathology compared to wild-type VSIV and the prototypic rVSIV vaccine vector. In spite of greatly increased in vivo attenuation, some of the rVSIV vectors elicited cell-mediated immune responses that were similar in magnitude to those induced by the much more virulent prototypic vector. These data demonstrate novel approaches to the rational attenuation of VSIV NV while retaining vector immunogenicity and have led to identification of an rVSIV N4CT1gag1 vaccine vector that has now successfully completed phase I clinical evaluation. IMPORTANCE: The work described in this article demonstrates a rational approach to the attenuation of vesicular stomatitis virus neurovirulence. The major attenuation strategy described here will be most likely applicable to other members of the Rhabdoviridae and possibly other families of nonsegmented negative-strand RNA viruses. These studies have also enabled the identification of an attenuated, replication-competent rVSIV vector that has successfully undergone its first clinical evaluation in humans. Therefore, these studies represent a major milestone in the development of attenuated rVSIV, and likely other vesiculoviruses, as a new vaccine platform(s) for use in humans.

Masked Face Recognition Using Histogram-Based Recurrent Neural Network.

Masked face recognition (MFR) is an interesting topic in which researchers have tried to find a better solution to improve and enhance performance. Recently, COVID-19 caused most of the recognition system fails to recognize facial images since the current face recognition cannot accurately capture or detect masked face images. This paper introduces the proposed method known as histogram-based recurrent neural network (HRNN) MFR to solve the undetected masked face problem. The proposed method includes the feature descriptor of histograms of oriented gradients (HOG) as the feature extraction process and recurrent neural network (RNN) as the deep learning process. We have proven that the combination of both approaches works well and achieves a high true acceptance rate (TAR) of 99 percent. In addition, the proposed method is designed to overcome the underfitting problem and reduce computational burdens with large-scale dataset training. The experiments were conducted on two benchmark datasets which are RMFD (Real-World Masked Face Dataset) and Labeled Face in the Wild Simulated Masked Face Dataset (LFW-SMFD) to vindicate the viability of the proposed HRNN method.

Interpersonal psychotherapy for traumatic grief following a loss due to COVID-19: a case report.

Interpersonal psychotherapy (IPT) is a highly regarded evidence-based psychotherapy that aims to alleviate the suffering of clients and improve their interpersonal functioning. Research has demonstrated the effectiveness of IPT in depressive, bipolar and eating disorders. IPT also focuses on grief and loss as a problem area to help clients address and process their grief symptoms, leading them to reach a phase of finding meaning. However, traumatic grief which is characterized by someone who has both symptoms of trauma and grief can further complicate treatment. As for Posttraumatic Stress Disorder (PTSD), IPT can be a choice of treatment by addressing perceived isolation and emotional dysregulation through mobilizing adequate social support. This case study highlights the efficacy of IPT in treating complicated grief with traumatic experiences caused by the loss of a loved one during the COVID-19 pandemic, without undergoing exposure-based therapy. The treatment course consisted of 12 sessions scheduled twice weekly, and the client received antidepressant medication augmented with antipsychotic medication. After undergoing IPT, the client experienced an improvement in symptoms, gradual recovery of functional disability, and more meaningful interpersonal relationships. The case study presented provides evidence to suggest that IPT is a promising treatment approach for individuals struggling with trauma related to grief.

Risk factors for imaging abnormalities after the first febrile urinary tract infection in infants ≤3 months old: a retrospective cohort study.

OBJECTIVES: To assess the association of clinical factors and investigation results (blood and urine) with imaging abnormalities (ultrasound of the kidneys, ureters and bladder; dimercaptosuccinic acid scan; and/or micturating cystourethrogram) and recurrent urinary tract infections (UTIs) in infants ≤3 months old presenting with their first febrile UTI. METHODS: We conducted a retrospective cohort study of infants ≤3 months old with first febrile UTI admitted from 2010 to 2016. Multivariable logistic regression model was used to analyse the association of imaging abnormalities and recurrent UTI with covariates selected a priori: age at presentation, maximum temperature, duration of illness at presentation, interval between start of antibiotics and fever resolution, C-reactive protein, total white cell count on the full blood count, bacteraemia, white cell count on the urinalysis and non-Escherichia coli growth in the urine culture (non-E. coli UTI). RESULTS: There were 190 infants but 12 did not undergo any imaging. Median age at presentation was 63 days (IQR 41-78). Twenty-four patients had imaging abnormalities. Non-E. coli UTI (adjusted OR (aOR) 5.01, 95% CI 1.65 to 15.24, p=0.004) was independently associated with imaging abnormalities, while bacteraemia (aOR 4.93, 95% CI 1.25 to 19.43, p=0.022) and non-E. coli UTI (aOR 5.06, 95% CI 1.90 to 13.48, p=0.001) were independently associated with recurrent UTI. CONCLUSION: Non-E. coli UTI at the first febrile UTI in infants ≤3 months old may be useful in predicting imaging abnormalities while bacteraemia and non-E. coli UTI may be useful to predict recurrent UTI.

Plasma Cell Leukemia with Successful Upfront Venetoclax in Combination with Allogeneic Transplantation.

BACKGROUND Plasma cell leukemia (PCL) is an aggressive form of plasma cell neoplasm. We report the first case of primary PCL successfully treated with upfront novel agents consisting of Venetoclax and daratumumab in combination with intensive chemotherapy and allogeneic transplantation. CASE REPORT A 59-year-old woman presented with epistaxis, gum bleeding, and blurred vision. On examination, she appeared pale, with multiple petechiae and hepatomegaly. Fundoscopy revealed retinal hemorrhages. Laboratory investigations revealed bicytopenia and leukocytosis, with mild coagulopathy and hypofibrinogenemia. Elevated globulin and calcium levels were also observed. Serum protein electrophoresis demonstrated IgG lambda paraproteinemia, with a serum-free light chain kappa-to-lambda ratio of 0.074. A skeletal survey revealed the presence of lytic lesions. Bone marrow investigations confirmed the presence of lambda-light-chain-restricted clonal plasma cells. FISH detected t(11;14) and 17p13.1 deletion. Therefore, a final diagnosis of primary PCL was made. The patient received 1 cycle of bortezomib, cyclophosphamide, and dexamethasone (VCD) and 5 cycles of Venetoclax-VCD, followed by an unsuccessful stem cell mobilization. One cycle of daratumumab in combination with bortezomib, lenalidomide, and dexamethasone (VRD) was then given. The patient achieved complete remission. She underwent allogeneic stem cell transplantation of an HLA-matched sibling donor. Post-transplant marrow assessment showed disease remission and absence of t(11;14) and 17p deletions. She was administered pamidronate and lenalidomide maintenance. She remained clinically well with a good performance status and no active graft-versus-host disease 18 months after transplant. CONCLUSIONS The success of our patient in achieving complete remission has highlighted the efficacy and safety of this novel therapy in the front-line management of PCL.

Purification of transcriptionally active multimeric plasmid DNA using zwitterionic detergent and carbonate apatite nano-particles.

Plasmid DNA is one of the indispensable components in molecular biology research and a potential biomaterial for gene therapy and DNA vaccination. Both quality and quantity of extracted plasmid DNA are of the great interests in cloning and subsequent expression of genes in vitro and in vivo for basic research and therapeutic interventions. Bacteria with extremely short generation times are the valuable source of plasmid DNA that can be isolated through a number of existing techniques. However, the current methods have some limitations in isolating high quality plasmid DNA since the multimeric plasmid which is believed to be more efficiently transcribed by RNA polymerase than the monomeric form, is almost lost during the extraction process. Recently, we developed a rapid isolation technique for multimeric plasmid based on generation of a 'protein aggregate' using a zwitterionic detergent and alkali. Here we have investigated the roles of different parameters in the whole extraction process to optimise the production of high quality multimeric plasmid DNA. Moreover, we have showed the advantageous effects of nanoparticles to effectively sediment the 'protein aggregate' for smooth elution of multimeric plasmid DNA from it. Finally, quality assessment study has revealed that the isolated multimeric DNA is at least 10 times more transcriptionally active than the monomeric form isolated by the commercially available Qiaget kit.

Use of Radiography for New Patients Presenting to a Chiropractic Teaching Clinic: A Cross-sectional Analysis.

OBJECTIVE: The aim of this study was to identify the number and type of indications for radiographs ordered in a chiropractic teaching clinic in Malaysia. METHODS: A cross-sectional retrospective analysis was conducted using the medical health records of new patients who presented to the International Medical University Bukit Jalil teaching clinic for chiropractic care between August 2018 and July 2019. Data about sociodemographic characteristics, region of presenting complaint, radiography ordering rates, and referral indications were collected. We compared indications reported in the patient records with those listed in the International Medical University Chiropractic Clinical Manual. We conducted χ2 and logistic regression analysis to identify the association between radiography indications and the number of radiographs ordered. RESULTS: Data were collected for 1451 patients (741 [51.1%] women and 700 [48.9%] men). The most common body region for the presenting complaint was the lumbar/pelvic region (39.0%), and the overall radiograph use rate was 2.7%, with the highest number of radiographs for the lumbar spine. CONCLUSION: For the patient files sampled in this study, the overall radiograph order rate in the International Medical University Bukit Jalil Chiropractic teaching clinic was 2.7%.

Demographics and Clinical Profiles of Patients Visiting a Chiropractic Teaching Clinic in Malaysia.

Objective: The objective of this study was to describe the demographics and clinical profiles of patients visiting a chiropractic teaching clinic in Malaysia. Methods: A retrospective descriptive study was conducted using existing medical records of all new patients who visited the International Medical University Bukit Jalil teaching clinic between August 2018 and July 2019. Sociodemographic and lifestyle factors, information on location of presenting complaints, duration of complaint and referral sources were reviewed. Descriptive analyses including mean, mode, standard deviations (SDs), and frequencies were performed. Results: Of the 1451 patients included in this study, the mean age was (SD) 34.3 (16.1) with 51.1% female. Most of the patients were Chinese (76.0%), followed by Malay (11.6%), Indian (7.72%), and others such as Punjabi and Sabah and Sarawak native (5.0%). Comparing referral sources, the main referrals were self-referred (26.6%) followed by friends and family referrals (25.0%) and other forms of social media and advertising (10.0%). The most frequent location of complaint was the lumbar and pelvic regions, 562 (38.73%) followed by head and neck 400 (27.57%), lower limb 173 (11.92%), upper limb 154 (10.61%), thoracic 133 (9.17%), and full spine 29 (2%). Conclusion: This study provides important information that allows better understanding of patients presenting to a chiropractic teaching clinic in Malaysia. Such findings may contribute to the benchmark data for future strategic planning to ensure sufficient exposure on case mix among chiropractic interns in Malaysia.

Occult Disseminated Metastatic Breast Carcinoma Presenting as Acquired Thrombotic Thrombocytopenic Purpura.

Cancer-related microangiopathic hemolytic anemia (MAHA) is a rare and life-threatening condition. We present a patient who had been treated for invasive lobular breast carcinoma in clinical remission with fever and hemolytic anemia. The peripheral blood film showed MAHA and thrombocytopenia, and a functional deficiency of ADAMTS13 activity of 23% consistent with acquired thrombotic thrombocytopenic purpura. Bone marrow aspirate and trephine biopsy confirmed metastatic carcinoma. Further evaluation revealed the involvement of multiple bone sites without recurrence of the primary tumor. The patient received a daily plasma exchange with cryosupernatant and was pulsed with corticosteroids. MAHA related to breast cancer appears to be a rare occurrence.

Impact of timely BCR-ABL1 monitoring before allogeneic stem cell transplantation among patients with BCR-ABL1-positive B-acute lymphoblastic leukemia.

BACKGROUND: With the emergence of tyrosine kinase inhibitors and the incorporation of stringent measurable residual disease (MRD) monitoring, risk stratification for BCR-ABL1-positive acute lymphoblastic leukemia (ALL) patients has changed significantly. However, whether this monitoring can replace conventional risk factors in determining whether patients need allogeneic stem cell transplantation is still unclear. This study aimed to determine the impact of BCR-ABL1 monitoring on the outcome of patients with BCR-ABL1-positive ALL after allogeneic stem cell transplantation. METHODS: We retrospectively analyzed the survival outcome of patients with BCR-ABL1-positive ALL based on the quantification of BCR-ABL1 at 3 timepoints: the end of induction (timepoint 1), post-consolidation week 16 (timepoint 2), and the end of treatment for patients who were either transplant-eligible or non-transplant eligible (timepoint 3). RESULTS: From 2006 to 2018, a total of 96 patients newly diagnosed with BCR-ABL1-positive ALL were treated with chemotherapy and tyrosine kinase inhibitors. Thirty-eight (41.3%) patients achieved complete remission, and 33 patients underwent allogeneic stem cell transplantation. Our data showed that pre-transplant MRD monitoring by real-time quantitative polymerase chain reaction had the highest correlation with survival in patients with BCR-ABL1-positive ALL, especially for those who underwent allogeneic stem cell transplantation. CONCLUSION: Patients without MRD pre-transplantation had superior survival compared with those who had MRD, and they had excellent long-term outcomes after allogeneic stem cell transplantation.

Epidemiology and Management of Children with Hypertensive Crisis: A Single-Center Experience.

Most children who present with hypertensive crisis have a secondary cause for hypertension. This study describes the epidemiology and management of children with hypertensive crisis. A retrospective cohort study was done in a tertiary pediatric hospital from 2009 to 2015. Thirty-seven patients were treated for hypertensive crisis. Twelve (32.4%) patients were treated for hypertensive emergency. The majority of our patients (33 [89.1%]) had a secondary cause of hypertension. The most common identifiable cause of hypertension was a renal pathology (18/37 [48.6%]). Oral nifedipine (23 [62.1%]) was the most frequently used antihypertensive, followed by intravenous labetalol (8 [21.6%]). There were no mortalities or morbidities. Hypertensive crisis in children is likely secondary in nature. Oral nifedipine and intravenous labetalol are both effective treatments.

Integration of Antiangiogenic Therapy with Cisplatin and Gemcitabine Chemotherapy in Patients with Nasopharyngeal Carcinoma.

PURPOSE: Induction cisplatin and gemcitabine chemotherapy is a standard treatment for locally advanced nasopharyngeal carcinoma (NPC). Inhibition of VEGF axis has been shown to promote maturation of microvasculature and improve perfusion. We conducted a four-arm study to assess the effect of two doses of either sunitinib or bevacizumab with chemotherapy in NPC. PATIENTS AND METHODS: Patients with treatment-naïve locally advanced NPC were treated with three cycles of 3-weekly cisplatin and gemcitabine preceded by 1 week of anti-VEGF therapy for each cycle, followed by standard concurrent chemoradiation: arm A patients received 7 days of 12.5 mg/day sunitinib; arm B 7 days of 25 mg/day sunitinib; arm C bevacizumab 7.5 mg/kg infusion; arm D bevacizumab 2.5 mg/kg infusion. Patients with metastatic NPC were treated with up to six cycles of similar treatment without concurrent chemoradiation. RESULTS: Complete metabolic response (mCR) by whole body 18FDG PET was highest in arm C (significant difference in four groups Fisher exact test P = 0.001; type 1 error = 0.05), with 42% mCR (95% confidence interval, 18-67) and 3-year relapse-free survival of 88% in patients with locally advanced NPC. Significant increase in pericyte coverage signifying microvascular maturation and increased immune cell infiltration was observed in posttreatment tumor biopsies in Arm C. Myelosuppression was more profound in sunitinib containing arms, and tolerability was established in arm C where hypertension was the most significant toxicity. CONCLUSIONS: Bevacizumab 7.5 mg/kg with cisplatin and gemcitabine was well tolerated. Promising tumor response was observed and supported mechanistically by positive effects on tumor perfusion and immune cell trafficking into the tumor.