Pulmonary function in patients with transfusion-dependent thalassemia and its associations with iron overload.

In patients with transfusion-dependent thalassemia (TDT), pulmonary function impairment has been reported but data are conflicting. Moreover, it remains unclear whether pulmonary dysfunction is associated with iron overload. This study aimed to evaluate the pulmonary function in patients with TDT and to investigate the associations between pulmonary dysfunction and iron overload. It was a retrospective observational study. 101 patients with TDT were recruited for lung function tests. The most recent ferritin levels (pmol/L) and the magnetic resonance imaging (MRI) measurements of the myocardial and liver iron status, as measured by heart and liver T2* relaxation time (millisecond, ms) respectively, were retrieved from the computerized medical records. Only data within 12 months from the lung function measurement were included in the analysis. The serum ferritin, and the cardiac and liver T2* relaxation time were the surrogate indexes of body iron content. The threshold of abnormality in lung function was defined as under 80% of the predicted value. 101 subjects were recruited with a mean age of 25.1 years (standard deviation (SD) 7.9 years). Thirty-eight (38%) and five (5%) demonstrated restrictive and obstructive lung function deficits, respectively. A weak correlation of FVC %Predicted and TLC %Predicted with MRI myocardial T2* relaxation time (rho = 0.32, p = 0.03 and rho = 0.33, p = 0.03 respectively) was observed. By logistic regression, MRI cardiac T2* relaxation time was negatively associated with restrictive lung function deficit (B - 0.06; SE 0.03; Odds ratio 0.94; 95% confidence interval (CI) 0.89-0.99; p = 0.023) after adjusting for age, sex and body mass index. Restrictive pulmonary function deficit was commonly observed in patients with TDT, and the severity potentially correlates with myocardial iron content. Monitoring of lung function in this group of patients, particularly for those with iron overload, is important.

Outcomes of adolescents with acute lymphoblastic leukaemia.

INTRODUCTION: Compared with young children who have acute lymphoblastic leukaemia (ALL), adolescents with ALL have unfavourable disease profiles and worse survival. However, limited data are available regarding the characteristics and outcomes of adolescents with ALL who underwent treatment in clinical trials. The aim of this study was to investigate the causes of treatment failure in adolescents with ALL. METHODS: We retrospectively analysed the outcomes of 711 children with ALL, aged 1-18 years, who were enrolled in five clinical trials of paediatric ALL treatment between 1993 and 2015. RESULTS: Among the 711 children with ALL, 530 were young children (1-9 years at diagnosis) and 181 were adolescents (including 136 younger adolescents [10-14 years] and 45 older adolescents [15-18 years]). Compared with young children who had ALL, adolescents with ALL were less likely to have favourable genetic features and more likely to demonstrate poor early response to treatment. The 10-year overall survival and event-free survival rates were significantly lower among adolescents than among young children (77.9% vs 87.6%, P=0.0003; 69.7% vs 76.5%, P=0.0117). There were no significant differences in the 10-year cumulative incidence of relapse, but the 10-year cumulative incidence of treatment-related death (TRD) was significantly greater among adolescents (7.2%) than among young children (2.3%; P=0.002). Multivariable analysis showed that both younger and older adolescents (vs young children) had worse survival and greater incidence of TRD. CONCLUSION: Adolescents with ALL had worse survival because they experienced a greater incidence of TRD. There is a need to investigate optimal treatment adjustments and novel targeted agents to achieve better survival rates (without excessive toxicity) among adolescents with ALL.

Successful haploidentical hematopoietic stem cell transplantation (HSCT) and durable engraftment by repeated donor lymphocyte infusions for a Chinese patient with transfusion-dependent hemoglobin (Hb) Hammersmith and massive splenomegaly.

BACKGROUND: Hemoglobin (Hb) Hammersmith is a rare form of unstable ß-chain hemoglobinopathy causing hemolytic anemia. This rare event led to a more serious transfusion-dependent phenotype in a patient. It was successfully cured by haploidentical hematopoietic stem cell transplantation (HSCT). METHODS AND RESULTS: A 9-year-old mainland Chinese male with a history of neonatal unconjugated hyperbilirubinemia was diagnosed to have hemoglobin (Hb) Hammersmith. He required regular blood transfusion but was unable to be transfused to desired parameters for 8 years prior to transplant due to social and geographical reasons. He subsequently developed marrow hyperplasia and progressive splenomegaly (down to umbilicus level), suggestive of extramedullary hematopoiesis. Eventually, the family came to Hong Kong and complied to a more intensive transfusion regimen and preconditioning chemotherapy 3 months prior to transplant. He underwent haploidentical HSCT using paternal TCRαß/CD45RA-depleted graft but suffered from graft rejection, despite splenic irradiation for massive splenomegaly. It was successfully salvaged with second HSCT with unmanipulated graft from the same donor with additional serotherapy and donor lymphocyte infusions. CONCLUSION: Allogenic haploidentical HSCT for hemoglobin Hammersmith is feasible but adequate immunosuppression during conditioning is crucial. Precise adoptive cell therapy can promote durable engraftment.

Optimization of a solid culture medium based on Monochamus alternatus for Cordyceps militaris fruiting body formation.

Monochamus alternatus (Coleoptera: Cerambycidae; M. alternatus), popularly known as the Japanese pine sawyer, is a vector of pinewood nematode (Bursaphelenchus xylophilus) that causes pine wilt disease. A solid medium culture with M. alternatus produced Cordyceps militaris fruiting bodies with the longest strips and the highest biological efficiency. Supplementing the original form of M. alternatus with oats resulted in slightly enhanced fruiting body production. The original form of M. alternatus showed higher production than its powder form. The solid culture medium was optimized using a response surface methodology, and the optimal medium contained the following: 8·5 g per bottle of M. alternatus and 11·5 g per bottle of oats mixed with 22·4 ml of water in a 300-ml cylindrical plastic bottle. The optimal culturing period for the fruiting body formation was 37·1 days. Under these conditions, a fruiting body dry weight of 38·0 g per bottle (actual value) was attained. The fruiting body produced using a solid culture medium based on M. alternatus had a cordycepin content of about 25 µg g-1 . The solid culture medium containing M. alternatus is highly efficient and eco-friendly, and its effectiveness in large-scale fruiting body production from C. militaris has been demonstrated.

Short-term neonatal and long-term infant outcome of late-preterm twins: nationwide population-based study.

OBJECTIVES: To evaluate the short- and long-term outcome of late-preterm compared with term birth in twin pregnancy. METHODS: This retrospective observational cohort study included all women who had a twin delivery between 1 January 2007 and 31 December 2010 recorded in the claims database of the Korea National Health Insurance, with at least one follow-up recorded in the database of the National Health Screening Program for Infants and Children. Outcomes were analyzed at the pregnancy level, with adverse outcome being defined as an adverse outcome in one or both twins, identified by a diagnosis according to the International Classification of Diseases 10th Revision. The primary short-term outcome was composite morbidity, which included any of the following: transient tachypnea, respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage and bronchopulmonary dysplasia. Long-term adverse outcome included any neurological or neurodevelopmental outcome, defined by prespecified neurological and developmental diagnoses; these were assessed by following up all neonates until the end of 2018, by which time they were 8-11 years of age. Outcomes were compared between twins delivered late preterm (34 + 0 to 36 + 6 weeks) and those delivered at term (≥ 37 weeks). RESULTS: Among 17 189 women who delivered twins at ≥ 34 weeks of gestation during the study period, 5032 (29.27%) women delivered in the late-preterm period. On multivariate analysis, compared with the twins delivered at term, the late-preterm twins had an increased risk for the primary short-term outcome of composite morbidity (adjusted odds ratio (aOR), 2.09; 95% CI, 1.90-2.30), including transient tachypnea (aOR, 1.85; 95% CI, 1.64-2.09), respiratory distress syndrome (aOR, 2.31; 95% CI, 2.04-2.62), necrotizing enterocolitis (aOR, 2.10; 95% CI, 1.20-3.69) and intraventricular hemorrhage (aOR, 2.13; 95% CI, 1.46-3.11). For the long-term outcome, the late-preterm twins also had an increased risk for any neurological or neurodevelopmental outcome (adjusted hazard ratio, 1.14; 95% CI, 1.07-1.21). CONCLUSIONS: Twins delivered in the late-preterm period have an increased risk for short- and long-term morbidity compared with twins delivered at term. These results should be considered when determining the timing of delivery in uncomplicated twin pregnancy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Outcomes of allogeneic transplantation for hemoglobin Bart's hydrops fetalis syndrome in Hong Kong.

BACKGROUND: Hemoglobin Bart's hydrops fetalis syndrome (BHFS) was once considered a fatal condition universally. Medical advances over the past three decades have resulted in increasing numbers of BHFS survivors. This retrospective review summarized local territory-wide experience and outcomes of BHFS patients who received allogeneic hematopoietic stem cell transplantation (HSCT) in Hong Kong. METHODS: All BHFS patients who underwent allogeneic HSCT in Hong Kong, either in one of the two former pediatric transplant centers (Queen Mary Hospital and Prince of Wales Hospital) on or before 2019 or in the single territory-wide pediatric transplant center (Hong Kong Children's Hospital) since 2019, from January 1, 1996, till December 31, 2020, were included. Basic demographic data, perinatal history, transplant details, long-term outcomes, and morbidities were reviewed. RESULTS: Total five allogeneic HSCT were performed in two males and three females at a median age of 22 months, which include one 8/8 matched-sibling bone marrow transplant, one 5/6 matched-sibling cord blood transplant with HLA-DR antigenic mismatch, two 12/12 matched-unrelated peripheral blood stem cell transplant (PBSCT), and one haploidentical PBSCT with TCRαß/CD45RA depletion from maternal donor. Neutrophil and platelet engrafted (>20 × 109 /L) at a median of 15 and 22 days, respectively. All achieved near full donor chimerism at 1 month. All patients survived and remained transfusion-independent without significant morbidities with median follow-up duration of 10 years. CONCLUSION: To conclude, local data demonstrated favorable outcome of allogeneic HSCT for BHFS patients, but sample number is small. Non-directive approach in counseling and international collaboration is recommended.

Is there a difference in treatment effect of different intra-articular drugs for temporomandibular joint osteoarthritis? A systematic review of randomized controlled trials.

A systematic review based on the PRISMA guidelines was conducted to investigate and compare treatment with hyaluronic acid (HA), corticosteroids, and blood products in patients with temporomandibular joint osteoarthritis (TMJOA). The MEDLINE/PubMed, Embase, and Cochrane Library databases were searched for articles published until September 25, 2019. Articles met the inclusion criteria if they reported patients with TMJOA, a comparison group, and a follow-up period of at least 6 months. The mean and standard deviation for TMJ pain and maximum mouth opening (MMO) were reported. Nine studies involving 443 patients were included. Injectables and Ringer's lactate solution or normal saline were reported to significantly improve TMJ pain and MMO. Regarding TMJ pain, two studies showed a significant superiority of plasma rich in growth factors (PRGF)/platelet-rich plasma (PRP) injections with or without arthrocentesis over HA, but HA showed a significant improvement compared to corticosteroids. For MMO, no injectable was found to be superior to Ringer's lactate or a normal saline control, but arthrocentesis + PRP resulted in MMO improvement compared to arthrocentesis + HA. Overall, all injectables in conjunction with arthrocentesis were efficient in alleviating pain and improving MMO in TMJOA patients; however, a meta-analysis was not possible due to heterogeneity across studies.

Induction of cell cycle arrest and apoptosis by tomentosin in hepatocellular carcinoma HepG2 and Huh7 cells.

Tomentosin, a sesquiterpene lactone, is known to possess various biological activities. However, its anticarcinogenic activity against human hepatocellular carcinoma (HCC) cells has not been investigated in detail. Thus, this study aimed to elucidate the cytotoxic mechanism of tomentosin in human HCC cell lines HepG2 and Huh7. WST-1, cell counting, and colony formation assay results showed that treatment with tomentosin decreased the viability and suppressed the proliferation rate of HepG2 and Huh7 cells in a dose- and time-dependent manner. Cell cycle analysis revealed increased population of cells at the SubG1 and G2/M stage, and decreased population of cells at the G0/1 stage in HepG2 and Huh7 cells treated with tomentosin. Annexin V/propidium iodide double staining and TUNEL assay results showed increased apoptotic cell population and DNA fragmentation in HepG2 and Huh7 cells treated with tomentosin. Western blotting analysis results showed that tomentosin treatment significantly increased the expression level of Bax, Bim (short form), cleaved PARP1, FOXO3, p53, pSer15p53, pSer20p53, pSer46p53, p21, and p27, but decreased the expression of Bcl2, caspase3, caspase7, caspase9, cyclin-dependent kinase 2 (CDK2), CDK4, CDK6, cyclinB1, cyclinD1, cyclinD2, cyclinD3, and cyclinE in a dose-dependent manner. Taken together, this study revealed that tomentosin, which acted through cell cycle arrest and apoptosis, may be a useful therapeutic option against HCC.

Severe cytomegalovirus gastritis after pembrolizumab in a patient with melanoma.

Immunotherapy has emerged as a standard of cancer treatment, with an increasing number of indications. Recently, opportunistic infections have been reported in several cases in which immunotherapy has led to an increased susceptibility to infection. The present case is the first report of cytomegalovirus (cmv) gastritis occurring in a patient with melanoma during immunotherapy without immune-related adverse events (iraes) and without the use of immunosuppressant agents. A 43-year-old woman presented with stage iii malignant melanoma. She underwent wide excision of skin, with lymph node dissection, and she started immunotherapy with a 3-week cycle of pembrolizumab. The patient demonstrated stable disease response, and no iraes were observed during her initial treatment courses. However, after the 9th treatment cycle, she began to experience epigastric pain that worsened significantly, requiring a visit to the emergency centre. Imaging by computed tomography (ct) and integrated positron-emission tomography/ct revealed severe diffuse gastroduodenitis with acute pancreatitis. Esophagogastroduodenoscopy showed diffuse oozing, hemorrhagic, edematous, and exfoliative mucosa involving the entire gastric wall, defined as acute hemorrhagic gastritis. Biopsies of the gastric wall revealed cmv infection. Those findings were consistent with a diagnosis of cmv gastritis, and the patient received antiviral therapy with ganciclovir. After treatment, she recovered enough to resume immunotherapy. This case report presents a rare occurrence of cmv gastritis related to immunotherapy. As more patients are treated with immunotherapy, incidences of cmv infections are expected to increase; a high index of clinical suspicion is therefore needed in symptomatic patients.

Palliative Liver Radiotherapy (RT) for Symptomatic Hepatocellular Carcinoma (HCC).

This study aims at evaluating the symptom response, response duration, and toxicity of single dose palliative liver radiotherapy (RT) for symptomatic HCC patients. We reviewed unresectable HCC patients treated with palliative RT in our institution. Eligible patients were unsuitable or refractory to trans-arterial chemoembolization (TACE) and stereotactic body radiotherapy (SBRT), with an index symptom of pain or abdominal discomfort. The primary outcome was the percentage of patients with clinical improvement of index symptom at 1 month. Secondary outcomes were response duration, toxicities, alpha-feto protein (AFP) response, and radiological response. Fifty-two patients were included in the study. The index symptom was pain in 34 patients (65.4%), and abdominal discomfort (34.6%) in 18 patients. At 1 month, 51.9% of patients had improvement of symptoms. Median time to symptom progression was 89 days (range: 12-392 days). Treatment was well tolerated with only 2 patients (3.8%) developing grade 3 GI toxicities. AFP response, radiological response rate, and disease control rate at 3 months were 48.6%, 15.1%, and 54.5% respectively. Half of the patients had improvement of index symptoms after receiving palliative liver RT with median response duration of 3 months. The treatment was well tolerated with minimal toxicities.

Effect of different doses of ketamine with low-dose rocuronium on intubation conditions in children: prospective randomized double blind trial.

OBJECTIVE: The effect of ketamine on intubation condition, when used as an induction agent with low-dose rocuronium, is unknown. This study aimed to compare the effects of three doses of ketamine used with 0.3 mg/kg rocuronium and 1 µg/kg fentanyl on intubation conditions in children undergoing short elective surgery. PATIENTS AND METHODS: The study was performed as a prospective, randomized double-blind clinical trial. A total of 60 children aged 2 to 12 years, who were scheduled for inguinal herniorrhaphy under general anesthesia, were randomly allocated into three groups on the basis of ketamine dose: 1 mg/kg (Group K1, n = 20), 1.5 mg/kg (Group K1.5, n = 20), and 2 mg/kg (Group K2, n = 20). The primary outcome was the intubation condition. Other assessments included hemodynamic data, recovery profile, adverse events in the postanesthetic care unit (PACU) and use of fentanyl as a rescue analgesic in the PACU were also assessed. RESULTS: The occurrence of a clinically acceptable intubation condition increased with the use of an increased dose (≥ 1.5 mg/kg) (K1/K1.5/K2: 30%/65%/65%; p=0.038, for trends p=0.028). Hemodynamic data, recovery profile and adverse events in PACU showed no difference among groups. Fentanyl dose used in the PACU was higher in K1 than K2 and the number of patients requiring rescue analgesics in the PACU decreased in accordance with the dose of ketamine (K1/K1.5/K2: 30%/15%/0%; p=.031, for trends p=0.013). CONCLUSIONS: Different intubation conditions were observed on the basis of ketamine dose used in conjunction with 0.3 mg/kg rocuronium and fentanyl 1 µg/kg. Ketamine dose ≥ 1.5 mg/kg with low-dose rocuronium should be used to improve intubation conditions in pediatrics.

Gliomas: survival differences between metropolitan and non-metropolitan counties.

BACKGROUND: For gliomas, metropolitan status has not been heavily explored in the context of short-term mortality or long-term observed survival. Larger populations are associated with proximity to academic universities/high-volume hospitals. METHODS: The SEER-18 registry was queried for patients with gliomas. The patients were further classified into two population groups based on rural-urban continuum codes: metropolitan or non-metropolitan. Demographics and clinical factors were compared between both groups. For observed survival, univariate and multivariate analyses occurred with Cox proportional hazards model. RESULTS: The non-metropolitan group constituted approximately 10.8% of all patients. Age at diagnosis of glioma was older for the non-metropolitan group compared to metropolitan group (51.60 years vs. 49.06 years). Relative to the metropolitan group, the non-metropolitan group exhibited a larger proportion of Caucasian, married, grade I and IV gliomas, no surgery, no GTR (for those who had surgery), and temporal/parietal/occipital locations. Other covariates (sex, tumor size, laterality, and radiation status) did not exhibit significant differences in proportions. From analysis of observed survival, independent predictors include population group, as well as age, gender, marital status, tumor location, tumor grade, laterality, GTR, and receipt of radiation. Short-term mortality was 11.68% and 13.04% for Metropolitan and non-metropolitan groups, respectively. Median survival was 15 months and 12 months for Metropolitan and non-metropolitan groups, respectively. CONCLUSIONS: About one-tenth of gliomas are treated at non-metropolitan sites. Key differences exist among patient/glioma characteristics based on metropolitan status. Overall, metropolitan status appears to influence short-term mortality and long-term observed survival for gliomas.

Causes of death in glioblastoma: insights from the SEER database.

BACKGROUND: Glioblastoma (GB) and its variants portend a poor prognosis. The predominant cause of death (COD) is related to the cancer diagnosis, but a significant subset is related to other causes. As GB is a systemic disease requiring systemic treatment, focus regarding all COD provides a comprehensive illustration of the disease. METHODS: The SEER-18 was queried for patients with cranial GB and its variants. Age, gender, race, marital status, tumor characteristics, treatment details, and follow-up data were acquired. The patients were classified into group A (death attributed to this cancer diagnosis) or group B (death attributed to causes other than this cancer diagnosis). RESULTS: From 1973 to 2013, 36,632 deaths (94%) constituted group A, and 2,324 deaths (5.9%) constituted group B. The latter significantly exhibited lower proportions of age <60, Caucasians, married status, frontal/brain stem/ventricle tumor locations, and receipt of radiation. From logistic regression, age >60, male gender, race, not married, tumor location, and no radiation were significant independent predictors for group B. The top known CODs in group B are diseases of heart, pneumonia and influenza, cerebrovascular diseases, accidents and adverse effects, and infections. CONCLUSIONS: CODs not attributed to GB remains a significant subset of all CODs. Many of these, particularly diseases of heart, are frequent comorbidities. Moreover, infection-related CODs after GB diagnosis appear more salient compared to CODs in the general population. Consideration of these CODs, and vigilant treatment aimed at these CODs, may improve overall care for GB patients.

Modern operative nuances for the management of eloquent high-grade gliomas.

INTRODUCTION: Despite advancements in the treatment of high-grade gliomas (HGG), the rate of tumor recurrence is high and survival rate for the patient is low. Gross total resection has shown increased survival but the location of the tumor in the eloquent brain poses significant risk of morbidity. In this report, we focus on modern surgical nuances for resection of tumors located in the eloquent brain. EVIDENCE ACQUISITION: Research of the literature was conducted using the following search terms: surgical resection of gliomas, high-grade gliomas, and the role of vascular encasement - from 1986-2018. An institutional experience from the first author of this paper was also reviewed for selection of our illustrative cases. EVIDENCE SYNTHESIS: Gross total resection remains the mainstay of therapy for high-grade gliomas. The resection of the peritumoral FLAIR, when possible, has been associated with increased survival but also has the potential to cause increased morbidity. In the eloquent brain, the resection of the tumor itself is possible if attention is given to the interface of the tumor and brain, or if a safe pseudo-interface is created by the surgeon. Tumor-seeding to the ventricular system needs to be avoided. Devascularization, dissection away from the brain, and retractorless brain surgery are key to successful surgical outcomes. Management of the venous and arterial invasion/encasement are also outlined in this report. Technical aspects are discussed with corresponding videos. CONCLUSIONS: High-grade gliomas involving eloquent brain areas require a tailored treatment plan. While the medical treatment is undergoing quick evolution, gross total resection still remains one of the key milestones of treatment for improved survival. Surgical techniques play key role. We propose that encasement and/or the invasion of arteries and veins, should be considered equally as important as the eloquent brain when contemplating the resection of gliomas.

Irradiation of pediatric glioblastoma cells promotes radioresistance and enhances glioma malignancy via genome-wide transcriptome changes.

Pediatric glioblastoma (GBM) is a relatively rare brain tumor in children that has a dismal prognosis. Surgery followed by radiotherapy is the main treatment protocol used for older patients. The benefit of adjuvant chemotherapy is still limited due to a poor understanding of the underlying molecular and genetic changes that occur with irradiation of the tumor. In this study, we performed total RNA sequencing on an established stable radioresistant pediatric GBM cell line to identify mRNA expression changes following radiation. The expression of many genes was altered in the radioresistant pediatric GBM model. These genes have never before been reported to be associated with the development of radioresistant GBM. In addition to exhibiting an accelerated growth rate, radioresistant GBM cells also have overexpression of the DNA synthesis-rate-limiting enzyme ribonucleotide reductase, and pro-cathepsin B. These newly identified genes should be concertedly studied to better understand their role in pediatric GBM recurrence and progression after radiation. It was observed that the changes in multiple biological pathways protected GBM cells against radiation and transformed them to a more malignant form. These changes emphasize the importance of developing a treatment regimen that consists of a multiple-agent cocktail that acts on multiple implicated pathways to effectively target irradiated pediatric GBM. An alternative to radiation or a novel therapy that targets differentially expressed genes, such as metalloproteases, growth factors, and oncogenes and aim to minimize oncogenic changes following radiation is necessary to improve recurrent GBM survival.

Molecular Markers of Therapy-Resistant Glioblastoma and Potential Strategy to Combat Resistance.

Glioblastoma (GBM) is the most common primary malignant tumor of the central nervous system. With its overall dismal prognosis (the median survival is 14 months), GBMs demonstrate a resounding resilience against all current treatment modalities. The absence of a major progress in the treatment of GBM maybe a result of our poor understanding of both GBM tumor biology and the mechanisms underlying the acquirement of treatment resistance in recurrent GBMs. A comprehensive understanding of these markers is mandatory for the development of treatments against therapy-resistant GBMs. This review also provides an overview of a novel marker called acid ceramidase and its implication in the development of radioresistant GBMs. Multiple signaling pathways were found altered in radioresistant GBMs. Given these global alterations of multiple signaling pathways found in radioresistant GBMs, an effective treatment for radioresistant GBMs may require a cocktail containing multiple agents targeting multiple cancer-inducing pathways in order to have a chance to make a substantial impact on improving the overall GBM survival.

Identification of radiation responsive genes and transcriptome profiling via complete RNA sequencing in a stable radioresistant U87 glioblastoma model.

The absence of major progress in the treatment of glioblastoma (GBM) is partly attributable to our poor understanding of both GBM tumor biology and the acquirement of treatment resistance in recurrent GBMs. Recurrent GBMs are characterized by their resistance to radiation. In this study, we used an established stable U87 radioresistant GBM model and total RNA sequencing to shed light on global mRNA expression changes following irradiation. We identified many genes, the expressions of which were altered in our radioresistant GBM model, that have never before been reported to be associated with the development of radioresistant GBM and should be concertedly further investigated to understand their roles in radioresistance. These genes were enriched in various biological processes such as inflammatory response, cell migration, positive regulation of epithelial to mesenchymal transition, angiogenesis, apoptosis, positive regulation of T-cell migration, positive regulation of macrophage chemotaxis, T-cell antigen processing and presentation, and microglial cell activation involved in immune response genes. These findings furnish crucial information for elucidating the molecular mechanisms associated with radioresistance in GBM. Therapeutically, with the global alterations of multiple biological pathways observed in irradiated GBM cells, an effective GBM therapy may require a cocktail carrying multiple agents targeting multiple implicated pathways in order to have a chance at making a substantial impact on improving the overall GBM survival.

Outcomes and morbidities of patients who survive haemoglobin Bart's hydrops fetalis syndrome: 20-year retrospective review.

INTRODUCTION: Haemoglobin Bart's hydrops fetalis syndrome was once considered a fatal condition. However, advances over the past two decades have enabled survival of affected patients. Data relating to their morbidities and outcomes will help medical specialists formulate a management plan and parental counselling. METHODS: All babies with the syndrome who survived beyond the neonatal period and were subsequently managed long-term in eight public hospitals in Hong Kong from 1 January 1996 to 31 December 2015 were included. Patient and parent characteristics, antenatal care, reasons for continuation of pregnancy, intrauterine interventions, perinatal course, presence of congenital malformations, stem-cell transplantation details, and long-term neurodevelopmental outcomes were reviewed. RESULTS: A total of nine patients were identified, of whom five were female and four male. The median follow-up duration was 7 years. All were Chinese and were homozygous for the Southeast Asian α-thalassaemia deletion. Five of the nine mothers received antenatal care at a public hospital and opted to continue the pregnancy after antenatal diagnosis and counselling. Despite intrauterine transfusions, all babies were born with respiratory depression and required intubation and mechanical ventilation during the neonatal period. Hypospadias was identified in all four male infants. Growth retardation, global developmental delay, and residual neurological deficits were noted in two-thirds of the patients. Haematopoietic stem-cell transplantation was performed in two patients, who became transfusion-independent. CONCLUSIONS: Survival of patients with Bart's hydrops fetalis syndrome is possible but not without short- and long-term complications; local epidemiology is comparable to that documented for an international registry. Detailed antenatal counselling of parents with a non-judgemental attitude and cautious optimism are imperative.

Molecular Targeting of Acid Ceramidase in Glioblastoma: A Review of Its Role, Potential Treatment, and Challenges.

Glioblastoma is the most common, malignant primary tumor of the central nervous system. The average prognosis for life expectancy after diagnosis, with the triad of surgery, chemotherapy, and radiation therapy, is less than 1.5 years. Chemotherapy treatment is mostly limited to temozolomide. In this paper, the authors review an emerging, novel drug called acid ceramidase, which targets glioblastoma. Its role in cancer treatment in general, and more specifically, in the treatment of glioblastoma, are discussed. In addition, the authors provide insights on acid ceramidase as a potential druggable target for glioblastoma.