Trends of Coagulation Parameters in Human Immunodeficiency Virus Patients.

Background and Objectives: HIV disease is recognized to cause inconsistencies in coagulation via various pathways during infection. Some studies have indicated that HIV-infected patients are prone to developing thrombocytopenia, thrombosis, or autoantibodies that may cause difficulties in diagnosis. This study is intended to measure the trend of coagulation parameters in Sudanese patients with HIV. Materials and Methods: A cross-sectional study was carried out in patients with HIV admitted to the Sudan National AIDS Program (SNAP) from January 2018 to December 2019. Prothrombin time (PT), partial thromboplastin time (PTT), thrombin time (TT), D-dimer (DD), hemoglobin (HB), total lymphocyte count (TLC), platelet count (PLT), and a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13), were evaluated among HIV Sudanese patients. Results: Out of the 44 HIV patients included, 6 (13.6%) were found to have thrombotic thrombocytopenic purpura-like events and 12 (27.2%) had antiphospholipid antibodies, of whom 8 (66.6%) showed anticardiolipin antibody (1gG (75%) and IgM (25%)) and 4 showed lupus anticoagulants. The HB, TLC, and PLT values were found to be significantly lower in HIV patients than in control (p = 0.000, 0.000, and 0.050, respectively). The PT and ADAMTS13 values showed no significant difference between HIV patients and control (p = 0.613 and 0.266, respectively). The PTT, TT, and DD values were found to be augmented in HIV patients versus the control (p = 0.000). Conclusions: Thrombotic thrombocytopenic purpura-like events among HIV Sudanese patients were explored. In addition, antiphospholipid antibodies were strikingly seen in these patients. Additional research is anticipated to confirm these diagnoses.

Supply and Demand for Radiation Oncologists in Canada: Workforce Planning Projections From 2020 to 2040.

PURPOSE: The number of Canadians diagnosed with cancer, and subsequent demand for radiation therapy, are expected to increase over time. This study aimed to update our needs-based workforce planning model to ensure appropriate staffing levels in the future. METHODS AND MATERIALS: The supply of radiation oncologists, by age group, sex, and full-time equivalent status, was projected from 2020 to 2040 using a recursive-aging, input-output model developed with seeding parameters derived from national sources. The demand for radiation oncologists until 2040 was estimated using referral patterns for radiation therapy and consultation workload metrics applied to projected annual cancer incident cases to calculate required full-time equivalent positions. Baseline model parameters were also applied to the 2005-2019 workforce and incident case data to evaluate preprojection supply and demand trends. RESULTS: Preprojection trends for 2005 to 2019 revealed accelerated staffing growth that transitioned from a workforce shortage to a surplus state in 2014 followed by substantial growth slowdown in 2016. The model predicts a transient surplus of radiation oncologists until 2026 followed by a projected deficit in subsequent years. Sensitivity analyses using the plausible range for each parameter continued to favor an undersupply, suggesting a trainee shortage unable to meet workforce expansion needs. Considering possible future declining trends in radiotherapy utilization and workload, calculations to inform corrective efforts in resident numbers resulted in 25 entry positions per year, up from 21 per year currently. Geographic distribution of trainees, relative to workforce and cancer incidence distributions, could be improved with more residency positions in Canadian regions outside Ontario. CONCLUSIONS: Demand for radiation therapy and radiation oncologists in Canada are expected to grow more quickly than future expansion in staffing levels. Our workforce planning model provides evidence for more trainee requirements to inform stakeholders of possible corrective actions to training programs and recruitment. Further research is needed to explore additional strategies to expand capacity and high-quality delivery of radiation therapy to meet the foreseeable increase in Canadian patients with cancer.

Endobronchially Implanted Real-Time Electromagnetic Transponder Beacon-Guided, Respiratory-Gated SABR for Moving Lung Tumors: A Prospective Phase 1/2 Cohort Study.

Purpose: Endobronchial electromagnetic transponder beacons (EMT) provide real-time, precise positional data of moving lung tumors. We report results of a phase 1/2, prospective, single-arm cohort study evaluating the treatment planning effects of EMT-guided SABR for moving lung tumors. Methods and Materials: Eligible patients were adults, Eastern Cooperative Oncology Group 0 to 2, with T1-T2N0 non-small cell lung cancer or pulmonary metastasis ≤4 cm with motion amplitude ≥5 mm. Three EMTs were endobronchially implanted using navigational bronchoscopy. Four-dimensional free-breathing computed tomography simulation scans were obtained, and end-exhalation phases were used to define the gating window internal target volume. A 3-mm expansion of gating window internal target volume defined the planning target volume (PTV). EMT-guided, respiratory-gated (RG) SABR was delivered (54 Gy/3 fractions or 48 Gy/4 fractions) using volumetric modulated arc therapy. For each RG-SABR plan, a 10-phase image-guided SABR plan was generated for dosimetric comparison. PTV/organ-at-risk (OAR) metrics were tabulated and analyzed using the Wilcoxon signed-rank pair test. Treatment outcomes were evaluated using RECIST (Response Evaluation Criteria in Solid Tumours; version 1.1). Results: Of 41 patients screened, 17 were enrolled and 2 withdrew from the study. Median age was 73 years, with 7 women. Sixty percent had T1/T2 non-small cell lung cancer and 40% had M1 disease. Median tumor diameter was 1.9 cm with 73% of targets located peripherally. Mean respiratory tumor motion was 1.25 cm (range, 0.53-4.04 cm). Thirteen tumors were treated with EMT-guided SABR and 47% of patients received 48 Gy in 4 fractions while 53% received 54 Gy in 3 fractions. RG-SABR yielded an average PTV reduction of 46.9% (P < .005). Lung V5, V10, V20, and mean lung dose had mean relative reductions of 11.3%, 20.3%, 31.1%, and 20.3%, respectively (P < .005). Dose to OARs was significantly reduced (P < .05) except for spinal cord. At 6 months, mean radiographic tumor volume reduction was 53.5% (P < .005). Conclusions: EMT-guided RG-SABR significantly reduced PTVs of moving lung tumors compared with image-guided SABR. EMT-guided RG-SABR should be considered for tumors with large respiratory motion amplitudes or those located in close proximity to OARs.

Potential Therapeutic Target and Vaccines for SARS-CoV-2.

The coronavirus has become the most interesting virus for scientists because of the recently emerging deadly SARS-CoV-2. This study aimed to understand the behavior of SARS-CoV-2 through the comparative genomic analysis with the closest one among the seven species of coronavirus that infect humans. The genomes of coronavirus species that infect humans were retrieved from NCBI, and then subjected to comparative genomic analysis using different bioinformatics tools. The study revealed that SARS-CoV-2 is the most similar to SARS-CoV among the coronavirus species. The core genes were shared by the two genomes, but there were some genes, found in one of them but not in both, such as ORF8, which is found in SARS-CoV-2. The ORF8 protein of SARS-CoV-2 could be considered as a good therapeutic target for stopping viral transmission, as it was predicted to be a transmembrane protein, which is responsible for interspecies transmission. This is supported by the molecular interaction of ORF8 with both the ORF7 protein, which contains a transmembrane domain that is essential to retaining the protein in the Golgi compartment, and the S protein, which facilitates the entry of the coronavirus into host cells. ORF1ab, ORF1a, ORF8, and S proteins of SARS-CoV-2 could be immunogenic and capable of evoking an immune response, which means that these four proteins could be considered a potential vaccine source. Overall, SARS-CoV-2 is most related to SARS-CoV. ORF8 could be considered a potential therapeutic target for stopping viral transmission, and ORF1ab, ORF1a, ORF8, and the S proteins of SARS-CoV-2 could be utilized as a potential vaccine source.

Factors Associated with Long-Term Prostate Cancer Survival after Palliative Radiotherapy to a Bone Metastasis and Contemporary Palliative Systemic Therapy: A Retrospective, Population-Based Study.

BACKGROUND: Radiation therapy (RT) is an established palliative treatment for bone metastases; however, little is known about post-radiation survival and factors which impact it. The aim of this study was to assess a population-based sample of metastatic prostate cancer patients receiving palliative radiation therapy to bone metastases and contemporary palliative systemic therapy and identify factors that impact long-term survival. MATERIALS/METHODS: This retrospective, population-based, cohort study assessed all prostate cancer patients receiving palliative RT for bone metastases at a Canadian provincial Cancer program during a contemporary time period. Baseline patient, disease, and treatment characteristics were extracted from the provincial medical physics databases and the electronic medical record. Post-RT Survival intervals were defined as the time interval from the first fraction of palliative RT to death from any cause or date of the last known follow-up. The median survival of the cohort was used to dichotomize the cohort into short- and long-term survivors following RT. Univariable and multivariable hazard regression analyses were performed to identify variables associated with post-RT survival. RESULTS: From 1 January 2018 until 31 December 2019, 545 palliative RT courses for bone metastases were delivered to n = 274 metastatic prostate cancer patients with a median age of 76 yrs (Interquartile range (IQR) 39-83) and a median follow-up of 10.6 months (range 0.2 to 47.9). The median survival of the cohort was 10.6 months (IQR 3.5-25 months). The ECOG performance status of the whole cohort was ≤2 in n = 200 (73%) and 3-4 in n = 67 (24.5%). The most commonly treated sites of bone metastasis were the pelvis and lower extremities n = 130 (47.4%), skull and spine n = 114 (41.6%), and chest and upper extremities n = 30 (10.9%). Most patients had CHAARTED high volume disease n = 239 (87.2%). On multivariable hazard regression analysis, an ECOG performance status of 3-4 (p = 0.02), CHAARTED high volume disease burden (p = 0.023), and non-receipt of systemic therapy (p = 0.006) were significantly associated with worse post-RT survival. CONCLUSION: Amongst metastatic prostate cancer patients treated with palliative radiotherapy to bone metastases and modern palliative systemic therapies, ECOG performance status, CHAARTED metastatic disease burden, and type of first-line palliative systemic therapy were significantly associated with post-RT survival durations.

Stereotactic ablative radiotherapy before resection to avoid delay for early-stage lung cancer or oligometastases during the COVID-19 pandemic: Pathologic outcomes from the SABR-BRIDGE protocol.

BACKGROUND: During coronavirus disease 2019 (COVID-19)-related operating room closures, some multidisciplinary thoracic oncology teams adopted a paradigm of stereotactic ablative radiotherapy (SABR) as a bridge to surgery, an approach called SABR-BRIDGE. This study presents the preliminary surgical and pathological results. METHODS: Eligible participants from four institutions (three in Canada and one in the United States) had early-stage presumed or biopsy-proven lung malignancy that would normally be surgically resected. SABR was delivered using standard institutional guidelines, with surgery >3 months following SABR with standardized pathologic assessment. Pathological complete response (pCR) was defined as absence of viable cancer. Major pathologic response (MPR) was defined as ≤10% viable tissue. RESULTS: Seventy-two patients underwent SABR. Most common SABR regimens were 34 Gy/1 (29%, n = 21), 48 Gy/3-4 (26%, n = 19), and 50/55 Gy/5 (22%, n = 16). SABR was well-tolerated, with one grade 5 toxicity (death 10 days after SABR with COVID-19) and five grade 2-3 toxicities. Following SABR, 26 patients underwent resection thus far (13 pending surgery). Median time-to-surgery was 4.5 months post-SABR (range, 2-17.5 months). Surgery was reported as being more difficult because of SABR in 38% (n = 10) of cases. Thirteen patients (50%) had pCR and 19 (73%) had MPR. Rates of pCR trended higher in patients operated on at earlier time points (75% if within 3 months, 50% if 3-6 months, and 33% if ≥6 months; p = .069). In the exploratory best-case scenario analysis, pCR rate does not exceed 82%. CONCLUSIONS: The SABR-BRIDGE approach allowed for delivery of treatment during a period of operating room closure and was well-tolerated. Even in the best-case scenario, pCR rate does not exceed 82%.

Do Sustainable Palliative Single Fraction Radiotherapy Practices Proliferate or Perish 2 Years after a Knowledge Translation Campaign?

In early 2017, the Canadian Partnership Against Cancer and CancerCare Manitoba undertook a comprehensive knowledge translation (KT) campaign to improve the utilization of single fraction radiotherapy (SFRT) over multiple fraction radiotherapy (MFRT) for palliative management of bone metastases. The campaign significantly increased short-term SFRT utilization. We assess the time-dependent effects of KT-derived SFRT utilization 12-24 months removed from the KT campaign in a Provincial Cancer Program. This study identified patients receiving palliative radiotherapy for bone metastases in Manitoba in the 2018 calendar year using the provincial radiotherapy database. The proportion of patients treated with SFRT in 2018 was compared to 2017. Logistic regression analyses identified risk factors associated with MFRT receipt. In 2018, 1008 patients received palliative radiotherapy for bone metastasis, of which 63.3% received SFRT, a small overall increase in SFRT use over 2017 (59.1%). However, 41.1% of ROs demonstrated year-over-year decreases in SFRT utilization, indicative of a time-dependent loss of SFRT prescription habits derived from KT. Although SFRT use increased slightly overall in 2018, evidence of compliance fatigue was observed, suggestive of a time-perishing property of RO prescription behaviours derived from KT methodologies. Verification of the study's findings in larger cohorts would be beneficial. These findings highlight the need for additional longitudinal KT reinforcement practices in the years following KT campaigns.

Evaluation of the ITV-margin and variables affecting bladder and mesorectal deformation during long course neoadjuvant radiotherapy for rectal cancer.

Internal target volume (ITV) margins were estimated by evaluating the movement of mesorectum and bladder during neoadjuvant long-course radiation therapy (RT) for rectal cancer. In this prospective study, 23 patients with rectal cancer had planning CT (pCT) and weekly cone beam CT (CBCT) in supine position during preoperative long-course RT. Mesorectal wall motion was analyzed based on the coordinates of the most anterior, posterior, left and right points on the pCT and CBCT. Overlap volume (OV) between the pCT bladder and CBCT mesorectum was generated. Variables that might affect relative bladder volume (ratio of CBCT to pCT bladder volumes), anterior mesorectal wall position, and OV were studied. ITV margins were also calculated. In females, smaller OV and less movement of the upper anterior mesorectal wall were identified, suggesting smaller ITV margins might be required compared to males. The relative bladder volume did not change significantly over time and was correlated with OV: the larger the relative bladder volume, the less the OV. ITV margin of 0.8 to 1.1 cm in right-left direction is satisfactory. Posteriorly, only 8 to 9 mm margin is required for upper and mid rectal regions but double of this is required for inferior third. Anteriorly, 1.3 cm margin is adequate for lower and mid rectal regions and 2.4 cm is required superiorly. An anisotropic ITV expansion of clinical target volume (CTV) for rectal cancer radiotherapy contouring provides a robust method to encompass the deformation of bladder and mesorectum. The ITV margin should take into account sex and distance from the anal verge.

Impact of Pre-Treatment NLR and Other Hematologic Biomarkers on the Outcomes of Early-Stage Non-Small-Cell Lung Cancer Treated with Stereotactic Body Radiation Therapy.

INTRODUCTION: We evaluated the association of pre-treatment immunologic biomarkers on the outcomes of early-stage non-small-cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS: In this retrospective study, all newly diagnosed early-stage NSCLC treated with SBRT between January 2010 and December 2017 were screened and included for further analysis. The pre-treatment neutrophil-lymphocyte ratio (NLR), monocyte lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) were calculated. Overall survival (OS) and recurrence-free survival (RFS) were estimated by Kaplan-Meier. Multivariable models were constructed to determine the impact of different biomarkers and the Akaike information criterion (AIC), index of adequacy, and scaled Brier scores were calculated. RESULTS: A total of 72 patients were identified and 61 were included in final analysis. The median neutrophil count at baseline was 5.4 × 109/L (IQR: 4.17-7.05 × 109/L). Median lymphocyte count was 1.63 × 109/L (IQR: 1.29-2.10 × 109/L), median monocyte count was 0.65 × 109/L (IQR: 0.54-0.83 × 109/L), median platelet count was 260.0 × 109/L (IQR: 211.0-302.0 × 109/L). The median NLR was 3.42 (IQR: 2.38-5.04), median MLR was 0.39 (IQR: 0.31-0.53), and median PLR was 156.4 (IQR: 117.2-197.5). On multivariable regression a higher NLR was associated with worse OS (p = 0.01; HR-1.26; 95% CI 1.04-1.53). The delta AIC between the two multivariable models was 3.4, suggesting a moderate impact of NLR on OS. On multivariable analysis, higher NLR was associated with poor RFS (p = 0.001; NLR^1 HR 0.36; 0.17-0.78; NLR^2 HR-1.16; 95% CI 1.06-1.26) with a nonlinear relationship. The delta AIC between the two multivariable models was 16.2, suggesting a strong impact of NLR on RFS. In our cohort, MLR and PLR were not associated with RFS or OS in multivariable models. CONCLUSIONS: Our study suggests NLR, as a biomarker of systemic inflammation, is an independent prognostic factor for OS and RFS. The nonlinear relationship with RFS may indicate a suitable immunological environment is needed for optimal SBRT action and tumoricidal mechanisms. These findings require further validation in independent cohorts.

A rare haematological disorder in a Sudanese child: Evans syndrome, case report and literature review.

Evans syndrome is a condition in which autoimmune-mediated red blood cells and platelet destruction happens consecutively. It may be associated with a reduction in neutrophil count as a result of immune neutropenia. No sex preference is known and it presents in all ages and any ethnic cohort. Generally, this syndrome tends to be chronic and is characterised by remission and exacerbation. We document a case of the immune-mediated disease associated with Epstein-Barr virus infection in an 8-year-old boy from eastern Sudan who presented with both immune thrombocytopenia purpura and autoimmune haemolytic anaemia. Complete blood count and peripheral blood picture revealed features consistent with immune haemolytic anaemia (rouleaux formation and spherocytes) and thrombocytopenia. Direct anti-human globulin test and indirect anti-human globulin test were positive. Evans syndrome is a potentially life-threatening condition due to the concomitant existence with antiplatelet and anti-erythrocyte antibodies distinguished by a positive antiglobulin test and possibly linked to other autoimmune or lymphoproliferative diseases.

Outcome of Locally Advanced Esophageal Cancer Patients Treated With Perioperative Chemotherapy and Chemoradiotherapy Followed by Surgery.

OBJECTIVES: Perioperative chemotherapy (P-CT) or neoadjuvant chemoradiation (C-RT) followed by surgical resection is the standard of care for locally advanced esophageal cancer (LAEC). We present an institutional review and outcome of patients with LAEC treated with neoadjuvant C-RT or P-CT followed by surgery. METHODS: Patients were identified through the Manitoba Cancer Registry. Overall survival (OS), recurrence-free survival (RFS), and time to recurrence (TTR) were compared using proportion hazard regression analysis. Metabolic and pathologic response rates were compared by the Fisher exact test. RESULTS: Sixty-seven patients were treated with C-RT and 32 with P-CT. Fifty-two percent of the patients had pretreatment and posttreatment positron emission tomography scans before surgery. Ninety-five percent of the patients in C-RT and 91% in P-CT had a partial metabolic response or stable disease. Sixty-one percent of C-RT and 34% of P-CT patients had tumor regression grade (TRG) 0 to 1; 39% of C-RT and 66% of P-CT had TRG 2 to 3 (P=0.018). Median OS was 37 and 18 months for patients with TRG 0 to 1 and 2 to 3, respectively (P=0.013, hazard ratio [HR]=1.96). Three-year OS was 43% versus 37% (P=0.37, HR=1.30), RFS was 34% versus 26% (P=0.87, HR=0.96), and median TTR was 30 versus 13 months (P=0.07, HR=0.59) for C-RT and P-CT, respectively. CONCLUSIONS: C-RT was associated with a higher degree of pathologically tumor regression. Patients with major tumor regression had a better outcome than those with minimal to poor response. There was a trend toward improved TTR with C-RT but no difference in OS or RFS.

Clinical Outcomes After Stereotactic Body Radiation Therapy for Early Stage Non-Small Cell Lung Cancer: A Single Institutional Study.

Introduction The standard of care for early-stage non-small cell lung cancer (NSCLC) is surgery. However, for medical inoperable patients stereotactic body radiation therapy (SBRT) is an alternative method. The aim of the study is to assess the overall survival (OS), progression-free survival (PFS) and local control (LC) of patients diagnosed with NSCLC in Manitoba, Canada, between 2013 and 2017 and managed with SBRT. Materials and methods This retrospective study included a total of 158 patients (60.13% of the population were females) that were diagnosed with stage I-II NSCLC and were treated with lung SBRT between 2013 and 2017 in Manitoba. Demographics and clinical data were retrospectively extracted from the electronic patient record. Kaplan-Meier and Cumulative incidence curves were used to describe the OS, PFS, and LC outcomes. Results From the 158 patients, 32 patients were treated with 60 Gy in eight fractions, while 121 patients were treated with 48 Gy in four fractions. Only 85 patients had biopsy-proven NSCLC. The median OS was 2.87 years (95% confidence interval [CI] 2.16-3.43). OS rates at one and two years were 85% and 66%, respectively. The median PFS was 2.03 years (95% CI 1.65-2.77). Furthermore, one-year and two-year PFS rates were 77% and 51%, respectively. Only 10 patients progressed locally at one year and 17 at two years, making the LC rate 93% at the one-year and 87% at the two-year mark. Conclusion These findings add to a growing evidence base supporting SBRT in the treatment of clinically suspected and biopsy-proven early-stage NSCLC patients.

Population-based Assessment of Intermittent Androgen Deprivation Therapy Utilization for Relapsed, Nonmetastatic, Hormone-sensitive Adenocarcinoma of the Prostate.

OBJECTIVES: Androgen deprivation therapy (ADT) is the standard of care for men with nonmetastatic hormone-sensitive prostate cancer (nmHSPC) after treatment failure. Although intermittent ADT (iADT) is noninferior to continuous ADT for prostate cancer outcomes, with superior quality of life and cost-to-benefit ratio, little is known regarding its real-world utilization. The authors aimed to determine the utilization of iADT in a Canadian Provincial Cancer Program for relapsed nmHSPC and identified risk factors associated with the nonreceipt of iADT. MATERIALS AND METHODS: This retrospective population-based cohort study used linked administrative databases to identify all patients with relapsed nmHSPC from 2012 to 2016 and quantified ADT prescription history. Patients were defined as iADT eligible if prostate-specific antigen (PSA) was <4 ng/mL and trending downwards on ≥2 sequential PSAs after ≥6 months of ADT. Univariable and multivariable logistic regression analyses were performed to determine factors associated with nonreceipt of iADT. RESULTS: A total of 601 men with relapsed, nmHSPC were included with a median age at relapse of 73 (range, 46 to 96), pre-ADT PSA of 12.2 ng/mL, and a median pre-ADT PSA doubling time of 7.8 months. 80.9% of the cohort were eligible to receive iADT and 74.4% were treated with iADT. On multivariable analysis, patients originally treated with surgery (odds ratio [OR], 0.19; 95% confidence interval [CI], 0.08-0.46) or having a Gleason Score ≥8 (OR, 0.30; 95% CI, 0.12-0.78) had decreased odds of receipt of iADT. Patients with longer PSA doubling times were more likely to receive iADT (OR, 2.71; 95% CI, 1.17-6.31). CONCLUSIONS: The utilization of iADT was relatively common for men in Manitoba during the study period, however, the uptake of iADT can be improved among identified subgroups.

Bracing for impact with new 4R's in the COVID-19 pandemic - A provincial thoracic radiation oncology consensus.

As COVID-19 pandemic continues to explode, cancer centers worldwide are trying to adapt and are struggling with this constantly changing scenario. Intending to ensure patient safety and deliver quality care, we sought consensus on the preferred thoracic radiation regimen in a Canadian province with 4 new R's of COVID era.

Overview on Emotional Behavioral Testing in Rodent Models of Pediatric Epilepsy.

Psychiatric and cognitive disturbances are the most common comorbidities of epileptic disorders in children. The successful treatment of these comorbidities faces many challenges including their etiologically heterogonous nature. Translational neurobehavioral research in age-tailored and clinically relevant rodent seizure models offers a controlled setting to investigate emotional and cognitive behavioral disturbances, their causative factors, and potentially novel treatment interventions. In this review, we propose a conceptual framework that provides a nonsubjective approach to rodent emotional behavioral testing with a focus on the clinically relevant outcome of behavioral response adaptability. We also describe the battery of neurobehavioral tests that we tailored to seizure models with prominent amygdalo-hippocampal involvement, including testing panels for anxiety-like, exploratory, and hyperactive behaviors (the open-field and light-dark box tests), depressive-like behaviors (the forced swim test), and visuospatial navigation (Morris water maze). The review also discusses the modifications we introduced to active avoidance testing in order to simultaneously test auditory and hippocampal-dependent emotionally relevant learning and memory. When interpreting the significance and clinical relevance of the behavioral responses obtained from a given testing panel, it is important to avoid a holistic disease-based approach as a specific panel may not necessarily mirror a disease entity. The analysis of measurable behavioral responses has to be performed in the context of outcomes obtained from multiple related and complementary neurobehavioral testing panels. Behavioral testing is also complemented by mechanistic electrophysiological and molecular investigations.

Role of thoracic consolidation radiation in extensive stage small cell lung cancer: A systematic review and meta-analysis of randomised controlled trials.

Extensive stage small cell lung cancer (ES-SCLC) carries a poor prognosis, and the thoracic progression is common. Consolidation radiation to thoracic disease (cRT) could improve progression-free survival (PFS) and overall survival (OS). We conducted an electronic search of PubMed and Embase with no language, year or publication status restrictions and evaluated randomised controlled trials (RCTs) addressing the role of cRT in ES-SCLC. Preferred Reporting of Systematic Reviews and Meta-Analyses guidelines for systematic review and Cochrane methodology for meta-analysis were followed. Effect estimates (hazard ratios [HRs] and confidence intervals [CIs]) and risk ratios were extracted, with a fixed/random-effects model created to estimate treatment effects. I2 statistics and heterogeneity statistics were performed. Comprehensive and systematic search identified 1107 records, after removal of duplicate records screened 922 records, assessed 31 full-text articles for eligibility and 3 RCTs with a total of 690 patients were included. Pooled analysis showed cRT significant improved PFS (p < 0.0001) with HR 0.72 (95% CI: 0.61-0.83, I2-0%). In addition, cRT significantly (p < 0.001) reduced the risk of thoracic progression as the first site of progression with a relative risk of 0.52 (95% CI: 0.44-0.61, I2-0%). OS analysis showed no significant (p = 0.36) benefit with HR of 0.88 (95% CI 0.66-1.18, I2-52%) with cRT. Pooled meta-analysis of 3 randomised controlled studies shows consolidation thoracic radiotherapy (RT) offers significant improvement in PFS and reduction in thoracic failures. Further research on subclassification of ES-SCLC (limited vs extensive metastasis), optimise strategy for RT integration (sequential vs concurrent) and optimal RT dose is needed to identify the subset of ES-SCLC likely to have significant OS benefit.

Lestaurtinib (CEP-701) modulates the effects of early life hypoxic seizures on cognitive and emotional behaviors in immature rats.

Hypoxic encephalopathy of the newborn is a major cause of long-term neurological sequelae. We have previously shown that CEP-701 (lestaurtinib), a drug with an established safety profile in children, attenuates short-term hyperexcitability and tropomyosin-related kinase B (TrkB) receptor activation in a well-established rat model of early life hypoxic seizures (HS). Here, we investigated the potential long-term neuroprotective effects of a post-HS transient CEP-701 treatment. Following exposure to global hypoxia, 10 day old male Sprague-Dawley pups received CEP-701 or its vehicle and were sequentially subjected to the light-dark box test (LDT), forced swim test (FST), open field test (OFT), Morris water maze (MWM), and the modified active avoidance (MAAV) test between postnatal days 24 and 44 (P24-44). Spontaneous seizure activity was assessed by epidural cortical electroencephalography (EEG) between P50 and 100. Neuronal density and glial fibrillary acidic protein (GFAP) levels were evaluated on histological sections in the hippocampus, amygdala, and prefrontal cortex at P100. Vehicle-treated hypoxic rats exhibited significantly increased immobility in the FST compared with controls, and post-HS CEP-701 administration reversed this HS-induced depressive-like behavior (p < 0.05). In the MAAV test, CEP-701-treated hypoxic rats were slower at learning both context-cued and tone-signaled shock-avoidance behaviors (p < 0.05). All other behavioral outcomes were comparable, and no recurrent seizures, neuronal loss, or increase in GFAP levels were detected in any of the groups. We showed that early life HS predispose to long-lasting depressive-like behaviors, and that these are prevented by CEP-701, likely via TrkB modulation. Future mechanistically more specific studies will further investigate the potential role of TrkB signaling pathway modulation in achieving neuroprotection against neonatal HS, without causing neurodevelopmental adverse effects.

Role of Stereotactic Body Radiation Therapy in Early Stage Small Cell Lung Cancer in the Era of Lung Cancer Screening: A Systematic Review.

With the obvious benefit from low dose computed tomography to reduce the lung cancer-specific mortality, lung cancer screening is on the rise. With the implementation of the screening programs, diagnosis of early stage lung cancer is expected to increase, and small cell lung cancer (SCLC) would account for 10% of screen-detected lung cancer. Apart from Concurrent chemoradiation (CRT), the present guidelines virtually do not support other options for radiation (RT). There is a paucity of data addressing the role of Stereotactic Body Radiation Therapy (SBRT) in SCLC and we conducted the current systematic review on this topic. We systematically searched literature using the electronic databases PubMed and Embase with no language, year or publication status restrictions. After removal of duplicate records, 3469 screened, 3446 excluded with reasons, 23 full-text articles were assessed for eligibility, and 7 studies (8 reports) were included. Unsuitability for surgery or refusal for surgery was the most common reason for the use of SBRT in early stage SCLC in the included studies. Variable patterns of SBRT-chemotherapy (CT) sequencing including concurrent, pre-CT and post-CT and radiation doses were noted. Within the reported studies overall survival (OS) at 1 year, 2 year and 3 year varied from 63% to 87%, 37% to 72%, and 35% to 72%, respectively. Distant metastasis was the most common pattern of failure ranging from 38% to 53%. There was no increase in the reported grade III toxicity. SBRT could be a potential option in stage I SCLC with comparable outcomes with no added toxicity. Acknowledging the limitations and absence of high-quality data, presently cautious interpretation is warranted and further studies are needed to establish the role of SBRT in SCLC.

Neonatal polycythaemia.

Neonatal polycythaemia has multifactorial causes, and can be designated as active (increased foetal erythropoiesis) or passive (red blood cell transfusion) polycythaemia. Hematocrit estimated from capillary blood (regularly obtained through "heel sticks" in newborns) is normally the principal laboratory feature facility by which polycythaemia is recognszed. An unusually high proportion of haematocrit builds the risk of hyperviscosity, microcirculatory hypoperfusion, and in the long run multisystem organ dysfunction. A report enclosed in this short communication gives a brief review of neonatal polycythaemia, its causes, management and complications.