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Docosahexaenoic acid (DHA) shows anti-inflammatory/proresolution effects in the brain. Higher red blood cell (RBC) DHA in humans is associated with improved cognitive performance and a lower risk for suicide. Here, we hypothesized that binding to the 18 kDa translocator protein (TSPO), a proxy for microglia levels, will be higher in individuals with low DHA relative to high DHA levels. We also postulated that higher TSPO would predict poor cognitive performance and impaired stress resilience.RBC DHA screening was performed in 320 healthy males. [sup11/supC]PBR28 positron emission tomography was used to measure binding to TSPO in 38 and 32 males in the lowest and highest RBC DHA quartiles. Volumes of distribution expressed relative to total plasma ligand concentration (VsubT/sub) was derived using an arterial input function-based kinetic analysis in 14 brain regions.[sup11/supC]PBR28 VsubT/subwas significantly lower (by 12% and 20% in C/T and C/C rs6971 genotypes) in males with low RBC DHA than in males with high RBC DHA. Regional VsubT/subwas correlated positively and negatively with RBC DHA and serum triglycerides, respectively. No relationships between VsubT/suband cognitive performance or stress resilience measures were present.Contrary to our hypothesis, we found lower TSPO binding in low-DHA than in high-DHA subjects. It is unclear as to whether low TSPO binding reflects differences in microglia levels and/or triglyceride metabolism in this study. Future studies with specific targets are necessary to confirm the effect of DHA on microglia. These results underscore the need to consider lipid parameters as a factor when interpreting TSPO positron emission tomography clinical findings.

There is experimental and clinical data to indicate the contribution of immune-escape mechanisms in relapsed/refractory pediatric leukemia. Studies have shown the accumulation of mutations that translate to peptides containing tumor-specific epitopes (neoantigens). The effectiveness of neoantigen-based vaccines has been shown in several clinical trials in adults. Though the initial results are encouraging, this knowledge must be developed to account for the uniqueness of pediatric cancer biology. We have completed the initial proof-of-concept analysis on a high-risk pediatric leukemia specimen and identified usable neoantigen sequences. We describe this approach, including the bioinformatics method and experimental model to verify their function that can be further broadened for personalized neoantigen prediction and testing for the generation of anticancer vaccines against high-risk pediatric leukemias.

Emerging experimental evidence suggests tau pathology spreads between neuroanatomically connected brain regions in a prion-like manner in Alzheimer's disease (AD). Tau seeding, the ability of prion-like tau to recruit and misfold naïve tau to generate new seeds, is detected early in human AD brains before the development of major tau pathology. Many antitumour drugs have been reported to confer protection against neurodegeneration, supporting the repurposing of approved and experimental or investigational oncology drugs for AD therapy. In this study, we evaluated whether antitumour drugs that abrogate the generation of seed-competent aggregates of tau Repeat 3 (R3) domain peptides can prevent tau seeding and toxicity in Tau-RD P301S FRET Biosensor cells and Caenorhabditis elegans. We demonstrate that drugs that interact with the N-terminal VQIVYK or the C-terminal region housing the Cys322 prevent R3 dimerisation, abolishing the generation of prion-like R3 seeds. Preformed R3 seeds (fibrils) capped with, or R3 seeds formed in the presence of VQIVYK- or Cys322-targeting drugs have a reduced potency to cause aggregation of naïve tau in biosensor cells and protect worms from aggregate toxicity. These findings indicate that VQIVYK- or Cys322-targeting drugs may act as prophylactic agents against tau seeding.

PURPOSE Retinoblastoma is the most frequent intraocular cancer in children. It is also one of the most common causes for enucleation and carries a significant morbidity rate in affected individuals. Hence, studies on its pathophysiological and growth regulatory mechanisms are urgently needed to identify more effective novel therapeutics. METHODS Using the Y79 retinoblastoma cell line, we investigated the electrophysiological and functional activities of the T-type voltage-gated calcium channel Cav3.1, that is constitutively expressed in these cells. We also analyzed the Akt and MAPK signaling pathways downstream of the epidermal growth factor receptor (EGFR) to understand the mechanism responsible for the inhibition of Cav3.1. RESULTS We demonstrate that the EGFR inhibitor Afatinib significantly reduced cell viability and Cav3.1 mRNA expression and electrophysiological activity. At low concentrations (1 µM), Afatinib reduced the amplitude of Cav3.1 current density, whereas at a high concentration (10 µM), it completely abolished the voltage-gated calcium current. Our results show that inhibition of the MAPK pathway by a specific inhibitor VX-11e affected the Cav3.1 current in a dose-dependent manner. VX-11e (50 nM-1 µM) treatment reduced Cav3.1 current densities in Y79 cells, with complete abolishment of Cav3.1 current at higher concentrations (5 µM). We also demonstrate that the specific inhibition of the Akt kinase (using MK-2206) had no effect on the Cav3.1 currents. CONCLUSION Our study provides a functional relationship between the MAPK pathway and EGFR signaling and indicates that the MAPK signaling pathway mediates the control of Cav3.1 by EGFR in retinoblastoma.

Background The primary aim was to investigate outcome of the decision making on duration of injection intervals between injection visits over the first 2 years of a treat and extend regimen. Method Consecutive patients receiving Aflibercept for treatment naive neovascular age-related macular degeneration between 01.01.2016 and 15.07.2017 were identified from our departmental register. Retrospective data collected on all visits over 24 months were classified into three groups: (A) Without Interval Decision Events (IDE)" Injection only" (B) IDE resulting in injection intervals of 5 weeks. The primary outcome was number of successful IDE relative to the total visits in Group C. Successful decision making was defined as absence of worsening of visual acuity (>5 L) or central retinal thickness (>50 microns) at the subsequent visit. Secondary visual and anatomical outcomes at 24 months were also evaluated. Results Data from 56 eyes of 50 patients were included in the study. Visual acuity improved by +7.11 L at 24 months. Forty one patients with unilateral therapy made 721 visits: 280 visits (38.8%) were group A; 164 visits (22.8%) were group B and 277 visits (38.4%) were group C. Average interval in Group C was 8.9 weeks (range 5-15). The success rate of extension was 95.31% (264/277 visits). Conclusion These metrics for evaluating the decision making aspect of disease activity monitoring may be useful for monitoring performance and have given us a more realistic view and expectations of what can be achieved using this regime to optimise the timing of injections.

Background: Most children with recurrent metastatic solid tumors have high mortality rates. Recent studies have shown that proteasome inhibition leads to effective tumor killing in cells that have acquired treatment resistance and metastatic properties. Objective: The purpose of this study was to test the potential of Carfilzomib (CFZ), a proteasome inhibitor, in refractory pediatric solid tumors which is currently unknown. Methods: A panel of pediatric solid tumor cell lines, including neuroblastoma, Ewing’s sarcoma, osteosarcoma, rhabdomyosarcoma and atypical teratoid rhabdoid tumor (ATRT), was used to evaluate the cytotoxic and proteasomal inhibitory effects of CFZ. A drug scheduling experiment was performed to determine the optimal dose and time to obtain effective cell killing. Combination studies of CFZ with chemotherapeutic drugs of different classes were performed to determine the extent of synergy. Results: CFZ showed effective cytotoxicity against all cell lines tested (mean IC50 = 7nM, range = 1-20nM) and activity in a fluorophore-tagged cell-based proteasome assay. Drug scheduling experiments showed that the minimum exposure of 4-8 hours/day is needed for effective cumulative killing. CFZ, when combined with chemotherapeutic drugs of different classes, synergistically enhanced the extent of cell death. Conclusions: CFZ showed cytotoxic activity against all the solid pediatric cancer cell lines tested. This study provides initial in vitro data on the potential of CFZ to treat pediatric solid tumors and supports further investigations into the components of drug scheduling, biological correlates and drug combinations for future early phase clinical trials in children.

Surgical skill of the surgeon can be improved by surgical simulation. Especially in ophthalmology, it is impossible to use real human/non-human primate eyes for ophthalmology surgery practice. However, surgical practice is most important for ophthalmologist. The retina laser surgery is one of the ophthalmology surgeries and it requires more surgical practice for surgeons to use the laser beam precisely to coagulate and fuse small areas of tissue. Dealing with the prospect of vision reduction or vision loss presents a peculiar problem and that can be highly stressful and frustrating for both doctors and patients. In this regard, training for indirect ophthalmoscopy and retinal photocoagulation is undergone using model eyes instead of real eyes. Properties and functioning of an existing model eye are huge and they differ from real human eye such as casings are completely rigid and focusing of retinal fundus is not completely covered. Therefore, this research concentrates to develop a model eye that assimilates close to the human eye by focussing on the maximum viewing area that is not done at the moment. Finally, the design and development of re-engineered model eye for retina laser is fabricated by additive manufacturing. Compared to existing plastic model eye, viewing area and viewing angle of the re-engineered model eye is increased by 16.66% and 6.14%, respectively. Due to design modifications and elimination of the insert, it can be reduced by 18.99% and 13.95% of height and weight of the top casing respectively. Developed re-engineered model eye will improve the surgical and diagnostic skill of the surgeon and increase their confidence and proficiency. It also augments the effective use of essential ophthalmic instruments. Additionally, it can reduce the surgical error and meet the existing demand of actual eyes for surgical practices.

Isolated systolic hypertension is the most common hemodynamic form of hypertension in the elderly. With a rapidly aging population, the prevalence of hypertension, particularly isolated systolic hypertension, is increasing steadily. Isolated systolic hypertension is associated with substantial mortality and morbidity, particularly of cerebrovascular disease. It is a rapidly growing public health concern and its management continues to remain a challenge to practicing physicians. Recent studies like the Systolic Blood Pressure Intervention Trial (SPRINT) and Heart Outcomes Prevention Evaluation (HOPE)-3 have implications for antihypertensive therapy in general and for the management of isolated systolic hypertension in particular. Keywords: Hypertension, Cardiovascular disease, Isolated Systolic Hypertension, Essential hypertension

Both PLMA and SLIPA were easy to insert (100% success) and ventilate with maximum sealing pressure of 30cm H2o (P = 0.4) with no muscle relaxant. No significant difference (P = 0.265) in intubation time between PLMA and ETT were observed in the study. A significant SpO2 change (P = 0.804, 0.561, 0.657, 0.248, 0.561) measured Pre op, Pre intubation, lmt, 3 mt and 5mts after intubation and there were no significant EtCO2 changes (P =0.861, 0.251, 0.44) measured after intubation was observed. Blood staining in 1/25 cases with PLMA and 2/25 cases with ETT with a P value of 0.561was seen.

Complete debridement and disinfection of the root canal system are the primary requirement for successful endodontic treatment. Enterococcus faecalis is the most commonly found organism in a high percentage of root canal failures as a single organism or as a major component of the flora. Primary goal of this study is to assess the antibacterial effect of phytochemical agents namely embelin, vilangin and phenyl vilangin, respectively, against E. faecalis. And this is the first time that these materials are reported for antibacterial activity against the pathogen, E. faecalis. Our second goal is to predict the interaction between the active structure and the protein in the binding mode, and the third goal is to screen for cytotoxicity by brine shrimp lethality bioassay. All the compounds showed low to elevated level of antibacterial activity. Particularly, compound embelin, as well as its combination with NaOCl in the ratio 1:1, exhibits zone of inhibition value of 29 ± 0.89 and 32 ± 0.98 mm at a concentration of 80 µL and the MIC value of embelin was found to be 78.10 µg/mL. All the compounds exhibit low toxicity to high toxicity. The LC50 value of tested compounds was in the range of 17.5–80.0 µL with respect to positive control (vincristine sulphate). The result of lethality reveals the phenyl vilangin exhibits very minimal toxicity even under higher concentration, and in future, it may be investigated further for biocompatibility studies. The results of molecular docking reveal that embelin showed good interaction against 2JER protein with a higher binding energy value of − 7.2. Hence, these finding reveals that embelin and phenyl vilangin may be used as root canal irrigants in future.

Background: Breast milk reduces morbidity and mortality in infants admitted to neonatal intensive care unit (NICU). Objectives: We determined predictors of procuring mother's own milk (MOM) among N...

AIM To identify the baseline demographic and clinical characteristics associated with diabetes-related distress (DRD) and factors associated with improvement in DRD after initiating use of the FreeStyle Libre (FSL) in people living with type 1 diabetes (T1D). METHODS The study was performed using baseline and follow-up data from the Association of British Clinical Diabetologists nationwide audit of people with diabetes who initiated use of the FSL in the United Kingdom. DRD was assessed using the two-item diabetes-related distress scale (DDS; defined as the average of the two-item score ≥3). People living with T1D were categorized into two groups: those with high DRD, defined as an average DDS score ≥3 and those with lower DRD, defined as a DDS score

We describe the rationale, aims and objectives and the methodology of data collection for the ABCD nationwide audit of individuals admitted to hospital with coronavirus (SARS-CoV-2; COVID-19) and diabetes. The audit was inspired and undertaken by the urgent need to understand the clinical course of COVID-19 in patients with diabetes admitted to hospital in the UK during the pandemic. We wished to understand the clinical behaviour of diabetes per se, post hospital admission and the factors with may be associated with admission to the Intensive Care Unit (ICU) and death due to COVID-19. This was a clinically-led audit. We used existing infrastructure and expertise to collect data using an electronic tool specifically designed and piloted by the steering group members. The clinical variables were chosen to fulfil the main aim of this audit as stated above, and factors influencing the clinical course of COVID-19 in individuals with both type 1 and type 2 diabetes at the time of admission to hospital and during the whole length of stay, until discharge or death from COVID-19. The data collected so far represent a large, multicentre audit with more than 3,500 admissions during the pandemic. We plan to continue collecting additional data and publish ongoing reports of interest to diabetes clinicians with the aim of enhancing knowledge and understanding and thereby improving clinical care of, and outcomes for, people with diabetes who are admitted to hospital with COVID-19 in the UK.

Background/Objective Newborn infant skin is functional but immature, and diapering products can play a significant role in infant diapered skin health. Previous work demonstrated a regimen consisting of a diaper with an emollient and apertures on the inner liner (topsheet) with an acidic, pH‐buffered wipe (Regimen A) lowered newborn skin pH and reduced the enzymatic activity on skin post‐stool cleaning versus a regimen without these features (Regimen B). This study extends these findings to determine the impact of Regimen A on diaper area erythema severity over a 2‐week use period. Methods This IRB‐approved, blinded, randomized, crossover study enrolled newborn infants >7 days and ≤8 weeks. Participants exclusively used two unique diaper and wipe combinations, Regimen A and Regimen B (non‐emollient, non‐aperture containing topsheet and wipe with limited buffering capacity), each for 14 days and preceded by a 3‐day washout regimen. Results Diapered skin pH was reduced during Regimen A use to values similar to that of a non‐diapered control site (chest), while use of Regimen B was associated with a more alkaline skin pH. Regimen A resulted in significantly fewer severe erythema episodes. At the site of highest erythema, the perianal space, the average erythema score was significantly lower and more newborns were free of erythema while using Regimen A vs. Regimen B (P

No in vivo human studies have examined the prevalence of Alzheimer’s disease (AD) neuropathology in individuals with alcohol-use disorder (AUD), although recent research suggests that a relationship between the two exists. Therefore, this study used Pittsburgh Compound-B ([11C]PiB) PET imaging to test the hypothesis that AUD is associated with greater brain amyloid (Aβ) burden in middle-aged adults compared to healthy controls. Twenty healthy participants (14M and 6F) and 19 individuals with AUD (15M and 4F), all aged 40–65 years, underwent clinical assessment, MRI, neurocognitive testing, and positron emission tomography (PET) imaging. Global [11C]PiB standard uptake value ratios (SUVRs), cortical thickness, gray matter volumes (GMVs), and neurocognitive function in subjects with AUD were compared to healthy controls. These measures were selected because they are considered markers of risk for future AD and other types of neurocognitive dysfunction. The results of this study showed no significant differences in % global Aβ positivity or subthreshold Aβ loads between AUD and controls. However, relative to controls, we observed a significant 6.1% lower cortical thickness in both AD-signature regions and in regions not typically associated with AD, lower GMV in the hippocampus, and lower performance on tests of attention as well as immediate and delayed memory in individuals with AUD. This suggest that Aβ accumulation is not greater in middle-aged individuals with AUD. However, other markers of neurodegeneration, such as impaired memory, cortical thinning, and reduced hippocampal GMV, are present. Further studies are needed to elucidate the patterns and temporal staging of AUD-related pathophysiology and cognitive impairment. Imaging β-amyloid in middle age alcoholics as a mechanism that increases their risk for Alzheimer’s disease; Registration Number: NCT03746366.

BACKGROUND Sepsis is a potentially life threatening medical emergency. It should be diagnosed at the earliest and treated effectively to prevent mortality. Therefore, there is a need for parameters which are simple, reliable and cost effective which help in predicting the prognosis and help in managing the patient with sepsis more efficaciously. METHODS A total of seventy patients, 42 male and 28 female patients, over a period of one year, who fulfilled the inclusion and exclusion criteria was included in the study. In this study various clinical variables and biochemical markers including serum lactate dehydrogenase (LDH) were compared among survivor and non–survivor groups and analysed. RESULTS In this study out of 70 patients, 36 patients [51.4 %] expired. Various clinical variables and biochemical markers including serum LDH [on day 1 & day 3], were compared among survivor and non–survivor groups and analysed. Pulse rate, mean arterial pressure (MAP), total leucocyte count, renal function test (RFT), liver function test (LFT), day 3 LDH levels and requirement of ventilator support showed statistically significant difference among the survivor and non-survivor groups. CONCLUSIONS Despite the recent medical advances, sepsis is a multiorgan disease with significant mortality. Hence, we need simple and effective parameters which are essential in assessing the prognosis and in guiding the treatment protocols. This study focused on simple clinical and biochemical parameters with special reference to LDH, which helped us in predicting the mortality. KEYWORDS Markers, Serum LDH, Sepsis, Survival

Purpose: To describe the magnitude and spectrum of abnormal ocular findings other than retinopathy of prematurity (ROP) detected during an ROP telescreening programme. Methods: Retrospective review of the records of all premature babies screened for ROP from August 2015 to December 2019. Results: A total 9105 babies were screened during the study period with total 17,075 imaging sessions. Non-ROP ocular abnormalities were seen in 566 eyes of 383 babies (4.2%) including 207 male (54%) and 176 female babies (46%). Posterior segment abnormalities were seen in 88.2% babies (338/383) with haemorrhage being the most common (77%, 295/383). Anterior segment pathologies were seen in 12% babies (46/383) with congenital cataract being the most common pathology requiring surgical intervention. Other findings included globe abnormalities in 0.8% babies (3/383), adnexal disorders in 0.5% babies (2/383) and squint in 0.3% babies (1/383). Rare life-threatening conditions such as retinoblastoma and lipaemia retinalis were also detected. Eighty-seven babies (22.7%) were diagnosed with referral-warranted non-ROP pathologies, with an overall prevalence of 1% (87/9105). Prompt surgical intervention was advised for 7.3% babies (28/383), 3.4% babies (13/383) were treated medically and 4.2% babies (16/383) needed visual rehabilitation for non-amenable pathologies. Conclusion: This is the largest study describing the magnitude and spectrum of neonatal ocular pathologies other than ROP in a cohort of premature babies. Digital imaging has a significant impact on early detection and timely intervention for various vision as well as life-threatening non-ROP pathologies, which would have been missed or delayed otherwise.

BACKGROUND Cluster headache is an unusual but particularly painful and crippling primary headache disorder with a prevalence of 1 in 1000 making study of the disease process a difficult task to master. These headaches are always unilateral characterised by recurrent short-lasting attacks of 15 - 180 minutes associated with ipsilateral autonomic signs. The diagnosis is mainly clinical, and it continues to be managed sub optimally as the chance of coming across such a condition is few and far between. This study was conducted to determine the incidence of cluster headache in a hospital population and study its association with age, gender and triggers. METHODS This is a cross sectional study of a total of 100 patients attending our Otorhinolaryngology department from June 2017 to June 2018 at Sri Muthukumaran Medical College Hospital & Research Centre with primary complaints of headache. Prior ethical committee clearance was obtained. Patients with chronic debilitating illness, chronic rhino sinusitis, headache following trauma or the presence of fever or any other acute illness were excluded from this study. The results were interpreted using Statistical Package for Social Sciences (SPSS) version 17. RESULTS Out of the total number of 100 patients with headache, only one patient, a 40-yearold male was diagnosed with cluster headache. CONCLUSIONS Hence, we conclude that the incidence of cluster headache in the total of 100 patients is only 1 % which makes it a quite rare condition. Diagnosis is clinical, hence effective history taking is mandatory. KEY WORDS Cluster Headache, Primary Headache, Trigeminal Autonomic Cephalgia, Cluster Attacks

Study objective To evaluate a surveillance protocol in managing the risk of hepatitis B virus (HBV) reactivation among lymphoma patients with resolved HBV infection receiving rituximab. Design Prospective, single-arm study. Setting National Cancer Centre, Singapore. Patients Lymphoma patients with resolved HBV infection and scheduled to receive rituximab-based treatment. Intervention Close monitoring of HBV DNA levels, ie. every 4-6 weeks during rituximab treatment, every 6-8 weeks in the first year post-treatment, and every 3-4 months in the second year post-treatment. Measurements The efficacy of the surveillance protocol was examined by evaluating the rates of reactivation-related events. Feasibility was evaluated based on patient adherence. An economic analysis using a cost-minimization approach was conducted to compare the costs between the surveillance protocol and universal prophylaxis with entecavir 0.5 mg daily up to 1 year after cessation of rituximab. Main results A total of 66 patients provided analyzable data with a follow-up period of 966.6 months. No hepatitis flare or reactivation-related events were detected. The median adherence rate to the surveillance protocol was 90.5%. Cost savings of US$946.40 per patient over the entire surveillance period were achieved if the surveillance protocol was adopted and was most affected by changes in prophylaxis duration and the cost of antiviral prophylaxis. Conclusions The surveillance protocol is an effective, feasible and cost-saving strategy to manage HBV reactivation among lymphoma patients with resolved HBV infection receiving rituximab.

The objective was to ascertain factors among deliveries complicated by shoulder dystocia (SD) and neonatal brachial plexus palsy (NBPP).At 11 hospitals, deliveries complicated by SD were identified. The inclusion criteria were vaginal delivery of non-anomalous, singleton at 34-42 weeks. Adjusted odds ratios (aOR) with 95% confidence intervals (CI) were calculated. Receiver operating characteristic (ROC) curves were created to evaluate the predictive value of the models for NBPP.Of the 62,939 individuals who delivered vaginally, 1,134 (1.8%) had SD and met other inclusion criteria. Among the analytic cohort, 74 (6.5%) had NBPP. The factor known before delivery which was associated with NBPP was diabetes (aOR = 3.87; 95% CI = 2.13-7.01). After delivery, the three factors associated with NBPP were: (1) birthweight of at least 4000 g (aOR = 1.83; 95% CI = 1.05-3.20); (2) calling for help during the SD (aOR = 4.09, 95% CI = 2.29-7.30), and (3) the duration of SD ≥120 sec (aOR = 2.47, 95% CI = 1.30-4.69). The AUC under the ROC curve for these independent factors was 0.79 (95% CI = 0.77 - 0.82).Few factors were identified that were associated with NBPP after SD, but they could not reliably predict which neonates will experience the complication.

Objective While it is generally considered that patients with diabetes mellitus (DM) have more distal peripheral arterial disease (PAD), there is little information on how individual vessels are affected. The aim of this study was to adapt Bollinger's scoring system for lower limb angiograms (DSAs) to include the distal and planter vessels. The reliability of this extension was tested and was used to compare the distribution of disease in two cohorts of patients with and without DM. Methods Patients who had undergone DSA ± angioplasty for PAD at a single centre between September 2010 and April 2014 were identified. Twenty-five patients' images were reviewed by four clinicians and scored using an extended version of the Bollinger score. A total of 153 patients with DM were matched, for age, sex, ethnicity, smoking, and hypertension, with 153 patients without DM. The infrainguinal vessels were divided into 16 arterial segments, including plantar vessels, and scored using the Bollinger score. The score ranges from 0 to 15. Fifteen represents an arterial segment with more than 50% of its length occluded. Interobserver reliability was tested using interclass correlation (ICC) and Cohen's kappa coefficient. Results The ICC demonstrated good agreement between observers (0.76 [0.72–0.79]) with good internal consistency (Cronbach's alpha 0.93). When the Bollinger scores were categorised, the results were weaker, Cohen's kappa ranged from 0.39 (standard error 0.033) to 0.54 (0.030). Patients with DM had a higher burden of disease in the anterior tibial and posterior tibial arteries with relative sparing of the peroneal artery and no difference in the plantar vessels. Conclusion It has been demonstrated that the Bollinger score can be extended to include the distal vessels. This amended scoring system can be used to compare the burden of distal disease in patients with PAD. How the score relates to clinical presentation and outcomes needs further investigation.

A previously healthy 27-year-old gravida 1, para 0 woman is admitted with preterm labor and loss of fluids at 28 weeks’ gestation. She receives antenatal steroids and obstetric ultrasonography shows bilateral cerebral ventriculomegaly and an absent stomach bubble. Before admission, her pregnancy had been uneventful and findings on early anomaly screening ultrasonography at 19 weeks’ gestation are normal. Serologic tests for maternal group B Streptococcus , cytomegalovirus, toxoplasma, and Treponema all have negative findings. The fetal tracing becomes non-reassuring and the neonate is born via emergency cesarean delivery. The neonate has apnea, hypotonia, and bradycardia at birth and does not respond to face mask ventilation. He undergoes intubation by 5 minutes after birth, with improvement in his heart rate, but he remains limp without any spontaneous breathing. His Apgar scores are 1, 2, and 3 at 1, 5, and 10 minutes after birth, respectively. Arterial and venous cord blood gases are 7.29 pH and 7.36 pH. Initial examination shows a preterm infant with appropriate weight, length, and head circumference for age, decorticate posturing, hypotonia of the lower extremities, …

Introduction Traumatic bronchial injury (TBI) is uncommon, difficult to diagnose and often missed. The incidence of TBI among blunt trauma patients is estimated to be around 0.5–2%. Bronchoplastic surgery is indicated in most cases to repair the tracheobronchial airway and preserve lung capacity. There is limited existing literature addressing the management of this condition in view of its rarity. The comprehensive management and outcomes of these patients are discussed. Methods The case notes of all patients who presented with persistent lung collapse due to trauma since July 2017 were reviewed retrospectively. Those patients requiring surgical intervention were included in the review. The mode of injury, clinical, radiological and bronchoscopy findings, concurrent injuries, type of surgery, length of stay (LOS) and operative outcomes were reviewed. Results Out of 11 patients who presented with persistent lung collapse post-blunt trauma, four (36%) were found to have structural bronchial disruption. All of them underwent successful repair of the injured bronchus, without the need of a pneumonectomy. The other seven patients were successfully treated conservatively. Conclusion The repair of the injured bronchus is essential in improving respiratory function and to prevent a pneumonectomy. Routine bronchoscopic evaluation should be performed for all suspected airway injuries as recommended in our management algorithm. Delayed presentations should not hinder urgent referral to thoracic centers for tracheobronchial reconstruction.

Introduction: Skin interventions have been implemented to reduce neonatal mortality, demonstrating the skin’s role in neonatal innate immunity. We examined the impact of birthweight and environmental conditions on skin integrity in infants receiving oil massage in rural Nepal. Methods: In a community-based cluster randomized controlled trial, 991 premature and full-term infants were grouped by birthweight as: (1) 920–1,560 g, (2) 1,570–2,450 g, (3) 2,460–2,990 g, and (4) 3,000–4,050 g and by high or low heat index (HI). Skin integrity was measured as erythema, rash, dryness, pH, protein concentration, and transepidermal water loss (TEWL). Results: Skin pH was higher for the smallest (group 1) than the largest infants (group 4) and higher for group 2 than 3 and 4. Arm and leg rash differed for all 4 groups, with the least amount of rash for the smallest babies. Erythema was lower for group 1 than all others. The lower day 1 values for pH, TEWL and protein at high versus low HI remained lower over 28 days. The pH reduction was faster at high HI. Erythema (arm, leg) was more severe at high HI. Rash severity was greater at high HI for arms and legs every day. Conclusions: Birthweight influenced the skin response to oil massage. The smallest infants had the lowermost skin irritation, suggesting diminished ability to mount an inflammatory response. High HI may be protective for premature infants in low resource settings.

Neurotrophic tyrosine receptor kinase gene fusions (NTRK) are oncogenic drivers present at a low frequency in most tumour types (80%) in a small number of rare tumours (e.g., infantile fibrosarcoma [IFS]) and considered mutually exclusive with other common oncogenic drivers. Health Canada recently approved two tyrosine receptor kinase (TRK) inhibitors, larotrectinib (for adults and children) and entrectinib (for adults), for the treatment of solid tumours harbouring NTRK gene fusions. In Phase I/II trials, these TRK inhibitors have demonstrated promising overall response rates and tolerability in patients with TRK fusion cancer who have exhausted other treatment options. In these studies, children appear to have similar responses and tolerability to adults. In this report, we provide a Canadian consensus on when and how to test for NTRK gene fusions and when to consider treatment with a TRK inhibitor for pediatric patients with solid tumours. We focus on three pediatric tumour types: non-rhabdomyosarcoma soft tissue sarcoma/unspecified spindle cell tumours including IFS, differentiated thyroid carcinoma, and glioma. We also propose a tumour-agnostic consensus based on the probability of the tumour harbouring an NTRK gene fusion. For children with locally advanced or metastatic TRK fusion cancer who have either failed upfront therapy or lack satisfactory treatment options, TRK inhibitor therapy should be considered.

We report the two cases who presented with sudden decreased vision and sub-internal limiting membrane (ILM) hemorrhage without a history of Valsalva maneuver, trauma, or hematological disorders. Multimodal imaging revealed the features suggestive of polypoidal choroidal vasculopathy (PCV) in addition to the sub-ILM hemorrhage. A provisional diagnosis of sub-ILM hemorrhage secondary to PCV was made and was treated with intravitreal Bevacizumab injection. Treatment resulted in the improved visual acuity along with the resolution of the sub-ILM hemorrhage. These cases highlight the possibility of isolated sub-ILM hemorrhage as a presenting fundus finding in PCV, which is previously unreported. This report also highlights the importance of multimodal imaging in diagnosing chorioretinal disorders with unusual presentation.

PURPOSE To report a case of idiopathic full-thickness macular hole in a young boy, which was managed surgically with good visual and anatomical outcomes. METHOD Single case report. RESULTS An 8-year-old boy presented for defective vision in the left eye noticed for the past 2 weeks with best-corrected visual acuity of 6/24. A large full-thickness macular hole was diagnosed clinically and was confirmed on optical coherence tomography. There was no clinical or tomographic findings suggestive of trauma or retinal degeneration. After observation for 8 weeks, the patient underwent macular hole surgery in the left eye including internal limiting membrane peeling and C3F8 gas tamponade. Intraoperatively abnormally tight vitreoretinal adherence was noted during the induction of posterior vitreous detachment. Optical coherence tomography at 1 month after surgery showed decrease in the size of macular hole suggestive of incomplete closure. Repeat optical coherence tomography at 3 months showed closed macular hole with mild foveal thinning and ellipsoid zone discontinuity with best-corrected visual acuity improving to 6/18. The tomographic features and best-corrected visual acuity remained stable at 6-month follow-up. CONCLUSION We hereby report the first case, to the best of our knowledge, of a truly idiopathic full-thickness macular hole in an 8-year-old boy. Surgical treatment offers the best outcomes in these cases and should be considered at the earliest without waiting for spontaneous closure unlike in the case of traumatic full-thickness macular hole.