Usefulness of skills in point of care ultrasound and simulation-based training as essential competencies in acute management of neonatal cardiac tamponade.

Peripherally inserted central catheter (PICC) insertion is a routine procedure in the neonatal intensive care unit required for prolonged intravenous fluid, nutrition and medication support. Neonatal cardiac tamponade is a serious and rare complication of PICC line insertion. Early detection by point of care ultrasound (POCUS) and management by pericardiocentesis improves the chances of survival. Regular simulation-based training sessions on a mannequin, along with knowledge of POCUS, can assist neonatologists and paediatricians for a quick and appropriate response in this emergency condition.

Neonatal nephrotic syndrome: all is not gloomy.

Congenital nephrotic syndrome (CNS) is a rare clinical syndrome with a constellation of proteinuria, hypoalbuminaemia and oedema, presenting within 3 months of birth. We present a rare case of neonatal nephrotic syndrome with a probable sepsis induced aetiology. The neonate was referred at day of life 15 with Klebsiella pneumonia sepsis and anasarca. On investigation, the patient had nephrotic range proteinuria, hypoalbuminaemia, generalised anasarca and ascites. The neonate was started on broad-spectrum antibiotics and furosemide. Genetic and other secondary causes of CNS were ruled out. With supportive management and resolution of sepsis, the neonate improved. This case highlights the rare cause of sepsis-induced nephrotic syndrome (NS), which required only supportive treatment without the need for aggressive management of CNS.

Double BCG vaccination in a neonate: implications, management and prevention.

Tuberculosis is a common cause of morbidity and mortality especially in low-income and middle-income countries like India. BCG vaccination is recommended for all neonates after birth in areas with a high tuberculosis disease burden. Here, we describe a case where a neonate received two doses of the BCG (Chennai strain) vaccine within a span of 4 days after birth due to a vaccination error. Parents were informed about the event. The infant was managed conservatively and followed up till 12 months of life for any possible complication. There were no serious adverse effects apart from the localised reaction and a double scar on the left arm. Measures to avoid any such error in the future and the need for reporting medication error has been highlighted. Parental concerns are frequent in such scenarios and should be actively addressed.

Extracerebral choroid plexus papilloma in a newborn: a rare presentation.

Choroid plexus papillomas (CPPs) are extremely rare lesions that originate in the central nervous system. Still rarely, these can occur in heterotopic locations. We report a case of aneonate who presented at fourth week of life with a small swelling in the left side of the oropharynx. There were no other symptoms. MRI scan revealed a cystic lesion with the possibility of lymphatic malformation or teratoma. Swelling which was gradually increasing in size was electively excised. Histopathological examination revealed it to be an extracerebral CPP. Postoperative period was uneventful, and baby had no further complications. CPP is a rare lesion and, almost always, cannot be anticipated before surgery. Imaging only helps in surgical planning. Complete excision is curative.

Smart e-Skin Cancer Care in Europe During and after the Covid-19 Pandemic: a Multidisciplinary Expert Consensus.

INTRODUCTION: Melanoma is the deadliest of all the skin cancers and its incidence is increasing every year in Europe. Patients with melanoma often present late to the specialist and treatment is delayed for many reasons (delay in patient consultation, misdiagnosis by general practitioners, and/or limited access to dermatologists). Beyond this, there are significant inequalities in skin cancer between population groups within the same country and between countries across Europe. The emergence of the COVID-19 pandemic only aggravated these health deficiencies. OBJECTIVES: The aim was to create an expert opinion about the challenges in skin cancer management in Europe during the post COVID-19 acute pandemic and to identify and discuss the implementation of new technologies (including e-health and artificial intelligence defined as "Smart Skin Cancer Care") to overcome them. METHODS: For this purpose, an ad-hoc questionnaire with items addressing topics of skin cancer care was developed, answered independently and discussed by a multidisciplinary European panel of experts comprising dermatologists, dermato-oncologists, patient advocacy representatives, digital health technology experts, and health technology assessment experts. RESULTS: After all panel of experts discussions, a multidisciplinary expert opinion was created. CONCLUSIONS: As a conclusion, the access to dermatologists is difficult and will be aggravated in the near future. This fact, together with important differences in Skin Cancer Care in Europe, suggest the need of a new approach to skin health, prevention and disease management paradigm (focused on integration of new technologies) to minimize the impact of skin cancer and to ensure optimal quality and equity.

Novel variant CPLANE 1: c.5051C>A (p.Ser1684Ter) in an Indian neonate with Joubert syndrome.

Joubert syndrome (JS) is a rare ciliopathy that presents with the triad of hypotonia, developmental delay and molar tooth sign (MTS) in brain MRI. Next-generation sequencing has identified about 35 genes which are known to cause JS of which CPLANE 1 mutation is found in 8%-10% of cases. We report a case of JS in an Indian neonate who presented with hypotonia, dysmorphic facies, polydactyly, syndactyly and occipital encephalocele. MRI of the brain revealed MTS, and compound heterozygous mutations in CPLANE 1 gene were detected by clinical exome sequencing, one of them a novel variant CPLANE 1: c.5051C>A (p.Ser1684Ter) in exon 26, which was inherited from the parents.

Economic Evaluation of Tirbanibulin for the Treatment of Actinic Keratosis in Scotland.

BACKGROUND: Tirbanibulin 1% ointment is a new treatment for actinic keratosis (AK) on the face or scalp. A health economic model was developed as part of a submission to the Scottish Medicines Consortium to evaluate the cost-effectiveness of tirbanibulin compared to the most frequently prescribed treatments. METHODS: A decision tree approach was used to calculate the costs and benefits of different treatment strategies for AK on the face or scalp over a one-year time horizon. Data on the relative efficacy of treatments, which were based on the probability of complete clearance of AK, were obtained from a network meta-analysis. Sensitivity and scenario analyses were performed to determine the robustness of the model results. RESULTS: Tirbanibulin is estimated to be cost saving versus diclofenac sodium 3%, imiquimod 5% and fluorouracil 5%. Tirbanibulin remains cost saving when inputs are varied in sensitivity and scenario analyses. While the complete clearance rates are deemed similar across comparators, tirbanibulin is associated with a lower rate of severe local skin reactions, and a shorter treatment duration, which may improve treatment adherence. CONCLUSIONS: Tirbanibulin is a cost saving intervention for the treatment of AK from the perspective of the Scottish Healthcare System.

A peek behind the curtain in the diagnosis and management of COVID­19­Associated Mucormycosis (CAM).

Coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) is responsible for a high mortality rate due to its unique and severe host-pathogen interactions. Critically ill or immunocompromised COVID-19 patients are more prone to suffer from aggressive mycoses. Probable victims include those with uncontrolled diabetes mellitus (DM), metabolic acidosis, prolonged neutropenia, increased ferritin levels, hypoxia, and prolonged hospitalization with/without mechanical ventilators and corticosteroids administration. The current review aims to outline the journey of patients with CAM as well as the advantages and disadvantages of the currently available diagnostic techniques. It also discussed the current status of treatment options and caveats in the management of mucormycosis. Multidisciplinary team, early diagnosis, controlling the predisposing condition(s), complete surgical debridement, effective antifungal therapies (e.g., amphotericin B, isavuconazole, and posaconazole), and implementing antifungal stewardship programs are imperative in CAM cases.

Superficial soft tissue sarcomas: 10­year survival outcomes.

Cutaneous sarcomas comprise a broad group of rare, heterogeneous mesenchymal tumours. The present report describes a single centre experience regarding the management and the outcomes of patients with superficial soft tissue sarcomas (SSTS). Key prognostic factors in predicting overall survival (OS) and local relapse-free survival were determined. Data from 66 patients with SSTS treated surgically within Edinburgh and Lothian were collected in the context of a service evaluation. Patient demographics, tumour specifics and treatment, as well as 5-year OS and local recurrence, were analysed. Kaplan-Meier analysis was applied for survival curves, and mortality rate estimation and Cox regression were used to establish independent predictors. The mean estimated OS time was 57.2 months, with a 95% CI between 55.0 and 59.5 months. The median OS time could not be estimated because there is no time point during which the survival function has a value <50%. The death risk for a person with SSTS was increased by 7.3% (odds ratio, 1.073; 95% CI, 1.012-1.138) for every additional year of life. The estimated mean local relapse time was 58.5 months, with a 95% CI between 56 and 61 months. The median local relapse time could not be estimated since there is no time point during which the local recurrence function has a value <50%. In conclusion, out of all independent variables considered, none could statistically significantly explicate local relapse recurrence time. It is important that these rare tumours are treated in the context of a multidisciplinary team with consensus guidelines to assist decision-making.

Visible-light driven excellent photocatalytic degradation of ofloxacin antibiotic using BiFeO3 nanoparticles.

The extensive exploration of multiferroic materials for degradation of contaminants and environmental remediation is promptly strengthened because of their distinct applications. BiFeO3, a prominent class of multiferroics, have received immense attention in recent times. Present study reports the synthesis of a highly crystalline BiFeO3 via facile combustion method. The prepared catalyst was characterized using different techniques like XRD, FTIR, FESEM, EDS, XPS, DRS and PL. From DRS results, the energy band gap of BiFeO3 was computed as 2.1 eV which was suitable enough for its exploration as a visible light photocatalyst. Therefore, BiFeO3 was efficiently utilized for the degradation of ofloxacin drug under the exposure of visible light. The obtained results depicted 80% ofloxacin degradation under optimized conditions (pH 8, 0.5 g/L catalyst dose and 10 mg/L drug concentration) in 180 min. Pseudo first order kinetics was followed with rate constant 0.0097 min-1, as inferred from the kinetic studies. Furthermore, 64% TOC reduction was attained by utilizing the prepared catalyst under optimum conditions. Additionally, the photocatalytic experiments showed excellent degradation efficiency even after five cycles which demonstrated good stability of the fabricated catalyst.

Giant Feeding Artery from Abdominal Aorta in Intralobar Pulmonary Sequestration.

Pulmonary sequestration (PS) is a rare congenital lung malformation. We present a case of newborn with antenatally diagnosed case of PS. The baby was delivered by cesarean section to primigravida mother at 38 + 3 weeks of gestation with birth weight of 2700 g. At 20 weeks of gestation, the antenatal ultrasound showed a triangular echogenic area in left lung supplied by feeding artery from descending aorta. The baby had respiratory distress soon after birth. Computerized tomographic pulmonary angiogram revealed abnormal blood supply of left lower lobe arising from descending aorta. The feeding vessel was abnormally large and was almost half of the diameter of the aorta. The baby underwent left lower lobectomy with double ligation of feeding artery at day 7 of life and was discharged on day 14 of life. Antenatal diagnosis of congenital lung malformation helps in careful planning of perinatal care and facilitates the early diagnosis and management.

Clinicopathological characteristics of individuals with coexisting melanoma and chronic lymphocytic leukaemia: a multicentre cohort study.

BACKGROUND: Individuals with a prior diagnosis of chronic lymphocytic leukaemia (CLL) have a higher risk of developing melanoma and exhibit poorer outcomes than patients without CLL. However, there are limited data reporting the clinicopathological features of melanoma diagnosed in patients with CLL. AIMS: To review clinicopathological characteristics of patients with coexisting diagnoses of melanoma and CLL. METHODS: A retrospective review was undertaken for patients with coexisting diagnoses of melanoma and CLL between 2005 and 2015 in 11 centres in the UK and Ireland. RESULTS: Overall, 46 cutaneous melanomas identified in 45 patients were included. In 28 (62.2%) patients, melanoma was diagnosed after an existing diagnosis of CLL. In this group, mean Breslow thickness was 2.7 mm (range 0.2-25 mm). Ten patients (35.7%) developed locoregional recurrence and 8 (28.6%) developed distant metastases. Melanoma-specific mortality was 5 of 28 (17.9%) and all-cause mortality was 13 of 28 (46.4%). In 17 patients, melanoma was diagnosed before CLL. In this group, mean BT was 2.9 mm (range 0.4-14 mm); five patients (29.4%) developed locoregional recurrence and three (17.6%) developed distant metastases. Melanoma-specific mortality was 1 of 17 (5.8%) and all-cause mortality was 5 of 17 (29.4%) in this group. CONCLUSIONS: To our knowledge, this is the first and largest cohort study to report clinicopathological data of coexisting melanoma and CLL in the UK and Ireland. Although the thickness of primary melanoma was not different before or after a CLL diagnosis, melanoma recurrence and melanoma-specific mortality appear to be more common in patients with a prior diagnosis of CLL.

Experience of Mass Intrahospital Neonatal Transport: Impact on Vitals.

Background Mass transport of neonates is required in cases of disasters and calamities such as fire. It may also be required when there is a need for the upgradation of infrastructure. Neonatal transport even for a short period is a period of stress for the neonate. Mass transport of neonates needs much planning, and even after diligent planning, may result in the destabilization of neonates. Objectives The objectives of this study were to assess the impact of mass intrahospital neonatal transport on the vital parameters of neonates, the occurrence of any adverse event during transport. To study the frequency of adverse events in mass intrahospital neonatal transport and factors related to it. Materials and methods This was a retrospective observational study on a cohort of 16 neonates who were transported to an alternate site in the hospital so that renovation and upscaling of the infrastructure of the newborn intensive care unit (NICU) could be undertaken. Site selection, preparation, and transport details were observed. Vital parameters pre and post-transport were noted, and the occurrence of adverse events during transport was documented and analyzed. Results Sixteen neonates were transported over a span of 90 minutes with a mean travel time of 5.62±3.03 minutes. There was a statistically significant rise in the heart rate of the neonates post transport (137.7±8.51vs 141.3±9.01, p-value .00769) though not clinically significant. Six point two-five percent (6.25%) of neonates deteriorated post transport and needed extra efforts for stabilization. Equipment malfunction was responsible for deterioration. Conclusion Unforeseen events can occur during neonatal transport. Despite adequate planning, preparation, and care during transport, it remains a period of stress for a neonate.

Role of DVET in severe neonatal sepsis in an era of high antibiotic resistance: a retrospective observational study.

AIM: Sepsis is a significant cause of mortality and morbidity in the NICU despite the potent armamentarium of antibiotics. Recently, there has been a considerable increase in antimicrobial resistance even to high-end 3rd line antibiotics. Thus, there is a need to look into adjunctive therapies. This study aims to study the role of double volume exchange transfusion (DVET) in reducing mortality due to severe sepsis. METHODS: All neonates with severe sepsis admitted in NICU from January 2017 to September 2019 were included in the study. Seven neonates who met inclusion criteria and received DVET were compared to 21 gestation and severity matched controls, who received standard therapy (ST) alone. The primary outcome studied was mortality before discharge in both the groups. Other results analyzed were the incidence of persistent thrombocytopenia and refractory shock. RESULTS: There was a significant reduction in mortality in the intervention group (57% vs. 71% (p = .004). There was also a significant reduction both in the incidence of refractory shock (71% vs. 75%; p = .01) and persistent thrombocytopenia (86% vs. 65%; p = .03) in the DVET group. No significant adverse effects occurred following DVET. CONCLUSIONS: In neonates with severe sepsis, DVET may be a useful adjunct therapy. It may reduce mortality and decreased the incidence of refractory shock and thrombocytopenia. DVET is a safe procedure in severely sick and septic neonates.

Treatment-resistant actinic keratoses are characterized by distinct clinical and histological features.

BACKGROUND: Actinic keratoses (AK) are generally treated to reduce the risk of progression into invasive cutaneous squamous cell carcinoma (cSCC). However, this risk of transformation is low, and rather than focusing on these lesions, current treatment studies report on complete clearance of AKs in an entire field. This study aimed to investigate treatment-resistant AKs (trAK) after field therapy compared to randomly chosen AKs prior to treatment. METHODS: AKs were clinically assessed according to the grade of hyperkeratosis and pain on palpation, prior to treatment. TrAKs were biopsied and compared to AKs which were biopsied prior to any treatment. AKs were evaluated regarding histological severity (AKI-III), their basal growth grading (PROI-III), acantholysis, elastosis, follicular extension of atypical keratinocytes and accompanying infiltrate. RESULTS: Two hundred eleven AKs in 171 patients were identified. TrAKs (N.=79) were significantly more painful (64.6% vs. 22.0%; P<0.0001), showing acantholysis (57.0% vs. 33.3%; P=0.0007); and with distinct basal proliferation (PROIII) (64.4% vs. 46.2%; P=0.0099) compared to the control group (N.=132). In a multivariate analysis using logistic regression, pain and PRO III graded lesions were significant independent (P<0.0001 and P=0.0179) predictors for trAKs. Focusing on individual histological features in the trAK group, AKs with grade AKIII, PROIII or follicular extension reaching the sebaceous gland were the most common findings with 51.9%, 64.6%, and 59.5% AKs demonstrating this, respectively. CONCLUSIONS: TrAKs are often painful, showing a distinct basal proliferation (PROIII) and acantholysis. As these features are also seen in invasive cSCCs, trAKs may represent a subgroup of AKs and, for this reason, it requires further evaluations.

Therapeutic Potential of Natural Compounds in Lung Cancer.

Lung cancer is a leading cause of cancer deaths worldwide. The management of lung cancer treatment is often ineffective as a result of the development of drug resistance, reactions to treatment, drug-drug interactions or non-specific targeting of the anticancer drugs. Natural compounds show promise and potential activity in lung cancer with very few side effects. While, the combinatorial action of an anti-cancer drug with a natural compound provides synergistic action which helps boost the overall therapeutic action against cancer cells. In cancer, there is a dysregulation of apoptosis which facilitates the cancer cell to survive, resulting in progression of cancer. Many cancer drugs cause mutations of genes that regulate cancer and should kill the cancer cell but lead to chemoresistance. There are many natural compounds that could specifically target different cell signalling pathways associated with cancer progression to provide a cytotoxic effect in the target cell. The importance of these compounds is emerging in many therapies developed with dual action often including a natural compound. In this review, we present a selection of these natural compounds and how they target lung cancer cells with a focus on the cell signalling pathways. Further work is required to delineate the potential action of natural compounds in the treatment against cancer.

In search of therapeutic candidates for HIV/AIDS: rational approaches, design strategies, structure-activity relationship and mechanistic insights.

The HIV/AIDS pandemic is a serious threat to the health and development of mankind, which has affected about 37.9 million people worldwide. The increasing negative health, economic and social impacts of this disease have led to the search for new therapeutic candidates for the mitigation of AIDS/HIV. However, to date, there is still no treatment that can cure this disease. Furthermore, the clinically available drugs have numerous severe side effects. Hence, the synthesis of novel agents from natural leads is one of the rational approaches to obtain new drugs in modern medicinal chemistry. This review article is an effort to summarize recent developments with regards to the discovery of novel analogs with promising biological potential against HIV/AIDS. Herein, we also aim to discuss prospective directions on the progress of more credible and specific analogues. Besides presenting design strategies, the present communication also highlights the structure-activity relationship together with the structural features of the most promising molecules, their IC50 values, mechanistic insights and some interesting key findings revealed during their biological evaluation. The interactions with the amino acid residues of the enzymes responsible for HIV-1 inhibition are also discussed. This collection will be of great interest for researchers working in this area.

Bubble CPAP splitting: innovative strategy in resource-limited settings.

BACKGROUND: Non-invasive respiratory support for neonates using bubble continuous positive airway pressure (bCPAP) delivery systems is now widespread owing to its safety, cost effectiveness and easy applicability. Many innovative solutions have been suggested to deal with the possible shortage in desperate situations like disasters, pandemics and resource-limited settings. Although splitting of invasive ventilation has been reported previously, no attempts to split non-invasive respiratory support have been reported. OBJECTIVE: The primary objective was to test the feasibility of splitting the bCPAP assembly using a T-piece splitter in a simulation model. METHODS: A pilot simulation-based study was done to split a single bCPAP assembly using a T-piece. Other materials consisted of a heated humidification system, an air oxygen blender, corrugated inspiratory and expiratory tubing, nasal interfaces and two intercostal chest tube drainage bags. Two pressure manometers were used simultaneously to measure delivered pressures at different levels of set bCPAPs at the expiratory limb of nasal interfaces. RESULTS: Pressures measured at the expiratory end of two nasal interfaces were 5.1 and 5.2 cm H2O, respectively, at a flow of 6 L/min and a water level of 5 cm H2O in both chest bags. When tested across different levels of set continuous positive airway pressure (3-8 cmH2O) and fractional inspired oxygen concentration (0.30-1.0), measured parameters corresponded to set parameters. CONCLUSION: bCPAP splitting using a T-piece splitter is a technically simple, feasible and reliable strategy tested in a simulation model. Further testing is needed in a simulated lung model.