A chylothorax in a young woman: The difficulties of medical management.

Lymphangioleiomyomatosis is a rare pulmonary disease affecting women of childbearing age. Whilst chylothorax is a well-recognized complication of the condition, management strategies aren't well-defined, have low success rates and are often only available at tertiary or specialist centres. We describe a case of a young woman referred to pleural clinic with a chylous effusion found to be secondary to lymphangioleiomyomatosis. Initial medical management was unsuccessful and recurrent drainages caused significant complications. Remission was ultimately achieved with a combination of mTOR inhibitors and interventional radiology techniques.

Twists and turns: A case report of cecal volvulus.

We present a case of a 22-year-old male presenting in the emergency room with colicky abdominal pain, vomiting, and abdominal distension for which an early computed tomography scan was done and diagnosed as cecal volvulus. Following diagnosis case was managed promptly by laparotomy with right hemicolectomy and primary anastomosis.

Landscape of cancer biomarker testing in England following genomic services reconfiguration: insights from a nationwide pathologist survey.

AIMS: Cancer diagnostics have been evolving rapidly. In England, the new National Health Service Genomic Medicine Service (GMS) provides centralised access to genomic testing via seven regional Genomic Laboratory Hubs. The PATHways survey aimed to capture pathologists' experience with current diagnostic pathways and opportunities for optimisation to ensure equitable and timely access to biomarker testing. METHODS: A nationwide survey was conducted with consultant pathologists from regional laboratories, via direct interviews based on a structured questionnaire. Descriptive analysis of responses was undertaken using quantitative and qualitative methods. RESULTS: Fifteen regional centres completed the survey covering a median population size of 2.5 (1.9-3.6) million (each for n=12). The median estimated turnaround time (calendar days) for standard molecular markers in melanoma, breast and lung cancers ranged from 2 to 3 days by immunohistochemistry (excluding NTRKfus in breast and lung cancers, and PD-L1 in melanoma) and 6-15 days by real-time-PCR (excluding KIT for melanoma), to 17.5-24.5 days by next-generation sequencing (excluding PIK3CA for breast cancer). Tests were mainly initiated by pathologists and oncologists. All respondents discussed the results at multidisciplinary team (MDT) meetings. The GMS roll-out was perceived to have high impact on services by 53% of respondents, citing logistical and technical issues. Enhanced education on new pathways, tissue requirements, report interpretation, providing patient information and best practice sharing was suggested for pathologists and other MDT members. CONCLUSION: Our survey highlighted the role of regional pathology within the evolving diagnostic landscape in England. Notable recommendations included improved communication and education, active stakeholder engagement, and tackling informatics barriers.

Health literacy correlates with abbreviated full-scale IQ in adolescent and young adults with sickle cell disease.

INTRODUCTION: Sickle cell disease (SCD) is a chronic condition with progressive neurocognitive deficits. Health literacy (HL) is essential during adolescence and young adulthood, as the transition to adult care requires healthcare decisions. HL is known to be low in SCD; however, relation between general cognitive ability and HL has not been investigated. METHODS: This cross-sectional study included adolescent and yound adults (AYAs) with SCD from two institutions. Logistic regression measured the association between HL, measured by the Newest Vital Sign tool, and general cognitive ability, measured with abbreviated full-scale intelligence quotient (FSIQ) on the Wechsler Abbreviated Scale of Intelligence. RESULTS: Our cohort contained 93 participants at two sites: 47 (51%) at Memphis, TN and 46 (49%) at St. Louis, MO, ranging from ages 15-45 years (mean = 21 years) and with a majority (70%) possessing a high school education or greater. Only 40/93 participants (43%) had adequate HL. Lower abbreviated FSIQ (p < .0001) and younger age at assessment (p = .0003) were associated with inadequate HL. For every standard score point increase in abbreviated FSIQ, the odds of having adequate HL compared to limited or possibly limited HL increase by 1.142 (95% confidence interval [CI]: 1.019-1.322) and 1.116 (95% CI: 1.045-1.209), respectively, after adjusting for age, institution, income, and educational attainment. CONCLUSIONS: Understanding and addressing HL is imperative in improving self-management and health outcomes. Among AYA with SCD, low HL was prevalent and influenced by abbreviated FSIQ. Routine screening for neurocognitive deficits and HL should be performed to guide development of interventions to adapt to the HL of AYA with SCD.

Synthesizing biochar-based slow-releasing fertilizers using vermicompost leachate, cow dung, and plant weed biomass.

Biochar-based slow-releasing fertilizers (BSRF) have been recommended widely for efficient soil nutrient management and crop production. In this study, we examined the N, P, and K release behaviour of pyrolysed (at 350 °C) cow dung (CDB), vermicompost (VCB), and Lantana (LB) weed and impregnated LB (LBVW) and CDB (CDBVW) with vermicompost leachate (1:1 v/v) under a lab-scale trial. BSRFs (CDB, VCB, LBVW and VCBVW) characterization (FT-IR, SEM-EDX and surface area analysis) was done and then tested for its suitability for soil-plant applications. Soil incubation study indicated the slow-releasing behaviour of BSRFs and overall P, N, and K release was found to be in the ranges of 72.3-84.5%, 73.1-79.0%, and 43.1-85.3%, respectively in different BSRFs setups. Furthermore, lab trials suggested the highest P (64.5%), N (75.3%), and K (86.8%) uptakes by the plant (Vigna radiata) in CDBVW and LBVW setups. Moreover, pot trails with moong bean (Vigna radiata) suggested a high growth in shoot and root and plant yield as well in seedlings cultivated with BSRFs. This study indicates that animal manure, vermicompost and terrestrial weed Lantana biochar can be used effectively to prepare BSRFs for efficient soil-plant nutrient management with multiple environmental benefits.

Gene Therapy and Hemophilia: Where Do We Go from Here?

Gene therapy for hemophilia using adeno-associated virus (AAV) derived vectors can reduce or eliminate patients' disease-related complications and improve their quality of life. Broad implementation globally will lead to societal gains and foster health equity. Several vector products each for factor IX (FIX) or factor VIII (FVIII) deficiency are in advanced clinical development. Safety data are reassuring. Efficacy data for up to 8 and 5 years, respectively, vary considerably among vector types and among individuals, but indicate significant reduction in bleeds and factor use. Products will soon be approved for marketing. This review highlights the relevant considerations for implementation of hemophilia gene therapy, specifically across a broad range of socioeconomic backgrounds globally, based on recent publications and our own experience. We address the current efficacy and safety data and relevant aspects of vector immunology. We then discuss pertinent implementation steps including pre-implementation and readiness assessments, considerations on cost, cost-effectiveness and payment models, approaches to education and informed consent, and the operational needs as well as the need for monitoring of health outcomes and implementation outcomes. To prevent a lag or complete lack of establishing access to this life-changing therapy option for all patients with hemophilia worldwide, adaptable pathways supported by collaborative and international efforts of all stakeholders are needed.

Lymphocyte predominance in blood, pleural fluid, and tumour stroma; a prognostic marker in pleural mesothelioma.

BACKGROUND: As promising novel treatments develop for malignant pleural mesothelioma (MPM), early prognostication has become increasingly important. Circulating and local inflammatory cells are known to play a significant role in other tumour types. We assessed the proportion of lymphocyte populations within blood, pleural fluid and tumour stroma to prognosticate patients with MPM at diagnosis. METHODS: Consecutive patients diagnosed with biopsy-proven MPM were prospectively recruited to an observational cohort study and followed up for a minimum of 7.5 years. Blood and pleural fluid results at presentation were extracted from the medical records. Biopsy specimens were independently reviewed by 2 pathologists who scored the degree of lymphocytic and neutrophilic infiltration. RESULTS: Baseline results were available for 184 patients. The predominant pleural fluid cell type was calculable for 84 patients and 118 patients had biopsy specimens available for review. A low blood neutrophil/lymphocyte ratio (NLR < 4) inferred a better prognosis with a median survival of 420 days versus 301 days (p < 0.01). Survival was better for patients with a lymphocyte-predominant pleural effusion (430 vs 306 days, p < 0.01). Lymphocyte infiltration of tumour stroma was also associated with improved survival (n = 92, survival 430 days) compared with neutrophilic or acellular samples (n = 26, survival 342 days p < 0.01). In multivariable modelling lymphocyte predominance in blood, pleural fluid and tumour stroma were all associated with a better prognosis. CONCLUSIONS: Lymphocyte predominance within tumour stroma, pleural fluid or blood infers a better prognosis in patients with MPM.

Suitability of endobronchial ultrasound-guided transbronchial needle aspiration samples for programmed death ligand-1 testing in non-small cell lung cancer, the Bristol experience.

Treatment for non-small cell lung cancer (NSCLC) is now personalised using molecular mutation testing. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) biopsy suitability for anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) mutation testing is established. Less is currently known about EBUS-TBNA suitability for PD-L1 (programmed death ligand-1) testing. To assess EBUS-TBNA biopsy adequacy for ALK, EGFR and PD-L1 testing, we conducted a prospective study of 279 consecutive NSCLC patients referred to a tertiary EBUS-TBNA centre in South West England. One hundred eight-four (62.6%) patients were found to have adenocarcinoma, 83 (28.2%) had squamous cell carcinoma, and 27 (9.2%) were identified as NSCLC-not otherwise specified. EGFR testing was successful in 166 of 168 patients (98.8%), ALK testing in all 115 and PD-L1 testing in 43 of 49 patients (88.2%). Previous EGFR and ALK testing did not affect biopsy PD-L1 testing success. PD-L1 testing failures occurred in three of five (60.0%) of 22G needle biopsies, one of five (20.0%) of 21G needle biopsies and two of 39 (5.1%) of 19G needle biopsies, P = .016. EBUS-TBNA biopsies are mostly suitable for PD-L1 testing. Larger needle size may improve PD-L1 (but not EGFR and ALK) testing success but requires further study in a controlled trial.

Understanding factors associated with continuation of intrauterine device use in Gujarat and Rajasthan, India: a cross-sectional household study.

The Government of India has promoted the expansion of access to and uptake of intrauterine devices (IUDs), during both the interval (IIUD) and postpartum (PPIUD) periods, as part of its Family Planning 2020 initiative. This study, conducted by EngenderHealth as part of the Expanding Access to IUD Services in India project, examines IIUD and PPIUD continuation rates over time and investigates factors associated with IUD continuation. We recruited respondents (N = 5024) through a repeated cross-sectional household study between February and December 2019. We identified respondents using IUD client data from public health facility registers in 20 districts of Gujarat and Rajasthan. We compared continuation rates for IIUD and PPIUD adopters and used regression analyses to measure the association between continuation and demographic, quality of care, and counselling variables. IIUD continuation rates decreased from 85.6% to 78.3% and PPIUD rates decreased from 78.5% to 70.7% between month 3 and month 12. Clients experiencing side effects or other problems were 15 times more likely to discontinue IUD use than clients who did not. Clients who received IUD counselling prior to insertion were more likely to continue than those who did not. IUD continuation increased significantly in cases where both partners jointly selected the method compared to situations where women decided alone. Several sociodemographic factors were associated with continuation. Our study demonstrates the value and benefits of programmes offering IUD services emphasising quality counselling and client-centred care to increase access, uptake, and continuation.

Using an educational intervention to assess and improve disease-specific knowledge and health literacy and numeracy in adolescents and young adults with haemophilia A and B.

INTRODUCTION: Health literacy (HL) and health numeracy (HN) are underestimated barriers to treatment adherence in patients with haemophilia. AIM: To test the ability of an educational intervention to improve knowledge, HL, HN, adherence and joint health in adolescent and young adult (AYA) males with haemophilia. METHODS: We performed a longitudinal pilot study of 41 participants aged 12-21 years with haemophilia A or B during two clinic visits 6-12 months apart. The first visit included a comprehensive pre-intervention assessment: demographics, knowledge survey, Montreal Cognitive Assessment testing, 5-question tool to assess baseline HN, assessment of HL with the Rapid Estimate of Adolescent Literacy in Medicine tool, history of adherence and Haemophilia Joint Health Score (HJHS). An educational intervention using a visual aid explained basic pharmacokinetic (PK) concepts and personal teaching regarding haemophilia treatment regimens was used during this visit. The second visit included a post-intervention assessment: a reassessment of knowledge, HL, HN, HJHS, adherence to prescribed therapy and number of joint bleeds since the pre-intervention visit. RESULTS: Forty-one males with haemophilia A or B were enrolled in the study. Of these, 33 completed the post-intervention assessment. Knowledge (p = .002) and HN (p = .05) were significantly improved post-intervention, although the HL, number of joint bleeds, adherence to prescribed therapy and HJHS were not. CONCLUSIONS: Participants with low HL and/or HN may benefit from alternate methods of education such as audiovisual material. Education using audiovisual materials improved knowledge and HN in this study; however, this did not affect adherence to prescribed therapy.

The not so innocent bystander: an unusual cause of progressive breathlessness.

This case report discusses a 76-year-old man who presented with symptomatic diffuse alveolar-septal and tracheobronchial amyloidosis with a low-grade monoclonal gammopathy. This patient had a combination of both symptomatic diffuse alveolar-septal interstitial disease and tracheobronchial amyloidosis, features that contradict the widely accepted presentations seen in this disease. First, tracheobronchial amyloidosis has been documented as localised disease without systemic involvement. Second, diffuse alveolar-septal interstitial disease is rarely identified with clinical symptoms unless there is significant cardiac involvement. This case highlights a number learning points in the diagnosis and management of systemic amyloid light chain amyloidosis;(1) There is a need for a high index of suspicion for diagnosis due to the potential subtlety of a plasma cell clone underlying AL amyloidosis, requiring serum-free light chain assays to increase sensitivity; (2) Haematological response and recovery of organ dysfunction are not a linear relationship due to the slower reversal of amyloid deposition; therefore, ongoing monitoring is required to identify those in need of repeated therapy. However, haematological response is a marker of overall survival and (3) Multisystem assessment and multidisciplinary collaboration are critical in optimising the care of patients with systemic AL amyloidosis.

Bioavailability Enhancement of Polymyxin B With Novel Drug Delivery: Development and Optimization Using Quality-by-Design Approach.

Polymyxin-B (Poly-B) is an effective antibiotic used to treat infections mainly caused due to sensitive gram-negative bacteria. They belong to the group of cyclic peptide antibiotics and are minimally absorbed from the gastrointestinal tract. This arises the need for bioavailability enhancement and is achieved in the present case using niosomes as carrier system. The Poly-B niosomes had been developed using Span 60 and cholesterol while optimization is achieved with quality-by-design (QBD) approach. In this QBD approach, 3 independent variables (Span 60:cholesterol, volume of phosphate-buffered saline [%], and amount of drug [mg]) each at 3 levels were studied. A total of 17 runs were suggested by the model which was further analyzed by optimizing 3 different responses (particle size, zeta potential, and entrapment efficiency [EE%]). The results had clearly shown that the optimum formulation selected by QBD was based on the criteria of attaining the maximum value of EE% and low value of size and zeta potential. Poly-B niosomes were further examined by in vitro antifungal, rat creatinine, and cytotoxicity assay. The pharmacokinetics and scintigraphy studies were also performed for in vivo behavior of Poly-B.

Digital pathology is a practical alternative to on-site intraoperative frozen section diagnosis in thoracic surgery.

AIMS: Telepathology uses digitised image transfer to allow off-site reporting of histopathology slides. This technology could facilitate the centralisation of pathology services, which may improve their quality and cost-effectiveness. The benefits may be most apparent in frozen section reporting, in which turnaround times (TATs) are vital. We moved from on-site to off-site telepathology reporting of thoracic surgery frozen section specimens in 2016. The aim of this study was to compare TATs before and after this service change. METHODS AND RESULTS: All thoracic frozen section specimens analysed 4 months prior and 4 months following the service change were included. Demographics, operation, sample type, time taken from theatre, time received by laboratory, time reported by laboratory, TAT, frozen section diagnosis, final histopathological diagnosis and final TNM staging were recorded. The results were analysed with spss statistical software version 24. In total, there were 65 samples from 59 patients; 34 before the change and 31 after the change. Specimens included 51 lung, six lymph node, three bronchial, three chest wall and two pleural biopsies. Before the change, the median TAT was 25 min [interquartile range (IQR) 20-33 min]. No diagnoses were deferred. No diagnoses were changed on subsequent paraffin analysis. After the change, with the use of digital pathology, the median TAT was 27.5 min (IQR 21.75-38.5 min). This difference was not significant (P = 0.581). Diagnosis was deferred in one case (3.23%). There was one (3.23%) mid-case technical failure resulting in the sample having to be transported by courier, resulting in a TAT of 106 min. No diagnoses were changed on subsequent paraffin analysis. CONCLUSIONS: There was no significant difference in reporting times between digital technology and an on-site service, although one sample was affected by a technical failure requiring physical transportation of the specimen for analysis. Our study was underpowered to detect differences in accuracy.

The effect of 19-gauge endobronchial ultrasound-guided transbronchial needle aspiration biopsies on characterisation of malignant and benign disease. The Bristol experience.

EBUS-TBNA is a recent mediastinal staging and diagnostic technique. We have previously reported superior characterisation with 21G biopsies over 22G biopsies for benign and malignant mediastinal nodes. A new 19G needle now exists but there are limited studies. We hypothesised 19G biopsies would improve both benign and malignant characterisation due to larger samples. We retrospectively analysed sequential patients referred for EBUS-TBNA with unexplained mediastinal adenopathy performed with 19G, 21G and 22G needles respectively (100 patients each). Contingency table analysis was performed.  There were no complications. Sensitivity for malignancy was highest in the 19G group (95.7% versus 94.7% and 87.5%, respectively). The 19G group had higher mean lymph node size (19.4mm versus 18.6mm and 13.5mm, respectively), the highest proportion of lymphoma (9% versus 5% and 0%, respectively), the lowest proportion of NSCLC-NOS (2% versus 12% and 5%, respectively), the highest proportion of subcharacterised benign disease (89.6% versus 69.8% and 37.9%, respectively). This large single centre retrospective UK study suggests the 19G needle appears safe with the suggestion of better sensitivity for malignancy subcharacterisation of benign disease but this requires further study in adequately powered comparative controlled studies with univariate and multivariate analysis.

Design and fabrication of a magnetically actuated non-invasive reusable drug delivery device.

We present a novel approach of designing and fabricating a noninvasive drug delivery device which is capable of delivering the drug to the target site in a controlled manner. The device utilizes a reservoir which can be reused once the drug has completely diffused from it. This micro-reservoir based fabricated device has been successfully tested using niosomes of insulin drug filled in, which was then sealed with a magnetic membrane of 20 µm thick and was actuated by applying magnetic field. The deflection of the membrane on application of magnetic field results in the drug release from the reservoir. The discharge of the drug solution and the release rates was controlled by external magnetic field. The simulation of the membrane deflection using COMSOL software was carried out to optimize the concentration of the ferrous nanopowder in PDMS matrix. The characterization of the devices was implemented in-vitro on water and in-vivo on Wistar rats. It was also validated using high-performance liquid chromatography (HPLC) by observing characteristic peak of insulin. The blood samples showed the retention time of 2.79 min at λmax of 280 nm which further authenticated the effectiveness of the proposed work. This noninvasive fabricated device provides reusability, precise control and can enable the patient or a physician to actively administrate the drug when required.

Methotrexate-Induced Neurotoxicity in Hispanic Adolescents with High-Risk Acute Leukemia-A Case Series.

Intrathecal methotrexate (IT MTX) and high-dose intravenous methotrexate (HD MTX) are important components of treatment in high-risk acute leukemia. We describe five Hispanic adolescents with high-risk acute leukemia at our institution who experienced MTX-induced neurotoxicity. All patients were eventually rechallenged with MTX. Two of the five patients had a second episode of neurotoxicity, but all patients recovered. Further studies should be performed to determine whether Hispanic patients are more susceptible to MTX neurotoxicity.