Polyethylene glycol-induced precipitation of interferon alpha-2a followed by vacuum drying: Development of a novel process for obtaining a dry, stable powder

Feasibility studies were performed on the development of a novel process based on polyethylene glycol (PEG)-induced precipitation of proteins followed by vacuum drying in the presence of sugars to obtain dry protein powders. Apparent solubility of interferon alpha-2a (IFNalpha2a) was determined in the presence of various PEGs and the effect of solution pH, ionic strength, and temperature was investigated. IFNalpha2a precipitate was dried at a shelf temperature of 25 degrees C at 100 mTorr either as it is or in the presence of mannitol and/or trehalose. The dried IFNalpha2a formulations were subjected to accelerated stability studies at 40 degrees C (3 months), and the stability was compared with that of a similar lyophilized formulation. The results indicated that more than 90% of the protein could be precipitated using 10% wt/vol PEG the protein could be precipitated using 10% wt/vol PEG 1450 at pH 6.5 at a solution ionic strength of 71 mM. Vacuum drying of the precipitate only resulted in the formation of insoluble aggregates of IFNalpha2a; however, this was prevented by the addition of either mannitol or trehalose. The addition of excess mannitol resulted in low residual moisture content and better handling of the final dried product. Accelerated storage stability did not show any aggregation and showed less than 5% formation of oxidized IFNalpha2a in the dried formulation containing IFNalpha2a: trehalose: mannitol in a 1:10:100 wt/wt ratio upon storage at 40 degrees C for 3 months. The stability of this vacuum dried formulation was comparable with that of a similar lyophilized formulation.     

Improvement in Thermal Storage Effectiveness of Paraffin with Addition of Aluminum Oxide Nanoparticles

The output of the latent heat storage devices (LHSDs), based on some phase change materials (PCMs), depends upon the thermophysical properties of the phase change material used. In this study, a paraffin-based nanofluid, blended with aluminum oxide (Al₂O₃) nanoparticles, is used as PCM for performance evaluation. A three-dimensional (3D) numerical model of regenerative type shell-and-tube LHSD is prepared using COMSOL Multiphysics^® 4.3a software to estimate the percentage of melt and the average temperature of the analyzed nanofluids. The results of this study are in close agreement with those reported in the literature, thereby ensuring the validation of the numerically predicted results. The effects of adding the nanoparticles on the rate of melting, as well as solidification and rate of stored/liberated energy, are studied. The results revealed that, by adding 10% nanoparticles of Al₂O₃, the melting rate of pure-paraffin-based LHSD improved by about 2.25 times. In addition, the rate of solidification was enhanced by 1.8 times. On the other hand, the heat of fusion and specific heat capacities were reduced, which, in turn, reduced the latent and sensible heat-storing capabilities. From the outcomes of the present research, it can be inferred that combining LHSD with a solar water heater may be used in technologies such as biogas generation.     

Use of convalescent plasma for managing severe COVID‐19 infection in 2‐month‐old infant

A 58‐day‐old female infant reported with complaints of fever, difficult breathing, loose stool, vomiting and refusal to feed for 4 days. Laboratory work showed anaemia, leucocytosis with elevated neutrophils and thrombocytopenia along with high C‐reactive protein and D‐dimer with bilateral patchy infiltrate on X‐ray and positivity for COVID‐19. Her blood culture was also positive for Gram‐negative bacilli (acinetobacter lwoffii). Along with antibiotics, she was given 50 ml convalescent plasma. She was off oxygen within 2 days and showed improvement in lung lesions, and RT‐PCR was negative by day 7 and discharged by day 10 of transfusion.     

Utility of response assessment PET-CT to predict residual disease in neck nodes: A comparison with the Histopathology

ObjectiveTo assess the ability of Positron Emission Tomography-Computed Tomography (PET-CT) scans to detect residual disease in neck nodes with the Histopathology (HPR) as the gold standard. To obtain a Standardized Uptake Value max cutoff in these patients to predict residual disease in neck.MethodsHead and neck squamous cell carcinoma patients who underwent Salvage neck dissection with or without primary site surgery post Concurrent Chemo-Radiotherapy (CCRT) during the period January 2008–December 2017 were included. All patients had response assessment PET-CT scan at 10–14 weeks. Agreement analysis was performed between PET-CT and HPR, fine needle aspiration cytology and HPR. Positive predictive value, Negative predictive value of PET-CT to detect residual neck nodal disease in comparison to HPR was analyzed. A Receiver Operating Characteristic (ROC) curve was plotted between the SUV max values and the HPR. A SUV max cutoff value was obtained from the ROC curve.ResultsA total of 75 patients were included. Thirty-one underwent salvage neck dissection along with surgery for primary disease and 45 underwent salvage neck dissection alone. PET-CT showed good agreement with the HPR to detect residual disease in neck nodes (Kappa = 0.604). PET-CT had a PPV and NPV of 87.5% and 79.15% respectively as compared against the HPR. A SUV max cutoff of 4.62 had a specificity of 92.3% and sensitivity of 73.5% to detect residual disease in neck nodes on the HPR.ConclusionPET-CT surveillance is an accepted treatment strategy. A neck node with SUV max of 4.62 and above is most likely to harbor residual nodal disease.Level of evidence: Level 2b     

Teaching for reducing diagnostic errors

Diagnostic errors, constituted by a missed, wrong, or delayed diagnosis detected later by additional tests or findings, are one of the most vexing issues in medicine. They are one of the commonest causes of patient-harm and also medical negligence claims. Although a variety of constructs have been proposed to explain diagnostic errors, the complex interplay of cognitive- and system-factors that underlie these errors is rarely clear to the clinicians. In this write-up, we discuss the reasons for diagnostic errors and how medical students can be trained to avoid such errors. The errors have been classified as Cognitive errors, System errors, and No-fault errors, and cognitive interventions to address each of these are detailed.     

Case report: Rare case of donor cell-derived T-cell acute lymphoblastic leukaemia in a female patient after receiving an allo-transplant from her male sibling

Donor-derived haematological neoplasms, in which recipients present with haematological malignancies that have evolved from transplant donor stem cells, have previously been described for myelodysplastic syndrome, myeloproliferative neoplasms, acute myeloid leukaemia and less often, leukaemias of lymphoid origin. Here we describe a rare and complex case of donor-derived T-cell acute lymphoblastic leukaemia with a relatively short disease latency of less than 4 years. Through genomic and in vitro analyses, we identified novel mutations in NOTCH1 as well as a novel activating mutation in STAT5B; the latter targetable with the clinically available drugs, venetoclax and ruxolitinib.     

Future applications of exosomes delivering resolvins and cytokines in facilitating diabetic foot ulcer healing

Type 2 diabetes mellitus (T2DM) increases the risk of many lethal and debilitating conditions. Among them, foot ulceration due to neuropathy, vascular disease, or trauma affects the quality of life of millions in the United States and around the world. Physiological wound healing is stalled in the inflammatory phase by the chronicity of inflammation without proceeding to the resolution phase. Despite advanced treatment, diabetic foot ulcers (DFUs) are associated with a risk of amputation. Thus, there is a need for novel therapies to address chronic inflammation, decreased angiogenesis, and impaired granulation tissue formation contributing to the non-healing of DFUs. Studies have shown promising results with resolvins (Rv) and anti-inflammatory therapies that resolve inflammation and enhance tissue healing. But many of these studies have encountered difficulty in the delivery of Rv in terms of efficiency, tissue targetability, and immunogenicity. This review summarized the perspective of optimizing the therapeutic application of Rv and cytokines by pairing them with exosomes as a novel strategy for targeted tissue delivery to treat non-healing chronic DFUs. The articles discussing the T2DM disease state, current research on Rv for treating inflammation, the role of Rv in enhancing wound healing, and exosomes as a delivery vehicle were critically reviewed to find support for the proposition of using Rv and exosomes in combination for DFUs therapy. The literature reviewed suggests the beneficial role of Rv and exosomes and exosomes loaded with anti-inflammatory agents as promising therapeutic agents in ulcer healing.     

Microbiome and metabolome in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease of unknown etiology, involving complex interactions between the gut microbiome and host immune response. The microbial dysbiosis is well documented in IBD and significantly influences the host metabolic pathways. Thus, a metabolomic fingerprint resulting from the influence of gut dysbiosis in IBD could aid in assessing the disease activity. PubMed, Medline, Science Direct, and Web of Science were searched for studies exploring the association between microbiome and metabolome in IBD patients in the last 5 years. Additionally, references of cited original articles and reviews were further assessed for relevant work. We provide a literature overview of the recent metabolomic studies performed on patients with IBD. The findings report alterations in the metabolite levels of these patients. We also discuss the gut dysbiosis observed in IBD and its influence on host metabolic pathways such as lipids, amino acids, short-chain fatty acids, and others. IBD, being a chronic idiopathic disease, requires routine monitoring. The available non-invasive markers have their limitations. The metabolite changes account for both dysbiosis and its influence on the host's immune response and metabolism. A metabolome approach would thus facilitate the identification of surrogate metabolite markers reflecting the disease activity.