Long-Term Effectiveness of Benralizumab in Eosinophilic Granulomatosis With Polyangiitis.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystemic disease characterized by eosinophilic tissue inflammation. Benralizumab, an anti-IL-5 receptor (anti-IL-5R) monoclonal antibody, induces rapid depletion of eosinophils; its longer-term effect in EGPA is unknown. OBJECTIVE: To assess the real-world effectiveness and clinical remission rates of anti-IL-5R therapy in EGPA. METHODS: We performed a retrospective cohort analysis of patients with EGPA, who commenced treatment with benralizumab. Clinical remission, assessed at 1 year and 2 years after the initiation of benralizumab, was defined as an absence of active vasculitis (Birmingham Vasculitis Activity Score of 0) and an oral corticosteroid (OCS) dose of ≤4 mg/d of prednisolone. "Super-responders" were defined as patients in remission and free of any significant relapses (asthma or extrapulmonary) over the preceding 12 months. The corticosteroid-sparing capacity of benralizumab, patient-reported outcome measures, and characteristics associated with clinical remission and super-responder status were also analyzed. RESULTS: A total of 70 patients completed at least 1 year of treatment with benralizumab, of whom 53 completed 2 years. Of 70 patients, 47 (67.1%) met the definition for clinical remission at 1 year, with a similar proportion in remission at 2 years. Excluding asthma-related relapses, 61 of 70 (87.1%) patients were relapse free at 1 year, and of the 53 who completed 2 years, 45 (84.9%) were relapse free. A total of 67.9% of patients no longer needed any OCS for disease control. No significant difference was seen between antineutrophilic cytoplasmic antibody (ANCA)-positive and ANCA-negative subgroups. CONCLUSIONS: In this real-world setting of patients with EGPA, treatment with benralizumab was well tolerated and resulted in corticosteroid-free clinical remission for the majority of patients.

Antibody predictors of mortality and lung function trends in myositis spectrum interstitial lung disease.

OBJECTIVES: The impact of autoantibody profiles on prognosis of idiopathic inflammatory myositis associated interstitial lung disease (IIM-ILD) and myositis spectrum ILD with Myositis Specific Antibodies (MSA) remains unclear. This retrospective cohort study examines whether serological profiles are associated with mortality and longitudinal lung function change. METHODS: Baseline clinical/demographic characteristics and follow-up lung function of consecutive adult patients with IIM-ILD or Interstitial Pneumonia with Autoimmune Features (IPAF) positive for MSAs were extracted from three hospitals. Univariate and multi-variate Cox-Proportional Hazards analyses were used to compare mortality between autoantibodies. Regression models were used to analyse lung function trends. RESULTS: Of 430 included patients, 81% met IIM criteria, 19% were IPAF-MSA. On univariate analysis, risk factors associated with mortality included higher age, Charlson Co-morbidity Index and CRP; and lower BMI, baseline TLCO% and FEV1%. Compared to anti-MDA5-negativity, anti-MDA5-positivity (MDA5+) was associated with high mortality in the first 3 months (HR 65.2. 95%CI 14.1, 302.0), while no significant difference was seen thereafter (HR 0.55, 95%CI 0.14, 2.28). On multi-variate analysis, combined anti-synthetase antibodies carried a reduced risk of mortality (HR 0.63), although individually, mortality was reduced in anti-Jo1 + (HR 0.61, 95%CI 0.4-0.87) and increased in anti-PL7+ patients (HR 2.07, 95%CI 1.44-2.99). Anti-MDA5+ was associated with slow improvement in %FVC over the first 3 years, while anti-PL7+ was linked with a slow decline from 12 months onwards. CONCLUSIONS: Among autoantibody profiles in myositis spectrum disorders, anti-MDA5+ and anti-PL7+ confer higher mortality risks. Survivors of an early peak of mortality in anti-MDA5+ disease appear to have a favourable prognosis.

Recent advances in microbial engineering approaches for wastewater treatment: a review.

In the present era of global climate change, the scarcity of potable water is increasing both due to natural and anthropogenic causes. Water is the elixir of life, and its usage has risen significantly due to escalating economic activities, widespread urbanization, and industrialization. The increasing water scarcity and rising contamination have compelled, scientists and researchers, to adopt feasible and sustainable wastewater treatment methods in meeting the growing demand for freshwater. Presently, various waste treatment technologies are adopted across the globe, such as physical, chemical, and biological treatment processes. There is a need to replace these technologies with sustainable and green technology that encourages the use of microorganisms since they have proven to be more effective in water treatment processes. The present review article is focused on demonstrating how effectively various microbes can be used in wastewater treatment to achieve environmental sustainability and economic feasibility. The microbial consortium used for water treatment offers many advantages over pure culture. There is an urgent need to develop hybrid treatment technology for the effective remediation of various organic and inorganic pollutants from wastewater.

Microbial engineering approaches for wastewater treatment.Current and emerging sources of water pollution are discussed.Various treatment technologies for wastewater treatment.Biological methods and microbes are used for degradation.Parameters responsible for the degradations processes of wastewater.

Steroid exposure and outcome in COVID-19 pneumonia.

Background: Corticosteroids are used to treat COVID-19 pneumonia. However, the optimal dose is unclear. This study describes the association between corticosteroid exposure with disease severity and outcome in COVID-19 pneumonia. Methods: This is a single-centre retrospective, observational study including adult ICU patients who received systemic corticosteroids for COVID-19 pneumonia between March 2020 and March 2021. We recorded patient characteristics, disease severity, total steroid exposure, respiratory support and gas exchange data, and 90-day mortality. Results: We included 362 patients. We allocated patients to groups with increasing disease severity according to the highest level of respiratory support that they received: high-flow nasal oxygen or continuous positive airway pressure (HFNO/CPAP) in 12.7%, invasive mechanical ventilation (IMV) in 61.6%, and extracorporeal membrane oxygenation (ECMO) in 25.7%. For these three groups, the median (inter-quartile range [IQR]) age was 61 (54-71) vs 58 (50-66) vs 46 (38-53) yr, respectively (P<0.001); median (IQR) APACHE (Acute Physiology and Chronic Health Evaluation) II scores were 12 (9-15) vs 14 (12-18) vs 15 (12-17), respectively (P=0.006); the median (IQR) lowest P a O 2 /FiO2 ratio was 15.1 (11.8-21.7) vs 15.1 (10.7-22.2) vs 9.5 (7.9-10.9) kPa, respectively (P<0.001). Ninety-day mortality was 9% vs 27% vs 37% (P=0.002). Median (IQR) dexamethasone-equivalent exposure was 37 (24-62) vs 174 (86-504) vs 535 (257-1213) mg (P<0.001). 'Pulsed' steroids were administered to 26% of the IMV group and 48% of the ECMO group. Patients with higher disease severity who received pulse steroids had a higher 90-day mortality. Conclusions: Corticosteroid exposure increased with the severity of COVID-19 pneumonia. Pulsed dose steroids were used more frequently in patients receiving greater respiratory support. Future studies should address patient selection and outcomes associated with pulsed dose steroids in patients with severe and deteriorating COVID-19 pneumonia.

Seasonal Variations in Bioaccumulation and Translocation of Toxic Heavy Metals in the Dominant Vegetables of East Kolkata Wetlands: a Case Study with Suggestive Ecorestorative Strategies.

In recent times, East Kolkata Wetlands (EKW), a designated Ramsar site in the eastern part of megacity Kolkata, has been threatened by toxic heavy metal (HM) pollution. Besides being a natural wetland supporting biodiversity, EKW serves as a significant food basket for the city. For assessing the magnitude of HM pollution in this wetland, the three most cultivated food crops of EKW, namely Lagenaria siceraria (bottle gourd), Abelmoschus esculentus (ladies' fingers), and Zea mays (maize), as well as the ambient soil samples, were collected during premonsoon, monsoon, and postmonsoon for 2 consecutive years (2016 and 2017). Predominant HMs like cadmium (Cd), chromium (Cr), mercury (Hg), and lead (Pb) were analyzed in the roots and edible parts of these plants, as well as in the ambient soil to evaluate the bioaccumulation factor (BF) and translocation factor (TF) of each HM in the three vegetables. It was observed that the HM content in the food crop species followed the order Z. mays > L. siceraria > A. esculentus. HMs accumulated in all three vegetables as per the order Pb > Cd > Cr > Hg. Monsoon seems to be threatening in terms of bioaccumulation and translocation of HMs as both BF and TF were highest in this season irrespective of the plant species. Hence it demands critical monitoring of HM pollution levels in this wetland and subsequent ecorestoration through distinctive plant growth-promoting rhizobacteria (PGPR)-assisted co-cultivation of these food crops with low-metal-accumulating, deep-rooted, high-biomass-yielding, and bioenergy-producing perennial grass species for minimizing HM intake.

Compassionate use of REGN-COV2 in the treatment of COVID-19 in a patient with impaired humoral immunity.

BACKGROUND: The role of antibodies in coronavirus disease 2019 (COVID-19) in patients with X-linked agammaglobulinaemia (XLA) has yet to be characterised and clinical courses observed in this cohort of patients have been heterogeneous. Whilst some exhibit spontaneous recovery, others have experienced a more protracted disease length. Previous reports have described successful use of convalescent plasma, however there is a paucity of information around the use of the REGN-COV2 antibody cocktail in these patients. CASE REPORT: A patient with XLA was admitted to hospital with COVID-19 and remained persistently symptomatic with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) swab positivity despite treatment with Remdesivir and dexamethasone. Attempts at modulating the immune response with anakinra were unsuccessful. Consent for compassionate use of REGN-COV2 was obtained with administration taking place on day 87 of his illness. This was followed by a period of convalescence and SARS-CoV-2 nasopharyngeal swab negativity. As a consequence of prolonged immunosuppression, the patient developed pneumocystis pneumonia. CONCLUSION: This case highlights the role of antibodies in clearing SARS-CoV-2 in a hypogammaglobulinaemic host and demonstrates the consequences of prolonged immunosuppression and delayed treatment. We propose that this may be of particular significance given the capacity of SARS-CoV-2 to develop advantageous mutations in a chronically infected host.

An In Vitro Study to Determine the Physicochemical, Mechanical, and Antibacterial Properties of a Novel Spirulina Containing Controlled Release Intrapocket Drug Delivery System.

CONTEXT: Periodontitis is primarily an inflammatory condition caused by an array of microorganisms present in dental plaque. Elimination or adequate suppression of periodontal pathogens in the subgingival microflora is essential for adequate periodontal healing to take place. The development of subgingivally placed controlled delivery systems has provided the possibility of effective intrapocket concentration levels of antibacterial agents for an extended period of time, resulting in an altered subgingival flora and enhanced healing of the attachment apparatus. Although a number of synthetic antimicrobial agents are being used as local drug delivery, currently, pharmaceutical technology development has focused on the ingredients derived from nature. Natural phytochemicals have proven to be worthy substitutes of their synthetic and chemical-laden counterparts owing to their extensive natural activity, advanced safety margins, and inferior costs so that they can be of huge benefits, especially to the lower socioeconomic population around the world and spirulina platensis (SP) is one such emerging remedy. AIMS: The aim of the study was to develop three controlled release drug delivery systems containing different concentrations of SP to be used inside the periodontal pockets. The study also aimed to determine the antimicrobial activity of all the three concentrations of SP drug delivery system against major periodontopathic microorganisms and to test the physicochemical properties of the delivery system that exhibited maximum antimicrobial efficacy so that the suitability of its use inside the periodontal pocket could be determined. SETTINGS AND DESIGN: The study was an in vitro experimental design. SUBJECTS AND METHODS: Three different controlled release SP hydrogels (4%, 6%, and 12%) to be used inside the periodontal pockets were developed and antibacterial properties against periodontal pathogens were assessed. The hydrogel exhibiting maximum antimicrobial efficacy was then tested of physicochemical and mechanical properties to determine its suitability of its use inside the periodontal pocket. STATISTICAL ANALYSIS USED: Data were analyzed using one-way analysis of variance. Post hoc Tukey honestly significant difference test was used for comparison within the group and between the different groups. RESULTS: 12% SP hydrogel was found to have maximum antimicrobial efficacy against major periodontal pathogens, and its physicochemical and mechanical properties were also optimum to be used inside the periodontal pocket. CONCLUSIONS: 12% SP hydrogel can act as a promising adjunct to periodontal mechanical therapy and may also reduce the chances of more invasive periodontal surgical procedures.

Steroid-sparing effects of benralizumab in patients with eosinophilic granulomatosis with polyangiitis.

Benralizumab reduces oral corticosteroid requirements in patients with EGPA and leads to improved patient-reported outcome measures https://bit.ly/2GI0vhf.

Veno-venous extracorporeal membrane oxygenation in coronavirus disease 2019: a case series.

BACKGROUND: The use of veno-venous extracorporeal membrane oxygenation (VV-ECMO) in severe hypoxaemic respiratory failure from coronavirus disease 2019 (COVID-19) has been described, but reported utilisation and outcomes are variable, and detailed information on patient characteristics is lacking. We aim to report clinical characteristics, management and outcomes of COVID-19 patients requiring VV-ECMO, admitted over 2 months to a high-volume centre in the UK. METHODS: Patient information, including baseline characteristics and clinical parameters, was collected retrospectively from electronic health records for COVID-19 VV-ECMO admissions between 3 March and 2 May 2020. Clinical management is described. Data are reported for survivors and nonsurvivors. RESULTS: We describe 43 consecutive patients with COVID-19 who received VV-ECMO. Median age was 46 years (interquartile range 35.5-52.5) and 76.7% were male. Median time from symptom onset to VV-ECMO was 14 days (interquartile range 11-17.5). All patients underwent computed tomography imaging, revealing extensive pulmonary consolidation in 95.3%, and pulmonary embolus in 27.9%. Overall, 79.1% received immunomodulation with methylprednisolone for persistent maladaptive hyperinflammatory state. Vasopressors were used in 86%, and 44.2% received renal replacement therapy. Median duration on VV-ECMO was 13 days (interquartile range 8-20). 14 patients died (32.6%) and 29 survived (67.4%) to hospital discharge. Nonsurvivors had significantly higher d-dimer (38.2 versus 9.5 mg·L-1, fibrinogen equivalent units; p=0.035) and creatinine (169 versus 73 µmol·L-1; p=0.022) at commencement of VV-ECMO. CONCLUSIONS: Our data support the use of VV-ECMO in selected COVID-19 patients. The cohort was characterised by high degree of alveolar consolidation, systemic inflammation and intravascular thrombosis.

COVID-19-related organ dysfunction and management strategies on the intensive care unit: a narrative review.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in a significant surge of critically ill patients and an unprecedented demand on intensive care services. The rapidly evolving understanding of pathogenesis, limited disease specific evidence, and demand-resource imbalances have posed significant challenges for intensive care clinicians. COVID-19 is a complex multisystem inflammatory vasculopathy with a significant mortality implication for those admitted to intensive care. Institutional strategic preparation and meticulous intensive care support are essential to maximising outcomes during the pandemic. The significant mortality variation observed between institutions and internationally, despite a single aetiology and uniform presentation, highlights the potential influence of management strategies on outcome. Given that optimal organ support and adjunctive therapies for COVID-19 have not yet been well defined by trial-based outcomes, strategies are predicated on existing literature and experiential learning. This review outlines the relevant pathophysiology and management strategies for critically ill patients with COVID-19, and shares some of the collective learning accumulated in a high volume severe respiratory failure centre in London.

Oral corticosteroid-sparing effects of reslizumab in the treatment of eosinophilic granulomatosis with polyangiitis.

Blockade of interleukin-5 with reslizumab appears to have significant oral corticosteroid sparing effects in patients with eosinophilic granulomatosis with polyangiitis and severe eosinophilic asthma http://bit.ly/2D2yYSK.

Multidisciplinary approach to connective tissue disease (CTD) related pleural effusions: a four-year retrospective evaluation.

BACKGROUND: CTD-related pleural effusions are rare and challenging to diagnose. Our lung inflammation service (with expertise in rheumatology, interstitial lung disease and respiratory failure) works closely with the pleural team. This study aims to review the multidisciplinary approach to CTD-related pleural effusions at a tertiary centre. METHODS: All patients with CTD-related pleural effusions at St Thomas' Hospital, London were included. Retrospective data were collected from Dec 2013 to 2016. RESULTS: The lung inflammation service performed an expert clinical assessment and targeted investigations. 11 patients (ages 23-77) were identified with CTD related pleural disease. 9 (82%) patients were given a new CTD diagnosis, with pleural disease as the first manifestation. The range of conditions were: rheumatoid arthritis [3] ,IgG4-related disease [2] ,adult Still's disease [2] ,vasculitis [1] ,SLE [1] ,drug-induced lupus [1] ,and Behcet's [1]. The pleural team review took place 1 day (median) after referral. 73% of diagnoses (8 patients) were achieved with local anaesthetic pleural interventions (a combination of: aspiration, drain, or percutaneous biopsy). This included 1 patient who required no pleural intervention. 1 required medical thoracoscopy, and 2 underwent thoracic surgery. Diagnoses were made by integrating all available evidence such as clinical assessment, imaging, and autoimmune serology. No diagnosis was achieved by pleural cytology or histology analysis alone. 8 (73%) were commenced on prednisolone acutely (vasculitis, SLE, drug-related lupus, 1 patient with rheumatoid arthritis, Behcet's, 2 patients with Adult Still's disease, 1 patient with IgG4-related disease). Of these 8, one patient with rheumatoid arthritis received IV methylprednisolone beforehand, one patient with IgG4-related disease was weaned off prednisolone to methothrexate, two patients with Adult Still's disease were on colchicine as well, and one patient with Behcet's was on cyclophosphamide as well. 7 (64%) were managed as outpatients; 4 required admission. The median time from pleural review to diagnosis was 53 days. CONCLUSIONS: Diagnosis can be challenging in patients presenting with pleural disease as the first manifestation of a CTD. We recommend a multidisciplinary approach in management.

Systemic Lupus Erythematosus and Antiphospholipid Antibody Syndrome.

Systemic lupus erythematosus (SLE) is a systemic inflammatory disease, characterized by an antibody response to nucleic antigens and involvement of any organ system. Pulmonary manifestations are frequent and include pleuritis, acute lupus pneumonitis, chronic interstitial lung disease, alveolar hemorrhage, shrinking lung syndrome, airway disease, pulmonary hypertension (PH), and thromboembolic disease. The antiphospholipid antibody syndrome (APLAS) is a systemic autoimmune disorder where different prothrombotic factors interact to induce arterial and venous thrombosis. The most common pulmonary manifestations are pulmonary thromboembolism and PH. This review will focus on the clinical presentation, diagnosis, and management of the SLE- and APLAS-associated pulmonary conditions.

Therapeutic plasma exchange as a novel treatment for severe intrahepatic cholestasis of pregnancy: Case series and mechanism of action.

INTRODUCTION: Intrahepatic cholestasis of pregnancy is characterised by pruritus and elevated serum bile acids. The pruritus can be severe, and pharmacological options achieve inconsistent symptomatic improvement. Raised bile acids are linearly associated with adverse fetal outcomes, with existing management of limited benefit. We hypothesised that therapeutic plasma exchange removes pruritogens and lowers total bile acid concentrations, and improves symptoms and biochemical abnormalities in severe cases that have not responded to other treatments. METHODS: Four women with severe pruritus and hypercholanemia were managed with therapeutic plasma exchange. Serial blood biochemistry and visual analogue scores of itch severity were obtained. Blood and waste plasma samples were collected before and after exchange; individual bile acids and sulfated progesterone metabolites were measured with HPLC-MS, autotaxin activity and cytokine profiles with enzymatic methods. Results were analysed using segmental linear regression to describe longitudinal trends, and ratio t tests. RESULTS: Total bile acids and visual analogue itch scores demonstrated trends to transiently improve following plasma exchange, with temporary symptomatic benefit reported. Individual bile acids (excluding the drug ursodeoxycholic acid), and the sulfated metabolites of progesterone reduced following exchange (P = .03 and P = .04, respectively), whilst analysis of waste plasma demonstrated removal of autotaxin and cytokines. CONCLUSIONS: Therapeutic plasma exchange can lower potentially harmful bile acids and improve itch, likely secondary to the demonstrated removal of pruritogens. However, the limited current experience and potential complications, along with minimal sustained symptomatic benefit, restrict its current use to women with the most severe disease for whom other treatment options have been exhausted.

Lesson of the month: selective use of cyclophosphamide in pregnancy for severe autoimmune respiratory disease.

We present the cases of two pregnant women who developed severe respiratory compromise in mid pregnancy, one due to rapidly progressive interstitial lung disease associated with mixed connective tissue disease and one secondary to diffuse alveolar haemorrhage due to antiglomerular basement membrane disease. Both were treated with high-dose steroids followed by pulsed intravenous cyclophosphamide. Both women went onto have live births although one baby was growth restricted and preterm. Neither baby had any evidence of congenital abnormalities.

Presence of Helicobacter pylori in subgingival plaque of periodontitis patients with and without dyspepsia, detected by polymerase chain reaction and culture.

BACKGROUND: Helicobacter pylori is an important gastrointestinal pathogen that is strongly associated with gastritis as well as peptic ulcer disease. Antimicrobial therapy frequently fails to cure H. pylori infection, which suggests there may be sanctuary sites where the organism resides. This study was aimed to assess the role of oral cavity as a reservoir of H. pylori by evaluating the occurrence of the organism in subgingival plaque of dyspeptic patients by polymerase chain reaction as well as culture. MATERIALS AND METHODS: Thirty chronic periodontitis patients whose biopsy specimens were found to be H. pylori positive with rapid urease test and histopathologic examination were considered as cases and 20 chronic periodontitis patients who never had any symptoms of gastritis or peptic ulcer were taken as controls. Subgingival plaque samples were collected and sent to microbiological laboratory for detection of H. pylori by 16S rRNA based polymerase chain reaction as well as culture. RESULTS: 60% of the samples were found to be positive with polymerase chain reaction in the case group when compared to 15% in the controls. Also, 30% of the cases were found to be positive with culture compared to none in controls. CONCLUSION: A higher frequency of detection of H. pylori in those patients with positive antral biopsy report was seen. Also, polymerase chain reaction was found to be more sensitive than culture for detection. Thus, we conclude that detection of H. pylori in dental plaque of dyspeptic patients cannot be neglected and might represent a risk factor for recolonization of stomach after systemic eradication therapy.