Exploring the immunopathology of type 2 inflammatory airway diseases

Significant advancements have been achieved in understanding the roles of different immune cells, as well as cytokines and chemokines, in the pathogenesis of eosinophilic airway conditions. This review examines the pathogenesis of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), marked by complex immune dysregulation, with major contributions from type 2 inflammation and dysfunctional airway epithelium. The presence of eosinophils and the role of T-cell subsets, particularly an imbalance between Treg and Th17 cells, are crucial to the disease’s pathogenesis. The review also investigates the pathogenesis of eosinophilic asthma, a unique asthma subtype. It is characterized by inflammation and high eosinophil levels, with eosinophils playing a pivotal role in triggering type 2 inflammation. The immune response involves Th2 cells, eosinophils, and IgE, among others, all activated by genetic and environmental factors. The intricate interplay among these elements, chemokines, and innate lymphoid cells results in airway inflammation and hyper-responsiveness, contributing to the pathogenesis of eosinophilic asthma. Another scope of this review is the pathogenesis of Eosinophilic Granulomatosis with Polyangiitis (EGPA); a complex inflammatory disease that commonly affects the respiratory tract and small to medium-sized blood vessels. It is characterized by elevated eosinophil levels in blood and tissues. The pathogenesis involves the activation of adaptive immune responses by antigens leading to T and B cell activation and eosinophil stimulation, which causes tissue and vessel damage. On the other hand, Allergic Bronchopulmonary Aspergillosis (ABPA) is a hypersensitive response that occurs when the airways become colonized by aspergillus fungus, with the pathogenesis involving activation of Th2 immune responses, production of IgE antibodies, and eosinophilic action leading to bronchial inflammation and subsequent lung damage. This analysis scrutinizes how an imbalanced immune system contributes to these eosinophilic diseases. The understanding derived from this assessment can steer researchers toward designing new potential therapeutic targets for efficient control of these disorders

Breathing New Life Into Acute Respiratory Care : Proactively Improving Long-Term Outcomes

Acknowledgements: Writing assistance was provided by Rachel Danks, RSD Medical Communications Ltd, Gloucestershire, UK.Peer reviewedPublisher PD

دراسة مختصرة حول أسانيد القراءات الشاذة

هذا البحث عبارة عن دراسة مختصرة حول أسانيد القراءات الشاذة؛ لما في ذلك من أهمية في الحكم على القراءة وتمييز صحيحها من ضعيفها. وقد قسَّمت البحث إلى: تمهيد، وأربعة مباحث، وخاتمة، وفهرس للمصادر والمراجع. التمهيد وفيه: القراءة المقبولة والمردودة. ولمحة عن القراءات الشاذة: (مفهومها، حكم القراءة بها، أشهر قراء القراءات الشاذة). ثم أربعة مباحث، وهي: الأول: الإسناد: (مفهومه، أهميته). الثاني: الكتب التي اهتمت بدراسة أسانيد القراءات. الثالث: المنهج العلمي في دراسة أسانيد القراءات. الرابع: دراسة تطبيقية على بعض أسانيد كتب القراءات الشاذة. وتوصل البحث إلى أن جمهور العلماء قد اتفقوا على أن شرط قبول القراءة هو التواتر، وعدم الاكتفاء بصحة السند. والقراءات هي الحاكمة لقواعد العربية. وأن من أنكر شرطًا من شروط القراءة يعتبر كافرًا وجاحدًا لكلام الله U. عدم جواز القراءة بالشاذ في الصلاة ولا في غيرها. وأن العبرة ليس بعلو السند وإنما بتوافر شروط العدالة والضبط في كل قارئ في السند. وجهالة الراوي تؤدي إلى ضعف السند. ولابد أن تكون طريقة التلقي التي تلقى بها الراوي مطابقة لصيغة التحمل في السند. وصحة السند واتصاله لا تكفي في الحكم على القراءة بأنها متواتر

Tolerability of Omalizumab in Asthma as a Major Compliance Factor: 10-Year Follow Up

BACKGROUND: There is a lack of data related to real life, long-term safety, tolerability and compliance of omalizumab treatment in asthma patients beyond 6 years. AIM: Study aimed to assess safety, tolerability, compliance and all reasons for treatment discontinuation during 10 years on omalizumab. SUBJECT AND METHODS: This is a retrospective, observational study of uncontrolled asthma patients receiving omalizumab for the last 10 years. All data were collected from patients’ files (demographics, adverse events, comorbidities, compliance index, reasons for discontinuation of omalizumab). Reactions to omalizumab were classified as local and systemic, and their severity as mild, moderate or severe. Reactions were either immediate (minutes to hours after drug administration) or delayed (after days). Compliance to omalizumab, defined as Compliance index (CI), was calculated by comparing milligrams of given to milligrams of prescribed dose/ per year. RESULTS: Out of 35 patients receiving omalizumab, 15 drop out at different time points mostly due to treatment efficacy or appearance of new comorbidities. Patients who continue for the next ten years had mild to moderate adverse events related to omalizumab. There was no increased risk of severe adverse events during 10 years on omalizumab. Patient’s treatment tolerability, despite mild to moderate adverse events, is in favour of compliance. CONCLUSION: Compliance with omalizumab mildly decreased over 10 years but was not affected by severe adverse events of treatment or new comorbidities. Although, omalizumab is safe medicine appearance of new comorbidities has to be closely followed up

Global, regional, and national burden of chronic kidney disease, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout. Methods The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function. Findings Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, −1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, −1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function. Interpretation Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI

Most common, real life factors affecting effectiveness of omalizumab asthma treatment: a 10-year study

Aim To assess efficacy of omalizumab in moderate to severe asthma and notable factors affecting it, such as treatment compliance during the period of ten years. This retrospective, observational real life study is the first of this kind in the Gulf region and one of the worldwide rare long term omalizumab treatment studies. Methods The treatment for 35 patients started in 2008. Twenty patients (ongoing group) proceeded with treatment and were assessed annually until 2017. Reasons for treatment discontinuation in 15 patients (drop-out group) were also assessed. Results Before starting omalizumab the ongoing group of patients had history of ≥2 asthma exacerbations per year, which significantly decreased during the first year of the treatment (p<0.001), and for 14 (70%) patients ≤1 exacerbation stayed during the next 10 years. Since 2014 six (30%) patients had had ≥2 annual asthma exacerbations (p<0.05 in 2013; p<0.05 in 2014; p<0.001 in 2015; p<0.01 in 2016; p<0.001 in 2017). At the same time there was a significant drop in compliance index (CI) (p<0.0001). Conclusion To our knowledge this is the first 10-year study of compliance and effectiveness, which may help finalize some practical suggestions to improve CI in clinical practice and to note acceptable variation in CI. It is important to recognize factors that can possibly affect effectiveness of the treatment and identify the patients who will have the best benefit from a long term omalizumab treatment

Uncommon presentation of complicated internal hernia through the appendices epiploicae ring of adhesion: a clinical case study

Background: Internal hernias are infrequent, yet serious, medical conditions with potentially severe consequences. An internal hernia resulting from an Appendices epiploicae (AE) ring is an especially rare cause, with a mere nine documented instances worldwide. Case report: This report presents the case of a 58-year-old male who suffered from an internal hernia originating from an AE ring. The condition led to a gangrenous small bowel, which was treated by laparotomy and resection of the affected segment, followed by primary anastomosis. The post-operative recovery was favorable. Conclusion: Internal hernias, although rare, warrant immediate attention and early intervention to preclude detrimental outcomes, as illustrated in this particular case

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Healthcare Management In Promoting Role Of Paramedics And Nurses In Critical Care; Review

Healthcare unit managers play a crucial role in promoting the importance of paramedics and nurses in critical care. They are responsible for ensuring the health and well-being of nurses and paramedics, as well as maintaining high-quality care. However, there is a lack of research focused on the actions and organizational strategies employed by healthcare unit managers to support nurses, as well as the specific working environments that facilitate such support. This paper utilizes a mixed methods approach, combining qualitative interviews and quantitative surveys with healthcare unit managers and nurses. The findings highlight the crucial role of healthcare unit managers\u27 accessibility to their nursing staff in promoting nurses. Additionally, the study emphasizes the importance of responsive support from the care unit managers\u27 superiors, administration, and managerial colleagues in creating favorable working conditions. The care unit manager\u27s own support was highly supported by the superior manager, and this support was positively connected with nurses

Systemic Corticosteroids in Asthma : A Call to Action From World Allergy Organization and Respiratory Effectiveness Group

Acknowledgments This manuscript was endorsed by the World Allergy Organization and the Respiratory Effectiveness Group. Editorial support was funded by AstraZeneca and was provided by Katherine Hardy, PhD of Helios Medical Communications, Oxford, Oxfordshire, UK Funding This manuscript was funded by a grant from AstraZeneca. The authors retained full control. AstraZeneca provided a review for scientific accuracy and did not participate in the content development.Peer reviewedPublisher PD