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Archives of Pathology & Laboratory... Jan 2022Because granulomas are represented in almost every disease category, the number of clinically and pathologically important granulomatous pulmonary diseases is large.... (Review)
Review
CONTEXT.—
Because granulomas are represented in almost every disease category, the number of clinically and pathologically important granulomatous pulmonary diseases is large. Their diagnosis by pathologists is particularly challenging because of their nonspecificity. A specific diagnosis can be achieved only when a granuloma-inciting agent(s) (eg, acid-fast bacilli, fungi, foreign bodies, etc) are identified microscopically or by culture; this does not occur in most cases. Furthermore, a specific diagnosis cannot be reached in a high percentage of cases. Although sarcoidosis and infectious diseases account for approximately half of pulmonary granulomatous diseases worldwide, there is significant geographic variation in their prevalence.
OBJECTIVES.—
To present updated information to serve as a guide to pathologic diagnosis of pulmonary granulomatous diseases, to address some commonly held misconceptions and to stress the importance of multidisciplinary coordination. Presentation of basic aspects of granulomas is followed by discussion of specific disease entities, such as tuberculous and nontuberculous Mycobacterial infections, fungal, bacterial, and parasitic infections, sarcoidosis, necrotizing sarcoid granulomatosis, berylliosis, hypersensitivity pneumonitis, hot tub lung, rheumatoid nodule, bronchocentric granulomatosis, aspirated, inhaled, and embolized foreign bodies, drug-induced granulomas, chronic granulomatous disease, common variable immunodeficiency, and granulomatous lesions associated with various types of cancer.
DATA SOURCES.—
Review of pertinent medical literature using the PubMed search engine and the author's practical experience.
CONCLUSIONS.—
Although the diagnosis of granulomatous lung diseases continues to present significant challenges to pathologists, the information presented in this review can be helpful in overcoming them. The importance of multidisciplinary coordination in cases where morphologic diagnosis is not possible cannot be overstated.
Topics: Alveolitis, Extrinsic Allergic; Granuloma; Humans; Lung; Lung Diseases; Sarcoidosis
PubMed: 33905479
DOI: 10.5858/arpa.2020-0543-RA -
Qatar Medical Journal 2019Sepsis, a medical emergency and life-threatening disorder, results from abnormal host response to infection that leads to acute organ dysfunction. Sepsis is a major...
Sepsis, a medical emergency and life-threatening disorder, results from abnormal host response to infection that leads to acute organ dysfunction. Sepsis is a major killer across all ages and countries and remains the most common cause of admission and death in the Intensive Care Unit (ICU). The true incidence remains elusive and estimates of the global burden of sepsis remain a wild guess. One study suggested over 19 million cases and 5 million sepsis-related deaths annually. Addressing the challenge, the World Health Assembly of the World Health Organisation (WHO) passed a resolution on better prevention, diagnosis, and management of sepsis. Despite thousands of articles and hundreds of trials, sepsis remains a major killer. The cornerstones of sepsis care remain early recognition, adoption of a systematic evidence-based bundle of care, and timely escalation to higher level of care. The bundle approach has been advocated since 2004 but underwent major modifications in subsequent years with more emphasis on the time-critical nature of sepsis and need to restore physiological variables within one hour of recognition. A shift from a three and six-hour bundle to one-hour bundle has been recommended. This single hour approach has been faced with an outcry and been challenged. Over several decades, the individual components of the sepsis bundle have not changed. Encountering a patient with suspected sepsis, one should measure lactate, obtain blood cultures, swiftly administer broad spectrum antimicrobials and fluids, and infuse vasopressors. A critical question arises: should we do this for all patients? Sepsis is not septic shock and guidelines did not make distinctive recommendations for each. Septic patients will present differently with some having more subtle signs and symptoms. Phenotypically, we do not know which patient with infection will develop a dysregulated host response and will succumb to sepsis and/or shock. The existing bundle lacks high quality evidence to support its recommendations and a blanket implementation for all patients with 'suspected' sepsis could be harmful. Indeed, a significant reduction of sepsis and septic shock in Australia and New Zealand was observed in a bundle-free region. Upon arrival in the ED, patients will be triaged. This is 'time zero'. Those with hypotension and hypoperfusion will be easily recognised and at most need to receive emergent care. Sepsis, per se, may not manifest clear cut signs and expertise to identify it is required. Those with non-specific symptoms may trigger an early warning scoring system and receive unnecessary antimicrobials and a large volume of intravenous (IV) fluids. Both therapies are not without significant side effects. Putting pressure on ED physicians to implement the 60-minute bundle without individualisation of care puts our patients at risk. Given the heterogenous nature and diverse pathobiological pathways, sepsis diagnosis can be challenging and both over and under-treatment can result. Established biomarkers such as procalcitonin and C-reactive protein lack specificity to rule out infection as the cause of inflammation. Currently, no laboratory test or biomarker helps predict which patients with infection or inflammation will develop organ dysfunction. A dire need for a specific sepsis biomarker exists. Modern molecular-based technologies are evolving and utilise polymerase chain reaction (PCR), nanotechnology, and microfluidics for point-of-care testing. Some devices identify causative microorganisms and their sensitivity in less than an hour. Catecholamines along with IV fluids are indicated to restore perfusion. However, inadvertent side effects may arise, especially at higher doses. Anti-adrenergic ß-blockers improve cardiac performance, enhance receptor responsiveness, and possess anti-inflammatory action. All are desirable in patients with septic shock. One randomised trial showed beneficial and protective effects of ß-blockers in septic shock. Rapidly acting titratable agents should be used in conjunction with appropriate hemodynamic monitoring and after adequate volume resuscitation. There is no consensus on target heart rate but an arbitrary cut off of 80-95 beats per minute is reasonable. Fluid resuscitation is the cornerstone of sepsis management. There is also compelling evidence that too much fluid is bad. Starch-based colloids should not be used in septic shock. Albumin is an alternative when large volumes are required but is not appropriate in traumatic brain injury. Balanced, less chloride and less acidic crystalloids are safer for the kidneys and are preferred over normal saline. Doses of IV fluids should be tailored to the patient's condition and a 30 ml/kg recommendation should be reviewed. Effective sepsis management requires adequate dosing of antimicrobials. Significant alteration of pharmacokinetics and pharmacodynamics is characteristic of septic shock. Accurate and effective dosing is challenging particularly in patients with multiple comorbidities and those receiving extracorporeal organ support. Underdosing results in treatment failure, whilst overdosing leads to toxicity and the risk of developing multi-drug resistant organisms. An individualised approach supported by therapeutic drug monitoring is suggested to ensure clinical efficacy. The search for a cure for sepsis is ongoing. A large prospective, randomised two-arm, parallel group study aims to recruit over 200 patients with septic shock across critical care units in Qatar. Evaluation of Hydrocortisone, Vitamin C, and Thiamine (HYVITS) examines the safety and efficacy of this triple therapy. Children are particularly vulnerable to sepsis. 1 in 6 children admitted with septic shock to ICU will die. As the majority of paediatric sepsis cases are community acquired, there is a strong need to raise awareness both for families and primary healthcare providers. Akin to adults, a bundle-approach to paediatric sepsis is strongly encouraged. National programs for paediatric sepsis have been established. The Qatar paediatric multidisciplinary sepsis program was established under the umbrella of the adult programme in 2017. A structured and standardised approach to sepsis across all neonate and paediatric facilities has been developed and implemented. Improvement in timely sepsis recognition and administration of antimicrobials within the golden hour has been observed. The program aims to achieve a 95% compliance to the paediatric sepsis bundle by the end of 2019. A screening tool and order set have been put in place and are presented in this special issue of Qatar Medical Journal. Pregnancy and childbirth are risk factors for sepsis. Multi-organ failure and death can result from puerperal sepsis. Sepsis is the direct and leading cause of maternal mortality in the UK. Attention to maternal sepsis with a tailored approach is encouraged. The Qatar National Sepsis Program developed a sepsis care pathway for pregnant women and during their early post-partum period. A broader, national -or better yet- a global approach to further sepsis management and outcome should be considered. There are a number of significant challenges to address. One such challenge is the inconsistency of the operational definition and diagnostic approaches for sepsis including coding and documentation. Significant deficiencies in healthcare systems have been highlighted by sepsis. This is most obvious in medium- and low-income countries. A major limitation to effective sepsis management is inadequate medical staffing and poor knowledge and awareness of sepsis. Both have a negative impact on sepsis outcome. Poor medical facilities in many countries pose significant challenges to sepsis care. Lack of critical care capacity - a global phenomenon - has been linked to poor outcome of sepsis cases and septic shock. This could be attributed to provision of suboptimal critical care, monitoring and critical interventions outside of the ICU. ICU availability is subject to inconsistency and inequity. Lack of adequate surgical capacity to accomplish timely source control adversely affects sepsis management. This, unfortunately, in medium- and low-income countries, is accompanied by inadequate medical supplies, diagnostic capacity, and manpower which increases sepsis mortality and morbidity. Antimicrobials are critical for sepsis care. A global concern is the development of multi-drug resistant organisms and the lack of novel antimicrobials and this adds pressure on those caring for septic patients. Effective antimicrobials should be utilised to eradicate infections. Misuse, inadequacy, inferior agents, and lack of timely access to effective and affordable agents significantly hinders patient's recovery from sepsis. Optimum sepsis outcome mandates attention to acute sepsis complications (e.g. acute renal or respiratory failure) as well as addressing post-discharge complications and disability. These challenging issues remain poorly studied or addressed. Sepsis and septic shock are major global health concerns. Progress has been achieved in understanding this life-threatening syndrome at a biological, metabolic, and cellular level. Efforts should be coordinated to improve sepsis care. Better and more accurate diagnostics are needed and governments are encouraged to invest in sepsis research and care. More integrated, inclusive, and focused research is desperately needed. Public education and increased awareness among primary healthcare providers are also critical to improve sepsis outcome.
PubMed: 31763206
DOI: 10.5339/qmj.2019.qccc.4 -
The Journal of Antimicrobial... Jul 2023Invasive candidiasis (IC) is a serious infection caused by several Candida species, and the most common fungal disease in hospitals in high-income countries. Despite... (Review)
Review
Invasive candidiasis (IC) is a serious infection caused by several Candida species, and the most common fungal disease in hospitals in high-income countries. Despite overall improvements in health systems and ICU care in the last few decades, as well as the development of different antifungals and microbiological techniques, mortality rates in IC have not substantially improved. The aim of this review is to summarize the main issues underlying the management of adults affected by IC, focusing on specific forms of the infection: IC developed by ICU patients, IC observed in haematological patients, breakthrough candidaemia, sanctuary site candidiasis, intra-abdominal infections and other challenging infections. Several key challenges need to be tackled to improve the clinical management and outcomes of IC patients. These include the lack of global epidemiological data for IC, the limitations of the diagnostic tests and risk scoring tools currently available, the absence of standardized effectiveness outcomes and long-term data for IC, the timing for the initiation of antifungal therapy and the limited recommendations on the optimal step-down therapy from echinocandins to azoles or the total duration of therapy. The availability of new compounds may overcome some of the challenges identified and increase the existing options for management of chronic Candida infections and ambulant patient treatments. However, early identification of patients that require antifungal therapy and treatment of sanctuary site infections remain a challenge and will require further innovations.
Topics: Humans; Adult; Antifungal Agents; Echinocandins; Candidiasis, Invasive; Candidemia
PubMed: 37220664
DOI: 10.1093/jac/dkad139 -
Wellcome Open Research 2022Human infection (or challenge) studies involve the intentional administration of a pathogen (challenge agent) to volunteers. The selection, isolation, development and...
Human infection (or challenge) studies involve the intentional administration of a pathogen (challenge agent) to volunteers. The selection, isolation, development and production of the challenge agent is one of the first steps in developing a challenge study and critical for minimising the risk to volunteers. Regulatory oversight for this production differs globally. Manufacturing agents within a Good Manufacturing Practice (GMP) facility reduces the risk of the manufacturing process by including processes such as confirming the identity of the challenge agent and ascertaining that it's pure and free from impurities. However, in some cases it's not possible or feasible to manufacture to GMP standards, for example where the challenge agent requires an intermediate vector for growth. There is lack of clear guidance on what the minimum requirements for high-quality safe manufacture outside of GMP facilities should be and here we describe the development of a considerations document for the selection and production of challenge agents to meet this need.
PubMed: 35505774
DOI: 10.12688/wellcomeopenres.17869.1 -
Acta Biomaterialia Apr 2020Globally, chronic wounds impose a notable burden to patients and healthcare systems. Such skin wounds are readily subjected to bacteria that provoke inflammation and... (Review)
Review
Globally, chronic wounds impose a notable burden to patients and healthcare systems. Such skin wounds are readily subjected to bacteria that provoke inflammation and hence challenge the healing process. Furthermore, bacteria induce infection impeding re-epithelialization and collagen synthesis. With an estimated global market of $20.4 billion by 2021, appropriate wound dressing materials e.g. those composed of biopolymers originating from nature, are capable of alleviating the infection incidence and of accelerating the healing process. Particularly, biopolymeric nanofibrous dressings are biocompatible and mostly biodegradable and biomimic the extracellular matrix structure. Such nanofibrous dressings provide a high surface area and the ability to deliver antibiotics and antibacterial agents locally into the wound milieu to control infection. In this regard, with the dangerous evolution of antibiotic resistant bacteria, antibiotic delivery systems are being gradually replaced with antibacterial biohybrid nanofibrous wound dressings. This emerging class of wound dressings comprises biopolymeric nanofibers containing antibacterial nanoparticles, nature-derived compounds and biofunctional agents. Here, the most recent (since 2015) developments of antibacterial biopolymeric nanofibrous wound dressings, particularly those made of biohybrids, are reviewed and their antibacterial efficiency is evaluated based on a comprehensive literature analysis. Lastly, the prospects and challenges are discussed to draw a roadmap for further progresses and to open up future research avenues in this area. STATEMENT OF SIGNIFICANCE: With a global market of $20.4 billion by 2021, skin wound dressings are a crucial segment of the wound care industry. As an advanced class of bioactive wound dressing materials, natural polymeric nanofibers loaded with antibacterial agents, e.g. antimicrobial nanoparticles/ions, nature-derived compounds and biofunctional agents, have shown a remarkable potential for replacement of their classic counterparts. Also, given the expanding concern regarding antibiotic resistant bacteria, such biohybrid nanofibrous wound dressings can outperform classical drug delivery systems. Here, an updated overview of the most recent (since 2015) developments of antibacterial biopolymeric nanofibrous wound dressings is presented. In this review, while discussing about the antibacterial efficiency of such systems, the prospects and challenges are highlighted to draw a roadmap for further progresses in this area.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bandages; Honey; Humans; Nanofibers; Oils, Volatile; Plant Extracts; Polysaccharides; Proteins; Wound Healing
PubMed: 32084600
DOI: 10.1016/j.actbio.2020.02.022 -
Frontiers in Robotics and AI 2021Multi-agent systems and multi-robot systems have been recognized as unique solutions to complex dynamic tasks distributed in space. Their effectiveness in accomplishing... (Review)
Review
Multi-agent systems and multi-robot systems have been recognized as unique solutions to complex dynamic tasks distributed in space. Their effectiveness in accomplishing these tasks rests upon the design of cooperative control strategies, which is acknowledged to be challenging and nontrivial. In particular, the effectiveness of these strategies has been shown to be related to the so-called exploration-exploitation dilemma: i.e., the existence of a distinct balance between exploitative actions and exploratory ones while the system is operating. Recent results point to the need for a dynamic exploration-exploitation balance to unlock high levels of flexibility, adaptivity, and swarm intelligence. This important point is especially apparent when dealing with fast-changing environments. Problems involving dynamic environments have been dealt with by different scientific communities using theory, simulations, as well as large-scale experiments. Such results spread across a range of disciplines can hinder one's ability to understand and manage the intricacies of the exploration-exploitation challenge. In this review, we summarize and categorize the methods used to control the level of exploration and exploitation carried out by an multi-agent systems. Lastly, we discuss the critical need for suitable metrics and benchmark problems to quantitatively assess and compare the levels of exploration and exploitation, as well as the overall performance of a system with a given cooperative control algorithm.
PubMed: 35178430
DOI: 10.3389/frobt.2021.771520 -
JMIR MHealth and UHealth Jul 2021As the world's population rapidly ages, the number of older adults with cognitive impairment will also increase. Several studies have identified numerous complex needs... (Review)
Review
BACKGROUND
As the world's population rapidly ages, the number of older adults with cognitive impairment will also increase. Several studies have identified numerous complex needs of people with dementia, which assistive technologies still fail to support. Recent trends have led to an increasing focus on the use of embodied conversational agents (ECAs) as virtual entities able to interact with a person through natural and familiar verbal and nonverbal communication. The use of ECAs could improve the accessibility and acceptance of assistive technologies matching those high-level needs that are not well covered to date.
OBJECTIVE
The aim of this thematic literature analysis was to map current studies in the field of designing ECAs for patients with dementia in order to identify the existing research trend and possible gaps that need to be covered in the near future. The review questions in this study were as follows: (1) what research frameworks are used to study the interaction between patients with dementia and ECAs? (2) what are the findings? and (3) what are the barriers reported in these studies?
METHODS
Separate literature searches were conducted in PubMed, Web of Science, Scopus, and Embase databases by using specific umbrella phrases to target the population (patients with dementia) and the technology-based intervention (embodied conversational agent). Studies that met the inclusion criteria were appraised through the Mixed Methods Appraisal Tool and then discussed in a thematic analysis.
RESULTS
The search process identified 115 records from the databases and study references. After duplicates (n=45) were removed, 70 papers remained for the initial screening. A total of 7 studies were finally included in the qualitative synthesis. A thematic analysis of the reviewed studies identified major themes and subthemes: the research frameworks used to gather users' perspectives on ECAs (theme 1), the insights shared by the 7 studies as well as the value of user involvement in the development phases and the challenge of matching the system functionalities with the users' needs (theme 2), and the main methodological and technical problems faced by each study team (theme 3).
CONCLUSIONS
Our thematic literature analysis shows that the field of ECAs is novel and poorly discussed in the scientific community and that more sophisticated study designs and proofs of efficacy of the approach are required. Therefore, by analyzing the main topic of the narrative review, this study underscores the challenge of synchronizing and harmonizing knowledge, efforts, and challenges in the dementia care field and its person-centered paradigm through the user-centered design approach. Enabling strict collaboration between interdisciplinary research networks, medical scientists, technology developers, patients, and their formal and informal caregivers is still a great challenge in the field of technologies for older adults.
Topics: Aged; Caregivers; Communication; Dementia; Humans
PubMed: 34269686
DOI: 10.2196/25381 -
Microbial Biotechnology Sep 2017Antibiotic resistant bacterial infections are a global public health challenge that has been increasing in severity and scope for the last few decades. Without creative... (Review)
Review
Antibiotic resistant bacterial infections are a global public health challenge that has been increasing in severity and scope for the last few decades. Without creative solutions to this problem, treatment of injuries and infections will become progressively more challenging. A better understanding of the human microbiome has led to a new appreciation for the role commensal microbes play in protecting us from pathogens, especially in the gut. Antibiotics lead to disruption of the gut microbial ecosystem, enabling colonization by antibiotic resistant bacterial pathogens. Many different lines of research have identified specific bacterial taxa and mechanisms that play a role in colonization resistance, and these lines of research may one day lead to microbial therapeutics targeting antibiotic resistant bacteria. Here, we discuss a few of these strategies and the challenges they will need to overcome in order to become an effective therapeutic.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Bacterial; Humans; Microbiota
PubMed: 28771951
DOI: 10.1111/1751-7915.12783 -
Clinics and Practice Mar 2023Telemedicine, telehealth, and E-health all offer significant benefits for pain management and healthcare services by fostering the physician-patient relationship in... (Review)
Review
Telemedicine, telehealth, and E-health all offer significant benefits for pain management and healthcare services by fostering the physician-patient relationship in otherwise challenging circumstances. A critical component of these artificial-intelligence-based health systems is the "agent-based system", which is rapidly evolving as a means of resolving complicated or straightforward problems. Multi-Agent Systems (MAS) are well-established modeling and problem-solving modalities that model and solve real-world problems. MAS's core concept is to foster communication and cooperation among agents, which are broadly considered intelligent autonomous factors, to address diverse challenges. MAS are used in various telecommunications applications, including the internet, robotics, healthcare, and medicine. Furthermore, MAS and information technology are utilized to enhance patient-centered palliative care. While telemedicine, E-health, and MAS all play critical roles in managing chronic pain, the published research on their use in treating chronic pain is currently limited. This paper discusses why telemedicine, E-health, and MAS are the most critical novel technologies for providing healthcare and managing chronic pain. This review also provides context for identifying the advantages and disadvantages of each application's features, which may serve as a useful tool for researchers.
PubMed: 36961067
DOI: 10.3390/clinpract13020042 -
Archives of Pathology & Laboratory... Dec 2017Historically, inhibitors to coagulation factor V (FV) most often have developed in patients treated with bovine thrombin, a topical hemostatic agent used during surgical... (Review)
Review
Historically, inhibitors to coagulation factor V (FV) most often have developed in patients treated with bovine thrombin, a topical hemostatic agent used during surgical procedures. With the advent of newer hemostatic agents, and the concurrent diminished use of bovine thrombin, the incidence of FV inhibitors has fallen. Nevertheless, FV inhibitors are occasionally seen on an idiopathic basis as well as in association with medications, malignancies, autoimmune disorders, pregnancy, and infections. Factor V inhibitors may present with life-threatening bleeding or thrombosis, or they may be discovered incidentally as a coagulation screening test abnormality. Management of patients with FV inhibitors is challenging and consists of control of bleeding and eradication of the inhibitor. In this short overview we review the role of platelet and plasma FV in hemostasis and discuss the unique characteristics, clinical features, diagnosis, treatment, and prognosis associated with FV inhibitors.
Topics: Animals; Autoantibodies; Cattle; Diagnosis, Differential; Factor V; Female; Hemorrhage; Hemostatics; Humans; Pregnancy; Thrombin
PubMed: 29189062
DOI: 10.5858/arpa.2016-0445-RS