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Health services delivery for IBD should take into consideration these patients' perspectives. A focus on improving patient education in these areas could help empower patients and alleviate doubts resulting in better disease management and improved healthcare outcomes.
The success of the Fontan procedure has led to increased survival of patients born with certain congenital heart disease to the point that new sequlae, as a result of Fontan circulation, are being discovered. Included among these is Fontan-associated liver disease (FALD). The purpose of this review is to present available literature on the perioperative management of the combined heart--liver transplantation (CHLT) in patients with FALD.
The perioperative management of a combined heart-liver transplant in a patient with Fontan circulation is complex. The patient is at risk for hemodynamic disturbances, significant blood loss, coagulopathies, and metabolic derangements. The maintenance of an appropriate transpulmonary pressure gradient is paramount to success. Postoperative management should be accomplished by a multidisciplinary care team. Limited series have demonstrated good outcomes in patients who have undergone CHLT.
The perioperative management of CHLT in patients with FALD is complex and available literature is limited. Future studies are needed to further assess proper perioperative management of patients with FALD who undergo CHLT.
The perioperative management of CHLT in patients with FALD is complex and available literature is limited. Future studies are needed to further assess proper perioperative management of patients with FALD who undergo CHLT.
To summarize the evolution of skin xenotransplantation and contextualize technological advances and the status of clinically applicable large animal research as well as prospects for translation of this work as a viable future treatment option.
Porcine xenografts at the start of the millennium were merely biologic dressings subject to rapid rejection. Since then, numerous important advances in swine to nonhuman primate models have yielded xenotransplant products at the point of clinical translation. Critical genetic modifications in swine from a designated pathogen-free donor herd have allowed xenograft survival reaching 30 days without preconditioning or maintenance immunosuppression. Further, xenograft coverage appears not to sensitize the recipient to subsequent allograft placement and vice versa, allowing for temporary coverage times to be doubled using both xeno and allografts.
Studies in large animal models have led to significant progress in the creation of living, functional skin xenotransplants with clinically relevant shelf-lives to improve the management of patients with extensive burns.
Studies in large animal models have led to significant progress in the creation of living, functional skin xenotransplants with clinically relevant shelf-lives to improve the management of patients with extensive burns.
Human islet transplantation has proven to be a highly effective treatment for patients with labile type 1 diabetes mellitus, which can free patients from daily glucose monitoring and insulin injections. selleck chemical However, the shortage of islet donors limits its' broad application. Porcine islet xenotransplantation presents a solution to the donor shortage and recent advances in genetic modification and immunosuppressive regimens provide renewed enthusiasm for the potential of this treatment.
Advances in genetic editing technology are leading to multigene modified porcine islet donors with alterations in expression of known xenoantigens, modifications of their complement and coagulation systems, and modifications to gain improved immunological compatibility. Recent NHP-based trials of costimulation blockade using CD154 blockade show promising improvements in islet survival, whereas results targeting CD40 are less consistent. Furthermore, trials using IL-6 receptor antagonism have yet to demonstrate improvement in glucose control and suffer from poor graft revascularization.
This review will detail the current status of islet xenotransplantation as a potential treatment for type I diabetes mellitus, focusing on recent advances in porcine xenogeneic islet production, assessment in nonhuman primate preclinical models, the outcome of human clinical trials and review barriers to translation of xenoislets to the clinic.
This review will detail the current status of islet xenotransplantation as a potential treatment for type I diabetes mellitus, focusing on recent advances in porcine xenogeneic islet production, assessment in nonhuman primate preclinical models, the outcome of human clinical trials and review barriers to translation of xenoislets to the clinic.
Recent attempts at mapping Typhoid epidemiology have revealed an enormous burden of disease in developing countries. Countries hitherto believed to have a low incidence, such as the African subcontinent, on accurate mapping were found to have a significant burden of disease. Drug resistance, because of rampant overuse of antibiotics, has driven selection pressure to extensively drug-resistant typhoid becoming a reality in the Indian subcontinent. With widespread travel, importation of this variety of typhoid to nonendemic countries is likely to lead to outbreaks in a nonimmune population.
A strain of extensively drug-resistant Salmonella Typhi isolated in Pakistan in 2016 has been responsible for multiple outbreaks in Pakistan and multiple travel-related cases all over the world in United States, UK, and Australia. This novel strain belongs to H58 lineage harbouring a plasmid encoding additional resistance elements like blaCTX-M-15 and a qnrS fluoroquinolone resistance gene. This resistance pattern has rendered many therapeutic options like Ceftriaxone and Fluoroquinolones clinically inactive impacting care in endemic and traveller populations alike.
Changing epidemiology and drug resistance in typhoid indicates that it may be prudent to vaccinate nonimmune travellers travelling to typhoid endemic areas, especially the Indian subcontinent.
Changing epidemiology and drug resistance in typhoid indicates that it may be prudent to vaccinate nonimmune travellers travelling to typhoid endemic areas, especially the Indian subcontinent.
Giardiasis remains a common cause of diarrhea and intestinal enteropathy globally. Here we give an overview of clinical treatment studies and discuss potential mechanisms and molecular targets for in-vitro testing of drug resistance.
Giardia is a cause of disease both in diarrheal and nondiarrheal cases. The prevalence of treatment refractory giardiasis is increasing. Recent studies reveal 5-nitroimidazole refractory infection occurs in up to 50% of cases. Mechanisms of drug resistance are not known. Placebo controlled studies of drug efficacy, taking the self-limiting course of giardiasis into account, has not been reported. No randomized controlled trials of treatment of refractory infection have been performed the last 25 years. link2 Based on the clinical studies reported, combination treatment with a 5-nitroimidazole and a benzimidazole is more effective than repeated courses of 5-nitroimidazole or monotherapies in refractory cases. Quinacrine is effective in refractory cases, but potentially severe side effects limit its use.
A combination of a 5-nitroimidazole and albendazole or mebendazole, and quinacrine monotherapy, are rational choices in nitroimidazole refractory infections, but randomized controlled studies are needed. Further research into more recent clinical isolates is necessary to uncover mechanisms for the increase in metronidazole refractory giardiasis observed during the last decade.
A combination of a 5-nitroimidazole and albendazole or mebendazole, and quinacrine monotherapy, are rational choices in nitroimidazole refractory infections, but randomized controlled studies are needed. Further research into more recent clinical isolates is necessary to uncover mechanisms for the increase in metronidazole refractory giardiasis observed during the last decade.
Focusing on the key developments since January 2019, this review aims to inform policymakers and clinical practitioners on the latest on evolving global polio epidemiology and scientific advancements to guide strategies for eradication.
An upsurge in wild poliovirus type 1 cases in Pakistan and Afghanistan and an expansion of type 2 circulating vaccine-derived poliovirus transmission in multiple countries threaten the remarkable progress made over past several decades by the global eradication program. These challenges have also spurred innovation on multiple fronts, including earlier detection, enhanced environmental surveillance and safer and more affordable vaccine options.
A concerted effort to adapt program strategies to address context-specific challenges and continued focus on innovations to enhance detection and response capabilities will be the key to achieve and sustain eradication of all types of polioviruses.
A concerted effort to adapt program strategies to address context-specific challenges and continued focus on innovations to enhance detection and response capabilities will be the key to achieve and sustain eradication of all types of polioviruses.
Several types of Escherichia coli cause acute diarrhea in humans and are responsible for a large burden of disease globally. The purpose of this review is to summarize diarrheagenic Escherichia coli (DEC) pathotype definitions and discuss existing and emerging molecular, genomic, and gut microbiome methods to detect, define, and study DEC pathotypes.
DEC pathotypes are currently diagnosed by molecular detection of unique virulence genes. However, some pathotypes have defied coherent molecular definitions because of imperfect gene targets, and pathotype categories are complicated by hybrid strains and isolation of pathotypes from asymptomatic individuals. Recent progress toward more efficient, sensitive, and multiplex DEC pathotype detection has been made using emerging PCR-based technologies. Genomics and gut microbiome detection methods continue to advance rapidly and are contributing to a better understanding of DEC pathotype diversity and functional potential.
DEC pathotype categorizations and detection methods are useful but imperfect. The implementation of molecular and sequence-based methods and well designed epidemiological studies will continue to advance understanding of DEC pathotypes. Additional emphasis is needed on sequencing DEC genomes from regions of the world where they cause the most disease and from the pathotypes that cause the greatest burden of disease globally.
DEC pathotype categorizations and detection methods are useful but imperfect. link3 The implementation of molecular and sequence-based methods and well designed epidemiological studies will continue to advance understanding of DEC pathotypes. Additional emphasis is needed on sequencing DEC genomes from regions of the world where they cause the most disease and from the pathotypes that cause the greatest burden of disease globally.
To review the roles of enteric adenovirus types 40 and 41 and nonenteric adenoviruses in the global burden of pediatric diarrhea.
Large studies using highly sensitive, type-specific molecular diagnostics have demonstrated a substantial and previously under-estimated burden of pediatric diarrheal disease because of enteric infections with adenovirus types 40/41. However, the true epidemiology of adenovirus 40/41 remains incompletely understood. Similarly, additional adenovirus types may also be implicated as agents of community-acquired pediatric gastroenteritis but current data are too limited to elucidate their epidemiological role(s), if any.
Efforts at global diarrhea control in low-income and middle-income countries will require combating pediatric gastroenteritis because of enteric adenovirus infections. Future research in these settings using type-specific molecular diagnostics or strain genotyping to fully characterize the epidemiology of adenovirus 40/41 infections, identify non-40/41 adenoviruses significantly associated with gastroenteritis, and develop vaccines effective at preventing adenovirus diarrhea is warranted.
