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Therapeutic Advances in Gastroenterology Jan 2017Mitochondrial disorders (MIDs) due to respiratory-chain defects or nonrespiratory chain defects are usually multisystem conditions [mitochondrial multiorgan disorder... (Review)
Review
Mitochondrial disorders (MIDs) due to respiratory-chain defects or nonrespiratory chain defects are usually multisystem conditions [mitochondrial multiorgan disorder syndrome (MIMODS)] affecting the central nervous system (CNS), peripheral nervous system, eyes, ears, endocrine organs, heart, kidneys, bone marrow, lungs, arteries, and also the intestinal tract. Frequent gastrointestinal (GI) manifestations of MIDs include poor appetite, gastroesophageal sphincter dysfunction, constipation, dysphagia, vomiting, gastroparesis, GI pseudo-obstruction, diarrhea, or pancreatitis and hepatopathy. Rare GI manifestations of MIDs include dry mouth, paradontosis, tracheoesophageal fistula, stenosis of the duodeno-jejunal junction, atresia or imperforate anus, liver cysts, pancreas lipomatosis, pancreatic cysts, congenital stenosis or obstruction of the GI tract, recurrent bowel perforations with intra-abdominal abscesses, postprandial abdominal pain, diverticulosis, or pneumatosis coli. Diagnosing GI involvement in MIDs is not at variance from diagnosing GI disorders due to other causes. Treatment of mitochondrial GI disease includes noninvasive or invasive measures. Therapy is usually symptomatic. Only for myo-neuro-gastro-intestinal encephalopathy is a causal therapy with autologous stem-cell transplantation available. It is concluded that GI manifestations of MIDs are more widespread than so far anticipated and that they must be recognized as early as possible to initiate appropriate diagnostic work-up and avoid any mitochondrion-toxic treatment.
PubMed: 28286566
DOI: 10.1177/1756283X16666806 -
Langenbeck's Archives of Surgery Aug 2023Most studies on minimally invasive pancreatoduodenectomy (MIPD) combine patients with pancreatic and periampullary cancers even though there is substantial heterogeneity... (Meta-Analysis)
Meta-Analysis Review
The clinical implication of minimally invasive versus open pancreatoduodenectomy for non-pancreatic periampullary cancer: a systematic review and individual patient data meta-analysis.
BACKGROUND
Most studies on minimally invasive pancreatoduodenectomy (MIPD) combine patients with pancreatic and periampullary cancers even though there is substantial heterogeneity between these tumors. Therefore, this study aimed to evaluate the role of MIPD compared to open pancreatoduodenectomy (OPD) in patients with non-pancreatic periampullary cancer (NPPC).
METHODS
A systematic review of Pubmed, Embase, and Cochrane databases was performed by two independent reviewers to identify studies comparing MIPD and OPD for NPPC (ampullary, distal cholangio, and duodenal adenocarcinoma) (01/2015-12/2021). Individual patient data were required from all identified studies. Primary outcomes were (90-day) mortality, and major morbidity (Clavien-Dindo 3a-5). Secondary outcomes were postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), blood-loss, length of hospital stay (LOS), and overall survival (OS).
RESULTS
Overall, 16 studies with 1949 patients were included, combining 928 patients with ampullary, 526 with distal cholangio, and 461 with duodenal cancer. In total, 902 (46.3%) patients underwent MIPD, and 1047 (53.7%) patients underwent OPD. The rates of 90-day mortality, major morbidity, POPF, DGE, PPH, blood-loss, and length of hospital stay did not differ between MIPD and OPD. Operation time was 67 min longer in the MIPD group (P = 0.009). A decrease in DFS for ampullary (HR 2.27, P = 0.019) and distal cholangio (HR 1.84, P = 0.025) cancer, as well as a decrease in OS for distal cholangio (HR 1.71, P = 0.045) and duodenal cancer (HR 4.59, P < 0.001) was found in the MIPD group.
CONCLUSIONS
This individual patient data meta-analysis of MIPD versus OPD in patients with NPPC suggests that MIPD is not inferior in terms of short-term morbidity and mortality. Several major limitations in long-term data highlight a research gap that should be studied in prospective maintained international registries or randomized studies for ampullary, distal cholangio, and duodenum cancer separately.
PROTOCOL REGISTRATION
PROSPERO (CRD42021277495) on the 25th of October 2021.
Topics: Humans; Pancreaticoduodenectomy; Duodenal Neoplasms; Prospective Studies; Pancreas; Postoperative Complications; Laparoscopy; Pancreatic Neoplasms; Retrospective Studies
PubMed: 37581763
DOI: 10.1007/s00423-023-03047-4 -
Cytotherapy Apr 2021The therapeutic potential of naturally secreted micro- and nanoscale extracellular vesicles (EVs) makes them attractive candidates for regenerative medicine and... (Review)
Review
The therapeutic potential of naturally secreted micro- and nanoscale extracellular vesicles (EVs) makes them attractive candidates for regenerative medicine and pharmaceutical science applications. To date, the results of numerous publications have shown the practicality of using EVs to replace mesenchymal stromal cells (MSCs) or liposomes. This article presents a systematic review of pre-clinical studies conducted over the past decade of MSC-derived EVs (MSC-EVs) used in animal models of disease. The authors searched the relevant literature in the PubMed and Scopus databases (9358 articles), and 690 articles met the inclusion criteria. The eligible articles were placed in the following disease categories: autoimmune, brain, cancer, eye, gastrointestinal, heart, inflammation/transplantation, liver, musculoskeletal, pancreas, spinal cord and peripheral nervous system, respiratory system, reproductive system, skin, urinary system and vascular-related diseases. Next, the eligible articles were assessed for the rate of publication and global distribution, methodology of EV isolation and characterization, route of MSC-EV administration, length of follow-up, source of MSCs and animal species. The current review classifies and critically discusses the technical aspects of these MSC-EV animal studies and discusses potential relationships between methodological details and the effectiveness of MSC-EVs as reported by these pre-clinical studies.
Topics: Animals; Brain; Extracellular Vesicles; Inflammation; Mesenchymal Stem Cells; Regenerative Medicine
PubMed: 33541780
DOI: 10.1016/j.jcyt.2020.12.009 -
Inflammatory Bowel Diseases Apr 2024Patients undergoing organ transplantation are often on immunosuppressing medications to prevent rejection of the transplant. The data on use of concomitant... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients undergoing organ transplantation are often on immunosuppressing medications to prevent rejection of the transplant. The data on use of concomitant immunosuppression for inflammatory bowel disease (IBD) and organ transplant management are limited. This study sought to evaluate the safety of biologic and small molecule therapy for the treatment of IBD among solid organ transplant recipients.
METHODS
Medline, Embase, and Web of Science databases were systematically searched for studies reporting on safety outcomes associated with the use of biologic and small molecule therapy (infliximab, adalimumab, certolizumab, golimumab, vedolizumab, ustekinumab, and tofacitinib) in patients with IBD postsolid organ transplant (eg, liver, kidney, heart, lung, pancreas). The primary outcome was infectious complications. Secondary outcomes included serious infections, colectomy, and discontinuation of biologic therapy.
RESULTS
Seven hundred ninety-seven articles were identified for screening, yielding 16 articles for the meta-analyses with information on 163 patients. Antitumor necrosis factor α (Anti-TNFs; infliximab and adalimumab) were used in 8 studies, vedolizumab in 6 studies, and a combination of ustekinumab or vedolizumab and anti-TNFs in 2 studies. Two studies reported outcomes after kidney and cardiac transplant respectively, whereas the rest of the studies included patients with liver transplants. The rates of all infections and serious infections were 20.09 per 100 person-years (100-PY; 95% CI, 12.23-32.99 per 100-PY, I2 = 54%) and 17.39 per 100-PY (95% CI, 11.73-25.78 per 100-PY, I2 = 21%), respectively. The rates of colectomy and biologic medication discontinuation were 12.62 per 100-PY (95% CI, 6.34-25.11 per 100-PY, I2 = 34%) and 19.68 per 100-PY (95% CI, 9.97-38.84 per 100-PY, I2 = 74%), respectively. No cases of venous thromboembolism or death attributable to biologic use were reported.
CONCLUSION
Biologic therapy is overall well tolerated in patients with solid organ transplant. Long-term studies are needed to better define the role of specific agents in this patient population.
Topics: Humans; Adalimumab; Biological Products; Inflammatory Bowel Diseases; Infliximab; Organ Transplantation; Ustekinumab
PubMed: 37300512
DOI: 10.1093/ibd/izad108 -
Clinical and Applied... 2020Simultaneous pancreas-kidney (SPK) transplantation remains the most effective treatment for providing consistent and long-term euglycemia in patients having type 1...
Simultaneous pancreas-kidney (SPK) transplantation remains the most effective treatment for providing consistent and long-term euglycemia in patients having type 1 diabetes with renal failure. Thrombosis of the pancreatic vasculature continues to contribute significantly to early graft failure and loss. We compared the rate of thrombosis to graft loss and systematically reviewed risk factors impacting early thrombosis of the pancreas allograft following SPK transplantation. We searched the MEDLINE, EMBASE, The Cochrane Library, and PREMEDLINE databases for studies reporting thrombosis following pancreas transplantation. Identified publications were screened for inclusion and synthesized into a data extraction sheet. Sixty-three studies satisfied eligibility criteria: 39 cohort studies, 22 conference abstracts, and 2 meta-analyses. Newcastle-Ottawa Scale appraisal of included studies demonstrated cohort studies of low bias risk; 1127 thrombi were identified in 15 936 deceased donor, whole pancreas transplants, conferring a 7.07% overall thrombosis rate. Thrombosis resulted in pancreatic allograft loss in 83.3% of reported cases. This review has established significant associations between donor and recipient characteristics, procurement and preservation methodology, transplantation technique, postoperative management, and increased risk of early thrombosis in the pancreas allograft. Further studies examining the type of organ preservation fluid, prophylactic heparin protocol, and exocrine drainage method and early thrombosis should also be performed.
Topics: Female; Humans; Kidney Transplantation; Male; Pancreas Transplantation; Thrombosis; Transplantation, Homologous; Treatment Outcome
PubMed: 33052066
DOI: 10.1177/1076029620942589 -
Transplant International : Official... 2023Renal transplantation improves quality of life and prolongs survival in patients with end-stage kidney disease, although challenges exist due to the paucity of suitable... (Meta-Analysis)
Meta-Analysis Review
Renal transplantation improves quality of life and prolongs survival in patients with end-stage kidney disease, although challenges exist due to the paucity of suitable donor organs. This has been addressed by expanding the donor pool to include AKI kidneys. We aimed to establish whether transplanting such kidneys had a detrimental effect on graft outcome. The primary aim was to define early outcomes: delayed graft function (DGF) and primary non-function (PNF). The secondary aims were to define the relationship to acute rejection, allograft survival, eGFR and length of hospital stay (LOS). A systematic literature review and meta-analysis was conducted on the studies reporting the above outcomes from PubMed, Embase, and Cochrane Library databases. This analysis included 30 studies. There is a higher risk of DGF in the AKI group (OR = 2.20, < 0.00001). There is no difference in the risk for PNF (OR 0.99, = 0.98), acute rejection (OR 1.29, = 0.08), eGFR decline ( = 0.05) and prolonged LOS ( = 0.11). The odds of allograft survival are similar (OR 0.95, = 0.54). Transplanting kidneys from donors with AKI can lead to satisfactory outcomes. This is an underutilised resource which can address organ demand.
Topics: Humans; Kidney Transplantation; Quality of Life; Kidney; Tissue Donors; Acute Kidney Injury; Graft Survival; Delayed Graft Function; Retrospective Studies; Graft Rejection
PubMed: 37275464
DOI: 10.3389/ti.2023.11232 -
Journal of Nephrology Sep 2022Transplant nephropathology is a highly specialized field of pathology comprising both the evaluation of organ donor biopsy for organ allocation and post-transplant graft... (Review)
Review
BACKGROUND
Transplant nephropathology is a highly specialized field of pathology comprising both the evaluation of organ donor biopsy for organ allocation and post-transplant graft biopsy for assessment of rejection or graft damage. The introduction of digital pathology with whole-slide imaging (WSI) in clinical research, trials and practice has catalyzed the application of artificial intelligence (AI) for histopathology, with development of novel machine-learning models for tissue interrogation and discovery. We aimed to review the literature for studies specifically applying AI algorithms to WSI-digitized pre-implantation kidney biopsy.
METHODS
A systematic search was carried out in the electronic databases PubMed-MEDLINE and Embase until 25th September, 2021 with a combination of the key terms "kidney", "biopsy", "transplantation" and "artificial intelligence" and their aliases. Studies dealing with the application of AI algorithms coupled with WSI in pre-implantation kidney biopsies were included. The main theme addressed was detection and quantification of tissue components. Extracted data were: author, year and country of the study, type of biopsy features investigated, number of cases, type of algorithm deployed, main results of the study in terms of diagnostic outcome, and the main limitations of the study.
RESULTS
Of 5761 retrieved articles, 7 met our inclusion criteria. All studies focused largely on AI-based detection and classification of glomerular structures and to a lesser extent on tubular and vascular structures. Performance of AI algorithms was excellent and promising.
CONCLUSION
All studies highlighted the importance of expert pathologist annotation to reliably train models and the need to acknowledge clinical nuances of the pre-implantation setting. Close cooperation between computer scientists and practicing as well as expert renal pathologists is needed, helping to refine the performance of AI-based models for routine pre-implantation kidney biopsy clinical practice.
Topics: Algorithms; Artificial Intelligence; Biopsy; Humans; Intelligence; Kidney
PubMed: 35441256
DOI: 10.1007/s40620-022-01327-8 -
Journal of Tissue Engineering 2019A bioartificial endocrine pancreas is proposed as a future alternative to current treatment options. Patients with insulin-secretion deficiency might benefit. This is... (Review)
Review
A bioartificial endocrine pancreas is proposed as a future alternative to current treatment options. Patients with insulin-secretion deficiency might benefit. This is the first systematic review that provides an overview of scaffold materials and techniques for insulin-secreting cells or cells to be differentiated into insulin-secreting cells. An electronic literature survey was conducted in PubMed/MEDLINE and Web of Science, limited to the past 10 years. A total of 197 articles investigating 60 different materials met the inclusion criteria. The extracted data on materials, cell types, study design, and transplantation sites were plotted into two evidence gap maps. Integral parts of the tissue engineering network such as fabrication technique, extracellular matrix, vascularization, immunoprotection, suitable transplantation sites, and the use of stem cells are highlighted. This systematic review provides an evidence-based structure for future studies. Accumulating evidence shows that scaffold-based tissue engineering can enhance the viability and function or differentiation of insulin-secreting cells both in vitro and in vivo.
PubMed: 31700597
DOI: 10.1177/2041731419884708 -
Clinical Transplantation Oct 2022Portal inflow modulation (PIM) aimed at reducing portal hyperperfusion is commonly used in living donor liver transplantation (LDLT) to reduce the risk of small-for-size... (Review)
Review
Does modification of portal pressure and flow enhance recovery of the recipient after living donor liver transplantation? A systematic review of literature and expert panel recommendations.
BACKGROUND
Portal inflow modulation (PIM) aimed at reducing portal hyperperfusion is commonly used in living donor liver transplantation (LDLT) to reduce the risk of small-for-size syndrome (SFSS). Many different techniques, both pharmacological and surgical have been used for this purpose. There is, however, little consensus on the best method of PIM, its exact role in preventing SFSS and on early post-LDLT recovery.
OBJECTIVES
To identify whether modifications of portal pressures and flows enhance recovery after LDLT and to provide international expert panel recommendations.
DATA SOURCES
Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central.
METHODS
Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel.
PROSPERO ID
CRD42021260997.
RESULTS
Five hundred and ninety four articles were identified through databases' search. Of the 24 included for a final review by the working group (WG), there were five randomized control trials, four prospective studies and 15 retrospective series. Six outcome measures which were likely to influence early recovery after LDLT, especially in small-for-size grafts (SFSG) were shortlisted. These included acute kidney injury, SFSS, morbidity including sepsis, length of ICU and hospital stay, morbidity of the PIM technique and overall mortality. The WG noted that PIM in this subset of LDLT recipients had a beneficial effect on all the outcomes measures.
CONCLUSIONS
Considering all decision domains, the panel recommends pre- and intraoperative actual graft weight validation, portal pressure/flow measurements, and a comprehensive donor evaluation for the determination of potentially small-for-size/ small-for-flow grafts as mandatory. (Quality of Evidence: Moderate | Grade of Recommendation: Strong) Pharmacological PIM helps improve early renal function in LDLT recipients. (Quality of Evidence: High | Grade of Recommendation: Strong) In selected patients with SFSG, PIM helps reduce SFSS/EAD and sepsis. (Quality of Evidence: Moderate | Grade of Recommendation: Strong) PIM in the form of splenectomy has increased morbidity compared to splenic artery ligation (SAL). (Quality of Evidence: Low | Grade of Recommendation: Strong) In LDLT recipients with SFSG, PIM may help reduce morbidity/mortality. (Quality of Evidence: Low | Grade of Recommendation: Strong) In LDLT recipients with SFSG, modification of portal pressures and flows enhances recovery after LDLT. (Quality of Evidence: Moderate | Grade of Recommendation: Strong).
Topics: Humans; Living Donors; Liver Transplantation; Portal Pressure; Retrospective Studies; Prospective Studies; Graft Survival; Organ Size; Liver
PubMed: 35344628
DOI: 10.1111/ctr.14657 -
Transplant Infectious Disease : An... Dec 2022We aimed to analyze the humoral and cellular response to standard and booster (additional doses) COVID-19 vaccination in solid organ transplantation (SOT) and the risk... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We aimed to analyze the humoral and cellular response to standard and booster (additional doses) COVID-19 vaccination in solid organ transplantation (SOT) and the risk factors involved for an impaired response.
METHODS
We did a systematic review and meta-analysis of studies published up until January 11, 2022, that reported immunogenicity of COVID-19 vaccine among SOT. The study is registered with PROSPERO, number CRD42022300547.
RESULTS
Of the 1527 studies, 112 studies, which involved 15391 SOT and 2844 healthy controls, were included. SOT showed a low humoral response (effect size [ES]: 0.44 [0.40-0.48]) in overall and in control studies (log-Odds-ratio [OR]: -4.46 [-8.10 to -2.35]). The humoral response was highest in liver (ES: 0.67 [0.61-0.74]) followed by heart (ES: 0.45 [0.32-0.59]), kidney (ES: 0.40 [0.36-0.45]), kidney-pancreas (ES: 0.33 [0.13-0.53]), and lung (0.27 [0.17-0.37]). The meta-analysis for standard and booster dose (ES: 0.43 [0.39-0.47] vs. 0.51 [0.43-0.54]) showed a marginal increase of 18% efficacy. SOT with prior infection had higher response (ES: 0.94 [0.92-0.96] vs. ES: 0.40 [0.39-0.41]; p-value < .01). The seroresponse with mRNA-12723 mRNA was highest 0.52 (0.40-0.64). Mycophenolic acid (OR: 1.42 [1.21-1.63]) and Belatacept (OR: 1.89 [1.3-2.49]) had highest risk for nonresponse. SOT had a parallelly decreased cellular response (ES: 0.42 [0.32-0.52]) in overall and control studies (OR: -3.12 [-0.4.12 to -2.13]).
INTERPRETATION
Overall, SOT develops a suboptimal response compared to the general population. Immunosuppression including mycophenolic acid, belatacept, and tacrolimus is associated with decreased response. Booster doses increase the immune response, but further upgradation in vaccination strategy for SOT is required.
Topics: Humans; Abatacept; COVID-19; COVID-19 Vaccines; Mycophenolic Acid; Organ Transplantation; Transplant Recipients
PubMed: 35924679
DOI: 10.1111/tid.13926