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Communications Medicine Apr 2024Islet autoantibodies form the foundation for type 1 diabetes (T1D) diagnosis and staging, but heterogeneity exists in T1D development and presentation. We hypothesized...
BACKGROUND
Islet autoantibodies form the foundation for type 1 diabetes (T1D) diagnosis and staging, but heterogeneity exists in T1D development and presentation. We hypothesized that autoantibodies can identify heterogeneity before, at, and after T1D diagnosis, and in response to disease-modifying therapies.
METHODS
We systematically reviewed PubMed and EMBASE databases (6/14/2022) assessing 10 years of original research examining relationships between autoantibodies and heterogeneity before, at, after diagnosis, and in response to disease-modifying therapies in individuals at-risk or within 1 year of T1D diagnosis. A critical appraisal checklist tool for cohort studies was modified and used for risk of bias assessment.
RESULTS
Here we show that 152 studies that met extraction criteria most commonly characterized heterogeneity before diagnosis (91/152). Autoantibody type/target was most frequently examined, followed by autoantibody number. Recurring themes included correlations of autoantibody number, type, and titers with progression, differing phenotypes based on order of autoantibody seroconversion, and interactions with age and genetics. Only 44% specifically described autoantibody assay standardization program participation.
CONCLUSIONS
Current evidence most strongly supports the application of autoantibody features to more precisely define T1D before diagnosis. Our findings support continued use of pre-clinical staging paradigms based on autoantibody number and suggest that additional autoantibody features, particularly in relation to age and genetic risk, could offer more precise stratification. To improve reproducibility and applicability of autoantibody-based precision medicine in T1D, we propose a methods checklist for islet autoantibody-based manuscripts which includes use of precision medicine MeSH terms and participation in autoantibody standardization workshops.
PubMed: 38582818
DOI: 10.1038/s43856-024-00478-y -
Journal of Clinical Medicine Nov 2023Patients with locally advanced gastric cancer (LAGC) often require multivisceral resection (MVR) of the involved organs to achieve R0 resection and local disease... (Review)
Review
Patients with locally advanced gastric cancer (LAGC) often require multivisceral resection (MVR) of the involved organs to achieve R0 resection and local disease control. The aim of the present study was to systematically review all available literature on the postoperative and long-term outcomes of MVR for gastric cancer. The PubMed database was systematically searched by two independent investigators for studies concerning MVR for LAGC. In total, 30 original studies with 3362 patients met our inclusion criteria. R0 resection was achieved in 67.77% (95% CI, 65.75-69.73%) of patients. The spleen, colon and pancreas comprised the most frequently resected organs in the context of MVR. Pancreatic fistulae (10.08%, 95% CI, 7.99-12.63%), intraabdominal abscesses (9.92%, 95% CI, 7.85-12.46%) and anastomotic leaks (8.09%, 95% CI, 6.23-10.45%) constituted the most common postoperative complications. Using the available data, we estimated the mean 1-year survival at 62.2%, 3-year survival at 33.05%, and 5-year survival at 30.21% for the entire cohort. The survival rates were mainly correlated with lymphatic invasion, tumor size and patient age. Therefore, gastrectomy, together with MVR, is feasible and may offer a survival advantage compared to gastrectomy alone or no other surgical treatment in a selected group of patients. Consequently, both patient and tumor characteristics should be carefully assessed to optimize candidate selection.
PubMed: 38068412
DOI: 10.3390/jcm12237360 -
Journal of Clinical Medicine Mar 2024(1) This study comprehensively compared robotic pancreatic surgery with vascular resection (RPS-VR) to other surgical procedures in the treatment of pancreatic ductal... (Review)
Review
(1) This study comprehensively compared robotic pancreatic surgery with vascular resection (RPS-VR) to other surgical procedures in the treatment of pancreatic ductal adenocarcinoma (PDAC). (2) A systematic review of relevant literature was conducted to assess a range of crucial surgical and oncological outcomes. (3) Findings indicate that robotic surgery with vascular resections (VRs) significantly prolongs the duration of surgery compared to other surgical procedures, and they notably demonstrate an equal hospital stay. While some studies reported a lower conversion rate and a higher rate of blood loss and blood transfusion in the RPS-VR group, others found no significant disparity. Furthermore, RPS-VR consistently correlated with comparable recurrence rates, free margins R0, postoperative mortality, and complication rates. Concerning the last one, certain reviews reported a higher rate of major complications. Overall survival and disease-free survival remained comparable between the RPS-VR and other surgical techniques in treating PDAC. (4) The analysis emphasizes how RPS-VR is a resembling approach in terms of surgical outcomes and aligns with existing literature findings in this field.
PubMed: 38610766
DOI: 10.3390/jcm13072000 -
Infectious Diseases & Clinical... Sep 2023This study aimed to determine the effect of prophylactic use of carbapenems for acute pancreatitis on clinical outcomes. (Review)
Review
OBJECTIVE
This study aimed to determine the effect of prophylactic use of carbapenems for acute pancreatitis on clinical outcomes.
MATERIALS AND METHODS
It was conducted according to the preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines by using the keywords "Pancrea AND carbapenem OR imipenem OR ertapenem OR meropenem OR doripenem." Primer outcomes were mortality, surgical intervention, and pancreatic and non-pancreatic infection. Subgroup analyses were also performed to reduce the risk of bias.
RESULTS
Ten studies with 4038 patients were included in the meta-analyses. While eight of ten were randomized controlled trials, two were observational studies. The prophylactic use of carbapenems had no statistically significant effect on mortality (OR=0.82, 95% CI=0.65-1.04, I²=0%) and surgical intervention. (OR=0.81, 95% CI=0.57-1.17, I²=0%). However, the real impact of prophylaxis on reducing the incidence of mortality and surgical intervention was uncertain due to the insufficient sample size. The prophylactic use of carbapenems was significantly associated with a lower risk of peripancreatic (OR=0.37, 95% CI=0.25-0.55, I²=61%) and non-pancreatic infection risk (OR=0.60, 95% CI=0.46-0.78, I²=65%). The definitions of infection in the articles were not clear, and the diagnostic approach to infection was based on subjective criteria. In addition, there was inadequate collateral damage and safety assessments. In high-quality studies with a low risk of bias, prophylactic carbapenems had no effect on peripancreatic infection (RR=1.54, 95% CI=0.65-3.47, I²=0%) and non-pancreatic infection (RR=0.72, 95% CI=0.48-1.07, I²=0%).
CONCLUSION
Although there is a reduction in the infection risk, routine carbapenem use in acute pancreatitis cases should not be recommended based on current evidence. Cooperation with Infectious Disease specialists and developing diagnostic algorithms are required instead of routine prophylaxis to prevent infection, especially non-pancreatic infection.
PubMed: 38633556
DOI: 10.36519/idcm.2023.239 -
World Journal of Gastrointestinal... Aug 2023Post-operative pancreatic fistula (POPF) is the primary cause of morbidity following pancreaticoduodenectomy. Rates of POPF have remained high despite well known risk...
BACKGROUND
Post-operative pancreatic fistula (POPF) is the primary cause of morbidity following pancreaticoduodenectomy. Rates of POPF have remained high despite well known risk factors. The theory that hypoperfusion of the pancreatic stump leads to anastomotic failure has recently gained interest.
AIM
To define the published literature with regards to intraoperative pancreas perfusion assessment and its correlation with POPF.
METHODS
A systematic search of available literature was performed in November 2022. Data extracted included study characteristics, method of assessment of pancreas stump perfusion, POPF and other post-pancreatic surgery specific complications.
RESULTS
Five eligible studies comprised two prospective non-randomised studies and three case reports, total 156 patients. Four studies used indocyanine green fluorescence angiography to assess the pancreatic stump, with the remaining study assessing pancreas perfusion by visual inspection of arterial bleeding of the pancreatic stump. There was significant heterogeneity in the definition of POPF. Studies had a combined POPF rate of 12%; intraoperative perfusion assessment revealed hypoperfusion was present in 39% of patients who developed POPF. The rate of POPF was 11% in patients with no evidence of hypoperfusion and 13% in those with evidence of hypoperfusion, suggesting that not all hypoperfusion gives rise to POPF and further analysis is required to analyse if there is a clinically relevant cut off. Significant variance in practice was seen in the pancreatic stump management once hypoperfusion was identified.
CONCLUSION
The current published evidence around pancreas perfusion during pancreaticoduodenectomy is of poor quality. It does not support a causative link between hypoperfusion and POPF. Further well-designed prospective studies are required to investigate this.
PubMed: 37701689
DOI: 10.4240/wjgs.v15.i8.1799 -
International Journal of Surgery... Aug 2023Pancreatectomy is the only curative treatment available for pancreatic cancer and a necessity for patients with challenging pancreatic pathology. To optimize outcomes,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pancreatectomy is the only curative treatment available for pancreatic cancer and a necessity for patients with challenging pancreatic pathology. To optimize outcomes, postsurgical complications such as clinically relevant postoperative pancreatic fistula (CR-POPF) should be minimized. Central to this is the ability to predict and diagnose CR-POPF, potentially through drain fluid biomarkers. This study aimed to assess the utility of drain fluid biomarkers for predicting CR-POPF by conducting a diagnostic test accuracy systematic review and meta-analysis.
METHODS
Five databases were searched for relevant and original papers published from January 2000 to December 2021, with citation chaining capturing additional studies. The QUADAS-2 tool was used to assess the risk of bias and concerns regarding applicability of the selected studies.
RESULTS
Seventy-eight papers were included in the meta-analysis, encompassing six drain biomarkers and 30 758 patients with a CR-POPF prevalence of 17.42%. The pooled sensitivity and specificity for 15 cut-offs were determined. Potential triage tests (negative predictive value >90%) were identified for the ruling out of CR-POPF and included postoperative day 1 (POD1) drain amylase in pancreatoduodenectomy (PD) patients (300 U/l) and in mixed surgical cohorts (2500 U/l), POD3 drain amylase in PD patients (1000-1010 U/l) and drain lipase in mixed surgery groups (180 U/l). Notably, drain POD3 lipase had a higher sensitivity than POD3 amylase, while POD3 amylase had a higher specificity than POD1.
CONCLUSIONS
The current findings using the pooled cut-offs will offer options for clinicians seeking to identify patients for quicker recovery. Improving the reporting of future diagnostic test studies will further clarify the diagnostic utility of drain fluid biomarkers, facilitating their inclusion in multivariable risk-stratification models and the improvement of pancreatectomy outcomes.
Topics: Humans; Pancreatic Fistula; Pancreas; Pancreatectomy; Pancreaticoduodenectomy; Postoperative Complications; Drainage; Biomarkers; Amylases; Risk Factors
PubMed: 37216227
DOI: 10.1097/JS9.0000000000000482 -
Seminars in Nuclear Medicine Mar 2024The gastrin-releasing peptide receptor (GRPR) is known to be overexpressed in breast cancer, making it a promising target for both imaging and therapy within a... (Review)
Review
The gastrin-releasing peptide receptor (GRPR) is known to be overexpressed in breast cancer, making it a promising target for both imaging and therapy within a theranostic framework. Various radioligands targeting GRPR have undergone investigation in preclinical and clinical studies related to breast cancer. This systematic scoping review aimed to assess the current evidence on GRPR-targeted radioligands for diagnostic and therapeutic applications in breast cancer. The methodology followed the PRISMA-ScR protocol. The literature search was conducted in September 2023 and encompassed MEDLINE, Embase, Cochrane, and Scopus databases. We included original peer-reviewed studies focused on breast cancer patients or in vivo breast cancer models. Two reviewers performed the study selection process independently. Data were extracted, synthesized, and categorized into preclinical and clinical studies, further subdivided based on radioligand properties. A total of 35 original studies were included in the review, with three of them evaluating therapeutic outcomes. The results indicated that GRPR-radioantagonists are superior to GRPR-agonists, exhibiting preferable in vivo stability, rapid, specific tumor targeting, and enhanced retention. Both preclinical and clinical evaluations demonstrated renal excretion and high uptake in normal GRPR-expressing tissue, primarily the pancreas. A significant positive correlation was observed between GRPR and estrogen-receptor expression. In the clinical setting, GRPR-radioligands effectively detected primary tumors and, to a lesser extent, lymph node metastases. Moreover, GRPR-targeted radioantagonists successfully identified distant metastases originating from various sites in advanced metastatic disease, strongly correlated with positive estrogen receptor expression. Preclinical therapeutic evaluation of GRPR-radioligands labeled with lutetium-177 showed promising tumor responses, and none of the studies reported any observed or measured side effects, indicating a safe profile. In conclusion, the evidence presented in this review indicates a preference for GRPR-targeted antagonists over agonists, owing to their superior kinetics and promising diagnostic potential. Clinical assessments suggested diagnostic value for GRPR-targeted theranostics in breast cancer patients, particularly those with high estrogen receptor expression. Nevertheless, in the therapeutic clinical context, paying attention to the radiation dose administered to the pancreas and kidneys is crucial.
Topics: Humans; Female; Receptors, Bombesin; Breast Neoplasms; Precision Medicine; Receptors, Estrogen
PubMed: 38342656
DOI: 10.1053/j.semnuclmed.2024.01.004 -
Medicina (Kaunas, Lithuania) Apr 2024: The pancreas, ensconced within the abdominal cavity, requires a plethora of sophisticated imaging modalities for its comprehensive evaluation, with ultrasonography... (Review)
Review
: The pancreas, ensconced within the abdominal cavity, requires a plethora of sophisticated imaging modalities for its comprehensive evaluation, with ultrasonography serving as a primary investigative technique. A myriad of pancreatic pathologies, encompassing pancreatic neoplasia and a spectrum of inflammatory diseases, are detectable through these imaging strategies. Nevertheless, the intricate anatomical confluence and the pancreas's deep-seated topography render the visualization and accurate diagnosis of its pathologies a formidable endeavor. The objective of our paper is to review the best diagnostic imagistic tools for the pancreas. : we have gathered several articles using Prisma guidelines to determine the best imagistic methods. The imperative of pancreatic scanning transcends its diagnostic utility, proving to be a pivotal element in a multitude of clinical specialties, notably surgical oncology. Within this domain, multidetector computed tomography (MDCT) of the pancreas holds the distinction of being the paramount imaging modality, endorsed for its unrivaled capacity to delineate the staging and progression of pancreatic carcinoma. In synergy with MDCT, there has been a notable advent of avant-garde imaging techniques in recent years. These advanced methodologies, including ultrasonography, endoscopic ultrasonography, contrast-enhanced ultrasonography, and magnetic resonance imaging (MRI) conjoined with magnetic resonance cholangiopancreatography (MRCP), have broadened the horizon of tumor characterization, offering unparalleled depth and precision in oncological assessment. Other emerging diagnostic techniques, such as elastography, also hold a lot of potential and promise for the future of pancreatic imaging. Fine needle aspiration (FNA) is a quick, minimally invasive procedure to evaluate lumps using a thin needle to extract tissue for analysis. It is less invasive than surgical biopsies and usually performed as an outpatient with quick recovery. Its accuracy depends on sample quality, and the risks include minimal bleeding or discomfort. Results, guiding further treatment, are typically available within a week. Elastography is a non-invasive medical imaging technique that maps the elastic properties and stiffness of soft tissue. This method, often used in conjunction with ultrasound or MRI, helps differentiate between hard and soft areas in tissue, providing valuable diagnostic information. It is particularly useful for assessing liver fibrosis, thyroid nodules, breast lumps, and musculoskeletal conditions. The technique is painless and involves applying gentle pressure to the area being examined. The resulting images show tissue stiffness, indicating potential abnormalities. Elastography is advantageous for its ability to detect diseases in early stages and monitor treatment effectiveness. The procedure is quick, safe, and requires no special preparation, with results typically available immediately. : The assembled and gathered data shows the efficacy of various techniques in discerning the nature and extent of neoplastic lesions within the pancreas. : The most common imaging modalities currently used in diagnosing pancreatic neoplasms are multidetector computed tomography (MDCT), endoscopic ultrasound (EUS), and magnetic resonance imaging (MRI), alongside new technologies, such as elastography.
Topics: Humans; Pancreatic Neoplasms; Ultrasonography; Magnetic Resonance Imaging; Multidetector Computed Tomography; Pancreas
PubMed: 38792878
DOI: 10.3390/medicina60050695 -
Diagnostics (Basel, Switzerland) Oct 2023Idiopathic acute pancreatitis (IAP) presents a diagnostic challenge and refers to cases where the cause of acute pancreatitis remains uncertain despite a comprehensive... (Review)
Review
Idiopathic acute pancreatitis (IAP) presents a diagnostic challenge and refers to cases where the cause of acute pancreatitis remains uncertain despite a comprehensive diagnostic evaluation. Endoscopic ultrasound (EUS) has emerged as a valuable tool in the diagnostic workup of IAP. This review explores the pivotal role of EUS in detecting the actual cause of IAP and assessing its accuracy, timing, safety, and future technological improvement. In this review, we investigate the role of EUS in identifying the actual cause of IAP by examining the available literature. We aim to assess possible existing evidence regarding EUS accuracy, timing, and safety and explore potential trends of future technological improvements in EUS for diagnostic purposes. Following PRISMA guidelines, 60 pertinent studies were selected and analysed. EUS emerges as a crucial diagnostic tool, particularly when conventional imaging fails. It can offer intricate visualization of the pancreas, biliary system, and adjacent structures. Microlithiasis, biliary sludge, chronic pancreatitis, and small pancreatic tumors seem to be much more accurately identified with EUS in the setting of IAP. The optimal timing for EUS is post-resolution of the acute phase of the disease. With a low rate of complications, EUS poses minimal safety concerns. EUS-guided interventions, including fine-needle aspiration, collection drainage, and biopsies, aid in the cytological analysis. With high diagnostic accuracy, safety, and therapeutic potential, EUS is able to improve patient outcomes when managing IAP. Further refinement of EUS techniques and cost-effectiveness assessment of EUS-guided approaches need to be explored in multicentre prospective studies. This review underscores EUS as a transformative tool in unraveling IAP's enigma and advancing diagnostic and therapeutic strategies.
PubMed: 37892077
DOI: 10.3390/diagnostics13203256 -
Diabetes Therapy : Research, Treatment... Feb 2024The MiniMed™ 780G is a second-generation automated insulin delivery system that implements a modified proportional-integral-derivative algorithm with some features of... (Review)
Review
The MiniMed™ 780G is a second-generation automated insulin delivery system that implements a modified proportional-integral-derivative algorithm with some features of an MD-Logic artificial pancreas algorithm. The system may deliver automatic correction boluses up to every 5 min, and it allows the user to choose between three glucose target setpoints (100, 110 and 120 mg/dL). We aimed to review the current evidence on this device in children, adolescents, and young adults living with type 1 diabetes. We screened 783 papers, but only 31 manuscripts were included in this review. Data on metabolic outcomes show that this system is safe as regards severe hypoglycaemia and diabetic ketoacidosis. The glycated haemoglobin may drop to levels about 7%, with CGM reports showing a time in range of 75-80%. The time above range and the time below range are within the recommended target in most of the subjects. Few studies evaluated the psychological outcomes. This system seems to be more effective than the first-generation automated insulin delivery systems. The MiniMed™ 780G has been associated with an improvement in sleep quality in subjects living with diabetes and their caregivers, along with an improvement in treatment satisfaction. Psychological distress is as reduced as the glucose control is improved. We also discuss some case reports describing particular situations in clinical practice. Finally, we think that data show that this system is a further step towards the improvement of the treatment of diabetes as concerns both metabolic and psychological outcomes.
PubMed: 38038896
DOI: 10.1007/s13300-023-01501-6