bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exome sequencing as a diagnostic tool in chronic kidney disease: ready for clinical application?
Authors: Leveson James , Oates Thomas M. 
Published: September 2020

Purpose of review
Patients who develop chronic kidney disease at an early age, or from an uncertain cause, may benefit from genomic sequencing approaches to define causative mutations and inform subsequent management.

Recent findings
Whole-exome sequencing has been used to investigate the molecular genetic variants associated with chronic kidney disease in both specific phenotypes such as steroid-resistant nephrotic syndrome, and in large cohorts of patients not selected for a certain diagnosis. These studies have shown that whole-exome sequencing is able to find a genetic variant in a significant number of patients. Often these variants may reclassify the diagnosis, the variants may have ramifications for the patient's management, and some variants may be previously undescribed in the literature.

Summary
Whole-exome sequencing is likely to become widely used in the investigation of chronic kidney disease, especially in certain phenotypes.
Fluid management in chronic kidney disease: what is too much, what is the distribution, and how to manage fluid overload in patients with chronic kidney disease?
Authors: de Ruiter Anna , Bello Aminu , Braam Branko 
Published: September 2020

Purpose of review
Assessment of fluid status to reach normovolemia in patients with chronic kidney disease (CKD) continues to be a tough task. Besides clinical observation, technological methods have been introduced, yet, the best approach is still uncertain. The present review looks at fluid overload in CKD from three perspectives: the critical fluid threshold leading to adverse cardiovascular outcomes, fluid distribution and its clinical correlates, and direct effect of fluid overload on vascular function related to disturbance of the sodium–skin axis and endothelial glycocalyx dysfunction.

Recent findings
To determine fluid status, both the absolute and relative fluid overload is used as parameter in clinical practice. In addition, the definition of fluid overload is ambivalent and its relation to symptom burden has not been studied well. Studies on the impact of distribution of fluid are scarce and the limited evidence suggests differences based on the cause of CKD. So far, no standardized technologies are available to adequately determine fluid distribution. After discovering the ‘third compartment’ of total body sodium in skin and muscle tissue and its potential direct effect on vascular function, other biomarkers such as VEGF-C are promising.

Summary
We propose a multimodal clinical approach for volume management in CKD. Because there are currently no studies are available demonstrating that correction of fluid overload in CKD will lead to better outcome, these are strongly needed.
Extracellular vesicles: a novel window into kidney function and disease
Authors: Sun In O. , Kwon Soon Hyo 
Published: September 2020

Purpose of review
There has been an increasing interest in extracellular vesicles as potential diagnostic, prognostic or therapeutic biomarkers for various kidney diseases, as extracellular vesicles mediate cell-cell or intercellular communication. This review explores the current state of knowledge regarding extracellular vesicles as a tool for examining kidney physiology and disease.

Recent findings
Urinary extracellular vesicles may be useful as biomarkers to detect abnormal function in renal endothelial and tubular cells as well as podocytes. Recent studies suggest that urinary extracellular vesicles may facilitate early diagnosis and/or monitoring in acute kidney injury, glomerular disease, autosomal dominanat polycyst kidney disease and urinary tract malignancies. Circulating extracellular vesicles may serve as biomarkers to assess cardiovascular disease.

Summary
Urinary and circulating extracellular vesicles have gained significant interest as potential biomarkers of renal diseases. Analysis of extracellular vesicles may serve as a logical diagnostic approach for nephrologists as well as provide information about disease pathophysiology.
Volume management in haemodialysis patients
Authors: See Emily J. , Polkinghorne Kevan R. 
Published: September 2020

Purpose of reviewAccumulating evidence supports the important contribution of volume-related metrics to morbidity and mortality in patients receiving chronic haemodialysis. The purpose of this review is to summarize recent advances in the understanding and management of volume status in this high-risk group.Recent findingsDelivery of optimal volume management involves three key components: accurate estimation of volume status, correction of extracellular fluid overload and prevention of intradialytic instability. The lack of a gold standard for assessing volume status makes accurate estimation difficult to achieve; clinical examination has insufficient sensitivity and specificity, while tools to assist in the objective measurement of extracellular fluid volume require further validation. Hypervolemia is common in patients on chronic haemodialysis and substantially increases the risk of morbidity and mortality. Rapid correction of hypervolemia should be avoided due to the risk of precipitating intradialytic hypotension and hypoperfusion of vital end-organs, including the heart, brain, liver, gut and kidneys. Evidence-based interventions to aid in normalizing extracellular fluid volume are urgently needed; several targeted strategies are currently being evaluated. Many centres have successfully implemented local protocols and programmes to enhance volume management.SummaryAchieving normal volume status is a fundamental goal of haemodialysis. Novel methods of assessing and restoring extracellular fluid volume while maintaining intradialytic stability are currently undergoing evaluation. Implementation of volume-related strategies into clinical practice is feasible and may improve patient outcome.
Getting the basics right: the monitoring of arteriovenous fistulae, a review of the evidence
Authors: Bodington Richard , Greenley Sarah , Bhandari Sunil 
Published: September 2020

Purpose of review
Despite being the preferred vascular access for haemodialysis, the arteriovenous fistula (AVF) remains prone to a number of complications, the most common of these being thrombosis secondary to stenosis. This has resulted in the widespread use of monitoring and surveillance programmes. Surveillance uses more resources than monitoring and has not been convincingly shown to improve outcomes. The evidence supporting the use of the various monitoring tools has been relatively neglected and has not been the focus of literature review. This narrative review is the first to appraise the evidence for the use of physical examination, access recirculation, Kt/V and dynamic venous pressures (DVP) as monitoring tools in mature AVF.

Recent findings
The vastly increased number of data points for access recirculation, Kt/V and DVP produced as standard by online clearance monitoring (OCM) on modern dialysis machines is likely to have significantly changed the utility of these metrics in the prediction of AVF failure. Algorithms have been developed to highlight those of highest risk of failure.

Summary
The evidence supporting the use of monitoring in the prediction of AVF failure is predominantly observational, underpowered and more than 20 years old. Access recirculation and Kt/V appears to have higher utility in AVF than in arteriovenous grafts. We suggest that the development of OCM necessitates the reevaluation of these tools.
Are borderline changes real rejection? Current viewpoints
Authors: Park Sook Hyeon , Friedewald John J. 
Published: September 2020

Purpose of review
The clinical significance and treatment of borderline changes are controversial. The lowest detectable margin for rejection on histology is unclear. We review recent evidence about borderline changes and related biomarkers.

Recent findings
Borderline change (Banff ≥ t1i1) is associated with progressive fibrosis, a greater propensity to form de-novo DSA, and reduced graft survival. Isolated tubulitis appears to have similar kidney allograft outcomes with normal controls, but this finding should be validated in a larger, diverse population. When borderline change was treated, a higher chance of kidney function recovery and better clinical outcomes were observed. However, spontaneous borderline changes resolution without treatment was also observed. Various noninvasive diagnostic biomarkers have been developed to diagnose subclinical acute rejection, including borderline changes and ≥ Banff 1A TCMR. Biomarkers using gene expression and donor-derived cell-free DNA, and HLA DR/DQ eplet mismatch show potential to diagnose subclinical acute rejection (borderline change and ≥Banff 1A TCMR), to avoid surveillance biopsy, or to predict poor kidney allograft outcomes.

Summary
Borderline changes are associated with poor kidney allograft outcomes, but it remains unclear if all cases of borderline changes should be treated. Novel biomarkers may inform physicians to aid in the diagnosis and treatment.
More precise donor–recipient matching: the role of eplet matching
Authors: Wiebe Chris , Nickerson Peter W. 
Published: September 2020

Purpose of review
A precise understanding of the alloimmune risk faced by individual recipients at the time of transplant is an unmet need in transplantation. Although conventional HLA donor–recipient mismatch is too imprecise to fulfil this need, HLA molecular mismatch increases the precision in alloimmune risk assessment by quantifying the difference between donors and recipients at the molecular level.

Recent findings
Within each conventional HLA mismatch the number, type, and position of mismatched amino acids create a wide range of HLA molecular mismatches between recipients and donors. Multiple different solid organ transplant groups from across the world have correlated HLA molecular mismatch with transplant outcomes including de novo donor-specific antibody development, antibody-mediated rejection, T-cell-mediated rejection, and allograft survival.

Summary
All alloimmunity is driven by differences between donors and recipients at the molecular level. HLA molecular mismatch may represent an advancement compared to traditional HLA antigen mismatch as a fast, reproducible, cost-effective way to improve alloimmune risk assessment at the time of transplantation to move the field towards precision medicine.
Innate and adaptive immunity in celiac disease
Authors: Anderson Robert P. 
Published: September 2020

Purpose of review
The current review is prompted by recent studies indicating that adaptive immunity could be sufficient to explain rapid onset symptoms as well as many chronic effects of gluten in celiac disease.

Recent findings
Gluten re-exposure in treated celiac disease drives a coordinated systemic cytokine release response implicating T-cell activation within 2 h. Instead of direct effects of gluten on innate immunity, long lasting memory CD4+ T cells activated within 2 h of ingesting gluten or injecting purified gluten peptides now appear to be responsible for acute digestive symptoms. In addition, memory B cells and plasma cells specific for gluten and transglutaminase 2, rather than innate immune cells, are the preferred antigen-presenting cells for gluten in the gut. A variety of innate immune stimuli such as transient infections and local intestinal microbiome, not necessarily gluten itself, may contribute to disease initiation and transition to overt intestinal mucosal injury. Gluten-specific adaptive immunity in the gut and blood are now shown to be closely linked, and systemic cytokine release after gluten provides an additional explanation for extraintestinal manifestations of celiac disease.

Summary
Clinical studies utilizing cytokines as new biomarkers for gluten immunity promise to improve understanding of clinical effects of gluten, accelerate therapeutics development, and augment diagnosis.
Endoscopic diagnosis and management of gastric subepithelial lesions
Authors: McCarty Thomas R. , Ryou Marvin 
Published: September 2020

Purpose of review
The purpose of this manuscript is to provide an in-depth review of gastric subepithelial lesions (SELs) and describe the current approach to endoscopic diagnosis and management of these lesions.

Recent findings
Gastric SELs are a relatively frequent finding on routine endoscopy (incidence 0.2–3%). A systematic approach to diagnosis and management is key because many SELs are of little consequence, while others carry a high risk of malignant transformation. Because esophagogastroduodenoscopy (EGD) cannot delineate depth of invasion or subepithelial appearance, endoscopic ultrasound (EUS) should be considered a first-line modality. Recent data suggest EUS-guided fine needle biopsy (FNB) may be superior to traditional fine needle aspiration (FNA) for the diagnosis of gastric SELs due to its ability to obtain histologic specimens for immunohistochemical staining. Alternative techniques for tissue sampling (combined with simultaneous resection) include submucosal resection, endoscopic submucosal dissection (ESD), submucosal tunnelling with endoscopic resection (STER) or endoscopic full-thickness resection (EFTR).

Summary
This review details the endoscopic diagnosis and management of gastric SELs. Although EUS-guided sampling remains a first-line strategy (preferably with FNB), recent techniques including ESD, STER and EFTR have the potential to provide additional diagnostic and therapeutic options.
Advances in the treatment of gastric cancer
Authors: Ilson David H. 
Published: September 2020

Purpose of review
To provide an up-to-date review on the management of cancers of the stomach and esophagogastric junction (EGJ).

Recent findings
Microsatellite instable (MSI) high status in gastric cancer may portend a relatively good prognosis and indicate that adjuvant chemotherapy is of no added benefit to primary surgical management. In the preoperative treatment of HER2 (ErbB2)-positive EGJ adenocarcinoma with chemoradiotherapy, the addition of trastuzumab, a recombinant humanized mAb directed against the extracellular domain of Her2, failed to improve outcome over conventional chemoradiotherapy alone. Escalating the dose of radiation in combined chemoradiotherapy regimens did not improve survival over conventional dose radiotherapy in the nonoperative management of EGJ cancer. The use of proton vs. conventional external beam radiation therapy, although potentially less toxic, did not improve therapy outcome with preoperative or definitive chemoradiotherapy in EGJ cancer. In metastatic HER2-positive gastric cancer, after disease progression on trastuzumab, continuation of trastuzumab did not improve progression free or overall survival compared with second-line chemotherapy alone. However, in the setting or prior trastuzumab therapy in metastatic HER2-positive gastric cancer, the new agent trastuzumab deruxtecan achieved significant rates of response, progression free and overall survival compared with standard chemotherapy. After initial chemotherapy for metastatic esophagogastric cancer, maintenance therapy with the anti PDL-1 agent avelumab was no better than chemotherapy alone.

Summary
MSI high gastric cancer has a better prognosis and may not require adjuvant chemotherapy. Trastuzumab, added to preoperative chemoradiotherapy in HER2-positive esophageal adenocarcinoma, does not improve outcome. Dose escalation of radiotherapy in the nonoperative management of EGJ cancer does not improve local control or survival, and proton therapy may not achieve superior outcomes compared with external beam radiotherapy. In metastatic HER2-positive gastric cancer, continuing trastuzumab into second-line chemotherapy does not add benefit; however, the novel agent trastuzumab deruxtecan has substantial activity after prior trastuzumab-based therapy.
Human babesiosis: recent advances and future challenges
Authors: Lobo Cheryl A. , Singh Manpreet , Rodriguez Marilis 
Published: September 2020

Purpose of review
As human babesiosis caused by apicomplexan parasites of the Babesia genus is associated with transfusion-transmitted illness and relapsing disease in immunosuppressed populations, it is important to report novel findings relating to parasite biology that may be responsible for such pathology. Blood screening tools recently licensed by the FDA are also described to allow understanding of their impact on keeping the blood supply well tolerated.

Recent findings
Reports of tick-borne cases within new geographical regions such as the Pacific Northwest of the USA, through Eastern Europe and into China are also on the rise. Novel features of the parasite lifecycle that underlie the basis of parasite persistence have recently been characterized. These merit consideration in deployment of both detection, treatment and mitigation tools such as pathogen inactivation technology. The impact of new blood donor screening tests in reducing transfusion transmitted babesiosis is discussed.

Summary
New Babesia species have been identified globally, suggesting that the epidemiology of this disease is rapidly changing, making it clear that human babesiosis is a serious public health concern that requires close monitoring and effective intervention measures. Unlike other erythrocytic parasites, Babesia exploits unconventional lifecycle strategies that permit host cycles of different lengths to ensure survival in hostile environments. With the licensure of new blood screening tests, incidence of transfusion transmission babesiosis has decreased.
Role of complement in alloimmunization and hyperhemolysis
Authors: Chonat Satheesh , Mener Amanda , Verkerke Hans , Stowell Sean R. 
Published: September 2020

Purpose of review
The purpose of this review is to summarize the role of complement in regulating the removal of a target alloantigen following an incompatible red blood cell (RBC) transfusion, the formation of alloantibodies following RBC alloantigen exposure, and the development of hyperhemolysis in patients with sickle cell disease (SCD).

Recent findings
Recent studies demonstrate that complement can accelerate alloantibody-mediated removal of target alloantigens from the RBC surface following incompatible transfusion. Complement also influences alloantigen availability during developing alloimmune responses and serves as a unique mediator of CD4 T-cell-independent alloantibody formation following RBC alloantigen exposure. Finally, alternative complement pathway activation appears to play a key role in the development of acute hemolytic episodes in patients with SCD, providing a potential druggable target to prevent acute complications in patients with this disease.

Summary
Recent studies suggest that complement can regulate a wide variety of processes germane to hematology, from transfusion complications to baseline hemolysis in patients with SCD. As the role of complement in various disease processes becomes more fully understood, the ability to leverage recently developed complement modulating drugs will only continue to enhance providers’ ability to favorably intervene in many hematological diseases.
Optimizing leukapheresis product yield and purity for blood cell-based gene and immune effector cell therapy
Authors: Shi Patricia A. 
Published: September 2020

Purpose of review
A critical common step for blood-based ex-vivo gene and immune effector cell (IEC) therapies is the collection of target cells for further processing and manufacturing, often accomplished through a leukapheresis procedure to collect mononuclear cells (MNCs). The purpose of this review is to describe strategies to optimize the apheresis product cell yield and purity for gene and IEC therapies. Relevant data from the conventional bone marrow transplant literature is described where applicable.

Recent findings
Product yield is affected by three main factors: the peripheral blood concentration of the target cell, optimized by mobilizing agents, donor interventions or donor selection; the volume of peripheral blood processed, tailored to the desired product yield using prediction algorithms; and target cell collection efficiency, optimized by a variety of device and donor-specific considerations. Factors affecting product purity include characteristics of the donor, mobilizing agent, device, and device settings.

Summary
Strategies to optimize product yield and purity for gene and IEC therapies are important to consider because of loss of target cell numbers or function with downstream steps and detrimental effects of nontarget cells on further manufacturing and patient outcome.
Community health workers: improving population health through integration into healthcare systems
Authors: Pinto Desiree , Carroll-Scott Amy , Christmas Tracy , Heidig Maura , Turchi Renee 
Published: September 2020

Purpose of review
The purpose of this review is to describe the role, responsibilities, hiring, training, and retention of community health workers (CHWs) on clinical care teams in the United States.

Recent findings
CHWs are unique members of clinical care teams because of their ability to foster a deep trust and understanding with patients by sharing similar life experiences, participating in home visits, and providing constant support and advocacy. By partnering with CHWs, other clinical care members also gain a better understanding of their patients allowing them to deliver more culturally competent, patient/family-centered care. CHWs when incorporated into interdisciplinary teams have shown to lower healthcare costs, reduce hospital stays and admissions, and improve health outcomes and quality of life for children and families. However, the lack of standardization among CHW programs makes it difficult to quantify the overall effect and impact of integrating CHWs into clinical care teams.

Summary
CHWs are able to improve health outcomes and address social determinants of health when properly integrated into clinical care teams. However, without adequate support, integration, funding, and training, CHWs are not able to reach their full potential. The standardization of CHWs’ responsibilities and training, like other clinical care team members, is lacking within the United States, making it a challenge to evaluate programs and maintain sustainable funding for these vital members of the clinical care team.
Current concepts of polycystic ovary syndrome pathogenesis
Authors: Rosenfield Robert L. 
Published: September 2020

Purpose of review
This review provides a model for understanding polycystic ovary syndrome (PCOS) pathophysiology and updates the evidence on which it is based. Then, it highlights complimentary molecular genetic and epigenetic advances in understanding PCOS cause.

Recent findings
Important studies into PCOS cause built on the 2014 discovery of a novel regulatory protein variant that underlies the typical PCOS steroidogenic abnormalities: DENND1A.V2 (differentially expressed in normal and neoplastic development, isoform 1A, variant 2). Over 30 DENND1A gene variants have been found, the vast majority upstream of the coding sequence and potentially regulatory. These variants are individually uncommon but collectively plausibly cause 50% of PCOS. Anti-Müllerian hormone (AMH)/AMH receptor variants with decreased function possibly cause 6.7% of PCOS. DENNND1A was recently reported to belong to a signaling network that upregulates luteinizing hormone receptor expression and insulin mitogenic signaling. Prenatal androgen administration has proven to be a potent epigenetic regulator that causes transgenerational epigenomic changes in a mouse PCOS model with similarities to those in human PCOS and PCOS daughters.

Summary
In addition to finding how gene variants contribute to PCOS pathogenesis, better understanding of androgen epigenetic mechanisms of action in diverse tissues can be expected to expand our understanding of PCOS pathogenesis.