•Comparing race-free CKD-EPI 2009 and 2021 equations in British Columbia, Canada.•The new CKD-EPI 2021 equation resulted in reclassifying 11.86% of individuals.•The new CKD-EPI 2021 equation ...primarily affected the stage G3a to G2.•The reclassification was statistically significant for the non-renal versus renal patients.•The study emphasizes the potential impact of adopting the CKD-EPI 2021 equation.
Clinical laboratories in British Columbia, Canada implemented the CKD-EPI 2009 equation without the race variable for estimated glomerular filtration rate (eGFR) reporting since 2014. As more clinical laboratories adopt the new CKD-EPI 2021 equation, the study aims to compare these two race-free CKD-EPI eGFR equations using the laboratory data from a large tertiary hospital in BC and evaluate the impact on reclassification of eGFR category.
Serum/plasma creatinine results and demographic data were collected from Vancouver General Hospital laboratory. The CKD-EPI 2009 without the race variable and CKD-EPI 2021 equations were computed. eGFR and its distributions were compared and reclassification of eGFR category was assessed across the full cohort and in specific patient populations.
The analysis included 58,763 patients. The median age was 57 years, with women comprising 51 % of the population. The median of eGFR changed from 85 to 90 mL/min/1.73 m2 using the CKD-EPI 2009 equation without the race variable and the CKD-EPI 2021 equation, respectively. The CKD-EPI 2021 equation reclassified 11.86 % of patients, mainly from G3a (45–59 mL/min/1.73 m2) to G2 (60–89 mL/min/1.73 m2). There was statistical significance between the non-renal and the renal population reclassified from G5 (<15 mL/min/1.73 m2) to G4 (15–29 mL/min/1.73 m2).
Using laboratory data representative of local populations, we observed an overall positive shift to higher eGFR, with 11.86 % of individuals having improved eGFR categories based on the CKD-EPI 2021 equation. This study provides insights into clinical implications at both the individual and population levels. The data-based approach is the first step towards adopting the CKD-EPI 2021 equation within the province.
The aims of this systematic review were to determine which blood-based molecules have been evaluated as possible biomarkers to diagnose chronic obstructive pulmonary disease (COPD) exacerbations ...(AECOPD) and to ascertain the quality of these biomarker publications. Patients of interest were those that have been diagnosed with COPD. MEDLINE, EMBASE, and CINAHL databases were searched systematically through February 2015 for publications relating to AECOPD diagnostic biomarkers. We used a modified guideline for the REporting of tumor MARKer Studies (mREMARK) to assess study quality. Additional components of quality included the reporting of findings in a replication cohort and the use of receiver-operating characteristics area-under-the curve statistics in evaluating performance. 59 studies were included, in which the most studied biomarkers were C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). CRP showed consistent elevations in AECOPD compared to control subjects, while IL-6 and TNF-α had variable statistical significance and results. mREMARK scores ranged from 6 to 18 (median score of 13). 12 articles reported ROC analyses and only one study employed a replication cohort to confirm biomarker performance. Studies of AECOPD diagnostic biomarkers remain inconsistent in their reporting, with few studies employing ROC analyses and even fewer demonstrating replication in independent cohorts.
Mutations in PIEZO1 (Piezo type mechanosensitive ion channel component 1) cause human lymphatic malformations. We have previously uncovered an ORAI1 (ORAI calcium release-activated calcium modulator ...1)-mediated mechanotransduction pathway that triggers lymphatic sprouting through Notch downregulation in response to fluid flow. However, the identity of its upstream mechanosensor remains unknown. This study aimed to identify and characterize the molecular sensor that translates the flow-mediated external signal to the Orai1-regulated lymphatic expansion.
Various mutant mouse models, cellular, biochemical, and molecular biology tools, and a mouse tail lymphedema model were employed to elucidate the role of Piezo1 in flow-induced lymphatic growth and regeneration.
Piezo1 was found to be abundantly expressed in lymphatic endothelial cells. Piezo1 knockdown in cultured lymphatic endothelial cells inhibited the laminar flow-induced calcium influx and abrogated the flow-mediated regulation of the Orai1 downstream genes, such as KLF2 (Krüppel-like factor 2), DTX1 (Deltex E3 ubiquitin ligase 1), DTX3L (Deltex E3 ubiquitin ligase 3L,) and NOTCH1 (Notch receptor 1), which are involved in lymphatic sprouting. Conversely, stimulation of Piezo1 activated the Orai1-regulated mechanotransduction in the absence of fluid flow. Piezo1-mediated mechanotransduction was significantly blocked by Orai1 inhibition, establishing the epistatic relationship between Piezo1 and Orai1. Lymphatic-specific conditional Piezo1 knockout largely phenocopied sprouting defects shown in Orai1- or Klf2- knockout lymphatics during embryo development. Postnatal deletion of Piezo1 induced lymphatic regression in adults. Ectopic Dtx3L expression rescued the lymphatic defects caused by Piezo1 knockout, affirming that the Piezo1 promotes lymphatic sprouting through Notch downregulation. Consistently, transgenic Piezo1 expression or pharmacological Piezo1 activation enhanced lymphatic sprouting. Finally, we assessed a potential therapeutic value of Piezo1 activation in lymphatic regeneration and found that a Piezo1 agonist, Yoda1, effectively suppressed postsurgical lymphedema development.
Piezo1 is an upstream mechanosensor for the lymphatic mechanotransduction pathway and regulates lymphatic growth in response to external physical stimuli. Piezo1 activation presents a novel therapeutic opportunity for preventing postsurgical lymphedema. The Piezo1-regulated lymphangiogenesis mechanism offers a molecular basis for Piezo1-associated lymphatic malformation in humans.
There are currently no accepted and validated blood tests available for diagnosing acute exacerbations of chronic obstructive pulmonary disease (AECOPD). In this study, we sought to determine the ...discriminatory power of blood C-reactive protein (CRP) and N-terminal prohormone brain natriuretic peptide (NT-proBNP) in the diagnosis of AECOPD requiring hospitalizations. The study cohort consisted of 468 patients recruited in the COPD Rapid Transition Program who were hospitalized with a primary diagnosis of AECOPD, and 110 stable COPD patients who served as controls. Logistic regression was used to build a classification model to separate AECOPD from convalescent or stable COPD patients. Performance was assessed using an independent validation set of patients who were not included in the discovery set. Serum CRP and whole blood NT-proBNP concentrations were highest at the time of hospitalization and progressively decreased over time. Of the 3 classification models, the one with both CRP and NT-proBNP had the highest AUC in discriminating AECOPD (cross-validated AUC of 0.80). These data were replicated in a validation cohort with an AUC of 0.88. A combination of CRP and NT-proBNP can reasonably discriminate AECOPD requiring hospitalization versus clinical stability and can be used to rapidly diagnose patients requiring hospitalization for AECOPD.
Abstract
Background
Combining abdominoplasty with liposuction is a common practice for optimal patient aesthetic outcomes. In the past, several practitioners have argued against liposuction due to ...the potential for vascular insufficiency, especially with central liposuction. Despite these concerns for flap damage with resultant necrosis, the incidence of this complication has not been comprehensively investigated.
Objectives
The authors therefore examined the incidence of necrotic complications, including skin and fat necrosis as well as partial/total flap loss, in patients who underwent abdominoplasty alone (AA) or abdominoplasty with partial or circumferential liposuction (APCL).
Methods
Literature searches were performed in PubMed/Medline and Embase with no query limits. For the systematic review, data from the studies were extracted into a form including primary author, publication year, study design, number of AA and APCL patients, abdominal zone(s) treated with liposuction, average lipoaspirate volume, follow-up time, necrotic complications, and revision procedures. A meta-analysis was separately performed for 13 studies that included patients who underwent both AA and APCL.
Results
The overall rate of necrotic complications was lower in the APCL group (0.39%) compared with the AA group (1.01%). The incidence of necrotic complications was low for all patients, with a pooled partial flap loss rate of 0.24% and a pooled skin necrosis rate of 0.23%. The forest plots revealed that patients who underwent APCL do not face a higher risk of skin necrosis or revision compared with those who underwent AA.
Conclusions
Performing APCL is a safe combined procedural approach and can confer added benefits of improved patient satisfaction and aesthetic outcomes.
Level of Evidence: 4
•Explore different models of Hospital at Home programs.•Emphasize the crucial roles of clinical laboratories in bolstering Hospital at Home initiatives.•Focus on two key quality requirements for ...laboratory testing in Hospital at Home programs: sample integrity and turnaround times.•Discuss opportunities and barriers for maximizing laboratory support in Hospital at Home programs.
The Hospital at Home (HaH) program has experienced accelerated growth in major Canadian provinces, driven in part by technological advancements and evolving patient needs during the COVID-19 pandemic. As an increasing number of hospitals pilot or implement these innovative programs, substantial resources have been allocated to support clinical teams. However, it is crucial to note that the vital roles played by clinical laboratories remain insufficiently acknowledged.
This mini review aims to shed light on the diverse functions of clinical laboratories, spanning the preanalytical, analytical, and post-analytical phases within the HaH program context. Additionally, the review will explore recent advancements in clinical testing and the potential benefits of integrating new technologies into the HaH framework. Emphasizing the integral role of clinical laboratories, the discussion will address the current barriers hindering their active involvement, accompanied by proposed solutions.
The capacity and efficiency of the HaH program hinge on sustained collaborative efforts from various teams, with clinical laboratories as crucial team players. Recognizing and addressing the specific challenges faced by clinical laboratories is essential for optimizing the overall performance and impact of the HaH initiative.
Head and neck lymphedema (HNL) is a disfiguring disease affecting over 90% of patients treated for head and neck cancer. Animal models of lymphedema are used to test pharmacologic and microsurgical ...therapies; however, no animal model for HNL is described in the literature to date. In this study we describe the first reproducible rat model for HNL. Animals were subjected to two surgical protocols: (1) lymphadenectomy plus irradiation; and (2) sham surgery and no irradiation. Head and neck expansion was measured on post-operative days 15, 30 and 60. Magnetic resonance imaging (MRI) was acquired at the same time points. Lymphatic drainage was measured at day 60 via indocyanine green (ICG) lymphography, after which animals were sacrificed for histological analysis. Postsurgical lymphedema was observed 100% of the time. Compared to sham-operated animals, lymphadenectomy animals experienced significantly more head and neck swelling at all timepoints (P < 0.01). Lymphadenectomy animals had significantly slower lymphatic drainage for 6 days post-ICG injection (P < 0.05). Histological analysis of lymphadenectomy animals revealed 83% greater subcutis thickness (P = 0.008), 22% greater collagen deposition (P = 0.001), 110% greater TGFβ1
cell density (P = 0
04), 1.7-fold increase in TGFβ1 mRNA expression (P = 0.03), and 114% greater T-cell infiltration (P = 0.005) compared to sham-operated animals. In conclusion, animals subjected to complete lymph node dissection and irradiation developed changes consistent with human clinical postsurgical HNL. This was evidenced by significant increase in all head and neck measurements, slower lymphatic drainage, subcutaneous tissue expansion, increased fibrosis, and increased inflammation compared to sham-operated animals.
Soft tissue sarcomas are a heterogenous group of malignant tumors that represent approximately 1% of adult malignancies. Although these tumors occur throughout the body, the majority involved the ...lower extremity. Management may involve amputation but more commonly often includes wide local resection by an oncologic surgeon and involvement of a plastic surgeon for reconstruction of larger and more complex defects. Postoperative wound complications are challenging for the surgeon and patient but also impact management of adjuvant chemotherapy and radiation therapy. To explore risk factors for wound complications, we reviewed our single-institution experience of lower-extremity soft tissue sarcomas from April 2009 to September 2016. We identified 127 patients for retrospective review and analysis. The proportion of patients with wound complications in the cohort was 43.3%. Most notably, compared with patients without wound complications, patients with wound complications had a higher proportion of immediate reconstruction (34.5% vs 15.3%; P = 0.05) and a marginally higher proportion who received neoadjuvant radiation (30.9% vs 16.7%; P = 0.06).
Abstract
Cranioplasties are common procedures in plastic surgery. The use of tissue expansion (TE) in staged cranioplasties is less common. We present two cases of cranioplasties with TE and ...systematically review literature describing the use of TE in staged cranioplasties and postoperative outcomes. A systematic review was performed by querying multiple databases. Eligible articles include published case series, retrospective reviews, and systematic reviews that described use of TE for staged bony cranioplasty. Data regarding study size, patient demographics, preoperative characteristics, staged procedure characteristics, and postoperative outcomes were collected. Of 755 identified publications, 26 met inclusion criteria. 85 patients underwent a staged cranioplasty with TE. Average defect size was 122 cm
2
, and 30.9% of patients received a previous reconstruction. Average expansion period was 14.2 weeks. The most common soft tissue closures were performed with skin expansion only (75.3%), free/pedicled flap (20.1%), and skin graft (4.7%). The mean postoperative follow-up time was 23.9 months. Overall infection and local complication rates were 3.53 and 9.41%, respectively. The most common complications were cerebrospinal fluid leak (7.1%), hematoma (7.1%), implant exposure (3.5%), and infection (3.5%). Factors associated with higher complication rates include the following: use of alloplastic calvarial implants and defects of congenital etiology (
p
= 0.023 and 0.035, respectively). This is the first comprehensive review to describe current practices and outcomes in staged cranioplasty with TE. Adequate soft tissue coverage contributes to successful cranioplasties and TE can play a safe and effective role in selected cases.
Secondary lymphedema is a debilitating disease caused by lymphatic dysfunction characterized by chronic swelling, dysregulated inflammation, disfigurement, and compromised wound healing. Since there ...is no effective cure, animal model systems that support basic science research into the mechanisms of secondary lymphedema are critical to advancing the field.
Over the last decade, lymphatic research has led to the improvement of existing animal lymphedema models and the establishment of new models. Although an ideal model does not exist, it is important to consider the strengths and limitations of currently available options. In a systematic review adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we present recent developments in the field of animal lymphedema models and provide a concise comparison of ease, cost, reliability, and clinical translatability.
The incidence of secondary lymphedema is increasing, and there is no gold standard of treatment or cure for secondary lymphedema.
As we iterate and create animal models that more closely characterize human lymphedema, we can achieve a deeper understanding of the pathophysiology and potentially develop effective therapeutics for patients.