Time Of Procurement Research Articles

Analysis of organ procurement time data

Analysis of organ procurement time data

Estimasi Waktu Untuk Pengadaan Material Berdasarkan Time Schedule Pada Proyek Pembangunan Ruko Kawasan SP Plaza Batu Aji

The research aims to estimate the time for material procurement based on time schedule in Batu Aji SP Plaza Area. The method used in the determining the estimated time is conventional method in which the scheduling process is made in the form of a barchart to be more easily understood by readers and also makes scheduling more orderly and systematic. The estimated results of material procurement until arrived the project location is 15 days and the average real field procurement is 12 days, so it can be concluded that the material procurement process in the construction of Ruko Kawasan SP Plaza does not occure material delays for structural work, wall work and roof work.

Immune Checkpoint Profiling of TP53 Mutant and Wild-Type Myeloid Malignancies: TP53 Mutations Direct Immune Tolerance Via an Immunosuppressive Phenotype

Background Augmenting adaptive immunity through immune checkpoint blockade introduced a paradigm shift in the treatment of cancer patients. Although aberrant mRNA upregulation of several immune checkpoints (e.g. PDL1) has been described in CD34+ cells of myelodysplastic syndrome (MDS) patients compared to normal controls (Yang et al ., 2014), clinical investigations of checkpoint inhibitors in myeloid malignancies to-date have shown low response rates to monotherapy with a lack of response biomarkers. MDS is genetically heterogeneous evidenced by the array of somatic gene mutations that may impact differential checkpoint display. In concordance, our interrogation of the AML TCGA dataset identified TP53 mutant (MT) AML as an immunologically distinct subset with checkpoint upregulation. Therefore, our goal was to comprehensively characterize checkpoint molecules by lineage and stage of maturation in MDS to discern relationships with immune cell subsets in molecularly defined cohorts.Patients and Methods Utilizing the Moffitt Cancer Center tissue core and MDS database, bone marrow mononuclear cells were obtained from genetically profiled MDS (n=23), CMML (n=5) and secondary AML patients (n=22). NGS of up to 54 genes was performed at the time of sample acquisition with 5% VAF threshold and 500x minimum depth of coverage. Multi-color flow cytometry acquisition of immune checkpoints with a myeloid and lymphoid panel (Table 1) was performed using a BD LSRII, and analysis was conducted using FlowJo v10.3. Clinical variables and outcomes of patients were characterized at the time of sample procurement. Mann-Whitney and Kruskal-Wallis tests were used for comparative analyses. Median values of each checkpoint were calculated to compare outcomes of patients with increased versus decreased expression. Kaplan-Meier curves were used to estimate OS and analyzed from the date of sample collection. Multivariate Cox regression models were created to adjust for clinical characteristics.Results A total of 50 patients were analyzed (25 TP53 MT and wildtype (WT), respectively) with a median age of 72 years and male predominance (58%). Overall 38% of patients (n=19) were treatment naïve while 40% were HMA refractory (n=20). TP53 MT patients had significantly higher percentage of PDL1+ hematopoietic stem cells (HSC; Lin-/CD34+/CD38-,15.5% v 5.7%; P=0.008) with a non-significant increase in progenitor cells (HPC; Lin-/CD34+/CD38+, 15.4% v 9.2%; P=0.3). Additionally, PD1+/CD71+ erythroid progenitors (6.5% v 28.1%; P <0.0001)) and granulocytic myeloid derived suppressor cells (MDSC-G (Lin-/CD33+/ CD38-/CD11b+/CD14-); 10 v 23.7%; P=0.001) were significantly decreased in TP53 MT versus WT patients. The percentage of PDL1+ HSC or HPC were similar in HMA-naïve versus HMA-failure or patients actively on HMA (P=0.61 and P=0.84, respectively). More importantly, TP53 MT patients were enriched for an immune suppressive/anergic profile with increased % of TIM3+ MDSC-G (4% v 2%, P=0.04) and decreased % of OX40 cytotoxic T-cells (2.2 v 2.9%; P=0.006). As TP53 MT strongly predicts for inferior OS (P <0.0001), survival was similarly predictive with checkpoint alterations associated with TP53 MT.Although there was no difference in % of T-regulatory cells (T-regs; CD3+/CD4+/ CD25+/CD127dim/-) in TP53 MT versus WT patients (P=0.75), there was a trend for increased ICOS+ T-regs in TP53 MT patients (16.9% v 13%; P=0.09). Increased ICOS+ T-regs was associated with inferior OS in the total cohort (5.7 v 13.3 months, P=0.003)) and TP53 WT cohort (5.5 months vs NR, P=0.01)). In multivariable analysis incorporating age, BMT status, HMA failure, and revised international prognostic scoring system (IPSS-R) category, increased ICOS+ T-regs remained an independent co-variate for inferior OS in both the total cohort (HR 2.28, 95% CI 1.13 to 4.62; P= 0.02) and TP53 WT cohort (HR 4.69, 95% CI 1.33 to 16.56; P= 0.02)).Conclusion In patients with MDS and sAML, immune checkpoint expression is heterogeneous in HSCs and immune cell subsets. TP53 mutation portends an immunologically distinct, immune evasive phenotype that may be the predominant driver of their poor prognosis. Increased % of tumor infiltrating ICOS+ T-regs is highly predictive of outcome, independent of TP53 mutation status. We conclude that comprehensive immune checkpoint profiling may offer rationale for targeted immunomodulatory therapeutic strategies. [Display omitted] DisclosuresSallman:Celgene: Research Funding. Komrokji:Celgene: Honoraria; Novartis: Honoraria, Speakers Bureau. Lancet:Boehringer Ingelheim: Consultancy; Celgene: Consultancy; Bio-Path Holdings: Consultancy; Janssen: Consultancy; Pfizer: Other: Institutional research funding, Research Funding; Erytech: Consultancy; Jazz Pharmaceuticals: Consultancy; BioSight: Consultancy; Novartis: Consultancy. Padron:Incyte: Honoraria, Research Funding.

Whole Blood Thiamine in Organ Donors After the Neurologic Determination of Death.

Metabolic resuscitation of organ donors and the attenuation of oxidative stress incurred by organs following brain death and transplantation have the potential to improve organ yield and allograft function. Thiamine (vitamin B1) is a vital coenzyme in both energy metabolism and the production of antioxidants that has not been studied in the donor population. To determine the frequency of subclinical thiamine deficiency in brain-dead organ donors and its correlation with demographics, length of hospitalization, donor management, lactic acidosis, and the requirement for vasoactive support. Prospective cohort study of brain-dead donors managed at a single organ procurement organization's organ recovery facility. A total 64 donors were enrolled; 24 donors had thiamine levels drawn upon arrival and 40 donors had levels drawn at the time of organ procurement. Whole blood thiamine levels were inversely correlated with the time from death (P = .007) and 20% (8/40) of donors had levels below the normal range at the time of organ procurement. Demographic features of the donor were not associated with thiamine levels although longer hospital stays prior to death were associated with lower levels (P < .05). The presence and resolution of lactic acidosis was not associated with whole blood thiamine level. Higher thiamine levels were associated with earlier discontinuation of vasoactive support (P = .04). Whole blood thiamine deficiency was not uncommon at the time of organ procurement. Thiamine may be associated with the requirement for hemodynamic support.

Endoscopic Ultrasound–guided Fine-needle Biopsy With or Without Rapid On-site Evaluation for Diagnosis of Solid Pancreatic Lesions: A Randomized Controlled Non-Inferiority Trial

The benefit of rapid on-site evaluation (ROSE) on the diagnostic accuracy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) has never been evaluated in a randomized study. This trial aimed to test the hypothesis that in solid pancreatic lesions (SPLs), diagnostic accuracy of EUS-FNB without ROSE was not inferior to that of EUS-FNB with ROSE. A noninferiority study (noninferiority margin, 5%) was conducted at 14 centers in 8 countries. Patients with SPLs requiring tissue sampling were randomly assigned (1:1) to undergo EUS-FNB with or without ROSE using new-generation FNB needles. The touch-imprint cytology technique was used to perform ROSE. The primary endpoint was diagnostic accuracy, and secondary endpoints were safety, tissue core procurement, specimen quality, and sampling procedural time. Eight hundred patients were randomized over an 18-month period, and 771 were analyzed (385 with ROSE and 386 without). Comparable diagnostic accuracies were obtained in both arms (96.4% with ROSE and 97.4% without ROSE, P= .396). Noninferiority of EUS-FNB without ROSE was confirmed with an absolute risk difference of 1.0% (1-sided 90% confidence interval, -1.1% to 3.1%; noninferiority P < .001). Safety and sample quality of histologic specimens were similar in both groups. A significantly higher tissue core rate was obtained by EUS-FNB without ROSE (70.7% vs. 78.0%, P= .021), with a significantly shorter mean sampling procedural time (17.9 ± 8.8 vs 11.7 ± 6.0 minutes, P < .0001). EUS-FNB demonstrated high diagnostic accuracy in evaluating SPLs independently on execution of ROSE. When new-generation FNB needles are used, ROSE should not be routinely recommended. (ClinicalTrial.gov number NCT03322592.).

Acts that Kill and Acts that Do Not

In response to recent debates on the need to abandon the Dead Donor Rule (DDR) to facilitate vital-organ transplantation, I claim that, through a detailed philosophical analysis of the Uniform Determination of Death Act (UDDA) and the DDR, some acts that seem to violate DDR in fact do not, thus DDR can be upheld. The paper consists of two parts. First, standard apparatuses of the philosophy of language, such as sense, referent, truth condition, and definite description are employed to show that there exists an internally consistent and coherent interpretation of UDDA which resolves the Reduction Problem and the Ambiguity Problem that allegedly threaten the UDDA framework, and as a corollary, the practice of Donation after the Circulatory Determination of Death (DCDD) does not violate DDR. Second, an interpretation of the DDR, termed ‘No Hastening Death Rule’ (NHDR), is formulated so that, given that autonomy and non-maleficence principles are observed, the waiting time for organ procurement can be further shortened without DDR being violated.

O49: EFFECT OF AFIMOXIFENE (Z-4-HYDROXYTAMOXIFEN) ON ADIPOSE-DERIVED STEM CELLS

Abstract Background Adipose-derived stem cells (ADSCs) are a promising cell source for adipose tissue engineering. Currently, novel breast reconstruction techniques using ADSCs are actively being explored. Systemic chemo- &amp; hormonal therapy may impede tissue regeneration in breast cancer patients. However, the effect of hormonal therapy on ADSCs and their regenerative capabilities is poorly understood. Aims The current study aims to analyse the effect of Afimoxifene, an active metabolite of Tamoxifen, on proliferation and viability of ADSCs in vitro Method Lipoaspirates or adipose tissue were obtained with informed consent from breast cancer patients and healthy controls. The isolated ADSCs were subjected to single or multiple dose(s) of Z-4-Hydroxytamoxifen (12.5nM, 25nM, 50nM, 100nM and 1μM) and, analyzed on days 1, 3 and 5, using CellTitre 96 ® AQueous Cell proliferation assay. T47D and MDA-MB-231 cell lines were used as positive and negative controls, respectively. Result ADSCs were obtained from a total of 3 patients. ADSCs were isolated from a cancer patient with/without active disease at the time of sample procurement and healthy subjects opting for elective cosmetic procedures. Morphology, CFU assay and adipogenic differentiation assay were used to validate stem cell population. Afimoxifene demonstrated no statistically significant reduction in the viability or proliferation of the ADSCs, irrespective of the dose- or time-dependent exposure or cancer status (p &amp;gt;0.05). Conclusion Afimoxifene has no deleterious effect on viability or proliferation of human ADSCs up to 1μM concentration. Key words Adipose-derived stem cells, Afimoxifene, Breast reconstruction, Hormone therapy, Tamoxifen. Take-home message Afimoxifene has no deleterious effect on viability or proliferation of human ADSCs up to 1μM concentration

Isolation of Human Primary Valve Cells for In vitro Disease Modeling.

Calcific aortic valve disease (CAVD) is present in nearly a third of the elderly population. Thickening, stiffening, and calcification of the aortic valve causes aortic stenosis and contributes to heart failure and stroke. Disease pathogenesis is multifactorial, and stresses such as inflammation, extracellular matrix remodeling, turbulent flow, and mechanical stress and strain contribute to the osteogenic differentiation of valve endothelial and valve interstitial cells. However, the precise initiating factors that drive the osteogenic transition of a healthy cell into a calcifying cell are not fully defined. Further, the only current therapy for CAVD-induced aortic stenosis is aortic valve replacement, whereby the native valve is removed (surgical aortic valve replacement, SAVR) or a fully collapsible replacement valve is inserted via a catheter (transcatheter aortic valve replacement, TAVR). These surgical procedures come at a high cost and with serious risks; thus, identifying novel therapeutic targets for drug discovery is imperative. To that end, the present study develops a workflow where surgically removed tissues from patients and donor cadaver tissues are used to create patient-specific primary lines of valvular cells for in vitro disease modeling. This protocol introduces the utilization of a cold storage solution, commonly utilized in organ transplant, to reduce the damage caused by the often-lengthy procurement time between tissue excision and laboratory processing with the benefit of greatly stabilizing cells of the excised tissue. The results of the present study demonstrate that isolated valve cells retain their proliferative capacity and endothelial and interstitial phenotypes in culture upwards of several days after valve removal from the donor. Using these materials allows for the collection of control and CAVD cells, from which both control and disease cell lines are established.

POS-707 USE OF HYPOTHERMIC MACHINE PERFUSION IN KIDNEY TRANSPLANTATION

Delayed graft function (DGF) is associated with an increased risk of graft loss. The use of cold hypothermic machine perfusion (HMP) has been shown to reduce the incidence of DGF in kidney transplant recipients (KTRs), especially when extended-criteria donors (ECDs) are used. In addition, HMP can improve graft survival in the first years after transplantation. However, there is a paucity of data on the determinants of HMP use in real-life setting. We aimed to determine the factors associated with the use of MP in a cohort of donors and KTRs. We collected data on consecutive brain-dead donors admitted to an organ procurement organization (OPO) and their KTRs between June 2013 and December 2018 in 5 adult transplant centers across the province of Quebec in Canada. There is no standardized protocol for the use of HMP in the province of Quebec. The use of HMP is left at the discretion of the surgeon recovering organs. However, a HMP device was available for every organ recovered at the organ procurement organization. Generalized estimating equations were used to predict the use of HMP. The cohort included 159 deceased donors and their 281 KTRs. Thirty-three percent of donors were ECDs, and 59% of KTRs received organs placed on HMP. The median cold ischemia time (CIT) was 12.4 (IQR 7.9-16.2) hours. In univariate analysis, none of the donors’ characteristics were associated with the use of HMP. ECD represented 33% of KTR on HMP vs. 34% of those not receiving HMP (p=0.82). For KTRs, in univariate analysis, race (non-Caucasian), CIT, use of basiliximab/alemtuzumab, year of transplant and KTR center were associated with the use of HMP. We further identified the characteristics of KTR centers associated with HMP use. In multivariate analysis, longer CIT (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.06-1.22), longer distance between KTR center and OPO (OR 0.11, 95%CI 0.04-0.29), as well as KTR after 2013 remained significantly associated with use of HMP. We found that use of HMP was strongly associated with the transplant center where the surgeons practiced, suggesting that surgeon preference/training plays an important role in determining the use of HMP. Availability of HMP at the time of organ procurement might also be limited by logistic issues such as difficulty in returning the device to the OPO. Further studies aimed at determining the reasons underlying the barriers precluding the use of HMP could help increasing it use.

The Association of Time to Organ Procurement on Short- and Long-Term Outcomes in Kidney Transplantation.

Transplant centers in Europe aim to minimize the time from brain death to organ procurement (procurement delay), but evidence to justify this is scarce. In the United States, procurement times are significantly longer. Our objective was to analyze how procurement delay associates with kidney allograft outcomes. Kidney transplantations from brain-dead donors were retrospectively analyzed from the Finnish Kidney Transplant Registry and the Scientific Registry of Transplant Recipients in the United States. Multivariable models were adjusted with donor and recipient characteristics, and the relationship between procurement delay and outcomes was modeled with cubic spline functions. In total, 2388 and 101,474 kidney transplantations in Finland and the United States were included, respectively. The median procurement delay was 9.8 hours (interquartile range, 7.8-12.4) in Finland and 34.8 hours (interquartile range, 26.3-46.3) in the United States. A nonlinear association was observed between procurement delay and the risk of delayed graft function, with highest risk seen in short and very long procurement delays. In multivariable models, the lowest risk of delayed graft function was associated with procurement delay between 20 and 50 hours. In multivariable models, longer procurement delay was linearly associated with lower risk of graft loss (hazard ratio, 0.90/1 h longer; 95% confidence interval, 0.88 to 0.92; P<0.001). Acute rejection rates, for which data were only available from Finland, were not associated with procurement delay. Longer procurement delay was associated with noninferior or even better kidney allograft outcomes.

Abstract PS19-16: Utility of rapid autopsy in cancer research: Unexpected findings and lessons learned from warm autopsies of metastatic breast cancer patients

Abstract Metastatic disease is understudied largely because of inaccessibility to quality specimens for research use. The Legacy Project, a rapid or “warm”, autopsy program at City of Hope, seeks to overcome this challenge by collecting tissue from metastatic patients immediately (within 6 hours) after their death. This paradigm serves as a specimen resource to address many clinically relevant questions, such as disease heterogeneity and mechanisms driving disease progression. Using this model, we uncovered clinically relevant disease information that is normally unavailable while a subject is alive. In this study, 9 metastatic breast cancer patients and their families were approached and consented prior to death. The cohort includes a diversity of clinical presentations in terms of disease subtype, progression history, organ involvement, and final cause of death. A total of 533 specimens were collected across 9 subjects. The average time from death to specimen acquisition was 6.1 hours (range: 4.03 - 7.66 hours; median: 5.71 hours). Total number of specimens collected from each participant ranged from 38-75, with an average of 60 across all patients; the mean number of tumor-positive specimens collected was 29 (range 12-46); the mean number of non-cancer specimens collected was 31 (range 25-45). In patients with primary estrogen receptor (ER) positive disease, we observed variable heterogeneity in estrogen, progesterone, and ki67 status across metastatic lesions. Furthermore, we observed a profound shift in disease phenotype towards end of life, trending towards complete loss of hormone receptor expression and stark increase of Ki67 levels. At the time of procurement, one third of subjects exhibited clinically unidentified diseased sites in organs not commonly associated with breast cancer metastases a, including ovary, kidney, and pancreas. In two other instances, “resolved” bone specimens (as measured by absence of FTG uptake in PET/CT imaging) were later determined to be &amp;gt;30% tumor positive when assessed by H&amp;E. While these preliminary findings generate more questions than answers regarding mechanisms of metastatic progression and resistance to therapy, they highlight the utility of rapid autopsy in a research setting. We suggest that many unanswered clinical questions can be addressed through interrogation of post-mortem tissues and we urge research institutions to thoughtfully consider adoption of the “rapid autopsy” model. Citation Format: Eliza R Bacon, Kena Ihle, Colt Egelston, Weihua Guo, Diana Simons, Peter P Lee, James Waisman. Utility of rapid autopsy in cancer research: Unexpected findings and lessons learned from warm autopsies of metastatic breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS19-16.

L’insuffisance rénale aiguë du donneur en mort encéphalique : une réelle contre-indication à la transplantation rénale ?

The shortage of kidney transplants encourages the expansion of the limits of eligibility criteria for donation. Many donors who are brain dead display acute renal failure at the time of death; is this a real contraindication to harvesting? The aim of this study was to assess kidney graft survival from donors after brain death with confirmed acute renal failure, with or without anuria previous donation. All of the transplants performed in two university hospitals between 2010and 2017were analyzed retrospectively. All patients who underwent single kidney transplant from a brain-dead donor with acute renal failure (ARF) were included in this study. ARI was defined here by a decrease over 50% of glomerular filtration rate (GFR) to a threshold below 45mL/min/1.73m2at the time of kidney procurement. Kidney graft survival, incidence of delayed graft function (DGF) and the GFR at 12months were analyzed. Analysis of kidney transplant survival based on pre-implantation biopsies was additionally done. One hundred and sixty four patients were transplanted with a kidney from donor with ARF during the selected period. At the admission in ICU the average GFR was 67,7±19mL/min/1,73m2. At the time of donation, the average age of donors was 56.4±17.7years, the GFR was 33.7±8.0mL/min/1.73m2 16% of donors were anuric. Cold ischemia time (CIT) was 16.8±5.0hours. The average age of recipients was 55.6±14.1years. 81% of the cases were primary transplants. Graft function took place within 7.8±9.4days after transplantation. There were two non-primary functions (PNF). One hundred and fifty two patients (93%) had a functional graft at 12months. The mean GFR at 12months was 46.8±20.1mL/min/1.73m2and 122patients (73%) had a GFR greater than 30mL/min/1.73m2. Seventy-one percent of preimplantation biopsies revealed acute tubular necrosis (ATU); no cortical necrosis was observed. Survival of theses grafts was 85%, comparable to the total population of study (P=0,21) CONCLUSION: The acute renal failure of the brain-dead donor should not alone be systematically a contraindication to harvesting and kidney transplantation.

Centralized Procurement and Delivery Times: Evidence from a Natural Experiment in Italy

We study how delivery times and prices for hospital medical devices respond to the introduction of centralized procurement. Our identification strategy leverages a legislative change in Italy that mandated centralized purchases for a sub-set of devices. The statutory centralization generated a reduction in prices and an increase in delivery times for centralized purchases relative to non-centralized purchases. We use data on quantities and on suppliers to discuss the mechanisms potentially underlying our findings.

IDENTIFICATION OF PERMISSIBLE AREAS OF PREPARATION OF MEDICINAL VEGETABLE RAW MATERIALS NEAR TRANSPORT LINES

The purpose of the work is to study the permissible distance for the collection of medicinal plant raw materials near transport highways of different degrees of loading. The study was carried out in the Voronezh region on the example of eight different types of medicinal vegetable raw materials (Herring grass bitter, avian mountain grass, five-foot desert grass, plain thousand-year-old grass, double-ground nettle leaves, large planter leaves, common pajma flowers, core lip flowers) Collected in time of procurement along and at different distance from roads and railways of different degree of load in different natural zones, regulated by normative documentation. In the analyzed samples, the content of standardized biologically active substances, as well as heavy metals, pesticides, radionuclides, was previously estimated and full compliance with pharmacopoeia requirements was shown. In this work, the analysis was carried out on the level of ash insoluble in hydrochloric acid in the medicinal plant raw material, which makes it possible to estimate contamination of the raw material with dust particles. On the basis of the obtained data using the mathematical simulation method, the permissible distances from the transport lines, which can be recommended for the collection of safe medicinal plant raw materials, have been identified: Distance from major roads and highways loaded by road in forest natural zone conditions – at least 230 m, in forest steppe zone conditions – at least 300 m, in steppe zone conditions devoid of wood and shrub vegetation, – Not less than 660 m, near non-high-speed roads characterized by low traffic load – not less than 160 m, near railway lines – not less than 130 m. The obtained results can be recommended for safe collection of medicinal vegetable raw materials.

A Hybrid Mehta-Heuristic algorithm for optimization location-routing problem of facilities in four echelon supply chain

During the last three decades, the concept of integrated decision making in the supply chain becomes one of the essential aspects of supply chain management (SCM). This concept explores the interdependence between facility location, flow allocation between facilities, transportation system structure, and inventory control system. This study presents a new form of the location-routing problem of facilities under uncertainty in a supply chain network for deteriorating items through taking environmental considerations, cost, and procurement time and customer satisfaction into account, to simultaneously minimize total system costs, maximal delivery time and emissions across the entire network and maximize customer satisfaction. The research problem is formulated in a mixed-integer nonlinear multi-objective programming. In order to solve the model, the combination of the two Benders decomposition algorithm and Lagrange multiplier liberalization, as well as the combination of red deer algorithm and annealing simulation, was proposed. For validation, the results of the proposed algorithm in different size examples are compared with the results of the exact method solution by MATLAB software. The mean error of the proposed algorithm for the objective function is less than 4% compared to the exact method in solving the sample problems. Besides, the results of the algorithm performance are investigated based on standard indices. The computational results show the efficiency of the algorithm for a wide range of problems with different sizes. The location decisions are interdependent, and the process of determining the optimal values of these variables interact together, which can lead to an optimal system.

The implementation of lean construction and six sigma concepts in light brick installation: A case study in Cordova apartment project

PT Adhi Perkasa Gedung is a construction company engaged in building construction that is a subsidiary of PT Adhi Karya (Persero). Sustainability has become a significant issue this decade, as well as construction projects. Construction companies are required to be able to manage their resources effectively and efficiently through the completion of environmentally friendly projects. PT Adhi Perkasa Gedung as the construction contractor for the Cordova Apartment, strives to minimize waste in light brick installation. The light brick is used as a bulkhead between rooms in the apartment. The problems that occur are the waiting time of light brick procurement, product defects, material handling, and installation process errors. The purpose of this study is to minimize waste in light brick installation using lean construction and six sigma methods. The results of this study indicate the existence of rework due to installation process errors, material quality.

Acute Kidney Injury in Deceased Organ Donors and Kidney Transplant Outcomes: A National Cohort Study Using a Novel Data Source.

The aim of this study was to determine graft function and survival for kidney transplants from deceased donors with acute kidney injury (AKI) that persists at the time of organ procurement. Kidneys from donors with AKI are often discarded and may provide an opportunity to selectively expand the donor pool. Using Organ Procurement and Transplantation Network and DonorNet data, we studied adult kidney-only recipients between May 1, 2007 and December 31, 2016. DonorNet was used to characterize longitudinal creatinine trends and urine output. Donor AKI was defined using KDIGO guidelines and terminal creatinine ≥1.5 mg/dL. We compared outcomes between AKI kidneys versus "ideal comparator" kidneys from donors with no or resolved AKI stage 1 plus terminal creatinine <1.5mg/dL. We fit proportional hazards models and hierarchical linear regression models for the primary outcomes of all-cause graft failure (ACGF) and 12-month estimated glomerular filtration rate (eGFR), respectively. We identified 7660 donors with persistent AKI (33.2% with AKI stage 3) from whom ≥1 kidney was transplanted. Observed rates of ACGF within 3 years were similar between recipient groups (15.5% in AKI vs 15.1% ideal comparator allografts, P = 0.2). After risk adjustment, ACGF was slightly higher among recipients of AKI kidneys (adjusted hazard ratio 1.05, 95% confidence interval: 1.01-1.09). The mean 12-month eGFR for AKI kidney recipients was lower, but differences were not clinically important (56.6 vs 57.5 mL/min/1.73m 2 for ideal comparator kidneys; P < 0.001). There were 2888 kidneys discarded from donors with AKI, age ≤65 years, without hypertension or diabetes, and terminal creatinine ≤4 mg/dL. Kidney allografts from donors with persistent AKI are often discarded, yet those that were transplanted did not have clinically meaningful differences in graft survival and function.

C4 article: Implications of COVID-19 in transplantation.

A novel coronavirus has had global impact on individual health and health care delivery. In this C4 article, contributors discuss various aspects of transplantation including donor and recipient screening, management of infected patients, and prevention of coronavirus disease (COVID). Donor screening with SARS‐CoV‐2 nucleic acid testing (NAT) close to the time of procurement is recommended. Many programs are also screening all potential recipients at the time of admission. The management of COVID has evolved with remdesivir emerging as a new potential option for transplant recipients. Dexamethasone has also shown promise and convalescent plasma is under study. Prevention strategies for transplant candidates and recipients are paramount. Pediatric‐specific issues are also discussed. Strategies for the psychological well‐being of patients and providers are also imperative, in addition to future research priorities for transplantation.

An Automated High-Throughput Fluorescence In Situ Hybridization (FISH) Assay Platform for Use in the Identification and Optimization of siRNA-Based Therapeutics.

Since the revolutionary discovery of RNA interference (RNAi) more than 20 years ago, synthetic small interfering RNAs (siRNAs) have held great promise as therapeutic agents for treating human diseases by the specific knockdown of disease-causing gene products. To facilitate the development of siRNA therapeutics, a robust, high-throughput in vitro assay for measuring gene silencing is imperative during the initial siRNA lead sequence identification and, later, during the lead optimization with chemically modified siRNAs. There are several potential assays for measuring gene expression. Quantitative reverse transcription PCR (qRT-PCR) has been widely used to quantitate messenger RNA (mRNA). This method has a few disadvantages, however, such as the requirement for RNA isolation, complementary DNA (cDNA) generation, and PCR reaction, which are labor-intensive, limit the assay throughput, and introduce variability. We chose a high-content imaging assay, bDNA FISH, that combines the branched DNA (bDNA) technology with fluorescence in situ hybridization (FISH) to measure gene silencing by siRNAs because it is sensitive and robust with a short reagent procurement and assay development time. We also built a fully automated liquid-handling platform for executing bDNA FISH assays to increase throughput, and the system has a capacity of generating 192 concentration-response curves in a single run. We have successfully developed and executed the bDNA FISH assays for multiple targets using this automated platform to identify and optimize siRNA candidate molecules. Examples of the bDNA FISH assay for selected targets are presented.

A Systematic Review of Clinical Characteristics and Histologic Descriptions of Acute Tubular Injury

IntroductionThe term “acute tubular injury” (ATI) represents histopathologic renal tubular injury and often manifests clinically as acute kidney injury (AKI). Studies systematically summarizing the clinical presentation and histological changes in human ATI are limited.MethodsWe used a comprehensive search strategy to search human studies of ATI from 1936 to July 2019. We extracted study characteristics, clinical characteristics, and histologic descriptions of ATI by bright field, immunofluorescence, electron microscopy, and immunohistochemistry. We compared ATI histology as a function of tissue procurement type, timing, and etiologies.ResultsWe included 292 studies comprising a total of 1987 patients. The majority of studies (222 of 292, 76%) were single-center case reports. The mean age of included patients was 47 years. In native kidney biopsy cases, baseline, peak, and latest creatinine were 1.3 mg/dl, 7.19 mg/dl, and 1.85 mg/dl respectively, and biopsy was performed mostly after peak creatinine (86.7%, 391 of 451). We identified 16 histologic descriptions of tubular injury, including tubular cell sloughing (115 of 292, 39.4%), tubular epithelial flattening/simplification (110 of 292, 37.7%), tubular dilatation (109 of 292, 37.3%), and tubular cell necrosis (93 of 292, 31.8%). There was no difference in tubular injury histology among different tissue procurement types (native kidney biopsy, transplant kidney biopsy, and autopsy), among different etiologies, or between different tissue procurement timing (before or after creatinine peaks in native kidneys). Electron microscopy and immunohistochemistry were used in a minority of studies.ConclusionATI manifests with diverse histologic changes. Efforts to establish protocols to harmonize biopsy practices, to handle kidney biopsy for tissue interrogation, and to report results across clinical practice are needed to improve our understanding of this complex disease.