Durvalumab with or without tremelimumab versus the EXTREME regimen as first-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck: KESTREL, a randomized, open-label, phase III study.

BACKGROUND: Patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have a poor prognosis. The phase III KESTREL study evaluated the efficacy of durvalumab [programmed death-ligand 1 (PD-L1) antibody] with or without tremelimumab [cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody], versus the EXTREME regimen in patients with R/M HNSCC. PATIENTS AND METHODS: Patients with HNSCC who had not received prior systemic treatment for R/M disease were randomized (2 : 1 : 1) to receive durvalumab 1500 mg every 4 weeks (Q4W) plus tremelimumab 75 mg Q4W (up to four doses), durvalumab monotherapy 1500 mg Q4W, or the EXTREME regimen (platinum, 5-fluorouracil, and cetuximab) until disease progression. Durvalumab efficacy, with or without tremelimumab, versus the EXTREME regimen in patients with PD-L1-high tumors and in all randomized patients was assessed. Safety was also assessed. RESULTS: Durvalumab and durvalumab plus tremelimumab were not superior to EXTREME for overall survival (OS) in patients with PD-L1-high expression [median, 10.9 and 11.2 versus 10.9 months, respectively; hazard ratio (HR) = 0.96; 95% confidence interval (CI) 0.69-1.32; P = 0.787 and HR = 1.05; 95% CI 0.80-1.39, respectively]. Durvalumab and durvalumab plus tremelimumab prolonged duration of response versus EXTREME (49.3% and 48.1% versus 9.8% of patients remaining in response at 12 months), correlating with long-term OS for responding patients; however, median progression-free survival was longer with EXTREME (2.8 and 2.8 versus 5.4 months). Exploratory analyses suggested that subsequent immunotherapy use by 24.3% of patients in the EXTREME regimen arm contributed to the similar OS outcomes between arms. Grade 3/4 treatment-related adverse events (TRAEs) for durvalumab, durvalumab plus tremelimumab, and EXTREME were 8.9%, 19.1%, and 53.1%, respectively. CONCLUSIONS: In patients with PD-L1-high expression, OS was comparable between durvalumab and the EXTREME regimen. Durvalumab alone, and with tremelimumab, demonstrated durable responses and reduced TRAEs versus the EXTREME regimen in R/M HNSCC.

Uniformity calibration for large area XY strip parallel plate ionization chamber.

Demand for large area parallel plate ionization chamber (PPIC) or large area ionization chamber (LAIC) has risen in recent years due to several advantages of the large effective area in monitoring therapeutic radiation beams. PPICs are designed for the measurements of beam profile and dosimetry in radiation therapy quality assurance (QA) procedures.Objective. Heterogeneous responses over the large sensitive area pose an undeniable concern for the straightforward applications of PPICs in clinical dosimetry. Uniformity calibration for the detector response is thus essential for the accurate performance of each PPIC unit.Approach.A large area XY strip PPIC, characterized by a large effective area of 345.44 × 345.44 mm2and 256 readout channels, was investigated in this study. A new systematic uniformity calibration is developed to improve the lateral response of the PPIC over the measurements for both narrow beams and large square field beams. A 2D response map of the PPIC was obtained by a spot-scanning method using a compact x-ray tube (mini x-ray). The mini x-ray, providing stable radiation (uncertainty <0.1%), was moved with a step size of 20 mm in 2 dimensions across the entire PPIC surface to collect a complete spot scan. Different uniformity calibration methods were introduced for the measurement of the PPIC by adopting the information from the detector 2D response map.Main results.Deviation of the detector response, before calibration, was observed to reach about 7% for the testing PPIC unit which is much higher than the recommended uniformity response of 1% (IAEA TRS-398). The uniformity response of the PPIC improved significantly to less than 1% across the detector surface after calibration.Significance.The proposed methods enable the practical application of PPIC in routine clinical dosimetry and can be reliably adopted by any radiation facility to perform daily and monthly QA.

Differential effects of aquatic anaesthetics on the pharmacokinetics of antibiotics: Examples using florfenicol in Nile tilapia (Oreochromis niloticus).

Anaesthetics are commonly applied in pharmacokinetic (PK) studies to assure smooth handling of experimental procedures or to promote animal welfare. However, the influence of anaesthetics on the PK of co-administered drug is generally unknown but assumes ignorable. The goal of the study was to investigate the effect of tricaine methanesulfonate (MS-222), 2-phenoxyethanol (2-PE) and eugenol (EUG) on the PK of florfenicol (FF) in Nile tilapia. Twenty-eight fish were repeatedly exposed to 90 ppm EUG, 300 ppm MS-222 or 900 ppm 2-PE before FF oral administration (15 mg/kg) and each successive blood sampling. The serum concentration-time profiles were analysed by a 2-compartmental model, and the generated parameters in the control (without anaesthetic) and anaesthetic groups were statistically compared. The results demonstrated that the serum concentrations of each anaesthetic were similar at every FF sampling times (70 µg/ml for MS-222; 277 µg/ml for 2-PE; and 61 µg/ml for EUG). In comparison with the control group, the repeated use of MS-222 did not result in a statistical difference in most of the PK parameters. In contrast, the elimination half-lives of the 2-PE and EUG groups were significantly longer whereas the absorption and distribution half-lives of the 2-PE group were significantly shorter than the control, resulting in altered optimal dosages in the simulation modelling. Whether or not the numbers and extent of PK parameters change mitigate subsequent estimations of other PK-derived secondary values such as dosing regimen and withdrawal time remains to be elucidated, but the auxiliary use of anaesthetics in PK studies should not assume uninfluential.

Identification of circulating biomarkers for differentiating patients with papillary thyroid cancers from benign thyroid tumors.

BACKGROUND: This study aimed to identify the potential circulating biomarkers of protein, mRNAs, and long non-coding RNAs (lncRNAs) to differentiate the papillary thyroid cancers from benign thyroid tumors. METHODS: The study population of 100 patients was classified into identification (10 patients with papillary thyroid cancers and 10 patients with benign thyroid tumors) and validation groups (45 patients with papillary thyroid cancers and 35 patients with benign thyroid tumors). The Sengenics Immunome Protein Array-combined data mining approach using the Open Targets Platform was used to identify the putative protein biomarkers, and their expression validated using the enzyme-linked immunosorbent assay. Next-generation sequencing by Illumina HiSeq was used for the detection of dysregulated mRNAs and lncRNAs. The website Timer v2.0 helped identify the putative mRNA biomarkers, which were significantly over-expressed in papillary thyroid cancers than in adjacent normal thyroid tissue. The mRNA and lncRNA biomarker expression was validated by a real-time polymerase chain reaction. RESULTS: Although putative protein and mRNA biomarkers have been identified, their serum expression could not be confirmed in the validation cohorts. In addition, seven lncRNAs (TCONS_00516490, TCONS_00336559, TCONS_00311568, TCONS_00321917, TCONS_00336522, TCONS_00282483, and TCONS_00494326) were identified and validated as significantly downregulated in patients with papillary thyroid cancers compared to those with benign thyroid tumors. These seven lncRNAs showed moderate accuracy based on the area under the curve (AUC = 0.736) of receiver operating characteristic in predicting the occurrence of papillary thyroid cancers. CONCLUSIONS: We identified seven downregulated circulating lncRNAs with the potential for predicting the occurrence of papillary thyroid cancers.

Synthetic cathinone poisoning from ingestion of drug-laced "instant coffee packets" in Taiwan.

BACKGROUND: Synthetic cathinone abuse is a global health issue. Synthetic cathinones emerged in Taiwan in 2009, and their prevalence rapidly rose. They are usually made into "instant coffee packets," and these so-called "toxic coffee packets" may also contain psychoactive drugs other than synthetic cathinones. Due to the diversity of the ingredients, clinical presentations can be complex. METHODS: Retrospective analysis of emergency department (ED) patients who reported ingesting toxic coffee packets at three Chang-Gung Memorial Hospitals located in northern Taiwan between January, 2015 and December, 2019. RESULTS: Sixty patients were included. Their mean age was 28.85 ± 9.24 years and 47(78.33%) were male. The most common presentations were palpitation, agitation, hallucination, and altered consciousness. Tachycardia and hypertension were common, while hyperthermia was observed in only three patients. Three patients (5%) developed rhabdomyolysis, and one underwent transient hemodialysis. Most patients were discharged from the ED, but 15(25%) were admitted, of whom nine (15%) were admitted to the intensive care unit (ICU), and one eventually died. Confirmation tests (mass-spectrometry-based analysis) were available in 10 patients; all reported positive for at least one type of synthetic cathinone. Polysubstance exposure was common. In multivariate logistic regression analyses, Glasgow coma scale ≤13 and the presence of seizure were associated with ICU admission. CONCLUSION: Patients who report ingesting toxic coffee packets are very likely to have been exposed to synthetic cathinones. Polysubstance exposure is common following ingestion. Cardiovascular and neurological symptoms are the main presentations, and severe complications such as rhabdomyolysis and life-threatening dysrhythmia can occur.

Cryo-FIB preparation of whole cells and tissue for cryo-TEM: use of high-pressure frozen specimens in tubes and planchets.

The desire to study macromolecular complexes within their cellular context requires the ability to produce thin samples suitable for cryo-TEM (cryo-transmission electron microscope) investigations. In this paper, we discuss two similar approaches, which were developed independently in Utrecht (the Netherlands) and Albany (USA). The methods are particularly suitable for both tissue samples and cell suspensions prepared by a high-pressure freezer (HPF). The workflows are explained with particular attention to potential pitfalls, while underlying principles are highlighted ('why to do so'). Although both workflows function with a high success rate, full execution requires considerable experience and remains demanding. In addition, throughput is low. We hope to encourage other research groups worldwide to take on the challenge of improving the HPF- cryo-FIB-SEM - cryo-TEM workflow. We discuss a number of suggestions to this end. LAY DESCRIPTION: Life is ultimately dictated by the interaction of molecules in our bodies. Highly complex equipment is being used and further developed to study these interactions. The present paper describes methods to prepare small, very thin lamellae (area of 5×5 µm2 , thickness 50-300 nm) of a cell to be studied in a cryo-transmission electron microscope (cryo-TEM). Special care must be taken to preserve the natural state of molecules in their natural environment. In the case of cryo-TEM, the samples must be frozen and kept frozen to be compatible with the vacuum conditions in the microscope. The frozen condition imposes technical challenges which are addressed. Two approaches to obtain the thin lamellae are described. Both make use of a focused ion beam (FIB) microscope. The FIB allows removal of material with nanometre precision by focusing a beam of ionised atoms (gallium ions) onto the sample. Careful control of the FIB allows cutting out of the required thin lamellae. In both strategies, the thin lamellae remain attached to the original sample, and the ensemble of sample with section and sample holder is transported from the FIB microscope to the TEM while being kept frozen.

Hemogram-based decision tree for predicting the metabolic syndrome and cardiovascular diseases in the elderly.

BACKGROUND: This study aimed to build a hemogram-based decision tree to evaluate the association between current probability of metabolic syndrome (MetS) and prediction of future hypertension, type 2 diabetes and cardiovascular diseases (CVD) risk. METHODS: A total of 40 395 elder participants (≥60 years) were enrolled in a standard health examination program in Taiwan from January 1999 to December 2014. A decision tree classification of the presence or absence of MetS at baseline, using age, sex and hemogram (white blood cell, hemoglobin and platelet) as independent variables, was conducted for the randomly assigned training (70%) and validation (30%) groups. Participants without MetS at baseline (n = 25 643) were followed up to observe whether they developed MetS, hypertension, type 2 diabetes or CVD in the future. RESULTS: Modest accuracy of the decision tree in the training and validation groups with area under the curves of 0.653 and 0.652, respectively, indicated an acceptable generalizability of results. The predicted probability of baseline MetS was obtained from decision tree analysis. Participants without MetS at baseline were categorized into three equally sized groups according to the predicted probability. Participants in the third tertile had significantly higher risks of future MetS (hazard ratio 1.40, 95% confidence interval 1.25-1.58); type 2 diabetes (1.46, 1.17-1.83); hypertension (1.14, 1.01-1.28); and CVD (1.21, 1.01-1.44), compared with those in the first tertile. CONCLUSIONS: Execution of hemogram-based decision tree analysis can assist in early identification and prompt management of elderly patients at a high risk of future hypertension, type 2 diabetes and CVD.

Associations between comorbidity and quality of life outcomes after total joint replacement.

PURPOSE: We examined associations between self-reported and clinician-assessed comorbidity and quality of life (QOL) outcomes after hip and knee replacement. METHODS: This is a cross-sectional, questionnaire-based national survey. Participants aged 45 years or older (n = 409) were recruited from the New Zealand Joint Registry six months after a total hip (THR), total knee (TKR) or unicompartmental knee replacement (UKR). The main outcome QOL was measured using an 8-item short form of the World Health Organisation Quality of Life (WHOQOL-Bref) questionnaire six months following joint replacement surgery. The WHOQOL is a generic and non-health condition specific measure of QOL. RESULTS: Participants were on average 68 years of age, with more men (54%) than women (46%). Number of coexisting conditions and body mass index were correlated with age, pain and function scores, and QOL (p < 0.01), but not with each other. Linear regression analyses showed that comorbidities such as number of comorbid conditions and BMI had moderate associations with QOL outcomes. CONCLUSION: This study showed that general QOL outcomes following hip and knee joint replacement, while generally high, were associated with comorbidity burden and BMI. Future prospective research examining change in QOL before and following surgery would help to advance understandings of the various factors that contribute to patient satisfaction with their joint replacement.

A systematic review and meta-analysis of cancer patients affected by a novel coronavirus.

BACKGROUND: Cancer patients with COVID-19 disease have been reported to have double the case fatality rate of the general population. MATERIALS AND METHODS: A systematic search of PubMed/MEDLINE, Embase, Cochrane Central, Google Scholar, and MedRxiv was done for studies on cancer patients with COVID-19. Pooled proportions were calculated for categorical variables. Odds ratio and forest plots were constructed for both primary and secondary outcomes. The random-effects model was used to account for heterogeneity between studies. RESULTS: This systematic review of 31 studies and meta-analysis of 181,323 patients from 26 studies involving 23,736 cancer patients is the largest meta-analysis to the best of our knowledge assessing outcomes in cancer patients affected by COVID-19. Our meta-analysis shows that cancer patients with COVID-19 have a higher likelihood of death (odds ratio, OR 2.54), which was largely driven by mortality among patients in China. Cancer patients were more likely to be intubated, although ICU admission rates were not statistically significant. Among cancer subtypes, the mortality was highest in hematological malignancies (OR 2.43) followed by lung cancer (OR 1.8). There was no association between receipt of a particular type of oncologic therapy and mortality. Our study showed that cancer patients affected by COVID-19 are a decade older than the normal population and have a higher proportion of co-morbidities. There was insufficient data to assess the association of COVID-directed therapy and survival outcomes in cancer patients. Despite the heterogeneity of studies and inconsistencies in reported variables and outcomes, these data could guide clinical practice and oncologic care during this unprecedented global health pandemic. CONCLUSION: Cancer patients with COVID-19 disease are at increased risk of mortality and morbidity. A more nuanced understanding of the interaction between cancer-directed therapies and COVID-19-directed therapies is needed. This will require uniform prospective recording of data, possibly in multi-institutional registry databases.

Use of rehabilitation after hip and knee replacement in New Zealand: a national survey.

AIMS: Our objective was to describe rehabilitation used before and after joint replacement in New Zealand and evaluate variation based on geography and ethnicity. METHODS: In this descriptive cross-sectional questionnaire-based study we recruited participants 45 years or older (n=608) from the New Zealand Joint Registry six months after primary total hip, total knee or uni-compartmental knee replacement. RESULTS: The cohort was predominantly New Zealand European (89.9%). The average age of participants was 68.2 years. Less rehabilitation was used pre-operatively (31.0%) than post-operatively (79.6%) and total hip replacement participants reported using less rehabilitation (63.3%) than those after total knee (90.7%) or uni-compartmental knee (80.3%) replacement (p<0.01). There were trends towards more pre-operative rehabilitation for participants living in larger urban areas, most evident for total hip replacement (p<0.05). CONCLUSIONS: Participants reported generally positive outcomes six months after primary total hip, knee and uni-compartmental knee replacement. However, differences in use of rehabilitation services before and after joint replacement were evident depending on joint replaced. Broadening setting options for rehabilitation might improve use of rehabilitation resources.

Gaussian Thermal Operations and The Limits of Algorithmic Cooling.

The study of thermal operations allows one to investigate the ultimate possibilities of quantum states and of nanoscale thermal machines. Whilst fairly general, these results typically do not apply to continuous variable systems and do not take into account that, in many practically relevant settings, system-environment interactions are effectively bilinear. Here we tackle these issues by focusing on Gaussian quantum states and channels. We provide a complete characterization of the most general Gaussian thermal operation acting on an arbitrary number of bosonic modes, which turn out to be all embeddable in a Markovian dynamics, and derive necessary and sufficient conditions for state transformations under such operations in the single-mode case, encompassing states with nonzero coherence in the energy eigenbasis (i.e., squeezed states). Our analysis leads to a no-go result for the technologically relevant task of algorithmic cooling: We show that it is impossible to reduce the entropy of a system coupled to a Gaussian environment below its own or the environmental temperature, by means of a sequence of Gaussian thermal operations interspersed by arbitrary (even non-Gaussian) unitaries. These findings establish fundamental constraints on the usefulness of Gaussian resources for quantum thermodynamic processes.

Ascending aorta replacement vs. total aortic arch replacement in the treatment of acute type A dissection: a meta-analysis.

OBJECTIVE: Acute type A aortic dissection (ATAAD) is a severe, rapidly progressing disease which typically requires patients to undergo emergency surgical intervention. Despite advancements in surgical procedures, still, ATAAD remains a surgical emergency associated with high mortality. The aim of this systematic review and meta-analysis was to compare whether either ascending aorta replacement (AR) or total aortic arch replacement (TR) leads to improved short- and long-term clinical outcomes. MATERIALS AND METHODS: A search of PubMed, Embase, Science Direct, Web of Science, SciELO, BIOSIS, and China National Knowledge Infrastructure (CNKI) databases were supplemented by searching through bibliographies of key articles. Thereafter, data on early and late prognostic factors were extracted. A systematic review and meta-analysis of 15 studies were performed to compare whether either AR or TR leads to a reduction in the risk of in-hospital and short-term mortality, postoperative complications, re-operation rate, and long-term mortality. RESULTS: A total of 15 cohort studies (n = 2822 patients with ATAAD; AR with HA, partial arch = 1911, TR = 911) were deemed eligible and included in the meta-analysis. Compared with TR, AR led to a significantly lower risk of in-hospital mortality (RR = 0.77; 95% CI: 0.61-0.96), shorter cardiopulmonary bypass time (CPB, mean difference = -53.09; 95% CI: -56.68--49.50), circulatory arrest time (CA, mean difference = -8.09; 95% CI: -9.04-7.15), and antegrade cerebral perfusion (ACP, mean difference = -28.62; 95% CI: -30.23--27.00). Differences in the incidence rates of neurological dysfunctions and renal dialysis were not significant. The pooled rate of aortic re-operation was lower in TR group (AR 7.6% vs. TR 5.3%), albeit not significantly (risk ratio = 1.39; 95% CI: 0.94-2.07; p = 0.10). CONCLUSIONS: These findings demonstrate that AR is associated with a lower early mortality rate and shorter operative times overall. Nevertheless, the incidence of postoperative complications in patients undergoing AR is comparable to that of patients undergoing TR. Further prospective follow-up data needs to be collected and analyzed to discern whether there are statistically significant differences in the risks of re-operation and long-term mortality between AR and TR procedures.

Joint replacement rehabilitation and the role of funding source.

OBJECTIVE: To examine associations between funding source, use of rehabilitation and outcomes after total joint replacement and to evaluate variations based on demographic characteristics. DESIGN: Cross-sectional, questionnaire-based national survey. SUBJECTS: Participants aged 45 years or older (n = 522) who received either private or public funding for their surgery, were recruited from the New Zealand Joint Registry 6 months after a total hip, total knee or unicompartmental knee replacement. RESULTS: The cohort was predominantly New Zealand European (90%), aged 68 years, with more men (55%) than women (45%). Privately funded participants were younger, had higher levels of education and employment, and lower rates of comorbidities at the time of surgery. Privately funded participants also reported spending less time on the surgical waiting list, were less likely to participate in pre-surgical rehabilitation, but reported more weeks of post-surgical rehabilitation and better patient-reported outcomes in terms of pain, function and quality of life, compared with their publicly funded counterparts. CONCLUSION: Factors already known to impact on joint replacement outcomes were associated with funding source in this cohort. Socio-economic differences and inequities between private and public systems exist consistent with limited available prior research. In this cross-sectional study, no clinically significant differences in outcomes between the groups were identified. Prospective research will help to clarify whether funding source directly affects joint replacement rehabilitation outcomes.

Combination immunosuppressant therapy and lupus nephritis outcome: a hospital-based study.

Lupus nephritis (LN) is the leading cause of mortality in lupus patients. This study aimed to investigate the treatment outcome and renal histological risk factors of LN in a tertiary referral center. Between 2006 and 2017, a retrospective observational study enrolled 148 biopsy-proven LN patients. After propensity score matching, 75 cases were included for further analysis. The classification and scoring of LN were assessed according to the International Society of Nephrology/Renal Pathology Society. Treatment response was evaluated by daily urine protein and urinalysis at two years after commencing induction treatment and the development of end-stage renal disease (ESRD). In total, 50.7% patients achieved complete remission (CR) or partial remission (PR), while 49.3% patients were categorized as nonresponders. Therapeutic responses in terms of CR/PR rates were associated with Systemic Lupus Erythematosus Disease Activity Index scores (odds ratio (OR): 1.34, 95% confidence interval (CI): 1.12-1.60, p = 0.001). Moreover, higher baseline creatinine levels (hazard ratio (HR): 2.10, 95% CI: 1.29-3.40, p = 0.003), higher renal activity index (HR: 1.30, 95% CI: 1.07-1.58, p = 0.008) and chronicity index (HR: 1.40, 95% CI: 1.06-1.85, p = 0.017) predicted ESRD. Among pathological scores, cellular crescents (HR: 4.42, 95% CI: 1.01-19.38, p = 0.049) and fibrous crescents (HR: 5.93, 95% CI: 1.41-24.92, p = 0.015) were independent risk factors for ESRD. In conclusion, higher lupus activity was a good prognostic marker for renal remission. Renal histology was predictive of ESRD. Large-scale prospective studies are required to verify the efficacy of mycophenolate in combination with azathioprine or cyclosporine in LN patients.

A luminescence-based assay for evaluating bactericidal antibody to Borrelia burgdorferi in vaccinated horses' serum.

BACKGROUND: Current serological tests cannot discriminate between bactericidal Borrelia burgdorferi antibodies from others that are merely a response to Borrelia antigenic stimulation. OBJECTIVE: To develop a sensitive and convenient luminescence-based serum bactericidal assay (L-SBA) to identify serum borreliacidal activity. STUDY DESIGN: Prospective validation study and method comparison. METHODS: Serum samples were obtained either from archives of the Animal Health Diagnostic Center at Cornell University (N = 7) or from a vaccination trial (N = 238). Endogenous complement-inactivated serum sample was incubated with exogenic complement and B. burgdorferi ML23 pBBE22luc, which is able to process luciferin with luciferase and produce luminescence in viable Borrelia. After incubation, a light signal can be detected by using a luminometer to calculate the borreliacidal antibody titre. RESULTS: Components of the reaction mixture including spirochetes and complement from various sources and concentrations were tested to identify a reliable recipe for our complement-mediated L-SBA. We also applied this L-SBA on measuring bactericidal antibody activities and calculated the half inhibitory concentration (IC50 ) of serum samples from clinical collections. Furthermore, we analysed the L-SBA titres and anti-outer surface protein A (OspA) antibody levels from vaccinated horses using the multiplex assays and found that there is a relationship between results generated using these two different assays. The increases of L-SBA titres correlated with increases of anti-OspA antibody titre in sera (r = 0.423). MAIN LIMITATIONS: Immunoreactivity of commercial complement may differ from different batches. Clinical protection of borreliacidal antibody levels has not been determined. CONCLUSIONS: The L-SBA provided a sensitive and easy-operating platform for the evaluation of bactericidal antibody to B. burgdorferi, and we anticipated L-SBA would function well as an evaluation tool of vaccine efficiency in the future.

Effective Decision-Making and Decisional Regret in Living Kidney Donors of Taiwan.

BACKGROUND: While most living kidney donors are satisfied with their decision and do not regret donating, few studies have been conducted on the determinants related to the effectiveness and regret of the decision. This study aims to explore the relationship between basic attributes, quality of life, positive affect, negative affect, effectiveness of decision-making, and regret in living kidney donors. METHODS: In this cross-sectional study, living kidney donors were recruited from urology and kidney transplant outpatient services. The structured questionnaire used to collect the data included the Positive and Negative Affect Schedule, Medical Outcomes Study 12-Item Short-Form Health Survey, Decision Conflict Scale, and Decision Regret Scale. RESULTS: The findings indicate that living donors with better health status, 24-hour creatinine clearance, physical health-related quality of life (HRQOL), and positive affect experienced greater feelings of effective decision-making. Moreover, women and donors with better physical HRQOL, positive affect, and decision effectiveness were less regretful about the decision of kidney donation. CONCLUSION: Health status, physical HRQOL, and positive affect are related to decision validity and regret of living donors. Therefore, clinical care providers should regularly assess the mood and health of living kidney donors. Furthermore, activities promoting their health should be encouraged, especially for men.

Designing Triple Adult Liver Grafts From an Ideal Deceased Liver.

Splitting deceased donor livers and creating 3 grafts from a whole liver may be feasible and shorten the waiting time for organ donation in patients with high mortality rates. We hypothesized that it might be reasonable to procure 3 grafts for donation from one deceased donor liver by splitting the liver into left (segment II, III, IV), right anterior (segment V, VIII), and right posterior lobes (segment VI, VII) for liver transplantation according to the portal system trifurcated variations. We designed the right anterior branch with the main portal trunk and middle hepatic artery to become inflow of right anterior lobe, the left portal vein and left hepatic artery to become the inflow of left lobe and right posterior branch, and right hepatic artery to become the inflow of right posterior lobe. We retrospectively reviewed the volumetric computed tomography and magnetic resonance cholangiopancreatography of 153 liver donors. The hepatic and portal veins, hepatic artery, and biliary system were reorganized and classified. The volumetric proportions of the liver grafts were measured. Trifurcation of the portal vein variation was found in approximately 13.7% of portal systemic variations. The left lobe accounted for 29.18% of the total liver volume, the right anterior lobe, 35.22%, and the right posterior lobe, 35.6%. We validated this principle by dissecting the explanted liver and identified the triple grafts' weights, percentages, vessels, and biliary ducts system. The splitting of deceased donor livers into 3 split liver grafts for use in liver transplantation surgery can be clinically useful.

Impact of Positive Donor-Specific HLA Antibodies Crossmatch on Graft Survival in ABO-Incompatible Liver-Kidney Transplantation: A Case Report.

We present a patient with positive donor-specific antibodies (DSA) and crossmatch of ABO-incompatible (ABOi) combined liver and kidney transplantation (CLKT). Antibody-mediated rejection did not occur and the graft had survived for over one year at the time of writing without infectious complications. A 56-year-old man with positive DSA and positive crossmatch underwent living donor CLKT. The preoperative protocol for ABOi consisted of a single dose of rituximab and total plasma exchange (TPE). The result of anti-B antibody titer for IgG was 1:32. The evaluations of complement-dependent cytotoxicity and flow cytometry cross-match revealed a change from T+/B+ to T-/B+. The patient required adult living donor CLKT. Acute rejection episodes were treated using antithymocyte globulin, and the kidney required 7 days' treatment to recover. No further rejection and infectious episodes have been observed in past 13 months since the transplant. DSA and crossmatches are important for antibody detection and analysis. In the rituximab era, TPE can be used to achieve a successful decrease in antibody titer. In countries with a severe shortage of cadaveric organ donors, it may be possible to select ABOi candidate donors with positive DSA and crossmatch.