Post-transplant outcomes and financial burden of donation after circulatory death donor liver transplant after the implementation of acuity circle policy.

BACKGROUND: After implementation of the Acuity Circles (AC) allocation policy, use of DCD liver grafts has increased in the United States. METHODS: We evaluated the impact of AC on rates of DCD-liver transplants (LT), their outcomes, and medical costs in a single practice. Adult LT patients were classified into three eras: Era 1 (pre-AC, 1/01/2015-12/31/2017); Era 2 (late pre-AC era, 1/01/2018-02/03/2020); and Era 3 (AC era, 05/10/2020-09/30/2021). RESULTS: A total of 520 eligible LTs were performed; 87 were DCD, and 433 were DBD. With each successive era, the proportion of DCD increased (Era 1: 11%; Era 2: 20%; Era 3: 24%; p < .001). DCD recipients had longer ICU stays, higher re-admission/re-operation rates, and higher incidence of ischemic cholangiopathy compared to those with DBD. Direct, surgical, and ICU costs during first admission were higher with DCD than DBD (+8.0%, p < .001; +4.2%, p < .001; and +33.3%, p = .001). DCD-related costs increased after Era 1 (Direct: +4.9% [Era 2 vs. 1] and +12.4% [Era 3 vs. 1], p = .04; Surgical: +17.7% and +21.7%, p < .001). In the AC era, there was a significantly higher proportion of donors ≥50 years, and more national organ sharing. Compared to DCD from donors <50 years, DCD from donors ≥50 years was associated with significantly higher total direct, surgical, and ICU costs (+12.6%, p = .01; +9.5%, p = .01; +84.6%, p = .03). CONCLUSIONS: The proportion of DCD-LT, especially from older donors, has increased after the implementation of AC policies. These changes are likely to be associated with higher costs in the AC era.

Isolation, Characterization, and Antiproliferative Activity of Terpenoids from the Tropical Plant Turraea delphinensis.

The isolation, structure determination, and biological evaluation of constituents from the organic extract of Turraea delphinensis Wahlert (Meliaceae) resulted in the isolation of 51 secondary metabolites, including 14 new terpenoids (six cycloartanes, four tirucallanes/euphanes, three limonoids, and a 7-keto sterol). Among the new compounds, 1 is the first triterpenoid with a trioxaspiro[4.4]nonane side chain, while 11-13 are the first 17-γ-lactone tetranortriterpenoids with four oxygenated functional groups at C-1, -3, -6, and -7. The isolated compounds were evaluated for antiproliferative activity against five human tumor cell lines, including a vinblastine-resistant cell line.

Caged Xanthones and Biphenyls Isolated from the Tropical Plant Garcinia lateriflora.

Four cytotoxic heptacyclic caged-xanthones [gambogefic acids B-E (1-4)], a cytotoxic hexacyclic caged-xanthone [garcilatelic acid (5)], and four biphenyl derivatives [garcilatelibiphenyls A-D (6-9)] were newly isolated in a phytochemical study of a 50% MeOH/CH2Cl2 extract of Garcinia lateriflora (Clusiaceae). The isolated compounds were evaluated for antiproliferative activity against five human tumor cell lines including a vincristine-resistant line. The new caged-xanthones displayed potent activity with IC50 values from 0.5 to 6.7 µM against all tested tumor cell lines.

Unusual Vilasinin-Class Limonoids from Trichilia rubescens.

Eight vilasinin-class limonoids, including the unusually chlorinated rubescins K-M (1-3), the 2,3-epoxylated rubescin N (4), and rubescins O-R (5-8), were newly isolated from Trichilia rubescens. The structures of the isolated compounds were determined through spectroscopic and spectrometric analyses, as well as ECD calculations. The natural occurrence of chlorinated limonoids 1-3 was confirmed by chemical methods and HPLC analysis of a roughly fractionated portion of the plant extract. Eight selected limonoids, including previously known and new compounds, were evaluated for antiproliferative activity against five human tumor cell lines. All tested limonoids, except 8, exhibited significant potency, with IC50 values of <10 µM; in particular, limonoid 14 strongly inhibited tumor cell growth, with IC50 values of 0.54-2.06 µM against all tumor cell lines, including multi-drug-resistant cells.

Effects of the implementation of acuity circle policy on waitlist and post-transplant outcomes of liver re-transplantation.

BACKGROUND: Acuity circle (AC) policy implementation improved the waitlist outcomes for certain liver transplant (LT)-candidates. The impact of the policy implementation for liver retransplant (reLT) candidates is unknown. METHODS: Using Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) data from January, 2018 to September, 2021, we investigated the effect of the AC policy on waitlist and post-LT outcomes among patients who had previously received a LT. Patients were categorized by relisting date: Pre-AC (Era 1: January 1, 2018-February 3, 2020; n = 750); and Post-AC (Era 2: February 4, 2020-June 30, 2021; n = 556). Patient and donor characteristics, as well as on-waitlist and post-reLT outcomes were compared across eras. RESULTS: In Era 2, the probability of transplant within 90 days overall and among patients relisted > 14 days from initial transplant (late relisting) were significantly higher compared to Era 1 (subdistribution hazard ratio [sHR] 1.40, 95% CI 1.18-1.64, p < .001; sHR 1.52, 95% CI 1.23-1.88, p = .001, respectively). However, there was no difference by era among patients relisted ≤14 days from initial transplant (early relisting; sHR 1.21, 95% CI .93-1.57, p = .15). Likewise, among early relisting patients, risks for 180-day graft loss and mortality were significantly higher in Era 2 versus Era 1 (adjusted hazard ratio [aHR] 5.77, 95% CI 1.71-19.51, p = .004; and aHR 8.22, 95% CI 1.85-36.59, p = .005, respectively); for late relisting patients, risks for these outcomes were similar across eras. CONCLUSION: Our results show that the implementation of AC policy has improved transplant rates and reduced waiting time for reLT candidates listed > 14 days from initial transplant. However, the impact upon early relisting patients may be mixed.

A New Bis-indole Alkaloid, Spermaocymine A, and an Anthraquinone from Spermacoce ocymoides.

A phytochemical study on Spermacoce ocymoides has led to the isolation of a novel bis-indole alkaloid, spermaocymine A (2), together with the known alkaloid 4-methyl-borreverine (1), as well as an anthraquinone, 8-hydroxy-2-(hydroxymethyl)-1-methoxyanthracene-9,10-dione (3). The structures of the isolated compounds were elucidated by analyzing spectroscopic and spectrometric data, including one-dimensional (1D)- and 2D-NMR and high resolution (HR)-MS. Newly isolated alkaloid 2 was a C-3,14-stereoisomer of 1, the first natural stereoisomer of related bis-indoles containing an indeno[1,2-b]indole skeleton with an epiminoethano bridge. When 1-3 were assayed against five tumor cell lines including multi-drug resistant cells, compound 1 exhibited potent antiproliferative activity with IC50 values of 6.2-11.5 µM.

Chemical Components in Hedera rhombea Leaves and Their Cytotoxicity.

Two novel triterpene glycosides (1 and 2), 17 known triterpene glycosides (3-19), two known flavonoid glycosides (20 and 21), and two known norsesquiterpene glucosides (22 and 23) were isolated from Hedera rhombea (Araliaceae) leaves. The structures of 1 and 2 were determined by spectroscopic analysis, including two-dimensional NMR spectroscopy, and chromatographic analysis of the hydrolyzed products. The cytotoxicity of the isolated triterpene glycosides (1-19) against HL-60 human promyelocytic leukemia cells was evaluated. Compounds 9, 10, and 11 were cytotoxic to HL-60 cells with IC50 values of 7.2, 21.9, and 32.8 µM, respectively. Other compounds isolated from the leaves were not cytotoxic at sample concentrations of 50 µM.

Retusone A, a Guaiane-Type Sesquiterpene Dimer from Wikstroemia retusa and Its Inhibitory Effects on Histone Acetyltransferase HBO1 Expression.

Retusone A (1), a new sesquiterpene dimer consisting of two guaiane-type sesquiterpenoids, and oleodaphnal (2) were isolated from heartwood of Wikstroemia retusa (Thymelaeaceae). The planar structure of 1 was elucidated on the basis of HRESIMS and NMR spectroscopic data, and the relative stereochemistry was established by X-ray diffraction analysis. The absolute configuration of 1 was determined by electronic circular dichroism. Compound 1 suppressed luciferase reporter gene expression driven by the HBO1 (histone acetyltransferase binding to ORC1) gene promoter in human breast cancer MCF7 cells. Compound 1 also decreased the expression of endogenous HBO1 mRNA and protein, and inhibited proliferation of the cells. These results suggest that retusone A (1), which has a unique dimeric sesquiterpenoid structure with inhibitory activity against HBO1 expression, may contribute to the development of a novel therapeutic candidate for the treatment of breast cancer.

Multimodal treatment for acute empyema based on the patient's condition, including patients who are bedridden: A single center retrospective study.

BACKGROUND: The incidence of acute empyema has increased in various countries; some elderly patients with acute empyema have contraindications for surgery under general anesthesia. Therefore, suitable management based on a patient's clinical condition is required. METHODS: We evaluated the different surgical and nonsurgical therapeutic approaches available for patients with acute empyema. This was a retrospective study of 57 patients with acute empyema who received treatment in our department between May 2015 and February 2019. For patients who did not initially improve with drainage or drainage combined with fibrinolytic therapy, surgery, or additional percutaneous drainage was performed based on their general condition. We compared several clinical factors pertaining to the patients who underwent surgical versus nonsurgical treatment. RESULTS: Our study showed that the patients with a performance status of 0-2 and an American Society of Anesthesiologists physical status classification of class II or lower underwent surgery safely without major operative complications. The combination of repeated drainage of the pleural cavity and fibrinolytic therapy appeared to be a reasonable nonsurgical management option for patients in poor overall condition. CONCLUSION: For an aging population, we think that the combination of repeated pleural cavity drainage procedures and fibrinolytic therapy is a reasonable nonsurgical strategy for the management of patients with acute empyema.

Paliasanines A-E, 3,4-Methylenedioxyquinoline Alkaloids Fused with a Phenyl-14-oxabicyclo[3.2.1]octane Unit from Melochia umbellata var. deglabrata.

Five new quinoline alkaloids, paliasanines A-E (1-5), and 17 known compounds (6-22) were isolated from a methanol extract of Melochia umbellata var. deglabrata leaves. Their chemical structures were elucidated by analysis of HRMS and 1D and 2D NMR spectroscopic data. Compounds 1-5 are the first naturally occurring 3,4-methylenedioxyquinolines incorporating an oxabicyclo[3.2.1]octane unit. Compounds 6 and 7 displayed selective cytotoxicity (IC50 5.9-8.4 µM) against A549 and MCF-7 cell lines, while compounds 1-5 were not active. Compounds 1-3 did not exhibit an anti-HIV effect in MT4 cells, although the related quinolone derivative waltherione A exhibited significant activity. These preliminary results indicate that the 3-methoxy-4-quinolone skeleton might be preferred for both antiproliferative and anti-HIV activities.

Prenylated Acetophloroglucinol Dimers from Acronychia trifoliolata: Structure Elucidation and Total Synthesis.

The isolation of 12 secondary metabolites, including seven new acetophenone monomers, from the 50% CH3OH/CH2Cl2 extract (N089419-L/6) of Acronychia trifoliolata was reported previously. In the present work, three new prenylated acetophenone dimers (1-3) and five known dimers (4-8) were isolated, and their structures were elucidated by using various NMR spectroscopic techniques and HRMS. Among the new dimers, an unprecedented 4-isobutyl-3-isopropyltetrahydro-2H-pyran ring was observed in the structure of 1. This study is the first to report the formation of a 2H-pyran ring between two prenylated acetophloroglucinols. Only four related dimers have been reported before, and they were formylated phloroglucinol dimers from the family Eucalypteae. Compounds 2 and 3 are acrovestone-like dimers, and the structure of 3 was confirmed by total synthesis. The evaluation of the antiproliferative activity of isolated and synthesized acrovestone-like dimers indicated that a double bond in the prenyl-like moiety as found in the more active compounds might be important for mediating activity, while the pendant isobutyl group seems to be less important.

Spiro[3.5]nonenyl Meroterpenoid Lactones, Cryptolaevilactones G-L, an Ionone Derivative, and Total Synthesis of Cryptolaevilactone M from Cryptocarya laevigata.

A CH3OH-CH2Cl2 (1:1) extract (N025439) of the leaves and twigs of Cryptocarya laevigata furnished eight new compounds, 1-8. Based on extensive 1D and 2D NMR spectroscopic data examination, the new δ-lactone derivatives 1-6 are monoterpene-polyketide hybrids containing a unique spiro[3.5]nonenyl moiety. Their trivial names, cryptolaevilactones G-L, follow those of the related known meroterpenoids cryptolaevilactones A-F. Cryptolaevilactone L (6) contains 11,12-cis-oriented substituents, while the other cryptolaevilactones contain trans-oriented groups. The structure of the linear δ-lactone 7, cryptolaevilactone M, was characterized from various spectroscopic data analysis, and the absolute configuration was determined by total synthesis through stereoselective allylation and Grubbs olefin metathesis. Compound 8 was elucidated to be an ionone derivative with a 3,4-syn-diol functionality.

Isolation, Structure Elucidation, and Antiproliferative Activity of Butanolides and Lignan Glycosides from the Fruit of Hernandia nymphaeifolia.

Seven new butanolides, peltanolides A-G (1-7), and two lignan glucosides, peltasides A (8) and B (9), along with eleven known compounds, 10-20, were isolated from a crude CH3OH/CH2Cl2 (1:1) extract of the fruit of Hernandia nymphaeifolia (Hernandiaceae). The structures of 1-9 were characterized by extensive 1D and 2D NMR spectroscopic and HRMS analysis. The absolute configurations of newly isolated compounds 1-9 were determined from data obtained by optical rotation and electronic circular dichroism (ECD) exciton chirality methods. Butanolides and lignan glucosides have not been isolated previously from this genus. Several isolated compounds were evaluated for antiproliferative activity against human tumor cell lines. Lignans 15 and 16 were slightly active against chemosensitive tumor cell lines A549 and MCF-7, respectively. Furthermore, both compounds displayed significant activity (IC50 = 5 µM) against a P-glycoprotein overexpressing multidrug-resistant tumor cell line (KB-VIN) but were less active against its parent chemosensitive cell line (KB).

Corymbulosins I-W, Cytotoxic Clerodane Diterpenes from the Bark of Laetia corymbulosa.

The isolation studies of a crude MeOH/CH2Cl2 (1:1) extract (N005829) of the bark of Laetia corymbulosa yielded 15 new clerodane diterpenes, designated corymbulosins I-W (1-15), as well as four known diterpenes, 16-19. The structures of 1-15 were characterized on the basis of extensive 1D and 2D NMR and HRMS analyses. The absolute configurations of newly isolated compounds 1-15, as well as known 16-19, which were reported previously with only relative configurations, were determined through ECD experiments, X-ray analysis, chemical methods, including Mosher esterification, and comparison of their spectroscopic data. The isolated compounds were evaluated for cytotoxicity against human cancer cell lines. Flow cytometric and immunocytochemical observations of cells treated with cytotoxic clerodanes demonstrated that the chromatin was fragmented and dispersed with formation of apoptotic microtubules.

Kleinhospitine E and Cycloartane Triterpenoids from Kleinhovia hospita.

A novel cycloartane triterpenoid alkaloid, kleinhospitine E (1), six new cycloartane triterpenoids (2-7), three known cycloartane triterpenoids (8-10), and taraxerone (11) were isolated from a methanol extract of Kleinhovia hospita. Their structures were elucidated by 1D- and 2D-NMR spectroscopy as well as HRMS analysis. The absolute configurations of all isolated compounds were determined from their ECD spectra by comparison with theoretical values. Kleinhospitine E (1) is the first cycloartane alkaloid possessing an unusual γ-lactam with an oxopropylidene side chain. Compounds 2, 3, and 6 were assigned as cycloartane triterpenoids with a 9α,10α-cyclopropyl ring, which is found rarely among naturally occurring compounds, while 4 and 5 were established as isomers of compound 3 containing a 21,23-diacetal side chain. Biological evaluation revealed that compounds 4 and 9 exhibited more potent antiproliferative activities against a multidrug-resistant tumor cell line compared with its parent chemosensitive cell line. Furthermore, compound 6 exhibited submicromolar anti-HIV activity.

Antiproliferative Alkaloids from Alangium longiflorum, an Endangered Tropical Plant Species.

Alangium longiflorum is currently in extinction crisis, which will likely severely hamper further phytochemical investigation of this plant species from new collections. A crude extract of leaves of A. longiflorum (N33539), collected for the U.S. National Cancer Institute in 1989, showed potent cancer cell line antiproliferative activity. A phytochemical study resulted in the isolation of 17 secondary metabolites, including two new tetrahydroisoquinoline alkaloids, 8-hydroxytubulosine (1) and 2'- O- trans-sinapoylisoalangiside (2), as well as a new sinapolyloxylupene derivative (3). Using in-house assays and NCI-60 panel screening, compound 1 displayed broad-spectrum inhibitory activity at submicromolar levels against most tested tumor cell lines, except for drug-transporter-overexpressing cells. Compound 1 caused accumulation of sub-G1 cells with no effect on cell cycle progression, suggesting that this substance is an apoptosis inducer.

Cardiovascular disease in kidney transplant recipients: Japan Academic Consortium of Kidney Transplantation (JACK) cohort study.

BACKGROUND: The number of kidney transplant recipients (KTRs) from diabetic nephropathy (DN) and with cardiovascular disease (CVD) history has increased worldwide. Nevertheless, epidemiologic evidence of CVD in KTRs remains limited. METHODS: We investigated post-transplant CVD in 1614 adult KTRs between 1990 and 2014. CVD was defined according to the international classification of diseases (ICD-10). All-cause mortality was also investigated. Final follow-up was performed in March 2016. The KTRs were categorized into four groups according to DN and CVD at surgery. RESULTS: During the follow-up period, 309 KTRs experienced CVDs and 124 KTRs died. The 15-year cumulative CVDs rate was 87% in KTRs with both DN and CVD history, and the rate in KTRs without those was 22.3%. DN and CVD were associated with increased risk of post-transplant CVD [hazard ratio (HR), 3.44; 95% confidence interval (CI), 2.03-5.82; P < 0.001], and the impact marked increased after 7.5 years follow-up period (HR, 16.56; 95% CI, 6.56-41.8; P < 0.001). DN and CVD in KTRs were associated with mortality (HR, 3.32; 95% CI, 1.34-8.22; P = 0.009), and post-transplant CVD was the leading cause (35.5%) of overall death. However, DN and CVD were not associated with increased graft failure rate. CONCLUSIONS: The risk of post-transplant CVDs incidence in KTRs with DN and CVD history is high, and it increases during the late transplant period. Appropriate routine cardiovascular screening and evaluation are needed to reduce late-onset CVD incidence.

Lumbar Arterial Bleeding Treated with Endovascular Aneurysm Repair: A Report of 4 Patients.

BACKGROUND: Lumbar arterial bleeding is a severe condition. Surgical exploration is not indicated because of its rich collateral flow. Transarterial embolization (TAE) is reportedly effective, but there have been cases of failure. It may be a time-consuming procedure for patients with multiple bleeding sources or those with poor vital signs. In this case series, we used endovascular aneurysm repair (EVAR) instead of TAE. METHOD: In this case series, we described 4 male patients (2 with traumatic injury, 1 with iatrogenic injury, and 1 with drug-induced hypocoagulability) with lumbar arterial bleeding. The reasons we chose EVAR are because 2 patients had poor vital signs, one patient was a technically difficult case for selective cannulation, and one patient had accompanying aortic dissection. RESULT: In all patients, EVAR was performed successfully, and hemostasis was obtained although one patient died of pneumonia on postoperative day 23. CONCLUSIONS: EVAR is an effective alternative for lumbar arterial bleeding although TAE is a first choice of treatment.

Stomach resection with intraoperative fluoroscopy in laparoscopic distal gastrectomy for early gastric cancer.

BACKGROUND: In Japan, laparoscopic distal gastrectomy (LDG) is common for early gastric cancer. Formerly, we used to verify the location of the marking clip to decide the proximal incisional line with our hand, through a small epigastric incision. In 2015, we introduced intracorporeal reconstruction and started to decide the incisional line using intraoperative fluoroscopy. Herein, we aimed to evaluate the efficacy and safety of intraoperative fluoroscopy in LDG. PATIENTS AND METHODS:: A total of 19 patients were included in this retrospective observational study. On the day before operation, we endoscopically clipped several points located 2 cm proximal to the tumour edge to cover about half of the tumour. After lymph node dissection, we incised the stomach with an endoscopic linear stapling device, including the previously placed clips, guided by intraoperative fluoroscopy. Reconstruction was performed in all patients who underwent Billroth I and Roux-en-Y procedures. RESULTS: No complications were observed during pre-operative endoscopic clipping or intraoperatively. On pathological examination, all resected specimens had negative margins, and the mean distance from the tumour edge was 28.5 ± 16.5 (13-60) mm. CONCLUSION: Stomach resection with intraoperative fluoroscopic guidance was safe and effective.

Corymbulosins D-H, 2-Hydroxy- and 2-Oxo-clerodane Diterpenes from the Bark of Laetia corymbulosa.

A bioactive CH3OH-CH2Cl2 (1:1) extract of the bark of Laetia corymbulosa provided five new clerodane diterpenes with an isozuelanin skeleton, designated as corymbulosins D-H (1-5), as well as the known corymbulosins B (6) and C (7), for which the relative configurations were not previously determined. The structures of 1-5 were characterized on the basis of 1D and 2D NMR spectroscopic and HRMS analysis. The absolute configurations of all isolated compounds 1-7 were verified through chemical methods, including modified Mosher esterifications or oxidation of the hydroxy group at C-2, ECD experiments, and spectroscopic data comparison. The isolated compounds were evaluated for antiproliferative activity against a small panel of human cancer cell lines.