γδ T Cells Support Pancreatic Oncogenesis by Restraining αß T Cell Activation.

Inflammation is paramount in pancreatic oncogenesis. We identified a uniquely activated γδT cell population, which constituted ∼40% of tumor-infiltrating T cells in human pancreatic ductal adenocarcinoma (PDA). Recruitment and activation of γδT cells was contingent on diverse chemokine signals. Deletion, depletion, or blockade of γδT cell recruitment was protective against PDA and resulted in increased infiltration, activation, and Th1 polarization of αßT cells. Although αßT cells were dispensable to outcome in PDA, they became indispensable mediators of tumor protection upon γδT cell ablation. PDA-infiltrating γδT cells expressed high levels of exhaustion ligands and thereby negated adaptive anti-tumor immunity. Blockade of PD-L1 in γδT cells enhanced CD4(+) and CD8(+) T cell infiltration and immunogenicity and induced tumor protection suggesting that γδT cells are critical sources of immune-suppressive checkpoint ligands in PDA. We describe γδT cells as central regulators of effector T cell activation in cancer via novel cross-talk.

Efficacy and Safety of NVX-CoV2373 in Adults in the United States and Mexico.

BACKGROUND: NVX-CoV2373 is an adjuvanted, recombinant spike protein nanoparticle vaccine that was shown to have clinical efficacy for the prevention of coronavirus disease 2019 (Covid-19) in phase 2b-3 trials in the United Kingdom and South Africa, but its efficacy had not yet been tested in North America. METHODS: We conducted a phase 3, randomized, observer-blinded, placebo-controlled trial in the United States and Mexico during the first half of 2021 to evaluate the efficacy and safety of NVX-CoV2373 in adults (≥18 years of age) who had not had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Participants were randomly assigned in a 2:1 ratio to receive two doses of NVX-CoV2373 or placebo 21 days apart. The primary objective was to determine vaccine efficacy against reverse-transcriptase-polymerase-chain-reaction-confirmed Covid-19 occurring at least 7 days after the second dose. Vaccine efficacy against moderate-to-severe disease and against different variants was also assessed. RESULTS: Of the 29,949 participants who underwent randomization between December 27, 2020, and February 18, 2021, a total of 29,582 (median age, 47 years; 12.6% ≥65 years of age) received at least one dose: 19,714 received vaccine and 9868 placebo. Over a period of 3 months, 77 cases of Covid-19 were noted - 14 among vaccine recipients and 63 among placebo recipients (vaccine efficacy, 90.4%; 95% confidence interval [CI], 82.9 to 94.6; P<0.001). Ten moderate and 4 severe cases occurred, all in placebo recipients, yielding vaccine efficacy against moderate-to-severe disease of 100% (95% CI, 87.0 to 100). Most sequenced viral genomes (48 of 61, 79%) were variants of concern or interest - largely B.1.1.7 (alpha) (31 of the 35 genomes for variants of concern, 89%). Vaccine efficacy against any variant of concern or interest was 92.6% (95% CI, 83.6 to 96.7). Reactogenicity was mostly mild to moderate and transient but was more frequent among NVX-CoV2373 recipients than among placebo recipients and was more frequent after the second dose than after the first dose. CONCLUSIONS: NVX-CoV2373 was safe and effective for the prevention of Covid-19. Most breakthrough cases were caused by contemporary variant strains. (Funded by Novavax and others; PREVENT-19 ClinicalTrials.gov number, NCT04611802.).

Portable hypothermic oxygenated machine perfusion for organ preservation in liver transplantation: A randomized, open-label, clinical trial.

BACKGROUND AND AIMS: In liver transplantation, cold preservation induces ischemia, resulting in significant reperfusion injury. Hypothermic oxygenated machine perfusion (HMP-O 2 ) has shown benefits compared to static cold storage (SCS) by limiting ischemia-reperfusion injury. This study reports outcomes using a novel portable HMP-O 2 device in the first US randomized control trial. APPROACH AND RESULTS: The PILOT trial (NCT03484455) was a multicenter, randomized, open-label, noninferiority trial, with participants randomized to HMP-O 2 or SCS. HMP-O 2 livers were preserved using the Lifeport Liver Transporter and Vasosol perfusion solution. The primary outcome was early allograft dysfunction. Noninferiority margin was 7.5%. From April 3, 2019, to July 12, 2022, 179 patients were randomized to HMP-O 2 (n=90) or SCS (n=89). The per-protocol cohort included 63 HMP-O 2 and 73 SCS. Early allograft dysfunction occurred in 11.1% HMP-O 2 (N=7) and 16.4% SCS (N=12). The risk difference between HMP-O 2 and SCS was -5.33% (one-sided 95% upper confidence limit of 5.81%), establishing noninferiority. The risk of graft failure as predicted by Liver Graft Assessment Following Transplant score at seven days (L-GrAFT 7 ) was lower with HMP-O 2 [median (IQR) 3.4% (2.4-6.5) vs. 4.5% (2.9-9.4), p =0.024]. Primary nonfunction occurred in 2.2% of all SCS (n=3, p =0.10). Biliary strictures occurred in 16.4% SCS (n=12) and 6.3% (n=4) HMP-O 2 ( p =0.18). Nonanastomotic biliary strictures occurred only in SCS (n=4). CONCLUSIONS: HMP-O 2 demonstrates safety and noninferior efficacy for liver graft preservation in comparison to SCS. Early allograft failure by L-GrAFT 7 was lower in HMP-O 2 , suggesting improved early clinical function. Recipients of HMP-O 2 livers also demonstrated a lower incidence of primary nonfunction and biliary strictures, although this difference did not reach significance.

Living Donor Liver Transplantation for Hepatocellular Carcinoma Within and Outside Traditional Selection Criteria: A Multicentric North American Experience.

OBJECTIVE: To evaluate long-term oncologic outcomes of patients post-living donor liver transplantation (LDLT) within and outside standard transplantation selection criteria and the added value of the incorporation of the New York-California (NYCA) score. BACKGROUND: LDLT offers an opportunity to decrease the liver transplantation waitlist, reduce waitlist mortality, and expand selection criteria for patients with hepatocellular carcinoma (HCC). METHODS: Primary adult LDLT recipients between October 1999 and August 2019 were identified from a multicenter cohort of 12 North American centers. Posttransplantation and recurrence-free survival were evaluated using the Kaplan-Meier method. RESULTS: Three hundred sixty LDLTs were identified. Patients within Milan criteria (MC) at transplantation had a 1, 5, and 10-year posttransplantation survival of 90.9%, 78.5%, and 64.1% versus outside MC 90.4%, 68.6%, and 57.7% ( P = 0.20), respectively. For patients within the University of California San Francisco (UCSF) criteria, respective posttransplantation survival was 90.6%, 77.8%, and 65.0%, versus outside UCSF 92.1%, 63.8%, and 45.8% ( P = 0.08). Fifty-three (83%) patients classified as outside MC at transplantation would have been classified as either low or acceptable risk with the NYCA score. These patients had a 5-year overall survival of 72.2%. Similarly, 28(80%) patients classified as outside UCSF at transplantation would have been classified as a low or acceptable risk with a 5-year overall survival of 65.3%. CONCLUSIONS: Long-term survival is excellent for patients with HCC undergoing LDLT within and outside selection criteria, exceeding the minimum recommended 5-year rate of 60% proposed by consensus guidelines. The NYCA categorization offers insight into identifying a substantial proportion of patients with HCC outside the MC and the UCSF criteria who still achieve similar post-LDLT outcomes as patients within the criteria.

Liver Histology Predicts Liver Regeneration and Outcome in ALPPS: Novel Findings From A Multicenter Study.

BACKGROUND AND AIMS: Alterations in liver histology influence the liver's capacity to regenerate, but the relevance of each of the different changes in rapid liver growth induction is unknown. This study aimed to analyze the influence of the degree of histological alterations during the first and second stages on the ability of the liver to regenerate. METHODS: This cohort study included data obtained from the International ALPPS Registry between November 2011 and October 2020. Only patients with colorectal liver metastases were included in the study. We developed a histological risk score based on histological changes (stages 1 and 2) and a tumor pathology score based on the histological factors associated with poor tumor prognosis. RESULTS: In total, 395 patients were included. The time to reach stage 2 was shorter in patients with a low histological risk stage 1 (13 vs 17 days, P ˂0.01), low histological risk stage 2 (13 vs 15 days, P <0.01), and low pathological tumor risk (13 vs 15 days, P <0.01). Regarding interval stage, there was a higher inverse correlation in high histological risk stage 1 group compared to low histological risk 1 group in relation with future liver remnant body weight ( r =-0.1 and r =-0.08, respectively), and future liver remnant ( r =-0.15 and r =-0.06, respectively). CONCLUSIONS: ALPPS is associated with increased histological alterations in the liver parenchyma. It seems that the more histological alterations present and the higher the number of poor prognostic factors in the tumor histology, the longer the time to reach the second stage.

Harmonizing Definitions and Perspectives in Extreme Liver Surgery: A Delphi Experts Consensus.

OBJECTIVE: To propose to our community a common language about extreme liver surgery. BACKGROUND: The lack of a clear definition of extreme liver surgery prevents convincing comparisons of results among centers. METHODS: We used a two-round Delphi methodology to quantify consensus among liver surgery experts. For inclusion in the final recommendations, we established a consensus when the positive responses (agree and totally agree) exceeded 70%. The study steering group summarized and reported the recommendations. In general, a five-point Likert scale with a neutral central value was used, and in a few cases multiple choices. Results are displayed as numbers and percentages. RESULTS: A two-round Delphi study was completed by 38 expert surgeons in complex hepatobiliary surgery. The surgeon´s median age was 58 years old (52-63) and the median years of experience was 25 years (20-31). For the proposed definitions of total vascular occlusion, hepatic flow occlusion and inferior vein occlusion, the degree of agreement was 97%, 81% and 84%, respectively. In situ approach (64%) was the preferred, followed by ante situ (22%) and ex situ (14%). Autologous or cadaveric graft for hepatic artery or hepatic vein repair were the most recommended (89%). The use of veno-venous bypass or portocaval shunt revealed the divergence depending on the case. Overall, 75% of the experts agreed with the proposed definition for extreme liver surgery. CONCLUSION: Obtaining a consensus on the definition of extreme liver surgery is essential to guarantee the correct management of patients with highly complex hepatobiliary oncological disease. The management of candidates for extreme liver surgery involves comprehensive care ranging from adequate patient selection to the appropriate surgical strategy.

Update to 'A Contemporary Systematic Review on Liver Transplantation for Unresectable Liver Metastasis of Colorectal Cancer'.

Colorectal cancer is the second most common cause of cancer-related death worldwide, and half of patients present with colorectal liver metastasis (CRLM). Liver transplant (LT) has emerged as a treatment modality for otherwise unresectable CRLM. Since the publication of the Lebeck-Lee systematic review in 2022, additional evidence has come to light supporting LT for CRLM in highly selected patients. This includes reports of >10-year follow-up with over 80% survival rates in low-risk patients. As these updated reports have significantly changed our collective knowledge, this article is intended to serve as an update to the 2022 systematic review to include the most up-to-date evidence on the subject.

First record of ectoparasites (Phthiraptera and Acari) from the Andean condor (Vultur gryphus) in Colombia.

Several species of ectoparasites, including chewing lice and mites are closely associated with their hosts. The Andean condor (Vultur gryphus) is globally listed as vulnerable by the IUCN and its population has been steadily declining in recent decades suggesting a potential extinction of associated entomofauna. The purpose of this study was to record the species of ectoparasites infesting three individuals of Andean condor found dead in the 'Páramo del Almorzadero' Santander Department, Northeastern Colombia. One juvenile (male) and two adults (male and female) Andean condors received for necropsy were carefully examined for ectoparasite infestation. Specimens were collected and preserved in ethanol (70%) for taxonomic studies. Morphologic identification and morphometric records were made under light microscopy. Some specimens were also prepared for scanning electron microscopy and others were subjected to DNA extraction to amplify and obtain sequences of the cytochrome-C oxidase subunit I (COI) gene for phylogenetic analyses. Lice were collected from the juvenile condor and the adult female and identified as Falcolipeurus assesor (Phthiraptera: Ischnocera) in the juvenile condor (8 females, 19 males and 8 nymphs) and the adult (1 female); Colpocephalum trichosum (Phthiraptera: Amblycera) in the juvenile (19 females, 24 males and 1 nymph) and the adult (2 females, 2 males and 3 nymphs); and Cuculiphilus zonatus (Phthiraptera: Amblycera) in the juvenile (40 females, 43 males and 15 nymphs) and the adult (1 male and 2 nymphs). Moreover, one mite collected from the juvenile condor was identified as Ancyralges cathartinus (Acari: Astigmata) (1 female). Morphometric data was obtained for the adult stages of F. assesor (6 females and 13 males), C. trichosum (9 females and 9 males) and C. zonatus (10 females and 10 males). We obtained the first DNA sequences of COI for F. assessor, and C. trichosum, where phylogenetic tree analysis showed that F. assessor is more closely related to Falcolipeurus marginalis, and C. trichosum to Colpocephalum kelloggi. This represents the first record of parasites in Andean condor from Colombia and contributes to the knowledge of chewing lice and mites associated with an endemic and endangered bird species. Further studies on Andean condor ectoparasites should be focused on documenting host-parasite interactions and potential health impacts in these wild birds.

Varias especies de ectoparásitos, incluidos piojos masticadores y ácaros están estrechamente asociados a sus hospedadores. El cóndor andino (Vultur gryphus) está catalogado por la UICN como una especie vulnerable y su población ha ido disminuyendo constantemente en las últimas décadas, lo que sugiere una posible extinción de la entomofauna asociada. El propósito de este estudio fue registrar las especies de ectoparásitos infestando a tres individuos de cóndor andino encontrados muertos en el Páramo del Almorzadero, Departamento de Santander, Noreste de Colombia. Un cóndor andino juvenil (macho) y dos adultos (macho y hembra) recibidos para necropsia fueron examinados cuidadosamente para detectar infestación por ectoparásitos. Los especímenes fueron recolectados y preservados en etanol (70%) para estudios taxonómicos. La identificación morfológica y los registros morfométricos se ejecutaron bajo microscopía óptica. Algunas muestras también se prepararon para microscopía electrónica de barrido y otras se sometieron a extracción de ADN para amplificar y obtener secuencias del gen de la subunidad I (COI) del citocromo­C oxidasa para análisis filogenéticos. Los piojos recolectados del cóndor juvenil y de la hembra adulta se identificaron como Falcolipeurus assesor (Phthiraptera: Ischnocera) en el cóndor juvenil (8 hembras, 19 machos y 8 ninfas) y en el adulto (1 hembra); Colpocephalum trichosum (Phthiraptera: Amblycera) en el juvenil (19 hembras, 24 machos y 1 ninfa) y en el adulto (2 hembras, 2 machos y 3 ninfas); y Cuculiphilus zonatus (Phthiraptera: Amblycera) en el juvenil (40 hembras, 43 machos y 15 ninfas) y en el adulto (1 macho y 2 ninfas). Además, un ácaro recolectado del cóndor juvenil fue identificado como Ancyralges cathartinus (Acari: Astigmata) (1 hembra). Se obtuvieron datos morfométricos para los estadios adultos de F. assesor (6 hembras y 13 machos), C. trichosum (9 hembras y 9 machos) y C. zonatus (10 hembras y 10 machos). Secuencias de ADN basadas en COI para las especies F. assesor y C. trichosum son reportadas por la primera vez, donde el análisis filogenetico mostró que F. assesor está más estrechamente relacionado con Falcolipeurus marginalis y C. trichosum con Colpocephalum kelloggi. Este representa el primer registro de parásitos en cóndor andino de Colombia y contribuye al conocimiento de los piojos masticadores y ácaros asociados a una especie de ave endémica de los Andes y en peligro de extinción. Otros estudios sobre los ectoparásitos del cóndor andino deberían centrarse en documentar las interacciones hospedador­parásito y los posibles impactos en la salud de estas aves silvestres.

Hyperparasitism in bat flies (Diptera: Streblidae): new records and interaction networks in the Neotropics.

Hyperparasitism is defined as the interaction where one parasite is infected by another parasite. In bat flies (Streblidae and Nycteribiidae), both hyperparasites and microparasites (bacteria, viruses, fungi, and arthropods such as mites) have been documented. Fungi belonging to the order Laboulbeniales are microscopic parasites of a wide diversity of arthropod hosts. Three genera exclusively target bat flies: Arthrorhynchus, which parasitizes species within Nycteribiidae in the Eastern Hemisphere, while genus Gloeandromyces and Nycteromyces parasitize Streblidae in the Western Hemisphere. Among the hyperparasitic arthropods, mites of family Neothrombidiidae, particularly the monospecific genus Monunguis, are known to parasitize bat flies. Here we present the first records of the hyperparasites Monunguis streblida and Gloeandromyces pageanus f. polymorphus parasitizing Streblidae bat flies in Colombia and a summary of these hyperparasitic interactions in the Neotropics. We detected fungi and mites parasitizing bat flies that were collected in the Magdalena River Basin, Colombia, in field expeditions in 2018, 2022, and 2023. We identified 17 bat flies and two species of hyperparasites, specifically M. streblida and the fungi Gloeandromyces. Our search for reports of these interactions in the Neotropics revealed that seven species of Trichobius (Streblidae) are parasitized by M. streblida, whereas Paratrichobius longicrus (Streblidae) is parasitized by Gloeandromyces pageanus f. polymorphus. These interactions have been reported in 11 countries, but our records are the first of M. streblida and Laboulbeniales fungi parasitizing bat flies in Colombia. So far, a total of 14 species of fungi and one species of mite have been associated with 19 species of bat flies, which in turn, are linked to 15 species of Neotropical bats.

Fused hip conversion to total hip arthroplasty with the direct anterior approach: surgical technique on a regular surgical table under fluoroscopic guidance.

PURPOSE: Conversion of a fused hip to a total hip arthroplasty (THA) is technically challenging due to the loss of anatomical references. Here, a reproducible technique using the direct anterior approach (DAA) with a regular surgical table under fluoroscopic guidance is described, which has several advantages over traditional such as lateral or posterior approaches. METHODS: There were reported 11 cases of ankylosis hip that were converted to THA using the same surgical technique protocol. Clinical and radiographic outcomes were recorded at 3.2 years of follow-up. A detailed preoperative evaluation was performed, including a pelvis radiological evaluation and magnetic resonance image (MRI) to assess the integrity of the periarticular soft tissue and flexor muscles. RESULTS: The DAA has considerable advantages, such as allowing more precise targeting during surgery, avoiding the risk of pseudoarthrosis due to the absence of a trochanteric osteotomy, preserving the abductors, and allowing an easier-to-use of intraoperative fluoroscopy due to the supine position. Besides, the use of a standard table reduces surgical time and allows assessment of limb length, hip stability, and impingement in all planes in an intraoperative dynamic range, which decreases postoperative complications. CONCLUSION: Conversion from hip fusion to THA is a rare and complex procedure. The use of DAA with a standard table and fluoroscopy helps to avoid high complications since it allows a dynamic intra-operative examination of the range of motion to rule out impingements, reduces the risk of dislocation, and allows leg lengthening verification.

Differentially Expressed Genes Involved in Primary Resistance to Immunotherapy in Patients with Advanced-Stage Pulmonary Cancer.

In the last few years, nivolumab has become the standard of care for advanced-stage lung cancer patients. Unfortunately, up to 60% of patients do not respond to this treatment. In our study, we identified variations in gene expression related to primary resistance to immunotherapy. Bronchoscopy biopsies were obtained from advanced non-small cell lung cancer (NSCLC) patients previously characterized as responders or non-responders after nivolumab treatment. Ten tumor biopsies (from three responders and seven non-responders) were analyzed by the differential expression of 760 genes using the NanoString nCounter platform. These genes are known to be involved in the response to anti-PD1/PD-L1 therapy. All the patients were treated with nivolumab. Examining the dysregulated expression of 24 genes made it possible to predict the response to nivolumab treatment. Supervised analysis of the gene expression profile (GEP) revealed that responder patients had significantly higher levels of expression of CXCL11, NT5E, KLRK1, CD3G, GZMA, IDO1, LCK, CXCL9, GNLY, ITGAL, HLA-DRB1, CXCR6, IFNG, CD8A, ITK, B2M, HLA-B, and HLA-A than did non-responder patients. In contrast, PNOC, CD19, TP73, ARG1, FCRL2, and PTGER1 genes had significantly lower expression levels than non-responder patients. These findings were validated as predictive biomarkers in an independent series of 201 patients treated with nivolumab (22 hepatocellular carcinomas, 14 non-squamous cell lung carcinomas, 5 head and neck squamous cell carcinomas, 1 ureter/renal pelvis carcinoma, 120 melanomas, 4 bladder carcinomas, 31 renal cell carcinomas, and 4 squamous cell lung carcinomas). ROC curve analysis showed that the expression levels of ITK, NT5E, ITGAL, and CD8A were the best predictors of response to nivolumab. Further, 13/24 genes showed an adverse impact on overall survival (OS) in an independent, large series of patients with NSCLC (2166 cases). In summary, we found a strong association between the global GEP of advanced NSCLC and the response to nivolumab. The classification of NSCLC patients based on GEP enabled us to identify those patients who genuinely benefited from treatment with immune checkpoint inhibitors (ICIs). We also demonstrated that abnormal expression of most of the markers comprising the genomic signature has an adverse influence on OS, making them significant markers for therapeutic decision-making. Additional prospective studies in larger series of patients are required to confirm the clinical utility of these biomarkers.

Cemented vs cementless stems for revision arthroplasties due to Vancouver B2 periprosthetic hip fracture.

PURPOSE: According to Vancouver classification, B2 type fractures are most often treated with removal of the loose stem and implantation of a long stem that bypasses the fracture site. However, there is a controversy about the stem fixation that should be used: cemented or cementless. Hence, this study aims to compare cemented and cementless stems in prosthetic revision due to Vancouver B2 (VB2) periprosthetic hip fracture. METHODS: A retrospective study was done including all the patients treated with stem exchange due to VB2 periprosthetic hip fracture in a tertiary hospital between 2015 and 2022. Patients were divided into two groups according to the stem fixation used: cemented or cementless. Functional outcomes, hospital stay, surgical time, complication rate, and mortality were compared between the two groups of patients. RESULTS: Of the 30 included patients, 13 (43.4%) were treated with cementless stems and 17 (56.7%) with cemented stems. There were no statistically significant differences in age, gender, anesthesia risk scale (ASA) or functional capacity prior to the intervention. Patients treated with cementless stems had a higher complication and reintervention rate than those treated with cemented stems: 62 and 45% versus 34 and 6% (p = 0.035; p = 0.010), respectively. Furthermore, in the group of cementless stems a higher proportion of non-union was found (53.8% vs. 17.6%; p = 0.037). Also, the hospital stay (33 vs. 24 days; p = 0.037) and the time to full weight-bearing (21 days vs. 9 days; p < 0.001) were longer in the cementless stem group. CONCLUSION: Cemented fixation in stem revision due to Vancouver B2 periprosthetic hip fracture could be an optimal option with faster recovery which could decrease the rate of complications and reintervention, without compromising the fracture healing and patient mortality. Thus, this option can be considered when an anatomical reduction can be obtained, especially in elderly patients with multiple comorbidities in which a less aggressive surgical option should be considered.

Vancouver B2 periprosthetic hip fractures treatment: fix or replace? A retrospective study comparing both techniques.

INTRODUCTION: Vancouver B2 periprosthetic hip fractures involve stem stability and they have been classically treated with revision surgery. Crucial factors such as age, clinical comorbidities and functional status are often neglected. The current study aims to compare clinical outcomes between patients treated with open reduction and internal fixation (ORIF) or femoral stem exchange. METHODS: This is a retrospective study that includes all Vancouver B2 periprosthetic hip fractures in a tertiary referral hospital from 2016 to 2020. Patients were divided into two groups: Group 1. Patients treated with an ORIF and Group 2. Patients treated with stem replacement. The outcomes that were compared between groups included demographic data, functional capacity, complications and mortality. RESULTS: 29 periprosthetic Vancouver B2 fractures were finally analyzed. 11 (37.9%) were treated with ORIF (Group 1) and 18 (62.1%) by stem replacement (Group 2). Surgery time (143 vs. 160 min), hemoglobin drop (1.8 vs. 2.5 g/dL) and hospital stance (25.5 vs. 29.6 days) were shorter in Group 1. According to complications, 18.2% of patients in the ORIF group had orthopedic complications compared with 44.4% in the revision group. In the revision group, 3 cases needed a two-stage revision and one of these revisions ended up with a resection arthroplasty (Girdlestone). The first-year mortality rate was 27% in Group 1 and 11% in Group 2. DISCUSSION: ORIF treatment seems to be a less aggressive and complex procedure which can lead to a faster general recovery. Revision surgery can imply a higher risk of orthopedic complications which can be severe and may require further aggressive solutions. The ORIF group mortality was similar to the proximal femur fracture rate (20-30%). In conclusion, ORIF treatment seems to be a good option especially in fragile patients with low functional demand when anatomical reduction is possible.

Medical Assistance in Dying (MAiD) as a Source of Liver Grafts: Honouring the Ultimate Gift.

OBJECTIVE: To report the clinical outcomes of liver transplants from donors after medical assistance in dying (MAiD) versus donors after cardiac death (DCD) and deceased brain death (DBD). SUMMARY BACKGROUND DATA: In North America, the number of patients needing liver transplants exceeds the number of available donors. In 2016, MAiD was legalized in Canada. METHODS: All patients undergoing deceased donor liver transplantation at Toronto General Hospital between 2016 and 2021 were included in the study. Recipient perioperative and postoperative variables and donor physiological variables were compared among 3 groups. RESULTS: Eight hundred seven patients underwent deceased donor liver transplantation during the study period, including DBD (n=719; 89%), DCD (n=77; 9.5%), and MAiD (n=11; 1.4%). The overall incidence of biliary complications was 6.9% (n=56), the most common being strictures (n=55;6.8%), highest among the MAiD recipients [5.8% (DBD) vs. 14.2% (DCD) vs. 18.2% (MAiD); P =0.008]. There was no significant difference in 1 year (98.4% vs. 96.4% vs. 100%) and 3-year (89.3% vs. 88.7% vs. 100%) ( P =0.56) patient survival among the 3 groups. The 1- and 3- year graft survival rates were comparable (96.2% vs. 95.2% vs. 100% and 92.5% vs. 91% vs. 100%; P =0.37). CONCLUSION: With expected physiological hemodynamic challenges among MAiD and DCD compared with DBD donors, a higher rate of biliary complications was observed in MAiD donors, with no significant difference noted in short-and long-term graft outcomes among the 3 groups. While ethical challenges persist, good initial results suggest that MAiD donors can be safely used in liver transplantation, with results comparable with other established forms of donation.

The High Incidence of Occult Carcinoma in Total Hepatectomy Specimens of Patients Treated for Unresectable Colorectal Liver Metastases With Liver Transplant.

OBJECTIVE: To describe the rate of occult carcinoma deposits in total hepatectomy specimens from patients treated with liver transplant (LT) for colorectal liver metastases (CRLM). BACKGROUND: Previous studies have shown that patients with CRLM treated with systemic therapy demonstrate a high rate of complete radiographic response or may have disappearing liver metastases. However, this does not necessarily translate into a complete pathologic response, and residual invasive cancer may be found in up to 80% of the disappearing tumors after resection. METHODS: Retrospective review of 14 patients who underwent LT for CRLM, at 2 centers. Radiographic and pathologic correlation of the number of tumors and their viability before and after LT was performed. RESULTS: The median (interquartile range) number of tumors at diagnosis was 11 (4-23). The median number of chemotherapy cycles was 24 (16-37). Hepatic artery infusion was used in 5 patients (35.7%); 6 (42.9%) underwent surgical resection, and 5 (35.7%) received locoregional therapy. The indication for LT was unresectability in 8 patients (57.1%) and liver failure secondary to oncologic treatment in the remaining 6 (42.9%). Before LT, 7 patients (50%) demonstrated fluorodeoxyglucose-avid tumors and 7 (50%) had a complete radiographic response. Histopathologically, 11 patients (78.6%) had a viable tumor. Nine (64.2%) of the 14 patients were found to have undiagnosed metastases on explant pathology, with at least 22 unaccounted viable tumors before LT. Furthermore, 4 (57.1%) of the 7 patients who demonstrated complete radiographic response harbored viable carcinoma on explant pathology. CONCLUSIONS: A complete radiographic response does not reliably predict a complete pathologic response. In patients with unresectable CRLM, total hepatectomy and LT represent a promising treatment options to prevent indolent disease progression from disappearing CRLM.

Quasi-Diamond Platelet-Shaped Zinc Oxide Nanostructures Display Enhanced Antibacterial Activity.

The current study compares the antibacterial activity of zinc oxide nanostructures (neZnO). For this purpose, two bacterial strains, Escherichia coli (ATCC 4157) and Staphylococcus aureus (ATCC 29213) were challenged in room light conditions with the aforementioned materials. Colloidal and hydrothermal methods were used to obtain the quasi-round and quasi-diamond platelet-shape nanostructures. Thus, the oxygen vacancy (VO ) effects on the surface of neZnO are also considered to assess its effects on antibacterial activity. The neZnO characterization was achieved by X-ray diffraction (XRD), a selected area electron diffraction (SAED) and Raman spectroscopy. The microstructural effects were monitored by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Furthermore, optical absorption ultraviolet visible spectrophotometry (UV-Vis) and X-ray photoelectron spectroscopy (XPS) analyses complement the physical characterization of these nanostructures; neZnO caused 50 % inhibition (IC50 ) at concentrations from 0.064 to 0.072 mg/mL for S. aureus and from 0.083 to 0.104 mg/mL for E. coli, indicating an increase in activity against S. aureus compared to E. coli. Consequently, quasi-diamond platelet-shaped nanostructures (average particle size of 377.6±10 nm) showed enhanced antibacterial activity compared to quasi-round agglomerated particles (average size of 442.8±12 nm), regardless of Vo presence or absence.

The Current State of Liver Transplantation for Colorectal Liver Metastases in the United States: A Call for Standardized Reporting.

BACKGROUND: Current success in transplant oncology for select liver tumors, such as hepatocellular carcinoma, has ignited international interest in liver transplantation (LT) as a therapeutic option for nonresectable colorectal liver metastases (CRLM). In the United States, the CRLM LT experience is limited to reports from a handful of centers. This study was designed to summarize donor, recipient, and transplant center characteristics and posttransplant outcomes for the indication of CRLM. METHODS: Adult, primary LT patients listed between December 2017 and March 2022 were identified by using United Network Organ Sharing database. LT for CRLM was identified from variables: "DIAG_OSTXT"; "DGN_OSTXT_TCR"; "DGN2_OSTXT_TCR"; and "MALIG_TY_OSTXT." RESULTS: During this study period, 64 patients were listed, and 46 received LT for CRLM in 15 centers. Of 46 patients who underwent LT for CRLM, 26 patients (56.5%) received LTs using living donor LT (LDLT), and 20 patients received LT using deceased donor (DDLT) (43.5%). The median laboratory MELD-Na score at the time of listing was statistically similar between the LDLT and DDLT groups (8 vs. 9, P = 0.14). This persisted at the time of LT (8 vs. 12, P = 0.06). The 1-, 2-, and 3-year, disease-free, survival rates were 75.1, 53.7, and 53.7%. Overall survival rates were 89.0, 60.4, and 60.4%, respectively. CONCLUSIONS: This first comprehensive U.S. analysis of LT for CRLM suggests a burgeoning interest in high-volume U.S. transplant centers. Strategies to optimize patient selection are limited by the scarce oncologic history provided in UNOS data, warranting a separate registry to study LT in CRLM.

Longitudinal incremental propensity score interventions for limited resource settings.

Many real-life treatments are of limited supply and cannot be provided to all individuals in the population. For example, patients on the liver transplant waiting list usually cannot be assigned a liver transplant immediately at the time they reach highest priority because a suitable organ is not immediately available. In settings with limited supply, investigators are often interested in the effects of treatment strategies in which a limited proportion of patients receive an organ at a given time, that is, treatment regimes satisfying resource constraints. Here, we describe an estimand that allows us to define causal effects of treatment strategies that satisfy resource constraints: incremental propensity score interventions (IPSIs) for limited resources. IPSIs flexibly constrain time-varying resource utilization through proportional scaling of patients' natural propensities for treatment, thereby preserving existing propensity rank ordering compared to the status quo. We derive a simple class of inverse-probability-weighted estimators, and we apply one such estimator to evaluate the effect of restricting or expanding utilization of "increased risk" liver organs to treat patients with end-stage liver disease.

Aromatic Bromination Abolishes Deficits in Visuospatial Learning Induced by MDMA ("Ecstasy") in Rats While Preserving the Ability to Increase LTP in the Prefrontal Cortex.

It has recently been demonstrated that aromatic bromination at C(2) abolishes all typical psychomotor, and some key prosocial effects of the entactogen MDMA in rats. Nevertheless, the influence of aromatic bromination on MDMA-like effects on higher cognitive functions remains unexplored. In the present work, the effects of MDMA and its brominated analog 2Br-4,5-MDMA (1 mg/kg and 10 mg/kg i.p. each) on visuospatial learning, using a radial, octagonal Olton maze (4 × 4) which may discriminate between short-term and long-term memory, were compared with their influence on in vivo long-term potentiation (LTP) in the prefrontal cortex in rats. The results obtained indicate that MDMA diminishes both short- and long-term visuospatial memory but increases LTP. In contrast, 2Br-4,5-MDMA preserves long-term visuospatial memory and slightly accelerates the occurrence of short-term memory compared to controls, but increases LTP, like MDMA. Taken together, these data are consistent with the notion that the modulatory effects induced by the aromatic bromination of the MDMA template, which abolishes typical entactogenic-like responses, might be extended to those effects affecting higher cognitive functions, such as visuospatial learning. This effect seems not to be associated with the increase of LTP in the prefrontal cortex.