Metroticket approach in a retrospective cohort study to predict overall survival after surgical resection for intermediate stage hepatocellular carcinoma.

BACKGROUND: Surgical resection is a curative therapy for early-stage hepatocellular carcinoma (HCC) patients meeting the Milan criteria as well as a widely used therapy in intermediate-stage HCC. However, intermediate-stage HCC encompasses a wide spectrum of disease and there is a lack of good predictive models for the long-term clinical outcome of HCC patients currently. Here, we adopt Mazzaferro's Metroticket 2.0 to create a robust survival prediction model for intermediate-stage HCC patients undergoing surgical resection. Our algorithm considers age, AFP levels, ALBI score, and nodule size/number to generate survival estimates in an accessible graph format. Importantly, our model surpasses the American Joint Committee on Cancer staging model and was validated with independent US patient data. METHODS: We conducted a retrospective analysis of OS and RFS in early- and intermediate-stage HCC patients treated with liver resection, including a training cohort in Singapore and a validation cohort in North Carolina, USA. RESULTS: We recorded 278 deaths (35.0%) and 428 patients (53.9%) in the first 5-years after surgical resection; higher ALBI score, higher lnAFP, more advanced age and higher tumour burden index were identified as significant parameters. The overall predictive capability of our model, with the inclusion of AFP, is reflected with a UNO's C-statistic of 0.655, which is 1.11 times better than the 0.5895 C-statistic of the 8th AJCC TNM Staging model. CONCLUSIONS: Our modified Metroticket model allows for more granular and better-informed prognostication. This will help surgeons and patients make accurate comparisons between the clinical outcomes of surgical resection and other non-surgical treatments.

GATA4 downregulation enhances CCL20-mediated immunosuppression in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a deadly cancer with a high global mortality rate, and the downregulation of GATA binding protein 4 (GATA4) has been implicated in HCC progression. In this study, we investigated the role of GATA4 in shaping the immune landscape of HCC. METHODS: HCC tumor samples were classified into "low" or "normal/high" based on GATA4 RNA expression relative to adjacent non-tumor liver tissues. The immune landscapes of GATA4-low and GATA4-normal/high tumors were analyzed using cytometry by time-of-flight, bulk/spatial transcriptomic analyses and validated by multiplex immunofluorescence. RESULTS: GATA4-low tumors displayed enrichment in exhausted programmed cell death protein 1+ T cells, immunosuppressive regulatory T cells, myeloid-derived suppressor cells, and macrophages, highlighting the impact of GATA4 downregulation on immunosuppression. Spatial and bulk transcriptomic analyses revealed a negative correlation between GATA4 and C-C Motif Chemokine Ligand 20 (CCL20) expression in HCC. Overexpressing GATA4 confirmed CCL20 as a downstream target, contributing to an immunosuppressive tumor microenvironment, as evidenced by increased regulatory T cells and myeloid-derived suppressor cells in CCL20-high tumors. Lastly, the reduced expression of GATA4 and higher expression of CCL20 were associated with poorer overall survival in patients with HCC, implicating their roles in tumor progression. CONCLUSIONS: Our study reveals that GATA4 downregulation contributes to an immunosuppressive microenvironment, driven by CCL20-mediated enrichment of regulatory T cells and myeloid-derived suppressor cells in HCC. These findings underscore the critical role of GATA4 reduction in promoting immunosuppression and HCC progression.

Esrra regulates Rplp1-mediated translation of lysosome proteins suppressed in metabolic dysfunction-associated steatohepatitis and reversed by alternate day fasting.

OBJECTIVE: Currently, little is known about the mechanism(s) regulating global and specific protein translation during metabolic dysfunction-associated steatohepatitis (MASH; previously known as non-alcoholic steatohepatitis, NASH). METHODS: Unbiased label-free quantitative proteome, puromycin-labelling and polysome profiling were used to understand protein translation activity in vitro and in vivo. RESULTS: We observed a global decrease in protein translation during lipotoxicity in human primary hepatocytes, mouse hepatic AML12 cells, and livers from a dietary mouse model of MASH. Interestingly, proteomic analysis showed that Rplp1, which regulates ribosome and translation pathways, was one of the most downregulated proteins. Moreover, decreased Esrra expression and binding to the Rplp1 promoter, diminished Rplp1 gene expression during lipotoxicity. This, in turn, reduced global protein translation and Esrra/Rplp1-dependent translation of lysosome (Lamp2, Ctsd) and autophagy (sqstm1, Map1lc3b) proteins. Of note, Esrra did not increase its binding to these gene promoters or their gene transcription, confirming its regulation of their translation during lipotoxicity. Notably, hepatic Esrra-Rplp1-dependent translation of lysosomal and autophagy proteins also was impaired in MASH patients and liver-specific Esrra knockout mice. Remarkably, alternate day fasting induced Esrra-Rplp1-dependent expression of lysosomal proteins, restored autophagy, and reduced lipotoxicity, inflammation, and fibrosis in hepatic cell culture and in vivo models of MASH. CONCLUSIONS: Esrra regulation of Rplp1-mediated translation of lysosome/autolysosome proteins was downregulated during MASH. Alternate day fasting activated this novel pathway and improved MASH, suggesting that Esrra and Rplp1 may serve as therapeutic targets for MASH. Our findings also provided the first example of a nuclear hormone receptor, Esrra, to not only regulate transcription but also protein translation, via induction of Rplp1.

Clinical Recommendations for Improving Palliative Nursing Care for Patients With a Left Ventricular Assist Device.

Nurses who care for patients with a left ventricular assist device (LVAD) are highly skilled clinicians who manage unique technological demands and complex complications within this specialized patient population. There is a demonstrated need and benefit for palliative care for patients with a LVAD, yet palliative consults are often underused, and the quality of consultation for these patients is poorly understood. Rarely, if at all, do nurses receive formal training on how to navigate the palliative care needs of patients with a LVAD, which includes preparedness planning, caregiver support, device/body image acceptance, and end-of-life care. In addition, there is a need for literature to address specifically how nurses in their role and scope of practice can improve palliative care for patients with a LVAD. The purpose of this article was to present recommendations to equip palliative care nurses to best serve the needs of patients with a LVAD, wherein they can partner with and advance their colleagues in cardiology to improve their delivery of primary palliative care.

The association between tumour heterogeneity and immune evasion mechanisms in hepatocellular carcinoma and its clinical implications.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. The emergence of combination therapy, atezolizumab (anti-PDL1, immune checkpoint inhibitor) and bevacizumab (anti-VEGF) has revolutionised the management of HCC. Despite this breakthrough, the best overall response rate with first-line systemic therapy is only about 30%, owing to intra-tumoural heterogeneity, complex tumour microenvironment and the lack of predictive biomarkers. Many groups have attempted to classify HCC based on the immune microenvironment and have consistently observed better outcomes in immunologically "hot" HCC. We summarised possible mechanisms of tumour immune evasion based on the latest literature and the rationale for combination/sequential therapy to improve treatment response. Lastly, we proposed future strategies and therapies to overcome HCC immune evasion to further improve treatment outcomes of HCC.

Real-World Data on the Diagnosis, Treatment, and Management of Hepatocellular Carcinoma in the Asia-Pacific: The INSIGHT Study.

Introduction: Hepatocellular carcinoma (HCC) is the sixth most commonly diagnosed cancer and the third leading cause of cancer death worldwide. While there has been rapid evolution in the treatment paradigm of HCC across the past decade, the extent to which these newly approved therapies are utilized in clinical practice in the real world is, however, unknown. The INSIGHT study was an investigator-initiated, multi-site longitudinal cohort study conducted to reflect real-world epidemiology and clinical practice in Asia-Pacific in the immediate 7-year period after the conclusion of the BRIDGE study. Methods: Data were collected both retrospectively (planned 30% of the total cohort size) and prospectively (planned 70%) from January 2013 to December 2019 from eligible patients newly diagnosed with HCC from 33 participating sites across 9 Asia-Pacific countries. Results: A total of 2,533 newly diagnosed HCC patients (1,052 in retrospective cohort and 1,481 in prospective cohort) were enrolled. The most common risk factor was hepatitis B in all countries except Japan, Australia, and New Zealand, where the prevalence of hepatitis C and diabetes were more common. The top three comorbidities reported in the INSIGHT study include cirrhosis, hypertension, and diabetes. We observe high heterogeneity in the first-line treatment recorded across countries and across disease stages, which significantly affects survival outcomes. Stratification by factors such as etiologies, tumor characteristics, the presence of extrahepatic metastases or macrovascular invasion, and the use of subsequent lines of treatment were performed. Conclusion: The INSIGHT study describes a wide spectrum of clinical management practices in HCC, where patient demographics, differential costs, and patient access to therapies may lead to wide geographical variations through the patient's treatment cycle, from diagnosis to clinical outcome. The high heterogeneity in patient outcomes demonstrates the need for more robust and clinical management strategies to be designed and adopted to bring about better patient outcomes.

Pilot study of a community pharmacist led program to treat hepatitis C virus among people who inject drugs.

Background: People who inject drugs (PWID) are a key population for treatment with direct-acting antiviral medications (DAAs) to eliminate hepatitis C virus (HCV). We developed a Pharmacist, Physician, and Patient Navigator Collaborative Care Model (PPP-CCM) for delivery of HCV treatment; this study describes clinical outcomes related to HCV treatment (initial evaluation, treatment initiation, completion, and cure), as well as patient satisfaction. Methods: We conducted a single-arm prospective pilot study of adult PWID living with HCV. Participants completed baseline and six-month follow-up surveys, and treatment and outcomes were abstracted from electronic health records. Primary outcome was linkage to pharmacist for HCV evaluation; secondary outcomes included DAA initiation, completion, and cure, as well as patient-reported satisfaction. Results: Of the 40 PWID enrolled, mean age was 43.6 years, 12 (30 %) were female, 20 (50 %) were non-white, and 15 (38 %) were unhoused. Thirty-eight (95 %) were successfully linked to the pharmacist for initial evaluation. Of those, 21/38 (55 %) initiated DAAs, and 16/21 (76 %) completed treatment. Among those completing treatment who had viral load data to document whether they achieved "sustained virologic response", i.e. cure, 10/11 (91 %) were found to be cured. There was high satisfaction with 100 % responding "agree or strongly agree" that they had a positive experience with the pharmacist. Conclusion: Nearly all participants in this pilot were successfully linked to the pharmacist for evaluation, and more than half were started on DAAs; results provide preliminary evidence of feasibility of pharmacist-led models of HCV treatment for PWID. Clinicaltrialsgov registration number: NCT04698629.

Evaluation of a new dengue 3 controlled human infection model for use in the evaluation of candidate dengue vaccines.

All four serotypes of dengue virus (DENV) cause the full spectrum of disease. Therefore, vaccines must protect against all serotypes. To evaluate candidate vaccines, a human challenge model of dengue serotype 3 (rDEN30Δ30) was developed. All challenge virus recipients safely met the primary endpoint of viremia and secondary endpoints of rash and seroconversion to DENV-3.

Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): a randomised, open-label, multicentre, phase 3 trial.

BACKGROUND: No adjuvant treatment has been established for patients who remain at high risk for hepatocellular carcinoma recurrence after curative-intent resection or ablation. We aimed to assess the efficacy of adjuvant atezolizumab plus bevacizumab versus active surveillance in patients with high-risk hepatocellular carcinoma. METHODS: In the global, open-label, phase 3 IMbrave050 study, adult patients with high-risk surgically resected or ablated hepatocellular carcinoma were recruited from 134 hospitals and medical centres in 26 countries in four WHO regions (European region, region of the Americas, South-East Asia region, and Western Pacific region). Patients were randomly assigned in a 1:1 ratio via an interactive voice-web response system using permuted blocks, using a block size of 4, to receive intravenous 1200 mg atezolizumab plus 15 mg/kg bevacizumab every 3 weeks for 17 cycles (12 months) or to active surveillance. The primary endpoint was recurrence-free survival by independent review facility assessment in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT04102098. FINDINGS: The intention-to-treat population included 668 patients randomly assigned between Dec 31, 2019, and Nov 25, 2021, to either atezolizumab plus bevacizumab (n=334) or to active surveillance (n=334). At the prespecified interim analysis (Oct 21, 2022), median duration of follow-up was 17·4 months (IQR 13·9-22·1). Adjuvant atezolizumab plus bevacizumab was associated with significantly improved recurrence-free survival (median, not evaluable [NE]; [95% CI 22·1-NE]) compared with active surveillance (median, NE [21·4-NE]; hazard ratio, 0·72 [adjusted 95% CI 0·53-0·98]; p=0·012). Grade 3 or 4 adverse events occurred in 136 (41%) of 332 patients who received atezolizumab plus bevacizumab and 44 (13%) of 330 patients in the active surveillance group. Grade 5 adverse events occurred in six patients (2%, two of which were treatment related) in the atezolizumab plus bevacizumab group, and one patient (<1%) in the active surveillance group. Both atezolizumab and bevacizumab were discontinued because of adverse events in 29 patients (9%) who received atezolizumab plus bevacizumab. INTERPRETATION: Among patients at high risk of hepatocellular carcinoma recurrence following curative-intent resection or ablation, recurrence-free survival was improved in those who received atezolizumab plus bevacizumab versus active surveillance. To our knowledge, IMbrave050 is the first phase 3 study of adjuvant treatment for hepatocellular carcinoma to report positive results. However, longer follow-up for both recurrence-free and overall survival is needed to assess the benefit-risk profile more fully. FUNDING: F Hoffmann-La Roche/Genentech.

CD38 marks the exhausted CD8+ tissue-resident memory T cells in hepatocellular carcinoma.

Introduction: Despite recent advances in immunotherapy for hepatocellular carcinoma (HCC), the overall modest response rate underscores the need for a better understanding of the tumor microenvironment (TME) of HCC. We have previously shown that CD38 is widely expressed on tumor-infiltrating leukocytes (TILs), predominantly on CD3+ T cells and monocytes. However, its specific role in the HCC TME remains unclear. Methods: In this current study, we used cytometry time-of-flight (CyTOF), bulk RNA sequencing on sorted T cells, and single-cell RNA (scRNA) sequencing to interrogate expression of CD38 and its correlation with T cell exhaustion in HCC samples. We also employed multiplex immunohistochemistry (mIHC) for validating our findings. Results: From CyTOF analysis, we compared the immune composition of CD38-expressing leukocytes in TILs, non-tumor tissue-infiltrating leukocytes (NIL), and peripheral blood mononuclear cells (PBMC). We identified CD8+ T cells as the dominant CD38-expressing TILs and found that CD38 expression was significantly higher in CD8+ TRM in TILs than in NILs. Furthermore, through transcriptomic analysis on sorted CD8+ TRM from HCC tumors, we observed a higher expression of CD38 along with T cell exhaustion genes, including PDCD1 and CTLA4, compared to the circulating memory CD8 T cells from PBMC. This was validated by scRNA sequencing that revealed co-expression of CD38 with PDCD1, CTLA4, and ITGAE (CD103) in T cells from HCC tumors. The protein co-expression of CD38 and PD-1 on CD8+ T cells was further demonstrated by mIHC on HCC FFPE tissues, marking CD38 as a T cell co-exhaustion marker in HCC. Lastly, the higher proportions of CD38+PD-1+ CD8+ T cells and CD38+PD-1+ TRM were significantly associated with the higher histopathological grades of HCC, indicating its role in the aggressiveness of the disease. Conclusion: Taken together, the concurrent expression of CD38 with exhaustion markers on CD8+ TRM underpins its role as a key marker of T cell exhaustion and a potential therapeutic target for restoring cytotoxic T cell function in HCC.

Radiation dose during interventional cardiology procedures: portable C-arm vs. a new generation fluoroscopy system.

INTRODUCTION: Occupational exposure to ionizing radiation poses health risks for veterinary interventionalists. There are limited veterinary studies evaluating radiation dose in the cardiac catheterization laboratory. The purpose of this study was to report direct radiation dose exposure to patients during common interventional cardiology procedures and compare these doses between two fluoroscopy units. ANIMALS: One hundred and fifty-four client-owned dogs. MATERIALS AND METHODS: Patient dose during procedures using a portable C-arm were retrospectively analyzed and compared to those performed in a contemporary interventional suite. Fluoroscopy equipment, procedure type, operator, patient weight, fluoroscopy time, dose area product, and air kerma were recorded and statistically modeled using univariable and multivariable linear regression to evaluate the effect of each factor. RESULTS: Patient dose population (154 dogs), comprised 61 patent ductus arteriosus occlusions, 60 balloon pulmonary valvuloplasties, and 33 pacemaker implantations. Patient dose was significantly lower in the group utilizing a newer generation fluoroscopy unit vs. the group utilizing an older portable C-arm, positively correlated with patient weight, and highest during balloon pulmonary valvuloplasties compared to patent ductus arteriosus occlusions or pacemaker implantations (all P<0.010). DISCUSSION: Newer fluoroscopy systems can be equipped with technologies that improve image quality while reducing patient dose and radiation exposure to interventional personnel. CONCLUSIONS: We documented a significant reduction in patient radiation dose using a newer fluoroscopy system as compared to an older portable C-arm for interventional cardiology procedures in animals. Improved knowledge of patient radiation dose factors may promote better radiation safety protocols in veterinary interventional cardiology.

Affirmative Palliative Care for Transgender and Gender Nonconforming Individuals.

ABSTRACT: Nurses have a professional and ethical responsibility to provide inclusive, affirmative palliative care to transgender and gender nonconforming (TGNC) individuals experiencing life-limiting illness or injury. In accordance with standards for professional nursing and health organizations, nurses must continue to take tangible steps to achieve a level of care that is affirming, holistic, nonprejudicial, and collaborative. Providing quality care for TGNC individuals requires informed, competent integration of palliative nursing care, gender-affirmative care, and trans-person-centered health care within nursing practice. An interdisciplinary national team of experts collaborated to identify ways nurses could better uphold their professional responsibilities to TGNC individuals with serious illness. The purposes of this article are to: 1) describe elements of TGNC-inclusive palliative nursing care; and 2) present eight concrete recommendations to achieve affirmative clinical practice for TGNC patients living with life-limiting illness and their family of origin and/or family of choice. These recommendations address professional development, communication, medication reconciliation, mental health, dignity and meaning, social support and caregivers, spiritual beliefs and religion, and bereavement care.

Preoperative Predictors of Early Recurrence After Liver Resection for Multifocal Hepatocellular Carcinoma.

BACKGROUND: Liver transplantation remains the optimal treatment for multifocal hepatocellular carcinoma (HCC). However, due to resource constrains, other therapeutic modalities such as liver resection (LR), are frequently utilized. LR, however, has to be balanced against potential morbidity and mortality along with the risks of early recurrence leading to futile surgery. In this study, we evaluated preoperative factors, including inflammatory indices, in predicting early (< 1 year) recurrence in patients who underwent LR for multifocal HCC. METHODS: This was a post hoc analysis of 250 consecutive patients with multifocal HCC who underwent LR. RESULTS: After exclusion of 10 patients with 30-day/in-hospital mortality, 240 were included of which 134 (55.8%) developed early recurrence. Hepatitis B/C aetiology, 3/ > more hepatic nodules and elevated alpha-fetoprotein (AFP) ≥ 200 ng/ml were significant independent preoperative predictors of early recurrence. The early recurrence rate was 72.1% when 2 out of 3 significant predictive factors were present. The conglomerate of all 3 factors predicted early recurrence of 100% with a statistically significant association between number of predictive factors and early recurrence (p < 0.001). CONCLUSION: Better patient selection via the use of preoperative predictive factors of early recurrence such as hepatitis B/C aetiology, ≥ 3 nodules and elevated AFP ≥ 200 ng/ml may assist in identifying patients in whom LR is deemed futile and improve resource allocation.

Multi-region sampling with paired sample sequencing analyses reveals sub-groups of patients with novel patient-specific dysregulation in Hepatocellular Carcinoma.

BACKGROUND: Conventional differential expression (DE) testing compares the grouped mean value of tumour samples to the grouped mean value of the normal samples, and may miss out dysregulated genes in small subgroup of patients. This is especially so for highly heterogeneous cancer like Hepatocellular Carcinoma (HCC). METHODS: Using multi-region sampled RNA-seq data of 90 patients, we performed patient-specific differential expression testing, together with the patients' matched adjacent normal samples. RESULTS: Comparing the results from conventional DE analysis and patient-specific DE analyses, we show that the conventional DE analysis omits some genes due to high inter-individual variability present in both tumour and normal tissues. Dysregulated genes shared in small subgroup of patients were useful in stratifying patients, and presented differential prognosis. We also showed that the target genes of some of the current targeted agents used in HCC exhibited highly individualistic dysregulation pattern, which may explain the poor response rate. DISCUSSION/CONCLUSION: Our results highlight the importance of identifying patient-specific DE genes, with its potential to provide clinically valuable insights into patient subgroups for applications in precision medicine.

An evaluation of detailed animal characteristics influencing the lactation production efficiency of spring-calving, pasture-based dairy cattle.

Selection for feed efficiency, the ratio of output (e.g., milk yield) to feed intake, has traditionally been limited on commercial dairy farms by the necessity for detailed individual animal intake and performance data within large animal populations. The objective of the experiment was to evaluate the effects of individual animal characteristics (animal breed, genetic potential, milk production, body weight (BW), daily total dry matter intake (TDMI), and energy balance) on a cost-effective production efficiency parameter calculated as the annual fat and protein (milk solids) production per unit of mid-lactation BW (MSperBWlact). A total of 1,788 individual animal intake records measured at various stages of lactation (early, mid, and late lactation) from 207 Holstein-Friesian and 200 Jersey × Holstein-Friesian cows were used. The derived efficiency traits included daily kilograms of milk solids produced per 100 kg of BW (dMSperBWint) and daily kilograms of milk solids produced per kilogram of TDMI (dMSperTDMI). The TDMI per 100 kg of BW was also calculated (TDMI/BWint) at each stage of lactation. Animals were subsequently either ranked as the top 25% (Heff) or bottom 25% (Leff) based on their lactation production efficiency (MSperBWlact). Dairy cow breed significantly affected animal characteristics over the entire lactation and during specific periods of intake measurements. Jersey crossbred animals produced more milk, based on a lower TDMI, and achieved an increased intake per kilogram of BW. Similarly, Heff produced more milk over longer lactations, weighed less, were older, and achieved a higher TDMI compared with the Leff animals. Both Jersey × Holstein-Friesian and Heff cows achieved superior production efficiency due to lower maintenance energy requirements, and consequentially increased milk solids production per kilogram of BW and per kilogram of TDMI at all stages of lactation. Indeed, within breed, Heff animals weighed 20 kg less and produced 15% more milk solids over the total lactation than Leff. In addition, Heff achieved increased daily milk solids yield (+0.16 kg) and milk solids yield per kilogram of TDMI (+ 0.23 kg/kg DM) during intake measurement periods. Moreover, the strong and consistently positive correlations between MSperBWlact and detailed production efficiency traits (dMSperBWint, dMSperTDMI) reported here demonstrate that MSperBWlact is a robust measure that can be applied within commercial grazing dairy systems to increase the selection intensity for highly efficient animals.

The psychological burden of disease among patients undergoing cervical spine surgery: Are we underestimating our patients' inherent disability?

BACKGROUND: Studies have utilized psychological questionnaires to identify the psychological distress among certain surgical populations. RESEARCH QUESTION: Is there an additional psychological burden among patients undergoing surgical treatment for their symptomatic degenerative cervical disease? MATERIALS AND METHODS: Patients>18 years of age with symptomatic, degenerative cervical spine disease were included and prospectively enrolled. Correlations and multivariable logistic regression analysis assessed the relationship between these mental health components (PCS, FABQ) and the severity of disability described by the NDI, EQ-5D, and mJOA score. Patient distress scores were compared to previously published benchmarks for other diagnoses. RESULTS: 47 patients were enrolled (age: 56.0 years,BMI: 29.7kg/m2). Increasing neck disability and decreasing EQ-5D were correlated with greater PCS and FABQ(all P<0.001). Patients with severe psychological distress at baseline were more likely to report severe neck disability, while physician-reported mJOA had weaker associations. Compared to historical controls of lumbar patients, patients in our study had greater levels of psychological distress, as measured by FABQ (40.0 vs. 17.6; P<0.001) and PCS (27.4 vs. 19.3;P<0.001). DISCUSSION AND CONCLUSION: Degenerative cervical spine patients seeking surgery were found to have a significant level of psychological distress, with a large portion reporting severe fear avoidance beliefs and catastrophizing pain at baseline. Strong correlation was seen between patient-reported functional metrics, but less so with physician-reported signs and symptoms. Additionally, this population demonstrated higher psychological burden in certain respects than previously identified benchmarks of patients with other disorders. Preoperative treatment to help mitigate this distress, impact postoperative outcomes, and should be further investigated. LEVEL OF EVIDENCE: Level III.

Grazing season length and stocking rate affect milk production and supplementary feed requirements of spring-calving dairy cows on marginal soils.

The objective of this study was to investigate the effect of increasing stocking rate (SR) and extending grazing season (GS) length on pasture and animal productivity on a marginal, poorly draining soil type. The study was a multiyear (2017 to 2020, inclusive) whole farm systems evaluation with a 2 × 2 factorial experimental arrangement of treatments. The systems evaluated comprised 2 GS lengths, average (AGS; 205 d) and extended (EGS; 270 d), and the 2 whole farm stocking rates were medium (2.5 cows/ha) and high (2.9 cows/ha). We used this study design to create 4 grazing system intensities (500, 600, 700, and 800 cow grazing days per hectare per year). In 2017, cows were randomly allocated to 1 of the 4 whole farm systems precalving and remained on the same treatments for the duration of the study. We found no significant differences in total average annual pasture production [14,133 ± 538 kg of dry matter (DM) per hectare] or sward chemical composition between GS and SR treatments over the 4-yr period, with the exception of average crude protein content, which was lower for EGS (211 g/kg DM) compared with AGS (218 g/kg DM). Grazed pasture production was significantly increased in EGS treatments (+758 kg of DM/ha) compared with AGS (9,917 kg of DM/ha), whereas conserved silage DM production was greater for AGS (+716 kg of DM/ha) compared with EGS (3,583 kg of DM/ha). Neither GS nor SR had a significant effect on daily or cumulative lactation milk and fat plus protein production per cow (5,039 and ±440 kg, respectively). Increasing SR resulted in increased milk fat plus protein yield per hectare based on increased grazed pasture utilization. These results add further credence to the important additive contributions of both extended grazing and SR intensification to achieve high levels of grazed pasture utilization and milk production per hectare while reducing supplementary feed requirements within spring-calving grazing systems.

The effects of spring feeding strategy on pasture productivity, sward quality, and animal performance within intensive pasture-based dairy systems.

The objective of this research was to evaluate how different feeding strategies based on various pasture availability (PA) treatments within intensive seasonal production systems affected pasture production and utilization, sward quality, and the milk production, body weight (BW), and body condition score (BCS) of dairy cows. The performance data were obtained from a 3-yr experiment conducted previously (2018-2020, inclusive). In total, records from 208 spring-calving dairy cows were available for analysis. The animals were randomly allocated to 1 of 3 PA grazing treatments in spring that varied in average pasture cover (measured as herbage mass available above 3.5 cm) that was established via different pasture management strategies in the previous autumn. Thus, the opening average pasture cover across all paddocks on February 1 was 1,100 kg of dry matter (DM)/ha for high pasture availability (HPA), 880 for medium pasture availability (MPA), and 650 for low pasture availability (LPA), respectively. The measurements were taken over an 8-wk period during the first grazing rotation in spring, commencing on February 16 (±2 d) and finishing when all paddocks were grazed once on April 12 (±5 d). Paddocks that were part of the HPA treatment showed the highest pregrazing herbage masses and pregrazing sward heights (1,645 kg of DM/ha and 8.2 cm, respectively) compared with MPA (1,412 kg of DM/ha and 7.5 cm, respectively) and LPA (1,170 kg of DM/ha and 6.9 cm, respectively). Owing to the differences in PA, daily herbage allowance was greatest for HPA (11.7 kg of DM/cow), intermediate for MPA (10.2 kg of DM/cow), and lowest for LPA (8.8 kg of DM/cow), with the remaining feed deficit composed of additional daily grass silage supplementation (0.8, 1.5, and 2.8 kg of DM/cow for HPA, MPA, and LPA, respectively), while the daily concentrate and daily total feed allowance were equal between treatments during spring (2.7 and 15.0 kg of DM/cow). Despite salient differences in fresh pasture used, complementing pasture intake with grass silage did not affect daily or cumulative milk, solids-corrected milk, fat, or protein yield or milk constituents. Similarly, BW and BCS were also unaffected by PA treatment. The results highlight the importance of high spring pasture utilization and grazing efficiency achievable with higher pregrazing herbage masses, which also allow larger animal intakes from grazed pasture as the cheapest feed source during spring. Moreover, targeting an adequate pasture supply at the commencement of calving increases the grazing days per hectare and lowers the requirement for supplementary feed on farm, particularly when facing increasing variability in climatic conditions.

Intraoperative blood transfusion does not impact overall and recurrence-free survival after curative hepatectomy for hepatocellular carcinoma: A propensity-score-matched and inverse probability of treatment-weighted study.

INTRODUCTION: Our primary objective was to determine if receiving intraoperative blood transfusion was a significant prognostic factor for overall and recurrence-free survival after curative resection of hepatic cellular carcinoma (HCC). METHODOLOGY: Between 2001 and 2018, 1092 patients with histologically proven primary HCC who underwent curative liver resection were retrospectively reviewed. Primary study endpoints were recurrence-free survival (RFS) and overall survival (OS). The main analysis was undertaken using propensity-score matching (PSM) to minimize confounding and selection biases in the comparison of patients with or without transfusion. RESULTS: There were 220 patients who received and 666 patients who did not receive intraoperative blood transfusion. The PSM cohort consisted of 163 pairs of patients. After PSM, the only perioperative outcome that appeared to significantly affect whether patients would receive blood transfusion was median blood loss (p = 0.001). In the PSM cohort, whether patients received blood transfusion was neither associated with OS (p = 0.759) nor RFS (p = 0.830). When the volume of blood transfusion was analyzed as a continuous variable, no significant dose-response relationship between blood transfusion volume and HR for OS and RFS was noted. CONCLUSION: Intraoperative blood transfusion had no significant impact on the survival outcomes in patients who receive curative resection in primary HCC.