ESGO-ESMO-ESP consensus conference recommendations on ovarian cancer: pathology and molecular biology and early, advanced and recurrent disease.

The European Society of Gynaecological Oncology, the European Society for Medical Oncology (ESMO) and the European Society of Pathology held a consensus conference (CC) on ovarian cancer on 15-16 June 2022 in Valencia, Spain. The CC panel included 44 experts in the management of ovarian cancer and pathology, an ESMO scientific advisor and a methodologist. The aim was to discuss new or contentious topics and develop recommendations to improve and harmonise the management of patients with ovarian cancer. Eighteen questions were identified for discussion under four main topics: (i) pathology and molecular biology, (ii) early-stage disease and pelvic mass in pregnancy, (iii) advanced stage (including older/frail patients) and (iv) recurrent disease. The panel was divided into four working groups (WGs) to each address questions relating to one of the four topics outlined above, based on their expertise. Relevant scientific literature was reviewed in advance. Recommendations were developed by the WGs and then presented to the entire panel for further discussion and amendment before voting. This manuscript focuses on the recommendation statements that reached a consensus, their voting results and a summary of evidence supporting each recommendation.

System-level recommendations for improved wellness for gynecologic oncologists: A Society of Gynecologic Oncology Review.

Burnout and its negative sequelae are a persistent problem in gynecologic oncology, threatening the health of our physician workforce. Individual-level interventions such as stress management training, physical activity, and sleep hygiene only partially address this widespread, systemic crisis rooted in the extended work hours and stressful situations associated with gynecologic oncology practice. There is an urgent need for systematic, institution-level changes to allow gynecologic oncologists to continue the crucial work of caring for people with gynecologic cancer. We present recommendations for institution-level changes which are grounded in the framework presented by the National Plan for Health Workforce Well-Being by the National Academy of Medicine. These are aimed at facilitating gynecologic oncologists' well-being and reduction of burnout. Recommendations include efforts to create a more positive and inclusive work environment, decrease administrative barriers, promote mental health, optimize electronic medical record use, and support a diverse workforce. Implementation and regular evaluation of these interventions, with specific attention to at-risk groups, is an important next step.

Rumen-protected methionine supplementation during the transition period under artificially induced heat stress: impacts on cow-calf performance.

Dairy cows experiencing heat stress (HS) during the pre-calving portion of the transition period give birth to smaller calves and produce less milk and milk protein. Supplementation of rumen-protected methionine (RPM) has been shown to modulate protein, energy, and placenta metabolism, making it a potential candidate to ameliorate HS effects. We investigated the effects of supplementing RPM to transition cows under HS induced by electric heat blanket (EHB) on cow-calf performance. Six weeks before expected calving, 53 Holstein cows were housed in a tie-stall barn and fed a control diet (CON, 2.2% Met of MP) or a CON diet supplemented with Smartamine®M (MET, 2.6% Met of MP, Adisseo Inc., France). Four weeks pre-calving, all MET and half CON cows were fitted with an EHB. The other half of the CON cows were considered thermoneutral (TN), resulting in 3 treatments: CONTN (n = 19), CONHS (n = 17), and METHS (n = 17). Respiratory rate (RR), skin temperature (ST), and rectal temperature (RT) were measured thrice weekly and core body temperatures recorded bi-weekly. Post-calving body weights (BW) and BCS were recorded weekly, and DMI was calculated and averaged weekly. Milk yield was recorded daily and milk components were analyzed every third DIM. Biweekly AA and weekly nonesterified fatty acids (NEFA), ß-hydroxybutyrate (BHB), insulin, and glucose were measured from plasma. Calf birth weight and 24 h growth, thermoregulation, and hematology profile were measured and apparent efficiency of absorption (AEA) of immunoglobulins was calculated. Data were analyzed using the MIXED procedure of SAS with 2 preplanned orthogonal contrasts: CONTN vs. the average of CONHS and METHS (C1) and CONHS vs. METHS (C2). Relative to TN, EHB cows had increased RT during the post-calving weeks and increased RR and ST during the entire transition period. Body weight, BCS, DMI, and milk yield were not impacted by the EHB or RPM. However, protein % and SNF were lower in CONHS, relative to METHS cows. At calving, METHS dams had higher glucose concentrations, relative to CONHS, and during the post-calving weeks, the EHB cows had lower NEFA concentrations than TN cows. Calf birthweight and AEA were reduced by HS, while RR was increased by HS. Calf withers height tended to be shorter and RT were lower in CONHS, compared with MTHS heifers. Overall, RPM supplementation to transition cows reverts the negative impact of HS on blood glucose concentration at calving and milk protein % in the dams and increases wither height while decreasing RT in the calf.

Amplifying local serotonin signaling prior to dry-off hastens mammary gland involution and redevelopment in dairy cows.

The monoamine serotonin (5-hydroxytryptamine, 5-HT) has been reported to inhibit milk protein gene expression and increase mammary epithelial cell (MEC) tight junction permeability after milk stasis. We hypothesized that increasing serotonin synthesis and signaling within the mammary epithelium before milk stasis would increase systemic and local involution markers, and downregulate the expression of milk protein and tight junction during involution, leading to more efficient tissue growth during the redevelopment phase. Herein, we examined the outcomes of increasing local mammary 5-HT synthesis before milk stasis on involution biomarkers, mammary gland microstructure, and gene and protein expression during the dry period. Multiparous Holstein cows were administered intramammary infusions (via the teat canal) of sterile water (CON, 4 mL/teat, n = 7) or 5-hydroxy-l-tryptophan (5-HTP, serotonin precursor, 20 mg/teat, n = 7) once daily for 5 d before dry-off (d 0). Blood, milk, and mammary secretions were collected and analyzed for components and metabolites. Mammary secretions were collected 12 h after the last milking and on d 1 to 4 during the dry period at 1200 h. Mammary gland biopsies were performed on d 4 (i.e., involution phase) and d 36 (i.e., redevelopment phase) of the dry period for histological and molecular evaluation. Milk protein and tight junction gene expression was quantified via real-time PCR. Hematoxylin and eosin staining, immunohistochemistry (Ki67), and immunofluorescence (serotonin, cleaved caspase 3) were performed to visualize tissue microstructure and to quantify serotonin intensity and cell turnover. Data were analyzed in SAS (SAS Institute Inc.) using 2-way ANOVA. After d 0, mammary secretions of 5-HTP cows had increased concentrations of 5-HT, lactoferrin, and bovine serum albumin. On d 1, 5-HTP cows had greater α-lactalbumin concentrations in plasma relative to CON. Serotonin intensity was increased in the mammary tissue of 5-HTP cows on d 4, relative to CON. On d 4, milk protein and tight junction gene expression was downregulated, MEC number was reduced, and cleaved caspase 3 protein was greater in mammary tissue of 5-HTP cows, relative to CON. On d 36, milk protein genes were upregulated, and the lumen:outer alveolar area and Ki67-positive cells were increased in the mammary tissue of 5-HTP cows, relative to CON. Amplifying serotonin signaling in the mammary epithelium before milk stasis at dry-off achieves greater apoptosis, leading to a reduction in MEC, allowing for greater cell proliferation, which results in more MEC during the redevelopment phase preceding the onset of lactation.

Neoadjuvant Systemic Therapy (NAST) in Patients with Melanoma: Surgical Considerations by the International Neoadjuvant Melanoma Consortium (INMC).

Exciting advances in melanoma systemic therapies have presented the opportunity for surgical oncologists and their multidisciplinary colleagues to test the neoadjuvant systemic treatment approach in high-risk, resectable metastatic melanomas. Here we describe the state of the science of neoadjuvant systemic therapy (NAST) for melanoma, focusing on the surgical aspects and the key role of the surgical oncologist in this treatment paradigm. This paper summarizes the past decade of developments in melanoma treatment and the current evidence for NAST in stage III melanoma specifically. Issues of surgical relevance are discussed, including the risk of progression on NAST prior to surgery. Technical aspects, such as the definition of resectability for melanoma and the extent and scope of routine surgery are presented. Other important issues, such as the utility of radiographic response evaluation and method of pathologic response evaluation, are addressed. Surgical complications and perioperative management of NAST related adverse events are considered. The International Neoadjuvant Melanoma Consortium has the goal of harmonizing NAST trials in melanoma to facilitate rapid advances with new approaches, and facilitating the comparison of results across trials evaluating different treatment regimens. Our ultimate goals are to provide definitive proof of the safety and efficacy of NAST in melanoma, sufficient for NAST to become an acceptable standard of care, and to leverage this platform to allow more personalized, biomarker-driven, tailored approaches to subsequent treatment and surveillance.

SGO and the elephant that is still in the room: Wellness, burnout and gynecologic oncology.

OBJECTIVE: To measure wellness and burnout among gynecologic oncology clinicians and identify trends and at-risk populations to inform future interventions. METHODS: Gynecologic oncologist (GO) and advanced practice provider (APP) responses to the 2020 Society of Gynecologic Oncology State of the Society survey were analyzed. The Maslach Burnout Inventory criteria for burnout was used. Work-life balance was scored on a 5-point Likert scale. Chi-square tests were used to compare mental health factors and the prevalence of burnout. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for associations between burnout and gender. RESULTS: 543 survey responses were included for analysis. Most GO (54%) and all APP respondents were female. Female GOs were disproportionately affected by burnout particularly in the Northeast (female(F): 40.9% vs male(M): 19.1%, p = 0.007) and South (F: 42.5% vs M:22.9%, p = 0.01). Burnout in female GOs over 40 was 1.79 (CI: 1.13-2.83; p-value 0.01) times higher than similarly aged males. Females in non-private practice experienced burnout 1.66 times that of males in similar positions (CI: 1.18-2.94; p < 0.0001). Female GOs reported the worst work-life balance across all 5 domains. APPs and female GOs experienced more stress and feeling overwhelmed compared to men. GOs were more reluctant to see a mental health professional (p = 0.0003) or take medication (p = 0.009) than APPs. CONCLUSIONS: Burnout in gynecologic oncology persists in both genders and is felt most acutely by female GOs. APPs are not immune and would benefit from inclusion in future research to mitigate burnout in healthcare clinicians.

Effect of in utero exposure to hyperthermia on postnatal hair length, skin morphology, and thermoregulatory responses.

Skin and hair coat play important functions in maintaining homeostasis and thermoregulation for cattle, which can affect all modes of heat loss. Our objective was to investigate the effect of hyperthermia experienced in utero during late gestation on postnatal hair length, skin properties, and thermoregulation. Pregnant dams were heat stressed (n = 41) or actively cooled (n = 41) for the last ∼56 d of gestation and gave birth to heifers that were in utero heat stressed (IUHT) or in utero cooled (IUCL), respectively. Hair samples and skin tissue biopsies were collected from neck and rump locations at birth (d 0), 1 wk after weaning (d 63), and at 12 mo. Hair samples were also obtained at 4 and 8 mo. Skin tissue was stained with hematoxylin and eosin to visualize morphology. Hair length (short and long hairs, undercoat and topcoat, respectively), stratum corneum (SC) area, SC thickness, epidermis thickness, sweat gland (SWT) number, SWT cross-sectional area, SWT average size, sebaceous gland (SEB) number, SEB cross-sectional area, SEB average size, and sweat gland depth were assessed. Respiration rate, skin temperature, sweating rate, and rectal temperature was measured weekly from d 7 to 63. Additionally, thermoregulatory patterns were measured every 4 h over a 36-h interval beginning 4 d after weaning. Data were analyzed using PROC MIXED in SAS with a main effect of in utero treatment with location and time points analyzed separately. No difference in hair parameters were detected at d 0 or 12 mo. At d 63, IUHT heifers had longer average hair length (14.8 vs. 13.8 ± 0.2 mm, standard error), shorter undercoats (9.3 vs. 10.4 ± 0.3 mm), longer topcoats (19.6 vs. 17.1 ± 0.3 mm), and a greater difference between topcoat and undercoat (10.1 vs. 7.0 ± 0.4 mm). At 4 mo, IUHT heifers had longer average hair lengths (26.1 vs. 22.2 ± 1.0 mm) and longer topcoats (36.9 vs. 33.9 ± 1.1 mm), and at 8 mo, IUHT had longer average hair lengths (17.9 vs. 16.2 ± 0.6 mm), relative to IUCL. At d 0, IUHT heifers had more (13 vs. 9 ± 2 glands) but smaller average sized SEB (neck: 1,636 vs. 2,238 ± 243 µm2; rump: 2,100 vs. 3,352 ± 379 µm2) and reduced SC area (79,243 vs. 169,419 ± 13,071 µm2). At d 63, IUHT had fewer SEB (11 vs. 15 ± 2 glands), smaller SWT (0.16 vs. 0.23 ± 0.02 mm2), fewer SWT (16 vs. 23 ± 4 glands), and deeper SWT (0.5 vs. 0.4 ± 0.03 mm). At 12 mo, IUHT had greater distance from the skin surface to the most superficial SWT (0.016 vs. 0.015 ± 0.0004 mm), shorter distance to the deepest SWT (0.031 vs. 0.033 ± 0.001 mm), and smaller SWT (81.1 vs. 108.9 ± 10.8 µm2), relative to IUCL. When measured both weekly and hourly, IUHT heifers had higher rectal temperature and sweating rate. Overall, in utero hyperthermia triggers long-lasting hair and skin adaptations, possibly leading to differences in postnatal thermoregulation.

Late-gestation heat stress abatement in dairy heifers promotes thermoregulation and improves productivity.

Multiparous, nonlactating pregnant cows are negatively affected by heat stress, but the effect of heat stress on more thermotolerant pregnant heifers has received less attention. Our objective was to characterize the effect of late-gestation heat abatement on thermoregulatory responses and subsequent milk production of nulliparous Holstein heifers. Pregnant heifers, blocked by body condition score (BCS) and predicted transmitting ability (PTA) for milk, were enrolled in either heat stress (HT, shade of freestall barn; n = 16) or cooling (CL, shade of freestall barn, water soakers, and fans; n = 15) environments during the last 60 d of pregnancy (~8 weeks). Rectal temperature (RT; thermometer), respiration rate (RR; breaths/min), sweating rate (SR; VapoMeter, Delfin Technologies, Kuopio, Finland), and skin temperature (ST; infrared thermometer) were measured thrice weekly from enrollment to calving. Vaginal temperature (VT; i-button intravaginal device) was measured every 10 min for 7 consecutive days at wk -8, -6, -4, and -2 relative to calving and averaged hourly. Daily thermoregulatory patterns assessed by SR and ST, were measured every 4 h over a 36-h time interval at wk -6, -4, and -2 relative to calving. Upon calving, milk, protein, and fat yields were recorded twice daily for 15 wk. The average temperature-humidity index (Hobo Pro temperature probe, Onset Computer Corporation, Pocasset, MA) in the barn during the precalving period was 77 (minimum of 72, maximum of 82). Only heifers that gave birth to a female calf (CL = 12, HT = 14) were included in the statistical analysis. In the precalving period, CL heifers had lower RR (44.3 vs. 60.0 ± 1.6 breaths/min), RT (38.7 vs. 38.8 ± 0.04°C), unshaved ST (34.7 vs. 35.3 ± 0.17°C), and unshaved SR (19.0 vs. 35.2 ± 1.9 g/m2h), relative to HT heifers. Additionally, VT was lower in CL heifers during wk -4, and -2, specifically during early morning and early afternoon hours. When measured over a 36-h time interval, ST and SR were lower in CL heifers, when compared with HT heifers for all weeks. Notably, ST was reduced overnight and SR was reduced during the daytime. Cooled heifers had higher milk yield (35.8 vs. 31.9 ± 1.4 kg/d), when compared with HT heifers. Similar to multiparous cows, our data indicate that actively cooling heifers in late pregnancy is effective in promoting thermoregulation and results in elevated milk production postcalving.

Intraperitoneal chemotherapy following neoadjuvant chemotherapy and optimal interval tumor reductive surgery for advanced ovarian cancer.

OBJECTIVES: Intraperitoneal (IP) chemotherapy following neoadjuvant chemotherapy (NACT) and interval tumor reductive surgery (TRS) for advanced ovarian cancer is feasible, however, the impact on disease outcomes remains unclear. We compare outcomes of patients treated with IP chemotherapy versus intravenous (IV) chemotherapy following NACT and interval TRS. METHODS: In this retrospective review, patients with advanced ovarian cancer were included if they received NACT followed by optimal interval TRS between 1/2004 and 4/2017. Patients were excluded if they had an ECOG PS >1, received >6 cycles of NACT or postoperative chemotherapy, and/or received bevacizumab during primary therapy. Primary outcomes were progression free survival (PFS) and overall survival (OS). RESULTS: There were 134 patients included in this study, 37 (28%) received IP and 97 (72%) received IV chemotherapy postoperatively. Patients in the IV group were older (median 66.3 vs 59.7 years, p = 0.0039) though there were no differences in BMI, race, BRCA status, stage, or histology. Median PFS was 3 months longer in the IP group (14.5 versus 11.5 months, p = 0.028) however there was no significant difference in OS. On univariate analysis, increasing number of NACT cycles (HR 1.914, 95% CI 1.024-3.497) and residual disease at completion of TRS (HR 1.541, 95% CI 1.042-2.248) were associated with decreased PFS; IP chemotherapy was associated with increased PFS (HR 0.633, 95% CI 0.414-0.944). These associations remained on multivariate analysis. Toxicity was comparable between the groups. CONCLUSIONS: IP after NACT and optimal interval TRS was associated with in improved PFS compared to IV chemotherapy without significant differences in toxicity.

Pathologic and clinical tumor size discordance in early-stage cervical cancer: Does it matter?

OBJECTIVE: The objective of this study was to assess the rate of discordance between clinical and pathologic tumor size for women with stage IB1 cervical cancer (FIGO 2009 criteria), assess risk factors for discordance, and determine the impact of discordance on oncologic outcomes. METHODS: This was a secondary analysis of a prior multi-institutional retrospective review of patients diagnosed with stage IB1 (FIGO 2009 staging) cervical cancer undergoing radical hysterectomy between 2010 and 2017. Demographic, clinicopathologic, and oncologic data were collected. Pathologic upstaging was defined as having a preoperative diagnosis of stage IB1 cervical cancer with pathology demonstrating a tumor size >4 cm. Demographic and clinicopathologic data was compared using chi-square, fisher exact or 2-sided t-test. Survival was estimated using the Kaplan-Meier method. RESULTS: Of the 630 patients, 77 (12%) were upstaged. Patients who were upstaged had lower rates of preoperative conization (p < .001) or preoperative tumor sizes ≤2 cm (p < .001). Upstaged patients had increased odds of deep stromal invasion, lymphovascular space invasion, positive margins and positive lymph nodes. Almost 88% of upstaged patients received adjuvant therapy compared to 29% of patients with tumors ≤4 cm (odds 18.49, 95% CI 8.99-37.94). Finally, pathologic upstaging was associated with an increased hazard of recurrence (hazard ratio [HR] 1.95, 95% CI 1.03-3.67) and all-cause death (HR 2.31, 95% CI 1.04-5.11). CONCLUSIONS: Pathologic upstaging in stage IB1 cervical cancer is relatively common. Upstaging is associated with an 18-fold increased risk of receipt of adjuvant therapy. Patients undergoing preoperative conization and those with tumors <2 cm had lower risks of upstaging. Improvement in preoperative assessment of tumor size may better inform primary treatment decisions.

Pulmonary Metastasectomy in Colorectal Cancer: updated analysis of 93 randomized patients - control survival is much better than previously assumed.

AIM: Lung metastases from colorectal cancer are resected in selected patients in the belief that this confers a significant survival advantage. It is generally assumed that the 5-year survival of these patients would be near zero without metastasectomy. We tested the clinical effectiveness of this practice in Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC), a randomized, controlled noninferiority trial. METHOD: Multidisciplinary teams in 14 hospitals recruited patients with resectable lung metastases into a two-arm trial. Randomization was remote and stratified according to site, with minimization for age, sex, primary cancer stage, interval since primary resection, prior liver involvement, number of metastases and carcinoembryonic antigen level. The trial management group was blind to patient allocation until after intention-to-treat analysis. RESULTS: From 2010 to 2016, 93 participants were randomized. These patients were 35-86 years of age and had between one and six lung metastases at a median of 2.7 years after colorectal cancer resection; 29% had prior liver metastasectomy. The patient groups were well matched and the characteristics of these groups were similar to those of observational studies. The median survival after metastasectomy was 3.5 (95% CI: 3.1-6.6) years compared with 3.8 (95% CI: 3.1-4.6) years for controls. The estimated unadjusted hazard ratio for death within 5 years, comparing the metastasectomy group with the control group, was 0.93 (95% CI: 0.56-1.56). Use of chemotherapy or local ablation was infrequent and similar in each group. CONCLUSION: Patients in the control group (who did not undergo lung metastasectomy) have better survival than is assumed. Survival in the metastasectomy group is comparable with the many single-arm follow-up studies. The groups were well matched with features similar to those reported in case series.

Comparison of manual and semi-automatic registration in augmented reality image-guided liver surgery: a clinical feasibility study.

BACKGROUND: The laparoscopic approach to liver resection may reduce morbidity and hospital stay. However, uptake has been slow due to concerns about patient safety and oncological radicality. Image guidance systems may improve patient safety by enabling 3D visualisation of critical intra- and extrahepatic structures. Current systems suffer from non-intuitive visualisation and a complicated setup process. A novel image guidance system (SmartLiver), offering augmented reality visualisation and semi-automatic registration has been developed to address these issues. A clinical feasibility study evaluated the performance and usability of SmartLiver with either manual or semi-automatic registration. METHODS: Intraoperative image guidance data were recorded and analysed in patients undergoing laparoscopic liver resection or cancer staging. Stereoscopic surface reconstruction and iterative closest point matching facilitated semi-automatic registration. The primary endpoint was defined as successful registration as determined by the operating surgeon. Secondary endpoints were system usability as assessed by a surgeon questionnaire and comparison of manual vs. semi-automatic registration accuracy. Since SmartLiver is still in development no attempt was made to evaluate its impact on perioperative outcomes. RESULTS: The primary endpoint was achieved in 16 out of 18 patients. Initially semi-automatic registration failed because the IGS could not distinguish the liver surface from surrounding structures. Implementation of a deep learning algorithm enabled the IGS to overcome this issue and facilitate semi-automatic registration. Mean registration accuracy was 10.9 ± 4.2 mm (manual) vs. 13.9 ± 4.4 mm (semi-automatic) (Mean difference - 3 mm; p = 0.158). Surgeon feedback was positive about IGS handling and improved intraoperative orientation but also highlighted the need for a simpler setup process and better integration with laparoscopic ultrasound. CONCLUSION: The technical feasibility of using SmartLiver intraoperatively has been demonstrated. With further improvements semi-automatic registration may enhance user friendliness and workflow of SmartLiver. Manual and semi-automatic registration accuracy were comparable but evaluation on a larger patient cohort is required to confirm these findings.

Pre- and postnatal heat stress abatement affects dairy calf thermoregulation and performance.

Prenatal heat stress during late gestation exerts long-term effects on growth and productivity of the dairy calf. Further, direct exposure to heat stress during the preweaning period impairs calf thermoregulation and performance. We examined the effects of heat stress abatement during the prenatal period, postnatal period, or both on calf performance. We hypothesized that calves exposed to pre- and postnatal heat stress abatement would perform most optimally in terms of thermoregulation, growth, and health responses when compared with calves that are heat-stressed at any time in the pre- or postnatal periods. Holstein calves born to heat-stressed (HT) or cooled (CL) dams during late gestation (44 ± 5 d; prenatal HT or CL) were exposed to heat stress or cooling postnatally for 56 d (postnatal HT or CL), resulting in 4 treatments: HT-HT, HT-CL, CL-HT, and CL-CL; n = 12/treatment. Calves were administered 4 L of pooled colostrum and after 2 d of age allotted 10 L/d milk replacer and up to 3 kg/d concentrate in automatic feeder group pens (n = 6/pen). Postnatal cooling was achieved by 2 fans (average wind speed 2 m/s). Thermoregulatory responses (respiration rate and heart rate; rectal, body, and skin temperature), feed intake, growth parameters including average daily gain and medication events were recorded, and blood samples were collected weekly. Thermoregulatory responses were lower in postnatal CL calves compared with postnatal HT. In the afternoon, HT-HT calves had the highest respiration rate and rectal temperature, HT-CL calves had the lowest respiration rate, and CL-HT calves had the lowest heart rate compared with the other treatment groups. Prenatal CL calves weighed more at birth and weaning with a tendency for greater average daily gain compared with prenatal HT calves, whereas postnatal CL calves had increased milk replacer and concentrate intake and a tendency for reduced fever, infection, and total medication events relative to postnatal HT. Prenatal HT calves were esophageal tube fed more often than prenatal CL. Blood hematocrit and 24-h serum IgG concentration were greater in prenatal CL calves relative to prenatal HT. Prenatal heat stress abatement improves weight gain, hematocrit, and immunoglobulin transfer, whereas postnatal heat stress abatement modulates thermoregulatory responses, feed intake, and calf health. This study is the first to characterize the combined effects of pre- and postnatal heat stress or active cooling on the dairy calf.

Quality of life is significantly associated with survival in women with advanced epithelial ovarian cancer: An ancillary data analysis of the NRG Oncology/Gynecologic Oncology Group (GOG-0218) study.

OBJECTIVE: Evaluate association between baseline quality of life (QOL) and changes in QOL measured by FACT-O TOI with progression-free disease (PFS) and overall survival (OS) in advanced epithelial ovarian cancer (EOC). METHODS: Patients enrolled in GOG-0218 with completed FACT-O TOI assessments at baseline and at least one follow-up assessment were eligible. Baseline FACT-O TOI scores were sorted by quartiles (Q1-4) and outcomes compared between Q1 and Q2-4 with log-rank statistic and multivariate Cox regression adjusting for age, stage, post-surgical residual disease size, and performance status (PS). Trends in FACT-O TOI scores from baseline to the latest follow-up assessment were evaluated for impact on intragroup (Q1 or Q2-4) outcome by log-rank analysis. RESULTS: Of 1152 eligible patients, 283 formed Q1 and 869 formed Q2-4. Mean baseline FACT-O TOI scores were 47.5 for Q1 vs. 74.7 for Q2-4 (P<0.001). Q1 compared to Q2-4 had worse median OS (37.5 vs. 45.6months, P=0.001) and worse median PFS (12.5 vs. 13.1months, P=0.096). Q2-4 patients had decreased risks of disease progression (HR 0.974, 95% CI 0.953-0.995, P=0.018), and death (HR 0.963, 95% CI 0.939-0.987, P=0.003) for each five-point increase in baseline FACT-O TOI. Improving versus worsening trends in FACT-O TOI scores were associated with longer median PFS (Q1: 12.7 vs. 8.6months, P=0.001; Q2-4: 16.7 vs. 11.1months, P<0.001) and median OS (Q1: 40.8 vs. 16months, P<0.001; Q2-4: 54.4 vs. 33.6months, P<0.001). CONCLUSIONS: Baseline FACT-O TOI scores were independently prognostic of PFS and OS while improving compared to worsening QOL was associated with significantly better PFS and OS in women with EOC.

Engineering a gene silencing viral construct that targets the cat hypothalamus to induce permanent sterility: An update.

The intent of this contribution is to provide an update of the progress we have made towards developing a method/treatment to permanently sterilize cats. Our approach employs two complementary methodologies: RNA interference (RNAi) to silence genes involved in the central control of reproduction and a virus-based gene therapy system intended to deliver RNAi selectively to the hypothalamus (where these genes are expressed) via the systemic administration of modified viruses. We selected the hypothalamus because it contains neurons expressing Kiss1 and Tac3, two genes essential for reproduction and fertility. We chose the non-pathogenic adeno-associated virus (AAV) as a vector whose tropism could be modified to target the hypothalamus. The issues that must be overcome to utilize this vector as a delivery vehicle to induce sterility include modification of the wild-type AAV to target the hypothalamic region of the brain with a simultaneous reduction in targeting of peripheral tissues and non-hypothalamic brain regions, identification of RNAi targets that will effectively reduce the expression of Kiss1 and Tac3 without off-target effects, and determination if neutralizing antibodies to the AAV serotype of choice are present in cats. Successful resolution of these issues will pave the way for the development of a powerful tool to induce the permanent sterility in cats.

Cost-effectiveness of noninvasive liver fibrosis tests for treatment decisions in patients with chronic hepatitis B in the UK: systematic review and economic evaluation.

We compared the cost-effectiveness of various noninvasive tests (NITs) in patients with chronic hepatitis B and elevated transaminases and/or viral load who would normally undergo liver biopsy to inform treatment decisions. We searched various databases until April 2012. We conducted a systematic review and meta-analysis to calculate the diagnostic accuracy of various NITs using a bivariate random-effects model. We constructed a probabilistic decision analytical model to estimate health care costs and outcomes quality-adjusted-life-years (QALYs) using data from the meta-analysis, literature, and national UK data. We compared the cost-effectiveness of four decision-making strategies: testing with NITs and treating patients with fibrosis stage ≥F2, testing with liver biopsy and treating patients with ≥F2, treat none (watchful waiting) and treat all irrespective of fibrosis. Treating all patients without prior fibrosis assessment had an incremental cost-effectiveness ratio (ICER) of £28,137 per additional QALY gained for HBeAg-negative patients. For HBeAg-positive patients, using Fibroscan was the most cost-effective option with an ICER of £23,345. The base case results remained robust in the majority of sensitivity analyses, but were sensitive to changes in the ≥ F2 prevalence and the benefit of treatment in patients with F0-F1. For HBeAg-negative patients, strategies excluding NITs were the most cost-effective: treating all patients regardless of fibrosis level if the high cost-effectiveness threshold of £30,000 is accepted; watchful waiting if not. For HBeAg-positive patients, using Fibroscan to identify and treat those with ≥F2 was the most cost-effective option.

Alterations in coagulation following major liver resection.

The international normalised ratio is frequently raised in patients who have undergone major liver resection, and is assumed to represent a potential bleeding risk. However, these patients have an increased risk of venous thromboembolic events, despite conventional coagulation tests indicating hypocoagulability. This prospective, observational study of patients undergoing major hepatic resection analysed the serial changes in coagulation in the early postoperative period. Thrombin generation parameters and viscoelastic tests of coagulation (thromboelastometry) remained within normal ranges throughout the study period. Levels of the procoagulant factors II, V, VII and X initially fell, but V and X returned to or exceeded normal range by postoperative day five. Levels of factor VIII and Von Willebrand factor were significantly elevated from postoperative day one (p < 0.01). Levels of the anticoagulants, protein C and antithrombin remained significantly depressed on postoperative day five (p = 0.01). Overall, the imbalance between pro- and anticoagulant factors suggested a prothrombotic environment in the early postoperative period.

Outcome after surgical resection for duodenal adenocarcinoma in the UK.

BACKGROUND: Factors influencing long-term outcome after surgical resection for duodenal adenocarcinoma are unclear. METHODS: A prospectively created database was reviewed for patients undergoing surgery for duodenal adenocarcinoma in six UK hepatopancreaticobiliary centres from 2000 to 2013. Factors influencing overall survival and disease-free survival (DFS) were identified by regression analysis. RESULTS: Resection with curative intent was performed in 150 (84·3 per cent) of 178 patients. The postoperative morbidity rate for these patients was 40·0 per cent and the in-hospital mortality rate was 3·3 per cent. Patients who underwent resection had a better median survival than those who had a palliative surgical procedure (84 versus 8 months; P < 0·001). The 1-, 3- and 5-year overall survival rates for patients who underwent resection were 83·9, 66·7 and 51·2 per cent respectively. Median DFS was 53 months, and 1- and 3-year DFS rates were 80·8 and 56·5 per cent respectively. Multivariable analysis revealed that node status (hazard ratio 1·73, 95 per cent c.i. 1·07 to 2·79; P = 0·006) and lymphovascular invasion (hazard ratio 3·49, 1·83 to 6·64; P = 0·003) were associated with overall survival. CONCLUSION: Resection of duodenal adenocarcinoma in specialist centres is associated with good long-term survival. Lymphovascular invasion and nodal metastases are independent prognostic indicators.

Barriers to food intake in acute care hospitals: a report of the Canadian Malnutrition Task Force.

BACKGROUND: Poor food intake is common in acute care patients and can exacerbate or develop into malnutrition, influencing both recovery and outcome. Yet, research on barriers and how they can be alleviated is lacking. The present study aimed to (i) describe the prevalence of food intake barriers in diverse hospitals and (ii) determine whether patient, care or hospital characteristics are associated with the experience of these barriers. METHODS: Patients (n = 890; 87%) completed a validated questionnaire on barriers to food intake, including perceptions of food quality, just before their discharge from a medical or surgical unit in each of 18 hospitals across Canada. Scores were created for barrier domains. Associations between these barriers and selected patient characteristics collected at admission or throughout the hospital stay and site characteristics were determined using bivariate analyses. RESULTS: Common barriers were being interrupted at meals (41.8%), not being given food when a meal was missed (69.2%), not wanting ordered food (58%), loss of appetite (63.9%) and feeling too sick (42.7%) or tired (41.1%) to eat. Younger patients were more likely (P < 0.0001) to report being disturbed at meals (44.6%) than older patients (33.9%) and missing a meal for tests (39.0% versus 31.0%, P < 0.05). Patients who were malnourished, women, those with more comorbidity, and those who ate <50% of the meal reported several barriers across domains. CONCLUSIONS: The present study confirms that barriers to food intake are common in acute care hospitals. This analysis also identifies that specific patient subgroups are more likely to experience food intake barriers. Because self-reported low food intake in hospital was associated with several barriers, it is relevant to consider assessing, intervening and monitoring barriers to food intake during the hospital stay.