Assessment of fetal growth trajectory identifies infants at high risk of perinatal mortality.

OBJECTIVE: To analyze perinatal risks associated with three distinct scenarios of fetal growth trajectory in the latter half of pregnancy compared with a reference group. METHODS: This cohort study included women with a singleton pregnancy that delivered between 32 + 0 and 41 + 6 weeks' gestation and had two or more ultrasound scans, at least 4 weeks apart, from 18 + 0 weeks. We evaluated three different scenarios of fetal growth against a reference group, which comprised appropriate-for-gestational-age fetuses with appropriate forward-growth trajectory. The comparator growth trajectories were categorized as: Group 1, small-for-gestational-age (SGA) fetuses (estimated fetal weight (EFW) or abdominal circumference (AC) persistently < 10th centile) with appropriate forward growth; Group 2, fetuses with decreased growth trajectory (decrease of ≥ 50 centiles) and EFW or AC ≥ 10th centile (i.e. non-SGA) at their final ultrasound scan; and Group 3, fetuses with decreased growth trajectory and EFW or AC < 10th centile (i.e. SGA) at their final scan. The primary outcome was overall perinatal mortality (stillbirth or neonatal death). Secondary outcomes included stillbirth, delivery of a SGA infant, preterm birth, emergency Cesarean section for non-reassuring fetal status and composite severe neonatal morbidity. Associations were analyzed using logistic regression. RESULTS: The final study cohort comprised 5319 pregnancies. Compared to the reference group, the adjusted odds of perinatal mortality were increased significantly in Group 2 (adjusted odds ratio (aOR), 4.00 (95% CI, 1.36-11.22)) and Group 3 (aOR, 7.71 (95% CI, 2.39-24.91)). Only Group 3 had increased odds of stillbirth (aOR, 5.69 (95% CI, 1.55-20.93)). In contrast, infants in Group 1 did not have significantly increased odds of demise. The odds of a SGA infant at birth were increased in all three groups compared with the reference group, but was highest in Group 1 (aOR, 111.86 (95% CI, 62.58-199.95)) and Group 3 (aOR, 40.63 (95% CI, 29.01-56.92)). In both groups, more than 80% of infants were born SGA and nearly half had a birth weight < 3rd centile. Likewise, the odds of preterm birth were increased in all three groups compared with the reference group, being highest in Group 3, with an aOR of 4.27 (95% CI, 3.23-5.64). Lastly, the odds of composite severe neonatal morbidity were increased in Groups 1 and 3, whereas the odds of emergency Cesarean section for non-reassuring fetal status were increased only in Group 3. CONCLUSION: Assessing the fetal growth trajectory in the latter half of pregnancy can help identify infants at increased risk of perinatal mortality and birth weight < 3rd centile for gestation. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Effects of sodium chloride intake on urea-N recycling and renal urea-N kinetics in lactating Holstein cows.

The effects of high (2.5% of DM) versus normal dietary sodium chloride (NaCl) intake on renal urea-N kinetics and urea-N metabolism were investigated in 9 rumen-cannulated and multi-catheterized lactating dairy cows in a crossover design with 21-d periods. It was hypothesized that urinary urea-N excretion would be greater, and blood urea-N concentration lower in response to greater diuresis induced by high NaCl intake. Also, urea-N transport across ruminal and portal drained viscera (PDV) tissues was hypothesized to be affected by dietary sodium intake. A second experiment was conducted using 8 lactating cows in a crossover design with 14-d periods to test high NaCl (2.5% of DM) versus high KCl (3.2% of DM) intake on milk yield and milk urea-N concentrations. Experiment 1 showed that despite greater diuresis there was no effect of high NaCl intake on urinary urea-N excretion or blood urea-N concentration. The high NaCl intake did not affect rumen ammonia concentrations, total rumen VFA concentrations, ruminal venous - arterial concentration differences for ammonia, or ammonia absorption indicating that high NaCl did not adversely affect ruminal fermentation and microbial protein synthesis. High NaCl intake did not affect the total amount of urea-N transport from blood to gut, but ruminal venous - arterial concentration differences for urea-N were lower with high NaCl and ruminal extraction of arterial urea-N was numerically smaller, indicating that the ruminal epithelial urea-N transport was lower with high NaCl. Energy corrected milk yield was greater with high NaCl (3.2 ± 1.5 kg/d); however, milk urea-N concentrations were not affected by treatment. In experiment 2, ECM was greater with NaCl (1.4 ± 0.31 kg/d) compared with KCl (30.2 and 28.8 ± 0.91 kg ECM / d, respectively). Milk urea-N concentration was lower with KCl, suggesting a urea-N lowering effect in milk not evident with high NaCl intake. In conclusion, the present data show that dietary Na intake of 12-13 g/kg DM was followed by greater diuresis but did not impact urea-N excretion or blood urea-N concentration. High NaCl intake did not affect the total amount of urea-N transfer across PDV tissues. Energy corrected milk yield was greater with high NaCl compared with both control and feeding KCl, however, with KCl milk urea-N decreased.

Outcome of treatment with a 10-week COP protocol in cats with intermediate or large cell lymphoma: 27 cases (2014-2023).

OBJECTIVES: The aim of this retrospective clinical study was to evaluate and report response to treatment with a 10-week maintenance-free COP (COP-10) protocol in a cohort of 27 cats with intermediate or large cell lymphoma. Additionally, to identify any potential prognostic factors for predicting the treatment response. MATERIALS AND METHODS: The medical records of cats diagnosed with intermediate or large cell lymphoma in a single institution in the period 2014 to 2023 and treated with COP-10 as first-line treatment were reviewed. RESULTS: Twenty-seven cats were included in the study. The median age was 10 years, 67% of the cats were in stages I to II and the most common anatomical location was alimentary (37%). The overall response rate was 65%, with 38% of cats achieving complete remission and 27% partial remission. For cats achieving complete remission, the median progression-free interval and the median lymphoma-specific survival time were both 1,139 days. For cats in partial remission, the median progression-free interval and the median lymphoma-specific survival time were 53 and 210 days, respectively. Clinical stage was significantly related to treatment response and survival time. CLINICAL SIGNIFICANCE: Treatment with the short protocol COP-10 resulted in remission rates and durable first remissions for cats achieving complete remission comparable to responses seen with longer-duration chemotherapy protocols. The results from this study may impact economic and logistic decisions for owners, as well as the quality of life for patients in the future.

Phenotype analysis of families with TP53 germline variants at the Center for Familial Breast and Ovarian Cancer, Cologne.

PURPOSE: Tumor protein p53 (TP53) pathogenic variant (PV) carriers are identified during genetic testing for hereditary causes of cancer. PVs in TP53 are associated with the Li-Fraumeni syndrome (LFS), and thus, surveillance and preventive measures are important for TP53 PV carriers. However, the penetrance of TP53 PVs can be low if the Chompret criteria are not fulfilled. In this study, we compared the phenotypic characteristics of families that did and did not fulfill the LFS criteria according to Chompret. METHODS: The German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) database was used to identify index patients with a likely pathogenic/pathogenic TP53 variant and their family members. The study investigated the type of variant, pedigree, age of onset, number of primary tumors, and histological type of BC. RESULTS: TP53 PV were present in the index cases of 35 families, 57% (20/35) of which fulfilled the Chompret criteria. The median age of onset at first BC diagnosis was lower in families that fulfilled the Chompret criteria compared to those who did not. Four of all diseased individuals were minors (4%; 4/105) when malignancy was first diagnosed. Sarcomas and brain tumors occurred in 10% (10/105) and in 7% (7/105) of all diseased persons, respectively. BC was the most frequently occurring first tumor (60%; 62/105) and additional malignancy (45%; 20/44) in this cohort. Subsequent malignancies developed in 31% (20/65) of the individuals who fulfilled the Chompret criteria compared with 15% (6/40) of those who did not. CONCLUSION: The tumor spectrum and age of onset found in this study showed that tumors other than BC had low disease penetrance in TP53 PV carriers identified using the GC-HBOC criteria for genetic testing.

Single-Cell Transcriptomic Analysis of Salivary Gland Endothelial Cells.

Vascular endothelial cells have important tissue-specific functions in fibrosis and regeneration. In the salivary gland, endothelial cells are required for proper development, but their roles within adult glands are largely unknown. To identify ligand-receptor interactions between endothelial cells and other cell types that may be important during fibrosis and regeneration, we used a reversible ductal ligation injury. To induce injury, a clip was applied to the primary ducts for 14 d, and to induce a regenerative response, the clip was subsequently removed for 5 d. To identify endothelial cell-produced factors, we used single-cell RNA sequencing of stromal-enriched cells from adult female submandibular and sublingual salivary glands. Transcriptional profiles of homeostatic salivary gland endothelial cells were compared to endothelial cells of other organs. Salivary gland endothelial cells expressed many unique genes and displayed the highest overlap in gene expression with other fenestrated endothelial cells from the colon, small intestine, and kidney. Comparison of the 14-d ligated, mock-ligated, and 5-d deligated stromal-enriched transcripts and lineage tracing revealed that endothelial cells retain their identity following ligation and recovery from injury. CellChat and NATMI were used to predict changes in ligand-receptor interactions from endothelial cells to other cells in response to ligation and deligation. CellChat and NATMI predicted that after ligation, interactions with fibroblasts, epithelial cells, and glial cells were increased, and following deligation, interactions with pericyte, glia, fibroblasts, and immune cells were increased. Some of the highest-ranked interactions predicted in ligated compared to mock endothelial cells were between glial cells via Col4a2-Cd93 and Jag2-Notch1, as well as epithelial cells via Pecam1-Cd38, while in deligated compared to ligated endothelial cells, the top interactions were between fibroblasts via Ntf3-Ntrk2, glial cells via Hspg2-Itgb1, and pericytes via Jam2-F11r. Understanding salivary gland endothelial cell signaling will inform future endothelial cell-based regenerative therapies.

Patient preferences in geriatric wards, a survey of health care professionals' practice, experience and attitudes.

PURPOSE: We aimed to identify whether health care professionals (HCP) examine their patient and next-of-kin preferences, and to study whether medical decisions follow these preferences. METHOD: A cross-sectional web-based survey was conducted with multidisciplinary HCP from 12 geriatric wards in the South-Eastern Norway Regional Health Authority. RESULTS: Of the 289 HCPs responding (response rate 61%), mean age 37.8 years (SD 11.3), 235 (81.3%) women, 12.4 (SD 9.6) years of experience and 67 (23.2%) medical doctors, only half report clarifying patients' preferences. The majority reported that they did not inform, involve and treat in line with such preferences. However, 53% believe that HCP, patients and next-of-kin should make clinical decisions together. DISCUSSION: Our findings indicate a lack of engagement in conversation and inclusion of patient preferences when providing health interventions in geriatric wards. Measures for change of culture are needed.