Effect of physical exercise on cognitive function after chemotherapy in patients with breast cancer: a randomized controlled trial (PAM study).

BACKGROUND: Up to 60% of breast cancer patients treated with chemotherapy is confronted with cognitive problems, which can have a significant impact on daily activities and quality of life (QoL). We investigated whether exercise training improves cognition in chemotherapy-exposed breast cancer patients 2-4 years after diagnosis. METHODS: Chemotherapy-exposed breast cancer patients, with both self-reported cognitive problems and lower than expected performance on neuropsychological tests, were randomized to an exercise or control group. The 6-month exercise intervention consisted of supervised aerobic and strength training (2 h/week), and Nordic/power walking (2 h/week). Our primary outcome was memory functioning (Hopkins Verbal Learning Test-Revised; HVLT-R). Secondary outcomes included online neuropsychological tests (Amsterdam Cognition Scan; ACS), self-reported cognition (MD Anderson Symptom Inventory for multiple myeloma; MDASI-MM), physical fitness (relative maximum oxygen uptake; VO2peak), fatigue (Multidimensional Fatigue Inventory), QoL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; EORTC QLQ C-30), depression (Patient Health Questionnaire-9, Hospital Anxiety and Depression Scale; HADS), and anxiety (HADS). HVLT-R total recall was analyzed with a Fisher exact test for clinically relevant improvement (≥ 5 words). Other outcomes were analyzed using multiple regression analyses adjusted for baseline and stratification factors. RESULTS: We randomized 181 patients to the exercise (n = 91) or control group (n = 90). Two-third of the patients attended ≥ 80% of the exercise sessions, and physical fitness significantly improved compared to control patients (B VO2peak 1.4 ml/min/kg, 95%CI:0.6;2.2). No difference in favor of the intervention group was seen on the primary outcome. Significant beneficial intervention effects were found for self-reported cognitive functioning [MDASI-MM severity (B-0.7, 95% CI - 1.2; - 0.1)], fatigue, QoL, and depression. A hypothesis-driven analysis in highly fatigued patients showed positive exercise effects on tested cognitive functioning [ACS Reaction Time (B-26.8, 95% CI - 52.9; - 0.6) and ACS Wordlist Learning (B4.4, 95% CI 0.5; 8.3)]. CONCLUSIONS: A 6-month exercise intervention improved self-reported cognitive functioning, physical fitness, fatigue, QoL, and depression in chemotherapy-exposed breast cancer patients with cognitive problems. Tested cognitive functioning was not affected. However, subgroup analysis indicated a positive effect of exercise on tested cognitive functioning in highly fatigued patients. Trial Registration Netherlands Trial Registry: Trial NL5924 (NTR6104). Registered 24 October 2016, https://www.trialregister.nl/trial/5924 .

Predicting postoperative complications and their impact on quality of life and functional status in older patients with breast cancer.

BACKGROUND: The percentage of older patients undergoing surgery for early-stage breast cancer has decreased over the past decade. This study aimed to develop a prediction model for postoperative complications to better inform patients about the benefits and risks of surgery, and to investigate the association between complications and functional status and quality of life (QoL). METHODS: Women aged at least 70 years who underwent surgery for Tis-3 N0 breast cancer were included between 2013 and 2018. The primary outcome was any postoperative complication within 30 days after surgery. Secondary outcomes included functional status and QoL during the first year after surgery, as assessed by the Groningen Activity Restriction Scale and the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR23 questionnaires. A prediction model was developed using multivariable logistic regression and validated externally using data from the British Bridging the Age Gap Study. Linear mixed models were used to assess QoL and functional status over time. RESULTS: The development and validation cohorts included 547 and 2727 women respectively. The prediction model consisted of five predictors (age, polypharmacy, BMI, and type of breast and axillary surgery) and performed well in internal (area under curve (AUC) 0.76, 95 per cent c.i. 0.72 to 0.80) and external (AUC 0.70, 0.68 to 0.72) validations. Functional status and QoL were not affected by postoperative complication after adjustment for confounders. CONCLUSION: This validated prediction model can be used to counsel older patients with breast cancer about the postoperative phase. Postoperative complications did not affect functional status nor QoL within the first year after surgery even after adjustment for predefined confounders.

Surgery remains the standard of care for the majority of older patients with breast cancer. The percentage of older patients with breast cancer receiving surgery is decreasing. The reason for this decline is unknown, but it might be due to fear of complications. To better inform patients about the benefits and risks of surgery, the aim of this study was to develop a prediction model for complications after surgery. Another important aspect, especially for older adults with breast cancer, is quality of life, functional capacity, and ability to carry out daily tasks (functional status) after therapy. This study showed that quality of life and functional status did not decline after breast surgery, irrespective of the occurrence of postoperative complications.

De-escalation of axillary surgery in breast cancer patients treated in the neoadjuvant setting: a Dutch population-based study.

PURPOSE: An overall trend is observed towards de-escalation of axillary surgery in patients with breast cancer. The objective of this study was to evaluate this trend in patients treated with neoadjuvant systemic therapy (NST). METHODS: Patients with cT1-4N0-3 breast cancer treated with NST (2006-2016) were selected from the Netherlands Cancer Registry. Patients were classified by clinical node status (cN) and type of axillary surgery. Uni- and multivariable logistic regression analyses were performed to determine the clinicopathological factors associated with performing ALND in cN+ patients. RESULTS: A total of 12,461 patients treated with NST were identified [5830 cN0 patients (46.8%), 6631 cN+ patients (53.2%)]. In cN0 patients, an overall increase in sentinel lymph node biopsy (SLNB) only (not followed by ALND) was seen from 11% in 2006 to 94% in 2016 (p < 0.001). SLNB performed post-NST increased from 33 to 62% (p < 0.001). In cN+ patients, an overall decrease in ALND was seen from 99% in 2006 to 53% in 2016 (p < 0.001). Age (OR 1.01, CI 1.00-1.02), year of diagnosis (OR 0.47, CI 0.44-0.50), HER2-positive disease (OR 0.62, CI 0.52-0.75), clinical tumor stage (T2 vs. T1 OR 1.32, CI 1.06-1.65, T3 vs. T1 OR 2.04, CI 1.58-2.63, T4 vs. T1 OR 6.37, CI 4.26-9.50), and clinical nodal stage (N3 vs. N1 OR 1.65, CI 1.28-2.12) were correlated with performing ALND in cN+ patients. CONCLUSIONS: ALND decreased substantially over the past decade in patients treated with NST. Assessment of long-term prognosis of patients in whom ALND is omitted after NST is urgently needed.

Excision of both pretreatment marked positive nodes and sentinel nodes improves axillary staging after neoadjuvant systemic therapy in breast cancer.

BACKGROUND: Marking the axilla with radioactive iodine seed and sentinel lymph node (SLN) biopsy have been proposed for axillary staging after neoadjuvant systemic therapy in clinically node-positive breast cancer. This study evaluated the identification rate and detection of residual disease with combined excision of pretreatment-positive marked lymph nodes (MLNs) together with SLNs. METHODS: This was a multicentre retrospective analysis of patients with clinically node-positive breast cancer undergoing neoadjuvant systemic therapy and the combination procedure (with or without axillary lymph node dissection). The identification rate and detection of axillary residual disease were calculated for the combination procedure, and for MLNs and SLNs separately. RESULTS: At least one MLN and/or SLN(s) were identified by the combination procedure in 138 of 139 patients (identification rate 99·3 per cent). The identification rate was 92·8 per cent for MLNs alone and 87·8 per cent for SLNs alone. In 88 of 139 patients (63·3 per cent) residual axillary disease was detected by the combination procedure. Residual disease was shown only in the MLN in 20 of 88 patients (23 per cent) and only in the SLN in ten of 88 (11 per cent), whereas both the MLN and SLN contained residual disease in the remainder (58 of 88, 66 per cent). CONCLUSION: Excision of the pretreatment-positive MLN together with SLNs after neoadjuvant systemic therapy in patients with clinically node-positive disease resulted in a higher identification rate and improved detection of residual axillary disease.

ANTECEDENTES: En el cáncer de mama con ganglios positivos clínicamente tras el tratamiento neoadyuvante sistémico, se ha propuesto la utilización de iodo radioactivo (Marking Axilla with Radioactive Iodine, MARI) y de la biopsia de ganglio linfático centinela para la estadificación axilar. En este estudio se evaluó la tasa de identificación y detección de enfermedad residual cuando se combinó la exéresis de los ganglios linfáticos marcados antes del tratamiento (marked lymph nodes, MLN) junto con los ganglios centinela (sentinel lymph nodes, SLN). MÉTODOS: Se realizó un análisis retrospectivo multicéntrico de pacientes con cáncer de mama con ganglios positivos clínicamente que se sometieron a tratamiento neoadyuvante sistémico y en las que se combinaron ambas técnicas (con o sin disección axilar). Se calcularon las tasas de identificación y detección de enfermedad residual axilar para MLN y SLN por separado y en conjunto. RESULTADOS: En 138/139 pacientes se identificaron ≥ 1 MLN y/o SLN combinando ambas técnicas (tasa de identificación del 99,3%). La tasa de identificación fue de 92,8% para MLN y del 87,8% para SLN. Combinando ambas técnicas se detectó enfermedad axilar residual en 88/139 (63,3%) pacientes. Se detectó enfermedad residual en 20/88 (22,7%) pacientes utilizando únicamente MLN, en 10/88 (11,4%) pacientes utilizando únicamente SLN y en 58/88 (65,9%) combinando ambas técnicas. CONCLUSIÓN: La exéresis conjunta de los ganglios marcados con iodo radioactivo antes del tratamiento neoadyuvante sistémico y de los ganglios centinela después del tratamiento en pacientes con cN+ logró una tasa de identificación más alta y una mejor detección de la enfermedad axilar residual.

Prognosis of residual axillary disease after neoadjuvant chemotherapy in clinically node-positive breast cancer patients: isolated tumor cells and micrometastases carry a better prognosis than macrometastases.

PURPOSE: The aim of this study was to compare disease-free survival (DFS) and overall survival (OS) between clinically node-positive breast cancer patients, treated with neoadjuvant chemotherapy (NAC), with axillary pathologic complete response (ypN0), residual axillary isolated tumor cells or micrometastases (ypNitc/mi), and residual axillary macrometastases (ypN1-3). METHODS: All patients diagnosed with clinically node-positive primary invasive breast cancer treated with NAC and subsequent axillary lymph node dissection between 2005 and 2008 were retrospectively analyzed. Data were obtained from the Netherlands Cancer Registry. Patients were stratified by final pathological axillary status: ypN0, ypNitc/mi, or ypN1-3. The main outcome measures DFS and OS were analyzed using Kaplan-Meier survival analysis. Uni- and multivariable cox regression analyses were used to determine independent predictors for DFS and OS. RESULTS: A total of 1347 patients were included. Pathologic nodal status was ypN0 in 22.2%, ypNitc/mi in 3.8%, and ypN1-3 in 74.0% of patients. Overall, 5-year DFS was 57.8% and mean OS was 7.4 years. DFS and OS were comparable between ypN0 and ypNitc/mi (HR 1.38 (0.40-4.79, p = 0.613) and HR 0.92 (0.27-3.09, p = 0.889), respectively), but significantly different between ypN0 and ypN1-3 (HR 1.78 (1.06-3.00, p = 0.031) and HR 1.70 (1.07-2.71, p = 0.026), respectively). CONCLUSIONS: Clinically node-positive patients, treated with NAC, with axillary nodal status ypN0 or ypNitc/mi carry similar prognosis regarding DFS and OS. Axillary nodal status ypN1-3 is associated with a less favorable prognosis. Future studies should consider ypN0 and ypNitc/mi as one entity.

Temperature during the last week of incubation. I. Effects on hatching pattern and broiler chicken embryonic organ development.

We investigated the effects of an eggshell temperature (EST) of 35.6, 36.7, 37.8, and 38.9°C applied from d of incubation (E) 15, E17, and E19 on hatching pattern and embryonic organ development. A total of 2,850 first-grade eggs of a 43-week-old Ross 308 broiler breeder flock were incubated at an EST of 37.8°C until E15. From E15, E17, or E19 onward, eggs were incubated at an EST of 35.6, 36.7, 37.8, or 38.9°C. Moment of internal pipping (IP), external pipping (EP), and hatch was determined, and organ development was measured at E15, E17, E19, IP, EP, and hatch. A lower EST extended incubation duration compared to a higher EST. The lower incubation duration was mainly caused by the extended time until IP, whereas time between IP and hatch hardly varied between treatments. Relative heart weight was affected by EST already from 2 d after the start of EST treatment on E15, and effects became more pronounced at longer exposure time to various EST treatments. At hatch, the largest difference in relative heart weight was found between an EST of 35.6 and 38.9°C started at E15 (Δ=64.4%). From E17 onward, EST affected yolk-free body mass (YFBM) and relative stomach weight, where a lower EST resulted in a lower YFBM and relative stomach weight before IP and a higher YFBM and relative stomach weight after IP. From E19 onward, a lower EST resulted in a higher relative liver and spleen weight regardless of start time of treatment. Yolk weight and relative intestine weight were not affected by EST before and at E19, but a higher EST resulted in a higher yolk weight and lower relative intestine weight from IP onward. Based on the higher YFBM and higher relative organ growth found at hatch, we concluded that an EST lower than 37.8°C from E15 onward appears to be beneficial for optimal embryo development.

Impact of preoperative evaluation of tumour grade by core needle biopsy on clinical risk assessment and patient selection for adjuvant systemic treatment in breast cancer.

BACKGROUND: Histological characteristics are important when making a decision on adjuvant systemic treatment in breast cancer. Preoperative assessments of core needle biopsy (CNB) specimens are becoming increasingly relevant as novel minimally invasive ablative techniques are introduced, because a surgical specimen is no longer obtained with these methods. The clinical impact of potential underestimation of tumour grade on preoperative CNB on clinical decision-making was evaluated. METHODS: Histological tumour grade was reassessed on CNB and resection specimens from consecutive invasive ductal carcinomas diagnosed between 2010 and 2013. For each patient, the indication for systemic therapy was assessed, based on either CNB or surgical excision, in combination with clinical characteristics and imaging findings. The clinical impact of discordance between tumour grade on CNB versus the resection specimen was assessed. RESULTS: The analysis included 213 invasive ductal carcinomas in 199 patients. Discordance in tumour grade between CNB and the resection specimen was observed in 64 (30.0 per cent) of 213 tumours (κ = 0.53, 95 per cent c.i. 0.43 to 0.63). A decision on adjuvant treatment based on CNB would have resulted in overtreatment in seven (3.5 per cent) and undertreatment in three (1.5 per cent) of 199 patients. In the undertreated patients, incorrect omission of adjuvant systemic treatment would have increased the predicted 10-year mortality rate by 2.6-5.2 per cent and 10-year recurrence rate by 8.2-15.3 per cent based on the online risk assessment tool Adjuvant! CONCLUSION: The substantial discordance in tumour grading between CNB and resection specimens from breast cancer affects the indication for adjuvant therapy in only a small minority of patients with invasive ductal carcinoma. Assessment of tumour grade by CNB is feasible and accurate for the planning of postoperative treatment.

Interventional ductoscopy in patients with pathological nipple discharge.

BACKGROUND: Surgery is the intervention of choice for definitive diagnosis and treatment in women with pathological nipple discharge (PND). Ductoscopy has been reported to improve diagnosis, but as an interventional procedure it may also reduce the need for surgery. This study evaluated interventional ductoscopy in patients with PND. METHODS: A prospective study on ductoscopy was conducted in consecutive patients with PND, but without a suspected malignancy on routine diagnostic evaluation. Intraductal lesions were removed by ductoscopic extraction. Surgery was undertaken if there were suspicious ductoscopic findings or at the patient's request. Therapeutic efficacy was determined by cannulation success, detection and removal rates, symptom resolution and avoided surgery. RESULTS: Ductoscope introduction was successful in 71 (87 per cent) of 82 patients, with abnormalities visualized in 53 (65 per cent); these were mostly polypoid lesions (29 patients). The lesion was removed in 27 of 34 attempted ductoscopic extractions. Twenty-six (32 per cent) of the 82 patients underwent surgery, whereas surgery was avoided in 56 (68 per cent). After a median follow-up of 17 (range 3-45) months, 40 patients (49 per cent) no longer experienced symptoms of PND, 13 of 34 patients experienced an insufficient therapeutic effect after attempted ductoscopic extraction, and the outcome was unknown in two (2 per cent). Malignancy was diagnosed in four patients (5 per cent); two had been missed at ductoscopy and two at initial surgery after ductoscopy. CONCLUSION: Interventional ductoscopy is technically feasible and may help to avoid surgery in the majority of patients. As endoscopic removal of intraductal lesions is not always possible and malignancy can be the underlying cause of PND, ductoscopic instruments should be further optimized to allow definitive histological diagnosis.

Effect of eggshell temperature throughout incubation on broiler hatchling leg bone development.

Leg problems in broiler chickens may partly be prevented by providing optimal circumstances for skeletal development during incubation. One of the factors demonstrated to affect bone development is eggshell temperature (EST), which provides a reliable reflection of embryo temperature. The present experiment aimed to investigate the effect of EST on development and asymmetry of the femur, tibia, and metatarsus in broiler chicken hatchlings. Eggs were incubated from d 0 until hatch at 1 of 4 EST: low (36.9°C), normal (37.8°C), high (38.6°C), and very high (39.4°C). At hatch, chick quality was determined in terms of chick length, yolk-free body mass, navel score, and organ weights. Tibia, femur, and metatarsus were weighed, their length and width (mediolateral diameter) and depth (craniocaudal diameter) at the middle of the shaft were measured, and their ash content was determined. Relative asymmetry of the leg bones was determined from their relative dimensions. Hatchability, chick quality, and organ development were lower for very high EST compared with all other treatments. Very high EST resulted in lowest tibia and metatarsus lengths (-3.1 to -8.4%) compared with all other treatments, and lower metatarsus weight (-9.1%) and femur length (-4.9%) compared with high EST. Relative asymmetry and ash content did not differ among treatments and no relation between EST and bone parameters was found. To conclude, very high EST resulted in lower bone development, hatchability, and chick quality. Few differences in bone development and chick quality were found between low, normal, and high EST.

Effects of moment of hatch and feed access on chicken development.

The current study evaluated effects of hatch moment and immediate feed and water access within a 24-h hatch window on chicken growth and development. Five hundred four male chickens obtained from a 49-wk-old Ross 308 breeder flock were assigned to 72 cages based on hatching moment (early, midterm, or late; selected during periods of 475 to 481, 483 to 487, and 489 to 493 h after onset of incubation). At the end of each hatching period, chickens were moved to the grow-out facility and one-half of the chickens received feed and water ad libitum immediately. Remaining chickens received feed and water from 504 h after onset of incubation (d 0). Body weight gain and feed intake for each cage were recorded at d 0, 1, 4, 7, 11, and 18. Chickens were sampled at d 4 and 18 for organ and carcass development. Early hatchers had lower BW at placement compared with midterm and late hatchers but compensated for this afterward, resulting in a higher BW at d 4 (112.8, 107.1, and 103.3 g, respectively). From d 0 to 18, early hatchers tended to have higher BW gain than both other groups. Relative breast meat yield at d 18, expressed as percentage of carcass weight, was higher for early (30.4%) than midterm (28.5%) and late hatchers (27.8%). Up to d 7, direct feed access resulted in higher BW gain (6.1%) and feed intake (4.2%) compared with delayed feed access. No effect of moment of feed access on feed efficiency or organ weights was found. Direct feed access resulted in a higher weight:length ratio of the jejunum (12.5%) and ileum (7.5%) at d 4 compared with delayed feed access. These results suggest that early hatchers have a different developmental and growth pattern than midterm or late hatchers within a 24-h hatch window. A mild delay in feed access after hatch affects growth and development during the first week after hatch.

Temperature and CO2 during the hatching phase. I. Effects on chick quality and organ development.

The objective of this study was to investigate the effect of eggshell temperature (EST) and carbon dioxide (CO2) concentration during only the hatching phase on embryonic development and chick quality. Three batches of eggs were incubated at an EST of 37.8°C until d of incubation (E) 19. From E19, embryos were incubated at low (36.7°C), normal (37.8°C), or high (38.9°C) EST and at low (0.2%) or high (1%) CO2 concentration. Organ growth and embryo and chick quality were measured at E19, internal pipping (IP), hatch, and 12 h after hatch. A few interactions between EST and CO2 were found at IP, hatch, and 12 h after hatch, but all of these interactions were temporary and in most cases weak. High EST resulted in a lower relative heart weight compared with low ( = 0.05) and normal EST ( = 0.06) at IP, compared with low ( = 0.11) and normal EST ( = 0.08) at hatch, and compared with low ( = 0.11) and normal EST ( = 0.08) at 12 h after hatch. At hatch, high EST resulted in a lower YFBM compared with low EST ( = 0.65). At 12 h after hatch, high EST resulted in a lower relative liver weight compared with low EST ( = 0.12). At low EST, greater relative intestinal weight was found compared with normal ( = 0.41) and high EST ( = 0.37). The effect of CO2 solely was found at 12 h after hatch at which a higher relative heart weight ( = 0.05) and a higher relative lung weight ( = 0.0542) was found at high CO2 compared with low CO2. High EST during only the hatching phase negatively affected chick development, mainly expressed by the lower relative heart weight at IP, hatch, and 12 h after hatch and lower YFBM at hatch. The resolving effect of CO2 demonstrates that CO2 only seem to have a temporary effect during the hatching phase.

Temperature and CO2 during the hatching phase. II. Effects on chicken embryo physiology.

The objective of this study was to investigate the effect of eggshell temperature (EST) and carbon dioxide concentration during only the hatching phase on physiological characteristics of embryos and chicks. Three groups of eggs were incubated at an EST of 37.8°C until d 19 of incubation (E19). From E19, embryos were incubated at a low (36.7°C), normal (37.8°C), or high (38.9°C) EST and at a low (0.2%) or high (1.0%) CO2 concentration. For E19, internal pipping (IP), hatch, and 12 h after hatch, blood parameters were analyzed and hepatic glycogen was determined. At IP, hatch, and 12 h after hatch, interactions were found between EST and CO2, but all these interactions were temporary and in most cases weak. High EST resulted in a lower hepatic glycogen concentration compared with low ( = 21.1) and normal EST ( = 14.43) at IP, and a lower hepatic glycogen concentration compared with low EST ( = 6.24) at hatch. At hatch, high EST resulted in lower hematocrit value ( = 2.4) and higher potassium ( = 0.5) compared with low EST. At 12 h after hatch, high EST resulted in a higher lactate concentration compared with low ( = 0.77) and normal EST ( = 0.65). And high EST resulted in higher potassium compared with low ( = 0.4) and normal EST ( = 0.3). An effect of CO2 solely was only found at IP, at which high CO2 resulted in a lower pH ( = 0.03) and a lower hepatic glycogen concentration ( = 7.27) compared with low CO2. High EST during only the hatching phase affected embryo and chick physiology, indicated by the lower hepatic glycogen levels at IP and hatch. High CO2 affected pH and hepatic glycogen at IP. Effects of CO2 were only found at low EST, which emphasizes the large effect of EST during the hatching phase.

Effect of relative humidity during incubation at a set eggshell temperature and brooding temperature posthatch on embryonic mortality and chick quality.

Previous studies have shown that RH during incubation of chicken eggs influences water loss from the egg and embryonic mortality. In those studies, eggshell temperatures (EST) were not monitored or controlled. Because RH influences the egg's heat loss through evaporation, EST might have been different between RH treatments, influencing embryonic mortality and development. To eliminate the effect of EST, in the current study eggs were incubated at an EST of 37.8°C from embryonic d (E) 0 until E18 and at a high (55 to 60%) or low (30 to 35%) RH from E2 until hatch. Embryonic mortality, hatch curve, and several chick quality characteristics (length, weight, navel quality, organ weights, and DM of the yolk free body mass and yolk) were determined on E18 and at hatch. Low RH increased egg weight loss between E0 and E18 (+3.0%) and third week embryonic mortality (+3.0% of fertile eggs) and decreased hatch of fertile eggs (-2.9% of fertile eggs) compared with high RH. Hatch duration and chick quality characteristics did not differ between RH treatments. To assess the effect of RH during incubation on posthatch performance under suboptimal conditions, hatchlings were brooded at a normal (35.0°C at d 0, decreasing to 27.0°C at d 4) or cold (27.8°C at d 0, decreasing to 25.6°C at d 4) temperature until 4 d posthatch. Incubation RH and brooding temperature significantly interacted with posthatch growth but not development. Both low and high RH × cold brooding temperature resulted in lower (-6.9 and -6.0 g, respectively) BW than high RH × normal brooding temperature at 4 d of age. The cold brooding temperature resulted in lower daily feed intake (-1.3 g/chick) than the normal brooding temperature. In conclusion, incubating eggs at a low RH compared with a high RH and maintaining the EST at 37.8°C decreased hatch of fertile eggs, but had little effect on chick quality or posthatch performance.

Effects of late incubation temperature and moment of first post-hatch feed access on neonatal broiler development, temperature preference, and stress response.

Early life experiences are known to be of great importance for later life. For instance, exposure to stress during early life can increase fearfulness at later age. In broilers, delayed feeding after hatch may cause metabolic stress. Besides, delayed feeding after hatch may affect neonatal broiler development and thermogenesis and consequently preferred ambient temperature. Moreover, these effects of feeding strategy may be dependent on late incubation temperature. To study this, eggs (n = 1,338) from a 54-wk-old Ross broiler breeder flock were incubated at 37.8°C (control) or 36.7°C (lower) eggshell temperature (EST) during late incubation (≥ embryonic d 17). At hatch, two feeding strategies were applied (direct access (early feeding) or 51 to 54 h delayed access (delayed feeding)). Broilers (n = 960) were equally divided over 32 pens and grown for 3 wk. Stress was assessed by determination of corticosterone in blood at 0 h, 48 h, 96 h and d 21 after hatch. Fearfulness was assessed by tonic immobility at d 13. Temperature preference was assessed at d 2 and d 12. Broiler development was determined at 0 h, 48 h, and 96 h after hatch. There was no EST × feeding strategy interaction for any parameter (P ≥ 0.07). Early feeding resulted in a 2.5× lower plasma corticosterone concentration at 48 h (P < 0.01) and a 2.2°C and 2.0°C lower preference temperature for d 2 and d 12 respectively (P = 0.01) compared to delayed feeding. Tonic immobility was not affected. In conclusion, early feeding reduces exposure to stress in the short term and stimulates thermoregulatory ability of broilers in the longer term.

An analysis of complication rates and the influence on patient satisfaction and cosmetic outcomes following oncoplastic breast surgery.

INTRODUCTION: This study aimed to evaluate complication rates, patient satisfaction, and cosmetic outcomes after oncoplastic breast-conserving surgery (OPS). Furthermore, outcome differences between volume displacement and volume replacement techniques and the effect of postoperative complications on outcomes were evaluated. METHODS: This was a prospective single-center study addressing patients who underwent OPS from 2017 to 2020. The BREAST-Q was used to measure patient satisfaction, and cosmetic outcomes were assessed by patient self-evaluation and panel evaluation based on medical photographs. RESULTS: A total of 75 patients were included. The overall complication rate was 18.7%, of which 4% required invasive interventions. Median BREAST-Q scores ranged from 56 to 100 and cosmetic outcomes were scored good to excellent in 60-86%. No differences in complications were observed between volume replacement and volume displacement techniques. Following volume displacement techniques, patients-reported higher BREAST-Q scores for the domain "physical well-being of the chest" and lower cosmetic outcomes scores for "mammary symmetry." Patients with complications scored significantly lower on several domains of the BREAST-Q and in various cosmetic outcome categories. CONCLUSION: In this cohort, an overall complication rate of 18.7% was observed. Patients were generally satisfied, and most cosmetic outcomes were good to excellent. Volume displacement or replacement techniques were performed for different indications and generally showed comparable results. Expected differences in physical discomfort and symmetry between both techniques were observed. In addition, the occurrence of complications resulted in lower patient satisfaction and cosmetic outcomes. These findings emphasize the importance of thorough preoperative counselling.

Broiler resilience to colibacillosis is affected by incubation temperature and post-hatch feeding strategy.

Colibacillosis is a poultry disease that negatively affects welfare and causes economic losses. Treatment with antibiotics raises concerns on antimicrobial resistance. Consequently, alternative approaches to enhance poultry resilience are needed. Access to feed and water directly after hatch (early feeding) may enhance resilience at later ages. Additionally, a high eggshell temperature (EST) during mid incubation may improve chick quality at hatch, supporting potential positive effects of early feeding. Effects of EST [37.8°C (control) or 38.9°C (higher)] during mid-incubation (embryo days 7-14) and feeding strategy (early feeding or 48 h delayed feeding) were tested in a 2 × 2 factorial arrangement. At hatch, Ì´ 1,800 broilers were divided over 36 pens and grown for 6 wk. At d 8 post hatch, avian pathogenic E. coli (APEC) was inoculated intratracheally as model to investigate broiler resilience against respiratory diseases. Incidence and severity of colibacillosis, local infection, and systemic infection were assessed at 6 moments between 3 h and 7 d postinoculation. Broilers were weighed daily during 13 d postinoculation and weekly thereafter. At higher EST, early feeding resulted in higher incidence of systemic infection compared to delayed feeding whereas at control EST, systemic infection was not different between feeding strategies. Regardless of EST, early compared to delayed feeding resulted in lower incidence of local infection, fewer BW deviations, and higher growth until d 35. In conclusion, early feeding could be considered as a strategy to enhance broiler resilience, but only when EST is not too high.

Effects of eggshell temperature pattern during incubation on primary immune organ development and broiler immune response in later life.

Eggshell temperature (EST) during incubation greatly affects embryo development, chick quality at hatch, and subsequently various broiler physiological systems. Until now, a constant EST of 37.8°C seems optimal. Data on effects of EST patterns on immune organ development and subsequent broiler immune response are, however, scarce. A higher EST of 38.9°C in week 2 and/or a lower EST of 36.7°C in week 3 of incubation potentially positively affect embryo immune organ development and broiler immune response post hatch. Broiler eggs (n = 468) were incubated at 4 different EST patterns (n = 117 eggs/treatment) from week 2 of incubation onward. Week 1 (embryonic age (E)0 < E7) EST was 37.8°C for all eggs. Week 2 (E7 < E14) EST was either 37.8°C (Control) or 38.9°C (Higher), and week 3 (E14 - /hatch) EST was either Control or 36.7°C (Lower). At hatch, histology of bursal follicles and jejunum villi and crypts were determined as well as heterophil to lymphocyte ratio (H:L) (n = 49). Posthatch, both sexes were grown in 8 pens/treatment for 6 wk (n = 320). Natural antibodies (NAb) were determined at day 14, 22, and slaughter (day 41 or 42) as an indicator of immunocompetence and response to a Newcastle disease (NCD) vaccination was determined by antibody levels at day 22 and slaughter (n = 128). Results showed no interaction EST week 2 × EST week 3, except for jejunum histology. Higher EST in week 2 resulted in lower cell density within bursal follicles (P = 0.02) and a tendency for lower H:L (P = 0.07) at hatch, and higher NCD titers at slaughter (P = 0.02) than Control EST. Lower EST in week 3 resulted at hatch in higher cell density within bursal follicles, higher H:L (both P < 0.05), and a tendency for a higher posthatch mortality rate than control EST (P = 0.10). In conclusion, higher EST in week 2 during incubation may benefit embryonic immune organ development and posthatch broiler immunocompetence, while lower EST in week 3 showed opposite indications.

Effects of incubation temperature pattern on broiler performance.

During incubation, development of embryos is affected by eggshell temperature (EST). A constant EST of 37.8°C has been considered so far to result in most optimal embryo development. However, it can be hypothesized that a higher EST in week 2 in combination with a lower EST in week 3 stimulates embryo development and subsequent grow-out performance. In this study, 468 eggs of a 44-week-old Ross 308 breeder flock were incubated at different incubation temperature patterns in a 2 × 2 factorial arrangement. In week 2, EST was either 37.8°C or 38.9°C, and in week 3, EST was either 37.8°C or 36.7°C. At hatch, chick quality was determined. Thereafter, 320 broilers were grown in 32 pens (8 replicates/treatment) for 6 wk. Weekly BW and ADFI were determined, and at day 40, slaughter yield from 128 broilers (4 per pen) was determined. Results showed that EST in week 2 did not interact with EST in week 3 for any variable. An EST of 38.9°C in week 2 resulted in a 1 mm longer chick length (P < 0.001) and 0.4 mmol/L lower blood glucose level (P = 0.04) at hatch than an EST of 37.8°C. Grow-out performance was not affected by EST in week 2 of incubation. An EST of 36.7°C in week 3 resulted in a 1 mm shorter chick length (P = 0.02), 1.0 mmol/L higher blood glucose level (P < 0.001), and higher relative heart (P = 0.01) and stomach weights (P = 0.03) at hatch than an EST of 37.8°C. Additionally, an EST of 36.7°C in week 3 resulted in lower BW, ADG, and ADFI on slaughter age (all P < 0.03) than an EST of 37.8°C. In conclusion, no interaction between EST in week 2 and 3 of incubation was found for any variable. A higher EST in week 2 had minor effects at hatching and during rearing, whereas a lower EST in week 3 seemed to result in better organ development, but resulted in lower grow-out performance.

Patterns of axillary staging and management in clinically node positive breast cancer patients treated with neoadjuvant systemic therapy: Results of a survey amongst breast cancer specialists.

INTRODUCTION: Various options for axillary staging after neoadjuvant systemic therapy (NST) are available for breast cancer patients with a clinically positive axillary node (cN+). This survey assessed current practices amongst breast cancer specialists. MATERIALS AND METHODS: A survey was performed amongst members of the European Society of Surgical Oncology and two UK-based Associations: the Association of Breast Surgery and the British Association of Surgical Oncology. The survey included 3 parts: 1. general information, 2. diagnostic work-up and 3. axillary staging after NST. RESULTS: A total of 310 responses were collected: parts 1, 2 and 3 were fully completed by 282 (91%), 270 (87.1%) and 225 (72.6%) respondents respectively. After NST, 153/267 (57.3%) respondents currently perform ALND routinely and 114 (42.7%) respondents perform less invasive restaging of the axilla with possible omission of ALND. In the latter group, 85% does and 15% does not use nodal response seen on imaging to guide the axillary restaging procedure. Regarding respondents that do use imaging: 95% would perform a less invasive staging procedure in case of complete nodal response on imaging (63% sentinel lymph node biopsy (SLNB), excision of a previously marked positive node with SLNB (21%) and without SLNB (11%)). In case of no nodal response on imaging 77% would perform ALND. CONCLUSION: Current axillary staging and management practices in cN + patients after NST vary widely. To determine optimal axillary staging and management in terms of quality of life and oncologic safety, breast specialists are encouraged to include patients in clinical trials/prospective registries.

Effect of warming profile at the onset of incubation on early embryonic mortality in long stored broiler eggs.

In 6 experiments, it was investigated whether the pattern of warming from storage temperature to incubation temperature affects early embryonic mortality in broiler eggs. The warming profile (WP) from 21°C to the final incubation temperature of 37.8°C was divided into 2 equal parts (above and below 29.4°C) and the duration of warming in both parts was varied (3 to 17 h). In all experiments, eggs were stored for 13 to 16 d at a storage temperature of 18±2°C. In experiment 1, embryo morphology was evaluated at several time points during a linear warming curve of 24 h from 21°C to an eggshell temperature (EST) of 37.8°C. Results from experiment 1 showed that during the 24 h of warming, embryos did not advance in morphological stage (P = 0.74).Results of experiment 2 and 3 showed that the duration of the WP below 29.4°C (3 to 17 h) had no effect on early embryonic mortality (P ≥ 0.77). Experiment 4 and 6 showed that in eggs from prime breeders, a slow WP (>12 h) above 29.4°C resulted in lower embryonic mortality during the first 2 d of incubation (on average 5.0%) compared to a fast WP of 3 to 6 h (on average 11.3%). In experiment 6, an interaction was found between WP and breeder flock age for embryonic mortality till day 7 of incubation (P = 0.002). Warming profile did not affect embryonic mortality during the first 7 d of incubation in eggs from the young breeder flock. However, in eggs from the prime breeder flock, a WP of 12 h in the first part of warming, followed by 17 h in the second part of warming (WP12-17) had 6.2% lower embryonic mortality in the first 7 d of incubation compared to WP12-3. It can be concluded that a slower WP above 29.4°C reduces early embryonic mortality in long stored eggs, especially those of prime breeder flocks. At this moment, it remains unclear which mechanisms are involved in this phenomenon.