Beta-blocker use and breast cancer outcomes: a meta-analysis.

PURPOSE: Beta blockers (BBs) are commonly used cardiovascular medications, and their association with breast cancer outcomes has been examined in several previous observational studies and meta-analyses. In this study, an updated meta-analysis was undertaken to ascertain the association between BBs and both breast cancer death (BCD) and breast cancer recurrence (BCR). METHODS: Articles were sourced from various databases up until the 14th of August 2023. Effect estimates were pooled using the random effects model, and the Higgins I2 statistic was computed to ascertain heterogeneity. Subgroup analyses were conducted by the potential for immortal time bias (ITB), the exposure period (prediagnosis vs postdiagnosis), and type of BB (selective vs non-selective). Publication bias was assessed using funnel plots and Egger's regression tests. RESULTS: Twenty-four studies were included. Pooled results showed that there was no statistically significant association between BB use and both BCD (19 studies, hazard ratio = 0.90, 95% CI 0.78-1.04) and BCR (16 studies, HR = 0.87, 95% CI 0.71-1.08). After removing studies with ITB, the associations were attenuated towards the null. There was no effect modification for either outcome when stratifying by the exposure period or type of BB. There was clear evidence of publication bias for both outcomes. CONCLUSION: In this meta-analysis, we found no evidence of an association between BB use and both BCD and BCR. Removing studies with ITB attenuated the associations towards the null, but there was no effect modification by the exposure period or type of BB.

Disrupted one-carbon metabolism in heifers negatively affects their health and physiology.

The objective of this study was to determine the dose-dependent response of one-carbon metabolite (OCM: methionine, choline, folate, and vitamin B12) supplementation on heifer dry matter intake on fixed gain, organ mass, hematology, cytokine concentration, pancreatic and jejunal enzyme activity, and muscle hydrogen peroxide production. Angus heifers (n = 30; body weight [BW] = 392.6 ±â€…12.6 kg) were individually fed and assigned to one of five treatments: 0XNEG: total mixed ration (TMR) and saline injections at days 0 and 7 of the estrous cycle, 0XPOS: TMR, rumen-protected methionine (MET) fed at 0.08% of the diet dry matter, rumen-protected choline (CHOL) fed at 60 g/d, and saline injections at days 0 and 7, 0.5X: TMR, MET, CHOL, 5-mg B12, and 80-mg folate injections at days 0 and 7, 1X: TMR, MET CHOL, 10-mg vitamin B12, and 160-mg folate at days 0 and 7, and 2X: TMR, MET, CHOL, 20-mg vitamin B12, and 320-mg folate at days 0 and 7. All heifers were estrus synchronized but not bred, and blood samples were collected on days 0, 7, and at slaughter (day 14) during which tissues were collected. By design, heifer ADG did not differ (P = 0.96). Spleen weight and uterine weight were affected cubically (P = 0.03) decreasing from 0XPOS to 0.5X. Ovarian weight decreased linearly (P < 0.01) with increasing folate and B12 injection. Hemoglobin and hematocrit percentage were decreased (P < 0.01) in the 0.5X treatment compared with all other treatments. Plasma glucose, histotroph protein, and pancreatic α-amylase were decreased (P ≤ 0.04) in the 0.5X treatment. Heifers on the 2X treatment had greater pancreatic α-amylase compared with 0XNEG and 0.5X treatment. Interleukin-6 in plasma tended (P = 0.08) to be greater in the 0XPOS heifers compared with all other treatments. Lastly, 0XPOS-treated heifers had reduced (P ≤ 0.07) hydrogen peroxide production in muscle compared with 0XNEG heifers. These data imply that while certain doses of OCM do not improve whole animal physiology, OCM supplementation doses that disrupt one-carbon metabolism, such as that of the 0.5X treatment, can induce a negative systemic response that results in negative effects in both the dam and the conceptus during early gestation. Therefore, it is necessary to simultaneously establish an optimal OCM dose that increases circulating concentrations for use by the dam and the conceptus, while avoiding potential negative side effects of a disruptive OCM, to evaluate the long-term impacts of OCM supplementation of offspring programming.

The feeding of one-carbon metabolites (including methionine and B vitamins) has been shown to improve fetal growth and milk production in species such as mice, sheep, and dairy cattle. Extending this to beef cattle around the time of breeding is a growing area of research. Our group previously determined that one-carbon metabolite supplementation to beef heifers altered the abundance of circulating methionine-folate cycle intermediates in a dose-dependent manner. Therefore, we aimed to determine a whole-body response to one-carbon metabolite supplementation in heifers by measuring the effects on specific physiological systems as well as a total systemic response. We determined that treatments that negatively altered the methionine-folate cycle yielded a fundamental negative whole-body response to supplementation.

Probing entanglement in a 2D hard-core Bose-Hubbard lattice.

Entanglement and its propagation are central to understanding many physical properties of quantum systems1-3. Notably, within closed quantum many-body systems, entanglement is believed to yield emergent thermodynamic behaviour4-7. However, a universal understanding remains challenging owing to the non-integrability and computational intractability of most large-scale quantum systems. Quantum hardware platforms provide a means to study the formation and scaling of entanglement in interacting many-body systems8-14. Here we use a controllable 4 × 4 array of superconducting qubits to emulate a 2D hard-core Bose-Hubbard (HCBH) lattice. We generate superposition states by simultaneously driving all lattice sites and extract correlation lengths and entanglement entropy across its many-body energy spectrum. We observe volume-law entanglement scaling for states at the centre of the spectrum and a crossover to the onset of area-law scaling near its edges.

A compendium of genetic regulatory effects across pig tissues.

The Farm Animal Genotype-Tissue Expression (FarmGTEx) project has been established to develop a public resource of genetic regulatory variants in livestock, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biological discovery and exploitation in animal breeding and human biomedicine. Here we show results from the pilot phase of PigGTEx by processing 5,457 RNA-sequencing and 1,602 whole-genome sequencing samples passing quality control from pigs. We build a pig genotype imputation panel and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We evaluate tissue specificity of regulatory effects and elucidate molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying 207 pig complex phenotypes and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, supporting the importance of pigs as a human biomedical model.

Operative vs Nonoperative Management of Unstable Medial Malleolus Fractures: A Randomized Clinical Trial.

Importance: Unstable ankle fractures are routinely managed operatively. However, because of soft tissue and implant-related complications, recent literature has reported on the nonoperative management of well-reduced medial malleolus fractures after fibular stabilization, but with limited evidence supporting the routine application. Objective: To assess the superiority of internal fixation of well-reduced (displacement ≤2 mm) medial malleolus fractures compared with nonfixation after fibular stabilization. Design, Setting, and Participants: This superiority, pragmatic, parallel, prospective randomized clinical trial was conducted from October 1, 2017, to August 31, 2021. A total of 154 adult participants (≥16 years) with a closed, unstable bimalleolar or trimalleolar ankle fracture requiring surgery at an academic major trauma center in the UK were assessed. Exclusion criteria included injuries with no medial-sided fracture, open fractures, neurovascular injury, and the inability to comply with follow-up. Data analysis was performed in July 2022 and confirmed in September 2023. Interventions: Once the lateral (and where appropriate, posterior) malleolus had been fixed and satisfactory intraoperative reduction of the medial malleolus fracture was confirmed by the operating surgeon, participants were randomly allocated to fixation (n = 78) or nonfixation (n = 76) of the medial malleolus. Main Outcome and Measure: Olerud-Molander Ankle Score (OMAS) 1 year after randomization (range, 0-100 points, with 0 indicating worst possible outcome and 100 indicating best possible outcome). Results: Among 154 randomized participants (mean [SD] age, 56.5 [16.7] years; 119 [77%] female), 144 (94%) completed the trial. At 1 year, the median OMAS was 80.0 (IQR, 60.0-90.0) in the fixation group compared with 72.5 (IQR, 55.0-90.0) in the nonfixation group (P = .17). Complication rates were comparable. Significantly more patients in the nonfixation group developed a radiographic nonunion (20% vs 0%; P < .001), with 8 of 13 clinically asymptomatic; 1 patient required surgical reintervention for this. Fracture type and reduction quality appeared to influence fracture union and patient outcome. Conclusions and Relevance: In this randomized clinical trial comparing internal fixation of well-reduced medial malleolus fractures with nonfixation, after fibular stabilization, fixation was not superior according to the primary outcome. However, 1 in 5 patients developed a radiographic nonunion after nonfixation, and although the reintervention rate to manage this was low, the future implications are unknown. These results support selective nonfixation of anatomically reduced medial malleolar fractures after fibular stabilization. Trial Registration: ClinicalTrials.gov Identifier: NCT03362229.

Ultrasound assessment of humeral shaft nonunion risk: a feasibility and proof of concept study.

PURPOSE: To determine the feasibility and reliability of ultrasound in the assessment of humeral shaft fracture healing and estimate the accuracy of 6wk ultrasound in predicting nonunion. METHODS: Twelve adults with a non-operatively managed humeral shaft fracture were prospectively recruited and underwent ultrasound scanning at 6wks and 12wks post-injury. Seven blinded observers evaluated sonographic callus appearance to determine intra- and inter-observer reliability. Nonunion prediction accuracy was estimated by comparing images for patients that united (n = 10/12) with those that developed a nonunion (n = 2/12). RESULTS: The mean scan duration was 8 min (5-12) and all patients tolerated the procedure. At 6wks and 12wks, sonographic callus (SC) was present in 11 patients (10 united, one nonunion) and sonographic bridging callus (SBC) in seven (all united). Ultrasound had substantial intra- (weighted kappa: 6wk 0.75; 12wk 0.75) and inter-observer reliability (intraclass correlation coefficient: 6wk 0.60; 12wk 0.76). At 6wks, the absence of SC demonstrated sensitivity 50%, specificity 100%, positive predictive value (PPV) 100% and negative predictive value (NPV) 91% in nonunion prediction (overall accuracy 92%). The absence of SBC demonstrated sensitivity 100%, specificity 70%, PPV 40% and NPV 100% in nonunion prediction (overall accuracy 75%). Of three patients at risk of nonunion (Radiographic Union Score for HUmeral fractures < 8), one had SBC on 6wk ultrasound (that subsequently united) and the others had non-bridging/absent SC (both developed nonunion). CONCLUSIONS: Ultrasound assessment of humeral shaft fracture healing was feasible, reliable and may predict nonunion. Ultrasound could be useful in defining nonunion risk among patients with reduced radiographic callus formation.

Pre-existing knee osteoarthritis and severe joint depression are associated with the need for total knee arthroplasty after tibial plateau fracture in patients aged over 60 years.

Aims: This study aims to determine the rate of and risk factors for total knee arthroplasty (TKA) after operative management of tibial plateau fractures (TPFs) in older adults. Methods: This is a retrospective cohort study of 182 displaced TPFs in 180 patients aged ≥ 60 years, over a 12-year period with a minimum follow-up of one year. The mean age was 70.7 years (SD 7.7; 60 to 89), and 139/180 patients (77.2%) were female. Radiological assessment consisted of fracture classification; pre-existing knee osteoarthritis (OA); reduction quality; loss of reduction; and post-traumatic OA. Fracture depression was measured on CT, and the volume of defect estimated as half an oblate spheroid. Operative management, complications, reoperations, and mortality were recorded. Results: Nearly half of the fractures were Schatzker II AO B3.1 fractures (n = 85; 47%). Radiological knee OA was present at fracture in 59/182 TPFs (32.6%). Primary management was fixation in 174 (95.6%) and acute TKA in eight (4.4%). A total of 13 patients underwent late TKA (7.5%), most often within two years. By five years, 21/182 12% (95% confidence interval (CI) 6.0 to 16.7) had required TKA. Larger volume defects of greater depth on CT (median 15.9 mm vs 9.4 mm; p < 0.001) were significantly associated with TKA requirement. CT-measured joint depression of > 12.8 mm was associated with TKA requirement (area under the curve (AUC) 0.766; p = 0.001). Severe joint depression of > 15.5 mm (hazard ratio (HR) 6.15 (95% CI 2.60 to 14.55); p < 0.001) and pre-existing knee OA (HR 2.70 (95% CI 1.14 to 6.37); p = 0.024) were independently associated with TKA requirement. Where patients with severe joint depression of > 15.5 mm were managed with fixation, 11/25 ultimately required TKA. Conclusion: Overall, 12% of patients aged ≥ 60 years underwent TKA within five years of TPF. Severe joint depression and pre-existing knee arthritis were independent risk factors for both post-traumatic OA and TKA. These features should be investigated as potential indications for acute TKA in older adults with TPFs.

Outcome Following Intramedullary Nailing of Tibial Diaphyseal Fractures: Suprapatellar Nail Insertion Results in Superior Radiographic Parameters But No Difference in Mid-Term Function.

BACKGROUND: The primary aim of this study was to compare the radiographic parameters (nail insertion-point accuracy [NIPA] and fracture malalignment) of patients who had undergone tibial intramedullary nailing via the suprapatellar (SP) and infrapatellar (IP) approaches. The secondary aims were to compare clinical outcomes and patient-reported outcomes (PROs) between these approaches. METHODS: All adult patients with an acute tibial diaphyseal fracture who underwent intramedullary nailing at a single level-I trauma center over a 4-year period (2017 to 2020) were retrospectively identified. The nailing approach (SP or IP) was at the treating surgeon's discretion. Intraoperative and immediate postoperative radiographs were reviewed to assess NIPA (mean distance from the optimal insertion point) and malalignment (≥5°). Medical records and radiographs were reviewed to evaluate the rates of malunion, nonunion, and other postoperative complications. The Oxford and Lysholm Knee Scores (OKS and LKS) and patient satisfaction (0 = completely dissatisfied, 100 = completely satisfied) were obtained via a postal survey at a minimum of 1 year postoperatively. RESULTS: The cohort consisted of 219 consecutive patients (mean age, 48 years [range, 16 to 90 years], 51% [112] male). There were 61 patients (27.9%) in the SP group and 158 (72.1%) in the IP group. The groups did not differ in baseline demographic or injury-related variables. SP nailing was associated with superior coronal NIPA (p < 0.001; 95% confidence interval [CI] for IP versus SP, 1.17 to 3.60 mm) and sagittal NIPA (p < 0.001; 95% CI, 0.23 to 0.97 mm) and with a reduced rate of malalignment (3% [2 of 61] versus 11% [18 of 158] for IP; p = 0.030). PROs were available for 118 of 211 patients (56%; 32 of 58 in the SP group and 86 of 153 in the IP group) at a mean of 3 years (range, 1.2 to 6.5 years). There was no difference between the SP and IP groups in mean OKS (36.5 versus 39.6; p = 0.246), LKS (71.2 versus 73.5; p = 0.696), or satisfaction scores (81.4 versus 79.9; p = 0.725). CONCLUSIONS: Compared with IP nailing, SP nailing of tibial shaft fractures was associated with superior NIPA and a reduced rate of intraoperative malalignment but not of malunion at healing. However, the superior NIPA may not be clinically important. Furthermore, there were no differences in PROs at mid-term follow-up. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Early- and mid-lactation milk traits are associated with piglet growth during lactation.

Preweaning piglet growth is tied to milk quality and consumption. To determine the relationship of milk traits from parity 1-4 dams and piglet growth, early- and mid-lactation (day 2 and day 16) milk samples were collected from 48 litters and analyzed for protein, fat, somatic cell count (SCC), lactose, other solids (solids excluding protein and fat), total solids, and milk urea nitrogen (MUN). There were no interactions of parity by day therefore only main effects were tested. Milk volume and percent MUN were greatest (P < 0.05) from fourth parity dams. Nulliparous dams had elevated (P < 0.05) SCC. Several milk traits were different by day. Percent milk protein, fat, and total solids were greater (P < 0.05) from day 2 milk, while percent milk lactose and other solids were greater (P < 0.05) from day 16 milk. Each milk trait was categorically identified as high, moderate, or low at », ½, or » distribution, respectively. Mixed models were used to determine the association of individual milk traits with piglet lactation growth (gain calculated from body weights at birth, day 10, and day 25 weaning; WN). Moderate levels of day 2 milk protein were associated with the greatest (P < 0.05) gain during lactation in comparison to low and high levels. High levels of day 2 milk lactose and day 2 other solids were both related (P < 0.05) to piglet gain over the lactation period. Evaluation of day 16 milk traits with piglet gain over lactation indicated high levels of fat, other solids, and total solids had the greatest (P < 0.05) gain in comparison to moderate and low levels of each trait. Within phase of lactation weight gain, association of day 2 or day 16 milk traits with early weight gain (birth to day 10) or late weight gain (day 10 to WN) were performed. The greatest (P < 0.05) early weight gains were associated with moderate levels of day 2 protein, high levels of day 2 lactose and day 2 other solids, and low levels of day 2 MUN. High levels of day 2 milk lactose and day 16 milk fat were associated (P < 0.05) with piglet gain during late lactation (day 10 to weaning). Genetic selection or improved management that allows for favorable milk traits at critical periods of lactation for improved weight gain will improve pig production.

Early piglet health and growth are reliant upon milk from the mother. Increasing the gain of a piglet by 0.45 kg at weaning has been linked to finished pigs going to market earlier reducing environmental and financial inputs for producers. Nursing mothers with the highest level of milk lactose early in nursing produced heavier piglets and sows with higher levels of milk fat midway through the nursing phase also had heavier piglets. This information will help identify nursing mothers and develop feed supplements to support the production of beneficial milk components that will improve piglet growth and health.

QuickDASH and PRWE Are Not Optimal Patient-Reported Outcome Measures After Distal Radial Fracture Due to Ceiling Effect: Potential Implications for Future Research.

BACKGROUND: The aim of this study was to determine the floor and ceiling effects for both the QuickDASH (shortened version of the Disabilities of the Arm, Shoulder and Hand [DASH] questionnaire) and the PRWE (Patient-Rated Wrist Evaluation) following a distal radial fracture (DRF). Secondary aims were to determine the degree to which patients with a floor or ceiling effect felt that their wrist was "normal" according to the Normal Wrist Score (NWS) and if there were patient factors associated with achieving a floor or ceiling effect. METHODS: A retrospective cohort study of patients in whom a DRF was managed at the study center during a single year was undertaken. Outcome measures included the QuickDASH, PRWE, EuroQol-5 Dimensions-3 Levels (EQ-5D-3L), and NWS. RESULTS: There were 526 patients with a mean age of 65 years (range, 20 to 95 years), and 421 (80%) were female. Most patients were managed nonsurgically (73%, n = 385). The mean follow-up was 4.8 years (range, 4.3 to 5.5 years). A ceiling effect was observed for both the QuickDASH (22.3% of patients with the best possible score) and the PRWE (28.5%). When defined as a score that differed from the best available score by less than the minimum clinically important difference (MCID) for the scoring system, the ceiling effect increased to 62.8% for the QuickDASH and 60% for the PRWE. Patients who had a ceiling score on the QuickDASH and the PWRE had a median NWS of 96 and 98, respectively, and those who had a score within 1 MCID of the ceiling score reported a median NWS of 91 and 92, respectively. On logistic regression analysis, a dominant-hand injury and better health-related quality of life were the factors associated with both QuickDASH and PRWE ceiling scores (all p < 0.05). CONCLUSIONS: The QuickDASH and PRWE demonstrate ceiling effects when used to assess the outcome of DRF management. Some patients achieving ceiling scores did not consider their wrist to be "normal." Future research on patient-reported outcome assessment tools for DRFs should aim to limit the ceiling effect, especially for individuals or groups that are more likely to achieve a ceiling score. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Evolution of 1/f Flux Noise in Superconducting Qubits with Weak Magnetic Fields.

The microscopic description of 1/f magnetic flux noise in superconducting circuits has remained an open question for several decades despite extensive experimental and theoretical investigation. Recent progress in superconducting devices for quantum information has highlighted the need to mitigate sources of qubit decoherence, driving a renewed interest in understanding the underlying noise mechanism(s). Though a consensus has emerged attributing flux noise to surface spins, their identity and interaction mechanisms remain unclear, prompting further study. Here, we apply weak in-plane magnetic fields to a capacitively shunted flux qubit (where the Zeeman splitting of surface spins lies below the device temperature) and study the flux-noise-limited qubit dephasing, revealing previously unexplored trends that may shed light on the dynamics behind the emergent 1/f noise. Notably, we observe an enhancement (suppression) of the spin-echo (Ramsey) pure-dephasing time in fields up to B=100 G. With direct noise spectroscopy, we further observe a transition from a 1/f to approximately Lorentzian frequency dependence below 10 Hz and a reduction of the noise above 1 MHz with increasing magnetic field. We suggest that these trends are qualitatively consistent with an increase of spin cluster sizes with magnetic field. These results should help to inform a complete microscopic theory of 1/f flux noise in superconducting circuits.

Differential attainment in higher surgical training: scoping pan-specialty spectra.

INTRODUCTION: This study aimed to evaluate differential attainment during higher surgical training (HST; all specialties) related to three ethnic cohorts: White UK (WUKG), Black and Minority Ethnic UK Graduates (BMEUKG), and International Medical Graduates (IMG). METHOD: Anonymised records of 266 HSTs (126 WUKG, 65 BMEUKG, 75 IMG; 7 years) in a single UK Statutory Education Body were examined. Primary effect measures were Annual Record of Competency Progression Outcome (ARCPO) and Fellowship of the Royal College of Surgeons (FRCS) pass. RESULTS: ARCPOs related to ethnicity and specialty were similar with the exception of general surgery (GS) trainees, four of whom received ARCPO 4 (GS 4.9% (75% BME; p=0.025) vs all other 0%). ARCPO 3 was commoner in women (22/76, (28.9%) than men 27/190 (14.2%), OR 2.46, p=0.006). FRCS pass rates (WUKG vs BMEUKG vs IMG) were 76.9%, 52.9% and 53.9% respectively (p=0.064) but unrelated to gender (M 70.4% vs F 64.3%). On multivariable analyses: ARCPO 3 was associated with Female gender and Maternity Leave (OR 8.05, p=0.001); FRCS pass with ethnicity (OR 0.21, p=0.028) and Hirsch Indices of ≥5 (OR 11.17, p=0.001). CONCLUSION: Differential attainment was plain with BMEUKG FRCS performance almost a third poorer than WUKG, and women twofold more likely to receive adverse ARCPOs, with return from statutory leave independently associated with training extension. Focused counter measures targeted at non-operative technical skills (including academic reach), Keeping in Touch, Return to Work, and re-induction programmed support are urgently needed for trainees at risk.

The Radiographic Union Score for ulnar fractures (RUSU) predicts ulnar shaft nonunion.

AIMS: To develop a reliable and effective radiological score to assess the healing of isolated ulnar shaft fractures (IUSF), the Radiographic Union Score for Ulna fractures (RUSU). METHODS: Initially, 20 patients with radiographs six weeks following a non-operatively managed ulnar shaft fracture were selected and scored by three blinded observers. After intraclass correlation (ICC) analysis, a second group of 54 patients with radiographs six weeks after injury (18 who developed a nonunion and 36 who united) were scored by the same observers. RESULTS: In the initial study, interobserver and intraobserver ICC were 0.89 and 0.93, respectively. In the validation study, the interobserver ICC was 0.85. The median score for patients who united was significantly higher than those who developed a nonunion (11 vs. 7, p < 0.001). A ROC curve demonstrated that a RUSU ≤ 8 had a sensitivity of 88.9% and specificity of 86.1% in identifying patients at risk of nonunion. Patients with a RUSU ≤ 8 (n = 21) were more likely to develop a nonunion (n = 16/21) than those with a RUSU ≥ 9 (n = 2/33; OR 49.6, 95% CI 8.6-284.7). Based on a PPV of 76%, if all patients with a RUSU ≤ 8 underwent fixation at 6 weeks, the number of procedures needed to avoid one nonunion would be 1.3. CONCLUSION: The RUSU shows good interobserver and intraobserver reliability and is effective in identifying patients at risk of nonunion six weeks after fracture. This tool requires external validation but may enhance the management of patients with isolated ulnar shaft fractures.

Post-diagnostic statin use and breast cancer-specific mortality: a population-based cohort study.

PURPOSE: Statins are the most widely prescribed cholesterol lowering medications and have been associated with both improved and unchanged breast cancer outcomes in previous studies. This study examines the association between the post-diagnostic use of statins and breast cancer outcomes (death and recurrence) in a large, representative sample of New Zealand (NZ) women with breast cancer. METHODS: Women diagnosed with a first primary breast cancer between 2007 and 2016 were identified from four population-based regional NZ breast cancer registries and linked to national pharmaceutical data, hospital discharges, and death records. Cox proportional hazard models were used to estimate the hazard of breast cancer-specific death (BCD) associated with any post-diagnostic statin use. RESULTS: Of the 14,976 women included in analyses, 27% used a statin after diagnosis and the median follow up time was 4.51 years. Statin use (vs non-use) was associated with a statistically significant decreased risk of BCD (adjusted hazard ratio: 0.74; 0.63-0.86). The association was attenuated when considering a subgroup of 'new' statin users (HR: 0.91; 0.69-1.19), however other analyses revealed that the protective effect of statins was more pronounced in estrogen receptor positive patients (HR: 0.77; 0.63-0.94), postmenopausal women (HR: 0.74; 0.63-0.88), and in women with advanced stage disease (HR: 0.65; 0.49-0.84). CONCLUSION: In this study, statin use was associated with a statistically significant decreased risk of breast cancer death, with subgroup analyses revealing a more protective effect in ER+ patients, postmenopausal women, and in women with advanced stage disease. Further research is warranted to determine if these associations are replicated in other clinical settings.

Distal radius malunion: outcomes following an ulnar shortening osteotomy.

PURPOSE: Positive ulnar variance following a distal radius malunion can lead to ulnar-sided wrist pain, loss of grip strength, and distal radioulnar joint impingement. The primary aim of this study is to describe upper limb-specific functional outcomes following ulnar shortening osteotomy (USO) for ulnar-sided wrist pain associated with malunion of the distal radius. METHODS: We retrospectively identified 40 adult patients from a single centre over a 9-year period that had undergone an USO for symptomatic malunion of the distal radius. The primary outcome was the patient-rated wrist evaluation (PRWE). Secondary outcomes were the QuickDASH, EQ-5D-5L, complications, and net promoter score (NPS). RESULTS: Outcomes were available for 37 patients (93%). The mean age was 56 years and 25 patients were female (68%). At a mean follow-up of 6 years (range 1-10 years) the median PRWE was 11 (IQR 0-29.5), the median QuickDASH 6.8 (IQR 0-29.5), and the median EQ-5D-5L index was 0.88 (IQR 0.71-1). The NPS was 73. Complications occurred in nine patients (24%) and included non-union (n = 4), early loss of fixation requiring revision surgery (n = 1), superficial wound infection (n = 2), neurological injury (n = 1), and further surgery for symptomatic hardware removal (n = 1). CONCLUSIONS: For patients with a symptomatic distal radius malunion where the predominant deformity is ulnar positive variance, this study has demonstrated that despite 1 in 4 patients experiencing a complication, USO can result in excellent patient reported outcomes with high levels of satisfaction. LEVEL OF EVIDENCE: III (Cohort Study).

Surgical Versus Nonsurgical Management of Humeral Shaft Fractures: A Systematic Review and Meta-Analysis of Randomized Trials.

INTRODUCTION: The aim was to compare surgical and nonsurgical management for adults with humeral shaft fractures in terms of patient-reported upper limb function, health-related quality of life, radiographic outcomes, and complications. METHODS: MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, PubMed, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, International Clinical Trials Registry, and OpenGrey (Repository for Grey Literature in Europe) were searched in September 2021. All published prospective randomized trials comparing surgical and nonsurgical management of humeral shaft fractures in adults were included. Of 715 studies identified, five were included in the systematic review and four in the meta-analysis. Data were extracted by two independent reviewers according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Methodological quality was assessed using the revised Cochrane risk-of-bias tool for randomized trials. Pooled data were analyzed using a random-effects model. RESULTS: The meta-analysis comprised 292 patients (mean age 41 [18 to 83] years, 67% male). Surgery was associated with superior Disabilities of the Arm, Shoulder and Hand (DASH) and Constant-Murley scores at 6 months (mean DASH difference 7.6, P = 0.01; mean Constant-Murley difference 8.0, P = 0.003), but there was no difference at 1 year (DASH, P = 0.30; Constant-Murley, P = 0.33). No differences in health-related quality of life or pain scores were found. Surgery was associated with a lower risk of nonunion (0.7% versus 15.7%; odds ratio [OR] 0.13, P = 0.004). The number needed to treat with surgery to avoid one nonunion was 7. Surgery was associated with a higher risk of transient radial nerve palsy (17.4% versus 0.7%; OR 8.23, P = 0.01) but not infection (OR 3.57, P = 0.13). Surgery was also associated with a lower risk of reintervention (1.4% versus 19.3%; OR 0.14, P = 0.04). CONCLUSIONS: Surgery may confer an early functional advantage to adults with humeral shaft fractures, but this is not sustained beyond 6 months. The lower risk of nonunion should be balanced against the higher risk of transient radial nerve palsy. LEVEL OF EVIDENCE: Level I.

One-carbon metabolite supplementation to heifers for the first 14 d of the estrous cycle alters the plasma and hepatic one-carbon metabolite pool and methionine-folate cycle enzyme transcript abundance in a dose-dependent manner.

The objective of this study was to determine the dose of folate and vitamin B12 in beef heifers fed rumen protected methionine and choline required to maintain increased B12 levels and intermediates of the methionine-folate cycle in circulation. Angus heifers (n = 30; BW = 392.6 ±â€…12.6 kg) were individually fed and assigned to one of five treatments: 0XNEG: Total mixed ration (TMR) and saline injections at day 0 and 7 of the estrous cycle, 0XPOS: TMR, rumen protected methionine (MET) fed at 0.08% of the diet DM, rumen protected choline (CHOL) fed at 60 g/d, and saline injections at day 0 and 7, 0.5X: TMR, MET, CHOL, 5 mg B12, and 80 mg folate at day 0 and 7, 1X: TMR, MET CHOL, 10 mg vitamin B12, and 160 mg folate at day 0 and 7, and 2X: TMR, MET, CHOL, 20 mg B12, and 320 mg folate at day 0 and 7. All heifers were estrus synchronized but not bred, and blood was collected on day 0, 2, 5, 7, 9, 12, and 14 of a synchronized estrous cycle. Heifers were slaughtered on day 14 of the estrous cycle for liver collection. Serum B12 concentrations were greater in the 0.5X, 1X, and 2X, compared with 0XNEG and 0XPOS on all days after treatment initiation (P < 0.0001). Serum folate concentrations were greater for the 2X treatment at day 5, 7, and 9 of the cycle compared with all other treatments (P ≤ 0.05). There were no differences (P ≥ 0.19) in hepatic methionine-cycle or choline analyte concentrations by treatment. Concentrations of hepatic folate cycle intermediates were always greater (P ≤ 0.04) in the 2X treatment compared with the 0XNEG and 0XPOS heifers. Serum methionine was greater (P = 0.04) in the 0.5X and 2X heifers compared with 0XNEG, and S-adenosylhomocysteine (SAH) tended (P = 0.06) to be greater in the 0.5X heifers and the S-adenosylmethionine (SAM):SAH ratio was decreased (P = 0.05) in the 0.5X treatment compared with the 0XNEG, 0XPOS, and 2X heifers. The hepatic transcript abundance of MAT2A and MAT2B were decreased (P ≤ 0.02) in the 0.5X heifers compared with the 0XNEG, 0XPOS, and 2X heifers. These data support that beef heifers fed rumen protected methionine and choline require 20 mg B12 and 320 mg folate once weekly to maintain increased concentrations of B12 and folate in serum. Furthermore, these data demonstrate that not all supplementation levels are equal in providing positive responses, and that some levels, such as the 0.5X, may result in a stoichiometric imbalance in the one-carbon metabolism pathway that results in a decreased SAM:SAH ratio.

The strategic inclusion of one-carbon metabolites, which include vitamins and minerals that are found in human prenatal vitamins, to beef cattle feeding and management protocols during the periconceptual period (the time around breeding) is a novel concept. Therefore, this study aimed to identify the feeding and injection doses of one-carbon metabolites in beef heifers to maintain increased circulating concentrations of one-carbon metabolites for use as a model from which other studies could base their treatments on. We determined that daily feeding of methionine and choline at 0.08% of dry matter and 60 g/d, respectively, and administration of vitamin B12 and folate at 20 mg and 320 mg once per week, respectively resulted in sustained elevated concentrations of one-carbon metabolites.

Weaning transition, but not the administration of probiotic candidate Kazachstania slooffiae, shaped the gastrointestinal bacterial and fungal communities in nursery piglets.

As in-feed antibiotics are phased out of swine production, producers are seeking alternatives to facilitate improvements in growth typically seen from this previously common feed additive. Kazachstania slooffiae is a prominent commensal fungus in the swine gut that peaks in relative abundance shortly after weaning and has beneficial interactions with other bacteriome members important for piglet health. In this study, piglets were supplemented with K. slooffiae to characterize responses in piglet health as well as fungal and bacterial components of the microbiome both spatially (along the entire gastrointestinal tract and feces) and temporally (before, during, and after weaning). Litters were assigned to one of four treatments: no K. slooffiae (CONT); one dose of K. slooffiae 7 days before weaning (day 14; PRE); one dose of K. slooffiae at weaning (day 21; POST); or one dose of K. slooffiae 7 days before weaning and one dose at weaning (PREPOST). The bacteriome and mycobiome were analyzed from fecal samples collected from all piglets at day 14, day 21, and day 49, and from organ samples along the gastrointestinal (GI) tract at day 21 and day 49. Blood samples were taken at day 14 and day 49 for cytokine analysis, and fecal samples were assayed for antimicrobial resistance. While some regional shifts were seen in response to K. slooffiae administration in the mycobiome of the GI tract, no remarkable changes in weight gain or health of the animals were observed, and changes were more likely due to sow and the environment. Ultimately, the combined microbiome changed most considerably following the transition from suckling to nursery diets. This work describes the mycobiome along the piglet GI tract through the weaning transition for the first time. Based on these findings, K. slooffiae administered at this concentration may not be an effective tool to hasten colonization of K. slooffiae in the piglet GI tract around the weaning transition nor support piglet growth, microbial gut health, or immunity. However, diet and environment greatly influence microbial community development.

Outcome Following Acute Suture Anchor Repair of the Ulnar Collateral Ligament of the Thumb.

Background: The aim of this study was to evaluate the outcomes following acute repair of the ulnar collateral ligament of the thumb metacarpophalangeal joint (thumb UCL) using a suture anchor technique. Methods: From 2011 to 2019, we retrospectively identified 40 adult patients from a single centre who had undergone an acute thumb UCL repair (≤6 weeks post-injury). The mean age of the study cohort was 37 years (range 16-70) and 68% (n = 27/40) were male. The short-term outcomes included postoperative complications and failure of repair. The long-term outcomes were QuickDASH, the EuroQol 5-Dimension (EQ-5D), Visual Analogue Scale (EQ-VAS), return to sport and work and satisfaction with outcome. Results: The outcomes survey was completed at a mean of 4.3 years (range 1.0-9.2) for 33 patients (83%). Postoperative complications included self-limiting sensory disturbance (7.5%, n = 3/40), superficial infection (requiring oral antibiotics; 5%, n = 2/40) and wound dehiscence (requiring surgical debridement and re-closure; 2.5%, n = 1/40). No failures of repair were reported. The mean QuickDASH was 3.7 (range 0-27.3), EQ-5D 0.821 (range -0.041 to 1) and EQ-VAS 84 (range 60-100). Of the 32 employed patients, all returned to work at a median of 0.5 weeks (range 0-416) and the mean QuickDASH Work Module was 4.1 (range 0-50). Of the 24 patients playing sport prior to injury, 96% (n = 23/24) returned at a median of 16 weeks (range 5-52) and the mean QuickDASH Sport Module was 4.6 (range 0-25). All the patients were satisfied with their outcome (mean satisfaction score 9.8/10 [8-10O]). Conclusions: Thumb UCL repair using a suture anchor technique is safe and effective up to 6 weeks post injury. Pain and stiffness may persist in the longer term, but most patients report excellent upper limb function and health-related quality of life. The majority return to work and sport and are highly satisfied with their outcome. Level of Evidence: Level IV (Therapeutic).