Category: 3. Business

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Ryanair has scrapped its loyalty programme after just eight months because passengers were costing the airline money by taking too many discounted flights.

The scheme offered early access to discounted tickets and free seat reservations on up to 12 journeys, for a flat fee of €79 or £79, and was capped at 250,000 passengers.

About 55,000 people signed up, generating €4.4mn in subscription fees for the business.

“However, our Prime members have received over €6mn in fare discounts, so this trial has cost more money than it generates,” said Ryanair marketing chief Dara Brady.

“This level of memberships, or subscription revenue does not justify the time and effort it takes to launch monthly exclusive Prime seat sales for our 55,000 Prime members.”

While those who paid for the service can continue using it until October next year, the airline on Friday said it would not sign up any new members.

“We are grateful to our 55,000 Prime members who signed up to this Prime trial over the last eight months, and they can rest assured that they will continue to enjoy exclusive flight and seat savings for the remainder of their 12-month membership,” added Brady.

Which? Travel concluded after the scheme was introduced that the “calculations Ryanair provides shows very few travellers would save money by subscribing”.

Chief executive Michael O’Leary earlier this year admitted that the airline had underpriced the scheme. 

Prime was the first time Ryanair had ventured from its zero-frills model to offer such a scheme. The airline took until 2014 to introduce allocated seating.

Rival Wizz Air already has an “all you can fly” offering that costs €499 a year. The London-listed carrier recently expanded the number of people who could sign up for the scheme.

EasyJet also has a loyalty programme that gives customers greater flexibility to change flights as well as faster boarding and access to premium seats for £249 a year.

Despite its loss from the scheme, Ryanair profits rose by 40 per cent over the summer owing to robust demand, helped by more Europeans holidaying within the region rather than travelling to the US.

CGA by NIQ’s latest Daily Drinks Tracker shows average sales in managed venues in the week to 8 November were 2.3% ahead of the same period in 2024. This was followed by growth of 0.5% in the following seven days to 15 November. 

Both figures are below the UK’s rate of inflation, as measured by the Consumer Prices Index. However, they reverse three consecutive weeks of negative trading in October, and raise hopes that some consumers are lifting their spending on the run-in to Christmas and New Year.  

Trading in early November was boosted by Bonfire Night and firework displays, as well as a busy programme of Premier League, Champions League and international football fixtures, plus big rugby union fixtures for England, Scotland and Wales. The start of Christmas markets may also have lifted footfall in many British cities and towns. 

However, the arrival of Storm Claudia curtailed visits to pubs and bars in some parts of the country towards the end of the fortnight—especially on Saturday 14 November, when sales dropped by 8.2% year-on-year. 

Live sport has been a boost to Long Alcoholic Drinks categories, with beer sales rising by 3.6% and 1.7% in the weeks to 8 and 15 November respectively. Cider performed even better, with growth of 5.5% and 2.9%. Soft drinks also had a positive fortnight, increasing by 5.4% and 1.3%. 

Trends in other drinks categories were less encouraging. On Premise sales of spirits fell by 3.8% and 2.0% in the two weeks. Wine had fractional growth of 0.1% in the week to 8 November, but sales then dipped 2.8% in the following seven days. 

Rachel Weller, NIQ’s commercial lead, UK & Ireland, said: “While sales growth in the first half of November has been marginal, it lifts optimism that consumers are starting to increase their visits to pubs and bars as Christmas occasions get into full swing. Storm Claudia was another reminder of the damage that bad weather can do to trading, and operators and suppliers will be keeping fingers crossed for bright days that bring people out of home in the weeks ahead. There’s all to play for this festive season, and after a tough 2025 it could make or break the year for many businesses.”

 

The Daily Drinks Tracker provides analysis of sales at managed licensed premises across Britain and is part of NIQ’s suite of research services delivering in-depth data on category, supplier and brand rate of sale performance. To learn more, click here and contact the NIQ team.

Blackstone (NYSE:BK) continues to expand its daat center footprint as artificial intelligence elevates demand for these buildings. Lenders also feel optimistic about data centers, based on Blackstone’s being able to refinance 10 data centers owned by subsidiary QTS in a $3.5 billion deal, according to BisNow.

Blackstone entered the data center industry when it acquired QTS Realty Trust in 2021 for $10 billion. QTS now operates more than 70 data centers, marking an eightfold increase in less than five years.

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Those facilities support more than three gigawatts of capacity, making it a viable option for hyperscalers like Meta Platforms (NASDAQ:META) and Amazon (NASDAQ:AMZN) that need more energy for their AI ambitions.

Blackstone’s latest refinance unlocks more capital from its data center portfolio. The funds give the firm flexibility to buy additional facilities or use the cash for other business segments.

Data centers require significant capital to go from concepts to finished buildings, and that’s part of the reason why companies like Blackstone are refinancing their existing properties. Financing makes it easier to build more facilities, and the strong demand for AI and cloud computing suggests that more capital will flow into the industry.

Trending: Forget Flipping Houses—This Fund Lets You Invest in Home Equity Like Wall Street Does

These facilities currently consume 5% of U.S. power, and that figure is set to double thanks to a $6.7 trillion buildout. Heavy data center concentrations are associated with higher electricity bills, according to CNBC. Higher energy costs and intense capital requirements haven’t stopped companies from building and scaling their data center portfolios.

Tech giants have also committed to lucrative deals that make these facilities more attractive in the long run. Meta announced a $27 billion joint venture with Blue Owl Capital (NYSE:OWL) in October to develop the Hyperion data center campus in Richland Parish, Louisiana.

The refinancing deal comes as interest rates continue to drop. The Federal Reserve has cut interest rates twice this year, with the possibility of a third rate cut in December. Lower rates make it more affordable for Blackstone and other firms to borrow money. As rates drop, demand for commercial-backed mortgage securities may increase.

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A long-term strike will likely impact public relations over the intermediate time horizon, but “in light of market volatility caused by tariffs and other factors, Starbucks would want to make this a short-term affair,” said Michael Duff, a professor at the Saint Louis University School of Law.

Starbucks, which has more than 17,000 coffeehouses in the U.S., said 99% of its locations in the country remain open.

“Regardless of the union’s plans, we do not anticipate any meaningful disruption,” a spokesperson for Starbucks said.

Striking baristas are demanding higher wages, improved working hours and the resolution of hundreds of unfair labor practice charges for union busting.

“The law allows management to hire replacements in this kind of strike, so the workers just don’t have a lot of leverage,” Harry Katz, a professor at the Cornell University School of Industrial and Labor Relations said.

Workers United said it represents over 11,000 baristas and about 550 Starbucks stores.

Starbucks Workers United has repeatedly targeted the company’s busy holiday season and Red Cup Day, when Starbucks hands out reusable red holiday-themed cups to customers for free on coffee purchases.

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Introduction

Recently, the concept of enhanced recovery after surgery (ERAS) has gained traction, giving rise to growing interest in the promotion of postoperative rehabilitation. This is to improve patients’ postoperative experiences and functional recovery at an early stage. Total knee arthroplasty (TKA) is a common surgical procedure performed in the elderly with the primary objective of relieving pain and improving mobility and enhancing the quality of life.¹

Frailty is a clinical syndrome characterized by diminished reserve function of multiple physiological systems,² which increases the vulnerability of an organism to internal and external stressors and reduces an individual’s ability to recover from stressful events (anesthesia and surgery). A study demonstrated a high prevalence of frailty in the elderly population undergoing surgical treatments, with rates ranging from 10% to 46%.² A limited number of previous studies also showed a correlation between preoperative frailty and poorer functional outcomes in hip and knee replacements.^3,4 The quality of postoperative recovery (QoR) is significantly lower in frail patients compared to non-frail patients.

One study showed that the physiological repair capacity of frail patients was impaired, rendering them susceptible to homeostatic imbalances in the presence of endogenous or exogenous stressors.⁵ This homeostatic imbalance is caused by dysfunctions in the regulation of multiple organ systems (eg, blood pressure, pulse, and blood glucose) has a significant impact on the recovery of the organism in the postoperative period.⁶ A recent report noted that in elderly patients undergoing non-cardiac surgery, frailty was associated with an increased incidence of intraoperative hypotension and a greater susceptibility to intraoperative hemodynamic instability.⁷ Intraoperative hemodynamic instability increases the risk of nonoperative complications after orthopedic surgery and reduces the quality of patient recovery.

This suggests a potential area for research and intervention if the mechanisms predicting surgical recovery outcomes in elderly debilitated patients include intraoperative hemodynamic dysregulation. Based on this theory, we designed a prospective randomized controlled clinical trial with the hypothesis that controlling intraoperative MAP at different levels would affect the quality of postoperative recovery in debilitated patients.

Methods

Study Design and Ethics

This was a single-center, single-blind, randomized controlled clinical trial. Ethical approval for this study was granted by the Ethics Committee of Lianyungang Clinical College of Nanjing Medical University (identifier: KF-20211008001-02, date: October 8, 2021). Before enrollment, written informed consent was obtained from all participants. This study was registered in the Chinese Clinical Trial Registry (ChiCTR2200057908). This clinical trial was conducted between March 2022 and December 2022. This manuscript has been prepared in accordance with the CONSORT guidelines.

Patients

The inclusion criteria were patients scheduled for elective unilateral total knee arthroplasty under general anesthesia, aged ≥ 65 years, American Society of Anesthesiologists (ASA) grade II–III, and frailty (FRAIL scale score ≥ 3). The patients were required to understand and voluntarily participate in the study and signed an informed consent form.

The exclusion criteria were patients with acute and critical illnesses (including acute heart failure, acute stroke, acute myocardial infarction, and severe infections), those with poorly controlled blood pressure (systolic blood pressure ≥ 160 mmHg and diastolic blood pressure ≥ 105 mmHg) after regular drug treatment, those who were completely disabled and unable to cooperate with the study, and those who were admitted to the ICU.

After informed consent was obtained, the enrolled patients were randomized 1:1 (computer-generated blocks) to the lower-level group (Group L) or the higher-level group (Group H) with sealed envelope allocation.

Although the anesthesiologist could not be blinded to the group assignments, much attention was paid to ensuring strict blinding during the data collection and follow-up periods. The remaining investigators, patients, family members, and surgeons were blinded to group assignments.

Anesthesia Management and Intervention

During the preoperative evaluation, each patient underwent a standard clinical evaluation the day before surgery. A set of inclusion and exclusion criteria was used to identify suitable subjects for the study. Once informed consent was obtained, basic patient information was recorded.

Anesthetic administration: Patients fasted for 8 hours and abstained from drinking for 4 hours before surgery. Noninvasive blood pressure, electrocardiogram, and pulse oxygen saturation were routinely monitored after admission to the operating room. After establishing venous access, radial artery catheterization was performed to monitor arterial blood pressure. General anesthesia was induced with 1–2 mg/kg propofol, 0.3–0.5 µg/kg sufentanil, and 0.6 mg/kg rocuronium. The depth of anesthesia was maintained with propofol 4–8 mg·kg⁻¹·h⁻¹, remifentanil 0.1–0.3 ug·kg⁻¹·min⁻¹. The bispectral index (BIS) was kept at a value of 40–60 by modulating the propofol dosage. End-tidal carbon dioxide tension was maintained within a range of 35–45 mmHg by adjusting the tidal volume or respiratory rate.

Ten minutes before the end of the surgical procedure, remifentanil was discontinued and propofol was terminated at the end of the operation. When the neuromuscular block spontaneously recovered to at least T2 reappearance, sugammadex sodium 2mg/kg was administered to counteract the effects of muscle relaxants and the patient was extubated in the operating room. Following extubation, patients were transferred to the post-anesthesia care unit (PACU), where invasive blood pressure, electrocardiogram, and pulse oxygen saturation were monitored for a minimum of 30 min until a modified Aldrete score of 9 was achieved.

Interventions: In Group L, the intraoperative MAP was maintained in the range of 65–85 mmHg, whereas in Group H, it was maintained in the range of 85–100 mmHg.^8,9 To maintain the basal volume status, 8–10 mL/kg of crystalloid was rapidly infused 15 min before induction. After endotracheal intubation, the infusion rate was adjusted to 7–8 mL·kg⁻¹·h⁻¹ of crystalloids.

The intraoperative blood pressure was controlled within the target range based on the following three aspects: blood volume, heart rate, and vasoactive drugs. Fluid and blood products were replenished to maintain adequate circulation volume based on the duration of fasting and intraoperative blood loss. Vasoactive drugs were used to regulate vascular tone; norepinephrine was administered for the first time at a dose of 4 ug, and urapidil was administered for the first time at a dose of 10 mg. If the MAP remained outside the target range after two minutes, it was added again according to the circumstances. If it was still challenging to maintain blood pressure within the target range after two consecutive additions, continuous infusion of norepinephrine or nitroglycerin was initiated at 0.03 mcg·kg⁻¹·min⁻¹, with titration increments or decrements of 0.03 mcg·kg⁻¹·min⁻¹ based on MAP level until MAP reached the target. Atropine 0.5 mg was given for HR <45 beats/minute persisting ≥1 min, repeatable after 5 min if unresolved. Esmolol 10 mg was administered for HR >100 beats/minute lasting ≥1 min, repeatable after 3 min if needed.

All patients received a multimodal analgesia regimen, which included a preoperative femoral nerve block (20 mL of 0.25% ropivacaine administered by the same anesthesiologist) and patient-controlled intravenous analgesia (150 mcg sufentanil diluted to 100 mL with saline; bolus dose: 1.5 mL, lockout interval: 15 min, basal rate: 2 mcg/h). The patients activated the button at the onset of moderate-to-severe or breakthrough pain. In cases of uncontrolled pain, analgesic medications such as flurbiprofen (100 mg) or intramuscular pethidine (50 mg), are available for analgesia.

Outcomes

The primary outcome was QoR-15 score on postoperative day 1 (POD1). The QoR-15 is a validated questionnaire based on a multidimensional patient-reported outcome measure for measuring postoperative QoR.¹⁰ This postoperative recovery status scale provides reproducible results. The ability to detect and measure clinically significant changes is a key feature of any health status tool used to predict patient prognosis.¹¹ The QoR-15 is a comprehensive measure of postoperative recovery, which is assessed in five areas: physical comfort (5 items), physical independence (2 items), emotional state (4 items), psychological support (2 items), and pain (2 items). The total score ranged from 0 (worst) to 150 (best).¹² Trained researchers administered the questionnaire daily (16:00–18:00) preoperatively and for 5 postoperative days. A QoR-15 score of 90 or less is defined as poor quality of recovery.¹³

Secondary outcomes included: The time-weighted average mean arterial pressure (TWA-MAP), the abbreviated mental test score (AMTS) at 30 days and 1-year postoperatively. The AMTS is a 10-item test that assesses recall, concentration, orientation, and registration.¹⁴ A score of 6 or below has been demonstrated to correlate well with dementia.¹⁵ QoR-15 scores on POD2-5, incidence of acute kidney injury (AKI) within 7 days postoperatively, incidence of myocardial injury after noncardiac surgery (MINS) within 48 hours and 1-year mortality postoperatively. AKI incidence was defined as a serum creatinine increase of at least 0.3 mg/dL within 48 h after surgery or an increase of at least 50% from the baseline serum creatinine level within 7 postoperative days. The peak-to-valley difference in serum creatinine level was used to determine the incidence of AKI. In summary, peak serum creatinine represents the highest value observed within 48 hours or 7 days after surgery, while minimum serum creatinine denotes the lowest value recorded during the 7-day preoperative period.¹⁶ MINS is defined as at least one postoperative cTn concentration exceeding the 99th percentile upper reference limit of the cTn assay.¹⁷

Adverse Events

Any adverse events that were spontaneously reported by patients or identified by investigators were meticulously recorded. A comprehensive account of all relevant details, including the time of occurrence, clinical presentation, management and duration of the event, and its regression and relationship with anesthesia management. In instances where abnormal laboratory test results were observed, patient follow-up was continued until the test results returned to normal or until it was determined that the results were unrelated to anesthesia management. The investigators determined and summarized the associations between adverse events and intervention. All severe adverse events, irrespective of whether they were deemed to be related to the study interventions, were registered and submitted to the local Medical Ethics Committee within 24 hours.

Statistical Analysis

The primary outcome was the score of the QoR-15 on POD1. The established minimum clinically important difference in the QoR-15 is 8.0, and the standard deviation (SD) of the QoR-15 scores after surgery is on the order of 16 (range of QoR-15 is 1–150).¹⁸ A minimum of 128 patients were required to achieve a power of >80% and an α of 0.05, to address the primary objective of comparing and describing the differences in the QoR-15 scores on POD1 between groups. Considering a 10% dropout rate, at least 71 patients were required for each randomized group. Ultimately, 142 patients were included in this study.

All analyses followed intention-to-treat principles. Missing data were handled via multiple imputation. SPSS software (version 26.0) was used for data analysis. The normality of the data was assessed using the Shapiro–Wilk normality test. Levene’s test was used to ascertain the homogeneity of variance. Normally distributed measurement data were expressed as mean ± standard deviation (SDs). Non-normally distributed measurement data are expressed as medians (inter-quartile range) and assessed using the Mann–Whitney U-test. Categorical variables are described as numbers (%) and were analyzed using the chi-squared test or Fisher’s exact test. Intergroup comparisons used t-tests or repeated-measures ANOVA. P value < 0.05 was considered statistically significant. Patient characteristics were compared using absolute standardized differences to report the baseline variations. Differences <0.414 were considered acceptable balance, calculated using the method described by Austin.¹⁹

Results

A total of 382 elderly patients who underwent elective total knee arthroplasty under general anesthesia were screened in this study between March 2022 and December 2022. The incidence of frailty was 38.7%, and 142 patients were included in this study. All 142 patients completed the study; however, there were 13 protocol deviations: four patients did not receive the allocated intervention, two patients were lost to follow-up in Group L, three patients did not receive the allocated intervention, and four patients were lost to follow-up in Group H (Figure 1).

Baseline, Intraoperative and Postoperative Characteristics

The baseline characteristics of the patients in both groups were well-balanced and showed no significant differences (Table 1). The intraoperative data are shown in Table 2. No statistically significant differences were observed in anesthesia time, operation time, total anesthetic drugs, or fluid infusion between the two groups (P > 0.05). Nevertheless, a statistically significant difference was observed in the vasoactive drugs used intraoperatively (P < 0.05). Group H used more norepinephrine, whereas Group L used more antihypertensive drugs. Table 2 also describes the postoperative recovery metrics associated with the two groups of patients, assessing the overall quality of postoperative recovery in various aspects. There was no significant difference between the two groups (P > 0.05).

Table 1 Demographic Characteristics and Preoperative Scores

Table 2 Intraoperative Data and Postoperative Recovery Profiles

TWA-MAP²⁰ was calculated as the area under the curve of the MAP measurements divided by the total measurement time. The TWA-MAP was 93.1 ±2.29 mmHg in Group H and 78.6 ±2.97 mmHg in Group L (P < 0.05, mean difference 95% CI −14.5 (−15.4, −13.6)). Figure 2 depicts the intraoperative MAP of the two groups of patients, with statistically significant differences in MAP at different intraoperative time points.

Figure 2 Comparison of MAP at different intraoperative time points between the two groups of patients. Abbreviation: MAP, mean arterial pressure. TWA-MAP, time-weighted average mean arterial pressure. Note: There were statistically significant differences in MAP at different intraoperative time points between the two groups. The TWA-MAP was 93.1 ±2.29 mmHg in Group H and 78.6 ±2.97 mmHg in Group L (P < 0.05, mean difference 95% CI −14.5 (−15.4, −13.6)).

Primary and Secondary Outcomes

Table 3 illustrates the global QoR-15 scores of the patients in both groups preoperatively and within five days postoperatively. The global QoR-15 scores on POD1 were significantly lower than the preoperative scores in both the groups. However, changes over time were not significantly different between the groups. There was no statistically significant difference in QoR-15 scores between the two groups both preoperatively and postoperatively (P > 0.05). The difference in QoR-15 values on POD1 between Groups L and H was not statistically significant (mean [SD] 99 [9.89] vs 98 [12.82], mean difference confidence interval (CI) 0.91 (−3.08–4.91)). In both groups, there were no significant interactions between group and time for the total QoR-15 score or the five dimensions of QoR-15. Figure 3 depicts the global QoR-15 and five-dimensional scores both before and five days after surgery.

Table 3 Primary and Secondary Outcomes

Figure 3 Global score and five dimensional scores of QoR-15 preoperatively and five days postoperatively in both groups. (A) Global score of QoR-15; Five dimensional scores of QoR-15: (B) Emotional state, (C) Physical comfort, (D) Psychological support, (E) Physical Independence, (F) Pain. Abbreviation: QoR-15, quality of recovery-15. Note: There were no significant interactions between group and time for the total QoR-15 score or the five dimensions of QoR-15.

There was no statistically significant difference in AMTS scores at 30 days and 1-year postoperatively between the two groups. Nevertheless, a greater proportion of patients in Group H exhibited scores below 6, a difference that was statistically significant at 30 days postoperatively (P < 0.05, mean difference 95% CI 0.169 (0.039, 0.289)). At 1-year postoperative follow-up, one patient in Group H died. The remaining secondary outcomes were not statistically significantly different (Table 3).

Discussion

The objective of this study was to compare the overall functional recovery of elderly frailty patients who underwent total knee arthroplasty with different levels of intraoperative blood pressure regulation. To the best of our knowledge, no studies have investigated the effect of intraoperative blood pressure on QoR in elderly frailty patients undergoing general anesthesia. The global QoR-15 score on POD 1 was 99 in Group L and 98 in Group H, with no statistical difference between the two groups and no significant group-time interaction effect.

According to a previous study²¹ investigating the effects of different blood pressure management protocols on QoR in elderly patients undergoing prolonged gynecological laparoscopic oncologic surgery, the overall QoR-40 score was significantly higher in the precision blood pressure management protocol at 24 h postoperatively than in the conventional blood pressure management protocol (P <0.001). The difference in outcomes between our study and that study may be due to the surgical approach, duration of surgery, and the blood pressure regulation protocol. Given that our study was a total knee surgery, the postoperative pain was greater compared with surgeries in other studies. Furthermore, the subjective perception of pain differed between studies, which had an impact on QoR-15 scores and may explain the difference in the statistical results.

In our study, a straightforward FRAIL scale was utilized to identify patients exhibiting defined frailty.²² The FRAIL scale is a tool for assessing frailty based on five components: fatigue, resistance, ambulation, illness, and loss of weight.²³ Each of the components was scored with one point for the presence or 0 for absence, for a total score ranging from 0 to 5. A score of 3 to 5 indicates frailty. Wang H et al²⁴ found that the prevalence of frailty in patients undergoing elective total joint arthroplasty, as assessed using the FRAIL scale, was 22.9%. In contrast, although the same FRAIL scale was used for frailty screening in the present study, the prevalence of frailty was 38.7%. The following reasons may be responsible for the observed differences. First, the types of surgeries included in the two studies differed. The study by Wang et al included patients with total hip and knee replacements, whereas our study only explored patients who underwent total knee replacement. The prevalence of frailty varies across socio-economic groups.²² Thirdly, the prevalence of frailty in older adults varies considerably across different study designs, including community samples, specialty clinics, and hospital settings.²⁵

Hypotensive anesthesia reduces blood loss and transfusions while improving surgical visibility in orthopedics, but significant blood pressure fluctuations may raise postoperative risks. Evidence suggests MAP thresholds impact outcomes: one retrospective study linked MAP <55 mmHg with cardiac/renal complications,²⁶ while an RCT found optimal outcomes at 80–95 mmHg versus higher or lower ranges. In addition, it must be acknowledged that the definition of hypotension was not standardized in the current study,²⁷ and all components of blood pressure can be used to define hypotension. However, the association between a mean arterial pressure below 65 mmHg and adverse outcomes has been widely established.

Some studies have suggested that hypotension differs from hypoperfusion, as organ perfusion depends on perfusion pressure, vascular resistance, and autoregulation.^28,29 Moreover, to maintain the target MAP in this study, many vasoactive drugs have been used to alter vascular resistance, which also affects organ perfusion and self-regulatory capacity. Therefore, the MAP of the two groups of patients in this study may not be representative of the actual level of organ perfusion. This may explain why there was no difference in the incidence of MINS and AKI in the postoperative period.

Healthy human functioning depends on an integrated network of several physiological systems (cardiovascular, metabolic, neuroendocrine, respiratory, and immune), so that the organism can maintain homeostasis against internal and external stressors. Frailty is a physiological state of impaired homeostasis, characterized by a multisystem reduction in reserve capacity and a loss of physiological complexity, which heightens vulnerability to stressors beyond the effect of chronological age alone.²⁹ Frailty stems from impaired regulatory network connectivity, specifically weakened feedback and feed-forward mechanisms, which reduces homeostatic resilience.³⁰ The current studies indicated that there was a reduction in the regulation of blood pressure in frail patients and that instability of blood pressure may be a marker of the frail state.^31,32 Consequently, our focus was on such patients and the identification of management measures that could enhance QoR. Nevertheless, FRAIL scale-stratified analysis revealed no significant association between intraoperative BP management and postoperative hospitalization duration or complications in frail patients. Furthermore, Mascha EJ et al conducted a retrospective analysis of 104,401 patients who underwent noncardiac surgery.³³ Their findings indicated that the 30-day mortality curve declined sharply with increasing TWA-MAP when the TWA-MAP was less than 85 mmHg. However, beyond this point, the curve gradually increased again, which may indicate that an optimal intraoperative blood pressure value that is either too high or too low is not conducive to postoperative recovery. In this study, the TWA-MAP of the two groups of patients was 85 mmHg on both sides. This may be one reason why the between-group comparison of QoR-15 scores in this study was not statistically significant.

This study has some limitations. First, the QoR-15 scale only considered the situation within five days after surgery and did not focus on the differences in the changes observed over the longer term after surgery. Second, this was a small sample, single-center study, and the findings may not be generalizable to other populations. Third, the study did not detect changes in the levels of frailty-associated cellular inflammatory factors, which may have resulted in the omission of some differences at the cellular level. Fourth, other known risk factors and their interactions with the frailty status were not assessed.

Conclusions

Under these conditions, MAP targets did not significantly alter recovery. Thus, patient frailty appears to be a more dominant predictor of outcomes than blood pressure management.

Abbreviations

MAP, Mean arterial pressure; QoR-15, Quality of Recovery-15; POD, Postoperative day; TWA-MAP, Time-weighted average mean arterial pressure; AMTS, Abbreviated mental test score; MINS, Myocardial injury after noncardiac surgery; AKI, Acute kidney injury; ERAS, Enhanced recovery after surgery; TKA, Total knee arthroplasty; QoR, Quality of postoperative recovery; ASA, American Society of Anesthesiologists; BIS, Bispectral index; PACU, Post-anesthesia care unit; SD, Standard deviation.

Data Sharing Statement

The datasets used and analyzed during the study are available from the corresponding author upon reasonable request.

Ethics Approval and Informed Consent

This randomized controlled trial adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Lianyungang Clinical College of Nanjing Medical University (identifier: KF-20211008001-02). This study obtained informed consent from all participants.

Acknowledgments

We wish to thank all the anesthesiologists and surgical teams for their support in this study. Also, we would like to express our sincere gratitude to Mr. Caifeng Wang for his valuable contributions to the revision of our manuscript, particularly in refining the figure formats and improving the textual details.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

This work was supported by Jiangsu Province Key Laboratory of Anesthesiology (201922), Lianyungang Science and Technology Project (JCYJ2305), and Zhongda Hospital Affiliated to Southeast University, Jiangsu Province High-Level Hospital Pairing Assistance Construction Funds (zdlyg14).

Disclosure

The authors declare that they have no competing interests in this section.

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13. Wessels E, Perrie H, Scribante J, et al. Quality of recovery following orthopedic surgery in patients at an academic hospital in South Africa. Anesthesia Analg. 2021;133:507–514. doi:10.1213/ANE.0000000000005594

14. Odor PM, Chis Ster I, Wilkinson I, Sage F. Effect of admission fascia iliaca compartment blocks on post-operative abbreviated mental test scores in elderly fractured neck of femur patients: a retrospective cohort study. BMC Anesthesiol. 2017;17(1):2. doi:10.1186/s12871-016-0297-8

15. Sheehan B. Assessment scales in dementia. Ther Adv Neurol Disord. 2012;5(6):349–358.

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17. Ruetzler K, Smilowitz NR, Berger JS, et al. Diagnosis and management of patients with myocardial injury after noncardiac surgery: a scientific statement from the american heart association. Circulation. 2021;144:144. doi:10.1161/CIRCULATIONAHA.120.052788

18. PS M, DB M, Galagher W, et al. Minimal clinically important difference for three quality of recovery scales. Anesthesiology. 2016;125:39–45. doi:10.1097/ALN.0000000000001158

19. Austin PC. Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity‐score matched samples. Stat Med. 2009;28:3083–3107. doi:10.1002/sim.3697

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21. Lan J, Lu X, Zhou X, et al. The influence of different blood pressure management schemes on the quality of postoperative anesthesia recovery in elderly patients undergoing long-time gynecological laparoscopic tumor surgery. Zhonghua Yi Xue Za Zhi. 2023;103:1296–1302. doi:10.3760/cma.j.cn112137-20221202-02557

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Shares of Sandisk climbed Friday as the data storage company joined the benchmark S&P 500 index.

Sandisk’s (SNDK) stock jumped close to 11% Friday morning before paring back much of its early gains. Its shares, which have been lifted by demand driven by the AI boom, are among the hottest around this year; the company was spun off from Western Digital (WDC) in February, and the stock is up more than 500% since. The company’s market capitalization is above $31 billion, according to Visible Alpha data.

The spot in the S&P 500 was available because of the completion of Omnicom Group’s (OMC) acquisition of Interpublic Group (IPG) earlier this week. The two previous companies to join the index, Solstice Advance Materials (SOLS) and Qnity (Q), were also the products of spinoffs.

Investors generally cheer the addition of companies’ shares to the S&P 500 and other major indexes, which is seen as giving them a short-term bump. Read Investopedia’s full coverage of today’s holiday-shortened trading here.

A few other index changes are also happening today. PTC Therapeutics (PTCT) is taking Sandisk’s spot in the S&P SmallCap 600; Upwork (UPWK) is also joining that index, replacing Premier, which was taken private.

This article originally appeared on OncLive®.

Use of a sequential “sandwich” strategy using CD22/CD19 chimeric antigen receptor (CAR) T-cell therapy followed by autologous stem cell transplant (ASCT) resulted in deep and durable remissions in patients with newly diagnosed Philadelphia chromosome (Ph)–negative B-cell acute lymphoblastic leukemia (B-ALL) who were unable to undergo or declined allogeneic hematopoietic stem cell transplant (allo-HSCT), according to findings from a phase 2 single-center study (NCT05470777).¹

Findings published in Cancer demonstrated that at a median follow-up of 28 months (range, 10-50), evaluable patients (n = 37) achieved a median overall survival (OS) and leukemia-free survival (LFS) that had not yet been reached. The 2-year OS rate was 97% (95% CI, 90%-100%), and the 2-year LFS rate was 72% (95% CI, 58%-90%). MRD clearance deepened throughout treatment.

Following induction chemotherapy, 92% of patients experienced a complete remission (CR), 54% had a multiparameter flow cytometry minimal residual disease (MFC-MRD)–negative CR, and no patients achieved next-generation sequencing (NGS) MRD–negative CR. After consolidation chemotherapy, 80% of evaluable patients (n = 35) remained in CR, 71% had an MFC-MRD–negative CR, and 23% (n = 5 of 22) had an NGS-MRD–negative CR. After the first CD22/CD19 CAR T-cell therapy infusion, all patients achieved MFC-MRD–negative CR, and 68% achieved NGS-MRD–negative CR. Following ASCT and a second CAR T-cell infusion, all patients remained in MFC-MRD–negative CR, and 93% achieved NGS-MRD–negative CR (n = 25 of 27).

Among the 35 patients who completed the full treatment sequence, all remained alive at the last follow-up, and most sustained durable MRD-negative remissions beyond 1 and 2 years. Survival outcomes were comparable across standard- and high-risk genetic subgroups, and although patients with residual NGS-detectable disease prior to transplantation were associated with a trend toward shorter LFS, this difference was not statistically significant.

“The CD22/CD19 CAR T-cells and [ASCT] sandwich strategy is a promising approach for treating Ph-negative B-ALL in adolescent/young adult [AYA] and adult patients, offering high efficacy with a favorable safety profile,” lead study author Chong-Sheng Qian, MD, PhD, of the Research Center for Hematologic Diseases at the Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, in Suzhou, China, and colleagues wrote in the publication. “Future studies with larger sample sizes and longer follow-up are warranted to further validate these findings and further explore allo-HSCT–free strategies.”

What was the design of the study?

This investigation was a phase 2, single-arm, open-label study conducted at a single center and approved by the institutional review board of the First Affiliated Hospital of Soochow University.^1,2 The study enrolled newly diagnosed AYA and adult patients with Ph-negative B-ALL who had CD19 and CD22 expression by MFC. Eligible patients were either unable to undergo allo-HSCT or declined transplantation.

The primary end point was overall survival, measured from the first day of the initial CAR T-cell infusion. Secondary end points included LFS, MRD-negativity rate and duration, incidence of adverse effects (AEs) following first CAR T-cell therapy infusion, and non-relapse mortality.¹ Exploratory analyses assessed survival outcomes of the studied “sandwich” CAR T-based strategy in comparison with an external cohort of patients who received allo-HSCT.

According to the study protocol, patients received induction and consolidation therapy prior to CAR T-cell sequencing. After induction and lymphocyte recovery, peripheral blood lymphocytes were collected via leukapheresis to manufacture CAR T cells. CD22- and CD19-directed CAR T cells were infused sequentially at a dose of 5 × 10⁶ cells/kg as the first infusion. Autologous stem cell mobilization and collection occurred 6 to 8 weeks later, followed by conditioning with a modified BuCy26 regimen and ASCT. A second course of CD22/CD19 CAR T cells was administered 2 days after ASCT. No maintenance therapy was used following the second CAR T-cell therapy infusion, except tyrosine kinase inhibitors for patients with Ph-like ALL harboring ABL-class fusions.

Per protocol, patients with MRD progression after the first CAR T-cell therapy infusion discontinued the sandwich approach and were considered for allo-HSCT or individualized salvage therapy.

What were the baseline patient characteristics of those patients enrolled?

A total of 38 patients were screened for eligibility, of whom 37 were enrolled; one patient was excluded due to active hepatitis B. The median age at enrollment was 28 years (range, 15-60 years), and 35% of the cohort were older than 35 years of age. Elevated baseline disease burden was observed in a subset of patients, with 6 individuals (16%) presenting with a white blood cell count of more than 30 × 10⁹/L at diagnosis. Most patients (89%) had Ph-negative B-ALL, and 4 patients (11%) were classified as having Ph-like B-ALL, including 2 with ABL-class alterations and 2 with JAK-STAT pathway abnormalities. Based on National Comprehensive Cancer Network genetic risk stratification criteria, 21 patients (57%) were categorized as high-risk, including those with adverse genetic features such as TP53 mutations, complex karyotypes, or ZNF384 rearrangements.

Of the 37 enrolled patients, 35 successfully completed the full sandwich strategy. One patient with Ph-like B-ALL in the ABL class did not receive the protocol-specified TKI, representing a protocol deviation. Two patients experienced relapse following the first CAR T-cell therapy infusion and therefore did not proceed with the remainder of the sandwich approach; both subsequently underwent allo-HSCT.

What was the safety profile observed in the study?

The safety profile of the sequential CD22/CD19 CAR T-cell therapy and ASCT was consistent with expected toxicities of CAR T-cell therapy and high-intensity chemotherapy, with no unexpected signals. All patients experienced grade 3/4 hematologic toxicities, which reflected the treatment intensity; after the second CAR T-cell infusion, the median duration of neutropenia was 11 days, and thrombocytopenia lasted a median of 15 days.

Cytokine release syndrome (CRS) was generally mild: grade 1/2 CRS occurred in 22% of patients following the first CAR T-cell therapy infusion and in 34% of patients following the second infusion; no cases of grade 3 or higher CRS or immune effector cell–associated neurotoxicity syndrome were reported. No patients experienced severe organ toxicity. B-cell aplasia, a pharmacodynamic marker of CAR T-cell activity, was observed in all patients and persisted for a median of 170 days after the second infusion. Infectious complications included 2 cases of sepsis and 2 pulmonary infections, all of which were managed clinically. Importantly, no non-relapse mortality occurred.

References

1. Qian, C, Wang Z, Li Z, et al. A phase 2 trial of a “sandwich” strategy: sequential CD22/CD19 chimeric antigen receptor T‐cells therapy combined with autologous hematopoietic stem cell transplantation in patients with Philadelphia chromosome–negative B‐cell acute lymphoblastic leukemia. Cancer. 2025;131(22):e70168-e70168. doi10.1002/cncr.70168
2. CD22/CD19 CAR-T and auto-HSCT sandwich strategy as consolidation therapy for B-ALL. ClinicalTrials.gov Updated June 5, 2025. Accessed November 11, 2025. https://clinicaltrials.gov/study/NCT05470777

What’s going on here?

China and Hong Kong stocks are on track to end the week higher, powered by a sharp rebound in artificial intelligence (AI) and tech names, even as property developers and some consumer brands weigh on the rally.

What does this mean?

China’s CSI 300 and Shanghai Composite indexes both edged higher on Friday, extending their weekly gains, and Hong Kong’s Hang Seng Index is still up for the week despite a small daily dip. The real action has been in AI and tech: onshore AI-related stocks have surged about 6.5% this week after four straight weeks of losses, and Hong Kong–listed tech heavyweights have climbed nearly 4%. That suggests investors are leaning back toward growth and innovation plays as major indexes approach multi-year highs. Local broker Huaxi Securities expects that tilt to continue, projecting that by 2026 China’s market will be dominated by technology and high-dividend stocks – but also that higher indexes will come with sharper swings, making entry timing and technical signals more important. The rally still has weak spots, though: sportswear makers Anta Sports and Li Ning slipped after a Reuters report said they were among firms exploring a potential takeover of struggling German brand Puma, and state-backed developer Vanke’s Hong Kong shares fell nearly 2% to a record low on renewed debt-restructuring worries, echoed by softer bond prices.

Why should I care?

The bigger picture: Tech advances while traditional sectors struggle

Hong Kong’s market reflects a clear divide between digital winners and old-economy losers. The Hang Seng sits 33.34% higher than a year ago, though it’s slipped 1.46% over the past month. This week’s trading range—between 25,862 and 26,089—shows the market taking a breather after its big run. Tech and digital infrastructure companies attract buyer interest, while property and traditional sectors face headwinds. Long Forecast models suggest the index will trade sideways through 2028 before any meaningful breakout. Investors are voting with their wallets, backing companies with strong business models and avoiding those tied to yesterday’s economic playbook.

Zooming in: Markets wait for Beijing’s next move

The Hang Seng added just 18 points on November 27, trading in a tight range between 25,862 and 26,089 this week. Most investors are sitting on their hands until China’s Central Economic Work Conference in December. Beijing did announce plans to boost consumption—including rural consumer goods upgrades and support for pet-related sectors (yes, really)—but these moves barely rippled the market. Until the conference delivers concrete policy signals, expect more of the same quiet trading. The market’s essentially in wait-and-see mode, with any big moves likely on hold until Beijing shows its cards.