Autophagy perturbation represents an emerging therapeutic strategy in cancer. Although LATS1 and LATS2 kinases, core components of the mammalian Hippo pathway, have been shown to exert tumor ...suppressive activities, here we report a pro-survival role of LATS1 but not LATS2 in hepatocellular carcinoma (HCC) cells. Specifically, LATS1 restricts lethal autophagy in HCC cells induced by sorafenib, the standard of care for advanced HCC patients. Notably, autophagy regulation by LATS1 is independent of its kinase activity. Instead, LATS1 stabilizes the autophagy core-machinery component Beclin-1 by promoting K27-linked ubiquitination at lysine residues K32 and K263 on Beclin-1. Consequently, ubiquitination of Beclin-1 negatively regulates autophagy by promoting inactive dimer formation of Beclin-1. Our study highlights a functional diversity between LATS1 and LATS2, and uncovers a scaffolding role of LATS1 in mediating a cross-talk between the Hippo signaling pathway and autophagy.
Relatively little is known about the characteristics of patients who visit the emergency department (ED) for an acute allergic reaction. Although anaphylaxis guidelines suggest treatment with ...epinephrine, teaching about self-injectable epinephrine, and referral to an allergist, current ED management remains uncertain.
The objective of this study was to describe the management of food-related acute allergic reactions.
The Multicenter Airway Research Collaboration performed a chart review study in 21 North American EDs. Investigators reviewed a random sample of 678 charts of patients who presented with food allergy (International Classification of Diseases–ninth revision codes 693.1, 995.0, 995.3, and 995.60-995.69).
Patients had an average age of 29 years; the cohort was 57% female and 40% white. A variety of foods provoked the allergic reaction, including nuts (21%), crustaceans (19%), fruit (12%), and fish (10%). Although exposure to these foods can be life threatening, only 18% of patients came to the ED by ambulance. In the ED, 72% of patients received antihistamines, 48% received systemic corticosteroids, and 16% received epinephrine; 33% received respiratory treatments such as inhaled albuterol. Among patients with severe reactions (55% of total), 24% received epinephrine. Overall, 97% of patients were discharged to home. At ED discharge, 16% of patients were prescribed self-injectable epinephrine, and 12% were referred to an allergist.
Although guidelines suggest specific approaches for the management of acute allergic reactions, ED concordance for food allergy appears low. These findings support a new collaboration between professional organizations in allergy and emergency medicine and the development of educational programs and materials for ED patients and staff.
Background
Previous studies have shown that, overall, quality of life (QoL) decreases within the first 3–6 months after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + ...HIPEC), returning to baseline levels by 6–12 months. This systematic review aims to evaluate the factors affecting QoL after CRS + HIPEC within 12 months of surgery.
Methods
Electronic databases were investigated searching for articles reporting QoL with validated questionnaires up to September 2019. Risk of bias was assessed with the methodological index for non-randomized studies tool. The primary outcomes were short-term (< 6 months after surgery) and medium-term (6–12 months after surgery) determinants of QoL after CRS + HIPEC. Secondary outcomes were QoL and reported symptoms over time.
Results
We included 14 studies that used 12 different questionnaires. The reported data were collected prospectively or retrospectively for 1556 patients (dropout < 50% in four studies). Overall, studies showed diminished QoL within 3 months after surgery and a recovery to baseline or greater by 12 months. QoL was negatively influenced by higher age, female sex, prolonged operation time, extensive disease, residual disease, adjuvant chemotherapy, complications, stoma placement, and recurrent disease. QoL results were comparable between studies, with dropout rates above and below 50%.
Conclusions
QoL returns to baseline levels within 12 months after CRS + HIPEC provided the disease does not recur, and this recovery process is influenced by several factors.
Enhanced recovery after surgery protocols emphasize the importance of early postoperative mobilization. However, literature quantifying actual physical activity after major abdominal cancer surgery ...is scarce and inconclusive.
A single-center prospective cohort study was conducted at the University Medical Center Groningen from 2019 to 2021. Patients’ postoperative physical activity was measured using an accelerometer, with the primary aim of assessing daily physical activity. Secondary aims were identifying patient-related factors associated with low physical activity and studying the consequences of low physical activity in terms of complication rate and length of hospital stay.
143 patients included (48 % male; mean age 65 years), 38.5 %, 24.5 %, 19.6 %, and 14 % underwent pancreatic, hepatic, colorectal, or cytoreductive surgery with hyperthermic intraperitoneal chemotherapy, respectively. Median daily step count was low; from median 71 steps on the first to 918 steps on the seventh postoperative day. An association between physical activity and age (OR 3.597, p = 0.013), preoperative weight loss ≥10 % (OR 4.984, p = 0.004), Eastern Cooperative Oncology Group performance status ≥2 (OR 4.016, p = 0.001), midline laparotomy (OR 2.851, p = 0.025), and operation duration (OR 1.003, p = 0.044) was found. An association was observed between physical activity and the occurrence of complications (OR 3.197, p = 0.039) and prolonged hospital stay (β 4.068, p = 0.013).
Postoperative physical activity is low in patients undergoing major abdominal cancer surgery and is linked to postoperative outcomes. Although physical activity should be encouraged in all patients, patient-specific risk factors were identified that can aid early recognition of patients at risk of low physical activity.
Near-infrared spectroscopy (NIRS) has experienced widespread use as an analytical tool in the last 3 decades. Researchers today are exploring ways of applying NIRS that expand beyond compositional ...analyses into process control. Processes such as meat tenderness evaluation, curd cutting, and dough mixing have traditionally been controlled by highly skilled master craftsmen; new NIRS research applications are demonstrating that these complex processes can be monitored and controlled in situ to produce consistent, high quality end products with online NIRS technology. Additionally, researchers also now have the potential ability to develop new nondestructive spectroscopic techniques to probe the underlying molecular evolution of these products during processing.
Generalized loss of muscle mass is associated with increased morbidity and mortality in patients with cancer. The gold standard to measure muscle mass is by using computed tomography (CT). However, ...the aim of this prospective observational cohort study was to determine whether point-of-care ultrasound (POCUS) could be an easy-to-use, bedside measurement alternative to evaluate muscle status. Patients scheduled for major abdominal cancer surgery with a recent preoperative CT scan available were included. POCUS was used to measure the muscle thickness of mm. biceps brachii, mm. recti femoris, and mm. vasti intermedius 1 day prior to surgery. The total skeletal muscle index (SMI) was derived from patients’ abdominal CT scan at the third lumbar level. Muscle force of the upper and lower extremities was measured using a handheld dynamometer. A total of 165 patients were included (55% male; 65 ± 12 years). All POCUS measurements of muscle thickness had a statistically significant correlation with CT-derived SMI (r ≥ 0.48; p < 0.001). The strongest correlation between POCUS muscle measurements and SMI was observed when all POCUS muscle groups were added together (r = 0.73; p < 0.001). Muscle strength had a stronger correlation with POCUS-measured muscle thickness than with CT-derived SMI. To conclude, this study indicated a strong correlation between combined muscle thickness measurements performed by POCUS- and CT-derived SMI and measurements of muscle strength. These results suggest that handheld ultrasound is a valid tool for the assessment of skeletal muscle status.
A search for mixing between active neutrinos and light sterile neutrinos has been performed by looking for muon neutrino disappearance in two detectors at baselines of 1.04 and 735 km, using a ...combined MINOS and MINOS+ exposure of 16.36×10^{20} protons on target. A simultaneous fit to the charged-current muon neutrino and neutral-current neutrino energy spectra in the two detectors yields no evidence for sterile neutrino mixing using a 3+1 model. The most stringent limit to date is set on the mixing parameter sin^{2}θ_{24} for most values of the sterile neutrino mass splitting Δm_{41}^{2}>10^{-4} eV^{2}.
Skeletal muscle loss is often observed in intensive care patients. However, little is known about postoperative muscle loss, its associated risk factors, and its long-term consequences. The aim of ...this prospective observational study is to identify the incidence of and risk factors for surgery-related muscle loss (SRML) after major abdominal surgery, and to study the impact of SRML on fatigue and survival.
Patients undergoing major abdominal cancer surgery were included in the MUSCLE POWER STUDY. Muscle thickness was measured by ultrasound in three muscles bilaterally (biceps brachii, rectus femoris, and vastus intermedius). SRML was defined as a decline of 10 per cent or more in diameter in at least one arm and leg muscle within 1 week postoperatively. Postoperative physical activity and nutritional intake were assessed using motility devices and nutritional diaries. Fatigue was measured with questionnaires and 1-year survival was assessed with Cox regression analysis.
A total of 173 patients (55 per cent male; mean (s.d.) age 64.3 (11.9) years) were included, 68 of whom patients (39 per cent) showed SRML. Preoperative weight loss and postoperative nutritional intake were statistically significantly associated with SRML in multivariable logistic regression analysis (P < 0.050). The combination of insufficient postoperative physical activity and nutritional intake had an odds ratio of 4.00 (95 per cent c.i. 1.03 to 15.47) of developing SRML (P = 0.045). No association with fatigue was observed. SRML was associated with decreased 1-year survival (hazard ratio 4.54, 95 per cent c.i. 1.42 to 14.58; P = 0.011).
SRML occurred in 39 per cent of patients after major abdominal cancer surgery, and was associated with a decreased 1-year survival.
Cancer survivors with diabetes tend to have worse glycemic control after their cancer diagnosis, which may increase the risk of cardiovascular diseases. We aimed to investigate whether glycemic ...control differs between colorectal cancer (CRC) survivors and those without cancer, among patients with type 2 diabetes being treated in the Dutch primary care. The Zwolle Outpatient Diabetes project Integrating Available Care database was linked with the Dutch Cancer Registry (n = 71,648, 1998–2014). The cases were those with stage 0–III CRC, and the controls were those without cancer history. The primary and secondary outcomes were the probability of reaching the glycated hemoglobin (HbA1c) target and the mean of HbA1c during follow-up, respectively. Mixed linear modeling was applied, where the status of CRC was a time-varying variable. Among the 57,330 patients included, 705 developed CRC during follow-up. The mean probability of reaching the HbA1c target during follow-up was 73% versus 74% (p = 0.157) for CRC survivors versus those without cancer, respectively. The mean HbA1c was 51.1 versus 50.8 mmol/mol (p = 0.045) among CRC survivors versus those without cancer, respectively. We observed a clinically comparable glycemic control among the CRC survivors without cancer, indicating that glycemic control for CRC survivors can be delegated to primary care professionals.
We use 73 h of stereoscopic data taken with the MAGIC telescopes to investigate the very high-energy (VHE) gamma-ray emission of the Crab pulsar. Our data show a highly significant pulsed signal in ...the energy range from 50 to 400 GeV in both the main pulse (P1) and the interpulse (P2) phase regions. We provide the widest spectra to date of the VHE components of both peaks, and these spectra extend to the energy range of satellite-borne observatories. The good resolution and background rejection of the stereoscopic MAGIC system allows us to cross-check the correctness of each spectral point of the pulsar by comparison with the corresponding (strong and well-known) Crab nebula flux. The spectra of both P1 and P2 are compatible with power laws with photon indices of 4.0 ± 0.8 (P1) and 3.42 ± 0.26 (P2), respectively, and the ratio P1/P2 between the photon counts of the two pulses is 0.54 ± 0.12. The VHE emission can be understood as an additional component produced by the inverse Compton scattering of secondary and tertiary e± pairs on IR-UV photons.
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