Impact of the interval between neoadjuvant immunotherapy and surgery on prognosis in esophageal squamous cell carcinoma (ESCC): a real-world study.

BACKGROUND: The time interval between neoadjuvant immunotherapy and surgery is 6 weeks for esophageal squamous cell carcinoma (ESCC), but whether delayed surgery affects prognosis remains unclear. METHODS: Clinical data of locally advanced ESCC who underwent neoadjuvant immunotherapy followed by esophagectomy from November 2019 to December 2022 were collected. The surgery outcomes and prognosis were compared between short-interval (time to surgery ≤ 6 weeks) and long-interval groups (time to surgery > 6 weeks). RESULTS: 152 patients were enrolled totally, with a ratio of 91:61 between short-interval and long-interval groups. The rate of pathological complete response in the short-interval and long-interval groups were 34.1% and 24.6% (P = 0.257). Delayed surgery did not have a significantly impact on the number of lymph node dissections (P = 0.133), operative duration (P = 0.689), blood loss (P = 0.837), hospitalization duration (P = 0.293), chest drainage duration (P = 0.886) and postoperative complications (P > 0.050). The 3-year Overall survival (OS) rates were 85.10% in the short-interval group, and 82.07% in the long-interval group (P = 0.435). The 3-year disease-free survival (DFS) rates were 83.41% and 70.86% in the two groups (P = 0.037). Subgroup analysis revealed that patients with a favorable response to immunotherapy (tumor regression grade 0) exhibited inferior 3-year OS (long-interval vs. short-interval: 51.85% vs. 91.08%, P = 0.035) and DFS (long-interval vs. short-interval: 47.40% vs. 91.08%, P = 0.014) in the long-interval group. CONCLUSIONS: Delayed surgery after neoadjuvant immunotherapy does not further improve pathological response; instead, it resulted in a poorer DFS. Especially for patients with a favorable response to immunotherapy, delayed surgery increases the risk of mortality and recurrence.

Local Confinement Effects of Block Copolymers Driving Self-Assembly of Nanoparticles into Discrete Pancake-Shaped Superlattices.

The utilization of polymer conformations to construct a variety of superlattices is a common method within the field. However, this technique often results in only long-range ordering rather than the formation of distinct superlattices. In this study, a well-organized array of discrete pancake-shaped superlattices (DPSs) is successfully obtained through the utilization of air-liquid interface self-assembly, facilitated by the confined environment created by a block copolymer. It is crucial to note that both the self-assembly behavior and resulting morphologies of the DPSs can be precisely tuned by adjusting several experimental parameters, most notably the concentration and molecular architecture of the block copolymers. Furthermore, this work provides valuable insights into the formation processes and mechanisms underpinning the DPSs. The approach described here is both straightforward and efficacious, establishing a strong foundation for subsequent research and the development of non-close-packed superlattice structures.

Intracerebral Nanoparticle Transport Facilitated by Alzheimer Pathology and Age.

Nanoparticles have emerged as potential transporters of drugs targeting Alzheimer's disease (AD), but their design should consider the blood-brain barrier (BBB) integrity and neuroinflammation of the AD brain. This study presents that aging is a significant factor for the brain localization and retention of nanoparticles, which we engineered to bind with reactive astrocytes and activated microglia. We assembled 200 nm-diameter particles using a block copolymer of poly(lactic-co-glycolic acid) (PLGA) and CD44-binding hyaluronic acid (HA). The resulting PLGA-b-HA nanoparticles displayed increased binding to CD44-expressing reactive astrocytes and activated microglia. Upon intravascular injection, nanoparticles were localized to the hippocampi of both APP/PS1 AD model mice and their control littermates at 13-16 months of age due to enhanced transvascular transport through the leaky BBB. No particles were found in the hippocampi of young adult mice. These findings demonstrate the brain localization of nanoparticles due to aging-induced BBB breakdown regardless of AD pathology.

Correlation between depression and intimacy in lung cancer patients and their family caregivers.

BACKGROUND: Cancer impacts both patients and their family caregivers. This study aimed to explore the interdependence between depression and intimacy in lung cancer patients and their family caregivers, providing the basis for developing a patient-caregiver centered dyadic intervention. METHODS: This cross-sectional study recruited 182 dyads of lung cancer patients and their family caregivers using a convenient sampling. The depression subscale of the Hospital Anxiety and Depression Scale (HADS) and the Mutuality Scale (MS) were used to measure participants' depression and intimacy respectively; and the correlation between depression and intimacy in patients and caregivers was analyzed by establishing the actor-partner interdependence model. RESULTS: Thirty four percent of the patients and 19.2% of the caregivers were at risk of depression, with an intimacy score of 2.67 ± 0.74 points and 2.6 ± 0.86 points, respectively; Pearson correlation analysis showed that there was a positive correlation between the depression score (r = 0.226, P < 0.01) and intimacy score (r = 0.344, P < 0.01) in patients and caregivers; and the results of actor-partner interdependence model showed that caregivers' depression had an actor effect on their own intimacy (b = -0.054, P = 0.004) as well as a partner effect on patients' intimacy (b = -0.041, P = 0.011). However, patients' depression has no influence on the intimacy of patients or caregivers. CONCLUSIONS: There is an interdependent relationship between depression and intimacy in lung cancer patients and family caregivers. Therefore, dyadic interventions can help them to cope with cancer together.

Model-based roentgen stereophotogrammetric analysis using elementary geometrical shape models: 10 years results of an uncemented acetabular cup component.

BACKGROUND: Non-cemented acetabular cup components demonstrated different clinical performance depending on their surface texture or bearing couple. However, clinical osseointegration needs to be proved for each total joint arthroplasty (TJA) design. Aim of this study was to detect the in vivo migration pattern of a non-cemented cup design, using model-based roentgen stereophotogrammetric analysis with elementary geometrical shape models (EGS-RSA) to calculate early cup migration. METHODS: Interchangeable applicability of the model-based EGS-RSA method next to gold standard marker-based RSA method was assessed by clinical radiographs. Afterwards, in vivo acetabular cup migration for 39 patients in a maximum follow up of 120 months (10 years) was calculated using model-based EGS-RSA. RESULTS: For the axes with the best predictive capability for acetabular cup loosening, mean (±SD) values were calculated for migration and rotation of the cup. The cup migrated 0.16 (±0.22) mm along the cranio-caudal axis after 24 months and 0.36 (±0.72) mm after 120 months, respectively. It rotated - 0.61 (±0.57) deg. about the medio-lateral axis after 24 months and - 0.53 (±0.67) deg. after 120 months, respectively. CONCLUSIONS: Interchangeable applicability of model-based EGS-RSA next to gold standard marker-based RSA method could be shown. Model-based EGS-RSA enables an in vivo migration measurement without the necessity of TJA specific surface models. Migration of the investigated acetabular cup component indicates significant migration values along all the three axes. However, migration values after the second postoperative year were within the thresholds reported in literature, indicating no risk for later aseptic component loosening of this TJA design.

Patient-Family Caregiver Concordance of Symptom Assessment for Esophageal Cancer Patients Undergoing Esophagectomy.

BACKGROUND: Esophageal cancer patients suffer from multiple and severe symptoms during the postoperative recovery period. Family caregivers play a vital role in assisting patients to cope with their symptoms. OBJECTIVE: To examine the concordance of esophageal cancer patients and their caregivers on assessing patients' symptoms after surgery and identify predictors associated with the symptom concordance. METHODS: In this cross-sectional study, 213 patient-caregiver dyads completed general information questionnaires, the Memorial Symptom Assessment Scale, the Depression Subscale of Hospital Anxiety and Depression Scale, the Mutuality Scale, and the Zarit Burden Interview (for caregivers). Data were analyzed using intraclass correlation coefficients, paired t tests, and binary logistic regression. RESULTS: At the dyad level, agreement of patients' and caregivers' reported symptoms ranged from poor to fair. At the group level, patients reported significantly higher scores than caregivers in most symptoms. Of the 213 dyads, 119 (55.9%) were identified as concordant on symptom assessment. Patients' nasogastric tube, perceived mutuality, caregivers' educational background, and dyad's communication frequency with each other could predict their concordance of symptom assessment. CONCLUSIONS: There were relatively low agreements between esophageal cancer patients and caregivers on assessing patients' symptoms, and caregivers tended to underestimate patients' symptoms. The dyad's symptom concordance was influenced by patient-, caregiver-, and dyad-related factors. IMPLICATIONS FOR PRACTICE: Having an awareness of the incongruence on assessing symptoms between esophageal cancer patients and caregivers may help healthcare professionals to comprehensively interpret patients' symptoms and develop targeted dyadic interventions to improve their concordance, contributing to optimal symptom management and health outcomes.

Incidence and risk factors of postoperative nausea and vomiting in lung cancer patients following lobectomy and application of analgesic pumps.

OBJECTIVE: To investigate the occurrence rate and risk factors of postoperative nausea and vomiting (PONV) in lung cancer patients following lobectomy and application of analgesic pumps. METHODS: This retrospective study reviewed clinical data from patients that had undergone lobectomy for lung cancer under general anaesthesia. The risk factors of PONV were analysed using binary logistic regression models. RESULTS: A total of 203 patients (97 females) were enrolled. The rate of PONV was 29.6% (60 of 203 patients) for all patients, 42.3% (41 of 97 patients) for female patients and 17.9% (19 of 106 patients) for male patients. Female patients undergoing thoracotomy (odds ratio [OR] 7.770, 95% confidence interval [CI] 1.747, 34.568) or having surgery durations ≥120 min (OR 4.493, 95% CI 1.502, 12.851) were significantly more susceptible to PONV. The risk of PONV in female patients that received postoperative dolasetron (100 mg, once a day) was significantly lower (OR 0.075, 95% CI 0.007, 0.834). For male patients, the risk of PONV was significantly lower in those with a body mass index ≥24 kg/m2 (OR 0.166; 95% CI 0.035, 0.782). CONCLUSION: Female and male patients have different risk factors for PONV following lobectomy for lung cancer and application of analgesic pumps.

Shear-Resistant, Biological Tethering of Nanostimulators for Enhanced Therapeutic Cell Paracrine Factor Secretion.

Mesenchymal stromal cells (MSCs) secreting multiple growth factors and immunomodulatory cytokines are promising for regenerative medicine. To further enhance their secretory activity, efforts have emerged to tether nanosized carriers of secretory stimuli, named nanostimulators, to the MSC surface by forming nonchemical bonds. Despite some successes, there is a great need to improve the retention of nanostimulators during transport through a syringe needle, where high shear stress exerted on the cell surface separates them. To this end, we hypothesize that poly(lactic-co-glycolic acid)-block-hyaluronic acid (PLGA-HA) conjugated with integrin-binding RGD peptides, denoted PLGA-HA-RGD, can form nanostimulators that remain on the cell surface stably during the injection. The resulting HA-CD44 and RGD-integrin bonds would synergistically increase the adhesion strength of nanostimulators. Interestingly, nanostimulators prepared with PLGA-HA-RGD show 3- to 6-fold higher retention than those made with PLGA-HA. Therefore, the PLGA-HA-RGD nanostimulators induced MSCs to secrete 1.5-fold higher vascular endothelial growth factors and a 1.2-fold higher tissue inhibitor of matrix metalloproteinase-1 as compared to PLGA-HA nanostimulators. Consequently, MSCs tethered with PLGA-HA-RGD nanostimulators served to stimulate endothelial cell activities to form a blood vessel-like endothelial lumen with increased length and number of junctions. The nanostimulator design strategy would also be broadly applicable to regulate, protect, and home a broad array of therapeutic or immune cells by tethering carriers with bioactive molecules of interest.

Follow-up study on symptom distress in esophageal cancer patients undergoing repeated dilation.

BACKGROUND: Repeated endoscopic probe dilatation is the most preferred treatment for esophageal stenosis which may cause high levels of symptom distress in the patient's home rehabilitation stage. AIM: To explore the changes in the symptom distress level and its correlation with the dilation effect in patients with esophageal carcinoma undergoing repeated dilations for lumen stenosis. METHODS: The difference (R2-R1) between the diameter of the esophageal stenosis opening (R1) of the patients before dilation (R1) and after dilation (R2) was calculated to describe the extent and expansion of the esophageal stenosis before and after dilation. The M.D. Anderson Symptom Inventory was used to describe the symptom distress level of patients with dilation intermittence during their stay at home and to explore the correlation between the dilation effect and symptom distress level. RESULTS: The diameter of the esophagus (R1) increased before each dilation in patients undergoing esophageal dilation (P < 0.05). The diameter (R2) increased after dilation (P < 0.05); the dilation effect (R2-R1) decreased with the number of dilations (P < 0.05). The total symptom distress score significantly increased with the number of dilations (P < 0.05). The symptom distress scores of the patients were negatively correlated (P < 0.05) with the previous dilation effect (R2-R1) and the esophageal diameter (R2) after the previous dilation. After the 1st to 4th dilations, the patient's symptom distress score was negatively correlated with the esophageal diameter (R12) before the next dilation, while there was no significant correlation (P > 0.05) with the other dilations. CONCLUSION: In patients who have undergone repeated dilations, better effect stands for lower symptom distress level and the increase in symptom distress has a prompt effect on the severity of the next occurrence of restenosis.

Surface Tethering of Inflammation-Modulatory Nanostimulators to Stem Cells for Ischemic Muscle Repair.

Stem cell transplantation has been a promising treatment for peripheral arterial diseases in the past decade. Stem cells act as living bioreactors of paracrine factors that orchestrate tissue regeneration. Prestimulated adipose-derived stem cells (ADSCs) have been proposed as potential candidates but have been met with challenges in activating their secretory activities for clinical use. Here, we propose that tethering the ADSC surface with nanoparticles releasing tumor necrosis factor α (TNFα), named nanostimulator, would stimulate cellular secretory activity in situ. We examined this hypothesis by complexing octadecylamine-grafted hyaluronic acid onto a liposomal carrier of TNFα. Hyaluronic acid increased the liposomal stability and association to CD44 on ADSC surface. ADSCs tethered with these TNFα carriers exhibited up-regulated secretion of proangiogenic vascular endothelial growth factor and immunomodulatory prosteoglandin E2 (PGE2) while decreasing secretion of antiangiogenic pigment epithelium-derived factors. Accordingly, ADSCs tethered with nanostimulators promoted vascularization in a 3D microvascular chip and enhanced recovery of perfusion, walking, and muscle mass in a murine ischemic hindlimb compared to untreated ADSCs. We propose that this surface tethering strategy for in situ stimulation of stem cells would replace the costly and cumbersome preconditioning process and expedite clinical use of stem cells for improved treatments of various injuries and diseases.

Catalytic microgelators for decoupled control of gelation rate and rigidity of the biological gels.

Fibrin gels have been extensively used for three-dimensional cell culture, bleeding control, and molecular and cell therapies because the fibrous networks facilitate biomolecular and cell transport. However, a small window for gelation makes it difficult to handle the gels for desired preparation and transport. Several methods developed to control gelation rates often alter the microstructure, thereby affecting the mechanical response. We hypothesized that a particle designed to discharge thrombin cargos in response to an external stimulus, such as H2O2, would provide control of the gelation rate over a broad range while strengthening the gel. We examined this hypothesis by assembling poly (lactic-co-glycolic acid) (PLGA) particles loaded with thrombin and MnO2 nanosheets that decompose H2O2 to O2 gas. The resulting particles named as catalytic microgelator were mixed with fibrinogen solution or blood containing 0.2mM H2O2. Due to the increased internal pressure, these particles released a 3-fold larger mass of thrombin than PLGA particles loaded only with thrombin. As a consequence, catalytic microgelators increased the gelation time by one order of magnitude and the elastic modulus by a factor of two compared with the fibrin gel formed by directly mixing fibrinogen and thrombin in solution. These catalytic microgelators also served to clot blood, unlike PLGA particles loaded with thrombin. The resulting blood clot was also more rigid than the blood clot formed by thrombin solution. The results of this study would serve as a new paradigm in controlling gelation kinetics of pre-gel solution and mechanical properties of the post-gel matrix.

Surface tethering of stem cells with H2O2-responsive anti-oxidizing colloidal particles for protection against oxidation-induced death.

Mesenchymal stem cells are the new generation of medicine for treating numerous vascular diseases and tissue defects because of their ability to secrete therapeutic factors. Poor cellular survival in an oxidative diseased tissue, however, hinders the therapeutic efficacy. To this end, we hypothesized that tethering the surface of stem cells with colloidal particles capable of discharging antioxidant cargos in response to elevated levels of hydrogen peroxide (H2O2) would maintain survival and therapeutic activity of the stem cells. We examined this hypothesis by encapsulating epigallocatechin gallate (EGCG) and manganese oxide (MnO2) nanocatalysts into particles comprising poly(d,l-lactide-co-glycolide)-block-hyaluronic acid. The MnO2 nanocatalysts catalyzed the decomposition of H2O2 into oxygen gas, which increased the internal pressure of particles and accelerated the release of EGCG by 1.5-fold. Consequently, stem cells exhibited 1.2-fold higher metabolic activity and 2.8-fold higher secretion level of pro-angiogenic factor in sub-lethal H2O2 concentrations. These stem cells, in turn, performed a greater angiogenic potential with doubled number of newly formed mature blood vessels. We envisage that the results of this study will contribute to improving the therapeutic efficacy of a wide array of stem cells.

Diatom Microbubbler for Active Biofilm Removal in Confined Spaces.

Bacterial biofilms form on and within many living tissues, medical devices, and engineered materials, threatening human health and sustainability. Removing biofilms remains a grand challenge despite tremendous efforts made so far, particularly when they are formed in confined spaces. One primary cause is the limited transport of antibacterial agents into extracellular polymeric substances (EPS) of the biofilm. In this study, we hypothesized that a microparticle engineered to be self-locomotive with microbubbles would clean a structure fouled by biofilm by fracturing the EPS and subsequently improving transports of the antiseptic reagent. We examined this hypothesis by doping a hollow cylinder-shaped diatom biosilica with manganese oxide (MnO2) nanosheets. In an antiseptic H2O2 solution, the diatoms doped by MnO2 nanosheets, denoted as diatom bubbler, discharged oxygen gas bubbles continuously and became self-motile. Subsequently, the diatoms infiltrated the bacterial biofilm formed on either flat or microgrooved silicon substrates and continued to generate microbubbles. The resulting microbubbles merged and converted surface energy to mechanical energy high enough to fracture the matrix of biofilm. Consequently, H2O2 molecules diffused into the biofilm and killed most bacterial cells. Overall, this study provides a unique and powerful tool that can significantly impact current efforts to clean a wide array of biofouled products and devices.

Migration measurement of the cemented Lubinus SP II hip stem - a 10-year follow-up using radiostereometric analysis.

In a previous radiostereometric analysis (RSA) of the Lubinus SP II (Link, Hamburg, Germany), which is one of the most often used cemented hip stems worldwide, our research group detected a very small but statistically significant distal migration of -0.03±0.17 mm 2 years after surgery compared to the postoperative radiograph. Maximum subsidence occurred between 6 and 12 months. The implant appeared to have stabilized after 2 years. The mean value of maximum total point motion (MTPM) was 0.99±0.69 mm, which was detected 2 years after surgery. The purpose of this study was to analyze the migration pattern and to verify the predictive value of short-term RSA of the Lubinus SP II stem after 10 years. After a follow-up of 5 and 10 years, 38 and 27 out of 100 patients remained available for further assessment, respectively. No statistically significant implant translation or rotation was found along or about the axes of the global coordinate system 5 and 10 years after surgery with respect to the postoperative radiograph. Furthermore, the MTPM was stable in both follow-up periods. The results suggest that the Lubinus SP II hip stem is still stable 10 years after surgery, supporting that determining prognosis by short-term RSA follow-up of 2 years could be an appropriate tool for appraisal of implant behavior 10 years after surgery.

Radiostereometric migration analysis of the Cerafit femoral stem: 28 patients followed for 2 years.

Radiostereometric analysis (RSA) is the gold standard evaluating micromovements after total hip arthroplasty. The aim of this study was to investigate the migratory pattern of an uncemented femoral stem during the first 2 years after surgery. We followed 28 patients with a mean age of 57 (SD 13) years for the first two postoperative years. Radiostereometric analysis was used to measure the translation and rotation of the femoral component. The Harris hip score (HHS) was determined to evaluate the clinical outcome. No stem had to be revised. The mean HHS advanced from 35 (SD 11) preoperative to 89 (SD 10) 1 year after surgery. At the end of the observation period, mean subsidence of the stem was 0.26 mm (SD 0.82). Maximum total point motion (MTPM) was 1.23 mm (SD 1.22). The main distal migration took place up to 6 weeks after surgery with nearly no further subsidence up to 2 years postoperatively. All the measured migrations of the hip stem were very small. Results of the HHS demonstrate good clinical outcome. Long-term RSA is necessary to assess possible late migration of the Cerafit standard femoral stem.