Pressure induces peritoneal fibrosis and inflammation through CD44 signaling.

Peritoneal dialysis (PD) is a widely used sustainable kidney replacement therapy. Prolonged use of PD fluids is associated with mesothelial-mesenchymal transition, peritoneal fibrosis, and eventual ultrafiltration (UF) failure. However, the impact of pressure on the peritoneum remains unclear. In the present study, we hypothesized increased pressure is a potential contributing factor to peritoneal fibrosis and investigated the possible mechanisms. In vitro experiments found that pressurization led to a mesenchymal phenotype, the expression of fibrotic markers and inflammatory factors in human mesothelial MeT-5A cells. Pressure also increased cell proliferation and augmented cell migration potential in MeT-5A cells. The mouse PD model and human peritoneum equilibrium test (PET) data both showed a positive association between higher pressure and increased small solute transport, along with decreased net UF. Mechanistically, we found that significant upregulation of CD44 in mesothelial cells upon pressurization. Notably, the treatment of CD44 neutralizing antibodies prevented pressure-induced phenotypic changes in mesothelial cells, while a CD44 inhibitor oligo-fucoidan ameliorated pressure-induced peritoneal thickening, fibrosis, and inflammation in PD mice. To conclude, intraperitoneal pressure results in peritoneal fibrosis in PD via CD44-mediated mesothelial changes and inflammation. CD44 blockage can be utilized as a novel preventive approach for PD-related peritoneal fibrosis and UF failure.

Continuous cuff pressure control on middle-aged and elderly patients undergoing endoscopic submucosal dissection of the esophagus effect of airway injury.

OBJECTIVE: Assessment of the effect of continuous cuff pressure control on airway injury in middle-aged and elderly patients undergoing endoscopic submucosal dissection (ESD). METHOD: A total of 104 eligible middle-aged and elderly patients requiring esophageal ESD from July 2022-September 2023 at the First Affiliated Hospital of Nanchang University were selected and randomly divided into two groups: the group undergoing general anesthesia tracheal intubation with continuous control of cuff pressure after intubation (Group A, n = 51) and the group undergoing general anesthesia tracheal intubation with continuous monitoring without control of cuff pressure (Group B, n = 53). After endotracheal intubation in Group A, under the guidance of an automatic cuff pressure controller, the air was used to inflate the tracheal cuff until the cuff pressure was 25-30cmH2O. The cuff pressure after intubation was recorded, and then the cuff pressure parameters were directly adjusted in the range of 25-30cmH2O until tracheal extubation after the operation. After endotracheal intubation, patients in Group B inflated the tracheal cuff with clinical experience, then monitored and recorded the cuff pressure with a handheld cuff manometer and instructed the cuff not to be loosened after being connected to the handheld cuff manometer-continuous monitoring until the tracheal extubation, but without any cuff pressure regulation. The patients of the two groups performed esophageal ESD. The left recumbent position was taken before the operation, and the cuff's pressure was recorded. Then, insert the gastrointestinal endoscope to find the lesion site and perform appropriate CO2 inflation to display the diseased esophageal wall for surgical operation fully. After determining the location, the cuff pressure of the two groups was recorded when the cuff pressure was stable. After the operation, the upper gastrointestinal endoscope was removed and the cuff pressure of the two groups was recorded. Postoperative airway injury assessment was performed in both groups, and the incidence of sore throat, hoarseness, cough, and blood in sputum was recorded. The incidence of postoperative airway mucosal injury was also observed and recorded in both groups: typical, episodic congestion spots and patchy local congestion. RESULT: The incidence of normal airway mucosa in Group A was higher than that in Group B (P < 0.05). In comparison, the incidence of occasional hyperemia and local plaque congestion in Group A was lower than in Group B (P < 0.05). CONCLUSION: Continuous cuff pressure control during operation can reduce airway injury in patients with esophageal ESD and accelerate their early recovery after the operation.

Utilization of local pressure devices in pain management during injections: scoping review.

OBJECTIVE: to map scientific evidence regarding the use of local pressure devices in pain relief during injection procedures in patients. METHODS: scoping review, following the recommendations of the JBI Manual for Evidence Synthesis and PRISMA-ScR, with searches conducted in the PubMed, EMBASE, CINAHL, LILACS, and PsycINFO databases, without temporal restrictions and with a cutoff date of March 2023. RESULTS: a total of 1,514 studies were identified, with 20 articles included in the final sample. The ShotBlocker® device was utilized during subcutaneous and intramuscular injections in children and adults, proving beneficial in reducing pain, anxiety, and fear associated with the procedure. FINAL CONSIDERATIONS: the ShotBlocker® is a low-cost, easy-to-use device that can enhance nursing clinical practice during painful procedures. However, studies involving the Brazilian Pikluc® device are scarce. Further research involving both local pressure devices is recommended.

Associations between body mass index and interface pressure after 3 h loading in healthy adults.

AIM OF THE STUDY: The purpose of this study was to determine the associations between body mass index and interface pressure after 3 h loading in healthy adults and to establish a foundation for the development of interventions tailored to body mass index. MATERIAL AND METHODS: A secondary data analysis based on a clinical trial involving 75 adults was conducted. Data were analyzed using descriptive statistics, repeated measure ANOVA, and ANCOVA. The statistics program IBM SPSS Statistics 27.0 was used for data analysis. RESULTS: Loading caused a significant increase in average pressure in the obesity group compared to the underweight group. There was a significant increase in risk area ratio calculated based on 30 mmHg and 45 mmHg in both obesity and overweight groups compared to the underweight group. On both support surfaces, average pressure, peak pressure, and risk area ratio were higher in the obese group compared to the normal weight group. However, these differences were not statistically significant. CONCLUSION: Given the emphasized risk of pressure injuries, long-term observation of body mass index-specific changes in interface pressure can provide crucial evidence for pressure injury prevention nursing. The results of this study suggest the need to implement pressure injury prevention interventions that consider the pressure characteristics according to BMI.

Risk factor evaluation of cuff pressure of >30 cmH2O to stop air leakage during mechanical ventilation: A prospective observational study.

AIM: The commonly recommended endotracheal tube cuff pressure is 20-30 cmH2O. However, some patients require a cuff pressure of >30 cmH2O to prevent air leakage. The study aims to determine the risk factors that contribute to the endotracheal tube cuff pressure of >30 cmH2O to prevent air leakage. DESIGN: A multi-centre prospective observational study. METHODS: Eligible patients undergoing mechanical ventilation in the intensive care unit of three hospitals between March 2020 and July 2022 were included. The endotracheal tube cuff pressure to prevent air leakage was determined using the minimal occlusive volume technique. The patient demographics and clinical information were collected. RESULTS: A total of 284 patients were included. Among these patients, 55 (19.37%) patients required a cuff pressure of >30 cmH2O to prevent air leakage. The multivariate logistic regression results revealed that the surgical operation (odds ratio [OR]: 8.485, 95% confidence interval [CI]: 1.066-67.525, p = 0.043) was inversely associated with the endotracheal tube cuff pressure of >30 cmH2O, while the oral intubation route (OR: 0.127, 95% CI: 0.022-0.750, p = 0.023) and cuff inner diameter minus tracheal area (OR: 0.949, 95% CI: 0.933-0.966, p < 0.001) were negatively associated with the endotracheal tube cuff pressure of >30 cmH2O. Therefore, a significant number of patients require an endotracheal tube cuff pressure of ＞30 cmH2O to prevent air leakage. Several factors, including the surgical operation, intubation route, and difference between the cuff inner diameter and tracheal area at the T3 vertebra, should be considered when determining the appropriate cuff pressure during mechanical ventilation.

Prediction of tissue deformation based on mechanical and physiological factors in the prone position during surgery.

AIM: This study aimed to predict tissue deformation based on the pressure applied while lying in the prone position and physiological factors. METHODS: Healthy volunteers were instructed to lie on mattresses of four different hardness levels (50, 87.5, 175, and 262.5 N). The order in which the mattresses were used was randomized per participant. Pressure at the iliac crests was measured using a pressure mapping sensor sheet. Participants were placed in the prone position for 10 min, with pressure data used from the latter 5 min. For the tissue deformation at the iliac crests, our previous study data were used. Multiple regression analysis was used to identify predictive mechanical and physiological factors. RESULTS: The distance between the left and right greater trochanters, maximum interface pressure and age were significant predictors for compression of the skin and soft tissue. Significant predictors of internal soft tissue displacement were the distances between the left and right anterior superior iliac spines and greater trochanters. No factors predicted skin surface displacement. CONCLUSIONS: Our study provided predictive factors that may be measured easily in a clinical setting to reduce the risk of pressure ulcers during surgery in the prone position.

Red light photobiomodulation rescues murine brain mitochondrial respiration after acute hypobaric hypoxia.

Low-level laser therapy, or photobiomodulation, utilizes red or near-infrared light for the treatment of pathological conditions due to the presence of intracellular photoacceptors, such as mitochondrial cytochrome c oxidase, that serve as intermediates for the therapeutic effects. We present an in-detail analysis of the effect of low-intensity LED red light irradiation on the respiratory chain of brain mitochondria. We tested whether low-level laser therapy at 650 nm could alleviate the brain mitochondrial dysfunction in the model of acute hypobaric hypoxia in mice. The irradiation of the mitochondrial fraction of the left cerebral cortex with low-intensity LED red light rescued Complex I-supported respiration during oxidative phosphorylation, normalized the initial polarization of the inner mitochondrial membrane, but has not shown any significant effect on the activity of Complex IV. In comparison, the postponed effect (in 24 h) of the similar transcranial irradiation following hypoxic exposure led to a less pronounced improvement of the mitochondrial functional state, but normalized respiration related to ATP production and membrane polarization. In contrast, the similar irradiation of the mitochondria isolated from control healthy animals exerted an inhibitory effect on CI-supported respiration. The obtained results provide significant insight that can be beneficial for the development of non-invasive phototherapy.

Critical Pressure of Intramural Delamination in Aortic Dissection.

Computational models of aortic dissection can examine mechanisms by which this potentially lethal condition develops and propagates. We present results from phase-field finite element simulations that are motivated by a classical but seldom repeated experiment. Initial simulations agreed qualitatively and quantitatively with data, yet because of the complexity of the problem it was difficult to discern trends. Simplified analytical models were used to gain further insight. Together, simplified and phase-field models reveal power-law-based relationships between the pressure that initiates an intramural tear and key geometric and mechanical factors-insult surface area, wall stiffness, and tearing energy. The degree of axial stretch and luminal pressure similarly influence the pressure of tearing, which was ~88 kPa for healthy and diseased human aortas having sub-millimeter-sized initial insults, but lower for larger tear sizes. Finally, simulations show that the direction a tear propagates is influenced by focal regions of weakening or strengthening, which can drive the tear towards the lumen (dissection) or adventitia (rupture). Additional data on human aortas having different predisposing disease conditions will be needed to extend these results further, but the present findings show that physiologic pressures can propagate initial medial defects into delaminations that can serve as precursors to dissection.

Identification of Risk Factors for Intraoperative Acquired Pressure Injury in Patients Undergoing Neurosurgery: A Retrospective Single-Center Study.

BACKGROUND Risk factors for intraoperative acquired pressure injury (IAPI) in patients undergoing various surgical procedures have been described in previous studies. However, whether risk factors for IAPI in patients undergoing neurosurgery differ remains unknown. The aim of the present study was to explore independent risk factors for IAPI in patients undergoing neurosurgery. MATERIAL AND METHODS Data from 465 patients who underwent neurosurgery between October 2017and December 2018 and who were at high risk of IAPIs were retrospectively analyzed. Independent risk factors for IAPI were evaluated using univariate and multivariate logistic regression models. RESULTS Sixty-nine IAPIs (14.8%) in 465 patients undergoing neurosurgery were assessed. Multivariate logistic regression analyses showed that being overweight (odds ratio [OR] 2.685; 95% confidence interval [CI] 1.206-5.975; P=0.016), prone position (OR 7.502, 95% CI 2.470-22.787. P<0.001), lateral position (OR 15.301, 95% CI 4.903-47.753, P<0.001), use of a head frame (OR 3.716, 95% CI 1.431-9.653, P=0.007), surgical times of 4 to 8 h (OR 7.276, 95% CI 2.249-23.542, P<0.001), and surgical times ≥8 h (OR 173.248, 95% CI 32.629-919.896, P<0.001) all were associated with an increased risk of IAPI in patients undergoing neurosurgery. The factors associated with reduced risk of IAPI were high serum albumin levels (OR 0.099, 95% CI 0.016-0.608, P=0.013) and use of memory sponge pads (OR 0.064, 95% CI 0.020-0.202, P<0.001). CONCLUSIONS The present study indicates that being overweight, prone and lateral positioning, use of a head frame, and longer surgical times are associated with an increased risk of IAPI in patients undergoing neurosurgery. Prospective studies should be conducted to verify these findings and consideration should be given to use of these factors in clinical practice to identify high-risk patients.

Myopalladin knockout mice develop cardiac dilation and show a maladaptive response to mechanical pressure overload.

Myopalladin (MYPN) is a striated muscle-specific immunoglobulin domain-containing protein located in the sarcomeric Z-line and I-band. MYPN gene mutations are causative for dilated (DCM), hypertrophic, and restrictive cardiomyopathy. In a yeast two-hybrid screening, MYPN was found to bind to titin in the Z-line, which was confirmed by microscale thermophoresis. Cardiac analyses of MYPN knockout (MKO) mice showed the development of mild cardiac dilation and systolic dysfunction, associated with decreased myofibrillar isometric tension generation and increased resting tension at longer sarcomere lengths. MKO mice exhibited a normal hypertrophic response to transaortic constriction (TAC), but rapidly developed severe cardiac dilation and systolic dysfunction, associated with fibrosis, increased fetal gene expression, higher intercalated disc fold amplitude, decreased calsequestrin-2 protein levels, and increased desmoplakin and SORBS2 protein levels. Cardiomyocyte analyses showed delayed Ca2+ release and reuptake in unstressed MKO mice as well as reduced Ca2+ spark amplitude post-TAC, suggesting that altered Ca2+ handling may contribute to the development of DCM in MKO mice.

Selective Inhibition of NLRP3 Inflammasome Reverses Pressure Overload-Induced Pathological Cardiac Remodeling by Attenuating Hypertrophy, Fibrosis, and Inflammation.

Activation of the NLRP3 inflammasome promotes pathological cardiac remodeling induced by pressure overload. However, the therapeutic effects of NLRP3 inhibition after cardiac remodeling remain unknown. The present study aimed to investigate whether the selective NLRP3 inhibitor, MCC950, could reverse transverse aortic constriction (TAC)-induced cardiac remodeling. Mice were divided into four groups based on the treatment given: sham, sham + MCC950, TAC, and TAC + MCC950. MCC950 (10 mg/kg, intraperitoneal injection, once per day) was administered from two weeks after TAC or sham surgery for four weeks. Echocardiography, histological analysis, RT-PCR, and Western blotting were performed to explore the function of MCC950 after TAC. We found that MCC950 reversed cardiac dysfunction after TAC. MCC950 attenuated cardiac hypertrophy by down-regulating calcineurin expression and inhibiting MAPK activation. Further, it also alleviated cardiac fibrosis post-TAC by inhibiting the TGF-ß/Smad4 pathway, and reduced cardiac inflammation and macrophage infiltration post-TAC, including both M1 and M2 macrophages. Taken together, MCC950 can attenuate cardiac remodeling due to pressure overload by inhibiting hypertrophy, fibrosis, and inflammation. Our study provides a basis for the clinical application of NLRP3 inhibitors in the treatment of non-ischemic heart failure.

Pressure-Measuring Devices for Compression Therapy in Venous Leg Ulcers: A Comprehensive Review.

OBJECTIVE: To investigate the evolution of pressure-measuring devices used in compression treatment for venous leg ulcers and assess the most practical and effective devices to determine optimal pressure in compression therapy. DATA SOURCES: Relevant information was retrieved from databases including Google Scholar, PubMed, Wiley Online, and ScienceDirect without publication date restrictions. The keywords included venous leg ulcer, compression therapy, pressure measuring device, pressure sensor, and wireless system. STUDY SELECTION: Studies included in the review had to be published in English and discuss or compare pressure-measuring devices/sensors for compression therapy, the development of alternative sensors, and the applications of wireless technologies. Veterinary studies, conference proceedings, and unpublished articles were excluded. Applicable studies and articles were critically evaluated and synthesized. DATA EXTRACTION: After abstract review, 39 studies were identified. During full-text review, study details were collected using a data extraction form and organized into tables. Device attributes, accuracy, price, and limitations were categorized and analyzed. DATA SYNTHESIS: Studies disagree on the effectiveness and user-friendliness of existing pressure-measuring devices. These devices often impact user comfort and convenience, which are crucial factors in the adoption and use of wearable devices. Potential solutions for pressure-measuring devices with promising technologies were proposed: four feasible alternative sensors are described that could improve comfort and facilitate prolonged use under bandages. Advanced communication technologies may provide more convenience for users and practitioners. CONCLUSIONS: Conventional pressure-measuring devices used in compression therapy are not designed for the user's comfort and convenience. The use of flexible and stretchy pressure sensors (e-skin) provides good biocompatibility, conformability, and comfort and when integrated with near-field communication technology could address the drawbacks of current pressure-measuring devices.

Mechanical Pressure Driving Proteoglycan Expression in Mammographic Density: a Self-perpetuating Cycle?

Regions of high mammographic density (MD) in the breast are characterised by a proteoglycan (PG)-rich fibrous stroma, where PGs mediate aligned collagen fibrils to control tissue stiffness and hence the response to mechanical forces. Literature is accumulating to support the notion that mechanical stiffness may drive PG synthesis in the breast contributing to MD. We review emerging patterns in MD and other biological settings, of a positive feedback cycle of force promoting PG synthesis, such as in articular cartilage, due to increased pressure on weight bearing joints. Furthermore, we present evidence to suggest a pro-tumorigenic effect of increased mechanical force on epithelial cells in contexts where PG-mediated, aligned collagen fibrous tissue abounds, with implications for breast cancer development attributable to high MD. Finally, we summarise means through which this positive feedback mechanism of PG synthesis may be intercepted to reduce mechanical force within tissues and thus reduce disease burden.

Evaluation of pain susceptibility by taking blood pressure in patients with infections: A prospective comparative study.

ABSTRACT: Pain sensitization leading to polyalgia can be observed during infectious diseases. The blood pressure cuff-evoked pain threshold (BPCEPT) has been used in previous studies as a screening tool for fibromyalgia.We aimed to use the BPCEPT as a screening test for detecting pain sensitization in patients suffering from infectious diseases. We also investigated whether specific factors were associated with pain sensitization.We performed a prospective comparative study including all patients of our infectious diseases center in a 1-year period. We created a positive control group of patients suffering from fibromyalgia and a negative control group of "apparently healthy" patients consulting for vaccination.The blood pressure (BP) cuff was inflated until the patient signaled that they experienced pain, and this pressure value was noted.A total of 2355 patients were included. The positive control group had significantly lower values of the BPCEPT than all other groups. Among hospitalized patients with infectious diseases, a low BPCEPT was significantly associated with high temperature (P < .0001), older age (P = .002), being a woman (P = .004), high serum glutamic-oxaloacetic transaminase (P = .007), and high C reactive protein levels (P = .02). Moreover, in multivariate analysis, respiratory infection, meningitis, urinary tract infection, febrile neutropenia, and Q fever were independently associated with a low BPCEPT. A significant negative dynamic correlation between the BPCEPT and temperature was also observed (P < .001).We demonstrated for the first time in a large sample of patients that the BPCEPT method can be used to detect pain susceptibility. We observed a significant dynamic correlation between pain sensitization and temperature. Additionally, pain sensitization was associated with some diseases, suggesting that they trigger pain sensitivity.

The effect of total compression time and rate (slope) of compression on the incidence of symptomatic Eustachian tube dysfunction and middle ear barotrauma: a Phase II prospective study.

Eustachian tube dysfunction (ETD) and middle ear barotrauma (MEB) are common reported complications during hyperbaric oxygen treatment. Our Phase I study data was the first to demonstrate a statistically significant decrease in the occurrence of symptomatic ETD and MEB. The Phase I Trial suggested the total time interval and rate (slope) of compression (ROC) may be a determining factor in ETD and MEB. This Phase II study investigates an optimal rate of compression to reduce ETD and MEB when considering each multiplace treatment (with multiple patients) as the unit of observation as a group, rather than for each individual patient. Data were collected prospectively on 1,244 group patient-treatment exposures, collectively including 5,072 individual patient-treatment/exposures. We randomly assigned patient-treatment group exposures to four different time interval and rate (slope) of compression. These compression rates and slopes were identical to those used in the Phase I trial. All patients experiencing symptoms of MEB requiring compression stops were evaluated post treatment for the presence of ETD and MEB using the O'Neill Grading System (OGS) for ETD. Data were analyzed using the IBM-SPSS statistical software program. A statistically significant decrease in the number of compression holds was observed in the 15-minute compression schedule, correlating to the results observed in the Phase I trial. The 15-minute linear compression profile continues to demonstrate the decreased need for patient symptomatic compression stops (as in the Phase I trial) using a USN TT9 during elective hyperbaric oxygen treatments in a Class A multiplace hyperbaric chamber. Trial Registration: ClinicalTrials.gov Identifier: NCT04776967.