The hepatocyte epidermal growth factor receptor (EGFR) pathway regulates the cellular interactome within the liver fibrotic niche.

Liver fibrosis is the consequence of chronic liver injury in the presence of an inflammatory component. Although the main executors of this activation are known, the mechanisms that lead to the inflammatory process that mediates the production of pro-fibrotic factors are not well characterized. Epidermal growth factor receptor (EGFR) signaling in hepatocytes is essential for the regenerative processes of the liver; however, its potential role in regulating the fibrotic niche is not yet clear. Our group generated a mouse model that expresses an inactive truncated form of the EGFR specifically in hepatocytes (ΔEGFR mice). Here, we have analyzed the response of WT and ΔEGFR mice to chronic treatment with carbon tetrachloride (CCl4), which induces a pro-inflammatory and fibrotic process in the liver. The results indicated that the hallmarks of liver fibrosis were attenuated in CCl4-treated ΔEGFR mice when compared with CCl4-treated WT mice, coinciding with a faster resolution of the fibrotic process and ameliorated damage. The absence of EGFR activity in hepatocytes induced changes in the pattern of immune cells in the liver, with a notable increase in the population of M2 macrophages, more related to fibrosis resolution, as well as in the population of lymphocytes related to eradication of the damage. Transcriptome analysis of hepatocytes, and secretome studies of extracellular media from in vitro experiments, allowed us to elucidate the specific molecular mechanisms regulated by EGFR that mediate hepatocyte production of both pro-fibrotic and pro-inflammatory mediators; these have consequences for the deposition of extracellular matrix proteins, as well as for the immune microenvironment. Overall, our study uncovered novel mechanistic insights regarding EGFR kinase-dependent actions in hepatocytes that reveal its key role in chronic liver damage. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Early expression of monomeric and oligomeric alpha-synuclein and reduction of tyrosine hydroxylase following intranigral injection of lipopolysaccharide.

BACKGROUND: The insoluble tangles of alpha-synuclein (α-syn) protein in the nigrostriatal circuit, characteristic of synucleinopathy, originate from low molecular weight oligomers, whose appearance and dissemination are related to neuroinflammation. These oligomeric forms of α-syn are considered highly cytotoxic but transient, so knowing the timing in which they appear remains challenging. Therefore, this study aimed to analyze the abundance of oligomeric forms of α-syn and tyrosine hydroxylase (TH) between 3 and 7 days after inducing neuroinflammation with lipopolysaccharide (LPS). METHODS AND RESULTS: LPS (2.5 µg/2.5 µL) was stereotaxically injected in the substantia nigra (SN) of adult male Wistar rats, which were sacrificed 3, 5 and 7 days after this intervention. The brains were processed for semi quantitative Western blot, along with brains from control and sham animals. Our results show an increased expression of α-syn monomer (15 kDa) only 3 days after LPS infusion, and the formation of 50 KDa and 60 kDa α-syn oligomers in the SN and striatum (STR) between 3 and 7 days after LPS infusion. Furthermore, the presence of these oligomers was accompanied by a decrease in the expression of nigral TH. CONCLUSION: These findings highlight the rapidity with which potentially toxic forms of α-syn appear in the nigrostriatal circuit after a neuroinflammatory challenge, in addition to allowing us to identify specific oligomers and a temporal relation with neurodegeneration of TH-positive cells. Knowledge of the timing and location in which these small oligomers appear is essential to developing therapeutic strategies to prevent its formation.

An extract of Hibiscus sabdariffa improves short-term memory in rats with experimental diabetic hyperglycemia.

BACKGROUND: Calyxes of Hibiscus sabdariffa (Hs) contain anthocyanins, that normalize blood glucose levels (BGL) in diabetic patients. Diabetes also causes memory alterations, which could hypothetically decrease with the consumption of Hs. OBJECTIVES: To investigate the effect of dietary supplementation with a Hs extract on working memory and BGL in rats. METHODS: Diabetic hyperglycemia (DHG) was induced with streptozotocin (STZ, 55 mg/kg i.p.) in Wistar rats. After 72 h DHG was confirmed, and the consumption of Hs extract began (50 mg/Kg/day). BGL and body weight (BW) were measured at 10, 20 and 30 days after DHG induction in controls and treated animals. Learning and short-term memory were evaluated after 30 days with Novel Object Recognition Test (NOR) and Barnes Maze (BM). The gross hippocampal structure was histologically analyzed. RESULTS: STZ-treated animals presented low BW and persistent DHG (BGL <300 mg/dL). Diabetic animals consuming the Hs extract had a dual response: some showed BGL comparable to controls, while others had levels comparable to diabetic animals not consuming extract. Diabetic animals that consumed the Hs extract had a better performance in NOR and BM than the diabetic animals not consuming the extract. At the histological level, hippocampal morphological differences were observed between diabetic animals that consumed the extract and those that did not. DISCUSSION: The Hs extract used here could be a good co-adjuvant in the treatment of DHG, aimed at mitigating memory deficits and high BGL. These beneficial effects could be attributed to the anthocyanin content in the extract.

Efficacy of Hypothermic Compression Bandages in Cardiac Device Surgical Wounds: A Randomized Controlled Trial.

BACKGROUND: Pocket hematoma is the most prevalent complication with cardiac implantable electronic devices (CIEDs), especially in patients who are undergoing oral anticoagulation and/or antiplatelet therapy. OBJECTIVE: To evaluate the efficacy of hypothermic compression bandaging versus conventional compression bandaging for the prevention of surgical wound hematoma of CIEDs in patients who are undergoing chronic anticoagulant drug use and/or antiplatelet therapy. METHODS: This was a single-center randomized prospective study. The intervention group received a hypothermic compression bandage, and the control group received a conventional compression bandage. The primary endpoint was the appearance of hematoma 10 days after the intervention. RESULTS: A total of 310 patients participated in the study. The mean age of the participants was 73.77 ± 10.68 years, and 74.8% were men. In the intervention group, 5.88% (n = 18) of patients developed ecchymosis, and 1.3% (n = 4) developed mild hematoma. In the control group, 5.88% (n = 18) of patients developed ecchymosis, and 2.9% (n = 9) developed mild hematoma. No patient in either group had a severe hematoma. No significant differences were observed between the two types of dressing in any of the three degrees of hematoma. CONCLUSIONS: This study demonstrated that compression bandaging with or without hypothermic therapy effectively prevents pocket hematoma of CIEDs in patients at high risk of bleeding.

Assessment of emotional distress in palliative care: Edmonton Symptom Assessment System-revised (ESAS-r) vs Distress Thermometer.

OBJECTIVES: To evaluate the sensitivity and specificity of the Distress Thermometer (DT) as a screening tool for emotional distress in oncological palliative care patients and to compare the DT with the Edmonton Symptom Assessment System-revised (ESAS-r) and the gold standard to determine the most appropriate assessment method in palliative psychological care. METHODS: Data were collected from psychological screening tests (ESAS-r and DT), and clinical interviews (gold standard) were conducted by a clinical psychologist specialist in palliative oncology from January 2021 to January 2022 in an oncology palliative care service. RESULTS: The sample consisted of 356 first-time patients with a diagnosis of advanced cancer in palliative care. The most frequently reported oncological diagnoses were gastrointestinal tract (49.3%) and breast (18.3%). Most patients were female (n = 206; 57.9%), 60.4% were married/with a partner, 55.4% had between 6 and 9 years of schooling, and a median age of 57 (range, 46-65) years. The cutoff of the DT was 5, with a sensitivity of 75.88% and specificity of 54.3%. Emotional problems (sadness and nervousness) had a greater area under the curve (AUC) when measured using the DT than the ESAS-r; however, only in the case of the comparative sadness and discouragement was the difference between the AUC marginally significant. SIGNIFICANCE OF RESULTS: The use of the DT as a screening tool in oncological palliative care is more effective in the evaluation of psychological needs than the ESAS-r. The DT, in addition to evaluation by an expert psychologist, allows for a more comprehensive identification of signs and symptoms to yield an accurate mental health diagnosis based on the International Classification of Diseases-11th Revision and/or Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition.

Integration of the geriatric palliative care in oncological care of elderly patient with cancer.

OBJECTIVES: The objective of this article is to describe the profile of the population attended to by the palliative geriatrics clinic and to evaluate the symptomatic control derived from the care provided. METHODS: During 2017 a model based on a holistic approach was implemented, in this model the team geriatric palliative care plays a fundamental role by being part of the palliative care team and functioning as a liaison with the oncology team and other required services. We outlined the profile of 100 patients aged 70 and older seen between 2017 and 2019 at our geriatric palliative care clinic. Descriptive statistics were used. In addition, the symptoms and the care clinic model effect on the symptomatic control were analyzed, as well as the complexity of patients in palliative care with IDC-Pal. RESULTS: The patients median age was 83.5 years. Patients were classified by type of management: 47% within the supportive care group and 53% with palliative care only; 58% had metastatic disease and 84% presented at least 1 comorbidity. Frailty was observed in 78% and a Karnofsky scale of 60 or less was observed in 59% of the overall population. SIGNIFICANCE OF RESULTS: Elderly cancer patients have a complex profile and may have multiple needs. Integrating geriatric palliative care can help to provide better and personalized care along with symptomatic control. Further studies are required to establish the ideal care model for these patients. Importantly, a personalized treatment with a geriatric palliative care specialist is a key element.

Utilization of medical interventions in hospitalized Mexican adults with cancer at the end of life in a referral hospital: The importance of early palliative care.

OBJECTIVES: To investigate the impact of early vs. late palliative care (PC) on the frequency of admissions to acute hospital settings and the utilization of end-of-life (EoL) interventions in cancer decedents. METHODS: In this single-center, cross-sectional study, we examined the frequency of intensive care unit (ICU) and emergency department (ED) admissions among adult cancer decedents between 2018 and 2022 in a referral hospital in México. Additionally, we assessed EoL medical interventions, categorizing patients into 3 groups: those who received early PC (EPC), late PC (LPC), and those who did not receive PC (NPC). RESULTS: We analyzed data from 1762 patients, averaging 56 ± 16.3 years old, with a predominant representation of women (56.8%). PC was administered to 45.2% of patients, but EPC was limited to only 12.3%. The median time from the initiation of PC to death was 5 days (interquartile range: 2.0-31.5). Hematological malignancies were the most prevalent, affecting 21.5% of patients. EPC recipients demonstrated notable reductions in ICU and ED admissions, as well as diminished utilization of chemotherapy, radiotherapy (RT), antibiotics, blood transfusions, and surgery when compared to both LPC and NPC groups. EPC also exhibited fewer medical interventions in the last 14 days of life, except for RT. SIGNIFICANCE OF RESULTS: The findings of this study indicate that a significant proportion of EoL cancer patients receive PC; however, few receive EPC, emphasizing the need to improve accessibility to these services. Moreover, the results underscore the importance of thoughtful deliberation regarding the application of EoL medical interventions in cancer patients.

Synergistic effect of two formulations of hypochlorous acid in the treatment of 346 chronic ulcers.

Our objective was to assess the efficacy of two successive applications of hypochlorous acid, first as a liquid and then as a gel because liquid hypochlorous acid is effective but has little residual effect, while the gel form has more residual power, and compare it with that of other products. An experimental non-randomised study was carried out, treating 346 chronic ulcers in 220 patients. The antiseptic treatment has been divided into 'hypochlorous acid' (Clortech), 'hypochlorous acid liquid + gel' (Clortech + Microdacyn60R -hydrogel) and 'Others' (Prontosan or Chlorhexidine or Microdacyn60R -hydrogel). Bivariate and multivariate studies analysed the characteristics of the patients and their ulcers, including size, symptoms, signs, treatments received and their duration, and so on. The ulcers were complicated, of long evolution, and most had a vascular origin. On average, antiseptic treatment lasted 14 weeks. At the time of their discharge, or last treatment in the clinics, 59% of the ulcers had healed completely, 9.5% worsened, and 6.9% had become infected during this period. In the bivariate and multivariate studies, we took as reference the 'others' treatments that showed no significant differences in healing time or infection rates compared with liquid hypochlorous acid 100-500 mg/L alone. However, hypochlorous acid liquid + gel showed a synergistic effect, with a higher probability of achieving complete healing (four times) and a lower probability of infection (a fifth), compared to the 'other' antiseptics. In conclusion, a synergistic effect was found with the successive application of hypochlorous acid in liquid followed by gel, an effect that increased healing probability and decreased the risk of the ulcer becoming infected.

Impact of severe lymphopenia on the early prediction of clinical outcome in hospitalized patients with pneumococcal community-acquired pneumonia.

PURPOSE: To evaluate the impact of an optimal and reproducible cutoff value set according to a predefined lymphopenia scale as an early predictor of in-hospital mortality and other outcomes in patients hospitalized with pneumococcal pneumonia and positive urinary antigen at admission to the emergency department. METHODS: An observational cohort study was conducted based on analysis of a prospective registry of consecutive immunocompetent adults hospitalized for pneumococcal pneumonia in two tertiary hospitals. Generalized additive models were constructed to assess the smooth relationship between in-hospital mortality and lymphopenia. RESULTS: We included 1173 patients. Lymphopenia on admission was documented in 686 (58.4%). No significant differences were observed between groups regarding the presence of comorbidities. Overall, 299 (25.5%) patients were admitted to intensive care and 90 (7.6%) required invasive mechanical ventilation. Fifty-nine (5%) patients died, among them 23 (38.9%) in the first 72 h after admission. A lymphocyte count < 500/µL, documented in 282 (24%) patients, was the predefined cutoff point that best predicted in-hospital mortality. After adjustment, these patients had higher rates of intensive care admission (OR 2.9; 95% CI 1.9-4.3), invasive mechanical ventilation (OR 2.2; 95% CI 1.2-3.9), septic shock (OR 1.8; 95% CI 1.1-2.9), treatment failure (OR 2.1; 95% CI 1.2-3.5), and in-hospital mortality (OR 2.2; 95% 1.1-4.9). Severe lymphopenia outperformed PSI score in predicting early and 30-day mortality in patients classified in the higher-risk classes. CONCLUSION: Lymphocyte count < 500/µL could be used as a reproducible predictor of complicated clinical course in patients with an early diagnosis of pneumococcal pneumonia.

Lack of EGFR catalytic activity in hepatocytes improves liver regeneration following DDC-induced cholestatic injury by promoting a pro-restorative inflammatory response.

Despite the well-known hepatoprotective role of the epidermal growth factor receptor (EGFR) pathway upon acute damage, its specific actions during chronic liver disease, particularly cholestatic injury, remain ambiguous and unresolved. Here, we analyzed the consequences of inactivating EGFR signaling in the liver on the regenerative response following cholestatic injury. For that, transgenic mice overexpressing a dominant negative mutant human EGFR lacking tyrosine kinase activity (ΔEGFR) in albumin-positive cells were submitted to liver damage induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), an experimental model resembling human primary sclerosing cholangitis. Our results show an early activation of EGFR after 1-2 days of a DDC-supplemented diet, followed by a signaling switch-off. Furthermore, ΔEGFR mice showed less liver damage and a more efficient regeneration following DDC injury. Analysis of the mechanisms driving this effect revealed an enhanced activation of mitogenic/survival signals, AKT and ERK1/2-MAPKs, and changes in cell turnover consistent with a quicker resolution of damage in response to DDC. These changes were concomitant with profound differences in the profile of intrahepatic immune cells, consisting of a shift in the M1/M2 balance towards M2 polarity, and the Cd4/Cd8 ratio in favor of Cd4 lymphocytes, overall supporting an immune cell switch into a pro-restorative phenotype. Interestingly, ΔEGFR livers also displayed an amplified ductular reaction, with increased expression of EPCAM and an increased number of CK19-positive ductular structures in portal areas, demonstrating an overexpansion of ductular progenitor cells. In summary, our work supports the notion that hepatocyte-specific EGFR activity acts as a key player in the crosstalk between parenchymal and non-parenchymal hepatic cells, promoting the pro-inflammatory response activated during cholestatic injury and therefore contributing to the pathogenesis of cholestatic liver disease. © 2022 The Pathological Society of Great Britain and Ireland.

Incidence of cardiac anomalies in congenital vertebral deformity: systematic review and meta-analysis of 2910 patients.

PURPOSE: This study aimed to analyze the overall incidence of cardiac abnormalities in patients with congenital scoliosis and the possible influencing factors. METHODS: PubMed, Embase, and Cochrane Library were searched for relevant studies. The quality of the studies was assessed independently by two authors using the methodological index for nonrandomized studies (MINORS) criteria. The following data were extracted from the included studies: bibliometric data, number of patients, number of patients with cardiac anomalies, gender, types of deformity, diagnostic method, type of cardiac anomaly, location, and other associated anomalies. The Review Manager 5.4 software was used to group and analyze all the extracted data. RESULTS: This meta-analysis included nine studies and identified that 487 of 2,910 patients with congenital vertebral deformity had cardiac anomalies diagnosed by ultrasound (21.05%, 95% CI of 16.85-25.25%). The mitral valve prolapse was the most frequent cardiac anomaly (48.45%) followed by an unspecified valvular anomaly (39.81) and an atrial septal defect (29.98). A diagnosis of cardiac anomalies was highest in Europe (28.93%), followed by USA (27.21%) and China (15.33%). Females and formation defects were factors significantly associated with increased incidence of cardiac anomalies: 57.37%, 95% CI of 50.48-64.27% and 40.76%, 95% CI of 28.63-52.89%, respectively. Finally, 27.11% presented associated intramedullary anomalies. CONCLUSIONS: This meta-analysis revealed that the overall incidence of cardiac abnormalities detected in patients with congenital vertebral deformity was 22.56%. The incidence rate of cardiac anomalies was higher in females and those with formation defects. The study offers guidance for ultrasound practitioners to accurately identify and diagnose the most common cardiac anomalies.

Meta-analysis on the efficacy and safety of anterior vertebral body tethering in adolescent idiopathic scoliosis.

PURPOSE: In this meta-analysis, we analyzed the efficacy and safety of anterior vertebral body tethering in patients with adolescent idiopathic scoliosis. METHODS: We performed a literature search and analyzed the following data: baseline characteristics, efficacy measures (corrections of the main thoracic curve, proximal thoracic curve, and thoracolumbar curve, thoracic kyphosis, lumbosacral lordosis, rib hump, lumbar prominence and SRS-22 scores, and complications. Analyses were performed with Cochrane's Review Manager version 5.4. RESULTS: Twelve studies met the inclusion criteria. Significant corrections of the main thoracic (MD 22.51, 95% CI 12.93 to 32.09) proximal thoracic (MD 10.14°, 95% CI 7.25° to 13.02°), and thoracolumbar curve (MD 12.16, 95% CI 9.14 to 15.18) were found. No statistically significant corrections were observed on the sagittal plane assessed by thoracic kyphosis (MD - 0.60°, 95% CI - 2.45 to 1.26; participants = 622; studies = 4; I2 = 36%) and lumbosacral lordosis (MD 0.19°, 95% CI - 2.16° to 2.54°). Significant corrections were identified for rib hump (MD 5.26°, 95% CI 4.19° to 6.32°) and lumbar prominence (MD 1.20°, 95% CI 0.27° to 2.13°) at final follow-up. Significant improvements of total SRS-22 score (MD - 0.96, 95% CI - 1.10 to - 0.83) were achieved at final follow-up. The most common complication was overcorrection (8.0%) and tether breakage (5.9%), with a reoperation rate of 10.1%. CONCLUSIONS: Anterior vertebral body tethering is effective to reduce the curve in the coronal plane and clinical deformity. Maximum correction is achieved at one year. The method should, however, be optimized to reduce the rate of complications.

Efficacy of perioperative gabapentin use in patients with idiopathic scoliosis undergoing fusion surgery: a systematic review and meta-analysis.

PURPOSE: This study aimed to assess whether the perioperative use of gabapentin was associated with decreased opioid use. METHODS: A meta-analysis was performed using PubMed, Embase, Scopus, and Cochrane Library. The randomized clinical trials included were focused on patients with adolescent idiopathic scoliosis who underwent posterior fusion surgery and were treated with gabapentin versus placebo medicine. The primary outcomes were opioid consumption at 24, 48, 72, and 96 h; time to introduction of oral medication, length of hospital stay, and period of urinary catheterization were also recorded. Data were combined using the Review Manager 5.4 software. RESULTS: Four randomized clinical trials with a pool of 196 adolescent patients (mean age: 14.8 ± 2.0 years) were included. At 24 and 48 h after surgery, opioid consumption was significantly lower in the gabapentin group: (standardized mean difference [SMD]: -0.50; 95% confidence interval [CI] - 0.79 to - 0.22) and (SMD: - 0.59; 95% CI - 0.88 to - 0.30), respectively. At 72 and 96 h, there were no significant differences between studies: (SMD: - 0.19; 95% CI - 0.52 to 0.13) and (SMD: 0.12; 95% CI - 0.25 to 0.50), respectively. Regarding the administration type, there were significant differences in favor of the 15 mg/kg subgroup with 600 mg at 48 h (SMD: - 0.69; 95% CI - 1.08 to - 0.30). There were no significant differences concerning the time to introduction of oral medication (MD: - 0.08; 95% CI - 0.39 to 0.23), hospitalization time (MD: - 0.12; 95% CI - 0.40 to 0.16), or period of urinary catheterization (SMD: - 0.27; 95% CI - 0.58 to 0.05). CONCLUSIONS: Gabapentin decreased opioid consumption during the first 48 h. Doses of 15 mg/kg showed superiority in reducing opioid consumption in the first 48 h. LEVEL OF EVIDENCE I: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

Long-Term Analysis of Aerosol Concentrations Using a Low-Cost Sensor: Monitoring African Dust Outbreaks in a Suburban Environment in the Canary Islands.

This study presents the results of the long-term monitoring of PM10 and PM2.5 concentrations using a low-cost particle sensor installed in a suburban environment in the Canary Islands. A laser-scattering Nova Fitness SDS011 sensor was operated continuously for approximately three and a half years, which is longer than most other studies using this type of sensor. The impact of African dust outbreaks on the aerosol concentrations was assessed, showing a significant increase in both PM10 and PM2.5 concentrations during the outbreaks. Additionally, a good correlation was found with a nearby reference instrument of the air quality network of the Canary Islands' government. The correlation between the PM10 and PM2.5 concentrations, the effect of relative humidity, and the stability of the sensor were also investigated. This study highlights the potential of this kind of sensor for long-term air quality monitoring with a view to developing extensive and dense low-cost air quality networks that are complementary to official air quality networks.

Validation of the Mexican version of the Schedule of Attitudes Toward Hastened Death in patients undergoing palliative care in Mexico.

OBJECTIVES: The Schedule of Attitudes Toward Hastened Death (SAHD) has emerged as a valid and reliable tool to assess the wish to hasten death (WTHD) among patients diagnosed with advanced cancer; however, the instrument has never been culturally adapted and validated for patients in Mexico. This study sought to validate and abbreviate the SAHD tool for use among patients attending the Palliative Care Service of the Instituto Nacional de Cancerología in Mexico. METHODS: The SAHD was culturally adapted from a previously published validation in patients from Spain. Eligible patients included Spanish literate subjects treated as outpatients in the Palliative Care Service, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-3. Patients were asked to answer the Mexican version of SAHD (SAHD-Mx) instrument and the Brief Edinburgh Depression Scale (BEDS). RESULTS: A total of 225 patients were included in the study. Median positive response in the SAHD-Mx was 2 (range 0-18). Positive correlation was identified between the SAHD-Mx scale and ECOG performance status (r = 0.188, p = 0.005), as well as BEDS (r = 0.567, p < 0.001). SAHD-Mx displayed strong internal consistency (alpha = 0.85) and adequate reliability from test-retest phone interviews (r = 0.567, p < 0.001). Using the confirmatory factor analysis model, a factor was identified and the number of items was reduced to 6, including items 4, 5, 9, 10, 13, and 18. SIGNIFICANCE OF RESULTS: The SAHD-Mx emerges as an adequate tool, with appropriate psychometric characteristics, for assessing WTHD among patients diagnosed with cancer undergoing palliative care in Mexico. .

Short-chain fatty acids during pregnancy in multiple sclerosis: A prospective cohort study.

BACKGROUND AND PURPOSE: Short-chain fatty acids (SCFAs) can have pro- or anti-inflammatory properties, but their relationship with multiple sclerosis (MS) relapses during pregnancy remains unknown. This study aimed to explore SCFA profiles in MS patients during pregnancy and to assess their association with the appearance of relapses during pregnancy and postpartum. METHODS: We prospectively included 53 pregnant MS patients and 21 healthy control women. Patients were evaluated during pregnancy and puerperium. SCFAs were measured by liquid chromatography-mass spectrometry. RESULTS: Sixteen patients (32%) had relapses during pregnancy or puerperium, and 37 (68%) did not. All MS patients showed significant increases in acetate levels during pregnancy and the postpartum period compared to non-MS women. However, propionate and butyrate values were associated with disease activity. Their values were higher in nonrelapsing patients and remained similar to the control group in relapsing patients. The variable that best identified active patients was the propionate/acetate ratio. Ratios of <0.36 during the first trimester were associated with higher inflammatory activity (odds ratio = 165, 95% confidence interval = 10.2-239.4, p < 0.01). Most nonrelapsing patients showed values of >0.36, which were similar to those in healthy pregnant women. CONCLUSIONS: Low propionate/acetate ratio values during the first trimester of gestation identified MS patients at risk of relapses during pregnancy and the postpartum period.

Guselkumab effectiveness and survival in patients with psoriasis and psoriatic arthritis: Multicenter analysis in daily clinical practice by the Spanish Psoriasis Group.

Guselkumab is a monoclonal antibody that selectively blocks the p19 subunit of interleukin 23 and has been approved for the treatment of moderate to severe psoriasis and active psoriatic arthritis in adult patients due to its efficacy in different clinical trials. Therefore, itis important to know the performance of guselkumab in this setting of patients in clinical practice given that a high percentage of them are not represented in these clinical trials. Our objective was to evaluate the effectiveness and tolerability of guselkumab in clinical practice in the first patients with psoriasis and psoriatic arthritis treated since the date of its approval for psoriasis in Spain, in joint dermatology-rheumatology clinics. A multicenter retrospective data collection was carried out, in which 14 hospitals participated, including a total of 90 patients with psoriatic arthritis confirmed by a rheumatologist. Data collection was recorded at baseline and at weeks 12, 24, and 52 for both the articular and cutaneous domains. Ninety PsA patients started treatment with guselkumab and therefore were included in this study. The vast majority had already failed to at least to one biologic therapyprior guselkumab prescription. The median age was 55 years, 61% were female and 46% had a BMI ≥ 30 kg/m2 . Sixty-nine percent suffered from peripheral arthritis, and in 34% an axial involvement was also detected; dactylitis or enthesitis was present in 24% and 29% of patients, respectively. Guselkumab was effective in controlling both articular and skin manifestations of PsA patients. Absolute PASI significantly decreased from 10.5 to 4.8, 1.9 and 1.3 at weeks 12, 24, and 52, respectively. In 29 out of 61 (48%) of cases, DAPSA was moderate or high, and patients showed a significant reduction in DAPSA at 12, 24, and 52 weeks of treatment (mean DAPSA values at baseline and follow up were 29, 20, 16, and 14, respectively). Patients with DAPSA in low activity or in remission at the time of initiation of guselkumab maintained response at the end of the study period. No new safety concerns were detected. Seventy-eight out of 90 patients (84.4%) persisted on treatment after 2 years follow-up. Our experience suggests that guselkumab isan effective drug for PsA and PsO patients in clinical practice with good tolerability and no additional safety signals, making it a new therapeutic alternative for the treatment of PsA and PsO patients.

Assessment of the efficacy of a Crisis Intervention Team (CIT): experience in the Esplugues Mental Health Center (Barcelona).

AIM: Crisis Resolution Teams (CRT) have shown positive clinical and service-use results in various countries but evidence in the south of Europe is scarce. The aim is to assess the impact of the Crisis Intervention Team (CIT) in Spain with respect to the course of symptomatology and mental health services use in patients served. METHODS: Prospective observational cohort study. Assessment of the psychopathological severity (HoNOS scale) of the clinical course (CGI scale) and use of medical services. RESULTS: A positive clinical course was observed following the intervention. The mean difference in HoNOS (Health of the Nation Outcome Scales) scores between baseline and discharge was 7 points (p < 0.05). On discharge, more than 60% of patients had improved their symptomatology according to the CGI scale (Clinical Global Impression) and most were discharged due to improvement or goal achievement. A tendency to reduction in the number of admissions to acute units and day hospital was observed, along with fewer emergency room visits. In contrast, an increase in the number of admissions to subacute units was seen. During the intervention, the median number of visits to the center was 15 and the median duration of care provision by the CIT was 39 days. CONCLUSIONS: The CIT intervention promotes patients' clinical improvement and has a positive impact in terms of reducing acute hospitalizations and emergency room visits.

Meta-analysis of the efficacy of ketamine in postoperative pain control in adolescent idiopathic scoliosis patients undergoing spinal fusion.

PURPOSE: In this meta-analysis, we aim to compare ketamine use versus a control group (saline solution) during induction of anesthesia in adolescent idiopathic scoliosis patients undergoing fusion surgery in terms of postoperative opioid consumption, pain control, and side effects. METHODS: A PubMed search of studies published over the last 20 years using the descriptor/terms "ketamine AND scoliosis" was performed. Baseline characteristics of each article were obtained and efficacy measures analyzed (morphine equivalent treatment at 24, 48, and 72 h postoperatively, complications (vomiting/nausea and pruritus), length of hospital stay (days); and pain score (VAS)) (Review Manager 5.4 software package). RESULTS: Five randomized clinical trials were included. Morphine administration showed statistically significant differences at 24 and 48 h (MD - 0.15, 95% CI - 0.18 to - 0.12) and (MD - 0.26, 95% CI - 0.31 to - 0.21) between the ketamine and control (saline solution), respectively. No intergroup differences were found regarding nausea/vomiting and pruritus (OR 0.77, 95% CI 0.35 to 1.67) and (OR 0.71, 95% CI 0.31 to 1.62), respectively, same as for the pain score (MD - 0.75, 95% CI - 1.71 to 0.20). CONCLUSIONS: The use intraoperative and postoperative continuous low doses of ketamine significantly reduces opioid use throughout the first 48 h in patients with AIS who undergo posterior spinal fusion.

Lecciones aprendidas y retos en la integración de cuidados paliativos en oncología. Experiencia en el Instituto Nacional de Cancerología.

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