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RESUMO Devido à importância médica, veterinária, ambiental e forense do califorídeo Chrysomya putoria (Diptera), foi avaliado o desempenho apresentado por estágios imaturos criados em carne de cavalo. Os espécimes foram colocados em câmaras aclimatizadas reguladas a 30 ºC, 60 ± 10% UR e 14 horas de fotofase. Os estágios larval e pupal concluíram seu desenvolvimento em 4,16 e 4,12 dias, respectivamente. As larvas pós-alimentação e pupas com 24h de idade pesaram, em média, 58,06 e 40,10mg, respectivamente. As taxas de emergência registradas foram de 65% nas condições experimentais propostas. Como os compostos orgânicos voláteis são diferentes na decomposição de um animal para outro, este trabalho e outros realizados com a mesma dieta são os mais apropriados para estimativa de intervalo post mortem envolvendo cavalos.

Abstract Mormodica charantia (Curcubitaceae) is a plant with great medicinal potential, also used as an alternative of mosquitoes control as demonstrated by previous studies. We evaluated the larvicidal activity of crude extracts of ethyl acetate, methanol and hexane from flowers and fruits of M. charantia against Aedes aegypti (Culicidae). Flowers and fruits were macerated in methanol, ethyl acetate and hexane. Bioassays were performed with application of the extracts at final concentrations of 1 - 200 µg/mL in the middle of the third instar larvae of A. aegypti (L3). The results showed high toxicity to ethyl acetate extracts from flowers and fruits at concentrations of 200 µg/mL and 100 µg/mL, with 97% and 87% of larvae mortality (L3), respectively. Hexane extract demonstrated low toxicity, while methanol extract exhibited 78% larval mortality. The data suggested that the ethyl acetate extracts of flowers and fruits of M. charantia can effectively contribute to larvicidal activity. In addition, purification of M. charantia extracts may lead to a promising larvicidal activity to control the A. aegypti population.

The potential of fluorescence spectroscopy for the classification of olive oils was investigated. Synchronous fluorescence spectra were collected in the region of 240-700 nm with the wavelength intervals of 10, 30, 60 and 80 nm. Successive projection algorithm (SPA) was applied for the determination of representative wavelengths while the linear discriminant analysis (LDA) method was used to classify olive oils. The classification error of the method was low (0,9-6,4%) for measurements collected at all wavelength intervals. The best classification accuracy was obtained for synchronous fluorescence intensities acquired at 10 selected wavelengths with the wavelength interval equal to 10 nm.

This in vitro study aimed at estimating the disappearance rates of 14 terpenes and terpenoids after 24-h incubation with mixed bacteria from caprine rumens. These compounds comprised nine monoterpene hydrocarbons (δ-3-carene, p-cymene, β-myrcene, (E)- and (Z)-β-ocimene, α-phellandrene, α-terpinene, γ-terpinene and α-terpinolene), four oxygenated monoterpenes ((E)- and (Z)-linalool oxide, 4-terpinenol, α + γ terpineol) and one sesquiterpene hydrocarbon (β-cedrene). They were individually exposed to goat rumen microflora for 24 h in 70 ml culture tubes at an input level of 0.5 ml/l. Terpenoids were the least degraded, 100% of (E)-linalool oxide, 95% of (Z)-linalool oxide, 91% of 4-terpinenol and 75% of terpineol remained intact after 24-h incubation. In contrast, α-terpinolene concentration in fermentation broth extracts was below quantification limit, thus indicating an extensive, if not complete, degradation by rumen bacteria. Only 2% of the initial amounts of α-phellandrene were recovered. The other monoterpenes and β-cedrene were partly degraded, with losses ranging from 67% for δ-3-carene to 90% for (E)-β-ocimene. The corresponding rates of disappearance were between 2.67 and 4.08 μmol/ml inoculum per day.

Virginal gigantomastia (VGM) is a benign disease of the breasts without a clearly established etiology. The treatment of VGM remains a problem. The conservative treatment is not effective while surgery is too traumatic. Most specialists recommend subcutaneous mastectomy with immediate implant reconstruction or reduction mammoplasty. The reduction mammoplasty with adjuvant hormone therapy is a variant of treatment of young patients with a risk of recurrence. We present a case of a patient with VGM who was operated in 2014. Reduction mammoplasty was performed. After 9 years, the patient had a relapse and second surgery, resection of the breasts with reduction mammoplasty. Tissues with cysts, fibrosis, hamartomas, and fibroadenomas were dissected. Histopathology revealed extensive fibrosis with hamartomas and fibroadenomas. The immunohistochemical examination of the breast tissue showed a high level (70%) of estrogen and progesterone receptors expression. We prescribed hormone therapy with tamoxifen 10 mg per day. Dynamic monitoring of the treatment result and control of the disease remission was carried out. Breast-conserving surgery performed in such patients can help alleviate the psychological, social, and physical disorders caused by VGM.

Introduction: Celiac plexus radioablation (CPR) is an emerging non-invasive interventional treatment for severe pain associated with cancer-related damage to the celiac plexus. Due to its complex aetiology, such pain often responds poorly to conventional analgesics, and high doses of these medications can cause toxicity. Celiac plexus radiosurgery employs advanced radiotherapy techniques to administer a high single dose of 25 Gy to the anatomically defined celiac plexus, aiming to reduce pain intensity and enhance patients' quality of life., Material and Methods: The safety and efficacy of CPR have been validated in a prospective single-arm clinical trial that included 125 patients., Results: The positive outcomes of this trial led to the integration of CPR into pain management guidelines; however, the novel approach to radiotherapy planning might be initially challenging to grasp., Conclusions: In this article, we provide a brief overview of the method along with a comprehensive, Polish and English-language guide on how to perform CPR and manage patients, based on our clinical experience., Competing Interests: None., (Copyright © 2024 Termedia.)

Objectives: The Polish criteria for "intrauterine death" include fetal demise after 22 weeks of gestation, weighing > 500 g and body length at least 25 cm, when the gestational age is unknown. The rate of fetal death in Poland in 2015 is 3:10,000. In 2020, 1,231 stillbirths were registered., Material and Methods: An analysis using 142,662 births in the period between 2015-2020 in 11 living in Poland. The first subgroup was admitted as patients > 22 to the beginning of the 30th week of pregnancy (n = 229), and the second from the 30th week of pregnancy inclusively (n = 179). In the case of women from both subgroups, there was a risk of preterm delivery close to hospitalization., Results: It was found that stillbirth in 41% of women in the first pregnancy. For the patient, stillbirth was also the first in his life. The average stillbirth weight was 1487 g, the average body length was 40 cm. Among fetuses up to 30 weeks, male fetuses are born more often, in subgroup II, the sex of the child was usually female. Most fetal deaths occur in mothers < 15 and > 45 years of age., Conclusions: According to the Polish results of the origin of full-term fetuses > 30 weeks of gestation for death in the concomitant antenatal, such as placental-umbilical and fetal hypoxia, acute intrapartum effects rarely, and moreover < 30 Hbd fetal growth restriction (FGR), occurring placental-umbilical, acute intrapartum often.

Introduction: Over the past decade, left atrial appendage occlusion (LAAO) has emerged as an established alternative to oral anticoagulation for patients diagnosed with atrial fibrillation (AF). The LARIAT device stands as the sole available epicardial system for complete percutaneous left atrial appendage (LAA) closure., Aim: To present the extended outcomes (spanning over 9 years of observation) in patients with AF who underwent epicardial LAAO. The presented results constitute the longest observation in world literature., Material and Methods: A prospective, single-center study was conducted on 121 patients undergoing LAAO with the LARIAT system. Incidence of thromboembolic events and severe bleeding and mortality rates were documented. The reduction in the risk of thromboembolism and bleeding after LAAO was quantified., Results: The mean follow-up duration was 74.18 months. The average CHADS 2 score was 1.9 ±1.0, CHA 2 DS 2 -VAS score was 2.8 ±1.5, and HAS-BLED score was 2.7 ±1.0. The mean annual thromboembolic event rate was 0.7%, resulting in a 75% reduction in estimated thromboembolic risk. The annual occurrence of major bleeding complications was 0.8%, leading to a 67.9% reduction in estimated bleeding risk. The overall annual mortality rate was 1.2%., Conclusions: Epicardial LAAO employing the LARIAT device yields commendable long-term outcomes by reducing stroke and bleeding risk., Competing Interests: Bartus K: Recipient of research grant funded by the National Science Centre., (Copyright: © 2023 Polish Society of Cardiothoracic Surgeons (Polskie Towarzystwo KardioTorakochirurgów) and the editors of the Polish Journal of Cardio-Thoracic Surgery (Kardiochirurgia i Torakochirurgia Polska).)

Importance: Advance directive (AD) designation is an important component of advance care planning (ACP) that helps align care with patient goals. However, it is underutilized in high-risk surgical patients with cancer, and multiple barriers contribute to the low AD designation rates in this population., Objective: To assess the association of early palliative care integration with changes in AD designation among patients with cancer who underwent surgery., Design, Setting, and Participants: This cohort study was a retrospective analysis of a prospectively maintained registry of adult patients who underwent elective surgery for advanced abdominal and soft tissue malignant tumors at a surgical oncology clinic in a comprehensive cancer center with expertise in regional therapeutics between June 2016 and May 2022, with a median (IQR) postoperative follow-up duration of 27 (15-43) months. Data analysis was conducted from December 2022 to April 2023., Exposure: Integration of ACP recommendations and early palliative care consultations into the surgical workflow in 2020 using electronic health records (EHR), preoperative checklists, and resident education., Main Outcomes and Measures: The primary outcomes were AD designation and documentation. Multivariable logistic regression was performed to assess factors associated with AD designation and documentation., Results: Among the 326 patients (median [IQR] age 59 [51-67] years; 189 female patients [58.0%]; 243 non-Hispanic White patients [77.9%]) who underwent surgery, 254 patients (77.9%) designated ADs. The designation rate increased from 72.0% (131 of 182 patients) before workflow integration to 85.4% (123 of 144 patients) after workflow integration in 2020 (P = .004). The AD documentation rate did not increase significantly after workflow integration in 2020 (48.9% [89 of 182] ADs documented vs 56.3% [81 of 144] ADs documented; P = .19). AD designation was associated with palliative care consultation (odds ratio [OR], 41.48; 95% CI, 9.59-179.43; P < .001), palliative-intent treatment (OR, 5.12; 95% CI, 1.32-19.89; P = .02), highest age quartile (OR, 3.79; 95% CI, 1.32-10.89; P = .01), and workflow integration (OR, 2.05; 95% CI, 1.01-4.18; P = .048). Patients who self-identified as a race or ethnicity other than non-Hispanic White were less likely to have designated ADs (OR, 0.36; 95% CI, 0.17-0.76; P = .008). AD documentation was associated with palliative care consulation (OR, 4.17; 95% CI, 2.57- 6.77; P < .001) and the highest age quartile (OR, 2.41; 95% CI, 1.21-4.79; P = .01)., Conclusions and Relevance: An integrated ACP initiative was associated with increased AD designation rates among patients with advanced cancer who underwent surgery. These findings demonstrate the feasibility and importance of modifying clinical pathways, integrating EHR-based interventions, and cohabiting palliative care physicians in the surgical workflow for patients with advanced care.

Introduction: Palliative care for advanced cancer patients has been associated with improvements in symptom management and quality of life (QoL). Patients with peritoneal metastases undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) often report symptoms adversely affecting QoL. We characterized and compared symptoms elucidated by palliative care versus surgical providers in this setting., Methods: CRS/HIPEC patients who saw both surgical oncology and palliative care providers from 2016 to 2020 at a tertiary care center were identified from a retrospective database. Documentation of QoL-associated symptoms in surgical oncology and palliative care visits was recorded and analyzed., Results: A total of 118 patients were included in this study. The most common primary histologies were appendiceal (36.4%) and colorectal (28.8%). Symptoms most frequently reported by palliative care were pain (60.2%) and fatigue (54.2%). The median number of symptoms documented was three (2, 5) in palliative care notes and two (0, 3) in surgical oncology notes (P < 0.001). Palliative care providers documented most symptoms statistically more frequently than surgical oncology providers., Conclusions: Patients who underwent CRS/HIPEC experienced various QoL-associated symptoms. Palliative care providers elicited more symptoms than surgical oncology providers. Additional studies are needed to explore the impact on outcomes of perioperative palliative care in this challenging patient population., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: To assess the experience and knowledge of Polish women up to 50 years of age about fertility and its disorders., Material and Methods: A self-composed questionnaire consisting of 44 questions, divided into six sections, was available in social media from January until February 2020. The answers to 13 single-choice questions were analyzed to assess the level of knowledge. Statistical analysis was performed with the use of Statistica 13.0, with p value < 0.05 considered significant., Results: A total of 3,321 correctly filled out questionnaires were obtained. The average result was 8.88 out of 13 single- choice questions regarding the basics of the menstrual cycle and infertility (median 9, standard deviation [SD] 2.21). As many as 65.2% of respondents did not know which days in the cycle were fertile days. The women who had been and/or were pregnant at the time of survey, more often answered better than those, who had never given birth. They had a better mean score of 13 single-choice questions compared to those who had never been pregnant (9.02 vs 8.61, p < 0.001). Respondents who obtained information about infertility from doctors in 86.97% knew that regular intercourse meant 2-3 times per week in comparison to 79.7% of those who were not educated by medical practitioners (p < 0.0001). 69.8% respondents from the first group knew that the test of ovarian reserve existed in comparison to 55.63% of women from the second group (p < 0.0001)., Conclusions: The research has shown that the knowledge about fertility and its disorders is not satisfying among Polish women.

Background and Objectives: Probability of target attainment (PTA) curves are commonly used to support dose recommendations of antibiotics for different patient groups. In this study we propose PTA analysis to optimize sugammadex dosing in children., Methods: This study involved data from an observational cohort study of 30 American Society of Anesthesiologists (ASA) Physical Status I and II children undergoing surgery requiring muscle relaxation. All patients received 0.6 mg/kg rocuronium, with sugammadex administered at the end of surgery in three different doses (0.5, 1.0, and 2.0 mg/kg) to reverse the neuromuscular blockade., Results: The data were analyzed using a population Bayesian-based approach. The developed model was used to simulate pharmacokinetic-pharmacodynamic profiles for different patient groups and dosing regimens before the PTA analysis was performed to translate these simulations into a clinically useful measure. The target was defined as neuromuscular blockade reversal measured by Train-of-Four (TOF ratio > 90%) at 1.5, 3, and 5 min post sugammadex dose. The sugammadex doses leading to 90% PTA were determined for different patients' body weights, rocuronium doses, and time gaps between rocuronium and sugammadex administration assuming the model, priors, and gathered data. For comparison, PTA curves for a range of clinical scenarios are provided to illustrate the usefulness of PTA analysis in selecting the appropriate dose for a given patient., Conclusions: The proposed PTA analysis is useful to support the sugammadex dose selection in different clinical scenarios., Trial Registration: The study was registered by ClinicalTrials.gov under number NCT04851574 on 21 April 2021., (© 2022. The Author(s).)

Type II endoleak is one of the most common and problematic complications after endovascular aneurysm repair. It has been suggested that the inferior mesenteric artery (IMA) embolization could prevent further adverse events and postoperative complications. This article is a systematic review and meta-analysis following PRISMA guidelines. The Medline, PubMed, Embase, and Cochrane databases were used to identify studies that investigated the effect of IMA embolization on the occurrence of type II endoleaks and secondary interventions in a group of patients with abdominal aortic aneurysm who underwent EVAR compared with results after EVAR procedure without embolization. A random effects meta-analysis was performed. Of 3510 studies, 6 studies involving 659 patients were included. Meta-analysis of all studies showed that the rate of secondary interventions was smaller in patients with IMA embolization (OR, 0.17; SE, 0.45; 95% CI, 0.07 to 0.41; p < 0.01; I2 = 0%). The occurrence of type II endoleaks was also smaller in the embolization group (OR, 0.37; SE, 0.21; 95% CI, 0.25 to 0.57; p < 0.01; I2 = 16.20%). This meta-analysis suggests that IMA embolization correlates with lower rates of type II endoleaks and secondary interventions.

Background: In recent years, the introduction of single-cell RNA sequencing (scRNA-seq) has enabled the analysis of a cell's transcriptome at an unprecedented granularity and processing speed. The experimental outcome of applying this technology is a [Formula: see text] matrix containing aggregated mRNA expression counts of M genes and N cell samples. From this matrix, scientists can study how cell protein synthesis changes in response to various factors, for example, disease versus non-disease states in response to a treatment protocol. This technology's critical challenge is detecting and accurately recording lowly expressed genes. As a result, low expression levels tend to be missed and recorded as zero - an event known as dropout. This makes the lowly expressed genes indistinguishable from true zero expression and different than the low expression present in cells of the same type. This issue makes any subsequent downstream analysis difficult., Results: To address this problem, we propose an approach to measure cell similarity using consensus clustering and demonstrate an effective and efficient algorithm that takes advantage of this new similarity measure to impute the most probable dropout events in the scRNA-seq datasets. We demonstrate that our approach exceeds the performance of existing imputation approaches while introducing the least amount of new noise as measured by clustering performance characteristics on datasets with known cell identities., Conclusions: ccImpute is an effective algorithm to correct for dropout events and thus improve downstream analysis of scRNA-seq data. ccImpute is implemented in R and is available at https://github.com/khazum/ccImpute ., (© 2022. The Author(s).)

Depression, anxiety, and aggression accompany neuropathic pain. Effective treatment of these comorbidities enhances the outcomes of pain management. Therefore, the study was designed to analyze the relationship between the intensity of depression, anxiety, and aggression and the pharmacotherapy applied in the daily practice of treating neuropathic pain. The aim of the study was to evaluate the frequency of using antidepressants (ADs), benzodiazepine anxiolytics (BDAs), and hypnotics, and the influence of administering these on the intensity of depression, anxiety, and aggression in patients diagnosed with neuropathic pain. A multi-center survey was conducted among 421 patients. An evaluation of the severity of depression, anxiety, and aggression was made using the Hospital Anxiety and Depression Scale-Modified Version (HADS-M). Among the patients treated due to neuropathic pain, ADs are used much more often than BDAs and hypnotics. Depression was well controlled, while anxiety was identified as a possible uncontrolled therapeutic problem in these patients, despite the correlation between the frequency of AD and hypnotics usage and the severity of anxiety. We also found that women show a higher level of intensity in both anxiety and depression, but this does not influence the frequency of their being administered ADs, BDAs, and hypnotics.

A minimally invasive approach to radical prostatectomy offers improved ambulation and discharge times. Postoperative pain control is one of the key factors that facilitates rapid recovery. With the aim to assure adequate analgesia and minimize the use of opioids, application of truncal nerve blocks has been proposed in a number of endoscopic procedures. The aim of this double-blind, placebo-controlled study was to evaluate the efficacy of bilateral posterior quadratus lumborum block (pQLB) in alleviating pain and reducing postoperative opioid demand in patients following endoscopic extraperitoneal and laparoscopic prostatectomy. We enrolled 50 patients who were diagnosed with prostate cancer and scheduled for prostatectomy. They were randomized to receive preoperative, ultrasound-guided pQLB with the use of either 30 ml of 0.375 % ropivacaine (ropivacaine group) or 30 ml of 0.9 % NaCl (placebo group). Our primary endpoint was opioid consumption in the first 24 hours after surgery. Secondary endpoints were pain intensity at predefined timepoints and the incidence of nausea and vomiting and pruritus. No differences were detected between the ropivacaine and placebo groups in intravenous oxycodone consumption during the first 24 hours after surgery. Similarly, there were no differences in pain intensity at any of the timepoints assessed. The rate of nausea and vomiting was equal in both groups and pruritus was not observed. Application of bilateral pQLB does not reduce opioid consumption after minimally invasive prostatectomy., (Copyright © 2022 Horosz et al.)

Objectives: Hyperglycemia in pregnancy (HIP) is one of the most common complications of pregnancy. Recently adopted new criteria for the diagnosis of HIP as well as the greater prevalence of risk factors could have a significant impact on HIP prevalence. The objective of the study was to assess the rates of HIP and the associated complications., Material and Methods: This was a retrospective analysis of clinical records from pregnant women who delivered in eight tertiary hospitals in Poland in 2016., Results: The number of pregnant women with hyperglycemia totaled 1280 (7.25%), including gestational diabetes mellitus (GDM) in 1169 (6.62%) women and pregestational diabetes mellitus (PGDM) in 111 (0.63%). In addition to dietary modifications, 477 (41% of the GDM group) women received medical treatment (GDMG2). In women with PGDM multiple daily insulin injections (MDI) were used in 53 (47.7%) cases, continuous subcutaneous insulin infusions (CSII) in 57 (51.3%) cases and one woman was treated with metformin. The rate of cesarean sections was 69.4% and 62.9% for PGDM and GDM, respectively. Large-for-gestational-age (LGA) infants accounted for 38% and 21% of births in the PGDM and GDM groups, respectively. Of note are high rates of hyperbilirubinemia in infants born to mothers treated with insulin (13.5% for PGDM and 14.4% for GDMG2) vs infants born to mothers with diet (GDMG1) (3.4%)., Conclusions: In Poland, the prevalence of HIP has nearly doubled in the past twenty years. Even with appropriate management, HIP is a significant risk factor for a cesarean section delivery, bearing an LGA infant and adverse neonatal outcomes.

Background: Central sensitization is an amplification of neuronal signaling within the central nervous system. The Central Sensitization Inventory was introduced in 2012. A Polish version of the CSI (CSI-Pol) was developed in 2019, but it was not psychometrically validated. The aim of this study was to validate the CSI-Pol in a sample of Polish-speaking patients with chronic spinal pain and compare them with a group of healthy control subjects., Methods: The CSI-Pol was administered to 151 patients with chronic spinal pain recruited from two centers. It was re-administered 7 days later. The psychometric properties were then evaluated, including test-retest reliability, construct validity, factor structure and internal consistency. We correlated the CSI-Pol with functional scales, depression and social support scales and compared CSI-Pol scores in the clinical subjects with 30 healthy control subjects recruited from medical staff and their families., Results: The CSI-Pol demonstrated excellent internal consistency (Cronbach's α =0,933) and test-retest reliability (Intraclass Correlation Coefficients - ICC =0.96), as well as significant positive associations with other patient-reported scales, including the Neck Disability Index (r = 0.593), Revised Oswestry Low Back Pain Disability Questionnaire (r = 0.422), and other measures of functional and depressive states. An exploratory factor analysis resulted in a 4-factor model. CSI-Pol scores in the clinical sample (35.27 ± 17.25) were significantly higher than the control sample (23.3 ± 8.9)., Conclusion: The results of this study suggest that the CSI-Pol may be a useful clinical tool for assessing central sensitization related symptoms and guiding appropriate treatment in Polish-speaking patients with spinal pain., (© 2021. The Author(s).)

Background: Explored whether increased support for spiritual concerns between the healthcare team and patients through the provision of a Spiritual Care Advocate (SCA) would improve end of life outcomes in a metastatic cancer population., Design: Newly diagnosed metastatic cancer patients were recruited at the University of Chicago Medical Center and received spiritual support from a Spiritual Care Advocate during chemotherapy treatments. The final sample consisted of 42 patients (58% of those approached) who completed the baseline survey and had known survival status., Measurement: Patients completed pre/post surveys measuring spiritual support and palliative quality of life. Baseline measurements of religious practice and externalizing religious health beliefs were also obtained. Receipt of aggressive EOL care was derived from the electronic medical record., Result: Median age was 61 years, with 48% Black, and predominantly male (62%). Of the 42 patients, 30 (70%) had died by the time of this analysis. Perceived spiritual support from the medical team increased in 47% of those who received non-aggressive EOL care and by 40% in those who received aggressive EOL care (p=0.012). Patient perceptions of spiritual support from the medical community increased from 27% at baseline to 63% (p=0.005) after the SCA intervention. Only 20% of recipients received aggressive treatments at end of life., Conclusion: The SCA model improved the perceived spiritual support between the healthcare team and patients. Although limited by a small sample size, the model was also associated with an improvement in EOL patients' quality of life, spiritual wellbeing, and decreased aggressive EOL care.

Background: Several opioids have pharmacogenomic associations impacting analgesic efficacy. However, germline pharmacogenomic testing is not routinely incorporated into supportive oncology. We hypothesized that CYP2D6 profiling would correlate with opioid prescribing and hospitalizations., Materials and Methods: We analyzed 61,572 adult oncology patients from 2012 to 2018 for opioid exposures. CYP2D6 metabolizer phenotype (ultra-rapid [UM], normal metabolizer [NM], intermediate [IM], or poor [PM]), the latter two of which may cause inefficacy of codeine, tramadol, and standard-dose hydrocodone, was determined for patients genotyped for reasons unrelated to pain. The primary endpoint was number of opioid medications received during longitudinal care (IM/PMs vs. NMs). Secondary endpoint was likelihood of pain-related hospital encounters., Results: Most patients with cancer (n = 34,675, 56%) received multiple opioids (average 2.8 ± 1.6/patient). Hydrocodone was most commonly prescribed (62%), followed by tramadol, oxycodone, and codeine. In the CYP2D6 genotyped cohort (n = 105), IM/PMs received a similar number of opioids (3.4 ± 1.4) as NMs (3.3 ± 1.9). However, IM/PMs were significantly more likely to experience pain-related hospital encounters compared with NMs, independent of other variables (odds ratio [OR] = 5.4; 95% confidence interval [CI], 1.2-23.6; p = .03). IM/PMs were also more likely to be treated with later-line opioids that do not require CYP2D6 metabolism, such as morphine and hydromorphone (OR = 3.3; 95% CI, 1.1-9.8; p = .03)., Conclusion: CYP2D6 genotype may identify patients with cancer at increased risk for inadequate analgesia when treated with typical first-line opioids like codeine, tramadol, or standard-dose hydrocodone. Palliative care considerations are an integral part of optimal oncology care, and these findings justify prospective evaluation of preemptive genotyping as a strategy to improve oncology pain management., Implications for Practice: Genomic variation in metabolic enzymes can predispose individuals to inefficacy when receiving opioid pain medications. Patients with intermediate and/or poor CYP2D6 metabolizer status do not adequately convert codeine, tramadol, and hydrocodone into active compounds, with resulting increased risk of inadequate analgesia. This study showed that patients with cancer frequently receive CYP2D6-dependent opioids. However, patients with CYP2D6 intermediate and poor metabolizer status had increased numbers of pain-related hospitalizations and more frequently required the potent non-CYP2D6 opioids morphine and hydromorphone. This may reflect inadequate initial analgesia with the common "first-line" CYP2D6-metabolized opioids. Preemptive genotyping to guide opioid prescribing during cancer care may improve pain-related patient outcomes., (© 2021 AlphaMed Press.)

Background: Currently, immunosuppression schemes are age-independent; however, physiological changes may alter drugs' pharmacokinetics in the older population. We compared mycophenolic acid (MPA) and its glucuronide metabolite (MPAG) pharmacokinetics among patients aged <60 and >60 years on the seventh day after renal transplantation., Methods: We included 7 and 10 renal transplant recipients, aged >60 and <60 years, respectively, treated with mycophenolate mofetil. MPA and MPAG concentrations were determined using the high-performance liquid chromatography method with ultraviolet detection (HPLC-UV). Noncompartmental pharmacokinetic analysis was performed., Results: In patients aged >60 years, mean MPA and MPAG concentrations before the next dose and ratio of MPAG area under the concentration-time curve (AUC 0-12 ) to MPA AUC 0-12 were higher by 1.6-fold, 1.4-fold, and 1.9-fold, respectively. Other MPAG concentrations appeared to be slightly higher (1.2- to 1.5-fold) in older patients. MPA apparent clearance was similar in both groups, whereas volume of distribution at steady state was slightly higher (1.6-fold) in patients aged >60 years. The variability of most MPA and some MPAG pharmacokinetics was greater in patients aged >60 years. The MPA AUC 0-12 target was achieved in 40% and 14% of patients aged <60 and >60 years, respectively. The highest MPAG concentrations and AUC 0-12 were observed for patients with the lowest glomerular filtration rate., Conclusions: Higher variability of MPA and MPAG pharmacokinetic parameters, MPA AUC 0-12 above the reference range, higher values of MPAG pharmacokinetics in patients with lower glomerular filtration rates, as well as lower proportion of patients achieving MPA targets all indicate the need for therapeutic drug monitoring in renal transplant recipients aged >60 years and to verify target MPA AUC 0-12 for this population., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The efficacy of neuropathic pain control remains unsatisfactory. Despite the availability of a variety of therapies, a significant proportion of patients suffer from poorly controlled pain of this kind. Consequently, new drugs and treatments are still being sought to remedy the situation. One such new drug is mirogabalin, a selective ligand for the α2δ subunits of voltage-gated calcium channels (VGCC) developed by Sankyo group for the management of neuropathic pain. In 2019 in Japan, mirogabalin was approved for peripheral neuropathic pain following the encouraging results of clinical trials conducted with diabetic peripheral neuropathic pain (DPNP) and postherpetic neuralgia (PHN) patients. The ligand selectivity of mirogabalin for α2δ-1 and α2δ-2 and its slower dissociation rate for α2δ-1 than for α2δ-2 subunits of VGCC may contribute to its strong analgesic effects, wide safety margin, and relatively lower incidence of adverse effects compared to pregabalin and gabapentin. This article discusses the mechanism of action of mirogabalin, presents data on its pharmacodynamics and pharmacokinetics, and reviews the available experimental and clinical studies that have assessed the efficacy and safety of the drug in the treatment of selected neuropathic pain syndromes.

Core body temperature is strictly regulated (± 0.2 °C) and coordinated at the level of central nervous system located in the hypothalamus via several protective effector mechanisms that prevent overcooling and overheating. The central regulation permits both circadian and monthly variations of even 1°C; under normal conditions, however, the activation of effective protective mechanisms prevents even the slightest overcooling and core temperature elevation at any moment of the day.

Background: Left atrial appendage closure (LAAC) became an alternative method for stroke prevention in patients with non-valvular atrial fibrillation (AF) intolerant to long term oral anticoagulation therapy. This study aimed to compare endocardial (Amulet and LAmbere occluders) and epicardial (Lariat) LAAC techniques., Methods: A retrospective, observational case-control study included 223 consecutive CHA 2 DS 2 -VAS score-matched patients with AF who underwent LAAC in two centers., Results: There were 55 matched cases with the mean CHA2DS2-VASs score 4.4 ± 1.22 (p = 1). Overall follow-up was 308.2 patient-years. The Endocardial group patients were older and more often females with congestive heart failure and peripheral vascular disease. The epicardial group more frequently had a stroke/transient ischemic attack history. There were no differences in hypertension, diabetes mellitus, and indications for procedure between both groups. The mean HAS-BLED score was significantly higher in the endocardial group than in the epicardial group (4.3 ± 0.9 vs. 3.7 ± 1.3, p = .011). There were no differences in annual rates of thromboembolic events (2.6% vs 0.5%) and annual stroke (0.87% vs. 0%) between the endocardial and epicardial groups., Conclusion: Endocardial and Epicardial LAAC techniques show comparable implantation outcomes and safety profile and stroke prevention in patients with AF. Future randomized studies are needed to corroborate these initial results and assess long term mortality., (© 2020 Wiley Periodicals LLC.)

The optimal intrathecal dose of local anaesthetic for caesarean section (CS) anaesthesia is still being debated. We performed a study to compare the effectiveness and safety of spinal anaesthesia with 12.5 mg of hyperbaric bupivacaine and a dosing regimen of conventional doses adjusted to parturient height. One hundred and forty parturients scheduled for elective CS were enrolled. The fixed-dose group (FD) received a spinal block with 12.5 mg of hyperbaric bupivacaine with fentanyl, whereas the adjusted-dose group (AD) received a height-adjusted dose of bupivacaine (9-13 mg) with fentanyl. Sensory block ≥ T5 dermatome within 10 min and no need for supplementary analgesia were set as the composite primary outcome (success). Rates of successful blocks and complications were compared. Complete data were available for 134 cases. Spinal anaesthesia was successful in 58 out of 67 patients in the FD group and 57 out of 67 in the AD group ( p > 0.05). Eight spinals in each group failed to produce a block ≥ T5 in 10 min, and one patient in the FD group and two in the AD group required i.v. analgesics despite sensory block ≥ T5. No differences were noted in terms of hypotension, bradycardia and nausea between the FD and AD groups. Compared to the height-adjusted dose regimen based on conventional doses of hyperbaric bupivacaine, the fixed dose regimen of 12.5 mg was equally effective and did not increase the risk of spinal block-related complications.

Objective: Pain management in persons with mild to moderate dementia poses unique challenges because of altered pain modulation and the tendency of some individuals to perseverate. We aimed to test the impact of an e-learning module about pain in communicative people with dementia on third-year medical students who had or had not completed an experiential geriatrics course., Design: Analysis of pre- to postlearning changes and comparison of the same across the student group., Setting: University of Pittsburgh School of Medicine and Saint Louis University School of Medicine., Subjects: One hundred four University of Pittsburgh and 57 Saint Louis University medical students., Methods: University of Pittsburgh students were randomized to view either the pain and dementia module or a control module on pain during a five-day geriatrics course. Saint Louis University students were asked to complete either of the two modules without the context of a geriatrics course. A 10-item multiple choice knowledge test and three-item attitudes and confidence questionnaires were administered before viewing the module and up to seven days later., Results: Knowledge increase was significantly greater among students who viewed the dementia module while participating in the geriatrics course than among students who viewed the module without engaging in the course (P < 0.001). The modules did not improve attitudes in any group, while student confidence improved in all groups., Conclusions: Medical students exposed to e-learning or experiential learning demonstrated improved confidence in evaluating and managing pain in patients with dementia. Those exposed to both educational methods also significantly improved their knowledge., (Published by Oxford University Press on behalf of the American Academy of Pain Medicine 2020. This work is written by US Government employees and is in the public domain in the US.)

Anorexia and cachexia, nausea and vomiting, and constipation are gastrointestinal symptoms that commonly accompany serious illness. Basic science and clinical research continue to improve the understanding of their pathophysiology. Thorough assessment necessitates history, physical examination, and laboratory and diagnostic testing. Pharmacologic management attempts to counteract or reverse the underlying pathophysiologic mechanisms that accompany each symptom, which may benefit from a multimodal approach to achieve adequate control. Future improvements in management require investments in clinical research to determine the efficacy of novel agents along with comparator studies to better understand which treatments should be used in what sequence or combination., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Shivering during caesarean section (CS) under spinal anaesthesia is a common phenomenon. It could not only alter patient's physiology by increasing oxygen consumption but also affect the parturient's experience of childbirth. Shivering is thought to be associated with intraoperative hypothermia, but the risk factors and exact mechanism remain unclear., Methods: We conducted a prospective, observational study to examine the potential risk factors for intraoperative shivering, including anxiety levels. Two hundred patients undergoing elective CS under spinal anaesthesia were recruited. Parturient anxiety levels were evaluated using the State-Trait Anxiety Inventory (STAI) questionnaire. Age, weight, height, BMI, anxiety level, number of previous deliveries, sensory block level, level of education, temperature difference during surgery and American Society of Anesthesiologists score were investigated as potential risk factors. Stepwise logistic regression was used to assess the predictors for shivering., Results: Data from 155 parturients were analysed. Shivering incidence was 21.9% (34 parturients). The statistical model predicted 8.5% of a shivering incidence variability (R-square Nagelkerke = 0.085). Out of all measured variables, only the number of previous deliveries [(W) = 4.295 Exp(B) = 0.562 P < .05] and STAI-X1 [(W) = 4.127 Exp(B) = 1.052 P < .05] were significant. In our model, the risk of shivering decreased by 44% with every previous delivery and increased by 5.2% with each 1-point increase in STAI-X1., Conclusion: We failed to prove a strong correlation between the measured variables and shivering. Our findings, however, support the hypothesis, that to a limited extent, anxiety promotes shivering during CS., (© 2019 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Fentanyl is a popular intraoperative analgesic linked with the development of opioid tolerance (OT) or opioid-induced hyperalgesia (OIH). The development of OIH or OT may lead to several issues such as delayed healing after surgery and timely discharge. Moreover, it causes discomfort in patients with higher pain scores, greater use of analgesics, and other associated side effects. The current study aimed at determining whether the amount of intraoperatively administered fentanyl affects the onset of acute postoperative pain. The current retrospective study was conducted on 56 patients undergoing laparoscopic sleeve gastrectomy. In patients receiving relatively large doses of fentanyl intraoperatively (over 3 µg/kg body weight), the onset of acute postoperative pain accelerated significantly, in comparison with the ones receiving lower doses., Competing Interests: Conflict of Interests:The authors declared no conflict of interest., (Copyright © 2019, Author(s).)

To be successful plant pathogens, microbes use "effector proteins" to manipulate host functions to their benefit. Identifying host targets of effector proteins and characterizing their role in the infection process allow us to better understand plant-pathogen interactions and the plant immune system. Yeast two-hybrid analysis and coimmunoprecipitation were used to demonstrate that the Phytophthora infestans effector AVIRULENCE 2 (PiAVR2) interacts with all three BRI1-SUPPRESSOR1-like (BSL) family members from potato ( Solanum tuberosum ). Transient expression of BSL1, BSL2, and BSL3 enhanced P. infestans leaf infection. BSL1 and BSL3 suppressed INFESTIN 1 elicitin-triggered cell death, showing that they negatively regulate immunity. Virus-induced gene silencing studies revealed that BSL2 and BSL3 are required for BSL1 stability and show that basal levels of immunity are increased in BSL -silenced plants. Immune suppression by BSL family members is dependent on the brassinosteroid-responsive host transcription factor CIB1/HBI1-like 1. The P. infestans effector PiAVR2 targets all three BSL family members in the crop plant S. tuberosum These phosphatases, known for their role in growth-promoting brassinosteroid signaling, all support P. infestans virulence and thus can be regarded as susceptibility factors in late blight infection., (© 2019 The author(s). All Rights Reserved.)