bluuebunny/crossref_metadata_2025 huggingface dataset:
Unravelling Impaired Hypoalgesia at Rest and in Response to Exercise in Patients with Chronic Whiplash-Associated Disorders: Effects of a Single Administration of Selective Serotonin Reuptake Inhibitor versus Selective Norepinephrine Reuptake Inhibitor
Authors: De Kooning Margot , Coppieters Iris , Huysmans Eva , Nijs Jo , Meeus Mira , Voogt Lennard , Hendriks Erwin , Ickmans Kelly
Published: July 2023

(1) Background: Noradrenaline and serotonin have modulatory roles in pain signaling and in exercise-induced hypoalgesia. Patients with chronic whiplash-associated disorders often show impaired exercise-induced hypoalgesia. Therefore, this study aimed to examine the isolated effect of activating serotonergic or noradrenergic descending pathways on hypoalgesia at rest and in response to exercise in patients with chronic WAD by using respectively a single dose of a selective serotonin reuptake inhibitor (SSRI) and a selective norepinephrine reuptake inhibitor (NRI). (2) Methods: Twenty-five people with chronic WAD participated in this double-blind randomized controlled crossover experiment. Serotonin and noradrenaline concentrations were modulated by the oral ingestion of a single dose of citalopram (i.e., SSRI) or atomoxetine (i.e., SNRI). Quantitative sensory testing (including pressure pain thresholds and conditioned pain modulation) was measured before and after exercise in combination with no medication (1), atomoxetine (2), or citalopram (3) at three different test days. (3) Results: Random-intercept linear mixed models analysis was used to analyze pain outcomes (i.e., pain at rest and exercise-induced hypoalgesia) before and after exercise over the three conditions in patients with chronic WAD. No differences in pain at rest were found between the three conditions before exercise. The effect of exercise on pain outcome measures was not influenced by medication intake. The occupational status of the participants had a significant influence on the effect of exercise and medication on pain outcomes (p < 0.05). Patients working full-time had some positive effect of atomoxetine on pain facilitation (p < 0.05). Unemployed patients had some negative effect of citalopram on pain tolerance and experienced exercise-induced hypoalgesia (p < 0.05). (4) Conclusions: A single dose of citalopram or atomoxetine did not result in changes in hypoalgesia at rest and in response to exercise. These results do not support the use of SSRI or selective NRI to overcome impaired hypoalgesia at rest or in response to exercise in people with chronic WAD. Effect of exercise and medication on pain in patients with chronic WAD is influenced by the occupational status.
Desktop Virtual Reality Offers a Novel Approach to Minimize Pain and Anxiety during Burn Wound Cleaning/Debridement in Infants and Young Children: A Randomized Crossover Pilot Study
Authors: Alrimy Taima , Alhalabi Wadee , Malibari Areej , Alzahrani Fatma , Alrajhi Sharifah , Yamani Ayman , Ahmed Halah , Abduljawad Amro , Nasser Essam , ALattar Samar , Alharby Buthinah , Khalid Hasna , Alhalabi Mohammed , Hoffman Hunter G. , Mason Keira P.
Published: July 2023

Although most scald burn injuries involve children under six, because of the challenges of using head mounted displays with young children there is very little research exploring the use of VR in children under six. The current clinical pilot study measured the analgesic effectiveness of our new desktop VR system (with no VR helmet) in children under six during burn wound care (a within-subjects design with randomized treatment order). Between December 2021–April 2022, nine children with burn injuries (10 months to 5 years age, mean = 18 months) participated. The mean burn size was 10% Total Body Surface Area, range 2–22%. Using nurse’s ratings, VR significantly reduced children’s pain during burn wound care by 40% on the observational Faces, Legs, Activity, Crying, and Consolability (FLACC) pain scale. Specifically, non-parametric within-subject sign tests compared nurse’s ratings of the young patients’ pain during burn wound care using usual pain medications with no VR = 6.67, (SD = 2.45) vs. adjunctive Animal Rescue World VR (VR = 4.00, SD = 2.24, p < 0.01). The observational Procedure–Behavior Checklist (PBCL) nurse’s scale measured a 34% reduction in anxiety with VR as compared to pharmacologic treatment alone (p < 0.005). Similarly, when using single graphic rating scales the patients’ parents reported a significant 36% decrease in their child’s pain during VR (p < 0.05), a 38% (p < 0.005) decrease in their child’s anxiety during VR, and a significant increase in patients’ joy during VR. It can be concluded that during burn wound care with no distraction (traditional pain medications), children under 6 years old experienced severe pain during a 10 min burn wound cleaning session. During burn wound care combining desktop virtual reality and traditional pain medications, the same pediatric patients experienced only mild pain during burn wound cleaning/debridement. VR significantly reduced the children’s pain and anxiety during burn wound care.
Biomarkers for Immune Checkpoint Inhibitors in Renal Cell Carcinoma
Authors: Martin Spencer D. , Bhuiyan Ishmam , Soleimani Maryam , Wang Gang
Published: July 2023

Immune checkpoint inhibitor (ICI) therapy has revolutionized renal cell carcinoma treatment. Patients previously thought to be palliative now occasionally achieve complete cures from ICI. However, since immunotherapies stimulate the immune system to induce anti-tumor immunity, they often lead to adverse autoimmunity. Furthermore, some patients receive no benefit from ICI, thereby unnecessarily risking adverse events. In many tumor types, PD-L1 expression levels, immune infiltration, and tumor mutation burden predict the response to ICI and help inform clinical decision making to better target ICI to patients most likely to experience benefits. Unfortunately, renal cell carcinoma is an outlier, as these biomarkers fail to discriminate between positive and negative responses to ICI therapy. Emerging biomarkers such as gene expression profiles and the loss of pro-angiogenic proteins VHL and PBRM-1 show promise for identifying renal cell carcinoma cases likely to respond to ICI. This review provides an overview of the mechanistic underpinnings of different biomarkers and describes the theoretical rationale for their use. We discuss the effectiveness of each biomarker in renal cell carcinoma and other cancer types, and we introduce novel biomarkers that have demonstrated some promise in clinical trials.
Percutaneous Fixation for Traumatic Symphysis Pubis Disruption—Are the Results Superior Compared to Open Techniques? A Systematic Review and Meta-Analysis of Clinical and Biomechanical Outcomes
Authors: Kitridis Dimitrios , Tsikopoulos Konstantinos , Givissis Panagiotis , Chalidis Byron
Published: July 2023

Introduction: Open reduction and reconstruction plate and screws fixation (RPSF) is considered the gold standard for the treatment of traumatic symphysis pubis diastasis (SPD). Percutaneous cannulated screw fixation (PCSF) has recently gained popularity as it may reduce operative time and morbidity. The current systematic review aims to compare the clinical and radiological outcomes of PCSF and RPSF in traumatic SPD and analyze the biomechanical effectiveness of PCSF. Material and Methods: The Medline, Scopus, and Cochrane databases were searched until February 2023. The primary outcomes were the incidence of implant failure and revision surgery and the amount of displacement of symphysis pubis. Secondary outcomes were the intraoperative blood loss, the scar length, the operative time, the wound infection, and the patients’ functional improvement. Results: Six clinical trial studies with a total of 184 patients and nine biomechanical studies were included. There was no significant difference between the two groups regarding the incidence of implant failure, the prevalence of revision surgery, and the amount of postoperative loss of reduction (p > 0.05 for all outcomes). The intraoperative blood loss (14.9 ± 4.2 mL for PCSF versus 162.7 ± 47.6 mL for PCSF, p < 0.001) and the incision length (1.7 ± 0.9 mL for PCSF versus 8 ± 1.4 mL for PCSF, p < 0.001) were significantly lower after PCSF. The mean operative time was 37 ± 19.1 min for PCSF and 68.9 ± 13.6 min for RPSF (p < 0.001). The infection rate was less frequent in the PCSF group (3% for PCSF versus 14.3% for RPSF, p = 0.01). One clinical trial reported better functional recovery after PCSF. In all biomechanical studies, the threshold for implant failure was beyond the applied forces corresponding to daily activities. Conclusions: PCSF for traumatic SPD is associated with less operative time, less blood loss, and a lower infection rate when compared to conventional plate techniques without increasing the incidence of postoperative fixation failure and revision surgery. Moreover, PCSF has been proven to be biomechanically sufficient for stabilization. Therefore, it should be considered an efficient and viable alternative for the reconstruction of SPD when closed reduction can be adequately achieved.
The Effect of Transcutaneous Posterior Tibial Nerve Stimulation on Pain and Quality of Life in Patients with Fibromyalgia: A Single-Blind, Randomized Controlled Trial
Authors: Sarı İlker Fatih , İlhanlı İlker , Mızrak Tuba , Kulaklı Fazıl , Kasap Zerrin
Published: July 2023

This study aimed to investigate the effectiveness of posterior tibial nerve stimulation (PTNS) in reducing pain, improving quality of life, and decreasing disease severity in patients with fibromyalgia. This prospective, single-blind, randomized controlled trial included female patients newly diagnosed with fibromyalgia who had started duloxetine treatment (30 mg/day). The patients in the study group received six sessions of posterior tibial nerve stimulation, twice weekly, 3–4 days apart, in addition to duloxetine; the controls received duloxetine only. The patients were evaluated three times (at baseline, 1st month, and 3rd month). Pain was evaluated using a numeric rating scale, the short-form McGill Pain Questionnaire, and quality of life with a 36-item short-form health survey (SF-36). Patient functional status and disease severity were evaluated using the fibromyalgia impact questionnaire (FIQ). A total of 64 patients met the inclusion criteria: 22 were ultimately included in the study group and 30 in the control group. Statistical improvements in pain and FIQ scores were observed after treatment in both groups. The SF-36 scores indicated improved vitality only in the 1st month in both groups, with no significant changes in the other quality-of-life subscales in either group. There was no statistical difference between the two groups in terms of changes in pain, FIQ, and SF-36 scores compared with baseline at the 1st month and 3rd month. The addition of PTNS to pharmacological treatment did not contribute to the reduction in pain or improvement in quality of life in fibromyalgia either in the 1st or 3rd month. NIH Clinical Trial Registration Number NCT05937711.
The Impact of COVID-19 on Menstrual Cycle in Women
Authors: Błażejewski Grzegorz , Witkoś Joanna
Published: July 2023

Background: The COVID-19 pandemic has become the largest and most diverse to threaten the health of humanity since the 1918 influenza pandemic. Methods: This study involved 113 women who had suffered from COVID-19. The study was conducted as interviews with each woman during visits to a clinic prior to the start of their post-COVID-19 physiotherapy treatment cycle. The aim of this study was to assess the prevalence of changes in the women’s monthly cycles related to COVID-19, as well as to analyse correlations between dependent variables relating to changes in the monthly cycle and independent variables relating to other factors, such as age, weight, number and type of vaccinations, and time since illness. Additionally, the study assesses correlations between the monthly cycle and COVID-19 symptoms persisting after the illness (long COVID). Results: Women who reported more symptoms of COVID-19 were more likely to report changes in their menstrual cycle occurring after the SARS-CoV-2 infection, compared with women whose disease course was mild. Women who declared that COVID-19 affected their monthly cycles most often indicated increases in abdominal, lower abdominal, and joint and muscle pain, as well as in the severity of headaches during monthly bleeding. A small percentage of women indicated that their monthly cycles were longer and their regularity disrupted. Conclusions: This study shows that the more COVID-19 symptoms a woman had, the more often there were noted changes in monthly cycle. The same relationship was also found for persistent long COVID symptoms. The longer the time lapse since the COVID-19 infection, the less frequently changes in the monthly cycle were recorded.
Stroke in Young Adults
Authors: Bukhari Syed , Yaghi Shadi , Bashir Zubair
Published: July 2023

Stroke in young adults is associated with significant morbidity, and its prevalence is rising in the United States. This is partly attributed to a rise in the prevalence of traditional risk factors including hypertension, hypercholesterolemia, obesity, diabetes mellitus, smoking and heart disease. In addition, there are non-modifiable risk factors comprising migraine, pregnancy and postpartum state, illicit drug use, oral contraceptives and hypercoagulable state. The mechanisms causing stroke in young adults are unique and include cervical dissection, cardioembolic phenomenon, vasculitis and vasculopathy, connective tissue disease, patent foramen ovale and cerebral venous thrombosis. The diagnosis of stroke in the young population can be challenging given its myriad clinical presentations. In this document, we provide an overview of the epidemiology of stroke in young adults, explore mechanisms that may explain increasing rates of stroke in this population, and provide a critical updated overview of the existing literature on the management and prevention of stroke in young adults.
Extracorporeal Photopheresis as a Possible Therapeutic Approach for Adults with Severe and Critical COVID-19 Non-Responsive to Standard Treatment: A Pilot Investigational Study
Authors: Szabó Bálint Gergely , Reményi Péter , Tasnády Szabolcs , Korózs Dorina , Gopcsa László , Réti Marienn , Várkonyi Andrea , Sinkó János , Lakatos Botond , Szlávik János , Bekő Gabriella , Bobek Ilona , Vályi-Nagy István
Published: July 2023

Background: The optimal approach for adult patients hospitalized with severe and critical coronavirus disease 2019 (COVID-19), non-responsive to antiviral and immunomodulatory drugs, is not well established. Our aim was to evaluate feasibility and safety of extracorporeal photopheresis (ECP) in this setting. Methods: A prospective, single-center investigational study was performed between 2021 and 2022 at a tertiary referral center for COVID-19. Patients diagnosed with COVID-19 were screened, and cases with severe or critical disease fulfilling pre-defined clinical and biochemical criteria of non-response for >5 days, despite remdesivir, dexamethasone and immunomodulation (tocilizumab, baricitinib, ruxolitinib), were consecutively enrolled. After patient inclusion, two ECP sessions on two consecutive days per week for 2 weeks were applied. Patients were followed-up per protocol from study inclusion, and clinical, virological and radiological outcomes were assessed at the end of treatment (EOT) +28 days. Results: A total of seven patients were enrolled. At inclusion, four out of seven (57.1%) were admitted to the ICU, all patients had ongoing cytokine storm. Additionally, 3/7 (42.9%) had radiological progression on chest CT. At EOT+28 days, 2/7 (28.6%) patients died due to non-ECP-related causes. Among the survivors, no additional requirement for intensive care unit admission or radiological progression was observed, and invasive mechanical ventilation could be weaned off in 1/5 (20.0%). All patients achieved whole-blood SARS-CoV-2 RNAemia clearance, while 3/7 (42.9%) no longer showed detectable respiratory SARS-CoV-2 RNA. According to immune biomarker profiling, ECP mainly facilitated a decrease in plasma IL-6 and IL-17A levels, as well as the physiological regeneration of peripheral blood immunocyte subpopulations, notably CD8+/CD45RO+ memory T-cells. No safety signals were identified. Conclusions: ECP appears to be a safe and feasible option for adults hospitalized with severe or critical COVID-19 who do not respond to pharmacological interventions. Further trial data are warranted to assess its optimal use. Trial registration: ClinicalTrials.gov NCT05882331 (retrospectively registered).
Heterogeneous Damage to the Olfactory Epithelium in Patients with Post-Viral Olfactory Dysfunction
Authors: Kikuta Shu , Han Bing , Yamasoba Tatsuya
Published: July 2023

Objectives: Post-viral olfactory dysfunction (PVOD) is a neurogenic disorder caused by a common cold virus. Based on the homology of deduced amino acid sequences, olfactory sensory neurons (OSNs) in both mice and humans express either class I or class II odorant receptor genes encoding class I and class II OSNs. The purpose of this study was to determine whether OSN damage in PVOD occurs uniformly in both neuron types. Materials and methods: The characteristics of PVOD patients were compared with those of patients with chronic rhinosinusitis (CRS) or post-traumatic olfactory dysfunction (PTOD). Briefly, subjects underwent orthonasal olfaction tests using five different odors (T&T odors) and a retronasal olfaction test using a single odor (IVO odor). The regions in the mouse olfactory bulb (OB) activated by the T&T and the IVO odors were also examined. Results: Multivariate analysis of 307 cases of olfactory dysfunction (PVOD, 118 cases; CRS, 161 cases; and PTOD, 28 cases) revealed that a combination of responses to the IVO odor, but not to the T&T odors, is characteristic of PVOD, with high specificity (p < 0.001). Imaging analysis of GCaMP3 mice showed that the IVO odor selectively activated the OB region in which the axons of class I OSNs converged, whereas the T&T odors broadly activated the OB region in which axons of class I and class II OSNs converged. Conclusions: A response to T&T odors, but not IVO odor, in PVOD suggests that class I OSNs are injured preferentially, and that OSN damage in PVOD may occur heterogeneously in a neuron-type-dependent manner.
Circulating microRNA Profiles for Premature Cardiovascular Death in Patients with Kidney Failure with Replacement Therapy
Authors: Kuscu Canan , Mallisetty Yamini , Naik Surabhi , Han Zhongji , Berta Caleb J. , Kuscu Cem , Kovesdy Csaba P. , Sumida Keiichi
Published: July 2023

Introduction: Patients with kidney failure with replacement therapy (KFRT) suffer from a disproportionately high cardiovascular disease burden. Circulating small non-coding RNAs (c-sncRNAs) have emerged as novel epigenetic regulators and are suggested as novel biomarkers and therapeutic targets for cardiovascular disease; however, little is known about the associations of c-sncRNAs with premature cardiovascular death in KFRT. Methods: In a pilot case-control study of 50 hemodialysis patients who died of cardiovascular events as cases, and 50 matched hemodialysis controls who remained alive during a median follow-up of 2.0 years, we performed c-sncRNAs profiles using next-generation sequencing to identify differentially expressed circulating microRNAs (c-miRNAs) between the plasma of cases and that of controls. mRNA target prediction and pathway enrichment analysis were performed to examine the functional relevance of differentially expressed c-miRNAs to cardiovascular pathophysiology. The association of differentially expressed c-miRNAs with cardiovascular mortality was examined using multivariable conditional logistic regression. Results: The patient characteristics were similar between cases and controls, with a mean age of 63 years, 48% male, and 54% African American in both groups. We detected a total of 613 miRNAs in the plasma, among which five miRNAs (i.e., miR-129-1-5p, miR-500b-3p, miR-125b-1-3p, miR-3648-2-5p, and miR-3150b-3p) were identified to be differentially expressed between cases and controls with cut-offs of p < 0.05 and log2 fold-change (log2FC) > 1. When using more stringent cut-offs of p-adjusted < 0.05 and log2FC > 1, only miR-129-1-5p remained significantly differentially expressed, with higher levels of miR-129-1-5p in the cases than in the controls. The pathway enrichment analysis using predicted miR-129-1-5p mRNA targets demonstrated enrichment in adrenergic signaling in cardiomyocytes, arrhythmogenic right ventricular cardiomyopathy, and oxytocin signaling pathways. In parallel, the circulating miR-129-1-5p levels were significantly associated with the risk of cardiovascular death (adjusted OR [95% CI], 1.68 [1.01–2.81] for one increase in log-transformed miR-129-1-5p counts), independent of potential confounders. Conclusions: Circulating miR-129-1-5p may serve as a novel biomarker for premature cardiovascular death in KFRT.
Efficacy and Safety of Ticagrelor versus Clopidogrel in Dialysis Patients with Coronary Syndromes: A Systematic Review and Meta-Analysis
Authors: Burlacu Alexandru , Floria Mariana , Brinza Crischentian , Covic Adrian
Published: July 2023

(1) Background: The optimal antiplatelet therapy for end-stage kidney disease (ESKD) patients on chronic dialysis presenting with acute or chronic coronary syndromes (ACS or CCS) remains uncertain. This meta-analysis aimed to compare the efficacy and safety endpoints of ticagrelor and clopidogrel in ESKD patients requiring dialysis and presenting with ACS or CCS. (2) Methods: Studies were included comparing ticagrelor and clopidogrel in ESKD patients on chronic dialysis with ACS or CCS. The primary composite efficacy outcome was a combination of all-cause and cardiovascular mortality, recurrent myocardial infarction or coronary revascularization, and ischemic or hemorrhagic stroke. The primary safety outcome was major and non-major bleeding events. (3) Results: Five observational studies met the eligibility criteria. The pooled analysis showed no significant difference in the primary composite efficacy outcome between ticagrelor and clopidogrel (p = 0.40). Similarly, the 2 groups had no significant differences in all-cause mortality (p = 0.82) or cardiovascular mortality (p = 0.79). Ticagrelor did not show a significantly different risk of coronary revascularization (p = 0.35) or recurrent myocardial infarction (p = 0.41) compared to clopidogrel. Also, the risk of stroke was similar (p = 0.21). The 2 groups had no significant difference in the primary composite safety outcome (p = 0.22) or major bleeding events (p = 0.27). (4) Conclusions: In ESKD patients on chronic dialysis with ACS or CCS, there was no significant difference in efficacy or safety outcomes between ticagrelor and clopidogrel. Further randomized controlled trials are needed to establish the optimal antiplatelet therapy in this population.
Diagnosis of Froin’s Syndrome by Parallel Analysis of Ventriculoperitoneal Shunt and Lumbar Cerebrospinal Fluid in a Patient with Cervical Spinal Stenosis
Authors: Fries Franca Laura , Kleiser Benedict , Schwarz Patricia , Tieck Maria P. , Laichinger Kornelia , Mengel Annerose , Ziemann Ulf , Kowarik Markus C.
Published: July 2023

Elevated protein levels in cerebrospinal fluid (CSF) can occur in various pathologies and are sometimes difficult to interpret. We report a 62-year-old male patient with subacute neurological deterioration, progressive tetraparesis, and cytoalbumin dissociation in the lumbar CSF. The patient had a pre-existing cervical spinal stenosis with mild tetraparesis. Based on the initial cytoalbumin dissociation (protein 938 mg/dL, 4 leucocytes/µL), Guillain–Barré syndrome was initially considered. For further diagnosis, a CSF sample was taken from a pre-existing ventriculoperitoneal shunt, which showed a normal protein and cell count considering the patient’s age (protein 70 mg/dL, 1 leucocyte/µL). In conclusion, we suggest that intermediate aggravation of tetraparesis was due to pneumonia with septic constellation, and the cytoalbumin dissociation was interpreted as Froin’s syndrome (FS) due to spinal stenosis. In this unique case, we were able to prove the -often suspected- case of FS by parallel analysis of ventriculoperitoneal shunt and lumbar CSF. The triad of xanthochromia, high protein levels, and marked coagulation was first described by Georges Froin and occurs in various processes leading to severe spinal stenosis. The altered composition of lumbar CSF might be due to impaired CSF circulation; however, the exact mechanisms of this phenomenon require further investigation.
Perioperative Renal Ultrasonography of Arterio-to-Venous Coupling Predicts Postoperative Complications after Major Laparoscopic Urologic Surgery
Authors: Brusasco Claudia , Tavazzi Guido , Cucciolini Giada , Di Nicolò Pierpaolo Di , Wong Adrian , Di Domenico Antonia Di , Germinale Federico , Dotta Federico , Micali Marco , Coccolini Federico , Santori Gregorio , Dazzi Federico , Introini Carlo , Corradi Francesco
Published: July 2023

Point-of-care ultrasonography (POCUS) with concomitant venous and arterial Doppler assessment enables clinicians to assess organ-specific blood supply. To date, no studies have investigated the usefulness of including a comprehensive perioperative POCUS assessment of patients undergoing major laparoscopic surgery. The primary aim of the present study was to evaluate whether the combined venous and arterial renal flow evaluation, measured at different time points of perioperative period, may represent a clinically useful non-invasive method to predict postoperative acute kidney injury (AKI) after major laparoscopic urologic surgery. The secondary outcome was represented by the development of any postoperative complication at day 7. We included 173 patients, subsequently divided for analysis depending on whether they did (n = 55) or did not (n = 118) develop postoperative AKI or any complications within the first 7 days. The main results of the present study were that: (1) the combination of arterial hypoperfusion and moderate-to-severe venous congestion inferred by POCUS were associated with worst outcomes (respectively, HR:2.993, 95%CI:1.522–5.884 and HR:8.124, 95%CI:3.542–18, p < 0.001); (2) high intra-operative abdominal pressure represents the only independent determinant of postoperative severe venous congestion (OR:1.354, 95%CI:1.017–1.804, p = 0.038); (3) the overall number of complications relies on the balance between arterial inflow and venous outflow in order to ensure the adequacy of peripheral perfusion; and (4) the overall reliability of splanchnic perfusion assessment by Doppler is high with a strong inter-rater reliability (ICC:0.844, 95%CI:0.792–0.844). The concomitant assessment of arterial and venous Doppler patterns predicts postoperative complications after major laparoscopic urologic surgery and may be considered a useful ultrasonographic biomarker to stratify vulnerable patients at risk for development of postoperative complications.
Efficacy and Safety of S1P1 Receptor Modulator Drugs for Patients with Moderate-to-Severe Ulcerative Colitis
Authors: Bencardino Sarah , D’Amico Ferdinando , Faggiani Ilaria , Bernardi Francesca , Allocca Mariangela , Furfaro Federica , Parigi Tommaso Lorenzo , Zilli Alessandra , Fiorino Gionata , Peyrin-Biroulet Laurent , Danese Silvio
Published: July 2023

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that negatively impacts patients’ quality of life. In the last decades, the therapeutic options available for the management of patients with moderate to severe UC have increased significantly, including not only biological drugs but also small molecules. However, there is a persistent need to develop new drugs that act on new targets while minimizing the risk of adverse events. Sphingosine-1-phosphate (S1P) is a membrane-derived lysophospholipid. The S1P gradient between tissues and the circulatory system has a key role in regulating the trafficking of immune cells as autoreactive B and T lymphocytes. S1P receptor modulators could be a safe and efficacious alternative mechanism for reducing inflammation in immune-mediated disorders, including UC, by reducing lymphocyte egress from the lymph nodes to the bloodstream. Several S1P receptor modulators have been developed and tested in UC. Ozanimod is already approved by Food and Drug Administration (FDA) and European Medical Agency (EMA), while etrasimod and VTX002 are still under approval. Oral administration route, rapidity and reliable safety profile are the main advantages of this class of drugs. The aim of this review is to summarize the available evidence for the efficacy, safety, and pharmacokinetics of ozanimod, etrasimod, and VTX002 in UC.
The Association between the L3 Skeletal Muscle Index Derived from Computed Tomography and Clinical Outcomes in Patients with Urinary Tract Infection in the Emergency Department
Authors: An Jinjoo , Choi Seung Pill , Oh Jae Hun , Zhu Jong Ho , Kim Sung Wook , Kim Soo Hyun
Published: July 2023

The occurrence of a critical event during a urinary tract infection (UTI) can have a significant impact on mortality. This study aimed to investigate the association between the skeletal muscle index (SMI) and critical events in patients with a UTI. From April 2019 to March 2022, a total of 478 patients who met the diagnostic criteria of a UTI and underwent an abdominal CT were included in this study. Multivariate binary logistic regression analysis was used to assess independent predictors of critical events. The primary outcome was any critical event, defined as the initiation of dialysis, invasive ventilation, initiation of vasoactive medications, cardiac arrest, or death. The UTI patients were divided into two groups: those with a low SMI (n = 93) and those with a high SMI (n = 385). In multivariate analysis, a low SMI, diabetes mellitus, altered mentality, lactate levels, and creatinine levels were identified as significant predictors of critical events. A low SMI is an independent factor associated with the occurrence of critical events in UTI patients during hospitalization. Patients with a low SMI, indicating muscle wasting, may have less resilience to infections and a higher risk of experiencing severe complications. Considering the SMI along with other clinical factors can help health care providers assess and manage UTI patients.
Debridement, Antibiotics and Implant Retention: A Systematic Review of Strategies for Treatment of Early Infections after Revision Total Knee Arthroplasty
Authors: Hulleman Caspar W. J. , de Windt Tommy S. , Veerman Karin , Goosen Jon H. M. , Wagenaar Frank-Christiaan B. M. , van Hellemondt Gijs G.
Published: July 2023

Goal: The purpose of this review is to provide a systematic and comprehensive overview of the available literature on the treatment of an early prosthetic joint infection (PJI) after revision total knee arthroplasty (TKA) and provide treatment guidelines. Methods: This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The search was conducted using the electronic databases of PubMed, Trip, Cochrane, Embase, LILACS and SciElo. After the inclusion of the relevant articles, we extracted the data and results to compose a treatment algorithm for early and acute PJI after revision TKA. Results: After applying the in- and exclusion criteria, seven articles were included in this systematic review focusing on debridement, antibiotics and implant retention (DAIR) for PJI following revision TKA, of which one was prospective and six were retrospective. All studies were qualified as level IV evidence. Conclusions: The current literature suggests that DAIR is a valid treatment option for early infections after revision TKA with success rates of 50–70%. Repeat DAIR shows success rates of around 50%. Further research should be aimed at predicting successful (repeat/two-stage) DAIRs in larger study populations, antibiotic regimes and the cost effectiveness of a second DAIR after revision TKA.
Urinary Calcium Is Associated with Serum Sclerostin among Stone Formers
Authors: Rodrigues Fernanda Guedes , Ormanji Milene Subtil , Pietrobom Igor Gouveia , Matos Ana Cristina Carvalho de , De Borst Martin H. , Heilberg Ita Pfeferman
Published: July 2023

Background: Sclerostin plays an important role in bone metabolism and adipose tissue. Animal studies suggest that sclerostin influences urinary calcium (UCa), but this relationship has not been evaluated in stone formers (SFs). We aimed to investigate the association of UCa with serum sclerostin, bone mineral density (BMD), and body composition among SFs. Methods: Clinical and laboratorial data were retrieved from medical records. Determinants of UCa were studied using linear regression. Results: A total of 107 SFs (35.8 ± 9.3 years, 54% male) with eGFR 99.8 ± 14.5 mL/min/1.73 were studied. Subjects were split by sex and grouped into tertiles of UCa levels. Men in the highest UCa tertile had higher body mass index (BMI) and serum sclerostin, lower lean mass, and a trend towards higher fat mass. Women in the highest tertile had higher BMI and a trend towards higher serum sclerostin. Hypertension and metabolic syndrome, but not lower BMD, were more prevalent in the highest UCa tertile for both sexes. Sclerostin was positively correlated with fat mass and inversely correlated with lean mass among men, but not among women. BMD corrected for BMI at lumbar spine was inversely associated with UCa in a univariate analysis, but only serum sclerostin, hypertension, and NaCl intake were independent determinants of UCa in the multivariate model. Conclusion: The present findings disclose that in addition to hypertension and salt intake, serum sclerostin is associated with urinary calcium in stone formers, suggesting that in addition to the hormones traditionally thought to alter calcium reabsorption in the kidney, sclerostin may play a significant additional role, warranting further investigation.
Metabolic Syndrome and Its Components Have a Different Presentation and Impact as Cardiovascular Risk Factors in Psoriatic and Rheumatoid Arthritis
Authors: Atzeni Fabiola , La Corte Laura , Cirillo Mariateresa , Giallanza Manuela , Galloway James , Rodríguez-Carrio Javier
Published: July 2023

Patients with chronic inflammatory arthritis have a higher cardiovascular (CV) risk than the general population. Traditional CV risk factors are clearly implicated, while the impact of metabolic syndrome (MetS) is less defined. The aim of this study was to compare MetS prevalence and impact on the CV risk in psoriatic arthritis (PsA) versus rheumatoid arthritis (RA). A retrospective analysis of real-world data of PsA and RA patients referred to a rheumatology clinic was conducted. The following data were extracted and compared: demographic data; clinical data; presence of traditional CV risk factors and MetS. Univariate and multivariate models were used to compare the impact of MetS and its components in patients with PsA versus RA. Overall, 170 patients were included (PsA: 78; RA; 92). The two groups differed significantly in mean age, disease duration, and presence of MetS, while other variables were comparable. Univariate and multivariate analysis identified distinct predictors of MetS in PsA (hypertension) and RA (dyslipidemia). The history of CV events was similar in the two groups. Predictors of CV events were MetS and most of its components in PsA, while dyslipidemia was the strongest predictor in RA. These associations were stronger in PsA than in RA. In conclusion, the impact of MetS and its components is different in PsA and RA. The association of these risk factors with CV events is stronger in PsA than in RA. This suggests the implication of different mechanisms, which may require distinct strategies for the prevention of CV events in PsA and RA.
A New Mechanical Mouth Opener for Dynamic Magnetic Resonance Imaging of the Temporomandibular Joint
Authors: Knezevic Milica Jeremic , Knezevic Aleksandar , Boban Jasmina , Maletin Aleksandra , Milekic Bojana , Koprivica Daniela Djurovic , Mijatov Ivana , Puskar Tatjana
Published: July 2023

(1) Background: During the magnetic resonance imaging (MRI) of the temporomandibular joint (TMJ), it is necessary to scan the joints in the closed- and open-jaw position, as well as in the maximally open-jaw position. In order to examine both joints in these positions, an MRI compatible mouth opener is required, which allows the articular surfaces to maintain their position stably. (2) Methods: In this study, we included 200 patients aged 18 to 65, with various levels of clinical severity. The mouth opener is made of polymethyl methacrylate and used for dynamic imaging of TMJ. It is in the form of an arrow, with incisures on upper and lower surfaces 1 mm apart and these match possible variations in jaw opening. All the patients were scanned with mouth opener and, immediately after this scanning, with syringe (20 ccm) as a standard device used for mouth opening in clinical setting. (3) Results: A total of 200 MR examinations of TMJs were performed and the mechanical mouth opener was successfully applied without artifacts in all patients. The mouth opener device proved to be adequate in case of MRI of the TMJ for different ranges of mouth opening with the proper protocol for provoked imaging, because the incisures are located at a distance of 1 mm and no objective artifacts were observed in any examination that degraded the diagnostic quality of the examination. (4) Conclusions: The design of the acrylate mouth opener is precisely defined, and it has a purpose in the MRI diagnosis of TMJ disorders.
Prognostic Usefulness of Motor Unit Number Index (MUNIX) in Patients Newly Diagnosed with Amyotrophic Lateral Sclerosis
Authors: Risi Barbara , Cotti Piccinelli Stefano , Gazzina Stefano , Labella Beatrice , Caria Filomena , Damioli Simona , Poli Loris , Padovani Alessandro , Filosto Massimiliano
Published: July 2023

The MUNIX technique allows us to estimate the number and size of surviving motor units (MUs). Previous studies on ALS found correlations between MUNIX and several clinical measures, but its potential role as a predictor of disease progression rate (DPR) has not been thoroughly evaluated to date. We aimed to investigate MUNIX’s ability to predict DPR at a six-month follow up. Methods: 24 ALS patients with short disease duration (<24 months from symptoms’ onset) were enrolled and divided according to their baseline DPR into two groups (normal [DPR-N] and fast [DPR-F] progressors). MUNIX values were obtained from five muscles (TA, APB, ADM, FDI, Trapezius) and averaged for each subject. Results: MUNIX was found to predict DPR at follow up in a multivariable linear regression model; namely, patients with lower MUNIX values were at risk of showing greater DPR scores at follow up. The result was replicated in a simple logistic regression analysis, with the dichotomic category “MUNIX-Low” as the independent variable and the outcome “DPR-F” as the dependent variable. Conclusions: our results pave the way for the use of the MUNIX method as a prognostic tool in early ALS, enabling patients’ stratification according to their rates of future decline.
Exploring the Role of CD74 and D-Dopachrome Tautomerase in COVID-19: Insights from Transcriptomic and Serum Analyses
Authors: Ralchev Ralchev Nikola , Lyubenova Bradyanova Silviya , Valerieva Doneva Yana , Mihaylova Nikolina , Vikentieva Elefterova-Florova Elena , Ivanov Tchorbanov Andrey , Munoz-Valle José Francisco , Petralia Maria Cristina , Checconi Paola , Nicoletti Ferdinando , Fagone Paolo
Published: July 2023

The COVID-19 pandemic has posed a significant threat to public health worldwide. While some patients experience only mild symptoms or no symptoms at all, others develop severe illness, which can lead to death. The host immune response is believed to play a crucial role in determining disease severity. In this study, we investigated the involvement of CD74 and D-DT in COVID-19 patients with different disease severities, by employing an in silico analysis of a publicly available transcriptomic dataset and by measuring their serum levels by ELISA. Our results showed a significant increase in MIF levels in PBMCs from COVID-19 patients, as well as a significant increase in the D-DT levels in PBMCs. However, we observed no modulation in the serum levels of D-DT. We also observed a concordant reduction in the serum levels and PBMCs expression levels of CD74. Furthermore, we found a negative correlation between CD74 serum levels and IL-13. In conclusion, our study sheds light on the involvement of CD74 and D-DT in COVID-19, with potential implications for disease severity and treatment. Further studies are needed to fully elucidate the mechanisms underlying these observations and to explore the potential therapeutic value of targeting CD74 and IL-13 in COVID-19.
Sex-Based Differences in Rotational Atherectomy and Long-Term Clinical Outcomes
Authors: Ayoub Mohamed , Lutsch Selina , Behnes Michael , Akin Muharrem , Schupp Tobias , Akin Ibrahim , Rudolph Volker , Westermann Dirk , Mashayekhi Kambis
Published: July 2023

Present research on the influence of gender on the treatment of coronary artery disease (CAD) and the outcome after percutaneous coronary intervention (PCI) is inconsistent. Sex differences in the presentation of CAD and the success after treatment have been described. We intend to compare the male and female sex in the procedure and the long-term outcome of Rotational Atherectomy (RA). A total of 597 consecutive patients (20.3% female and 79.7% male, mean age 75.3 ± 8.9 years vs. 72.7 ± 9 years, p < 0.001) undergoing Rotational Atherectomy between 2015 and 2020 were enrolled in the analysis. Demographic and clinical data were registered. In-hospital, 1-year, and 3-year MACCEs (major adverse cardiac and cerebrovascular events) were calculated. Women presented more often with myocardial infarction (23.9% vs. 14.9%, p = 0.017). The intervention was mainly performed via femoral access compared to radial access (65.4% vs. 33.6%, p = 0.002). Women had a smaller diameter of the balloon predilatation compared to men (2.8 ± 0.5 mm vs. 3.15 ± 2.4 mm, p < 0.05) and a smaller maximum diameter of the implanted stent (3.5 ± 1.2 mm vs. 4.10 ± 6.5 mm, p = 0.01). In-hospital, 1-year-, and 3-year MACCEs did not differ between the sexes. After a multivariate analysis, no difference between men and women could be detected. In conclusion, this analysis shows differences between women and men in periprocedural characteristics but does not show any differences after RA regarding in-hospital, 1-year-, and 3-year MACCEs.
Pancreatic Fistulas: Current Evidence and Strategy—A Narrative Review
Authors: Meierhofer Clara , Fuegger Reinhold , Biebl Matthias , Schoefl Rainer
Published: July 2023

Pancreatic fistulas are highly feared complications following surgery on or near the pancreas, abdominal trauma, or severe inflammation. These fistulas arise from leaks in the pancreatic ductal system, leading to various complications such as abscesses, delayed gastric emptying, and hemorrhage. Severe cases present with sepsis or organ failure, dramatically increasing mortality and morbidity. Risk factors include smoking, high BMI, male gender, age, and surgery-related factors like prolonged operation time and non-ligation of the main pancreatic duct. Therefore, treatment options and preventive measurements have become a hot topic in recent years. Studies have investigated the use of fibrin sealants, different closure methods, and less invasive surgical techniques. Treatment options consist of conservative measurements and the use of percutaneous drainage, prophylactic transpapillary stenting, and surgery in severe cases. As EUS has become widely available, transmural stenting started to influence the management of pancreatic fluid collections (PFCs). However, studies on its use for the management of pancreatic fistulas are lacking. Medical treatment options like somatostatin analogs and pasireotide have been investigated but yielded mixed results.
In Vitro and In Vivo Evaluation of Epidermal Growth Factor (EGF) Loaded Alginate-Hyaluronic Acid (AlgHA) Microbeads System for Wound Healing
Authors: Ali Maqsood , Kwak Si Hyun , Byeon Je Yeon , Choi Hwan Jun
Published: July 2023

The management of skin injuries is one of the most common concerns in medical facilities. Different types of biomaterials with effective wound-healing characteristics have been studied previously. In this study, we used alginate (Alg) and hyaluronic acid (HA) composite (80:20) beads for the sustained release of epidermal growth factor (EGF) delivery. Heparin crosslinked AlgHA beads showed significant loading and entrapment of EGF. Encapsulated beads demonstrated biocompatibility with rat L929 cells and significant migration at the concentration of AlgHAEGF100 and AlgHAEGF150 within 24 h. Both groups significantly improved the expression of Fetal Liver Kinase 1 (FLK-1) along with the Intercellular Adhesion Molecule-1 (ICAM-1) protein in rat bone Mesenchymal stem cells (rbMSCs). In vivo assessment exhibited significant epithelialization and wound closure gaps within 2 weeks. Immunohistochemistry shows markedly significant levels of ICAM-1, FLK-1, and fibronectin (FN) in the AlgHAEGF100 and AlgHAEGF150 groups. Hence, we conclude that the EGF-loaded alginate-hyaluronic acid (AlgHA) bead system can be used to promote wound healing.
Nearshore Observations and Modeling: Synergy for Coastal Flooding Prediction
Authors: Postacchini Matteo , Melito Lorenzo , Ludeno Giovanni
Published: July 2023

Coastal inundation has recently started to require significant attention worldwide. The increasing frequency and intensity of extreme events (sea storms, tsunami waves) are highly stressing coastal environments by endangering a large number of residential areas, ecosystems, and tourist facilities, and also leading to potential environmental risks. Predicting such events and the generated coastal flooding is thus of paramount importance and can be accomplished by exploiting the potential of different tools. An example is the combination of remote sensors, like marine radars, with numerical models. Specifically, while instruments like X-band radars are able to precisely reconstruct both wave field and bathymetry up to some kilometers off the coast, wave-resolving Boussinesq-type models can reproduce the wave propagation in the nearshore area and the consequent coastal flooding. Hence, starting from baseline simulations of wave propagation and the conversion of water elevation results into radar images, the present work illustrates the reconstruction of coastal data (wave field and seabed depth) using a specifically suited data processing method, named the “Local Method”, and the use of such coastal data to run numerical simulations of coastal inundation in different scenarios. Such scenarios were built using two different European beaches, i.e., Senigallia (Italy) and Oostende (Belgium), and three different directional spreading values to evaluate the performances in cases of either long- or short-crested waves. Both baseline and inundation simulations were run using the FUNWAVE-TVD solver. The overall validation of the methodology, in terms of maximum inundation, shows its good performance, especially in cases of short-crested wind waves. Furthermore, the application on Oostende Beach demonstrates that the present methodology might work using only open-access tools, providing an easy investigation of coastal inundation and potential low-cost integration into early warning systems.