bluuebunny/crossref_metadata_2025 huggingface dataset:
Mild Acquired von Willebrand Syndrome and Cholestasis in Pediatric and Adult Patients with Fontan Circulation
Authors: Meinel Katharina , Korak Felicitas , Dusleag Martin , Strini Tanja , Baumgartner Daniela , Burmas Ante , Sallmon Hannes , Zieger Barbara , Schlagenhauf Axel , Koestenberger Martin
Published: February 2023

Background: Hemodynamic alterations in Fontan patients (FP) are associated with hemostatic dysbalance and Fontan-associated liver disease. Studies of other hepatopathologies indicate an interplay between cholestasis, tissue factor (TF), and von Willebrand factor (VWF). Hence, we hypothesized a relationship between the accumulation of bile acids (BA) and these hemostatic factors in FP. Methods: We included 34 FP (Phenprocoumon n = 15, acetylsalicylic acid (ASA) n = 16). BA were assessed by mass spectrometry. TF activity and VWF antigen (VWF:Ag) were determined by chromogenic assays. VWF collagen-binding activity (VWF:CB) was assessed via ELISA. Results: Cholestasis was observed in 6/34 FP (total BA ≥ 10 µM). BA levels and TF activity did not correlate (p = 0.724). Cholestatic FP had lower platelet counts (p = 0.013) from which 5/6 FP were not treated with ASA. VWF:Ag levels were increased in 9/34 FP and significantly lower in FP receiving ASA (p = 0.044). Acquired von Willebrand syndrome (AVWS) was observed in 10/34-FP, with a higher incidence in cholestatic FP (4/6) (p = 0.048). Conclusions: Cholestasis is unexpectedly infrequent in FP and seems to be less frequent under ASA therapy. Therefore, ASA may reduce the risk of advanced liver fibrosis. FP should be screened for AVWS to avoid bleeding events, especially in cholestatic states.
Post-Inflammatory Hypopigmentation: Review of the Etiology, Clinical Manifestations, and Treatment Options
Authors: Rao Medha , Young Katherine , Jackson-Cowan Ladonya , Kourosh Arianne , Theodosakis Nicholas
Published: February 2023

Post-inflammatory hypopigmentation is a common acquired pigmentary disorder that is more prominent in skin of color, leading to great cosmetic and psychosocial implications. Often, a diagnosis with a pigmentary disorder can negatively impact an individual’s health-related quality of life and may result in stigma. Although most cases of post-inflammatory hypopigmentation resolve spontaneously over time, a systematic diagnostic approach can help with identifying the underlying etiology and informing treatment strategies. It can be due to cutaneous inflammation, sequelae of inflammatory or infectious dermatoses, or dermatologic procedures. Therefore, a thorough understanding of the epidemiology, patient history, physical exam findings, and clinical features of post-inflammatory hypopigmentation phenomenon can explain the primary cause to providers and allow for patient education. It is also important to understand the various therapeutic approaches available and the efficacy of these options, which will inform providers to choose the appropriate therapy for patients. Although algorithms exist for classifying acquired disorders of hypopigmentation, there are no established algorithms for the diagnosis and treatment of post-inflammatory hypopigmentation, which warrants further exploration and discourse.
The Relationship between Social Support and Anxiety Symptoms in Informal Carers: A Systematic Review and Meta-Analysis
Authors: Priego-Cubero Emilia , Orgeta Vasiliki , López-Martínez Catalina , del-Pino-Casado Rafael
Published: February 2023

Background: Providing care can be challenging for informal carers and increases the risk of mental health problems, such as experiencing clinical symptoms of anxiety. While strengthening social support for informal carers is a common recommendation to reduce this risk, no systematic review or meta-analysis to date has examined the relationship between social support and anxiety symptoms in informal carers. The aim of our study was to systematically review the current evidence on the association between perceived and received social support and anxiety symptoms in informal carers of dependent adults and older people, and to comment on the quality of the evidence. Methods: We searched PubMed, CINAHL (EBSCO), PsycINFO (ProQuest), Scopus, and LILACS up to 31 March 2021 for articles reporting on the association between caregiver anxiety symptoms and social support. A random-effects model was used to pool estimates, and each study was rated for quality using pre-specified criteria. Publication bias was assessed using a funnel plot and Egger’s regression test, which was adjusted using trim and fill analysis. Results: From the 2180 identified articles, 35 studies met our inclusion criteria, reporting on 5036 informal carers in total. We found a moderate negative association between perceived social support and caregiver anxiety symptoms (r = −0.31, 95% CI = −0.35, −0.27) and a small, negative association between received social support and caregiver anxiety (r = −0.15, 95% CI = −0.22, −0.08). Conclusion: The levels of perceived social support showed a significant negative association with caregiver anxiety symptoms. Policymakers and those working directly with informal carers should consider the development of targeted social support interventions that specifically enhance the levels of perceived social support to reduce symptoms of anxiety in informal carers.
Daytime Variation of Chloral Hydrate-Associated Sedation Outcomes: A Propensity-Matched Cohort Study
Authors: Cui Yu , Guo Langtao , Xu Li , Mu Qixia , Wu Qunying , Kang Lu , Chen Qin , He Yani , Liu Hong
Published: February 2023

Background: Physiological processes influencing a drugs’ efficacy change substantially over the course of the day. However, it is unclear whether there is an association between the sedative success rate of chloral hydrate and the time of day. We conducted a retrospective study of 41,831 cases, to determine if there was a difference in sedation success rate with chloral hydrate in children seen in the morning and afternoon. Methods: Patients who accepted the sedation service were included. Eligible patients were divided into two cohorts of morning and afternoon cases, according to the time of day when the initial dose of chloral hydrate was administered. To ensure that the two groups were comparable, a propensity score matching method was utilized. Results: The success rate with the initial dose of chloral hydrate was higher in patients who received sedation services in the afternoon. In the subgroup analysis, the afternoon cases had a higher sedation success rate compared to the morning cases in male patients; whereas, in female patients, no difference was detected between the morning versus afternoon cases. Conclusions: These results show that the afternoon cases had a higher sedation success rate than the morning cases, despite the afternoon cases receiving relatively lower initial dose than the morning cases. However, the clinical significance remains to be discussed, and further prospective studies are needed to validate the findings.
Investigating the Ischaemic Phase of Skin NADH Fluorescence Dynamics in Recently Diagnosed Primary Hypertension: A Time Series Analysis
Authors: Pawlak-Chomicka Regina , Chomicki Wojciech , Krauze Tomasz , Uruski Paweł , Guzik Maria , Piskorski Jarosław , Tykarski Andrzej , Guzik Przemysław
Published: February 2023

The reduced form of nicotinamide adenine dinucleotide (NADH) is crucial in cellular metabolism. During hypoxia, NADH accumulation results from anaerobic cytoplasmic glycolysis and impaired mitochondrial function. This study aimed to compare the dynamic changes in the 460-nm forearm skin fluorescence, which reflects cellular NADH content, during transient ischaemia between healthy individuals and patients with newly diagnosed, untreated essential hypertension (HA). Sixteen healthy volunteers and sixty-five patients with HA underwent non-invasive measurement of forearm skin NADH content using the Flow Mediated Skin Fluorescence (FMSF) method at rest and during a 100-s transient ischaemia induced by inflation of the brachial cuff. The fluorescent signal was sampled at 25 Hz. All samples were normalised to the end of the ischaemic phase, which is the most stable phase of the whole recording. Slope values of 1 s linear regressions were determined for every 25-sample neighbouring set. The 1-s slopes in the early phase of skin ischaemia, indicating quicker hypoxia-induced NADH accumulation in skin, were significantly higher in patients with HA than in healthy individuals. These findings suggest that some protecting mechanisms postponing the early consequences of early cellular hypoxia and premature NADH accumulation during skin ischaemia are impaired in patients with untreated HA. Further studies are needed to investigate this phenomenon.
Immediate Effects of Myofascial Release Treatment on Lumbar Microcirculation: A Randomized, Placebo-Controlled Trial
Authors: Brandl Andreas , Egner Christoph , Reer Rüdiger , Schmidt Tobias , Schleip Robert
Published: February 2023

(1) Background: Inflammatory processes in the thoracolumbar fascia (TLF) lead to thickening, compaction, and fibrosis and are thought to contribute to the development of nonspecific low back pain (nLBP). The blood flow (BF) of fascial tissue may play a critical role in this process, as it may promote hypoxia-induced inflammation. The primary objective of the study was to examine the immediate effects of a set of myofascial release (MFR) techniques on the BF of lumbar myofascial tissue. The secondary objectives were to evaluate the influence of TLF morphology (TLFM), physical activity (PA), and body mass index (BMI) on these parameters and their correlations with each other. (2) Methods: This study was a single-blind, randomized, placebo-controlled trial. Thirty pain-free subjects (40.5 ± 14.1 years) were randomly assigned to two groups treated with MFR or a placebo intervention. Correlations between PA, BMI, and TLFM were calculated at baseline. The effects of MFR and TLFM on BF (measured with white light and laser Doppler spectroscopy) were determined. (3) Results: The MFR group had a significant increase in BF after treatment (31.6%) and at follow-up (48.7%) compared with the placebo group. BF was significantly different between disorganized and organized TLFM (p < 0.0001). There were strong correlations between PA (r = −0.648), PA (d = 0.681), BMI (r = −0.798), and TLFM. (4) Conclusions: Impaired blood flow could lead to hypoxia-induced inflammation, possibly resulting in pain and impaired proprioceptive function, thereby likely contributing to the development of nLBP. Fascial restrictions of blood vessels and free nerve endings, which are likely associated with TLFM, could be positively affected by the intervention in this study.
A Prospective Observational Study on Short and Long-Term Outcomes of COVID-19 Patients with Acute Hypoxic Respiratory Failure Treated with High-Flow Nasal Cannula
Authors: Medeiros Kyle J. , Valsecchi Carlo , Winterton Dario , Morais Caio A. , Delgado Eduardo Diaz , Smith Shaun , Safaee Fakhr Bijan , Ranjeva Sylvia , Capriles Martin , Gaulton Timothy , Li Matthew D. , Fintelmann Florian , Tahir Ismail , Carroll Ryan , Bittner Edward A. , Hibbert Kathryn A. , Thompson Boyd Taylor , Hardin Charles C. , Santiago Roberta RS , La Vita Carolyn J. , Cereda Maurizio , Berra Lorenzo
Published: February 2023

(1) The use of high-flow nasal cannula (HFNC) combined with frequent respiratory monitoring in patients with acute hypoxic respiratory failure due to COVID-19 has been shown to reduce intubation and mechanical ventilation. (2) This prospective, single-center, observational study included consecutive adult patients with COVID-19 pneumonia treated with a high-flow nasal cannula. Hemodynamic parameters, respiratory rate, inspiratory fraction of oxygen (FiO2), saturation of oxygen (SpO2), and the ratio of oxygen saturation to respiratory rate (ROX) were recorded prior to treatment initiation and every 2 h for 24 h. A 6-month follow-up questionnaire was also conducted. (3) Over the study period, 153 of 187 patients were eligible for HFNC. Of these patients, 80% required intubation and 37% of the intubated patients died in hospital. Male sex (OR = 4.65; 95% CI [1.28; 20.6], p = 0.03) and higher BMI (OR = 2.63; 95% CI [1.14; 6.76], p = 0.03) were associated with an increased risk for new limitations at 6-months after hospital discharge. (4) 20% of patients who received HFNC did not require intubation and were discharged alive from the hospital. Male sex and higher BMI were associated with poor long-term functional outcomes.
Successful Pregnancy and Delivery at Term Following Intravenous Immunoglobulin Therapy with Heparin for Unexplained Recurrent Pregnancy Loss Suspected of Immunological Abnormalities: A Case Report and Brief Literature Review
Authors: Mitsui Junichiro , Ota Kuniaki , Takayanagi Yuko , Nako Yurie , Tajima Makiko , Fukui Atsushi , Kawai Kiyotaka
Published: February 2023

About 60% of cases of recurrent pregnancy loss have unexplained etiology. Immunotherapy for unexplained recurrent pregnancy loss is still unestablished. A 36-year-old woman, not obese, had a stillbirth at 22 gestational weeks and a spontaneous abortion at 8 weeks. She had been examined for recurrent pregnancy loss at previous clinics with no significant findings. When she visited our clinic, a hematologic test showed a Th1/Th2 ratio imbalance. Ultrasonography, hysteroscopy, and semen analysis showed no abnormalities. She successfully conceived by embryo transfer in hormone replacement therapy cycle. However, she had a miscarriage at 19 weeks. The baby had no deformities, but a chromosomal test was not performed, according to the parents’ will. The placenta pathologically suggested hemoperfusion problems. Her and her husband’s chromosomal tests showed normal karyotypes. Other examinations revealed a repeated Th1/Th2 ratio imbalance and a high resistance index of uterine radial artery blood flow. She was administered low-dose aspirin, intravenous immunoglobulin, and unfractionated heparin after the second embryo was transferred. Her baby was healthily born by cesarean section at 40 weeks. Intravenous immunoglobulin therapy can be a choice for recurrent miscarriage without risk factors because it has clinically beneficial influences on the patient’s immunological aberration.
Association of Sonographic Sarcopenia and Falls in Older Adults Presenting to the Emergency Department
Authors: Wongtangman Thiti , Thatphet Phraewa , Shokoohi Hamid , McFadden Kathleen , Ma Irene , Al Saud Ahad , Vivian Rachel , Hines Ryan , Gullikson Jamie , Morone Christina , Parente Jason , Perkisas Stany , Liu Shan W.
Published: February 2023

Background and Objective: To determine the association between point-of-care-ultrasonography (POCUS)-measured sarcopenia and grip strength, as well as the history of prior-year falls among older adults admitted to the emergency department observation unit (EDOU). Materials and Methods: This cross-sectional observational study was conducted over 8 months at a large urban teaching hospital. A consecutive sample of patients who were 65 years or older and admitted to the EDOU were enrolled in the study. Using standardized techniques, trained research assistants and co-investigators measured patients’ biceps brachii and thigh quadriceps muscles via a linear transducer. Grip strength was measured using a Jamar Hydraulic Hand Dynamometer. Participants were surveyed regarding their history of falls in the prior year. Logistic regression analyses assessed the relationship of sarcopenia and grip strength to a history of falls (the primary outcome). Results: Among 199 participants (55% female), 46% reported falling in the prior year. The median biceps thickness was 2.22 cm with an Interquartile range [IQR] of 1.87–2.74, and the median thigh muscle thickness was 2.91 cm with an IQR of 2.40–3.49. A univariate logistic regression analysis demonstrated a correlation between higher thigh muscle thickness, normal grip strength, and history of prior-year falling, with an odds ratio [OR] of 0.67 (95% conference interval [95%CI] 0.47–0.95) and an OR of 0.51 (95%CI 0.29–0.91), respectively. In multivariate logistic regression, only higher thigh muscle thickness was correlated with a history of prior-year falls, with an OR of 0.59 (95% CI 0.38–0.91). Conclusions: POCUS-measured thigh muscle thickness has the potential to identify patients who have fallen and thus are at high risk for future falls.
Prognostic Value of the Radiographic Assessment of Lung Edema Score in Mechanically Ventilated ICU Patients
Authors: Filippini Daan F. L. , Hagens Laura A. , Heijnen Nanon F. L. , Zimatore Claudio , Atmowihardjo Leila N. , Schnabel Ronny M. , Schultz Marcus J. , Bergmans Dennis C. J. J. , Bos Lieuwe D. J. , Smit Marry R.
Published: February 2023

Introduction: The Radiographic Assessment of Lung Edema (RALE) score provides a semi-quantitative measure of pulmonary edema. In patients with acute respiratory distress syndrome (ARDS), the RALE score is associated with mortality. In mechanically ventilated patients in the intensive care unit (ICU) with respiratory failure not due to ARDS, a variable degree of lung edema is observed as well. We aimed to evaluate the prognostic value of RALE in mechanically ventilated ICU patients. Methods: Secondary analysis of patients enrolled in the ‘Diagnosis of Acute Respiratory Distress Syndrome’ (DARTS) project with an available chest X-ray (CXR) at baseline. Where present, additional CXRs at day 1 were analysed. The primary endpoint was 30-day mortality. Outcomes were also stratified for ARDS subgroups (no ARDS, non-COVID-ARDS and COVID-ARDS). Results: 422 patients were included, of which 84 had an additional CXR the following day. Baseline RALE scores were not associated with 30-day mortality in the entire cohort (OR: 1.01, 95% CI: 0.98–1.03, p = 0.66), nor in subgroups of ARDS patients. Early changes in RALE score (baseline to day 1) were only associated with mortality in a subgroup of ARDS patients (OR: 1.21, 95% CI: 1.02–1.51, p = 0.04), after correcting for other known prognostic factors. Conclusions: The prognostic value of the RALE score cannot be extended to mechanically ventilated ICU patients in general. Only in ARDS patients, early changes in RALE score were associated with mortality.
A Clinical Prediction Rule for Thrombosis in Critically Ill COVID-19 Patients: Step 1 Results of the Thromcco Study
Authors: Ramírez Cervantes Karen L. , Mora Elianne , Campillo Morales Salvador , Huerta Álvarez Consuelo , Marcos Neira Pilar , Nanwani Nanwani Kapil Laxman , Serrano Lázaro Ainhoa , Silva Obregón J. Alberto , Quintana Díaz Manuel
Published: February 2023

The incidence of thrombosis in COVID-19 patients is exceptionally high among intensive care unit (ICU)-admitted individuals. We aimed to develop a clinical prediction rule for thrombosis in hospitalized COVID-19 patients. Data were taken from the Thromcco study (TS) database, which contains information on consecutive adults (aged ≥ 18) admitted to eight Spanish ICUs between March 2020 and October 2021. Diverse logistic regression model analysis, including demographic data, pre-existing conditions, and blood tests collected during the first 24 h of hospitalization, was performed to build a model that predicted thrombosis. Once obtained, the numeric and categorical variables considered were converted to factor variables giving them a score. Out of 2055 patients included in the TS database, 299 subjects with a median age of 62.4 years (IQR 51.5–70) (79% men) were considered in the final model (SE = 83%, SP = 62%, accuracy = 77%). Seven variables with assigned scores were delineated as age 25–40 and ≥70 = 12, age 41–70 = 13, male = 1, D-dimer ≥ 500 ng/mL = 13, leukocytes ≥ 10 × 103/µL = 1, interleukin-6 ≥ 10 pg/mL = 1, and C-reactive protein (CRP) ≥ 50 mg/L = 1. Score values ≥28 had a sensitivity of 88% and specificity of 29% for thrombosis. This score could be helpful in recognizing patients at higher risk for thrombosis, but further research is needed.
Near-Infrared Spectroscopy Demonstrates the Benefit of Erythracytapheresis in Sickle Cell Disease Adult Patients with Cerebral Vasculopathy
Authors: Martino Suella , Turki Rym Chouk , Zouiti Fouzia , Fort Romain , Pakdaman Sadaf , Forté Stéphanie , Menouche Dehbia , Calvet David , Rupp Thomas , Pirenne France , Bartolucci Pablo
Published: February 2023

Background: Cerebral vasculopathy can induce chronic cerebral hypoperfusion leading to stroke in patients with sickle cell disease (SCD) and is treated by blood exchange transfusion (BET). However, no prospective clinical study has demonstrated the benefit of BET in adults with SCD and cerebral vasculopathy. Near Infrared Spectroscopy (NIRS) is a recent non-invasive method complementary to Magnetic Resonance Imaging (MRI). We evaluated cerebral perfusion using NIRS during erythracytapheresis in patients with SCD with and without steno-occlusive arterial disease. Methods: We conducted a monocentric, prospective study in 16 adults with SCD undergoing erythracytapheresis in 2014. Among them, 10 had cerebral steno-occlusive arterial disease. NIRS measured the relative amounts of oxyhemoglobin (OxyHb), deoxyhemoglobin (DeoxyHb) and total hemoglobin (Total Hb) in brain tissue and in muscle. Results: In cerebral hemispheres associated with steno-occlusive arterial disease, we observed a significant increase of OxyHb and Total Hb during BET, without modification of DeoxyHb. Conclusion: Using NIRS during BET showed that BET improves cerebral perfusion in adult patients with SCD with cerebral vasculopathy.
Persistent Hypochloremia Is Associated with Adverse Prognosis in Patients Repeatedly Hospitalized for Heart Failure
Authors: Nozaki Yuji , Yoshihisa Akiomi , Sato Yu , Ohara Himika , Sugawara Yukiko , Abe Satoshi , Misaka Tomofumi , Sato Takamasa , Oikawa Masayoshi , Kobayashi Atsushi , Yamaki Takayoshi , Nakazato Kazuhiko , Takeishi Yasuchika
Published: February 2023

Background: Hypochloremia reflects neuro-hormonal activation in patients with heart failure (HF). However, the prognostic impact of persistent hypochloremia in those patients remains unclear. Methods: We collected the data of patients who were hospitalized for HF at least twice between 2010 and 2021 (n = 348). Dialysis patients (n = 26) were excluded. The patients were divided into four groups based on the absence/presence of hypochloremia (<98 mmol/L) at discharge from their first and second hospitalizations: Group A (patients without hypochloremia at their first and second hospitalizations, n = 243); Group B (those with hypochloremia at their first hospitalization and without hypochloremia at their second hospitalization, n = 29); Group C (those without hypochloremia at their first hospitalization and with hypochloremia at their second hospitalization, n = 34); and Group D (those with hypochloremia at their first and second hospitalizations, n = 16). Results: a Kaplan–Meier analysis revealed that all-cause mortality and cardiac mortality were the highest in Group D compared to the other groups. A multivariable Cox proportional hazard analysis revealed that persistent hypochloremia was independently associated with both all-cause death (hazard ratio 3.490, p < 0.001) and cardiac death (hazard ratio 3.919, p < 0.001). Conclusions: In patients with HF, prolonged hypochloremia over two hospitalizations is associated with an adverse prognosis.
The Pleiotropic Role of Vitamin K in Multimorbidity of Chronic Obstructive Pulmonary Disease
Authors: Piscaer Ianthe , Janssen Rob , Franssen Frits M. E. , Schurgers Leon J. , Wouters Emiel F. M.
Published: February 2023

Although defined by the presence of airflow obstruction and respiratory symptoms, patients with chronic obstructive pulmonary disease (COPD) are characterized by multimorbidity. Numerous co-occurring conditions and systemic manifestations contribute to the clinical presentation and progression of COPD; however, underlying mechanisms for multimorbidity are currently not fully elucidated. Vitamin A and vitamin D have been related to COPD pathogenesis. Another fat-soluble vitamin, vitamin K, has been put forward to exert protective roles in COPD. Vitamin K is an unequivocal cofactor for the carboxylation of coagulation factors, but also for extra-hepatic proteins including the soft tissue calcification inhibitor matrix Gla-protein and the bone protein osteocalcin. Additionally, vitamin K has been shown to have anti-oxidant and anti-ferroptosis properties. In this review, we discuss the potential role of vitamin K in the systemic manifestations of COPD. We will elaborate on the effect of vitamin K on prevalent co-occurring chronic conditions in COPD including cardiovascular disorders, chronic kidney disease, osteoporosis, and sarcopenia. Finally, we link these conditions to COPD with vitamin K as a connecting factor and provide recommendations for future clinical studies.
Impact and Modification of the New PJI-TNM Classification for Periprosthetic Joint Infections
Authors: Lunz Andre , Lehner Burkhard , Voss Moritz N. , Knappe Kevin , Jaeger Sebastian , Innmann Moritz M. , Renkawitz Tobias , Omlor Georg W.
Published: February 2023

The comprehensive “PJI-TNM classification” for the description of periprosthetic joint infections (PJI) was introduced in 2020. Its structure is based on the well-known oncological TNM classification to appreciate the complexity, severity, and diversity of PJIs. The main goal of this study is to implement the new PJI-TNM classification into the clinical setting to determine its therapeutic and prognostic value and suggest modifications to further improve the classification for clinical routine use. A retrospective cohort study was conducted at our institution between 2017 and 2020. A total of 80 consecutive patients treated with a two-stage revision for periprosthetic knee joint infection were included. We retrospectively assessed correlations between patients’ preoperative PJI-TNM classification and their therapy and outcome and identified several statistically significant correlations for both classifications, the original and our modified version. We have demonstrated that both classifications provide reliable predictions already at the time of diagnosis regarding the invasiveness of surgery (duration of surgery, blood and bone loss during surgery), likelihood of reimplantation, and patient mortality during the first 12 months after diagnosis. Orthopedic surgeons can use the classification system preoperatively as an objective and comprehensive tool for therapeutic decisions and patient information (informed consent). In the future, comparisons between different treatment options for truly similar preoperative baseline situations can be obtained for the first time. Clinicians and researchers should be familiar with the new PJI-TNM classification and start implementing it into their routine practice. Our adjusted and simplified version (“PJI-pTNM”) might be a more convenient alternative for the clinical setting.
CRB-65 for Risk Stratification and Prediction of Prognosis in Pulmonary Embolism
Authors: Keller Karsten , Schmitt Volker H. , Sagoschen Ingo , Münzel Thomas , Espinola-Klein Christine , Hobohm Lukas
Published: February 2023

Background: Pulmonary embolism (PE) is accompanied by high morbidity and mortality. The search for simple and easily assessable risk stratification scores with favourable effectiveness is still ongoing, and prognostic performance of the CRB-65 score in PE might promising. Methods: The German nationwide inpatient sample was used for this study. All patient cases of patients with PE in Germany 2005–2020 were included and stratified for CRB-65 risk class: low-risk group (CRB-65-score 0 points) vs. high-risk group (CRB-65-score ≥1 points). Results: Overall, 1,373,145 patient cases of patients with PE (76.6% aged ≥65 years, 47.0% females) were included. Among these, 1,051,244 patient cases (76.6%) were classified as high-risk according to CRB-65 score (≥1 points). The majority of high-risk patients according to CRB-65 score were females (55.8%). Additionally, high-risk patients according to CRB-65 score showed an aggravated comorbidity profile with increased Charlson comorbidity index (5.0 [IQR 4.0–7.0] vs. 2.0 [0.0–3.0], p < 0.001). In-hospital case fatality (19.0% vs. 3.4%, p < 0.001) and MACCE (22.4% vs. 5.1%, p < 0.001) occurred distinctly more often in PE patients of the high-risk group according to CRB-65 score (≥1 points) compared to the low-risk group (= 0 points). The CRB-65 high-risk class was independently associated with in-hospital death (OR 5.53 [95%CI 5.40–5.65], p < 0.001) as well as MACCE (OR 4.31 [95%CI 4.23–4.40], p < 0.001). Conclusions: Risk stratification with CRB-65 score was helpful for identifying PE patients being at higher risk of adverse in-hospital events. The high-risk class according to CRB-65 score (≥1 points) was independently associated with a 5.5-fold increased occurrence of in-hospital death.
Predicting Heart Failure in Patients with Atrial Fibrillation: A Report from the Prospective COOL-AF Registry
Authors: Krittayaphong Rungroj , Chichareon Ply , Komoltri Chulalak , Sairat Poom , Lip Gregory Y. H.
Published: February 2023

Background: This study aimed to determine risk factors and incidence rate and develop a predictive risk model for heart failure for Asian patients with atrial fibrillation (AF). Methods: This is a prospective multicenter registry of patients with non-valvular AF in Thailand conducted between 2014 and 2017. The primary outcome was the occurrence of an HF event. A predictive model was developed using a multivariable Cox-proportional model. The predictive model was assessed using C-index, D-statistics, Calibration plot, Brier test, and survival analysis. Results: There were a total of 3402 patients (average age 67.4 years, 58.2% male) with mean follow-up duration of 25.7 ± 10.6 months. Heart failure occurred in 218 patients during follow-up, representing an incidence rate of 3.03 (2.64–3.46) per 100 person-years. There were ten HF clinical factors in the model. The predictive model developed from these factors had a C-index and D-statistic of 0.756 (95% CI: 0.737–0.775) and 1.503 (95% CI: 1.372–1.634), respectively. The calibration plots showed a good agreement between the predicted and observed model with the calibration slope of 0.838. The internal validation was confirmed using the bootstrap method. The Brier score indicated that the model had a good prediction for HF. Conclusions: We provide a validated clinical HF predictive model for patients with AF, with good prediction and discrimination values.
Graphene-Doped Polymethyl Methacrylate (PMMA) as a New Restorative Material in Implant-Prosthetics: In Vitro Analysis of Resistance to Mechanical Fatigue
Authors: Selva-Otaolaurruchi Eduardo , Fernández-Estevan Lucía , Solá-Ruiz María , García-Sala-Bonmati Fernando , Selva-Ribera Inmaculada , Agustín-Panadero Rubén
Published: February 2023

Background and Purpose: Provisional prostheses in restorations over several implants with immediate loading in completely edentulous patients increase the risk of frequent structural fractures. An analysis was performed of the resistance to fracture of prosthetic structures with cantilevers using graphene-doped polymethyl methacrylate (PMMA) resins and CAD-CAM technology. Methods: A master model was produced with four implants measuring 4 mm in diameter and spaced 3 mm apart, over which 44 specimens representing three-unit fixed partial prostheses with a cantilever measuring 11 mm were placed. These structures were cemented over titanium abutments using dual cure resin cement. Twenty-two of the 44 units were manufactured from machined PMMA discs, and 22 were manufactured from PMMA doped with graphene oxide nanoparticles (PMMA-G). All of the samples were tested in a chewing simulator with a load of 80 N until fracture or 240,000 load applications. Results: The mean number of load applications required for temporary restoration until the fracture was 155,455 in the PMMA-G group versus 51,136 in the PMMA group. Conclusions: Resistance to fracture under cyclic loading was three times greater in the PMMA-G group than in the PMMA group.
Investigation of the Pathogenic Mechanism of Ciprofloxacin in Aortic Aneurysm and Dissection by an Integrated Proteomics and Network Pharmacology Strategy
Authors: Chen Zhaoran , Wu Jianqiang , Wang Wei , Tang Xiaoyue , Zhou Lei , Lv Yanze , Zheng Yuehong
Published: February 2023

Aortic aneurysm and dissection (AAD) is a life-threatening disease worldwide. Recently, fluoroquinolones have been reported to significantly increase the risk of AAD. This study aimed to investigate the potential functional mechanism and molecular targets of fluoroquinolones in relation to AAD by an integrated proteomic and network pharmacology strategy. A total of 1351 differentially expressed proteins were identified in human aortic vascular smooth muscle cells (VSMCs) after ciprofloxacin (CIP) stimulation. The functional analysis emphasized the important roles of metabolism, extracellular matrix homeostasis, mitochondrial damage, focal adhesion, and apoptosis in CIP-stimulated VSMCs. CIP targets were predicted with online databases and verified by molecular docking. Protein–protein interaction (PPI) analysis and module construction of the 34 potential CIP targets and 37 selected hub molecules after CIP stimulation identified four critical target proteins in the module: PARP1, RAC1, IGF1R and MKI67. Functional analysis of the PPI module showed that the MAPK signalling pathway, focal adhesion, apoptosis, regulation of actin cytoskeleton, and PI3K-Akt signalling pathway were significantly enriched. Our results will provide novel insights into the pathogenic mechanism of fluoroquinolones in aortic diseases.
Asymmetry of Gray- and White-Matter Volume and Metabolites in the Central-Vestibular System in Healthy Individuals
Authors: Kwon Ki Jin , Byun Jae Yong
Published: February 2023

This study was designed to determine whether there was an asymmetry of structure and neurochemical activity of the interhemispheric vestibular-cortical system between healthy individuals and patients with vestibular failure. Previous studies have identified differences in gray-matter-volume (GMV) and white-matter-volume (WMV) asymmetry in the central-vestibular system and in concentrations of brain metabolites in the parietal lobe 2 (PO2) between patients with vestibulopathy and healthy controls. However, a comparison of the left and right sides in the healthy controls has not been made conclusively. This study included 23 healthy right-handed volunteers, and was carried out between March 2016 and March 2020. A three-dimensional T1-weighted image was used to calculate the GMV and WMV of the central-vestibular network on both sides, and proton magnetic resonance spectroscopy (H1MRS) was employed to analyze the brain metabolites in the PO2 area. The relative ratios of N-acetylaspartate (NAA)/tCr, tNAA/tCr, glycerophosphocholine (GPC)/tCr, Glx/tCr, and myo-inositol/tCr were quantified from the proton-MRS data. GMV and WMV differed significantly between the right and left vestibular-cortical regions. The GMVs of the right PO2, caudate, insula, and precuneus were significantly higher than those of the same locations on the left side; however, in the Rolandic operculum, the GMV on the left was significantly higher than on the right. In the PO2, Rolandic operculum, thalamus, and insula, the WMV on the left side was higher than on the right side of the corresponding location. However, the right caudate and precuneus WMV were higher than the left at the same location. In the H1MRS study, the Glx/tCr and GPC/tCr ratios on the left side were significantly higher than on the right. In comparison, the NAA/tCr and tNAA/tCr ratios showed contrasting results. The NAA/tCr ratio (r = −0.478, p = 0.021), tNAA/tCr ratio (r = −0.537, p = 0.008), and Glx/tCr ratio (r = −0.514, p = 0.012) on the right side showed a significant negative correlation with the participants’ age. There was no relationship between GMV and metabolites on either side. Brain structure and concentrations of brain metabolites related to the vestibular system may differ between the two hemispheres in healthy individuals. Therefore, the asymmetry of the central-vestibular system should be considered when performing imaging.
Sepsis-Associated Delirium: A Narrative Review
Authors: Tokuda Rina , Nakamura Kensuke , Takatani Yudai , Tanaka Chie , Kondo Yutaka , Ohbe Hiroyuki , Kamijo Hiroshi , Otake Kosuke , Nakamura Atsuo , Ishikura Hiroyasu , Kawazoe Yu ,   J-STAD (Japan Sepsis Treatment and Diagnosis) Study Group
Published: February 2023

Delirium is characterized by an acutely altered mental status accompanied by reductions in cognitive function and attention. Delirium in septic patients, termed sepsis-associated delirium (SAD), differs in several specific aspects from the other types of delirium that are typically encountered in intensive care units. Since sepsis and delirium are both closely associated with increased morbidity and mortality, it is important to not only prevent but also promptly diagnose and treat SAD. We herein reviewed the etiology, pathogenesis, risk factors, prevention, diagnosis, treatment, and prognosis of SAD, including coronavirus disease 2019 (COVID-19)-related delirium. Delirium by itself not only worsens long-term prognosis, but it is also regarded as an important factor affecting the outcome of post-intensive care syndrome. In COVID-19 patients, the difficulties associated with adequately implementing the ABCDEF bundle (Assess, prevent, and manage pain; Both spontaneous awakening and breathing trials: Choice of analgesia and sedation; Delirium assess, prevent, and manage; Early mobility and exercise; Family engagement/empowerment) and the need for social isolation are issues that require the development of conventional care for SAD.
Overcoming Barriers to Tobacco Cessation and Lung Cancer Screening among Racial and Ethnic Minority Groups and Underserved Patients in Academic Centers and Community Network Sites: The City of Hope Experience
Authors: Presant Cary A. , Ashing Kimlin , Raz Dan , Yeung Sophia , Gascon Brenda , Stewart Alexis , Macalintal Jonjon , Sandoval Argelia , Ehrunmwunsee Loretta , Phillips Tanyanika , Salgia Ravi , Merla Amartej , Subbiah Shanmuga , El-Hajjouie Michelle , Staley Jeffrey , Graves Heather , Pathak Ranjan , Dingal Shaira , Sampath Sagus , Laksana Beverly , Joseph Thomas , Eugenio Tricia , Degoma Veronica , Burns Kathleen , Phillips Sarah , Tan Tingting , Tarkshian Kelly , Sun Virginia , Amini Arya , Davy Khristie , Cronkhite Janet , Cianfrocca Mary , Brown Susan , Fong Yuman , Rosen Steven
Published: February 2023

Background: Tobacco control is important for cancer patient health, but delivering effective low-dose CT (LDCT) screening and tobacco cessation is more difficult in underserved and patients from racial and ethnic minority groups. At City of Hope (COH), we have developed strategies to overcome barriers to the delivery of LDCT and tobacco cessation. Methods: We performed a needs assessment. New tobacco control program services were implemented focusing on patients from racial and ethnic minority groups. Innovations included Whole Person Care with motivational counseling, placing clinician and nurse champions at points of care, training module and leadership newsletters, and a patient-centric personalized medicine Personalized Pathways to Success (PPS) program. Results: Emphasis on patients from racial and ethnic minority groups was implemented by training cessation personnel and lung cancer control champions. LDCT increased. Tobacco use assessment increased and abstinence was 27.2%. The PPS pilot program achieved 47% engagement in cessation, with self-reported abstinence at 3 months of 38%, with both results slightly higher in patients from racial and ethnic minority groups than in Caucasian patients. Conclusions: Tobacco cessation barrier-focused innovations can result in increased lung cancer screening and tobacco cessation reach and effectiveness, especially among patients from racial and ethnic minority groups. The PPS program is promising as a personalized medicine patient-centric approach to cessation and lung cancer screening.
Plasma Troponins Identify Patients with Very Low-Risk Acute Pulmonary Embolism
Authors: Karolak Bartosz , Ciurzyński Michał , Skowrońska Marta , Kurnicka Katarzyna , Pływaczewska Magdalena , Furdyna Aleksandra , Perzanowska-Brzeszkiewicz Katarzyna , Lichodziejewska Barbara , Pacho Szymon , Machowski Michał , Bienias Piotr , Wiśniewska Małgorzata , Gołębiowski Marek , Pruszczyk Piotr
Published: February 2023

Introduction: Although in the non-vitamin K oral anticoagulants (NOAC) era majority of low-risk acute pulmonary embolism (APE) patients can be treated at home, identifying those at very low risk of clinical deterioration may be challenging. We aimed to propose the risk stratification algorithm in sPESI 0 point APE patients, allowing them to select candidates for safe outpatient treatment. Materials and methods: Post hoc analysis of a prospective study of 1151 normotensive patients with at least segmental APE. In the final analysis, we included 409 sPESI 0 point patients. Cardiac troponin assessment and echocardiographic examination were performed immediately after admission. Right ventricular dysfunction was defined as the right ventricle/left ventricle ratio (RV/LV) > 1.0. The clinical endpoint (CE) included APE-related mortality and/or rescue thrombolysis and/or immediate surgical embolectomy in patients with clinical deterioration. Results: CE occurred in four patients who had higher serum troponin levels than subjects with a favorable clinical course (troponin/ULN: 7.8 (6.4–9.4) vs. 0.2 (0–1.36) p = 0.000). Receiver operating characteristic (ROC) analysis showed that the area under the curve for troponin in the prediction of CE was 0.908 (95% CI 0.831–0.984; p < 0.001). We defined the cut-off value of troponin at >1.7 ULN with 100% PPV for CE. In univariate and multivariate analysis, elevated serum troponin level was associated with an increased risk of CE, whereas RV/LV > 1.0 was not. Conclusions: Solely clinical risk assessment in APE is insufficient, and patients with sPESI 0 points require further assessment based on myocardial damage biomarkers. Patients with troponin levels not exceeding 1.7 ULN constitute the group of “very low risk” with a good prognosis.
Effect of Opioid Receptor Activation and Blockage on the Progression and Response to Treatment of Head and Neck Squamous Cell Carcinoma
Authors: Levi Lirit , Hikri Elad , Popovtzer Aron , Dayan Avraham , Levi Amir , Bachar Gideon , Mizrachi Aviram , Shoffel-Havakuk Hagit
Published: February 2023

Recent studies suggest that opioids have a role in the progression of HNSCC mediated by mu opioid receptors (MOR), however, the effects of their activation or blockage remains unclear. Expression of MOR-1 was explored in seven HNSCC cell lines using Western blotting (WB). XTT cell proliferation and cell migration assays were performed on four selected cell lines (Cal-33, FaDu, HSC-2, and HSC-3), treated with opiate receptor agonist (morphine), antagonist (naloxone), alone and combined with cisplatin. All four selected cell lines display an increased cell proliferation and upregulation of MOR-1 when exposed to morphine. Furthermore, morphine promotes cell migration, while naloxone inhibits it. The effects on cell signaling pathways were analyzed using WB, demonstrating morphine activation of AKT and S6, key proteins in the PI3K/AKT/mTOR axis. A significant synergistic cytotoxic effect between cisplatin and naloxone in all cell lines is observed. In vivo studies of nude mice harboring HSC3 tumor treated with naloxone demonstrate a decrease in tumor volume. The synergistic cytotoxic effect between cisplatin and naloxone is observed in the in vivo studies as well. Our findings suggest that opioids may increase HNSCC cell proliferation via the activation of the PI3K/Akt/mTOR signaling pathway. Moreover, MOR blockage may chemo-sensitize HNSCC to cisplatin.
Report of a Novel Molecular Profile in Malignant Insulinoma
Authors: Burns Laura , Naimi Bita , Ronan Matthew , Xu Huihong , Weber Horst Christian
Published: February 2023

Pancreatic neuroendocrine tumors, or pNETs, represent a rare and clinically heterogenous subset of pancreatic neoplasms. One such pNET, the insulinoma, is found to be malignant in just 4% of all insulinomas. Due to the exceedingly uncommon occurrence of these tumors, there is controversy regarding the optimal evidence-based management for these patients. We therefore report on a 70-year-old male patient admitted with 3 months of episodic confusion with concurrent hypoglycemia. The patient was found to have inappropriately elevated endogenous insulin levels during these episodes, and somatostatin-receptor subtype 2 selective imaging revealed a pancreatic mass metastatic to local lymph nodes, spleen, and the liver. Fine needle aspiration of pancreatic and liver lesions confirmed the diagnosis of a low grade pancreatic neuroendocrine tumor. Molecular analysis of tumor tissue revealed a novel mutational profile consistent with pNET. The patient was initiated on octreotide therapy. However, treatment with octreotide alone demonstrated limited efficacy in controlling the patient’s symptoms, prompting consideration of other therapies.
Usefulness of Systemic Venous Ultrasound Protocols in the Prognosis of Heart Failure Patients: Results from a Prospective Multicentric Study
Authors: Torres-Arrese Marta , Mata-Martínez Arantzazu , Luordo-Tedesco Davide , García-Casasola Gonzalo , Alonso-González Rodrigo , Montero-Hernández Esther , Cobo-Marcos Marta , Sánchez-Sauce Beatriz , Cuervas-Mons Valentín , Tung-Chen Yale
Published: February 2023

Mortality and re-admission rates for decompensated acute heart failure (AHF) is increasing overall and risk stratification might be challenging. We sought to evaluate the prognostic role of systemic venous ultrasonography in patients hospitalized for AHF. We prospectively recruited 74 AHF patients with a NT-proBNP level above 500 pg/mL. Then, multi-organ ultrasound assessments (lung, inferior vena cava (IVC), pulsed-wave Doppler (PW-Doppler) of hepatic, portal, intra-renal and femoral veins) were performed at admission, discharge, and follow-up (for 90 days). We also calculated the Venous Excess Ultrasound System (VExUS), a new score of systemic congestion based on IVC dilatation and pulsed-wave Doppler morphology of hepatic, portal and intra-renal veins. An intra-renal monophasic pattern (area under the curve (AUC) 0.923, sensitivity (Sn) 90%, specificity (Sp) 81%, positive predictive value (PPV) 43%, and negative predictive value (NPV) 98%), a portal pulsatility > 50% (AUC 0.749, Sn 80%, Sp 69%, PPV 30%, NPV 96%) and a VExUS score of 3 corresponding to severe congestion (AUC 0.885, Sn 80%, Sp 75%, PPV 33%, and NPV 96%) predicted death during hospitalization. An IVC above 2 cm (AUC 0.758, Sn 93.l% and Sp 58.3) and the presence of an intra-renal monophasic pattern (AUC 0. 834, sensitivity 0.917, specificity 67.4%) in the follow-up visit predicted AHF-related re-admission. Additional scans during hospitalization or the calculation of a VExUS score probably adds unnecessary complexity to the assessment of AHF patients. In conclusion, VExUS score does not contribute to the guidance of therapy or the prediction of complications, compared with the presence of an IVC greater than 2 cm, a venous monophasic intra-renal pattern or a pulsatility > 50% of the portal vein in AHF patients. Early and multidisciplinary follow-up visits remain necessary for the improvement of the prognosis of this highly prevalent disease.