Prospective Monocentric Study Research Articles

Impact of Cross-Linking Procedure on Perioperative Quality of Life in Keratoconus Patients.

To evaluate the effect of crosslinking (CXL) with riboflavin for keratoconus (KC) therapy on quality of life (QoL): comparison of keratoconus patients with and without treatment. Prospective monocentric study. We recruited patients with progressive KC and with stable disease. Patients with progressive disease received cross-linking treatment; patients with stable disease were monitored. We compared QoL in both groups over 6 months and detected the influence of cross-linking treatment on QoL. QoL was assessed by NEI-VFQ-25, EQ-5D 5L, and EQ-Visual analog scale (VAS). In the evaluation of the Nei VFQ, the subgroups LFVFS and LFSES were calculated. We enrolled 31 eyes of 31 patients in the intervention group and 37 eyes of 37 patients in the control group. Medians with standard deviations (SD) were calculated. All QoL-tests showed equal scores at baseline in both groups. At V2, one day after the treatment, EQ-VAS (56.4), LFVFS (57.4), and EQ5D5L (0.59) were significantly reduced. At V3 (one week after treatment), all results returned to baseline level. LFSES was not affected by the treatment. It remained stable (V2 85.4, V3 84.3). Comparing the baseline scores with the follow-up scores at month 6, we found a significant increase in QoL in all tests in the intervention group. Otherwise, the quality of life in the control group did not change over time. Cross-linking led only to a short-term reduction in QoL. Although the treatment is painful for a few days, no effect on general quality of life LVSES has been demonstrated. QoL already returned to baseline after one week and the patients were not limited anymore.

The presence of senescent peripheral T-cells is negatively correlated to COVID-19 vaccine-induced immunity in cancer patients under 70 years of age.

Cancer patients are at risk of severe COVID-19 infection, and vaccination is recommended. Nevertheless, we observe a failure of COVID-19 vaccines in this vulnerable population. We hypothesize that senescent peripheral T-cells alter COVID-19 vaccine-induced immunity. We performed a monocentric prospective study and enrolled cancer patients and healthy donors before the COVID-19 vaccination. The primary objective was to assess the association of peripheral senescent T-cells (CD28-CD57+KLRG1+) with COVID-19 vaccine-induced immunity. Eighty cancer patients have been included, with serological and specific T-cell responses evaluated before and at 3 months post-vaccination. Age ≥ 70 years was the principal clinical factor negatively influencing the serological (p=0.035) and specific SARS-CoV-2 T-cell responses (p=0.047). The presence of senescent T-cells was correlated to lower serological (p=0.049) and specific T-cell responses (p=0.009). Our results sustained the definition of a specific cut-off for senescence immune phenotype (SIP) (≥ 5% of CD4 and ≥ 39.5% of CD8 T-cells), which was correlated to a lower serological response induced by COVID-19 vaccination for CD4 and CD8 SIPhigh (p=0.039 and p=0.049 respectively). While CD4 SIP level had no impact on COVID-19 vaccine efficacy in elderly patients, our results unraveled a possible predictive role for CD4 SIPhigh T-cell levels in younger cancer patients. Elderly cancer patients have a poor serological response to vaccination; specific strategies are needed in this population. Also, the presence of a CD4 SIPhigh affects the serological response in younger patients and seems to be a potential biomarker of no vaccinal response.

Clinical utility of plasma ctDNA sequencing monitoring and tumor molecular profile exploration in endometrial carcinoma: A Caribbean prospective cohort from Martinique.

e17625 Background: A higher incidence of agressive endometrial cancer (EC) has been reported amongst the Martinican population. Indeed, there are respectively 25%, 12% and 3 % of high grade serous carcinoma, carcinosarcoma and clear cell uterine carcinoma, all with poor prognosis. Genomic stratification helps to improve the management of patients with EC. Indeed, localized EC molecular classification discriminated the benefit of adjuvant therapy according to molecular subgroups. However, collecting tissue samples in EC remains challenging. The aim of our study was to assess the clinical utility of ctDNA monitoring in EC and tumor tissue molecular profiling in high grade non endometrioid EC. Methods: We conducted a prospective monocentric study including high grade non endometrioid EC patients enrolled in the EndoNGS trial (NCT04932525). Each patient underwent molecular analysis to define the tumor molecular landscape. A comparative analysis “tumor-germline” including microsatellite instability and panel gene sequencing was then performed. ctDNA was profiled using dPCR and RT PCR. Results: From May 2020 to September 2021, 25 patients with high grade non endometriod EC were included. Median age at diagnosis was 72 years (60-88). FIGO stage at diagnosis was I, II, III and IV in 28%, 4%, 32% and 24% respectively. 10 patients out 25 received radiochemotherapy. Only 6 underwent exclusive radiotherapy and 13 received adjuvant platinum chemotherapy addjuvant to surgery. All tumor had MSS and none harbored a POLE mutation. 19 patients underwent molecular profiling according to a panel of 80 genes. The analysis identified 30 mutations: 22 pathogenic missenses, 3 nonsenses and 5 frameshift mutations. A TP53 mutation was observed in 89.5 % of cases. We identified 26% hotspot mutations. The other mutations are infrequent or not described in TGCA database. TP53 mutation analysis reported 15 missenses, one frameshift and one nonsense mutation. Moreover 88% of TP53 mutated tumors were affected by biallelic inactivation. In this population, variants in PIK3CA represent 26% compared to 42% reported from TGCA database and none PPP2R1A and FBXW7 mutations have been detected compared to 32% and 24% for PPP2R1A and FBXW7 respectively. ctDNA abondance was correlated to the stage. 10 patients had positive ctDNA at diagnosis (9 were stage III and 1 stage IV). In 3 patients, ctDNA became negative during therapy (radiochemotherapy). During course of disease, 15 relapsed, (with a median 12 month relapse free period) amongst which 10 had positive ctDNA. Conclusions: We reported for the first time the molecular profiling of aggressive EC in a homogenous carribbean cohort from Martinique. Overall, our analysis demonstrates that genomic profiling with a large panel of ctDNA in localized EC is reliable and feasible; ctDNA monitoring was associated to early relapse.

Particularities of COVID-19 infection in chronic hemodialysis patients in Sub-Saharan Africa: experience from Senegal (West Africa)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appeared in December 2019 in China and has rapidly become a major global health concern. Patients with end-stage renal disease receiving dialysis treatment are very exposed to the SARS-CoV-2 during their frequent visits to healthcare facilities and immune induced by uremia. The aim of our work was to describe the particularity of COVID-19 infection in hemodialysis patients in sub-Saharan Africa and in Ziguinchor, south of Senegal, particularly. To do this, we conducted a monocentric prospective study over a period of 16 months at the Ziguinchor hemodialysis center and compared our results to a study that focuses on the seroprevalence of SARS-CoV-2 in chronic hemodialysis patients. We found a low prevalence of COVID-19 infection while the majority of our patients were in contact with the virus.

Serum butyrylcholinesterase as a marker of COVID-19 mortality: Results of the monocentric prospective observational study

The COVID-19 pandemic represents an excessive burden on health care systems worldwide and the number of patients who require special care in the clinical setting is often hard to predict. Consequently, there is an unmet need for a reliable biomarker that could predict clinical outcomes of high-risk patients. Lower serum butyrylcholinesterase (BChE) activity was recently linked with poor outcomes of COVID-19 patients. In line with this, our monocentric observational study on hospitalized COVID-19 patients focused on changes in serum BChE activity in relation to disease progression. Blood samples from 148 adult patients of both sexes were collected during their hospital stay at the Clinics of Infectiology and Clinics of Anesthesiology and Intensive Care, Trnava University Hospital in alignment with routine blood tests. Sera were analyzed using modified Ellman's method. Patient data with information about the health status, comorbidities and other blood parameters were collected in pseudonymized form. Our results show a lower serum BChE activity together with progressive decline of BChE activity in non-survivors, while higher stable values were present in discharged or transferred patients requiring further care. Lower BChE activity was associated with higher age and lower BMI. Moreover, we observed a negative correlation of serum BChE activity with the routinely used inflammatory markers, C-reactive protein and interleukin-6. Serum BChE activity mirrored clinical outcomes of COVID-19 patients and thus serves as a novel prognostic marker in high-risk patients.

P107 EARLY TRANSITION FROM CANGRELOR TO ORAL P2Y12I IS NOT ASSOCIATED WITH INCREASE OF ADVERSE EVENTS

Abstract Intro Cangrelor, an intravenous P2Y12 receptor inhibitor (P2Y12i), characterized by rapid onset and offset of antiplatelet action, is approved by guidelines for patients P2Y12i naïve undergoing percutaneous coronary intervention (PCI). Cangrelor infusion duration and time of transition to oral P2Y12i are still debated, although there is a general indication to an infusion of at least 2 hours. The aim of our study is to evaluate the efficacy and the safety of an early transition to oral P2Y12i strategy. Methods Our prospective observational monocentric study enrolled consecutive patients who received Cangrelor during PCI (bolus + infusion iv starting at time of PCI). Clopidogrel and Prasugrel were administered immediately upon discontinuation of Cangrelor infusion, while Ticagrelor was started up to 30 min before Cangrelor was discontinued. Transition was defined as early when Cangrelor infusion duration was less than 2 hours. Endpoints of interest were major adverse cardiac events (MACE) defined as the composite of death, myocardial infarction (MI), stroke and target vessel revascularization (TLR) and stent thrombosis (ST). Safety endpoints were bleeding events divided as major events (BARC 3–5) and minor events (BARC 1–2). Results 133 patients were enrolled: mean age was 69,3±11 years, men were 97 (73%), diabetics 24 (18%). 112 (84%) presented with acute coronary syndrome (tab1). 90% of interventions were done by radial approach, 19% of patients received Clopidogrel as oral P2Y12i. In–hospital MACE were 3, in absence of fatal events; 2 cases of MI (type 4a). The only case of ST was observed with OCT performed during staged PCI of non culprit lesion, with patient totally asymptomatic, without troponin increase and on Clopidogrel as oral P2Y12i. There were 2 BARC 3 events. Patients who received early transition strategy did not presented significant differences of ischemic/bleeding events (tab2). Conclusions Cangrelor demonstrated efficacy and safety in patients undergoing PCI. An early transition strategy to oral P2Y12i was not associated with an increase in both efficacy and safety adverse events in this early phase of our study.

Évolution de l’empathie d’étudiants en 4e année de médecine après un module obligatoire de formation à la relation thérapeutique

IntroductionSome studies have reported a decline in medical students’ clinical empathy during their first-year internships. Empathic skills in doctor–patient relationships have proven to have substantial benefit on the physiological as well as psychological parameters, and on the patients’ and physicians’ satisfaction. A range of experiential and interactive training modules have the potential to limit this decline and even foster the development of empathy, and yet French medical schools do not routinely implement such non-technical training. Moreover, there is no consensus about the concept of empathy, and previous studies rarely coordinate their definition with the method chosen to implement how it is measured. This study aims to evaluate the effectiveness of a training module that combines human simulations (simulated patient interviews and role-playing) and Balint groups in order to develop medical students’ empathy as a measured cognitive attribute, declarative knowledge, and their correlation. MethodsWe implemented a monocentric prospective study of fourth-year medical students from the Île-de-France area, which included pre/post-test assessment. First-year clinical interns initially completed five role-play sessions of one hour and a half each, with a group of 12 to 14 students led by a trained senior medical doctor. The sessions addressed successively issues of the doctor–patient relationship, breaking bad news scenarios, management of chronic conditions, violence and aggression, inappropriate treatment requests, or communication about medical errors. A pre-briefing session provided oral and written instruction and promoted a non-judgmental approach. Then two students role-played the doctor–patient interaction. Finally, a three-stage debriefing supported reflective learning. Subsequently, the students attended six Balint group sessions of one hour and a half each, within the same groups. One of the students was encouraged to bring up a challenging clinical situation. Then, the trained Balint supervisor invited all the students to share their observations, so as to explore the assumptions, beliefs and emotions raised by this account, and to collectively reframe the multiple perspectives on the case. At the end of the year, each student carried out two ten-minute consultations with a simulated patient, without an observer. The clinical scenarios were an HIV diagnosis disclosure and resisting a request for a prescription for antibiotics for a common cold. After each simulation, the simulated patient (SP) provided direct feedback to the student, with at times additional feedback given by their supervisor. The SP feedback was focused on empathy. The level of the medical students’ empathy was assessed using the self-reported Jefferson Scale of Empathy, which measures their declarative knowledge through multiple-choice questions. ResultsOf the 100 students who completed the empathy questionnaires, we found a statistically significant difference between the pre (108.8±11.9) and post-test (113.7±10.4; P<0.001). On the three JSPE-MS subscales, two students reported a statistically significant improvement (perspective taking; and the ability to put themselves in the patient's shoes). Of the 101 students who completed the knowledge questionnaires, we found a significant difference between the pre (2.3±1.1) and post-test (2.9±1.2; P<0.001). Moreover, a weak correlation was found (r=0.256) between improvements of empathy and knowledge assessments. DiscussionThese results in the French context are consistent with those reported in international literature on the benefits of implementing simulation training and Balint groups to limit the decline of empathy during the medical students’ first clinical internships. These results are further reinforced by the consistency between the definition of empathy and the implementation of a means to measure it as a cognitive dimension. The reliance on self-assessment of empathy might lessen the validity of these results and stresses the need for a wider multidimensional approach. The quality of the evidence is also limited by a monocentric, non-randomized and non-controlled design, which calls for further research. ConclusionThe use of human simulations combined with Balint groups seems to support the development of the cognitive empathy of medical students in the French context. Given the recent developments in remote learning worldwide to comply with social distancing measures, their online translation into role-played tele-consultations would appear to be a very topical opportunity, while also avoiding the inherent limitations of virtual reality to address non-technical skills.

Multiparametric Dynamic Ultrasound Approach for Differential Diagnosis of Primary Liver Tumors.

A correct differentiation between hepatocellular carcinoma (HCC) and intracellular cholangiocarcinoma (ICC) is essential for clinical management and prognostic prediction. However, non-invasive differential diagnosis between HCC and ICC remains highly challenging. Dynamic contrast-enhanced ultrasound (D-CEUS) with standardized software is a valuable tool in the diagnostic approach to focal liver lesions and could improve accuracy in the evaluation of tumor perfusion. Moreover, the measurement of tissue stiffness could add more information concerning tumoral environment. To explore the diagnostic performance of multiparametric ultrasound (MP-US) in differentiating ICC from HCC. Our secondary aim was to develop an US score for distinguishing ICC and HCC. Between January 2021 and September 2022 consecutive patients with histologically confirmed HCC and ICC were enrolled in this prospective monocentric study. A complete US evaluation including B mode, D-CEUS and shear wave elastography (SWE) was performed in all patients and the corresponding features were compared between the tumor entities. For better inter-individual comparability, the blood volume-related D-CEUS parameters were analyzed as a ratio between lesions and surrounding liver parenchyma. Univariate and multivariate regression analysis was performed to select the most useful independent variables for the differential diagnosis between HCC and ICC and to establish an US score for non-invasive diagnosis. Finally, the diagnostic performance of the score was evaluated by receiver operating characteristic (ROC) curve analysis. A total of 82 patients (mean age ± SD, 68 ± 11 years, 55 men) were enrolled, including 44 ICC and 38 HCC. No statistically significant differences in basal US features were found between HCC and ICC. Concerning D-CEUS, blood volume parameters (peak intensity, PE; area under the curve, AUC; and wash-in rate, WiR) showed significantly higher values in the HCC group, but PE was the only independent feature associated with HCC diagnosis at multivariate analysis (p = 0.02). The other two independent predictors of histological diagnosis were liver cirrhosis (p < 0.01) and SWE (p = 0.01). A score based on those variables was highly accurate for the differential diagnosis of primary liver tumors, with an area under the ROC curve of 0.836 and the optimal cut-off values of 0.81 and 0.20 to rule in or rule out ICC respectively. MP-US seems to be a useful tool for non-invasive discrimination between ICC and HCC and could prevent the need for liver biopsy at least in a subgroup of patients.

Educational level-dependent melanoma awareness in a high-risk population in Switzerland.

The worldwide incidence of melanoma has been increasing rapidly in recent decades with Switzerland having one of the highest rates in Europe. Ultraviolet (UV) radiation is one of the main risk factors for skin cancer. Our objective was to investigate UV protective behavior and melanoma awareness in a high-risk cohort for melanoma. In this prospective monocentric study, we assessed general melanoma awareness and UV protection habits in at-risk patients (≥100 nevi, ≥5 dysplastic nevi, known CDKN2A mutation, and/or positive family history) and melanoma patients using questionnaires. Between 01/2021 and 03/ 2022, a total of 269 patients (53.5% at-risk patients, 46.5% melanoma patients) were included. We observed a significant trend toward using a higher sun protection factor (SPF) in melanoma patients compared with at-risk patients (SPF 50+: 48% [n=60] vs. 26% [n=37]; p=0.0016). Those with a college or university degree used a high SPF significantly more often than patients with lower education levels (p=0.0007). However, higher educational levels correlated with increased annual sun exposure (p=0.041). Neither a positive family history for melanoma, nor gender or Fitzpatrick skin type influenced sun protection behavior. An age of ≥ 50 years presented as a significant risk factor for melanoma development with an odd's ratio of 2.32. Study participation resulted in improved sun protection behavior with 51% reporting more frequent sunscreen use after study inclusion. UV protection remains a critical factor in melanoma prevention. We suggest that melanoma awareness should continue to be raised through public skin cancer prevention campaigns with a particular focus on individuals with low levels of education.

Respiratory Syncytial Virus-Load Kinetics and Clinical Course of Acute Bronchiolitis in Hospitalized Infants: Interim Results and Review of the Literature.

Respiratory Syncytial Virus (RSV) bronchiolitis is the leading cause of hospitalization in infants. The role of RSV load in disease severity is still debated. We present the interim results of a prospective monocentric study enrolling previously healthy infants hospitalized for RSV bronchiolitis, collecting nasopharyngeal aspirates every 48 h from admission to discharge, and evaluating RSV load dynamics in relation to clinical outcome measures of bronchiolitis severity, including: need, type and duration of oxygen therapy, length of hospitalization, and the bronchiolitis clinical score calculated at admission. The results showed that the highest viral replication occurs within the first 48 hours after admission, with a significant decrease at subsequent time points (p < 0.0001). Moreover, higher RSV-RNA values were associated with the need for oxygen therapy (p = 0.03), particularly high-flow nasal cannula type (p = 0.04), and longer duration of respiratory support (p = 0.04). Finally, higher RSV load values were correlated with lower white blood cells, especially lymphocyte counts and C-reactive protein levels (p = 0.03, p = 0.04, and p = 0.01, respectively), as well as with patients of a younger age (p = 0.02). These data suggest that RSV may actively contribute to the clinical severity of bronchiolitis, together with other potential non-viral factors.

Interstitial pneumonia with autoimmune features: monocentric prospective study

To study demographic, clinical, serological and morphological features of interstitial pneumonia with autoimmune features (IPAF), compare survival in IPAF and interstitial lung disease in connective tissue diseases (CTD-ILD), and identify predictors of mortality and transformation to CTD in the IPAF group. The IPAF group included 48 patients (75.0% women, median age 57.5 years), CTD-ILD - 49 patients (79.6% women, median age 60.0 years). The analysis of demographic, clinical, laboratory and instrumental data was performed, as well as comparison of survival with the Kaplan-Meier method and the log-rank test in the IPAF and CTD-ILD groups. In the IPAF group, predictors of mortality and the development of CTD were studied with multivariate regression analysis. Duration of observation period did not differ significantly in the IPAF and CTD-ILD groups (40.0 and 37.0 months, respectively). Clinical criteria of IPAF were observed in 25 (52.1%) patients, serological - in 44 (91.7%), morphological - in 44 (91.7%). Mortality in the IPAF group was significantly higher than in the CTD-ILD group (29.2 and 6.1%, respectively; p=0.023). The presence of diabetes mellitus, CT-pattern of usual interstitial pneumonia, and an initial low forced vital capacity value were independent predictors of mortality in the IPAF group. During the observation period, the development of CTD was noted in 4 (8.3%) patients with IPAF. The independent predictor of the CTD development was the increased C-reactive protein level. IPAF is characterized by a lower survival rate compared to CTD-ILD, and a relatively low risk of CTD transformation.

Evaluation of the impact of pharmaceutical trainings and tools on the proper use of medicines in pediatrics.

Introduction: After sixyears of medication errors' (MEs) collection and analysis in a pediatric unit of a French University Hospital, the number of MEs was no longer decreasing. We then decided to set up pharmaceutical training and tools and evaluate their impact on the occurrence of ME. Materials and methods: This monocentric prospective study was carried out in the form of audits of prescriptions, preparations, and administrations before and after intervention (A1 and A2). After the analysis of A1 results, feedback was given to the teams, some tools for the proper use of medication (PUM) were distributed, and A2 was conducted. Finally, A1 and A2 results were compared. Results: Each audit included 202 observations. A total of 120MEs were identified during A1 and 54 for A2 (p < 0.0001). The observation rate with at least 1ME decreased from 39.11% to 21.29% (p < 0.0001), and no observation had more than twoMEs during A2 in contrast to A1 (n = 12). Human factors were responsible for the majority of MEs. The audit feedback allowed professionals to feel concerned about ME. The PUM tools received an average satisfaction rating of 9/10. The staff had never participated in this type of training, and all felt it was useful to apply PUM. Conclusion: This study showed a significant impact of pharmaceutical training and tools on the pediatric PUM. Clinical pharmaceutic actions allowed us to reach our objectives and satisfied all the staff. They must, therefore, be continued to limit human factors' impact and thus contribute to the safety of drug management in pediatrics.

Elexacaftor – Tezacaftor – Ivacaftor treatment improves systemic infection parameters and Pseudomonas aeruginosa colonization rate in patients with cystic fibrosis a monocentric observational study

Background & aimsThe CFTR-modulating therapy Elexaftor – Tezacaftor - Ivacaftor (ETI) has been widely prescribed since its approval in 2020 in the European Union. The aim of this study was to methodically evaluate the effects of an ETI treatment on clinical, biochemical data and Pseudomonas colonization in order to demonstrate its efficacy. MethodsThis prospective monocentric study comprised 69 patients diagnosed with cystic fibrosis aged at least 12 years and treated with ETI between September 2020 and November 2021. Clinical and laboratory data of each patient and study visit were collected before and after 24 weeks of ETI treatment. Follow-up status of Pseudomonas aeruginosa (PsA) colonization was assessed after one year of therapy by regularly determined sputum or throat swab samples. ResultsMarked improvements biochemical markers of systemic inflammation as white blood cell count, levels of immunoglobulins A, G and M and albumin within 24 weeks of therapy were observed. ETI treatment proved to be effective as seen by amelioration of lung function and sweat chloride concentration. Assessment of PsA colonization status revealed a conversion from a positive to negative detection in 36% of the cases after one year of therapy. ConclusionsETI treatment effectively improves systemic inflammation parameters and shows promising results in PsA status conversion.

1230 Vitiligo-like-depigmentation in patients with melanoma under immunotherapy: A monocentric prospective observational study

1230 Vitiligo-like-depigmentation in patients with melanoma under immunotherapy: A monocentric prospective observational study

The role of integrated psychological support in breast cancer patients: a randomized monocentric prospective study evaluating the Fil-Rouge Integrated Psycho-Oncological Support (FRIPOS) program

PurposeThis study examined the effects of Fil-Rouge Integrated Psycho-Oncological Support (FRIPOS) in a group of women with breast cancer compared with a group receiving treatment as usual (TAU).MethodsThe research design was a randomized, monocentric, prospective study with three time points of data collection: after the preoperative phase (T0), in the initial phase of treatments (T1), and 3 months after the start of treatments (T2). The FRIPOS group (N = 103) and the TAU group (N = 79) completed a sociodemographic questionnaire, the Symptom Checklist-90-R (SCL-90-R) at T0; the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30 and EORTC QLQ-BR23 at T1; and SCL-90-R, EORTC QLQ-C30, and EORTC QLQ-BR23 at T2.ResultsA series of independent and paired t tests showed that patients in the FRIPOS group performed better on all scales related to symptomatic manifestations and on some quality of life scales (fatigue, dyspnea, and sleep disturbances) at T2. In addition, a series of ten multiple regressions were performed to predict each SCL subscale at T2 from the SCL score at T0 and the EORTC QLQ-C30 scores at T2. In nine of ten regression models (all except somatization), both FRIPOS group membership and QoL subscale contributed significantly to prediction.ConclusionsThis study suggests that patients in the FRIPOS group have more benefits in emotional, psychological, and collateral symptoms than patients in the TAU group and that these improvements are due to integrated psycho-oncology care.

Prognostic Performance of Bedside Lung Ultrasound Score (LUSS) and ROX Index in Hypoxemic Respiratory Failure Due to COVID-19

Background: Noninvasive ventilation, mainly helmet CPAP, was widely used during the COVID-19 pandemic, even outside of intensive care units. Both the ROX index and the LUS score (LUSS) have been proposed as tools to predict negative outcomes in patients with hypoxemia treated with noninvasive ventilation (NIV) outside of ICUs. We aim to evaluate whether the combination of LUSS with the ROX index improves the predictive performance of these indices in patients with hypoxemia due to COVID-19 pneumonia, treated with NIV outside of ICUs. Methods: This is a monocentric prospective observational study conducted at the university teaching hospital Fondazione IRCCS San Gerardo dei Tintori (Monza, Italy) from February to April 2021. LUSS and ROX were collected at the same time in noninvasively ventilated patients outside of the ICU. An LUS exam was performed by 3 emergency medicine attending physicians with at least 5 years' experience in point-of-care ultrasonography using a 12-zone system. To evaluate the accuracy of the prognostic indices in predicting a composite outcome (endotracheal intubation and mortality), ROC curves were used. A logistic multivariable model was used to explore the predictors of the composite outcome of endotracheal intubation and in-hospital mortality. An unadjusted Kaplan-Meier analysis was used to explore the association with the composite outcome of survival without invasive mechanical ventilation at the 30-day follow-up by stratifying the 3 indices by their best cut-offs. Results: A total of 79 patients were included in the statistical analysis and stratified into 2 groups based on the presence of a negative outcome, which was reported in 24 patients out of 79 (30%). A great proportion of patients (66 patients-84%) were treated with helmet CPAP. All three indices (LUSS, ROX and LUSS/ROX) were independently associated with negative outcomes in the multivariable analyses. Although the comparison between the AUROC of LUSS or ROX versus LUSS/ROX did not reveal a statistically significant difference, we observed a trend toward a higher accuracy for predicting negative outcomes using the LUSS/ROX index as compared to using LUSS. With the Kaplan-Maier approach, all three indices stratified by the best cut-off reported a significant association with the outcome of 30-day survival without mechanical ventilation. Conclusions: A multimodal noninvasive approach that combines ultrasound (i.e., LUSS) and a bedside clinical evaluation (i.e., the ROX index) may help clinicians to predict outcomes and to identify patients who would benefit the most from invasive respiratory support.

Correlation of Myocardial Native T1 and Left Ventricular Reverse Remodeling after Valvular Surgery

Myocardial native T1 is a known cardiovascular magnetic resonance (CMR) imaging biomarker to quantify diffuse myocardial fibrosis in valvular cardiomyopathy. We hypothesized that diffuse myocardial fibrosis assessed by preoperative T1 mapping might correlate with LV reverse remodeling after valvular surgery. A prospective monocentric cohort study was conducted including 79 consecutive patients with valvular cardiomyopathy referred for surgical treatment of severe aortic or severe functional mitral regurgitation. Native T1 values were assessed by CMR before surgery. LV geometry parameters (i.e., LVEDV, LVESV) were obtained by 2D transthoracic echocardiography before and six months after surgery. Postoperative change of LV geometry parameters was calculated as delta (∆) variable (i.e., six months value minus baseline value). Mean native T1 was 1047 ± 39 ms, mean ∆LVEDV was -33 ± 42 mL, and mean ∆LVESV was -15 ± 27 mL. Native T1 values correlated with ∆LVEDV (Pearson r = 0.29; p = 0.009) and ∆LVESV (Pearson r = 0.29; p = 0.015). Native T1 values < 1073 ms were identified as independent predictor of postoperative reduction of LVEDV (HR 3.0; 95%-CI: 1.1-8.0; p = 0.03) and LVESV (HR 2.9; 95%-CI: 1.1-7.4; p = 0.03). Diffuse myocardial fibrosis assessed by myocardial native T1 correlates with LV reverse remodeling at six months after valvular surgery. T1 mapping may be a valuable tool to predict LV reverse remodeling in valvular heart disease.

Urinary biomarkers to predict acute kidney damage and mortality in COVID-19.

Acute kidney injury (AKI) is a frequent condition in patients hospitalized for COVID-19. There are only a few reports on the use of urinary biomarkers in COVID-19 and no data so far comparing the prognostic use of individual biomarkers in the prediction of adverse outcomes. We performed a prospective mono-centric study on the value of urinary biomarkers in predicting the composite endpoint of a transfer to the intensive care unit, the need for renal replacement therapy, mechanical ventilation, and in-hospital mortality. 41 patients hospitalized for COVID-19 were enrolled in this study. Urine samples were obtained shortly after admission to assess neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), calprotectin, and vascular non-inflammatory molecule-1 (vanin-1). We identified calprotectin as a predictor of a severe course of the disease requiring intensive care treatment (AUC 0.728, p=0.016). Positive and negative predictive values were 78.6% and 76.9%, respectively, using a cut-off concentration of 127.8ng/mL. NGAL tended to predict COVID-19-associated AKI without reaching statistical significance (AUC 0.669, p=0.053). The best parameter in the prediction of in-hospital mortality was NGAL as well (AUC 0.674, p=0.077). KIM-1 and vanin-1 did not reach significance for any of the investigated endpoints. While KIM-1 and vanin-1 did not provide prognostic clinical information in the context of COVID-19, the present study shows that urinary calprotectin is moderately predictive of the need for intensive care unit (ICU) admission, and NGAL may be modestly predictive of AKI in COVID-19. Calprotectin and NGAL show promise as potential helpful adjuncts in the identification of patients at increased risk of poor outcomes or complications in COVID-19.

Assessment of neutrophil subsets and immune checkpoint inhibitor expressions on T lymphocytes in liver transplantation: A preliminary study beyond the neutrophil-lymphocyte ratio.

Background: Advanced stages of cirrhosis are characterized by the occurrence of progressive immune alterations known as CAID (Cirrhosis Associated Immune Dysfunction). In advanced cirrhosis, liver transplantation (LT) remains the only curative treatment. Sepsis, shares many similarities with decompensated cirrhosis in terms of immuno-inflammatory response. In both conditions, the neutrophil-lymphocyte ratio (NLR) is associated with poor outcomes. Based on alterations in sepsis, we hypothesized that we could observe in cirrhotic and LT patients more detailed neutrophil and lymphocyte phenotypes. To this end, along with leukocyte count, we assessed immature neutrophils, LOX-1+ MDSC and PD-1 and TIM-3 lymphocyte expressions in cirrhotic patients before transplantation in association with liver disease severity and during the first month after transplantation. Methods: We conducted a prospective monocentric study including cirrhotic patients registered on LT waiting-list. Blood samples were collected at enrolment before LT and for 1month post-LT. In addition to NLR, we assessed by whole blood flow cytometry the absolute count of immature neutrophils and LOX-1+ MDSC as well as the expressions of immune checkpoint receptors PD-1 and TIM-3 on T lymphocytes. Results: We included 15 healthy volunteers (HV) and 28 patients. LT was performed for 13 patients. Pre-LT patients presented with a higher NLR compared to HV and NLR was associated with cirrhosis severity. Increased immature neutrophils and LOX-1+ MDSC counts were observed in the most severe patients. These alterations were mainly associated with acute decompensation of cirrhosis. PD-1 and TIM-3 expressions on T lymphocytes were not different between patients and HV. Post-LT immune alterations were dominated by a transitory but tremendous increase of NLR and immature neutrophils during the first days post-LT. Then, immune checkpoint receptors and LOX-1+ MDSC tended to be overexpressed by the second week after surgery. Conclusion: The present study showed that NLR, immature neutrophils and LOX-1+ MDSC counts along with T lymphocyte count and checkpoint inhibitor expression were altered in cirrhotic patients before and after LT. These data illustrate the potential interest of immune monitoring of cirrhotic patients in the context of LT in order to better define risk of sepsis. For this purpose, larger cohorts of patients are now necessary in order to move forward a more personalised care of LT patients.

Novel Biomarkers for Early Detection of Acute Kidney Injury and Prediction of Long-Term Kidney Function Decline after Partial Nephrectomy

Identifying acute kidney injury (AKI) within few hours of onset is certainly helpful. However, early prediction of a long-term eGFR decline may be an even more important goal. Our aim was to identify and compare serum [creatinine, kineticGFR, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL)] and urinary (NephroCheck, NGAL, proteinuria, albuminuria, acantocytes at urinary sediment) predictors of AKI that might efficiently predict long-term GFR decline after robotic Nephron-Spearing Surgery (rNSS). Monocentric prospective observational study. Patients scheduled for rNSS for suspected localized Renal Cell Carcinoma from May 2017 to October 2017 were enrolled. Samples were collected preoperatively and postoperatively (timepoints: 4 h, 10 h, 24 h, 48 h), while kidney function was re-assessed up to 24 months. 38 patients were included; 16 (42%) developed clinical AKI. The eGFR decline at 24 months was more pronounced after postoperative AKI (-20.75 vs. -7.20, p < 0.0001). KineticGFR at 4 h (p = 0.008) and NephroCheck at 10 h (p = 0.001) were, at multivariable linear regression analysis, efficient predictors of post-operative AKI and long-term eGFR decline if compared to creatinine (R2 0.33 vs. 0.04). NephroCheck and kineticGFR have emerged as promising noninvasive, accurate, and early biomarkers of postoperative AKI and long-term GFR decline after rNSS. Combining NephroCheck and kineticGFR in clinical practice would allow to identify high risk of postoperative AKI and long-term GFR decline as early as 10 h after surgery.