Prognostic Cut-off Value Research Articles

Prognostic value of neutrophil to lymphocyte ratio and platelet indices in cats with feline panleukopenia

The aim of this study was to ascertain the prognostic significance of the neutrophil to lymphocyte ratio (NLR) and platelet indices during hospital admission in cats with feline panleukopenia (FPV). A prospective observational study was conducted on 24 cats diagnosed with FPV. The results of the study demonstrated a significant decrease in NLR, platelet count (PLT), and platelet concentration (PCT) in the FPV survivor group compared to the control group. Furthermore, these parameters exhibited a notable decline in the FPV non-survivor group when compared to both the control group and the FPV survivor group. In contrast, mean platelet volume (MPV) and platelet distribution width (PDW) were significantly elevated in the FPV non-surviving cats compared to the control group. Moreover, receiver operating characteristic (ROC) curve analysis was employed to identify a prognostic cut-off value for predicting the prognosis of cats with FPV. The positive predictive values (PPVs) for survival were determined to be 90 %, 95 %, 85 %, 85 %, 85 %, and 75 %, respectively, using cut-off values of NLR (≤ 0.29), PLT (≤ 202.5 ×10³/µL), PCT (≤ 0.19 %), MPV (≥ 10.3 fL), and PDW (≥ 34.9 %). Based on the sensitivity, specificity and positive predictive values obtained from the ROC analysis, it was concluded that the NLR, MPV, and PLT are excellent biomarkers for determining prognosis in cats with FPV. Nevertheless, the PLT level is of greater significance, exhibiting a higher AUC.

Gender-specific differences in severe tricuspid regurgitation. Finding from a TR multicentre CMR registry

Abstract Background Observational studies have suggested that severe tricuspid regurgitation (TR) is more prevalent in women than in men, although the pathophysiological causes that justify this difference are unknown. Purpose 1) to assess clinical and imaging differences by Cardiac Magnetic Resonance (CMR) between men and women and 2) to examine the relationship between gender and all-cause mortality in a multicentre cohort of patients with at least severe TR. Methods The study-enrolled patients with at least severe TR assessed by 2D echocardiography who underwent a contemporary cardiac magnetic resonance (CMR) study. The primary outcome was all-cause mortality. Results 318 patients with severe TR recruited from 5 tertiary care hospitals were included in this study (70 ± 11 years, 67% female, 73% NYHA I or II). Regarding the etiology, 10% were primary TR, 1% CIED-related TR, 46 % atrial secondary TR and 43% ventricular secondary TR. Women showed a non-significant tend to lower prevalence of comorbidities, lower BNP and significantly lower creatinine values (table). Regarding CMR variables, women showed smaller indexed right ventricle (RV) volumes higher RVEF and lower TR regurgitant volume (table, p<0.05 for all). Left ventricle (LV) volumes were smaller and LVEF higher in women compared to men (p<0.001). During a median follow-up of 28 months (IQR: 10-54 months), there were 61 deaths (19%) with an estimated 5-year survival of 74%. Cumulative all-cause mortality was significantly worse in men compared to women (27% vs. 15%, p<0.001, figure). Male gender was significantly associated with all-cause mortality independently of age, RV volumes, RVEF and LVEF (HR 2,2 [1.34-3,68], p =0.002). Different cut-off values of index RV volumes and EF were predictive of mortality in men and women. In men a RV-EDV >110 ml/m2 and RVEF<57%; in women a RV-EDV >90 ml/m2 and RVEF< 60% were predictive of all-cause mortality (p<0.01). Conclusion Severe TR is more prevalent in women; however, it shows lower RV remodeling, better RV function and lower rate of events compared to men. Different prognostic RV cut-off values are provided based on CMR data.Gender differencesKaplan Meier Curves

Mortality and heart failure in patients with severe tricuspid regurgitation. Impact of RV volumes and function by CMR.

Abstract Background Beyond symptoms, right ventricle (RV) dilatation and dysfunction are established criteria for intervention in patients with significant tricuspid regurgitation (TR); however defined thresholds to support intervention are lacking. As a result, the optimal timing for intervention remains controversial and it is commonly undertaken at a late stage. Purpose To describe prognostic cut-off values of RV size and function by Cardiac Magnetic Resonance in a multicentre cohort of patients with at least severe TR. Methods The study enrolled patients with at least severe TR assessed by 2D echocardiography who underwent a contemporary cardiac magnetic resonance (CMR) study. Conventional parameters of biventricular volume and function were assessed in all patients. A combined endpoint of hospital admission due to heart failure (HF) and all-cause mortality was defined. Results 318 patients with severe TR recruited from 5 tertiary care hospitals were included in this study (70 ± 11 years, 67% female, 73% NYHA I or II). Regarding the etiology, 10% were primary TR, 1% CIED-related TR, 46 % atrial secondary TR and 43% ventricular secondary TR. After a median follow-up of 28 months (IQR: 10-54 months), 42% of the patients (n=134) experienced the combined endpoint (n=113 were admitted due to HF, n=61 died). After adjusting for age, NYHA class, comorbidities, type of TR and LVEF in a multivariate Cox proportional model (LR Chi-Square: 88.01, p<0.001), RV-EDV and RVEF were independently associated with all-cause mortality and heart failure (adjusted HR for RV-EDV per ml/m2 =1.008 [1.005-1.012], p<0.001 and RVEF HR per 1%=0.961 [0.942-0.981], p<0.001). Thresholds of RV-EDV ≥ 93 ml/m2, RV-ESV ≥ 39 ml/m2 and RVEF ≤ 58% held the best accuracy to predict outcomes (figure). In multivariable analysis, prognostic cut-off values of RV-EDV, RV-ESV and RVEF was associated with 1.91, 2.03, and 1.76-fold increased risk of HF or all-cause mortality respectively (RV-EDV HR: 1.91 [1.34-2.71], p<0.001, RV-ESV HR 2.03 [1.42-2.89], p<0.001 and RVEF HR1.76 [1.25-2.49], p=0.001). Conclusion RV size and function are crucial for determining optimal timing for TR intervention. CMR remains the gold standard to assess RV remodeling. Cut-off values of RV volume and function by CMR are defined in a multicentre cohort of patients based on outcome data; proposed thresholds differ from those previously established by echocardiography.Kaplan Meier curves

The relationship between circulating tumor cells in peripheral blood and clinical characteristics of pediatric neuroblastoma and prognostic evaluation

This study investigates the correlation between circulating tumor cells (CTCs) in peripheral blood and the clinical characteristics and prognosis of advanced pediatric neuroblastoma (NB). We conducted a retrospective analysis of 144 children with advanced NB who underwent comprehensive treatment. Detailed clinical data were collected, and CTCs were detected using a negative enrichment method combined with immunofluorescence technology. Prognostic evaluation criteria and cutoff values for CTCs were established using ROC curve analysis. Univariate and Cox multivariate regression analyses identified independent risk factors impacting prognosis. Patients were categorized into high and low-expression groups based on optimal cutoff values determined with X-tile software. The high expression group had a significantly higher incidence of disease progression (p < 0.001), maximum tumor diameter ≥10 cm (p = 0.004), undifferentiated subtype (p = 0.034), and stage IV disease (p = 0.007) compared to the low expression group. CTCs were notably higher in patients with progression compared to those with mitigation (p < 0.001), in those with maximum tumor diameter ≥10 cm compared to <10 cm (p < 0.001), and in stage IV compared to stage III patients (p = 0.036). The AUC values for maximum tumor diameter, degree of differentiation, and tumor stage were 0.703, 0.669, 0.574, and 0.598, respectively. The detection of CTCs provides significant insights into the clinical characteristics and prognosis of advanced pediatric NB, highlighting its potential as a prognostic tool.

Energy Loss Index and Dimensionless Index Outperform Direct Valve Planimetry in Low-Gradient Aortic Stenosis.

Background/Objectives: Among patients with suspected severe aortic stenosis (AS), discordance between effective orifice area (EOA) and transvalvular gradients is frequent and requires a multiparametric workup including flow assessment and calcium-scoring to confirm true severe AS. The aim of this study was to assess direct planimetry, energy loss index (Eli) and dimensionless index (DI) as stand-alone parameters to identify non-severe AS in discordant cases. Methods: In this prospective cohort study, we included consecutive AS patients > 70 years with EOA < 1.0 cm2 referred for valve replacement between 2014 and 2017. AS severity was retrospectively reassessed using the multiparametric work-up recommended in the 2021 ESC/EACTS guidelines. DI and ELi were calculated, and valve area was measured by direct planimetry on transesophageal echocardiography. Results: A total of 101 patients (mean age 82 y; 57% male) were included. Discordance between EOA and gradients was observed in 46% and non-severe AS found in 24% despite an EOA < 1 cm2. Valve planimetry performed poorly, with an area under the ROC curve (AUC) of 0.64. At a cut-off value of >0.82 cm2, sensitivity and specificity to identify non-severe AS were 67 and 66%, respectively. DI and ELi showed a higher diagnostic accuracy, with an AUC of 0.77 and 0.76, respectively. Cut-off values of >0.24 and >0.6 cm2/m2 identified non-severe AS, with a high specificity of 79% and 91%, respectively. Conclusions: Almost one in four patients with EOA < 1 cm2 had non-severe AS according to guideline-recommended multiparametric assessment. Direct valve planimetry revealed poor diagnostic accuracy and should be interpreted with caution. Usual prognostic cut-off values for DI > 0.24 and ELI > 0.6 cm2/m2 identified non-severe AS with high specificity and should therefore be included in the assessment of low-gradient AS.

Prognostic Value and Relative Cutoffs of Triglycerides Predicting Cardiovascular Outcome in a Large Regional-Based Italian Database.

Despite longstanding epidemiologic data on the association between increased serum triglycerides and cardiovascular events, the exact level at which risk begins to rise is unclear. The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension has conceived a protocol aimed at searching for the prognostic cutoff value of triglycerides in predicting cardiovascular events in a large regional-based Italian cohort. Among 14 189 subjects aged 18 to 95 years followed-up for 11.2 (5.3-13.2) years, the prognostic cutoff value of triglycerides, able to discriminate combined cardiovascular events, was identified by means of receiver operating characteristic curve. The conventional (150 mg/dL) and the prognostic cutoff values of triglycerides were used as independent predictors in separate multivariable Cox regression models adjusted for age, sex, body mass index, total and high-density lipoprotein cholesterol, serum uric acid, arterial hypertension, diabetes, chronic renal disease, smoking habit, and use of antihypertensive and lipid-lowering drugs. During 139 375 person-years of follow-up, 1601 participants experienced cardiovascular events. Receiver operating characteristic curve showed that 89 mg/dL (95% CI, 75.8-103.3, sensitivity 76.6, specificity 34.1, P<0.0001) was the prognostic cutoff value for cardiovascular events. Both cutoff values of triglycerides, the conventional and the newly identified, were accepted as multivariate predictors in separate Cox analyses, the hazard ratios being 1.211 (95% CI, 1.063-1.378, P=0.004) and 1.150 (95% CI, 1.021-1.295, P=0.02), respectively. Lower (89 mg/dL) than conventional (150 mg/dL) prognostic cutoff value of triglycerides for cardiovascular events does exist and is associated with increased cardiovascular risk in an Italian cohort.

Exploring the significance of tumor volume in endometrial cancer: Clinical pathological features, prognosis, and adjuvant therapies.

To assist clinicians in formulating treatment strategies for endometrial cancer (EC), this retrospective study explores the relationship between tumor volume and clinical pathological features, as well as prognosis, in patients undergoing staging surgery. Preoperative pelvic MRI examinations were conducted on 234 histologically confirmed EC patients. The ITK-SNAP software was employed to manually delineate the region of interest in the MRI images and calculate the tumor volume (MRI-TV). The analysis focused on investigating the relationship between MRI-TV and the clinical pathological features and prognosis of EC patients. Larger MRI-TV was found to be associated with various adverse prognostic factors (G3, deep myometrial invasion, cervical stromal invasion, lymphovascular space invasion, lymph node metastasis, advanced international federation of gynecology and obstetrics staging, and receipt of adjuvant therapy). The receiver operating characteristic curve indicated that MRI-TV ≥ 8 cm3 predicted deep myometrial invasion, and MRI-TV ≥ 12 cm3 predicted lymph node metastasis. Penalized spline (P-spline) regression analysis identified 14 cm3 of MRI-TV as the optimal prognostic cutoff value. MRI-TV ≥ 14 cm3 was an independent prognostic factor for overall survival and disease-free survival. For patients with MRI-TV ≥ 14 cm3, the disease-free survival rate with adjuvant therapy was superior to that of the sole staging surgery group. This study demonstrates a significant correlation between MRI-TV and clinical pathological features and prognosis in EC. For patients with MRI-TV ≥ 14 cm3, staging surgery followed by adjuvant therapy was superior to sole staging surgery.

STREI: a new index of right heart function in isolated severe tricuspid regurgitation by speckle-tracking echocardiography.

Right ventricular (RV) performance determines clinical management in severe tricuspid regurgitation (TR). Right atrial (RA) function complements RV assessment in TR. This study aimed to design a novel index by speckle-tracking echocardiography (STREI index) integrating RA and RV strain information and to evaluate the clinical utility of combining RV and RA strain for prediction of cardiovascular (CV) outcomes. Consecutive patients with at least (≥) severe TR evaluated in the Heart Valve Clinic (n = 300) were prospectively included. An additional independent TR cohort was included for external validation (n = 50). STREI index was developed with the formula: [2 ∗ RV-free wall longitudinal strain (RV-FWLS)] + reservoir RA strain (RASr). The composite endpoint included hospital admission due to heart failure and all-cause mortality. A total of 176 patients with ≥severe TR were finally included. STREI index identified a higher percentage of patients with RV dysfunction compared with conventional parameters. After a median follow-up of 2.2 years (interquartile range: 12-41 months), a total of 38% reached the composite endpoint. STREI values were predictors of outcomes independently of TR severity and RV dimensions. The combination of prognostic cut-off values of RASr (<10%) and RV-FWLS (>-20%) (STREI stratification) stratified four different groups of risk independently of TR severity, RV dimensions, and clinical status (adj HR per stratum 1.89 (1.4-2.34), P < 0.001). Pre-defined cut-off values achieved similar prognostic performance in the validation cohort (n = 50). STREI index is a novel parameter of RV performance that independently predicts CV events. The combination of RA and RV strain stratifies better patients' risk, reflecting a broader effect of TR on right heart chambers.

Low Levels of Circulating Tumor Cells Correlate with Favorable Clinical Outcome and Unique Biological Features in Newly Diagnosed Multiple Myeloma Patients

Introduction Circulating tumor cells (CTCs) have been proposed as a prognostic biomarker in newly-diagnosed MM (NDMM) but their low frequency questions their use in clinical practice. Lower CTC levels (cut-off &amp;lt;0.01-0.07%) correlate with a favorable prognostic outcomes in transplant-eligible (TE) patients (pts); however, several issues remain to be addressed. On clinical grounds, it remains unclear whether there is a similar prognostic cut-off value for transplant-ineligible (TI) pts. Furthermore, it is not clear whether the CTCs mimic the characteristics of a single (main)-site bone marrow (ΒΜ) myeloma cells or if they represent the total disease burden, i.e. in cases with extramedullary or macrofocal disease. Moreover, there is limited information of the biological factors that may lead myeloma cells to egress their primary BM site. Methods BM and matched peripheral blood (PB) samples from 550 NDMM pts (210 TE, 340 TI) were evaluated with NGF (median LOD 2.1x10 -6) for the presence of myeloma cells. Various multivariable regression models including CTCs, R-ISS, cytogenetic status and LDH were assessed to define the optimal clinical CTC cut-off. The BM niche profiling was examined with mass cytometry (CyTOF, n=15 pts, 8 with no CTCs, 7 with CTCs higher than the cut-off) and various multicolor flow cytometry panels (n=199 pts including 56 pts with no CTCs) that allowed the detection of 32 distinct immune populations. Results The median value of CTCs was 0.01% of total PB cells (range: 0.0002%-63%) and in 57/550 (10.4%) pts CTCs could not be detected. Increased levels of CTCs correlated with ISS III stage (median: 0.037%, 0.007% and 0.002% for pts with ISS-3, ISS-2 and ISS-1, respectively; p&amp;lt;0.0001), high risk cytogenetics (median: 0.038% vs. 0.006% in standard risk, p&amp;lt;0.0001), and higher levels of b2-microglobulin and BM infiltration. Median follow-up was 41 months (range: 5-66 months). PFS and OS were gradually worsened towards a CTCs log increment, independently of ISS, cytogenetic status and LDH. Hence, pts with undetectable CTCs had the most favorable prognosis with a 5-year PFS and OS of 83% and 97% respectively. The optimal clinical CTCs cut-off that stratified pts into two distinct prognostic groups was defined at the level of 0.02%, which was common for both TE (median PFS: NR in both high and low CTC subsets; p&amp;lt;0.01) and TI subgroups (median PFS: 47 for low vs. 23 months for high CTCs subset, p&amp;lt;0.0001). Importantly, this cut-off, together with the phenotypic classification of pts (MGUS-like, MM-like etc.) could be incorporated in the established R-ISS system, providing an improved ptnts' stratification. The 2-year achievement of MRD negativity was 45%, 67% and 73% for pts with high, low and undetectable CTCs and median time for MRD negativity was 34, 17 and 12 months, respectively (p&amp;lt;0.001). Of note, pts with high CTCs who achieved MRD negativity, modulated their unfavorable risk status and showed similar PFS with those who had low CTCs. In 73/493 (14.8%) pts with detectable CTCs, there was an obvious phenotypic inconsistency between BM myeloma cells and CTCs, either in regard to the relative ratio of the detected (sub)clones, or the appearance of ≥1 phenotypically distinct clonal populations, which were present only in BM or PB. Pts with phenotypic inconsistencies had higher CTC levels and more often diffuse MRI patterns than those with a phenotypic agreement (frequency: 40% vs. 10%; p&amp;lt;0.01). To better understand the heterogeneous dissemination of myeloma cells to PB, we compared the BM niche profiles of pts with high CTC levels (&amp;gt;10 -3) and those with no CTCs. The analyses highlighted clear differences in the BM composition of the two groups with the BM of pts with no CTCs showing significantly lower levels of T cells, NK cells, TAMs and an increased naïve/memory B cell ratio. Of note, no differences were observed in the prevalence of immunosuppressive cell subsets (Tregs, MDSCs) between the two groups. Discussion The presence of CTCs at levels &amp;gt;0.02% confers an adverse prognostic factor for NDMM pts, irrespective of their transplant status. On the contrary, pts with no CTCs have the more favorable outcome and share unique microenvironmental features, which may eliminate CTCs dissemination. Since the liquid biopsy seems to be a better representative of the entire tumor load than a single tissue biopsy, the CTC analysis serves as the new hallmark for the real-time evaluation of a patient's disease and immune status.

Prognostic potential of inflammatory markers, oxidative status, thrombocyte indices, and renal biochemical markers in neonatal calf diarrhoea-induced systemic inflammatory response syndrome

The study aimed to assess the prognostic value of inflammatory markers, indicators of oxidative stress, thrombocyte indices, and renal biochemical markers in neonatal calf diarrhoea (NCD) induced by systemic inflammatory response syndrome (SIRS) upon admission. A prospective, observational, and case-control study was conducted on 56 calves diagnosed with NCD. Mean concentrations of interleukin-6 (IL-6), malondialdehyde (MDA), glutathione (GSH), mean platelet volume (MPV), platelet distribution width (PDW), blood urea nitrogen (BUN), and creatinine (Crea) were measured. Furthermore, the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were also calculated for SIRS survivors [SIRS (survivor)] and non-survivors [SIRS (non-survivor)] induced by NCD. A prognostic cut-off value for predicting the prognosis of the SIRS’s induced by NCD was obtained via receiver operating characteristic (ROC) curve analysis. Upon admission, the SIRS (non-survivor) calves had significantly higher (P < .001) average levels of IL-6, MDA, BUN, Crea, MPV, and PDW compared to the SIRS (survivor) calves and significantly lower (P < .001) average levels of GSH. Despite an apparent increase in the NLR and PLR values of calves diagnosed with SIRS, no significant difference was found between the survival and non-survivor SIRS cases. Positive predictive values (PPVs) for survival were determined as 100 %, 100 %, 80 %, 100 %, 80 %, and 80 %, respectively, using cut-off values of IL-6 (≤259.67 ng/L), MDA (≤2.87 nmol/mL), MPV (≤12.5 fL), PDW (≤34.25 %), BUN (≤168.3 mg/dL), and Crea (≤2.11 mg/dL). The determined threshold values are those obtained upon admission to the hospital. Based on the sensitivity, specificity, and PPVs derived from the ROC analysis, it has been concluded that IL-6, MDA, MPV, PDW, BUN, and Crea are the most relevant biomarkers used for predicting the prognosis of NCD-induced SIRS in calves. Furthermore, it is also noteworthy that IL-6 exhibited the highest effectiveness among all biomarkers.

Prognostic Potential of Thrombocyte Indices, Acute Phase Proteins, Electrolytes and Acid-Base Markers in Canine Parvovirus Infected Dogs With Systemic Inflammatory Response Syndrome

Dogs with canine parvovirus enteritis (CPVE) that develop systemic inflammatory response syndrome (SIRS) frequently have a poor prognosis. The aim of the study was to assess the prognostic potential of thrombocyte indices, acute phase proteins, electrolytes, and acid-base markers in CPVE puppies with SIRS (CPVE-SIRS+) at admission. A case-controlled, prospective, and observational study was performed on 36 CPVE puppies. Mean concentrations of C-reactive protein (CRP), albumin, thrombocyte count, mean platelet volume (MPV), platelet distribution width (PDW), sodium (Na+), potassium (K+), chloride (Cl−) and ionized calcium (iCa) were measured and strong ion difference 3 (SID3), ATOT-albumin and ATOT-total protein were determined in CPVE-SIRS+ survivors and nonsurvivors. A prognostic cut-off value for predicting the disease outcome was determined by receiver operating characteristic (ROC) curve analysis. The mean values of MPV, PDW and CRP were significantly higher and the mean values of albumin, Cl− and ATOT-albumin were significantly lower in CPVE-SIRS+ nonsurvivor than CPVE-SIRS+ survivor puppies on the day of admission, but the thrombocyte count, Na+, K+, iCa, SID3 and ATOT- total protein values did not differ significantly. The positive predictive values (PPVs) for survival using cut-off value of MPV (≤15.08 fL), PDW (≤14.85%), CRP (≤180.7 mg/L), albumin (≥1.795 g/dL), Cl− (≥96.00 mmol/L), and ATOT-albumin (≥7.539) were determined as 100%, 100%, 100%, 80%, 100%, and 80%, respectively with better area under ROC curve and sensitivity. Based on sensitivity, specificity, and PPVs from ROC analysis, it is concluded that the determination of Cl− concentration and MPV at admission followed by CRP will serve as the most appropriate biomarkers in predicting the disease outcome of CPVE puppies that develop SIRS.

IMP3 Expression as a Potential Tumour Marker in High-Risk Localisations of Cutaneous Squamous Cell Carcinoma: IMP3 in Metastatic cSCC.

High IMP3 expression is correlated with a worse outcome. Until now, there have been no data about IMP3 expression and clinical outcome for high-risk localisation of squamous cell carcinoma of the skin (cSCC). One-hundred twenty-two patients with cSCC of the lip and ear were included, and IMP3 expression in the tumours was immunohistochemically assessed in different evaluation approaches. Subsequently, subgroups were analysed in a matched pair approach and correlated with clinical pathologic parameters. In the following, different IMP3 analysis methods were tested for clinical suitability. We found a significant correlation between IMP3 expression and risk for lymph node metastasis, local relapse, and progression-free survival. On basis of our data, we suggest a prognostic benefit cutoff value for high (>50%) and low (<50%) IMP3 expression. Thus, IMP3 expression has a high scientific potential for further studies and could potentially be used as a prognostic marker in diagnostic and therapeutic decision-making.

Prognostic cardiovascular cut-off values of dietary caffeine in a cohort of unselected men and women from general population

Background and aimsAmong an unselected cohort of men and women from general population (n = 1.668), the prognostic effects of being over the cut-off of all-source dietary caffeine intake were studied. Methods and resultsPrognostic cut-off values for coronary events, incident heart failure (HF), cerebrovascular events (CBV) and arrhythmic events (ARR) were found by means of the receiver-operating-characteristic curves method. Those for HF (>230 mg/day), for CBV (>280 mg/day) and for ARR (>280 mg/day) were confirmed in multivariate Cox analysis adjusted for age, body mass index, circulating thyroid hormone, diabetes mellitus, arterial hypertension, smoking, dietary intake of ethanol, basal heart rate, low-density-lipoprotein cholesterol, forced expiratory volume in 1 s and β-blocking therapy. Being over these cut-off values was associated to a reduced hazard ratio during the follow-up in the whole cohort (HR 0.678, 95%CI 0.567–0.908, p = 0.009 for HF; 0.651, 95%CI 0.428–0.994, p = 0.018 for CBV; 0.395, 95%CI 0.395–0.933, p = 0.022 for ARR) and in men (0.652, 0.442–0.961, p = 0.029; 0.432, 0.201–0.927, p = 0.03; 0.553, 0.302–1.000, p = 0.05, respectively) but not in women. The caffeine-induced risk decrease observed in the whole cohort is therefore entirely attributable to men. In the case of HF, heart rate entered the risk equation in a positive manner without rejecting caffeine. The –163C>A polymorphism of the CYP1A2 gene, codifying for ability to metabolize caffeine, introduced in sensitivity analysis, did not alter the prognostic models. ConclusionMen introducing >230 mg/day caffeine show a reduced risk of HF, and those introducing >280 mg/day a reduced risk of CBV and ARR independent of genetic pattern.

Predictive Value of Perioperative Cardiac Troponin I in Patients Undergone Liver Transplantation: A Retrospective Cohort Study.

To examine the change rule and clinical significance of cardiac troponin I (cTnI) in the perioperative period of liver transplantation in adults, as well as its association with 28-day mortality. This was a retrospective cohort study: patients who underwent elective orthotopic liver transplantation (OLT) in Beijing Chao-Yang Hospital between June 2015 and June 2020 were selected, and plasma cTnI values were collected through the electronic medical record system within 7 days after surgery. Furthermore, the baseline clinical data of these patients were collected, and the change curve of cTnI values following liver transplantation was plotted. Using univariate and multivariate logistic regression models, the relationship between the level of postoperative cTnI and short-term mortality was investigated. The primary study endpoint was mortality within 28 days after surgery. We included 414 patients who had undergone liver transplantation in this study, 48 of whom died within 28 days after surgery. cTnI, a specific marker of myocardial injury, could predict that the postoperative cardiovascular complications were higher in the death group and significantly affect the short-term prognosis of patients; however, its prognostic cut-off value was approximately 0.545 ng/mL (13×URL), indicating that a minor elevation of cTnI after liver transplantation did not significantly affect the prognosis. Moreover, a comparison of the baseline data and postoperative ICU management scores of the two groups revealed that diabetes, maximum value of cTnI >0.545 ng/mL within 7 days, and the need for postoperative renal replacement therapy (RRT) were independent prognostic factors of death within 28 days after liver transplantation. Within 7 days after surgery, an increase in cTnI to the maximum value of 0.545 ng/mL (13×URL) could have a significant impact on the short-term prognosis of patients. Diabetes and postoperative RRT were two independent prognostic factors for liver transplantation perioperative mortality.

Estimating prognostic relevant cutoff values for a multiplex PCR detecting BCR::ABL1 in chronic myeloid leukemia patients on tyrosine kinase inhibitor therapy in resource-limited settings

The prognosis of chronic myeloid leukemia (CML) on tyrosine kinase inhibitor (TKI) treatment is based on the quantification of BCR::ABL1 fusion gene transcript copy number, harmonized by an international scale (IS) based on TaqMan-based real-time quantitative PCR (qRT-PCR). In Ethiopia, as in most low- and middle-income countries (LMICs), access to standard diagnostic, follow-up, and prognostic tools is very limited, and it has been challenging to strictly follow international guidelines. This seriously compromises clinical outcome, despite the availability of TKIs through the Glivec International Patient Assistance Program (GIPAP). Multiplex PCR (mpx-PCR), conventionally regarded as a “screening tool,” offers a potential solution to this problem. A total of 219 samples from confirmed CML patients were assayed. In reference to qRT-PCR, the AUC of ROC curve for mpx-PCR was 0.983 (95% CI: 0.957 to 0.997). At the optimum cut-off value, equivalent to BCR::ABL1 (IS) transcript copy number of 0.6%, the specificity and sensitivity were 93% and 95%, respectively, with 94% accuracy. Albeit the sensitivity and accuracy of mpx-PCR decrease below the optimum cutoff of 0.6% (IS), the specificity at 0.1% (IS) was 100%, making it an attractive means to rule-out relapse and drug non-adherence at later stages of treatment, which is particularly an issue in a low income setting. We conclude that the relative simplicity and low cost of mpx-PCR and prognostic relevant cutoff values (0.1–0.6% IS) should allow its use in peripheral clinics and thus maximize the positive impact of TKIs made available through GIPAP in most LMICs.

Inflammation-Based Prognostic Scores in Pancreatic Cancer Patients—A Single-Center Analysis of 1294 Patients within the Last Decade

Inflammatory properties are known to promote tumor progression leading to an impaired median overall survival (mOS). Various small studies have focused on a wide range of inflammation-based prognostic indicators. By using sufficient data from 1294 out of 2323 patients diagnosed with pancreatic cancer between 2009 and 2021 at our cancer center, inflammatory markers such as the neutrophil to lymphocyte ratio (NRL), the platelet to lymphocyte ratio (PLR), the lymphocyte to monocyte ratio (LMR) and the CRP to albumin ratio (CAR) were evaluated. We identified a new combined score, termed the inflammatory benchmark index (IBI). We performed univariate and multivariate overall survival analyses and identified optimal prognostic cut-off values for each parameter. In univariate analyses, advanced age (p < 0.001), gender (p < 0.001), tumor stage (p < 0.001), CA19-9 (p = 0.001), NLR (p = 0.001), LMR (p = 0.004), PLR (p = 0.004), CAR (p = 0.001) and IBI (p = 0.001) were identified as prognostic markers. In multivariate analyses advanced age (p < 0.001), gender (p = 0.001), tumor stage (p < 0.001), CA19-9 (p < 0.001), NLR (p = 0.001), LMR (p = 0.038), CAR (p < 0.001) and IBI (p < 0.001) were independent prognostic markers. These findings emphasize the impact of inflammation in pancreatic cancer, provide easily accessible prognostic values for the clinician, and may be useful as stratification parameters for trials aimed at patient inflammation or immune response.

BORDERLİNE MÜSİNÖZ OVER TÜMÖRLERİNDE Kİ67'NİN PROGNOSTİK DEĞERİ

Objective&#x0D; Ovarian borderline tumors (OBTs) are an intermediate&#x0D; type of ovarian neoplasm. Ovarian mucinous borderline&#x0D; tumors (MBT) are the second most common subtype&#x0D; of OBT. Because of their uncertain pathogenesis&#x0D; and biological behaviour they cannot be classified&#x0D; clearly into benign and malign categories. There is a&#x0D; need to identify a parameter that provides more prog-&#x0D; nostic information about the clinical course and can be&#x0D; evaluated easily in routine practice. Ki67 is a routinely&#x0D; used immunohistochemical marker that is strongly associated&#x0D; with cellular proliferation, including tumor cells.&#x0D; We aimed in this study to evaluate the prognostic&#x0D; significance and to determine prognostic cut-off value&#x0D; of Ki67 counting in the MBTs and to investigate its relationship&#x0D; with clinicopathologic features, recurrence,&#x0D; and long term survival status and also to provide more&#x0D; information to the literature.&#x0D; Material and Method&#x0D; A total of 20 cases diagnosed with ovarian mucinous&#x0D; borderline tumors were identified. Immunohistochemical&#x0D; studies were performed on the most representative&#x0D; sample of the tumor. Positive signal was nuclear and it&#x0D; was evaluated by two pathologists.&#x0D; Results&#x0D; Ki67 proliferating index (P.I) value with a median of&#x0D; 15%(1-47%) and a mean of 16% Ki67 P.I. reached&#x0D; statistically significance at 20% cut-off value with&#x0D; progression and at 30% cut-off value with 5-year OS.&#x0D; (p=0.021 and p=0.032, respectively). Although the&#x0D; Ki67 P.I. tended to increase with age, there was no&#x0D; statistical association between Kİ67 P.I. and other clinicopathological&#x0D; parameters including tumor size, laterality,&#x0D; capsule integrity, intraepithelial carcinoma and&#x0D; focal atypia.&#x0D; Conclusion&#x0D; In our study, recurrence was more frequent when Ki67&#x0D; was greater than 20%, and 5-year survival was lower&#x0D; when Ki67 was greater than 30%, suggesting that&#x0D; the Ki67 index was associated with a more aggressive&#x0D; course and death. Therefore, we predicted that&#x0D; Ki 67 would be useful in determining the frequency of&#x0D; follow-up of patients and predicting their prognosis.&#x0D; However, we think that this result should be supported&#x0D; by larger series.

Prognostic value of B-type natriuretic peptide for nursing- and healthcare-associated pneumonia and aspiration pneumonia in comparison with procalcitonin and A-DROP score: a prospective cohort study.

Pneumonia in elderly patients who require nursing care is becoming more and more common among the aging populations of developed countries, and treatment is an important topic worldwide. A simpler prognostic indicator would be expected to improve the treatment of pneumonia. This single-center, prospective cohort study aimed to compare the usefulness of B-type natriuretic peptide (BNP), procalcitonin (PCT), and the A-DROP score, which have been reported to correlate with pneumonia prognoses, such as aspiration pneumonia (AP). We included patients who were admitted to the Kanazawa Medical University Himi Municipal Hospital with a diagnosis of either nursing- and healthcare-associated pneumonia (NHCAP) or AP between January 1, 2012 and July 31, 2019. We collected demographic, clinical, and laboratory characteristics and outcome data from electronic medical records, and calculated A-DROP scores. The primary outcome was 30-day mortality. We evaluated correlations with the primary outcome using the chi-square test, Fisher exact test, t-test, Cox-regression analysis, and receiver operating characteristic curve analysis. Of the 1,215 patients with pneumonia, 297 were eligible for the study, of whom 37 (12%) died whin 30 days. After univariate analysis, we performed Cox proportional-hazards analysis for BNP, PCT, A-DROP score, albumin, C-reactive protein, and disseminated intravascular coagulation, which were significantly correlated with the primary outcome in univariate analysis. As a result, only BNP showed a significant correlation (P=0.008, 95% CI: 1.30-6.06). No significant correlation was obtained in PCT (P=0.529) and A-DROP score (P=0.107). Furthermore, we generated receiver operating characteristic curve to estimate the prognostic cut-off values of BNP for the primary outcome of NHCAP and AP. The optimal cut-off value of BNP for predicting death was 179.3 pg/mL (sensitivity 62.2%, specificity 76.2%, negative likelihood ratio 0.50%, positive likelihood ratio 2.61%). And, BNP yielded the highest area under the curve (0.72) in comparison with PCT (0.67) and A-DROP score (0.69). BNP may be a more clinically useful prognostic factor for NHCAP and AP than PCT or A-DROP score, and should be considered as a routine test at the beginning of these treatments.

Predictive Value of MRI in Hypoxic-Ischemic Encephalopathy Treated with Therapeutic Hypothermia.

Hypoxic-ischemic encephalopathy (HIE) is a severe pathology, and no unique predictive biomarker has been identified. Our aims are to identify associations of perinatal and outcome parameters with morphological anomalies and ADC values from MRI. The secondary aims are to define a predictive ADC threshold value and detect ADC value fluctuations between MRIs acquired within 7 days (MR0) and at 1 year (MR1) of birth in relation to perinatal and outcome parameters. Fifty-one term children affected by moderate HIE treated with hypothermia and undergoing MRI0 and MRI1 were recruited. Brain MRIs were evaluated through the van Rooij score, while ADC maps were co-registered on a standardized cerebral surface, on which 29 ROIs were drawn. Statistical analysis was performed in Matlab, with the statistical significance value at 0.05. ADC0 < ADC1 in the left and right thalami, left and right frontal white matter, right visual cortex, and the left dentate nucleus of children showing abnormal perinatal and neurodevelopmental parameters. At ROC analysis, the best prognostic ADC cut-off value was 1.535 mm2/s × 10-6 (sensitivity 80%, specificity 86%) in the right frontal white matter. ADC1 > ADC0 in the right visual cortex and left dentate nucleus, positively correlated with multiple abnormal perinatal and neurodevelopmental parameters. The van Rooij score was significantly higher in children presenting with sleep disorders. ADC values could be used as prognostic biomarkers to predict children's neurodevelopmental outcomes. Further studies are needed to address these crucial topics and validate our results. Early and multidisciplinary perinatal evaluation and the subsequent re-assessment of children are pivotal to identify physical and neuropsychological disorders to guarantee early and tailored therapy.

Study to Determine a Prognostic Cutoff Values of the Coagulation Analyte D-dimer for ICU Admission among COVID-19 Patients.

The measured D-dimer levels in coronavirus disease-2019 (COVID-19) patients have no specific cutoff to find the progression of coagulopathy and severity. This study aimed to determine prognostic cutoff values of D-dimer for intensive care unit (ICU) admission among COVID-19 patients. This cross-sectional study was conducted in Sree Balaji Medical College and Hospital, Chennai, during a period of 6 months. This study included 460 COVID-19-positive individuals. The mean age was 52.2 ± 12.53 years. Patients with mild illness have D-dimer value 461.8 ± 221, whereas moderate and severe COVID illness patients have D-dimer values of 1915.2 ± 699.9 and 7937.6 ± 2045.2, respectively. D-dimer cutoff value of 1036.9 is shown to be a prognostic cutoff value for COVID-19 patients admitted in the ICU with 99% sensitivity and 17% specificity. The area under curve (AUC) was considered excellent (AUC = 0.827, 95% Cl: 0.78-0.86, p-value < 0.0001) indicative of high sensitivity. The D-dimer value of 1036.9 ng/mL was found to be the optimum cutoff for the patients to predict the severity of the COVID-19-positive patients admitted in the ICU. Anton MC, Shanthi B, Vasudevan E. Study to Determine a Prognostic Cutoff Values of the Coagulation Analyte D-dimer for ICU Admission among COVID-19 Patients. Indian J Crit Care Med 2023;27(2):135-138.