Outcomes of concurrent versus sequential icotinib therapy and chemotherapy in advanced non‐small cell lung cancer with sensitive EGFR mutations

AbstractTo explore a better treatment strategy for patients with advanced non‐small cell lung cancer harboring sensitive epidermal growth factor receptor mutations, a total of 271 patients were retrospectively analyzed. The patients were divided into two groups: the combination group (58 cases), which received concurrent icotinib, pemetrexed, and platinum treatment, and the sequential group (213 cases), which received the sequential pemetrexed and platinum therapy, followed by icotinib treatment. The primary end points were progression‐free survival (PFS) and PFS on the subsequent line of therapy (PFS2). PFS in the combination group was significantly higher compared with that in the sequential group (16.89 months vs. 9.90 months; p < 0.001). PFS in the combination group was also significantly higher than PFS2 in the sequential group (16.89 months vs. 14.05 months; p = 0.009). The overall survival (OS) of the patients was 33.22 months (95% confidence interval (CI): 26.99–37.01) in the combination group and 26.47 months (95% CI: 25.05–26.95) in the sequential group (p < 0.001). The combination group’s objective response rate was superior to that of the sequential group (79.31% vs. 52.11%; p < 0.001). Propensity score matching also revealed that icotinib therapy combined with chemotherapy extended the PFS, PFS2, and OS of the patients (p < 0.0001, p = 0.003, and p = 0.001, respectively). The combination group’s objective response rate was also better compared with the sequential group (79.31% vs. 51.72%; p = 0.001). In conclusion, our study demonstrated icotinib combined with chemotherapy can improve survival efficacy better than the separated two‐line therapy. Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

For advanced non‐small cell lung cancer (NSCLC) harboring activating EGFR mutants, EGFR‐tyrosine kinase inhibitors (TKIs) are the standard first‐line treatment. Unfortunately, most patients with NSCLC harboring EGFR mutations acquire EGFR‐TKI resistance after EGFR‐TKI treatment for about 10–14 months. Studies have indicated that chemotherapy plus EGFR‐TKIs may have combined effects on the growth of NSCLC cells. However, until now, there has been no study comparing the concurrent and sequential EGFR‐TKIs plus chemotherapy.

• WHAT QUESTION DID THIS STUDY ADDRESS?

We retrospectively analyzed the efficacy and safety of concurrent versus sequential icotinib and chemotherapy in untreated NSCLC with sensitive EGFR mutations.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

In the patients with NSCLC with sensitive EGFR mutations, the first‐line pemetrexed plus platinum combined with icotinib better improved PFS, PFS2, and objective response rate compared with first‐line icotinib and second‐line pemetrexed plus platinum.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

The results of this paper provide guidance for the strategy choice in the treatment of patients with NSCLC.     

Dramatic response to immunotherapy in an epidermal growth factor receptor-mutant non-small cell lung cancer: A case report

BACKGROUNDThe advent of immune checkpoint inhibitors (ICIs) has revolutionized the management of several types of solid cancers, including lung cancer, by boosting the body''s natural tumor killing response. However, it is undeniable that only a small proportion of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations can achieve long-term responses and benefit from immunotherapy.CASE SUMMARYHerein, we report the case of a 48-year-old man diagnosed with stage IV lung adenocarcinoma with an EGFR L858R mutation who was administered pembrolizumab monotherapy followed by pemetrexed and achieved a 10-month progression-free survival interval. In this case report, we show that ICIs were effective for our patient with EGFR-mutated NSCLC and discuss the characteristics of patients who can benefit from immunotherapy.CONCLUSIONWe suggest that patients with EGFR-mutated NSCLC with high PD-L1 expression (defined as ≥ 25%), the L858R mutation, smoking history, or pemetrexed pretreatment may benefit from immunotherapy.     

A simple prognostic index based on admission vital signs data among patients with sepsis in a resource-limited setting

IntroductionIn sub-Saharan Africa, vital signs are a feasible option for monitoring critically ill patients. We assessed how admission vital signs data predict in-hospital mortality among patients with sepsis. In particular, we assessed whether vital signs data can be incorporated into a prognostic index with reduced segmentation in the values of included variables.MethodsSubjects were patients with sepsis hospitalized in Uganda, who participated in two cohort studies. Using restricted cubic splines of admission vital signs data, we predicted probability of in-hospital death in the development cohort and used this information to construct a simple prognostic index. We assessed the performance of the index in a validation cohort and compared its performance to that of the Modified Early Warning Score (MEWS).ResultsWe included 317 patients (167 in the development cohort and 150 in the validation cohort). Based on how vital signs predicted mortality, we created a prognostic index giving a score of 1 for: respiratory rates ≥30 cycles/minute; pulse rates ≥100 beats/minute; mean arterial pressures ≥110/<70 mmHg; temperatures ≥38.6/<35.6°C; and presence of altered mental state defined as Glasgow coma score ≤14; 0 for all other values. The proposed index (maximum score = 5) predicted mortality comparably to MEWS. Patients scoring ≥3 on the index were 3.4-fold (95% confidence interval (CI) 1.6 to 7.3, P = 0.001) and 2.3-fold (95% CI 1.1 to 4.7, P = 0.031) as likely to die in hospital as those scoring 0 to 2 in the development and validation cohorts respectively; those scoring ≥5 on MEWS were 2.5-fold (95% CI 1.2 to 5.3, P = 0.017) and 1.8-fold (95% CI 0.74 to 4.2, P = 0.204) as likely to die as those scoring 0 to 4 in the development and validation cohorts respectively.ConclusionAmong patients with sepsis, a prognostic index incorporating admission vital signs data with reduced segmentation in the values of included variables adequately predicted mortality. Such an index may be more easily implemented when triaging acutely-ill patients. Future studies using a similar approach may develop indexes that can be used to monitor treatment among acutely-ill patients, especially in resource-limited settings.     

The combination of fibrinogen concentrations and the platelet-to-lymphocyte ratio predicts survival in patients with advanced lung adenocarcinoma treated with EGFR-TKIs

ObjectiveThis study aimed to identify a predictive marker of response to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with EGFR-mutant advanced lung adenocarcinoma.MethodsA cohort of 190 patients with EGFR-mutant advanced lung adenocarcinoma was analyzed. Receiver operating characteristic curve analysis was used to evaluate the optimal cutoffs for fibrinogen levels, the neutrophil-to-lymphocyte ratio (NLR), and the platelet-to-lymphocyte ratio (PLR) for predicting progression-free survival (PFS). Univariate and multivariate survival analyses were performed to identify factors correlated with PFS and overall survival (OS).ResultsHigh NLR was associated with worse performance status. In univariate analysis, fibrinogen levels, NLR, and PLR were correlated with OS and PFS. In multivariate analysis, all three variables remained predictive of OS, whereas only fibrinogen levels and PLR were independent prognostic factors for PFS. Furthermore, the combination of fibrinogen levels and PLR (F-PLR score) could stratify patients into three groups with significantly different prognoses, and the score was independently predictive of survival.ConclusionThe F-PLR score predicted the prognosis of patients with EGFR-mutant advanced lung adenocarcinoma who received EGFR-TKIs, and this score may serve as a convenient blood-based marker for identifying high-risk patients.     

Relationship between the first pass effect and the platelet-lymphocyte ratio in acute ischemic stroke

PurposeThe aim of this study was to evaluate the relationship between platelet-lymphocyte ratio (PLR) and first pass effect (FPE) in patients with acute ischemic stroke (AIS). Our secondary goal was to investigate other laboratory, demographic or technical parameters that may be related to FPE and to search for independent predictors of FPE.Materials and methodsPatients who underwent mechanical thrombectomy (MT) in our hospital between January 2017 and February 2020 were reviewed. Patients were divided into two groups: FPE and non-FPE. Demographic features, laboratory parameters, pretreatment imaging and clinical features, angiographic and clinical outcomes were recorded and compared between the two groups. Logistic regression analysis was performed to analyze the independent predictors and a predictive model was produced for demonstrating the possibility to achieve FPE.ResultsThe study consisted of 83 patients (37 female, 46 male; mean age 62.69 ± 15.16) who were treated by MT. FPE was achieved in 32 patients (32/83, 38.6%). PLR was higher in the non-FPE group (195.35 ± 101.49) when compared to the FPE group (103.17 ± 37.06). A PLR value of <126.3 and female sex were found as independent predictors of FPE. Our predictive model estimated the chance of FPE as 77.9% in female patients who had PLR values lower than 126.3 while it was 77.1% when only using the PLR cutoff value.ConclusionsHigh levels of PLR were associated with the failure of FPE. High values of PLR may be considered as a negative predictor for FPE achievement prior to MT in patients with AIS.     

Correlation between the platelet‐to‐lymphocyte ratio and diabetic foot ulcer in patients with type 2 diabetes mellitus

ObjectiveTo investigate the correlation between the platelet‐to‐lymphocyte ratio (PLR) and diabetic foot ulcer (DFU) in patients with type 2 diabetes mellitus (T2DM).MethodFrom January 2018 to August 2019, 206 patients with T2DM admitted to the Central Hospital of Wuhan, China, were enrolled in this study, including 104 patients with DFU (DFU group) and 102 patients without DFU (T2DM group). During the same period, 90 healthy subjects were randomly screened as normal controls (NC group). The correlation between PLR and DFU in patients with T2DM was explored by comparing the PLR of the subjects in the three groups.ResultsThe PLRs of the DFU and T2DM groups were higher than that of the NC group, whereas the PLR of the DFU group was higher than that of the T2DM group (p < 0.05). PLR was positively correlated with the Wagner DFU grade (p < 0.001). Based on logistic regression analysis, PLR was found to be an independent risk factor for DFU (OR =1.029, 95% CI: 1.019 ~ 1.039, p < 0.001). The receiver operating characteristic curve analysis of the PLR showed that the area under the curve of the PLR for predicting diabetic foot ulcer was 0.776 (p < 0.001), and the analysis determined that the optimal critical value of the PLR for predicting DFU was 147.6.ConclusionThe PLR is significantly elevated in patients with DFU and positively correlated with the Wagner DFU grade, which might be a valuable marker for early diagnosis and assessment of severity of DFU.     

Prognostic significance of mean platelet volume in patients with lung cancer: a meta-analysis

ObjectiveThe mean platelet volume (MPV) is a measure of platelet size, and it is considered a surrogate marker of platelet activation. Because the correlation between platelet count/size and lung cancer prognosis remains unclear, this meta-analysis comprehensively evaluated the prognostic significance of MPV among patients with lung cancer.MethodsA systematic search of PubMed, Embase, Google Scholar, and additional sources of relevant studies were conducted with no language restrictions from inception to 7 May 2021. Overall survival (OS) and disease-free survival (DFS)/progression-free survival (PFS), as well as their hazard ratios (HR) and 95% confidence intervals (CIs), were pooled to evaluate the relationship between MPV and survival. The study protocol was registered on PROSPERO.ResultsEleven studies involving 2421 patients with lung cancer were included in our analysis. Nine studies including only patients with non-small cell lung cancer were included in the meta-analysis. Our analysis revealed no significant associations of MPV with OS (HR = 1.09, 95% CI = 0.84–1.41) and DFS/PFS (HR = 1.13, 95% CI = 0.58–2.20).ConclusionPretreatment MPV levels did not display prognostic significance in patients with NSCLC. Large-scale prospective studies and a validation study considering ethnicity and lung cancer staging are warranted.     

Clinical classification of tissue perfusion based on the central venous oxygen saturation and the peripheral perfusion index

IntroductionWe investigated whether combining the peripheral perfusion index (PI) and central venous oxygen saturation(ScvO₂) would identify subsets of patients for assessing the tissue perfusion and predicting outcome during the resuscitation in critically ill patients.MethodsA total of 202 patients with central venous catheters for resuscitation were enrolled in this prospective observational study. The arterial, central venous blood gas and the PI were measured simultaneously at the enrollment (T0) and 8 h (T8) after early resuscitation. Based on the distribution of the PI in healthy population, a cutoff of PI ≥1.4 was defined as a normal PI. Moreover, the critical value of PI was defined as the best cutoff value related to the mortality in the study population. The PI impairment stratification is defined as follows: a normal PI(≥1.4), mild PI impairment (critical value < PI < 1.4) and critical PI impairment (PI ≤ critical value).ResultsThe PI at T8 was with the greatest AUC for prediction the 30-day mortality and PI is an independent risk factor for 30-day mortality. Moreover, a cutoff of PI < 0.6 is related to poor outcomes following resuscitation. So, based on cutoffs of ScvO₂ (70 %) and critical PI (0.6) at T8, we assigned the patients to four categories: group 1 (PI ≤ 0.6 on ScvO₂ < 70 %), group 2 (PI ≤ 0.6 on ScvO₂ ≥ 70 %), group 3 (PI > 0.6 on ScvO₂ < 70 %), and group 4 (PI > 0.6 on ScvO₂ ≥ 70 %). The combination of low ScvO₂(<70 %) and PI(≤0.6) was associated with the lowest survival rates at 30 days [log rank (Mantel–Cox) = 87.518, p < 0.0001]. The sub-group patients who had high ScvO₂(>80 %) at T8 were with low mortality and high PI. Moreover, the normal PI (≥1.4) did not show a better outcome than mild impaired PI (0.6-1.4) patients who had a normalized ScvO₂(>70 %) after resuscitation. The PI was correlated with the lactate, P(v-a)CO₂, and ScvO₂ in all the measurements (n = 404). These relationships are strengthened with abnormal PI (PI < 1.4) but not with normal PI (PI ≥ 1.4).ConclusionComplementing ScvO₂ assessment with PI can better identify endpoints of resuscitation and adverse outcomes. Pursuing a normalized PI (≥1.4) may not result in better outcomes for a mild impaired PI after ScvO₂ is normalized.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-015-1057-8) contains supplementary material, which is available to authorized users.     

Prognostic value of the albumin–globulin ratio and albumin–globulin score in patients with multiple myeloma

ObjectiveThe albumin–globulin ratio (AGR) has been identified as a promising prognostic predictor of mortality in patients with hematological malignancies. This study investigated the prognostic significance of AGR in patients with multiple myeloma.MethodsTwo hundred patients diagnosed with multiple myeloma from January 2010 to October 2018 were retrospectively analyzed and followed up until December 2019. Kaplan–Meier curves and multivariate Cox regression analysis were applied to detect the prognostic value of AGR.ResultsThe median follow-up period was 36 months. The optimal cutoff of AGR was 1.16 according to receiver operating characteristic curve analysis. High AGR was significantly correlated with better overall survival (OS) and progression-free survival (PFS). Multivariate analysis revealed that low AGR was an independent prognostic factor for worse OS (hazard ratio [HR] = 1.82, 95% confidence interval [CI] = 1.15–2.94) and PFS (HR = 1.53, 95% CI = 1.09–2.17).ConclusionsAGR may represent a potential prognostic biomarker in patients with multiple myeloma.Mini Abstract: We demonstrated that high AGR was associated with a favorable overall survival and progression-free survival in patients with multiple myeloma.     

Prediction of severity and outcomes of colon ischaemia using a novel prognostic model: a clinical multicenter study

ObjectiveTo identify risk factors of disease severity and between mild and severe colon ischaemia (CI) patients and to improve clinical outcomes, this study aimed to explore a novel scoring model.MethodsRetrospective analyses of hospital records between January 2009 and December 2019 were included. Clinical manifestations, mortality, Oakland score, laboratory tests, colonoscopy, and histopathology were collected. Risk factors of severe CI were determined by univariate and multivariate logistic regression and used for the predicting model.ResultsA total of 203 patients with CI were included. Serum C-reactive protein (CRP) and albumin ratio (CAR) were much higher in the severe CI group compared with that of the mild CI group (3.33 ± 1.78 versus 0.68 ± 0.97, p < .001). The Oakland score was much higher in the severe CI group (12.00 ± 3.02 versus 8.77 ± 1.63, p < .001). The histopathological finding of fibrin thrombi was an independent risk factor that predicted poor outcomes (20.00% versus. 1.09%, p < .001). Patients present with CAR ≥3.33, Oakland score ≥12, and histopathological fibrin thrombi were independent risk factors. In addition, the final scoring model was 0.042 × Oakland score + 1.040 × CAR + 3.412 × fibrin thrombi, the area under the curve (AUC) was 0.960 (95% confidence interval:0.930–0.990), and the sensitivity and specificity of the novel scoring model were 95% and 92%, respectively.ConclusionsThe novel prognostic model was established to predict CI severity and clinical outcomes efficiently.

Key messages

• In this article, we discuss the scoring model for clinical outcomes of colon ischaemia patients.
• In our study, the sensitivity and specificity of a novel scoring model are very high.
• Thus, laboratory tests (CRP albumin ratio), Oakland score, and histopathological findings (fibrin thrombi) can be assessed efficiently for colon ischaemia outcomes.

     

Clinical implications of cardiac troponin-I in patients with hypertensive crisis visiting the emergency department

ObjectivesCardiac troponin-I (cTnI) is a representative marker of myocardial injury. Elevation of cTnI is frequently observed in patients with hypertensive crisis, but few studies have examined its prognostic significance in hypertensive crisis. We aimed to determine whether cTnI could predict all-cause mortality in patients with hypertensive crisis visiting the emergency department (ED).MethodsThis observational study included patients aged ≥18 years who visited an ED between 2016 and 2019 for hypertensive crisis, defined as systolic blood pressure (BP) ≥180 mmHg and/or diastolic BP ≥110 mmHg. Among 6467 patients, 3938 who underwent a cTnI assay were analysed.ResultsAmong the 3938 patients, 596 (15.1%) had cTnI levels above the 99th percentile upper reference limit (elevated cTnI >40 ng/L) and 600 (15.2%) had cTnI levels between the detection limit (≥10 ng/L) and the 99th percentile upper reference limit (detectable cTnI). The 3-year all-cause mortality in the elevated, detectable and undetectable cTnI groups were 41.6%, 36.5% and 12.8%, respectively. After adjusting for confounding variables, elevated cTnI patients (adjusted hazard ratio [HR], 2.01; 95% confidence interval [CI], 1.61–2.52) and detectable cTnI patients (adjusted HR, 1.64; 95% CI, 1.32–2.04) showed a significantly higher risk of 3-year all-cause mortality than did patients with undetectable cTnI.ConclusionsIn patients with hypertensive crisis, elevated cTnI levels provide useful prognostic information and permit the early identification of patients with an increased risk of death. Moreover, putatively normal but detectable cTnI levels also significantly correlated with a higher risk of all-cause mortality. Intensive treatment and follow-up strategies are needed for patients with hypertensive crisis with elevated and detectable cTnI levels.

Key messages

1. Cardiac troponin-I level was an independent prognostic factor for all-cause mortality in patients with hypertensive crisis.
2. Detectable but normal range cardiac troponin-I, which was considered clinically insignificant, also had a prognostic impact on all-cause mortality comparable to elevated cardiac troponin-I levels.

     

Predictive value of sub classification of focal segmental glomerular sclerosis in Oxford classification of IgA nephropathy

BackgroundThe Oxford classification of IgA nephropathy (IgAN) was revised in 2016 which lacked sufficient evidence for prognostic value of subclassification of focal segmental glomerular sclerosis (S lesion), and the proper proportion of S lesion for subclassification remains undetermined.AimThis study aimed to explore the predictive value of the new subclassification of S score on renal outcomes of IgAN patients.Methods348 patients with IgAN-associated S lesion were enrolled. According to the optimal cut-off of 25% established by receiver operating characteristic (ROC) curves, we divided S1 patients into two groups: S1a group (S lesion < 25%) and S1b group (S lesion ≥ 25%). IgAN patients with mild lesion (M0E0S0T0C0) were set as the control group. The clinical features at renal biopsy, pathological findings, and follow-up parameters (follow-up time ranged from 1 to 5 years) were collected. We used univariate and multivariate analyses to assess whether the subclassification of S score could refine risk prediction and clinical utility.ResultsWe demonstrated that S lesion ≥ 25% was associated with a more rapid GFR loss and a lower rate of complete remission of proteinuria even adjusted for multiple clinic pathological variables, compared to S1a group (All p values <.05). And the ratio of glomeruli with T lesion and crescents were higher in patients with S lesion ≥ 25%. Data showed that IgAN patients with S lesion ≥ 25% were at an increased risk of poor renal outcomes even with immunosuppression.ConclusionThis study might recommend new subclassification of S scores (S0 (no S lesion), S1 (S lesion <25% of glomeruli), and S2 (S lesion ≥ 25% of glomeruli)) for the Oxford classification. This model may also help to evaluate pros and cons of immunosuppressive therapy in IgAN patients with different level of S lesion.

KEY MESSAGES

• S lesion ≥ 25% is an independent risk factor for poor renal outcome in IgAN patients.
• This new subclassification of S scores may help to evaluate pros and cons of immunotherapy in IgAN patients with different level of S lesion.

     

Patient-reported outcomes,health-related quality of life,and acute medication use in patients with a ≥ 75% response to eptinezumab: subgroup pooled analysis of the PROMISE trials

BackgroundPROMISE-1 and PROMISE-2 evaluated the preventive efficacy, tolerability, and safety of eptinezumab, a calcitonin gene-related peptide–targeted monoclonal antibody, in adults with episodic (EM) and chronic migraine (CM), finding significant reductions in migraine frequency. This post hoc analysis compared patient-reported outcomes (PROs), health-related quality of life (HRQoL) and acute medication use in patients with a ≥ 75% migraine responder rate (MRR) after treatment with eptinezumab to patients with a ≥ 50– < 75% MRR.MethodsPROMISE-1 and PROMISE-2 were phase 3, randomized, double-blind, placebo-controlled studies. This analysis included patients from both studies treated with eptinezumab 100 mg or 300 mg who experienced ≥ 75% and ≥ 50–< 75% MRR over Weeks 1–12 (wks1–12). In both studies, HRQoL was measured by the 36-item Short-Form Health Survey (SF-36) and acute medication usage. PROMISE-2 also included the 6-item Headache Impact Test (HIT-6), patient-identified most bothersome symptom (PI-MBS), and Patient Global Impression of Change (PGIC).ResultsIn PROMISE-1, a total of 115/443 (26.0%; 100 mg, n = 49, 300 mg, n = 66) and 120/443 (27.0%; 100 mg, n = 61, 300 mg, n = 59) eptinezumab-treated patients achieved ≥ 75% and ≥ 50–< 75% MRR over wks1–12, respectively. In PROMISE-2, a total of 211/706 (30.0%; 100 mg, n = 95; 300 mg, n = 116) and 209/706 (29.6%; 100 mg, n = 110, 300 mg, n = 99) eptinezumab-treated patients achieved ≥ 75% and ≥ 50–< 75% MRR over wks1–12, respectively. EM and CM patients with ≥ 75% and ≥ 50–< 75% MRR over wks1–12 showed reduced use of acute headache medication and increased HRQoL to normative levels across SF-36 domains of bodily pain, social functioning, and physical functioning. In CM patients with ≥ 75% and ≥ 50–< 75% MRR over wks1–12, the mean change in HIT-6 total score with eptinezumab (pooled) was − 11.7 and − 7.6, respectively. “Very much” or “much” improvement responses were reported in 41.8% and 16.5% on PI-MBS and 36.2% and 20.0% on PGIC in ≥ 75% and ≥ 50–< 75% MRR, respectively.ConclusionEptinezumab treatment induced a ≥ 75% MRR over wks1–12 in the majority of patients. This patient subgroup reported substantial improvements in PROs associated with headache-related life impact and HRQoL, and reductions in acute headache medication use, which were more marked than those in the ≥ 50–< 75% responders. This study supports the clinical meaningfulness of ≥ 75% MRR for patients with either EM or CM.Trial registrationClinicalTrials.gov identifiers: {"type":"clinical-trial","attrs":{"text":"NCT02559895","term_id":"NCT02559895"}}NCT02559895 (PROMISE-1), {"type":"clinical-trial","attrs":{"text":"NCT02974153","term_id":"NCT02974153"}}NCT02974153 (PROMISE-2).Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-022-01386-z.     

Fremanezumab in the prevention of high-frequency episodic and chronic migraine: a 12-week,multicenter, real-life,cohort study (the FRIEND study)

BackgroundFremanezumab has demonstrated to be effective, safe, and tolerated in the prevention of episodic or chronic migraine (CM) in randomized, placebo-controlled trials (RCTs). Real-life studies are needed to explore drug effects in unselected patients in routine circumstances and to provide higher generalizability results. This study explores the effectiveness, safety, and tolerability of fremanezumab in a real-life population of individuals affected by high-frequency episodic (HFEM: 8–14 days/month) or CM.MethodsThis is a 12-week multicenter, prospective, cohort, real-life study. We considered all consecutive patients affected by HFEM or CM visited at 9 Italian headache centers from 28/07/2020 to 11/11/2020. Eligible patients were given subcutaneous fremanezumab at the doses of 225 mg monthly or 675 mg quarterly, according to their preference. Primary study endpoints were the change in monthly migraine days (MMDs) in HFEM and monthly headache days (MHDs) in CM patients at weeks 9–12 compared to baseline. Secondary endpoints encompassed variation in monthly analgesic intake (MAI), Numerical Rating Scale (NRS), HIT-6 and MIDAS scores, and ≥ 50%, ≥ 75% and 100% responder rates at the same time intervals.ResultsSixty-seventh number migraine patients had received ≥ 1 subcutaneous fremanezumab dose and were considered for safety analysis, while 53 patients completed 12 weeks of treatment and were included also in the effectiveness analysis. Fremanezumab was effective in both HFEM and CM, inducing at week 12 a significant reduction in MMDs (-4.6, p < 0.05), MHDs (-9.4, p < 0.001), MAI (-5.7, p < 0.05; -11.1, p < 0.001), NRS (-3.1, p < 0.001; -2.5, p < 0.001), and MIDAS scores (-58.3, p < 0.05; -43.7; p < 0.001). HIT-6 was significantly reduced only in HFEM patients (-18.1, p < 0.001). Remission from CM to episodic migraine and from MO to no-MO occurred in 75% and 67.7% of the patients. The ≥ 50%, ≥ 75% and 100% responder rates at week 12 were 76.5%, 29.4% and 9.9% in HFEM and 58.3%, 25% and 0% in CM. Younger age emerged as a positive response predictor (OR = 0.91; 95% CI 0.85–0.98, p = 0.013). Treatment-emergent adverse events were uncommon (5.7%) and mild. No patient discontinued fremanezumab for any reason.ConclusionsFremanezumab seems more effective in real-life than in RCTs. Younger age emerges as a potential response predictor.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-022-01396-x.     

Analysis of risk factors associated with flexor pollicis longus injury after volar plating of distal radius fractures

ObjectiveThis study was performed to analyze the risk factors associated with flexor pollicis longus (FPL) attrition or rupture after volar plating of distal radius fractures.MethodsThree hundred thirty-eight patients with distal radius fractures were included in this retrospective study. Univariate analysis and multivariate logistic regression analysis were performed to predict risk factors.ResultsUnivariate analysis showed that sex, volar tilt, the Soong grade, the plate-to-critical line distance (PCLD), the plate-to-volar rim distance (PVRD), and the time of plate removal were significantly associated with FPL attrition or rupture. Multivariate logistic regression analysis demonstrated that decreased volar tilt, Soong grade 2, PCLD of >2 mm, PVRD of <3 mm, and plate removal at ≥1 year were the risk factors significantly associated with FPL attrition or rupture.ConclusionsReduced volar tilt, Soong grade 2, PCLD of >2 mm, and PVRD of <3 mm appear to be risk factors that are significantly associated with FPL attrition or rupture. The findings of this study also suggest that the risk of tendon rupture is lower if a Soong grade 2 plate is removed, the PCLD is >2 mm, the PVRD is <3 mm, or reduced volar tilt is achieved earlier (at <1 year).     

Systemic immune-inflammation index is a promising non-invasive biomarker for predicting the survival of urinary system cancers: a systematic review and meta-analysis

ObjectiveSystemic immune-inflammation index (SII) has been reported in numerous studies to effectively predict the survival outcomes of urinary system cancers; however no agreement has been reached. This meta-analysis aimed to explore the prognostic significance of pre-treatment SII in tumours of the urinary system.MethodsRelevant published articles were selected from Web of Science, PubMed, Embase, and the Cochrane Library up to 30 August 2020. The hazard ratios (HRs) with 95% confidence intervals (CIs) were computed to estimate the associations of pre-treatment SII with overall survival (OS), progression-free survival (PFS), cancer-specific survival (CSS) in urinary system cancers.Results13 papers were included in our meta-analysis. From the combined data, we found that a high pre-treatment SII indicated a markedly worse OS (HR = 1.98; 95% CI: 1.75–2.23; p < .001), PFS (HR: 2.08; 95% CI: 1.32–3.26; p = .002), and CSS (HR: 2.41, 95% CI: 1.73–3.35, p < .001). Additionally, patients with an elevated SII value might have undesirable pathological characteristics, including a large tumour size, a poor differentiation grade, and an advanced tumour stage (all p < .001).ConclusionsPre-treatment SII could be used as a non-invasive and promising biomarker to indicate the prognosis of urinary system cancer patients.

KEY MESSAGES:

• This meta-analysis evaluates the predictive value of systemic immune-inflammation index (SII) for patients with urinary system cancer.
• A high pre-treatment SII indicates a poor prognosis.
• SII can serve as a promising non-invasive biomarker to help clinicians assess the prognosis and develop treatment strategies for urinary system cancer patients.

     

Early response to eptinezumab indicates high likelihood of continued response in patients with chronic migraine

BackgroundA clinical ability to describe the response trajectory of patients receiving preventive migraine treatment could expedite and improve therapeutic management decisions. This post hoc analysis of the PROMISE-2 study evaluated the consistency and predictive power of Month 1 treatment response on later response in patients with chronic migraine.MethodsPROMISE-2 was a double-blind, placebo-controlled trial that randomized adults with chronic migraine to eptinezumab 100 mg, 300 mg, or placebo administered IV every 12 weeks for up to 24 weeks (2 infusions over 6 study months). Migraine responder rates (MRRs) were calculated from monthly migraine days over 4-week intervals compared with baseline. Patients were grouped by MRR during Month 1 (< 25%, 25–< 50%, 50–< 75%, and ≥ 75%), with the number of subsequent study months (Months 2–6) with ≥50% and ≥ 75% MRR calculated in each subgroup. A similar analysis was conducted using Patient Global Impression of Change (PGIC) rating to define Month 1 subgroups (very much improved, much improved, minimally improved, and no change/worse) and rates of very much improved or much improved PGIC during Months 2–6.ResultsIn the eptinezumab 100 mg, 300 mg, and placebo groups, respectively, 194/356 (54.5%), 212/350 (60.6%), and 132/366 (36.1%) patients were ≥ 50% migraine responders during Month 1. More eptinezumab-treated patients were ≥ 75% migraine responders (100 mg, 110/356 [30.9%]; 300 mg, 129/350 [36.9%]; placebo, 57/366 [15.6%]) and more placebo-treated patients were < 25% migraine responders (eptinezumab 100 mg, 103/356 [28.9%]; 300 mg, 80/350 [22.9%]; placebo, 153/366 [41.8%]). Among patients who achieved ≥75% migraine response in Month 1, more than one-third attained ≥75% migraine response for all 5 subsequent study months and more than two-thirds achieved ≥75% migraine response for ≥3 months. More than two-thirds of those in the very much improved (PGIC) subgroup at Month 1 were much or very much improved for all 5 subsequent months.ConclusionsIn this post hoc analysis of data from PROMISE-2, more eptinezumab-treated than placebo-treated patients were early (Month 1) responders, and most early responders went on to achieve a high level of response for at least half of the 24-week treatment period. Potential for later response in early non-responders was also observed.Trial registrationClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT02974153","term_id":"NCT02974153"}}NCT02974153; registered November 23, 2016.     

Real-world impact of fremanezumab on migraine symptoms and resource utilization in the United States

BackgroundFremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), is approved for migraine prevention in adults. Real-world data on the effectiveness of fremanezumab are limited. This retrospective, observational cohort study assessed patient-reported migraine symptoms, health care resource utilization (HCRU), and direct medical costs before and after fremanezumab treatment initiation.MethodsData were extracted from September 2018 through June 2020 from the Midwest component of EMRClaims+®, an integrated health services database containing > 20 million medical records from national commercial insurance claims, Medicare claims, and regional electronic medical records. Patients included in the cohort analysis were aged ≥ 18 years and were administered fremanezumab, with enrollment or treatment history for ≥ 6 months prior (pre-index) to initiating fremanezumab (index date) and ≥ 1 month after the index date (post-index), and without pregnancy or pregnancy-related encounters during the study period. Patient-reported headache frequency, migraine pain intensity (MPI), composite migraine symptoms, and HCRU were assessed pre-index and ≥ 1 month after fremanezumab initiation. Wilcoxon signed-rank tests were used to compare means of migraine symptoms and outcomes and HCRU before and after fremanezumab initiation.ResultsOverall, 172 patients were eligible for analysis. Of patients who self-reported (n = 129), 83.7% reported improvement in headache frequency or symptoms after fremanezumab treatment. Specifically, headache frequency decreased by 63% after fremanezumab initiation: mean (standard deviation) headache frequency was 22.24 (9.29) days per month pre-index versus 8.24 (7.42) days per month post-index (P < 0.0001). Mean MPI also decreased by 18% after fremanezumab initiation: MPI was 5.47 (3.19) pre-index versus 4.51 (3.34) post-index (P = 0.014). Mean emergency room (ER) visits per month decreased from 0.72 to 0.54 (P = 0.003), and mean outpatient visits per month decreased from 1.04 to 0.81 (P < 0.001). Mean hospitalizations per month decreased, but the results did not reach statistical significance (P = 0.095). Hospitalization and ER costs decreased, while outpatient costs increased, from pre-index to post-index, but differences were not statistically significant (P ≥ 0.232).ConclusionsSignificant reductions in headache frequency, MPI, and HCRU were observed after fremanezumab initiation in patients with migraine in a US real-world setting.