Mecapegfilgrastim for the prophylaxis of chemotherapy-induced neutropenia in locally advanced nasopharyngeal carcinoma: A prospective phase II clinical study.

BACKGROUND: Induction chemotherapy of docetaxel plus cisplatin (TP) is myelosuppressive, leading to severe neutropenia and febrile neutropenia (FN). Herein, we aimed to investigate the efficacy and safety of mecapegfilgrastim in the prevention of neutropenia in patients with locally advanced nasopharyngeal carcinoma who received the TP regimen. METHODS: A total of 30 treatment-naive patients with locally advanced nasopharyngeal carcinoma were included in this study. Mecapegfilgrastim 6 mg was injected 24-48 h after the completion of induction chemotherapy with the TP regimen. RESULTS: The incidence of grade ≥3 neutropenia during the three induction chemotherapy cycles was 6.7% (95% CI, 0.8%-22.1%). In the first cycle of chemotherapy, the incidence of grade ≥3 neutropenia was 3.3% (95% CI, 0.1%-17.2%). No FN or antibiotic usage was reported. All 30 patients completed the induction chemotherapy cycles. CONCLUSION: Mecapegfilgrastim effectively reduced the incidence of chemotherapy-induced neutropenia and FN in patients with locally advanced nasopharyngeal carcinoma.

Efficacy and safety of variceal embolization for primary prophylaxis in cirrhosis patients with challenges in standard treatments: preliminary results.

Objectives: Nonselective beta blockers (NSBBs) or endoscopic therapies are currently recommended by guidelines for preventing the first variceal bleed in patients with high-risk varices. However, there is a lack of detailed treatment strategies for patients who are intolerant to both NSBBs and endoscopic approaches. Our study aimed to assess the efficacy and safety of variceal embolization as a primary prophylaxis method in cirrhosis patients who are not suitable candidates for NSBBs or endoscopic treatments. Methods: The study included 43 cirrhotic patients with high-risk varices who were candidates for primary prophylaxis against variceal bleeding. These patients underwent variceal embolization at the Xijing Hospital between January 2020 and June 2022. The primary endpoint was the occurrence of bleeding from varices, and the secondary endpoints were the recurrence of varices and the emergence of complications. Results: The procedure of variceal embolization had a success rate of 93.0% (40 out of 43 patients). Over a 2-year follow-up period, the rate of variceal bleeding was 11.6% (5 out of 43 patients), the recurrence rate of varices was 14.0% (6 out of 43 patients), and the rate of severe complications was limited to 2.3% (1 out of 43 patients). Conclusion: Variceal embolization is a viable primary prophylactic intervention for cirrhotic patients who are at risk of variceal bleeding when standard treatments, such as NSBBs or endoscopic therapies, are difficult to perform.

How to Prevent Atopic Dermatitis (Eczema) in 2024: Theory and Evidence.

Atopic dermatitis (AD) or eczema is a chronic inflammatory skin disease characterized by dry, itchy, and inflamed skin. We review emerging concepts and clinical evidence addressing the pathogenesis and prevention of AD. We examine several interventions ranging from skin barrier enhancement strategies to probiotics, prebiotics, and synbiotics; and conversely, from antimicrobial exposure to vitamin D and omega fatty acid supplementation; breastfeeding and hydrolyzed formula; and house dust mite avoidance and immunotherapy. We appraise the available evidence base within the context of the Grades of Recommendation, Assessment, Development, and Evaluation approach. We also contextualize our findings in relation to concepts relating AD and individual-patient allergic life trajectories versus a linear concept of the atopic march and provide insights into future knowledge gaps and clinical trial design considerations that must be addressed in forthcoming research. Finally, we provide implementation considerations to detect population-level differences in AD risk. Major international efforts are required to provide definitive evidence regarding what works and what does not for preventing AD.

Predicting response to non-selective beta-blockers with liver-spleen stiffness and heart rate in patients with liver cirrhosis and high-risk varices.

INTRODUCTION: Non-selective beta-blockers (NSBB) are used for primary prophylaxis in patients with liver cirrhosis and high-risk varices (HRVs). Assessing therapeutic response is challenging due to the invasive nature of hepatic venous pressure gradient (HVPG) measurement. This study aims to define a noninvasive machine-learning based approach to determine response to NSBB in patients with liver cirrhosis and HRVs. METHODS: We conducted a prospective study on a cohort of cirrhotic patients with documented HRVs receiving NSBB treatment. Patients were followed-up with clinical and elastography appointments at 3, 6, and 12 months after NSBB treatment initiation. NSBB response was defined as stationary or downstaging variceal grading at the 12-month esophagogastroduodenoscopy (EGD). In contrast, non-response was defined as upstaging variceal grading at the 12-month EGD or at least one variceal hemorrhage episode during the 12-month follow-up. We chose cut-off values for univariate and multivariate model with 100% specificity. RESULTS: According to least absolute shrinkage and selection operator (LASSO) regression, spleen stiffness (SS) and liver stiffness (LS) percentual decrease, along with changes in heart rate (HR) at 3 months were the most significant predictors of NSBB response. A decrease > 11.5% in SS, > 16.8% in LS, and > 25.3% in HR was associated with better prediction of clinical response to NSBB. SS percentual decrease showed the highest accuracy (86.4%) with high sensitivity (78.8%) when compared to LS and HR. The multivariate model incorporating SS, LS, and HR showed the highest discrimination and calibration metrics (AUROC = 0.96), with the optimal cut-off of 0.90 (sensitivity 94.2%, specificity 100%, PPV 95.7%, NPV 100%, accuracy 97.5%).

Primary prophylaxis implementation and long-term joint outcomes in Swedish haemophilia A patients.

INTRODUCTION: Primary prophylaxis is the gold standard in severe haemophilia A (SHA) but time to escalate the prophylaxis regimen varies. AIM: Assess prophylaxis implementation and long-term joint health outcomes in SHA with primary prophylaxis. METHODS: Adult male patients born after 1980, with SHA on primary prophylaxis, started before the age of 3 years and second joint bleed, and no history of FVIII inhibitors, were enrolled. Repeated joint-health examinations were performed with HJHS or HEAD-US; VERITAS-PRO assessed adherence. RESULTS: Thirty patients were enrolled with, at inclusion, median age 33.5 years, annualized bleed rate and joint bleed rate 0, and FVIII consumption 4232 IU/kg/year, respectively. The median age was 1.2 years, at prophylaxis start once weekly with a median FVIII dose of 47.7 IU/kg, and 1.7 years, by the time escalation to a final regimen had occurred, with a median infusion frequency of thrice weekly and FVIII dose 41.7 IU/kg, respectively. Older age correlated with later transition to escalated prophylaxis (p < .001). Longer time to escalated prophylaxis correlated to more bleeds (p < .001). Median HJHS increased slowly, reaching 4 at 35-40 years. HJHS at 15-20 years correlated with higher HJHS afterwards. Median total HEAD-US score was 1 and correlated with HJHS (p < .001). Median VERITAS-PRO score was 36, indicating good treatment adherence. CONCLUSION: Primary prophylaxis is effective but does not completely prevent the gradual development of arthropathy in SHA. Joint assessments with HJHS should start at an early age, as they correlate with arthropathy in later life. Prophylaxis escalation should proceed expeditiously to prevent bleeds.

The Use of Granulocyte Colony-Stimulating Factor as Primary Prophylaxis in Patients Undergoing Chemotherapy: An Experience of Moroccan Oncologists.

Febrile neutropenia (FN) is a frequent and serious emergency for oncologic patients undergoing chemotherapy. Using granulocyte colony-stimulating factor (G-CSF) as primary prophylaxis of febrile neutropenia is an integral part of the management of cancer patients. Our study aims to identify the challenges that prevent Moroccan oncologists from prescribing G-CSF for primary prevention. Seventy doctors participated in our study, with a participation rate of 35.35%. Twenty-two participants had at least five years of experience in oncology. Most participants were medical oncologists (82.9%), and two-thirds of them practiced in teaching hospitals. Regarding the use of G-CSF in primary prevention, all participants complied with the recommendations for FN risk assessment and the prescription of G-CSF for prophylaxis in patients at high risk of FN (>20%). However, their use in intermediate-risk patients remains limited mainly by the cost of these drugs (45.7% of participants). FN remains a dreadful complication in oncology. Since the introduction of G-CSF into standard oncology practice, particularly in primary prevention, the management of certain patients has improved considerably. Nevertheless, the indications for G-CSF in our context, essentially in intermediate-risk patients, are uncertain.

Pre-emptive transjugular intrahepatic portosystemic shunt in pediatric cystic fibrosis-related liver disease and portal hypertension: prospective long-term results.

PURPOSE: Portal hypertension (PHT) and its sequelae are the most clinically important manifestations in cystic fibrosis-related liver disease (CFLD). This paper aimed to evaluate the safety and efficacy of a pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) to prevent PHT-related complications in pediatric patients with CFLD. METHODS: This was a prospective single-arm study on pediatric patients with CFLD, signs of PHT, and preserved liver function who underwent a pre-emptive TIPS in a single tertiary CF center between 2007 and 2012. The long-term safety and clinical efficacy were assessed. RESULTS: A pre-emptive TIPS was performed on seven patients with a mean age of 9.2 years (± standard deviation: 2.2). The procedure was technically successful in all patients, with an estimated median primary patency of 10.7 years [interquartile range (IQR) 0.5-10.7)]. No variceal bleeding was observed during the median follow-up of 9 years (IQR 8.1-12.9). In two patients with advanced PHT and rapidly progressive liver disease, severe thrombocytopenia could not be stopped. Subsequent liver transplantation revealed biliary cirrhosis in both patients. In the remaining patients with early PHT and milder porto-sinusoidal vascular disease, symptomatic hypersplenism did not occur, and liver function remained stable until the end of the follow-up. Inclusion for pre-emptive TIPS was discontinued in 2013 following an episode of severe hepatic encephalopathy. CONCLUSION: TIPS is a feasible treatment with encouraging long-term primary patency to avoid variceal bleeding in selected patients with CF and PHT. However, as the progression of liver fibrosis, thrombocytopenia, and splenomegaly is inevitable, the clinical benefits due to pre-emptive placement appear to be minor.

Improving primary prophylaxis of variceal bleeding by adapting therapy to the clinical stage of cirrhosis. A competing-risk meta-analysis of individual participant data.

BACKGROUND & AIMS: Non-selective ß-blockers (NSBBs) and endoscopic variceal-ligation (EVL) have similar efficacy preventing first variceal bleeding. Compensated and decompensated cirrhosis are markedly different stages, which may impact treatment outcomes. We aimed to assess the efficacy of NSBBs vs EVL on survival in patients with high-risk varices without previous bleeding, stratifying risk according to compensated/decompensated stage of cirrhosis. METHODS: By systematic review, we identified RCTs comparing NSBBs vs EVL, in monotherapy or combined, for primary bleeding prevention. We performed a competing-risk, time-to-event meta-analysis, using individual patient data (IPD) obtained from principal investigators of RCTs. Analyses were stratified according to previous decompensation of cirrhosis. RESULTS: Of 25 RCTs eligible, 14 failed to provide IPD and 11 were included, comprising 1400 patients (656 compensated, 744 decompensated), treated with NSBBs (N = 625), EVL (N = 546) or NSBB+EVL (N = 229). Baseline characteristics were similar between groups. Overall, mortality risk was similar with EVL vs. NSBBs (subdistribution hazard-ratio (sHR) = 1.05, 95% CI = 0.75-1.49) and with EVL + NSBBs vs either monotherapy, with low heterogeneity (I2 = 28.7%). In compensated patients, mortality risk was higher with EVL vs NSBBs (sHR = 1.76, 95% CI = 1.11-2.77) and not significantly lower with NSBBs+EVL vs NSBBs, without heterogeneity (I2 = 0%). In decompensated patients, mortality risk was similar with EVL vs. NSBBs and with NSBBs+EVL vs. either monotherapy. CONCLUSIONS: In patients with compensated cirrhosis and high-risk varices on primary prophylaxis, NSBBs significantly improved survival vs EVL, with no additional benefit noted adding EVL to NSBBs. In decompensated patients, survival was similar with both therapies. The study suggests that NSBBs are preferable when advising preventive therapy in compensated patients.

Comparison of endoscopic ultrasound-guided primary and secondary prophylaxis for gastric variceal bleeding.

OBJECTIVES: Endoscopic ultrasound (EUS)-guided injection of cyanoacrylate (CYA) for primary prophylaxis (PP) of gastric varices (GV) is controversial. This study evaluates the safety and efficacy of this intervention. METHODS: Patients treated for PP of GV bleeding by EUS injection of CYA with or without coils were identified. Endoscopic techniques, outcomes, and adverse events (AEs) were reviewed and compared with a group treated for secondary prophylaxis (SP). Patients were followed until: (i) loss to follow-up; (ii) GV bleeding; (iii) interventional radiology or surgery decompression; (iv) liver transplant; or (v) death or comfort care. RESULTS: One hundred and nineteen patients (61 men; mean 59 ± 12 years) underwent EUS for PP (n = 24) or SP (n = 95). The PP group was treated with CYA alone (n = 18) or with coils (n = 4). Eight (33%) mild (n = 6) or moderate (n = 2) AEs and no index GV bleeding occurred during a mean of 6.1 ± 5.9 months follow-up. Repeat EUS in 22 (92%) PP patients showed 7 (32%) residual GVs, which were retreated with CYA alone (n = 6) or with coils (n = 1). Two (29%) mild (n = 1) or moderate (n = 1) AEs occurred after repeat EUS and 1/22 (5%) index GV bleed occurred during a mean 23 ± 25 months follow-up. Compared to the SP group, the PP group had lower Model for End-stage Liver Disease (MELD) score (P = 0.03), fewer GV stigmata (P < 0.001), required less CYA (P = 0.019) during index EUS, and had a longer time between index and surveillance EUS (P = 0.014). The incidence of AEs and GV bleeding between the two groups were similar. CONCLUSION: Posttreatment GV bleeding and AEs are similar following EUS-guided primary and secondary GV prophylaxis.

Norfloxacin versus alternative antibiotics for prophylaxis of spontaneous bacteria peritonitis in cirrhosis: a systematic review and meta-analysis.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a life-threatening complication in patients with advanced cirrhosis. Prophylactic Norfloxacin used to be considered effective in SBP prevention, but in recent years its efficacy has been partially compromised by increasing quinolone-resistant bacteria. However, whether the effects of alternative prophylactic regimens are superior to norfloxacin remains controversial. The goal of this study is to compare the effects of norfloxacin with other antibiotics in SBP prophylaxis for cirrhotic patients. METHODS: We systematically searched Pubmed, Embase, and Cochrane Library Databases. Two reviewers independently identified relevant random control trials (RCTs) comparing the role of norfloxacin and other antibiotics in SBP prevention. RESULTS: Eight studies comprising 1043 cirrhotic patients were included in this study. Norfloxacin and alternative antibiotics displayed comparable effects in SBP prophylaxis, survival benefit, overall infection prevention, and safety. Subgroup analyses revealed that rifaximin prophylaxis could reduce the recurrence of SBP with fewer adverse events but failed to improve overall survival compared with norfloxacin. CONCLUSIONS: Other antibiotics are a reasonable alternative to norfloxacin in the prophylaxis of SBP. Rifaximin prophylaxis could be an alternative choose of antibiotic for SBP prevention because of its better protective effect and safety.

Impact of timing of prophylaxis commencement, F8 genotype and age on factor consumption and health-related quality of life in patients with severe haemophilia A.

INTRODUCTION: The timing of prophylaxis and F8 genotype can impact treatment outcomes in adults with severe haemophilia A (HA). AIM: To investigate how F8 genotype, timing, and type of prophylaxis influence arthropathy, bleeding rates, factor consumption and health-related quality of life (HRQoL). METHODS: Thirty-eight patients with severe HA were enrolled. Bleeding events were recorded retrospectively during median 12.5 months. F8 gene variants were classified as null or non-null. Joint health and HRQoL were assessed with HJHS and EQ-5D-5L, respectively. RESULTS: The median age at prophylaxis start was 1.25 years in the primary prophylaxis group (N = 15, median age 26 years) and 31.5 years in the secondary group (N = 22, 45 years), respectively. There were significant differences in the medians of HJHS (4 vs. 20, p < .001), EQ-5D-5L index (0.9647 vs. 0.904, p = .022), EQ VAS (87 vs. 75, p = .01) and FVIII consumption (3883 vs. 2737 IU/kg/year, p = .02), between the primary and secondary groups, respectively. Median annualized bleeding rate (ABR) was 0 for both groups. Twenty-five null and thirteen non-null F8 gene variants were identified. In the secondary prophylaxis group, lower median FVIII consumption (1926 vs. 3370 IU/kg/year) was shown for non-null compared to null variants, respectively, with similar ABR and HJHS. CONCLUSION: Delayed prophylaxis start with intermediate dose intensity prevents bleeds but at a cost of more arthropathy and reduced HRQoL, compared to higher intensity primary prophylaxis. Non-null F8 genotype may allow lower factor consumption with similar HJHS and bleeding rates, compared to null genotype.

Efficacy of regional cooling + oral dexamethasone for primary prevention of hand-foot syndrome associated with pegylated liposomal doxorubicin.

PURPOSE: Pegylated liposomal doxorubicin (PLD)-induced hand-foot syndrome (HFS) frequently lowers the quality of life of ovarian cancer patients. Wrist and ankle cooling, having a limited preventive effect, has been the commonest supportive HFS care. In this study, we retrospectively assessed the primary preventive effect of a combination of regional cooling and oral dexamethasone therapy (cooling + oral Dex) on HFS. METHODS: This study is a single-arm retrospective, observational study. Recurrent ovarian cancer patients were administered PLD ± bevacizumab. We retrospectively examined the efficacy of hands and feet cooling (from the start of PLD to the end) + oral Dex (day 1-5: 8 mg/day, day 6, 7: 4 mg/day) for primary HFS prevention. RESULTS: This study included 74 patients. The initial dose of PLD was 50 mg/m2 and 40 mg/m2 for 32 (43.2%) and 42 (56.8%) patients, respectively. HFS of Grade ≥ 2 and Grade ≥ 3 developed in five (6.8%) and one (1.4%) patient(s), respectively. The incidence of ≥ Grade 2 and ≥ Grade 3 HFS was much lower than those reported in previous studies. Dose reduction was required in 13 patients (17.6%) mainly because of neutropenia or mucositis; there was no HFS-induced dose reduction. Meanwhile, PLD therapy was discontinued mainly because of interstitial pneumonia (4 patients) and HFS (one patient). CONCLUSIONS: We demonstrated the efficacy of regional cooling and oral Dex for primary prevention of PLD-induced HFS. Although future prospective studies are needed to confirm its efficacy, this combination therapy can be considered for primary prevention of HFS in ovarian cancer patients on PLD.

Pneumocystis jirovecii pneumonia in patients with decompensated cirrhosis: a case series.

OBJECTIVES: Pneumocystis jirovecii pneumonia (PCP) incidence is increasing in people without HIV. Decompensated liver cirrhosis is not currently considered a risk factor for PCP. The aim of this paper is to describe a case series of patients with decompensated liver cirrhosis and PCP. METHODS: All consecutive patients hospitalized with decompensated cirrhosis and microbiology-confirmed PCP at Policlinico Modena University Hospital from January 1, 2016 to December 31, 2021 were included in our series. RESULTS: Eight patients were included. All patients had advanced-stage liver disease with a model for end-stage liver disease score above 15 (6/8 above 20). Four were on an active orthotopic liver transplant waiting list at the time of PCP diagnosis. Five patients did not have any traditional risk factor for PCP, whereas the other three were on glucocorticoid treatment for acute-on-chronic liver failure. All patients were treated with cotrimoxazole, except two who died before the diagnosis. Five patients died (62.5%), four of them within 30 days from PCP diagnosis. Of the remaining three, one patient underwent liver transplantation. CONCLUSION: Although further studies are needed, liver cirrhosis can be an independent risk factor for PCP in patients with decompensated cirrhosis that is mainly due to severe alcoholic hepatitis and who are on corticosteroids therapy, and primary prophylaxis for PCP should be considered.

Pegfilgrastim in Supportive Care of Hodgkin Lymphoma.

Neutropenia and febrile neutropenia are common and potentially life-threating events associated with chemotherapy treatment in Hodgkin lymphoma (HL). Neutropenia-related infectious events could be an issue both for direct clinical consequences and for delay in treatment delivery, affecting final outcomes in a potentially highly curable disease. Pegfilgrastim is the pegylated form of filgrastim, the recombinant form of human G-CSF, capable of prevent and mitigate neutropenic effects of chemotherapy, when adopted as primary prophylaxis in several hematological malignancies. No updated version of major international guidelines provides clear indication on prophylaxis use of pegfilgrastim in HL to prevent febrile neutropenia episodes in HL. Moreover, to date, scarce and non-uniform clinical experiences evaluating pegfilgrastim as prophylaxis in HL are present in the literature. Herein, we propose a brief summary of the literature data about efficacy and safety of the use of pegfilgrastim as primary prophylaxis in HL during chemotherapy treatment.

ASEPTIC: primary antibiotic prophylaxis using co-trimoxazole to prevent SpontanEous bacterial PeritoniTIs in Cirrhosis-study protocol for an interventional randomised controlled trial.

BACKGROUND: Bacterial infection is a major cause of mortality in patients with cirrhosis. Spontaneous bacterial peritonitis (SBP) is a serious and common infection in patients with cirrhosis and ascites. Secondary prophylactic antibiotic therapy has been shown to improve outcomes after an episode of SBP but primary prophylaxis to prevent the first episode of SBP remains contentious. The aim of this trial is to assess whether primary antibiotic prophylaxis with co-trimoxazole improves overall survival compared to placebo in adults with cirrhosis and ascites. METHODS: The ASEPTIC trial is a multicentre, placebo-controlled, double-blinded, randomised controlled trial (RCT) in England, Scotland, and Wales. Patients aged 18 years and older with cirrhosis and ascites requiring diuretic treatment or paracentesis, and no current or previous episodes of SBP, are eligible, subject to exclusion criteria. The trial aims to recruit 432 patients from at least 30 sites. Patients will be randomised in a 1:1 ratio to receive either oral co-trimoxazole 960 mg or an identical placebo once daily for 18 months, with 6 monthly follow-up visits thereafter (with a maximum possible follow-up period of 48 months, and a minimum of 18 months). The primary outcome is overall survival. Secondary outcomes include the time to the first incidence of SBP, hospital admission rates, incidence of other infections (including Clostridium difficile) and antimicrobial resistance, patients' health-related quality of life, health and social care resource use, incidence of cirrhosis-related decompensation events, liver transplantation, and treatment-related serious adverse events. DISCUSSION: This trial will investigate the efficacy, safety, and cost-effectiveness of co-trimoxazole for patients with liver cirrhosis and ascites to determine whether this strategy improves clinical outcomes. Given there are no treatments that improve survival in decompensated cirrhosis outside of liver transplant, if the trial has a positive outcome, we anticipate widespread adoption of primary antibiotic prophylaxis. TRIAL REGISTRATION: ClinicalTrials.gov NCT043955365 . Registered on 18 April 2020. Research ethical approval was granted by the Research Ethics Committee (South Central - Oxford B; REC 19/SC/0311) and the Medicines and Healthcare products Regulatory Agency (MHRA).

Associations Between Endoscopic Primary Prophylaxis and Rebleeding in Liver Cirrhosis Patients with Esophagogastric Variceal Bleeding.

Aim: To identify the association between endoscopic primary prophylaxis and the risk of rebleeding in patients with liver cirrhosis receiving endoscopic therapy. Methods: This cohort study involved in 944 liver cirrhosis patients with esophagogastric variceal bleeding (EGVB) receiving endoscopic therapy. All participants were divided into two groups: rebleeding group (n = 425) and non-rebleeding group (n = 519) according to the occurrence of rebleeding in patients. Rebleeding indicated any bleeding after endoscopic therapy for the first bleeding of esophagogastric varices in liver cirrhosis patients. Univariate and multivariate logistic analyses were employed to identify the association between endoscopic primary prophylaxis and rebleeding in patients with liver cirrhosis after endoscopic therapy. Results: In total, 425 patients rebleeded at the end of the follow-up. The risk of rebleeding in patients with endoscopic primary prophylaxis decreased by 0.773 times (OR = 0.227, 95%CI: 0.139-0.372, P < 0.001) after adjusting covariables. Subgroups were divided according to the Child-Pugh (CP) score, and the results revealed that the risk of rebleeding in patients with endoscopic primary prophylaxis decreased by 0.858 times in Grade A patients (OR = 0.142, 95%CI: 0.066-0.304, P < 0.001) and 0.804 times in Grade B patients (OR = 0.196, 95%CI: 0.085-0.451, P < 0.001) compared with patients without endoscopic primary prophylaxis, but showed no difference in Grade C patients. Conclusion: Endoscopic primary prophylaxis was associated with a decreased risk of rebleeding in liver cirrhosis patients with EGVB after endoscopic therapy, which suggested that clinicians should pay more attention to endoscopic primary prophylaxis to prevent the occurrence of rebleeding in these patients.

G-CSF primary prophylaxis use and outcomes in patients receiving chemotherapy at intermediate risk for febrile neutropenia: a scoping review.

INTRODUCTION: Febrile neutropenia (FN) is a major dose-limiting toxicity of myelosuppressive chemotherapy, and several patients receiving chemotherapy are at intermediate risk of developing FN. However, the guidelines remain less clear regarding the use of granulocyte colony-stimulating factors (G-CSFs) for this population and insights about real-world prophylaxis patterns and FN outcomes are needed. AREAS COVERED: This scoping review summarizes the variability in real-world G-CSF prophylaxis treatment patterns, incidence of FN, and associated outcomes among patients receiving chemotherapy at intermediate risk of FN. G-CSF PP use varied across the included studies (N = 23). Overall, there was a trend for reduced FN incidence among patients who received G-CSF PP vs. those who did not. G-CSF PP was also associated with a lower incidence of FN-related dose delays and reductions and fewer hospitalization days. Gaps in the literature of real-world studies exist, particularly around incorporating FN risk factor assessment, patient-reported outcomes, and health economic outcomes. EXPERT OPINION: Further studies are warranted to determine the impact of G-CSF PP use on clinical, quality of life, and economic outcomes in patients with intermediate FN risk, which could optimize care for this subgroup of patients, resulting in better population-based FN-related outcomes.

Carvedilol reduces the risk of decompensation and mortality in patients with compensated cirrhosis in a competing-risk meta-analysis.

BACKGROUND & AIMS: Whether non-selective ß-blockers can prevent decompensation of cirrhosis warrants clarification. Carvedilol might be particularly effective since its intrinsic vasodilatory activity may ameliorate hepatic vascular resistance, a major mechanism of portal hypertension in early cirrhosis. We assessed whether carvedilol may prevent decompensation and improve survival in patients with compensated cirrhosis and clinically significant portal hypertension (CSPH). METHODS: By systematic review we identified randomized-controlled trials (RCTs) comparing carvedilol vs. control therapy (no-active treatment or endoscopic variceal ligation [EVL]) in patients with cirrhosis and CSPH without previous bleeding. We performed a competing-risk time-to-event meta-analysis using individual patient data (IPD) obtained from principal investigators of RCTs. Only compensated patients were included. Primary outcomes were prevention of decompensation (liver transplantation and death were competing events) and death (liver transplantation was a competing event). Models were adjusted using propensity scores for baseline covariates with the inverse probability of treatment weighting (IPTW) approach. RESULTS: Among 125 full-text studies evaluated, 4 RCTs were eligible. The 4 provided IPD and were included, comprising 352 patients with compensated cirrhosis, 181 treated with carvedilol and 171 controls (79 received EVL and 92 placebo). Baseline characteristics were similar between groups. Standardized differences were <10% by IPTW. The risk of developing decompensation of cirrhosis was lower with carvedilol than in controls (subdistribution hazard ratio [SHR] 0.506; 95% CI 0.289-0.887; p = 0.017; I2 = 0.0%, Q-statistic-p = 0.880), mainly due to a reduced risk of ascites (SHR 0.491; 95% CI 0.247-0.974; p = 0.042; I2 = 0.0%, Q-statistic-p = 0.384). The risk of death was also lower with carvedilol (SHR 0.417; 95% CI 0.194-0.896; p = 0.025; I2 = 0.0%, Q-statistic-p = 0.989). CONCLUSIONS: Long-term carvedilol therapy reduced decompensation of cirrhosis and significantly improved survival in compensated patients with CSPH. This suggests that screening patients with compensated cirrhosis for CSPH to enable the prompt initiation of carvedilol could improve outcomes. PROSPERO REGISTRATION NUMBER: CRD42019144786. LAY SUMMARY: The transition from compensated cirrhosis to decompensated cirrhosis is associated with markedly reduced life expectancy. Therefore, preventing decompensation in patients with compensated cirrhosis would be associated with greatly improved patient outcomes. There has been controversy regarding the use of non-selective ß-blockers (portal pressure-lowering medications) in patients with cirrhosis and elevated portal blood pressure (portal hypertension). Herein, using a competing-risk meta-analysis to optimize sample size and properly investigate cirrhosis as a multistate disease and outcomes as time-dependent events, we show that carvedilol (a non-selective ß-blocker) is associated with a reduced risk of decompensating events and improved survival in patients with cirrhosis and portal hypertension.

The Real-World Experience of the Biosimilar (Grastofil®) to the Reference Biologic (Neupogen®) in Breast Cancer and Lymphoma: A Canadian Single-Centre Retrospective Study.

Febrile neutropenia (FN) is a common side effect of cytotoxic chemotherapy that may result in poor treatment outcomes. The short acting granulocyte colony stimulating factors (G-CSF) act to stimulate granulocytes to increase production of white blood cells. The filgrastim biosimilar is useful, as it may provide a cheaper and equally effective treatment to FN. This study explored the usage of the filgrastim biosimilar (Grastofil®) and the reference biologic (Neupogen®) in breast cancer and lymphoma patients. A retrospective chart review of patients receiving Grastofil® from January 2017 to June 2019 or Neupogen® for primary prophylaxis of FN from January 2013 to December 2017 was conducted. The endpoints included the incidence of FN and the occurrence of dose reduction (DR) and dose delay (DD). One hundred and fifty-three Grastofil® patients were matched to 153 Neupogen® patients. This cohort was further split into breast cancer (n = 275) and non-Hodgkin's lymphoma (n = 31) cohorts. After adjusting for chemotherapy cycles, the biosimilar filgrastim was non-inferior to the reference biologic based on FN incidence in addition to related outcomes including DR and DD.

Effective Letermovir Prophylaxis of CMV infection post allogeneic hematopoietic cell transplantation: Results from the French temporary authorization of use compassionate program.

We report the results of the French Temporary Authorization of Use (ATU) compassionate program of letermovir for primary prophylaxis conducted in 21 transplant centers. Patients were CMV seropositive allogeneic hematopoietic cell transplantation recipients and at high risk for CMV infection. Primary prophylaxis was defined as initiation of letermovir between day 0 and day +28 post-transplant. Between November 2017 and January 2019, 96 patients with a median age of 56 years received letermovir and follow-up data were available for 78 patients. The median time from transplant to letermovir initiation was 4 days, and the median duration of exposure to letermovir was 78 days, with 57 patients still on treatment at the cutoff date. Letermovir was temporarily discontinued in 4 patients (5.1%) and stopped in 39 patients (50.0%), in most cases due to planned end of treatment (n = 16, 20.5%). Fifteen patients (19.2%) each presented one positive CMV PCR, in median 13 days after letermovir initiation. Clinically significant CMV infection was reported in 5 patients (6.4%). No CMV disease was reported. At least one adverse drug reaction was reported for 12 patients (15.4%). In this early access program, letermovir was effective with comparable results of the phase 3 study with a low rate of clinically significant CMV infection, including in patients who were at high-risk for CMV infection.