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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. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion This retrospective study aimed to assess the efficacy of prophylactic antibiotics in preventing ascending cholangitis following Kasai portoenterostomy (KPE). Data from 72 patients treated across four tertiary centres in Israel from 2008 to 2018 were analysed.Clinical and laboratory data were collected from biliary atresia (BA) diagnosis until liver transplantation (LT) or study completion.Median age at KPE was 58.5 days. Successful KPE was achieved in 23 (32%) patients. Ascending cholangitis occurred in 6/23 (26%) successful KPE cases and 15/45 (33%) unsuccessful cases. Primary antibiotic prophylaxis (49% of patients) was associated with earlier onset of cholangitis (median 77 vs 239 days, p = 0.016). During follow‐up, 39% underwent LT, with a 5‐year survival with native liver (SNL) of 54%.Prophylactic antibiotics did not reduce cholangitis rates post‐KPE in our cohort. Further research is essential to optimise management strategies for infants with BA. [ABSTRACT FROM AUTHOR]

Background: Co-trimoxazole is a mainstay for primary Pneumocystis jirovecii pneumonia (PJP) prophylaxis in people living with human immunodeficiency virus (PLWH) whose CD4 count is <200 cells/mm³. However, there is limited evidence of the outcome of co-trimoxazole to prevent PJP after early initiation of highly active antiretroviral therapy era. Objective: To assess co-trimoxazole's efficacy and side effects in primary PJP prophylaxis in PLWH. Materials and Methods: A retrospective study was performed from January 2010 to December 2019 at a single medical university hospital in Thailand. Adults aged 18 or older who received combination antiretroviral therapy (cART), had baseline CD4 <200 cells/mm³, and were not diagnosed with PJP before the cART were enrolled. Patients with a history of sulfa allergy who received co-trimoxazole for treatment of other diseases, received drugs that had a therapeutic effect on Pneumocystis jirovecii, or lost important data were excluded. Results: A total of 1,249 individuals, 227 patients (126 PLWH received co-trimoxazole and 101 PLWH did not receive co-trimoxazole [control group]) complied with eligibility conditions for analysis. The median (IQR) age was 34.7 (27.8 to 42.7) years. The median (IQR) baseline CD4 count in co-trimoxazole and control group were 52 (26 to 106) and 107 (75 to 151) cells/mm³ (p<0.001), respectively. The prevalence of PJP after cART initiation in co-trimoxazole group and control group were 0.8% and 1.0% (p=1.00), respectively. The all-cause mortality rate in the co-trimoxazole group was 3.2%, while there was no death in the control group. Conclusion: There is no significant difference between the rate of PJP in PLWH who receive and do not receive co-trimoxazole prophylaxis. Primary PJP prophylaxis in all PLWH whose CD4 count <200 cells/mm³ may not be necessary for the era of highly effective cART, and the guideline recommendation should be reconsidered. [ABSTRACT FROM AUTHOR]

Abstract Background Pneumocystis jirovecii pneumonia (PcP) is an opportunistic infection associated with immunocompromised patients. The development of novel immunotherapies has promoted the incidence of PcP. This study describes the clinical course and outcome of PcP in chimeric antigen receptor (CAR) T cell recipients with hematological malignancies. Methods This is a retrospective case series of CAR-T recipients diagnosed with PcP in our center. The cases were all confirmed by metagenomic next-generation sequencing of clinical samples. The demographic, clinical, and outcome data were retrieved from the patients’ medical charts and electronic medical record system. Results In total, 8 cases of PcP were identified. The underlying malignancies included T-acute lymphoblastic leukemia (ALL) (n = 1), diffuse large B cell lymphoma (DLBCL) (n = 4), and B-ALL (n = 3). One patient received short-term sulfamethoxazole-trimethoprim (SMZ-TMP) while the others had no prophylaxis. Four patients had neutropenia/lymphopenia at the diagnosis of PcP, and two patients had immunosuppressants within one month before PcP manifestation. The median time from CAR-T infusion to PcP diagnosis was 98.5 days (range 52–251). Seven patients recovered from PcP after proper management while one died of septic shock. Conclusion PcP can occur after different CAR-T product, and the long-term depletion of immune cells seems to be related to PcP. SMZ-TMP is effective in this setting. More real-world experience of CAR-T therapy is required to assess the incidence and outcome of PcP in this population.

Background: Pneumocystis jirovecii pneumonia (PcP) is an opportunistic infection associated with immunocompromised patients. The development of novel immunotherapies has promoted the incidence of PcP. This study describes the clinical course and outcome of PcP in chimeric antigen receptor (CAR) T cell recipients with hematological malignancies. Methods: This is a retrospective case series of CAR-T recipients diagnosed with PcP in our center. The cases were all confirmed by metagenomic next-generation sequencing of clinical samples. The demographic, clinical, and outcome data were retrieved from the patients' medical charts and electronic medical record system. Results: In total, 8 cases of PcP were identified. The underlying malignancies included T-acute lymphoblastic leukemia (ALL) (n = 1), diffuse large B cell lymphoma (DLBCL) (n = 4), and B-ALL (n = 3). One patient received short-term sulfamethoxazole-trimethoprim (SMZ-TMP) while the others had no prophylaxis. Four patients had neutropenia/lymphopenia at the diagnosis of PcP, and two patients had immunosuppressants within one month before PcP manifestation. The median time from CAR-T infusion to PcP diagnosis was 98.5 days (range 52–251). Seven patients recovered from PcP after proper management while one died of septic shock. Conclusion: PcP can occur after different CAR-T product, and the long-term depletion of immune cells seems to be related to PcP. SMZ-TMP is effective in this setting. More real-world experience of CAR-T therapy is required to assess the incidence and outcome of PcP in this population. [ABSTRACT FROM AUTHOR]

Venous thromboembolism remains a major cause of morbidity and mortality among ambulatory cancer patients, necessitating effective risk assessment and prevention strategies. Despite the availability of risk assessment models and guidelines recommending primary thromboprophylaxis with low-molecular-weight heparins or direct oral anticoagulants, the application of these strategies is inconsistent. This review provides an overview of the current state-of-the-art venous thromboembolism risk assessment and thromboprophylaxis in ambulatory patients with cancer, focusing on existing risk assessment models and the latest guideline recommendations. Finally, it summarizes gaps in knowledge, discusses future directions, and highlights recent advances and state-of-the-art research presented at the 2024 International Society on Thrombosis and Haemostasis Congress in Bangkok, Thailand.

"Eliminate rheumatic fever (RF) and minimize the burden of rheumatic heart disease by 2025" is the goal of World Heart Federation (WHF). The most important step to achieve the goal of WHF is the implementation of the prevention and control of RF in India. The program can be implemented with minimal fund allocation from government making use of the existing manpower in the government and private health sector and schools with the concurrence of National Health Mission, Ministry of Health and Family Welfare, Ministry of Public Education and under the guidance of Cardiological Society of India, National Rheumatic Heart Consortium, Rheumatic Heart Club India, Association of Physicians of India, Indian Academy of Pediatrics, and Association of Otolaryngologists of India. By the successful implementation of this program, the children of 5--15 years in India can be protected from RF. India eradicated smallpox in 1980 and Polio 2012. With this program, we can start our efforts to eliminate RF by 2025. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background & Aims: Non‐selective β‐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. [ABSTRACT FROM AUTHOR]

ObjectivesNonselective 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.MethodsThe 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.ResultsThe 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).ConclusionVariceal 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.

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.

Abstract 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.

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. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy of carvedilol and propranolol for prophylaxis of variceal bleeding in cirrhotic patients. Study Design: Randomized Controlled Trial. Setting: Department of Gastroenterology and Hepatology, PIMS, Islamabad. Period: 1st January 2022 to 31st of December 2022. Material & Methods: A total of 260 patients reporting at the department suffering from liver cirrhosis with medium or large esophageal varices and had never reported for variceal bleeding previously. The patients were randomized in to 2 equal groups of 130 each through computer generated randomization. Patients in Group-A were started on dose of carvedilol 6.25mg once daily initially for 1 week, subsequently titrated to twice daily 6.25mg and titrated up if needed to maximum of 25mg twice daily. Patients in Group-B received a dosage of propranolol 20 mg BID which then escalated weekly in 20 mg steps if needed and doses were adjusted as per targeted heart rate and systolic BP. Patients were followed up over 1 year for any event of variceal bleeding. Results: Mean overall age in this study was 42.13±10 years. The ratio of male patients was higher than female patients (60% VS 40%). Carvedilol prevented variceal bleeding in 86.15% of the patients while propranolol was effective in preventing variceal bleeding in 75.38% of the patients. Hence carvedilol was significantly more effective than propranolol in preventing variceal bleeding (p=0.02). Conclusion: Carvedilol is significantly more effective in prophylaxis of variceal bleeding than propranolol in patients with medium or large esophageal varices. [ABSTRACT FROM AUTHOR]

According to the latest proposals from the Baveno VII conference, endoscopic screening for esophageal varices (EV) to tailor primary prophylaxis is required in patients with decompensated cirrhosis; liver stiffness ≥ 20 kPa or platelets ≤ 150 G/l with no "immediate" indication for betablockers; liver stiffness ≥ 20 kPa or platelets ≤ 150 G/l and contraindication or intolerance to betanbockers. Endoscopic screennig for EV is no longer required in patients: with compensated cirrhosis and an "immediate" indication for betablockers; with liver stiffness < 20 kPa and platelets > 150 G/l (in this case, these tests should be repeated every year). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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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. [ABSTRACT FROM AUTHOR]

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.

Background/Purpose: Esophageal variceal bleeding (EVB) is a medical emergency in patients with portal hypertension (PHT). However, studies on the long-term outcomes of prophylactic endoscopic variceal ligation (EVL) in pediatric-onset PHT are lacking. Methods: Between 1999 and 2020, patients who received EVL in the Electronic Report System of the Pediatric Endoscopy Unit were included in this retrospective study. EVL was classified as primary prophylaxis when it was performed for esophageal varices (EVs) without previous bleeding. If it was implemented in acute EVB, the subsequent EVL was classified as secondary prophylaxis. Results: Fifty-eight patients aged 10 months to 33 years with 31 males were included. Thirty-eight patients were classified as primary prophylaxis group, and twenty, secondary prophylaxis group. The primary prophylaxis group experienced fewer 5-year EVB events than the secondary prophylaxis group (cumulative risk: 14.4% versus 32.4%). Still, it didn't significantly affect overall survival and biliary atresia transplant-free survival. Long-term mortality was significantly associated with higher serum direct bilirubin levels (≥0.55 mg/dL) and lower albumin levels (≤2.54 mg/dL) at the first EVL. Aspartate aminotransferase-to-platelet ratio index (APRI) with a cut-off value of 1.24 helped to predict EV presence at the initial esophagogastroduodenoscopy (EGD) (AUROC = 0.762, sensitivity 75.0%, and specificity 66.7%). Conclusion: Primary prophylactic EVL, despite reducing acute EVB, may not change overall survival and biliary atresia transplant-free survival. APRI > 1.24 may predict EV presence at the first EGD and help to schedule a surveillance EGD. Higher direct bilirubin and lower albumin levels at the first EVL may relate to long-term mortality.

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.

Whether non-selective β-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). 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. 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). 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. CRD42019144786. 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 β-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 β-blocker) is associated with a reduced risk of decompensating events and improved survival in patients with cirrhosis and portal hypertension. [Display omitted] • Carvedilol significantly decreases the risk of decompensation in patients with cirrhosis and CSPH, mainly by reducing risk of ascites. • Even more importantly, carvedilol significantly improves survival in compensated patients. • Early initiation of carvedilol could prevent disease progression in patients with compensated cirrhosis and CSPH. • Patients with compensated cirrhosis should be screened for CSPH, so that treatment can be started early. [ABSTRACT FROM AUTHOR]

Venous thromboembolism occurring in the form of thrombosis or pulmonary embolism is an interdisciplinary problem of modern medicine. It is the third most common acute cardiovascular disease after myocardial infarction and stroke. Its incidence and risk of occurrence increase with age and the presence of multimorbidity and reduction in the patient's functional capacity. Given the above, the patient receiving palliative care appears to be at particular risk of developing venous thromboembolism, and the physician caring for them should have clear guidelines for prevention. The first part of this paper presents an analysis of the available literature on assessing risk factors and the incidence of venous thromboembolism. [ABSTRACT FROM AUTHOR]

Simple Summary: Pegfilgrastim, the pegylated form of filgrastim (recombinant human GCSF) is widely adopted as supportive care for preventing neutropenia or febrile neutropenia episodes during chemotherapy. Neutropenia is directly cause of potentially severe infections and indirectly cause of treatment delivery delay. No guidelines address the pegfilgrastim role in the specific setting of Hodgkin lymphoma (HL). Since HL is a young-adult disease and shows mostly a very a favorable outcome after chemotherapy, treatment delay or dose reduction could potentially affect negatively the outcome. The aim of our review is to explore the current scientific literature on pegfilgratim use in HL, evaluating both observational than prospective trial. Moreover, analyzing the latter, we aim to define some practical suggestion about primary prophylaxis with pegfilgrastim in HL. 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. [ABSTRACT FROM AUTHOR]

Background/purpose: Esophageal variceal bleeding (EVB) is a medical emergency in patients with portal hypertension (PHT). However, studies on the long-term outcomes of prophylactic endoscopic variceal ligation (EVL) in pediatric-onset PHT are lacking.Methods: Between 1999 and 2020, patients who received EVL in the Electronic Report System of the Pediatric Endoscopy Unit were included in this retrospective study. EVL was classified as primary prophylaxis when it was performed for esophageal varices (EVs) without previous bleeding. If it was implemented in acute EVB, the subsequent EVL was classified as secondary prophylaxis.Results: Fifty-eight patients aged 10 months to 33 years with 31 males were included. Thirty-eight patients were classified as primary prophylaxis group, and twenty, secondary prophylaxis group. The primary prophylaxis group experienced fewer 5-year EVB events than the secondary prophylaxis group (cumulative risk: 14.4% versus 32.4%). Still, it didn't significantly affect overall survival and biliary atresia transplant-free survival. Long-term mortality was significantly associated with higher serum direct bilirubin levels (≥0.55 mg/dL) and lower albumin levels (≤2.54 mg/dL) at the first EVL. Aspartate aminotransferase-to-platelet ratio index (APRI) with a cut-off value of 1.24 helped to predict EV presence at the initial esophagogastroduodenoscopy (EGD) (AUROC = 0.762, sensitivity 75.0%, and specificity 66.7%).Conclusion: Primary prophylactic EVL, despite reducing acute EVB, may not change overall survival and biliary atresia transplant-free survival. APRI > 1.24 may predict EV presence at the first EGD and help to schedule a surveillance EGD. Higher direct bilirubin and lower albumin levels at the first EVL may relate to long-term mortality. [ABSTRACT FROM AUTHOR]

Background: Primary endoscopic prophylaxis in pediatric gastroesophageal varices is not universally practiced. We aimed to determine the role of primary endoscopic prophylaxis in preventing variceal bleeding in gastroesophageal varices in children. Methods: We reviewed all children with gastroesophageal varices seen in our unit from 2000 to 2019. Primary prophylaxis was defined as endoscopic procedure without a preceding spontaneous bleeding and secondary prophylaxis as preceded by spontaneous bleeding. High-risk varices were defined as presence of grade III esophageal varices, cardia gastric varices or cherry red spots on the varices. Outcome measures (spontaneous rebleeding within 3 months after endoscopic procedure, number of additional procedures to eradicate varices, liver transplant [LT], death) were ascertained. Results: Sixteen of 62 (26%) patients (median [± S.D.] age at diagnosis = 5.0 ± 4.3 years) with varices had primary prophylaxis, 38 (61%) had secondary prophylaxis while 8 (13%) had no prophylaxis. No difference in the proportion of patients with high-risk varices was observed between primary (88%) and secondary (92%; P = 0.62) prophylaxis. As compared to secondary prophylaxis, children who had primary prophylaxis were significantly less likely to have spontaneous rebleeding (6% vs. 38%; P = 0.022) and needed significantly fewer repeated endoscopic procedures (0.9 ± 1.0 vs. 3.1 ± 2.5; P = 0.021). After 8.9 ± 5.5 years of follow-up, overall survival was 85%; survival with native liver was 73%. No statistical difference was observed in the eventual outcome (alive with native liver) between primary and secondary (71% vs. 78%, P = 0.78). Conclusion: Children with PHT who had primary prophylaxis had less subsequent spontaneous rebleeding and needed fewer additional endoscopic procedures as compared to secondary prophylaxis but did not have an improved eventual outcome. Screening endoscopy in all children who have signs of PHT and primary prophylaxis in high-risk esophageal varices should be considered before eventual LT.

Purpose: This study sought to compare the efficacy of prophylactic long-acting and standard granulocyte colony-stimulating factor (G-CSF) on febrile neutropenia, early infections, and treatment delay in patients with newly diagnosed multiple myeloma (MM) receiving the therapeutic regimen of bortezomib, lenalidomide, and dexamethasone (VRd). Methods: A prospective study with 68 consecutive patients with MM was conducted in three regional hospitals. Participants were randomly treated with the VRd regimen in combination with prophylactic long-acting G-CSF (treatment group) or prophylactic standard G-CSF (control group). The primary endpoints were the incidence rates of febrile neutropenia, early infection, and treatment delays. The secondary endpoint was clinical outcomes. Results: Thirty-three patients were assigned to the treatment group, and thirty-five patients were assigned to the control group. The incidence of febrile neutropenia was 6.1% and 17.1% in the treatment and control groups, respectively (p = 0.297). However, the rates of early infection and treatment delay were markedly lower in the treatment group than in the control group (6.1% vs. 25.7% and 9.1% vs. 31.4%; p < 0.05). Notably, all early infections occurred during the first four cycles of VRd therapy, and the most common type of infection was pneumonia. No significant difference in clinical efficacy was found between the two groups. All participants achieved at least partial remission. Conclusions: Prophylactic administration of domestic long-acting G-CSF markedly reduced the rates of early infection and treatment delay as compared with standard G-CSF in patients newly diagnosed with MM. Notably, all early infections occurred during the first four cycles of VRd therapy. As such, it seems appropriate to administer long-acting G-CSF with the aim of primary prophylaxis of early infection in the setting of newly diagnosed MM. [ABSTRACT FROM AUTHOR]

Background: The Nippon Storm Study was a prospective observational study designed to gather clinical data on implantable cardioverter-defibrillator (ICD) therapy in Japanese patients. Objective: The purpose of this subanalysis was to compare the incidence of ICD therapy in patients with left ventricular dysfunction owing to coronary artery disease (CAD) for primary and secondary prophylaxis of sudden cardiac death. Methods: We analyzed data of 493 patients with CAD and ICDs (men, 87%; age, 68 ± 10 years; left ventricular ejection fraction, 36% ± 13%; primary prophylaxis, 36%). All patients were followed up for at least 2 years. Propensity score matching was used to select patient subgroups for comparison: 133 patients with ICD for primary prophylaxis and 133 with ICD for secondary indications. Results: There were no significant differences between primary and secondary prophylaxis groups with respect to the incidence of appropriate ICD therapy within 2 years (0.153 vs 0.239; hazard ratio, 1.565 [95% confidence interval (CI), 0.898–2.727]; P = .114). Two-year electrical storm risks were 3.3% and 9.6% with HR = 3.236 (95% CI, 1.058–9.896; P = .039) in patients with primary and secondary prophylaxis, respectively. Conclusion: The incidence of ICD therapy received by patients with CAD for primary and secondary prophylaxis was not significantly different based on our propensity score–matched analysis. However, secondary-prophylaxis ICD therapy seems to be associated with a significantly higher risk for electrical storm than primary-prophylaxis ICD therapy.

AimTo identify the association between endoscopic primary prophylaxis and the risk of rebleeding in patients with liver cirrhosis receiving endoscopic therapy.MethodsThis 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.ResultsIn 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

• This is a series of eight patients with advanced liver disease who developed Pneumocystis jirovecii pneumonia (PCP) • Advanced liver disease can be a risk factor for PCP • Prophylaxis for PCP could be considered in patients with decompensated cirrhosis 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

The natural history of antiphospholipid antibodies (aPL) carriers is not well-established. The objectives of the present study were (a) to study the probability of developing clinical criteria of antiphospholipid syndrome (APS), (b) to identify potential risk factors for developing thrombosis and/or obstetric complications, (c) to study the association between the antibody profile and development of APS, and (d) to determine the efficacy of primary prophylaxis. We retrospectively analyzed 138 subjects with positive aPL who did not fulfill clinical criteria for APS. The mean follow-up time was 138 ± 63.0 months. Thirteen patients (9.4%) developed thrombosis after an average period of 73.0 ± 48.0 months. Independent risk factors for thrombosis were smoking, hypertension, thrombocytopenia, and triple aPL positivity. Low-dose acetyl salicylic acid did not prevent thrombotic events. A total of 28 obstetric complications were detected in 92 pregnancies. During the follow-up, only two women developed obstetric APS. Prophylactic treatment in pregnant women was associated with a better outcome in the prevention of early abortions. The thrombosis rate in patients with positive aPL who do not meet diagnostic criteria for APS is 0.82/100 patients-year. Smoking, hypertension, thrombocytopenia, and the aPL profile are independent risk factors for the development of thrombosis in aPL carriers. Although the incidence of obstetric complications in this population is high (31.6%), only a few of them meet APS criteria. In these women, prophylactic treatment might be effective in preventing early abortions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This article deals with the general recommendations on vaccination and postexposure prophylaxis, which can be utilized for cuts and needlestick injuries. Cuts and needlestick injuries among surgeons are common occupational accidents. These should be interpreted as acute or emergency situations, especially if there was contact with infectious index patients or the danger of infection cannot be excluded. This results in high economic costs but also in the individual confrontation with an infectious disease that is definitely incurable. The aim of this review is to highlight the general and occupational vaccine recommendations for surgeons. In addition, background information and legal principles are presented. There is a duty to provide and to obtain information about effective protective measures against infectious diseases from cuts and needlestick injuries even for surgeons. In addition, primary prophylaxis, vaccination recommendations, and postexposure prophylaxis after cuts and needlestick injuries as well as the TOP principle are presented. The TOP principle comprises technical, organizational and person-related protective measures. [ABSTRACT FROM AUTHOR]

Introduction: Cancer patients receiving myelosuppressive chemotherapy are vulnerable to febrile neutropenia (FN) which contributes to poor treatment outcomes. The use of granulocyte colony-stimulating factors is administered to prevent chemotherapy-induced neutropenia. The introduction of biosimilars has allowed for greater cost-savings while maintaining safety and efficacy. This retrospective study assessed the incidence of FN and related treatment outcomes and the cost minimization of a pegfilgrastim biosimilar and its reference. Methods: A retrospective chart review of breast cancer patients receiving (neo) adjuvant chemotherapy from February 2017 to May 2020 was conducted. The endpoints included the incidence of FN, the occurrence of dose reduction (DR), dose delay (DD) and pain. A cost minimization analysis was performed from a third-party payer perspective. Results: One hundred Neulasta® and 74 Lapelga® patients were included in the first-cycle analysis. The rate of FN in cycle 1 for Neulasta® and Lapelga® was 2/100 and 4/74, respectively; risk difference (RD) = 3.4%; 95% CI: –2.4 to 9.2%. Eighty-three Neulasta® and 59 Lapelga® patients were included in the all-cycle analyses, where DR was reported in 76 (15%) Neulasta® cycles vs 33 (10%) Lapelga® cycles (RD = –3.6, 95% CI: –10.2 to 2.9). DD was reported in 20 (4%) Neulasta® cycles vs. 11 (3.5%) Lapelga® cycles (RD = –0.3; 95% CI: –2.7 to 2.0). Adverse events were similar between groups. Cost minimization using a cohort of 20,000 patients translated into an incremental savings of $21,606,800 CAD for each cycle. Conclusion: The biosimilar pegfilgrastim was non-inferior to the reference biologic based on FN incidence in addition to related outcomes including DR and DD. [ABSTRACT FROM AUTHOR]

Background: Invasive fungal infections (IFI) following allogeneic stem cell transplant (allo- HCT) are associated with high morbidity and mortality. Primary prophylaxis using voriconazole has been shown to decrease the incidence of IFI. Methods: We conducted a retrospective analysis at the Bone Marrow Transplant (BMT) unit of the American University of Beirut including 195 patients who underwent allo-HCT for hematological malignancies and received voriconazole as primary prophylaxis for IFI. The primary endpoints were based on the incidence of IFI at day 100 and day 180, and the secondary endpoint based on fungal-free survival. Results: For the study, 195 patients who underwent allo-HCT between January 2015 and March 2021 were included. The median age at transplant was 43 years. Of the patients, 63% were male, and the majority of patients were diagnosed with acute myeloid leukemia (AML) (60%). Voriconazole was given for a median of 90 days and was interrupted in 20 patients. The majority of IFI cases were probable invasive aspergillosis (8%). The incidence of IFI including proven, probable and possible IFI was 34%. The incidence of proven and probable IFI was 5% were 8%, respectively. The incidence of proven-probable (PP-IFI) was 5.1% at day 100 and 6.6% at day 180. The majority of PP-IFI cases were invasive aspergillosis (8%). A univariate analysis of patients, transplant characteristics and IFI showed a significant correlation between the type of donor, disease status before transplant, graft-versus-host disease prophylaxis used and incidence of IFI. Only disease status post-transplant showed a significant correlation with fungal-free survival in the multivariate analysis. Conclusion: Primary prophylaxis with voriconazole in allo-HCT is associated with a low incidence of IFI. More studies are required to compare various antifungal agents in this setting. [ABSTRACT FROM AUTHOR]

Portal hypertensive bleeding is a major complication of portal hypertension (PHT) with high morbidity and mortality. A lot of advances have been made in our understanding of screening, risk stratification, and management strategies for portal hypertensive bleeding including acute variceal bleeding leading to improved overall outcomes in patients with PHT. A number of guidelines on variceal bleeding have been published by various societies in the past few years. The Indian Society of Gastroenterology (ISG) Task Force on Upper Gastrointestinal Bleeding (UGIB) felt that it was necessary to bring out a standard practice guidance document for the use of Indian health care providers especially physicians, gastroenterologists, and hepatologists. For this purpose, an expert group meeting was convened by the ISG Task Force to deliberate on this matter and write a consensus guidance document for Indian practice. The delegates including gastroenterologists, hepatologists, radiologists, and surgeons from different parts of the country participated in the consensus development meeting at Coorg in 2018. A core group was constituted which reviewed all published literature on portal hypertensive UGIB with special reference to the Indian scenario and prepared unambiguous statements on different aspects for voting and consensus in the whole group. This consensus was produced through a modified Delphi process and reflects our current understanding and recommendations for the diagnosis and management of portal hypertensive UGIB in Indians. Intended for use by the health care providers especially gastroenterologists and hepatologists, these consensus statements provide an evidence-based approach to risk stratification, diagnosis, and management of patients with portal hypertensive bleeding. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the efficacy and safety profiles of first‐line etoposide, ifosfamide and cisplatin and primary prophylaxis with pegfilgrastim as first‐line chemotherapy for disseminated germ cell cancer. Methods: This study reviewed 154 consecutive patients with previously untreated disseminated germ cell cancer who received first‐line etoposide, ifosfamide and cisplatin between 1995 and 2020. Of these, 54 patients were managed with primary prophylaxis using pegfilgrastim (primary prophylaxis group), and 100 were managed with the therapeutic use of short‐acting granulocyte colony‐stimulating factor (non‐primary prophylaxis group). Results: The International Germ Cell Cancer Collaborative Group classification identified 90 (58%)/40 (26%)/24 (16%) patients with good/intermediate/poor prognosis, respectively. Overall, 139 patients (90%) were disease free after etoposide, ifosfamide and cisplatin with/without post‐chemotherapy surgery. The median relative dose intensity of etoposide, ifosfamide and cisplatin was 96%, and there was a significant difference between the primary prophylaxis and non‐primary prophylaxis groups (100% vs 90%, P < 0.01). The 5‐year salvage treatment‐free and overall survival rates were 83% and 94%, respectively. In total, 138 patients (90%) developed grade 4 hematological toxicities, and there were no treatment‐related deaths due to myelosuppression. Grade 4 neutropenia was less commonly observed in the primary prophylaxis group compared with the non‐primary prophylaxis group (80% vs 95%, P < 0.01). Conclusions: This is the largest study of first‐line etoposide, ifosfamide and cisplatin, and its sufficient efficacy and safety profiles are confirmed in current clinical practice. Primary prophylaxis using pegfilgrastim might further improve the feasibility of etoposide, ifosfamide and cisplatin. [ABSTRACT FROM AUTHOR]

Purpose: Our study aimed to compare the median and average last dose level reached with DA-R-EPOCH, which includes the chemotherapy agents etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab, in patients using filgrastim versus pegfilgrastim as febrile neutropenia primary prophylaxis. Methods: A retrospective, single-center chart review from January 1, 2014, to September 30, 2019, at The University of Kansas Health System identified patients > 18 years old who received at least four cycles of DA-R-EPOCH in an inpatient or outpatient setting for any subtype of lymphoma along with at least one dose of filgrastim or pegfilgrastim. Data was collected to compare dosing levels reached, appropriate discontinuation of daily filgrastim when ANC > 5000 cells/mm3, completion of at least twice weekly complete blood count (CBC) monitoring after chemotherapy administration, the incidence of infections, FN, hospitalizations from infections or FN, and bone pain. Results: We hypothesized that patients receiving pegfilgrastim will achieve similar median and average dose levels of DA-EPOCH, event-free survival rates, overall response rates, completion of at least twice weekly CBC monitoring, and incidence of infections, FN, hospitalizations for infections or FN, and bone pain compared to patients receiving filgrastim. Conclusions: The use of pegfilgrastim as a supportive care agent resulted in similar efficacy and safety outcomes compared to filgrastim with DA-R-EPOCH in terms of dose intensity levels and incidence of infections, FN, and bone pain. [ABSTRACT FROM AUTHOR]

Primary endoscopic prophylaxis in pediatric gastroesophageal varices is not universally practiced. We aimed to determine the role of primary endoscopic prophylaxis in preventing variceal bleeding in gastroesophageal varices in children. We reviewed all children with gastroesophageal varices seen in our unit from 2000 to 2019. Primary prophylaxis was defined as endoscopic procedure without a preceding spontaneous bleeding and secondary prophylaxis as preceded by spontaneous bleeding. High-risk varices were defined as presence of grade III esophageal varices, cardia gastric varices or cherry red spots on the varices. Outcome measures (spontaneous rebleeding within 3 months after endoscopic procedure, number of additional procedures to eradicate varices, liver transplant [LT], death) were ascertained. Sixteen of 62 (26%) patients (median [± S.D.] age at diagnosis = 5.0 ± 4.3 years) with varices had primary prophylaxis, 38 (61%) had secondary prophylaxis while 8 (13%) had no prophylaxis. No difference in the proportion of patients with high-risk varices was observed between primary (88%) and secondary (92%; P = 0.62) prophylaxis. As compared to secondary prophylaxis, children who had primary prophylaxis were significantly less likely to have spontaneous rebleeding (6% vs. 38%; P = 0.022) and needed significantly fewer repeated endoscopic procedures (0.9 ± 1.0 vs. 3.1 ± 2.5; P = 0.021). After 8.9 ± 5.5 years of follow-up, overall survival was 85%; survival with native liver was 73%. No statistical difference was observed in the eventual outcome (alive with native liver) between primary and secondary (71% vs. 78%, P = 0.78). Children with PHT who had primary prophylaxis had less subsequent spontaneous rebleeding and needed fewer additional endoscopic procedures as compared to secondary prophylaxis but did not have an improved eventual outcome. Screening endoscopy in all children who have signs of PHT and primary prophylaxis in high-risk esophageal varices should be considered before eventual LT. [ABSTRACT FROM AUTHOR]

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tie, Yuan, Zhu, Li, Gou, Han, Niu, Xu, Wang and Shi.)

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., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

We investigate the impact of granulocyte-colony stimulating factor (G-CSF) primary prophylaxis (G-PP, N = 83) versus no G-PP (N = 579) on safety and efficacy of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A + AVD) in the ECHELON-1 study of previously untreated stage III/IV classical Hodgkin lymphoma. G-PP was associated with lower incidence of ≥ grade 3 neutropenia (29% versus 70%) and febrile neutropenia (11% versus 21%). Fewer dose delays (35% versus 49%), reductions (20% versus 26%), and hospitalizations (29% versus 38%) were observed. Seven neutropenia-associated deaths occurred in the A + AVD arm; none received G-PP. A + AVD with G-PP was associated with decreased risk of a modified progression-free survival event by 26% compared with A + AVD alone (95% CI: 0.40–1.37). G-PP reduced the rate and severity of adverse events, including febrile neutropenia, reduced treatment delays, dose reductions, and discontinuations, and may thus improve efficacy outcomes. These data support G-PP for all patients treated with A + AVD. [ABSTRACT FROM AUTHOR]

Objective To evaluate the cost effectiveness of primary prophylaxis (PP) with pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF), PP with recombinant human granulocyte colony stimulating factor (rhG-CSF) and no prophylaxis in women with early-stage breast cancer in China. Methods Two phase Markov models were constructed for a hypothetial cohort of patients aged 45 with stage II breast carrer. The first phase model costs and outcomes of 4 cycles docetaxel combined with cyclophosphamide [TC x 4, febrile neutropenia (FN) risk> 20%] chemotherapy, which assumptions based on literature reviews, including FN rates [base-case (deterministic sensitivity dialysis range), 0.29 (0.24-0.35)] and related events [FN case-fatality, 3.4 (2.7-4. 1)]. Second phase modelled the long term survival which was link with the radative dose intensity (RDI) [mortality, hazard, and ratio (HR) of RDI < 85% vs 85%, I.45 (1.00-2.32) ]. Clinical effectiveness, therapeutic costs, and economic utilities were estimated from peer-reviewed publications and expert opinions in case of unavailability of published evidences. Results Compared to rhG-CSF PP and no prophylaxis, the cost of PEG-rhG-CSF PP increased to 5 208.19 RMB and 5 222.73 RMB, respectively. The quality-adjusted life-years (QALYs) enhanced to 0.066 and 0.297, respectively. Accordingly, the incremental cost effectiveness ratios (ICERs), are 79 146.3 RMB m1d 17 558.77 RMB per QALY, which were both below the willingness to pay (WTP) threshold of three times GDP per capita (I8,000 RMB) recommended hy the WHO. Sensitivity analysis suggested that the more clinically effective the primary prophylaxis with PEG-rhG-GSF is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will he. And the lower the mortality HR of RDI<85%· vs 85%, is the more cost-effective primary prophylaxis with PEG-rhG-CSF will he. Conclusion Although the cost of PP PEGrhG-CSF is higher, considering the additional benefits, the administrating of PP PEG-rhG-CSF is likely to he a cost-effective alternative to PP rhG-CSf and no prophylaxis in patients with early stage hrcast cancer whose FN risks are more than 20% in China. [ABSTRACT FROM AUTHOR]

Background Asymptomatic patients colonized with Clostridioides difficile are at risk of developing C. difficile infection (CDI), but the factors associated with disease onset are poorly understood. Our aims were to identify predictors of hospital-onset CDI (HO-CDI) among colonized patients and to explore the potential benefits of primary prophylaxis to prevent CDI. Methods We conducted a retrospective cohort study in a tertiary academic institution. Colonized patients were identified by detecting the tcdB gene by polymerase chain reaction on a rectal swab. Univariate and multivariate logistic regression analyses were used to identify predictors of HO-CDI. Results There were 19 112 patients screened, from which 960 (5%) colonized patients were identified: 513 met the inclusion criteria. Overall, 39 (7.6%) developed a HO-CDI, with a 30-day attributable mortality of 15%. An increasing length of stay (adjusted odds ratio [aOR] per day, 1.03; P =.006), exposure to multiple classes of antibiotics (aOR per class, 1.45; P =.02), use of opioids (aOR, 2.78; P =.007), and cirrhosis (aOR 5.49; P =.008) were independently associated with increased risks of HO-CDI, whereas the use of laxatives was associated with a lower risk of CDI (aOR 0.36; P =.01). Among the antimicrobials, B-lactam with B-lactamase inhibitors (OR 3.65; P <.001), first-generation cephalosporins (OR 2.38; P =.03), and carbapenems (OR 2.44; P =.03) correlated with the greatest risk of HO-CDI. By contrast, patient age, the use of proton pump inhibitors, and the use of primary prophylaxis were not significant predictors of HO-CDI. Conclusions This study identifies several factors that are associated with CDI among colonized patients. Whether modifying these variables could decrease the risk of CDI should be investigated. [ABSTRACT FROM AUTHOR]

Objective: To determine efficacy of diclofenac suppository in reducing post-ERCP pancreatitis (PEP) and identify risk factors for PEP. Methods: This is a placebo-based prospective study at Department of Medicine & Gastroenterology, Services Institute of Medical Sciences / Services Hospital, Lahore performed from January 2018 to June 2019. Patients were randomized to receive diclofenac suppository or glycerine suppository before ERCP. Both groups were compared for PEP using chi square x2 test while risk factors for PEP were determined using binary logistic regression. Results: Total of 165 patients with mean age 49.1(±15.2) and male to female ratio 1/1.6 (63/102) were included. Among 82 (49.7%) patients in diclofenac group, 8 (9.7%) developed pancreatitis while 19(22.9%) of 83(50.3%) in placebo group had PEP (p value 0.02). After multivariate analysis, age>45 years (p value 0.014, OR 3.2), Bilirubin >3 mg/dl (p value 0.004 OR 3.58), time to cannulation> 5 minutes (p value<0.000 OR 9.2), use of precut (p value< 0.000 OR 4.9), pancreatic duct cannulation (p value 0.000 OR 5.46) and total procedure time >30 minutes (p value 0.01 OR 3.92) were risk factors for PEP. Conclusion: Pre-procedure Diclofenac suppository reduces post-ERCP pancreatitis. Age > 45 years, serum bilirubin > 3 mg/dl, cannulation time > 5 minutes, use of precut, pancreatic duct cannulation and procedure time > 30 minutes are risk factors for post-ERCP pancreatitis. [ABSTRACT FROM AUTHOR]