e19053 Background: Ruxolitinib, an elective Janus Kinase (JAK) 1/2 inhibitor, has been approved by FDA for the treatment of steroid-refractory chronic graft-versus-host-disease (SR cGVHD) after the failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older. However, it remains underutilized despite promising results in the treatment of SR cGVHD. Methods: We did a comprehensive literature search across various data sets, including PubMed, Cochrane, and Embase, and presented data in ASH and ASCO. A review of the most recent data is summarized in this abstract. Results: Two retrospective cohort studies and one pilot prospective study evaluated ruxolitinib in SR cGVHD. In a retrospective cohort study by Yang et al., 36 patients with SR cGVHD treated with ruxolitinib showed complete response (CR) in 27.8% of patients with complete disappearance of cGVHD symptoms and partial response (PR) with symptom relief of 52.7% at a dose of 2.5 to 10 mg two times daily with ruxolitinib tapering one week after symptoms improvement. In the pilot prospective study by Mozo et al., 12 pediatric patients with SR cGVHD received ruxolitinib at a dose of 2.5 to 10 mg two times daily and showed CR in 8.3% of patients and PR in 82.7% of patients. Morozova et al. conducted a prospective pilot study in 20 patients with primary or secondary myelofibrosis who were treated with pre-transplant ruxolitinib 45 mg/day from ruxolitinib (45 mg) starting from seven days before transplant to 2 days before the transplant, and 15 mg from day five after transplant to day 100 after transplant along with cyclophosphamide 50 mg/kg on days three and four after transplant. PR was observed in 47.1% of patients at 6 months with the incidence of cGVHD of 20%. In Phase III trial by Zeiser et al. reported CR of 6.7% and PR of 43% in 165 patients treated with ruxolitinib at a dose of 10 mg daily for 6 cycles (28 days/cycle). The most common all-grade adverse events are listed here. Conclusions: Ruxolitinib was recently approved by FDA for the treatment of SR GVHD and should be utilized more due to its high effectiveness and tolerable safety profile.[Table: see text]
Background: Hepatic veno-occlusive disease (VOD) also termed as sinusoidal obstruction syndrome (SOS) is a lethal complication seen after haematopoietic stem cell transplantation (HSCT). There are a limited number of options for prevention of this fatal complication. Recombinant thrombomodulin (rTM), an endothelial anticoagulant co-factor, has been shown to help prevent veno-occlusive complications after stem cell transplantation. Various trials have shown safety and efficacy of recombinant thrombomodulin in preventing SOS. Methods: A search was performed on PubMed, Cochrane, Embase, and Web of Science. We used the following keywords, "thrombomodulin" AND "stem cell transplantation" from the inception of literature till June 2020. Out of 239 articles, we screened and included nine trials (N=850) in the systematic review and meta-analysis. We extracted the data for VOD episodes, graft vs host disease (GVHD) episodes and survival after stem cell transplantation. We excluded case reports, preclinical trials, review articles, meta-analysis, and trials not providing any information about the above-mentioned. We used the R programming language (version 4.0.2) to conduct a meta-analysis. Results: Total number of patients tested was 356 in thrombomodulin group and 494 in control group. The age range was 16 to 74 years. Thrombomodulin group had 254 males and control group had 190 (Table 1.). For VOD, risk ratio (RR) was 0.53 (I2= 0%, 95% CI=0.32-0.89) in favor of rTM vs heparin or no therapy for prevention of VOD after stem cell transplantation (Fig 1.). rTM was effective in prevention of transplant-associated thrombotic microangiopathy (TA-TMA) after HSCT. RR was 0.48 (I2= 62%, 95% CI=0.20-1.17) with significant lower incidence of TMA in rTM group (Fig 2.). In a trial, seven of nine patients recovered from TA-TMA in the rTM group, but none recovered in the control group who received various therapies including fresh frozen plasma, therapeutic plasma exchange(TPE) or others (p=0.003) (Fujiwara et al). The risk of GVHD was also significantly lower in rTM group and RR was 0.48 (I2= 64%, 95% CI=0.32-0.72) which again favours rTM vs heparin or no therapy (Fig 3.). Ishii et al showed that stepwise multivariate logistic regression analyses revealed that anti-coagulation therapy without rTM was an independent risk factor for aGVHD (p=0.000, odds ratio=3.006) and VOD (p=0.015, odds ratio=2.65). Yakushijin et al compared rTM with Defibrotide and found similar complete remission (CR) rate and the overall survival (OS) at day 100 in both the groups. Therefore, rhTM could be one of the potential novel candidate for SOS treatment. Use of rTM improved the survival rate of patients with disseminated intravascular coagulation (DIC), diagnosed according to the criteria established by the Ministry of Health, Labor and Welfare of Japan, at day 100 (83% vs. 50%, P = 0.026) and significantly prolonged the OS of these patients (P = 0.044). The Kaplan-Meier curves clearly showed the improved non-relapse-related mortality of patients who received rTM after HSCT (Ikezoe et al). Mean DIC scores improved significantly with the use of rhTM (p = 0.003; DIC withdrawal rate 91.7%). FDP and CRP levels were also significantly decreased (p = 0.042 and p = 0.001). The recovery rate from DIC at 28 days was significantly better in rTM than in antithrombin or heparin group (p = 0.011) (Inoue et al). The mean peak plasminogen activator inhibitor type one (PAI- 1) level was significantly lower in the rTM group vs heparin and ursodiol group (P = 0.04), and the mean peak activated protein C (APC) level was significantly higher in the rTM group (P = 0.01) (Yamamoto et al). No serious grade 3 or 4 adverse events were reported by trials. Conclusion: This systematic review and meta-analysis shows that prophylactic rTM (380 units/kg) has a beneficial role in the prevention of post- HSCT SOS complication in patients that are at high risk of developing the condition. It appears to help improve treatment-related mortality and overcome the poor survival rates. Additional randomized clinical trials are needed to establish efficacy and safety of rTM to prevent VOD and to confirm these results. Disclosures Anwer: Celgene: Research Funding; Millennium Pharmaceuticals: Research Funding; Astellas Pharma: Research Funding; Acetylon Pharmaceuticals: Research Funding; Seattle Genetics: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Speakers Bureau; AbbVie Pharmaceuticals: Research Funding; Incyte Pharmaceuticals: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Speakers Bureau.
Background: Hospital associated Methicillin-resistant Staphylococcus aureus (MRSA) is a serious health concern, as its infection is associated with high rates of mortality and morbidity. Health care professionals around the globe are concerned by the increased prevalence of these bacteria in the hospital environment. With this background in mind, this study was conducted to determine the frequency of nasal colonization of methicillin-resistant staphylococcus in attendants of admitted patients in a tertiary care hospital in Pakistan. Material and Methods: A cross-sectional study was conducted in Holy Family Hospital, Rawalpindi, Pakistan from 10th May to 31st August, 2016. Attendants of sixty admitted patients were selected by simple random sampling. Two nasal swabs samples were obtained from these attendants; the first at the beginning of the study with a hospital stay of less than 12 hours, and the second when their stay in the hospital had exceeded 48 hours. The samples were cultured on Cystine lactose electrolyte deficient agar, Mannitol Salt Agar, and Nutrient Agar. The colonies were subjected to Gram staining, catalase test, coagulase test, and methicillin/oxacillin sensitivity using the Kirby-Bauer’s disc diffusion method. Frequencies and percentages were calculated. Chi-Square test was applied and statistical significance calculated for the demographic data. Results: The first culture report (at <12 hours hospital stay) showed that 46/60 (76.7%) attendants were not found to have any resistant strain of Staphylococcus. These 46 attendants were then subjected to a second culture (after 48 hours hospital stay), which showed that 24/46 (52.2%) were now colonized with methicillin-resistant Staphylococcus species (MRSA; n=7 and MR other than S. aureus; n=17). There was no statistically significant difference between colonization of isolates and relationship to gender, age, residence, and co-morbid conditions. Conclusions: The frequency of colonization with resistant strains of Staphylococcus aureus in attendants of admitted patients increased after being exposed to the hospital environment for more than forty-eight hours.
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