Key Points• TKIs impair B-cell immune responses in CML through off-target inhibition of kinases important for B-cell signaling.• Our results call for close monitoring of patients on TKI to assess the long-term impact of impaired B-cell function.Tyrosine kinase inhibitors (TKIs) have significant off-target multikinase inhibitory effects. We aimed to study the impact of TKIs on the in vivo B-cell response to vaccination. Cellular and humoral responses to influenza and pneumococcal vaccines were evaluated in 51 chronic phase chronic myeloid leukemia (CML) patients on imatinib, or second-line dasatinib and nilotinib, and 24 controls. Following vaccination, CML patients on TKI had significant impairment of IgM humoral response to pneumococcus compared with controls (IgM titer 79.0 vs 200 U/mL, P 5 .0006), associated with significantly lower frequencies of peripheral blood IgM memory B cells. To elucidate whether CML itself or treatment with TKI was responsible for the impaired humoral response, we assessed memory B-cell subsets in paired samples collected before and after imatinib therapy. Treatment with imatinib was associated with significant reductions in IgM memory B cells. In vitro coincubation of B cells with plasma from CML patients on TKI or with imatinib, dasatinib, or nilotinib induced significant and dose-dependent inhibition of Bruton's tyrosine kinase and indirectly its downstream substrate, phospholipase-C-g2, both important in B-cell signaling and survival. These data indicate that TKIs, through off-target inhibition of kinases important in B-cell signaling, reduce memory B-cell frequencies and induce significant impairment of B-cell responses in CML. (Blood. 2013;122(2):227-238)

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Background Biliary leaks and anastomotic strictures are common early anastomotic biliary complications (EABCs) following liver transplantation. However, there are no large multicentre studies investigating their clinical impact or risk factors. This study aimed to define the incidence, risk factors and impact of EABC. Methods The NHS registry on adult liver transplantation between 2006 and 2017 was reviewed retrospectively. Adjusted regression models were used to assess predictors of EABC, and their impact on outcomes. Results Analyses included 8304 liver transplant recipients. Patients with EABC (9·6 per cent) had prolonged hospitalization (23 versus 15 days; P < 0·001) and increased chance for readmission within the first year (56 versus 32 per cent; P < 0·001). Patients with EABC had decreased estimated 5-year graft survival of 75·1 versus 84·5 per cent in those without EABC, and decreased 5-year patient survival of 76·9 versus 83·3 per cent; both P < 0.001. Adjusted Cox regression revealed that EABCs have a significant and independent impact on graft survival (leak hazard ratio (HR) 1·344, P = 0·015; stricture HR 1·513, P = 0·002; leak plus stricture HR 1·526, P = 0·036) and patient survival (leak HR 1·215, P = 0·136, stricture HR 1·526, P = 0·001; leak plus stricture HR 1·509; P = 0·043). On adjusted logistic regression, risk factors for EABC included donation after circulatory death grafts, graft aberrant arterial anatomy, biliary anastomosis type, vascular anastomosis time and recipient model of end-stage liver disease. Conclusion EABCs prolong hospital stay, increase readmission rates and are independent risk factors for graft loss and increased mortality. This study has identified factors that increase the likelihood of EABC occurrence; research into interventions to prevent EABCs in these at-risk groups is vital to improve liver transplantation outcomes.

on outcomes. A lower risk of late relapse was seen with several cGVHD specific variables (P\0.0001), i.e., mild, moderate or severe cGVHD; de novo or progressive cGVHD; or involvement of any organ with cGVHD. These results demonstrate a protective effect of cGVHD on late relapse only in CML. In addition, presence of cGVHD by 1 year after HCT was associated with a higher risk of TRM and inferior OS in all patients (CML, AML, ALL, MDS). Since the protective effect of cGVHD on late relapse was seen only in CML patients, more aggressive measures to control cGVHD may be beneficial especially in AML, ALL and MDS patients after high intensity conditioning regimen.

Retraction: “Genistein enhances the effect of epidermal growth factor receptor tyrosine kinase inhibitors and inhibits nuclear factor kappa B in nonsmall cell lung cancer cell lines” by Gadgeel SM, Ali S, Philip PA, Wozniak A, Sarkar FH. The above article, published in Wiley Online Library (http://wileyonlinelibrary.com), has been retracted by agreement amongst the journal Editor in Chief, Fadlo R. Khuri; Wiley Periodicals, Inc.; and the American Cancer Society following an investigation by Wayne State University into the research activities of the second and last authors. The investigation found that the Western blot images of Figures 4A, 4B, and 4C were re‐ordered and manipulated to misrepresent the results. The investigation committee concluded that this undermined the scientific basis of the publication, that no credible replacement data were available, and advised that the publication should be retracted. REFERENCE

OBJECTIVES To assess systemic immune-compromised comorbidities in patients presenting with odontogenic infections that extend to fascial spaces. This study was designed to investigate the incidence of immune-compromising systemic comorbidities among patient presenting with odontogenic infections.METHODOLOGY This cross-sectional study was performed at the Department of Maxillofacial Surgery, Hayatabad Medical Complex (HMC) Peshawar from October 2018 through April 2019. However, patients older than 10 years of age, presenting with fascial space infections other than odontogenic cause, secondary fascial space infections and patients with multiple organ failure were excluded. The odontogenic infections were categorized according to their anatomical location. The prevalence of comorbidities was also assessed.RESULTSA total of 145 patients were included, where the male to female ratio was 3.8:1, mean age ~ 56 ± 14.74 years (range: 12-80 years) and mean duration of the odontogenic infections was 5± 1.2 days. The submandibular space was the most frequent site involved in odontogenic infections with a frequency of 60 (41.4%), followed by buccal space with 44 (30.3%) patients &    canine space with 31 (21.4%) patients. Of the 79 patients with comorbidities out of total 145 patients, diabetes mellitus was recorded in 60 patients. Other comorbidities included hypertension, renal and hepatic impairment. CONCLUSION Diabetes mellitus was the most common immune compromising comorbidity presented in patients with odontogenic infections extending in fascial spaces. Assessment of diabetes in routine dental practice is emphasized to avoid exacerbation of the odontogenic infections.