Pain quality patterns in delayed onset muscle soreness of the lower back suggest sensitization of fascia rather than muscle afferents: a secondary analysis study.

Delayed onset muscle soreness (DOMS) of the lower back is considered a surrogate for acute low back pain (aLBP) in experimental studies. Of note, it is often unquestioningly assumed to be muscle pain. To date, there has not been a study analyzing lumbar DOMS in terms of its pain origin, which was the aim of this study. Sixteen healthy individuals (L-DOMS) were enrolled for the present study and matched to participants from a previous study (n = 16, L-PAIN) who had undergone selective electrical stimulation of the thoracolumbar fascia and the multifidus muscle. DOMS was induced in the lower back of the L-DOMS group using eccentric trunk extensions performed until exhaustion. On subsequent days, pain on palpation (100-mm analogue scale), pressure pain threshold (PPT), and the Pain Sensation Scale (SES) were used to examine the sensory characteristics of DOMS. Pain on palpation showed a significant increase 24 and 48 h after eccentric training, whereas PPT was not affected (p > 0.05). Factor analysis of L-DOMS and L-PAIN sensory descriptors (SES) yielded a stable three-factor solution distinguishing superficial thermal ("heat pain ") from superficial mechanical pain ("sharp pain") and "deep pain." "Heat pain " and "deep pain" in L-DOMS were almost identical to sensory descriptors from electrical stimulation of fascial tissue (L-PAIN, all p > 0.679) but significantly different from muscle pain (all p < 0.029). The differences in sensory description patterns as well as in PPT and self-reported DOMS for palpation pain scores suggest that DOMS has a fascial rather than a muscular origin.

Influence of hyperthermic intraperitoneal chemotherapy on renal blood perfusion.

PURPOSE: Hyperthermic intraperitoneal chemotherapy (HIPEC) is accompanied with an increased risk of acute kidney injury (AKI). Whether AKI is induced by chemotoxicity or hyperthermia-related changes in renal perfusion remains controversial. The influence of HIPEC on renal perfusion has not been evaluated in patients yet. METHODS: Renal blood perfusion was assessed in ten patients treated with HIPEC by intraoperative renal Doppler pulse-wave ultrasound. Ultrasound (US) examinations were performed pre-, intra-, and postoperative with analyses of time-velocity curves. Patient demographics, surgical details, and data regarding renal function were recorded perioperatively. For evaluation of renal Doppler US to predict AKI, patients were divided in two groups with (AKI +) and without (AKI -) kidney injury. RESULTS: Throughout HIPEC perfusion, neither significant nor consistent changes in renal perfusion could be observed. Postoperative AKI occurred in 6 of 10 participating patients. Intraoperative renal resistive index (RRI) values > 0.8 were observed in one patient developing stage 3 AKI according KDIGO criteria. At 30 min in perfusion, RRI values were significantly higher in AKI + patients. CONCLUSION: AKI is a common and frequent complication after HIPEC, but underlying pathophysiology remains elusive. High intraoperative RRI values may indicate an increased risk of postoperative AKI. Present data challenges the relevance of hyperthermia-derived hypothesis of renal hypoperfusion with prerenal injury during HIPEC. More attention should be drawn towards chemotoxic-induced hypothesis of HIPEC-induced AKI and caution applying regimens containing nephrotoxic agents in patients. Further confirmatory and complementary studies on renal perfusion as well as pharmacokinetic HIPEC studies are required.

Effects of Maximal Eccentric Trunk Extensor Exercise on Lumbar Extramuscular Connective Tissue: A Matched-Pairs Ultrasound Study.

Recently, it has been shown that the extramuscular connective tissue (ECT) is likely involved in delayed onset muscle soreness (DOMS). Therefore, the aim of the present study was to investigate the effects of maximal trunk extension eccentric exercise (EE) on ECT thickness, self-reported DOMS, ECT stiffness, skin temperature, and possible correlations between these outcomes. Healthy adults (n = 16, 29.34 ± 9.87 years) performed fatiguing EE of the trunk. A group of highly active individuals (TR, n = 8, > 14 h of sport per week) was compared with a group of less active individuals (UTR, n = 8, < 2 h of sport per week). Ultrasound measurements of ECT thickness, stiffness with MyotonPro and IndentoPro, skin temperature with infrared thermography, and pain on palpation (100 mm visual analog scale, VAS) as a surrogate for DOMS were recorded before (t0), immediately (t1), 24 h (t24), and 48 h (t48) after EE. ECT thickness increased after EE from t0 to t24 (5.96 mm to 7.10 mm, p = 0.007) and from t0 to t48 (5.96 mm to 7.21 mm, p < 0.001). VAS also increased from t0 to t24 (15.6 mm to 23.8 mm, p < 0.001) and from t0 to t48 (15.6 mm to 22.8 mm, p < 0.001). Skin temperature increased from t1 to t24 (31.6° Celsius to 32.7° Celsius, p = 0.032) and t1 to t48 (31.6° Celsius to 32.9° Celsius, p = 0.003), while stiffness remained unchanged (p > 0.05). Correlation analysis revealed no linear relationship between the outcomes within the 48-hour measurement period. The results may confirm previous findings of possible ECT involvement in the genesis of DOMS in the extremities also for the paraspinal ECT of trunk extensors. Subsequent work should focus on possible interventions targeting the ECT to prevent or reduce DOMS after strenuous muscle EE.

Sodium Thiosulfate Reduces Acute Kidney Injury in Patients Undergoing Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy with Cisplatin: A Single-Center Observational Study.

BACKGROUND: Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) represents a multimodal treatment concept for patients with peritoneal surface malignancies. The use of intraperitoneal cisplatin (CDDP) is associated with a risk of acute kidney injury (AKI). The aim of this study is to evaluate the protective effect of perioperative sodium thiosulfate (STS) administration on kidney function in patients undergoing CRS and CDDP-based HIPEC. PATIENTS AND METHODS: We retrospectively analyzed clinical data of all patients who underwent CRS and CDDP-based HIPEC at our hospital between March 2017 and August 2020. Patients were stratified according to the use of sodium thiosulfate (STS vs. no STS). We compared kidney function and clinical outcome parameters between both groups and determined risk factors for postoperative AKI on univariate and multivariate analysis. AKI was classified according to acute kidney injury network (AKIN) criteria. RESULTS: Of 238 patients who underwent CRS and CDDP-based HIPEC, 46 patients received STS and 192 patients did not. There were no significant differences in baseline characteristics. In patients who received STS, a lower incidence (6.5% vs. 30.7%; p = 0.001) and severity of AKI (p = 0.009) were observed. On multivariate analysis, the use of STS (OR 0.089, p = 0.001) remained an independent kidney-protective factor, while arterial hypertension (OR 5.283, p < 0.001) and elevated preoperative urea serum level (OR 5.278, p = 0.032) were predictors for postoperative AKI. CONCLUSIONS: The present data suggest that STS protects patients from AKI caused by CRS and CDDP-based HIPEC. Further prospective studies are needed to validate the benefit of STS among kidney-protective strategies.

Systematic review and meta-analysis of endoscopic ultrasound drainage for the management of fluid collections after pancreas surgery.

BACKGROUND: The outcomes of endoscopic ultrasonography-guided drainage (EUSD) in treatment of pancreas fluid collection (PFC) after pancreas surgeries have not been evaluated systematically. The current systematic review and meta-analysis aim to evaluate the outcomes of EUSD in patients with PFC after pancreas surgery and compare it with percutaneous drainage (PCD). METHODS: PubMed and Web of Science databases were searched for studies reporting outcomes EUSD in treatment of PFC after pancreas surgeries, from their inception until January 2022. Two meta-analyses were performed: (A) a systematic review and single-arm meta-analysis of EUSD (meta-analysis A) and (B) two-arm meta-analysis comparing the outcomes of EUSD and PCD (meta-analysis B). Pooled proportion of the outcomes in meta-analysis A as well as odds ratio (OR) and mean difference (MD) in meta-analysis B was calculated to determine the technical and clinical success rates, complications rate, hospital stay, and recurrence rate. ROBINS-I tool was used to assess the risk of bias. RESULTS: The literature search retrieved 610 articles, 25 of which were eligible for inclusion. Included clinical studies comprised reports on 695 patients. Twenty-five studies (477 patients) were included in meta-analysis A and eight studies (356 patients) were included in meta-analysis B. In meta-analysis A, the technical and clinical success rates of EUSD were 94% and 87%, respectively, with post-procedural complications of 14% and recurrence rates of 9%. Meta-analysis B showed comparable technical and clinical success rates as well as complications rates between EUSD and PCD. EUSD showed significantly shorter duration of hospital stay compared to that of patients treated with PCD. CONCLUSION: EUSD seems to be associated with high technical and clinical success rates, with low rates of procedure-related complications. Although EUSD leads to shorter hospital stay compared to PCD, the certainty of evidence was low in this regard.

Halting the vicious cycle within the multiple myeloma ecosystem: blocking JAM-A on bone marrow endothelial cells restores angiogenic homeostasis and suppresses tumor progression.

Interactions of malignant multiple myeloma (MM) plasma cells (MM-cells) with the microenvironment control MM-cell growth, survival, drug-resistance and dissemination. As in MM microvascular density increases in the bone marrow (BM), we investigated whether BM MM endothelial cells (MMECs) control disease progression via the junctional adhesion molecule A (JAM-A). Membrane and cytoplasmic JAM-A levels were upregulated in MMECs in 111 newly diagnosed (NDMM) and 201 relapsed-refractory (RRMM) patients compared to monoclonal gammopathy of undetermined significance (MGUS) and healthy controls. Elevated membrane expression of JAM-A on MMECs predicted poor clinical outcome. Mechanistically, addition of recombinant JAM-A to MMECs increased angiogenesis whereas its inhibition impaired angiogenesis and MM growth in 2D and 3D in vitro cell culture and chorioallantoic membrane-assays. To corroborate these findings, we treated MM bearing mice with JAM-A blocking mAb and demonstrated impaired MM progression corresponding to decreased MM-related vascularity. These findings support JAM-A as an important mediator of MM progression through facilitating MM-associated angiogenesis. Collectively, elevated JAM-A expression on bone marrow endothelial cells is an independent prognostic factor for patient survival in both NDMM and RRMM. Blocking JAM-A restricts angiogenesis in vitro, in embrio and in vivo and represents a suitable druggable molecule to halt neoangiogenesis and MM progression.

Transplantation programs facing lack of empirical evidence on SARS-CoV-2 vaccination: A society recommendation consensus update.

BACKGROUND: Since phase III trials for the most prominent vaccines excluded immunocompromised or immunosuppressed patients, data on safety and efficacy of SARS-CoV-2 vaccines for recipients of solid organ transplantations are scarce. AIMS: Our study offers a synthesis of expert opinions aligned with available data addressing key questions of the clinical management of SARS-CoV-2 vaccinations for transplant patients. METHOD: An online research was performed retrieving available recommendations by national and international transplantation organizations and state institutions on SARS-CoV2 vaccination management for transplant recipients. RESULTS: Eleven key statements were identified from recommendations by 18 national and international societies, and consensus for the individual statements was evaluated by means of the Society Recommendation Consensus score. The highest consensus level (SRC A) was found for prioritized access to vaccination for transplant patients despite anticipation of a weakened immune response. All currently authorized vaccines can be considered safe for transplant patients (SRC A). The handling of immunosuppressive medication, the timely management of vaccines, and other aspects were aligned with available expert opinions. CONCLUSION: Expert consensus can be determined for crucial aspects of the implementation of SARS-CoV-2 vaccination programs. We hereby offer a tool for immediate decision-making until empirical data becomes available.

Solid organ transplantation programs facing lack of empiric evidence in the COVID-19 pandemic: A By-proxy Society Recommendation Consensus approach.

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has a drastic impact on national health care systems. Given the overwhelming demand on facility capacity, the impact on all health care sectors has to be addressed. Solid organ transplantation represents a field with a high demand on staff, intensive care units, and follow-up facilities. The great therapeutic value of organ transplantation has to be weighed against mandatory constraints of health care capacities. In addition, the management of immunosuppressed recipients has to be reassessed during the ongoing coronavirus disease 2019 (COVID-19) pandemic. In addressing these crucial questions, transplant physicians are facing a total lack of scientific evidence. Therefore, the aim of this study was to offer an approach of consensus-based guidance, derived from individual information of 22 transplant societies. Key recommendations were extracted and the degree of consensus among different organizations was calculated. A high degree of consensus was found for temporarily suspending nonurgent transplant procedures and living donation programs. Systematic polymerase chain reaction-based testing of donors and recipients was broadly recommended. Additionally, more specific aspects (eg, screening of surgical explant teams and restricted use of marginal donor organs) were included in our analysis. This study offers a novel approach to informed guidance for health care management when a priori no scientific evidence is available.

Peritoneal metastasis in gastric cancer: results from the German database.

BACKGROUND: Patients with peritoneal metastases of gastric cancer have a poor prognosis with a median survival of 7 months. A benefit of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) could be shown in several selected patient cohorts but remains controversial. The aim of this study was, to reflect the results of a national German HIPEC registry initiated by the German Society of General and Visceral Surgery (DGAV). METHODS: The DGAV HIPEC registry StuDoQ|Peritoneum documents patients with peritoneal malignancy contributed from 52 hospitals. All consecutive documented patients from 2011 until 2016 (n = 3078) were treated with CRS and HIPEC and were analysed. A total of 315 (10%) suffered from gastric cancer and were analysed. RESULTS: A complete data set of 235 patients was available for this study, including 113 male (48.1%) and 122 female (51.9%) patients with a median age of 53.4 years (SD ± 11.9). The median PCI was 8.0 (range 1-30). A complete cytoreduction was achieved in 121 patients (71.6%). Postoperative complications (Clavien-Dindo grades 3-4) occurred in 40 patients (17%). The median overall survival (OS) time was 13 months. The 5-year survival rate was 6%. According to the PCI from 0-6 (n = 74); 7-15 (n = 70) and 16-39 (n = 24) the median OS differs significantly (18 months vs. 12 months vs. 5 months; p = 0.002). CONCLUSIONS: CRS and HIPEC in selected patients with gastric cancer and peritoneal spread can improve survival when they are treated in centers. An accurate staging and patient selection are of major importance to achieve long-term survival.

The efficacy of treatment options for patients with gastric cancer and peritoneal metastasis.

BACKGROUND: Patients with peritoneal metastases of gastric cancer have a poor prognosis and median survival of 7 months. This study compared treatment options and outcomes based on the Peritoneal Cancer Index (PCI). METHODS: This retrospective analysis included patients with gastric cancer treated between August 2008 and December 2017 with synchronous peritoneal metastases only diagnosed by laparoscopy. The three treatments were as follows: (1) cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in combination with pre- and postoperative systemic chemotherapy (n = 58), (2) laparotomy/laparoscopy without CRS, but HIPEC in combination with pre- and postoperative systemic chemotherapy (n = 11), and (3) systemic chemotherapy only (n = 19). RESULTS: A total of 88 patients aged 54.6 ± 10.9 years with mean PCI of 14.3 ± 11.3 were included. The PCI was significantly lower in group 1 (8.3 ± 5.7) than in group 2 (23.9 ± 11.1, p < 0.001) and group 3 (27.3 ± 9.3, p < 0.001). Mean time from diagnosis to laparoscopy was 5.2 ± 2.9 months. The median overall survival was 9.8 ± 0.7 for group 1, 6.3 ± 3.0 for group 2 and 4.9 ± 1.9 months for group 3 (p < 0.001). Predictors for deteriorated overall patient survival included > 4 cycles of preoperative chemotherapy (HR 4.49, p < 0.001), lymph-node metastasis (HR 3.53, p = 0.005), PCI ≥ 12 (HR 2.11, p = 0.036), and incompleteness of cytoreduction (HR 4.30, p = 0.001) in patients treated with CRS and HIPEC. CONCLUSION: CRS and HIPEC showed convincing results in selected patients with PCI < 12 and complete cytoreduction. Prolonged duration (> 4 cycles) of preoperative intravenous chemotherapy reduced patient survival in patients suitable for CRS and HIPEC.

Safety of extraperitoneal rectal resection and ileo- or colorectal anastomosis without loop ileostomy in patients with peritoneal metastases treated with CRS and HIPEC.

AIM: Extraperitoneal rectal resection combined with complete peritonectomy of the pelvis in patients with peritoneal metastases is associated with a high rate of morbidity and mortality due to anastomotic leakage (AL). Therefore, many centers tend to perform loop ileostomy to reduce the clinical impact of AL. The aim of this study was to analyze the need for protective stoma creation in this patient group to avoid major complications and mortality in the case of AL. METHOD: We analyzed 53 patients who underwent extraperitoneal rectal resection from 409 consecutive patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) at our department between January 1997 and December 2016. RESULTS: Mean age of the patients was 56.7 (SD 12.2) years and the mean Peritoneal Cancer Index was 24.6 (SD 12.0). Complete cytoreduction was achieved in 33 patients (62.3%). Six patients received an ileostomy or a colostomy, 5 of 6 with permanent intention. One patient (2.1%) developed AL postoperatively. Overall, 21 patients (39.6%) developed surgical complications, while 41 (77.3%) developed medical complications. The mortality rate was 7.5% (n = 4). In total, 26 patients (49.1%) developed Clavien-Dindo class-III/IV complications. CONCLUSIONS: These results demonstrate the safety of colorectal anastomosis in combination with HIPEC in the absence of loop ileostomy. Loop ileostomy may be omitted for patients with low risk for AL in experienced centers with adequate post-operative care, possibilities for post-operative assessment and radiological intervention to avoid stoma related complications and increase the quality of life of patients with peritoneal metastases. This article is protected by copyright. All rights reserved.

Predictive value of peritoneal cancer index for survival in patients with mucinous peritoneal malignancies treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: a single centre experience.

OBJECTIVES: This study investigated the correlation between the peritoneal carcinomatosis index (PCI) and patient outcome depending on the tumour type. BACKGROUND: Peritoneal surface malignancy (PSM) treatment depends on tumour type. Mucinous PSM (m-PSM) is associated with a better prognosis than non-mucinous PSM (nm-PSM). The PCI's predictive ability has not yet been evaluated. METHODS: We analysed 123 patients with PSM treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) between 2008 and 2015. The m-PSM group (n = 75) included patients with appendiceal cancer (n = 15), colorectal cancer (n = 21), or low-grade appendiceal mucinous neoplasm (n = 39); the nm-PSM group (n = 48) included patients with gastric (n = 18) or colorectal (n = 30) cancer. The PCI's predictive ability was evaluated by multiple Cox-proportional hazard regression analysis and Kaplan-Meier curves. RESULTS: The 5-year survival and PCI were higher in m-PSM patients (67.0%; 20.5 ± 12.1) than in nm-PSM patients (32.6%; p = 0.013; 8.9 ± 6.0; p < 0.001). Colorectal nm-PSM patients with PCI ≥16 had a worse 2-year survival (25.0%) vs. patients with PCI <16 (79.1%; log rank = 0.009), but no significant effect was observed in patients with m-PSM (66.7% vs. 68.1%; p = 0.935). Underlying disease (HR 5.666-16.240), BMI (HR 1.109), and PCI (HR 1.068) significantly influenced overall survival in all patients. CONCLUSIONS: PCI is prognostic in nm-PSM, but not in m-PSM. CRS and HIPEC may benefit not only patients with low PCI, but also those with high PCI and m-PSM.

The microprocessor component, DGCR8, is essential for early B-cell development in mice.

microRNAs (miRNAs) are important posttranscriptional regulators during hematopoietic lineage commitment and lymphocyte development. Mature miRNAs are processed from primary miRNA transcripts in two steps by the microprocessor complex, consisting of Drosha and its partner DiGeorge Critical Region 8 (DGCR8), and the RNAse III enzyme, Dicer. Conditional ablations of Drosha and Dicer have established the importance of both RNAses in B- and T-cell development. Here, we show that a cre-mediated B-cell specific deletion of DGCR8 in mice results in a nearly complete maturation block at the transition from the pro-B to the pre-B cell stage, and a failure to upregulate Ig µ heavy chain expression in pro-B cells. Furthermore, we found that the death of freshly isolated DGCR8-deficient pro-B cells could be partially prevented by enforced Bcl2 expression. We conclude from these findings that the microprocessor component DGCR8 is essential for survival and differentiation of early B-cell progenitors.

Prognostic Significance of Tumor Necrosis in Hilar Cholangiocarcinoma.

BACKGROUND: Tumor necrosis and peritumoral fibrosis have both been suggested to have a prognostic value in selected solid tumors. However, little is known regarding their influence on tumor progression and prognosis in hilar cholangiocarcinoma (HC). METHODS: Surgically resected tumor specimens of HC (n = 47) were analyzed for formation of necrosis and extent of peritumoral fibrosis. Tumor necrosis and grade of fibrosis were assessed histologically and correlated with clinicopathological characteristics, tumor recurrence, and patients' survival. Univariate Kaplan-Meier analysis and a stepwise multivariable Cox regression model were applied. RESULTS: Mild peritumoral fibrosis was evident in 12 tumor samples, moderate peritumoral fibrosis in 20, and high-grade fibrosis in 15. Necrosis was evident in 19 of 47 tumor samples. Patients with tumors characterized by necrosis showed a significantly decreased 5-year recurrence-free survival (37.9 vs. 25.7 %; p < .05) and a significantly decreased 5-year overall survival (42.6 vs. 12.4 %; p < .05), when compared with patients with tumors showing no necrosis. R status, tumor recurrence, and tumor necrosis were of prognostic value in the univariate analysis (all p < .05). Multivariate survival analysis confirmed tumor necrosis (p = .038) as the only independent prognostic variable. CONCLUSIONS: The assessment of tumor necrosis appears as a valuable additional prognostic tool in routine histopathological evaluation of HC. These observations might have implications for monitoring and more individualized multimodal therapeutic strategies.

Blocking TWEAK-Fn14 interaction inhibits hematopoietic stem cell transplantation-induced intestinal cell death and reduces GVHD.

Inhibition of the tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) system reduces intestinal cell death and disease development in several models of colitis. In view of the crucial role of TNF and intestinal cell death in graft-versus-host disease (GVHD) and the ability of TWEAK to enhance TNF-induced cell death, we tested here the therapeutic potential of Fn14 blockade on allogeneic hematopoietic cell transplantation (allo-HCT)-induced intestinal GVHD. An Fn14-specific blocking human immunoglobulin G1 antibody variant with compromised antibody-dependent cellular cytotoxicity (ADCC) activity strongly inhibited the severity of murine allo-HCT-induced GVHD. Treatment of the allo-HCT recipients with this monoclonal antibody reduced cell death of gastrointestinal cells but neither affected organ infiltration by donor T cells nor cytokine production. Fn14 blockade also inhibited intestinal cell death in mice challenged with TNF. This suggests that the protective effect of Fn14 blockade in allo-HCT is based on the protection of intestinal cells from TNF-induced apoptosis and not due to immune suppression. Importantly, Fn14 blockade showed no negative effect on graft-versus-leukemia/lymphoma (GVL) activity. Thus, ADCC-defective Fn14-blocking antibodies are not only possible novel GVL effect-sparing therapeutics for the treatment of GVHD but might also be useful for the treatment of other inflammatory bowel diseases where TNF-induced cell death is of relevance.

miR-148a promotes plasma cell differentiation and targets the germinal center transcription factors Mitf and Bach2.

B cells undergo affinity maturation and class switch recombination of their immunoglobulin receptors during a germinal center (GC) reaction, before they differentiate into long-lived antibody-secreting plasma cells (PCs). Transcription factors such as Bach2 and Mitf are essential during this process, as they delay premature differentiation of GC B cells by repressing Blimp-1 and IRF4, two transcription factors required for terminal PC differentiation. Therefore, Bach2 and Mitf expression must be attenuated in activated B cells to allow terminal PC differentiation, but the precise mechanism remains enigmatic. Here, we provide evidence that miR-148a, a small noncoding microRNA, fosters PC differentiation and survival. Next-generation sequencing revealed that miR-148a is the most abundant microRNA in primary human and murine PCs, and its expression is upregulated in activated murine B cells and coincides with Blimp-1 synthesis. miR-148a targets Bach2, Mitf and proapoptotic factors such as PTEN and Bim. When prematurely expressed, miR-148a promotes the differentiation and survival of plasmablasts and reduces frequencies of IgG1(+) cells in primary B-cell cultures. In summary, we propose that miR-148a is a new player in the regulatory network controlling terminal PC differentiation and could, therefore, be a therapeutic target for interfering with PC differentiation and survival.

Prognostic significance of TIE2-expressing monocytes in hilar cholangiocarcinoma.

BACKGROUND AND OBJECTIVES: Angiopoietins (Angs) play a pivotal role in angiogenesis and inflammation, and are associated with prognosis in malignancies. Monocyte express Ang-receptor TIE2 and correlate with prognosis in cancer. We aimed to investigate the prognostic value of Angs and TIE2-expressing monocytes (TEMs) in cholangiocarcinoma. METHODS: We analyzed surgically resected tumor specimens of hilar cholangiocarcinoma (n = 47) for distribution of Angs (Ang 1/Ang 2) and TEMs, as defined by co-expression of CD14 and Ang receptor TIE2. Ang expression and abundance of TEMs were correlated with clinicopathologic characteristics, tumor recurrence and patients' survival. RESULTS: High Ang 1 expression correlated with reduced metastasis (P < 0.05). Patients characterized by invading Ang-receptor bearing TEMs in tumor showed lower tumor recurrence (P < 0.05). Furthermore, TEMs in tumor and tumor invasive front correlated with increased survival (P < 0.05). TEMs in tumor invasive front were confirmed as independent prognosticator in multivariate survival analysis (P < 0.05). CONCLUSIONS: High Ang 1 expression in hilar cholangiocarcinoma and infiltration of TEMs defines a subgroup of patients with beneficial tumor characteristics and prolonged survival. Besides suggested functional links between Ang expression and recruitment of TEMs, our data have possible clinical implications as novel diagnostic tools. J. Surg. Oncol. 2016;114:91-98. © 2016 Wiley Periodicals, Inc.

Inferior graft survival of hepatitis B core positive grafts is not influenced by post-transplant hepatitis B infection in liver recipients--5-year single-center experience.

Nonoptimal liver grafts, and among them organs from anti-HBc+ donors, are increasingly used for liver transplantation. In this retrospective study including 1065 adult liver transplantations performed between 1977 and 2012, we analyzed long-term patient and graft survival and occurrence of HBV infection. A total of 52 (5.1%) patients received an anti-HBc+ graft. The 10-year graft and patient survival of these recipients were 50.9% and 59.0% compared to 72.0% and 76.5% (P = 0.001; P = 0.004) of patients receiving anti-HBc- grafts, respectively. Cox regression model showed that high urgency allocation (P = 0.003), recipient age (P = 0.027), anti-HCV+ recipients (P = 0.005), and anti-HBc+ organs (P = 0.048) are associated with decreased graft survival. Thirteen of 52 (25.0%) patients receiving anti-HBc+ grafts developed post-transplant HBV infection within a mean of 2.8 years. In this study, antiviral prophylaxis did not have significant impact on HBV infection, but long-term survival (P = 0.008). Development of post-transplant HBV infection did not affect adjusted 10-year graft survival (100% vs. 100%; P = 1). Anti-HBc+ liver grafts can be transplanted with reasonable but inferior long-term patient and graft survival. The inferior graft survival is not, however, related with post-transplant HBV infection as long as early diagnosis and treatment take place.