Selenium-Enriched Cardamine violifolia Alleviates LPS-Induced Hepatic Damage and Inflammation by Suppressing TLR4/NODs-Necroptosis Signal Axes in Piglets.

Selenium-enriched Cardamine violifolia (SEC), a cruciferous plant, exerts excellent antioxidant and anti-inflammatory capacity, but its effect on hepatic function is unclear. This study investigated the effect and potential mechanism of SEC on hepatic injury induced by lipopolysaccharide (LPS). Twenty-four weaned piglets were randomly allotted to treatment with SEC (0.3 mg/kg Se) and/or LPS (100 µg/kg). After 28 days of the trial, pigs were injected with LPS to induce hepatic injury. These results indicated that SEC supplementation attenuated LPS-induced hepatic morphological injury and reduced aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities in plasma. SEC also inhibited the expression of pro-inflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) after the LPS challenge. In addition, SEC improved hepatic antioxidant capacity via enhancing glutathione peroxidase (GSH-Px) activity and decreasing malondialdehyde (MDA) concentration. Moreover, SEC downregulated the mRNA expression of hepatic myeloid differentiation factor 88 (MyD88) and nucleotide-binding oligomerization domain proteins 1 (NOD1) and its adaptor molecule receptor interacting protein kinase 2 (RIPK2). SEC also alleviated LPS-induced hepatic necroptosis by inhibiting RIPK1, RIPK3, and mixed-lineage kinase domain-like (MLKL) expression. These data suggest that SEC potentially mitigates LPS-induced hepatic injury via inhibiting Toll-like receptor 4 (TLR4)/NOD2 and necroptosis signaling pathways in weaned piglets.

Application of opioid-free general anesthesia for gynecological laparoscopic surgery under ERAS protocol: a non-inferiority randomized controlled trial.

BACKGROUND: Enhanced recovery after surgery (ERAS) is now widely used in various surgical fields including gynecological laparoscopic surgery, but the advantages of opioid-free anesthesia (OFA) in gynecological laparoscopic surgery under ERAS protocol are inexact. AIMS: This study aims to assess the effectiveness and feasibility of OFA technique versus traditional opioid-based anesthesia (OA) technique in gynecological laparoscopic surgery under ERAS. METHODS: Adult female patients aged 18 ~ 65 years old undergoing gynecological laparoscopic surgery were randomly divided into OFA group (Group OFA, n = 39) with esketamine and dexmedetomidine or OA group (Group OA, n = 38) with sufentanil and remifentanil. All patients adopted ERAS protocol. The primary outcome was the area under the curve (AUC) of Visual Analogue Scale (VAS) scores (AUCVAS) postoperatively. Secondary outcomes included intraoperative hemodynamic variables, awakening and orientation recovery times, number of postoperative rescue analgesia required, incidence of postoperative nausea and vomiting (PONV) and Pittsburgh Sleep Quality Index (PSQI) perioperatively. RESULTS: AUCVAS was (Group OFA, 16.72 ± 2.50) vs (Group OA, 15.99 ± 2.72) (p = 0.223). No difference was found in the number of rescue analgesia required (p = 0.352). There were no between-group differences in mean arterial pressure (MAP) and heart rate (HR) (p = 0.211 and 0.659, respectively) except MAP at time of surgical incision immediately [(Group OFA, 84.38 ± 11.08) vs. (Group OA, 79.00 ± 8.92), p = 0.022]. Times of awakening and orientation recovery in group OFA (14.54 ± 4.22 and 20.69 ± 4.92, respectively) were both longer than which in group OA (12.63 ± 3.59 and 18.45 ± 4.08, respectively) (p = 0.036 and 0.033, respectively). The incidence of PONV in group OFA (10.1%) was lower than that in group OA (28.9%) significantly (p = 0.027). The postoperative PSQI was lower than the preoperative one in group OFA (p = 0.013). CONCLUSION: In gynecological laparoscopic surgery under ERAS protocol, OFA technique is non-inferior to OA technique in analgesic effect and intraoperative anesthesia stability. Although awakening and orientation recovery times were prolonged compared to OA, OFA had lower incidence of PONV and improved postoperative sleep quality. TRIAL REGISTRATION: ChiCTR2100052761, 05/11/2021.

Comparative Effects of Dexmedetomidine and Midazolam on Dreaming of Patients Undergoing Flexible Bronchoscopy During General Anesthesia.

BACKGROUND The aim of this study was to compare the effects of dexmedetomidine versus midazolam on the dreaming of patients undergoing flexible bronchoscopy during general anesthesia. MATERIAL AND METHODS Patients undergoing flexible bronchoscopy under general anesthesia were randomly divided into a dexmedetomidine group (Group D, n=40) and a midazolam group (Group M, n=40). In group D, patients received 0.5 µg/kg dexmedetomidine and in group M patients received 0.05 mg/kg midazolam intravenously 10 min prior to induction. After bronchoscopy and recovery, a modified Brice questionnaire was used to immediately evaluate the incidence of dreaming of patients. Dreamers were required to complete a 5-point Likert scale survey regarding the contents of their dreams (emotion, voice and movement, memorability) if dreaming was reported. Ramsay Sedation Scale score (Ramsay score) and Visual Analogue Scale (VAS) score were assessed and recorded. RESULTS Patients in group D had higher Ramsay scores and VAS scores (2.9±0.6 and 79.4±4.0, respectively) than group M (2.4±0.7 and 75.0±6.0, respectively), with a statistically significant difference (P<0.05) between groups. The incidence and memorability of dreaming were significantly lower in group D (17.5%) than group M (37.5%, P<0.05), whereas no significant difference was found in emotion, voice, and movement scores of dreaming. CONCLUSIONS Compared to midazolam, pre-injection of dexmedetomidine before induction significantly decreased the incidence of dreaming in patients undergoing flexible bronchoscopy during general anesthesia, without producing undesirable effects on the content of dreams (most of them were pleasant), produces a more efficacious sedation effect during the recovery period and improves the comfort level and satisfaction of patients.

A novel method of Uniblocker placement: extraluminal technique supported by trachea length measurement: A CONSORT-compliant article.

BACKGROUND: The use of bronchial blockers has been increased for one-lung ventilation; however, the placement of bronchial blockers is time consuming. The objective of this study was to compare the novel extraluminal technique of Uniblocker placement supported by trachea length measurement on computerized tomography images with conventional intraluminal Uniblocker placement method. METHODS: Seventy adult patients undergoing left side thoracic surgery were included in the study. All the patients were randomly assigned to one of two groups: conventional intraluminal intubation group (CV-IN group, n = 35) or extraluminal CT guided group (CT-EX group, n = 35). The primary endpoints were the optimal positions of Uniblocker and the injuries of bronchi and carina. The secondary outcomes included the time of Uniblocker placement, the adequacy of lung collapse, the incidences of Uniblocker displacement, sore throat, and hoarseness postoperative. RESULTS: In the CV-IN group, 19 of 35 Uniblockers went to the left main-stem bronchus on the initial blind insertion and 15 of 35 Uniblockers were considered as in optimal depth, whereas in the CT-EX group, 32 of 35 Uniblockers went to the left main-stem bronchus on the initial blind insertion and 31 of 35 Uniblockers were considered as in optimal depth (P < .01). The incidence of bronchi and carina injuries was obviously lower in the CT-EX group (occurred in 1 of 35 cases) than that in the CV-IN group (occurred in 8 of 35 cases) (P < .05). The time of Uniblocker placement took 145.4 s in the CV-IN group and 85.4 s in the CT-EX group (P < .01). The malpositions of Uniblocker, the degree of pulmonary collapse and the adverse events postoperative such as sore throat and hoarseness were not significantly different between the two groups (P > .05). CONCLUSION: The novel extraluminal technique of Uniblocker placement supported by trachea length measurement on computerized tomography images was proved to be more rapid, more accurate and less complications than conventional intraluminal Uniblocker placement method.

Comparative effects of fentanyl versus sufentanil on cerebral oxygen saturation and postoperative cognitive function in elderly patients undergoing open surgery.

This study was aimed to systematically evaluate the effects of fentanyl and sufentanil on intraoperative cerebral oxygen saturation changes and postoperative cognitive function in elderly patients undergoing open surgery. Ninety-six elderly patients who had undergone open surgery under general anesthesia were randomly divided into fentanyl group (F group, anesthesia by fentanyl, 4 g/kg) and sufentanil group (S group, anesthesia by sufentanil, 0.4 µg/kg). There were no significant differences between the F group and S group in the general characteristics of patients. Compared to the F group, the S group had a better effect on suppressing the stress response, maintaining a stable hemodynamic status and achieving better anesthesia effects. The anesthesia recovery time of the S group was significantly shorter than that of the F group. There was no significant difference between the two groups in the intraoperative and postoperative agitation. Patient's waking time and extubation time were significantly shorter in the S group than the F group. The VAS scores in the S group were significantly lower than those in the F group at each time point. The Ramsay scores in the S group were significantly higher than those in the F group at each time point. The cerebral oxygen saturation (SctO2) levels in both groups were significantly increased following anesthesia induction and intubation compared to that of the awake state (P < 0.05), and SctO2 was significantly decreased during the surgery in both groups. The changes in SctO2 levels were not significantly different between the two groups (P > 0.05). The SctO2 level was significantly higher during surgery than that after intubation. Compared with the F group, the relative value of SctO2 decline in the S group was smaller. Compared to the day before surgery, the Montreal Cognitive Assessment (MoCA) scores of both groups were significantly reduced after surgery. At 1 day post-surgery, the MoCA scores of the S group were significantly higher and the incidence of postoperative cognitive dysfunction (POCD) was significantly lower compared to the F group. POCD occurred in three patients (6.2%) in the S group, and the ratio was significantly lower than that in the F group (11.9%) (P < 0.05). It showed a consistent trend with the SctO2 status during the surgery. The relative value of SctO2 decline in the S group was significantly smaller than that in the F group. The reduction of cognitive function in the S group was significantly lower than that in the F group. These results indicate that the changes in SctO2 are a good prediction of the incidence of POCD.

Cuffed Versus Uncuffed Endotracheal Tubes in Pediatrics: A Meta-analysis.

BACKGROUND: Cuffed and uncuffed endotracheal tubes are commonly used for pediatric patients in surgery and emergency situations. It is still controversial which approach should be adopted. The purpose of the study was to compare the application of cuffed and uncuffed endotracheal tubes in pediatric patients. METHODS: We searched PubMed, Web of Science and Cochrane Library for clinical trials, which compared the two applications in children. The study characteristics and clinical data were summarized by two independent reviewers. Meta-analysis of the data was done using Revman 5.3 software. RESULTS: 6 studies with 4141 cases were included in this meta-analysis. The pooling analysis showed that more patients need tube changes in uncuffed than cuffed tubes (OR: 0.07, 95% CI: 0.05-0.10, P < 0.00001). However, there were no differences on intubation duration, reintubation occurrence, accidental extubation rate, croup occurrence and racemic epinephrine use during the intubation process. Also we didn't find any differences on laryngospasm and stridor occurrence after extubation. CONCLUSIONS: Our study demonstrated that uncuffed endotracheal tubes increased the need for tube changes. Other incidences or complications between the two groups had no differences. Cuffed tubes may be an optimal option for pediatric patients. But more trials are needed in the future.

Chemical and genetic inhibition of STAT3 sensitizes hepatocellular carcinoma cells to sorafenib induced cell death.

Hepatocellular carcinoma (HCC) has become the second leading cause of cancer related death, with an increasing death rate in recent years. For advanced HCC, sorafenib is the first-line FDA approved drug, with no more than 3 months' overall survival advantage. Recently, a novel strategy has been proposed to improve sorafenib efficacy through enhancing the ability of sorafenib to induce cell death. STAT3 plays a key role in cancer development and recurrence by promoting cell proliferation, survival and immune evasion through its well-established function as a transcription factor in cancer. Notably, STAT3 transcription activity, indicated by its phosphorylation on Y705 is heterogeneous in different liver cancer cell lines. And sorafenib attenuates STAT3 phosphorylation on Y705. However, the role of STAT3 in sorafenib induced cell death is still largely unknown. Here, we show that liver cancer cells also exhibit heterogeneous sensitivities to sorafenib induced cell death, which co-relates with the STAT3-Y705 phosphorylation levels and JAK1/2 expression levels in Hep3B, Huh7 and HepG2 cells. Furthermore, overexpression or knockdown of STAT3 could switch HCC cells between resistant and sensitive to sorafenib induced cell death, which could be partially due to its regulation on Mcl-1, an anti-apoptotic protein. Finally, both inhibitors of STAT3 SH2 domain (S3i-201) or STAT3 upstream kinases JAKs (JAK inhibitor I) could synergistically enhance sorafenib induced cell death. Taken together, these data strongly suggest that STAT3 is not only a downstream effector of sorafenib, but also a key regulator of cellular sensitivity to sorafenib induced cell death, which provide support for the notion to develop STAT3-targeting drugs to improve clinical efficacy of sorafenib in liver cancer.

Chest Computed Tomography Image for Accurately Predicting the Optimal Insertion Depth of Left-Sided Double-Lumen Tube.

OBJECTIVE: The main objective of this study was to assess the feasibility and accuracy of measuring the distance between the vocal cord and carina using chest computer tomography (CT) as a guide for the intubation of a left-sided double-lumen tube (LDLT). DESIGN: Single-center, prospective, randomized study. SETTING: Local hospital in China. PARTICIPANTS: Sixty adult patients undergoing elective thoracic surgery requiring an LDLT for one lung ventilation were enrolled in this study. INTERVENTIONS: Patients were randomly allocated to the following 2 groups: blind intubation group (B group, n = 30) or chest computed tomography-guided group (C group, n = 30). The placement of the LDLT was accomplished using 1 of the 2 intubation methods. After intubation, an independent anesthesiologist evaluated the position of the LDLT and carina and bronchial injuries using fiber optic bronchoscopy. The number of optimal positions, the time for LDLT intubation, the time for fiber optic bronchoscope confirmation, and carina and bronchial injuries were recorded. RESULTS: Sixteen of 30 intubations in the B group were in optimal position, whereas 27 of 30 intubations in the C group were in optimal position; the difference was statistically significant (p < 0.01). The time for intubation of the LDLT took 118.0 ± 26.2 seconds in the B group and 71.5 ± 8.7 seconds in the C group (p < 0.01). The time for position confirmation using fiber optic bronchoscope took 40.8 ± 15.8 seconds in the B group and 18.7 ± 7.9 seconds in the C group (p < 0.05). The incidences of carina and bronchial injuries were obviously lower in the C group (occurred in 3 of 30 cases) than in the B group (11 of 30 cases) p < 0.05. The incidences of postoperative sore throat and hoarseness showed no significant differences between the 2 groups (p > 0.05). CONCLUSION: This study demonstrated that the method of measuring the distance between the vocal cord and carina according to the chest CT as a guide for the intubation of LDLT is more effective and more accurate than the blind intubation method.

Role of positioning posterior cord on coracoid approach brachial plexus block guided by nerve stimulator: Compared with guided by ultrasound.

BACKGROUND: Coracoid approach is efficient and safe for brachial plexus block, and is guided by nerve stimulator or ultrasound in general. Many trials have proved that ultrasonic guidance was more efficacious than nerve stimulator guidance. We hypothesized that positioning posterior cord could enhance the anesthesia effect of coracoid approach brachial plexus block (CABPB) guided by nerve stimulator. METHODS: Eighty patients were randomized into 2 groups to receive CABPB with positioning posterior cord guided by nerve stimulator (group A) or CABPB guided by ultrasound (group B). Success rate, procedure time, and onset time of sensory or motor block were recorded. RESULTS: Success rate was similar in 2 groups (89.7% in group A vs 87.5% in group B, P > .05). Procedure time was longer in group A (8 minutes), as compared with group B (4 minutes; P < .05). The difference of onset time of sensory and motor block was not significant between the 2 groups. The onset time of sensory and motor block for musculocutaneous nerve was significantly shorter in group A, as compared with group B (P < .05). CONCLUSION: The 2 technologies are equivalent regarding success rate, safety, and onset time of sensory or motor block. Positioning posterior cord in CABPB guided by nerve stimulator is efficacious for upper extremity surgery.(URL: http://www.chictr.org.cn/listbycreater.aspx ID: ChiCTR-INR-16009091 DATE: 25/8/2016).

A comparison of extraluminal and intraluminal use of the Uniblocker in left thoracic surgery: A CONSORT-compliant article.

BACKGROUND: The aim of this study was to assess the feasibility and safety issues concerning extraluminal use of the Uniblocker for one-lung ventilation (OLV) in the left thoracic surgery. METHODS: Forty patients undergoing elective left thoracic surgery were included in this study, and all patients were randomly allocated to extraluminal use of Uniblocker group (E group, n = 20) or intraluminal use of Uniblocker group (I group, n = 20). Time for intubation, time for verification of the correct position of Uniblocker, incidence of Uniblocker displacement, index of pulmonary collapse, mean arterial pressure, heart rate, peak airway pressure, oxygen saturation in two-lung ventilation, and 30 minutes after OLV, bronchial damage after OLV, sore throat, and hoarseness postoperative were recorded. RESULTS: The time for positioning Uniblocker was 112.6 ±â€Š31.2 seconds in intraluminal use group, whereas the time for positioning Uniblocker was significantly shorter in extraluminal use group (63.4 ±â€Š15.8 seconds). The incidence of main bronchial injury, the time of intubation, the incidence of Uniblocker malposition after initial placement, the time of OLV, the degree of pulmonary collapse, mean arterial pressure, heart rate, peak airway pressure, oxygen saturation in two-lung ventilation, and 30 minutes after OLV, the incidence of sore throat and hoarseness postoperative have no statistical significance (P > .05). CONCLUSION: Extraluminal use of the Uniblocker was proved to be a more rapid and more accurate method than conventional intraluminal use of the Uniblocker for OLV in left thoracic surgery.

Slit2/Robo1 Mediation of Synaptic Plasticity Contributes to Bone Cancer Pain.

Synaptic plasticity is fundamental to spinal sensitivity of bone cancer pain. Here, we have shown that excitatory synaptogenesis contributes to bone cancer pain. New synapse formation requires neurite outgrowth and an interaction between axons and dendrites, accompanied by the appositional organization of presynaptic and postsynaptic specializations. We have shown that Slit2, Robo1, and RhoA act as such cues that promote neurite outgrowth and guide the axon for synapse formation. Sarcoma inoculation induces excitatory synaptogenesis and bone cancer pain which are reversed by Slit2 knockdown but aggravated by Robo1 knockdown. Synaptogenesis of cultured neurons are inhibited by Slit2 knockdown but enhanced by Robo1 knockdown. Sarcoma implantation induces an increase in Slit2 and decreases Robo1 and RhoA, while Slit2 knockdown results in an increase of Robo1 and RhoA. These results have demonstrated a molecular mechanism of synaptogenesis in bone cancer pain.

Transplant Outcomes for Children with T Cell Acute Lymphoblastic Leukemia in Second Remission: A Report from the Center for International Blood and Marrow Transplant Research.

Survival for children with relapsed T cell acute lymphoblastic leukemia (T-ALL) is poor when treated with chemotherapy alone, and outcomes after allogeneic hematopoietic cell transplantation (HCT) is not well described. Two hundred twenty-nine children with T-ALL in second complete remission (CR2) received an HCT after myeloablative conditioning between 2000 and 2011 and were reported to the Center for International Blood and Marrow Transplant Research. Median age was 10 years (range, 2 to 18). Donor source was umbilical cord blood (26%), matched sibling bone marrow (38%), or unrelated bone marrow/peripheral blood (36%). Acute (grades II to IV) and chronic graft-versus-host disease occurred in, respectively, 35% (95% confidence interval [CI], 27% to 45%) and 26% (95% CI, 20% to 33%) of patients. Transplant-related mortality at day 100 and 3-year relapse rates were 13% (95% CI, 9% to 18%) and 30% (95% CI, 24% to 37%), respectively. Three-year overall survival and disease-free survival rates were 48% (95% CI, 41% to 55%) and 46% (95% CI, 39% to 52%), respectively. In multivariate analysis, patients with bone marrow relapse, with or without concurrent extramedullary relapse before HCT, were most likely to relapse (hazard ratio, 3.94; P = .005) as compared with isolated extramedullary disease. In conclusion, HCT for pediatric T-ALL in CR2 demonstrates reasonable and durable outcomes, and consideration for HCT is warranted.

Hematopoietic stem cell transplantation for infantile osteopetrosis.

We report the international experience in outcomes after related and unrelated hematopoietic transplantation for infantile osteopetrosis in 193 patients. Thirty-four percent of transplants used grafts from HLA-matched siblings, 13% from HLA-mismatched relatives, 12% from HLA-matched, and 41% from HLA-mismatched unrelated donors. The median age at transplantation was 12 months. Busulfan and cyclophosphamide was the most common conditioning regimen. Long-term survival was higher after HLA-matched sibling compared to alternative donor transplantation. There were no differences in survival after HLA-mismatched related, HLA-matched unrelated, or mismatched unrelated donor transplantation. The 5- and 10-year probabilities of survival were 62% and 62% after HLA-matched sibling and 42% and 39% after alternative donor transplantation (P = .01 and P = .002, respectively). Graft failure was the most common cause of death, accounting for 50% of deaths after HLA-matched sibling and 43% of deaths after alternative donor transplantation. The day-28 incidence of neutrophil recovery was 66% after HLA-matched sibling and 61% after alternative donor transplantation (P = .49). The median age of surviving patients is 7 years. Of evaluable surviving patients, 70% are visually impaired; 10% have impaired hearing and gross motor delay. Nevertheless, 65% reported performance scores of 90 or 100, and in 17%, a score of 80 at last contact. Most survivors >5 years are attending mainstream or specialized schools. Rates of veno-occlusive disease and interstitial pneumonitis were high at 20%. Though allogeneic transplantation results in long-term survival with acceptable social function, strategies to lower graft failure and hepatic and pulmonary toxicity are urgently needed.

Transplantation Outcomes for Children with Hypodiploid Acute Lymphoblastic Leukemia.

Children with hypodiploid acute lymphoblastic leukemia (ALL) have inferior outcomes despite intensive risk-adapted chemotherapy regimens. We describe 78 children with hypodiploid ALL who underwent hematopoietic stem cell transplantation between 1990 and 2010. Thirty-nine (50%) patients had ≤ 43 chromosomes, 12 (15%) had 44 chromosomes, and 27 (35%) had 45 chromosomes. Forty-three (55%) patients underwent transplantation in first remission (CR1) and 35 (45%) underwent transplantation in ≥ second remission (CR2). Twenty-nine patients (37%) received a graft from a related donor and 49 (63%) from an unrelated donor. All patients received a myeloablative conditioning regimen. The 5-year probabilities of leukemia-free survival, overall survival, relapse, and treatment-related mortality for the entire cohort were 51%, 56%, 27%, and 22%, respectively. Multivariate analysis confirmed that mortality risks were higher for patients who underwent transplantation in CR2 (hazard ratio, 2.16; P = .05), with number of chromosomes ≤ 43 (hazard ratio, 2.15; P = .05), and for those who underwent transplantation in the first decade of the study period (hazard ratio, 2.60; P = .01). Similarly, treatment failure risks were higher with number of chromosomes ≤ 43 (hazard ratio, 2.28; P = .04) and the earlier transplantation period (hazard ratio, 2.51; P = .01). Although survival is better with advances in donor selection and supportive care, disease-related risk factors significantly influence transplantation outcomes.

Haematopoietic stem cell transplantation for refractory Langerhans cell histiocytosis: outcome by intensity of conditioning.

Patients with Langerhans cell histiocytosis (LCH) refractory to conventional chemotherapy have a poor outcome. There are currently two promising treatment strategies for high-risk patients: the first involves the combination of 2-chlorodeoxyadenosine and cytarabine; the other approach is allogeneic haematopoietic stem cell transplantation (HSCT). Here we evaluated 87 patients with high-risk LCH who were transplanted between 1990 and 2013. Prior to the year 2000, most patients underwent HSCT following myeloablative conditioning (MAC): only 5 of 20 patients (25%) survived with a high rate (55%) of transplant-related mortality (TRM). After the year 2000 an increasing number of patients underwent HSCT with reduced intensity conditioning (RIC): 49/67 (73%) patients survived, however, the improved survival was not overtly achieved by the introduction of RIC regimens with similar 3-year probability of survival after MAC (77%) and RIC transplantation (71%). There was no significant difference in TRM by conditioning regimen intensity but relapse rates were higher after RIC compared to MAC regimens (28% vs. 8%, P = 0·02), although most patients relapsing after RIC transplantation could be salvaged with further chemotherapy. HSCT may be a curative approach in 3 out of 4 patients with high risk LCH refractory to chemotherapy: the optimal choice of HSCT conditioning remains uncertain.

Increasing incidence of chronic graft-versus-host disease in allogeneic transplantation: a report from the Center for International Blood and Marrow Transplant Research.

Although transplant practices have changed over the last decades, no information is available on trends in incidence and outcome of chronic graft-versus-host disease (cGVHD) over time. This study used the central database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to describe time trends for cGVHD incidence, nonrelapse mortality, and risk factors for cGVHD. The 12-year period was divided into 3 intervals, 1995 to 1999, 2000 to 2003, and 2004 to 2007, and included 26,563 patients with acute leukemia, chronic myeloid leukemia, and myelodysplastic syndrome. Multivariate analysis showed an increased incidence of cGVHD in more recent years (odds ratio = 1.19, P < .0001), and this trend was still seen when adjusting for donor type, graft type, or conditioning intensity. In patients with cGVHD, nonrelapse mortality has decreased over time, but at 5 years there were no significant differences among different time periods. Risk factors for cGVHD were in line with previous studies. This is the first comprehensive characterization of the trends in cGVHD incidence and underscores the mounting need for addressing this major late complication of transplantation in future research.

Effect of cord blood processing on transplantation outcomes after single myeloablative umbilical cord blood transplantation.

Variations in cord blood manufacturing and administration are common, and the optimal practice is not known. We compared processing and banking practices at 16 public cord blood banks (CBB) in the United States and assessed transplantation outcomes on 530 single umbilical cord blood (UCB) myeloablative transplantations for hematologic malignancies facilitated by these banks. UCB banking practices were separated into 3 mutually exclusive groups based on whether processing was automated or manual, units were plasma and red blood cell reduced, or buffy coat production method or plasma reduced. Compared with the automated processing system for units, the day 28 neutrophil recovery was significantly lower after transplantation of units that were manually processed and plasma reduced (red cell replete) (odds ratio, .19; P = .001) or plasma and red cell reduced (odds ratio, .54; P = .05). Day 100 survival did not differ by CBB. However, day 100 survival was better with units that were thawed with the dextran-albumin wash method compared with the "no wash" or "dilution only" techniques (odds ratio, 1.82; P = .04). In conclusion, CBB processing has no significant effect on early (day 100) survival despite differences in kinetics of neutrophil recovery.

Outcomes after hematopoietic stem cell transplantation for children with I-cell disease.

Mucolipidosis type II (MLII), or I-cell disease, is a rare but severe disorder affecting localization of enzymes to the lysosome, generally resulting in death before the 10th birthday. Although hematopoietic stem cell transplantation (HSCT) has been used to successfully treat some lysosomal storage diseases, only 2 cases have been reported on the use of HSCT to treat MLII. For the first time, we describe the combined international experience in the use of HSCT for MLII in 22 patients. Although 95% of the patients engrafted, overall survival was low, with only 6 patients (27%) alive at last follow-up. The most common cause of death post-transplant was cardiovascular complications, most likely due to disease progression. Survivors were globally delayed in development and often required complex medical support, such as gastrostomy tubes for nutrition and tracheostomy with mechanical ventilation. Although HSCT has demonstrated efficacy in treating some lysosomal storage disorders, the neurologic outcome and survival for patents with MLII were poor. Therefore, new medical and cellular therapies should be sought for these patients.

Transplantation for children with acute myeloid leukemia: a comparison of outcomes with reduced intensity and myeloablative regimens.

The safety and efficacy of reduced-intensity conditioning (RIC) regimens for the treatment of pediatric acute myeloid leukemia is unknown. We compared the outcome of allogeneic hematopoietic cell transplantation in children with acute myeloid leukemia using RIC regimens with those receiving myeloablative-conditioning (MAC) regimens. A total of 180 patients were evaluated (39 with RIC and 141 with MAC regimens). Results of univariate and multivariate analysis showed no significant differences in the rates of acute and chronic graft-versus-host disease, leukemia-free, and overall survival between treatment groups. The 5-year probabilities of overall survival with RIC and MAC regimens were 45% and 48%, respectively (P = .99). Moreover, relapse rates were not higher with RIC compared with MAC regimens (39% vs 39%; P = .95), and recipients of MAC regimens were not at higher risk for transplant-related mortality compared with recipients of RIC regimens (16% vs 16%; P = .73). After carefully controlled analyses, we found that in this relatively modest study population, the data supported a role for RIC regimens for acute myeloid leukemia in children undergoing allogeneic hematopoietic cell transplantation. The data also provided justification for designing a carefully controlled randomized clinical trial that examines the efficacy of regimen intensity in this population.