Perforated appendicitis due to fishbone.

Appendicitis is a common condition in daily clinical practice. Appendicitis due to foreign bodies is uncommon and may result from obstruction or perforation mechanism. We present a rare case of a 43-year-old male patient who was diagnosed with perforated appendicitis due to a fish bone by imaging studies and confirmed postoperatively. Confirming the fish bone causing the perforation on images is sometimes difficult, requiring the radiologist to actively search and determine the source. In addition to appendectomy, the surgeon also needs to pay attention to removing all foreign objects and treating perforations of surrounding organs.

Determination of the growth performance and reproductive season of wild Channa lucius (Cuvier, 1831) populations of genus Channa (Channidae, Perciformes) in the Mekong Delta, Vietnam.

This study aimed to investigate the growth and spawning characteristics of wild Channa lucius (Cuvier, 1831) populations in the Mekong Delta, Vietnam. The study was carried out from March 2011 to February 2012. The length-weight relationship of C. lucius was determined according to the equations W = 0.0044L3.2494 , R2  = 0.9157 (female fish) and W = 0.0047L3.2178 , R2  = 0.9434 (male fish). The length and weight of the body for female fish ranged from 16.3 to 36.0 cm and 49.0 to 550.0 g, and for male fish, from 14.6 to 38.2 cm and 46.0 to 639.0 g, respectively. Female and male fish had almost similar lengths at first maturity (21.3958 cm for females and 21.3952 cm for males). The condition factor of female fish ranged from 0.842 to 0.864 and for male fish ranged from 0.848 to 0.874. The gonadosomatic index of female fish was highest in June (1.68%) and lowest in November (0.69%); that of male fish was highest in June (0.53%) and lowest in September (0.15%). The sexual maturity rate (SMR) of female fish peaked in May, with SMRs of 33.3% (stage III) and 58.3% (stage IV). In conclusion, C. lucius has a positive allometric range (b > 3), reaching sexual maturity when its length reaches 21.39 cm for both sexes, and the spawning season begins in December but peaks in May and June.

Thumb carpometacarpal arthroplasty and trapeziectomy using a tenodesis screw compared to ligament reconstruction.

This study aimed to compare the results of patients treated with a thumb carpometacarpal (CMC) suspension arthroplasty using an interference screw technique with patients that were treated by trapeziectomy and ligament reconstruction. A retrospective chart review was conducted of patients over 18 years old who required surgical treatment for thumb CMC joint arthritis treated by a single surgeon. Patients included in the study followed the same preoperative and postoperative protocol. Information related to functional outcomes was collected (pinch and grip strength, pain, Kapandji score, proximal migration of first metacarpal bone). One hundred and five patients were included, 77% were female, age at the time of the study was 62.7 years old; 74 (70%) patients were treated with the tenodesis screw (TS) technique and 31 (30%) with trapeziectomy and ligament reconstruction (TZLR). Patients were followed for a mean of 8.4 months. Postoperative pain was 1.2 in the TS group and 0.6 in the TZLR group; Kapandji score was 8.3 in the TS group and 9 in the TZLR group; in the TS group, the grip strength was 26.2kg and key pinch strength was 6.15kg; in the TZLR group, grip strength was 12.8kg and key pinch strength was 4.7kg. Proximal migration was 0.4cm in the TZLR group and 0.6cm in the TS group. The use of tenodesis screw and half of the flexor carpi radialis had minor advantages, such as increasing the grip and key pinch strength without differences relative the non-operated thumb, minimal migration of the first metacarpal bone compared with the other technique.

Combining Linker Design and Linker-Exchange Strategies for the Synthesis of a Stable Large-Pore Zr-Based Metal-Organic Framework.

A Zr(IV)-based metal-organic framework (MOF), termed reo-MOF-1 [Zr6O8(H2O)8(SNDC)4], composed of 4-sulfonaphthalene-2,6-dicarboxylate (HSNDC2-) linkers and Zr6O8(H2O)8(CO2)8 clusters was synthesized by solvothermal synthesis. Structural analysis revealed that reo-MOF-1 adopts the reo topology highlighted with large cuboctahedral cages (23 Å). This structure is similar to that found in DUT-52 (fcu topology), however, reo-MOF-1 lacks the body-centered packing of the 12-connected Zr6O4(OH)4(CO2)12 clusters, which is attributed to the subtle, but crucial influence in the bulkiness of functional groups on the linkers. The control experiments, where the ratio of H3SNDC/naphthalene-2,6-dicarboxylate linkers was varied, also support our finding that the bulky functionalities play a key role for defect-controlled synthesis. The reo-MOF-1A framework was obtained by linker exchange to yield a chemically and thermally stable material despite its large pores. Remarkably, reo-MOF-1A exhibits permanent porosity (Brunauer-Emmett-Teller and Langmuir surface areas of 2104 and 2203 m2 g-1, respectively). Owing to these remarkable structural features, reo-MOF-1A significantly enhances the yield in Brønsted acid-catalyzed reactions.

A pilot study of surgical telementoring for leg fasciotomy.

INTRODUCTION: Acute extremity compartment syndrome requires rapid decompression. In remote locations, distance, weather and logistics may delay the evacuation of patients with extremity trauma beyond the desired timeline for compartment release. The aim of this study was to establish the feasibility of performing telementored surgery for leg compartment release and to identify methodological issues relevant for future research. METHODS: Three anaethetists and one critical care physician were recruited as operators. They were directed to perform a two-incision leg fasciotomy on a Thiel-embalmed cadaver under the guidance of a remotely located orthopaedic surgeon. The operating physician and the surgeon (mentor) were connected through software that allows for real-time supervision and the use of a virtual pointer overlaid onto the surgical field. Two experienced orthopaedic traumatologists independently assessed the adequacy of compartment decompression and the presence of iatrogenic complications. RESULTS: 14 of 16 compartments (in four leg specimens) were felt to have been completely released. The first evaluator considered that the deep posterior compartment was incompletely released in two specimens. The second evaluator considered that the superficial posterior compartment was incompletely released in two specimens. The only complication was a large laceration of the soleus muscle that occurred during a period of blurred video signal attributed to a drop in bandwidth. CONCLUSIONS: This study suggests that surgical telementoring may enable physicians to safely perform two-incision leg fasciotomy in remote environments. This could improve the chances of limb salvage when compartment syndrome occurs far from surgical care. We found interobserver variation in the assessment of compartment release, which should be considered in the design of future research protocols.

Overexpression of SOX4 correlates with poor prognosis of acute myeloid leukemia and is leukemogenic in zebrafish.

The SOX4 transcription factor is a key regulator of embryonic development, cell-fate decision, cellular differentiation and oncogenesis. Abnormal expression of SOX4 is related to malignant tumor transformation and cancer metastasis. However, no reports are available regarding the clinical significance of SOX4 in acute myeloid leukemia (AML) and the role of SOX4 in leukemogenesis. In the current study, we found that AML patients with low bone marrow (BM) SOX4 expression had higher remission rates and longer overall survival than those with high SOX4 expression, regardless of age, white blood cell count at diagnosis, karyotype profile and NPM1/FLT3-ITD status. To elucidate the role of SOX4 in leukemogenesis, we generated a transgenic zebrafish model that overexpressed human SOX4 in the myeloid lineage Tg(spi1-SOX4-EGFP). These transgenic zebrafish showed, at 5 months of age, increased myelopoiesis with dedifferentiation in kidney marrow. At 9 months of age, their kidney structure was significantly effaced and distorted by increased infiltration of myeloid progenitor cells. These results suggest that SOX4 is not only an independent prognostic factor of AML, but also an important molecular factor in leukemogenesis.

Clinico-biological significance of suppressor of cytokine signaling 1 expression in acute myeloid leukemia.

Suppressor of cytokine signaling 1 (SOCS1) protein, which encodes a member of signal transducers and activators of transcription-induced inhibitors, takes part in a negative regulation of cytokine signaling. The mechanism of SOCS1 in tumor carcinogenesis is complex and there have been no studies concerning the clinic-biologic implication of SOCS1 expression in acute myeloid leukemia (AML). Here, we first identified that higher bone marrow (BM) SOCS1 expression was closely associated with older age, FLT3-ITD, NPM1 and DNMT3A mutations, but negatively correlated with CEBPA mutation in patients with de novo AML. Compared to patients with lower SOCS1 expression, those with higher expression had lower complete remission rates and shorter overall survival. Further, higher expression of SOCS1 in the BM was an independent unfavorable prognostic factor irrespective of age, white blood cell, cytogenetics and gene mutations. Next, we generated zebrafish model overexpressing SOCS1 by spi1 promoter, which showed kidney marrow from adult SOCS1 zebrafish had increased myelopoiesis, myeloid progenitors and the kidney or spleen structure were effaced and distorted, mimicking leukemia phenotype. The SOCS1/FLT3-ITD double transgenic fish could further facilitate the leukemic process. The results indicate SOCS1 plays an important role in AML and its higher expression serves as a new biomarker to risk-stratify AML patients.

Randomised controlled trial comparing marksmanship following application of a tourniquet or haemostatic clamp in healthy volunteers.

BACKGROUND: In a care under fire situation, a first line response to haemorrhage is to apply a tourniquet and return fire. However, there is little understanding of how tourniquets and other haemorrhage control devices impact marksmanship. METHODS: We compared the impact of the iTClamp and the Combat Application Tourniquet (CAT) on marksmanship. Following randomisation (iTClamp or CAT), trained marksmen fired an AR15 at a scaled silhouette target in prone unsupported position (shooting task). Subjects then attempted to complete the shooting task at 5, 10, 15, 30 and 60 min post-haemorrhage control device application. RESULTS: All of the clamp groups (n=7) completed the 60 min shooting task. Five CAT groups (n=6) completed the 5 min shooting task and one completed the 5 and 10 min shooting task before withdrawing. Four CAT groups were stopped due to unsafe handling; two stopped due to pain. When examining hits on mass (HOM) for the entire shooting task, there was no significant difference between tourniquet and iTClamp HOM at 5 min (p=0.18). However, there was a significant difference at 10 min, p=0.003 with tourniquet having significantly fewer HOM (1.7±2.7 HOM) than the iTClamp (8.1±3.3 HOM) group. The total effective HOM for the entire 60 min shooting task showed that the iTClamp group achieved significantly (p=0.001) more HOM than the tourniquet group. Over the entire 60 min shooting exercise, the iTClamp group achieved a median 72% (52/72) of available HOM while the tourniquet group obtained 19% (14/72). CONCLUSIONS: Application of a tourniquet to the dominant arm negates effective return of fire in a care under fire setting after a brief time window. Haemorrhage control devices that preserve function may have a role in care under fire situations, as preserving effectiveness in returning fire has obvious operational merits.

Fibrinogen in the initial resuscitation of severe trauma (FiiRST): a randomized feasibility trial.

BACKGROUND: Decreased plasma fibrinogen concentration shortly after injury is associated with higher blood transfusion needs and mortality. In North America and the UK, cryoprecipitate transfusion is the standard-of-care for fibrinogen supplementation during acute haemorrhage, which often occurs late during trauma resuscitation. Alternatively, fibrinogen concentrate (FC) can be beneficial in trauma resuscitation. However, the feasibility of its early infusion, efficacy and safety remain undetermined. The objective of this trial was to evaluate the feasibility, effect on clinical and laboratory outcomes and complications of early infusion of FC in trauma. METHODS: Fifty hypotensive (systolic arterial pressure ≤100 mm Hg) adult patients requiring blood transfusion were randomly assigned to either 6 g of FC or placebo, between Oct 2014 and Nov 2015 at a tertiary trauma centre. The primary outcome, feasibility, was assessed by the proportion of patients receiving the intervention (FC or placebo) within one h of hospital arrival. Plasma fibrinogen concentration was measured, and 28-day mortality and incidence of thromboembolic events were assessed. RESULTS: Overall, 96% (43/45) [95% CI 86-99%] of patients received the intervention within one h; 95% and 96% in the FC and placebo groups, respectively (P=1.00). Plasma fibrinogen concentrations remained higher in the FC group up to 12 h after admission with the largest difference at three h (2.9 mg dL - 1 vs. 1.8 mg dL - 1; P<0.01). The 28-day mortality and thromboembolic complications were similar between groups. CONCLUSIONS: Early infusion of FC is feasible and increases plasma fibrinogen concentration during trauma resuscitation. Larger trials are justified.

Comprehensive mutational analysis of primary and relapse acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is a subtype of myeloid leukemia characterized by differentiation block at the promyelocyte stage. Besides the presence of chromosomal rearrangement t(15;17), leading to the formation of PML-RARA (promyelocytic leukemia-retinoic acid receptor alpha) fusion, other genetic alterations have also been implicated in APL. Here, we performed comprehensive mutational analysis of primary and relapse APL to identify somatic alterations, which cooperate with PML-RARA in the pathogenesis of APL. We explored the mutational landscape using whole-exome (n=12) and subsequent targeted sequencing of 398 genes in 153 primary and 69 relapse APL. Both primary and relapse APL harbored an average of eight non-silent somatic mutations per exome. We observed recurrent alterations of FLT3, WT1, NRAS and KRAS in the newly diagnosed APL, whereas mutations in other genes commonly mutated in myeloid leukemia were rarely detected. The molecular signature of APL relapse was characterized by emergence of frequent mutations in PML and RARA genes. Our sequencing data also demonstrates incidence of loss-of-function mutations in previously unidentified genes, ARID1B and ARID1A, both of which encode for key components of the SWI/SNF complex. We show that knockdown of ARID1B in APL cell line, NB4, results in large-scale activation of gene expression and reduced in vitro differentiation potential.

Genetic alterations and their clinical implications in older patients with acute myeloid leukemia.

A number of patient-specific and leukemia-associated factors are related to the poor outcome in older patients with acute myeloid leukemia (AML). However, comprehensive studies regarding the impact of genetic alterations in this group of patients are limited. In this study, we compared relevant mutations in 21 genes between AML patients aged 60 years or older and those younger and exposed their prognostic implications. Compared with the younger patients, the elderly had significantly higher incidences of PTPN11, NPM1, RUNX1, ASXL1, TET2, DNMT3A and TP53 mutations but a lower frequency of WT1 mutations. The older patients more frequently harbored one or more adverse genetic alterations. Multivariate analysis showed that DNMT3A and TP53 mutations were independent poor prognostic factors among the elderly, while NPM1 mutation in the absence of FLT3/ITD was an independent favorable prognostic factor. Furthermore, the status of mutations could well stratify older patients with intermediate-risk cytogenetics into three risk groups. In conclusion, older AML patients showed distinct genetic alterations from the younger group. Integration of cytogenetics and molecular mutations can better risk-stratify older AML patients. Development of novel therapies is needed to improve the outcome of older patients with poor prognosis under current treatment modalities.

Prognostic significance of NPM1 mutation-modulated microRNA-mRNA regulation in acute myeloid leukemia.

Distinct microRNA (miRNA) and mRNA signatures were reported in nucleophosmin (NPM1)-mutated acute myeloid leukemia (AML). However, it remains unknown whether the mutation participates in the dynamic interaction between miRNA and mRNA. In this study, we aimed to investigate the role of NPM1 mutation in modulating miRNA-mRNA regulation (MMR). From the sample-paired miRNA/mRNA microarrays of 181 de novo AML patients, we found that MMR was dynamic and could be affected by NPM1 mutation. By a systematic framework, we identified 493 NPM1 mutation-modulated MMR pairs, where the strength of MMR was significantly attenuated in patients carrying NPM1 mutations, compared to those with wild-type NPM1. These miRNAs/mRNAs were associated with pathways implicated in cancer and known functions of NPM1 mutation. Such modulation of MMR was validated in two independent cohorts as well as in cells with different NPM1 mutant burdens. Furthermore, we showed that the regulatory strength of nine MMR pairs could predict patients' outcomes. Combining these pairs, a scoring system was proposed and shown to predict survival in discovery and validation data sets, independent of other known prognostic factors. Our study provides novel biological insights into the role of NPM1 mutation as a modulator of MMR, based on which a novel prognostic marker is proposed in AML.

TP53 mutations in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution.

The TP53 mutation is frequently detected in acute myeloid leukemia (AML) patients with complex karyotype (CK), but the stability of this mutation during the clinical course remains unclear. In this study, TP53 mutations were identified in 7% of 500 patients with de novo AML and 58.8% of patients with CK. TP53 mutations were closely associated with older age, lower white blood cell (WBC) and platelet counts, FAB M6 subtype, unfavorable-risk cytogenetics and CK, but negatively associated with NPM1 mutation, FLT3/ITD and DNMT3A mutation. Multivariate analysis demonstrated that TP53 mutation was an independent poor prognostic factor for overall survival and disease-free survival among the total cohort and the subgroup of patients with CK. A scoring system incorporating TP53 mutation and nine other prognostic factors, including age, WBC counts, cytogenetics and gene mutations, into survival analysis proved to be very useful to stratify AML patients. Sequential study of 420 samples showed that TP53 mutations were stable during AML evolution, whereas the mutation was acquired only in 1 of the 126 TP53 wild-type patients when therapy-related AML originated from different clone emerged. In conclusion, TP53 mutations are associated with distinct clinic-biological features and poor prognosis in de novo AML patients and are rather stable during disease progression.

A 3-microRNA scoring system for prognostication in de novo acute myeloid leukemia patients.

As a highly heterogeneous disease, acute myeloid leukemia (AML) needs fine risk stratification to get an optimal outcome of patients. MicroRNAs have florid biological functions and have critical roles in the pathogenesis and prognosis in AML. Expression levels of some single microRNAs are influential for prognosis, but a system integrating several together and considering the weight of each should be more powerful. We thus analyzed the clinical, genetic and microRNA profiling data of 138 de novo AML patients of our institute. By multivariate analysis, we identified that high expression of hsa-miR-9-5p and hsa-miR-155-5p were independent poor prognostic factors, whereas that of hsa-miR-203 had a trend to be a favorable factor. We constructed a scoring system from expression of these three microRNAs by considering the weight of each. The scores correlated with distinct clinical and biological features and outperformed single microRNA expression in prognostication. In both ours and another validation cohort, higher scores were associated with shorter overall survival, independent of other well-known prognostic factors. By analyzing the mRNA expression profiles, we sorted out several cancer-related pathways highly correlated with the microRNA prognostic signature. We conclude that this 3-microRNA scoring system is simple and powerful for risk stratification of de novo AML patients.

SETBP1 mutations drive leukemic transformation in ASXL1-mutated MDS.

Mutations in ASXL1 are frequent in patients with myelodysplastic syndrome (MDS) and are associated with adverse survival, yet the molecular pathogenesis of ASXL1 mutations (ASXL1-MT) is not fully understood. Recently, it has been found that deletion of Asxl1 or expression of C-terminal-truncating ASXL1-MTs inhibit myeloid differentiation and induce MDS-like disease in mice. Here, we find that SET-binding protein 1 (SETBP1) mutations (SETBP1-MT) are enriched among ASXL1-mutated MDS patients and associated with increased incidence of leukemic transformation, as well as shorter survival, suggesting that SETBP1-MT play a critical role in leukemic transformation of MDS. We identify that SETBP1-MT inhibit ubiquitination and subsequent degradation of SETBP1, resulting in increased expression. Expression of SETBP1-MT, in turn, inhibited protein phosphatase 2A activity, leading to Akt activation and enhanced expression of posterior Hoxa genes in ASXL1-mutant cells. Biologically, SETBP1-MT augmented ASXL1-MT-induced differentiation block, inhibited apoptosis and enhanced myeloid colony output. SETBP1-MT collaborated with ASXL1-MT in inducing acute myeloid leukemia in vivo. The combination of ASXL1-MT and SETBP1-MT activated a stem cell signature and repressed the tumor growth factor-ß signaling pathway, in contrast to the ASXL1-MT-induced MDS model. These data reveal that SETBP1-MT are critical drivers of ASXL1-mutated MDS and identify several deregulated pathways as potential therapeutic targets in high-risk MDS.

Elevated BDNF mRNA expression in the medial prefrontal cortex after d-amphetamine reinstated conditioned place preference in rats.

Drug addiction behavior that is established and maintained by psychostimulants has been shown to be associated with the expression of brain-derived neurotrophic factor (BDNF) in the mesolimbic dopamine (DA) system. Cocaine has been used for most prior studies testing this effect of psychostimulants and therefore relatively little is known about its counterpart amphetamine (AMP). To fill this gap, the present study was designed to test whether BDNF mRNA expression levels in the DA terminal regions were changed specifically by d-AMP-induced conditioned place preference (CPP) followed by drug-primed reinstatement. The dose of d-AMP, 1mg/kg, was confirmed to significantly induce CPP. Using this dose, a group of rats was initially subjected to d-AMP CPP, which was followed by entry into an extinction protocol with an additional 3-day withdrawal before a drug-primed reinstatement test was carried out. Following extinction of d-AMP CPP, a lower dose of d-AMP, namely 0.75mg/kg, was able to significantly reinstate CPP. The BDNF mRNA levels in the selected brain areas were determined by real-time polymerase chain reaction (PCR) after the CPP and reinstatement. The BDNF mRNA level in the medial prefrontal cortex (mPFC) was significantly increased after the reinstatement, but not the CPP test. And, none of the other four assessed brain areas showed any change in BDNF mRNA level after d-AMP CPP or reinstatement. These findings support the notion that BDNF is involved in drug-seeking behavior and indicate that d-AMP reinstatement after extinction may be linked to an increase in BDNF mRNA expression in the mPFC.