Nitric oxide synthase 2 genetic variation rs2297514 associates with a decreased susceptibility to extremity post-traumatic osteomyelitis in a Chinese Han population.

Background: Previous studies have indicated that nitric oxide synthase 2 (NOS2) genetic variations are involved in delayed fracture healing and fracture non-union. Whether these genetic variants associate with the development of osteomyelitis (OM) remains unclear. Here, we analyzed the potential relationships between NOS2 genetic variations and the risk of developing post-traumatic OM (PTOM) in a Chinese Han population. Methods: Altogether 704 participants, including 336 PTOM patients and 368 healthy controls, were genotyped of rs2297514 and rs2248814 of the NOS2 gene using the SNaPshot genotyping method. Results: Outcomes showed that the frequency of allele C of rs2297514 in the patient group was significantly lower than that in the control group (48.7% vs. 54.5%, P = 0.029, OR = 0.792, 95% CI 0.642 - 0.976). In addition, significant associations were found between rs2297514 and susceptibility to PTOM by the recessive model (P = 0.007, OR = 0.633, 95% CI 0.453 - 0.884), and the homozygous model (P = 0.039, OR = 0.648, 95% CI 0.429 - 0.979). Moreover, patients with the CC genotype of rs2297514 had lower inflammatory biomarkers levels than the TT genotype, especially for the C-reactive protein (CRP) level (median: 4.1 mg/L vs. 8.9 mg/L, P = 0.027). However, no significant relationship was noted between rs2248814 and the risk of developing PTOM. Conclusion: In this Chinese cohort, rs2297514 is correlated with a decreased risk of PTOM development, with genotype CC as a protective factor.

Explainable machine learning model for predicting furosemide responsiveness in patients with oliguric acute kidney injury.

BACKGROUND: Although current guidelines didn't support the routine use of furosemide in oliguric acute kidney injury (AKI) management, some patients may benefit from furosemide administration at an early stage. We aimed to develop an explainable machine learning (ML) model to differentiate between furosemide-responsive (FR) and furosemide-unresponsive (FU) oliguric AKI. METHODS: From Medical Information Mart for Intensive Care-IV (MIMIC-IV) and eICU Collaborative Research Database (eICU-CRD), oliguric AKI patients with urine output (UO) < 0.5 ml/kg/h for the first 6 h after ICU admission and furosemide infusion ≥ 40 mg in the following 6 h were retrospectively selected. The MIMIC-IV cohort was used in training a XGBoost model to predict UO > 0.65 ml/kg/h during 6-24 h succeeding the initial 6 h for assessing oliguria, and it was validated in the eICU-CRD cohort. We compared the predictive performance of the XGBoost model with the traditional logistic regression and other ML models. RESULTS: 6897 patients were included in the MIMIC-IV training cohort, with 2235 patients in the eICU-CRD validation cohort. The XGBoost model showed an AUC of 0.97 (95% CI: 0.96-0.98) for differentiating FR and FU oliguric AKI. It outperformed the logistic regression and other ML models in correctly predicting furosemide diuretic response, achieved 92.43% sensitivity (95% CI: 90.88-93.73%) and 95.12% specificity (95% CI: 93.51-96.3%). CONCLUSION: A boosted ensemble algorithm can be used to accurately differentiate between patients who would and would not respond to furosemide in oliguric AKI. By making the model explainable, clinicians would be able to better understand the reasoning behind the prediction outcome and make individualized treatment.

The global, regional, and national burden of acute pancreatitis in 204 countries and territories, 1990-2019.

BACKGROUND: Acute pancreatitis is a common and potentially lethal gastrointestinal disease, but literatures for the disease burden are scarce for many countries. Understanding the current burden of acute pancreatitis and the different trends across various countries is essential for formulating effective preventive intervenes. We aimed to report the incidence, mortality, and disability-adjusted life-years (DALYs) caused by acute pancreatitis in 204 countries and territories between 1990 and 2019. METHODS: Estimates from the Global Burden of Disease Study 2019 (GBD 2019) were used to analyze the epidemiology of acute pancreatitis at the global, regional, and national levels. We also reported the correlation between development status and acute pancreatitis' age-standardized DALY rates, and calculated DALYs attributable to alcohol etiology that had evidence of causation with acute pancreatitis. All of the estimates were shown as counts and age-standardized rates per 100,000 person-years. RESULTS: There were 2,814,972.3 (95% UI 2,414,361.3-3,293,591.8) incident cases of acute pancreatitis occurred in 2019 globally; 1,273,955.2 (1,098,304.6-1,478,594.1) in women and 1,541,017.1 (1,307,264.4-1,814,454.3) in men. The global age-standardized incidence rate declined from 37.9/100,000 to 34.8/100,000 during 1990-2019, an annual decrease of 8.4% (5.9-10.4%). In 2019, there were 115,053.2 (104,304.4-128,173.4) deaths and 3,641,105.7 (3,282,952.5-4,026,948.1) DALYs due to acute pancreatitis. The global age-standardized mortality rate decreased by 17.2% (6.6-27.1%) annually from 1.7/100,000 in 1990 to 1.4/100,000 in 2019; over the same period, the age-standardized DALY rate declined by 17.6% (7.8-27.0%) annually. There were substantial differences in the incidence, mortality and DALYs across regions. Alcohol etiology attributed to a sizable fraction of acute pancreatitis-related deaths, especially in the high and high-middle SDI regions. CONCLUSION: Substantial variation existed in the burden of acute pancreatitis worldwide, and the overall burden remains high with aging population. Geographically targeted considerations are needed to tailor future intervenes to relieve the burden of acute pancreatitis in specific countries, especially for Eastern Europe.

Nomogram for predicting transmural bowel infarction in patients with acute superior mesenteric venous thrombosis.

BACKGROUND: The prognosis of acute mesenteric ischemia (AMI) caused by superior mesenteric venous thrombosis (SMVT) remains undetermined and early detection of transmural bowel infarction (TBI) is crucial. The predisposition to develop TBI is of clinical concern, which can lead to fatal sepsis with hemodynamic instability and multi-organ failure. Early resection of necrotic bowel could improve the prognosis of AMI, however, accurate prediction of TBI remains a challenge for clinicians. When determining the eligibility for explorative laparotomy, the underlying risk factors for bowel infarction should be fully evaluated. AIM: To develop and externally validate a nomogram for prediction of TBI in patients with acute SMVT. METHODS: Consecutive data from 207 acute SMVT patients at the Wuhan Tongji Hospital and 89 patients at the Guangzhou Nanfang Hospital between July 2005 and December 2018 were included in this study. They were grouped as training and external validation cohort. The 207 cases (training cohort) from Tongji Hospital were divided into TBI and reversible intestinal ischemia groups based on the final therapeutic outcomes. Univariate and multivariate logistic regression analyses were conducted to identify independent risk factors for TBI using the training data, and a nomogram was subsequently developed. The performance of the nomogram was evaluated with respect to discrimination, calibration, and clinical usefulness in the training and external validation cohort. RESULTS: Univariate and multivariate logistic regression analyses identified the following independent prognostic factors associated with TBI in the training cohort: The decreased bowel wall enhancement (OR = 6.37, P < 0.001), rebound tenderness (OR = 7.14, P < 0.001), serum lactate levels > 2 mmol/L (OR = 3.14, P = 0.009) and previous history of deep venous thrombosis (OR = 6.37, P < 0.001). Incorporating these four factors, the nomogram achieved good calibration in the training set [area under the receiver operator characteristic curve (AUC) 0.860; 95%CI: 0.771-0.925] and the external validation set (AUC 0.851; 95%CI: 0.796-0.897). The positive and negative predictive values (95%CIs) of the nomogram were calculated, resulting in positive predictive values of 54.55% (40.07%-68.29%) and 53.85% (43.66%-63.72%) and negative predictive values of 93.33% (82.14%-97.71%) and 92.24% (85.91%-95.86%) for the training and validation cohorts, respectively. Based on the nomogram, patients who had a Nomo-score of more than 90 were considered to have high risk for TBI. Decision curve analysis indicated that the nomogram was clinically useful. CONCLUSION: The nomogram achieved an optimal prediction of TBI in patients with AMI. Using the model, the risk for an individual patient inclined to TBI can be assessed, thus providing a rational therapeutic choice.

Risk of venous thromboembolism associated with totally implantable venous access ports in cancer patients: A systematic review and meta-analysis.

BACKGROUND: Totally implantable venous access ports (TIVAPs) for chemotherapy are associated with venous thromboembolism (VTE). We aimed to quantify the incidence of TIVAP-associated VTE and compare it with external central venous catheters (CVCs) in cancer patients through a meta-analysis. METHODS: Studies reporting on VTE risk associated with TIVAP were retrieved from medical literature databases. In publications without a comparison group, the pooled incidence of TIVAP-related VTE was calculated. For studies comparing TIVAPs with external CVCs, odds ratios (ORs) were calculated to assess the risk of VTE. RESULTS: In total, 80 studies (11 with a comparison group and 69 without) including 39 148 patients were retrieved. In the noncomparison studies, the overall symptomatic VTE incidence was 2.76% (95% confidence interval [CI]: 2.24-3.28), and 0.08 (95 CI: 0.06-0.10) per 1000 catheter-days. This risk was highest when TIVAPs were inserted via the upper-extremity vein (3.54%, 95% CI: 2.94-4.76). Our meta-analysis of the case-control studies showed that TIVAPs were associated with a decreased risk of VTE compared with peripherally inserted central catheters (OR = 0.20, 95% CI: 0.09-0.43), and a trend for lower VTE risk compared with Hickman catheters (OR = 0.75, 95% CI: 0.37-1.50). Meta-regression models suggested that regional difference may significantly impact on the incidence of VTE associated with TIVAPs. CONCLUSIONS: Current evidence suggests that the cancer patients with TIVAP are less likely to develop VTE compared with external CVCs. This should be considered when choosing the indwelling intravenous device for chemotherapy. However, more attention should be paid when choosing upper-extremity veins as the insertion site.

The risk of bloodstream infection associated with totally implantable venous access ports in cancer patient: a systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to provide evidence-based guidance to better understand the risk of central line-associated bloodstream infection (CLABSI) in cancer patients who received totally implantable venous access ports (TIVAPs) compared with those who received external central venous catheters (CVCs). METHODS: A systematic search of PubMed, Web of science, Embase, and the Cochrane Library was carried out from inception through Oct 2018, with no language restrictions. Trials examining the risk of CLABSI in cancer patients who received TIVAPs compared with those who received external CVCs were included. Two reviewers independently reviewed, extracted data, and assessed the risk of bias of each study. A random-effect model was used to estimate relative risks (RRs) with 95% CIs. RESULTS: In all, 26 studies involving 27 cohorts and 5575 patients reporting the incidence of CLABSI in patients with TIVAPs compared with external CVCs were included. Pooled meta-analysis of these trials revealed that TIVAPs were associated with a significant lower risk of CLABSI than were external CVCs (relative risk [RR], 0.44; 95% confidence interval [CI], 0.31-0.62; P < 0.00001), which was confirmed by trial sequential analysis for the cumulative z curve entered the futility area. Subgroup analyses demonstrated that CLABSI reduction was greatest in adult patients (RR [95% CI], 0.35 [0.22-0.56]) compared with pediatric patients who received TIVAPs (RR [95% CI], 0.55 [0.38-0.79]). CONCLUSIONS: TIVAP can significantly reduce the risk of CLABSI compared with external CVCs.

[Effect of bile duct ligation and recanalization on rat hepatocyte epithelial-mesenchymal phenotype and NOX4 protein expression].

OBJECTIVE: To observe epithelial-mesenchymal phenotypes and oxidative stress related protein expressions of the liver cells in a rat model of liver fibrosis induced by bile duct ligation and recanalization. METHODS: Twenty-four male Wistar rats were randomized into 4 groups, including a sham-operated group, two bile duct ligation groups with ligation for 2 and 4 weeks, and a bile duct ligation group with a 2-week ligation followed by a 2-week recanalization. HE staining and Masson staining were used to assess liver fibrosis in the rats, and immunohistochemistry and Western blotting were employed to detect expressions of the epithelial and mesenchymal marker proteins and oxidative stress-related proteins. RESULTS: Compared with the sham-operated group, the rats with bile duct ligation showed obvious liver fibrosis, which worsened as the ligation time extended, accompanied by significantly increased expression of α-SMA, collagen I, NOX(4) and vimetin and reduced E-cadherin expression. Compared with the rats with bile duct ligation for 4 weeks, the rats in bile duct ligation-recanalization group showed obviously lessened liver fibrosis, significantly lowered expressions of NOX(4) and mesenchymal cell maker proteins, and enhanced expressions of epithelial cell marker proteins. CONCLUSION: Bile duct ligation up-regulates mesenchymal phenotype-related proteins and NOX(4) protein expression and down-regulates the expression of epithelial phenotype-related proteins, and these changes can be reversed by subsequent bile duct recanalization.

[Hybrid operation for acute left leg deep venous thrombosis secondary to left iliac vein compression syndrome: analysis of 36 cases].

OBJECTIVE: To evaluate the surgical techniques for acute left deep venous thrombosis (LDVT) secondary to left iliac vein compression syndrome (IVCS). METHODS: Thirty-six patients with acute LDVT secondary to IVCS received inferior vena cava filter placement, and in 2 of the cases, stent implantation was canceled for acute episode of obsolete DVT. The remaining 34 patients underwent left femoral venotomy for iliofemoral thrombectomy with Fogarty catheter and distal femoral vein thrombus removal by sequential compression of the legs, followed by implantation of stent-graft (2 cases) or bare-metal stents (32 cases) in the left common iliac veins. With routine anticoagulation and thrombolytic treatments, the patients were regularly examined for postoperative blood flow in the affected limb. RESULTS: In 2 of the cases undergoing bare-metal stent implantation, the residue thrombi were squeezed into the stent by balloon, which was managed subsequently with local thrombolysis. One patient with bare-metal stent implantation received a secondary stenting for posterior stent displacement. Three patients had self-limited bleeding due to decreased serum FBG. Significant improvements were achieved at 3, 6, 30 and 180 days postoperatively in the circumferences of the affected limb (P<0.05) and in the levels of D-dimer (P=0.011), and FBG level showed no significant variations (F=1.163, P=0.345). The total rate of excellent outcomes was 83.3% (26/34) with a total effective rate of 91.2% (31/34) in these cases. CONCLUSIONS: Thrombectomy to revascularize the inflow tract and stent implantation to enlarge stenosed iliac veins are key issues in treatment of acute LDVT secondary to IVCS.

Spironolactone lowers portal hypertension by inhibiting liver fibrosis, ROCK-2 activity and activating NO/PKG pathway in the bile-duct-ligated rat.

OBJECTIVE: Aldosterone, one of the main peptides in renin angiotensin aldosterone system (RAAS), has been suggested to mediate liver fibrosis and portal hypertension. Spironolactone, an aldosterone antagonist, has beneficial effect on hyperdynamic circulation in clinical practice. However, the mechanisms remain unclear. The present study aimed to investigate the role of spionolactone on liver cirrhosis and portal hypertension. METHODS: Liver cirrhosis was induced by bile duct ligation (BDL). Spironolactone was administered orally (20 mg/kg/d) after bile duct ligation was performed. Liver fibrosis was assessed by histology, Masson's trichrome staining, and the measurement of hydroxyproline and type I collagen content. The activation of HSC was determined by analysis of alpha smooth muscle actin (α-SMA) expression. Protein expressions and protein phosphorylation were determined by immunohistochemical staining and Western blot analysis, Messenger RNA levels by quantitative real time polymerase chain reaction (Q-PCR). Portal pressure and intrahepatic resistance were examined in vivo. RESULTS: Treatment with spironolactone significantly lowered portal pressure. This was associated with attenuation of liver fibrosis, intrahepatic resistance and inhibition of HSC activation. In BDL rat liver, spironolactone suppressed up-regulation of proinflammatory cytokines (TNFα and IL-6). Additionally, spironolactone significantly decreased ROCK-2 activity without affecting expression of RhoA and Ras. Moreover, spironolactone markedly increased the levels of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS and the activity of NO effector-protein kinase G (PKG) in the liver. CONCLUSION: Spironolactone lowers portal hypertension by improvement of liver fibrosis and inhibition of intrahepatic vasoconstriction via down-regulating ROCK-2 activity and activating NO/PKG pathway. Thus, early spironolactone therapy might be the optional therapy in cirrhosis and portal hypertension.

[Association of peripheral blood hypoxia-inducible factor-1α with metastasis of colorectal cancer].

OBJECTIVE: To explore the relationship between hypoxia-inducible factor-1α (HIF-1α) mRNA levels in the peripheral blood and the metastasis of colorectal cancer. METHODS: HIF-1α mRNA in the peripheral blood was detected by RT-PCR in 40 patients with colorectal cancer and 20 healthy subjects. RESULTS: Seventeen patients with colorectal cancer showed positivity for HIF-1α mRNA, showing a significantly higher positivity rate (42.5%) than the healthy subjects (P<0.05). The expression of HIF-1α mRNA is closely related to the staging of colorectal cancer (CRC). CONCLUSION: HIF-1α mRNA may serve as a potential marker in the detection of metastasis of colorectal cancer.

[Efficacy of regional administration of urokinase and argatroban via small saphenous vein catheter for treatment of acute deep venous thrombosis in the lower limb].

OBJECTIVE: To investigate the clinical value of local regional administration of urokinase and argatroban through small saphenous vein (SSV) catheter in the treatment of acute deep venous thrombosis in the lower limb (LDVT). METHODS: Fifty-six patients with acute LDVT were prospectively randomized into the study group (21 cases, 24 limbs) and control group (35 cases, 36 limbs) for treatment with urokinase and argatroban regionally administered via the SSV catheter and with the same agents given via the peripheral vein, respectively. The patients were examined for changes in serum fibrinogen (FBG) and D-dimer and the perimeter of the affected limbs, and the complications in relation to the agents were observed. RESULTS: By corrected Chi-square test, the incidence of complications was significantly lower in the study group than in the control group (1/21 vs 4/36, χ(2)=1.92, P≤0.05). Wilcoxon's sign rank test suggested no statistically significant difference between the two groups in the total effective rate (95.8% vs 94.4%, V=0.52, P>0.05), but the total excellent rate differed significantly between them (83.3% vs 55.6%, V=2.36, P≤0.05). Serum FBG underwent no significant variations in the study group during thrombolysis (P>0.05), but decreased significantly in the control group (P≤0.05). The decreases in serum D-dimer and perimeter of the affected limbs occurred earlier in the study group than in the control group (P≤0.05). CONCLUSION: Regional administration of urokinase and argatroban via small saphenous vein catheter can promote the thrombolytic effect and reduce the risk of hemorrhage in the treatment of LDVT.

[Clinical analysis of 286 cases of abdominal trauma with gastrointestinal tract laceration].

OBJECTIVE: To improve the diagnosis and treatment of abdominal injury. METHODS: The clinical data of 286 patients with gastrointestinal tract laceration admitted between 2004 and 2009 to our hospital was analyzed. RESULTS: The duration after trauma was 15 min to 2 days. Of the 286 patients eventually confirmed by laparotomy, 273 were cured, 3 showed improvement and 10 died. CONCLUSION: Abdominal trauma in patients with gastrointestinal tract laceration, Abdominal puncture diagnosis and orthostatic abdominal X-ray are rapid and effective diagnostic methods for gastrointestinal tract laceration in patients with abdominal trauma. Laparotomy is the primary treatment measures and should be performed as early as possible.

[Application of intraoperative colon irrigation in primary resection and anastomosis of left colorectal cancer with intestinal obstruction].

OBJECTIVE: To study the application of intraoperative irrigation of the colon in primary resection and anastomosis of left colorectal cancer with intestinal obstruction. METHODS: The clinical data were analyzed in 58 patients with left colon rectal cancer and intestinal obstruction undergoing intraoperative irrigation of the colon for primary anastomosis, and the results were compared with 58 patients receiving conventional primary tumor resection. RESULTS: The mean intraoperative blood loss or postoperative hospital stay was comparable between the two groups, but the patients undergoing colon irrigation had significantly delays in the recovery of bowel movement. CONCLUSION: With strict control of the surgery indication, intraoperative colon irrigation can be safe and feasible in primary resection and anastomosis of left colorectal cancer with intestinal obstruction.

[Effect of Helicobacter pylori eradication on childhood acute idiopathic thrombocytopenic purpura].

OBJECTIVE: To evaluate the effect of Helicobacter pylor (Hp) eradication in children with acute idiopathic thrombocytopenic purpura (ITP). METHODS: Ninety-three children with acute ITP and Hp infection were divided into two groups and treated with prednisone and Hp eradication (group A, 51 cases) or with prednisone without Hp eradication (group B, 42 cases). RESULTS: The Hp eradication rate was 94.1% in group A. No difference was found in the therapeutic effects on IPT between the two groups, but the recurrence rate in one year in group A was significantly lower than that in group B. CONCLUSION: NHp eradication does not obviously enhance the therapeutic effect on childhood acute ITP, but can decrease the relapse rate in one year. HP eradication therapy is recommended in children with acute ITP and Hp infection.