Differential expression of the human kallikrein gene 14 (KLK14) in normal and cancerous prostatic tissues

BACKGROUND: Many members of the human kallikrein gene family are differentially expressed in cancer and a few have potential as diagnostic/prognostic markers. KLK14 is a newly discovered human kallikrein gene that is mainly expressed in the central nervous system and endocrine tissues. Since KLK14 was found to be regulated by steroid hormones in prostate cancer cell lines, we hypothesized that it will be differentially expressed in prostate cancer tissues compared to their normal counterparts. METHODS: Matched prostate tissue samples from the cancerous and non-cancerous parts of the same prostates were obtained from 100 patients who underwent radical prostatectomy. Quantitative analysis of KLK14 expression levels were performed by real-time RT-PCR using SYBR Green I dye on the LightCycler trade mark system. Associations with clinico-pathological parameters were analyzed. RESULTS: KLK14 overexpression in the cancerous compared to non-cancerous tissue was found in 74% of patients (P < 0.001). Mean level of expression was 154 arbitrary units (Au) in cancerous tissues and 14.2 Au in the non-cancerous tissues. The ratio of the cancerous to non-cancerous KLK14 expression values was higher in patients with late stage (stage III) compared to stage II (P = 0.002), and in grade 3 compared to grade 1/2 tumors (P = 0.001). A statistically significant increase was also observed in patients with higher in Gleason score (>6) compared to Gleason score = 6 tumors (P = 0.027). No correlation was found between KLK14 tissue expression levels and serum prostate-specific antigen. CONCLUSIONS: KLK14 expression is significantly higher in cancerous compared to non-cancerous prostatic tissue. The up-regulation of the KLK14 gene in advanced and more aggressive tumors may indicate a possible role for the hK14 protein in tumor spread and opens the possibility of hK14 being a candidate new marker for prostate cancer diagnosis and prognosis.     

Developing and validating of Ramathibodi Appendicitis Score (RAMA-AS) for diagnosis of appendicitis in suspected appendicitis patients

Background

Diagnosis of appendicitis is still clinically challenging where resources are limited. The purpose of this study was to develop and externally validate Ramathibodi Appendicitis Score (RAMA-AS) in aiding diagnosis of appendicitis.

Methods

A two-phase cross-sectional study (i.e., derivation and validation) was conducted at Ramathibodi Hospital (for derivation) and at Thammasat University Hospital and Chaiyaphum Hospital (for validation). Patients with abdominal pain and suspected of having appendicitis were enrolled. Multiple logistic regression was applied to develop a parsimonious model. Calibration and discrimination performances were assessed. In addition, our RAMA-AS was compared with Alvarado’s score performances using ROC curve analysis.

Results

The RAMA-AS consisted of three domains with seven predictors including symptoms (i.e., progression of pain, aggravation of pain, and migration of pain), signs (i.e., fever and rebound tenderness), and laboratory tests (i.e., white blood cell count (WBC) and neutrophil). The model fitted well with data, and it performed better discrimination than the Alvarado score with C-statistics of 0.842 (95% CI 0.804, 0.881) versus 0.760 (0.710, 0.810). Internal validation by bootstrap yielded Sommer’s D of 0.686 (0.608, 0.763) and C-statistics of 0.848 (0.846, 0.849). The C-statistics of two external validations were 0.853 (0.791, 0.915) and 0.813 (0.736, 0.892) with fair calibrations.

Conclusion

RAMA-AS should be a useful tool for aiding diagnosis of appendicitis with good calibration and discrimination performances.

     

Ultrasound-guided bilateral rectus sheath block vs. conventional local analgesia in single port laparoscopic appendectomy for children with nonperforated appendicitis

Introduction

Despite its minimally invasive approach, laparoscopic surgery can cause considerable pain. Regional analgesic techniques such as the rectus sheath block (RSB) offer improved pain management following elective umbilical hernia repair in the pediatric population. This effect has not been examined in laparoscopic single-incision surgery in children. We sought to compare the efficacy of bilateral ultrasound-guided RSB versus local anesthetic infiltration (LAI) in providing postoperative pain relief in pediatric single-incision transumbilical laparoscopic assisted appendectomy (TULA) with same-day discharge.

Emergency subtotal hepatectomy: a new concept for acetaminophen-induced acute liver failure: temporary hepatic support by auxiliary orthotopic liver transplantation enables long-term success

INTRODUCTION: Acetaminophen (paracetamol) overdose (AOD) has recently emerged as the leading cause of acute liver failure (ALF) in the United States, with an incidence approaching that seen in the United Kingdom. We describe a new way to treat AOD ALF patients fulfilling King's College criteria for "super-urgent" liver transplantation. METHODS: Beginning in June 1998, we have been piloting a clinical program of subtotal hepatectomy and auxiliary orthotopic liver transplantation (ALT) for AOD ALF. Our technique is based on the following principles: (1) subtotal hepatectomy; (2) auxiliary transplantation of a whole liver graft; (3) gradual withdrawal of immunosuppression after recovery. Results were compared with patients who had undergone an orthotopic liver transplantation (OLT) for AOD ALF in the same period. Quality of life comparisons were made using the SF36 questionnaire. RESULTS: Thirteen patients underwent this procedure between June 1998 and March 2005. Median survival is 68 months (range, 0-102 m). Actual survival data show that 9 of 13 patients are alive (69%) compared with 7 of 13 OLT patients (54%). One ALT patient required a retransplantation with an OLT due to hepatic vein thrombosis, and immunosuppression is therefore maintained. The other 8 surviving ALT patients are off immunosuppression. These 8 ALT patients have normal liver function and have a better quality of life compared with the 7 surviving OLT patients. CONCLUSION: Our results with this new technique are encouraging: 69% actual survival, no long-term immunosuppression requirement, and improved quality of life in the 62% successful cases.     

Impact of Early versus Late Amniotomy on Induction of Labor in Nulliparous Women after Vaginally Administered Misoprostol: A Randomized Clinical Trial

Objective::To investigate the effect of early versus late amniotomy after induction of labor (IOL) with vaginally administered misoprostol.Methods::This randomi...     

Electrospun Nanofibers Revisited: An Update on the Emerging Applications in Nanomedicine

Electrospinning (ES) has become a straightforward and customizable drug delivery technique for fabricating drug-loaded nanofibers (NFs) using various biodegradable and non-biodegradable polymers. One of NF’s pros is to provide a controlled drug release through managing the NF structure by changing the spinneret type and nature of the used polymer. Electrospun NFs are employed as implants in several applications including, cancer therapy, microbial infections, and regenerative medicine. These implants facilitate a unique local delivery of chemotherapy because of their high loading capability, wide surface area, and cost-effectiveness. Multi-drug combination, magnetic, thermal, and gene therapies are promising strategies for improving chemotherapeutic efficiency. In addition, implants are recognized as an effective antimicrobial drug delivery system overriding drawbacks of traditional antibiotic administration routes such as their bioavailability and dosage levels. Recently, a sophisticated strategy has emerged for wound healing by producing biomimetic nanofibrous materials with clinically relevant properties and desirable loading capability with regenerative agents. Electrospun NFs have proposed unique solutions, including pelvic organ prolapse treatment, viable alternatives to surgical operations, and dental tissue regeneration. Conventional ES setups include difficult-assembled mega-sized equipment producing bulky matrices with inadequate stability and storage. Lately, there has become an increasing need for portable ES devices using completely available off-shelf materials to yield highly-efficient NFs for dressing wounds and rapid hemostasis. This review covers recent updates on electrospun NFs in nanomedicine applications. ES of biopolymers and drugs is discussed regarding their current scope and future outlook.     

Left ventricular rotational deformation changes by speckle tracking imaging before and 24 hours after transcatheter closure of large secundum atrial septal defects in children

Background: Large atrial septal defects (ASDs) in children cause increased volume overload of the right side of the heart which in turn lead to impairment of left ventricular (LV) performance. Aim: The aim of this study was to evaluate immediate LV rotational deformation changes in children with large ASDs post-device closure and removal of right ventricle (RV) volume overload. Patients and Methods: Twenty children who underwent transcatheter closure (TCC) of large secundum ASDs were included in the study. LV rotational deformation was assessed pre- and 24 hours post-device closure using speckle tracking imaging (STI). Results: 55% were females with mean age 6.1 ± 3.5 years. LV peak basal clockwise rotation improved significantly (−6.9 ± 2.6° before vs −10.3 ± 4.1° after TCC, P = .005), and time to peak clockwise rotation (345.1 ± 124.7 milliseconds (ms) before vs 282.2 ± 82.9 ms after closure, P = .02). There was no significant difference in apical rotational parameters including peak counterclockwise rotation (P > .05 for both). LV twist (11.3 ± 3.8° before vs 17.5 ± 7.1° after closure, P = .001) and torsion (2.1 ± 0.7°/cm before vs 3.1 ± 1.2°/cm after closure, P = .01) were significantly improved, mainly as the result of improvement of LV basal rotation. LV revealed a significant increase in LV end-diastolic volumes (P = .02) 24 hour after TCC with no significant change (P > .05) in end-systolic volumes after closure. Conclusion: Increased peak LV twisting and torsion were attributed to the improved peak systolic clockwise basal rotation after TCC of large ASDs in children.     

Accuracy and trending of non-invasive hemoglobin measurement during different volume and perfusion statuses

The evolution of non-invasive hemoglobin measuring technology would save time and improve transfusion practice. The validity of pulse co-oximetry hemoglobin (SpHb) measurement in the perioperative setting was previously evaluated; however, the accuracy of SpHb in different volume statuses as well as in different perfusion states was not well investigated. The aim of this work is to evaluate the accuracy and trending of SpHb in comparison to laboratory hemoglobin (Lab-Hb) during acute bleeding and after resuscitation. Seventy patients scheduled for major orthopedic procedures with anticipated major blood loss were included. Radical-7 device was used for continuous assessment of SpHb, volume status [via pleth variability index (PVI)] and perfusion status [via perfusion index (PI)]. Lab-Hb and SpHb were measured at three time-points, a baseline reading, after major bleeding, and after resuscitation. Samples were divided into fluid-responsive and fluid non-responsive samples, and were also divided into high-PI and low-PI samples. Accuracy of SpHb was determined using Bland–Altman analysis. Trending of SpHb was evaluated using polar plot analysis. We obtained 210 time-matched readings. Fluid non-responsive samples were 106 (50.5%) whereas fluid responsive samples were 104 (49.5%). Excellent correlation was reported between Lab-Hb and SpHb (r?=?0.938). Excellent accuracy with moderate levels of agreement was also reported between both measures among all samples, fluid non-responsive samples, fluid-responsive samples, high-PI samples, and low-PI samples [Mean bias (limits of agreement): 0.01 (??1.33 and 1.34) g/dL, ??0.08 (??1.27 and 1.11) g/dL, 0.09 (??1.36 and 1.54) g/dL, 0.01 (??1.34 to 1.31) g/dL, and 0.04 (??1.31 to 1.39) g/dL respectively]. Polar plot analysis showed good trending ability for SpHb as a follow up monitor. In conclusion, SpHb showed excellent correlation with Lab-Hb in fluid responders, fluid non-responders, low-PI, and high PI states. Despite a favorable mean bias of 0.01 g/dL for SpHb, the relatively wide levels of agreement (??1.3 to 1.3 g/dL) might limit its accuracy. SpHb showed good performance as a trend monitor.