A Sewing Needle in the Liver: 6 Years Later

A 27-year-old male patient was admitted for renal colic. In the radiographic findings of his kidney-ureter-bladder, a 6-cm-long sewing needle was detected in the right upper abdominal region. The needle displayed a direction toward the diaphragm, and the center of the needle had a radiolucent discontinuity. He refused to be operated. No complication was observed during the 6-year follow-up. Foreign bodies in the liver are generally recommended to be removed. This case is the first one in the literature with a needle in the liver remaining for 6 years without a change of location or causing a complication.     

Analytical validation of genotyping assays in the biomarker laboratory

High-throughput, whole-genome association studies conducted in various diseases and therapeutic settings are identifying an increasing number of single nucleotide polymorphisms that may predict patient responses and ultimately guide therapeutic decision-making. In order to confirm the candidate genetic markers emerging from these studies, there is a commensurate need for pharmacogenomic laboratories to design and analytically validate targeted genotyping assays capable of rapidly querying the identified individual single nucleotide polymorphisms of interest in large confirmatory clinical studies. In recent years, a number of increasingly complex technologies have been applied to the qualitative and semi-quantitative analysis of polymorphisms and mutations in DNA. The different approaches available for targeted DNA sequence analysis are characterized by various pros and cons that often present technology-specific challenges to the analytical validation of these assays prior to their use in clinical studies. Several key principles in the analytical validation of genotyping assays--including assay specificity, sensitivity, reproducibility and accuracy--are covered in this review article, with specific attention paid to three major end point detection technologies currently employed in targeted genotyping analysis: matrix-assisted laser desorption ionization time-of-flight mass spectrometry, Pyrosequencing and Taqman-based allelic discrimination. Thorough assessment of the performance of genotyping assays during analytical validation, and careful use of quality controls during sample analysis, will help strengthen the quality of pharmacogenomic data used to ultimately confirm the validity of exploratory biomarkers in DNA.     

A prospective, randomized trial comparing the efficacy of dexamethasone and betamethasone for the treatment of antepartum HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome

OBJECTIVE: This study was undertaken to determine whether dexamethasone or betamethasone is superior for the antepartum treatment of HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. STUDY DESIGN: This prospective, randomized, clinical investigation compared intravenously administered dexamethasone and intramuscularly administered betamethasone in the treatment of gravid women with HELLP syndrome. Efficacy end points included laboratory values (platelet count, lactate dehydrogenase activity, aspartate aminotransferase activity) and clinical parameters (mean arterial pressure, urinary output). RESULTS: Forty patients were enrolled in the study, 19 in the dexamethasone arm and 21 in the betamethasone arm. The adjusted time-averaged changes from baseline were significant for aspartate aminotransferase activity (dexamethasone, -20.4 +/- 9.6 U/L; betamethasone, 9.9 +/- 8.9 U/L; P =.029), mean arterial pressure (dexamethasone, -15.6 +/- 1.4 mm Hg; betamethasone, -8.1 +/- 1.4 mm Hg; P <.001), and urinary output (dexamethasone, 12.9 +/- 8.6 mL/h; betamethasone, -11.9 +/- 8.2 mL/h; P =.043). CONCLUSION: Intravenously administered dexamethasone appears to be more effective than intramuscularly administered betamethasone for the antepartum treatment of mothers with HELLP syndrome.     

Function and health status outcomes in a randomized trial comparing preoperative and postoperative radiotherapy in extremity soft tissue sarcoma.

PURPOSE: Morbidity associated with wound complications may translate into disability and quality-of-life disadvantages for patients treated with radiotherapy (RT) for soft tissue sarcoma (STS) of the extremities. Functional outcome and health status of extremity STS patients randomized in a phase III trial comparing preoperative versus postoperative RT is described. PATIENTS AND METHODS: One hundred ninety patients with extremity STS were randomized after stratification by tumor size dichotomized at 10 cm. Function and quality of life were measured by the Musculoskeletal Tumor Society Rating Scale (MSTS), the Toronto Extremity Salvage Score (TESS), and the Short Form-36 (SF-36) at randomization, 6 weeks, and 3, 6, 12, and 24 months after surgery. RESULTS: One hundred eighty-five patients had function data. Patients treated with postoperative RT had better function with higher MSTS (25.8 v 21.3, P <.01), TESS (69.8 v 60.6, P =.01), and SF-36 bodily pain (67.7 v 58.5, P =.03) scores at 6 weeks after surgery. There were no differences at later time points. Scores on the physical function, role-physical, and general health subscales of the SF-36 were significantly lower than Canadian normative data at all time points. After treatment arm was controlled for, MSTS change scores were predicted by a lower-extremity tumor, a large resection specimen, and motor nerve sacrifice; TESS change scores were predicted by lower-extremity tumor and prior incomplete excision. When wound complication was included in the model, patients with complications had lower MSTS and TESS scores in the first 2 years after treatment. CONCLUSION: The timing of RT has minimal impact on the function of STS patients in the first year after surgery. Tumor characteristics and wound complications have a detrimental effect on patient function.     

Dexamethasone compared with betamethasone for glucocorticoid treatment of postpartum HELLP syndrome

Objectives: To compare the efficacy of dexamethasone and betamethasone to ameliorate the course of postpartum hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. Methods: A prospective, mixed randomized/non-randomized clinical investigation of patients with postpartum HELLP syndrome. Treatment with either dexamethasone or betamethasone was continued until there was evidence of disease recovery. Results: Baseline characteristics of both the dexamethasone (n=18) and betamethasone (n=18) groups were similar. Although the time to discharge from the obstetrical recovery room was not statistically significant between groups, reduction in mean arterial blood pressure was more pronounced in the dexamethasone group as compared with the betamethasone group (−15.3±1.4 mmHg vs. −7.5±1.4 mmHg, respectively, P<0.01). Patients in the dexamethasone group required less antihypertensive treatment than the betamethasone group (6% vs. 50%, P=0.01) and also had a decreased need for readmission to the obstetrical recovery room (0% vs. 22%, P=0.03). Conclusion: This investigation supports the use of dexamethasone as the superior glucocorticoid to use for patients with postpartum HELLP syndrome.     

Time-domain NIRS system based on supercontinuum light source and multi-wavelength detection: validation for tissue oxygenation studies

We present and validate a multi-wavelength time-domain near-infrared spectroscopy (TD-NIRS) system that avoids switching wavelengths and instead exploits the full capability of a supercontinuum light source by emitting and acquiring signals for the whole chosen range of wavelengths. The system was designed for muscle and brain oxygenation monitoring in a clinical environment. A pulsed supercontinuum laser emits broadband light and each of two detection modules acquires the distributions of times of flight of photons (DTOFs) for 16 spectral channels (used width 12.5 nm / channel), providing a total of 32 DTOFs at up to 3 Hz. Two emitting fibers and two detection fiber bundles allow simultaneous measurements at two positions on the tissue or at two source-detector separations. Three established protocols (BIP, MEDPHOT, and nEUROPt) were used to quantitatively assess the system’s performance, including linearity, coupling, accuracy, and depth sensitivity. Measurements were performed on 32 homogeneous phantoms and two inhomogeneous phantoms (solid and liquid). Furthermore, measurements on two blood-lipid phantoms with a varied amount of blood and Intralipid provide the strongest validation for accurate tissue oximetry. The retrieved hemoglobin concentrations and oxygen saturation match well with the reference values that were obtained using a commercially available NIRS system (OxiplexTS) and a blood gas analyzer (ABL90 FLEX), except a discrepancy occurs for the lowest amount of Intralipid. In-vivo measurements on the forearm of three healthy volunteers during arterial (250 mmHg) and venous (60 mmHg) cuff occlusions provide an example of tissue monitoring during the expected hemodynamic changes that follow previously well-described physiologies. All results, including quantitative parameters, can be compared to other systems that report similar tests. Overall, the presented TD-NIRS system has an exemplary performance evaluated with state-of-the-art performance assessment methods.     

Maternal mortality associated with HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome.

OBJECTIVE: The aim of this study was to determine factors contributing to deaths among women with HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. STUDY DESIGN: Information from multiple sources was scrutinized to distinguish and profile maternal deaths associated with HELLP syndrome. RESULTS: Information was available regarding 54 maternal deaths. According to HELLP syndrome classification 60.0% had class 1 disease, 35.6% had class 2 disease, and 4.4% had class 3 disease. Events associated with maternal deaths included cerebral hemorrhage (45%), cardiopulmonary arrest (40%), disseminated intravascular coagulopathy (39%), adult respiratory distress syndrome (28%), renal failure (28%), sepsis (23%), hepatic hemorrhage (20%), and hypoxic ischemic encephalopathy (16%). Delay in diagnosis of HELLP syndrome was implicated in 22 of 43 patients' deaths (51.1%). CONCLUSIONS: It appears that (1) most maternal deaths occurred among women with class 1 HELLP syndrome, (2) delay in diagnosis was associated with mortal consequences, and (3) hemorrhage in the hepatic or central nervous system or vascular insult to the cardiopulmonary or renal system were associated with increased mortality risk.     

Role of C825T polymorphism of GNbeta3 gene in preeclampsia.

OBJECTIVE: The main objective of the study was to understand the role of C825T polymorphism that generates a splice variant in the beta3 subunit of heterotrimeric G-protein in preeclampsia. RESULTS: We analyzed genomic DNA of 151 women with preeclampsia (72 Caucasians and 79 African-Americans) and 198 women with normal delivery (102 Caucasians and 96 African-Americans) for C825T polymorphism of GNbeta3 gene. The T-allele frequency in Caucasian women with preeclampsia was 0.42 as compared to 0.25 in normal pregnant women (p = 0.0004) and in African-American women with preeclampsia was 0.82 as compared to 0.68 in normal pregnant women (p = 0.0028). CONCLUSIONS: Results of these experiments show that the allele frequency of C825T polymorphism is significantly different in women with preeclampsia compared with women with normal delivery in Caucasian as well as African-American population.