Open fractures of the proximal humerus treated with the Ilizarov method

We followed 12 patients who had been treated with the Ilizarov method for open proximal humeral fractures for more than 3 years. No wound infection occurred. Avascular necrosis and nonunion were each detected in 1 patient. According to Neer's criteria, the outcome was excellent or satisfactory in 8 patients.     

Myocardial perfusion is preserved in patients with psoriasis without clinically evident cardiovascular disease

Background  Psoriasis is associated with a premature atherosclerosis due to the chronic inflammatory process. To evaluate the effect of disease process on myocardial perfusion, we planned to perform 99mTc-MIBI myocardial perfusion single photon emission computed tomography (SPECT) in patients with psoriasis.
Methods  The study group consisted of 28 psoriasis patients (17 men, 11 women), aged 18-76 years, and mean age 41.2 ± 14.1 years. The patients were selected among those who were older than 18 years and longer than 10 years of disease duration with more than two times of systemic treatment. All patients underwent 99mTc-MIBI myocardial perfusion SPECT with the same day protocol.
Results  We detected various risk factors including smoking habits in 7, family history of cardiovascular disease in 4, hypertension in 1, hyperlipidemia in 9 patients. We completed myocardial perfusion SPECT for each patient and found normal perfusion pattern in SPECT images.
Conclusion  We detected that myocardial perfusion is preserved in the patients with psoriasis. The majority of acute heart attacks are caused by noncritical coronary stenosis and this may be an explanation for increased cardiovascular risk in these patients despite normal coronary perfusion.     

A comparison of external fixation and locked intramedullary nailing in the treatment of femoral diaphysis fractures from gunshot injuries

Introduction

We studied the safety and incidence of complications from the treatment of gunshot-induced femur diaphysis fractures with locked intramedullary nailing in comparison to external fixation.

Methods

Patients who had femoral diaphysis fracture operations due to gunshot injuries (107 femurs of 99 patients) between 2003 and 2014 were retrospectively reviewed, and 66 femurs of 60 patients were place into two groups (Group A: intramedullary nailing—38 femurs of the 36 patients; Group B: external fixator—28 femurs of 24 patients). The mean follow-up was 76.3 months (22–131). The study outcomes were patient complications, infection rate, union time, need for secondary surgery, functional assessment with lower extremity functional scale, and radiological evaluation with orthoroentgenograms.

Results

The mean age of the patients was 37.3 ± 7.4 years in Group A and 39 ± 6.1 years in Group B. There was no significant difference between the two groups in age, gender or follow-up. There were two deep infections (5.2%) in Group A and one deep infection (3.5%) in Group B. Delayed union was observed in four patients (10.5%) in Group A and in two patients (7.1%) in Group B. There was one non-union (2.6%) and one non-union (3.5%) in Group A and Group B, respectively. There was no significant difference between the two groups in incidence of union, delayed union or deep infection. The mean union time was 3.1 ± 2.5 months in Group A and 5.8 ± 1.4 months in Group B. The union time was significantly lower in the intramedullary nailing group (p = 0.023). There were no significant differences between the two groups in regards to radiological and functional evaluation.

Discussion

This study showed similar complication rates and functional results both for external fixator and intramedullary nailing for the treatment of femoral diaphysis fractures due to gunshot injuries.

Level of evidence

Level 3 retrospective comparative clinical study.

     

Clinical Validation and Implementation of a Targeted Next-Generation Sequencing Assay to Detect Somatic Variants in Non-Small Cell Lung,Melanoma, and Gastrointestinal Malignancies

We tested and clinically validated a targeted next-generation sequencing (NGS) mutation panel using 80 formalin-fixed, paraffin-embedded (FFPE) tumor samples. Forty non-small cell lung carcinoma (NSCLC), 30 melanoma, and 30 gastrointestinal (12 colonic, 10 gastric, and 8 pancreatic adenocarcinoma) FFPE samples were selected from laboratory archives. After appropriate specimen and nucleic acid quality control, 80 NGS libraries were prepared using the Illumina TruSight tumor (TST) kit and sequenced on the Illumina MiSeq. Sequence alignment, variant calling, and sequencing quality control were performed using vendor software and laboratory-developed analysis workflows. TST generated ≥500× coverage for 98.4% of the 13,952 targeted bases. Reproducible and accurate variant calling was achieved at ≥5% variant allele frequency with 8 to 12 multiplexed samples per MiSeq flow cell. TST detected 112 variants overall, and confirmed all known single-nucleotide variants (n = 27), deletions (n = 5), insertions (n = 3), and multinucleotide variants (n = 3). TST detected at least one variant in 85.0% (68/80), and two or more variants in 36.2% (29/80), of samples. TP53 was the most frequently mutated gene in NSCLC (13 variants; 13/32 samples), gastrointestinal malignancies (15 variants; 13/25 samples), and overall (30 variants; 28/80 samples). BRAF mutations were most common in melanoma (nine variants; 9/23 samples). Clinically relevant NGS data can be obtained from routine clinical FFPE solid tumor specimens using TST, benchtop instruments, and vendor-supplied bioinformatics pipelines.In modern oncologic practice, patients with advanced-stage non-small cell lung cancer (NSCLC),^{1, 2} melanoma,^{3, 4} and colorectal adenocarcinoma^{5, 6} are often treated with targeted therapies as standard of care or after enrollment in clinical trials. Molecular mutation analysis is the preferred testing modality to guide therapeutic decision making and/or eligibility for biological studies. Therefore, laboratory-developed mutation assays require robust workflows that produce high-quality sequence information from routine clinical specimens, namely formalin-fixed, paraffin-embedded (FFPE) samples. As molecular testing transitions from an ancillary tool to a seminal requirement for optimal oncologic patient management, multiplex sequencing assays with clearly defined content and bioinformatics workflows are essential for accurate and consistent results, reporting, and patient management.Published guidelines endorse which genes to test in a particular tumor type and provide timeframes for receipt of actionable results, but they also grant individual laboratories autonomy to perform mutation testing using any suitable validated method.² Historically at our institution, single-gene mutation analysis for clinically relevant genes was performed either in-house or at a Clinical Laboratory improvement Amendment–certified reference laboratory. Depending on the result, reflex testing was performed for additional genes per mutation frequency or designated algorithms. Unfortunately, this approach introduced considerable turn-around time delays and unnecessary cost, particularly when send-out testing was required. Therefore, we sought testing modalities that could analyze multiple clinically relevant mutations simultaneously, accurately, and expeditiously.Next-generation sequencing (NGS) technologies have revolutionized genomic medicine by allowing high-throughput, parallel sequencing of the human genome.⁷ Currently, however, a large proportion of clinical NGS endeavors are supported by larger academic institutions with shared access to established genomic and bioinformatics research infrastructures, and routine clinical implementation of NGS is complicated by mitigating factors, such as clinical performance, laboratory expertise, lengthy turn-around times, and cost.⁸ Thus, we investigated affordable methods to detect clinically relevant somatic mutations in NSCLC, melanoma, and gastrointestinal (GI) malignancies that generated high-quality sequencing data from FFPE samples, and offered manageable turn-around times. Targeted amplicon-based library preparation methods combined with parallel sequencing offered a practical solution, and recent studies have demonstrated the utility of this approach.^{9, 10}Reversible terminal dideoxynucleotide sequencing chemistry by Illumina (San Diego, CA) consistently generates accurate and reproducible sequencing data.^{11, 12} To use this chemistry for clinical testing, we purchased the bench-top NGS sequencer, the Illumina MiSeq, and paired it with the MiSeq-compatible Illumina TruSight tumor (TST) 26-target amplicon-based library preparation kit. TST targets 26 genes and 174 amplicons selected from College of American Pathologists/National Comprehensive Cancer Network guidelines, relevant publications, and late-phase pharmaceutical clinical trials (Supplemental Table S1). TST offered several advantages over other commercially available mutation testing kits, such as bidirectional targeting of the positive and negative DNA strands, full-exon coverage as opposed to hotspot analysis, and robust vendor-supplied bioinformatics techniques optimized for somatic variant detection. More important, TST library preparation is optimized for FFPE samples, multiple safeguards exist to detect FFPE variant artifacts, and deep sequencing of TST libraries consistently yields high depths of coverage of targeted regions.Somatic mutation testing for many of the TST genes has clinical utility in a wide variety of solid tumors. For example, testing for CTNNB1 exon 3 is performed clinically for diagnostic and prognostic purposes in pediatric desmoid tumors, select PIK3CA hotspot mutations are positive prognostic factors for breast carcinoma, and multiple exons in PDGFRA and KIT are routinely tested in GI stromal tumors to predict response to targeted therapies. More important for our intended validation purposes, all of the clinically relevant genes and regions mutated in NSCLC, melanoma, and colonic adenocarcinoma that were tested in our routine clinical practice were represented. In addition, we could easily incorporate the TST NGS into a 5 business day workflow model, and a cost-analysis demonstrated a reasonable cost per test.Last, TST NGS data are processed from raw sequence (FASTQ) to called variants with on-board MiSeq Reporter software version 2.3, and variant annotations can be performed with Illumina''s VariantStudio software version 2.1 software using standard desktop and laptop computers. The ease of library preparation, sequencing, and data analysis with tools provided by a single vendor best fit our clinical priorities and the resources available at our academic molecular pathology laboratory.Herein, we present our results from the clinical validation of TST NGS using 80 sequenced samples that were selected from 100 FFPE patient samples (40 NSCLCs, 30 melanomas, and 30 GI malignancies). During our validation, we achieved high depths of coverage for multiple clinically relevant variants when multiplexing 8 to 12 samples on a single MiSeq flow cell. TST NGS consistently demonstrated sensitivities comparable to reference assays, showed 100% concordance with known variants, detected novel variants in many samples, and uncovered variants missed by less-sensitive testing modalities. The TST variant-calling pipeline was robust and showed high concordance when compared with an alternative analysis pipeline, and we used an in-house custom Java program to assess laboratory-defined quality control (QC) metrics and streamline clinical reporting (developed by G.H.S., Emory University, http://github.com/ghsmith/coverageQc). More important, although the results detailed herein represent the experience of a single institution, the data and validation strategies shown herein are broadly applicable to most clinical molecular laboratories interested in offering NGS for NSCLCs, melanomas, and GI malignancies as well as many other solid tumors.     

Sonographic evaluation of gallbladder volume and ejection fraction in obese women without gallstones

PURPOSE: Obese people have an increased incidence of gallstones. Although the exact pathogenic mechanisms of gallstone development are unknown, impaired gallbladder emptying has been suggested as a possible underlying mechanism. Our aim was to investigate this possibility by evaluating gallbladder motility and related factors in obese and nonobese women without gallstones. METHODS: This study included 79 obese women and 25 nonobese healthy women. Using real-time sonography, we evaluated fasting and postprandial (15th-, 30th-, 45th-, 60th-, 75th-, 90th-, 120th-, and 150th-minute) gallbladder volumes and ejection fractions. The smallest postprandial volume was considered the residual volume. RESULTS: Mean (+/- standard deviation) fasting and residual gallbladder volumes were 43.2 +/- 18.3 cm(3) and 21.4 +/- 11.2 cm(3), respectively, in the obese women and 28.1 +/- 12.3 cm(3) and 7.9 +/- 3.4 cm(3), respectively, in the nonobese women. Maximal ejection fraction was 49 +/- 19% in obese women and 63 +/- 29% in nonobese women (p = 0.001). The fasting and residual volumes and the postprandial volumes at all time points were higher in obese women than in nonobese women (p < 0.001). In addition, 15th-, 30th-, 45th-, 60th-, 75th-, and 90th-minute postprandial ejection fractions were lower in obese women than in nonobese women (p < 0.001). Positive correlations were found between fasting gallbladder volume and body mass index and body fat weight and between residual volume and body mass index, waist circumference, body fat percentage, and body fat weight (p < 0.05 for all comparisons). CONCLUSIONS: Our results show that fasting and postprandial gallbladder volumes are higher and that postprandial gallbladder motility is lower in obese than in nonobese women. There are positive correlations between fasting gallbladder volume and body weight, body mass index, and body fat weight.     

Open fixation in flail chest: review of 64 patients

The strategy for treatment of flail chest remains controversial. Various alternatives were assessed by reviewing the records of 64 patients treated from 1991 through 2000. Patients were classified according to therapeutic approach: group 1 was 27 patients who underwent open fixation of the fractured ribs, group 2 was 19 patients managed by intermittent positive-pressure ventilation, and group 3 was 18 patients managed mainly by synchronized intermittent mandatory ventilation. Two patients initially treated by ventilation underwent successful open fixation. In group 1, ventilatory support was required in 21 (77.8%) patients postoperatively, the mean duration of ventilation was 3.1 days, mean hospital stay was 18.3 days, morbidity was 11.1% (3/27), and mortality was 11.1%. In groups 2 and 3, the mean time for stabilization of paradoxical chest wall movement was 6.6 days, and mean duration of ventilation was 7.2 days. Mortality was 27.0% (10/37) in patients treated nonsurgically; 21.0% (4/19) in group 2, and 33.3% (6/18) in group 3. In groups 2 and 3, pain control required epidural analgesia in 13 (35.1%) cases, intercostal nerve blockade in 16 (43.2%), and narcotic or nonnarcotic parenteral analgesia in 8 (21.6%). Open fixation is a successful treatment modality for traumatic flail chest.     

Unusual complication of aortic dissections: intimo–intimal intussusception

Angiography with a pre-diagnosis of acute coronary syndrome was performed in a 76-year-old female patient presenting to another hospital with symptoms of chest pain and syncope. Upon determination of type III aortic dissection, the patient was referred to our clinic. On CT angiography, the ascending aortic diameter was 57 mm and no dissection flap was observed. There was a filling defect suggestive of intimo–intimal intussusception at the level of the aortic arch, occlusion of the left arteria carotid communis, and a double-channel aorta extending from the left subclavian artery to the iliac artery. On transoesophageal echocardiography, the ascending aorta was seen to be larger than normal and no dissection flap was observed. There were findings suggestive of haematoma and intimo–intimal intussusception at the proximal part of the aortic arch. The dissection flap causing occlusion in the vascular structures was resected. Supracoronary graft replacement of the ascending aorta was performed. Transoesophageal echocardiography is an invasive investigative method with high sensitivity and specificity for the diagnosis of intimo–intimal intussusception.