Skeletonised retrograde distal perforator island fasciocutaneous flaps for leg and foot defects.

Defects involving the distal leg and foot are frequently encountered following various aetiological factors. Paucity of local tissue causes surgeons to resort to the retrograde peninsular flap, the cross leg flap or the free flap. With specific knowledge of perforators, the fasciocutaneous flap from the calf area can be transferred to the defect in a single stage based on skeletonised distal perforators. The surgical anatomy, flap planning and procedure have been detailed. Nineteen patients were treated during the period 1995 to 2005. The perforators were identified preoperatively by audio Doppler. The flaps were marked and dissected proximal to the defect skeletonising the distal perforators under loupe magnification and transferred to the defect in a single stage. The donor site was skin grafted. Out of 19 cases, 16 flaps healed uneventfully, one flap necrosed completely and in two cases there was marginal necrosis. The cases were followed up for 2-10 years with an average of 6 years. With detailed knowledge of perforators one can safely reconstruct distal moderate-size defects of the lower limb in a single stage, thus having the benefits of free tissue transfer without resorting to microsurgery. This technique has proved to be an advancement in the reconstructive repertoire allowing flaps of non conventional dimensions to be perfused by skeletonised perforators.     

Investigation of the dopamine D5 receptor gene (DRD5) in adult attention deficit hyperactivity disorder

Several lines of evidence from neuroimaging, pharmacology and genetics support the involvement of the dopaminergic system in the etiology of Attention Deficit Hyperactivity Disorder (ADHD). Previous candidate gene studies have investigated the association between a dinucleotide (CA)_n repeat polymorphism, located 18.5 kb from the start codon of the DRD5 gene, and ADHD. Association between the 148 bp allele and ADHD has been reported in some studies, however replication of the finding has not been consistent. We tested for an association between the (CA)_n repeat and adult ADHD in a sample comprised of 119 families with adult ADHD probands and 88 unrelated adult ADHD cases with a corresponding number of controls matched for age, ethnicity and sex. In the family sample we found a non-significant trend for association between the 148 bp allele and ADHD (Z = 1.91, p = 0.055). An excess of non-transmissions was detected for the 150 and 152 bp alleles (Z = −2.26, p = 0.023; Z = −2.20, p = 0.028). Quantitative analysis performed using the Brown Attention Deficit Disorder Scale (BADDS) showed association between the 150 bp allele and lower total score (p = 0.011), and lower effort (p = 0.008), activation (p = 0.008) and attention (p = 0.01) cluster scores. We did not replicate association findings in the case–control group, likely due to the lack of statistical power of this sample. Our findings add to the literature suggesting DRD5 (CA)_n repeat has a modest effect in modulating susceptibility to adult ADHD but further studies are required.     

Clinical Concept-Based Radiology Reports Classification Pipeline for Lung Carcinoma

Rising incidence and mortality of cancer have led to an incremental amount of research in the field. To learn from preexisting data, it has become important to capture maximum information related to disease type, stage, treatment, and outcomes. Medical imaging reports are rich in this kind of information but are only present as free text. The extraction of information from such unstructured text reports is labor-intensive. The use of Natural Language Processing (NLP) tools to extract information from radiology reports can make it less time-consuming as well as more effective. In this study, we have developed and compared different models for the classification of lung carcinoma reports using clinical concepts. This study was approved by the institutional ethics committee as a retrospective study with a waiver of informed consent. A clinical concept-based classification pipeline for lung carcinoma radiology reports was developed using rule-based as well as machine learning models and compared. The machine learning models used were XGBoost and two more deep learning model architectures with bidirectional long short-term neural networks. A corpus consisting of 1700 radiology reports including computed tomography (CT) and positron emission tomography/computed tomography (PET/CT) reports were used for development and testing. Five hundred one radiology reports from MIMIC-III Clinical Database version 1.4 was used for external validation. The pipeline achieved an overall F1 score of 0.94 on the internal set and 0.74 on external validation with the rule-based algorithm using expert input giving the best performance. Among the machine learning models, the Bi-LSTM_dropout model performed better than the ML model using XGBoost and the Bi-LSTM_simple model on internal set, whereas on external validation, the Bi-LSTM_simple model performed relatively better than other 2. This pipeline can be used for clinical concept-based classification of radiology reports related to lung carcinoma from a huge corpus and also for automated annotation of these reports.

     

Upper Airway Obstruction in Patients with Goiter Studied by Flow Volume Loops and Effect of Thyroidectomy

The patient with goiter and his or her physician frequently overlook symptoms of upper respiratory obstruction. Conventional radiology is the accepted method for detecting upper airway obstruction in these patients. Flow volume loops provide additional information on airflow dynamics. Twenty-five patients of goiter undergoing surgery were evaluated for upper airway obstruction by symptomatology, conventional radiology, and flow volume loops. Flow volume loops were repeated 1 month after surgery. Ten (40%) patients had mild symptoms on direct questioning. Tracheal deviation, compression, or both were noted in eight (32%) patients on radiology. Flow volume loops detected upper airway obstruction in 15 (60%) patients. Surgery resulted in normalization of all preoperative abnormal curves. The flow volume loop is a simple noninvasive method for detecting upper airway obstruction in patients with goiter. Abnormal upper airway dynamics are present in more patients with goiter than previously recognized, and relief of this obstruction should be an important aspect of thyroid surgery.     

Role of neutrophils in the synergistic liver injury from monocrotaline and bacterial lipopolysaccharide exposure.

Synergistic liver injury develops in Sprague-Dawley rats from administration of a small, noninjurious dose (7.4 x 10(6) EU/kg) of bacterial lipopolysaccharide (LPS) given 4 h after a nontoxic dose (100 mg/kg) of the pyrrolizidine alkaloid, monocrotaline (MCT). Previous studies demonstrated that liver injury is mediated through inflammatory factors, such as Kupffer cells and tumor necrosis factor alpha (TNF-alpha), rather than through simple interaction between MCT and LPS. In the present study, the hypothesis that neutrophils (polymorphonuclear leukocytes or PMNs) are causally involved in this injury model is tested, and the interdependence between PMNs and other inflammatory components is explored. Hepatic PMN accumulation and the appearance of cytokine-induced neutrophil chemoattractant-1 in plasma preceded the onset of liver injury, suggesting that PMNs contribute to toxicity. Hepatic PMN accumulation was partially dependent on TNF-alpha. Prior depletion of PMNs in MCT/LPS-cotreated animals resulted in attenuation of both hepatic parenchymal cell (HPC) and sinusoidal endothelial cell (SEC) injury at 18 h. PMN depletion did not, however, protect against early SEC injury that occurred before the onset of HPC injury at 6 h. This observation suggests that SEC injury is not entirely dependent on PMNs in this model. In vitro, MCT caused PMNs to degranulate in a concentration-dependent manner. These results provide evidence that PMNs are critical to the HPC injury caused by MCT/LPS cotreatment and contribute to the progression of SEC injury.     

双相恶性子宫肿瘤:一例报道及文献复习(英文)

We present a rare case of a 50-year old lady who presented with pain abdomen and bleeding per vaginum of 3 months duration. Per vaginal examination revealed an exophytic growth arising from vault. Histopathological examination of the vault biopsy showed malignant neoplasm with features suggestive of carcinosarcoma of vault with immunohistochemistry showing stromal cells positive for CD10 and negative for SMA. Ki67 index was 40%-50%. She received external beam radiotherapy to pelvis 50.4 Gy/25 fractions but did not respond to the same. The lesion was not surgically resectable and hence referred to the division of medical oncology for chemotherapy. She was started on ifosphamide with cisplatin with growth factor support. It was planned to do a reassessment after 3 cycles of chemotherapy, but patient succumbed to the illness.     

Combined melanocytic and sweat gland neoplasm: cell subsets harbor an identical HRAS mutation in phacomatosis pigmentokeratotica

Phacomatosis pigmentokeratotica (PPK) is characterized by the co‐existence of epidermal nevi and large segmental speckled lentiginous nevi of the papulosa type. PPK, previously explained as ‘twin spot’ mosaicism due to the postzygotic crossing‐over of two homozygous recessive mutations, has recently been shown to derive from one postzygotic activating RAS mutation. Epidermal nevi, including those in PPK, are known to give rise to neoplasms such as trichoblastoma and basal cell carcinoma. Within speckled lentiginous nevi, Spitz nevi and melanoma have been well documented. We report a case of PPK with a combined melanocytic and adnexal neoplasm presenting where the nevi conjoined. Using next‐generation sequencing techniques, we were able to identify the same HRAS G13R mutation within both components of the tumor, and to show the absence of additional mutated modifier genes in a panel of 300 cancer‐related genes. Given the genetic findings in this rare tumor‐type, we suggest that this case may be used as a model for understanding the development of biphenotypic neoplasia or intratumoral heterogeneity in some cases.     

The genomic landscape of fibrolamellar hepatocellular carcinoma: whole genome sequencing of ten patients

Fibrolamellar hepatocellular carcinoma is a rare, malignant liver tumor that often arises in the otherwise normal liver of adolescents and young adults. Previous studies have focused on biomarkers and comparisons to traditional hepatocellular carcinoma, and have yielded little data on the underlying pathophysiology. We performed whole genome sequencing on paired tumor and normal samples from 10 patients to identify recurrent mutations and structural variations that could predispose to oncogenesis. There are relatively few coding, somatic mutations in this cancer, putting it on the low end of the mutational spectrum. Aside from a previously described heterozygous deletion on chromosome 19 that encodes for a functional, chimeric protein, there were no other recurrent structural variations that contribute to the tumor genotype. The lack of a second-hit mutation in the genomic landscape of fibrolamellar hepatocellular carcinoma makes the DNAJB1-PRKACA fusion protein the best target for diagnostic and therapeutic advancements. The mutations, altered pathways and structural variants that characterized fibrolamellar hepatocellular carcinoma were distinct from those in hepatocellular carcinoma, further defining it as a distinct carcinoma.