Study of placenta in sickle cell disorders

Remarkable changes are seen on gross and microscopic examination of placenta of patients with sickle cell disorders, hence the present study was undertaken to find out the pathological changes seen in the placenta of sickle cell disorder patients, as compared to control and to study the effect of maternal sickling on the fetus. It includes total 73 cases, of which 10 were of control group and 63 were from patients with sickle cell disorders, which included 47 sickle cell trait (AS) and 16 sickle cell disease (SS) patients. In group II, 9 (14.28%) patients with SS pattern developed complications during pregnancy, in the form of vaso-occlusive and hemolytic crises. Pregnancy induced hypertension was seen in 4 (25%) out of 16 SS and 11 (23.40%) of the 47 AS patients. Urinary tract infection (UTI) was seen in 6 (37.5%) out of 16 SS and 8 (17.02%) out of 47 AS patients. Placentae in sickle cell disorders showed pathological changes in the form of infarction, calcification, sickled red blood cells and hemorrhage in intervillous spaces, increased syncytial knots, fibrinoid necrosis, stromal fibrosis, hyalinised villi and compensatory proliferation of trophoblastic cells.     

Delayed High Output Heart Failure due to Arteriovenous Fistula Complicated with Herniated Disc Surgery

A 36-year-old male presented with progressive exertional dyspnea over months. Physical examination showed jugular venous distension, lung crecipitations, femoral bruit and pitting pedal edema. Echocardiogram showed a dilated right ventricle with severe pulmonary hypertension and a non collapsing inferior vena cava (IVC). On right heart catheterization, IVC oxygen saturation was noted at 92% suggesting arterial mixing; a computed tomography of the abdomen showed a fistula between the right common iliac artery to the right common iliac vein at L4 level and a massive IVC; this was linked to trauma from a disectomy done 16 years ago at L4–L5 level. Endovascular sealing with a 16 × 60 mm bifurcated stent graft (S & G Biotech, Seoul, Korea) was performed which led to complete resolution of the patient’s dyspnea. Iatrogenic vascular injury during lumbar disc surgery, although rare, can lead to high output cardiac failure developing over months to years.     

DNA damage induced by industrial solid waste leachates in Drosophila melanogaster: a mechanistic approach

Genomic stability requires that error-free genetic information be transmitted from generation to generation, a process that is dependent upon efficient DNA repair. Industrial leachates which contain mixtures of diverse chemicals are a major environmental concern. The interaction between these chemicals may have synergistic, antagonistic, or simply additive effects on biological systems. In the present study, the Comet assay was used to measure the DNA damage produced by leachates of solid wastes from flashlight battery, pigment, and tanning factories in the midgut cells and brain ganglia of Drosophila melanogaster mutants deficient in DNA repair proteins. Larvae were allowed to feed for 48 or 72 hr on diets containing 0.1, 0.5, and 2.0% (v/v) of the leachates. Physicochemical analysis run on the solid wastes, leachates, and treated larvae detected elevated levels of heavy metals. Leachates produced significantly greater levels of DNA damage in mutant strains mei41 (deficient in cell cycle check point protein), mus201 (deficient in excision repair protein), mus308 (deficient in postreplication repair protein), and rad54 (deficient in double strand break repair protein) than in the OregonR(+) wild-type strain. Larvae of the ligaseIV mutant (deficient in double strand break repair protein) were hypersensitive only to the pigment plant waste leachate. Conversely, the dnase2 mutant (deficient in protein responsible for degrading fragmented DNA) was more sensitive to DNA damage induction from the flashlight battery and tannery waste leachates. Our data demonstrate that repair of DNA damage in organisms exposed to leachates is dependent upon several DNA repair proteins, indicative of the involvement of multiple overlapping repair pathways. The study further suggests the usefulness of the Comet assay for studying the mechanisms of DNA repair in Drosophila.     

Loss of DLC1 is an independent prognostic factor in patients with oral squamous cell carcinoma

Deleted in liver cancer (DLC1), a Rho GTPase-activating protein, was observed to be differentially expressed in oral squamous cell carcinoma in comparison with normal tissues using tissue proteomics. In the current study, we investigated the clinical significance of loss of DLC1 expression in different stages of development of oral squamous cell carcinoma to determine its potential as a biomarker for oral dysplasia and prognosis of oral squamous cell carcinoma. Immunohistochemical analysis of DLC1 expression was carried out in oral squamous cell carcinoma patients (n=214), dysplasia (n=51), hyperplastic squamous mucosa (n=45), and histologically normal oral tissues (n=80), and correlated with clinicopathological parameters and disease prognosis over 91 months for oral squamous cell carcinomas. Loss of DLC1 expression was observed in oral squamous cell carcinoma (64%), oral dysplasia (31%), hyperplastic squamous mucosa (22%), and normal mucosa (16%). Significant loss of DLC1 expression was observed in oral squamous cell carcinomas as compared with dysplasia (P<0.001, odds ratio=3.8, 95% CI=2.0-7.3), suggesting it may be an important event involved in cancer progression. Among oral squamous cell carcinomas, the loss of DLC1 expression was significantly associated with poor prognosis (P=0.021, hazards ratio (HR)=1.8, 95% CI=1.1-2.9). Multivariate analysis revealed loss of DLC1 (P=0.023, HR=2.1, 95% CI=1.2-3.9) and histopathological grade (P=0.015, HR=1.7, 95% CI=1.1-2.7) to be independent predictors for disease-free survival in oral squamous cell carcinoma patients in comparison with known prognostic factors, viz. tumor stage, nodal status, and overall stage. Loss of DLC1 expression emerged as an important biomarker for predicting patients diagnosed with oral dysplasia at high risk of transformation upon future validation in longitudinal studies. Loss of DLC1 expression is a poor prognostic marker for oral squamous cell carcinoma patients.     

Circulating microparticle tissue factor,thromboembolism and survival in pancreaticobiliary cancers

Background

Tissue factor (TF), the physiologic initiator of coagulation, is over-expressed in pancreatic cancer, and is associated with a pro-coagulant and pro-angiogenic state. We hypothesized that in patients with pancreaticobiliary cancers (PBC), elevated circulating microparticle-associated TF (MP-TF) activity would be associated with thrombosis and worsened survival.

Patients and Methods

Clinical data and plasma were obtained for consecutive patients with PBC seen at Roswell Park Cancer Institute from 2005-08. MP-TF activity levels were measured using a TF-dependent FXa generation assay.

Results

The study population comprised 117 patients, including pancreatic (n = 80), biliary (n = 34) or unknown primary histologically consistent with PBC (n = 3). Of these, 52 patients (44.5%) experienced thromboembolism, including pulmonary embolism (n = 15), deep venous thrombosis (n = 21) and other arterial or venous events (n = 32). Mean TF was 2.15 (range 0.17- 31.01) pg/mL. Median survival was 98.5 days for MP-TF activity ≥ 2.5 pg/mL versus 231 days for MP-TF activity < 2.5 pg/mL (p < 0.0001). In multivariate analysis, elevated MP-TF activity was associated with both VTE (OR 1.4, 95% CI 1.1-1.6) and mortality (HR 2.5, 95% CI 1.4-4.5).

Conclusions

Elevated circulating MP-TF activity is associated with thrombosis and worsened survival in patients with PBC. MP-TF activity as a prognostic biomarker warrants further prospective evaluation.     

Sudden unexpected death in epilepsy in lamotrigine randomized‐controlled trials

Purpose: Nonrandomized studies of the relationship of antiepileptic drugs (AEDs) with sudden unexpected death in epilepsy (SUDEP) may be susceptible to confounding by tonic–clonic seizure frequency, polypharmacy, and other potential risk factors for SUDEP. We evaluated the risk of SUDEP with lamotrigine (LTG) compared to active comparators and placebo in randomized controlled clinical trials conducted by GlaxoSmithKline (GSK) between 1984 and 2009. Methods: Among 7,774 subjects in 42 randomized clinical trials, there were 39 all‐cause deaths. Ten deaths occurred >2 weeks after discontinuation of study medication and were excluded. Narrative summaries of deaths were independently reviewed by three clinical experts (TT, LH, DF), who were blinded to randomized treatment arm. The risk of definite or probable SUDEP was compared between treatment arms for each trial type (placebo‐controlled, active‐comparator, crossover), using exact statistical methods. Key Findings: Of 29 on‐treatment deaths, eight were definite/probable SUDEP, four were possible SUDEP, and 17 were non‐SUDEP. The overall, unadjusted rate of definite/probable SUDEP for LTG was 2.2 events per 1,000‐patient years (95% confidence interval [95% CI] 0.70–5.4). The odds ratios (OR) for on‐treatment, definite/probable SUDEP in LTG arms relative to comparator arms, adjusted for length of exposure and trial, were the following: placebo‐controlled, OR 0.22 (95% CI 0.00–3.14; p = 0.26); active‐comparator, OR 2.18 (95% CI 0.17–117; p = 0.89); and placebo‐controlled cross‐over, OR 1.08 (95% CI 0.00–42.2; p = 1.0). Significance: There was no statistically significant difference in rate of SUDEP between LTG and comparator groups. However, the CIs were wide and a clinically important effect cannot be excluded.     

Surgical robotics and laparoscopic training drills

PURPOSE: We investigated the impact of robotics on surgical skills by comparing traditional laparoscopy with the da Vinci Surgical System in the performance of various laparoscopic training drills. SUBJECTS AND METHODS: Twenty-one surgeons performed eight timed drills of increasing difficulty with a laparoscopic trainer and the da Vinci Surgical System (Intuitive Surgical Sunnyvale, CA). The mean time to drill completion, drill time variance, and statistical analysis were performed. Surgeons were also questioned about their perception of the robotic technology following completion of the drill series. RESULTS: The mean time required to complete the first drill was 69 seconds with laparoscopy and 57 seconds with the robotic system. The mean times for drill two were 67 seconds with laparoscopy and 44 seconds with robotics; for drill three, the times were 88 seconds for laparoscopy and 61 seconds for robotics, and for drill four, 186 seconds with laparoscopy and 71 seconds with robotics. Only the first drill failed to show a statistically significant difference between the laparoscopic and robotic groups. CONCLUSIONS: The robotic system allowed surgeons to complete drills faster than traditional laparoscopy. Novice laparoscopic surgeons performed three of the four drills faster robotically than did expert laparoscopic surgeons. These findings may indicate that the attributes of the robotic system level the playing field between surgeons of different skill levels. The next generation of surgeons must focus on this evolving technology and its application in the operating room of the future.     

Emergency radiologic approach to mastoid air cell fluid

Emergency Radiology - Mastoid air cell fluid is a commonly seen, but often dismissed finding. Given the location of the mastoid portion of the temporal bone and its location adjacent to vital...     

A comparison of 2 methods of vaginal cuff closure during robotic hysterectomy

ObjectiveTo compare 2 methods of vaginal cuff closure with regard to safety, ease of use, and postoperative outcome.MethodsAll patients undergoing robotic-assisted total hysterectomy by a gynecologic oncologist from July 1, 2010, to July 1, 2011, at Northwestern Memorial Prentice Women's Hospital were included in a retrospective analysis. Providers used either 2–0 monofilament synthetic absorbable suture to close the vaginal cuff in a running fashion, secured with an absorbable suture clip at the angles and then knotted in the middle, or 2–0 absorbable unidirectional barbed suture with a welded-loop closure in a running fashion.ResultsA total of 134 patients underwent robotic-assisted total hysterectomy. The 2–0 tied monofilament closure was used in 58 patients, and the 2–0 barbed knotless closure was used in 76 patients. There were no instances of vaginal cuff dehiscence or vaginal cuff cellulitis. Rates of vaginal spotting and bleeding were comparable between the groups (12.0% spotting in the monofilament suture group vs 13.0% spotting in the barbed suture group). All vaginal cuff bleeding resolved on its own without significant intervention.ConclusionThe use of either a 2–0 welded-loop unidirectional barbed suture or a 2–0 monofilament absorbable suture to close the vaginal cuff is safe and well tolerated.