Transcranial Doppler screening in sickle cell disease: The implications of using peak systolic criteria

AIM: To compare time average maximum mean velocity(TAMV) and peak systolic velocity(PSV) criteria of Trans Cranial Doppler(TCD) in their ability to predict abnormalities on magnetic resonance imaging(MRI)/magnetic resonance angiogram(MRA) in patients with sickle cell disease. METHODS: A retrospective evaluation was performed of the outcomes in all patients with a Transcranial Doppler examination at our institution since the implementation of the hospital picture archiving and communication system(PACS) system in January 2003 through December 2012. All ultrasound imaging exams were performed by the same technologist with a 3 MHz transducer. Inclusion criteria was based upon the Transcranial Doppler procedure code in our PACS which had an indication of sickle cell disease in the history. The patient’s age and gender along with the vessel with the highest time averaged mean velocity as well as the highest peak systolic velocity was recorded for analysis. A subset of the study cohort also had subsequent MR imaging and Angiograms performed within 6 mo of the TCD examination. MRI results were categorized as having a disease related abnormality(vessel narrowing, collateral formation/moya-moya, or abnormal fluid attenuation inversion recovery signal in parenchyma indicative of prior stroke) or normal. The MRI results formed the comparison standards for TCD exams in evaluating intracranial injury. Sensitivity and specificity for the two TCD criteria(TAMV and PSV) were calculated to determine which could be a better predictor for intracranial vasculopathy /clinically occult strokes.RESULTS: The study cohort for our institution was 110patients with a total of 291 TCD examinations. These patients had a mean age of 7.6 years with a range from 2-18 years of age. Sixty-two of the 110 patients(56%) had two or more TCD exams. Thirty-seven patients(34%) had at least one MRI following a TCD examination. Of the 291 TCD examinations, 46(16%) were conditional or abnormal by TAMV criteria. One hundred and sixteen(40%) were conditional or abnormal by PSV criteria. All studies that were abnormal by TAMV were also abnormal by PSV criteria. Seventy of the 116(60%) studies which were conditional or abnormal by peak systolic criteria would not have been identified by time averaged mean maximum velocity criteria. The most frequent location of highest velocity measurement was noted to be in the middle cerebral artery regardless of whether it was measured by PSV or TAMV. From the 37 patients having one or more MRIs, 43 MRI exams were performed within 6 mo of a TCD examination. Twenty two(51%) MRIs had a disease related abnormality reported. When evaluating conditional or abnormal exams by PSV criteria against follow-up MRI/MRA, the sensitivity was 73% [16/(16 + 6)] and specificity was 81% [17/(4 + 17)]. When evaluating conditional or abnormal exams by TAMV criteria by follow-up MRI/MRA as the gold standard, the sensitivity was 41% [9/(9 + 13)] and the specificity was 100% [21/(21 + 0)]. In using conditional or abnormal criteria from PSV and TAMV to predict abnormalities on followup MRI/MR Angiogram, PSV was more sensitive(73% vs 41%) while TAMV was more specific(100% vs 81%). CONCLUSION: Based on the data obtained at our institution and using the assumption that the best screening test is the one with the highest sensitivity, the peak systolic velocity could be the measurement of choice for TCD screening.     

Periodontal conditions, oral Candida albicans and salivary proteins in type 2 diabetic subjects with emphasis on gender

Background  

The association between periodontal conditions, oral yeast colonisation and salivary proteins in subjects with type 2 diabetes (T2D) is not yet documented. The present study aimed to assess the relationship between these variables in type 2 diabetic subjects with reference to gender.     

A preclinical pipeline to evaluate migrastatics as therapeutic agents in metastatic melanoma

Background Metastasis is a hallmark of cancer and responsible for most cancer deaths. Migrastatics were defined as drugs interfering with all modes of cancer cell invasion and thus cancers’ ability to metastasise. First anti-metastatic treatments have recently been approved.Methods We used bioinformatic analyses of publicly available melanoma databases. Experimentally, we performed in vitro target validation (including 2.5D cell morphology analysis and mass spectrometric analysis of RhoA binding partners), developed a new traceable spontaneously metastasising murine melanoma model for in vivo validation, and employed histology (haematoxylin/eosin and phospho-myosin II staining) to confirm drug action in harvested tumour tissues.Results Unbiased and targeted bioinformatic analyses identified the Rho kinase (ROCK)-myosin II pathway and its various components as potentially relevant targets in melanoma. In vitro validation demonstrated redundancy of several RhoGEFs upstream of RhoA and confirmed ROCK as a druggable target downstream of RhoA. The anti-metastatic effects of two ROCK inhibitors were demonstrated through in vivo melanoma metastasis tracking and inhibitor effects also confirmed ex vivo by digital pathology.Conclusions We proposed a migrastatic drug development pipeline. As part of the pipeline, we provide a new traceable spontaneous melanoma metastasis model for in vivo quantification of metastasis and anti-metastatic effects by non-invasive imaging.Subject terms: Skin cancer, Cancer models, Drug discovery, Metastasis     

Fast-track anesthesia in lateral mini-thoracotomy for transapical transcatheter valve implantation

BackgroundPatients who undergo transapical transcatheter aortic/mitral valve implantation are at higher risk of morbidity and mortality than those undergoing transvascular procedures. In addition, these patients have prolonged intensive care and hospital courses. Fast-track anesthesia could reduce perioperative complications and admission stays in such patients.MethodsThis retrospective single-center study, evaluates six high-risk patients undergoing transapical valve implantation between 01/2020 till 01/2021. All patients received a paravertebral block (PVB) as part of a fast-track approach. The airway was secured with a Gastro-double-lumen laryngeal mask which includes one orifice was for ventilation and one for the transesophageal echocardiography probe. Anesthesia was maintained with a volatile anesthetic (Sevoflurane MAC 1%). Immediately post procedure, all patients were awakened and admitted to the intermediate/intensive-care unit.ResultsThree patients were females, mean age =71±6 years, patients’ risk profiles were high (mean Log. EuroSCORE-I 22% & STS-PROM 10%). No incidents of re-intubation, atelectasis/pneumonia, low output syndrome, stroke, dialysis, pacemaker implantation or operative mortality were reported. One patient (16.7%) underwent re-exploration for bleeding and developed a wound infection. Postoperative pain scores showed that no patient required additional analgesics after the initial eight hours post procedure. Mean postoperative intermediate/intensive-care stay was 13.8±3.2 hours and patients were mobilized early and discharged to the normal ward.ConclusionsFast-track anesthesia using paravertebral-blockade for transcatheter transapical valve replacement in high-risk patients is a possible anesthetic approach. An effective PVB, in addition to a double-lumen laryngeal mask, provide an alternative strategy to conventional general anesthesia. These promising results could encourage further consideration of this approach in similar cardiac surgery patients.