Simple genetic diagnosis of hairy cell leukemia by sensitive detection of the BRAF-V600E mutation

Hairy cell leukemia (HCL) is a distinct clinicopathologic entity that responds well to purine analogs but is sometimes difficult to differentiate from HCL-like disorders (e.g., splenic marginal zone lymphoma and HCL variant). We recently identified the BRAF-V600E mutation as the disease-defining genetic event in HCL. In this study, we describe a new, simple, and inexpensive test for genetics-based diagnosis of HCL in whole-blood samples that detects BRAF-V600E through a sensitive allele-specific PCR qualitative assay followed by agarose-gel electrophoresis. This approach detected BRAF-V600E in all 123 leukemic HCL samples investigated containing as few as 0.1% leukemic cells. BRAF-V600E was detected at different time points during the disease course, even after therapy, pointing to its pivotal role in HCL pathogenesis and maintenance of the leukemic clone. Conversely, 115 non-HCL chronic B-cell neoplasms, including 79 HCL-like disorders, were invariably negative for BRAF-V600E. This molecular assay is a powerful tool for improving the diagnostic accuracy in HCL.     

Prognostic value of pulsed tissue Doppler imaging for the assessment of left ventricular systolic function in patients with nonischemic dilated cardiomyopathy

There is still some debate regarding the prognostic significance of left ventricular longitudinal systolic dysfunction as assessed by tissue Doppler (TD) imaging in patients with chronic heart failure (HF), since previous studies have included patients with postischemic wall motion abnormalities. Thus, this study was designed to ascertain whether TD-derived longitudinal systolic dysfunction may influence the outcome of patients with nonischemic chronic HF. In 200 consecutive patients with chronic HF secondary to dilated cardiomyopathy and no history of ischemic heart disease, peak systolic mitral annular velocity (S(m) ) was measured by pulsed TD at the septal and lateral annular sites. The end points were cardiac death or hospitalization for worsening HF. Mean follow-up duration was 30 months. In a time independent analysis, averaged S(m) calculated as the average of septal and lateral S(m) , resulted to be a significant predictor of outcome in the study population (area under receiver-operator characteristic curve: cardiovascular death, 0.69, P < 0.0001; cardiovascular events, 0.64, P = 0.0005). In a time-dependent analysis, average S(m) was associated with both cardiovascular death (hazard ratio 0.832, P = 0.0019) and cardiovascular events (hazard ratio 0.904, P = 0.039), independently of other clinical risk factors and echocardiographic parameters of systolic function. Septal S(m) but not lateral S(m) was independently associated with the outcome measures. In conclusion, the assessment of systolic mitral annular velocity by pulsed TD is a useful indicator for prognostic stratification of patients with nonischemic dilated cardiomyopathy and chronic HF.     

Prognostic power of proadrenomedullin in community-acquired pneumonia is independent of aetiology

Biomarkers are useful in community-acquired pneumonia (CAP). Recently, midregional (MR) proadrenomedullin (proADM) has been shown to be of potential prognostic use. We sought to determine whether this prognostic role depends on the cause of CAP. We conducted a prospective cohort study of immunocompetent patients with CAP. Pneumonia Severity Index (PSI) and CURB-65 score (confusion (abbreviated mental test score of ≤ 8), urea ≥ 7 mol · L(-1), respiratory rate ≥ 30 breaths · min(-1), blood pressure <90 mmHg systolic or <60 mmHg diastolic, and age ≥ 65 yrs), blood C-reactive protein, procalcitonin, MR-proADM, and microbiological studies were systematically performed. Patients were grouped as bacterial, viral/atypical and mixed CAP, and were followed up at 30, 90 and 180 days, and 1 yr. We recruited 228 CAP patients. Identification of at least one pathogen was achieved in 155 (68%) patients. MR-proADM levels closely correlated with increasing severity scores, and showed an important predictive power for complications and short- and long-term mortality (1 yr). Its addition to PSI and CURB-65 significantly improved their prognostic accuracy. A MR-proADM cut-off of 0.646 nmol · L(-1) identified 92% of patients scored as PSI classes IV and V as high risk. MR-proADM outcome prediction power was not affected by different aetiologies. MR-proADM has high short- and long-term prognostic accuracy, and increases the accuracy of clinical scores. The prognostic value of MR-proADM is not modified by different possible CAP aetiologies.     

Oral health status in children with acute lymphoblastic leukemia

Leukemia is a malignancy of the bone marrow. Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy and accounts for nearly 75% of all newly diagnosed leukemias and 25% of all malignancies in childhood. The aim of the present study was to review the oral health status in children with ALL. Databases were explored using various combinations of the following keywords: "acute lymphoblastic leukemia", "children", "inflammation", "pediatric", "periodontal disease" and "periodontitis". Oral inflammatory conditions including chelitis, gingivitis, herpetic gingivostomatitis, mucositis, oral candidiasis, periodontitis and ulcerations are common manifestations in children with ALL. RESULTS: Periodontal inflammatory conditions and oral mucositis were reported to be significantly higher in children with ALL as compared to healthy controls. Tooth morphological disorders including agenesis, microdontia, short roots and developmental defects in the enamel and dentin were more often observed in children with ALL as compared to healthy controls. Children with ALL have a reduced salivary flow rate, which makes them more susceptible to dental caries as compared to healthy children. Malocclusion due to microdontia may also trigger temporomandibular joint disorders in children with ALL; however, this relationship needs further investigations. CONCLUSION: Oral inflammatory conditions including mucositis and gingivitis are common in children with ALL as compared to healthy children. Tooth morphological disorders including microdontia and enamel and dentin are common manifestations in children with ALL.     

Eculizumab Improves Posttransplant Thrombotic Microangiopathy Due to Antiphospholipid Syndrome Recurrence but Fails to Prevent Chronic Vascular Changes

Thrombotic microangiopathy (TMA) is one of the hallmark vascular lesions of antiphospholipid syndrome nephropathy (APSN). These lesions are at high risk of recurrence after kidney transplantation. The complement pathway is thought to be active in this process. We used eculizumab to treat three consecutive kidney transplant recipients with posttransplant TMA due to APSN recurrence that was resistant to plasmapheresis and explored the complement deposition and apoptotic and vascular cell markers on the sequential transplant biopsies. Treatment with eculizumab resulted in a rapid and dramatic improvement of the graft function in all three patients and in improvement of the TMA lesions within the graft. None of these patients had TMA flares after eculizumab was withdrawn. At the time of TMA diagnosis, immunofluorescence studies revealed intense C5b‐9 and C4d depositions at the endothelial cell surface of the injured vessels. Moreover, C5b‐9 colocalized with vessels exhibiting a high rate of apoptotic cells. Examination of sequential biopsies during eculizumab therapy showed that TMA lesions, C4d and apoptotic markers were rapidly cleared but the C5b‐9 deposits persisted for several months as a footprint of the TMA. Finally, we noticed that complement inhibition did not prevent the development of the chronic vascular changes associated with APSN. Eculizumab seems to be an efficient method for treating severe forms of posttransplant TMA due to APSN recurrence. Terminal complement inhibition does not prevent the development of chronic APSN.     

Open Surgical Simulation—A Review

BackgroundSurgical simulation has benefited from a surge in interest over the last decade as a result of the increasing need for a change in the traditional apprentice model of teaching surgery. However, despite the recent interest in surgical simulation as an adjunct to surgical training, most of the literature focuses on laparoscopic, endovascular, and endoscopic surgical simulation with very few studies scrutinizing open surgical simulation and its benefit to surgical trainees. The aim of this review is to summarize the current standard of available open surgical simulators and to review the literature on the benefits of open surgical simulation.Current State of Open Surgical SimulationOpen surgical simulators currently used include live animals, cadavers, bench models, virtual reality, and software-based computer simulators. In the current literature, there are 18 different studies (including 6 randomized controlled trials and 12 cohort studies) investigating the efficacy of open surgical simulation using live animal, bench, and cadaveric models in many surgical specialties including general, cardiac, trauma, vascular, urologic, and gynecologic surgery. The current open surgical simulation studies show, in general, a significant benefit of open surgical simulation in developing the surgical skills of surgical trainees. However, these studies have their limitations including a low number of participants, variable assessment standards, and a focus on short-term results often with no follow-up assessment.Future of Open Surgical SimulationThe skills needed for open surgical procedures are the essential basis that a surgical trainee needs to grasp before attempting more technical procedures such as laparoscopic procedures. In this current climate of medical practice with reduced hours of surgical exposure for trainees and where the patient’s safety and outcome is key, open surgical simulation is a promising adjunct to modern surgical training, filling the void between surgeons being trained in a technique and a surgeon achieving fluency in that open surgical procedure. Better quality research is needed into the benefits of open surgical simulation, and this would hopefully stimulate further development of simulators with more accurate and objective assessment tools.     

Intracranial suppurations in the African child: a severe but preventable complication

Introduction

Intracranial suppurations (ICS) are collections of pus of infectious origin in the skull. The authors present their experience.

Patients and method

All children operated for ICS at the Central Hospital of Yaoundé from January 2000 to December 2008 were retrospectively included.

Results

Thirty-five patients were recruited: 26 (74.29 %) males and 9 (25.71 %) females. These represent 82.9 % of all ICS operated in our institution. ICS represented 14.3 % of intracranial space-occupying lesions. The mean age was 8.34 years. They presented with headaches (80.77 %), altered consciousness (20 %), convulsions (76 %), vomiting (20 %), unilateral motor deficit (69.23 %), speech disorders (12 %), and fever (89.29 %). Bergman’s triad (51.86 %) was frequent. The primary infection was: meningitis, eight cases (22.85 %); sinusitis, six cases (17.14 %); head trauma, five cases (14.28 %); otitis media, one case (2.85 %); suppurations of the face, three cases (8.56 %); cardiopathy, one case (2.85 %); and craniotomy, one case (2.85 %). In seven cases (20 %), the origin was unknown. The lesions were empyema in 23 cases (65.71 %), cerebral abscess in 8 cases (22.85 %) and pyoventriculitis in 2 cases (5.72 %). The surgical procedures were burr holes (88.89 % of empyemas) and trepano-puncture–aspiration (75 % of abscesses). The mortality (21.42 %) and morbidity (42.85 %) were recorded.

Conclusion

ICS are frequent but preventable (early treatment of the primary infection) pathologies of childhood in developing countries. Burr hole drainage (empyemas) and puncture–aspiration (abscesses) are simple, safe, and effective techniques.     

Long-term proper name anomia after removal of the uncinate fasciculus

A previous study reporting on 44 patients who underwent awake surgery for a left frontal or temporal glioma resection demonstrated the removal of the uncinate fasciculus to have consequences on language 3 months post-surgery. At this time-point, patients with a temporal glioma who had undergone uncinate removal showed the worst overall performance with a significant impairment in naming of famous faces and objects compared to patients without removal. Also, verbal fluency was mildly impaired. We report a longer-term follow-up (9–12 months) in a selected group of 17 patients (six female, age range 27–64) who did not suffer any tumour recurrence in this timeframe. MRI and DTI were performed before and after surgery. While verbal fluency on categorical cue and object naming recovered to the same level as before surgery, proper naming remained significantly impaired even after 12 months (P = 0.032) in patients with uncinate removal, demonstrating this structure to be crucial for that function and supporting the hypothesis that subcortical connectivity is relevant to allow plasticity. We thus argued that the left frontal and temporal poles connected by means of the uncinate fasciculus constitute a dedicated circuit for naming of unique entities.     

Mobilizing political support proved critical to a successful switch from tOPV to bOPV in Kano,Nigeria 2016

Background

Kano is one of the high-risk states for polio transmission in Northern Nigeria. The state reported more cases of wild polioviruses (WPVs) than any other state in the country. The Nigeria Demographic and Health Survey of 2013 indicated that OPV3 coverage in the routine immunization (RI) programmewas 57.9%. Additionally, serial polio seroprevalence studies conducted from 2011 to 2015 in the eightmetropolitan LGAs indicated low immunity levels against all three polio serotypes in children below one year. Areas with sub-optimal RI coverage such as Kanothat fail to remove all tOPV during the tOPV-bOPV switchwill be at increased risk of VDPV2 circulation.

Methods

We assessed the impact of political leadership engagement in mobilizing other stakeholders on the outcomes of the bOPV-tOPV switch in Kano State from February to May 2016 using nationally-selected planning and outcome indicators.

Results

A total of 670 health facilities that provide RI services were assessed during the pre-switch activities. Health workers were aware of the switch exercise in 520 (95.1%) of the public health facilities assessed. It was found that health workers knew what to do should tOPV be found in any of the 521 (95.2%)public health facilities assessed. However, there was a wide disparity between the public and private health practitioners’ knowledge on basic concepts of the switch.There was 100% withdrawal of tOPV from the state and the seven zonal cold stores. Unmarked tOPVwas found in the cold chain system in 2 (4.5%) LGAs. Only one health facility (0.8%) had tOPV in the cold chain. No tOPVwas identified outside the cold chain without the “Do not use” sticker in any of the health facilities.

Conclusion

The engagement of the political leadership to mobilize other key stakeholders facilitated successful implementation of the tOPV-bOPVswitch exercise and provided opportunity to strengthen partnerships with the private health sector in Kano State.