Epidemiology,clinical picture and long-term outcomes of FIP1L1-PDGFRA-positive myeloid neoplasm with eosinophilia: Data from 151 patients

FIP1L1-PDGFRA-positive myeloid neoplasm with eosinophilia (F/P+ MN-eo) is a rare disease: robust epidemiological data are lacking and reported issues are scarce, of low sample-size and limited follow-up. Imatinib mesylate (IM) is highly efficient but no predictive factor of relapse after discontinuation has yet been identified. One hundred and fifty-one patients with F/P+ MN-eo (143 males; mean age at diagnosis 49 years; mean annual incidence: 0.18 case per million population) were included in this retrospective nationwide study involving all French laboratories who perform the search of F/P fusion gene (study period: 2003-2019). The main organs involved included the spleen (44%), skin (32%), lungs (30%), heart (19%) and central nervous system (9%). Serum vitamin B12 and tryptase levels were elevated in 74/79 (94%) and 45/57 (79%) patients, respectively, and none of the 31 patients initially treated with corticosteroids achieved complete hematologic remission. All 148 (98%) IM-treated patients achieved complete hematologic and molecular (when tested, n = 84) responses. Forty-six patients eventually discontinued IM, among whom 20 (57%) relapsed. In multivariate analysis, time to IM initiation (continuous HR: 1,01 [0.99-1,03]; P = .05) and duration of IM treatment (continuous HR: 0,97 [0,95-0,99]; P = .004) were independent factors of relapse after discontinuation of IM. After a mean follow-up of 80 (56) months, the 1, 5- and 10-year overall survival rates in IM-treated patients were 99%, 95% and 84% respectively. In F/P+ MN-eo, prompt initiation of IM and longer treatment durations may prevent relapses after discontinuation of IM.     

Clinical manifestations of autosomal recessive polycystic kidney disease (ARPKD): kidney-related and non-kidney-related phenotypes

Autosomal recessive polycystic kidney disease (ARPKD), although less frequent than the dominant form, is a common, inherited ciliopathy of childhood that is caused by mutations in the PKHD1-gene on chromosome 6. The characteristic dilatation of the renal collecting ducts starts in utero and can present at any stage from infancy to adulthood. Renal insufficiency may already begin in utero and may lead to early abortion or oligohydramnios and lung hypoplasia in the newborn. However, there are also affected children who have no evidence of renal dysfunction in utero and who are born with normal renal function. Up to 30 % of patients die in the perinatal period, and those surviving the neonatal period reach end stage renal disease (ESRD) in infancy, early childhood or adolescence. In contrast, some affected patients have been diagnosed as adults with renal function ranging from normal to moderate renal insufficiency to ESRD. The clinical spectrum of ARPKD is broader than previously recognized. While bilateral renal enlargement with microcystic dilatation is the predominant clinical feature, arterial hypertension, intrahepatic biliary dysgenesis remain important manifestations that affect approximately 45 % of infants. All patients with ARPKD develop clinical findings of congenital hepatic fibrosis (CHF); however, non-obstructive dilation of the intrahepatic bile ducts in the liver (Caroli’s disease) is seen at the histological level in only a subset of patients. Cholangitis and variceal bleeding, sequelae of portal hypertension, are life-threatening complications that may occur more often in advanced cases of liver disease. In this review we focus on common and uncommon kidney-related and non-kidney-related phenotypes. Clinical management of ARPKD patients should include consideration of potential problems related to these manifestations.     

The Behavioral Intervention Technology Model: An Integrated Conceptual and Technological Framework for eHealth and mHealth Interventions

A growing number of investigators have commented on the lack of models to inform the design of behavioral intervention technologies (BITs). BITs, which include a subset of mHealth and eHealth interventions, employ a broad range of technologies, such as mobile phones, the Web, and sensors, to support users in changing behaviors and cognitions related to health, mental health, and wellness. We propose a model that conceptually defines BITs, from the clinical aim to the technological delivery framework. The BIT model defines both the conceptual and technological architecture of a BIT. Conceptually, a BIT model should answer the questions why, what, how (conceptual and technical), and when. While BITs generally have a larger treatment goal, such goals generally consist of smaller intervention aims (the "why") such as promotion or reduction of specific behaviors, and behavior change strategies (the conceptual "how"), such as education, goal setting, and monitoring. Behavior change strategies are instantiated with specific intervention components or “elements” (the "what"). The characteristics of intervention elements may be further defined or modified (the technical "how") to meet the needs, capabilities, and preferences of a user. Finally, many BITs require specification of a workflow that defines when an intervention component will be delivered. The BIT model includes a technological framework (BIT-Tech) that can integrate and implement the intervention elements, characteristics, and workflow to deliver the entire BIT to users over time. This implementation may be either predefined or include adaptive systems that can tailor the intervention based on data from the user and the user’s environment. The BIT model provides a step towards formalizing the translation of developer aims into intervention components, larger treatments, and methods of delivery in a manner that supports research and communication between investigators on how to design, develop, and deploy BITs.     

Immunohistochemical and clinical evaluation of cathepsin expression in soft tissue sarcomas

Lysosomal proteases are known to enhance the spread of epithelial tumour cells, but little is known of the possible role of proteases in the growth of soft tissue sarcomas (STS). We investigated the expression of cathepsins D, B, S, H, L and procathepsin L in frozen sections of 34 STS from 34 patients by immunohistochemistry (IHC). Cathepsins D, B and H were relatively highly expressed in STS (77–91%). The expression rate of cathepsins S and L and of procathepsin L was lower (40–66%). Cathepsin S and L expression showed a moderate (P = 0.078 andP = 0.019) and procathepsin L a strong (P = 0.00001) correlation with the survival rate of STS patients. Cathepsin S expression is also correlated with the local recurrence rate (P < 0.01). Lysosomal proteases may play a role in STS progression, and cathepsin expression may also have, significance as a prognostic factor in STS.     

An unusual complication of missed appendicitis

A case of necrotizing fasciitis complicating missed appendicitis with perforation and abscess formation in a 63-year-old diabetic is presented. The case emphasizes the importance of thorough, conservative evaluation and management in elderly diabetic patients. The ED management of patients with necrotizing fasciitis is also briefly reviewed.     

Subclavian steal with ipsilateral vertebral artery occlusive disease

The classical subclavian steal syndrome is a larcenous vertebrobasilar insufficiency, secondary to retrograde flow in the vertebral artery. The authors present their experience with an unusual variant of subclavian steal in which the ipsilateral vertebral artery was completely or partially occluded, or arose from the aortic arch. These patients had symptoms typical of vertebrobasilar insufficiency--dizziness or brain stem transient ischemic attacks--despite steal through relatively small cervical collaterals to the obstructed subclavian artery. Physical findings of diminished pulses and blood pressure in the involved upper extremity are similar to those in the common form of subclavian steal. The alternate collaterals found in these patients are documented by angiography and other potential collaterals are reviewed. All three symptomatic patients were treated successfully by carotid-subclavian bypass or anastomosis of the subclavian to the common carotid artery. They have remained asymptomatic for 1 1/2 to 3 years following operation. The potential for development of subclavian steal in the absence of a vertebral artery to provide collateral flow adds another reason for abandoning vertebral artery ligation as an alternative treatment for the subclavian steal syndrome.     

Dynamic cervical plates: biomechanical evaluation of load sharing and stiffness.

STUDY DESIGN: An in vitro biomechanical study using a simulated cervical corpectomy model to compare the load-sharing properties and stiffnesses of two static and two dynamic cervical plates. OBJECTIVES: To evaluate the load-sharing properties of the instrumentation with a full-length graft and with 10% graft subsidence and to measure the stiffness of the instrumentation systems about the axes of flexion-extension, lateral bending, and axial torsion under these same conditions. SUMMARY OF BACKGROUND DATA: No published reports comparing conventional and dynamic cervical plates exist. METHODS: Six specimens of each of the four plate types were mounted on ultra-high molecular weight polyethylene-simulated vertebral bodies. A custom four-axis spine simulator applied pure flexion-extension, lateral bending, and axial torsion moments under a constant 50 N axial compressive load. Load sharing was calculated through a range of applied axial loads up to 120 N. The stiffness of each construct was calculated in response to +/-2.5 Nm moments about each axis of rotation with a full-length graft, a 10% shortened graft, and no graft. ANOVA and Fisher's post hoc test were used to determine statistical significance (alpha < or = 0.05). RESULTS: The two locked cervical plates (CSLP and Orion) and the ABC dynamic plate were similar in flexion-extension, lateral bending, and torsional stiffness. The DOC dynamic plate was consistently less stiff. The Orion plate load shared significantly less than the other three plates with a full graft. Both the ABC and the DOC plates were able to load share with a shortened graft, whereas the conventional plates were not. CONCLUSIONS: All plates tested effectively load share with a full-length graft, whereas the two dynamic cervical plates tested load share more effectively than the locked plates with simulated graft subsidence. The effect of dynamization on stiffness is dependent on plate design.     

Activity in the paracingulate and cingulate sulci during word generation: an fMRI study of functional anatomy.

The supracallosal medial frontal cortex can be divided into three functional domains: a ventral region with connections to the limbic system, an anterior dorsal region with connections to lateral prefrontal systems, and a posterior dorsal region with connections to lateral motor systems. Lesion and functional imaging studies implicate this medial frontal cortex in speech and language generation. The current functional magnetic resonance imaging (fMRI) study of word generation was designed to determine which of these three functional domains was substantially involved by mapping individual subjects' functional activity onto structural images of their left medial frontal cortex. Of 28 neurologically normal right-handed participants, 21 demonstrated a prominent paracingu- late sulcus (PCS), which lies in the anterior dorsal region with connections to lateral prefrontal systems. Activity increases for word generation centered in the PCS in 18 of these 21 cases. The posterior dorsal region also demonstrated significant activity in a majority of participants (16/28 cases). Activity rarely extended into the cingulate sulcus (CS) (3/21 cases) when there was a prominent PCS. If there was no prominent PCS, however, activity did extend into the CS (6/7 cases). In no case was activity present on the crest of the cingulate gyrus, which is heavily connected to the limbic system. Thus, current findings suggest that medial frontal activity during word generation reflects cognitive and motor rather than limbic system participation. The current study demonstrates that suitably designed fMRI studies can be used to determine the functional significance of anatomic variants in human cortex.