Multisystem Langerhans cell histiocytosis: Literature review and case report

Langerhans cell histiocytosis (LCH) refers to a group of diseases of unknown etiology, typically discovered in childhood, characterized by the accumulation of Langerhans cells (white blood cells with large cell nuclei that may contain cytoplasmic histiocytosis X bodies) involving one or more organ systems, including bones, lungs, pituitary gland, skin, lymph nodes, and liver. This disease is also known as histiocytosis X or eosinophilic granuloma. Pulmonary LCH is common (identified in 40% of LCH patients) and may be isolated to the lung or involve other organs. Although LCH is characterized by clonal cell proliferation, adult LCH is considered likely to represent the manifestation of an aberrant immune response to an unspecified antigenic stimulus rather than a manifestation of tumor proliferation. We report a very complicated clinical case of LCH, with multiple organ damage that received a variety of different diagnoses. An LCH diagnosis was confirmed based on postoperative spinal cord pathology results and immunohistochemistry examinations. This case report highlights the clinical, laboratory, and imaging signs observed in this case that should be noted to help doctors more quickly recognize, diagnose, and treat similar cases.     

Pulsed dye laser treatment of capillary malformations in infants at 2‐weekly versus 3‐monthly intervals,reducing the need for general anaesthesia

Capillary malformations (CM) cause significant psychosocial complications. Pulsed dye laser (PDL) treatment at 6–12‐weekly intervals under general anaesthesia (GA) commencing in infants at 6 months of age remains the standard of care in order to achieve maximal improvement prior to school age. The safety of repeated GA in children is controversial. Shortening the time between treatments increases the number that can be delivered prior to 6 months of age, thus reducing the number of subsequent treatments needed under GA. We investigated the safety and effectiveness of more frequent PDL treatment of CM in infancy via a pilot, prospective patient‐controlled study of 10 patients. Using 595 nm (Vbeam) PDL, the entire CM was treated initially, then half the CM randomly allocated to 2‐weekly and half to 3‐monthly intervals for two further treatments. Photographs of the CM taken 3 months after treatment completion were evaluated by an independent, blinded dermatologist. Nine infants completed the study. Three infants (33%) had more improvement on the 2‐weekly treated side and four (44%) had more improvement on the 3‐monthly treated side. Two patients (22%) showed no difference between sides. Treatments were well tolerated without complications. We conclude that 2‐weekly PDL treatments of CM in infants aged under 6 months is effective and well tolerated without adverse effects. Our preliminary data suggest a possible superior efficacy with 3‐monthly treatment intervals; however, larger studies are warranted for stronger evidence. More frequent non‐GA treatment of CM in infants should be further investigated to decrease the risk of repeated GA exposure in young children.     

A Study of the Growth Patterns of Breast Carcinoma Using 3D Reconstruction: A Pilot Study

Lumpectomy with microscopically clear margins is a safe and effective approach for surgical management of breast carcinoma. Margins are positive for tumor in 18–50% of lumpectomies, as it is not possible to accurately determine the shape or microscopic borders of a tumor preoperatively or intraoperatively. We examined the 3D microanatomy and growth patterns of common breast carcinoma subtypes to provide guidance for lumpectomy surgery. Prospective consent was obtained for the use of excess tissue from patients undergoing lumpectomy or mastectomy for breast carcinoma. Tissue blocks from nine breast carcinomas were serially sectioned. Hematoxylin and eosin‐stained slides at 100 μm intervals were scanned using a Nanozoomer (Hamamatsu, Japan) microscopic‐resolution scanner. Three‐dimensional reconstructions of tumors were created from scanned images using Reconstruct, open‐access software. Breast carcinoma subtypes demonstrated characteristic growth patterns within breast tissue, which may have implications for lumpectomy surgery. Invasive ductal carcinomas showed a spherical shape, with a spiculated surface representing tumor cells infiltrating into surrounding parenchyma. Ductal carcinoma in situ appeared to spread along the duct system, creating dilated, tortuous, tumor‐filled ducts. The invasive lobular carcinomas examined had a haphazard, linear, infiltrative growth pattern, different from the shape seen in ductal carcinomas. Our preliminary work suggests that invasive ductal and invasive lobular carcinomas appear to have distinct growth patterns in three dimensions and ductal carcinoma in situ appears to grow in a linear fashion along the duct network. The microanatomy studies described have the potential to guide refinements in breast lumpectomy technique.     

The Use of an Automated,Portable Glucose Control System for Overnight Glucose Control in Adolescents and Young Adults With Type 1 Diabetes

OBJECTIVE

A key milestone in progress towards providing an efficacious and safe closed-loop artificial pancreas system for outpatient use is the development of fully automated, portable devices with fault detection capabilities to ensure patient safety. The ability to remotely monitor the operation of the closed-loop system would facilitate future physician-supervised home studies.

RESEARCH DESIGN AND METHODS

This study was designed to investigate the efficacy and safety of a fully automated, portable, closed-loop system. The Medtronic Portable Glucose Control System (PGCS) consists of two subcutaneous glucose sensors, a control algorithm based on proportional-integral-derivative with insulin feedback operating from a BlackBerry Storm smartphone platform, Bluetooth radiofrequency translator, and an off-the-shelf Medtronic Paradigm Veo insulin pump. Participants with type 1 diabetes using insulin pump therapy underwent two consecutive nights of in-clinic, overnight, closed-loop control after a baseline open-loop assessment.

RESULTS

Eight participants attended for 16 overnight studies. The PGCS maintained mean overnight plasma glucose levels of 6.4 ± 1.7 mmol/L (115 ± 31 mg/dL). The proportion of time with venous plasma glucose <3.9, between 3.9 and 8 (70 and 144 mg/dL), and >8 mmol/L was 7, 78, and 15%, respectively. The proportion of time the sensor glucose values were maintained between 3.9 and 8 mmol/L was greater for closed-loop than open-loop (84.5 vs. 46.7%; P < 0.0001), and time spent <3.3 mmol/L was also reduced (0.9 vs. 3%; P < 0.0001).

CONCLUSIONS

These results suggest that the PGCS, an automated closed-loop device, is safe and effective in achieving overnight glucose control in patients with type 1 diabetes.Intensive management of type 1 diabetes is necessary to achieve near-normal glucose levels to obtain A1C values associated with a reduced risk of microvascular and macrovascular complications. Large-scale studies have revealed that in some patients, such efforts are associated with an increased risk of severe hypoglycemia (1). The effects of intensive management on the incidence of severe hypoglycemia may be even greater in children and adolescents (2), particularly in the setting of diminished counterregulatory hormone responses (3,4). Despite the development of insulin analogs and increasing use of insulin pump therapy, approximation of physiologic insulin delivery has not been achievable by most. Presently, children with an A1C <7% spend approximately one-quarter of each 24-h period with glucose levels >11.1 mmol/L (200 mg/dL) (3). Even with use of sensor-augmented pump therapy, the epitome of technology currently available to patients, one-third or less patients achieve an A1C target <7% (5,6), and the incidence of severe hypoglycemia is not reduced.Currently, there are two principal approaches to β-cell replacement therapy. Islet-cell transplantation has demonstrated promising results in recovery of hypoglycemia awareness and reduction in episodes of hypoglycemia (7). Unfortunately, there are risks associated with immunosuppressive therapy (8), and currently, <75% of patients are insulin-independent 4 years after transplant (7). The second and, arguably, more promising therapeutic approach to β-cell replacement is a closed-loop artificial pancreas incorporating a continuous glucose sensor, insulin pump, and control algorithm.Commercially available insulin pumps and glucose sensors are considered sufficiently accurate for use in a closed-loop system (9,10). Despite the delays inherent in absorption and action of insulin delivered subcutaneously, previous studies have demonstrated superiority of such systems over standard pump therapy (11–18). Automation of insulin delivery is not a novel concept (11,12); however, the closed-loop system in many reports was not fully automated. In some studies, sensor glucose was entered manually every 5 to 15 min (15–17) or changes to the pump delivery rate were made manually by a physician or research nurse (13–17). Furthermore, insulin delivery in studies published to date was based on a control algorithm contained in a desktop or laptop computer (11–18), implying that the system was not readily portable or practical in an ambulatory setting. A key milestone in progress toward making a closed-loop artificial pancreas system available for outpatient use is the development of fully automated, portable devices with fault detection capabilities to ensure safety. An additional desirable feature of these devices is the ability to remotely monitor the operation of the closed-loop system via data transmitted over a wireless network, facilitating future physician-supervised home studies.The Medtronic Portable Glucose Control System (PGCS) is a portable, automated, closed-loop device consisting of a BlackBerry Storm smartphone (Research in Motion, Waterloo, ON, Canada), an unmodified Medtronic Paradigm Veo insulin pump, two MiniLink REAL-Time Transmitters (Medtronic Minimed, Northridge, CA) modified to transmit at 1-min rather than 5-min intervals, two Enlite glucose sensors (Medtronic Minimed), and a Medtronic custom-built radiofrequency translator, as illustrated in Fig. 1.Open in a separate windowFigure 1The components of the Medtronic PGCS.In this study, we describe the safety and efficacy of the PGCS, an automated closed-loop device, focusing on overnight glucose control in adolescents and young adults with type 1 diabetes.     

In vivo tracking in cardiac stem cell-based therapy

Cell-based therapy has been heralded as a promising, novel therapeutic strategy for cardiovascular diseases. Despite a rapid transition from animal studies to clinical trials, there remain numerous unresolved, and at times, controversial issues with respect to underlying molecular mechanisms. In parallel, recent advances in the field of molecular imaging has provided a means to bridge the gap in knowledge through in vivo stem cells tracking. Herein, we review current in vivo imaging techniques and future directions for tracking the effects of cell-based therapy.     

Genome comparison of virulent and avirulent strains of the Pichinde arenavirus

A virulent (P18) strain of the Pichinde arenavirus produces a disease in guinea pigs that somewhat mimics human Lassa fever, whereas an avirulent (P2) strain of this virus is attenuated in infected animals. It has been speculated that the composition of viral genomes may confer the degree of virulence in an infected host; the complete sequence of the viral genomes, however, is not known. Here, we provide for the first time genomic sequences of the S and L segments for both the P2 and P18 strains. Sequence comparisons identify three mutations in the GP1 subunit of the viral glycoprotein, one in the nucleoprotein NP, and five in the viral RNA polymerase L protein. These mutations, alone or in combination, may contribute to the acquired virulence of Pichinde virus infection in animals. The three amino acid changes in the variable region of the GP1 glycoprotein subunit may affect viral entry by altering its receptor-binding activity. While NP has previously been shown to modulate host immune responses to viral infection, we found that the R374 K change in this protein does not affect the NP function of suppressing interferon-beta expression. Four out of the five amino acid changes in the L protein occur in a small region of the protein that may contribute to viral virulence by enhancing its function in viral genomic RNA synthesis.