An Assessment of Imaging Informatics for Precision Medicine in Cancer.

Objectives: Precision medicine requires the measurement, quantification, and cataloging of medical characteristics to identify the most effective medical intervention. However, the amount of available data exceeds our current capacity to extract meaningful information. We examine the informatics needs to achieve precision medicine from the perspective of quantitative imaging and oncology. Methods: The National Cancer Institute (NCI) organized several workshops on the topic of medical imaging and precision medicine. The observations and recommendations are summarized herein. Results: Recommendations include: use of standards in data collection and clinical correlates to promote interoperability; data sharing and validation of imaging tools; clinician's feedback in all phases of research and development; use of open-source architecture to encourage reproducibility and reusability; use of challenges which simulate real-world situations to incentivize innovation; partnership with industry to facilitate commercialization; and education in academic communities regarding the challenges involved with translation of technology from the research domain to clinical utility and the benefits of doing so. Conclusions: This article provides a survey of the role and priorities for imaging informatics to help advance quantitative imaging in the era of precision medicine. While these recommendations were drawn from oncology, they are relevant and applicable to other clinical domains where imaging aids precision medicine.

Membrane interactions and antimicrobial effects of layered double hydroxide nanoparticles.

Membrane interactions are critical for the successful use of inorganic nanoparticles as antimicrobial agents and as carriers of, or co-actives with, antimicrobial peptides (AMPs). In order to contribute to an increased understanding of these, we here investigate effects of particle size (42-208 nm) on layered double hydroxide (LDH) interactions with both bacteria-mimicking and mammalian-mimicking lipid membranes. LDH binding to bacteria-mimicking membranes, extraction of anionic lipids, as well as resulting membrane destabilization, was found to increase with decreasing particle size, also translating into size-dependent synergistic effects with the antimicrobial peptide LL-37. Due to strong interactions with anionic lipopolysaccharide and peptidoglycan layers, direct membrane disruption of both Gram-negative and Gram-positive bacteria is suppressed. However, LDH nanoparticles cause size-dependent charge reversal and resulting flocculation of both liposomes and bacteria, which may provide a mechanism for bacterial confinement or clearance. Taken together, these findings demonstrate a set of previously unknown behaviors, including synergistic membrane destabilization and dual confinement/killing of bacteria through combined LDH/AMP exposure, of potential therapeutic interest.

Does registration of serial MRI improve diagnosis of dementia?

INTRODUCTION: We aimed to assess the value of a second MR scan in the radiological diagnosis of dementia. METHODS: One hundred twenty subjects with clinical follow-up of at least 1 year with two scans were selected from a cognitive disorders clinic. Scans were reviewed as a single first scan (method A), two unregistered scans presented side-by-side (method B) and a registered pair (method C). Scans were presented to two neuroradiologists and a clinician together with approximate scan interval (if applicable) and age. Raters decided on a main and subtype diagnosis. RESULTS: There was no evidence that differences between methods (expressed as relative odds of a correct response) differed between reviewers (p = 0.17 for degenerative condition or not, p = 0.5 for main diagnosis, p = 0.16 for subtype). Accordingly, results were pooled over reviewers. For distinguishing normal/non-progressors from degenerative conditions, the proportions correctly diagnosed were higher with methods B and C than with A (p = 0.001, both tests). The difference between method B and C was not statistically significant (p = 0.18). For main diagnosis, the proportion of correct diagnoses were highest with method C for all three reviewers; however, this was not statistically significant comparing with method A (p = 0.23) or with method B (p = 0.16). For subtype diagnosis, there was some evidence that method C was better than method A (p = 0.01) and B (p = 0.048). CONCLUSIONS: Serial MRI and registration may improve visual diagnosis in dementia.

Identification of cervical intraepithelial neoplasia (CIN) using UV-excited fluorescence and diffuse-reflectance tissue spectroscopy.

BACKGROUND AND OBJECTIVE: The diagnostic potentials of ultraviolet-excitation fluorescence spectroscopy and diffuse-reflectance spectroscopy of tissue are assessed in a study to identify cervical intraepithelial neoplasia (CIN) in vivo. A multivariate algorithm is used to classify tissue into normal tissues, CIN I, and CIN II/III categories, based on spectral characteristics of biopsied tissue sites. STUDY DESIGN/MATERIALS AND METHODS: An optical instrument with the capability of measuring fluorescence and diffuse-reflectance spectra from 120 locations uniformly distributed over the surface of the cervix is described. Using this device, these optical spectra of the cervix were measured on women referred for colposcopy due to an abnormal Pap smear. RESULTS: UV fluorescence differentiates CIN II/III lesions from normal squamous tissue with a sensitivity and specificity of 91 and 93%, respectively. CIN I is distinguished from normal tissue with a sensitivity of 86% and a specificity of 87%. CONCLUSION: Optical spectroscopy shows promise for the detection of pre-cancerous cervical lesions in vivo. The fluorescence and reflectance methods are complementary in their ability to differentiate different tissue types, making the use of the two techniques together more diagnostic than the use of either method separately.

Bilateral double dome: a case report.

The authors present an unusual case of nasal tip deformity of the nose not mentioned in the literature. The nose tip presented hypertrophy of all the components of the crura and the cranial part of the lateral crus was rotated externally and widened. An extra dome was present bilaterally between the medial crus and the medial part of the lateral crus. This increased the columella show and made it deformed like a break in the middle of the columella. An open-approach rhinoplasty was performed and the alar cartilages were reshaped.

Correction of sideburn defects after facelift operations.

The senior author has been using micrografts for correction of male pattern baldness since 1978. He has also been using these small grafts for correction of temporal hairline and loss of sideburn due to rhytidectomies, burns, avulsions, irradiation, and alopecia triangularis congenitas circumscripta [1,2]. Technique and results are presented.

Effects of cooling micrografts in hair transplantation surgery.

BACKGROUND: When isolating hair grafts in hair transplantation procedures, it is generally recommended to preserve the grafts at a low temperature (1 degrees C- 4 degrees C) in order to enhance the survival rate of the grafted hairs. This study was carried out to test the real benefits provided by cold-storing hair grafts. OBJECTIVE: The aim of this study was to evaluate, in an in vitro model, the effects of cooling micrografts during hair transplantation procedures to experimentally assess the soundness of this approach to enhance the survival and growth rates of hair micrografts. METHODS: A total of 240 anagen hair follicles were obtained from 10 healthy male patients. Follicles were thus randomly assigned to one of the following groups: group A (control; n = 120 follicles), or group B (experimental; n = 120 follicles). Follicles from group A were preserved for 5 hours at room temperature (26 degrees C), and follicles from group B were preserved for 5 hours at 1 degrees C. Immediately after that 5-hour period, follicles from both groups were then cultured for 10 days. The length of each follicle was measured immediately following the 5-hour test period and at the end of the 10-day culture period. RESULTS: No statistically significant differences were found between the survival and growth rates of follicles from the control (survival rate = 87%, mean 10-day growth rate = 2.68 mm) and experimental (survival rate = 88%, mean 10-day growth rate = 2.54 mm) groups. CONCLUSION: Although, at present, it is generally assumed that lowering the metabolism of grafts by reducing their temperature may be of some utility for enhancing their survival rate, our data indicate of that there are no effects when performing hair transplantation surgery.

Serial scalp reductions: a biomechanical approach.

BACKGROUND: Several technical aspects of scalp-reduction procedures still need to be clearly elucidated: in particular, (a) the quantitative effects provided by different amounts of subgaleal undermining, (b) the immediate gains provided by increasing amount of tension when advancing a scalp flap, and (c) the eventual benefits provided by galeotomies. OBJECTIVE: The aim of the present paper is to report on some biomechanical properties of scalp flaps as related to serial scalp reduction procedures for correction of male pattern baldness. METHODS: Data were collected by stepwise loading of 20 scalp flaps, obtained by a reversed-Y scalp incision, after increasing amounts of undermining, as well as after performing three galeotomies. RESULTS: Increasing amounts of tension (while advancing a scalp flap) affect the compliance of a scalp flap in a non-linear fashion; increasing amounts of undermining permit obtaining significant, but not proportional, gains; performing galeotomies is a useful adjunct to decrease the amount of closing tension when performing scalp-reduction procedures. CONCLUSION: When performing serial scalp reductions, to take into account the biomechanics of scalp flaps may be of some utility in obtaining an optimal result.

Scalp extension--a quantitative study.

The authors have compared the results of scalp reductions with extenders with their earlier results of scalp reductions without extenders. The extenders seem to prevent "stretch-back" and provide 30 to 86% more effectiveness when a second reduction is performed 4 weeks later.

Anchoring galeal flaps for scalp reduction procedures.

This article describes an operative technique, based on the use of three anchoring galeal flaps, aimed at reducing the percentage of "stretch-back" that occurs after performing scalp reduction procedures. In 12 male patients undergoing a midline scalp reduction procedure, three rectangular (2 x 3 cm) galeal flaps in direct continuity with the longitudinal margin of the left scalp flap were sutured individually to the galeal undersurface of the right scalp flap to draw the two scalp flaps toward the midline of the scalp and to relieve the wound margins of closing tension. Tattoo marks were placed on the patient's scalp at the level of the vertical lines drawn through the external auditory meatuses (A1-A2) and 6 cm more posterior (B1-B2) to measure the movement and stretching of the scalp. The results were compared with those obtained from a control group of 13 male patients who underwent the same surgical procedure but without the use of the anchoring galeal flaps. Mean stretch-back (as measured 4 weeks postoperatively) at level A1-A2 was 8.3 mm in the control group and 1.6 mm in the experimental group. The mean stretch-back at level B1-B2 was 7.7 mm in the control group and 0.9 mm in the experimental group. A statistically significant difference (p < 0.005) was found between data from the control and experimental groups regarding the above-reported stretch-back values at both levels. The use of the described galeal flaps allowed us to obtain an 80.93-percent and an 88.09-percent stretch-back reduction at levels A1-A2 and B1-B2, respectively, 1 month postoperatively.

Power boosting the grafts in hair transplantation surgery. Evaluation of a new storage medium.

BACKGROUND: When performing hair transplantation procedures, it is of the foremost importance to try to obtain the maximum survival rate possible of transplanted micrografts. OBJECTIVE: Aim of this study was to evaluate, in an in vitro model, the effects of preserving micrografts, for five hours, in an enriched storage medium in order to enhance the survival rate of hair micrografts. METHODS: A total of 200 human anagen hair follicles was obtained from ten male patients. Follicles were thus randomly assigned to one of the following group: Group A (control; n = 100 follicles), preserved for five hours in saline, and Group B (experimental; n = 100 follicles), preserved for five hours in a storage medium, containing adenosine triphosphate-magnesium chloride and deferoxamine mesylate. Isolated hair follicles from both Groups were then cultured for 10 days. RESULTS: A statistically significant difference was found between the survival rate of experimental (98%) and control follicles (87%). CONCLUSION: In our opinion, a "metabolic preconditioning" of micrografts by means of storing them for 5 hours in the described medium may be of some utility in augmenting the survival rate of hair grafts when performing hair transplantation surgery.

Aesthetic reconstruction of the vertex area of the scalp. Case report.

A 62-year-old woman had a defect in the vertex of the scalp that was created by the excision of a basal cell carcinoma. This was closed with three local, hair-bearing, rhomboid flaps. This allowed us to reconstruct the natural whorl pattern of hair in this region.

Endoscopic transthoracic dorsal sympathectomy for the treatment of upper extremity hyperhidrosis: a new minimally invasive approach.

Palmar and axillary hyperhidrosis are best treated surgically by endoscopic transthoracic upper dorsal sympathectomy. At present, this methodology relies on (at least) double trocar insertion (per side), carbon dioxide insufflation, or both. We present a new minimally invasive endoscopic transthoracic technique, performed by a single-entry specifically modified thoracoscope and without the need for carbon dioxide insufflation, with the aim to reduce the drawbacks associated with the above-mentioned, currently adopted endoscopic technique. In our opinion, this "single-entry" technique, compared with the other reported approaches, should theoretically minimize any damage to the intercostal neurovascular bundle, while avoiding the complications related to carbon dioxide insufflation.

Follicular bisection in hair transplantation surgery: an in vitro model.

The aim of this study was to evaluate, in an in vitro model, the survival and growth rates of transversely sectioned human hair follicles to assess experimentally the soundness of this approach as a future possible method for "duplicating" available donor hair grafts in hair transplantation procedures. A total of 300 human anagen hair follicles was obtained from 10 healthy male patients. Follicles were thus randomly assigned to one of the following groups: group A (control; n = 100 follicles), cultured intact as dissected, and group B (experimental; n = 200 follicles), transversely transected, parallel to the epidermal surface and immediately below the bulge area, to obtain 200 lower-half follicles and 200 upper-half follicles. Isolated hair follicles from both groups were maintained in culture for 10 days. The length of each follicle was measured immediately following isolation and at the end of the 10-day culture period. No statistically significant differences were found between the growth rate of intact follicles (mean 10-day growth rate = 2.71 mm) and of lower-half follicles (mean 10-day growth-rate = 2.64 mm), whereas a statistically significant difference was found between the growth rate of follicles from the two above-mentioned groups and the growth rate of the "upper-half" follicles (mean 10-day growth rate = 1.07 mm). Histologic analysis demonstrated that both intact and lower-half follicles maintained a normal histologic appearance, whereas in upper-half follicle sections we invariably detected a region of intense cell proliferation, reminiscent of a regenerated follicular papilla, surrounding the lowermost part of the follicle. In our opinion, the reported in vitro survival rate of transected human hair follicles might represent an interesting starting point in striving to augment the number of donor hairs available during a hair transplantation procedure.

Effects of galeotomies on scalp flaps.

The aim of the present study was to evaluate how much a relaxing incision of the galea aponeurotica affects the biomechanical properties of a scalp flap to quantify the surgery-related advantages provided by this procedure. Twenty scalp flaps, created by a reverse-Y incision down to and through the galea aponeurotica together with undermining (in the layer between the galea and the pericranium) to within 1 cm of the external auditory canal were studied. Data were collected by stepwise loading the scalp flaps before and after performing three full-thickness galeotomies lengthwise and parallel to the sagittal scalp incision. The tension/ extension ratio characteristics were computed, and loading curves as well as mean stiffness values were measured. A statistically significant difference (-16.6 g per millimeter) was found between the slope (computed as Young's modulus) of the curves obtained before and after performing the galeotomies. This value corresponded to a mean 40% reduction of the closing tension attained with each galeotomy. In the closing-tension interval 500 g to 1,500 g, the mean gain of length of the flap per galeotomy was 1.67 mm. These data confirm the usefulness of galeotomies for lengthening the scalp flaps and for diminishing the tension on wound margins when closing scalp defects.

Rhomboid minigrafts in hair restoration surgery.

BACKGROUND: The transplantation of large numbers of three- to five-hair minigrafts has superseded the use of traditional punch grafts in hair restoration surgery. The minigrafts are usually designed and cut in a square or rectangular shape for implantation into the recipient slits. Transplanting a large number of these grafts into the recipient slits can lead to a high frequency of complications, especially in cases in which there is a need for dense packing of grafts. The complications include excess graft compression resulting in extrusion or retraction into the slit. This in turn can lead to piggybacking or insertion of two grafts per slit with the resultant effect of cyst formation, cobblestoning, and hypertrophic scar formation. OBJECTIVE: To develop an optimal shape of minigrafts to match the recipient slits. METHODS: The authors have calculated the optimum geometric configuration for a minigraft in a linear slit and have developed the correct cutting instrument and preparation technique for its production. This rhomboid minigraft design maximizes the graft stability in the slit and therefore its survival, and also minimizes the risk of complications. RESULTS: The described technique shows that the transplanted rhomboid minigrafts remain well anchored in the recipient slits and results in an excellent clinical outcome. CONCLUSION: The rhomboid minigrafting technique (1.5 x 1.5 mm in size) seems to accommodate the grafts better into the recipient slits than the standard shape rectangular minigrafts. It thereby better facilitates the insertion of the grafts in the slits and reduces the frequency of graft extrusion as well as graft compression.

Undermining of the scalp: quantitative effects.

The aim of the present study was to evaluate to what extent undermining affects the closing-tension of scalp defects to quantify the surgery-related benefits provided by this procedure. Data were collected by stepwise loading in 10 patients, 20 scalp flaps (obtained by a reversed Y scalp incision), and three different degrees of subgaleal undermining (1, 5, and 15 cm). The obtained data confirmed the value of undermining to diminish the tension on wound margins when closing a scalp defect. There was a progressive decrease in tension required to advance the wound edge when the amount of undermining was sequentially increased. Most of this reduction occurred with the 5-cm undermining, although statistically the 15-cm undermining also resulted in a significant decrease in the tension required to close the defect. Mean 83.3- and 92.2-percent reductions of the closing tension were obtained with 5 cm and 15 cm of undermining, respectively, compared with that achieved by the 1-cm undermining with the same width of defect.

Biomechanical properties of scalp flaps and their correlations to reconstructive and aesthetic surgery procedures.

BACKGROUND/AIMS: In formulating an accurate pre-operative plan when performing plastic surgery, the biomechanical properties of the soft-tissues involved should always be taken into account. No study has yet been carried out regarding the tensiometric peculiarities of the human scalp. The aim of the present study was to measure the load-elongation properties of the human scalp, in an attempt to characterize it through the constants of a stress-strain theory. This would provide plastic surgeons with information needed to test the soundness of the various surgical techniques currently adopted, as well as a way to better plan a reconstructive or aesthetic procedure on the scalp. METHODS: Data were collected by stepwise loading 20 scalp flaps, obtained by a reversed-Y scalp incision down to and through the galea aponeurotica, together with 1 -cm undermining, on the subgaleal layer, along both sides of the sagittal scalp incision. RESULTS: The tissue's stress response to displacement was visualized as a three-phase characteristic. Initially linear (load range: 0 to 500 g), the scalp's compliance gradually reduced (load range: 500 to 1500 g) and eventually demonstrated an exponential stress-strain characteristic of rapidly increasing stiffness (load range: 1500 to 5000 g). Young's modulus E was derived from the mean-values curve, and was found to be equal to 117.1 g/ mm. CONCLUSIONS: These data have practical implication for studying the effects of complex surgical closures on the one-dimensional stress distribution of the scalp, while allowing the use of analytical methods to predict the consequences of closure design in various plastic surgery procedures on the scalp.

Evaluation of lip augmentation with Gore-Tex facial implant.

Although numerous materials, including autogenous, homogeneous, and alloplastic materials, have been used for lip augmentation with varying degrees of success, no ideal one has been found to achieve a soft and long-lasting result. Gore-Tex implant has been successfully used in cardiovascular surgery. So far, it has not been used much in lip augmentation. In this study, a Gore-Tex SAM facial implant (1.8 mm in diameter) was used for lip augmentation in 23 lips of 17 female patients. In 10 consecutive lips with three segments of the implant each, a computer-assisted imaging system was used to scrutinize the results. The results have shown that the three segments of the implant enhanced the lip projection with about 0.98 mm in mean (p < 0.01) and the exposed vermillion width with about 1. 94 mm (p < 0.01) in the over 6 months follow-ups. No major complications, only some minor ones, were seen. For lip augmentation, we find that only minor changes can be achieved with three segments of the Gore-Tex facial implant. We feel that it is safe and believe it gives a permanent result which is not the case with collagen injection and usually not the case with lipofilling despite reinjections. Furthermore, we consider the implant quite expensive at present.