Stress testing reveals gaps in clinic readiness of image-based diagnostic artificial intelligence models.

Artificial intelligence models match or exceed dermatologists in melanoma image classification. Less is known about their robustness against real-world variations, and clinicians may incorrectly assume that a model with an acceptable area under the receiver operating characteristic curve or related performance metric is ready for clinical use. Here, we systematically assessed the performance of dermatologist-level convolutional neural networks (CNNs) on real-world non-curated images by applying computational "stress tests". Our goal was to create a proxy environment in which to comprehensively test the generalizability of off-the-shelf CNNs developed without training or evaluation protocols specific to individual clinics. We found inconsistent predictions on images captured repeatedly in the same setting or subjected to simple transformations (e.g., rotation). Such transformations resulted in false positive or negative predictions for 6.5-22% of skin lesions across test datasets. Our findings indicate that models meeting conventionally reported metrics need further validation with computational stress tests to assess clinic readiness.

Mutations induced by Bleomycin, 4-nitroquinoline-1-oxide, and hydrogen peroxide in the rpoB gene of Escherichia coli: Perspective on Mutational Hotspots.

We report the mutational spectra in a segment of the E. coli rpoB gene of bleomycin (BLEO), 4-nitroquinoline-1-oxide (NQO), and hydrogen peroxide (H2O2). We compare these spectra with those of other mutagens and repair deficient strains in the same rpoB system, and review the key elements determining mutational hotspots and outline the questions that remain unanswered. We consider three tiers of hotspots that derive from 1) the nature of the sequence change at a specific base, 2) the direct nearest neighbors and 3) some aspect of the larger sequence context or the local 3D-structure of segments of DNA. This latter tier can have a profound effect on mutation frequencies, even among sites with identical nearest neighbor sequences. BLEO is dependent on the SOS-induced translesion Pol V for mutagenesis, and has a dramatic hotspot at a single mutational site in rpoB. NQO is not dependent on any of the translesion polymerases, in contrast to findings with plasmids treated in vitro and transformed into E. coli. The rpoB system allows one to monitor both G:C -> A:T transitions and G:C -> T:A transversions at the same site in 11 cases, each site having the identical sequence context for each of the two mutations. The combined preference for G:C -> A:T transitions at these sites is 20-fold. Several of the favored sites for hydrogen peroxide mutagenesis are not seen in the spectra of BLEO and NQO mutations, indicating that mutagenesis from reactive oxygen species is not a major cause of BLEO or NQO mutagenesis, but rather specific adducts. The variance in mutation rates at sites with identical nearest neighbors suggests that the local structure of different DNA segments is an important factor in mutational hotspots.

Neurocutaneous disease: Cutaneous neuroanatomy and mechanisms of itch and pain.

Few sources of information exist regarding cutaneous innervation and how to apply this basic neurologic science to the clinical treatment of itch, as often performed on a daily basis by dermatologists. We address the types of nerve fibers that innervate the skin and their different components and discuss the similarities and differences between itch and pain. We hope that increased knowledge of this topic will improve the recognition and treatment of neuropathic itch.

Neurocutaneous disease: Neurocutaneous dysesthesias.

Dysesthesia is a generic term for a cutaneous symptom--such as pruritus, burning, tingling, stinging, anesthesia, hypoesthesia, tickling, crawling, cold sensation, or even pain--without a primary cutaneous condition in a well-defined location that is often caused by nerve trauma, impingement, or irritation. There are multiple types of dysesthesias depending on the body location and the nerves involved. While location, exact symptoms, and etiologies might vary, the underlying theme is that these conditions are of neurologic origin and have dermatologic consequences. For many of these conditions, the symptoms are localized to the skin, and patients frequently present to the dermatologist; it is important for dermatologists to be knowledgeable about these symptoms and their underlying causes. In part II of this continuing medical education review, the primary diagnoses associated with underlying cutaneous dysesthesias will be explored, including scalp dysesthesia, trigeminal trophic syndrome, meralgia paresthetica, notalgia paresthetica, and brachioradial pruritus. The typical demographics in terms of symptoms, location, and patient populations will be discussed in addition to the specific etiologies, workups, and possible treatment options.

A randomized prospective study of lumpectomy margin assessment with use of MarginProbe in patients with nonpalpable breast malignancies.

BACKGROUND: The presence of tumor cells at the margins of breast lumpectomy specimens is associated with an increased risk of ipsilateral tumor recurrence. Twenty to 30 % of patients undergoing breast-conserving surgery require second procedures to achieve negative margins. This study evaluated the adjunctive use of the MarginProbe device (Dune Medical Devices Ltd, Caesarea, Israel) in providing real-time intraoperative assessment of lumpectomy margins. METHODS: This multicenter randomized trial enrolled patients with nonpalpable breast malignancies. The study evaluated MarginProbe use in addition to standard intraoperative methods for margin assessment. After specimen removal and inspection, patients were randomized to device or control arms. In the device arm, MarginProbe was used to examine the main lumpectomy specimens and direct additional excision of positive margins. Intraoperative imaging was used in both arms; no intraoperative pathology assessment was permitted. RESULTS: In total, 596 patients were enrolled. False-negative rates were 24.8 and 66.1 % and false-positive rates were 53.6 and 16.6 % in the device and control arms, respectively. All positive margins on positive main specimens were resected in 62 % (101 of 163) of cases in the device arm, versus 22 % (33 of 147) in the control arm (p < 0.001). A total of 19.8 % (59 of 298) of patients in the device arm underwent a reexcision procedure compared with 25.8 % (77 of 298) in the control arm (6 % absolute, 23 % relative reduction). The difference in tissue volume removed was not significant. CONCLUSIONS: Adjunctive use of the MarginProbe device during breast-conserving surgery improved surgeons' ability to identify and resect positive lumpectomy margins in the absence of intraoperative pathology assessment, reducing the number of patients requiring reexcision. MarginProbe may aid performance of breast-conserving surgery by reducing the burden of reexcision procedures for patients and the health care system.

Acquired epidermodysplasia verruciformis in a child with atopic dermatitis.

A 4-year-old girl with an established diagnosis of atopic dermatitis, previously severe and treated with cyclosporine, developed widespread papules that demonstrated changes consistent with epidermodysplasia verruciformis on biopsy. Human papilloma virus (HPV) typing was performed and was consistent with epidermodysplasia verruciformis-type HPV (type 5). These lesions rapidly resolved with a 2-week course of imiquimod. Rapid resolution and no family history of epidermodysplasia verruciformis make this most consistent with acquired epidermodysplasia verruciformis. This case is the first reported case of acquired epidermodysplasia verruciformis in a child without the human immunodeficiency virus and may be linked to cyclosporine use, which also has never been previously reported.

Nonuremic calciphylaxis associated with histologic changes of pseudoxanthoma elasticum.

Calciphylaxis is a rare condition characterized by medial calcification of small- and medium-sized vessels that subsequently leads to ischemic necrosis. Calciphylaxis most often occurs in patients with end-stage renal disease and secondary hyperparathyroidism. We present a unique case of calciphylaxis in which the patient did not have end-stage renal disease. Instead, primary hyperparathyroidism and/or alcoholic cirrhosis were the more likely causes of her calciphylaxis. In addition, our case demonstrated not only calciphylaxis but also fragmentation and calcification of elastic fibers within the dermis, changes that are most often seen in pseudoxanthoma elasticum. This is the first reported case of calciphylaxis, to our knowledge, with histopathologic changes of pseudoxanthoma elasticum in a patient who is nonuremic.

Pilot trial of cryoprobe-assisted breast-conserving surgery for small ultrasound-visible cancers.

BACKGROUND: Stereotactic and ultrasonography-guided large core needle biopsy has replaced wire localization biopsy as the diagnostic method of choice. Lumpectomy alternatives are being sought to eliminate the need for preoperative wire localization, to facilitate easier and more accurate resection, and to decrease positive margin rates. Cryoprobe-assisted lumpectomy (CAL) was investigated as an alternative. METHODS: Patients with ultrasonographically visible breast cancers that otherwise would have required wire localization participated. Before lumpectomy, a cryoprobe (Visica; Sanarus, Pleasanton, CA) was inserted through a 3-mm skin incision and directed by ultrasonography through the center of the tumor. An ice ball was created that enveloped the tumor plus an adjacent 5-10 mm of sonographically normal breast tissue. RESULTS: Twenty-four CAL procedures were performed and all lesions were successfully localized. Mean (+/-SD) tumor size was 1.2 +/-.4 cm (range,.7-2.0 cm). Mean dimensions of the ice ball before excision were 3.9 +/-.3 cm by 2.5 +/-.5 cm, and the ice margin around the tumor was 8 +/- 2 mm. The size of the ice ball was controlled to the millimeter, and the ice ball itself provided a precise template around which to dissect. The margin re-excision rate was 5.6% among patients with an ice margin greater than 6 mm. CONCLUSIONS: CAL is a superior alternative to wire localization. Ultrasonographic visualization of the ice ball allows the size of the margin and tissue resected to be individually tailored and accurate within millimeters. The created template allows a precise lumpectomy, adding a dimension of control not previously realized with any other technology.

The use of sestamibi imaging in parathyroid hyperplasia.

The authors describe a 42-year-old man with parathyroid hyperplasia secondary to chronic renal failure. Parathyroidectomy was indicated because of persistent hypercalcemia and an increasing parathyroid hormone level despite medical management. A parathyroid sestamibi scan was performed immediately before operation and a gamma-detecting probe was used during operation. Six parathyroid glands weighing nearly 21 g were present. Without the use of the gamma-detecting probe during operation, one of the glands would have been missed. The efficacy of sestamibi scanning with parathyroid hyperplasia is discussed.