Sources of performance variability in deep learning-based polyp detection.

PURPOSE: Validation metrics are a key prerequisite for the reliable tracking of scientific progress and for deciding on the potential clinical translation of methods. While recent initiatives aim to develop comprehensive theoretical frameworks for understanding metric-related pitfalls in image analysis problems, there is a lack of experimental evidence on the concrete effects of common and rare pitfalls on specific applications. We address this gap in the literature in the context of colon cancer screening. METHODS: Our contribution is twofold. Firstly, we present the winning solution of the Endoscopy Computer Vision Challenge on colon cancer detection, conducted in conjunction with the IEEE International Symposium on Biomedical Imaging 2022. Secondly, we demonstrate the sensitivity of commonly used metrics to a range of hyperparameters as well as the consequences of poor metric choices. RESULTS: Based on comprehensive validation studies performed with patient data from six clinical centers, we found all commonly applied object detection metrics to be subject to high inter-center variability. Furthermore, our results clearly demonstrate that the adaptation of standard hyperparameters used in the computer vision community does not generally lead to the clinically most plausible results. Finally, we present localization criteria that correspond well to clinical relevance. CONCLUSION: We conclude from our study that (1) performance results in polyp detection are highly sensitive to various design choices, (2) common metric configurations do not reflect the clinical need and rely on suboptimal hyperparameters and (3) comparison of performance across datasets can be largely misleading. Our work could be a first step towards reconsidering common validation strategies in deep learning-based colonoscopy and beyond.

Amputation in patients with complex regional pain syndrome: a comparative study between amputees and non-amputees with intractable disease.

AIMS: Amputation in intractable cases of complex regional pain syndrome (CRPS) remains controversial. The likelihood of recurrent Complex Regional Pain Syndrome (CRPS), residual and phantom limb pain and persistent disability after amputation is poorly described in the literature. The aims of this study were to compare pain, function, depression and quality of life between patients with intractable CRPS who underwent amputation and those in whom amputation was considered but not performed. PATIENTS AND METHODS: There were 19 patients in each group, with comparable demographic details. The amputated group included 14 men and five women with a mean age of 31 years (sd 12) at the time of CRPS diagnosis. The non-amputated group consisted of 12 men and seven women and their mean age of 36.8 years (sd 8) at CRPS diagnosis. The mean time from CRPS diagnosis to (first) amputation was 5.2 years (sd 4.3) and the mean time from amputation to data collection was 6.6 years (sd 5.8). All participants completed the following questionnaires: Short-Form (SF) 36, Short Form McGill Pain questionnaire (SF-MPQ), Pain Disability Index (PDI), the Beck Depression Inventory (BDI) and a clinical demographic questionnaire. RESULTS: The amputation group showed consistently better results compared to the non-amputation group in the following parameters: median pain intensity (VAS): 80 (inter-quartile range (IQR) 13 to 92) vs 91 (IQR 85 to 100); p = 0.007; median SF-MPQ score 28 (IQR 9 to 35) vs 35 (IQR 31 to 38), p = 0.025; median PDI: 42 (IQR 11 to 64) vs 58 (IQR 50 to 62), p = 0.031; median BDI: 19 (IQR 5 to 28) vs 27 (IQR 21 to 32), p = 0.061 (borderline significant) and in six of the eight SF-36 domains. TAKE HOME MESSAGE: Amputation should be considered as a form of treatment for patients with intractable CRPS.

[Postoperative Osteomyelitis of a Distal Phalanx Caused by Raoultella ornithinolytica]. / Postoperative Osteomyelitis einer Endphalanx am Finger durch Raoultella ornithinolytica.

We report on a case of osteomyelitis of a distal phalanx of the right ring finger of a 62-year-old patient, which occurred 11 months after transosseous-transungual refixation of a closed flexor digitorum profundus tendon avulsion caused by Raoultella ornithinolytica. R. ornithinolytica is an encapsulated Gram-negative aerobic bacillus. In the literature only 13 cases of human infection by R. ornithinolytica are mentioned. To the best of our knowledge, this is the first case of an osteomyelitis caused by R. ornithinolytica.

Targeted disruption of the mouse Npal3 gene leads to deficits in behavior, increased IgE levels, and impaired lung function.

The non-imprinted in Prader-Willi/Angelman syndrome (NIPA) proteins are highly conserved receptors or transporters. Translocation of NIPA genes were found in patients with Prader-Willi syndrome, and loss-of-function of the NIPA1 gene was identified in hereditary spastic paraplegia. The family of NIPA-like domain containing (NPAL) proteins is closely related to the NIPA proteins, but to date nothing is known about their function. Here, we could demonstrate that both human NPAL3 and mouse NPAL3 are ubiquitously expressed and encode highly conserved proteins. To further elucidate the function of the Npal3 gene, knockout (Npal3(-/-)) mice were generated. Intensive phenotypic analyses revealed that disruption of the Npal3 gene results in a pleiotropic phenotype. The function of the nervous system was impaired in both mutant males and females which could be demonstrated in behavioral tests. In addition, in NPAL3 mutants the number of NK cells was decreased and changes in IgM, IgG(2), and IgA were observed, indicating that the immune system is also affected. Interestingly, increased IgE levels as well as impaired lung functions were observed in mutant males but not in mutant females. It should be noted that the human Npal3 gene is located at 1p36.12-->p35.1, and atopic diseases were previously linked to this genomic region. Thus, the Npal3(-/-) mice could serve as a valuable model system for studying atopic diseases.

The German Mouse Clinic: a platform for systemic phenotype analysis of mouse models.

The German Mouse Clinic (GMC) is a large scale phenotyping center where mouse mutant lines are analyzed in a standardized and comprehensive way. The result is an almost complete picture of the phenotype of a mouse mutant line--a systemic view. At the GMC, expert scientists from various fields of mouse research work in close cooperation with clinicians side by side at one location. The phenotype screens comprise the following areas: allergy, behavior, clinical chemistry, cardiovascular analyses, dysmorphology, bone and cartilage, energy metabolism, eye and vision, host-pathogen interactions, immunology, lung function, molecular phenotyping, neurology, nociception, steroid metabolism, and pathology. The German Mouse Clinic is an open access platform that offers a collaboration-based phenotyping to the scientific community (www.mouseclinic.de). More than 80 mutant lines have been analyzed in a primary screen for 320 parameters, and for 95% of the mutant lines we have found new or additional phenotypes that were not associated with the mouse line before. Our data contributed to the association of mutant mouse lines to the corresponding human disease. In addition, the systemic phenotype analysis accounts for pleiotropic gene functions and refines previous phenotypic characterizations. This is an important basis for the analysis of underlying disease mechanisms. We are currently setting up a platform that will include environmental challenge tests to decipher genome-environmental interactions in the areas nutrition, exercise, air, stress and infection with different standardized experiments. This will help us to identify genetic predispositions as susceptibility factors for environmental influences.

Increased excitability in the primary motor cortex and supplementary motor area in patients with phantom limb pain after upper limb amputation.

Using functional magnetic resonance imaging and single slice FLASH technique, we investigated reorganization of the hand representation of the primary sensorimotor cortex (SMC) in 16 patients with upper extremity amputation. Patients were asked to perform finger tapping with the intact hand, repetitive eye closing and anteflexion of the amputation stump or intact shoulder. Six normal volunteers served as control. In the normal volunteers activations during shoulder anteflexion, finger tapping and eye closure were located within the central sulcus in a medio-lateral fashion. Patients demonstrated invasion of the face or shoulder representation into the hand representation of the amputated limb. Eight phantom limb pain patients showed significantly greater activation in SMC and supplementary motor area (SMA) in contrast to eight patients without phantom limb pain. We conclude, that different parts of the motor system are affected in patients with phantom limb pain--possibly in the sense of an up-regulation of excitability.

Structural and functional cortical abnormalities after upper limb amputation during childhood.

Functional reorganization has been well documented in the human adult brain after amputation of the arm. To assess the effects of amputation on the developing brain, we investigated six patients with upper limb amputation in early childhood and one with right dysmelia. Transcranial magnetic stimulation indicated contralateral cortical disinhibition and enlargement of the excitable area of the stump. FMRI data corroborated these plastic changes and also showed an ipsilateral functional reorganization. In the T1-weighted MRI, we found structural deformities of the contralateral and ipsilateral central sulcus in three patients and a contralateral atrophic parietal lobule in two patients. Therefore, arm amputation in childhood affects functional organization as well as anatomical structure in both hemispheres.

Decrease in phantom limb pain associated with prosthesis-induced increased use of an amputation stump in humans.

The experience of phantom limb pain, non-painful phantom limb sensation and telescoping was ascertained by questionnaire in a group of upper extremity amputees wearing a functionally effective Sauerbruch prosthesis which permits extensive use of the affected limb and in a group of patients wearing a cosmetic prosthesis that did little to increase the utilization of the amputation stump. The Sauerbruch prosthesis group exhibited a significant and large decrease in amount of phantom limb pain while the cosmetic prosthesis group showed no change. Neither group experienced a decrease in non-painful phantom limb sensation or telescoping. The amount of phantom limb pain has been found to be highly correlated with the amount of injury-related, afferent-decrease cortical reorganization. It is possible that the increased use of the amputation stump induced by wearing a Sauerbruch prosthesis produced a countervailing use-dependent, afferent-increase type of cortical reorganization that reversed the phantom limb pain. These preliminary results require replication. Their therapeutic implications are discussed.

Abnormal motor cortex organization contralateral to early upper limb amputation in humans.

We performed both a functional magnetic resonance imaging (fMRI) study using single slice FLASH technique and an investigation with transcranial magnetic stimulation (TMS) in a 21-year-old patient. He had suffered a left upper extremity amputation at age 7. Anteflexion of the amputation stump produced an unusual, broad activation contralateral to the movement. TMS revealed an enlarged cortical motor output area of the deltoid muscle at the amputation stump. Application of paired magnetic stimulation demonstrated decreased intracortical inhibition (ICI). A T1-weighted image indicated a lack of the characteristic shape of the central sulcus contralateral to the amputation. In addition to previous functional studies, these new structural data suggest that maturation of the central sulcus develops in response to daily practice of the contralateral hand, possibly until adolescence.

Cerebral lymphoma in AIDS. Clinical, radiological, neuropathological and immunopathological study.

Neuropathological findings from 8 individual cases of cerebral lymphomas in AIDS patients with consideration of the clinical, radiological, immunopathological, and other pertinent data selected from a series of 80 patients between 1985 and 1989 were studied. A wide variation in pathology was noted among our cases. It has been shown that lymphoma as a neuropathological diagnosis can coexist with a wide range of other characteristics, including toxoplasmosis, glial nodules, neuronophagia, degeneration, bleeding, hypoxia, progressive multifocal leucoencephalopathy, and myelopathy, although none of these attributes appeared more than casually interrelated. In general, the late-stage manifestations of lymphoma as were observed in this study, tended to be poorly localized, often simultaneously meningeal, perivascular, and diffuse in character. An important distinction between cerebral lymphomas of AIDS and non-AIDS patients is the highly atypical, clinically unreliable computer tomographic signals observed in several of our cases. Five of the six immunopathological investigations showed a preponderance of B-cell markers, corresponding in toto to high-grade non-Hodgkin lymphoma. One case exhibited immunohistological markers typical of Hodgkin's lymphoma (antibody CD-30). Of 6 obtainable serum specimens from our 8 cases, 4 showed high (greater than 2000) IgG titers against the EBNA-1 antigen of Epstein-Barr virus (EBV), of these three had IgM titers further supporting viral reactivation. One showed a normal IgG titer, yet with a significantly raised IgM titer.

Selective desensitization to seminal plasma protein fractions after immunotherapy for postcoital anaphylaxis.

A 24-year-old white woman reported sexual intercourse-related pruritus, hives, wheezing, and dyspnea within 5 minutes after ejaculation. Systemic reactions (SRs) were prevented by use of condoms. Prick testing confirmed sensitization to five Sephadex G-100-separated fractions of her husband's seminal plasma. The intradermal end point threshold concentrations (ETC) were 10(-4) and 10(-1) micrograms of protein per milliliter to fractions 2 and 3, respectively. Leukocyte histamine release studies exhibited 100% release to fraction 2 and 37% release to fraction 3. A 2-day protocol of rapid immunotherapy (IT) was performed with subcutaneous incremental doses of human seminal plasma (HuSePl) fractions 2 and 3. The patient experienced an SR after receiving a cumulative dose of 38.55 micrograms of fraction 2 on day 1. On day 2, rapid IT with fraction 2 was administered until the patient experienced a mild SR after having received a cumulative dose of 102.8 micrograms. There was a one-log10 increase in the intradermal ETC to both fractions 2 and 3 at the end of day 2. IT was continued three times weekly for 4 months until the patient tolerated 100 micrograms doses of both fractions 2 and 3. At 4 months, coitus was resumed without SRs, and HuSePl IT was stopped. The intradermal ETC to fractions 1, 3, 4, and 5 was increased 6 months after cessation of HuSePl injections, but there was a one-log decrease in the ETC to fraction 2. Our experience demonstrated that systemic tolerance can be achieved by parenteral administration of selected HuSePl fractions. Partial immunologic desensitization of patients with anaphylactic sensitivity can be achieved.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunologic and clinical correlates of bronchial challenge responses to Bermuda grass pollen extracts.

We have studied 26 patients with asthma who had positive skin tests for Bermuda grass pollen antigen (BGP) with history, immunologic assays, and bronchial challenge with BGP. In these patients IgE anti-BGP RAST titers were higher in those with positive, 6.8 +/- 4.4% (mean +/- SEM) compared to those with negative bronchial challenges, 2.7 +/- 0.4% (p less than 0.02). Historical data did not predict bronchial challenge response. IgG4 anti-BGP RAST was not different in patients with positive and negative challenges but was markedly increased, 15.3 +/- 11.9%, in patients who had previously had BGP immunotherapy when compared to untreated patients, 3.6 +/- 5.1% (p less than 0.01). IgE anti-Bermuda grass appears to be the major contributor to susceptibility to BGP bronchial challenge. IgG4 anti-Bermuda grass is apparently unrelated to the sensitivity to challenge but appears to be a significant component of the immunologic response to immunotherapy.

Studies of complement activation and IgG subclass restriction of anti-thyroglobulin.

Using a sensitive radioimmunoassay, it was demonstrated that autoantibodies to human thyroglobulin (hTg) did not activate complement upon interaction with solid phase adsorbed hTg. Since IgG4 immunoglobulins do not activate complement, we studied sera containing large amounts of anti-thyroglobulin (anti-Tg) with a sensitive radioimmunoassay for IgG4 anti-Tg. Antibodies of the IgG4 subclass were detected in the sera of each of the eight patients studied and not in control subjects. Quantitative assays of IgG4 anti-Tg were performed by comparing the removal of anti-Tg and total IgG4 during immunoadsorption of anti-Tg. The contribution of IgG4 anti-Tg antibodies to the total quantity of anti-Tg ranged from 6 to 30%, an amount inadequate to explain the lack of complement activation by anti-Tg.