Performance of an ultra-fast deep-learning accelerated MRI screening protocol for prostate cancer compared to a standard multiparametric protocol.

OBJECTIVES: To establish and evaluate an ultra-fast MRI screening protocol for prostate cancer (PCa) in comparison to the standard multiparametric (mp) protocol, reducing scan time and maintaining adequate diagnostic performance. MATERIALS AND METHODS: This prospective single-center study included consecutive biopsy-naïve patients with suspected PCa between December 2022 and March 2023. A PI-RADSv2.1 conform mpMRI protocol was acquired in a 3 T scanner (scan time: 25 min 45 sec). In addition, two deep-learning (DL) accelerated sequences (T2- and diffusion-weighted) were acquired, serving as a screening protocol (scan time: 3 min 28 sec). Two readers evaluated image quality and the probability of PCa regarding PI-RADSv2.1 scores in two sessions. The diagnostic performance of the screening protocol with mpMRI serving as the reference standard was derived. Inter- and intra-reader agreements were evaluated using weighted kappa statistics. RESULTS: We included 77 patients with 97 lesions (mean age: 66 years; SD: 7.7). Diagnostic performance of the screening protocol was excellent with a sensitivity and specificity of 100%/100% and 89%/98% (cut-off ≥ PI-RADS 4) for reader 1 (R1) and reader 2 (R2), respectively. Mean image quality was 3.96 (R1) and 4.35 (R2) for the standard protocol vs. 4.74 and 4.57 for the screening protocol (p < 0.05). Inter-reader agreement was moderate (κ: 0.55) for the screening protocol and substantial (κ: 0.61) for the multiparametric protocol. CONCLUSION: The ultra-fast screening protocol showed similar diagnostic performance and better imaging quality compared to the mpMRI in under 15% of scan time, improving efficacy and enabling the implementation of screening protocols in clinical routine. CLINICAL RELEVANCE STATEMENT: The ultra-fast protocol enables examinations without contrast administration, drastically reducing scan time to 3.5 min with similar diagnostic performance and better imaging quality. This facilitates patient-friendly, efficient examinations and addresses the conflict of increasing demand for examinations at currently exhausted capacities. KEY POINTS: Time-consuming MRI protocols are in conflict with an expected increase in examinations required for prostate cancer screening. An ultra-fast MRI protocol shows similar performance and better image quality compared to the standard protocol. Deep-learning acceleration facilitates efficient and patient-friendly examinations, thus improving prostate cancer screening capacity.

Evidence of stage progression in a novel, validated fluorescence-navigated and microsurgical-assisted secondary lymphedema rodent model.

Secondary lymphedema (SL)is a frequent and devastating complication of modern oncological therapy and filarial infections. A lack of a reliable preclinical model to investigate the underlying mechanism of clinical stage progression has limited the development of new therapeutic strategies. Current first line treatment has shown to be merely symptomatic and relies on lifetime use of compression garments and decongestive physiotherapy. In this study, we present the development of a secondary lymphedema model in 35 rats using pre- and intraoperative fluorescence-guided mapping of the lymphatics and microsurgical induction. In contrast to the few models reported so far, we decided to avoid the use of radiation for lymphedema induction. It turned out, that the model is nearly free of complications and capable of generating a statistically significant limb volume increase by water displacement measurements, sustained for at least 48 days. A translational, accurate lymphatic dysfunction was visualized by a novel VIS-NIR X-ray ICG-Clearance-Capacity imaging technology. For the first-time SL stage progression was validated by characteristic histological alterations, such as subdermal mast cell infiltration, adipose tissue deposition, and fibrosis by increased skin collagen content. Immunofluorescence confocal microscopy analysis suggested that stage progression is related to the presence of a characteristic α SMA+/HSP-47+/vimentin+ fibroblast subpopulation phenotype. These findings demonstrate that the in-vivo model is a reliable and clinically relevant SL model for the development of further secondary lymphedema therapeutic strategies and the analysis of the veiled molecular mechanisms of lymphatic dysfunction.

Craniocervical manual lymphatic drainage and its impact on intracranial pressure - a pilot study.

BACKGROUND AND PURPOSE: Theoretical considerations and the results of animal studies indicate that manual lymphatic drainage (MLD) might have an impact on intracranial pressure (ICP). There is a lack of clinically qualitative investigations on patients with severe cerebral diseases. METHODS: Between April 2013 and January 2015 a prospective observational study was performed on patients who were undergoing intracranial pressure measurement and treatment with MLD. ICP, cerebral perfusion pressure, mean arterial pressure (MAP), heart rate and oxygen saturation were recorded continuously 15 min before the procedure, during MLD (22 min) and for 15 min after the procedure. For analysis the data treatment units were divided into two groups: patients with a mean baseline ICP <15 mmHg (group 1) and patients with a mean ICP ≥15 mmHg before MLD (group 2). RESULTS: A total of 133 treatment units (61 patients) were analysed (group 1 n = 99; group 2 n = 34). The mean baseline ICP was 10.4 mmHg overall, and 8.3 mmHg and 18.6 mmHg respectively in group 1 and group 2; ICP significantly decreased during therapy with MLD and this persisted during the follow-up period in group 2. MAP did not show any significant differences between the different periods. CONCLUSIONS: Our data showed a significant reduction of ICP during therapy with craniocervical MLD in patients with severe cerebral diseases.

[Bilateral hand salvage of subtotal left hand amputation and complex right wrist destruction]. / Extremitätenerhalt bei subtotaler Handamputation links und komplexer Handgelenkzerstörung rechts.

Complex injuries of the hand and wrist lead to severe loss of function. Complex trauma of the upper extremities may lead to severe disabilities and therefore meticulous reconstruction is of utmost importance to enable good functional outcome and to assure an adequate quality of life. We demonstrate the case of a patient who suffered from complex bilateral injuries at the wrist level including a subtotal amputation of the left hand and third degree open wrist destruction on the contralateral side. Due to the immediate bilateral operation including the unilateral use of an osteocutaneous free fibula flap, both hands could be salvaged in this case. Severe hand and wrist injuries also require intensive postoperative treatment including intensive physiotherapy, occupational therapy, pain therapy and psychological support to achieve a good functional result.

Indocyanine green fluorescence-guided sentinel node biopsy: a meta-analysis on detection rate and diagnostic performance.

BACKGROUND: Indocyanine green (ICG) fluorescence-guided sentinel node biopsy (SLNB) has been successfully employed in various kinds of tumors. Clinical results of previous studies on this technique are at different levels of evidence. This Meta-analysis was conducted to provide a more precise estimation on its clinical performance. METHODS: Eligible studies were identified from systematical PubMed and EMBASE searches; data were extracted. A Meta-analysis was performed to generate pooled detection rate, sensitivity, specificity, diagnostic odds ratio (DOR) and summary receiver operator characteristic curves. RESULTS: Fifteen published articles were included. Clinical data of 513 patients were obtained. The pooled detection rate, the pooled sensitivity, the pooled specificity, the pooled DOR and their 95% confidence intervals (95% CI) were 0.96 (0.91-0.99), 0.87 (0.79-0.92), 1.00 (0.99-1.00) and 150.13 (57.42-392.56), respectively. Significant heterogeneities existed among studies. Significant publication bias was found in detection rate. The concentration < 5 mg/ml subgroup and the injected volume ≥2 ml subgroup had higher DORs, sensitivities and detection rates than the concentration ≥ 5 mg/ml subgroup and the injected volume <2 ml subgroup, respectively. CONCLUSION: Based on this Meta-analysis, this technique could be valued promising for detecting the presence of LN metastases. ICG injection with reduced concentration and larger volume may provide improved performance.

Current techniques for lymphatic imaging: State of the art and future perspectives.

Techniques for lymphatic imaging are aiming at accurate, simple and minimal-invasive approaches with less side-effects and repetitive application. Limitations are emerging in conventional techniques, and new techniques have shown their advantages in high resolution and sensitivity as well as transcutaneous imaging. In the present review, these techniques and their applications are reviewed and elucidated, aiming at a better understanding of recent advancements and current trends of lymphatic imaging as well as promising techniques for future research.

[Aspects of microsurgical reconstruction for lower extremity defects]. / Aspekte der mikrochirurgischen Rekonstruktion an der unteren Extremität.

The interdisciplinary approach to lower extremity reconstruction between orthopaedic and plastic surgeons is the basis for an efficient soft-tissue coverage. The joint team and the transfer of local, regional and free flaps have been shown to reduce the rate of amputation. After the spread of microsurgical techniques and further innovations, e. g., bony reconstruction by vascularized bone grafts, microsurgery now plays an important role in lower extremity reconstruction. Main considerations for the microsurgical approach are the choice of flap type aiming at good functional results with a stable soft-tissue coverage. The use of innervated flaps and functioning muscle transfer have led to an increased patient satisfaction and quality of life. Timing of reconstruction has been shown to have an impact on the results of microsurgical reconstruction. The importance of "composite tissue allotransplantation - CTA" applied for lower extremity reconstruction has to be evaluated in further studies.

Performance of a New HPV Cervi-Collect Collection and Transportation Kit.

Background. Liquid-based Pap (L-Pap) media are used for Pap and human papillomavirus (HPV) testing. Objectives. To compare RealTime High Risk (HR) HPV testing of a new collection kit (Cervi-Collect) and PreservCyt L-Pap specimens. To determine ease of use and safety of Cervi-Collect. Methods. L-Pap samples (n = 203) were tested with HC2 and RealTime HR HPV and Cervi-Collect with RealTime HR HPV. Discordant samples were genotyped. Results. L-Pap and Cervi-Collect specimens tested by RealTime HR HPV showed 93.1% agreement (Kappa 0.86). RealTime HR HPV and HC2 on L-Pap had 90.3% agreement (Kappa 0.80). RealTime HR HPV on Cervi-Collect and HC2 on L-Pap showed 88.2% agreement (Kappa 0.76). Sixteen of 21 samples which were HC2 negative and RealTime HR HPV positive on L-Pap or Cervi-Collect contained HR HPV genotypes. Eleven healthcare collectors were in strong agreement on a usability and safety questionnaire. Conclusion. Cervi-Collect samples were easy to collect and showed strong agreement with L-Pap samples tested with RealTime HR HPV or HC2.

An aid to the diagnosis of genetic disorders underlying adult-onset renal failure: a literature review.

Several genetic disorders can present in adult patients with renal insufficiency. Genetic renal disease other than ADPKD accounts for ESRD in 3% of the adult Dutch population. Because of this low prevalence and their clinical heterogeneity most adult nephrologists are less familiar with these disorders. As a guideline to differential diagnosis, we provide an overview of the clinical manifestations and the pathogenesis of the main genetic disorders with chronic renal insufficiency surfacing in adulthood and add an algorithm plus 4 tables. We also indicate where molecular genetics nowadays can be of aid in the diagnostic process. The following disorders are discussed by mode of inheritance: 1) Autosomal dominant: autosomal dominant polycystic kidney disease, nephropathies associated with uromodulin (medullary cystic disease and familial juvenile hyperuricemic nephropathy), renal cysts and diabetes syndrome, nail-patella syndrome, glomerulopathy with fibronectin deposits. 2) Not autosomal dominant: Nephronophthisis, Fabry disease, primary oxalosis, Adenine Phosphoribosyl Transferase deficiency, Alport syndrome, Lecithin-cholesterol acyltransferase deficiency, adult-onset cystinosis.

The endoplasmic reticulum in apoptosis and autophagy: role of the BCL-2 protein family.

Apoptosis is essential for normal development and maintenance of homeostasis, and disruption of apoptotic pathways is associated with multiple disease states, including cancer. Although initially identified as central regulators of apoptosis at the level of mitochondria, an important role for BCL-2 proteins at the endoplasmic reticulum is now well established. Signaling pathways emanating from the endoplasmic reticulum (ER) are involved in apoptosis initiated by stimuli as diverse as ER stress, oncogene expression, death receptor (DR) ligation and oxidative stress, and the BCL-2 family is almost invariably implicated in the regulation of these pathways. This also includes Ca(2+)-mediated cross talk between ER and mitochondria during apoptosis, which contributes to the mitochondrial dynamics that support the core mitochondrial apoptosis pathway. In addition to the regulation of apoptosis, BCL-2 proteins at the ER also regulate autophagy, a survival pathway that limits metabolic stress, genomic instability and tumorigenesis. In cases where apoptosis is inhibited, however, prolonged autophagy can lead to cell death. This review provides an overview of ER-associated apoptotic and autophagic signaling pathways, with particular emphasis on the BCL-2 family proteins.

The coronary-subclavian-vertebral steal syndrome (CSVSS).

OBJECTIVE: Reverse flow in the internal thoracic artery (ITA) after coronary bypass surgery due to an occlusion or severe stenosis of the subclavian artery is a rare situation. Symptoms can be recurrent and intermittent angina pectoris in the case of a coronary-subclavian steal (CSSS) or-in addition with cerebral symptoms-in the case of a coronary-subclavian-vertebral steal syndrome (CSVSS). METHOD: We describe the cases of four patients with recurrent angina pectoris 5, 11, and 14 years as well as directly after coronary bypass surgery with LITA grafts to LAD. In two patients there was the additional aspect of vertebral steal symptoms with dizziness and intermittent drop attacks. RESULTS: A PTA of the subclavian occlusions in three cases was not feasible, so that three patients were operated on by extrathoracal approach and carotido-subclavian bypass (CSB) in two cases, and local thrombendarteriectomy of the subclavian and vertebral artery (TEA)+ -patchplasty in one case. Patient 4 was treated by PTA and stent placement into the subclavian artery. Antegrade flow in all four LITAs could be achieved resulting in immediate relief from angina pectoris and cerebral symptoms. Patients 1 and 3 showed no further symptoms with equal BP of the upper extremities and anterograde flow in the LITA grafts and vertebral artery at 10-month follow-up. Patient 2 unfortunately died from an unrelated cause (asthmatic state) 4 months after the operation despite an uneventful recovery. CONCLUSION: The occurrence of a CSSS or CSVSS after coronary bypass surgery with retrograde flow in the ITA graft (as described in our four patients) is a rare, but potentially hazardous, situation. If the subclavian occlusion is not amenable to endovascular strategies, the extrathoracal approach by CSB or local TEA and patchplasty provides an excellent means with good midterm and long-term results.

[Sonography of the thyroid]. / Sonographische Diagnostik der Schilddrüse.

According to its superficial anatomical location the thyroid gland is easily accessible by sonography. Ultrasound is a reliable examination to detect various pathologies of the thyroid gland and it should always be combined with a sonography of the surrounding soft tissues and vessels. Sonography allows an exact documentation of the size, volume and parenchymal echostructure of the thyroid gland as well as detection of various diffuse and focal abnormalities of the gland itself and of the surrounding structures. The presented article gives an overview of the sonographic diagnoses and differential diagnoses of various diffuse and focal pathologies of the thyroid gland as well as some recommendations regarding their possible further diagnostic approach.

Preeclamptic women are deficient of interleukin-10 as assessed by cytokine release of trophoblast cells in vitro.

BACKGROUND: It is well known that the acceptance of the fetoplacental unit in human pregnancy requires maternal immune tolerance, which is thought to be regulated locally by the placenta. Therefore an anti-inflammatory cytokine such as IL-10 plays a critical role in different pregnancy disorders including preeclampsia. In the present study, we examined the expression of both proinflammatory (TNF-alpha, IL-1beta, IL-2) and immunoregulatory (IL-6, IL-10) cytokines from normal term and preeclamptic patients in human trophoblast cultures. METHODS: Eleven patients with preeclampsia and 11 patients with a normal pregnancy at term were included in the study. Trophoblast cells isolated from placentas were cultured up to 48 h under standard tissue culture conditions and cytokine release was determined by ELISA. IL-10 synthesis was significantly decreased in the third trimester in preeclamptic patients in comparison with the control group. RESULTS: There were no significant differences in IL-1beta, IL-2, IL-6 or TNF-alpha expression but a significant alteration in IL-10 release in trophoblast cultures in vitro in term placentas from preeclamptic patients compared with normal pregnancy. CONCLUSIONS: Because IL-10 is a potent regulator of anti-inflammatory immune response these abnormalities may be associated with the inadequate placental development in preeclampsia.

[Multilocular Castleman's Disease of the mixed type. An rare differential diagnosis in lymphadenopathy with weakness, weight loss and night-sweats]. / Multilokulärer Morbus Castleman vom gemischten Typ - Eine seltene Differenzialdiagnose bei Lymphadenopathie mit Schwäche, Gewichtsverlust und Nachtschweiss

HISTORY AND CLINICAL FINDINGS: A 36 years old nurse had been suffering from prolonged weakness, weight-loss of 6 kg, night-sweat and painful swelling of neck lymph nodes for one year. On admission she was in a reduced physical condition. Nuchal, cervical and inguinal lymphnodes were enlarged bilaterally. INVESTIGATIONS: Computed tomography showed enlarged lymph nodes in the neck and inguinally. Histology of the biopsies revealed the diagnosis of the mixed variant of Castleman's Disease. TREATMENT AND COURSE: A steroid treatment was initiated, administering 100 mg prednisone for 2 weeks, 75 mg for another 2 weeks and 50 mg for a month. The dose was then gradually reduced by steps of 10 mg. After 3 months the patient's physical state and lymph nodes were normalized. So treatment was terminated and the nurse was able to take up work again. CONCLUSION: If confronted with general lymphadenopathy associated with B-symptoms even without fever a Castleman's Disease should be taken into consideration. The prognosis of the multivariant form is uncertain. Transformation to malignant lymphoma is frequent.

Germ-line transcripts of the immunoglobulin lambda J-C clusters in the mouse: characterization of the initiation sites and regulatory elements.

Transcription of unrearranged immunoglobulin gene segments strongly correlates with their accessibility to the V(D)J recombination machinery. The regulatory mechanisms governing this germ-line transcription are still poorly defined. In order to identify new regulatory elements, we first carried out a detailed characterization of the transcription initiation sites for the J-C germ-line transcripts, using rapid amplification of 5' cDNA ends, assisted by a template switching mechanism at the 5'-end of the RNA. Transcripts were observed that initiated heterogeneously, starting up to 293 (lambda1), 116 bp (lambda2) and 79 bp (lambda3) upstream from the respective Jlambda gene segment. Additional RT-PCR analysis revealed the existence of germ-line transcripts of lambda and also of kappa that initiate even more upstream of these transcription initiation sites, although their frequencies were low. Promoter activity was detected in vitro 5' of Jlambda2, with the minimal promoter activity mapping to the region between positions -35 and -120. In addition, computer analysis allowed the prediction of a nuclear scaffold/matrix attachment (S/MAR) region between the two J-C gene clusters at each hemi-locus. This region between the lambda1/lambda3 clusters binds to the nuclear matrix in vitro, and J-C lambda1 germ-line transcription initiates a short distance downstream from this S/MAR element.

Genes for human general transcription initiation factors TFIIIB, TFIIIB-associated proteins, TFIIIC2 and PTF/SNAPC: functional and positional candidates for tumour predisposition or inherited genetic diseases?

TFIIIB, TFIIIC2, and PTF/SNAPC are heteromultimeric general transcription factors (GTFs) needed for expression of genes encoding small cytoplasmic (scRNAs) and small nuclear RNAs (snRNAs). Their activity is stimulated by viral oncogenes, such as SV40 large T antigen and Adenovirus E1A, and is repressed by specific transcription factors (STFs) acting as anti-oncogenes, such as p53 and pRb. GTFs role as final targets of critical signal transduction pathways, that control cell proliferation and differentiation, and their involvement in gene expression regulation suggest that the genes encoding them are potential proto-oncogenes or anti-oncogenes or may be otherwise involved in the pathogenesis of inherited genetic diseases. To test our hypothesis through the positional candidate gene approach, we have determined the physical localization in the human genome of the 11 genes, encoding the subunits of these GTFs, and of three genes for proteins associated with TFIIIB (GTF3BAPs). Our data, obtained by chromosomal in situ hybridization, radiation hybrids and somatic cell hybrids analysis, demonstrate that these genes are present in the human genome as single copy sequences and that some cluster to the same cytogenetic band, alone or in combination with class II GTFs. Intriguingly, some of them are localized within chromosomal regions where recurrent, cytogenetically detectable mutations are seen in specific neoplasias, such as neuroblastoma, uterine leyomioma, mucoepidermoid carcinoma of the salivary glands and hemangiopericytoma, or where mutations causing inherited genetic diseases map, such as Peutz-Jeghers syndrome. Their molecular function and genomic position make these GTF genes interesting candidates for causal involvement in oncogenesis or in the pathogenesis of inherited genetic diseases.

Familial neurohypophysial diabetes insipidus in a large Dutch kindred: effect of the onset of diabetes on growth in children and cell biological defects of the mutant vasopressin prohormone.

Familial neurohypophysial diabetes insipidus (FNDI) is an autosomal dominant trait in which expression of a mutant vasopressin prohormone reduces vasopressin production. We investigated the NP85 Cys-->Gly mutant vasopressin prohormone in a large kindred in The Netherlands. We demonstrate that growth retardation is an important early sign in two children from this kindred, which recuperates by substitution therapy with 1-desamino-8-D-arginine vasopressin. To obtain clues about the basis for the dominant inheritance of FNDI, we analyzed the trafficking and processing of the mutant vasopressin prohormone in cell lines by metabolic labeling and immunoprecipitation. The mutant vasopressin prohormone was retained in the endoplasmic reticulum and thus was not processed to vasopressin. This defect was not caused by dimerization of the vasopressin prohormone via its unpaired cysteine residue. High level expression of the mutant vasopressin prohormone in cell lines resulted in strong accumulation in the endoplasmic reticulum and an altered morphology of this organelle. We hypothesize that disturbance of the endoplasmic reticulum results in dysfunction and ultimately cell death of the cells expressing the mutant prohormone. Our data support the hypothesis that FNDI is a progressive neurodegenerative disease with delayed onset of symptoms. Its treatment requires early detection of symptoms for which growth parameters are useful.

Acute deep vein thrombosis: early mobilization does not increase the frequency of pulmonary embolism.

Outpatient treatment for acute symptomatic deep vein thrombosis (DVT) was shown to be safe for most patients. However, little is known whether patients treated on an outpatient basis were ambulating or predominantly resting, a factor which may be decisive for the outcome. In the present study 129 DVT patients were randomized to either strict immobilization for 4 days or to ambulate for > or = 4 hours per day under supervision in order to show, whether the old concept of temporary immobilization is superior to early mobilization or not. The DVT diagnosis was based on duplex sonography; all patients were screened for PE at baseline and at day 4 by pulmonary ventilation-perfusion scanning, and were followed up for a total of 3 months. Clinically, changes in leg circumferences and leg pain were evaluated. The frequency of PE at baseline was 53.0% and 44.9% in the immobile and the mobile groups, respectively. During the 4 days observation period new PEs were found in 10.0% and in 14.4% of the immobilized and the ambulating patients (delta 4.4%; 95% CI -0.5 to 13.8; chi2 = 0.596, p = 0.44). The occurrence of new PE was related to the presence of PE at baseline but not to other potential predictors. The magnitude of a decrease in leg circumferences and leg pain was comparable in both groups. No patient died during the 4 day observation period. The total 3 month mortality rate was 3.9% (5 patients; 2 from the immobile, 3 from the ambulating group). All 5 patient suffered from malignancies. The results of this study show in accordance with the trial hypothesis that, regarding the frequency of PE, immobilization is not superior to early mobilization, suggesting that early mobilization is safe.