[Ultrasound of nerves of the lower extremities]. / Nervensonographie der unteren Extremitäten.

The ability to visualize the nerves of the lower extremities differs from that of the upper extremities in sonography because the soft tissue cover is significantly larger in some cases. Landmarks are also defined for the lower extremities, which enable precise visualization of the nerves. Nerves and muscles are to be understood as a functional unit. In addition to the clarification of nerve compression syndromes, polyneuropathies and nerve tumors, sonography is also used to visualize muscle atrophy.

Cytomegalovirus-positive Posner-Schlossman syndrome: to compare differences in retinal vessel area density between the affected and non-affected eye using optical coherence tomography angiography.

PURPOSE: To analyse differences in the retinal microvasculature in eyes with cytomegalovirus (CMV)-positive Posner-Schlossman syndrome (PSS) compared to the non-affected eyes using optical coherence tomography angiography (OCTA). METHODS: In this monocentric, observational prospective case series, 25 patients with unilateral CMV-positive PSS were included. We compared the vessel area densities (VAD) in the macula, optic disc, and peripapillary region in PSS-affected and non-affected eyes using OCTA. We compared the visual fields (VF) of the affected and healthy eyes of each patient. The mean deviation (MD) of the VF was analysed together with the retinal nerve fibre layer (RNFL) thickness to evaluate the strength of correlation with the VAD parameters. RESULTS: The VAD of the peripapillary superficial vascular complex (SVC) is significantly reduced in CMV-positive PSS-affected eyes (46.1 ± 9.3% versus 50.1 ± 6.3%, p = 0.008, adjusted p = 0.048). The VAD of the deeper macular, papillary, and peripapillary layers showed no differences between the affected and non-affected eyes. The mean deviation and the retinal nerve fibre layer thickness had correlations with the VAD of the macula (r = 0.451, p = 0.001, r = 0.553, p < 0.001), the peripapillary SCV (r = 0.430, p = 0.002, r = 0.723, p < 0.001), and the papillary region (r = 0.512, p < 0.001, r = 0.292, p = 0.039). Patients receiving systemic antiviral therapy (SAT) showed better VAD of the peripapillary choriocapillary layer (p = 0.001, no therapy: 31.4 ± 1.9%, SAT: 35.0 ± 1.6%), and choroidal layer (p = 0.009, no therapy: 34.2 ± 0.3%, SAT: 36.3 ± 1.8%) compared to those with no SAT. CONCLUSION: A lower peripapillary VAD in the SVC might indicate vascular dysfunction as a sign of glaucomatous damage. SAT might have positive effects on the microcirculation in the deep retinal and choroidal layers. TRIAL REGISTRATION: TRN: DRKS00028266, https://www.drks.de/drks_web/ .

XEN® implantation: an effective strategy to stop glaucoma progression despite prior minimally invasive glaucoma surgery.

PURPOSE: The aim of this study was to evaluate whether XEN® implantation is a reasonable and safe method to lower the intraocular pressure (IOP) and amount of medication for adult primary open-angle glaucoma (POAG) over a 3-year period. The influence of the type of anesthesia, previous glaucoma surgery, and postoperative interventions on the outcome were examined. METHODS: In this retrospective study, 96 eyes were included. XEN® implantation was performed as sole procedure under general (n = 86) or local anesthesia (n = 10). IOP and number of glaucoma medication were assessed preoperatively: day 1, week 6, month 3, 6, 12, 24, and 36. Further outcome parameters were Kaplan-Meier success rates, secondary intervention, and complication rates. RESULTS: IOP decreased from 20.7 ± 5.1 to 12.8 ± 2.5 mmHg at the 36-month follow-up (p < 0.001) and glaucoma therapy was reduced from 3.3 ± 0.8 to 1.2 ± 1.6 (36 months, p < 0.001). Transient postoperative hypotony was documented in 26 eyes (27.1%). General anesthesia resulted in a significant improvement of the survival rate compared to local anesthesia (77% vs. 50%, p = 0.044). Prior iStent inject®, Trabectome®, or SLT laser had no significant impact, such as filter bleb revision. The number of postoperative needlings had a significantly negative influence (p = 0.012). CONCLUSION: XEN® implantation effectively and significantly lowers the IOP and number of glaucoma therapy in POAG in the 36-month follow-up with a favorable profile of side effects and few complications. In case of IOP, general anesthesia has a significant positive influence on the survival rate, whereas prior SLT or MIGS does not have significant impact.

Graft failure rate and complications after Descemet membrane endothelial keratoplasty in eyes with pre-existing glaucoma.

PURPOSE: To evaluate the outcome of Descemet Membrane Endothelial Keratoplasty (DMEK) in eyes with pre-existing glaucoma. DESIGN: In this retrospective, observational case series we included data of 150 consecutive DMEKs in eyes with pre-existing glaucoma of 150 patients after excluding data of the second treated eye of each patient and of re-DMEKs during follow-up. Cumulative incidences of IOP elevation (IOP > 21 mmHg or ≥ 10 mmHg increase in IOP from preoperative value), post-DMEK glaucoma (need of an additional intervention due to worsening of the IOP), graft rejection, and graft failure rate were analyzed using Kaplan-Meier survival analysis. COX regression analysis was used to evaluate independent risk factors. RESULTS: The 36-month cumulative incidence of IOP elevation was 53.5% [95 CI 43.5-63.5%] and of post-DMEK glaucoma 36.3% [95 CI 26.3-46.3%]. Graft rejection occurred with a 36-month cumulative incidence of 9.2% [CI 95% 2.3-16.1]. None of the analyzed risk factors increased the risk for the development of graft rejection. The 36-month cumulative incidence of graft failure was 16.6% [CI 95% 8.4-24.8]. Independent risk factors for graft failure were the indication for DMEK "status after graft failure" (n = 16) compared to Fuchs' dystrophy (n = 74) (p = 0.045, HR 8.511 [CI 95% 1.054-68.756]) and pre-existing filtrating surgery via glaucoma drainage device (GDD) (n = 10) compared to no surgery/iridectomy (n = 109) (p = 0.014, HR 6.273 [CI 95% 1.456-27.031]). CONCLUSION: The risks of postoperative complications (IOP elevation, post-DMEK glaucoma, graft rejection, and graft failure) in patients with pre-existing glaucoma are high. In particular, pre-existing filtrating surgery via GDD implantation-but not trabeculectomy-and DMEK after graft failure increase the risk of graft failure.

Checkpoint-inhibitor induced Polyserositis with Edema.

BACKGROUND: As immune checkpoint inhibitors (ICI) are increasingly being used due to effectiveness in various tumor entities, rare side effects occur more frequently. Pericardial effusion has been reported in patients with advanced non-small cell lung cancer (NSCLC) after or under treatment with immune checkpoint inhibitors. However, knowledge about serositis and edemas induced by checkpoint inhibitors in other tumor entities is scarce. METHODS AND RESULTS: Four cases with sudden onset of checkpoint inhibitor induced serositis (irSerositis) are presented including one patient with metastatic cervical cancer, two with metastatic melanoma and one with non-small cell lung cancer (NSCLC). In all cases treatment with steroids was successful in the beginning, but did not lead to complete recovery of the patients. All patients required multiple punctures. Three of the patients presented with additional peripheral edema; in one patient only the lower extremities were affected, whereas the entire body, even face and eyelids were involved in the other patients. In all patients serositis was accompanied by other immune-related adverse events (irAEs). CONCLUSION: ICI-induced serositis and effusions are complex to diagnose and treat and might be underdiagnosed. For differentiation from malignant serositis pathology of the punctured fluid can be helpful (lymphocytes vs. malignant cells). Identifying irSerositis as early as possible is essential since steroids can improve symptoms.

Macular, papillary and peripapillary perfusion densities measured with optical coherence tomography angiography in primary open angle glaucoma and pseudoexfoliation glaucoma.

PURPOSE: To compare the blood flow situation in primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG) using optical coherence tomography angiography (OCTA). METHODS: In this prospective study a total of 26 POAG and 23 PXG eyes were included. All patients underwent a complete ophthalmological examination including standard automated perimetry, stereoscopic photographs of the optic disc, peripapillary retinal nerve fibre layer analysis and examination of vascular parameters of the optic nerve head (ONH), the peripapillary region and macula using OCTA. In addition to the vascular parameters recorded by the device, the vascular images were graphically evaluated using Image J. All recorded vascular parameters were compared between both groups and correlated to structural and functional parameters. RESULTS: The mean superficial perifoveal plexus perfusion density (PD) was significantly lower in PXG eyes than compared to POAG eyes using OCTA (32.57% ± 3.57% vs. 34.92% ± 2.11%, p = 0.007). The mean PD parameters for the superficial peripapillary plexus (40.98% ± 3.04% vs. 42.09% ± 2.29%, p = 0.152) as well as the size of the foveal avascular zone (FAZ) (0.23 mm2 ± 0.1 mm2 vs. 0.23 mm2 ± 0.09 mm2) did not differ between both groups. Additional graphic evaluation using Image J showed no significant difference for superficial perifoveal plexus PD (32.97% ± 1.11% vs. 33.35% ± 0.95%, p = 0.194) and peripapillary plexus PD (46.65% ± 0.83% vs. 46.95% ± 0.5%, p = 0.127) between the groups. Retinal nerve fibre layer (RNFL) thickness correlated significantly with peripapillary plexus PD for both OCTA data and Image J data (p < 0.001, p = 0.032). CONCLUSION: The severity of the glaucoma seems to be crucial for peripapillary and macular perfusion densities, and not the form of glaucoma. An additional graphic evaluation is a possible step that could be implemented to improve the comparability of OCTA scans and to optimize the possibility of quantitative perfusion analysis in the case of deviating quality criteria.

"An uncomfortable topic": Health professionals' perspectives on child protection capacities, training offers and the potential need for action in Germany.

BACKGROUND: Child maltreatment, due to its high prevalence and often long-lasting (health and/or psycho-social) consequences, is one of the main reasons for global health inequalities. The medical field offers many opportunities to support affected children. This gives physicians and other health professionals the opportunity to provide protective measures and therapies to affected children at an early stage. However, the level of training concerning child protection is often too low among health professionals. This can affect the quality of care as well as providing the appropriate treatment and thus, the long-term (health) burden. The present work aims to survey the state of knowledge and capacities of health professionals regarding child protection in medicine and elicit health professionals' perspectives who absolved a child protection online course on a potential need for action in Germany. METHODS: From June 2016 until February 2021, 3,360 health professionals were interviewed. Using quantitative and qualitative items, the questionnaire assessed demographic and professional background information as well as assessments regarding the awareness of child protection, abilities in child protection among health professionals and training offers in medicine. RESULTS: The analysis indicates that the topic of child protection in medicine is not as present as the high prevalence of child maltreatment would imply. The majority (94.0%; n = 3.159) of the health professionals stated that they need more knowledge and capacities regarding child protection in medicine. More than half of the health professionals assessed the importance of the issue of child protection as low among health professionals. The reasons cited included child protection as an uncomfortable topic, an unwillingness among managers, and a lack of training on the topic. CONCLUSIONS: There is too little awareness and importance regarding child protection in the medical field in Germany. Hence, it is difficult to ensure adequate care for those affected. Child protection topics should be mandatory in the training curricula of all health professionals, and quality standards for prevention and intervention should be implemented in medical institutions. Furthermore, networking in child protection has to be improved, and medical campaigns should address the topic to sensitize health professionals and society to the issue and to destigmatize the topic.

Osteoporosis Caused by Systemic Mastocytosis: Prevalence in a Cohort of 8392 Patients with Osteoporosis.

Indolent systemic mastocytosis (ISM) is a group of heterogenous diseases characterized by abnormal accumulation of mast cells in at least one organ. ISM can be a cause of osteoporosis. The aim of this study is to determine the prevalence, and the prognosis of ISM in a cohort of patients with osteoporosis. In this monocentric and retrospective study, patients with osteoporosis who did not receive a bone biopsy (cohort 1) and patients that subsequently received a diagnostic bone biopsy for differential diagnosis (cohort 2) are compared with patients who are diagnosed with ISM (cohort 3). A total of 8392 patients are diagnosed with osteoporosis. Out of these patients 1374 underwent a diagnostic bone biopsy resulting in 43 patients with ISM. These figures indicate that ISM is diagnosed in 0.5% of patients with osteoporosis and in 3.1% (men 5.8%) of patients who underwent bone biopsies. Patients with ISM sustained significantly more vertebral fractures in comparison to patients in cohort 2 (4.4 ± 3.6 versus 2.4 ± 2.5 vertebral fractures, p < 0.001) and women were significantly younger compared to cohort 2 (57.3 ± 12 versus 63.6 ± 12 years, p < 0.05). Only 33% showed an involvement of the skin (urticaria pigmentosa). ISM is a rare cause of osteoporosis (0.5%). However, in a subgroup of rather young male patients with osteoporosis the prevalence is more than 5%. Thus, ISM should be considered in premenopausal women and men presenting with vertebral fractures even if urticaria pigmentosa is not present.

S-ketamine and intranasal application: alternatives for the castration of male suckling piglets?

BACKGROUND: The intramuscular injection of ketamine and azaperone was proposed as a suitable anaesthesia for male suckling piglets for surgical castration. However, this can be opposed by massive defensive movements, hypothermia and tachycardia during castration and a long recovery period. The aim of the present study was to test whether the use of S-ketamine and/or a change in the route of application from intramuscular to intranasal could reduce stress responses and the duration of recovery compared to the intramuscular route and the use of racemic ketamine. Seventy-eight healthy, five-day-old male piglets were randomized to six treatment groups in a blinded experimental study, matched by litter and weight. Experimental groups were A (15 mg kg-1 S-ketamine + 2 mg kg-1 azaperone, i.m., surgical castration), B (15 mg kg-1 R/S-ketamine racemate + 2 mg kg-1 azaperone, i.m., surgical castration), C (30 mg kg-1 S-ketamine + 2 mg kg-1 azaperone, i.n., surgical castration), D (15 mg kg-1 R/S-ketamine racemate + 2 mg kg-1 azaperone, i.m.; not castrated), E (positive control group; no anesthesia, surgical castration) and F (negative control group; no anesthesia, not castrated). RESULTS: S-ketamine reduced the defensive movement score during castration to a similar extent to racemic ketamine when administered intramuscularly but not via the intranasal route. However, the effects of S-ketamine (both routes) on the increase in cortisol levels and decrease in body temperature were similar to those induced by racemic ketamine. A reduction of the long recovery time known for ketamine-azaperone anaesthesia could not be achieved with S-ketamine in the given dosage, regardless of the route of application. The intranasal administration of ketamine was difficult with the available formulation as the necessary amount exceeded the capacity of the nose cavity. CONCLUSIONS: Neither the use of S-ketamine nor intranasal administration can be suitable alternatives for the anaesthesia of male suckling piglets for castration.

Effect of Endothelial Culture Medium Composition on Platelet Responses to Polymeric Biomaterials.

Near-physiological in vitro thrombogenicity test systems for the evaluation of blood-contacting endothelialized biomaterials requires co-cultivation with platelets (PLT). However, the addition of PLT has led to unphysiological endothelial cell (EC) detachment in such in vitro systems. A possible cause for this phenomenon may be PLT activation triggered by the applied endothelial cell medium, which typically consists of basal medium (BM) and nine different supplements. To verify this hypothesis, the influence of BM and its supplements was systematically analyzed regarding PLT responses. For this, human platelet rich plasma (PRP) was mixed with BM, BM containing one of nine supplements, or with BM containing all supplements together. PLT adherence analysis was carried out in six-channel slides with plasma-treated cyclic olefin copolymer (COC) and poly(tetrafluoro ethylene) (PTFE, as a positive control) substrates as part of the six-channel slides in the absence of EC and under static conditions. PLT activation and aggregation were analyzed using light transmission aggregometry and flow cytometry (CD62P). Medium supplements had no effect on PLT activation and aggregation. In contrast, supplements differentially affected PLT adherence, however, in a polymer- and donor-dependent manner. Thus, the use of standard endothelial growth medium (BM + all supplements) maintains functionality of PLT under EC compatible conditions without masking the differences of PLT adherence on different polymeric substrates. These findings are important prerequisites for the establishment of a near-physiological in vitro thrombogenicity test system assessing polymer-based cardiovascular implant materials in contact with EC and PLT.

Survey of Rejection Prophylaxis Following Suture Removal in Penetrating Keratoplasty in Germany. / Umfrage zur Abstoßungsprophylaxe bei Fadenentfernung nach perforierender Keratoplastik in Deutschland.

BACKGROUND: Penetrating keratoplasty (PK) gets more and more reserved to cases of increasing complexity. In such cases, ocular comorbidities may limit graft survival following PK. A major cause for graft failure is endothelial graft rejection. Suture removal is a known risk factor for graft rejection. Nevertheless, there is no evidence-based regimen for rejection prophylaxis following suture removal. Therefore, a survey of rejection prophylaxis was conducted at 7 German keratoplasty centres. OBJECTIVE: The aim of the study was documentation of the variability of medicinal aftercare following suture removal in Germany. METHODS: Seven German keratoplasty centres with the highest numbers for PK were selected. The centres were sent a survey consisting of half-open questions. The centres performed a mean of 140 PK in 2018. The return rate was 100%. The findings were tabulated. RESULTS: All centres perform a double-running cross-stitch suture for standard PK, as well as a treatment for rejection prophylaxis with topical steroids after suture removal. There are differences in intensity (1 - 5 times daily) and tapering (2 - 20 weeks) of the topical steroids following suture removal. Two centres additionally use systemic steroids for a few days. DISCUSSION: Rejection prophylaxis following PK is currently poorly standardised and not evidence-based. All included centres perform medical aftercare following suture removal. It is assumed that different treatment strategies show different cost-benefit ratios. In the face of the diversity, a systematic analysis is required to develop an optimised regimen for all patients.

Efficacy of intraoperative specimen radiography as margin assessment tool in breast conserving surgery.

PURPOSE: To explore the ability of intraoperative specimen radiography (SR) to correctly identify positive margins in patients receiving breast conserving surgery (BCS). To assess whether the reoperation rate can be reduced by using this method. METHODS: This retrospective study included 470 consecutive cases receiving BCS due to a primarily diagnosed breast cancer. SR was carried out in two planes, assessing the specimen regarding the presence of the lesion and its relation to all margins. If indicated, re-excision of selective orientations was advised. Under consideration of gross inspection and the SR-findings, it was up to the surgeon whether to perform re-resections. The recommendations for re-excision were, separately for each orientation, compared to the histopathological results, serving as gold standard. RESULTS: Intraoperative SR was performed in 470 cases, thus 2820 margins were assessed. Of those, 2510 (89.0%) were negative and 310 (11.0%) positive. SR identified 2179 (77.3%) margins correctly as negative, whereas 331 (11.7%) clear margins were misjudged as positive. Of 310 infiltrated margins, SR identified 114 (4.0%) correctly, whereas 196 (7.0%) infiltrated margins were missed. This resulted in a sensitivity/specificity of 36.8%/86.8% and PPV/NPV of 25.6%/91.8%. Through targeted re-resections positive margins could be reduced by 31.0% [310 to 214 (7.6%)]. On case level, the rate of secondary procedures could be reduced by 37.0% [from 162 to 102 (21.7%)]. CONCLUSIONS: SR is a helpful tool to identify infiltrated margins and to reduce the rate of secondary surgeries by recommending targeted re-excisions of according orientations in order to obtain a final negative margin status.

Impact of difficult unfolding and attachment of the graft lamella on the long-term outcome after Descemet membrane endothelial keratoplasty.

PURPOSE: Unfolding and attachment of the posterior donor lamella may be the most challenging part in Descemet membrane endothelial keratoplasty (DMEK) procedure. We investigated the correlation of the difficulty degrees of this step to the postoperative clinical outcome 6 years after surgery. METHODS: One hundred sixty-nine consecutive DMEKs between September 2012 and August 2013 at the Charité-University Medicine Berlin were graded prospectively into 4 groups according to their grade of difficulty in unfolding and attachment of the graft lamella. Postoperative visual acuity, endothelial cell density, and rate of graft failure were measured after 1 year, after 2 years, and after 6 years and analyzed according to their grading group. RESULTS: Visual acuity improved significantly in all groups and did not differ significantly between the grading groups at any time point postoperatively. There was a significant decrease of endothelial cell density in all groups with a significantly higher endothelial cell loss in group IV compared with the other groups within the first 24 months after surgery. The graft failure rate was significantly higher in eyes graded III and IV than in groups I and II (p = 0.012). CONCLUSION: Although the endothelial cell loss and the graft failure rate increase significantly with a more difficult graft unfolding and attachment, DMEK surgery is a promising procedure with a good long-term postoperative outcome. A direct manipulation of the graft lamella for unfolding and centering by cannula or forceps should be avoided if possible to reduce the risk of an increased endothelial cell loss and a higher graft failure rate. TRIAL REGISTRATION: NCT02020044.

Influence of Selective Laser Trabeculoplasty (SLT) on the iStent inject® outcomes.

BACKGROUND: To evaluate the influence of Selective Laser Trabeculoplasty (SLT) on iStent inject® outcomes in open-angle glaucoma (OAG). METHODS: In this retrospective comparative cohort outcome study, 66 patients who were treated with two iStent inject® devices were included. Patients were divided into two subgroups consisting of patients without SLT treatment prior to surgery and patients who had been treated previously with 360° SLT but without sufficient response. Outcome measures included intraocular pressure (IOP) and number of antiglaucoma medications after 6 weeks with three, six, 12, and 24 month follow-ups. RESULTS: Mean preoperative IOP decreased from 20.4 ± 5.3 mmHg to 14.8 ± 3.0 mmHg for patients without SLT treatment prior to surgery (p = 0.001) and from 19.2 ± 4.5 mmHg to 14.0 ± 1.6 mmHg for patients with insufficient response to 360° SLT treatment (p = 0.027) at 12 months after iStent inject® implantation. No significant difference was found between the two groups (p >  0.05). The number of antiglaucoma medications did not change in both groups (p >  0.05) and showed no significant difference between the two groups (p >  0.05). CONCLUSION: Prior SLT treatment seems to have no negative influence on the IOP lowering-effect of iStent inject® implantation in patients with OAG. It is therefore an appropriate incremental procedure with no exclusion criterion for an iStent inject® implantation.

Three-year results of ab interno trabeculectomy (Trabectome): Berlin study group.

PURPOSE: To assess the long-term outcome of Trabectome surgery in the treatment of primary open angle glaucoma (POAG) and pseudoexfoliative glaucoma (PEX): 3-year results. METHODS: Trabectome surgery (NeoMedix, Tustin, CA, USA) was performed in 268 POAG patients (women 57.46%, men 42.54%, age 72.35 ± 9.63 years) and 98 PEX glaucoma patients (women 58.16%, men 41.84%, age 73.42 ± 8.54 years), and uncontrolled intraocular pressure (IOP). Parameters were examined preoperatively, 1 day, 6 weeks, 3, 6, 12, 24 and 36 months post surgery. Kaplan-Meier analysis was performed using Criteria A (IOP ≤ 21 mmHg or ≥20% reduction from preoperative IOP), Criteria B (IOP ≤ 18 mmHg or ≥20% IOP reduction), Criteria C (IOP ≤ 21 mmHg, with or without medication) and D (IOP ≤ 18 mmHg, with or without medication). Complete success was defined as IOP ≤ 21 mmHg (Criteria E) and IOP ≤ 18 mmHg without medication (Criteria F). RESULTS: IOP was reduced from 19.10 ± 4.11 mmHg to 14.27 ± 2.93 mmHg (p < 0.001) and glaucoma medication was decreased from 2.40±0.92 to 1.77±1.00 (p < 0.001) in POAG after 36 months. In PEX, IOP decreased from 22.49±9.40 mmHg to 14.57±5.05 mmHg after 36 months (p < 0.001). Medications dropped from 2.31±1.02 to 1.75±0.91 (p = 0.006). Kaplan-Meier analysis showed a success rate of 80.5% for POAG and 80.8% for PEX using criteria A (p = 0.933) and 62.4% for POAG and 73.7% for PEX using criteria B (p = 0.147) at 36 months postoperatively. Complete success showed a low survival rate (criteria E-13.5% in POAG and 7.9% in PEX, p = 0.070 and criteria F-12.8% in POAG and 5.9% in PEX, p = 0.083). CONCLUSIONS: Trabectome is a safe method to lower IOP in patients with POAG and PEX glaucoma in the long-term period. It is beneficial to inform patients prior to surgery about adjuvant glaucoma medication after the surgery.

Inter-rater reliability and double reading analysis of an automated three-dimensional breast ultrasound system: comparison of two independent examiners.

PURPOSE: Breast ultrasound could be a valuable tool complementary to mammography in breast cancer screening. Automated 3D breast ultrasound (ABUS) addresses challenges of hand-held ultrasound and could allow double reading analysis of ultrasound images. This trial assesses the inter-rater reliability and double reading analysis of an ABUS system. METHODS: To assess the reproducibility and diagnostic validity of the ABUS system, SomoV™, a blinded double reading analysis, was performed in 1019 patients (2038 breasts) by two examiners (examiner A/B) and compared to single reading results, as well as to the reference standard regarding its diagnostic validity. Cohen's kappa coefficients were calculated to measure the inter-rater reliability and agreement of the different diagnostic modalities. Patient comfort and time consumption for image acquisition and reading were analyzed descriptively as secondary objectives. RESULTS: Analysis of inter-rater reliability yielded agreement in 81.6% (κ = 0.37; p < 0.0001) showing fair agreement. Single reading analysis of SomoV™ exams (examiner A/examiner B) compared to reference standard showed good specificity (examiner A: 88.3%/examiner B: 84.5%), fair inter-rater agreement (examiner A: κ = 0.31/examiner B: κ = 0.31), and adequate sensitivity (examiner A: 53.1%/examiner B: 64.2%). Double reading analysis yielded good sensitivity and specificity (73.7 and 77.7%). Mammography (n = 1911) alone detected 160 of 176 carcinomas (sensitivity 90.1%). Adding SomoV™ to mammography would have detected 12 additional carcinomas, resulting in a higher sensitivity of 97.7%. CONCLUSION: SomoV™ is a promising technique with good sensitivity, high patient comfort, and fair inter-examiner reliability. It allows double reading analysis that, in combination with mammography, could increase detection rates in breast cancer screening.

Activation of the mouse odorant receptor 37 subsystem coincides with a reduction of novel environment-induced activity within the paraventricular nucleus of the hypothalamus.

Within the main olfactory system of mammals, a unique subsystem exists that is comprised of sensory neurons expressing odorant receptors (ORs) of the OR37 subfamily. These receptors are exclusive for mammals and are highly conserved across species. The mouse OR37 receptor subtypes A, B and C were shown to be activated by the long-chain aliphatic aldehydes pentadecanal, hexadecanal and heptadecanal, respectively. The search for biological sources of these compounds showed that bodily secretions from conspecifics activated the OR37A, B and C glomerulus. At the same time, the activity of cells in a target region of projection neurons from OR37 glomeruli, the paraventricular nucleus of the hypothalamus (PVN), was reduced compared with controls (clean test box). A large number of the activated cells in the PVN of mice that were placed into a clean test box were corticotropin-releasing hormone cells, indicating an induction of the stress axis due to the novel environment. The much lower number of activated cells of mice in a box enriched with bodily secretions from conspecifics indicated a reduced stress response. As bodily secretions from conspecifics activated the OR37 system and simultaneously reduced stress-induced activation of the PVN, it was tested whether the ligands for OR37 receptors could induce this effect. Indeed, a similarly reduced activity in the PVN was found in mice kept in a clean test box and exposed to a mixture of the OR37 ligands delivered via an air stream. These data indicate that the OR37 system may play a role in mediating a phenomenon called social buffering.

iStent inject in phakic open angle glaucoma.

BACKGROUND: The effectiveness and complication profile of the iStent inject implantation among different open angle glaucoma subgroups were analyzed. METHODS: In this retrospective cohort outcome study, 35 consecutive patients suffering from glaucoma (primary open angle glaucoma (POAG) N = 17, pseudoexfoliation glaucoma (PEX) N = 15, and pigmentary glaucoma (PG) N = 3) were treated with the iStent inject. The intraocular pressure (IOP) and the number of antiglaucoma medications before and after surgery were evaluated. RESULTS: In POAG, the mean IOP at 6 months measured 14.19 ± 1.38 mmHg with an average decrease of 33 % from preoperative IOP (p < 0.001), and 15.33 ± 1.07 mmHg with an average decrease of 35 % in PEX (p < 0.001), respectively. The number of antiglaucoma medications significantly decreased from 2.19 ± 0.91 to 0.88 ± 0.62 in POAG (p < 0.001) and from 2.33 ± 1.23 to 1.04 ± 0.30 in PEX (p < 0.001) after 6 months. In PG, IOP before surgery was 28.31 ± 3.21 mmHg and the number of antiglaucoma medications was 3.66 ± 0.57. One day after surgery, IOP decreased significantly to 12.33 mmHg ± 4.93 (p < 0.001). Within four weeks after surgery, IOP was raised above 30 mmHg in every patient. To exclude a steroid response, topical steroids were stopped, but IOP did not decrease. To exclude blockage, Nd:YAG - laser treatment of the visible opening of the iStents was performed. Since the IOP stayed high and escalation of antiglaucoma medication was insufficient to control IOP, trabeculectomy was performed. CONCLUSIONS: In conclusion, implantation of the iStent inject has the ability to lower the postoperative IOP significantly in POAG and PEX after a short follow-up of 6 months with a favorable risk profile. However, limitation of this surgical procedure in phakic PG may exist and need to be investigated in further studies.

Influence of the difficulty of graft unfolding and attachment on the outcome in Descemet membrane endothelial keratoplasty.

PURPOSE: Descemet membrane endothelial keratoplasty (DMEK) is a standard procedure in patients with endothelial corneal disorders. We investigated the difficulty of unfolding and attaching the graft lamella and its correlation to characteristics of the graft lamella donor, preoperative patient characteristics, and the postoperative outcome. METHODS: After preparation of the graft lamella, we prospectively graded the unfolding of the graft lamella in 169 consecutive DMEK procedures between September 2012 and August 2013 at the Charité-Universitätsmedizin Berlin with four different grades. Various donor characteristics and preoperative patient characteristics were analyzed and correlated to the grading. Additionally, visual acuity, corneal thickness and endothelial cell density were measured and correlated. RESULTS: Donor characteristics (age [range, 49 - 79 years], gender, endothelial cell density, total storage time, storage de-swelling time, postmortem time) did not correlate to the grading. Preoperative visual acuity significantly influenced the grade of unfolding and attaching of the graft lamella (p = 0.023), while all other preoperative parameters (age, gender, indication for DMEK, preoperative endothelial cell density and preoperative central corneal thickness) showed no correlation. Visual acuity improved significantly after surgery (p < 0.001, preoperative 0.73 ± 0.43 LogMAR versus 0.31 ±0.28 LogMAR after one month, 0.25 ± 0.29 LogMAR after three months, and 0.21 ± 0.25 LogMAR after six months). Visual acuity did not differ significantly between the grading groups at any time point postoperatively. After 6 months, the mean loss rate of endothelial cell density was 24.7 %. Grading group IV developed significantly higher endothelial loss after one month, after three months and after six months compared to the other groups (p = 0.039, p = 0.008, p = 0.048). Graft detachment requiring an additional intracameral air injection to fix the graft detachment (re-bubbling) occurred in 61 eyes (38.1 %). In eyes graded IV, more re-bubblings were necessary than in all other groups (grade I: 37.0 %; grade II: 44.7 %; grade III: 43.8 %; grade IV: 50.0 %; p = 0.128; df = 3; χ (2) = 5.676). CONCLUSION: There is no correlation between corneal donor tissue characteristics and the degree of difficulty of unfolding using graft lamella older than 49 years. Therefore, it is not possible to select grafts best suited for DMEK surgery on the basis of donor characteristics when the donor age is above 50 years. Preoperative visual acuity influences the grade of difficulty. The rate of graft detachments and endothelial cell loss increases significantly with a more difficult graft unfolding. The proposed grading system may therefore be relevant for postoperative management.