[Special medical outpatient care-3.5 years of outpatient specialist care in rheumatology : An inventory]. / Ambulante spezialfachärztliche Versorgung ­ 3,5 Jahre ASV in der Rheumatologie : Eine Bestandsaufnahme.

BACKGROUND: In 2012 the outpatient specialist medical care (ASV) was introduced as an intersectoral, interdisciplinary, outpatient care concept. As from 19 April 2018 there is the possibility to form teams for the ASV for rheumatic diseases in adults as well as in children and adolescents.. MATERIAL AND METHODS: Analysis of previously unpublished data of the National Confederation of Statutory Health Insurance (GKV-SV) and of data of the ASV service department and a comparison with data of standard healthcare services and with the previous care concept of outpatient care in hospitals (ABK). RESULTS: After its introduction for 3.5 years, the ASV in rheumatology for adult care has developed into a significant healthcare model for rheumatologists in private practices and hospitals. There were 57 teams consisting of 458 rheumatologists in ASV rheumatism for adults, which represent 44% of all rheumatologists involved in adult care. For children and adolescents, there were 7 teams with 19 pediatric rheumatologists, i.e. 8% of pediatric rheumatologists in health care. The number of patients treated was still significantly lower than the potential, but showed a strong increase. Almost 64,000 adults and 811 children and adolescents were treated in the ASV in the second quarter of 2021. OUTLOOK: Whether the facilitation of outpatient care and the introduction of hybrid diagnosis-related groups planned in the coalition agreement will spur the ASV development remains to be seen.

[Care atlas rheumatology : Approaches and concepts for improving care in outpatient rheumatology]. / Versorgungsatlas Rheumatologie : Ansätze und Konzepte zur Verbesserung der Versorgung in der ambulanten Rheumatologie.

Inflammatory rheumatic diseases affect 1.5 million adults and an estimated 20,000 children and adolescents throughout Germany. The successful treatment of these patients is largely based on the availability of high-quality medical care. To be able to provide sufficient care and prevent long waiting times even though the number of rheumatologists is below demand, efficient practice structures and approaches that go beyond standard care play an important role. The present study takes a look at the current state of rheumatological outpatient care as well as innovative care initiatives to support the service provision structures and to improve the care situation in rheumatology and points out: to ensure guideline-based care despite scarce resources, selective contracts, integrated outpatient specialist care (ASV), early or emergency consultation hours, disease management programs (DMP) and appropriate delegation of medical services play an important role. New care concepts increasingly focus on interdisciplinary cooperation (DMP and ASV), strengthened self-management through structured patient training (DMP) and targeted patient management through screening tools. To ensure an up to date and high-quality treatment in the long term, an increase in further training in rheumatology is necessary. This should be achieved by attracting more students and, if necessary, adjusting the training system.

Regeneration of corneal endothelial cells following keratoplasty in rats with bullous keratopathy.

PURPOSE: Little is known about the behavior of the endothelial cell (EC) layer following keratoplasty. In vitro experiments suggested that the peripheral endothelium might have a higher regenerative capacity than the central endothelium, and some authors hypothesized that endothelial progenitor cells are present in the limbal area. Thus, we analyzed the corneal endothelial regenerative capacity in vivo in a rat model of bullous keratopathy using either bullous central grafts or bullous peripheral recipient corneas to analyze differences in EC regeneration depending on central versus peripheral cell origin. METHODS: Bullous keratopathy was induced in Lewis rats with an intracameral injection of benzalkonium chloride (0.05%; BAK). Three days later, the central area of the bullous cornea was excised and used as a bullous graft, transplanted to a healthy, green fluorescent protein (GFP)-transgeneic Lewis receipient rat (group 'bullous graft'). In return, the mentioned rat eye with the bullous keratopathy received a healthy GFP-transgeneic corneal transplant (group 'bullous host'). A subgroup of these animals received a healthy, excentrically trephined including parts of the limbus (group 'bullous host, limbo-keratoplasty'). The grafts were monitored clinically for 7 weeks. Subsequently, the mean EC density was calculated on corneal whole mounts with Alizarin Red S staining. GFP was analyzed with confocal microscopy to determine EC origin. Untreated fellow eyes served as controls. RESULTS: BAK injection led to a significant decrease in the mean EC density with subsequent bullous keratopathy. In the control eyes, the mean EC density was 3,744 cells/mm² in the center and 2,811 cells/mm² in the periphery. In eyes with bullous keratopathy, only 233 cells/mm² in the center and 622 cells/mm² in the periphery were observed three days after BAK-injection. Bullous transplants in the group 'bullous graft' cleared, and GFP-positive cells were detected on the transplant. In contrast, no GFP-positive ECs were detected on the host cornea in the groups 'bullous host'. CONCLUSIONS: ECs from the peripheral cornea have the ability to cross the graft border and compensate for the pathologically altered/absent endothelium on the graft. In contrast, ECs derived from the central cornea remain central on the graft and do not replace or regenerate peripheral ECs in our model of bullous keratopathy.

Progesterone and estrogen receptors in conjunctival melanoma and nevi.

BACKGROUND: Since it has been observed that melanocytic lesions can alter their appearance during pregnancy, we analyzed whether hormone receptors are expressed in conjunctival nevi as well as conjunctival melanoma. We further analyzed whether the number of estrogen (ER) or progesterone receptors (PR) might be associated with the disease course in conjunctival melanoma. METHODS: Twenty-seven paraffin-embedded samples of conjunctival nevi and 27 conjunctival melanoma specimens were examined using immunohistological analysis with antibodies against PR and ER. The percentage of stained cells were analyzed, taking into account patient gender and age. Out of the melanoma group, all patients with complete data for tumor thickness, tumor localization, age at diagnosis, gender, and follow-up including recurrence, metastasis and tumor-related death were included in the second part of the study (n = 15), where hormone receptor rates were associated with tumor outcome, regarding recurrences, metastasis or death. Written consent was received from all included patients. RESULTS: Both nevi and melanomas showed high rates of PR- and ER-positive cells. In Nevi, 64 ± 25 % of cells stained positive for PR and 35 ± 34 % for ER. In melanoma specimens, 68 ± 30 % showed PR and 44 ± 34 % ER expression. Differences between men and women in expression rates were not statistically significant. Out of 15 melanoma patients (nine female, six male), 53 % (five women and three men) experienced 1-4 recurrences, and four patients developed metastases. The median estimated survival time was 12.2 years. A multivariate survival model taking into account known risk factors for prognosis in conjunctival melanoma confirmed tumor location to be an important predictive factor for outcome (p = 0.05). The rate of PR or ER did not show a statistically significant correlation with the disease course in our cohort. CONCLUSIONS: We observed that conjunctival melanocytic lesions express hormone receptors, which could explain why these tumors can alter their appearance under hormonal changes. Regarding the prognosis of conjunctival melanoma, no statistically significant correlation between hormone receptor expression and event-free survival was found in this analysis.

Host-derived endothelial regeneration of corneal transplants in a rat keratoplasty model.

BACKGROUND: It has been observed that formerly rejected opaque corneal transplants can regain clarity in the rat. We hypothesized that graft endothelium is regenerated by the host. Therefore, we used green fluorescent protein (GFP) transgenic rats to assess the origin of cells following keratoplasty. METHODS: Allogeneic corneal transplantations were carried out between Fischer strain rats as graft donors and GFP-transgenic Lewis rats as recipients. In a second group, syngeneic transplantations were performed between GFP-negative Lewis donors and GFP-positive Lewis recipients, where endothelial-cell-free grafts after mechanical endothelial debridement were used. All grafts were followed up clinically for signs of opacity and rejection. After 6 weeks, corneal flatmounts counterstained with DAPI were analyzed by confocal microscopy. RESULTS: Syngeneic transplantation of endothelial-cell-free grafts led to medium opacity levels without rejection and to subsequent clearing. All grafts showed a population of GFP-positive, host-derived endothelial cells on the graft after 6 weeks. In the allogeneic transplantation group, all grafts but one were rejected after a median of 17 days. While the graft that was not rejected maintained the GFP-negative transplant endothelium, all formerly rejected grafts showed GFP-positive endothelium on the transplant after 6 weeks, accompanied by clinical clearing of the graft. CONCLUSION: GPF positivity shows that in both a syngeneic and an allogeneic setting, the host-derived corneal endothelium can compensate for the endothelial cell loss of the graft. Following rejection, the grafts are repopulated by host-derived endothelial cells in the rat. This finding demonstrates a high regenerative capacity of the peripheral corneal endothelium in the rat, which should be considered whenever interpreting rat keratoplasty results.

Inhibition of corneal inflammation following keratoplasty by birch leaf extract.

The objective of this study was to determine the effect of birch leaf (Betula pendula) extract (BPE) on corneal inflammation following keratoplasty in the rat model. T cells were stimulated in vitro in the presence of BPE. Proliferation, activation phenotype and the number of apoptotic/necrotic cells in cell culture were analyzed by flow cytometry. Corneal transplantation was performed between Fisher and Lewis rats. Recipient rats were either treated with cyclosporine A at a low dosage (Low-dose CsA=LDCsA) or received LDCsA in combination with BPE (2×1ml/day). Clinical signs for corneal inflammation and rejection time points were determined. Infiltrating leukocytes were analyzed histologically. BPE specifically inhibited T cell proliferation in vitro by inducing apoptosis. The phenotype was not affected. In vivo, BPE significantly delayed the onset of corneal opacification (p<0.05). The amount of infiltrating CD45(+) leukocytes and CD4(+) T cells (p<0.001) was significantly reduced by BPE, whereas infiltration of CD163(+) macrophages was not significantly different between the two groups. BPE selectively induces apoptosis of activated T cells. Accordingly, BPE treatment significantly reduces infiltrating T cells and subsequent corneal opacification following keratoplasty. Our findings suggest BPE as a promising anti-inflammatory drug to treat corneal inflammation.

[Outpatient medical specialist care (ASV): A multiperspective study on status quo, challenges and perspectives]. / Ambulante Spezialfachärztliche Versorgung (ASV): eine multiperspektivische Studie zu Status quo, Herausforderungen und Perspektiven.

BACKGROUND: In 2012, the so-called ambulatory medical specialist care (ASV) was implemented in accordance with para. 116b of Book V of the German Social Code (SGB V), enabling physicians in outpatient practices and hospitals to treat patients with rare diseases or complex courses of disease in a uniform framework. The implementation, however, is slow. The Joint Federal Committee (G-BA) has therefore commissioned an evaluation of the ASV with the aim to examine the reasons for this and to provide recommendations for further development. METHODS: The health services research study "GOAL-ASV" (Innovation Fund, 01VSF19002) included a multi-perspective design with primary data collection as well as secondary data analyses. Data from the ASV service center and the central association of statutory health insurances and the notification forms of the extended state committees were analyzed. Data from the Robert Koch-Institute, the Federal Joint Committee, the National Association of Statutory Health Insurance Funds and a literature database analysis were used in order to estimate the proportion of insured persons qualifying for ASV. Care was examined by analyzing pseudonymized routine data from the statutory health insurances using selected indicators. Participating and not participating physicians were asked to complete an online survey. RESULTS: Since the start of ASV, 615,531 insured persons have been treated in this form of care. At the time of analysis, 509 teams were operating, with 26,540 physicians treating 102,898 patients by the end of March 2021 in all indications. This comprises less than 9.8 %. of all approx. 1.05 million eligible patients. Especially in the case of rare diseases, a low willingness of participation can be seen. In addition, there was a relevant proportion of multiple uses of physicians within and outside ASV at 31 percent as well as indications of passive participation of doctors. We found significant regional differences in type and scope of the notification procedure as well as the implementation of teams with 13.4 teams per 1 million inhabitants in Schleswig-Holstein and no team in Mecklenburg-Vorpommern. Patient benefits (84 %), interdisciplinary (82 %) and cross-sectoral cooperation (75 %) were cited as motivations for participation. The main barriers reported by the respondents were the complex and laborious notification procedure (60 %), the administrative and documentation effort during participation (50 %), insufficient billing figures (49 %), and a small proportion of patients (32 %) with a consecutively unfavorable assessment of the cost to income ratio due to the current reimbursement system. DISCUSSION: Nearly ten years after its introduction, the ASV has not become established nationwide. The reasons for this probably are the complex notification procedure and the reimburesement system for rare diseases. In the case of rare diseases, the risk of underuse is becoming apparent. CONCLUSION: Strategies to further develop the ASV should, in particular, simplify the notification procedure and reduce the obstacles during participation. The remuneration system should take more account of the specific care required.

Pilot study of a new posterior chamber phakic intraocular lens (epi.lens) for high myopia.

PURPOSE: To report the first safety and efficacy results of a new posterior chamber phakic intraocular lens (PIOL) (Epi.Lens, Acri.Tec/Carl Zeiss Meditec) implanted in the ciliary sulcus to correct high myopia. METHODS: The Epi.Lens was implanted for the first time in 48 consecutive eyes of 25 patients in an ongoing two-center clinical study. Pre- and postoperative manifest refraction, uncorrected (UDVA) and corrected distance visual acuity (CDVA), intraocular pressure, slit-lamp and funduscopic examination, and ultrasound biomicroscopy were evaluated. Follow-up examinations were performed at 1, 3, 6, 12, and 24 months postoperatively. For each patient, the latest follow-up data were considered. RESULTS: The study cohort consisted of highly myopic patients with mean preoperative manifest refraction spherical equivalent of -9.90 ± 2.53 D, which was reduced to -0.26 ± 0.84 D postoperatively. Two (4.2%) eyes lost one line of CDVA postoperatively, whereas 19 (40%) met and 27 (56%) eyes exceeded preoperative CDVA values, thus improving mean CDVA from 0.83 ± 0.30 to 1.03 ± 0.26. Mean postoperative UDVA (0.85 ± 0.37) was similar to preoperative CDVA (0.83 ± 0.30). When considering all eyes with good visual potential (preoperative CDVA ≥ 1.00 [20/20] [n=25]), 20 (80%) achieved postoperative UDVA ≥ 1.00 (20/20), and 24 (96%) achieved UDVA ≥ 0.80 (20/25). One lens with a small diameter showed contact of the Epi.Lens and crystalline lens with subsequent slight anterior subcapsular cataract; however, CDVA was 1.00 (20/20) at last follow-up 2 years postoperatively. CONCLUSIONS: The results of this Epi.Lens pilot study demonstrate good safety and efficacy. The preliminary data are encouraging, and longer follow-up results are anticipated.

NK cell depletion delays corneal allograft rejection in baby rats.

PURPOSE: Penetrating keratoplasty has a very poor outcome compared with adults if performed in the first years of life. Rejection in these young patients occurs even in the absence of known immunological risk factors. Recently, a baby rat model was introduced and an essential contribution of natural killer (NK) cells during allograft rejection was suggested. To analyze this, NK cells were depleted in baby rats before keratoplasty. METHODS: Allogeneic keratoplasty was performed between Lewis and Fisher rats. The recipient's ages were 10 and 3 weeks, respectively. NK cells were depleted by an intraperitoneal injection of a monoclonal antibody. All experiments were controlled by the injection of isotypic control antibodies and syngeneically. Survival rates were calculated and cellular infiltrates were analyzed histologically. RESULTS: NK cell depletion did delay median graft survival times in a statistically significantly way compared with the control animals (p<0.01). At median rejection time points, macrophages, CD4(+) T cells and CD25(+) leukocytes infiltrated to a greater extent in the depleted recipients. No significant changes in the cell numbers of infiltrating CD8(+) T cells were observed. CONCLUSIONS: We conclude that NK cells play a role during allograft rejection in baby rats, but their effect is replaceable. A greater infiltration of macrophages and CD4(+) T cells suggests that they might compensate for the missing NK cells' response in this experimental setting. Our results represent another step toward understanding the complex mechanisms of an accelerated corneal graft rejection in infant recipients.

Evaluation of ciliary sulcus diameter using ultrasound biomicroscopy in emmetropic eyes and myopic eyes.

PURPOSE: To measure the ciliary sulcus-to-sulcus (STS) diameter in 4 axes in emmetropic and myopic eyes using ultrasound biomicroscopy (UBM) and compare the measurements with automated horizontal white-to-white (WTW) diameter measurements. SETTING: University Eye Hospital Freiburg, Freiburg im Breisgau, Germany. DESIGN: Evaluation of diagnostic technology. METHODS: The STS diameter was measured at 0, 45, 90, and 135 degrees using 35 MHz UBM. The 0-degree WTW diameters were obtained using scanning-slit topography (Orbscan) and partial coherence interferometry (PCI) biometry (IOLMaster). The 0-degree STS and 90-degree STS were compared using the paired t test; the Pearson correlation was used to assess whether the 0-degree STS diameter could be predicted from the 0-degree WTW diameter. RESULTS: The mean SE refraction was -0.48 diopter (D) ± 0.35 (SD) in emmetropic eyes and -9.55 ± 3.70 D in myopic eyes. In 35 of 37 eyes, 90-degree STS was greater than 0-degree STS. The mean 90-degree STS was 12.51 ± 0.43 mm. The mean 0-degree STS was 12.19 ± 0.47 mm (P<.01). The mean 0-degree WTW diameters were 11.73 ± 0.37 mm (scanning-slit topography) and 12.20 ± 0.42 mm (PCI biometry). The correlations were good between 0-degree STS and 0-degree WTW with PCI biometry (r(2) = 0.82) and scanning-slit topography (r(2) = 0.86) in emmetropic eyes but weak between 0-degree STS and 0-degree WTW in myopic eyes (r(2) = 0.36 and r(2) = 0.40, respectively). CONCLUSIONS: Sulcus diameter measurements were most precise using UBM. The ciliary sulcus is vertically oval. The WTW diameter is not suitable for calculating a PC pIOL diameter, particularly in myopic eyes.