Keratin films for ocular surface reconstruction: Wound healing in an in-vivo model.

The most commonly used tissue substitute for ocular surface reconstruction is human amniotic membrane (AM). Because of its low biomechanical strength and intransparency there is a need to search for alternatives of consistent quality. This study, further explored the biocompatibility of Keratin Film (KF) and its ability to sustain corneal epithelial wound healing. In three equal groups of 5 New Zeeland white rabbits a 4 mm superficial keratectomy was created in the right eye. Five eyes received a KF, five a human AM graft and the remaining five no implant. All eyes were treated with ofloxacin and dexamethasone eye drops and followed up for 10 days. Corneal fluorescein staining, vascularization, and transparency were assessed using slit lamp biomicroscopy according to a standardized grading score during and at the end of follow-up. The corneal-scleral-button was excised and processed for histology. After 10 days all eyes which had received a KF showed complete epithelial healing and no signs of neovascularization. In the AM group 1 eye showed a persistent epithelial defect at day 10 and 2 eyes showed neovascularization at day 7 resolving at day 10. Transparency improved progressively both in the KF group as well as in the AM group towards the end of the follow. Histology showed a multilayer epithelium firmly adherent to the KF with no evidence of keratocyte migration or inflammatory reaction in the corneal stroma. In this study on rabbit eyes KF better supported corneal epithelial wound healing than amniotic membrane.

Rare periorbital, pseudocystic metastasis of squamous cell carcinoma of the bladder: Case report and review of the literature.

We present the case of a man in his fifties with a history of bladder carcinoma who presented with a large periorbital cystic lesion that was found to be a metastasis. Bladder carcinomas are a very rare cause of peri-/orbital metastasis. The primary tumor in this case predominately showed squamous cell differentiation and small areas of adenoid differentiation. To our knowledge only one previous case of orbital metastasis from squamous cell carcinoma of the bladder has been reported. Cyst formation in bladder cancer metastasis has not been reported and is very rare for orbital metastases in general. The pathogenesis of metastatic cyst development is not fully understood and may vary from case to case. A biopsy of an atypical cyst is indicated.

DMEK after penetrating keratoplasty: cohort with DMEK grafts and descemetorhexis larger than full-thickness graft.

PURPOSE: The study aims to evaluate visual outcome, central corneal thickness, and rebubbling rate in a cohort with oversized DMEK grafts after failed penetrating keratoplasty (PK). The unique feature of the study is a descemetorhexis diameter larger than the full-thickness graft, i.e., peripheral to the PK interface. METHODS: A monocentric, retrospective evaluation of all patients with endothelial graft failure after PK treated with an oversized DMEK graft and descemetorhexis outside of the PK interface (i.e., in host tissue) between January 2015 and July 2019 at the Department of Ophthalmology at the University of Düsseldorf (Germany) was performed. RESULTS: Eleven eyes of 10 patients were identified. Mean age was 69 years. On average (arithmetic mean ± standard deviation), 1.7 ± 1.0 previous PKs have been performed per eye in this cohort. The mean time between last PK and DMEK was 10.1 ± 7.3 years (range 2 to 23 years). In all cases, the graft diameter exceeded the diameter of the previous PK and descemetorhexis was performed in host tissue, that is, peripheral to the graft-host interface. Rebubbling was performed in 18.2% of the patients (n = 2 eyes) because of central graft detachment. Mean central corneal thickness showed a statistically significant improvement at 5.3 ± 3.5 months after surgery from 688.23 ± 151.01 to 527.75 ± 88 µm (p = 0.002). Visual acuity increased significantly by 5 lines from 1.24 ± 0.5 logMAR (range from 0.5 to 2) to 0.73 ± 0.76 logMAR (range from 0.1 to 2) within 3 months (p = 0.006). Excluding patients without visual potential and transplant failure, visual acuity improved significantly by 8 lines (p < 0.001), and stayed stable until the last follow-up at 15.1 ± 11.4 months (range 6 to 39 months, p < 0.001, n = 8) after surgery. CONCLUSION: DMEK can be successfully used to treat endothelial cell failure after PK, and can provide good postoperative results with regards to visual acuity. This study shows that stripping of Descemet's membrane (DM) peripheral to the PK interface is surgically feasible. Overlapping, larger DMEK grafts with more endothelial cells can be used without increasing rebubbling rates and may potentially improve long-term graft survival.

Does smoking have an impact on the immunological response to COVID-19 vaccines? Evidence from the VASCO study and need for further studies.

OBJECTIVES: The aim of this study was to investigate the possible impact of smoking on the humoral response to the BNT162b2 mRNA COVID-19 vaccine (also known as the BioNTech-Pfizer COVID-19 vaccine). STUDY DESIGN: A longitudinal sero-epidemiological study was conducted in sample of Italian healthcare workers (HCWs). METHODS: HCWs who were administered two doses of the BNT162b2 mRNA vaccine, 21 days apart, between December 2020 and January 2021, were invited to undergo multiple serology tests to identify SARS-CoV-2 S-RBD-specific immunoglobulin G (IgG) antibodies. Participants also responded to questions about their smoking status (i.e. current smokers vs non-smokers) in a survey. RESULTS: Sixty days after the completion of the vaccination cycle, serological analyses showed a difference in vaccine-induced IgG titre between current smokers and non-smokers, with median antibody titres of 211.80 AU/mL (interquartile range [IQR] 149.80-465.50) and 487.50 AU/mL (IQR 308.45-791.65) [P-value = 0.002], respectively. This significant difference in vaccine-induced IgG titres between current smokers and non-smokers remained after adjusting for age, sex, and previous infection with SARS-CoV-2. CONCLUSIONS: This study observed that vaccine-induced antibody titres decrease faster among current smokers than non-smokers. Further research to investigate the impact of smoking on the immunological response to COVID-19 and non-COVID-19 vaccines is required.

Conventional brain magnetic resonance imaging in the longitudinal evaluation of newly diagnosed systemic lupus erythematosus patients: a retrospective analysis from a single-centre cohort.

INTRODUCTION: Neuropsychiatric (NP) manifestations occur mostly in the early phases of the systemic lupus erythematosus (SLE) course. Nonspecific alterations are evident in conventional brain magnetic resonance imaging (MRI), regardless of clinically overt NP symptoms. The main aims of this study were to assess the prevalence of MRI abnormalities in newly diagnosed SLE, and to evaluate the impact of MRI changes during follow-up (FU) and the clinical course of NP symptoms. MATERIALS AND METHODS: Newly diagnosed SLE patients with a baseline brain MRI and with available repeated MRI during FU were retrospectively evaluated. White-matter lesions and atrophy were recorded, comparing NPSLE and non-NPSLE patients. Cox proportional hazard models were used to compare NP events during FU with MRI data. RESULTS: Forty-four patients were included, 22 with NP events attributed to SLE. The baseline MRI scan was abnormal in 21 patients (47.73%). New NP events occurred in 17 patients, and worsening was found in repeated MRIs in 12 (27.27%). A worsening of MRI was associated with higher occurrence of new NP events during FU (adjusted hazard ratio 3.946 (1.175-13.253)). CONCLUSION: Baseline MRI is useful in patients with an early diagnosis of SLE, allowing comparison with subsequent scans. In our study, radiological worsening of repeated brain MRI was associated with new NP events.

Intestinal anti-transglutaminase 2 immunoglobulin A deposits in children at risk for coeliac disease (CD): data from the PreventCD study.

In coeliac disease (CD), anti-tissue transglutaminase 2 immunoglobulin (Ig)A antibodies (anti-TG2) are produced and deposited in the intestine. PreventCD (www.preventcd.com) is a European multi-centre study, which investigates the influence of infant nutrition and that of genetic, immunological and other environmental factors on the risk of developing CD. The aim of the current study was to evaluate the appearance of intestinal anti-TG2 deposits in very early intestinal biopsies from at-risk infants and their predictive value for villous atrophy. Sixty-five small bowel biopsies, performed in 62 children, were investigated for the presence of intestinal anti-TG2 extracellular IgA deposits by using double immunofluorescence. The biopsies were performed in the presence of elevated serum levels of CD-associated antibodies and/or symptoms suggesting disease. Deposits of anti-TG2 IgA were present in 53 of 53 CD patients and three of three potential CD patients. In potential CD patients, mucosal deposits showed a patchy distribution characterized by some areas completely negative, whereas active CD patients had uniformly present and evident mucosal deposits. Only one of six patients without CD (negative for serum anti-TG2 and with normal mucosa) had intestinal deposits with a patchy distribution and a weak staining. Two of the 53 CD patients received a definitive diagnosis of CD after a second or third biopsy; mucosal deposits of anti-TG2 IgA were evaluated in all samples. Before developing villous atrophy, both patients had anti-TG2 deposits in normal mucosal architecture, antibodies in one patient being absent in serum. We demonstrated that in CD the intestinal deposits of anti-TG2 are a constant presence and appear very early in the natural history of disease.

[Peri-ocular Necrotising Fasciitis - Case Report and Overview]. / Periokuläre nekrotisierende Fasziitis ­ Fallbericht und Überblick.

Peri-ocular necrotising fasciitis is a very rare ophthalmological clinical picture and is potentially fatal. This disease is caused by bacterial infection of the fasciae, which rapidly spreads. The present article reports a typical case of the disease and gives an overview of the typical clinical signs and symptoms of peri-ocular necrotising fasciitis.

The diagnosis and clinical management of the neuropsychiatric manifestations of lupus.

Neuropsychiatric (NP) involvement in Systemic Lupus Erythematosus (SLE), can be a severe and troubling manifestation of the disease that heavily impacts patient's health, quality of life and disease outcome. It is one of the most complex expressions of SLE which can affect central, peripheral and autonomous nervous system. Complex interrelated pathogenetic mechanisms, including genetic factors, vasculopathy, vascular occlusion, neuroendocrine-immune imbalance, tissue and neuronal damage mediated by autoantibodies, inflammatory mediators, blood brain barrier dysfunction and direct neuronal cell death can be all involved. About NPSLE a number of issues are still matter of debate: from classification and burden of NPSLE to attribution and diagnosis. The role of neuroimaging and new methods of investigation still remain pivotal and rapidly evolving as well as is the increasing knowledge in the pathogenesis. Overall, two main pathogenetic pathways have been recognized yielding different clinical phenotypes: a predominant ischemic-vascular one involving large and small blood vessels, mediated by aPL, immune complexes and leuko-agglutination which it is manifested with more frequent focal NP clinical pictures and a predominantly inflammatory-neurotoxic one mediated by complement activation, increased permeability of the BBB, intrathecal migration of autoantibodies, local production of immune complexes and pro-inflammatory cytokines and other inflammatory mediators usually appearing as diffuse NP manifestations. In the attempt to depict a journey throughout NPSLE from diagnosis to a reasoned therapeutic approach, classification, epidemiology, attribution, risk factors, diagnostic challenges, neuroimaging techniques and pathogenesis will be considered in this narrative review based on the most relevant and recent published data.

Two-year follow-up after microsurgical discectomy and dynamic percutaneous stabilization in degenerate and herniated lumbar disc: clinical and neuroradiological outcome.

AIM: Lumbar disc herniation associated with back pain is often related to disc degeneration. Back pain after microdiscectomy often persists, prejudicing clinical outcome and quality of life. To this day, the evolution of disc degeneration after classical microdiscectomy has never been proven. Percutaneous dynamic stabilization after microdiscectomy has been proposed as a novel surgical strategy for treatment of back pain with herniated disc. However, clinical results are still debated and no evidences about the long-term evolution of back pain and relationships between neuroradiological imaging and clinical outcome have been provided. We report our preliminary observations concerning the clinical and neuroradiological outcome of 11 patients treated with microdiscectomy and dynamic percutaneous lumbo-sacral stabilization, after a long-term follow-up (2-years). METHODS: This was an uncontrolled case series. The study included 11 patients (3 F, 8 M) with L5-S1 discal herniation and degeneration underwent microdiscectomy and percutaneous dynamic stabilization, from December 2008 to November 2009. All the patients were symptomatic with back and leg pain non-responsive to long-term (8-12 months) medical and physical treatments. VAS and Satisfaction Index were used, respectively, for evaluation of clinical outcome and general postoperative patients' satisfaction. Modic and Pfirrmann scores were used for evaluation of neuroradiological outcome. All the patients underwent to microdiscectomy and implantation of the same percutaneous device for dynamic stabilization of the middle vertebral column during the same surgery. Modic, Pfirrmann, VAS and Satisfaction Index scores were collected before surgery and over the follow-up (45 days, 1 and 2 years). MRI and dynamic X-Ray 2 years after surgery were compared to the preoperative imaging. RESULTS: Motion preservation at the functional spinal unit after surgery was demonstrated in all the cases. All patients reported a reduction or complete resolution of back and leg pain, they were satisfied and came back to normal socio-professional life. No modification of the preoperative Pfirrmann was observed, even in those patients who experienced restoration of back pain. No surgical complications nor device failures were reported. CONCLUSION: Percutaneous minimally invasive lumbo-sacral dynamic stabilization after microdiscectomy seems a reliable and effective technique in order to obtain a resolution of back pain and seems to prevent the Pfirrmann worsening, over a long-term follow-up.

[Factors influencing the measurement of tear film lipid layer thickness with interferometry]. / Einflussfaktoren auf die Messung der Lipidschichtdicke des Tränenfilms mittels Interferometrie.

INTRODUCTION: The quantitative measurement of the tear film lipid layer thickness is a relatively new and promising method. However, so far it has not been investigated whether there is a diurnal or a day to day variability and whether certain factors are confounding the measurement of the lipid layer thickness. MATERIALS AND METHODS: In three different experimental settings, 10 subjects without known sicca syndrome were examined at three different time points on one day, on three different days and before and after therapeutic expression of the Meibomian glands. As a comparison, the parameters tear film break-up time, tear meniscus height, diagnostic expression of the Meibomian glands and subjective symptoms, determined using the OSDI (ocular surface disease index) questionnaire, were measured. RESULTS: The results of the study showed a smaller variation of the lipid layer thickness measurements during the day and from day to day compared to the tear film break-up time. The expression of the Meibomian glands significantly increased the lipid layer thickness. There was a correlation between the baseline values of tear film break-up time and the lipid layer thickness. DISCUSSION: Our data showed that the lipid layer thickness as measured with the Lipiview® interferometer appears to be a relatively constant parameter over time. In addition, the expression of the Meibomian glands could be identified as a potential confounding factor. In this study we included only healthy subjects without known sicca syndrome. For the future our findings need to be validated in dry eye patients.

[Psychopathologic risk assessment and self-esteem in patients undergoing hypospadias surgery]. / Valutazione del rischio psicopatologico e dell'autostima in pazienti operati per ipospadia.

AIMS: Although the long-term outcomes ofhypospadias surgery are considered important for psychosexual development, only a few attempts have been made to evaluate patient psico-pathology. MATERIAL AND METHODS: 20 out 40 patients who received under sealed cover two envelopes--the first containing the assessment tools, the other empty and prepaid for the answer--joined the study. The results came from the analysis of anamnestic interview specially created in order to gather information on how to access to surgery and the degree of information that the parents had from the surgeon, from the analysis of the CBCL (Child Behavior CheckList 2001:4-16 years) and TMA (Multidimensional self-esteem Test: the Italian version of the MSCS Multidimensional Self-Concept Scale). Of the 20 patients recruited, 15, aged from 9 to 18 years (mean age 12.5), age at operation between 2 and 5 years (mean age 3.3 yrs), have returned the questionnaires correctly compiled. Patient data were compared with those of a control group not suffering from genital pathology. RESULTS: From the CBCL: the area of the identification of the problems showed no significant differences between the study group and the control. The area of competence, altered in both groups, did not show statistically significant differences. From the analysis of TMA: there were no statistically significant differences between the two groups in sub-domains: Social, Competence, Affect, Family and Physical. Within the subdomain school the two groups differed significantly for low self-esteem in the group of surgical patients. CONCLUSION: The MST test indicate that hypospadias surgery does not change the global self-esteem but, surprisingly, at least in this patient population, only a lower self-esteem in school performance in the age group considered. This study may indicate the importance of psychological support during the transition from adolescence to adulthood.

[Advantages of the anterior and mid-shaft hypospadias repair in the first year of life]. / Vantaggi del trattamento dell'ipospadia anteriore e medio peniena nel primo anno di vita.

PURPOSE: Only a few studies have been performed on the evaluation of complications strictly related to the age at operation of hypospadias repair. The aim of our study was to evaluate the incidence of complications of surgical treatment of anterior and midshaft hypospadias in relation to the age at operation. MATERIALS AND METHODS: 108 patients from 2005 to 2011 were operated on by the same surgeon (AM) for anterior and mid-shaft hypospadias. The patients were divided into two groups according to their age: group A consisted of 48 patients who had undergone surgery before 12 months, group B consisted of 60 patients in whom surgery was performed after 12 months of age (2months -12 yrs). All patients were corrected with TIPU (Snodgrass technique). For the two groups was evaluated the rate ofperioperative complications (hematoma, edema, hemorrhage), suture dehiscence, fistula, stenosis. For the statistical analysis of complications was used the exact test of chi-square Fischer. RESULTS: At a mean follow-up of 36 months. Group A: 2/48 patients presented fistula after 2-6 weeks. Group B: 15/60 patients presented the following complications: 2 hematomas, 1 postoperative bleeding; 5 fistulas arising after 2-6 weeks, 3 minimal meatal regression; 4 thinning flow. The Fisher test was significant. CONCLUSIONS: The results of our study confirm that patients with hypospadias, operated within the first years of life, have a statistically lower rate of complications than patients treated at later dates. Therefore, the age is believed to be a pivotal prognostic factor for the functional and aesthetic results.

Regorafenib monotherapy as second-line treatment of patients with RAS-mutant advanced colorectal cancer (STREAM): an academic, multicenter, single-arm, two-stage, phase II study.

BACKGROUND: Maintaining angiogenesis inhibition and switching the chemotherapy backbone represent the current second-line therapy in patients with RAS-mutant metastatic colorectal cancer (mCRC). Regorafenib, an oral multikinase inhibitor, prolonged overall survival (OS) in the chemorefractory setting. MATERIALS AND METHODS: STREAM was an academic, multicenter, single-arm phase II trial, evaluating the activity of regorafenib in RAS-mutant mCRC, in terms of the rate of patients who were progression-free after 6 months from study entry (6mo-PF). Patients were pretreated with fluoropyrimidine, oxaliplatin, and bevacizumab. According to Simon's two-stage design, ≥18 patients 6mo-PF were needed in the overall population (N = 46). Secondary endpoints were safety, objective response rate (ORR), progression-free survival (PFS), and OS. Early metabolic response by [18F]2-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography ([18F]-FDG PET/CT) scan was an exploratory endpoint. EudraCT Number: 2015-001105-13. RESULTS: The number of patients 6mo-PF was 8/22 at the first stage and 14/46 in the overall population. The ORR was 10.9%, disease control rate was 54.6%, median (m)PFS was 3.6 months [95% confidence interval (CI) 1.9-6.7 months], mOS was 18.9 months (95% CI 10.3-35.3 months), and mPFS2 (from study entry to subsequent-line progression) was 13.3 months (95% CI 8.4-19.7 months). Long benefiter patients (>6mo-PF) significantly more often had a single metastatic site and lung-limited disease. No unexpected toxicity was reported. Grade ≥3 events occurred in 39.1% of patients, with hand-foot syndrome (13%), fatigue, and hyperbilirubinemia (6.5%) occurring mostly. Baseline metabolic assessment was associated with OS in the multivariate analysis, while early metabolic response was not associated with clinical outcomes. CONCLUSIONS: The study did not meet its primary endpoint. However, regorafenib was well tolerated and did not preclude subsequent treatments. Patients with good prognostic features (single metastatic site and lung-limited disease) reported clinical benefit with regorafenib. The exploratory metabolic analysis suggests that baseline [18F]-FDG PET/CT might be useful to select patients with a favorable outcome. A chemotherapy-free interval with regorafenib was associated with durable disease control in a selected group of patients with favorable clinical characteristics.

[Laparoscopic treatment of UPJ obstruction in ectopic pelvic kidneys in children]. / Trattamento laparoscopico dell'Ostruzione del Giunto Pielo-Ureterale nei reni ectopici in età pediatrica.

AIMS: To assess the feasibility and safety of a laparoscopic approach to UPJ obstruction (UPJO) in ectopic pelvic kidneys. MATERIAL AND METHODS: In a retrospective analysis we selected 14 children, aged 6 months to 17 years, 12 males, 2 females, who had been treated in our Department between January 2004 and June 2011. 9 patients presented ureteropelvic junction obstruction (in 3 cases pelvic stones coexisted) with normal/moderately reduced (> or = 25%) relative function at radionuclide scan (MAG3), 3 nonfunctioning kidneys associated or not to hypertension, 2 congenital hypo-dysplastic kidneys. The evaluation of each patient involved the medical history, ultrasound examination, VCUG, MAG3 diuresis renogram and MRI in some cases. Of the patients presenting UPJO, 5 underwent dismembered pyeloplasty with pyelolithotomy, if required, and 4 pelvic derotation with straightening of the uretero-pelvic junction. A previous cystoscopic placement of a Double J stent was utilized. This facilitated the identification and dissection around the pelvis. With the patient in Trendelenburg position we utilized an umbilical trocar and two trocar in the right and left iliac fossae; an additional trocar, when required, was inserted more cephalad on the midclavear line contralaterally to the lesion. The derotation of ureteropelvic junction was obtained by freeing the kidney's lower pole and by placing intraperitoneally the junction protected with a Double J stent. This was obtained by suturing the peritoneum behind the ureteropelvic junction resulting in a forward rotation of the major axis of the kidney and a straightening of the junction. The 5 patients presenting nonfunctioning ectopic kidneys underwent laparoscopic nephrectomy. While the removal of congenital hypoplasic kidneys resulted easy, the removal of nonfunctioning kidneys was more difficult due to their complex vascular situation and for the embryonic disposition. RESULTS: The operating time varied between 40 to 200 minutes. No patient required conversion to open surgery. The hypertension resolved after nephrectomy in all cases. 2 cases of dismembered pyeloplasty required a placement of Double J stent due the recurrence of symptoms and ! patient is waiting for redo operation. The pelvic derotation showed an improvement of diuretic MAG3 renogram and the function remained stable and patiens are symptoms-free. CONCLUSION: The UPJO in ectopic pelvic kidneys presents a large spectrum of presentation. The laparoscopic approach provides good surgical exposure, and operative times are acceptable compared to those of laparoscopic procedure in anatomically normal kidneys. It has also proved a very useful tool in the non-functioning kidney nephrectomy thank to the help of magnification in the identification of numerous aberrant vessels that are quite often found in the pelvic kidneys. The derotation of the pelvis seems a useful procedure in moderate obstruction even if a longer followup is needed.

[Beyond esthetics-Regenerative medicine for severe diseases of the adnexa oculi]. / Jenseits von Ästhetik ­ Regenerative Medizin bei schweren Erkrankungen der okulären Adnexe.

BACKGROUND: Restoration of eyelid and lacrimal functions are important steps on the way to an intact ocular surface. Clinically available substitute tissues or therapeutic options for eyelid reconstruction and lacrimal gland regeneration often reach their limits in patients with severe diseases of the adnexa oculi. Several approaches in regenerative medicine have been intensively researched and clinically tested in recent years. These range from reconstructive approaches with novel tissue matrices in the field of eyelid surgery to stem cell therapies to regenerate lacrimal gland function. MATERIAL AND METHODS: The state of the art in the current literature is presented and an overview of clinically applied or currently researched tissues for eyelid reconstruction is given. Furthermore, approaches in stem cell therapy of the lacrimal gland as well as own results are presented. RESULTS: Acellular dermis has been successfully used for eyelid reconstruction and represents a viable option in cases of limited availability of autologous tissue. In vitro grown cellular constructs or tissues with genetically modified cells have already been successfully applied in dermatology for the treatment of burns or severe genodermatoses. First studies on stem cell therapy for severe dry eye in Sjögren syndrome showed a safe and effective application of mesenchymal stem cells by injection into the lacrimal gland. CONCLUSION: Due to the limitations of currently available replacement tissues, there is a clinical need for the development of new materials for adnexa oculi reconstruction. Constructs grown in vitro with allogeneic and/or genetically engineered cells are slowly making their way into clinical practice. The efficacy and mode of action of stem cells in severe dry eye are subject matters of current clinical trials.

Repeated brain conventional MRI and SPECT evaluation in systemic lupus erythematosus patients with and without neuropsychiatric involvement: a follow up study.

OBJECTIVES: To assess the utility of a combined neuroimaging approach in the follow up of patients affected by systemic lupus erythematosus (SLE) with and without neuropsychiatric (NP) involvement. METHODS: Patients who underwent a first combined brain conventional magnetic resonance imaging (cMRI) and single photon emission computed tomography (SPECT) and later repeated the same examinations between 2001 and 2008 were retrieved from a large database. Clinical and neuroimaging data were analysed and their relationships evaluated at baseline and at follow up. RESULTS: Fifty SLE patients (38 with and 12 without NP involvement, mean age 36.8 yrs and mean disease duration at first instrumental evaluation 5.5 yrs) were enrolled. At baseline, the majority of them had a diffuse pattern of NP involvement. After a mean follow up period of 4 years all patients repeated neuroimaging and clinical evaluation. In 23 patients (22 with and 1 without NP manifestations at baseline) a new NP event occurred. Overall, neuroimaging remained unchanged or improved, but in some cases it worsened. No correlations were found between instrumental findings and clinical picture. CONCLUSIONS: In this study, the clinical features at baseline appeared to be a better predictor of future NP events than morphological and functional neuroimaging. Therefore the utility of repeating a combined instrumental evaluation (cMRI and SPECT) may be debatable especially for patients with diffuse NP involvement where the decision to perform serial combined neuroimaging examinations should be carefully assessed and based mainly on clinical judgement.

[Cooperation between the department of ophthalmology at the University of Düsseldorf (Germany) and the Fundación Visión in Asunción (Paraguay) as an example of the German hospital partnerships programm]. / Das deutsche Klinikpartnerschaftsprogramm am Beispiel der Kooperation der Klinik für Augenheilkunde des Universitätsklinikums Düsseldorf mit der Fundación Visión in Asunción (Paraguay).

BACKGROUND: A hospital partnership between the University Eye Hospital Düsseldorf (UAK Düsseldorf) and Fundación Visión in Asunción has existed since 2014 based on a memorandum of understanding. Fundación Visión plays a leading role in ophthalmological treatment and prevention of blindness in Paraguay. Since 2016 a program for the promotion of international hospital partnerships of the German government has been in place. MATERIAL AND METHODS: Following a written application in 2016 the hospital partnership Düsseldorf-Asunción is funded by the Federal Ministry for Economic Cooperation in Germany. The aim of the project was to establish modern minimally invasive corneal transplantation techniques with faster postoperative rehabilitation and less follow-up in Paraguay with the help of several activities within a defined schedule. Secondary aims were to obtain first data on the prevalence of eye diseases in a typical patient cohort of the Fundación Visión and to establish an infrastructure for modern eye banking techniques in Paraguay. RESULTS: First a Paraguayan surgeon was trained to carry out Descemet membrane endothelial keratoplasty (DMEK) transplantations in Germany. At the same time, the surgical instruments required for the DMEK technique were purchased and delivered to the Fundación Visión. In September 2018 the first lamellar corneal transplantations were successfully performed in Paraguay by the team from the Fundación Visión under the supervision of an experienced surgical team from Düsseldorf. Subsequently, the split cornea approach using a donor cornea for a posterior and an anterior lamellar keratoplasty (DMEK and DALK) was also implemented in Asunción. In November 2019 epidemiological data on eye diseases were collected during a field campaign of the Fundación Visión in a rural region of Paraguay. In the course of data collection an employee of the University Eye Hospital Düsseldorf learned small incision cataract surgery. In March 2019, a technician from the Fundación Visión was trained in Düsseldorf in corneal tissue culture techniques and preparation of amniotic membrane transplants in the Lions eye bank North-Rhine/Westfalia. CONCLUSION: With the aid of a supported hospital partnership modern minimally invasive corneal transplantation techniques can be successfully transferred to the eye hospital of a developing country and in return surgical skills can be taught to surgeons from Germany who are in training. Therefore, an efficient hospital partnership is the basis for a mutual exchange and is not purely one-way traffic.

High density of intraepithelial gammadelta lymphocytes and deposits of immunoglobulin (Ig)M anti-tissue transglutaminase antibodies in the jejunum of coeliac patients with IgA deficiency.

The diagnosis of coeliac disease (CD) represents a special challenge in selective immunoglobulin (Ig)A deficiency (IgAD). A high density of T cell receptor (TCR)gammadelta(+) intraepithelial lymphocytes (IELs) and intestinal IgA anti-tissue transglutaminase 2 (anti-TG2) antibody deposits are suggestive of CD. We analysed the density of TCRgammadelta(+) IELs and the deposition of IgM anti-TG2 antibodies in the jejunal mucosa of IgAD patients with and without CD. Immunohistochemical analyses for the number of CD3+ and TCRgammadelta(+) IELs and double immunofluorescence assay for IgM anti-TG2 antibody deposits were performed in biopsies from 25 children with IgAD (nine untreated CD, seven potential CD and nine without CD). Sixteen immunologically intact children without CD represented the controls. IgAD without CD had a higher number of CD3+ and TCRgammadelta(+) IELs than controls (P < 0.05), but lower than IgAD with CD (P < 0.01). No significant differences were noted between IgAD subjects without CD and those with potential CD. Furthermore, IgAD patients without CD showed a higher TCRgammadelta(+)/CD3+ ratio than the control group (P < 0.05), while the ratio was similar to subjects with CD and potential CD. Intestinal IgM anti-TG2 antibody deposits were present in six of seven of the IgAD patients with untreated CD, one of seven with potential CD and none of those without CD. Most of the patients with IgAD show immune activation in the jejunal mucosa. IgM anti-TG2 antibody deposits are present only in CD. Intestinal IgM anti-TG2 and immunohistochemical markers do not discriminate between IgAD and potential CD with IgAD. Therefore, the serum IgG CD-associated autoantibodies remains very important for the diagnosis of CD in IgAD.

Eye Socket Regeneration and Reconstruction.

Purpose: When an eye has become irreversibly blind or painful it is removed by enucleation or evisceration. The resulting anophthalmic socket usually receives a volume replacing implant and is subsequently fitted with a prosthetic shell for adequate cosmesis. Trauma, tumour or immunological pathomechanisms can induce loss of bone, orbital soft tissue volume, and conjunctival contraction or implant exposure, which result in difficult or impossible prosthesis wear. In this situation as well as in numerous diseases limited to the conjunctiva (e.g. Pterygium, or cicatrizing conjunctivitis) strategies to substitute the lost tissue are required.Methods: A review of the literature search using various electronic databases (PubMed and MEDLINE) was performed on indications, surgical techniques and materials used to restore the ocular socket.Results: Amniotic membrane and oral mucosa are still the most commonly used substitutes for the reconstruction of larger conjunctival defects and ocular socket reconstruction. However, due to limitations of clinical available grafts, synthetic scaffolds, biomaterials or tissue-engineered grafts have been described in preclinical studies but most of them have not been investigated adequately in clinical studies yet. In orbital volume replacement, porous and nonporous spheres are used and both show acceptable results. However, more clinical studies are required that directly compare the outcomes in patients with similar conditions. Dermofat graft remains a good option in case of sockets with significant orbital volume and conjunctival surface loss.Conclusion: Beyond established techniques using autologous or allogeneic tissue, various approaches of engineering tissue based on scaffolds and stem cell expansion techniques are currently under investigation and may become alternatives in socket reconstruction in the not too far future.