Cartilage repair strategies in the knee according to Dutch Orthopedic Surgeons: a survey study.

BACKGROUND: This study surveyed Dutch orthopedic surgeons on the management of cartilage defects in the knee and the adherence to the recently updated Dutch knee cartilage repair consensus statement (DCS). METHODS: A web-based survey was sent to 192 Dutch knee specialists. RESULTS: The response rate was 60%. Microfracture, debridement and osteochondral autografts are performed by the majority, 93%, 70% and 27% of respondents, respectively. Complex techniques are used by < 7%. Microfracture is mainly considered in defects 1-2 cm2 (by > 80%) but also in 2-3 cm2 (by > 40%). Concomitant procedures, e.g., malalignment corrections, are performed by 89%. Twenty-one percent of surgeons treat patients aged 40-60 years. Microfracture, debridement and autologous chondrocyte implantation are not considered to be highly affected by age > 40 years by any of the respondents (0-3%). Moreover, for the middle-aged there is a large spread in treatments considered. In case of loose bodies, the majority (84%) only performs refixation in the presence of attached bone. CONCLUSION: Small cartilage defects in ideal patients may be well treated by general orthopedic surgeons. The matter becomes complicated in older patients, or in case of larger defects or malalignment. The current study reveals some knowledge gaps for these more complex patients. Referral to tertiary centers might be indicated, as is stated by the DCS, and this centralization should enhance knee joint preservation. Since the data from present study are subjective, registration of all separate cartilage repair cases should fuel objective analysis of clinical practice and adherence to the DCS in the future.

Treatment of refractory subacute cuataneous lupus erythematosus with baricitinib.

We report on a patient who presented with refractory subacute cutaneous lupus erythematosus. The scaly annular and polycyclic patches/plaques, and hyperkeratotic lesions on multiple fingers improved rapidly after treatment with baricitinib.

Use of PET-CT in diagnostic workup of periprosthetic infection of hip and knee joints: significance in detecting additional infectious focus.

INTRODUCTION: The diagnosis and management of periprosthetic knee and hip infections as well as the identification and management of possible additional infectious foci is of great importance for successful therapy. This study analyses the importance of 18F deoxyglucose PET-CT (PET-CT) in the identification of additional infectious focus and subsequent impact on management of periprosthetic infection (PPI). MATERIAL AND METHODS: A retrospective analysis of the clinical data and findings in the period from January 2008 to December 2018 was carried out. One hundred and four patients with in-hospital treatment due to PPI of a hip or knee joint were identified and included in this study. All patients underwent a standardized clinical examination and further surgical and antibiotic therapy. The reevaluation of performed PET-CTs was specifically carried out with regard to the local PPI or detection of secondary foci. RESULTS: PET-CT successfully verified the PPI in 84.2% of the patients. A total of 78 possible additional foci were detected in PET-CT in 56 (53.8%) of the examined patients. Predilection sites for possible secondary foci were joints (42.3%), pulmonary (15.4%), ear-nose-throat (15.4%), spine (11.5%), and the musculocutaneous tissues (11.5%). Fifty-four positive PET-CT findings were confirmed clinically with need of additional adequate treatment. CONCLUSION: PET-CT is a valuable diagnostic tool to confirm periprosthetic joint infection. At the same time, the whole-body PET/CT may detect additional foci of infection with impact on subsequent treatment strategy. PET was of special value in detecting infections at distant locations far from the primary infected joint in significant number. These distant infection locations can be potential cause of a re-infection. This clearly reflects the need of their diagnosis.

PATHOLOGIC FINDINGS IN GENDER-AFFIRMING MASTECTOMY: A SYSTEMATIC REVIEW.

Following increased cultural awareness, expanded access to care, and decreased stigmatization, the number of transgender individuals seeking gender affirmation surgery such as gender-affirmation mastectomy (GAM) continues to rise. While post-mastectomy breast tissue is often sent for pathologic evaluation, few studies address the utility and standardization of this practice. This literature review evaluates the pathology findings in GAM specimens reported in the medical literature. A systematic review following PRISMA guidelines was performed to evaluate all medical publications related to pathology reports following GAM. The overall type and incidence of benign and malignant breast lesions were analyzed to elucidate which patient characteristics significantly affect the pathology findings. Overall, eight of 488 identified studies met inclusion criteria (1278 patients). The incidence of pre-malignant lesions was 2.42%, including flat epithelial atypia (0.08%), atypical hyperplasia (0.23%), atypical ductal hyperplasia (1.33%), atypical lobular hyperplasia (0.39%), and lobular carcinoma in situ (0.39%).Patient age, hormonal therapy, and family / patient history of breast cancer were inconsistently reported among included studies. Lack of standardized pathologic classification did not permit further statistical analysis. Although patients who undergo GAM are unlikely to have premalignant or malignant findings on breast pathology examination, pathologic evaluation of breast tissue remains common practice. Additional studies, which include a standardized method of pathologic evaluation, are necessary before practice guidelines can be recommended.

Spectroscopy along Flerovium Decay Chains: Discovery of

A nuclear spectroscopy experiment was conducted to study α-decay chains stemming from isotopes of flerovium (element Z=114). An upgraded TASISpec decay station was placed behind the gas-filled separator TASCA at the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt, Germany. The fusion-evaporation reactions ^{48}Ca+^{242}Pu and ^{48}Ca+^{244}Pu provided a total of 32 flerovium-candidate decay chains, of which two and eleven were firmly assigned to ^{286}Fl and ^{288}Fl, respectively. A prompt coincidence between a 9.60(1)-MeV α particle event and a 0.36(1)-MeV conversion electron marked the first observation of an excited state in an even-even isotope of the heaviest man-made elements, namely ^{282}Cn. Spectroscopy of ^{288}Fl decay chains fixed Q_{α}=10.06(1) MeV. In one case, a Q_{α}=9.46(1)-MeV decay from ^{284}Cn into ^{280}Ds was observed, with ^{280}Ds fissioning after only 518 µs. The impact of these findings, aggregated with existing data on decay chains of ^{286,288}Fl, on the size of an anticipated shell gap at proton number Z=114 is discussed in light of predictions from two beyond-mean-field calculations, which take into account triaxial deformation.

BCG scarring and improved child survival: a combined analysis of studies of BCG scarring.

Bacillus Calmette-Guérin (BCG) vaccine against tuberculosis (TB) is recommended at birth in TB-endemic areas. Currently, BCG vaccination programmes use "BCG vaccination coverage by 12 months of age" as the performance indicator. Previous studies suggest that BCG-vaccinated children, who develop a scar, have better overall survival compared with BCG-vaccinated children, who do not develop a scar. We summarized the available studies of BCG scarring and child survival. A structured literature search for studies with original data and analysis of BCG scarring and mortality were performed. Combined analyses on the effect of BCG scarring on overall mortality. We identified six studies covering seven cohorts, all from Guinea-Bissau, West Africa, with evaluation of BCG scarring amongst BCG-vaccinated children and follow-up for mortality. Determinants of BCG scarring were BCG strain, intradermal injection route, size of injection wheal, and co-administered vaccines and micronutrients. In a combined analysis, having a BCG scar vs. no BCG scar was associated with a mortality rate ratio (MRR) of 0.61 (95% CI: 0.51-0.74). The proportion with a BCG scar varied from 52 to 93%; the estimated effect of a BCG scar was not associated with the scar prevalence. The effect was strongest in the first (MRR = 0.48 (0.37-0.62)) and second (MRR = 0.63 (0.44-0.92)) year of life, and in children BCG-vaccinated in the neonatal period (MRR = 0.45 (0.36-0.55)). The effect was not explained by protection against TB. Confounding and genetic factors are unlikely to explain the strong association between BCG scarring and subsequent survival. Including "BCG scar prevalence" as a BCG vaccination programme performance indicator should be considered. The effect of revaccinating scar-negative children should be studied.

Identification of the New Isotope

In an experiment performed at Lawrence Berkeley National Laboratory's 88-inch cyclotron, the isotope ^{244}Md was produced in the ^{209}Bi(^{40}Ar,5n) reaction. Decay properties of ^{244}Md were measured at the focal plane of the Berkeley Gas-filled Separator, and the mass number assignment of A=244 was confirmed with the apparatus for the identification of nuclide A. The isotope ^{244}Md is reported to have one, possibly two, α-decaying states with α energies of 8.66(2) and 8.31(2) MeV and half-lives of 0.4_{-0.1}^{+0.4} and ∼6 s, respectively. Additionally, first evidence of the α decay of ^{236}Bk was observed and is reported.

Metabolite profiles evaluated, according to sex, do not predict resting energy expenditure and lean body mass in healthy non-obese subjects.

PURPOSE: Differences in resting energy expenditure (REE) between men and women mainly result from sex-related differences in lean body mass (LBM). So far, a little is known about whether REE and LBM are reflected by a distinct human metabolite profile. Therefore, we aimed to identify plasma and urine metabolite patterns that are associated with REE and LBM of healthy subjects. METHODS: We investigated 301 healthy male and female subjects (18-80 years) under standardized conditions in the cross-sectional KarMeN (Karlsruhe Metabolomics and Nutrition) study. REE was determined by indirect calorimetry and LBM by dual X-ray absorptiometry. Fasting blood and 24 h urine samples were analyzed by targeted and non-targeted metabolomics methods using GC × GC-MS, GC-MS, LC-MS, and NMR. Data were evaluated by predictive modeling of combined data using different machine learning algorithms, namely SVM, glmnet, and PLS. RESULTS: When evaluating data of men and women combined, we were able to predict REE and LBM with high accuracy (> 90%). This, however, was a clear effect of sex, which is supported by the high degree of overlap in identified important metabolites for LBM, REE, and sex, respectively. The applied machine learning algorithms did not reveal a metabolite pattern predictive of REE or LBM, when analyzing data for men and women, separately. CONCLUSIONS: We could not identify a sex independent predictive metabolite pattern for REE or LBM. REE and LBM have no impact on plasma and urine metabolite profiles in the KarMeN Study participants. Studies applying metabolomics in healthy humans need to consider sex specific data evaluation.

Fullerenes - how 25 years of charge transfer chemistry have shaped our understanding of (interfacial) interactions.

In this review article, we highlight over 25 years of fullerene research in charge transfer chemistry. The major thrust of this work is to illustrate interfacial interactions between fullerenes and porphyrins in electron donor-acceptor conjugates as well as self-assembled associates and co-crystallites all the way to organic photovoltaics. Hereby, the analysis of the fundamental proceses, namely, energy transfer, charge shift, charge separation as well as charge recombination stand at the forefront. Our examples, illustrate on how fine-tuning the structure leads to substantial alteration of interfacial interactions.

[Pulmonary involvement in rheumatoid arthritis]. / Lungenbeteiligung bei rheumatoider Arthritis.

Pulmonary involvement in patients with rheumatoid arthritis, in particular interstitial lung diseases (RA-ILD) is of great clinical importance. Patients should be asked about symptoms of pulmonary involvement and the lungs should be clinically examined even during the diagnostic procedure and regularly during the course of the disease. Before initiation of a basic pharmacological treatment an X­ray examination of thoracic organs is obligatory. In cases of conspicuous clinical or radiological findings, extended diagnostic procedures with lung function testing (body plethysmography with diffusion measurement) and high resolution computed tomography (CT) should be performed, depending on the findings. The differential diagnosis of interstitial lung alterations in patients with RA is broad and should consider side effects of the basis medication in addition to infectious causes. The optimal pharmacological treatment of RA-ILD is not sufficiently clarified. The value of methotrexate (MTX) has changed because, in contrast to previous assumptions, a better course could be observed under MTX treatment, at least in mild to moderate courses of RA-ILD. In the case of a clinically relevant RA-ILD, tumor necrosis factor (TNF) blockers should be avoided because a dramatic deterioration of pulmonary function has sometimes been observed. Among biological disease-modifying antirheumatic drugs (DMARD), rituximab and abatacept are currently preferred. The role of Janus kinase (JAK) inhibitors in RA-ILD is currently being discussed but limited data are available. Patients with RA-ILD benefit from a close collaboration between pulmonologists and rheumatologists.

[Challenges of primary hip arthroplasty with high hip dislocation]. / Herausforderungen der primären Hüftendoprothetik bei hoher Hüftluxation.

BACKGROUND: Endoprosthetic care of high hip dislocation is a surgical challenge. The hip anatomy is greatly altered in these patients, including a rather flat and small acetabulum with impaired bone quality and a relevant chance of a bony defect of the acetabular roof. Additionally, the front coverage and in some cases even the dorsal coverage of the hip are missing. The proximal femur is characterized with an increased antetorsion, a coxa valga position and an enlarged greater trochanter. The medullary cavity is narrowed, the offset is reduced, and the absolut leg length can be enlarged. Further anatomic variations can have been caused by previous surgeries. AIM OF THE TREATMENT: The goal of the endoprosthetic care is the re-creation of a hip with an anatomic center of rotation, an anatomic offset and equal leg length. TREATMENT: This can be achieved by a medial shift of the acetabular cup. An acetabular osteotomy including central cancellous bone graft or a bony graft to reinforce the acetabular roof might be necessary. In cases in which an anatomic acetabular cup placement is not possible, a more cranial placement can be done. Further strategies that are essential in several cases are shortening or re-orientation osteotomies of the femur, reaming of the medullary cavity and correct implant selection. Additionally, thorough soft tissue management is of main importance. Generally, the surgery should be well prepared preoperatively.

[Bone marrow edema-differential diagnosis of the femoral head necrosis]. / Das Knochenmarködem ­ Differenzialdiagnose zur aseptischen Hüftkopfnekrose.

In patients with hip pain, clinical examination is of only restricted value in the differential diagnosis. Besides a patient's age, their medical history is often helpful in finding the correct diagnosis. Additionally, imaging can give valuable hints for excluding or validating a differential diagnosis. Nowadays, magnetic resonance imaging (MRI) is often used as a primary imaging modality in Germany. These MRIs show a bone marrow edema (BME) in many different pathologies. BME occurs in transitory bone marrow edema and outside of the atraumatic femoral head necrosis, concomitant with coxarthrosis, arthritis, herniation pit, and osteoid osteoma, amongst other conditions. This article describes several frequent differential diagnoses and gives hints on how to find the correct diagnosis.

[Imaging and classification of avascular femoral head necrosis]. / Bildgebung und Klassifikation der aseptischen Hüftkopfnekrose.

Avascular femoral head necrosis (AVNFH) is difficult to diagnose on plain radiographs in early stages of the disease. Since early stages are often clinically occult, early use of MRI is required to rule out or verify a clinical suspicion. MRI and, in some cases, additional CT are the cornerstones of AVNFH diagnosis and classification. Anteroposterior radiography of the pelvis and a second plane of the involved hip remains the primary basic imaging examination for follow-up and to rule out other pathologies. Correct staging of adult disease has been shown to be the key factor in therapeutic decision-making. According to the German S3 guideline on diagnosis and treatment of AVNFH, use of the ARCO classification is recommended for staging. This paper presents the current status of diagnosis and classification of adult AVNFH. The criteria for ascribing disease to a particular ARCO stage are defined and critically discussed.

[S2e guideline: treatment of rheumatoid arthritis with disease-modifying drugs]. / S2e-Leitlinie: Therapie der rheumatoiden Arthritis mit krankheitsmodifizierenden Medikamenten.

BACKGROUND: Medication-based strategies to treat rheumatoid arthritis are crucial in terms of outcome. They aim at preventing joint destruction, loss of function and disability by early and consistent inhibition of inflammatory processes. OBJECTIVE: Achieving consensus about evidence-based recommendations for the treatment of rheumatoid arthritis with disease-modifying anti-rheumatic drugs in Germany. METHODS: Following a systematic literature research, a structured process among expert rheumatologists was used to reach consensus. RESULTS: The results of the consensus process can be summed up in 6 overarching principles and 10 recommendations. There are several new issues compared to the version of 2012, such as differentiated adjustments to the therapeutic regime according to time point and extent of treatment response, the therapeutic goal of achieving remission as assessed by means of the simplified disease activity index (SDAI) as well as the potential use of targeted synthetic DMARDs (JAK inhibitors) and suggestions for a deescalating in case of achieving a sustained remission. Methotrexate still plays the central role at the beginning of the treatment and as a combination partner in the further treatment course. When treatment response to methotrexate is inadequate, either switching to or combining with another conventional synthetic DMARD is an option in the absence of unfavourable prognostic factors. Otherwise biologic or targeted synthetic DMARDs are recommended according to the algorithm. Rules for deescalating treatment with glucocorticoids and-where applicable-DMARDs give support for the management of patients who have reached a sustained remission. DISCUSSION: The new guidelines set up recommendations for RA treatment in accordance with the treat-to-target principle. Modern disease-modifying drugs, now including also JAK inhibitors, are available in an algorithm.

Kidney Exchange to Overcome Financial Barriers to Kidney Transplantation.

Organ shortage is the major limitation to kidney transplantation in the developed world. Conversely, millions of patients in the developing world with end-stage renal disease die because they cannot afford renal replacement therapy-even when willing living kidney donors exist. This juxtaposition between countries with funds but no available kidneys and those with available kidneys but no funds prompts us to propose an exchange program using each nation's unique assets. Our proposal leverages the cost savings achieved through earlier transplantation over dialysis to fund the cost of kidney exchange between developed-world patient-donor pairs with immunological barriers and developing-world patient-donor pairs with financial barriers. By making developed-world health care available to impoverished patients in the developing world, we replace unethical transplant tourism with global kidney exchange-a modality equally benefitting rich and poor. We report the 1-year experience of an initial Filipino pair, whose recipient was transplanted in the United states with an American donor's kidney at no cost to him. The Filipino donor donated to an American in the United States through a kidney exchange chain. Follow-up care and medications in the Philippines were supported by funds from the United States. We show that the logistical obstacles in this approach, although considerable, are surmountable.

[Lymphocytic myocarditis in a patient with metastatic clear cell renal cell carcinoma treated with Nivolumab]. / Lymphozytäre Myokarditis unter Nivolumabtherapie bei metastasiertem klarzelligen Nierenzellkarzinom.

Immune checkpoint inhibitors against the PD-1 protein offer a new therapy option for many solid cancers. We report a patient with metastatic renal cell cancer treated with Nivolumab. As a rare immune-mediated adverse event, we describe a fatal lymphocytic myocarditis two weeks after starting immune therapy. The cause of death was first diagnosed at autopsy. This case report underlines the importance and need of clinical autopsies as an instrument of quality assurance and detection of rare therapy-induced adverse effects.

[Lymphoma in rheumatic diseases]. / Lymphome bei rheumatischen Erkrankungen.

Various systemic inflammatory diseases, such as rheumatoid arthritis (RA), Sjögren's syndrome and systemic lupus erythematosus (SLE) are associated with an increased risk for the development of lymphomas. Studies on patients with RA and Sjögren's syndrome have shown that there is a clear association of the incidence of lymphoma with the severity and activity of the disease and lymphomas in particular are diseases which preferentially occur in immunosuppressed patients; therefore, knowledge of the different lymphoma subtypes, their prognosis and treatment options are important for rheumatologists. Currently, there is no evidence for an increased risk of lymphoma with the available conventional basis therapies or biologic disease-modifying antirheumatic drugs (DMARDs). The decision on how to treat a patient with previous lymphoma who requires antirheumatic treatment is more difficult as patients with previous malignancies are not included in clinical studies and in registries a bias with respect to patient selection must be taken into consideration. Decisions on the treatment approach, therefore need to be individualized and interdisciplinary management together with the treating hematologist is warranted.

[Three Years Follow-up Study after Refractive Small Incision Lenticule Extraction (SMILE) Using 500 kHz Femtosecond Laser in "Fast Mode"]. / Drei Jahre Nachbeobachtung nach refraktiver Small Incision Lenticule Extraction (SMILE) mit einem 500-kHz-Femtosekundenlaser im "Fast Mode".

Background The aim of this clinical trial was to check the results of laser built-in settings 3 years after ReLEx SMILE for moderate and high myopia in unselected "real life" patients. Patients and Methods 50 myopic eyes of 27 patients were called in for examination after 3 years. 25 of these eyes with a preoperative myopia under - 6D comprised the "moderate myopia subgroup". All surgeries were performed with the 500 kHz VisuMax® femtosecond laser (Carl Zeiss Meditec AG, Jena) in the "fast mode" setting. Results The spherical equivalent (SE) of the entire group changed from - 6.18 D (± 1.91) prior to surgery to - 0.18 D (± 0.39) 3 years later. The preoperative SE in the moderate myopia subgroup changed from - 4.71 D (± 0.94) to - 0.04 D (± 0.23). 14 % of 50 eyes gained one line and 22 % lost one line of CDVA. The regression between month 3 and 36 was 0.07D for the entire group and 0.06 D for the moderate myopia subgroup. There were no late side effects. Primary undercorrection was predominantly seen in eyes over - 6 D. Conclusion ReLEx SMILE shows remarkable stability over the entire range of myopias after 3 years, however primary undercorrection occurs predominantly in eyes of - 6.0 D, which necessitates nomogram adjustment.

Refractive Lenticule Implantation for Correction of Ametropia: Case Reports and Literature Review.

The ReLEx® technique allows correction of refractive errors through the creation and extraction of refractive stromal lenticules. Contrary to excimer laser corneal refractive procedures, where the stromal tissue is photoablated, the extracted lenticules obtained with ReLEx® can be preserved. Recent studies and case reports have described autologous re-implantation and allogeneic implantation of refractive lenticules into femtosecond-laser created stromal pockets in order to reverse the refractive outcome of a myopic corneal refractive procedure, correct hyperopia, aphakia, presbyopia and treat keratoconus. The use of stromal lenticules has also been described for therapeutic purposes, with an allogenic lenticule being transplanted under a LASIK flap in order to restore corneal volume and reduce the refractive error in a case of excessive stromal tissue removal after LASIK. This review summarises the results of the latest case reports and studies that describe the implantation of cryopreserved or fresh refractive stromal lenticules and discusses the feasibility, safety and refractive outcomes of the procedure, on the basis of published literature as well as our own experience.

Incentivizing Authorization for Deceased Organ Donation With Organ Allocation Priority: The First 5 Years.

The allocation system of donor organs for transplantation may affect their scarcity. In 2008, Israel's Parliament passed the Organ Transplantation Law, which grants priority on waiting lists for transplants to candidates who are first-degree relatives of deceased organ donors or who previously registered as organ donors themselves. Several public campaigns have advertised the existence of the law since November 2010. We evaluated the effect of the law using all deceased donation requests made in Israel during the period 1998-2015. We use logistic regression to compare the authorization rates of the donors' next of kin in the periods before (1998-2010) and after (2011-2015) the public was made aware of the law. The authorization rate for donation in the period after awareness was substantially higher (55.1% vs. 45.0%, odds ratio [OR] 1.43, p = 0.0003) and reached an all-time high rate of 60.2% in 2015. This increase was mainly due to an increase in the authorization rate of next of kin of unregistered donors (51.1% vs. 42.2%). We also found that the likelihood of next-of-kin authorization for donation was approximately twice as high when the deceased relative was a registered donor rather than unregistered (89.4% vs. 44.6%, OR 14.27, p < 0.0001). We concluded that the priority law is associated with an increased authorization rate for organ donation.