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Background: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection represents a serious health risk, especially in chronically ill people. Multiple sclerosis (MS) is the most common chronic immune-mediated neurological disease. Vaccinations play an important role in the therapeutic MS management. This study aimed at determining MS patients’ attitudes toward vaccinations and governmental measures before and during the SARS-CoV-2 pandemic, including associations with sociodemographic and clinical variables. Methods: In a longitudinal, multicenter study, 200 MS patients were investigated regarding their vaccination attitudes before and after the first wave of the SARS-CoV-2 pandemic. Data on vaccination status and burden (physical, psychological, and social) experienced as caused by the pandemic and related governmental safety measures were registered. Results: Patients with progressive MS felt significantly more pandemic-burdened than patients with relapsing-onset MS (p < 0.001). Older patients were more frequently willing to get vaccinated against SARS-CoV-2 than younger patients (p < 0.001). After the first pandemic wave, patients with pre-pandemic willingness to comply with vaccination recommendations were more likely to accept recommended standard vaccinations (60% vs. 36%) and a possible SARS-CoV-2 vaccination than pre-pandemic nonwilling patients (66.7% vs. 42.0%). Conclusions: The vaccination topic was not immediately present in many patients before the pandemic. MS patients need comprehensive and understandable education meeting their concerns using evidence-based and convincing arguments on the subject of vaccination, particularly younger patients. Older patients are already more often willing to become vaccinated. Complete vaccination status is necessary to avoid multiple infections.

Background Olecranon osteotomies are frequently used to expose distal humeral intraarticular fractures. The step-cut olecranon osteotomy (SCOOT) is an augmented version of the oblique olecranon osteotomy, which has recently been evaluated biomechanically with tension band wiring (TBW) fixation. However, complications with TBW are common. In this study, we, therefore, compared the mean load to failure of TBW with compression screws for SCOOT fixation. We hypothesized a higher load to failure for the compression screw group. Methods We performed a SCOOT on 36 Sawbones. Eighteen were fixed with TBW, and another 18 with two compression screws. The humeroulnar joint was simulated using an established test setup, which allows the application of triceps traction force through a tendon model to the ulna, while the humeroulnar joint is in a fixed position. Eight models of each fixation group were tested at 20��, and eight at 70�� of flexion by isometrical loading until failure, which was defined as either a complete fracture or gap formation of more than 2 mm at the osteotomy site. Results At 20�� of flexion, mean load to failure was similar between the TBW group (1360 �� 238 N) and the compression screw group (1401 �� 261 N) (P = .88). Also, at 70�� of flexion, the mean load to failure was similar between the TBW group (1398 �� 215 N) and the compression screw group (1614 �� 427 N) (P = .28). Conclusions SCOOTs fixed with TBW and compression screws showed similar loads to failure. A SCOOT fixed with compression screws might be a valuable alternative for surgeons when treating intraarticular distal humeral fractures. However, future in vivo studies are necessary to confirm our results in a clinical setting.

Diante do elevado consumo e dos diversificados fitoterápicos disponíveis no mercado para uso associado ao exercício, é extremamente importante, sob o ponto de vista nutricional, a comprovação de seu uso para que não ocorra intoxicação. Além disso, a aplicação das plantas medicinais e fitoterápicas associada ao exercício físico apresenta mais um recurso alternativo na melhora da performance e na atenuação de efeitos deletérios causados pelo exercício de alta intensidade. Portanto, sugerimos a adoção de exercícios físicos associados a ingestão de suplementos oriundos de plantas com propriedades medicinais como possibilidades importantes para a manutenção e promoção da saúde, tanto na patologia como no desempenho físico e na atenuação de danos deletérios causados pelo estresse fisiológico associados às doenças crônicas.

Introdução: O treinamento intervalado de alta intensidade (HIIT) é capaz de promover melhora da saúde e condicionamento físico e contribuir para o aumento da capacidade cardiorrespiratória (VO2máx), da resistência muscular localizada e melhora da composição corporal. No entanto, seus efeitos sobre a aptidão física relacionada a saúde de crianças e adolescentes ainda não são bem esclarecidos. Objetivo: O objetivo do estudo foi analisar a eficácia do HIIT na aptidão física relacionada a saúde de crianças e adolescentes. Métodos: O presente estudo analisou artigos das bases de dados (SportDiscus, Web of Science, Medline via PubMed, Scopus, Scielo e Bireme). Foi aplicada a estratégia PICO para selecionar os artigos e o CONSORT para avaliar a qualidade dos ensaios clínicos randomizados. Foram encontrados 511 artigos. Desse total, 101 artigos foram elegíveis para a análise do resumo. Resultados: Ao final do processo de seleção resultaram em 10 artigos que compuseram os critérios de inclusão. Os resultados sugerem que entre as variáveis analisadas pelos artigos referentes a aptidão física relacionada a saúde, o HIIT demonstrou eficácia na VO2máx, índice de massa corporal e percentual de gordura nessa população. Conclusão: Contudo, não foi possível afirmar que o HITT promoveu ajustes na flexibilidade, na força e na resistência muscular localizada, sendo necessário maiores estudos para avaliar seus efeitos sobre a aptidão física relacionada a saúde

Purpose Recently introduced total knee arthroplasty (TKA) alignment strategies aim to restore the pre-arthritic alignment of an individual patient. The native alignment of a patient can only be restored with detailed knowledge about the native and osteoarthritic alignment as well as differences between them. The first aim of this study was to assess the alignment of a large series of osteoarthritic (OA) knees and investigate whether femoral and tibial joint lines vary within patients with the same overall lower limb alignment. The secondary aim was to compare the alignment of OA patients to the previously published data of non-OA patients. This information could be useful for surgeons considering implementing one of the new alignment concepts. Material Coronal alignment parameters of 2692 knee OA patients were measured based on 3D reconstructed CT data using a validated planning software (Knee-PLAN®, Symbios, Yverdon les Bains, Switzerland). Based on these measurements, patients' coronal alignment was phenotyped according to the functional knee phenotype concept. These phenotypes represent an alignment variation of either the overall alignment, the femoral joint line orientation or the tibial joint line orientation. Each phenotype is defined by a specific mean and covers a range of ± 1.5° from this mean. Mean values and distribution among the phenotypes are presented and compared between two populations (OA patients of this study and non-OA patients of a previously published study) as well as between HKA subgroups (varus, valgus and neutral) using t tests and Chi-square tests (p Results Femoral and tibial joint lines varied within patients with the same overall lower limb alignment. A total of 162 functional knee phenotypes were found (119 males, 136 females and 94 mutual phenotypes). Mean values differed between the OA and non-OA population, but differences were small ( Conclusion Differences between OA and non-OA knees are small regarding coronal femoral and tibial joint line orientation. Femoral and tibial joint line orientation of osteoarthritic patients can, therefore, be used to estimate their native coronal alignment and plan an individualized knee alignment. Level of clinical evidence III.

A posterior flexion instability due to insufficiency of the posterior cruciate ligament (PCL) in cruciate retaining (CR) total knee arthroplasty (TKA) is an important but underdiagnosed problem. We hereby suggest a diagnostic algorithm, as demonstrated by a case report of a male patient suffering from anterior knee pain and instability after CR TKA. Clinical examination was followed by standard anterior–posterior and lateral radiographs. Stress radiographs in 30° and 90° posterior drawer position enabled a dynamic examination of the instability. SPECT/CT was used to determine the TKA component position in all planes and investigate bone tracer uptake (BTU) patterns. At revision surgery, an absent PCL after CR TKA was noted and a semi-constrained TKA was implanted.

Intracranial arteriosclerosis has been increasingly recognized as a risk factor for cognitive impairment and even dementia. A possible mechanism linking intracranial arteriosclerosis to cognitive impairment and dementia involves structural brain changes including cerebral small vessel disease (CSVD). To assess whether intracranial carotid artery calcification (ICAC) and vertebrobasilar artery calcification (VBAC), as proxies for intracranial arteriosclerosis, are related to CSVD. Within the population-based Rotterdam Study, between 2003 and 2006 a computed tomography (CT)-based measurement of ICAC and VBAC and at least one magnetic resonance imaging (MRI) measurement of structural brain changes were performed from 2005 onwards in 1,489 participants. To estimate the burden of calcification independent of age, we computed age-adjusted percentile curves for ICAC and VBAC separately, based on the calcification volumes. Using the longitudinal MRI data, we assessed whether a larger calcification burden accelerates structural brain changes using appropriate statistical models for repeated outcome measures. A larger burden of ICAC and VBAC was associated with an increase of CSVD markers accelerating over time. A larger burden of ICAC and VBAC was not significantly (p > 0.05) associated with accelerated brain atrophy. Arteriosclerosis is related to accelerating structural brain changes over time.

We report the case of a 60-year-old female patient with a contained rupture of a proximal anastomotic pseudoaneurysm after previous open repair of a type IV thoracoabdominal aneurysm. A repeat open repair was considered to be too risky. We performed an urgent endovascular repair with a thoracic stent-graft and a surgeon-modified fenestrated aortic cuff with two fenestrations. The final angiogram and postoperative imaging studies showed complete aneurysm exclusion without any endoleak. Surgeon-modified fenestrated endovascular aortic repair is a feasible treatment option for emergency cases for which repeat open repair or custom-made complex endovascular repair is not an option.

The Rotterdam Study is an ongoing prospective, population-based cohort study that started in 1989 in the city of Rotterdam, the Netherlands. The study aims to unravel etiology, preclinical course, natural history and potential targets for intervention for chronic diseases in mid-life and late-life. It focuses on cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, otolaryngological, locomotor, and respiratory diseases. In response to the COVID-19 pandemic, a substudy was designed and embedded within the Rotterdam Study. On the 20th of April, 2020, all living non-institutionalized participants of the Rotterdam Study (n = 8732) were invited to participate in this sub-study by filling out a series of questionnaires administered over a period of 8 months. These questionnaires included questions on COVID-19 related symptoms and risk factors, characterization of lifestyle and mental health changes, and determination of health care seeking and health care avoiding behavior during the pandemic. As of May 2021, the questionnaire had been sent out repeatedly for a total of six times with an overall response rate of 76%. This article provides an overview of the rationale, design, and implementation of this sub-study nested within the Rotterdam Study. Finally, initial results on participant characteristics and prevalence of COVID-19 in this community-dwelling population are shown. Supplementary Information The online version contains supplementary material available at 10.1007/s10654-021-00789-7.

Background: The etiology of dementia may partly be underpinned by impaired lung function via systemic inflammation and hypoxia. Objective: To prospectively examine the association between chronic obstructive pulmonary disease (COPD) and subclinical impairments in lung function and the risk of dementia. Methods: In the Rotterdam Study, we assessed the risk of incident dementia in participants with Preserved Ratio Impaired Spirometry (PRISm; FEV1/FVC≥0.7, FEV1

Gait disorders in patients with Parkinson’s disease (PD) impact their mobility and self-dependence. Gait training and dual-task (DT)-training improve gait quality. This study aims to assess the feasibility of a specific, gradually intensified DT-training for PD patients with a special focus on gait performance under single task (ST) and DT conditions. Correlations to Freezing of Gait (FoG) were examined. 17 PD patients (70.1 ± 7.4 years, H&Y Stadium 2–3, FoG-Q 9.0 ± 5.5) participated in a four-week DT-training (1x/week, 60 min) with progressively increasing task difficulty and number of tasks. Gait performance (spatiotemporal parameters) was assessed during ST and DT conditions. The training improved DT gait performance, especially gait velocity + 0.11 m/s; (F(2,16) = 7.163; p = .0171; η2part = .309) and step length (+ 5.73 cm). Also, physical well-being and absolved walking distance improved significantly. Correlation analyses of the FoG score at baseline with relative change of gait metrics post-training revealed significant correlations with training-induced changes of step length and improvement of gait velocity. Overall, the developed DT-training was feasible and effective. Further studies should examine the long-term benefits and the optimal setting to achieve the highest impact. The study was registered in the DRKS (ID DRKS00018084, 23.1.20).

Introduction: High intensity interval training (HIIT) is a method that is widely used today. Objective: The present study aimed to evaluate the effects of HIIT on markers of oxidative stress and muscle damage in rats. Methods: The sample consisted of 60-day-old Wistar rats, divided into two groups: a control group (n=8) and an HIIT group (n=8). The training consisted of fourteen 20-second swimming sessions (loaded with weights equivalent to 14% of their body weight) with 10-second intervals between each session, performed for 12 consecutive days. Results: HIIT induced a reduction (−17.75%) in thiobarbituric acid reactive substances (an oxidative stress marker) in hepatic tissue (p=0.0482). There was also a reduction (−31.80%) in the HIIT group in the level of superoxide dismutase enzyme activity in the liver (p=0.0375). However, there were no differences between the groups in catalase, glutathione peroxidase, glutathione reductase, the total content of SH sulfhydryls, hydroperoxides, or carbonylated proteins in the hepatic tissue. No significant differences were found in any of these markers in the gastrocnemius muscle. The muscle damage markers creatinine kinase and lactate dehydrogenase were also similar between the groups in the gastrocnemius. Conclusion: The conclusion was that that short-term HIIT does not cause oxidative stress or muscle damage. Level of evidence I; High-quality randomized clinical trial with or without statistically significant difference, but with narrow confidence intervals. RESUMEN Introducción: El entrenamiento en intervalos de alta intensidad (HIIT) es un método muy utilizado actualmente. Objetivo: El presente estudio tuvo como objetivo evaluar los efectos del HIIT en corto plazo sobre marcadores de estrés oxidativo y daño muscular en ratones. Métodos: La muestra consistió en ratones Wistar con 60 días de edad, divididos en dos grupos: grupo control (n = 8) y grupo HIIT (n = 8). El entrenamiento consistió en catorce sesiones de natación de 20 segundos (con cargas equivalentes a 14% del peso corporal) con intervalos de 10 segundos entre cada sesión, realizadas durante 12 días consecutivos. Resultados: El HIIT indujo una reducción (-17,75%) de las sustancias reactivas al ácido tiobarbitúrico (un marcador de estrés oxidativo) en el tejido hepático (p = 0,0482). También hubo reducción (~31,80%) en el grupo HIIT en el nivel de enzima superóxido dismutasa en el hígado (p=0,0375). Sin embargo, no hubo diferencias entre los grupos con relación a catalasa, glutatión peroxidasa, glutatión reductasa, tenor total de sulfhidrilos SH, hidroperóxidos o proteínas carboniladas en el tejido hepático. No fue encontrada ninguna diferencia significativa en ninguno de esos marcadores en el músculo gastrocnemio. Los marcadores de lesión muscular, creatinina quinasa y lactato deshidrogenasa también fueron similares entre los grupos en el gastrocnemio. Conclusión: Fue posible concluir que el HIIT de corta duración no causa estrés oxidativo o daño muscular. Nivel de evidencia I; Estudio clínico aleatorizado de alta calidad con o sin diferencia estadísticamente significativa, pero con intervalos de información estrechos. RESUMO Introdução: O treinamento intervalado de alta intensidade (HIIT) é um método muito utilizado atualmente. Objetivo: O presente estudo objetivou avaliar os efeitos do HIIT em curto prazo sobre marcadores de estresse oxidativo e dano muscular em ratos. Métodos: A amostra consistiu em ratos Wistar com 60 dias de idade, divididos em dois grupos: grupo controle (n = 8) e grupo HIIT (n = 8). O treinamento consistiu em quatorze sessões de natação de 20 segundos (com cargas equivalentes a 14% do peso corporal) com intervalos de 10 segundos entre cada sessão, realizadas por 12 dias consecutivos. Resultados: O HIIT induziu uma redução (-17,75%) das substâncias reativas ao ácido tiobarbitúrico (um marcador de estresse oxidativo) no tecido hepático (p = 0,0482). Houve também redução (-31,80%) no grupo HIIT no nível de enzima superóxido dismutase no fígado (p = 0,0375). No entanto, não houve diferenças entre os grupos com relação a catalase, glutationa peroxidase, glutationa redutase, teor total de sulfidrilas SH, hidroperóxidos ou proteínas carboniladas no tecido hepático. Nenhuma diferença significativa foi encontrada em qualquer um desses mascadores no músculo gastrocnêmio. Os marcadores de lesão muscular, creatinina quinase e lactato desidrogenase, também foram semelhantes entre os grupos no gastrocnêmio. Conclusão: Foi possível concluir que o HIIT de curta duração não causa estresse oxidativo ou dano muscular. Nível de evidência I; Estudo clínico randomizado de alta qualidade com ou sem diferença estatisticamente significante, mas com intervalos de informação estreitos.

Early-life environmental factors have been suggested in the pathophysiology of dementia. Season of birth has previously been used as a proxy for these external exposures. We investigated the link between season of birth and the risk of dementia and further explored underlying pathways by studying structural brain changes on MRI. From the Dutch, population-based Rotterdam Study, 12,964 participants born between 1887 and 1960 were followed between 1990 and 2018 for dementia. Cox regression was conducted to assess the association between season of birth and dementia. In addition, we distinguished between mild and cold winters. The association of season of birth with structural brain markers on MRI was examined in 5237 participants. The risk of dementia in participants born in winter and fall was higher than of those born in summer (hazard ratio (HR) 1.15 [95% confidence interval (CI) 1.01–1.31] for winter and HR 1.17 [95% CI 1.01–1.33] for fall), especially for Alzheimer’s disease (HR 1.23 [1.06–1.43] for winter and HR 1.15 [95% CI 0.99–1.35] for fall). The risk was particularly increased for participants born in a cold winter. Except for slightly lower hippocampus in fall born participants (β − 0.03; 95% CI − 0.06 to 0.00), we did not find associations with brain imaging markers. In conclusion, winter and fall births were associated with a higher incidence of dementia, especially of AD. We did not find evidence for structural brain changes as an underlying mechanism. Supplementary Information The online version contains supplementary material available at 10.1007/s10654-021-00755-3.

Summary Background Allogeneic hematopoietic stem cell transplantation (alloHSCT) is frequently associated with impaired oral intake and malnutrition, which potentially increases morbidity and mortality. Therefore, nutrition is one of the major challenges in the post-transplant period. Methods To document the current clinical approach in nutritional treatment, we designed a questionnaire concerning the current practice in nutrition after alloHSCT and distributed it to German speaking centers performing alloHSCT in Germany, Austria and Switzerland between November 2018 and March 2020. Twenty-eight (39%) of 72 contacted centers completed the survey, 23 from Germany, two from Austria and three from Switzerland, representing 50% of alloHSCT activity within the participating countries in 2018. Results All centers reported having nutritional guidelines for patients undergoing alloHSCT, whereby 86% (n = 24) provided a low-microbial diet during the neutropenic phase. The criteria to start parenteral nutrition (PN) directly after alloHSCT seemed to be consistent, 75% (n = 21) of the corresponding centers started PN if the oral nutritional intake or the bodyweight dropped below a certain limit. In the setting of intestinal graft-versus-host disease (GvHD) the current practice appeared to be more heterogenous. About 64% (n = 18) of the centers followed a special diet, added food stepwise modulated by GvHD symptoms, while only four centers regularly stopped oral intake completely (intestinal GvHD grade >1). Half of the centers (54%, n = 15) applied a lactose-free diet, followed by 43% (n = 12) which provided fat- and 18% (n = 5) gluten-free food in patients with intestinal GvHD. Supplementation of micronutrients in acute intestinal GvHD patients was performed by 54% (n = 15) of the centers, whereas vitamin D (89%, n = 25) and vitamin B12 (68%, n = 19) was added regularly independently of the presence of GvHD. Only 5 (18%) participating centers ever observed a food-associated infection during hospitalization, whereas food-associated infections were reported to occur more often in the outpatient setting (64%, n = 18). Conclusion The survey documented a general consensus about the need for nutritional guidelines for patients undergoing alloHSCT. However, the nutritional treatment in clinical practice (i.e. lactose-, gluten- or fat-free in intestinal GvHD) as well as the use of food supplements was very heterogeneous. In line with current general recommendations the centers seemed to focus on safe food handling practice rather than providing a strict neutropenic diet. More high-quality data are required to provide evidence-based nutrition to patients during and after alloHSCT.

The purpose of this study was to describe the medial and lateral posterior tibial slope (MPTS and LPTS) on 3D-CT in a Caucasian population without osteoarthritis. It was hypothesised that standard TKA alignment techniques would not reproduce the anatomy in a high percentage of native knees. CT scans of 301 knees [male:female = 192:109; mean age 30.1 ( $$\pm$$ 6.1)] were analysed retrospectively. Tibial slope was measured medially and laterally in relation to the mechanical axis of the tibia. The proportion of MPTS and LPTS was calculated, corresponding to the “standard PTS” of 3°–7°. The proportion of knees accurately reproduced with the recommended PTS of 0°–3° for PS and 5°–7° for CR TKA were evaluated. Interindividual mean values of MPTS and LPTS did not differ significantly (mean (range); MPTS: 7.2° ( – 1.0°–19.0°) vs. LPTS: 7.2° ( − 2.4°–17.8°), n.s.). The mean absolute intraindividual difference was 2.9° (0.0°–10.8°). In 40.5% the intraindividual difference between MPTS and LPTS was > 3°. When the standard slope of 3°–7° medial and lateral was considered, only 15% of the knees were covered. The tibial cut for a PS TKA or a CR TKA changes the combined PTS (MPTS + LPTS) in 99.3% and 95.3% of cases, respectively. A high interindividual range of MPTS and LPTS as well as considerable intraindividual differences were shown. When implementing the recommended slope values for PS and CR prostheses, changes in native slope must be accepted. Further research is needed to evaluate the impact of altering a patient’s native slope on the clinical outcome. IV.

Background To establish trajectories of cognitive and motor function, and to determine the sequence of change across individual tests in community-dwelling individuals aged 45–90 years. Method Between 1997 and 2016, we repeatedly assessed cognitive function with 5 tests in 9514 participants aged 45–90 years from the population-based Rotterdam Study. Between 1999 and 2016, we measured motor function with 3 tests in 8297 participants. All participants were free from dementia, stroke, and parkinsonism. We assessed overall and education-specific cognitive and motor trajectories using linear mixed models with age as time scale. Next, we determined the sequence of change across individual tests. Results The number of assessments per participant ranged between 1 and 6 (mean interval, years [SD]: 5.1 [1.4]) for cognitive function, and 1 and 4 (5.4 [1.4]) for motor function. Cognitive and motor trajectories declined linearly between ages 45 and 65 years, followed by steeper declines after ages 65–70 years. Lower educated participants had lower cognitive function at age 45 years (baseline), and declined faster on most cognitive, but not on motor tests than higher educated participants. Up to a 25-year age difference between the fastest and slowest declining test scores was observed. Conclusions On a population-level, cognitive and motor function decline similarly. Compared to higher educated individuals, lower educated individuals had lower cognitive function at baseline, and a faster rate of decline thereafter. These educational-effects were not seen for motor function. These findings benefit the understanding of the natural course of cognitive and motor function during aging, and highlight the role of education in the preservation of cognitive but not motor function.

Background Meniscus allograft transplantation is a valuable surgical option for post-meniscectomy syndrome. For best results, the selected allograft should be as similar as possible to the original meniscus. Three-dimensional meniscus sizing could be a new approach to improve the accuracy of meniscus matching. The contralateral anatomy might therefore be a suitable reconstruction template. The purpose of this study was to compare the three-dimensional shape of the right and left menisci by bi-planar segmentation of magnetic resonance imaging (MRI) scans. Methods Three-dimensional surface models of healthy menisci were created based on 40 bilateral MRI scans. Manual segmentation was performed on the MRI data in sagittal and coronal planes. For side-to-side comparison, each left meniscus model was mirrored and then superimposed to its corresponding right meniscus model. Differences between the meniscus pairs were assessed by width, length, height and surface distances. Inter-reader reliability, as well as accuracy of bi-planar segmentation was assessed by two different readers. Results The meniscus pairs were not significantly different in terms of width, length and height (P = at least 0.138). Side difference of mean surface distances was 0.76 mm (± 0.13 standard deviation (SD)) for medial and 0.78 mm (± 0.15 SD) for lateral menisci. Inter-reader reliability was good to excellent (0.828–0.987). Conclusion The three-dimensional shapes of the left and right menisci are very similar. Therefore, the contralateral meniscus can be used as a template for three-dimensional meniscus allograft sizing. Three-dimensional meniscus segmentation and sizing can be performed accurately by combination of sagittal and coronal planes.

Suramin has been a primary early-stage treatment for African trypanosomiasis for nearly 100 yr. Recent studies revealed that trypanosome strains that express the variant surface glycoprotein (VSG) VSGsur possess heightened resistance to suramin. Here, we show that VSGsur binds tightly to suramin but other VSGs do not. By solving high-resolution crystal structures of VSGsur and VSG13, we also demonstrate that these VSGs define a structurally divergent subgroup of the coat proteins. The co-crystal structure of VSGsur with suramin reveals that the chemically symmetric drug binds within a large cavity in the VSG homodimer asymmetrically, primarily through contacts of its central benzene rings. Structure-based, loss-of-contact mutations in VSGsur significantly decrease the affinity to suramin and lead to a loss of the resistance phenotype. Altogether, these data show that the resistance phenotype is dependent on the binding of suramin to VSGsur, establishing that the VSG proteins can possess functionality beyond their role in antigenic variation. The co-crystal structure of VSGsur with the trypanocidal compound suramin directly links the binding of the drug to the resistance phenotype displayed by strains of Trypanosoma brucei expressing VSGsur. Therefore, VSGs can have a function beyond that of antigenic variation.

The aim of this study was to identify a folate receptor-α (FRα)–selective PET agent potentially suitable for the selection of patients who might profit from FRα-targeted therapies. The 6R and 6S isomers of (18)F-aza-5-methyltetrahydrofolate (MTHF) were assessed regarding their binding to FRα and FRβ, expressed on cancer and inflammatory cells, respectively, and compared with (18)F-AzaFol, the folic acid–based analog. Methods: FR selectivity was investigated using FRα-transfected (RT16) and FRβ-transfected (D4) CHO cells. The cell uptake of (18)F-folate tracers was investigated, and receptor-binding affinities were determined with the nonradioactive analogs. In vitro autoradiography of the (18)F-folate tracers was performed using RT16 and D4 tissue sections. Biodistribution studies and PET/CT imaging of the radiotracers were performed on mice bearing RT16 and D4 xenografts. Results: The uptake of (18)F-6R-aza-5-MTHF was high when using RT16 cells (62% ± 10% of added activity) but much lower when using D4 cells (5% ± 2%). The FRα selectivity of (18)F-6R-aza-5-MTHF was further demonstrated by its approximately 43-fold higher binding affinity to FRα (half-maximal inhibitory concentration [IC(50)], 1.8 ± 0.1 nM) than to FRβ (IC(50), 77 ± 27 nM). The uptake of (18)F-6S-aza-5-MTHF and (18)F-AzaFol was equal in both cell lines (52%–70%), with similar affinities to FRα (IC(50), 2.1 ± 0.4 nM and 0.6 ± 0.3 nM, respectively) and FRβ (0.8 ± 0.2 nM and 0.3 ± 0.1 nM, respectively). The autoradiography signal obtained with (18)F-6R-aza-5-MTHF was 11-fold more intense for RT16 than for D4 tissue sections. Biodistribution data showed high uptake of (18)F-6R-aza-5-MTHF in RT16 xenografts (81% ± 20% injected activity per gram [IA]/g 1 h after injection) but significantly lower accumulation in D4 xenografts (7.3% ± 2.1% IA/g 1 h after injection), which was also visualized using PET. The uptake of (18)F-6S-aza-5-MTHF and (18)F-AzaFol was similar in RT16 (53% ± 10% IA/g and 45% ± 2% IA/g, respectively) and D4 xenografts (77% ± 10% IA/g and 52% ± 7% IA/g, respectively). Conclusion: This study demonstrated FRα selectivity for (18)F-6R-aza-5-MTHF but not for (18)F-6S-aza-5-MTHF or (18)F-AzaFol. This characteristic, together with its favorable tissue distribution, makes (18)F-6R-aza-5-MTHF attractive for clinical translation to enable detection of FRα-positive cancer while preventing undesired accumulation in FRβ-expressing inflammatory cells.

Background: Currently, the two most common bariatric procedures are laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB). Long-term data comparing the two interventions in terms of their effect on body composition and bone mass density (BMD) are scarce. Objective: The aim of this study was to assess body composition and BMD at least 5 years after LSG and LRYGB. Setting: Department of Endocrinology and Nutrition, St. Claraspital Basel and St. Clara Research Ltd., Basel, Switzerland. Methods:Bariatric patients at least 5 years after surgery (LSG or LRYGB) were recruited, and body composition and BMD were measured by means of dual-energy X-ray absorptiometry. Data from body composition before surgery were included in the analysis. Blood samples were taken for determination of plasma calcium, parathyroid hormone, vitamin D3, alkaline phosphatase, and C-terminal telopeptide, and the individual risk for osteoporotic fracture assessed by the Fracture Risk Assessment Tool score was calculated. After surgery, all patients received multivitamins, vitamin D3, and zinc. In addition, LRYGB patients were prescribed calcium. Results: A total of 142 patients were included, 72 LSG and 70 LRYGB, before surgery: median body mass index 43.1, median age 45.5 years, 62.7% females. Follow-up after a median of 6.7 years. For LRYGB, the percentage total weight loss at follow-up was 26.3% and for LSG 24.1% (p = 0.243). LRYGB led to a slightly lower fat percentage in body composition. At follow-up, 45% of both groups had a T score at the femoral neck below –1, indicating osteopenia. No clinically relevant difference in BMD was found between the groups. Conclusions:At 6.7 years after surgery, no difference in body composition and BMD between LRYGB and LSG was found. Deficiencies and bone loss remain an issue after both interventions and should be monitored.

OBJECTIVES The goal of this study was to report the long-term outcomes of patients with Marfan syndrome who had aortic surgery on any aortic segment except for the replacement of the aortic root itself. METHODS An observational retrospective single-centre study was conducted with 115 Marfan syndrome patients who underwent 189 major aortic interventions from 1995 until 2018. Patients without aortic root replacement were identified and aortic root growth was analysed over time. RESULTS Eleven of 115 patients (9.5%) did not have aortic root replacement during a follow-up of 10.5 [standard deviation (SD) 5.7] years and a mean age at last follow-up of 53.9 (SD 13.4) years. Patients without root replacement did not suffer less frequently from any type of acute aortic dissection (type A 27% vs 25%, P = 0.999; type B 36% vs 25%, P = 0.474). Patients with native aortic roots did not undergo fewer aortic interventions than those with aortic root replacement [12/11, mean 1.09 (SD 0.54) operations/patient vs 177/104, mean 1.7 (SD 1.3); P = 0.128]. Progression of the aortic root dimension was 0.5 (SD 0.3) mm/year in the group of patients with native aortic roots. CONCLUSIONS Current data suggest that 10% of patients with Marfan syndrome with previous aortic surgery will be free from aortic root replacement until the sixth decade of life.

Objective To determine potential predictive associations between patient-/lesion-specific factors, clinical outcome and anterior ankle impingement in patients that underwent isolated autologous matrix-induced chondrogenesis (AMIC) for an osteochondral lesion of the talus (OLT). Design Thirty-five patients with a mean age of 34.7 ± 15 years who underwent isolated cartilage repair with AMIC for OLTs were evaluated at a mean follow-up of 4.5 ± 1.9 years. Patients completed AOFAS (American Orthopaedic Foot and Ankle Society) scores at final follow-up, as well as Tegner scores at final follow-up and retrospectively for preinjury and presurgery time points. Pearson correlation and multivariate regression models were used to distinguish associations between patient-/lesion-specific factors, the need for subsequent surgery due to anterior ankle impingement and patient-reported outcomes. Results At final follow-up, AOFAS and Tegner scores averaged 92.6 ± 8.3 and 5.1 ± 1.8, respectively. Both body mass index (BMI) and duration of symptoms were independent predictors for postoperative AOFAS and Δ preinjury to postsurgery Tegner with positive smoking status showing a trend toward worse AOFAS scores, but this did not reach statistical significance ( P = 0.054). Nine patients (25.7%) required subsequent surgery due to anterior ankle impingement. Smoking was the only factor that showed significant correlation with postoperative anterior ankle impingement with an odds ratio of 10.61 when adjusted for BMI and duration of symptoms (95% CI, 1.04-108.57; P = 0.047). Conclusion In particular, patients with normal BMI and chronic symptoms benefit from AMIC for the treatment of OLTs. Conversely, smoking cessation should be considered before AMIC due to the increased risk of subsequent surgery and possibly worse clinical outcome seen in active smokers.

ZUSAMMENFASSUNG Einleitung Es gibt keine wissenschaftliche Evidenz aus randomisiert-kontrollierten Studien, die für eine routinemäßige Anlage von subkutanen Drainagen bei körperformenden Eingriffen in der Plastischen Chirurgie spricht. Die vorliegende Studie untersucht, inwiefern sich ein Verzicht auf Wunddrainagen bei Abdominoplastik auf das Seromvolumen, die stationäre Verweildauer und postoperative Komplikationen auswirkt. Material und Methoden Die Studienteilnehmer wurden prospektiv in zwei Gruppen mit Anlage von Drainagen (MD) und ohne Anlage von Drainagen (OD) bei Abdominoplastik randomisiert. Einschlusskriterien waren eine Abdominoplastik mit horizontaler oder kombiniert horizontal/vertikaler Schnittführung unter Schonung der Scarpa-Faszie und ein BMI ≤ 30 kg/m2. Ausschlusskriterien beinhalteten eine simultane Liposuction des Operationsgebietes, bekannte Gerinnungsstörungen sowie ein ASA-Score ≥ 3. Das kumulative Seromvolumen über einen Beobachtungszeitraum von 4 Wochen wurde als primärer Endpunkt definiert. Die stationäre Verweildauer und revisionspflichtige Komplikationen stellten sekundäre Endpunkte dar. Resultate Bei 53 Studienteilnehmern wies das kumulative Seromvolumen keinen statistisch signifikanten Unterschied zwischen den beiden Studienpopulationen MD (30/53) und OD (23/53) auf (MMD 493 ± SD 407 ml; MOD 459 ± SD 624 ml; p = 0,812). Verglichen mit dem MD-Patientenkollektiv, konnte durch den Verzicht auf Wunddrainagen in der OD-Kohorte eine signifikant kürzere mittlere stationäre Verweildauer erzielt werden (MMD 5,1 ± SD 1,4 d; MOD 4,2 ± SD 1,5 d; p = 0,023). Beide Studiengruppen hatten identische Komplikationsraten (nMD = 1; nOD = 1). Schlussfolgerung Bezugnehmend auf die Ergebnisse der vorliegenden Erhebung, kann bei präadipösen Patienten (BMI ≤ 30 kg/m2) ein routinemäßiger Verzicht auf Drainagen bei Abdominoplastik (horizontale, kombiniert horizontale/vertikale Schnittführung) in Erwägung gezogen werden. Die Anlage von Drainagen sollte lediglich auf patientenindividueller Basis erfolgen.

The anterolateral thigh (ALT) perforator flap is a popular reconstructive tissue transfer. Consistent with the "hot/cold zone" concept for rapid dissection and thin flap harvest, reliable preoperative perforator mapping is mandatory. Color-coded duplex sonography (CCDS) has been shown to have the highest pooled sensitivity and positive predictive value to identify ALT perforating vessels. By reviewing this guide, the reader should learn: 1. Probe selection and basic/advanced device settings 2. Interpreting tissue morphology 3. Structured mapping approach 4. Pedicle position planning 5. Safe flap design 6. Assess subcutaneous course and flap's thickness for subfascial/epifascial/suprafascial harvest 7. Implement perforators identified into a tailor-made flap design including chimeric flaps.Experiences with ultrasound-guided flap design gained from 125 ALT perforator flap free tissue transfers performed in two reconstructive centers was the basis of our guide. Our structured method comprises standardized markings, patient positioning, and simple ergonomics. Basic and advanced CCDS settings, selection, and conventional probe guidance are outlined for the microsurgeon.Linear multifrequency probes (6-15 MHz) were used. Best preset programs were breast, thyroid, and vascular. Favorable device properties were depth focused to 2-5 cm, pulse repetition frequency (PRF/Scale) set low to 0.5-1.5 kHz/3-10 cm/s, color gain high, and wall filter (WF) low/off (50 Hz). Additional parameters were discussed. A 100% concordance rate was seen comparing preoperative perforator visualization with CCDS and intraoperative findings. Detailed picture and video material were demonstrated.CCDS is a powerful tool for preoperative perforator mapping in perforator flaps such as the ALT.

Background The privately owned companion dog is an emerging model in comparative medicine, notably because it shares the human environment including its risk factors, is affected by many analogous age-related diseases, receives comparable medical care, and has excellent veterinary medical data available. Past studies of dog lifespan have used academic, corporate or insurance data. While independent primary care data exist for the UK, none have as of yet been published for the US. This study analyzed data from three independent primary care US veterinary hospitals and identified factors that influence lifespan and mortality in a cohort of n = 20,970 privately owned dogs using Kaplan-Meier survival estimators and Cox Proportional Hazards modelling, including body size as a covariate. Results As previously reported, body size was negatively correlated with lifespan. Gonadectomy was associated with a longer lifespan, with the effect being stronger in females than in males. This lifespan advantage was conserved in gonadectomized female dogs that lived to at least ages 5 and 8 years. We did not find significant differences in lifespan between purebred and mixed breed dogs; however, breeds with larger effective population sizes and/or lower inbreeding coefficients had median survival times 3–6 months longer than breeds with smaller effective population sizes or higher inbreeding coefficients, indicating that these measures of genetic diversity may be affecting breed lifespans. We also found that dog breeds belonging to the “Mountain” ancestral group had median survival times that were 3.5–4.6 years shorter than other purebred dog groups, which remained significant even when correcting for body size. Conclusions Our findings show that it is possible to obtain and analyze data from independent veterinary clinics in the US, an approach that could be useful for studies of comparative epidemiology under the One Health and One Welfare paradigms. We also show that the lifespan effects of gonadectomy are not identical between the sexes and should be investigated separately by sex in future analyses. More research is needed to further clarify the influence of age at gonadectomy, as well as the factors leading to the observed differences in lifespan in the “Mountain” ancestral group and in dog breeds of varying inbreeding coefficients and effective population sizes.

Gentianaceae family (such as Coutoubea spicata) contains iridoids and flavonoids with antidiabetic properties. However, there is no information available about the antidiabetic effects of C. spicata when combined with resistance exercise training (RET). This study evaluated the effects of the ethanolic extract (EE) and ethyl acetate fraction (EAF) of C. spicata on biochemical markers, muscle damage, and oxidative stress in diabetic rats submitted to RET. Alloxan-induced diabetic rats were distributed into 4 groups (each group, n = 8) treated with distilled water (TD), EE, EAF, or metformin and submitted to RET. Two groups without the disease (each group, n = 8) (sedentary control and trained control), as well as a sedentary diabetic group (n = 8) were included. Body weight and glycemia were evaluated weekly. After 30 days, lipid/lipoprotein profile, aspartate aminotransferase, alanine aminotransferase, muscle damage ((creatine kinase (CK) and lactate dehydrogenase (LDH)), and oxidative stress (malondialdehyde (MDA), sulfhydryl groups (SH), and ferric reducing antioxidant power) were evaluated. MDA and SH for pancreas, liver, heart, and muscle were evaluated. C. spicata extract and fraction combined with RET recovered body weight and reduced glycemia, muscle damage (CK: 36.83% and 21.45%; LDH: 49.83% and 68.55%), and low-density lipoprotein cholesterol (70.63%; 59.18%) and improved redox status (MDA: 50.33%, 39.74%; and SH: 53.97%; 76.41%), respectively, when compared with the TD group. C. spicata plus RET promoted anti-hyperglycemic, lipid-reducing, and antioxidant effects in diabetic rats. Novelty C. spicata presents anti-hyperglycemic and lipid-lowering effects potentiated by RET. C. spicata reduces muscle injury and increases antioxidant defense.

This systematic review aimed to evaluate the variability of patellofemoral (PF) alignment and trochlear morphology in osteoarthritic knees. PF alignment of the knee was defined by the following parameters: the sulcus angle (SA), femoral trochlear depth (FTD), patellar tilt angle (PTA), lateral patellofemoral angle (LPFA), lateral femoral trochlear inclination (LFTI) and tibial tubercle–trochlear groove distance (TT–TG). The electronic databases MEDLINE and EMBASE were searched from database inception to the search date (February 19, 2019) and were screened for relevant studies. The PRISMA guidelines were followed. Articles reporting PF alignment measurements of osteoarthritic knees in patients over 40 years old were included. Data were extracted and methodological quality was assessed using a 14-item checklist. A total of 8 studies met the inclusion criteria. The studies reported mean values ± SD between 120° and 141.1° ± 7.7 for the SA; 5.8 mm ± 1.4 for the FTD; between − 0.1° ± 3.3 and 10.3° ± 5.7 for the PTA; between 5.8° ± 5.4 and 17° for the LPFA; between 23.2° ± 5.0 and 27.1° ± 4.4 for the LFTI; and 5.8 mm ± 5.4 for the TT-TG. PF alignment in the osteoarthritic knee is more variable than expected. This finding should encourage surgeons to consider the individual preoperative PF alignment more precisely with the aim of reducing anterior knee pain (AKP) after TKA. 3D-CT imaging might be of great value to analyse the PF alignment in an appropriate way. Level III.

Background Preoperative ultrasound (US)-guided perforator mapping has immensely simplified perforator flap planning. It may be executed by the microsurgeon. Device settings and selection of ultrasound modes are of utmost significance for detection of low-flow microvessels. The following study evaluates different US modes. Methods A prospective complete data acquisition was performed from July 2018 to June 2019 in a subset of patients who underwent US-guided flap planning. Multifrequency linear transducers were used applying five US modes. Brightness (B)-mode, color flow (CF), power Doppler (PD), pulse wave (PW), and B-flow modes were evaluated regarding applicability by microsurgeons. Peak systolic velocity (PSV), end diastolic velocity (EDV), and resistance index (RI) were chosen to evaluate flow characteristics. US results were correlated to intraoperative findings. Results A total number of eight patients (six males and two females) undergoing anterolateral thigh (ALT) or superficial circumflex iliac artery perforator (SCIP) flap surgery received an extensive standardized US-guided perforator characterization. Qualitative evaluation was performed in B-mode, color-coded duplex sonography (CCDS), PD, and B-flow mode. Quantitative assessment was executed using PW-mode and CCDS measuring the microvessels' diameter (mm) and flow characteristics (PSV, EDV, and RI). CCDS provided a mean diameter of 1.93 mm (range: 1.2–2.8 ± 0.51), a mean systolic peak of 16.9 cm/s (range: 9.9–33.4 ± 7.79), and mean RI of 0.71 (range: 0.55–0.87 ± 0.09) for lower limb perforators. All perforators located with US were verified by intraoperative findings. An optimized, time-effective US mapping algorithm was derived. Qualitative parameters may be evaluated with B-mode, CF, or B-flow. Smallest microvessels may be assessed in PD-mode. Lowering pulse-repetition frequency (PRF)/scale is mandatory to image low-flow microvessels as perforators. Quantitative information may be obtained using PW-mode and the distance-measuring tool in CF-mode. Image and video materials are provided. Conclusion CCDS proved to be a powerful tool for preoperative perforator characterization when using a structured approach and mapping algorithm. Different techniques may be applied for specific visualizations and performed by the microsurgeon.

BACKGROUND AND OBJECTIVES: In complex hand traumas nerves and vessels are often destructed without the possibility for primary repair. For bridging defects of nerves, veins and arteries grafts are necessary. Commonly nerve and vein grafts from adjacent donor sites as the wrist, forearm or cubital region are harvested. METHODS: This study is a retrospective cohort study. Between 2017 and 2019, 10 patients with complex hand injuries were treated. There were 8 males and 2 females, with an average age of 39 years (range 8–63 years). In all cases grafts were used of the dorsum of the foot for reconstructing of the severed digital nerves and arteries. All donor sites could be closed primarily. RESULTS: In 100% of cases nerves and veins of the dorsum of the foot showed a good size match as well as adequate length for a sufficient repair. The overall Hand Injury Severity Score (HISS) was determined with a median of 86 (range 57 to 286). In the area of the donor site no relevant complications were seen. CONCLUSIONS: In complex hand injuries the dorsum of the foot is a favorable donor site for nerve and vein graft harvest.

Background: Various clinical studies have provided estimates of life expectancy of patients with mild cognitive impairment (MCI) from outpatient clinics, but whether these apply to community-dwelling individuals at home or in primary care is uncertain. Methods: Within the population-based Rotterdam Study, we studied life expectancy with and without dementia in 648 community-dwelling persons with MCI and 6410 without MCI. Participants aged 60 years and older were assessed for MCI at baseline (2002–2014) and subsequently followed for the onset of dementia and death. We used multistate life tables to determine age-specific life expectancy with and without dementia by sex, educational attainment, and MCI subtype. Results: Total life expectancy for MCI ranged from 21.4 years (95% CI: 19.0–23.6) at age 60 to 2.6 years (1.6–3.6) at age 95. With advancing age, an increasing proportion of these years was lived with dementia (2.9 years [1.8–4.0] at age 60; 1.2 [0.2–2.2] at age 95). Women and higher educated individuals lived longer and lived more years with dementia. No differences in total life expectancy were observed by MCI subtype, although individuals with amnestic MCI lived a larger proportion of those years with dementia. Conclusions: Prognosis of MCI, in terms of life years lived with and without dementia, is more favorable in the general population than described in prior clinical observations, due likely to a substantial proportion of individuals with MCI in the clinic not seeking medical attention in an earlier stage.

Seasonal variation in cognitive function and underlying cerebral hemodynamics in humans has been suggested, but not consistently shown in previous studies. We assessed cognitive function in 10,276 participants from the population-based Rotterdam Study, aged 45 years and older without dementia, at baseline and at subsequent visits between 1999 and 2016. Seasonality of five cognitive test scores and of a summary measure of global cognition were determined, as well as of brain perfusion. Using linkage with medical records, we also examined whether a seasonal variation was present in clinical diagnoses of dementia. We found a seasonal variation of global cognition (0.05 standard deviations [95% confidence interval: 0.02–0.08]), the Stroop reading task, the Purdue Pegboard test, and of the delayed world learning test, with the best performance in summer months. In line with these findings, there were fewer dementia diagnoses of dementia in spring and summer than in winter and fall. We found no seasonal variation in brain perfusion. These findings support seasonality of cognition, albeit not explained by brain perfusion.

The purpose of this study was to determine the distribution of functional knee phenotypes in a non-osteoarthritic Asian population. The Stryker Orthopaedic Modeling and Analytics (SOMA) database was searched for CT scans of the lower limb meeting the following inclusion criteria: patient age at time of image >18 and

Treatment recommendations for fragility fractures of the pelvis (FFP) have been provided along with the good reliable FFP classification but they are not proven in large studies and recent reports challenge these recommendations. Thus, we aimed to determine the usefulness of the FFP classification determining the treatment strategy and favored procedures in six level 1 trauma centers. Sixty cases of FFP were evaluated by six experienced pelvic surgeons, six inexperienced surgeons in training, and one surgeon trained by the originator of the FFP classification during three repeating sessions using computed tomography scans with multiplanar reconstruction. The intra-rater reliability and inter-rater reliability for therapeutic decisions (non-operative treatment vs. operative treatment) were moderate, with Fleiss kappa coefficients of 0.54 (95% confidence interval [CI] 0.44–0.62) and 0.42 (95% CI 0.34–0.49). We found a therapeutic disagreement predominantly for FFP II related to a preferred operative therapy for FFP II. Operative treated cases were generally treated with an anterior–posterior fixation. Despite the consensus on an anterior–posterior fixation, the chosen procedures are highly variable and most plausible based on the surgeon’s preference.

BACKGROUND: Early detection and treatment of vascular complications in replanted digits is essential for the survival. The perfusion index (PI) represents a marker of peripheral perfusion as it shows the ratio of pulsatile to non-pulsatile blood flow. OBJECTIVE: To evaluate the feasibility and applicability of the PI as a monitoring tool for free flaps and replanted digits by measuring the inter- and intraindividual changes in PI. METHODS: Five patients were postoperatively monitored according to intern standards by hourly clinical evaluation. Additionally, a pulse oximeter with SET-technology® (Masimo Radial 7, Masimo Corporation, Irvine, USA) was added with a LNCS® Red TFA-1 SpO2 sensor (Masimo Corporation, Irvine, USA) and respectively a LNCS® Neo-3 neonatal finger clip to evaluate the perfusion via PI and SpO2. RESULTS: All patients showed sufficient perfusion in clinical controls. There was no detectable vascular complication during follow-up. Mean perfusion index was 0.93 with a median of 0.44. The patients showed a mean SpO2 of 90.59%with a median of 89.21%. CONCLUSION: Our results show a great intra- and interindividual range of PI and SpO2. SpO2 provided an even greater range than PI. Trends in intraindividual PI changes may be a promising monitoring tool for free flaps and replanted digits.

For a long time, the alignment goal for total knee arthroplasty (TKA) was a neutrally aligned limb with orthogonal joint lines to the mechanical axes (mechanical alignment). This had mainly to do with the belief of a better long-term durability because of more equal load distribution in mechanically aligned TKA. Recognizing the variability in individual knee alignment and compromised functional outcomes in TKA, there is an increasing interest among knee surgeons for more personalized, more anatomical alignment methods. Among those newer alignment concepts, the kinematic alignment method is the most promising one. The goal of the kinematic alignment concept is to restore the prearthritic alignment of a patient. To achieve this goal, surgeons need to have a profound knowledge of the individual native anatomy of the knee and its variability. This chapter provides a basis for all alignment methods and a detailed overview of the current knowledge regarding the variability of lower limb alignment. First, a review of the literature will be presented. Following the discussion of the literature, the functional knee phenotype concept is introduced. Based on these phenotypes, the difference between three alignment goals of the most common alignment concepts (mechanical, anatomical, and restricted kinematic) and the native alignment will be presented and thoroughly discussed.

Purpose The main purpose of this study was to determine whether there is a correlation between the change of tibial tuberosity-trochlear groove (TT-TG) distance and clinical outcomes after total knee arthroplasty (TKA). Methods A total of 52 knees undergoing TKA due to primary osteoarthritis were included in this retrospective study. All patients had pre- and postoperative CT scans. TT-TG distance was measured by two independent observers and the following alignment parameters were measured: hip-knee ankle angle (HKA), femoral mechanical angle (FMA), tibial mechanical angle (TMA), and posterior condylar angle (PCA). Clinical outcome was assessed using Knee Society Score (KSS) pre- and post-operatively and at a minimum of 12-month follow-up. Evidence of AKP was noted from follow-up reports. Pre- and postoperative scores were compared using a paired Student t-test. Pearson correlations were calculated to assess the influence of TT-TG on clinical outcome and of alignment parameters on the change in TT-TG. TT-TG between patients with and without AKP was compared using unpaired Student’s t-test (p Results Neither the absolute postoperative TT-TG nor the amount of change in TT-TG correlated with the post-operative KSS or the change in KSS. Post-operative TT-TG and change in TT-TG did not differ significantly between patients with and patients without AKP. Only the change in FMA showed a correlation with the change in TT-TG (p = 0.01, r = 0.36). Conclusion Despite a missing correlation between outcomes and TT-TG distance in this study, excessive TT-TG distance should be avoided. Furthermore, surgeons need to be aware that changes in femoral joint line orientation might affect TT-TG distance.

Background Smartphones and their built-in sensors allow for measuring functions in disease-related domains through mobile tests. This could improve disease characterization and monitoring, and could potentially support treatment decisions for multiple sclerosis (MS), a multifaceted chronic neurological disease with highly variable clinical manifestations. Practice effects can complicate the interpretation of both improvement over time by potentially exaggerating treatment effects and stability by masking deterioration. Objective The aim of this study is to identify short-term learning and long-term practice effects in 6 active tests for cognition, dexterity, and mobility in user-scheduled, high-frequency smartphone-based testing. Methods We analyzed data from 264 people with self-declared MS with a minimum of 5 weeks of follow-up and at least 5 repetitions per test in the Floodlight Open study, a self-enrollment study accessible by smartphone owners from 16 countries. The collected data are openly available to scientists. Using regression and bounded growth mixed models, we characterized practice effects for the following tests: electronic Symbol Digit Modalities Test (e-SDMT) for cognition; Finger Pinching and Draw a Shape for dexterity; and Two Minute Walk, U-Turn, and Static Balance for mobility. Results Strong practice effects were found for e-SDMT (n=4824 trials), Finger Pinching (n=19,650), and Draw a Shape (n=19,019) with modeled boundary improvements of 40.8% (39.9%-41.6%), 86.2% (83.6%-88.7%), and 23.1% (20.9%-25.2%) over baseline, respectively. Half of the practice effect was reached after 11 repetitions for e-SDMT, 28 repetitions for Finger Pinching, and 17 repetitions for Draw a Shape; 90% was reached after 35, 94, and 56 repetitions, respectively. Although baseline performance levels were highly variable across participants, no significant differences between the short-term learning effects in low performers (5th and 25th percentile), median performers, and high performers (75th and 95th percentile) were found for e-SDMT up to the fifth trial (β=1.50-2.00). Only small differences were observed for Finger Pinching (β=1.25-2.5). For U-Turn (n=15,051) and Static Balance (n=16,797), only short-term learning effects could be observed, which ceased after a maximum of 5 trials. For Two Minute Walk (n=14,393), neither short-term learning nor long-term practice effects were observed. Conclusions Smartphone-based tests are promising for monitoring the disease trajectories of MS and other chronic neurological diseases. Our findings suggest that strong long-term practice effects in cognitive and dexterity functions have to be accounted for to identify disease-related changes in these domains, especially in the context of personalized health and in studies without a comparator arm. In contrast, changes in mobility may be more easily interpreted because of the absence of long-term practice effects, even though short-term learning effects might have to be considered.

Objectives In recent years, increasing evidence pointed out the clinical importance of adipose tissue (AT) distribution in various patient populations. In particular, visceral adipose tissue (VAT), when compared to subcutaneous adipose tissue (SAT), was found to play a pivotal role in the development of inflammatory reaction. The aim of the present study was to examine whether body fat distribution has an impact on the development of systemic inflammatory response syndrome (SIRS) in patients with polytrauma. Methods In our retrospective study, we filtered our institution records of the German Trauma Registry (Trauma Register DGU) from November 2018 to April 2021 and included 132 adult polytrauma patients with injury severity score (ISS) &gt, 16. Subsequently, we measured the visceral and subcutaneous adipose tissue area based on whole-body CT scan and calculated the ratio of VAT to SAT (VSr). Thereafter, the patient population was evenly divided into three groups, respectively VSr value less than 0.4 for the first group (low ratio), 0.4–0.84 for the second group (intermediate ratio), and greater than 0.84 for the third group (high ratio). Considering the other influencing factors, the groups were further divided into subgroups in the respective analysis according to gender (male/female), BMI (&lt, 25 or ³25), and ISS (&lt, 26 or ³26). Result VSr was an independent factor from body mass index (BMI) (r2 = 0.003, p = 0.553). VSr in male patients was significantly higher (p &lt, 0.001). Patients with low VSr had higher ISS scores (p = 0.028). Polytrauma patients with higher VSr tended to have lower SIRS scores and significant differences of SIRS score were found on multiple days during the whole hospitalization period. In the low VAT/SAT group, male patients, and patients with BMI greater than 25, both exhibited higher SIRS scores during hospital stay (day 16: p = 0.01, day 22: p = 0.048 and p = 0.011, respectively). During hospitalization, patients with higher ISS score (³26) in the low VSr group was found to have higher SIRS score (day 16, p = 0.007). Over the hospital stay, serum markers of CRP, CK, and leukocyte in patients with low VSr were higher than those in patients in the intermediate and high VSr groups, with significant difference discovered on multiple days (day 16: 0.014, day 22: p = 0.048). Conclusion Lower VSr is associated with increased inflammatory response and worse clinical outcome in patients with polytrauma. Furthermore, VSr is an independent factor providing additional information to BMI.

Background During the Coronavirus Disease 2019 (COVID-19) pandemic, the number of consultations and diagnoses in primary care and referrals to specialist care declined substantially compared to prepandemic levels. Beyond deferral of elective non-COVID-19 care by healthcare providers, it is unclear to what extent healthcare avoidance by community-dwelling individuals contributed to this decline in routine healthcare utilisation. Moreover, it is uncertain which specific symptoms were left unheeded by patients and which determinants predispose to healthcare avoidance in the general population. In this cross-sectional study, we assessed prevalence of healthcare avoidance during the pandemic from a patient perspective, including symptoms that were left unheeded, as well as determinants of healthcare avoidance. Methods and findings On April 20, 2020, a paper COVID-19 survey addressing healthcare utilisation, socioeconomic factors, mental and physical health, medication use, and COVID-19–specific symptoms was sent out to 8,732 participants from the population-based Rotterdam Study (response rate 73%). All questionnaires were returned before July 10, 2020. By hand, prevalence of healthcare avoidance was subsequently verified through free text analysis of medical records of general practitioners. Odds ratios (ORs) for avoidance were determined using logistic regression models, adjusted for age, sex, and history of chronic diseases. We found that 1,142 of 5,656 included participants (20.2%) reported having avoided healthcare. Of those, 414 participants (36.3%) reported symptoms that potentially warranted urgent evaluation, including limb weakness (13.6%), palpitations (10.8%), and chest pain (10.2%). Determinants related to avoidance were older age (adjusted OR 1.14 [95% confidence interval (CI) 1.08 to 1.21]), female sex (1.58 [1.38 to 1.82]), low educational level (primary education versus higher vocational/university 1.21 [1.01 to 1.46), poor self-appreciated health (per level decrease 2.00 [1.80 to 2.22]), unemployment (versus employed 2.29 [1.54 to 3.39]), smoking (1.34 [1.08 to 1.65]), concern about contracting COVID-19 (per level increase 1.28 [1.19 to 1.38]) and symptoms of depression (per point increase 1.13 [1.11 to 1.14]) and anxiety (per point increase 1.16 [1.14 to 1.18]). Study limitations included uncertainty about (perceived) severity of the reported symptoms and potentially limited generalisability given the ethnically homogeneous study population. Conclusions In this population-based cross-sectional study, 1 in 5 individuals avoided healthcare during lockdown in the COVID-19 pandemic, often for potentially urgent symptoms. Healthcare avoidance was strongly associated with female sex, fragile self-appreciated health, and high levels of depression and anxiety. These results emphasise the need for targeted public education urging these vulnerable patients to timely seek medical care for their symptoms to mitigate major health consequences., Marije J. Splinter and colleagues assess the prevalence of healthcare avoidance during the COIVD-19 pandemic and investigate related determinants, Author summary Why was this study done? ➢ During the Coronavirus Disease 2019 (COVID-19) pandemic, consultation rates in both primary and specialist care declined compared to prepandemic levels, which can partially be attributed to the postponement or cancellation of elective and nonurgent medical care. ➢ It is unclear to what extent these declines in consultation rates could be related to healthcare avoidance by patients in the general population. ➢ To evaluate the collateral health damage of the COVID-19 pandemic, it is important to not only assess the prevalence of healthcare avoidance, but also for what symptoms healthcare was avoided and which determinants are associated with this behaviour. What did the researchers do and find? ➢ We sent out a paper questionnaire to 8,732 participants of the population-based Rotterdam Study containing several COVID-19–related subjects, such as healthcare utilisation, work status, mental and physical health, and concerns about contracting COVID-19. ➢ About 6,241 participants (73%) returned the questionnaire, of whom 5,656 participants (90.6%) were included in our analyses. We found that 1,142 of them (20.2%) avoided healthcare during the COVID-19 pandemic, often for symptoms that might have needed urgent medical evaluation, such as limb weakness (13.6%), palpitations (10.8%), and chest pain (10.2%). ➢ Determinants that were most strongly associated with healthcare avoidance were female sex, poor self-appreciated health, and high levels of depression and anxiety. What do these findings mean? ➢ The results of this population-based study suggest that healthcare avoidance contributed to the decline in consultation rates during the COVID-19 pandemic. Importantly, our findings suggest that this behaviour may be associated with certain vulnerable groups within the population. ➢ These findings should be interpreted in light of the limitations of this study, which include that the actual severity of the symptoms that were reported by participants is unknown, since they were not medically evaluated when they experienced these symptoms. ➢ The findings of this study can be used to develop policy interventions targeted to vulnerable individuals who may be more likely to exhibit healthcare avoiding behaviours.

Purpose The objectives of the work presented in this paper were to (1) implement a robust-optimization method for deliverable mixed-beam radiotherapy (MBRT) plans within a previously developed MBRT planning framework; (2) perform an experimental validation of the delivery of robust-optimized MBRT plans; and (3) compare PTV-based and robust-optimized MBRT plans in terms of target dose robustness and organs at risk (OAR) sparing for clinical head and neck and brain patient cases. Methods A robust-optimization method, which accounts for translational setup errors, was implemented within a previously developed treatment planning framework for MBRT. The framework uses a hybrid direct aperture optimization method combining column generation and simulated annealing. A robust plan was developed and then delivered to an anthropomorphic head phantom using the Developer Mode of a TrueBeam linac. Planar dose distributions were measured and compared to the planned dose. Robust-optimized and PTV-based plans were developed for three clinical patient cases consisting of two head and neck cases and one brain case. The plans were compared in terms of the robustness to 5 mm shifts of the target volume dose as well as in terms of OAR sparing. Results Using a gamma criterion of 3%/2 mm and a dose threshold of 10%, the agreement between film measurements and dose calculations was better than 97.7% for the total plan and better than 95.5% for the electron component of the plan. For the two head and neck patient cases, the average clinical target volume (CTV) dose homogeneity index (V95%–V107%) over all the considered setup error scenarios was on average 19% lower for the PTV-based plans and it had a larger standard deviation. The robust-optimized plans achieved, on average, a 20% reduction in the OAR doses compared to the PTV-based plans. For the brain patient case, the CTV dose homogeneity index was similar for the two plans, while the OAR doses were 22% lower, on average, for the robust-optimized plan. No clear trend in terms of electron contributions was found across the three patient cases, although robust-optimized plans tended toward higher electron beam energies. Conclusions A framework for robust optimization of deliverable MBRT plans has been developed and validated. PTV-based MBRT were found to not be robust to setup errors, while the dose delivered by the robust-optimized plans were clinically acceptable for all considered error scenarios and had better OAR sparing. This study shows that the robust optimization is a promising alternative to conventional PTV margins for MBRT., Medical Physics, 48 (11), ISSN:0094-2405, ISSN:2473-4209, ISSN:1522-8541