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Purpose/Objective Multiple tumorous lesions in one pituitary gland are rare and mostly described in case reports. Their incidences and combinations are defined in larger collectives. Therefore, we analyzed our large collection for double tumors and combinations of tumors, cysts, and inflammation. Methods The German Registry of Pituitary Tumors, including cases from 1990 to 2018, served as the database. Our collection comprises a total of 16,283 cases up until the end of 2018. Of these cases, 12,673 originated from surgical and 3,610 from autopsy material. All specimens were fixed in formalin and embedded in paraffin. The sections were stained with hematoxylin–eosin and PAS. Monoclonal (prolactin, TSH, FSH, LH, and α subunit) or polyclonal (GH and ACTH) antibodies were used to detect pituitary hormones in the lesions. Since 2017, antibodies against the transcription factors Pit-1, T-Pit, and SF-1 have been used in difficult cases. The criteria of the 2017 WHO classification have been basic principles for classification since 2018 (Osamura et al. 2017). For differentiation of other sellar tumors, such as meningiomas, chordomas, or metastases, the use of additional antibodies was necessary. For these cases, it was possible to use a broad antibody spectrum. Autopsy pituitaries were generally studied by H&E and PAS sections. If any lesions were demonstrated in these specimens, additional immunostaining was performed. Results Multiple tumorous lesions with more than one pituitary neuroendocrine tumor (PitNET) respectively adenoma make up 1.4% (232 cases) in our collection. Within the selected cases, synchronous multiple pituitary neuroendocrine tumors (PitNETs) account for 17.3%, PANCH cases (pituitary adenoma with neuronal choristoma) for 14.7%, PitNETs and posterior lobe tumors for 2.2%, PitNETs and metastases for 5.2%, PitNETs and mesenchymal tumors for 2.6%, PitNETs and cysts for 52.2%, and PitNETs and primary inflammation for 6.0%. The mean patient age was 53.8 years, with a standard deviation of 18.5 years. A total of 55.3% of the patients were female and 44.7% were male. From 1990 to 2018, there was a continuous increase in the number of multiple tumorous lesions. Conclusion From our studies, we conclude that considering possible tumorous double lesions during surgeries and in preoperative X-ray analyses is recommended.

To assess the potential influence of multifidus atrophy and fatty degeneration on the incidence of adjacent vertebral compression fractures within one year after the index fracture. In a retrospective cohort study, patients who underwent surgery for an OVCF were identified and baseline characteristics, fracture patterns and the occurrence of secondary adjacent fractures within one year were obtained by chart review. Multifidus muscle atrophy and fatty degeneration were determined on preoperative MRI or CT scans. In this analysis of 191 patients (mean age 77 years, SD 8, 116 female), OF type 3 was the most common type of OVCF (49.2%). Symptomatic adjacent OVCFs within one year after index fracture were observed in 23/191 patients (12%) at mean 12, SD 12 weeks (range 1–42 weeks) postoperatively. The mean multifidus muscle area was 264, SD 53 mm2 in patients with an adjacent vertebral fracture and 271, SD 92 mm2 in patients without a secondary fracture (p = 0.755). Mean multifidus fatty infiltration was graded Goutallier 2.2, SD 0.6 in patients with an adjacent fracture and Goutallier 2.2, SD 0.7 in patients without an adjacent fracture (p = 0.694). Pre-existing medication with corticosteroids was associated with the occurrence of an adjacent fracture (p = 0.006). Multifidus area and multifidus fatty infiltration had no significant effect on the occurrence of adjacent vertebral fractures within one year after the index fracture. Patients with a pre-existing medication with corticosteroids were more likely to sustain an adjacent fracture.

Purpose The aim of this systematically review is to detect differences between fractures located at the mid-thoracic spine compared to fractures of the thoracolumbar junction (TLJ) and the lumbar spine in osteoporotic vertebral body fractures. Methods This review is based on articles retrieved by a systematic search in the PubMed and Web of Science database for publications regarding osteoporotic fractures of the thoracolumbar spine with respect to the fracture location. Differences in prevalence, cause of fracture, fracture healing, and outcomes between the mid-thoracic spine and the TLJ and the lumbar spine were considered. Results Altogether, 238 articles could be retrieved from the literature search. A total of 222 articles were excluded. Thus, 16 remaining original articles were included in this systematic review comprising the topics prevalence, bone mineral density and regional blood flow, biomechanics, subsequent fractures, and outcome, respectively. The overall level of evidence of the vast majority of studies was moderate to low. Conclusion Several differences between osteoporotic fractures of the mid-thoracic spine compared to the TLJ and the lumbar spine could be identified. Thereby, osteoporotic mid-thoracic fractures seem to be particularly more related to frailty without a history of traumatic injury compared to osteoporotic fractures of the TLJ and the lumbar spine. Additionally, the presence of severe mid-thoracic fractures predicts subsequent fractures of the hip. In contrast, subsequent fractures of the spine are less likely.

Purpose Pituitary adenoma (PA) constitutes the third most common intracranial neoplasm. The mostly benign endocrine lesions express no hormone (null cell PA) or the pituitary hormone(s) of the cell lineage of origin. In 0.5–1.5% of surgical specimens and in up to 10% of autopsy cases, two or three seemingly separate PA may coincide. These multiple adenomas may express different hormones, but whether or not expression of lineage-restricted transcription factors and molecular features are distinct within multiple lesions remains unknown. Methods Searching the data bank of the German Pituitary Tumor Registry 12 double pituitary adenomas with diverse lineage were identified among 3654 adenomas and 6 hypophyseal carcinomas diagnosed between 2012 and 2020. The double adenomas were investigated immunohistochemically for expression of hormones and lineage markers. In addition, chromosomal gains and losses as well as global DNA methylation profiles were assessed, whenever sufficient material was available (n = 8 PA). Results In accordance with the literature, combinations of GH/prolactin/TSH–FSH/LH adenoma (4/12), GH/prolactin/TSH–ACTH adenoma (3/12), and ACTH–FSH/LH adenoma (3/12) were observed. Further, two out of 12 cases showed a combination of a GH/prolactin/TSH adenoma with a null-cell adenoma. Different expression pattern of hormones were confirmed by different expression of transcription factors in 11/12 patients. Finally, multiple lesions that were molecularly analysed in 4 patients displayed distinct copy number changes and global methylation pattern. Conclusion Our data confirm and extend the knowledge on multiple PA and suggest that such lesions may origin from distinct cell types.

Background Coronavirus disease 2019 vaccine ChAdOx1 nCov-19 may rarely lead to vaccine-induced thrombotic thrombocytopenia (VITT). Antibody-mediated, platelet factor 4 (PF4)-dependent platelet activation appears to resemble a key mechanism in VITT, partially comparable to heparin-induced thrombocytopenia. The use of PF4/heparin immunoassays has been proposed as part of a diagnostic approach, but their sensitivity has not been established. Methods Sera from 12 well-defined VITT patients were first studied by two different laboratories in functional assays. Sera where then used for an interlaboratory comparison, in which five different PF4/heparin immunoassays were used by four laboratories. Results Results for functional testing were highly concordant. VITT antibodies were also reliably detected by PF4/heparin enzyme-linked immunosorbent assays (ELISAs) (92–100%). In contrast, only 25% of VITT antibodies were reactive in a particle gel immunoassay (PaGIA), and 8% in a lateral flow assay (LFA). An automated chemiluminescence immunoassay (CLIA) was negative for all sera tested (0%). Conclusion It seems feasible to establish functional antibody testing for the confirmation of VITT. For the initial screening of suspected VITT cases, PaGIA, LFA, and CLIA are useless when applied as single tests. Only ELISA-based PF4/heparin immunoassays are sensitive enough to be incorporated in the diagnostic workup. However, a combination of a positive ELISA and a negative CLIA may be useful to identify VITT antibodies in the absence of confirmatory functional assays.

Study Design: Systematic review. Objectives: Postoperative spinal implant infections (PSII) are an increasing challenge in the daily clinical routine. This review summarizes existing knowledge in the field of PSII, including definitions, epidemiology, classifications, risk factors, pathogenesis, symptoms, diagnosis, and treatment. Methods: A systematic review was performed using a structured PubMed analysis, based on the PRISMA criteria. The search terminology was set as: “spinal implant associated infection OR spinal implant infection OR spinal instrumentation infection OR peri spinal implant infection.” PubMed search was limited to the categories randomized controlled trials (RCT), clinical trials, meta-analysis and (systematic) reviews, whereas case reports were excluded. Studies from January 2000 to December 2020 were considered eligible. A total of 572 studies were identified, 82 references included for qualitative synthesis, and 19 for detailed sub analysis (12 meta-analysis, 7 prospective RCT). Results: Structural problems in the field of PSII were revealed, including (1) limited level of evidence in clinical studies (missing prospective RCT, metanalyzes), (2) small patient numbers, (3) missing standardized definitions, (4) heterogeneity in patient groups, and (5) redundancy in cited literature. Conclusion: Evidence-based knowledge about spinal implant-associated infections is lacking. All involved medical fields should come together to define the term PSII and to combine their approaches toward research, training, and patient care.

ZusammenfassungDie fetale und neonatale Alloimmunthrombozytopenie (FNAIT) wird durch mütterliche Antikörper hervorgerufen, die gegen ein vom Vater ererbtes Blutgruppenmerkmal an fetalen Thrombozyten gerichtet sind. Während Teil 1 des Beitrags Ausgabe die Ätiologie, die Pathogenese und die Diagnostik der FNAIT thematisiert hatte, widmet sich dieser 2. Teil der Risikostratifizierung und Behandlung 1.

ZusammenfassungDie fetale und neonatale Alloimmunthrombozytopenie (FNAIT) wird durch mütterliche Antikörper hervorgerufen, die gegen ein vom Vater ererbtes Blutgruppenmerkmal an fetalen Thrombozyten gerichtet sind. Teil 1 des Beitrags stellt die Ätiologie, die Pathogenese und die Diagnostik der FNAIT dar, während Teil 2 die Risikostratifizierung und Behandlung der FNAIT thematisiert 1.

Vaccine administration is under way worldwide to combat the current COVID‐19 pandemic. The newly developed vaccines are highly effective with minimal adverse effects. Recently, the AstraZeneca ChadOx1 nCov‐19 vaccine has raised public alarm with concerns regarding the rare, but serious, development of thrombotic events, now known as vaccine‐induced immune thrombotic thrombocytopenia (VITT). These thrombotic events appear similar to heparin‐induced thrombocytopenia, both clinically and pathologically. In this manuscript, the ISTH SSC Subcommittee on Platelet Immunology outlines guidelines on how to recognize, diagnose and manage patients with VITT.

Introduction Because of the rarity of double heterozygosity for Factor V Leiden (FVL) and Prothrombin (FII) G20210A, little is known about the thrombotic phenotype in double heterozygotes. Material and methods In a retrospective cohort study of patients referred for a thrombophilia work-up, we investigated whether double heterozygotes (n = 138) exhibit a more severe thrombotic phenotype compared with single FVL or FIIG20210A heterozygotes, single FVL homozygotes, or wildtype carriers. Results The risk of venous thromboembolism (VTE) was higher for female but not male double heterozygotes compared with single heterozygotes (FVL: 2.51, 95%CI 1.55–4.08, FIIG20210A: 1.75, 95%CI 1.14–2.68) and wildtype carriers (HR 2.53, 95%CI 1.58–4.05) but not compared with FVL homozygotes (HR 1.31, 95%CI 0.94–1.83). Female double heterozygotes developed VTE nearly a decade earlier than wildtype carriers and FVL heterozygotes (mean 44.2 vs. 52.6 and 52.2 years), most often in association with oral contraceptives. Spontaneous VTE and arterial thromboembolic events were not more frequent in double heterozygotes compared with the other genotype groups. Deep vein thrombosis (DVT) of the lower limb was the predominant VTE location in double heterozygotes, atypical vein thrombosis was rare. A phenomenon that has been described as the FVL paradox, a higher proportion of isolated DVT than pulmonary embolism, was also found for double heterozygotes. Conclusion The thrombotic phenotype in double heterozygotes resembles the appearance of the thrombotic phenotype in FVL carriers but the thrombotic risk is aggravated by women-specific risk factors.

Misinterpretations of the p value and the introduction of bias through arbitrary analytical choices have been discussed in the literature for decades. Nonetheless, they seem to have persisted in empirical research, and criticisms of p value misuses have increased in the recent past due to the non-replicability of many studies. Unfortunately, the critical concerns that have been raised in the literature are scattered over many disciplines, often linguistically confusing, and differing in their main reasons for criticisms. Misuses and misinterpretations of the pvalue are currently being discussed intensely under the label “replication crisis” in many academic disciplines and journals, ranging from specialized scientific journals to Nature and Science. In a drastic response to the crisis, the editors of the journal Basic and Applied Social Psychology even decided to ban the use of pvalues from future publications at the beginning of 2015, a fact that has certainly added fuel to the discussions in the relevant scientific forums. Finally, in early March, the American Statistical Association released a brief formal statement on pvalues that explicitly addresses misuses and misinterpretations. In this context, we systematize the most serious flaws related to the pvalue and discuss suggestions of how to prevent them and reduce the rate of false discoveries in the future.

Purpose The aim of this study was to give a systematic overview over the rate and location of concomitant injuries, the probability of suffering from neurological deficits, and to give evidence of the timing of surgery in severely injured patients with unstable thoracic vertebral body fractures. Methods This review is based on articles retrieved by a systematic search in the PubMed and Web of Science database for publications up to November 2020 dealing with unstable fractures of the mid-thoracic spine. Results Altogether, 1109 articles were retrieved from the literature search. A total of 1095 articles were excluded. Thus, 16 remaining original articles were included in this systematic review depicting the topics timing of surgery in polytraumatized patients, outcome neurologic deficits, and impact of concomitant injuries. The overall level of evidence of the vast majority of studies is low. Conclusion The evidence of the available literature is low. The cited studies reveal that thoracic spinal fractures are associated with a high number of neurological deficits and concomitant injuries, particularly of the thoracic cage and the lung. Thereby, diagnostic algorithm should include computer tomography of the whole thoracic cage if there is any clinical sign of concomitant injuries. Patients with incomplete neurologic deficits benefit from early surgery consisting of decompression and long-segmental stabilization.

Although non-functioning pituitary tumors are frequent, diagnostic and therapeutic concepts are not well standardized. We here present the first German multidisciplinary guideline on this topic. The single most important message is to manage the patients by a multidisciplinary team (consisting at least of an endocrinologist, a neurosurgeon, and a (neuro-) radiologist). The initial diagnostic work-up comprises a detailed characterization of both biochemical (focusing on hormonal excess or deficiency states) and morphological aspects (with magnetic resonance imaging of the sellar region). An ophthalmological examination is only needed in presence of symptoms or large tumors affecting the visual system. Asymptomatic, hormonally inactive tumors allow for a 'wait and scan' strategy. In contrast, surgical treatment by an experienced pituitary surgeon is standard of care in case of (impending) visual impairment. Therapeutic options for incompletely resected or recurrent tumors include re-operation, radiotherapy, and observation; the individual treatment plan should be developed multidisciplinary. Irrespective of the therapeutic approach applied, patients require long-term follow-up. Patient with larger pituitary tumors or former surgery/radiotherapy should be regularly counseled regarding potential symptoms of hormonal deficiency states.

The current mainstay for the treatment of thrombotic antiphospholipid syndrome (APS) is anticoagulation with vitamin K antagonists (VKAs). The use of direct oral anticoagulants (DOACs) is under debate. We aimed to assess whether DOACs would be safe in APS patients presenting to the thrombosis clinic. A retrospective cohort study was conducted. All patients presenting to our thrombosis clinic between 2010 and 2017 with a diagnosis of APS taking either VKAs or DOACs were included. APS diagnosis was based on the revised Sapporo criteria. Clinical and laboratory data were collected from the electronic and physical patient files. Out of 200 patients, 81 received VKAs, and 119 DOACs. The two cohorts did not differ with regard to their initial clinical manifestation or additional prothrombotic risk factors. Only a small minority of patients was antiphospholipid antibody triple positive (VKA, 7.0% vs. DOAC, 4.2%). Number of on-treatment events was low (3 vs. 2). The hazard ratio for any thromboembolic event for patients taking DOACs was 0.78 (95% confidence interval, 0.12-5.19). Treatment with DOACs was not associated with an increased risk of recurrent thromboembolism in comparison with VKAs in this retrospective study. Our observation supports the assumption that in nontriple positive (low risk) APS patients, DOACs might be safe. Prospective data are urgently needed.

Purpose Hemiarthroplasty is widely accepted as the treatment of choice in elderly patients with a displaced intracapsular femoral neck fracture. Intraoperative greater trochanteric fractures thwart this successful procedure, resulting in prolonged recovery, inferior outcome, and increased risk of revision surgery. Hence, this study analyzed factors potentially associated with an increased risk for intraoperative greater trochanteric fracture. Methods This retrospective study included 512 hemiarthroplasties in 496 patients with a geriatric intracapsular femoral neck fracture from July 2010 to March 2020. All patients received the same implant type of which 90.4% were cemented and 9.6% non-cemented. Intra- and postoperative radiographs and reports were reviewed and particularly screened for greater trochanteric fractures. Results Female patients accounted for 74% and mean age of the patients was 82.3 (± 8.7) years. 34 (6.6%) intraoperative greater trochanteric fractures were identified. In relation to patient-specific factors, only a shorter prothrombin time was found to be significantly associated with increased risk of intraoperative greater trochanteric fracture (median 96%, IQR 82–106% vs. median 86.5%, IQR 68.8–101.5%; p = 0.046). Other factors associated with greater trochanteric fracture were a shorter preoperative waiting time and changes in perioperative settings. Outcome of patients with greater trochanteric fracture was worse with significantly more surgical site infection requiring revision surgery (17.6% vs. 4.2%, p = 0.005). Conclusion Prolonged prothrombin time, a shorter preoperative waiting time, and implementing new procedural standards and surgeons may be associated with an increased risk of a greater trochanteric fracture. Addressing these risk factors may reduce early periprosthetic infection which is strongly related to greater trochanteric fractures.

Background The long-term outcome of facet joint replacement (FJR) still is to be proven. Methods We present a prospective case series of 26 (male-to-female ratio of 1:1; mean age: 61 years) patients undergoing FJR with a follow-up of at least 1 year (range: 12–112; mean: 67 months). Visual analog scale (VAS) for back and leg pain, Oswestry Disability Index (ODI), and the 12-Item Short Form Health Survey (SF-12) were applied pre- and postoperatively (after 3, 6, and 12 months) as well as at the last follow-up (N = 24). Using X-rays of the lumbar spine (N = 20), the range of motion (ROM) and disk height in the indicator and adjacent levels were assessed. Results FJR was performed at L3/L4 (N = 7), L4/L5 (N = 17), and L5/S1 (N = 2). Mean VAS (mm) for back pain decreased from 71 to 18, mean VAS for right leg pain from 61 to 7, and from 51 to 3 for the left leg. Mean ODI dropped from 51 to 22% (for all p Conclusions In selected cases, long-term results of FJR show good outcome concerning pain, quality of life, preservation of lumbar spine motion, and protection of adjacent level.

Purpose To analyze the indications, radiological short-term outcomes, and complications of ankle fractures in geriatric patients treated with a triangular external fixator (AEF) until fracture healing. Furthermore, the effect of an additional osteosynthesis to AEF on the radiological outcome was investigated. Methods Retrospective analysis of ankle fractures treated in a Level I Trauma Center between 2005 and 2015 with an AEF in patients aged ≥ 65 years until fracture has healed. The combination of AEF and at least one additional osteosynthesis of a malleolus was defined as hybrid external fixator (HEF). At the time of AEF removal, a preserved ankle joint congruity was defined as good radiological outcome. Incongruity more than 2 mm was defined as poor radiologic results. Results 16 patients (13 women, 3 men) with a mean age of 74 years (SD 6.2) were treated with AEF until fracture healing, 9 with a single AEF and 7 with a HEF. Stabilization with HEF (n = 7 [100%]) showed higher rates of good radiological outcome than AEF alone (n = 4 [44%] of 9; p = 0.034). The duration of therapy did not differ between HEF and AEF (70 day vs 77 days). 4 patients (22%) required surgical revision. Conclusion It could be shown that osteosynthesis in addition to AEF leads to a better radiological short-term results than using AEF alone. Therefore, in the situation where an AEF is considered as the definitive treatment option for an ankle fracture in geriatric patients with expected or existing soft tissue problems, it should be done or completed as a HEF. Level of evidence Therapeutic level IV.

The prevalence of nonspecific pyogenic spondylodiskitis, associated with both a high morbidity and a high mortality, has increased in the last few decades. The diagnosis is often delayed because of the nonspecific clinical manifestation at the early stage. The reliability of radiographs is limited, particularly in early stage after the onset of infection. Computed tomography (CT) can reliably assess the bony condition with the possibility of spatial visualization. Contrast enhancement supports the detection of affected soft tissue. Magnetic resonance imaging (MRI) continues to be the gold standard in the diagnosis of spondylodiskitis. Sophisticated investigation protocols supported by gadolinium enhancement secure the diagnosis. MRI has a high resolution without radiation exposure. Different nuclear investigation techniques extend the diagnostic options. Reports of 18F-fluorodeoxyglucose-positron emission tomography (18-FDG-PET) are particularly promising to confirm the diagnosis. The drawback of the reduced image quality with respect to detailed anatomical information can be overcome by a combined simultaneous acquisition of CT or MRI. With respect to one of the greatest challenges, the differentiation between degenerative changes (Modic type 1) and infection at an early stage using differentiated MRI protocols and FDG-PET is promising. This overview presents a concise state-of-the-art look at radiologic investigations in case of suspected nonspecific pyogenic spondylodiskitis with the focus on a pragmatic approach.

Background In most patients having noncardiac surgery, blood pressure is measured with the oscillometric upper arm cuff method. Although the method is noninvasive and practical, it is known to overestimate intraarterial pressure in hypotension and to underestimate it in hypertension. A high-fidelity upper arm cuff incorporating a hydraulic sensor pad was recently developed. The aim of the present study was to investigate whether noninvasive blood pressure measurements with the new high-fidelity cuff correspond to invasive measurements with a femoral artery catheter, especially at low blood pressure. Methods Simultaneous measurements of blood pressure recorded from a femoral arterial catheter and from the high-fidelity upper arm cuff were compared in 110 patients having major abdominal surgery or neurosurgery. Results 550 pairs of blood pressure measurements (5 pairs per patient) were considered for analysis. For mean arterial pressure measurements, the average bias was 0 mmHg, and the precision was 3 mmHg. The Pearson correlation coefficient was 0.96 (P < 0.0001; 95% CI, 0.96 to 0.97), and the percentage error was 9%. Error grid analysis showed that the proportions of mean arterial pressure measurements done with the high-fidelity cuff method were 98.4% in zone A (no risk), 1.6% in zone B (low risk) and 0% in zones C, D, and E (moderate, significant, and dangerous risk, respectively). The high-fidelity cuff method detected mean arterial pressure values less than 65 mmHg with a sensitivity of 84% (95% CI, 74 to 92%) and a specificity of 97% (95% CI, 95% to 98%). To detect changes in mean arterial pressure of more than 5 mmHg, the concordance rate between the two methods was 99.7%. Comparable accuracy and precision were observed for systolic and diastolic blood pressure measurements. Conclusions The new high-fidelity upper arm cuff method met the current international standards in terms of accuracy and precision. It was also very accurate to track changes in blood pressure and reliably detect severe hypotension during noncardiac surgery. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

IntroductionIn pregnant women with a history of fetal and neonatal alloimmune thrombocytopenia (FNAIT), prenatal intervention in subsequent pregnancies may be required to prevent fetal bleeding. Several invasive and non-invasive protocols have been published: amniocentesis for fetal genotyping, fetal blood sampling for the determination of fetal platelet count, intrauterine platelet transfusions, and weekly maternal i.v. immunoglobulin (IVIG) infusion with or without additional corticosteroid therapy. This is the first retrospective study that report the experience with a non-invasive protocol focused on side effects of maternal IVIG treatment and neonatal outcome.MethodsPregnant women with proven FNAIT in history and an antigen positive fetus were treated with IVIG (1 g/kg/bw) every week. To identify potential IVIG-related hemolytic reactions isoagglutinin titer of each IVIG lot and maternal blood count were controlled. IVIG-related side effects were prospectively documented and evaluated. Furthermore, ultrasound examination of the fetus was performed before starting IVIG administration and continued regularly during treatment. Outcome of the index and subsequent pregnancy was compared. Corresponding data of the newborns were analyzed simultaneously.ResultsIVIG was started at 20 weeks of gestation (median). Compared to the index pregnancy, platelet counts of the newborns were higher in all cases. No intracranial hemorrhage occurred (Index pregnancies: 1 case). Platelet counts were 187 × 109/l (median, range 22–239, 95% CI) and one newborn had mild bleeding. No severe hemolytic reaction was observed and side effects were moderate.ConclusionAmong pregnant women with FNAIT history, the use of non-invasive fetal risk determination and maternal IVIG resulted in favorite outcome of all newborns. Invasive diagnostic or therapeutic procedures in women with a history of FNAIT should be abandoned.

The majority of traumatic vertebral fractures occur at the thoracolumbar junction and the lumbar spine and less commonly at the mid-thoracic and upper thoracic spine. In accordance, a high number of articles are dealing with thoracolumbar fractures focusing on the thoracolumbar junction. Nonetheless, the biomechanics of the thoracic spine differ from the thoracolumbar junction and the lumbar vertebral spine. The aim of this review is to screen the literature dealing with acute traumatic thoracic vertebral fractures in patients with normal bone quality. Thereby, the diagnostic of thoracic vertebral body fractures should include a CT examination. Ideally, the CT should include the whole thoracic cage particularly in patients suffering high energy accidents or in those with clinical suspicion of concomitant thoracic injuries. Generally, concomitant thoracic injuries are frequently seen in patients with thoracic spine fractures. Particularly sternal fractures cause an increase in fracture instability. In case of doubt, long segment stabilization is recommended in patients with unstable mid- und upper thoracic fractures, particularly in those patients with a high grade of instability.

Wirbelsaulenverletzungen im Kindesalter sind insgesamt sehr selten. Aktuelle einschlagige Studien mit grosen Fallzahlen, aus welchen sich evidenzbasierte Empfehlungen zu Diagnostik und Therapie von Wirbelsaulenverletzungen bei padiatrischen Patienten ableiten lassen, existieren nicht. Formulierung von Empfehlungen zu Diagnostik und Therapie von Verletzungen der Brust- und Lendenwirbelsaule im Kindesalter. Zunachst erfolgte eine Recherche von Primar-, aber auch Sekundarliteratur zum Themenkomplex Diagnostik und Therapie von Verletzungen der Wirbelsaule bei Kindern. Eine entsprechende interne Literaturdatenbank wurde angelegt und gepflegt. Im Zeitraum von April 2017 bis Dezember 2019 fanden sich die Mitglieder der Arbeitsgemeinschaft Wirbelsaulentrauma im Kindesalter der Sektion Wirbelsaule der Deutschen Gesellschaft fur Orthopadie und Unfallchirurgie zu einem Konsensusprozess zusammen. In 9 Arbeitstreffen wurden systematisch Empfehlungen zu Diagnostik und Therapie von Verletzungen der Wirbelsaule bei Kindern formuliert. Es konnten Empfehlungen zu Diagnostik und Therapie von Verletzungen der Brust- und Lendenwirbelsaule fur 3 Altersstufen (Altersstufe I: 0 bis 6 Jahre; Altersstufe II: 7 bis 9 Jahre; Altersstufe III: 10 bi s16 Jahre) formuliert werden. Die Prinzipien der Diagnostik und Therapie aus der Erwachsenenmedizin konnen nicht problemlos ubertragen werden. Wirbelsaulenverletzungen im Kindesalter sind selten und sollten der Behandlung in geeigneten Zentren zugefuhrt werden. Die MRT-Diagnostik sollte beim kardiopulmonal stabilen Kind mit Verdacht auf ein Monotrauma der Wirbelsaule als initiale Bildgebung indiziert werden. Die grundlegenden Therapieziele bei Verletzungen der Brust- und Lendenwirbelsaule im Kindesalter sind die Wiederherstellung der Stabilitat, der Schutz der neurogenen Strukturen und das Wiederherstellen der anatomisch korrekten Verhaltnisse. Bei der Indikationsstellung zur konservativen vs. operativen Therapie mussen das Korrektur- und Regenerationspotenzial der einzelnen Wirbelsaulenabschnitte in Abhangigkeit vom Patientenalter berucksichtigt werden. Die operative Stabilisierung soll v. a. uber minimalinvasive Techniken, im Sinne einer Instrumentierung ohne Spondylodese und fruhzeitiger Metallentfernung, erfolgen.

Generell stellen Wirbelsaulenverletzungen bei Kindern im Alter unter 16 Jahren eine seltene Verletzungsentitat dar. Fur Deutschland liegen keine belastbaren Daten bezuglich der Epidemiologie von Verletzungen der Wirbelsaule im Kindesalter vor. Gerade bei padiatrischen Patienten, bei denen sowohl die Anamnese, die klinische Untersuchung, aber auch die Durchfuhrung der bildgebenden Diagnostik haufig erschwert sind, mussen samtliche Hinweise auf eine Verletzung der Wirbelsaule mitberucksichtigt werden. Das Ziel der vorliegenden Studie war die Bereitstellung epidemiologischer Daten von padiatrischen Patienten mit Wirbelsaulenverletzungen in Deutschland, um diese zukunftig in die Entscheidungsfindung bei der Diagnostik und Therapie dieser Patienten einfliesen lassen zu konnen. Im Rahmen einer nationalen Multizenterstudie wurden retrospektiv Patientendaten innerhalb eines Zeitraums von 7 Jahren aus 6 Wirbelsaulenzentren erhoben. Neben den demografischen Daten wurden der Unfallmechanismus, die betroffene Wirbelsaulenregion und auch die Begleitverletzungen erhoben. Zudem erfolgte die Erfassung der bildgebenden Diagnostik sowie der jeweiligen Therapie. Es konnten 367 Kinder (weiblich: mannlich = 1:1,2) mit insgesamt 610 Verletzungen an der Wirbelsaule in die Studie eingeschlossen werden. Das mittlere Alter betrug 12 (±3,5) Jahre. Die haufigsten Unfallmechanismen in allen Altersgruppen waren ein Sturz aus unter 3 m Hohe sowie Verkehrsunfalle. Die bildgebende Diagnostik musste nur in Ausnahmefallen in Narkose durchgefuhrt werden. Wahrend jungere Kinder (0 bis 9 Jahre) eher Verletzungen im Bereich der Halswirbelsaule erlitten, zeigten sich Verletzungen der thorakolumbalen Wirbelsaule eher bei Kindern >10 Jahren. Die Kinder wiesen haufige Begleitverletzungen an Kopf und Extremitaten auf. Im Bereich der Wirbelsaule befanden sich weitere Verletzungen meist benachbart und nur selten in anderen Regionen. Rund 75 % der Kinder wurden konservativ behandelt. Die Ergebnisse unterscheiden sich von den Erkenntnissen aus der Erwachsenenmedizin und beschreiben spezielle Gegebenheiten fur padiatrische Patienten mit Wirbelsaulenverletzungen. Trotz gewisser Limitationen konnen sie so bei der Entscheidungsfindung uber die durchzufuhrende Diagnostik und Therapie dieser Patienten helfen.

Zusammenfassung Hintergrund Die Spondylodiszitis ist eine seltene Erkrankung mit steigender Inzidenz. Methodik In dieser retrospektiven Studie wurden 112 Patienten mit operativ versorgter Spondylodiszitis vom 01.01.2005 bis 31.12.2012 in einem Level-I-Wirbelsäulenzentrum hinsichtlich potenzieller prognostischer Kriterien nachuntersucht. Als Nachuntersuchungszeitraum galt der stationäre Aufenthalt. Analysiert wurden die Parameter Mortalität, Alter, Lokalisation der Spondylodiszitis, Abszess- und Erregernachweise, neurologischer Status und Body-Mass-Index (BMI). Ergebnisse Das Durchschnittsalter lag bei 68,3 Jahren (±12,9). Insgesamt sind 12 Patienten (10,7 %) während des stationären Aufenthalts verstorben. Ältere Patienten wiesen eine signifikant höhere Krankenhausmortalitätsrate auf (p = 0,008). Der Abszessnachweis gelang in 49,1 % der Fälle und ging mit signifikant längerer Liegedauer im Krankenhaus (p = 0,001) und auf der ITS (p = 0,001) sowie häufigeren Revisionen (p = 0,018) einher. Außerdem wiesen adipöse Patienten signifikant häufiger einen Abszess auf (p = 0,034). Mit S. aureus als häufigstem Erreger gelang der Keimnachweis insgesamt in 60,7 % der Fälle. Ein Keimnachweis war mit einer signifikant längeren Krankenhausliegedauer (p = 0,006) und häufigeren intensivmedizinischen Überwachungen verbunden (p = 0,017). Patienten mit einer Nephropathie wiesen eine signifikant erhöhte Mortalität, eine längere Liegedauer im Krankenhaus sowie ein gehäuftes Auftreten von Mehretagenbefällen auf. Schlussfolgerung Das hohe Alter, die positive Keimkultur, die Niereninsuffizienz und Abszesse können als prognostische Kriterien genutzt werden. Zu den Risikofaktoren für das Vorhandensein eines Abszesses können die lumbale Lokalisation der Spondylodiszitis, die Nephropathie sowie der Nachweis eines Erregers und die Adipositas gezählt werden.

Purpose The purpose of this study was to gain new insights into the epidemiologic characteristics of patients with atlas fractures and to retrospectively evaluate complication rates after surgical and non-surgical treatment. Methods In a retrospective study, consecutive patients diagnosed with a fracture of the atlas between 01/2008 and 07/2018 were analyzed. Data on epidemiology, concomitant injuries, fracture patterns and complications were obtained by chart and imaging review. Results In total, 189 patients (mean age 72 years, SD 19; 57.1% male) were treated. The most frequent trauma mechanism was a low-energy trauma (59.8%). A concomitant injury of the cervical spine was found in 59.8%, a combined C1/C2 injury in 56.6% and a concomitant fracture of the thoraco-lumbar spine in 15.4%. When classified according to Gehweiler, there were: 23.3% type 1, 22.2% type 2, 32.8% type 3, 19.0% type 4 and 1.1% type 5. Treatment of isolated atlas fractures (n = 67) consisted of non-operative management in 67.1%, halo fixation in 6.0% and open surgical treatment in 26.9%. In patients with combined injuries, the therapy was essentially dictated by the concomitant subaxial cervical injuries. Conclusions Atlas fractures occurred mainly in elderly people and in the majority of the cases were associated with other injuries of the head and spine. Most atlas fractures were treated conservatively. However, surgical treatment has become a safe and valid option in unstable fracture patterns involving the anterior and posterior arch (type 3) or those involving the articular surfaces (type 4). Level of evidence IV (Retrospective cohort study). Graphic abstract These slides can be retrieved under Electronic Supplementary Material.

The causative role of maternal, anti-human leukocyte antigen (anti-HLA) class I antibodies in foetal and neonatal alloimmune thrombocytopenia (FNAIT) remains controversial. Furthermore, in FNAIT cases caused by anti-human platelet antigen-1a (anti-HPA-1a) antibodies, the possible additive effect of maternal anti-HLA class I antibodies on outcomes is unclear. Among 817 mother-father-neonate trios of suspected FNAIT, we assessed the possible association of maternal anti-HLA class I antibodies with neonatal platelet count, and the incidence of FNAIT caused by anti-HPA-1a antibodies. In 144 FNAIT cases caused by anti-HPA-1a antibodies, we investigated the possible association of maternal anti-HLA class I antibodies with neonatal platelet count, birth weight, and the incidence of intracranial haemorrhage (n = 16). Maternal anti-HLA class I antibodies were not associated with neonatal platelet count in suspected cases of FNAIT. There was no significant interaction between the presence of anti-HLA class I antibodies and anti-HPA-1a antibodies. In FNAIT cases caused by anti-HPA-1a antibodies, there was no association between the presence of anti-HLA class I antibodies and neonatal platelet count, birth weight, or occurrence of intracranial haemorrhage. This study's findings do not support the concept that maternal anti-HLA class I antibodies represent a risk factor of FNAIT or disease severity.

The application of the Halo fixateur in case of spinal pathologies in childhood is a standardized technique. The halo fixateur may be used for treatment of injuries of the cervical spine, for additional stabilization following extended surgery at the cervical spine and their transitional regions as well as to achieve preoperative reduction in case of severe and rigid deformity. These indications are, referred to the early age, rare. However, the successful use of the Halo fixateur presumes a certain familiarity with the device and experiences regarding the underlying diseases to minimize related risks and to avoid possible complications. In this article the use and specific features regarding the application of the halo fixateur in childhood based on presented cases and the literature will be discussed.Die Anwendung des Halofixateurs ist bei Erkrankungen und Verletzungen der Wirbelsäule im Kindesalter auch heute noch ein Standardverfahren. Zur Anwendung kommt das Verfahren bei verschiedenen Indikationen. Dazu gehören der Einsatz bei Verletzungen der Halswirbelsäule (HWS), der Einsatz als additives Fixationssystem nach komplexer zervikaler Chirurgie und ihrer Übergangsregionen sowie der Einsatz zur präoperativen Traktion ausgeprägter und rigider Deformitäten. Diese Indikationen sind, bezogen auf das Kindesalter, insgesamt eher selten. Die erfolgreiche Anwendung des Halofixateursystems setzt jedoch eine gewisse Vertrautheit mit dem System und vor allem Erfahrungen mit den zugrunde liegenden Krankheitsbildern voraus, gerade auch, um immanente Risiken zu minimieren und Komplikationen zu vermeiden. Im folgenden Artikel soll auf die Anwendung und Besonderheiten des Halofixateurs im Kindesalter bei den o. g. Indikationsgruppen eingegangen und dies anhand von Beispielen und der Literatur diskutiert werden.

Odontoid fractures in geriatric patients represent an entity of increasing incidence with a high rate of morbidity and mortality. The optimal diagnostic and therapeutic management is being controversially discussed in the literature.In a consensus process and based on the current literature, the members of the working groups "Osteoporotic Fractures" and "Upper Cervical Spine" of the German Society for Orthopaedics and Trauma Surgery (DGOU) defined recommendations for the diagnostics and treatment of odontoid fractures in geriatric patients.For the diagnosis of odontoid fractures in symptomatic patients, computed tomography represents the gold standard, along with conventional radiographs. Magnetic resonance and dynamic imaging can be used as ancillary imaging modalities. With regard to fracture classification, the systems described by Anderson/D'Alonzo and by Eysel/Roosen have proved to be of value. A treatment algorithm was developed based on these classifications. Anderson/D'Alonzo type 1, type 3, and non-displaced type 2 fractures usually can be treated non-operatively. However, a close clinical and radiological follow-up is essential. In Anderson/D'Alonzo type 2 fractures, operative treatment is associated with better fracture healing. Displaced type 2 and type 3 fractures should be stabilized operatively. Type 2 fractures with suitable fracture patterns (Eysel/Roosen 2A/B) can be stabilized anteriorly. Posterior C I/II-stabilization procedures are well established and suitable for all fracture patterns.Frakturen des Dens axis beim geriatrischen Patienten stellen eine wachsende Entität mit hoher Morbidität und Mortalität dar. Die optimale Diagnostik und Behandlung der Verletzung in diesem Patientenkollektiv werden in der Literatur kontrovers diskutiert.In einem gemeinsamen Konsensusprozess erstellten die Mitglieder der Arbeitsgemeinschaft „Osteoporotische Frakturen“ und der Arbeitsgemeinschaft „Obere Halswirbelsäule“ der Sektion Wirbelsäule der Deutschen Gesellschaft für Orthopädie und Unfallchirurgie (DGOU) unter Berücksichtigung aktueller Literatur Empfehlungen zu Diagnostik und Behandlung von Frakturen des Dens axis bei geriatrischen Patienten.In der Diagnostik der Densfrakturen stellt beim symptomatischen Patienten neben der konventionellen Bildgebung die Computertomografie den Goldstandard dar. Kernspintomografie und Funktionsaufnahmen können ergänzende Informationen liefern. Zur Klassifikation haben sich die Systeme nach Anderson/DʼAlonzo und Eysel/Roosen bewährt. Anhand der genannten Klassifikationen wurde ein Behandlungsalgorithmus entwickelt: Anderson/DʼAlonzo Typ 1, Typ 3 und nicht dislozierte Frakturen vom Typ 2 können i. d. R. unter engmaschigen Verlaufskontrollen konservativ behandelt werden. Bei Frakturen vom Typ 2 nach Anderson/DʼAlonzo bietet die operative Behandlung den Vorteil höherer knöcherner Heilungsraten. Dislozierte Typ-2- und Typ-3-Frakturen sollten operativ stabilisiert werden. Bei geeignetem Frakturverlauf (Eysel/Roosen 2A/B) sind anteriore Verfahren möglich. Posteriore Verfahren zur C I/II-Stabilisation sind etabliert und bei allen Frakturtypen durchführbar.

BACKGROUND: The prevalence of osteoporotic vertebral body fractures in Europe is 18–26%. Although most of these injuries can be treated conservatively, the underlying concepts have not been defined clearly or uniformly. In this article, we present the current state of the evidence on the diagnosis and conservative treatment of osteoporotic fractures of the thoracic and lumbar vertebrae. METHODS: A systematic review of the literature up to May 2020 was carried out in the PubMed and Web of Science Core Collection databases. 549 articles were identified, of which 36 were suitable for inclusion in the review. Articles were sought in the areas of diagnosis, provision of physical aids, pharmacotherapy, physiotherapy, and treatments from the realm of alternative medicine. RESULTS: The primary diagnostic technique was conventional x-ray in two planes (with the patient standing, if possible), which had 51.3% sensitivity and 75% specificity. If a fracture was suspected, magnetic resonance imaging (MRI) of the entire spine and regional computed tomography (CT) were carried out. The overall state of the evidence on treatment is poor; the best available evidence is for exercise therapy and physiotherapy, which are supported by three level I and four level II studies. Improvements were seen mainly in mobility and a reduced fear of falling. The use of an active orthosis can be useful as well. No evidence was found on the use of drugs or alternative medicine exclusively in the conservative treatment of osteoporotic vertebral body fractures. CONCLUSION: It is reasonable to evaluate instability with imaging repeatedly, at regular intervals, over a period of six months. There is still a lack of reliable data on the optimal intensity and duration of physiotherapy, and on the use of orthoses.

Purpose This study aims primarily to investigate the outcome following surgical management of pertrochanteric fractures of patients over 90 years compared to the outcome of a control group below 90 years under special consideration of the timing of surgery. The second aim was to analyze potential risk factors for early deaths in very old patients. This study allows us to draw conclusions to minimize complications linked to this particular age segment. Methods The study group consisted of very old patients aged 90 years and older. Geriatric patients aged between 60 and 89 years of age were part of the control group. Type A1 pertrochanteric fractures were typically treated by dynamic hip crews, type A2 and A3 fractures by femoral nails. Full weight bearing physiotherapy was initiated on the day after surgery to improve mobility and muscle strength. Results A total of 71 patients belonged to the study group (mean age: 92.5 years ±2.3 years), whereas 223 patients formed the control group (mean age: 79.9 ± 7.4 years). The mortality rate and the number of detected and documented complications were significantly higher in the study group (p = 0.001; p = 0.009, respectively). Despite the significantly higher complication rate in the > 90-year-old patients, there was no significant difference in the mean length of in-hospital-stay between the both groups (> 90 yrs.: 12.1d; Conclusion The number of co-morbidities, number of daily-administered medications and the time between admission and surgery have no impact on the outcome. We noticed a longer period between admission and surgery in very old patients who survived. Patients with pertrochanteric fractures should be screened for multimorbidity and cognitive disorders in a standardized manner.

Inflammatory pituitary lesions account for 1.8% of all specimens from the German Pituitary Tumor Registry. They occure in 0.5% of the autoptical specimens and in 2.2% of the surgical cases. Women are significantly more often affected than men and are often younger when first diagnosed. In general, primary and secondary inflammation can be distinguished, with secondary types occurring more frequently (75.1%) than idiopathic inflammatory lesions (15.4%). In primary inflammation, the lymphocytic type is more common (88.5%) than the granulomatous type of hypophysitis (11.5%). The most common causes of secondary inflammation are Rathke’s cleft cysts (48.6%), followed by tumors (17.4%) such as the craniopharyngioma (9.1%), adenoma (5.5%) or germinoma (2.0%). More causes are tumor-like lesions (7.1%) such as xanthogranuloma (3.5%) or Langerhans histiocytosis (3.5%), abscesses (5.5%), generalized infections (5.1%), spreaded inflammations (4.7%) and previous surgeries (4.0%). In 1.6% of all specimens the reason for the inflammation remains unclear. The described classification of hypophysitis is important for specific treatment planning after surgery.

An increasing incidence of sacral insufficiency fractures in geriatric patients has been documented, representing a major challenge to our healthcare system. Determining the accurate diagnosis requires the use of sectional imaging, including computed tomography and magnetic resonance imaging. Initially, non-surgical treatment is indicated for the majority of patients. If non-surgical treatment fails, several minimally invasive therapeutic strategies can be used, which have shown promising results in small case series. These approaches are sacroplasty, percutaneous iliosacral screw fixation (S1 with or without S2), trans-sacral screw fixation or implantation of a trans-sacral bar, transiliac internal fixator stabilisation, and spinopelvic stabilisation. These surgical strategies and their indications are reported in detail. Generally, treatment-related decision making depends on the clinical presentation, fracture morphology, and attending surgeon's experience.Insuffizienzfrakturen des hinteren Beckenrings nehmen an Häufigkeit zu und stellen eine relevante Herausforderung für unser Gesundheitssystem dar. Zur Sicherung der Diagnose sollte ergänzend zu den konventionellen Röntgenaufnahmen eine Computertomografie und ggf. eine Magnetresonanztomografie erfolgen. Bei Versagen konservativer Therapieregime zeigen kleinere Serien minimalinvasiver operativer Therapieansätze vielversprechende Ergebnisse. Ziel dieser Übersichtsarbeit ist es, die aktuell eingesetzten Techniken der minimalinvasiven operativen Versorgung von Insuffizienzfrakturen des Sakrums aufzuführen und die jeweiligen Vor- und Nachteile darzulegen. Dies sind aktuell die Sakroplastie, die perkutane iliosakrale Verschraubung S I oder S I/S II, die transsakrale Verschraubung u. a. mithilfe des transsakralen „bar“ und von posterior horizontalen sowie lumbopelvinen Stabilisierungen. Im Allgemeinen hängt die Entscheidungsfindung zur Therapie vom klinischen Erscheinungsbild, der Frakturmorphologie und den Erfahrungen der behandelnden Chirurgen ab.

Brucellosis is a frequent zoonosis in some regions of the world and may cause various symptoms. Neurobrucellosis is a rare but serious complication of the infection. Our case report describes the course of neurobrucellosis in a patient who had received a ventriculoperitoneal shunt in his native country 13 years prior to diagnosis of brucellosis. He initially presented to us with symptoms of peritonitis, which misled us to perform abdominal surgery first. After the diagnosis of neurobrucellosis was confirmed and appropriate antibiotics were initiated, the symptoms soon disappeared. Although the ventriculoperitoneal shunt was subsequently removed, the patient did not develop a symptomatic hydrocephalus further on. This case displays the challenges in diagnosing an infection that occurred sporadically in Europe and may be missed by currently applied routine microbiological workup. Considering the political context, with increasing relocation from endemic areas to European countries, it is to be expected that the cases of brucellosis and neurobrucellosis will rise. Brucellosis should be considered and adequate investigations should be performed.

Introduction Incongruent stabilization of the distal tibiofibular joint (syndesmosis) results in poorer long-term outcome in malleolar fractures. The aim was to analyze whether the orientation of the syndesmotic stabilization would affect the immediate reduction imaged in computed tomography (CT). Materials and methods The syndesmotic congruity in 114 ankle fractures with stabilization of the syndesmosis were retrospectively analyzed in the post-operative bilateral CT scans. The incisura device angle (IDA) was defined and correlated with the side-to-side difference of Leporjärvi clear-space (ΔLCS), anterior tibiofibular distance (ΔantTFD) and Nault talar dome angle (ΔNTDA) regardless of the stabilization technique and separately for suture button system and syndesmotic screw. Asymmetric reduction was defined as ΔLCS > 2 mm and |ΔantTFD|> 2 mm. Results Regardless of the stabilization technique, no correlation between the IDA and the ΔLCS (r = 0.069), the ΔantTFD (r = 0.019) nor the ΔNTDA (r = 0.177) could be observed. There were no differences between suture button system and syndesmotic screw. Asymmetrical reduction was detected in 46% of the cases, while sagittal asymmetry was most common. No association was found between the orientation of stabilization device and occurrence of asymmetrical reduction (p > 0.05). The results of suture button system and syndesmotic screw were comparable in this respect (p > 0.05). Conclusion Poor correlation between the orientation of the stabilization device and the immediate post-operative congruity of the syndesmosis could be shown. In contrast to current literature, this study did not show difference of suture button system over syndesmotic screw in this regard. Careful adjustment of the fibula in anteroposterior orientation should be given special attention.

Background The increasing use of cranial tomographic imaging has led to the more frequent discovery of pituitary tumors. In this review, we discuss the clinical symptoms that point toward a pituitary tumor, the required diagnostic studies, the potential need for follow-up studies, and the indications for neurosurgical treatment. Methods This review is based on pertinent publications from the years 2005-2020 that were retrieved by a selective search in PubMed, as well as on the current German S2k guideline, which was created with the present authors playing a coordinating role, and on further guidelines from abroad. Relevant information from older reviews was also considered. Results The reported prevalence of pituitary tumors varies depending on the method of data acquisition. Autopsy studies yield a figure of 10.7%, while population-based studies reported 77.6-115.6 cases per 100 000 inhabitants. These lesions are nearly always benign, and 85% of them are pituitary adenomas. Pituitary adenomas measuring less than 1 cm in diameter are called microadenomas, while those measuring 1 cm or more are called macroadenomas. According to magnetic resonance imaging (MRI) studies, the prevalence of microadenomas in the general population is in the range of 10-38%, while that of macroadenomas is 0.16-0.3%. Pituitary adenomas can be either hormonally inactive or hormonally active. Half of all patients with hormonally inactive microadenomas display no endocrine abnormality, while 37-85% of patients with hormonally inactive macroadenomas manifest at least partial pituitary insufficiency. The clinical spectrum of pituitary tumors ranges from a fully asymptomatic state to visual disturbances, neurologic deficits, severe hormone excess (e.g., in Cushing disease), and life-threatening pituitary insufficiency. Pituitary adenomas are often diagnosed only after a latency of many years, even when they are symptomatic. If an imaging study shows the tumor to be in contact with the visual pathway, an ophthalmological evaluation should be performed. There are clear indications for surgery, e.g., imminent loss of vision, but most asymptomatic pituitary tumors can be observed only. Conclusion The manifestations of pituitary tumors are first recognized by primary care physicians. The further diagnostic evaluation of these patients should be carried out in standardized and interdisciplinary fashion.

We report 5 cases of prothrombotic immune thrombocytopenia after exposure to the ChAdOx1 vaccine (AZD1222, Vaxzevria) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients presented 5 to 11 days after first vaccination. The spectrum of clinical manifestations included cerebral venous sinus thrombosis, splanchnic vein thrombosis, arterial cerebral thromboembolism, and thrombotic microangiopathy. All patients had thrombocytopenia and markedly elevated D-dimer. Autoantibodies against platelet factor 4 (PF4) were detected in all patients, although they had never been exposed to heparin. Immunoglobulin from patient sera bound to healthy donor platelets in an AZD1222-dependent manner, suppressed by heparin. Aggregation of healthy donor platelets by patient sera was demonstrated in the presence of buffer or AZD1222 and was also suppressed by heparin. Anticoagulation alone or in combination with eculizumab or intravenous immunoglobulin (IVIG) resolved the pathology in 3 patients. Two patients had thromboembolic events despite anticoagulation at a time when platelets were increasing after IVIG. In summary, an unexpected autoimmune prothrombotic disorder is described after vaccination with AZD1222. It is characterized by thrombocytopenia and anti-PF4 antibodies binding to platelets in AZD1222-dependent manner. Initial clinical experience suggests a risk of unusual and severe thromboembolic events.

Reshaping plasmonic nanoparticles with laser pulses has been extensively researched as a tool for tuning their properties. However, in the absence of direct observations of the processes involved, ...

Investment decisions in renewable energies are known to be influenced by many diverse drivers, e.g. social, political, geographic, economic and psychological. Non-comprehensive models are problematic since missed interactions might introduce bias. We implement a robust modelling approach by (1) using a large data set with 1.4 million solar installations and (2) three different machine learning algorithms (deep neural networks, gradient boosting, random forests). Generalized linear models serve as baseline and comparison. A high prediction accuracy can be achieved on the county level with deep neural networks (adjusted R2 = 0.86) and gradient boosting (adjusted R2 = 0.87). The most important drivers are population per county, followed by type of urbanisation and social variables like unemployment, with varying degree of importance for the different machine-learning algorithms. Our approach points out both differences and agreements across methods and therefore a higher confidence in their interpretation.

ObjectiveTo determine the occurrence of intracranial haemorrhagic complications (IHC) on heparin prophylaxis (low-dose subcutaneous heparin, LDSH) in primary spontaneous intracerebral haemorrhage (ICH) (not oral anticoagulation-associated ICH, non-OAC-ICH), vitamin K antagonist (VKA)-associated ICH and non-vitamin K antagonist oral anticoagulant (NOAC)-associated ICH.MethodsRetrospective cohort study (RETRACE) of 22 participating centres and prospective single-centre study with 1702 patients with VKA-associated or NOAC-associated ICH and 1022 patients with non-OAC-ICH with heparin prophylaxis between 2006 and 2015. Outcomes were defined as rates of IHC during hospital stay among patients with non-OAC-ICH, VKA-ICH and NOAC-ICH, mortality and functional outcome at 3 months between patients with ICH with and without IHC.ResultsIHC occurred in 1.7% (42/2416) of patients with ICH. There were no differences in crude incidence rates among patients with VKA-ICH, NOAC-ICH and non-OAC-ICH (log-rank p=0.645; VKA-ICH: 27/1406 (1.9%), NOAC-ICH 1/130 (0.8%), non-OAC-ICH 14/880 (1.6%); p=0.577). Detailed analysis according to treatment exposure (days with and without LDSH) revealed no differences in incidence rates of IHC per 1000 patient-days (LDSH: 1.43 (1.04–1.93) vs non-LDSH: 1.32 (0.33–3.58), conditional maximum likelihood incidence rate ratio: 1.09 (0.38–4.43); p=0.953). Secondary outcomes showed differences in functional outcome (modified Rankin Scale=4–6: IHC: 29/37 (78.4%) vs non-IHC: 1213/2048 (59.2%); p=0.019) and mortality (IHC: 14/37 (37.8%) vs non-IHC: 485/2048 (23.7%); p=0.045) in disfavour of patients with IHC. Small ICH volume (OR: volume ConclusionsHeparin administration for venous thromboembolism (VTE) prophylaxis in patients with ICH appears to be safe regarding IHC among non-OAC-ICH, VKA-ICH and NOAC-ICH in this observational cohort analysis. Randomised controlled trials are needed to verify the safety and efficacy of heparin compared with other methods for VTE prevention.

Essentials A pilot study for External Quality Assessment for testing of HIT is described. The qualitative accordance for the PF4/heparin IgG test was 97.6%. The qualitative accordance for functional HIT tests was considerably lower. External Quality Assessment for functional HIT tests is required. SUMMARY: Objective Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening complication of heparin exposure. Diagnosis is most reliable using a combination of an enzyme immunoassay (EIA) that detects antibodies against platelet factor 4 (PF4)/heparin complexes ("antigen" assay) and a "functional" assay that detects platelet-activating properties of the pathogenic HIT antibodies. No External Quality Assessment (EQA) is available for a combination of the tests. Here we report on the results of the first international EQA. Methods The pilot EQA was organized by the Department of Transfusion Medicine, Universitätsmedizin Greifswald, Germany. Six serum samples of patients, which were referred to Greifswald for HIT diagnosis, and one negative control sample were distributed to seven participants in Germany, Canada, and Singapore. Participants were asked to report the optical density (OD) values of their local EIA test for IgG-specific antibodies against the PF4/heparin complexes and the results for a functional assay (HIPA or SRA). Consensus was defined as a minimum 70% agreement, i.e., agreement among at least five of the seven participating laboratories. Results and conclusion Six out of seven participants reported results for EIA, with a high quantitative accordance (97.6%). For the functional assay, consensus was reached for all samples except the negative control, for which some participants reported nonspecific reactivity. All HIT-negative samples were correctly diagnosed by all participants; for HIT-positive samples, consensus of 70% was reached. Although the limited availability of sample material is an obstacle to overcome, an EQA combining both EIA and functional testing is feasible.

Although the detection of a characteristic autoantibody can prove immune thrombocytopenia (ITP), this diagnosis is often based on the exclusion of other causes of thrombocytopenia. Direct glycoprotein (GP)-specific tests have the property required to demonstrate such a characteristic autoantibody. In contrast, platelet-associated immunoglobulin G or antibody detection in plasma or serum is an insufficient diagnostic test. Moreover, data for commercial capture assays are sparse and their use is currently not recommended. A significant drawback of direct GP-specific tests is their low sensitivity, and a negative test result has no relevance. It is therefore also useful to establish a diagnosis of (primarily) hyperdestructive thrombocytopenia. A full blood count together with the immature platelet fraction has an excellent positive predictive value for ITP. Plasma glycocalicin has no apparent diagnostic value in identifying ITP patients, and conflicting data for TPO preclude its use for diagnostic purposes.Obwohl der Nachweis charakteristischer Autoantikörper eine Immunthrombozytopenie (ITP) sichern kann, wird die Diagnose oft auf der Basis des Ausschlusses anderer Ursachen einer Thrombozytopenie gestellt. Direkte glykoprotein (GP)-spezifische Tests besitzen die erforderliche Eigenschaft zum Nachweis charakteristischer ITP-Antikörper. Die Bestimmung von plättchen-assoziiertem IgG oder der Nachweis von Autoantikörpern aus Serum oder Plasma ist hingegen unzureichend. Zudem liegen nur spärliche Daten für die Verwendung kommerzieller Capture-Systeme vor, ihre Verwendung kann gegenwärtig nicht empfohlen werden. Ein relevanter Nachteil der direkten GP-spezifischen Tests ist ihre niedrige Sensitivität, ein negatives Testergebnis hat daher keine diagnostische Relevanz. Es ist daher auch sinnvoll, frühzeitig eine (primär) hyperdestruktive Thrombozytopenie zu sichern. Ein Blutbild zusammen mit der immature platelet fraction hat einen sehr guten positiven prädiktiven Wert für die ITP. Die Studienergebnisse für Plasma-Glycocalicin und Thrombopoeitin sind unzureichend, ihre Verwendung als diagnostischer Marker kann momentan nicht empfohlen werden.

Background Isolated antibodies to DFS70 have been described in healthy individuals and are rarely found in patients with antinuclear antibody-associated autoimmune rheumatic diseases (AARD). However, no data is available on geographic differences in the prevalence of anti-DFS70 antibodies. We aimed to study the prevalence of anti-DFS70 antibodies in blood donor samples from several countries representing various ethnical backgrounds and geographic regions in the world. Methods Sera from apparently healthy blood donors (n≥300 per site) were collected in seven countries (USA, Italy, Spain, Germany, UK, Belgium and Brazil). All samples (n=2628) were tested for anti-DFS70 antibodies by QUANTA Flash DFS70 (Inova Diagnostics, Inc., San Diego, CA, USA). Results The prevalence of anti-DFS70 antibodies varied from 4/321 (1.2%, Italy) to 42/497 (8.5%, USA). Consequently, the prevalence of the antibodies was significantly higher in USA compared to all other countries (p Conclusions This is the first study to analyze the prevalence of anti-DFS70 antibodies in different geographic areas using a standardized assay. Our findings show that the antibodies are most prevalent in young females.

A retrospective, longitudinal cohort study.The purpose of this study was to examine whether Hounsfield units (HUs), as an alternative bone mineral density measurement to dual-energy X-ray absorptiometry and quantitative computed tomography, which lead to additional radiation exposure for patients, has an effect on the maintenance of reduction in bisegmental Cobb angle (CA) and cage subsidence in patients who receive bisegmental spine stabilization after traumatic thoracolumbar spine fractures.A total of 81 patients with a mean follow-up of 12 months were analyzed. CAs and cage subsidence were measured intraoperatively and at follow-up. HU was measured, and patients were subsequently assigned based on HU to three HU subgroups (group 1: HU 110 [poor bone quality (BQ)]; group 2: HU 180-110 [diminished BQ]; group 3: HU 180 [good BQ]).Following anterior stabilization, loss of reduction and cage subsidence differed between patients with poor and diminished BQ but not significantly, and both groups showed significantly more loss of reduction and cage subsidence than patients with good BQ.BQ, estimated with HU, had significant effects on cage subsidence and loss of reduction. We recommend measuring HU before surgery and applying additional treatment strategies, such as polymethylmethacrylate augmentation of endplates or anterior plates, for patients with HU 180. These slides can be retrieved under Electronic Supplementary Material.

Between 1996 and 2020, 12,565 cases were enrolled in the German Registry of Pituitary Tumors including 10,084 PitNETs (10,067 adenomas and 19 carcinomas obtained surgically and 193 adenomas diagnosed at autopsy) as well as 69 spindle cell tumors of the neurohypophysis (64 surgical specimens and 5 autopsies). In six patients (1 post mortem and 5 surgical specimens), PitNETs as well as posterior lobe tumors were found in the specimens. Two of the PitNETs were sparsely granulated prolactin-producing tumors, combined in one case with a granular cell tumor and in one case with a pituicytoma. One of the PitNETs revealed that autopsy was a sparsely granulated GH tumor combined with a neurohypophyseal granular cell tumor. Two PitNETs were null cell adenomas combined with a pituicytoma and a spindle cell oncocytoma, respectively. Further, one Crooke cell tumor was combined with a spindle cell oncocytoma. In five cases, the PitNETs were larger than the posterior lobe tumors and accounted for the clinical symptoms. Previously, four cases of co-existing pituitary anterior and posterior lobe tumors were described in the literature, comprising two ACTH PitNETs, one gonadotrophic PitNET and one null cell PitNET, each in combination with a pituicytoma. PitNETs and concomitant granular cell tumor or spindle cell oncocytoma, as observed in our cohort, have not been reported before.

Study Design: Systematic review. Objectives: Osteoporosis is one of the most common diseases of the elderly, whereby vertebral body fractures are in many cases the first manifestation. Even today, the consequences for patients are underestimated. Therefore, early identification of therapy failures is essential. In this context, the aim of the present systematic review was to evaluate the current literature with respect to clinical and radiographic findings that might predict treatment failure. Methods: We conducted a comprehensive, systematic review of the literature according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) checklist and algorithm. Results: After the literature search, 724 potentially eligible investigations were identified. In total, 24 studies with 3044 participants and a mean follow-up of 11 months (range 6-27.5 months) were included. Patient-specific risk factors were age >73 years, bone mineral density with a t-score 23 and a modified frailty index >2.5. The following radiological and fracture-specific risk factors could be identified: involvement of the posterior wall, initial height loss, midportion type fracture, development of an intravertebral cleft, fracture at the thoracolumbar junction, fracture involvement of both endplates, different morphological types of fractures, and specific MRI findings. Further, a correlation between sagittal spinal imbalance and treatment failure could be demonstrated. Conclusion: In conclusion, this systematic review identified various factors that predict treatment failure in conservatively treated osteoporotic fractures. In these cases, additional treatment options and surgical treatment strategies should be considered in addition to follow-up examinations.

Successful decarbonization of the electricity sector hinges on the support of the public, which is at risk when electricity generation emits local externalities. This paper estimates the impact of wind turbine deployment on granular measures of revealed preferences for renewable electricity in product and political markets. We address endogenous siting of turbines with a novel IV approach that exploits quasi-experimental variation in profitability. We find that nearby wind turbines significantly reduce citizens’ support, but this effect quickly fades with distance from the site. Our results shed light on how distance requirements and financial participation could enhance support for renewables.