Severe COVID-19 and its cardiopulmonary effects 6 and 18 months after hospital discharge.

Introduction: SARS-CoV-2 infection affects the cardiopulmonary system in the acute as well as long-term phase. The aim of the present study was to comprehensively assess symptoms and possible long-term impairments 6 and 18 months after hospitalization for severe COVID-19 infection. Methods: This prospective registry included patients with PCR-confirmed COVID-19 infection requiring hospitalization. Follow-up approximately 6 months post discharge comprised a detailed patient history, clinical examination, transthoracic echocardiography, electrocardiogram, cardiac magnetic resonance imaging (cMRI), chest computed tomography (CT) scan, pulmonary function test (PFT), six-minute walk test (6MWT) and a laboratory panel. At the time of the second follow-up visit at 18 months, patients without pathologic findings during the first study visit were contacted by phone to inquire about the course of their symptoms. In all other patients all initial examinations were repeated. Results: Two hundred Patients, who were hospitalized for COVID-19, were contacted by phone and were recruited for the study. Due to dropouts the second study visit was performed in 170 patients. A comparison between the two study visits at 6 and 18 months post discharge showed the following results: Six months after discharge, 73% and 18 months after discharge 52% fulfilled the criteria for Long COVID with fatigue being the most common symptom (49%). Echocardiography at 6 months post discharge showed an impaired left ventricular function in 8% of which 80% returned to normal. Six months post discharge, cMRI revealed pericardial effusion in 17% which resolved in 47% of the 15 patients who underwent a control cMRI. Signs of peri- or myocarditis were present in 5% of the patients and were resolved in all 4 patients who attended control studies. At 6 months, chest CT scans identified post-infectious residues in 24%. In the 25 repeated chest CT scans 20% showed full recovery. Length of in-hospital stay was identified as a significant predictor for persisting Long COVID (95% CI: 1.005-1.12, p = 0.03). Conclusion: Comparing 6 to 18 months, the prevalence of Long COVID decreased over time, but a high symptom burden remained. Structural and functional abnormalities were less frequent than the portrayed symptoms, and it thus remains a challenge to substantiate the symptoms.

Nivolumab for locally advanced and metastatic cutaneous squamous cell carcinoma (NIVOSQUACS study)-Phase II data covering impact of concomitant haematological malignancies.

BACKGROUND: Monoclonal antibodies, such as cemiplimab and pembrolizumab, against the programmed death receptor (PD)-1 have become the current standard of care and first-line treatment of advanced cutaneous squamous cell carcinoma (cSCC), proving remarkable clinical benefit and acceptable safety. OBJECTIVES: To assess efficacy and safety of the anti-PD-1 antibody nivolumab in patients with locally advanced and metastatic cSCC. METHODS: Patients received open-label nivolumab 240 mg intravenously every 2 weeks for up to 24 months. Patients with concomitant haematological malignancies (CHMs), either non-progressing or stable under active therapy, were eligible for inclusion. RESULTS: Of 31 patients with a median age of 80 years, 22.6% of patients achieved an investigator assessed complete response, resulting in an objective response rate (ORR) of 61.3% and a disease control rate (DCR) of 64.5%. Progression-free survival (PFS) was 11.1 months, and the median overall survival (OS) was not reached after 24 weeks of therapy. Median follow-up was 23.82 months. Subgroup analysis of the CHM cohort (n = 11; 35%) revealed an ORR of 45.5%, a DCR of 54.5%, a median PFS of 10.9 months, and median OS of 20.7 months. Treatment related adverse events were reported in 58.1% of all patients (19.4% grade 3, the remaining grade 1 or 2). PD-L1 expression and CD-8+ T-cell infiltration did not significantly correlate with clinical response, although a trend towards a shorter PFS of 5.6 months was observed with PD-L1 negativity and low CD8+ intratumoral infiltration. CONCLUSION: This study demonstrated robust clinical efficacy of nivolumab in patients with locally advanced and metastatic cSCCs and a tolerability comparable to data of other anti-PD-1 antibodies. Favourable outcomes were obtained despite involving the oldest hitherto reported study cohort for anti-PD-1 antibodies and a significant proportion of CHM patients prone to high risk tumours and an aggressive course otherwise typically excluded from clinical trials.

Real-World Data for Lenvatinib in Radioiodine-Refractory Differentiated Thyroid Cancer (RELEVANT): A Retrospective Multicentric Analysis of Clinical Practice in Austria.

BACKGROUND: Lenvatinib has proven efficacy in progressive, radioiodine- (RAI-) refractory thyroid cancer (TC). Dose reductions are commonly performed due to decreased tolerability and adverse effects. This retrospective multicenter study analyzed overall survival (OS) and progression-free survival (PFS) and tolerability in the Austrian patient population treated with lenvatinib. METHODS: Clinical data of 43 patients (25 males and 18 females) with a median age of 70 years (range: 39-91 years) and RAI-refractory TC with metastases to the lymph nodes (74%), lungs (86%), bone (35%), liver (16%), and brain (12%) were analyzed. The mean duration of treatment with lenvatinib was 26.6 ± 15.4 months with dosage reductions required in 39 patients (91%). RESULTS: PFS after 24 months was 71% (95% CI: 56-87), and overall survival (OS) was 74% (95% CI: 60-88), respectively. OS was significantly shorter (p=0.048) in patients with a daily maintenance dosage ≤ 10 mg (63%) (95% CI: 39-86) as compared to patients on ≥ 14 mg lenvatinib (82%) (95% CI: 66-98) daily. Dose reduction was noted in 39 patients (91%). Grade ≥3 toxicities (hypertension, diarrhea, weight loss, and palmar-plantar erythrodysesthesia syndrome) were most common leading to discontinuation of lenvatinib in 7 patients (16%). CONCLUSION: Lenvatinib showed sustained clinical efficacy in patients with metastatic RAI-refractory TC even with reduced maintenance dosages over years. The effects were comparable to the registration trial, although patients had a higher median age and, more commonly, dose reductions.

Differential regulation of TRP channel gene and protein expression by intervertebral disc degeneration and back pain.

Intervertebral disc (IVD) degeneration and consequent low back pain (LBP) are common and costly pathological processes that require improved treatment strategies. Transient Receptor Potential (TRP) channels constitute a family of multimodal ion channels that have recently emerged as contributors to disc pathologies and were thus proposed as potential therapeutic targets, although limited data on their presence and function in the IVD exist. The purpose of this study was to determine the mRNA and protein expression of TRP channels in non-degenerated and degenerated human IVD tissue (with different pain intensity and chronicity) using gene array, conventional qPCR and immunohistochemistry. We could demonstrate that 26 out of 28 currently known TRP channels are expressed in the IVD on the mRNA level, thereby revealing novel therapeutic candidates from the TRPC, TRPM and TRPML subfamilies. TRPC6, TRPM2 and TRPML1 displayed enhanced gene and protein expression in degenerated IVDs as compared to non-degenerated IVDs. Additionally, the gene expression of TRPC6 and TRPML1 was influenced by the IVD degeneration grade. Pain intensity and/or chronicity influenced the gene and/or protein expression of TRPC6, TRPM2 and TRML1. Interestingly, decreased gene expression of TRPM2 was observed in patients treated with steroids. This study supports the importance of TRP channels in IVD homeostasis and pathology and their possible application as pharmacological targets for the treatment of IVD degeneration and LBP. However, the exact function and activation of the highlighted TRP channels will have to be determined in future studies.

Accurate prediction of spontaneous lumbar curve correction following posterior selective thoracic fusion in adolescent idiopathic scoliosis using logistic regression models and clinical rationale.

INTRODUCTION: Accurate prediction of spontaneous lumbar curve correction (SLCC) after selective thoracic fusion (STF) remains difficult. This study sought to improve prediction accuracy of SLCC. The hypothesis was preoperative and intraoperative variables could predict SLCC < 20°. METHODS: A multicenter observational prospective analysis was conducted to determine predictors of SLCC in AIS patients that had posterior STF. Curve types included major thoracic curves (Lenke 1, 3-4).The primary outcome variable was to establish prediction models, and a postoperative lumbar curve (LC) ≤ 20° was defined as the target variable. Multivariate logistic regression models were established to study the relationship between selected variables and a LC ≤ 20° versus a LC > 20° at ≥ 2-year follow-up. Single and dual thresholds models in perspective of clinical rationales were applied to find models with the highest positive/negative predictive values (PPV/NPV). The secondary outcome measure was SRS scores at ≥ 2-year follow-up. RESULTS: 410 patients were included. At ≥ 2-year follow-up 282 patients had LC ≤ 20°. These patients had better SRS-22 scores than those with LC > 20° (P = 0.02). The postoperative LC and LC ≤ 20° were predicted by preoperative LC and LC-bending Cobb angle (P < 0.01, r = 0.4-0.6). Logistic regression models could be established to identify patients at risk for failing the target LC ≤ 20°.For preoperative LC and LC-bending, the prediction model achieved a NPV/PPV of 80%/72%. If the postoperative main thoracic curve is combined with the preoperative LC and a gray area for difficult decisions was allowed, model accuracy could even be improved (NPV/PPV = 96%/81%). CONCLUSION: An accurate prediction model for postoperative SLCC was established based on a large analysis of prospective STF cases. These models can support prediction and understanding of postoperative SLCC aiding in surgical decision making when contemplating a selective thoracic fusion. These slides can be retrieved under Electronic Supplementary Material.

Minimal invasive plating of distal radius fractures. A safe procedure?

BACKGROUND: Minimal invasive plate osteosynthesis (MIPO) with preservation of the pronator quadratus (PQ) muscle represents a new technique for stabilization of distal radius fractures. However, the complex anatomy of the distal radius metaphysis requires implants with features that address all morphologic specifics of this area to avoid complications, which are still reported with this technique. It was the aim of our anatomic investigation to evaluate the feasibility of plate insertion via a minimal transverse approach as well as the risk of soft- tissues compromise with the use of an implant, which is only partially adapted to the characteristics of distal radius metaphysis. METHODS: Twenty forearm specimens, conservated with Thiels method, have been used for this study. The majority (n = 19/20) of implants (2.4 mm small fragment juxta-articular locking compression/ LCP T-plate -5-hole; Depuy - Synthes®, Solothurn, Switzerland) could be inserted easily and all were seated proximal to the so called "watershed line" (n = 20/20). RESULTS: In a total of 8/20 specimens close contacts or potential compromise to neighboring soft- tissues was seen: perforation of the PQ muscle by the plate occurred in 2/20 specimens and was related to an extreme muscle morphology. In 7/20 specimens close contacts between the T-plate and other soft tissues were observed, which were exclusively located at the radial edge of the distal transverse bar. They affected the brachio-radialis tendon (elevation: 2/20, side-to-side contact: 3/20, overriding: 1/20) and the radial artery (elevation: 4/20, side-to-side contact: 2/20, overriding: 1/20). No significant differences of morphologic types of PQ muscle and the difficulty of plate insertion, adjustment on the bone, PQ muscle damage and contact to neighboring soft-tissues could be evaluated. CONCLUSIONS: Insertion of volar radius plates through a MIPO approach can be easily accomplished without detachment and damage to the PQ muscle even with grossly adapted implants. However, perfectly pre-shaped plates which are adapted to all anatomic aspects of the distal radius metaphysis are required to achieve optimal contact with the metaphyseal bone and to avoid potential complications.

Characteristics of deformity surgery in patients with severe and rigid cervical kyphosis (CK): results of the CSRS-Europe multi-centre study project.

INTRODUCTION AND PURPOSE: Little information exists on surgical characteristics, complications and outcomes with corrective surgery for rigid cervical kyphosis (CK). To collate the experience of international experts, the CSRS-Europe initiated an international multi-centre retrospective study. METHODS: Included were patients at all ages with rigid CK. Surgical and patient specific characteristics, complications and outcomes were studied. Radiographic assessment included global and regional sagittal parameters. Cervical sagittal balance was stratified according to the CSRS-Europe classification of sagittal cervical balance (types A-D). RESULTS: Eighty-eight patients with average age of 58 years were included. CK etiology was ankylosing spondlitis (n = 34), iatrogenic (n = 25), degenerative (n = 9), syndromatic (n = 6), neuromuscular (n = 4), traumatic (n = 5), and RA (n = 5). Blood loss averaged 957 ml and the osteotomy grade 4.CK-correction and blood loss increased with osteotomy grade (r = 0.4/0.6, p < .01). Patients with different preop sagittal balance types had different approaches, preop deformity parameters and postop alignment changes (e.g. C7-slope, C2-7 SVA, translation). Correction of the regional kyphosis angle (RKA) was average 34° (p < .01). CK-correction was increased in patients with osteoporosis and osteoporotic vertebrae (POV, p = .006). 22% of patients experienced a major long-term complication and 14% needed revision surgery. Patients with complications had larger preop RKA (p = .01), RKA-change (p = .005), and postop increase in distal junctional kyphosis angle (p = .02). The POV-Group more often experienced postop complications (p < .0001) and revision surgery (p = .02). Patients with revision surgery had a larger RKA-change (p = .003) and postop translation (p = .04). 21% of patients had a postop segmental motor deficit and the risk was elevated in the POV-Group (p = .001). CONCLUSIONS: Preop patient specific, radiographic and surgical variables had a significant bearing on alignment changes, outcomes and complication occurrence in the treatment of rigid CK.

Reverse shoulder arthroplasty combined with latissimus dorsi transfer: A systemic review.

Reverse shoulder arthroplasty (RSA) combined with latissimus dorsi transfer (LDT) is described for patients with cuff arthropathy and a combined loss of abduction and external rotation. The purpose of this systemic review was to present clinical and radiological outcomes following RSA combined with LDT. A comprehensive literature review was performed to identify studies reporting clinical and radiological results of RSA combined with LDT. Seven articles that describe the treatment of 116 patients were selected. Functional scores, range of motion, radiological outcome, complications, rehabilitation regime, surgical technique, patient demographics and indication were analyzed and discussed. All studies reported significant improvement in functional scores and abduction and external rotation. Complications occurred in 26% of patients. Although high-level studies are lacking, this systemic review shows that RSA combined with LDT is a reliable surgical method with which to treat patients with loss of active abduction and loss of external rotation. The available data are insufficient to draw conclusions regarding the long-term outcomes of this procedure. LEVEL OF EVIDENCE: IV.

Impact of Sagittal Balance on Clinical Outcomes in Surgically Treated T12 and L1 Burst Fractures: Analysis of Long-Term Outcomes after Posterior-Only and Combined Posteroanterior Treatment.

Objective. Long-term radiological and clinical outcome retrospective study of surgical treatment for T12 and L1 burst fractures in perspective of sagittal balance measures. Methods. Patients with age of 16-60 years, complete radiographs, early surgical treatment surgery, and follow-up (F/U) > 18 months were included and strict exclusion criteria applied. Regional and thoracolumbar kyphosis angles (RKA and TLA) were measured preoperatively and at final F/U, as were parameters of the spinopelvic sagittal alignment. Clinical outcomes were assessed using validated measures. Results. 36 patients with age mean age of 39 years and F/U of 69 months were included. 61% of patients were treated with bisegmental posterior instrumentation (POST-I) and 39% with combined posteroanterior instrumented fusion (PA-F). At F/U, several indicators for clinical outcomes showed a significant correlation with radiographic measures in the overall cohort with inferior clinical outcomes corresponding with increasing residual deformity and sagittal malalignment. Statistical analysis failed to reach level of significance for the differences between POST-I and PA-F group at final F/U. Only a strong trend towards better restoration of the thoracolumbar alignment was observed for the PA-F group in terms of the RKA and TLA. Conclusions. Results in a surgically treated cohort of T12 and L1 burst fracture patients indicate that superior clinical outcomes depend on restoration of sagittal alignment.

Maintenance of spontaneous lumbar curve correction following thoracic fusion of main thoracic curves in adolescent idiopathic scoliosis.

AIMS: The aims of our study were to provide long-term information on the behaviour of the thoracolumbar/lumbar (TL/L) curve after thoracic anterior correction and fusion (ASF) and to determine the impact of ASF on pulmonary function. PATIENTS AND METHODS: A total of 41 patients (four males, 37 females) with main thoracic (MT) adolescent idiopathic scoliosis (AIS) treated with ASF were included. Mean age at surgery was 15.2 years (11 to 27). Mean follow-up period was 13.5 years (10 to 18). RESULTS: For the TL/L curve, the mean curve flexibility evaluated with supine pre-operative bending radiographs was 78.6% (standard deviation 16.5%), with no significant loss of correction observed. On comparing patients with an increase of the TL/L curve increase (> 4º, n = 9, 22%) to those without, significant differences were observed in the correction rate of the MT curve at the final follow-up (p = 0.011), correction loss of the MT curve (p = 0.003) and the proportion of patients who had semi-rigid instrumentation (p = 0.003). Pre-operative percentage predicted forced vital capacity (%FVC) was 80%, dropping to 72% at final follow-up (p < 0.001). The Scoliosis Research Society questionnaire score was not significantly different between patients with and without a TL/L curve increase (p = 0.606). Spontaneous lumbar curve correction (SLCC) was maintained up to 18 years following selective ASF in most patients and demonstrated significant correlation with maintenance of MT curve correction. CONCLUSION: Maintenance of MT curve correction using rigid instrumentation provided stable SLCC over time. An observed 8% decrease in %FVC indicates that ASF should be reserved for patients with no or only mild pulmonary impairment. Cite this article: Bone Joint J 2016;98-B:997-1002.

Lateral Fasciectomy Sparing the Superficial Peroneal Nerve with Simultaneous Mesh Graft in Non-healing Lateral Leg Ulcers of Diverse Vascular Origins: Surgical Technique, Short- and Long-term Results from 44 Legs.

OBJECTIVES: The technique of lateral fasciectomy (LF) sparing the superficial peroneal nerve with mesh graft coverage is a novel treatment of non-healing lateral leg ulcers of various vascular origin affecting the fascia. We report short- and long-term results of LF for recalcitrant lateral leg ulcers. DESIGN: This study is a single center, retrospective case series of consecutive patients treated by LF. MATERIALS: From 827 ulcers treated at our institution, 44 recalcitrant lateral leg ulcers affecting the fascia (41 patients) underwent lateral fasciectomy between 2006 and 2013. METHODS: Preoperative indications, step-by-step surgical procedures, and perioperative care methodologies are presented. Long-term effects of healing and recurrence were clinically investigated or obtained through telephone interviews with relatives and local practitioners. RESULTS: Three discrete etiologies were identified: venous ulcers (n = 24), arterial-venous/mixed ulcers (n = 11), and arteriolar Martorell hypertensive leg ulcers (n = 9). Complete healing was achieved in 40 legs (91%) after 3 months, and in 43 of the affected legs (98%) in total. The median duration to complete healing was 64 days. There was no difference between the healing times of different etiologies. No local recurrence was observed during the follow-up period, which ranged from 1.8 to 8.7 years (median: 5.11, mean: 5.12). Twelve patients (27%) died within this period due to multimorbidity. CONCLUSIONS: Following lateral fasciectomy and mesh graft coverage, 43 legs (98%) healed in previously treatment resistant lateral leg ulcers.

Endovascular mechanical recanalization of acute ischaemic stroke in octogenarians.

BACKGROUND: Multiple studies have shown a clinical benefit of thrombectomy in acute ischaemic stroke, but most of them excluded octogenarians. The purpose of this study was to compare the outcomes between octogenarians and younger patients after thrombectomy. MATERIALS AND METHODS: One hundred and sixty-six patients with large cerebral artery occlusion and consecutive thrombectomy were evaluated and divided into two patient age groups: younger than 80 years and older than 80 years. We compared recanalization rates, complications experienced, disability, death after discharge and at a 90-day follow-up between these age groups. RESULTS: Sixty-eight percent of octogenarians and 72 % of younger patients were registered with successful recanalization (p = 1.0). There was no significant difference in symptomatic intracerebral haemorrhage between the groups (p = 0.32). However, octogenarians had a significantly lower rate of good clinical outcome (24 % vs. 48 %; p = 0.008) and a higher mortality rate (36 % vs. 12 %; p = 0.0013). CONCLUSION: Octogenarians have a lower chance of good clinical outcome and a higher mortality rate despite successful recanalization. Nevertheless, 24 % of octogenarians were documented with mRS ≤2. As this age group of octogenarians will grow prospectively, careful patient selection should be mandatory when considering octogenarians for thrombectomy. KEY POINTS: • Careful patient selection for thrombectomy should be mandatory in octogenarians. • Octogenarians have a higher mortality rate despite successful recanalization. • Nearly one-third of octogenarians were documented with a good clinical outcome.

Longitudinal change in quantitative meniscus measurements in knee osteoarthritis--data from the Osteoarthritis Initiative.

OBJECTIVE: We aimed to apply 3D MRI-based measurement technology to studying 2-year change in quantitative measurements of meniscus size and position. METHODS: Forty-seven knees from the Osteoarthritis Initiative with medial radiographic joint space narrowing had baseline and 2-year follow-up MRIs. Quantitative measures were obtained from manual segmentation of the menisci and tibia using coronal DESSwe images. The standardized response mean (SRM = mean/SD change) was used as measure of sensitivity to longitudinal change. RESULTS: Medial tibial plateau coverage decreased from 34.8% to 29.9% (SRM -0.82; p < 0.001). Change in medial meniscus extrusion in a central image (SRM 0.18) and in the central five slices (SRM 0.22) did not reach significance, but change in extrusion across the entire meniscus (SRM 0.32; p = 0.03) and in the relative area of meniscus extrusion (SRM 0.56; p < 0.001) did. There was a reduction in medial meniscus volume (10%; p < 0.001), width (7%; p < 0.001), and height (2%; p = 0.08); meniscus substance loss was strongest in the posterior (SRM -0.51; p = 0.001) and weakest in the anterior horn (SRM -0.15; p = 0.31). CONCLUSION: This pilot study reports, for the first time, longitudinal change in quantitative 3D meniscus measurements in knee osteoarthritis. It provides evidence of improved sensitivity to change of 3D measurements compared with single slice analysis. KEY POINTS: • First longitudinal MRI-based measurements of change of meniscus position and size. • Quantitative longitudinal evaluation of meniscus change in knee osteoarthritis. • Improved sensitivity to change of 3D measurements compared with single slice analysis.

Laparoscopic adenomectomy versus Eraser laser enucleation of the prostate.

PURPOSE: To evaluate functional outcomes and morbidity rates after laparoscopic adenomectomy (LA) and Eraser laser enucleation of the prostate (ELEP). MATERIALS AND METHODS: Forty patients with lower urinary tract symptoms suggesting bladder outlet obstruction, with a prostate heavier than 70 g on transrectal ultrasound, were selected to undergo laparoscopic adenomectomy or Eraser laser enucleation of the prostate. All patients were consecutively enrolled without randomization and assessed preoperatively, 3 and 6 months postoperatively. Baseline characteristics, perioperative data, and postoperative outcomes were compared. RESULTS: The total operating time was significantly longer in the LA group (138.8 ± 11.4 vs. 78.4 ± 10.0 min, p < 0.000001). Catheter removal was performed earlier (61.2 ± 21.3 vs. 174.0 ± 13.2 h, p < 0.000001) and the hospital stay was significantly shorter (62.4 ± 21.2 vs. 187.2 ± 12.6 h, p < 0.000001) in the ELEP group. The latter group experienced significantly less perioperative hemoglobin (Hb) loss (0.71 ± 0.25 vs. 2.15 ± 1.08 g/dl, p < 0.000001), and their postoperative Hb levels (14.1 ± 1.21 vs. 11.7 ± 1.31 g/dl, p < 0.000001) were significantly higher. The resected tissue was significantly greater in the LA group (58.5 ± 23.3 vs. 87.9 ± 22.4 g, p = 0.0002). Significant improvements in Qmax, Qol, and symptom scores from baseline to each follow-up time point were noted in both groups. No statistically significant difference in symptom scores or Qmax was registered between the LA and the ELEP group throughout the follow-up period. CONCLUSION: Laparoscopic adenomectomy and ELEP were equally effective for relieving bladder outflow obstruction and lower urinary tract symptoms. The advantages of ELEP include less blood loss, shorter catheterization times, and shorter hospital stays.

High interindividual variability in the CD4/CD8 T cell ratio and natalizumab concentration levels in the cerebrospinal fluid of patients with multiple sclerosis.

Strongly decreased leucocyte counts and a reduced CD4/CD8 T cell ratio in the cerebrospinal fluid (CSF) of natalizumab (NZB)-treated multiple sclerosis (MS) patients may have implications on central nervous (CNS) immune surveillance. With regard to NZB-associated progressive multi-focal leucoencephalopathy, we aimed at delineating a relationship between free NZB, cell-bound NZB, adhesion molecule (AM) expression and the treatment-associated shift in the CSF T cell ratio. Peripheral blood (PB) and CSF T cells from 15 NZB-treated MS patients, and CSF T cells from 10 patients with non-inflammatory neurological diseases and five newly diagnosed MS patients were studied. Intercellular adhesion molecule-1 (ICAM-1), leucocyte function antigen-1 (LFA-1), very late activation antigen-4 (VLA-4), NZB saturation levels, and T cell ratios were analysed by flow cytometry. NZB concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Lower NZB saturation levels (P<0.02) and a higher surface expression of ICAM-1 and LFA-1 (P<0.001) were observed on CSF CD8 T cells. CSF T cell ratios (0.3-2.1) and NZB concentrations (0.01-0.42 µg/ml) showed a pronounced interindividual variance. A correlation between free NZB, cell-bound NZB or AM expression levels and the CSF T cell ratio was not found. Extremely low NZB concentrations and a normalized CSF T cell ratio were observed in one case. The differential NZB saturation and AM expression of CSF CD8 T cells may contribute to their relative enrichment in the CSF. The reduced CSF T cell ratio appeared sensitive to steady-state NZB levels, as normalization occurred quickly. The latter may be important concerning a fast reconstitution of CNS immune surveillance.

Is loss in femorotibial cartilage thickness related to severity of contra-lateral radiographic knee osteoarthritis?--longitudinal data from the Osteoarthritis Initiative.

OBJECTIVE: Anti-catabolic disease modifying drugs (DMOADs) aim to reduce cartilage loss in knee osteoarthritis (KOA). Testing such drugs in clinical trials requires sufficient rates of loss in the study participants to occur, preferably at a mild disease stage where cartilage can be preserved. Here we analyze a "progression" model in mild radiographic KOA (RKOA), based on contra-lateral radiographic status. METHODS: We studied 837 participants (62.4 ± 9 yrs; 30 ± 4.9 kg/m²; 61.8% women) from the Osteoarthritis Initiative (OAI) with mild to moderate RKOA (Kellgren Lawrence grade [KLG] 2-3) and with/without Osteoarthritis Research Society International (OARSI) atlas radiographic joint space narrowing (JSN). These had quantitative measurements of subregional femorotibial cartilage thickness from magnetic resonance imaging (MRI) at baseline and 1-year follow-up. They were stratified by contra-lateral knee status: no (KLG 0/1), definite (KLG2) and moderate RKOA (KLG 3/4). RESULTS: KLG2 knees with JSN and moderate contra-lateral RKOA had (P = 0.008) greater maximum subregional cartilage loss -220 µm [95% confidence interval (CI) -255, -184 µm] than those without contra-lateral RKOA -164 µm [-187, -140 µm]. Their rate of subregional cartilage loss was similar and not significantly different (P = 0.61) to that in KLG 3 knees without contra-lateral RKOA (-232 µm; [-266; -198 µm]). The effect of contra-lateral RKOA status was less in KLG2 knees without JSN, and in KLG3 knees. CONCLUSION: KLG2 knees with JSN and moderate contra-lateral RKOA, display relatively high rates of subregional femorotibial cartilage loss, despite being at a relatively mild stage of RKOA. They may therefore provide a unique opportunity for recruitment in clinical trials that explore the efficacy of anti-catabolic DMOADs on structural progression.

Three-question dementia screening. Development of the Salzburg Dementia Test Prediction (SDTP).

BACKGROUND: To date, short dementia screenings are often limited by poor specificity or still take too much time with respect to the restricted resources of primary care physicians and the increasing number of dementia disorders. As a new instrument, the three-question dementia screening (SDTP, Salzburg Dementia Test Prediction) should be compared with the eight-item screening of Chen et al. and the CERAD battery (Consortium to Establish a Registry for Alzheimer's Disease), focusing on specificity and economy of time. MATERIALS AND METHODS: We tested 404 patients (243 women). The mean age of the subjects was 80.1 years (SD = 6.8) for men and 83.2 years (SD = 6.0) for women. The mean Mini-Mental State Examination (MMSE) score was 21.9 (SD = 5.8) for men and 21.1 (SD = 6.3) for women. Artificial neural networks (ANNs) were used to find a mathematical model that allows the total MMSE to be predicted with only three questions of the MMSE. This is achieved by multiplying the outcome of the three best predictor questions with a weighting coefficient, which was delineated by using ANNs. RESULTS: The Salzburg Dementia Test Prediction (SDTP) had a sensitivity of 94% (95% CI: 87-97%) for screening of possible dementia, when the MMSE (MMSE < 25/30) was used as the reference test method and 96% when the CERAD was used. The specificity was 68% (95% CI: 57-77%) if the MMSE was used and 70% if the whole test battery (CERAD) was used, which is as sensitive as and more specific than the eight-item screening. CONCLUSION: The SDTP is a time-saving instrument for screening of dementia, which is as sensitive as and more specific than the eight-item screening of Chen et al. and provides a prediction of the MMSE with high accuracy.

Relationship between knee pain and the presence, location, size and phenotype of femorotibial denuded areas of subchondral bone as visualized by MRI.

OBJECTIVE: Conflicting associations between imaging biomarkers and pain in knee osteoarthritis (OA) have been reported. A relation between pain and denuded areas of subchondral bone (dABs) has been suggested and this study explores this relationship further by relating the presence, phenotype, location and size of dABs to different measures of knee pain. METHODS: 633 right knees from the Osteoarthritis Initiative (OAI) (250 men, age 61.7 ± 9.6 yrs, BMI 29.4 ± 4.7 kg/m(2)) were included. Manual segmentation of the femorotibial cartilage plates was performed on 3 T coronal fast low angle shot with water excitation (FLASHwe) images. dABs were defined as areas where the subchondral bone was uncovered by cartilage. The following measures of pain were used: weightbearing-, non-weightbearing-, moderate-to-severe-, infrequent- and frequent knee pain. RESULTS: Using pain measures from subjects without dABs as a reference, those with at least one dAB had a 1.64-fold higher prevalence ratio [PR, 95% confidence interval (CI) 1.24-2.18] to have frequent and 1.45-fold higher for moderate-to-severe knee pain (95% CI 1.13-1.85). Subjects with dABs in central subregions had a 1.53-fold increased prevalence of having weightbearing pain (95% CI 1.20-1.97), especially when the central subregion was moderately (>10%) denuded (PR 1.81, 95% CI 1.35-2.42). Individuals with cartilage-loss-type dABs had a slightly higher prevalence (PR 1.13, 95% CI 1.00-1.27) of having frequent knee pain compared to individuals with intra-chondral-osteophyte-type dABs. CONCLUSION: This study supports a positive relation between femorotibial dABs and knee pain, especially when the dABs are located centrally (i.e., in weightbearing regions) or when the respective central subregion is moderately denuded.

Comparison of endovascular treatment versus conservative medical treatment in patients with acute basilar artery occlusion.

INTRODUCTION: Basilar artery occlusion (BAO) causes mortality up to 90%. METHODS: A total of 99 patients with BAO received either endovascular (endovascular mechanical recanalization and/or intra-arterial with optional intravenous thrombolysis [IVT] as bridging concept) or conservative medical treatment (IVT and/or medical oral therapy). Outcome parameters were measured in accordance with the thrombolysis in cerebral infarction (TICI), National Institutes of Health Stroke Scale (NIHSS), and modified Rankin Scale (mRS) scores. RESULTS: In all, 78% underwent endovascular and 22% conservative medical treatment. The NIHSS at admission was 20 in both the groups. Postprocedurally, 36% (95% confidence interval: 26%-48%) of the endovascular group and 9% (21%-64%) of the conservative group reached TICI 3 (P = .017). In all, 30% of the endovascular group and 9% of the conservative group were documented with TICI 2b (P = .057). At 90 days follow-up, 45% (31%-60%) of the endovascular-treated patientsand no patient (0%-25%) of the conservative-treated group reached mRS ≤2 (P = .012). CONCLUSION: Endovascular treatment of BAO provides a better chance to survive this severe condition with good clinical outcome.

Baseline and longitudinal change in isometric muscle strength prior to radiographic progression in osteoarthritic and pre-osteoarthritic knees--data from the Osteoarthritis Initiative.

OBJECTIVE: To test whether cross-sectional or longitudinal measures of thigh muscle isometric strength differ between knees with and without subsequent radiographic progression of knee osteoarthritis (KOA), with particular focus on pre-osteoarthritic female knees (knees with risk factors but without definite radiographic KOA). METHODS: Of 4,796 Osteoarthritis Initiative participants, 2,835 knees with Kellgren Lawrence grade (KLG) 0-3 had central X-ray readings, annual quantitative joint space width (JSW) and isometric muscle strength measurements (Good strength chair). Separate slope analysis of covariance (ANCOVA) models were used to determine differences in strength between "progressor" and "non-progressor" knees, after adjusting for age, body mass index, and pain. RESULTS: 466 participant knees exceeded the smallest detectable JSW change during each of two observation intervals (year 2→4 and year 1→3) and were classified as progressors (213 women, 253 men; 128 KLG0/1, 330 KLG2/3); 946 participant knees did not exceed this threshold in either interval and were classified as non-progressors (588 women, 358 from men; 288KLG0/1, 658KLG2/3). Female progressor knees, including those with KLG0/1, tended to have lower extensor and flexor strength at year 2 and at baseline than those without progression, but the difference was not significant after adjusting for confounders. No significant difference was observed in longitudinal change of muscle strength (baseline→year 2) prior to radiographic progression. No significant differences were found for muscle strength in men, and none for change in strength concomitant with progression. CONCLUSION: This study provides no strong evidence that (changes in) isometric muscle strength precedes or is associated with structural (radiographic) progression of KOA.