Long‐term Radiological and Clinical Outcome after Lumbar Spinal Fusion Surgery in Patients with Degenerative Spondylolisthesis: A Prospective 6‐Year Follow‐up Study

ObjectiveTo assess which radiological alignment parameters are associated with a satisfactory long‐term clinical outcome after performing lumbar spinal fusion for treating degenerative spondylolisthesis.MethodsThis single‐center prospective study assessed the relation between radiological alignment parameters measured on standing lateral lumbar spine radiographs and the patient‐reported outcome using four different questionnaires (COMI, EQ‐5D, ODI and VAS) as primary outcome measures (level of evidence: II). The following spinopelvic alignment parameters were used: gliding angle, sacral inclination, anterior displacement, sagittal rotation, lumbar lordosis, sacral slope, pelvic tilt and pelvic incidence. Furthermore, the length of stay and perioperative complications were documented. Only cases from 2013 to 2015 of low‐grade degenerative lumbar spondylolisthesis (Meyerding grades I and II) were considered. The patients underwent open posterior lumbar fusion surgery by pedicle screw instrumentation and cage insertion. The operative technique was either a posterior lumbar interbody fusion (PLIF) or a transforaminal lumbar interbody fusion (TLIF) performed by three different senior orthopedic surgeons. Exclusion criteria were spine fractures, minimally invasive techniques, underlying malignant diseases or acute infections, previous or multisegmental spine surgery as well as preoperative neurologic impairment. Of 89 initially contacted patients, 17 patients were included for data analysis (11 males, six females).ResultsThe data of 17 patients after mono‐ or bisegmental lumbar fusion surgery to treat low‐grade lumbar spondylolisthesis and with a follow‐up time of least 72 months were analyzed. The mean age was 66.7 ± 11.3 years. In terms of complications two dural tears and one intraoperative bleeding occurred. The average body mass index (BMI) was 27.6 ± 4.4 kg/m² and the average inpatient length of stay was 12.9 ± 3.8 days (range: 8–21). The long‐term clinical outcome correlated significantly with the change of the pelvic tilt (r _s = −0.515, P < 0.05) and the sagittal rotation (r _s = −0.545, P < 0.05). The sacral slope was significantly associated with the sacral inclination (r _s = 0.637, P < 0.01) and the pelvic incidence (r _s = 0.500, P < 0.05). In addition, the pelvic incidence showed a significant correlation with the pelvic tilt (r _s = 0.709, P < 0.01). The change of the different clinical scores over time also correlated significantly between the different questionnaires.ConclusionsThe surgical modification of the pelvic tilt and the sagittal rotation are the two radiological alignment parameters that can most accurately predict the long‐term clinical outcome after lumbar interbody fusion surgery.     

L-Serine Treatment is Associated with Improvements in Behavior,EEG, and Seizure Frequency in Individuals with GRIN-Related Disorders Due to Null Variants

Pathogenic missense variants in GRIN2A and GRIN2B may result in gain or loss of function (GoF/LoF) of the N-methyl-D-aspartate receptor (NMDAR). This observation gave rise to the hypothesis of successfully treating GRIN-related disorders due to LoF variants with co-agonists of the NMDAR. In this respect, we describe a retrospectively collected series of ten individuals with GRIN2A- or GRIN2B-related disorders who were treated with L-serine, each within an independent n-of-1 trial. Our cohort comprises one individual with a LoF missense variant with clinical improvements confirming the above hypothesis and replicating a previous n-of-1 trial. A second individual with a GoF missense variant was erroneously treated with L-serine and experienced immediate temporary behavioral deterioration further supporting the supposed functional pathomechanism. Eight additional individuals with null variants (that had been interpreted as loss-of-function variants despite not being missense) again showed clinical improvements. Among all nine individuals with LoF missense or null variants, L-serine treatment was associated with improvements in behavior in eight (89%), in development in four (44%), and/or in EEG or seizure frequency in four (44%). None of these nine individuals experienced side effects or adverse findings in the context of L-serine treatment. In summary, we describe the first evidence that L-serine treatment may not only be associated with clinical improvements in GRIN-related disorders due to LoF missense but particularly also null variants.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-021-01173-9.     

Vitamin-D Deficiency and Supplementation Altered the Network of the Coronary Arteries in a Rodent Model—In Situ Video Microscopic Technique

The aim of our study was to identify whether vitamin-D deficiency (VDD) can alter the geometry of the coronary-resistance-artery system. Male Wistar rats were divided into vitamin-D-deficient (VD−, n = 10) and vitamin-D-supplemented (VD+, n = 8) groups. After eight weeks, branches and segments of the left-anterior-descending-coronary-artery (LAD) network were analyzed by a video-microscopy technique. Segments were divided into 50 μm-long cylindrical ring units. VDD did not increase the number of morphological abnormalities. The number of segments did not differ between the groups (VD−: 210 and VD+: 224; pooled data of 8 networks). A larger lumen area of branches was found in VD+ group, while 1–4-order branches were lengthier in the VD− group. VD− rats had less rich coronary-resistance-artery networks in terms of 50 µm-long units. (VD−: 6365 vs. VD+: 6602; pooled data of 8 networks). VD+ animals were richer in the 100–350 µm outer diameter range, and VD− animals were richer in the 400–550 µm-diameter units. In VD− rats, 150–200 and 300 µm units were almost missing at higher flow distances from the orifice. Serum vitamin-D alterations caused by dietary changes can affect the geometry of the coronary-artery network, which may contribute to vitamin-D-dependent changes in cardiovascular mortality.     

Risk assessment in COVID‐19: Prognostic importance of cardiovascular parameters

BackgroundCardiovascular risk factors and comorbidities are highly prevalent among COVID‐19 patients and are associated with worse outcomes.HypothesisWe therefore investigated if established cardiovascular risk assessment models could efficiently predict adverse outcomes in COVID‐19. Furthermore, we aimed to generate novel risk scores including various cardiovascular parameters for prediction of short‐ and midterm outcomes in COVID‐19.MethodsWe included 441 consecutive patients diagnosed with SARS‐CoV‐2 infection. Patients were followed‐up for 30 days after the hospital admission for all‐cause mortality (ACM), venous/arterial thromboembolism, and mechanical ventilation. We further followed up the patients for post‐COVID‐19 syndrome for 6 months and occurrence of myocarditis, heart failure, acute coronary syndrome (ACS), and rhythm events in a 12‐month follow‐up. Discrimination performance of DAPT, GRACE 2.0, PARIS‐CTE, PREDICT‐STABLE, CHA2‐DS2‐VASc, HAS‐BLED, PARIS‐MB, PRECISE‐DAPT scores for selected endpoints was evaluated by ROC‐analysis.ResultsOut of established risk assessment models, GRACE 2.0 score performed best in predicting combined endpoint and ACM. Risk assessment models including age, cardiovascular risk factors, echocardiographic parameters, and biomarkers, were generated and could successfully predict the combined endpoint, ACM, venous/arterial thromboembolism, need for mechanical ventilation, myocarditis, ACS, heart failure, and rhythm events. Prediction of post‐COVID‐19 syndrome was poor.ConclusionRisk assessment models including age, laboratory parameters, cardiovascular risk factors, and echocardiographic parameters showed good discrimination performance for adverse short‐ and midterm outcomes in COVID‐19 and outweighed discrimination performance of established cardiovascular risk assessment models.     

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