Do Clinical Outcomes and Failure Rates Differ in Patients With Combined ACL and Grade 2 MCL Tears Versus Isolated ACL Tears?: A Prospective Study With 14-Year Follow-up

Background: A combined injury to the anterior cruciate ligament (ACL) and medial collateral ligament (MCL) is a common injury pattern encountered during clinical practice. Recent systematic reviews have found no consensus on the optimal method of managing this combined ligament injury pattern, and no long-term studies with modern techniques are available in the literature. Purpose: To compare 2 groups of patients who underwent isolated ACL reconstruction in terms of failures and clinical scores at long-term follow-up. In the first group were patients with isolated ACL tears (ACL group), while the second was composed of patients with combined ACL and MCL grade 2 tears (ACL + MCL group). Study Design: Cohort study; Level of evidence, 3. Methods: A total of 57 patients (37 in the ACL group and 20 in the ACL + MCL group) underwent isolated ACL reconstruction with a double-bundle technique between January and December 2005. Patients were contacted for scores on the International Knee Documentation Committee subjective form, Western Ontario and McMaster Universities Osteoarthritis Index, and Tegner activity scale as well as data regarding ipsilateral or contralateral revision ACL surgery. A 2-way analysis of variance for repeated measures was used to statistically assess the differences between the groups. Results: Overall, 49 patients (86%) completed the survey and were therefore included in the study. The minimum follow-up was 14.6 years (range, 14.1-15.2 years). There was a significant reduction in both groups of all the outcome scores between the intermediate and final-follow-up. The number of failures was 3 of 31 (9.7%) in the ACL group and 1 of 18 (5.5%) in the ACL + MCL group; this difference was not significant. Moreover, there were no clinical differences between the groups in terms of graft failures, contralateral lesions, and clinical scores. Conclusion: At 14-year follow-up, no clinical difference or increased failure rate was observed between the study groups, suggesting that isolated ACL reconstruction could represent an appropriate treatment for a combined ACL and MCL grade 2 lesion.

Clinical Interpretation of Working Volume and Weight Support in Upper Limb Robotic Neurorehabilitation after Stroke

In the past two decades, many studies reported the efficacy of upper limb robotic rehabilitation in patients after stroke, also in its chronic phase. Among the possible advantages of robotic therapy over conventional therapy are the objective measurements of kinematic and kinetic parameters during therapy, such as the spatial volume covered by the patient’s upper limb and the weight support provided by the robot. However, the clinical meaning and the usability of this information is still questioned. Forty patients with chronic stroke were enrolled in this study and assessed at the beginning of upper limb robotic therapy (Armeo® Power) and after two weeks (ten sessions) of therapy by recording the working volume and weight support provided by the robot and by administering six clinical scales to assess upper limb mobility, strength, spasticity, pain, neurological deficits, and independency. At baseline, the working volume significantly correlated with spasticity, whereas weight support significantly correlated with upper limb strength, pain, spasticity, and neurological deficits. After two weeks of robotic rehabilitation, all the clinical scores as well as the two parameters improved. However, the percentage changes in the working volume and weight support did not significantly correlate with any of the changes in clinical scores. These results suggest caution in using the robotic parameters as outcome measures because they could follow the general improvement of the patient, but complex relationships with clinical features are possible. Robotic parameters should be analyzed in combination with the clinical scores or other objective measures because they may be informative about therapy progression, and there is a need to combine their clinical, neuroscientific, and biomechanical results to avoid misleading interpretations.

S100B Protein as a Therapeutic Target in Multiple Sclerosis: The S100B Inhibitor Arundic Acid Protects from Chronic Experimental Autoimmune Encephalomyelitis

S100B is an astrocytic protein behaving at high concentration as a damage-associated molecular pattern molecule. A direct correlation between the increased amount of S100B and inflammatory processes has been demonstrated, and in particular, the inhibitor of S100B activity pentamidine has been shown to ameliorate clinical scores and neuropathologic-biomolecular parameters in the relapsing-remitting experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. This study investigates the effect of arundic acid (AA), a known inhibitor of astrocytic S100B synthesis, in the chronic experimental autoimmune encephalomyelitis, which is another mouse model of multiple sclerosis usually studied. By the daily evaluation of clinical scores and neuropathologic-molecular analysis performed in the spinal cord, we observed that the AA-treated group showed lower severity compared to the vehicle-treated mice, particularly in the early phase of disease onset. We also observed a significant reduction of astrocytosis, demyelination, immune infiltrates, proinflammatory cytokines expression and enzymatic oxidative reactivity in the AA-treated group. Overall, our results reinforce the involvement of S100B in the development of animal models of multiple sclerosis and propose AA targeting the S100B protein as a focused potential drug to be considered for multiple sclerosis treatment.

Serum Levels of TNF-α Are Increased in Patients with Rotator Cuff Tear and Sleep Disturbance

The purpose of this study was to determine serum levels of sleep-related cytokines in patients with rotator cuff tear (RCT) who were experiencing pain-related sleep disturbance. Peripheral blood samples before surgery were collected from 63 study participants and divided into three groups: RCT with sleep disturbance group; SD group (n = 21), RCT with normal sleep group; NS group (n = 21), and patients with chronic shoulder instability; control group (n = 21). Serum concentration levels of interleukin-1α (IL-1α), IL-1β, IL-2, IL-6, IL-8, IL-10, and tumor necrosis factor-α (TNF-α) were measured via ELISA. The associations between serum levels of sleep-related cytokines and clinical scores and the Pittsburgh Sleep Quality Index (PSQI) were analyzed. Serum concentration levels of TNF-α were significantly higher in the SD group compared with those of the NS and control groups (p ≤ 0.001 and 0.05). Serum levels of IL-8 and IL-10 were significantly higher in the SD group compared with those of control group (p = 0.01 and = 0.05), but did not differ significantly from that of the NS group. There were no associations between serum levels of sleep-related cytokines and all clinical scores. The current findings suggest that TNF-α may be associated with sleep disturbance in patients with RCT.

Clinical Scores in Veterinary Medicine: What Are the Pitfalls of Score Construction, Reliability, and Validation? A General Methodological Approach Applied in Cattle

Clinical scores are commonly used for cattle. They generally contain a mix of categorical and numerical variables that need to be assessed by scorers, such as farmers, animal caretakers, scientists, and veterinarians. This article examines the key concepts that need to be accounted for when developing the test for optimal outcomes. First, the target condition or construct that the scale is supposed to measure should be defined, and if possible, an adequate proxy used for classification should be determined. Then, items (e.g., clinical signs) of interest that are either caused by the target condition (reflective items) or that caused the target condition (formative items) are listed, and reliable items (inter and intra-rater reliability) are kept for the next step. A model is then developed to determine the relative weight of the items associated with the target condition. A scale is then built after validating the model and determining the optimal threshold in terms of sensitivity (ability to detect the target condition) and specificity (ability to detect the absence of the target condition). Its robustness to various scenarios of the target condition prevalence and the impact of the relative cost of false negatives to false positives can also be assessed to tailor the scale used based on specific application conditions.

Characteristics and Short-Term Surgical Outcomes of Patients with Recurrent Lumbar Disc Herniation after Percutaneous Laser Disc Decompression

Background and Objectives: Although percutaneous laser disc decompression (PLDD) is one of the common treatment methods for patients with lumbar disc herniation (LDH), the recurrence of LDH after PLDD is estimated at 4–5%. This study compares the preoperative clinical data and clinical outcomes of patients who underwent primary microendoscopic discectomy (MED) or MED following PLDD. Materials and Methods: We retrospectively analyzed 2678 patients who underwent MED for LDH. The PLDD group included patients with previous PLDD history at the same level of LDH, and a matched control group was created using propensity score matching for age, sex, and body mass index. Preoperative data, preoperative radiographic findings, and surgical data of the groups were compared. To compare postoperative changes in clinical scores between the groups, a mixed-effect model was used. Results: As a result, 42 patients (1.6%) had previously undergone PLDD, and a control group with 42 patients were created. The disc degeneration severity was not significantly different between the groups. However, Modic changes were more frequent in the PLDD group than in the matched control group (p = 0.028). There were no significant differences in dural adhesion rate or surgery-related complications including dural injury, length of stay, and recurrence rate of LDH after surgery. In addition, the improvement of clinical scores did not significantly differ between the two groups (p = 0.112, 0.913, respectively). Conclusions: We concluded that patients with recurrent LDH after PLDD have advanced endplate degeneration, which may reflect endplate injury from a previous PLDD. However, a previous history of PLDD does not have a negative impact on the clinical result of MED.

Prebiotic Galactooligosaccharide Supplementation in Adults with Ulcerative Colitis: Exploring the Impact on Peripheral Blood Gene Expression, Gut Microbiota, and Clinical Symptoms

Prebiotics may promote immune homeostasis and reduce sub-clinical inflammation in humans. This study investigated the effect of prebiotic galactooligosaccharide (GOS) supplementation in colonic inflammation. Seventeen patients with active ulcerative colitis (UC) consumed 2.8 g/d GOS for 6 weeks. At baseline and 6 weeks, gene expression (microarray), fecal calprotectin (ELISA), microbiota (16S rRNA), short-chain fatty acids (SCFAs; gas-liquid chromatography), and clinical outcomes (simple clinical colitis activity index (SCCAI), gastrointestinal symptom rating scale (GSRS), and Bristol stool form scale (BSFS)) were measured. Following prebiotics, clinical scores (SCCAI), fecal calprotectin, SCFAs, and pH were unchanged. Five genes were upregulated and two downregulated. Normal stool proportion (BSFS) increased (49% vs. 70%, p = 0.024), and the incidence (46% vs. 23%, p = 0.016) and severity (0.7 vs. 0.5, p = 0.048) of loose stool (GSRS), along with urgency (SCCAI) scores (1.0 vs. 0.5, p = 0.011), were reduced. In patients with a baseline SCCAI ≤2, prebiotics increased the relative abundance of Bifidobacterium from 1.65% (1.97) to 3.99% (5.37) (p = 0.046) and Christensenellaceae from 0.13% (0.33) to 0.31% (0.76) (p = 0.043). Prebiotics did not lower clinical scores or inflammation but normalized stools. Bifidobacterium and Christensenellaceae proportions only increased in patients with less active diseases, indicating that the prebiotic effect may depend on disease activity. A controlled study is required to validate these observations.

Double-high insert presents with worse mid-term outcomes in cruciate-retaining medial-pivotal total knee arthroplasty – a propensity score matched analysis with averaged 8-year follow-up

Background The aim of this study was to compare the mid-term clinical and radiographic outcomes between medial-pivotal (MP) insert and double-high (DH) insert used under cruciate-retaining condition in ADVANCE® total knee arthroplasty (TKA). Methods The follow-up was conducted for 158 consecutive patients underwent unilateral ADVANCE® TKA from January 2011 to April 2014. 84 MP inserts and 74 DH inserts were used under cruciate-retaining condition. A 1:1 propensity score matching (PSM) analysis was performed between MP insert and DH insert to compare the clinical and radiographic outcomes. Results After a 1:1 PSM, 120 patients (60 pairs) were matched between MP insert and DH insert. The baseline demographic parameters and clinical scores were comparable between the two groups. The postoperative clinical outcomes at an averaged 8-year follow-up of both groups were significantly improved. The range of motion (ROM) of DH group was better than that of MP group and equivalent Knee Society Function Score (KSFS) between the two groups was found. However, the Knee Society Score (KSS), Western Ontario and McMaster Universities Arthritis Index (WOMAC) score and Forgotten Joint Score (FJS) of MP group were found to be significantly superior than those of DH group. Comparable complication rate and revision rate were observed between the two groups. The radiographic results were also equally good between MP and DH group. Conclusions Although the mid-term clinical and radiographic outcomes of DH insert are fairly good, the clinical scores of DH group were worse than those of MP group.

Anti-Inflammatory Properties of Fructo-Oligosaccharides in a Calf Lung Infection Model and in Mannheimia haemolytica-Infected Airway Epithelial Cells

Emerging antimicrobial-resistant pathogens highlight the importance of developing novel interventions. Here, we investigated the anti-inflammatory properties of Fructo-oligosaccharides (FOS) in calf lung infections and in airway epithelial cells stimulated with pathogens, and/or bacterial components. During a natural exposure, 100 male calves were fed milk replacer with or without FOS for 8 weeks. Then, immune parameters and cytokine/chemokine levels in the bronchoalveolar lavage fluid (BALF) and blood were measured, and clinical scores were investigated. Calf primary bronchial epithelial cells (PBECs) and human airway epithelial cells (A549) were treated with Mannheimia haemolytica, lipopolysaccharides (LPS), and/or flagellin, with or without FOS pretreatment. Thereafter, the cytokine/chemokine levels and epithelial barrier function were examined. Relative to the control (naturally occurring lung infections), FOS-fed calves had greater macrophage numbers in BALF and lower interleukin (IL)-8, IL-6, and IL-1β concentrations in the BALF and blood. However, FOS did not affect the clinical scores. At slaughter, FOS-fed calves had a lower severity of lung lesions compared to the control. Ex vivo, FOS prevented M. haemolytica-induced epithelial barrier dysfunction. Moreover, FOS reduced M. haemolytica- and flagellin-induced (but not LPS-induced) IL-8, TNF-α, and IL-6 release in PBECs and A549 cells. Overall, FOS had anti-inflammatory properties during the natural incidence of lung infections but had no effects on clinical symptoms.