Mitochondrial DNA and Inflammation Are Associated with Cerebral Vessel Remodeling and Early Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus.

Cerebrovascular disease accounts for major neurologic disabilities in patients with type 2 diabetes mellitus (DM). A potential association of mitochondrial DNA (mtDNA) and inflammation with cerebral vessel remodeling in patients with type 2 DM was evaluated. A cohort of 150 patients and 30 healthy controls were assessed concerning urinary albumin/creatinine ratio (UACR), synaptopodin, podocalyxin, kidney injury molecule-1 (KIM-1), N-acetyl-ß-(D)-glucosaminidase (NAG), interleukins IL-17A, IL-18, IL-10, tumor necrosis factor-alpha (TNFα), intercellular adhesion molecule-1 (ICAM-1). MtDNA-CN and nuclear DNA (nDNA) were quantified in peripheral blood and urine by qRT-PCR. Cytochrome b (CYTB) gene, subunit 2 of NADH dehydrogenase (ND2), and beta 2 microglobulin nuclear gene (B2M) were assessed by TaqMan assays. mtDNA-CN was defined as the ratio of the number of mtDNA/nDNA copies, through analysis of the CYTB/B2M and ND2/B2M ratio; cerebral Doppler ultrasound: intima-media thickness (IMT)-the common carotid arteries (CCAs), the pulsatility index (PI) and resistivity index (RI)- the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs), the breath-holding index (BHI). The results showed direct correlations of CCAs-IMT, PI-ICAs, PI-MCAs, RI-ICAs, RI-MCAs with urinary mtDNA, IL-17A, IL-18, TNFα, ICAM-1, UACR, synaptopodin, podocalyxin, KIM-1, NAG, and indirect correlations with serum mtDNA, IL-10. BHI correlated directly with serum IL-10, and serum mtDNA, and negatively with serum IL-17A, serum ICAM-1, and NAG. In neurologically asymptomatic patients with type 2 DM cerebrovascular remodeling and impaired cerebrovascular reactivity may be associated with mtDNA variations and inflammation from the early stages of diabetic kidney disease.

Mitochondrial DNA Changes in Blood and Urine Display a Specific Signature in Relation to Inflammation in Normoalbuminuric Diabetic Kidney Disease in Type 2 Diabetes Mellitus Patients.

Mitochondrial dysfunction is an important mechanism contributing to the development and progression of diabetic kidney disease (DKD). Mitochondrial DNA (mtDNA) levels in blood and urine were evaluated in relation to podocyte injury and proximal tubule (PT) dysfunction, as well as to a specific inflammatory response in normoalbuminuric DKD. A total of 150 type 2 diabetes mellitus (DM) patients (52 normoalbuminuric, 48 microalbuminuric, and 50 macroalbuminuric ones, respectively) and 30 healthy controls were assessed concerning the urinary albumin/creatinine ratio (UACR), biomarkers of podocyte damage (synaptopodin and podocalyxin), PT dysfunction (kidney injury molecule-1 (KIM-1) and N-acetyl-ß-(D)-glucosaminidase (NAG)), and inflammation (serum and urinary interleukins (IL-17A, IL-18, and IL-10)). MtDNA-CN and nuclear DNA (nDNA) were quantified in peripheral blood and urine via qRT-PCR. MtDNA-CN was defined as the ratio of the number of mtDNA/nDNA copies via analysis of the CYTB/B2M and ND2/B2M ratio. Multivariable regression analysis provided models in which serum mtDNA directly correlated with IL-10 and indirectly correlated with UACR, IL-17A, and KIM-1 (R2 = 0.626; p < 0.0001). Urinary mtDNA directly correlated with UACR, podocalyxin, IL-18, and NAG, and negatively correlated with eGFR and IL-10 (R2 = 0.631; p < 0.0001). Mitochondrial DNA changes in serum and urine display a specific signature in relation to inflammation both at the podocyte and tubular levels in normoalbuminuric type 2 DM patients.

Combined Anterior Cruciate Ligament and Anterolateral Ligament Reconstruction Results in Superior Rotational Stability Compared with Isolated Anterior Cruciate Ligament Reconstruction in High Grade Pivoting Sport Patients: A Prospective Randomized Clinical Trial.

The purpose of the current randomized clinical trial (RCT) was to evaluate the clinical outcomes of combined anterior cruciate ligament (ACL) and anterolateral ligament (ALL) reconstruction and to compare them with those of isolated ACL reconstruction. The hypothesis was that combined ACL and ALL reconstruction will result in superior clinical outcomes in terms of the rotational stability of the knee. This prospective RCT included 57 patients (44 men and 13 women, mean age = 31 ± 7.1 years) who underwent ACL reconstruction either isolated (Group I: 25 patients) or combined with ALL reconstruction (Group II: 32 patients). The evaluation of the patients was done preoperatively and postoperatively at 6 weeks, 12 weeks, 6 months, and 12 months including a clinical examination (Lachman's test, Pivot shift's test, and Rolimeter differential anterior laxity), an objective clinical scores (objective: the International Knee Documentation Committee [IKDC] score) and a subjective clinical scores (subjective: IKDC's score, Lysholm's score, and Tegner's activity score). Postoperative complications of all the patients were recorded. There was a significant difference between the study groups at all follow-up intervals when evaluating the postoperative pivot shift test (p < 0.05) with a superior rotational stability in the group of combined ACL and ALL reconstruction. At the final follow-up evaluation, 36% of the patients from Group I and 6.2% in Group II had a grade I positive pivot shift test (p < 0.05). There was a statistically significant difference between the two groups regarding the number of patients with a grade A IKDC objective score (p < 0.05) at the 6- and 12-month follow-up intervals (p = 0.007). There was a significant difference concerning the IKDC subjective score between the two study groups in favor of the combined ACL and ALL reconstruction group at 12 months postoperatively (p = 0.048). Combined ACL and ALL reconstruction technique was demonstrated to be effective in obtaining a superior control of the rotational knee instability and to improve the clinical objective and subjective outcomes when compared with isolated ACL reconstruction in sports patients with high-grade pivoting shifts.

Return to physical activity and change in body mass index after hypoallergenic medial mobile-bearing unicompartmental knee arthroplasty.

BACKGROUND: The primary purpose of the present prospective study was to consecutively analyse the outcomes of the return to sports activity of patients with positive patch tests undergoing a medial mobile-bearing titanium niobium nitride (TiNbN) unicompartmental knee arthroplasty (UKA). The secondary purpose was to ascertain if a higher grade of physical activity leads to a reduction in the body mass index (BMI) of the patients. MATERIAL AND METHODS: Forty-one patients with positive skin patch tests were included in this prospective study. The clinical evaluation consisted of the University of California, Los Angeles (UCLA) activity scale and the High-Activity Arthroplasty Score (HAAS). Each patient was evaluated the day before surgery (T0), after 12.37 ± 0.70 months (T1), and on the day of the final follow-up, after 67.03 ± 18.2 months (T2). Furthermore, the BMI of each patient was analysed before surgery and during the final follow-up. RESULTS: The UCLA and HAAS mean preoperative values ranged from 3.68 ± 1.1.7 and 6.15 ± 0.76 to 6.1 ± 0.76 and 10.34 ± 1.3, respectively, at T1 (p < 0.0001) and to the final values of 6.34 ± 0.62 and 11.0 ± 8.9, respectively, at T2 (UCLA: T2 versus T1: p = 0.132; T2 versus T0: p < 0.0001; HAAS: T2 versus T1: p = 0.0027; T2 versus T0: p < 0.001). BMI ranged from a preoperative value of 27.97 ± 3.63 to a final value of 26.84 ± 3.11 (p < 0.0001). The only differences within the subgroups concerned patients with BMI ≥ 28, showing a superior HAAS at each follow-up (p < 0.05). A positive correlation was found between BMI and HAAS at T0 and T2 (p < 0.05). CONCLUSIONS: This is the first study to evaluate the rate of the return to sports activities and change in BMI following hypoallergenic UKA. The majority of patients reduced their weight following UKA and improved their physical activity, showing outcomes that were comparable to the standard cobalt-chrome (CoCr) prostheses, regardless of gender, age, BMI and implant size. LEVEL OF EVIDENCE: IV - Prospective Cohort Study. Trial registration researchregistry5978-Research Registry www.researchregistry.com.

Long noncoding RNAs may impact podocytes and proximal tubule function through modulating miRNAs expression in Early Diabetic Kidney Disease of Type 2 Diabetes Mellitus patients.

Aims: Long noncoding RNAs (lncRNAs) play key roles in the pathophysiology of DKD involving actions of microRNAs (miRNAs). The aims of the study were to establish the involvement of selected lncRNAs in the epigenetic mechanisms of podocyte damage and tubular injury in DKD of type 2 diabetes mellitus (DM) patients in relation to a particular miRNAs profile. Methods: A total of 136 patients with type 2 DM and 25 healthy subjects were assessed in a cross-sectional study concerning urinary albumin: creatinine ratio (UACR), eGFR, biomarkers of podocyte damage (synaptopodin, podocalyxin) and of proximal tubule (PT) dysfunction (Kidney injury molecule-1-KIM-1, N-acetyl-D-glucosaminidase-NAG), urinary lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), nuclear-enriched abundant transcript 1 (NEAT1), myocardial infarction-associated transcript (MIAT), taurine-upregulated gene 1 (TUG1), urinary miRNA21, 124, 93, 29a. Results: Multivariable regression analysis showed that urinary lncMALAT1 correlated directly with urinary synaptopodin, podocalyxin, KIM-1, NAG, miRNA21, 124, UACR, and negatively with eGFR, miRNA93, 29a (p<0.0001; R2=0.727); urinary lncNEAT1 correlated directly with synaptopodin, KIM-1, NAG, miRNA21, 124, and negatively with eGFR, miRNA93, 29a (p<0.0001; R2=0.702); urinary lncMIAT correlated directly with miRNA93 and 29a, eGFR (p<0.0001; R2=0.671) and negatively with synaptopodin, KIM-1, NAG, UACR, miRNA21, 124 (p<0.0001; R2=0.654); urinary lncTUG1 correlated directly with eGFR, miRNA93, 29a, and negatively with synaptopodin, podocalyxin, NAG, miRNA21, 124 (p<0.0001; R2=0.748). Conclusions: In patients with type 2 DM lncRNAs exert either deleterious or protective functions within glomeruli and PT. LncRNAs may contribute to DKD through modulating miRNAs expression and activities. This observation holds true independently of albuminuria and DKD stage.

Improving radiographic patello-femoral tracking in total knee arthroplasty with the use of a flexion spacer: a case-control study.

PURPOSE: The purpose of this study was to compare the effectiveness of a flexion spacer in the clinical and radiological outcomes of patients who underwent total knee arthroplasty (TKA) and to compare these patients to a group of patients subjected to the same type of surgery but without the use of a flexion spacer. It was hypothesized that patients who underwent TKA using a flexion spacer would have better clinical and radiological outcomes than those without a flexion spacer in both short- and medium-term follow-ups. METHODS: A consecutive series of patients undergoing TKA were included, yielding 20 patients in the study group. The control group was identified from the consultant database of the senior author, yielding 21 patients who underwent the same operation. All 41 patients received a Vanguard Knee System (Zimmer-Biomet, Warsaw, Indiana, USA). Cases were defined as those patients who had undergone TKA using a flexion spacer device for gap balancing; controls were defined as patients who had undergone TKA without the support of a flexion spacer device. Patients were clinically and radiographically evaluated at two consecutive follow-ups: T1-13.1 ± 1.3 months and T2-108 ± 6 months. Clinical evaluation was performed using the Knee Society Scoring System and the Western Ontario, McMaster Universities Osteoarthritis Index score. Radiographic evaluation included the femoral angle (α), the tibial angle (ß), the sagittal femoral (γ) angle and the tibial slope (δ). Furthermore, the lateral patellofemoral angle (LPFA) and the Caton-Deschamps index were evaluated. RESULTS: No statistically significant clinical differences were found between the two groups at T1 and T2; moreover, the clinical outcomes of the two groups were stable between the two follow-ups, with no significant improvement or worsening. Radiographic evaluation showed no difference in the two groups between T1 and T2; the only significant radiographic difference between the two groups concerned the LPFA (both at 30° and 60°) at each follow-up, which was significantly greater in cases than in controls (p = 0.001). CONCLUSIONS: The current study demonstrates that the use of a flexion spacer significantly improves radiographic patello-femoral tracking, although no significant clinical differences were found between the two groups. LEVEL OF EVIDENCE: Case-control study, level III.

Urinary proteins detected using modern proteomics intervene in early type 2 diabetic kidney disease - a pilot study.

Aim: An advanced proteomics platform for protein biomarker discovery in diabetic chronic kidney disease (DKD) was developed, validated and implemented. Materials & methods: Three Type 2 diabetes mellitus patients and three control subjects were enrolled. Urinary peptides were extracted, samples were analyzed on a hybrid LTQ-Orbitrap Velos Pro instrument. Raw data were searched using the SEQUEST algorithm and integrated into Proteome Discoverer platform. Results & discussion: Unique peptide sequences, resulted sequence coverage, scoring of peptide spectrum matches were reported to albuminuria and databases. Five proteins that can be associated with early DKD were found: apolipoprotein AI, neutrophil gelatinase-associated lipocalin, cytidine deaminase, S100-A8 and hemoglobin subunit delta. Conclusion: Urinary proteome analysis could be used to evaluate mechanisms of pathogenesis of DKD.

Combined Anatomic Anterior Cruciate Ligament and Anterolateral Ligament Reconstruction.

PURPOSE: The purpose of the current paper was to report the surgical technique of combined anatomic anterior cruciate ligament (ACL) and anterolateral ligament (ALL) reconstruction as well as the short term clinical results after this surgical procedure. MATERIAL AND METHODS: The current prospective study included 32 patients (5 females and 27 males) with combined ACL and ALL reconstruction performed between December 2015 and July 2016. The patients were included in the study taking into consideration the following criteria: chronic ACL lesion, high grade rotational instability (pivot shift grade II and III) and participation in high grade pivoting sports. Patient evaluation followed an established clinical and imaging protocol both preoperatively and at 6 and 12 weeks postoperatively. This included clinical knee stability testing (Lachman test, Pivot shift test), Rolimeter differential laxity testing, subjective and objective IKDC scores and Lysholm score and Tegner score. RESULTS: Postoperative stability at 6 weeks and 12 weeks as tested with Lachman test (p=0.02 and 0.01, respectively), pivot shift test (p=0.03 and 0.01, respectively) and the Rolimeter arthrometer (p=0.008 and 0.006, respectively) showed a statistically significant difference as compared to preoperative values. Postoperative scores at 6 weeks and 12 weeks as measured using objective IKDC form (p=0.008 and 0.006, respectively), subjective IKDC form (p=0.04 and 0.03, respectively) and Lysholm form (p=0.02 and 0.01, respectively) were statistically significant improved as compared to preoperative values. All patients had a negative Lachman test at 6 and 12 weeks postoperatively. One patient had a positive grade I pivot shift test at 6 weeks postoperatively and two patients had a positive grade I pivot shift test at 12 weeks postoperatively. Differential anteroposterior laxity as measured with the Rolimeter arthrometer improved from 7.19±1.96 mm preoperatively to 0.28±0.45 mm and 0.13±0.34 mm, at 6 weeks and 12 weeks postoperatively, respectively. According to the objective IKDC form, 29 patients were normal or nearly normal (grade A and B) at 6 weeks postoperatively and 31 patients were normal or nearly normal at 12 weeks postoperatively. Subjective IKDC score improved from 47.72±17.18 preoperatively to 56.52±11.74 and 73.38±14.28 at 6 and 12 weeks postoperatively, respectively. Lysholm score improved from 63.44±23.01 preoperatively to 80.41±11.94 and 90.47±8.22 at 6 and 12 weeks postoperatively, respectively. Improved Tegner activity scores were present at 12 weeks postoperatively as compared with 6 weeks postoperatively, but still lower as compared to pre-traumatic scores. No significant complications were present in the current study group. CONCLUSIONS: Combined ACL and ALL reconstruction is an effective surgical procedure, with improved postoperative clinical results and no significant short term complications. Longer follow-up is necessary in order to better evaluate the results of this procedure.

Romanian medicine, European medicine.

The aim of the present paper is to present the message transmitted by the Presidential Lecture given during the first congress of arthroscopy organised in Romania, in March 2016, by the Romanian Society of Arthroscopy and Sports Trauma (SRATS). The goal was to present the evolution of medical care in Romania over the years, with the remarkable progress made in the first half of the twentieth century and the current status of arthroscopic surgery as seen from the point of view of medical professionals, as well as from a governmental point of view.

Proximal Tibial Anterior Closing Wedge Osteotomy in Repeat Revision of Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Physicians should consider an increased posterior tibial slope (PTS) as a risk factor for graft failure when proposing anterior cruciate ligament (ACL) re-revision. PURPOSE: To describe the surgical technique of combined ACL revision and proximal tibial anterior closing wedge osteotomy and to evaluate its clinical outcome in cases of recurrent graft failure with associated increased tibial slope. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Between 2008 and 2010, 5 combined ACL re-revisions with proximal tibial anterior closing wedge osteotomy were retrospectively evaluated after a mean 31.6 months' follow-up (range, 23-45 months). All patients reported subjective knee instability preoperatively and demonstrated increased laxity on physical examination. Intrinsic risk factors for graft failure (excessive tibial slope) were identified in all cases. Preoperative and postoperative functional assessments included the International Knee Documentation Committee (IKDC) score along with the Lysholm score and Tegner activity scale. RESULTS: The mean Lysholm score was 46.2 preoperatively (range, 26-69) and 87.8 (range, 60-100) postoperatively. The mean IKDC subjective score was 39.5 (range, 21.8-64.4) before surgery and 79.1 (range, 48.3-98.9) at the last follow-up. The mean Tegner activity score was 7.4 (range, 5-9) before the latest ACL injury and 7.2 (range, 5-9) at the last follow-up. The mean PTS was 13.6° (range, 13°-14°) preoperatively and 9.2° (range, 8°-10°) postoperatively (P = .0005). The mean differential anterior laxity was 10.4 mm (range, 8-14 mm), and this significantly decreased to 2.8 mm (range, 2-4 mm) at the last follow-up. Using the Kellgren-Lawrence classification to evaluate the presence of arthritis, 1 patient was grade 1, 3 patients were grade 2, and 1 patient was grade 3. CONCLUSION: Combined ACL re-revision with proximal tibial anterior closing wedge osteotomy restores knee stability and function with satisfactory clinical outcomes in patients who experience recurrent ACL ruptures with an associated increased PTS.