Native knee kinematics is not reproduced after sensor guided cruciates substituting total knee arthroplasty.

PURPOSE: Gait analysis was used to evaluate knee kinematics in patients who underwent successful primary total knee arthroplasty (TKA) using two modern bi-cruciate substituting designs. The knee joint was balanced intraoperatively using real-time sensor technology, developed to provide dynamic feedback regarding stability and tibiofemoral load. The authors hypothesized that major differences exist in gait parameters between healthy controls and post-TKA patients. METHODS: Ten patients who underwent successful TKA using bi-cruciate substituting designs were evaluated at a minimum of 9 months postoperatively using three-dimensional knee kinematic analysis; a multi-camera optoelectronic system and a force platform were used. Sensor-extracted kinematic data included knee flexion angle at heel-strike (KFH), peak midstance knee flexion angle (MSKFA), maximum and minimum knee adduction angle (KAA) and knee rotational angle at heel-strike. Multiple gait analysis data from the study group were compared to a group of ten healthy controls who were matched by age, sex and BMI. Clinical outcome in the TKA group was also measured using the Knee injury and Osteoarthritis Outcome Score (KOOS). RESULTS: Clinically, at final follow-up, a statistically significant difference in pain, general symptoms, and activities of daily living was seen between the groups. From a gait analysis standpoint, TKA patients had significantly less rotation at heel strike (p = 0.04), lower late stance peak extension moments (p = 0.02), and less Knee Adduction Angle excursion during swing phase (p = 0.04) compared to the control group. No statistically significant difference was observed for knee flexion angle at heel strike, knee adduction moment, or peak knee flexion moment between the groups. CONCLUSIONS: Modern bi-cruciate substituting TKA designs failed to reproduce normal knee kinematics. The lack of full knee extension during the stance phase, absence of the "screw-home mechanism" typical of an ACL functioning knee, and the reduced fluctuation in knee adduction angle during the swing phase still represent major proprioceptive and muscular recruitment differences between normal and replaced knees.

Biomechanical considerations for an easily-restricted robot-assisted kinematic alignment: a surgical technique note.

BACKGROUND: In total knee arthroplasty, the normal kinematics of the knee may not be restored solely based on preoperative gait, fluoroscopic-based, and dynamic radiostereometric analyses. SURGICAL TECHNIQUE CASE PRESENTATION: This note introduced a 69-year-old male patient who sustained post-traumatic osteoarthritis of his right knee. He underwent robot-assisted total knee arthroplasty based on anatomical reproduction of knee stability during the swing phase of gait. The kinematic alignment was simply achieved within an easy-to-identified range after preoperative radiographic assessment, intraoperative landmarking and pre-validated osteotomy, and intraoperative range of motion testing. CONCLUSIONS: This novel technique allows personalized and imageless total knee arthroplasty. It provides a preliminary path in reproducing the anatomy alignment, natural collateral ligament laxity, and accurate component placement within safe-to-identified alignment boundaries.

Treating unexplained recurrent pregnancy loss based on lessons learned from obstetric antiphospholipid syndrome and inherited thrombophilia: A propensity-score adjusted retrospective study.

The efficacy of low molecular weight heparin (LMWH) is well-established in patients with obstetric antiphospholipid syndrome (O-APS). Their role in women with unexplained recurrent pregnancy loss (U-RPL) and late obstetrical complications (intrauterine growth restriction, IUGR and preeclampsia) is controversial. Here we compared rates of miscarriage and late obstetrical complications in RPL patients diagnosed with O-APS (n = 57) or hereditary thrombophilia (n = 25) (both assuming LMWH from the beginning of pregnancy) and in patients with a history of U-RPL (n = 118), assuming or not LMWH, followed at the 'Pregnancy at risk' and 'Recurrent pregnancy loss' outpatient clinics at the San Raffaele Hospital from April 2010 to April 2020. Patients with systemic autoimmune diseases other than primary O-APS were excluded. We tested for bivariate or multivariate associations among adverse pregnancy outcomes, the presence of thrombophilia and LMWH use by using chi-square test, Anova, propensity score adjusted univariate logistic regression and multivariate analysis as appropriate. U-RPL patients assuming LMWH from the beginning of pregnancy (group A) had a significantly lower rate of miscarriage compared to U-RPL patients who were not treated with LMWH (group B) (13 % vs. 41 % respectively, p 0.001) and similar pregnancy rates compared to both O-APS patients with a history of RPL taking LMWH (group C, 18 %) and RPL patients with thrombophilia and treated with LMWH (group D, 16 %). Our data highlight a protective effect of LMWH on miscarriage in patients with a history of U-RPL. In these patients, LMWH seems as effective as in O-APS and hereditary thrombophilia in reducing RPL.

Low incidence of intrauterine growth restriction in pregnant patients with systemic lupus erythematosus taking hydroxychloroquine.

Systemic lupus erythematosus (SLE) preferentially affects women of childbearing age. Miscarriages or fetal death, intrauterine growth restriction (IUGR), preterm delivery, preeclampsia and disease flares complicate pregnancy in SLE patients. Treatment is challenging due to the need to prevent disease exacerbations and limit obstetrical complications, while showing an acceptable safety profile for both the mother and the fetus. We collected data from 74 pregnancies in 53 SLE patients prospectively followed in a dedicated 'Pregnancy at risk' outpatient clinic from 2003 to 2019. Out of 74, 45 pregnancies patients were treated with hydroxychloroquine (HCQ). Mothers under HCQ therapy (HCQ+ patients) and those who did not receive HCQ (HCQ-) were homogeneous in terms of age and comorbidities. Disease activity prior to conception was slightly higher in HCQ+ patients. No significant difference was observed in terms of obstetrical history. In patients achieving a viable pregnancy, the rate of IUGR (4/39, 10% in HCQ+ vs 8/25, 32%, in HCQ- patients, p < .05) was significantly lower in HCQ+ patients. Conversely, HCQ+ patients displayed a significantly longer time to delivery (37.8 ± 1.72 vs. 36.3 ± 4.11 in HCQ- patients, p < .05). HCQ is safe in pregnant patients with SLE and protects against obstetrical complications.

Antiphosphatidylserine/prothrombin Antibodies in Antiphospholipid Syndrome with Intrauterine Growth Restriction and Preeclampsia.

OBJECTIVE: Antibodies that recognize the phosphatidylserine/prothrombin complex (antiphosphatidylserine/prothrombin antibodies; aPS/PT) might reveal enhanced thrombotic risk in patients with systemic lupus erythematosus. Little is known about their association with pregnancy complications in the antiphospholipid syndrome (APS). METHODS: We enrolled 55 patients with APS who were seeking pregnancy in 2 Italian hospitals. Antiphospholipid antibodies (aPL), including anticardiolipin antibodies, anti-ß2-glycoprotein I antibodies, lupus-like anticoagulant, and aPS/PT antibodies were assessed, and the patients were prospectively followed for 24 months. RESULTS: There were 65% (36/55) of the APS patients who had aPS/PT antibodies. Forty-seven pregnancies were followed, including 33 of aPS/PT+ patients. Forty-one of the 47 patients (87%) who initiated a pregnancy eventually gave birth to a child. The pregnancy duration and the mean newborn weight at delivery were significantly lower in aPS/PT+ than in aPS/PT- patients (33.1 ± 4.7 vs 36.2 ± 3.4 wks of gestation, respectively, and 2058 ± 964 g vs 2784 ± 746 g, respectively, p < 0.05). Late pregnancy complications, including intrauterine fetal death, preterm delivery, preeclampsia, and intrauterine growth restriction (IUGR), were more frequent in aPS/PT+ patients, independent of the therapy. Titers of aPS/PT IgG were significantly inversely correlated with the neonatal weight at delivery. Vascular injury, as reflected by thrombosis, fibrinoid necrosis, ischemic and hemorrhagic areas, and presence of chorangiomas characterized the IUGR placentas in the presence of aPS/PT. CONCLUSION: The aPS/PT antibodies might represent markers of aPL-related pregnancy complications, IUGR/preeclampsia in particular, and could help identify beforehand patients who may require additional treatment.

Eculizumab in a pregnant patient with laboratory onset of catastrophic antiphospholipid syndrome: A case report.

RATIONALE: Hypercoagulability and pregnancy morbidity are hallmarks of the antiphospholipid syndrome (APS). Catastrophic antiphospholipid syndrome (CAPS) is a potentially life-threatening omplication of APS, with widespread acute thrombotic microangiopathy (TMA) that can be precipitated by pregnancy and delivery and result in multiorgan damage. Unrestrained activation of the complement cascade is involved, favoring endothelial activation, tissue factor expression by leukocytes, and platelet aggregation. The complement block, which interrupts this amplification cycle, could prevent CAPS in patients with early TMA who face precipitating events. PATIENT CONCERNS: We present a nulliparous pregnant woman with APS at the 30 week of gestation who has developed thrombocytopenia, intravascular hemolysis, elevated creatinine, proteinuria, and hematuria. DIAGNOSES: These featurs were compatible with the diagnosis of CAPS. Consensually, serum C3 protein levels were rapidly decreasing, reflecting complement consumption. INTERVENTIONS: She was treated with eculizumab, a humanized monoclonal antibody against C5 that prevents the formation of the complement membrane attack complex. OUTCOMES: Laboratory parameters improved and the patient did not develop thrombosis or detectable organ/tissue damage. The patient safely delivered by cesarean section at week 32 of gestation a healthy 1640 g male infant. After 5 days, she received additional eculizumab, with complete resolution of the clinical condition. Low complement activity was detectable in the infant blood for a week after delivery. No infectious complication occurred. LESSONS: Inhibition of the terminal complement activation is safe and might be effective in patients with APS developing early TMA, enabling safe delivery and preventing thrombotic events both in the mother and in the newborn.

Association of genetic variants in the 3'UTR of HLA-G with Recurrent Pregnancy Loss.

Human Leukocyte Antigen (HLA)-G is involved in reprogramming immune responses at fetal-maternal interface during pregnancy. We evaluated the genetic diversity of the 3' Un-Translated Region (UTR) of HLA-G, previously associated with HLA-G mRNA post-transcriptional regulation, in women with unexplained Recurrent Pregnancy Loss (RPL), with 2 pregnancy losses (RPL-2, n=28), or 3 or more pregnancy losses (RPL-3, n=24), and in 30 women with a history of successful pregnancy. Results showed in RPL-2, but not in RPL-3, women compared to controls: i) higher frequency of the 14bp Ins allele, in single and in double copy; ii) significantly lower frequency of DelG/X genotype, iii) reduced frequency of the UTR-2, and UTR-3 haplotypes; iv) higher frequencies of the UTR-5, UTR-7, and UTR-8 haplotypes. This pilot study supports the relevance of performing 3'UTR HLA-G genetic screening, not limited to a specific polymorphism, but considering the extended haplotypes, as a possible predictor of pregnancy outcome.

Pregnancy outcomes in patients with systemic autoimmunity.

The impact of maternal systemic autoimmune diseases on pregnancy outcome is not unequivocally defined. We analysed the pregnancy outcome of 221 pregnancies from 181 autoimmune patients, consecutively followed in a single Italian reference centre from 2001 to 2009. All patients were prospectively followed with monthly visits. Pregnancy outcome was compared with the previous obstetrical history. The patient population comprised five groups: primary antiphospholipid syndrome (PAPS, 39 pregnancies), antiphospholipid syndrome associated with a rheumatic disease (APS/RD, 17 pregnancies), other RD (92 pregnancies), isolated autoantibodies (autoAbs) in the absence of a definite autoimmune disease (aAbs, 38 pregnancies) and reactive arthritis or spondyloarthropathies (35 pregnancies). Of these patients, 50.6% had previous pregnancy complications with an anamnestic live-birth rate of 43.4%. In these patients, complications dropped to 28.2% (44/156). This percentage was very similar to that observed in the 221 pregnancies (29.9%, 66/221) with a live-birth rate of 87.3%. Mean neonatal weight was 3018 ± 611 g; mean gestational age at delivery was 38.17 ± 2.79 weeks. Thus, 10.4% of pregnancies resulted in preterm delivery and 10.9% newborns had low weight at delivery. APS/RD patients had the worse outcome: 17.6% resulted in miscarriage, 14.3% resulted in growth restriction and 50% resulted in preterm delivery. This result was mainly due to patients with APS/systemic lupus erythematosus (SLE) that had the lowest gestational age at delivery (30.8 ± 3.56 weeks) and the lowest newborn weight (1499 ± 931 g). Results confirm that a strict follow-up and targeted treatments significantly improve pregnancy outcomes in autoimmune patients with PAPS, SLE and isolated autoAbs. The pregnancy outcome in patients with APS/SLE remains unsatisfactory.

Elevation of plasma levels of the long pentraxin 3 precedes preeclampsia in pregnant patients with type 1 diabetes.

Pregnancy complications, such as preeclampsia (PEc), have an increased incidence among patients with type 1 diabetes (T1DM), possibly because of maternal vascular involvement. The prototypic long pentraxin, pentraxin 3 (PTX3) is an acute phase reactant critically associated with vascular injury. PTX3 concentrations selectively increase in pregnant women with PEc. Here, we measured PTX3 levels in 37 consecutive pregnant patients with T1DM. Compared with PTX3 levels in healthy pregnant women at identical gestational ages, PTX3 was significantly elevated in pregnant women with diabetes. Patients with pre-existing nephropathy, a well-characterized microvascular complication of diabetes, have even higher PTX3 concentrations and worse maternal and fetal outcomes. Six/thirty-four diabetic non-nephropatic patients developed PEc: PTX3 levels rose abruptly weeks before PEc manifested (p = 0.0375). PTX3 may represent a valuable marker for early detection and prediction of PEc in patients with T1DM.