Safety and effectiveness of transjugular renal biopsy for systemic lupus erythematosus and antiphospholipid antibody syndrome patients taking antithrombotics.

BACKGROUND: Renal biopsy is the cornerstone of systemic lupus erythematosus (SLE) nephritis and antiphospholipid syndrome (APS) nephropathy management. However, transcutaneous renal biopsy (TCRB) is hampered by the antithrombotic treatment frequently prescribed for those diseases. Transjugular renal biopsy (TJRB) offers an attractive alternative for patients at increased risk of bleeding. The primary objective of the study was to describe the safety profile and diagnostic performance of TJRB in SLE and APS patients. METHODS: All SLE and/or APS patients who underwent a renal biopsy in our department (between January 2004 and October 2016) were retrospectively reviewed. Major complications were death, haemostasis nephrectomy, renal artery embolization, red blood cell transfusion, sepsis and vascular thrombosis; macroscopic haematuria, symptomatic perirenal/retroperitoneal bleeding and renal arteriovenous fistula without artery embolization were considered as minor complications. RESULTS: Two hundred and fifty-six TJRBs-119 without antithrombotics (untreated), 69 under aspirin and 68 on anticoagulants and 54 TCRBs without antithrombotics-were analysed. Their major and minor complication rates, respectively, did not differ significantly for the four groups: 0 and 8% for untreated TJRBs, 1 and 6% for aspirin-treated, 6 and 10% for anticoagulant-treated and 2 and 2% for TCRBs. The number of glomeruli sampled and the biopsy contribution to establishing a histological diagnosis was similar for the four groups. CONCLUSIONS: TJRBs obtained from SLE and APS patients taking antithrombotics had diagnostic yields and safety profiles similar to those of untreated TCRBs. Thus, TJRB should be considered for SLE and APS patients at risk of bleeding.

Placenta accrete after a frozen-thawed embryo transfer in a systemic lupus erythematosus patient treated with hydroxychloroquine.

Placenta accreta (PA) is a life-threatening disorder associated with decidual maldevelopment and a thin endometrium. Few cases of systemic lupus erythematosus (SLE) pregnancy complicated by PA have been reported, and the background pathophysiology remains elusive. Here, we report a case of PA in SLE pregnancy treated with hydroxychloroquine. A nulligravida woman with SLE, aged 41 years, visited our hospital because of infertility problems. Her SLE was treated with prednisolone and tacrolimus. We conducted assisted reproductive technology and gained several embryos. An artificial cycle successfully prepared the endometrium for embryo transfer with sufficient thickness. Over time, her SLE exacerbated, and we started hydroxychloroquine administration. Consequently, the endometrium did not respond to hormonal supplementation and remained thin, but we transferred the embryo and managed to achieve pregnancy. On the 38th week of gestation, we conducted labor induction because of elevated blood pressure. Induction was not effective, so we performed cesarean section; PA was observed. We performed compression suturing and were able to stop the hemorrhage. Postoperative uterine infarction and pelvic infection were successfully managed with conservative treatment. The present case highlights the use of hydroxychloroquine during endometrial development and contributes evidence regarding the pathogenesis of PA in pregnancy complicated by SLE.

Autologous peripheral blood haematopoietic stem cell transplantation for systemic lupus erythematosus: the observation of long-term outcomes in a Chinese centre.

OBJECTIVES: We aimed to evaluate the safety and long-term efficacy of autologous peripheral blood haematopoietic stem cell transplantation (APHSCT). METHODS: We did not want to evaluate the efficacy of antibodies but rather the clinical response by investigating progression-free survival and serologic response by assessing autoantibody titres and complement levels. RESULTS: Overall, 22 patients with SLE (17 females; median age, 23 years) undergoing APHSCT were included. The 3-year progression-free survival (PFS) was 77.27% at our centre. We found that all the patients survived over three years. The 5-year PFS and overall survival (OS) rate was 67.90% and 95.20%. The titres of antinuclear antibody (ANA), anti-double-stranded deoxyribonucleic acid antibody (anti-dsDNA), anti-Sm antibody, and 24-h urinary protein significantly decreased, while complements 3 (C3) and C4 normalised at 100 days after transplantation (p<0.05). Kidney re-biopsy revealed a decrease in immune complex deposits in patients with remission. The incidence of CMV reactivation was 59.09% after transplantation in 3 years. Pregnancy and childbirth were reported in three female patients after transplantation. The risk of post-transplantation complications persisted for many years. CONCLUSIONS: Immunoablation followed by APHSCT has the potential to induce long-term clinical and serologic remissions despite withdrawal of immunosuppressive maintenance therapy. While relapses may occur, in our small cohort of patients we found no predictive markers for relapse development by analysing antibody and complement levels and urinary proteinuria.

Systemic Lupus Erythematosus Is Associated With Increased Adverse Postoperative Renal Outcomes and Mortality: A Historical Cohort Study Using Administrative Health Data.

BACKGROUND: Systemic lupus erythematosus (SLE) is a common autoimmune connective tissue disease that mainly harms kidneys, heart, lungs, and nervous system. Effects of surgical stimulus and anesthesia combined with SLE-related pathologies may increase morbidity and mortality. Therefore, we aimed to evaluate the association between SLE (versus none) and postoperative renal, cardiac, and in-hospital mortality complications among patients undergoing major surgeries. METHODS: We obtained censuses of 2009 to 2011 inpatient hospital discharges across 7 states and conducted a retrospective cohort study by using International Classification of Diseases and Injuries, Version 9, diagnosis codes, procedure codes, and present-on-admission indicators. We included patients who had major surgery and matched each SLE discharge up to 4 control discharges for potential confounders. We assessed the association between matched SLE patients and controls on in-hospital renal complications, cardiovascular complications, and in-hospital mortality using separate logistic regression models. RESULTS: Among 8 million qualifying discharges, our sample contained 28,269 SLE patients matched with 13,269 controls. SLE was associated with a significantly higher risk of postoperative renal complications, with an estimated odds ratio (99% CI) of 1.33 (1.21, 1.46); P < .001. In addition, SLE was significantly associated with a higher risk of in-hospital mortality, with an estimated odds ratio (99% CI) of 1.27 (1.11, 1.47); P < .001. However, we found no significant association between SLE and cardiac complications, with an estimated odds ratio (99% CI) of 0.98 (0.83, 1.16), P = .79. CONCLUSIONS: This is, by far, the largest clinical study for postoperative outcomes of SLE patients with adequately powered statistical analyses. We concluded that SLE was associated with a higher risk of renal complications and in-hospital mortality but not cardiac events after major surgery. In SLE patients, more aggressive measures should be taken to prevent renal injury in the perioperative period.

Echocardiography in Infective Endocarditis: State of the Art.

PURPOSE OF REVIEW: In this review, we examine the central role of echocardiography in the diagnosis, prognosis, and management of infective endocarditis (IE). RECENT FINDINGS: 2D transthoracic echocardiography (TTE) and transesophageal echocardiography TEE have complementary roles and are unequivocally the mainstay of diagnostic imaging in IE. The advent of 3D and multiplanar imaging have greatly enhanced the ability of the imager to evaluate cardiac structure and function. Technologic advances in 3D imaging allow for the reconstruction of realistic anatomic images that in turn have positively impacted IE-related surgical planning and intervention. CT and metabolic imaging appear to be emerging as promising ancillary diagnostic tools that could be deployed in select scenarios to circumvent some of the limitations of echocardiography. Our review summarizes the indispensable and central role of various echocardiographic modalities in the management of infective endocarditis. The complementary role of 2D TTE and TEE are discussed and areas where 3D TEE offers incremental value highlighted. An algorithm summarizing a contemporary approach to the workup of endocarditis is provided and major societal guidelines for timing of surgery are reviewed.

Effect of nonmyeloablative unrelated fetal and neonatal murine peripheral blood mononuclear cell infusion on MRL/lpr mice.

For patients with refractory systemic lupus erythematosus (SLE), current medications are insufficient to control their condition, and new treatments are necessary. We investigated the effect of fetal and neonatal murine peripheral blood (FNPB) mononuclear cells on MRL/lpr lupus-prone mice. Female MRL/lpr mice were randomized to three groups (control, radiation and infusion groups). The infusion group had significantly better results for survival rate, body weight increase, reduction of spleen index, serum anti-ds-DNA antibody, antinuclear antibodies (ANA) and creatinine (Cr), 24 h urine protein and pathological renal tissue lesions than either the control or radiation group. Graft versus host disease (GVHD) was not observed in MRL/lpr mice in the infusion group. The infusion group also had better hematogenesis reconstruction than the radiation group. Flow cytometry analysis revealed a significant increase in Th1, CD8+ T and T reg cells and a reduction in Th2, CD4+ T and Th17 cells in the peripheral blood of the radiation and infusion groups compared with the control group. Immunocytochemical assay revealed a significant increase in serum transforming growth factor (TGF)-ß and a significant reduction in interleukin (IL)-17 in the radiation and infusion groups compared with the control group. Therefore, our study showed that FNPB mononuclear cell infusion has a significant role in regulating CD4+ T cells, Th1/Th2, Th17/T reg balance and their corresponding cytokines in MRL/lpr mice. The FNPB mononuclear cell infusion provided evidence in animals and suggested a potential clinical application for umbilical cord blood transplantation to treat SLE patients.

Laser therapy in the treatment of connective tissue diseases: a review.

BACKGROUND: Connective tissue diseases (CTD), including lupus erythematosus (LE), scleroderma, sarcoidosis, and dermatomyositis, present with clinically unique cutaneous manifestations often resistant to conventional therapy. The use of lasers in the treatment of various dermatologic conditions continues to expand, presenting an opportunity for incorporation of another mechanism of action in the treatment of CTD. OBJECTIVES: To review the use of laser therapy in the treatment of LE, scleroderma, sarcoidosis, and dermatomyositis. MATERIALS AND METHODS: A MEDLINE search was conducted to find articles detailing treatment of CTD with laser therapy. RESULTS: Thirty-nine published articles were identified. The outcomes and results of case reports were reviewed for each CTD when possible. CONCLUSIONS: Laser therapy offers novel and often effective treatment for recalcitrant cutaneous conditions in LE, scleroderma, sarcoidosis, and dermatomyositis. Review of the literature revealed a limited number of reports, many describing outdated technologies and techniques. It is therefore difficult to draw substantial conclusions regarding safety and the known association with photosensitivity. More-recent reports suggest that, with continued evolution of technology and understanding of CTD, lasers will have an expanding role in the treatment of cutaneous manifestations of CTD.

Isolated tricuspid valve repair for Libman-Sacks endocarditis.

Cardiac involvement is a well-known complication of systemic lupus erythematosus (SLE), which can involve most cardiac components, including pericardium, conduction system, myocardium, heart valves, and coronary arteries. Libman-Sacks (verrucous) endocarditis is the characteristic cardiac valvular manifestation. Although isolated tricuspid valve involvement is quite rare, we report a patient with SLE who had tricuspid stenosis caused by Libman-Sacks endocarditis. The patient underwent successful commisurotomy and Kay annuloplasty on the tricuspid valve under cardiopulmonary bypass.

Mitral valve surgery in patients with systemic lupus erythematosus.

Valvular heart disease is the common cardiac manifestation of systemic lupus erythematosus (SLE) with a tendency for mitral valve regurgitation. In this study we report a case of mitral valve replacement for mitral stenosis caused by Libman-Sacks endocarditis in the setting of SLE. In addition, we provide a systematic review of the literature on mitral valve surgery in the presence of Libman-Sacks endocarditis because its challenge on surgical options continues. Surgical decision depends on structural involvement of mitral valve and presence of active lupus nephritis and antiphospholipid antibody syndrome. Review of the literature has also shown that outcome is good in most SLE patients who have undergone valvular surgery, but association of antiphospholipid antibody syndrome with SLE has negative impact on the outcome.

Flatfoot Surgery for Flexible Progressive Collapsing Foot Deformity With Inflammatory Joint Diseases: A Report of 3 Cases.

CASE: Three cases of inflammatory joint diseases (systemic lupus erythematosus and ongoing juvenile idiopathic arthritis) with painful flexible progressive collapsing foot deformity (PCFD) underwent flatfoot surgery. All cases maintained sufficient radiological correction and achieved good clinical condition at final follow-up. CONCLUSION: Although the prospect for recurrence of the deformity is not clear, even in inflammatory joint diseases, flat foot surgery such as flexor digitorum longs transfer, spring ligament reconstruction, and lateral column lengthening could have a possibility to be indicated against PCFD, as long as disease activity could be well suppressed by drug therapy, subsequently subtalar and talonavicular joints could be preserved.

Spontaneous coronary artery dissection in a 35 year-old woman with systemic lupus erythematosus successfully treated by angioplasty.

Spontaneous coronary artery dissection (SCAD) is an unusual cause of acute myocardial ischaemia with complex pathophysiology; it has been associated with several conditions such as atherosclerosis, connective tissue disorders and the peripartum period. SCAD has exceptionally been reported (three published cases) in patients with systemic lupus erythematosus (SLE). In this work, we report the original case of a 35 year-old woman with a known history of SLE who presented with an acute coronary syndrome caused by an extensive dissection of the left anterior descending artery (LAD) and the diagonal and who was successfully treated by an intravascular ultrasound (IVUS)-guided percutaneous angioplasty.

Total hip arthroplasty for vascular necrosis of the femoral head in patients with systemic lupus erythematosus: a midterm follow-up study of 28 hips in 24 patients.

OBJECTIVE: Avascular necrosis of the femoral head is one of the most frequently reported complications in patients with systemic lupus erythematosus (SLE) and often requires total hip arthroplasty (THA). Our objective was to analyze the perioperative management, technical problems, clinical outcomes, and complications associated with THA in patients with SLE. METHODS: A total of 28 total hip arthroplasties performed for 24 patients with SLE, including 19 women and 5 men with a mean age of 38.8 years performed from 1998 to 2011 were retrospectively reviewed. SLE disease activity index and ASA class were evaluated preoperatively. WOMAC, HHS, and SF-36 scores were also evaluated in all cases pre- and post-operatively for functional recovery of the hip and health-related quality of life (HRQOL). RESULTS: The average SLE disease activity index was 3.5 points. Three patients were in ASA class I, 12 class II, and 9 were class III (37.5%). The average duration of follow-up was 67.5 months. None of the patients required a revision, and 3 patients died during the follow-up period. A statistically significant improvement in all scores was found comparing pre- and post-operative conditions (P < 0.001). The complication rate was 11.1% with 2 wound infections and 1 urinary tract infection. CONCLUSION: THA is an acceptable method for achieving functional recovery and increasing HRQOL in patients with SLE and ANFH who receive proper perioperative management.

Immunological reconstitution after autologous stem cell transplantation in patients with refractory systemic autoimmune diseases.

OBJECTIVE: High-dose chemotherapy followed by autologous haematopoietic stem cell transplantation (AHSCT) can be a salvage therapy for patients with severe, refractory systemic autoimmune diseases. The function of the newly rebuilt immune system is important, but little is known about immune reconstitution after AHSCT in autoimmune disorders. Our aim was to investigate the repopulation of different lymphocyte subsets in patients with systemic autoimmune diseases after AHSCT. METHODS: Twelve patients with severe refractory, autoimmune diseases were enrolled in the study: four with rheumatoid arthritis (RA), four with systemic sclerosis (SSc), three with systemic lupus erythematosus (SLE), and one with autoimmune overlap syndrome (myositis and RA). After stem-cell mobilization, CD34+ apheresis was carried out, followed by conditioning and AHSCT. After transplantation, peripheral lymphocyte subsets were regularly assessed by flow cytometry. RESULTS: The follow-up time was 24 months. The overall transplantation-related mortality (TRM) was 16.7% and the transplant-related toxicity was 33% 2 years after AHSCT. Regarding the immune reconstitution, CD56+ natural killer (NK) cells appeared in the earliest phase after transplantation, followed by CD8+ T cells. B cells and CD4+ T cells became normal within 150 days. The ratio of naive cells was low 30 days after AHSCT; however, naive B cells regenerated within 2 months whereas the repopulation of naive T cells took longer. After a short increase, the ratio of memory cells decreased 2 months after transplantation. Regulatory T (Treg) cells did not change significantly in the peritransplant period. Altogether approximately 5-6 months were required for the reconstitution of the peripheral immune network. CONCLUSIONS: AHSCT can be a salvage therapeutic modality in autoimmune patients who are refractory to other conventional therapies.

A systematic review and meta-analysis comparing complications following total hip arthroplasty for systemic lupus erythematosus versus for non-systemic lupus erythematosus.

BACKGROUND: Osteonecrosis of the femoral head is one of the most severe complications in systemic lupus erythematosus (SLE) patients. Total hip arthroplasty (THA) is an effective treatment for femoral head necrosis. However, there is no consensus on the specific effect of THA on SLE patients. The objective of the present study was to review the current evidence regarding rates of THA complications and postoperative function in systemic lupus erythematosus. METHODS: Two independent reviewers searched PubMed, Cochrane Library, and EMBASE from January 1, 2000, to December 29, 2021. The primary outcomes were postoperative complications, including deep vein thrombosis (DVT), hematoma, wound infection, dislocation, periprosthetic fracture, revision, mortality. RESULTS: A total of 179 articles yielded 28 studies eligible for inclusion with 10 studies used for meta-analysis. This study found a statistically significant difference in DVT, dislocation, wound infection, periprosthetic fracture, and revision. CONCLUSIONS: This meta-analysis shows that SLE patients with THA are at an increased risk of DVT, wound infection, dislocation, periprosthetic fracture, revision, periprosthetic joint infection, following THA in comparison with non-SLE patients with THA. There was no adequate evidence to support the notion that the risk of seroma or hematoma following THA is increased in SLE. Also, there was no significant difference in HHS scores between SLE patients and non-SLE patients after THA.

Surgical resection of lupus nephritis with pulmonary Aspergillus infection: a case report and review of the literature.

We report a 58-year-old Asian woman who was diagnosed with systemic lupus erythematosus (SLE) and lupus nephritis, together with a mixed pulmonary bacterial and fungal infection including Aspergillus. The infection did not respond well to the routine administration of anti-bacterial and anti-fungal drugs, and the patient's creatinine levels continued to rise and protein remained in her urine. The patient's SLE persisted without going into remission. Finally, surgical resection of the pulmonary aspergilloma brought the SLE back under control.

Hematopoietic stem cell transplant for systemic lupus erythematosus: Interferon regulatory factor 7 activation correlates with the IFN signature and recurrent disease.

The expression and activation of regulatory factors (IRF) and rinterferon (IFN) response genes were evaluated in a patient treated with autologous hematopoietic stem cell transplant (HSCT) for refractory systemic lupus erythematosus (SLE). In SLE patients, genetic variants of IRF5 and IRF7 have been associated with increased serum IFNα levels, suggesting a pathogenic role in the type I IFN response. Clinical and molecular analyses of an SLE patient treated with high-dose immunosuppressive therapy and autologous stem cell transplant was performed. Western blot analysis showed that induction of IRF7 protein expression correlated with recurrent lupus disease activity. In addition, phosphorylation of IRF3 and activation of 4 E-BP1, a translational repressor of IRF7, preceded the disease flare. In SLE post-transplant, recurrent disease activity and induction of IRF7 protein expression correlated with activation of the IFN signature. This unique trend in regulation of IRF warrants further mechanistic investigation and confirmation with increased numbers of SLE patients.

Regulatory T cell (Treg) subsets return in patients with refractory lupus following stem cell transplantation, and TGF-beta-producing CD8+ Treg cells are associated with immunological remission of lupus.

Compared with conventional drug therapy, autologous hemopoietic stem cell transplantation (HSCT) can induce very-long-term remission in refractory lupus patients. Herein, we show that in posttransplant patients, both CD4(+)CD25(high)FoxP3(+) and an unusual CD8(+)FoxP3(+) Treg subset return to levels seen in normal subjects; accompanied by almost complete inhibition of pathogenic T cell response to critical peptide autoepitopes from histones in nucleosomes, the major lupus autoantigen from apoptotic cells. In addition to a stably sustained elevation of FoxP3, posttransplant CD8 T cells also maintained markedly higher expression levels of latency-associated peptide (LAP), CD103, PD-1, PD-L1, and CTLA-4, as compared with pretransplant CD8 T cells that were identically treated by a one-time activation and rest in short-term culture. The posttransplant CD8 regulatory T cells (Treg) have autoantigen-specific and nonspecific suppressive activity, which is contact independent and predominantly TGF-beta dependent. By contrast, the pretransplant CD8 T cells have helper activity, which is cell contact dependent. Although CD4(+)CD25(high) Treg cells return during clinical remission of conventional drug-treated lupus, the posttransplant patient's CD8 Treg cells are considerably more potent, and they are absent in drug-treated patients in whom CD4 T cell autoreactivity to nucleosomal epitopes persists even during clinical remission. Therefore, unlike conventional drug therapy, hemopoietic stem cell transplantation generates a newly differentiated population of LAP(high)CD103(high) CD8(TGF-beta) Treg cells, which repairs the Treg deficiency in human lupus to maintain patients in true immunological remission.

Splenectomy for thrombocytopenia associated with systemic lupus erythematosus in 11 Chinese patients.

Since the role of splenectomy in treating thrombocytopenia associated with systemic lupus erythematosus has been controversial, the study was focused on determining the efficacy of splenectomy in the SLE-associated thrombocytopenia. Between 1980 and 2008, 11 patients with SLE underwent splenectomy for treating their thrombocytopenia. Surgical indications, operative mortality and morbidity, and haematological outcomes were followed in both short term (first 30 days) and long term (last recorded platelet count, last contact, or death). Indications for splenectomy included: thrombocytopenia refractory to (63.7%), dependent on (27.3%), or patient intolerance of (9%) medical treatments. Perioperative mortality and morbidity was 0%. The overall rate of early partial or complete response rate to splenectomy was 100%. After a median follow-up of 36 months, 9 (81.9%) patients had sustained complete or partial response without relapse. Eight (72.8%) of these patients required adjunctive medical therapy, whereas the other 1 (9%) did not. The remaining 2 (18.2%) patients relapsed, could not been subsequently salvaged to at least partial response with further treatments. The overall PR or CR to splenectomy combined with medical therapy was 81.8%. Splenectomy should be considered as a safe and efficacious therapy for the severe thrombocytopenia associated with SLE in some selected patients.

Long-term remission after successful pregnancy in autologous peripheral blood stem cell transplanted system lupus erythematosus patients.

Pregnancies in systemic lupus erythematosus (SLE) patients are high risk to both mother and fetus because of increased rates of complications. During the past years, we have treated many cases of SLE patients using autologous peripheral blood stem cell transplantation with good outcome after pregnancy. The rate of maternal hypertension and lupus nephritis was greatly reduced in autologous peripheral blood stem cell transplanted group (n = 11) when compared to non-transplant group (n = 39) (P < 0.05). In addition, the outcome of lupus flare activity of the mother after delivery is significantly better in transplanted group than that in non-transplanted group (P < 0.05). Here, we describe two typical cases of long duration (>6 years) of remission after successful pregnancy in refractory SLE patients post-autologous peripheral blood stem cell transplantation. Our report demonstrated that peripheral blood stem cell transplantation is safe and effective, thereby could be recommended as prior strategy in refractory SLE patients, especially for those women of child-bearing age who plan for pregnancy.